4^th International Conference and Exhibition on Immunology September 28-30, 2015 Houston, Texas, USA

Biography:

De-chu Christopher Tang founded VaxDome LLC in 2014 and Vaxin Inc. in 1997 in Birmingham, Alabama. He was an Assistant/Associate Professor at University of Alabama at Birmingham (1994-2004). He was one of the pioneers during the development of DNA vaccines, noninvasive skin-patch vaccines, adenovirus-vectored nasal vaccines, adenovirus-vectored poultry vaccines, as well as the protective innate-adaptive immunity duo platform technology. He was selected as a Distinguished Overseas Scientist by the South Korea KOFST Brain Pool Program in 2012; and was appointed as a Scientist at International Vaccine Institute in 2013.

Abstract:

We report that intranasal administration of an E1/E3-defective (E1E3) adenovirus serotype 5 (Ad5)-vectored influenza vaccine could induce seroconversion in human volunteers without appreciable adverse effects, even in subjects with pre-existing Ad5 immunity. Mice and ferrets were well protected against challenge by a lethal dose of an H5N1 avian influenza virus following intranasal instillation of an Ad5 vector encoding hemagglutinin (HA) in a single-dose regimen. Moreover, the E1E3 Ad5 particle itself without transgene could confer rapid-sustained-broad protection against influenza by inducing an anti-influenza state in a drug-like manner, conceivably by activating a specific arm of innate immunity. An Ad5 vector encoding HA thus consolidates drug and vaccine into a single package, which allows the Ad5 backbone to induce protective innate immunity capable of conferring nearly-immediate and prolonged (e.g., 1- 47 days) protection as the first wave against influenza; followed by HA-mediated adaptive immunity as the second wave before the innate immunity-associated anti-influenza state declines away. Overall, the work conceivably would foster the development of a novel noninvasive drug-vaccine duo platform technology capable of conferring rapid-sustained-broad protection against pathogens with neither the potential to induce drug resistance nor that to trigger harmful systemic inflammation.

Biography:

Xingmin Sun is an Assistant Professor in research focusing on Clostridium difficile infection at Tufts University, USA. He received his PhD (magna cum laude) in Natural Sciences from University of Kiel, Germany, and did his Post-doctoral training in Molecular Microbiology, Cell Biology & Biochemistry at Brown University, USA. He received Young Scientist Award from Federation of European Microbiological Societies in 2002, and Infectious Diseases Fellows Grant from American Society for Microbiology and the Infectious Diseases Society of America in 2008. His research is supported by NIH and private sectors. He is investigating C. difficile toxin-mediated signal transduction, leading to the production of proinflammatory mediators. He is also developing preventive and therapeutic approaches targeting C. diffcile toxins and proinflammatory mediators in Clostridium difficile infection.

Abstract:

Clostridium difficile is the major cause of hospital-acquired infectious diarrhea and colitis in developed countries. The pathogenicity of C. difficile is mainly mediated by the release of two potent large exotoxins, toxin A (TcdA) and toxin B (TcdB), both of which are pathogenic and require neutralization to prevent disease occurrence. We have constructed a novel recombinant fusion protein, designated mTcd138, containing the receptor binding domain of TcdA and the glucosyltransferase and cysteine proteinase domains of TcdB and expressed it in Bacillus megaterium. To ensure mTcd138 is atoxic, two point mutations were made in the glucosyltransferase domain of TcdB, which essentially eliminates the toxicity. Parenteral immunizations of mice with mTcd138 induced highly protective antibodies to both toxins and provided full protection against parenteral toxin challenges with lethal doses of toxins and infection with a hyper-virulent C. difficile strain UK6. Our studies demonstrate the potential of mTcd138 as a vaccine candidate against CDI in humans.

Biography:

Ildikó Molnár MD has completed her PhD at the age of 39 years at the candidate of science course (PhD) of Hungarian Academy of Science. Work and research connected her to Kenézy County and Teaching Hospital from 1977 to 2008. Now she is the chief of EndoMed, Immunoendocrinology, Private Outpatient Clinic from 2008. She is an expert in ELISA, Western and ECL blottings, colorimetric iodine measurement, as well as in allergy testing and bone density measurement with Hologic DEXA. She has published more than 48 papers in reputed journals, 16 chapters and 2 books.

Abstract:

Postmenopausal women demonstrate increased susceptibility to chronic inflammatory events. Estrogen deficiency increases the production of inflammatory cytokines such as IL-1, IL-6 and tumor necrosis factor-α (TNFα), as well as activates the IL-17 receptor signaling pathway. IL-17 (also known as IL-17A) is a new candidate in the chronic inflammatory diseases, produced by T helper 17 (Th17) lymphocytes and effects on neutrophil recruitment and granulopoesis. We studied the relationship between IL-17A serum levels and estrogen deficiency, as well as IL-17A-mediated osteoporosis in postmeno¬pausal women. Seventy-two post-menopausal and 22 pre-menopausal women formed the patient groups. Estradiol, osteoprotegerin (OPG), soluble receptor activator of NF-κB (sRANK) ligand, IL-17A were measured with enzyme-linked immunoassy (ELISA) and dual-energy X-ray absorptiometry (DXA) was carried out. High prevalence of elevated IL-17A serum levels were demonstrated in postmeno¬pausal women compared to premenopausal ones (3.5±0.56 vs 2.88±0.08 ng/ml, P<0.0001). IL-17A levels showed age-related dependency and a remarkable association with the postmenopausal period (P<0.05). Osteoporotic women demonstrated higher IL-17A, OPG and sRANK ligand serum levels than those who had osteopenia (3.65±0.61 vs. 3.31±0.43 ng/ml for IL-17A, P<0.007; 2.88±0.84 vs. 2.49±0.61 ng/mk for sRANK ligand, P<0.027; 1.43±0.07 vs. 1.39±0.07 ng/ml for OPG, P<0.038). IL-17A levels inversely correlated with total lumbar bone mineral densities (BMDs) (Pí0.0008, r=-0.279) and positively with sRANK ligand levels (P<0.0001, r=0.387). The results demonstrated a high prevalence of increased IL-17A serum levels in postmenopausal estrogen deficiency highlighting its role in chronic infflammatory events such as in bone loss and age-related susceptibility to chronic inflammatory diseases.

Biography:

Ahmad G Hegazi worked as a Professor of Microbiology & Immunology, National Research Center, Dept. Parasitology, 1997-2000, Chair of Faculty of Medicine, Zagazig University, 1981-1997, part-time Professor and Supervisor of Immunology Section, National Research Center, 1990- up till now. He is also Prof. of Microbiology & Immunology, African Federation of Apiculture Associations (AFAA), 2001- up till now, Standing Commission on Apitherapy (APIMONDIA), 1999 - up till now, Member of Standing Scientific Committee, National Research Center, 1998 –up till now. He was awarded the Excellent Medal of the First Class, 1995, received the Senior Scientist Prize of National Research Center, 1996, and won The Second Best Research Paper award from International Congress of Propolis, Argentina, 2000. He has published in Egyptian Journal of Immunology, 1995, was in the Editorial Board of The Egyptian Association of Immunologists, 1992 –1997, Secretary General, Referee in 37 international journals patents: 4 Patents Educational Activities. He has published 193 articles in national and international scientific journals, 6 books in English and 7 books in Arabic.

Abstract:

Objective: Examined cytokines in serum samples from 80 patients with multiple sclerosis treated with apitherapy in particular using bee sting therapy. Methods: Eighty patients with MS, their ages ranged between 26-71 years, were subjected to complete clinical and neurological history and examination to confirm the diagnosis. All cases were under their regular treatment they were divided into two main groups, Group I received honey, pollen, royal jelly and propolis and were treated with apiacupuncture 3 times weekly, for 12 months, in addition to their medical treatment, while group II remains on their ordinary medical treatment only. IFN-γ, interleukin (IL) 1β, IL-4, IL-6, IL-10, tumor necrosis factor alpha (TNFα) were detected. Apiacupuncture was done by bee stings for regulating the immune system. Results: Results revealed that 12 patients showed some improvement regarding their defects in gait, bowel control, constipation and urination, while 28 cases, showed some mild improvement in their movement in bed, and better improvement in bed sores, sensation, and better motor power, only six cases of them were able to stand for few minutes with support. The level of IFN-γ, (IL) 1β, IL-4, IL-10, TNF-α was significantly elevated in patients in Group II, and no significant differences were found for IL-6 between the 2 groups of treatment. The mean values of IgE level in both groups of M.S. patients were low but with no statistical significance, while by the end of the study there were an elevation in the levels of IgE for both groups which was statistically significant. Conclusion: Although Apitherapy is not a curable therapy in MS, but it can be used to minimize the clinical symptoms of MS and evaluating responses to specific therapies which can be included among programs of MS therapy. Cytokines in multiple sclerosis may help to identify mechanisms involved in the pathogenesis of the disease.

Biography:

Seema Bhargava is a medical postgraduate with a PhD as well. She has received several awards for her work, among them the James Willerson Clinical Award by the International Academy of Cardiovascular Sciences in 2013, during her Post-doctoral stint at University of Louisville, Kentucky, USA. Her research on homocysteine has involved its implication in occlusive vascular disease, neurological disease (including Alzheimer’s) and memory loss, resulting in implementation of several translational aspects at Sir Ganga Ram Hospital in diagnosis and management of vascular and neurological diseases. She continues to focus on identification of clinically relevant biochemical markers and their applications in neurology, Alzheimer’s disease, cardiovascular disease, and sepsis.

Abstract:

Introduction: The pathophysiology and morbidity/ mortality of sepsis are governed by the deterioration of the endovascular epithelium. There is a protective layer of the vascular endothelium - the glycocalyx - which lines blood vessels on the luminal side and protects it from direct insult. Amongst the components of this glycocalyx layer are Syndecan and Hyaluronan. When the glycocalyx is disrupted by cytokines released in response to pathogens, these components are released into circulation. It would therefore follow that their concentration in the serum would reflect the extent of insult and morbidity. Methods: Community acquired sepsis patients (147) were enrolled in the study from those who were admitted to the ICU of our tertiary care hospital. They were divided into three categories – sepsis, severe sepsis and septic shock. Another mode of grouping divided them into survivors and non-survivors. Syndecan and hyaluronan were measured in the serum of these patients on days 1, 3, 5 and 7 of admission. Statistical analysis was performed to evaluate their prognostic efficacy (Kruskaal Wallis and Mann Whitney U tests) and their correlation (Spearman’s correlation) to the SOFA and APACHE scores. Results: Both syndecan and hyaluronan were significantly different in all three categories (p=0.006 and 0.022 respectively) only on day 1. Syndecan differentiated between survivors and non-survivors on all days (p=0.010, 0.002, 0.027, 0.006 respectively, on days 1, 3, 5, 7); hyaluronan differentiated these two categories on days 3, 5, and 7 (p=0.019, 0.025, 0.003, respectively). Syndecan strongly correlated with the SOFA scores on days 1, 3 and 5 (p=0.000, 0.003, 0.000 respectively). Hyaluronan correlated significantly with SOFA on all days (p=0.006, 0.001, 0.003, 0.004 respectively, on days 1, 3, 5, and 7). Hyaluronan also exhibited significant correlation with the APACHE score (p=0.005). Conclusions: Both glycocalyx components correlate with the severity of illness on day 1 of admission. Syndecan is of better prognostic value than hyaluronan in predicting survival from day 1. Both correlate with the organ failure (SOFA) score. It was observed that concentration of both markers in serum started to fall after day 3. It is therefore suggested that, therapeutic agents, to protect and rejuvenate the glycocalyx, need to be identified and implemented within the first 3 days.

Biography:

Hasan Zaki, PhD is an Assistant Professor of Pathology, and studies gastrointestinal inflammation and cancer. His research interests include host-pathogen interaction, the role of pathogen sensors in intestinal inflammation and cancer, pathogenic mechanisms of inflammatory bowel disease and colorectal cancer and identifying immune checkpoints of gastrointestinal disorders that could be targeted for therapeutic intervention and drug development. He earned his Undergraduate and Master\'s degrees in Microbiology at the University of Dhaka, Bangladesh. He then joined the International Center for Diarrheal Disease Research, Bangladesh, where he studied immune responses against enteric pathogens. He did his Doctoral research in the Department of Microbiology at Kumamoto University School of Medicine, Kumamoto, Japan, where he investigated the molecular mechanisms of host defense function of nitric oxide during gastrointestinal infection caused by Salmonella typhimurium.

Abstract:

The inflammasome, a molecular platform for caspase-1 activation and subsequent maturation of proinflammatory cytokines IL-1 and IL-18, plays a central role in diverse inflammatory diseases. At least four different pathogen recognition receptors namely NLRP3, NLRP1b, NLRC4 and AIM2 can form the inflammasome complex through the interaction with caspase-1 via an adapter molecule ASC. We previously demonstrated that the NLRP3 inflammasome protects mice from experimental colitis and colorectal tumorigenesis. The NLRP3 inflammasome-dependent protection of intestinal inflammation and tumorigenesis is associated with increased damage in the epithelial barrier, suggesting a key role of the inflammasome in the regulation of intestinal epithelial cell physiology. Interestingly, caspase-1 activation is only partially suppressed in NLRP3-deficient mice, indicating the participation of other inflammasome pathways in intestinal homeostasis. However, the question remains which non-NLRP3 inflammasome pathways are functional in the intestinal milieu. In recent studies, we observed that intestinal microbial DNA is potent activators of the AIM2 inflammasome and Aim2-deficient mice are defective in caspase-1 activation in the colon during experimental colitis. This result is accompanied by increased colitis susceptibility in Aim2-deficient mice as characterized by increased body weight loss, higher inflammatory responses and exacerbated histological changes. Our study also shows that the AIM2 inflammasome regulates intestinal epithelial cell proliferation and antimicrobial peptide production. Taken together, microbial pattern molecules including DNA in the gut activate multiple inflammasome pathways in the intestine which critically contribute to intestinal homeostasis via regulation of the intestinal epithelial cell physiology.

Biography:

Michael Schnoor studied Chemistry and Biochemistry at the University of Münster, Germany and received his PhD in 2004. He then joined the lab of Dr. Parkos at Emory University, Atlanta, GA as Post-doc before moving to the Max-Planck-Institute of Molecular Biomedicine in Germany to investigate the importance of the actin-binding proteins cortactin and HS1 in leukocyte recruitment during inflammation. In November 2011, he accepted an appointment as PI at the Department for Molecular Biomedicine, Cinvestav, Mexico-City where he continues to investigate molecular mechanisms regulating vascular permeability and leukocyte extravasation. In 2012, he received the Pathologist-in-Training Merit Award from the American Society of Investigative Pathology.

Abstract:

Neutrophil extravasation is a critical step in innate immunity in response to tissue injury or invading pathogens. Inflammatory signals activate β2-integrins and facilitate neutrophil adhesion on to the endothelial apical surface and intraluminal crawling to the site of diapedesis. Hematopoietic cell-specific lyn substrate (HS1), the cortactin homologue in hematopoietic cells, regulates actin dynamics at the immune synapse and in neutrophils during migration. However, it is not yet known if HS1 plays a role in the regulation of the neutrophil extravasation cascade. Investigating HS1-deficient mice by intravital microscopy of the inflamed cremaster, we found an increased rolling velocity and a strong inhibition of neutrophil adhesion and transmigration. Additionally, HS1-deficient neutrophils showed disturbed polarization in response to both tumor necrosis factor-α and keratinocyte-derived chemokine (KC). These effects were not due to disturbed expression of adhesion molecules but could rather be explained by disturbed Rap1 activation causing reduced neutrophil adhesion in response to KC treatment. Interestingly, this process was dependent on PKA activation since PKA inhibition blocked KC-induced Rap1 activation. The importance of PKA for HS1-mediated support of extravasation was corroborated by the finding that PKA activation increased whereas inhibition reduced transmigration of WT neutrophils but not of HS1-KO neutrophils. However, HS1 is not a direct substrate of PKA but it co-immunoprecipitates with phosphorylated VASP. This interaction is also inhibited after PKA inhibition and may thus provide an important scaffold for Rap1 activation. Our results establish HS1 and PKA as critical signal mediators that coordinate the molecular machinery required for Rap1 activation and efficient neutrophil transmigration

Biography:

Maria da Graça Justo Araujo has completed her PhD at the Federal University of Rio de Janeiro, Brazil, as well as his Post-doctoral studies in Fanconi anemia. She is a Professor at the State University of Rio de Janeiro, working in the Department of biochemistry. She has worked with Fanconi anemia since 1994 and has contributed to research on this subject.

Abstract:

Fanconi anemia (FA) is a genetic disorder of genomic instability, with main clinical symptoms involving congenital abnormalities, infertility, bone marrow failure and a predisposition to the development of several types of cancer, especially acute myelogenous leukemia (AML) and head and neck carcinomas. Homozygous or bi-allelic mutations in one of 16 genes corresponding to distinct proteins prevent the repair of DNA damage caused by inter-strand cross-linking (ICL) agents and maintenance of genomic integrity during the replication process. The pathogenesis of FA affects cellular processes essential for the homeostasis of the organism, such as differentiation, proliferation and apoptosis, among other less evident, as the immune system that seems to reflect a primary defect of the disease. Peripheral cytokines such as TNF-, INF-, IL-10 and IL-1β may be increased in the blood of these patients, while lower levels IL-6 are observed. However, patients with advanced bone marrow failure seem to show a different profile, with increased levels of TGF-β and IL-6. The absolute number of total lymphocytes is reduced, more specifically the populations of B, T CD8+ and NK cells, as well as their activities. Changes are observed in the proportions normally seen among NK cell subpopulations, suggesting defects in the differentiation of these cells. Clinically, these changes are reflected in an increased susceptibility to various pathogens. Here, we will describe aspects of the diversity, plasticity and microenvironment of the immune system and how genomic instability can affect these mechanisms in the immune system of patients with FA.

Biography:

Ana Acacia Pinheiro has completed her PhD from Federal University of Rio de Janeiro and Post-doctoral studies from Bloomberg School of Public Health, Johns Hopkins University. She is the Adjunct Professor of the Instituto de Biofísica Carlos Chagas Filho from the Federal University of Rio de Janeiro. She has published 30 papers in reputed journals and has been serving as an Editorial Board Member of repute.

Abstract:

Malaria is a worldwide health problem leading to the death of millions of people. The disease is induced by different species of protozoa parasites from the genus Plasmodium. In humans, Plasmodium falciparum is the most dangerous species responsible for severe disease. Despite all efforts to establish the pathogenesis of malaria, it is far from being fully understood. In addition, resistance to existing drugs has developed in several strains and the development of new effective compounds to fight these parasites is a major issue. Recent discoveries indicate the potential role of the renin-angiotensin system (RAS) in malaria infection. Angiotensin receptors have not been described in the parasite genome, however several reports in the literature suggest a direct effect of angiotensin-derived peptides on different aspects of the host-parasite interaction. Here, we highlight new findings on the involvement of the RAS in parasite development and in the regulation of the host immune response in an attempt to expand our knowledge of the pathogenesis of this disease.

Biography:

Toshimasa Nakada graduated from the Hirosaki University School of Medicine in 1981 and acquired MD in 1988. I give medical care and study as a pediatrician at Aomori Prefectural Central Hospital from 1988. I am also clinical assistant professor of Hirosaki University of Medicine. Recent study is “ Effects of anti-inflammatory drugs on intravenous immunoglobulin therapy in the acute phase of Kawasaki disease “ (Pediatr Cardiol 36:335-339,2015).

Abstract:

Appropriate therapy during the acute phase of Kawasaki disease to prevent large coronary artery lesions (CAL) has not been established. The aim of this retrospective study was to investigate the usefulness of initial intravenous immunoglobulin (IVIG) monotherapy. In total, 200 pediatric patients who received IVIG therapy for Kawasaki disease between 1999 and 2014 at Department of Pediatrics, Aomori Prefectural Central Hospital were enrolled. An initial IVIG regimen of 2 g/kg/day, starting on day 5, was used as first-line therapy when possible. Second-line therapy was additional IVIG therapy, and third-line therapy was an urinastatin infusion or plasma exchange. All patients were divided into two groups. The S group comprised 129 patients who received initial IVIG monotherapy with delayed administration of anti-inflammatory drugs (ADs). The T group comprised 71 patients who received concomitant ADs with IVIG. Initial IVIG therapy resistance occurred in 50 of 200 patients (25%), and 16 patients (8%) received additional IVIG. Four patients received urinastatin and one patient received plasma exchange as third-line therapy. Before the 30th day, the prevalence of CAL was 7% (13/200); after 30 days, it was 3% (5/200). The prevalence of CAL before and after 30 days between the S vs. T groups were 2/129 vs. 11/71 (P<0.001) and 1/129 vs. 4/71 (P=0.055), respectively. Variable factors including IVIG resistance and responsiveness and relapse of the disease were associated with CAL development. Initial single IVIG therapy may be useful for the prevention of large CAL caused by different factors of Kawasaki disease.

Biography:

Lucia Gemma Delogu has completed her PhD from Sassari University and Post-doctoral studies from University of Southern California. She is Assistant Professor of Biochemistry at the University of Sassari, Italy. She has published more than 21 papers in reputed journals and 9 as first or Senior/Corresponding author.

Abstract:

Graphene oxide (GO) is gaining the interest of the scientific community for its revolutionary future applications i.e. for drug delivery. In this context, the possible immune cell impact of GO is a fundamental area of study for a translational application in medicine. We focused on the effects, on human lymphomonocytes (PBMCs) of two types of GOs, deeply characterized, which differed in lateral size dimension (GO-Small: 140 nm, and GO-Large 4 m). To clarify the immune impact of GOs we provided a wide range of assays looking at cells viability, cell activation, cytokines release and gene expression. We let in lights also the impact of GOs on immune response-related 84 genes. GOs didn’t impact the cell viability. In particular, the GO-Small modulated 16 genes (FR>4) compared to only 5 of GO-Large, evidencing a clear lateral dimension-dependent impact on cell activation. We confirmed the size-related effect at the protein level by multiplex ELISA. These evidences were also confirmed by microarray analysis on T and monocytes cell lines. GO-Small impact the immune cell activation, underlined by the over expression of genes such as CXCL10 ligand pathway and CXCR3 receptor. Data also evidenced the GO-Small-induced metabolism modulation in both cell types. Our work represents a comprehensive characterization of different sized GOs on immune cells giving crucial information for the chemical and physical design of graphene for biomedical applications i.e. as a new possible drug delivery systems and nanoimmunotherapy tools.

Biography:

V Kalarani has completed her PhD from Sri Venkateswara University, Tirupati, Andhra Pradesh, India and Post-doctoral studies in the University of Calgary, Canada. She is the Head and Chairperson Board of studies of Dept. of Biotechnology, S.P. Mahila Visvavidyalayam. She has published more than 40 papers in reputed journals, guided more than 20 Master’s projects and supervising 8 PhD students. She is also serving as an Evaluator / Adjudicator of many research programmes.

Abstract:

Indiscriminate use of antibiotics to prevent and control diseases affecting the health of fish has led to the development and propagation of antibiotic resistant bacteria in the aquatic ecosystems. Amongst the various alternatives proposed, the most widely accepted approach is the use of probiotics to enhance immunity in fish. In this experiment, we have used Bacillus subtilis as probiotic bacteria and studied the effect of dietary administration of B. subtilis (107 cfu /g-1) on the immune and humoral responses of L. rohita fed for 30(B1) and 60(B2) days. The results show that serum phagocytic activity significantly increased by 36%(B1) and 39%(B2); respiratory burst activity increased by 60%(B1) and 90%(B2); Myeloperoxidase activity increased by 26%(B1) and 71%(B2); serum IgM levels increased by 46%(B1) but decreased by 6%(B2) and serum lectins have increased by 20%(B1) and 46%(B2) in fish fed on diet supplemented with B. subtilis compared to those fed on normal diets. Similarly haemagglutination (70% and 90% respectively in B1 and B2 groups) and haemolytic activity (77% and 98% respectively in B1 and B2 groups) also increased significantly in fish fed on B. subtilis supplemented diets in B1 and B2 groups compared to those fed on control diets. Similar experiment was done using Terribacillus saccharophillus, isolated for the first time from laboratory reared L. rohita. It was found that T. saccharophillus (107 cfu /g-1) supplemented diet also significantly increased the immune responses, though to a lesser extent, in L. rohita. The results suggest that T. saccharophillus could also be used as a potent probiont similar to B. subtilis and will have potential applications in fish feed formulations and disease prevention.

Biography:

Ming-Yow Hung, Assistant Professor has studied coronary artery spasm and aortic stenosis for 10 years, during which he has authored more than 30 peer-reviewed reports. He has served on the editorial board for the Journal of the Taiwan Society of Echocardiography, and Enliven: Clinical Cardiology and Research. He is a Fellow of the American College of Cardiology and the American Heart Association, and has served on several review committees for Acta Cardiologica, Scientific World Journal, JACC: Cardiovascular Interventions, and Enliven: Clinical Cardiology and Research.

Abstract:

Coronary artery spasm (CAS), an intense vasoconstriction of coronary arteries causing vessel occlusion, plays an important role in myocardial ischemic syndromes including angina, acute myocardial infarction, and sudden cardiac death. Smoking, age and high-sensitivity C-reactive protein (hs-CRP) are risk factors for CAS. While high hs-CRP level has recently been found to be an important risk factor for CAS, its relationship with CAS may differ between genders. In patients with low hs-CRP levels, diabetes mellitus has been shown to contribute to CAS development in men but not in women; however, in patients with high hs-CRP levels, there are negative effects of diabetes mellitus and hypertension on CAS development, especially in women. In the mid 2000s, chronic inflammation was shown to be associated with CAS, as evidenced by elevated peripheral white blood cell and monocyte counts, hs-CRP, interleukin-6, and adhesion molecules. Calcific aortic valve stenosis (CAVS) is the most common form of acquired valvular heart disease. About 50% of patients with CAVS do not have coronary artery disease, suggesting related, but unique, pathophysiology. One of these pathways may involve the lipoprotein(a) (Lp[a]), lipoprotein-associated phospholipase A2 (Lp-PLA2), and oxidized phospholipids (OxPL) axis. Recently, a genome-wide association study showed that single nucleotide polymorphism (SNP) rs10455872 at the LPA gene locus was causally related to CAVS. A key proinflammatory property of Lp(a) may be its content of OxPL. Elevated levels of OxPL on apoB (OxPL/apoB) predict death, myocardial infarction, and stroke. Overall, these observations suggest plausible mechanisms through which Lp(a)–Lp-PLA2–OxPL may mediate CAVS.

Biography:

Seong-Woon Yu has completed his PhD from Seoul National University, Korea and postdoctoral studies from Johns Hopkins University School of Medicine. He was assistant professor at the Departments of Neurology, Pharmacology and Toxicology in Michigan State University and now is associate professor of the Department of Brain and Cognitive Sciences, DGIST, Daegu , Korea. His research efforts are focused on the mechanisms of cell death of neurons and neural stem cells during neurodegeneration. The molecular mechanisms regulating neuroinflammation is also his main research interest.

Abstract:

Translocator protein 18 kDa (TSPO) is a protein located on the outer membrane of mitochondria. TSPO is expressed mainly in glial cells in the central nervous system and its expression level is highly up-regulated during neuronal injury and neuroinflammation. We previously reported that TSPO acts as a negative regulator of microglia activation. However, it is not known yet whether TSPO is involved in inflammasome signaling. Inflammasomes are multiprotein complexes for caspase-1 activation and IL-1 processing and implicated in many inflammatory diseases. In this talk, I present the evidence that the prototypical TSPO ligand, Ro5-4864 (Ro5) inhibits NLRP3 inflammasome signaling in THP-1 cells using the canonical LPS-primed/ATP-induced NLRP3 inflammasome model. Ro5 efficiently blocked release of IL-1 and caspase-1, and reduced ASC speck formation and NLRP3 translocation to mitochondria. Ro5 also attenuated LPS/ATP-induced perturbation of mitochondrial function by preventing generation of mitochondrial superoxide and depolarization of mitochondrial membrane potential. These results indicate that the immune modulatory effect of the TSPO ligand Ro5 is through inhibition of NLRP3 inflammasome signaling, suggesting Ro5 as a promising agent with efficacy for NLRP3 inflammasome-associated diseases.

Biography:

Simon J Clark obtained his BSc in Biochemistry (with Immunology) at the University of Aberdeen in 2002 and subsequently spent a year working in industry on the development of diagnostic tests for cardiovascular disease. In 2003 he matriculated at Oxford to begin his DPhil studies investigating the interaction of complement factor H (FH), an innate immune regulator, with endogenous sugar molecules as a mechanism for host recognition. In 2006, he moved to the Faculty of Life Sciences, University of Manchester, to study further the regulation of innate immunity on extracellular matrices and successfully identified the sugar molecules that FH binds to in Bruch’s membrane, the site of AMD pathogenesis. He now works in the Faculty of Medicine and Human Sciences, University of Manchester, where he has taken up an MRC Career Development Fellowship. Recently, he identified another protein, made by alternative splicing of the FH gene; called factor H-like protein 1 (FHL-1) is actually the main complement regulator in Bruch’s membrane. He is now focusing his work on understanding how FHL-1 and the FHR proteins contribute to immune regulation around the human body.

Abstract:

A number of genetic alterations are associated with an increased risk of developing age-related macular degeneration (AMD): The leading cause of blindness in the western World. Many of the risk modifying mutations and polymorphisms arise in genes involved in the complement cascade, part of a host’s innate immune system. While much work has focused on the Y402H polymorphism in the main complement regulator factor H (FH), increasing evidence suggests this protein does not work alone in protecting Bruch’s membrane in the human eye, an important site of AMD pathogenesis. Factor H-like protein 1 (FHL-1) arises from an alternative splice variation of the CFH gene and retains all of the regulatory activity of FH: FHL-1 is also subject to the Y402H polymorphism. Furthermore, five factor H-related (FHR) proteins also exist and share varying degrees of homology with FH. Genetic changes in the region containing the FHR genes are also associated with AMD, including a protective deletion of the FHR1 and 3 genes. Using specific antibodies and targeted mass spectrometry, we identify the significant presence of FHL-1 in Bruch’s membrane. This is converse to the understanding that FH is the major regulator of complement. In this regard, we demonstrate local expression of FHL-1 and the fact that the full length FH protein is not able to diffuse through Bruch’s membrane from human sera. The presence of FHR proteins also adds weight to the hypothesis that they may well compete with FHL-1 to binding sites in Bruch’s membrane. An imbalance in this fine regulation based on genetics and driven via environmental or age-related factors, will lead to inappropriate complement activation and local inflammation. Here, the author will talk on current understanding of AMD pathogenesis, present new data and discuss therapeutic strategies for treating this devastating disease

Biography:

Melissa B. Aldrich is part of a team of scientists at the Center for Molecular Imaging of the Brown Institute for Molecular Medicine at UTHealth in Houston, Texas. Using near-infrared fluorescence lymphatic imaging (NIRFLI), the team conducts pre-clinical and clinical studies of lymphatics in primary and secondary lymphedema, lipedema, wound healing, rare adipose and venous disorders, and chylothorax. Dr. Aldrich’s education includes a B.A. in biochemistry from the University of Texas at Austin, a M.B.A. from the University of Houston, and a Ph.D. in immunology from the University of Texas Health Science Center-Houston. Her research work has shown that inflammatory cytokines affect lymphatic flow systemically, and that breast cancer-associated lymphedema is a systemic, progressive disease.

Abstract:

The response of the lymphatic system to inflammatory insult and infection is not completely understood. A chance observation in a human clinical study suggested that inflammation can systemically affect lymphatic pumping. Using a near-infrared fluorescence (NIRF) imaging system to noninvasively document propulsive function, we noted the short-term cessation of murine lymphatic propulsion as early as 4h following LPS injection. Notably, the effects were systemic, displaying bilateral lymphatic pumping cessation after a unilateral insult. Furthermore, IL-1β, TNF-α, and IL-6, cytokines that were found to be elevated in serum during lymphatic pumping cessation, were shown separately to acutely and systemically decrease lymphatic pulsing frequency and velocity following intradermal administration. Surprisingly, marked lymphatic vessel dilation and leakiness were noted in limbs contralateral to IL-1β intradermal administration, but not in ipsilateral limbs. The effects of IL-1β on lymphatic pumping were abated by pre-treatment with an inhibitor of inducible nitric oxide synthase, L-NIL (N-iminoethyl-L-lysine). The results suggest that lymphatic propulsion is systemically impaired within 4h of acute inflammatory insult, and that some cytokines are major effectors of lymphatic pumping cessation through nitric oxide-mediated mechanisms. These findings establish cytokines as mediators of lymphatic function in inflammatory and infectious states, and may have implications in the understanding of lymphedema and lipedema.

Biography:

Lucia Gemma Delogu has completed her PhD at the age of 26 years from Sassari University and postdoctoral studies from University of Southern California. She is assistant professor of Biochemistry at the University of Sassari, Italy. She has published more than 21 papers in reputed journals and 9 as first or senior/corresponding author.

Abstract:

Graphene oxide (GO) is gaining the interest of the scientific community for its revolutionary future applications i.e. for drug delivery [Geim AK et al. Nature Materials 2007]. In this context, the possible immune cell impact of GO is a fundamental area of study for a translational application in medicine [Goldberg MS, Cell 2015; Orecchioni M. et al. JTM 2014]. We focused on the effects, on human lymphomonocytes (PBMCs), of two types of GOs, deeply characterized, which differed in lateral size dimension (GO-Small: 140nm, and GO-Large 4m). To clarify the immune impact of GOs we provided a wide range of assays looking at cells viability, cell activation, cytokines release and gene expression. We let in lights also the impact of GOs on immune response-related 84 genes. GOs didn’t impact the cell viability. In particular, the GO-Small modulated 16 genes (FR >4) compared to only 5 of GO-Large, evidencing a clear lateral dimension-dependent impact on cell activation. We confirmed the size-related effect at the protein level by multiplex ELISA. These evidences were also confirmed by microarray analysis on T and monocytes cell lines. GO-Small impact the immune cell activation, underlined by the over expression of genes such as CXCL10 ligand pathway and CXCR3 receptor. Data also evidenced the GO-Small-induced methabolism modulation in both cell types. Our work represents a comprehensive characterization of different sized GOs on immune cells giving crucial information for the chemical and physical design of graphene for biomedical applications i.e. as a new possible drug delivery systems and nanoimmunotherapy tools.

Biography:

Robert H Schiestl has obtained his PhD from the University of Vienna. He was a Post-doctoral fellow at Edmonton, Alberta, Rochester, NY, and Chapel Hill, NC before working as a Professor at Harvard, where he stayed for 10 years. Since 15 years, he is working as a Professor at UCLA with 190 publications, 6 press releases, 10 patents and 2 startup companies.

Abstract:

To determine susceptibility of subpopulations of cells in the peripheral blood as well as of peripheral lymphoid organs to several types of DNA damage in genetic mouse models of spontaneous chronic intestinal inflammation and to determine the sufficiency of tumor necrosis factor α (TNF-α) in inducing this genotoxicity. By determining correlations of DNA damage to disease activity, we hope to substantiate systemic genotoxicity as a biomarker of inflammatory activity in intestinal inflammation. Peripheral blood subpopulations were isolated via magnetic bead sorting and cells from peripheral lymphoid organs were isolated incolitic IL-10 mice of various disease activity (3 and 6 months of age), Gαi2 mice (3 months of age) and in wild-type mice with no intestinal inflammation. DNA strand breaks were measured in cells with the alkaline comet assay with hOGG1 incubation to determine oxidative base damage and DNA double strand breaks specifically were quantified by γH2AX foci immune-staining. Recombinant mouse TNF-α or saline was injected (500 ng/mouse) into the tail vein of wild-type mice and peripheral blood was analyzed for DNA damage at several time points post injection. DNA single and double strand breaks were found in subpopulations of cells in the peripheral blood as well as in the peripheral lymphoid organs, which correlated to disease activity of mice with intestinal inflammation. CD4 and CD8 T-cells seemed most sensitive to DNA damage. TNF-α was sufficient to induce DNA damage in wild-type mice. Chronic intestinal inflammation induces systemic DNA damage, in which CD4 and CD8 T-cells are the most sensitive. TNF-α plays a role in inducing this damage though further mechanisms remain investigated. Levels of DNA damage in the peripheral blood correlated strongly to inflammatory activity and severity of disease, making DNA damage to leukocytes a good biomarker to diagnose and monitor disease in inflammatory bowel disease patients.

Biography:

Ammira S Al-Shabeeb AKIL has completed her PhD at 2010 and postdoctoral studies from University of New South Wales and University of Sydney, faculty of Medicine. She is assistant professor of molecular Immunology and virology, at University of Sharjah, UAE and also a visiting assistant professor at University of New South Wales, Sydney Australia. She has published more than 20 paper and conference proceeding in reputed journals and also a member of several scientific comities and organizations.

Abstract:

There is no longer a question as to whether viruses contribute to the pathogenesis of type 1diabetes (T1D). We now have evidence using next generation sequencing (NGS) of enteroviruses EVs isolated from children with islet autoimmunity (IA) demonstrating up to 10% change in the viral genome at the nucleotide level 10 days after inoculation into human islets. NGS:Full-length EV genomes were amplified as a single 7.4 kb fragment by RT-PCR, and NGS performed using the Illumina MiSeq sequencer. Phylogenetic analysis of the full-length viral consensus sequences performed using the neighbour joining and maximum likelihood method. Trees were constructed from alignment of complete genome sequences by using best-fit models and visualised using FigTree. Comparisons were performed with Viral Epidemiology Signature Pattern Analysis (VESPA). Two of the EVs from IA+ cases had an N to S amino acid (AA) substitution within the 2C protein, which became dominant after 10 days passage in the islets. EV isolate from another IA+ case has 5 AA differences within the capsid protein VP4 at residues 3, 16, 18, 50 and 61. VP4 has been shown in vitro to be a target of human antibodies that enhance CVB induced synthesis of interferon α (IFN-α). Antibodies directed towards the region 11-30 of the VP4 capsid enhance infection of peripheral blood cells with CVB4 in vitro. Therefore, our preliminary data suggest VP4 may be a determinant of ‘diabetogenicity’. Our novel NGS data will contribute to vaccine development from a global perspective and then reduce the future burden of T1D.

Biography:

Abstract:

The aim of this study was to compare the effects of aerobic exercise aerobic swimming insists on serum IL-6 and TNF-a and HS. CRP young women. This is a quasi-experimental study population included 100 women swimmers were in Mashhad. Age range 25 to 30 years and have 4 basic swimming skills were adequate. Total of 28 patients were randomly assigned into 2 groups (two groups of 14 each aerobic and anaerobic exercise, swimming) and 10 patients in the control group. Blood samples were taken to measure the factors and analyzing the data using descriptive and inferential statistics, Kolmogorov-Smirnov test and ANOVA (ANOVA) was conducted. The following results were obtained: Serum IL-6 levels between subjects, there were no significant differences(p=0/019). Serum levels of TNF-a significant difference between subjects there. (p=0/005) Between There were no significant differences in serumlevel of HS- CRP participants (p=0/001).

Conclusion:
According to this study, aerobic exercise and anaerobic swimming reduces the level of IL-6 and TNF-a and HS. CRP in subjects that this reduction was statistically significant.
Keywords: IL-6 and TNF-a and HS. CRP

Biography:

Abstract:

CMV remains an important opportunistic pathogen in solid organ transplantation, particularly in lung transplant recipients (LTRs). LTRs mismatched for CMV (donor+/recipient-; D+R-) are at high-risk for active CMV infection and increased mortality, however the immune correlates of viral control remain incompletely understood. We prospectively studied 23 D+R- LTRs during primary CMV infection to determine whether acute CD8+ T-cell parameters differentiated the capacity for viral control in early chronic infection. T-box transcription factors expression patterns of T-bet >Eomes differentiated LTR controllers from viremicrelapsers, and reciprocally correlated with granzyme B loading, and CMV phosphoprotein 65 (pp65)-specific CD8+IFN-+ and CD107a+ frequencies. LTR relapsers demonstrated reduced CD8+Ki67+ cells ex vivo and substantially impaired CD8+pp65-specific in vitro proliferative responses at 6 days, with concomitantly lower pp65-specific CD4+IL-2+ frequencies, as compared to LTR controllers. However, CMV-specific in vitro proliferative responses could be significantly rescued, most effectively with pp65 antigen and exogenous IL-2, resulting in an increased T-bet:Eomes balance, and enhanced effector function. Using class I CMV tetramers, we observed similar frequencies between relapsers and controllers, though reduced T-bet:Eomes balance in tetramer+ cells from relapsers, along with impaired CD8+ effector responses to tetramer-peptide re-stimulation. Together, these data show impaired CMV-specific CD8+ effector responses is not for complete lack of CMV-specific cells, but rather, underscores the importance of the T-bet:Eomes balance, with CMV-specific proliferation a key factor driving early T-bet expression and effector function in CD8+ T cells during primary infection, and differentiating the capacity of high-risk LTRs to establish immune control during early chronic infection.

Biography:

Abstract:

TNF- plays a very important role in the progression of various inflammatory diseases including rheumatoid arthritis. This study aims towards the designing, synthesis and evaluating the effects of the peptide inhibitors of TNF-. Trimerized form of TNF-α is the active one, which can bind to receptor resulting in the progression of inflammatory cascade. The phenomenon of trimer formation was targeted for designing the inhibitors. The peptides were designed in silico using various bioinformatic tools and synthesized by solid phase peptide synthesis (SPPS) process. The anti-TNF activity of four different peptides (peptide 1, 2, 3 and 4) was checked in-vitro. Effect of peptide-2 was found to show the most significant anti-TNFα activity. TNF-α induced cell death of Wehi-164 cells was evaluated through MTT assay. The peptide-induced inhibition of TNF-a resulted in reduced cell death and increased viability. The TNF-α induced nuclear translocation of NF-kB was visualized using immune cytochemical analysis using A549 cells. The Western blotting of the nuclear lysate showed under expression of NF-κB in the TNF-stimulated cells with peptide inhibition as compared to the cells untreated with peptides. This result was fairly corroborated with the Electrophoretic Mobility Shift Assay (EMSA) test of the nuclear lysates of the experimental cells. Peptide-2 showed a dose dependent inhibition on the TNF-α activity, with maximum effect at 200 μM of the peptide concentration (p < 0.05). No significant cytotoxicity was observed when stimulated with the peptides with the concentrations ranging between 50 and 400µM. To conclude, peptide-2 showed the highest anti- TNF activity among all the peptides tested and this peptide-2 appears to have potential of being a peptide drug, for which in-vivo studies and further trials are required.

Biography:

Abstract:

Major depressive disorder (MDD) and schizophrenia are associated with inflammatory processes. Studies have shown that these disorders exhibit increase in the level of one or more proinflammatory markers. However, these studies did not exclude patients with obvious inflammation (i.e., CRP46 mg/L). Therefore, a comprehensive study should include those inflammatory disorders. In the present study, the inflammatory natures of MDD and schizophrenia were investigated. To achieve this goal, serum levels of interleukin-6 (IL-6), interleukin-18 (IL-18), tumor necrosis factor alpha (TNFα), and soluble interleukin 2 receptor (sIL-2R) in depressed and schizophrenic patients were obtained and compared with those of the control group. Results showed a significant increase (po0.05) in serum levels of IL-6, IL-18, TNFα, and sIL-2R in MDD and schizophrenic patients compared with the control group. Also patients with schizophrenia group showed higher levels of the inflammatory markers than MDD and control groups. The current study concluded that the immunological response in the MDD and schizophrenic patients groups was significantly stimulated. These disorders may be considered an inflammatory disorder because of elevated levels of proinflammatory cytokines in spite of lacking an overt inflammation. Furthermore results of this study suggested the possibility of the use of anti-inflammatory drugs as adjuvant therapy in schizophrenic and depressive disorders.

Biography:

Abstract:

IFNλR1 and IL10R2 collectively construct a heterodimer, which is an acknowledged functional receptor for all type III interferons (IFNs). Expression of IFNλR1 is highly tissue specific, which can help in making type III IFNs as drug of choice as compared to its analogous, type I IFNs for treating hepatitis C in the near future. Although, expression of IFNλR1 also varies with the concentration of type I IFNs, but in this study it was shown that the expression of IFNλR1 varies with the protein titers of IFN-α, IFN-λ3 and the newly discovered IFN-λ4. High dosage of IFN-α reduces the expression of IFNλR1 in HepG2 cells, which can affect the antiviral activity of type III IFNs in vivo. We premeditated an experimental strategy to differentiate monocytes into DC, type I and type II macrophages in vitro and quantified the expression of the IFNλR1 by qPCR. The exposure of newly discovered IFN-λ4 to macrophages and DCs also raised the expression of its own receptor, which shows that expression of IFN-λ4 protein in hepatitis C patient may augment type I treatment and help ease off viral titers. The results of this study may help us in contributing some understanding towards the mechanisms involved in the selective expression of IFNLR1 and exceptionalities involved.

Biography:

Manuel Verdecia Jarque, MD, MSc is an Assistant Professor and has 18 years of experience as pediatric oncologist. He is the head of Oncopediatric Service of Infantil Sur hospital and the Provincial Chief of Childrenhood Cancer Control Program. He has published 10 papers in reputed journals and is the member of both IABC and Cuban Oncopaediatric special group.

Abstract:

The pediatric cancer prevails less than that in adults, but its tendency is to increase. In Cuba, 400 new cases arise each year, and between 50 and 60 in our Service are diagnosed from 2005. Brain tumors occupy the third place of all pediatric tumors, after the leukemia and lymphomas. 50-60 % of brain tumors originate in back cavity (astrocytomas, medulloblastomas and ependynomas), whereas 40-50 % remaining are supratentorial. Primitive neuro ectodermal tumors appear in any brain space. This study shows the experiences of a clinical trial, in which is combined the human monoclonal antibody Nimotuzumab with conventional oncologic therapies in intrinsic tumors of cerebral stalk and other localizations. The results show that female sex, astrocytoma (histologic variety) and infratentorial (topographically) prevail, in agreement with the literature. 50% of treated patients have a satisfactory response, whereas 50% remaining disease progression. The best response is obtained for infratentorial tumors. In conclusion, Nimotuzumab, as immunotherapy is feasible for pediatric patients with brain tumors and therefore may constitute another therapeutic option for them.

Biography:

Ampadu Yaw Andrew has completed his Master’s education in Biomedical Science in the University of Chester, UK. He has participated in different scientific academies such as, one organized by the Hannover Medical School in Hannover, Germany. Currently he is working as a lab manager in 37 military hospitals, at the Department of Pathology.

Abstract:

Higher temperature ranges have been found to be associated with the death of cells and the increase of intracellular HSP 72 in Jurkat cells. HSP 72 relates with membrane lipids and are released from cells when heat shocked. Depending on the localization of HSPs on the cell surface, either membrane bound or embedded, HSPs will possibly induce apoptotic cell death or protect cells from dying and other damages related to cellular stress. They may bring out the physiological response of the innate immunity such as the secretion of cytokine and cell activation, thereby promoting roles in stimulating cell protection, death and immune activation under normal physiological conditions and on exposure to stress stimuli. HSP72 is a significant marker for various environmental stresses and diseases; therefore this research seeks to describe the intracellular expression of endogenous HSP 72 by flow cytometry, under control conditions and in response to stress using various heat treatments with the control temperature set at 37°C.

Biography:

Ahmed M Elbana graduated in 2004 with Bachelor's degree in Medicine and Surgery from Alexandria University, Egypt. He worked as House Officer in Alexandria University Hospital till March 2006, ENT Resident in Alexandria University Hospital from Jan 2007 till Jan 2010, and as an ENT Registrar in Alexandria University Hospital from June 2010 till June 2011. He finished his Master degree in Otorhinolaryngology from Alexandria University, Egypt on June 2011 and is working as ENT Registrar in King Fahd Military Medical Complex (KFMMC) Dhahran in Kingdom of Saudi Arabia from 2011 to till now.

Abstract:

Objective:
This study assessed the possibility of mobilizing endogenous bone marrow derived stem cells (SCs) in rats using Granulocyte colony stimulating factor (G-CSF) to induce regeneration and repair to experimentally damaged inner ear hair cells induced in rats by intratympanic Amikacin injection.

Material & Methods:
The study included thirty adult Sprague Dawley male rats. Experimental induction of inner ear damage was done by repeated intratympanic injection of amikacin sulfate. Mobilization of bone marrow SCs was provoked by subcutaneous injection of GCSF. Cochlear integrity, induction of hearing loss and functional recovery of sensory hearing loss were assessed using Distortion Product Otoacoustic Emission (DPOAEs). The morphological alteration and recovery of the organ of Corti was assessed histologically using the light and scanning electron microscopes.

Results:
After six month duration, there was improvement in 50% of the sensorineural DPOAE results. Functional recovery coincided with the histological repair of structural components of organ of Corti.

Conclusion:
SCs mobilization by G-CSF is a promising alternative method for replacement therapy in sensorineural hearing loss.

Biography:

Manuel Verdecia Jarque M.D., MSc., Assistant Professor have 18 years of experience as pediatric oncologist. Head of Oncopediatric Service of Infantil Sur hospital. Provincial chief of Childrenhood Cancer Control Program. He has published 10 papers in reputed journals. Member of both IABC and Cuban Oncopaediatric special group.

Abstract:

The pediatric cancer prevails less than that in adults, but its tendency is to increase. In Cuba, 400 new cases arise each year, and between 50 and 60 in our Service are diagnosed from 2005. Brain tumors occupy the third place of all pediatric tumors, after the leukemia and lymphomas. 50-60 % of brain tumors originate in back cavity (astrocytomas, medulloblastomas and ependynomas), whereas 40-50 % remaining are supratentorial. Primitive neuroectodermal tumors appear in any brain space. This study shows the experiences of a clinical trial, in which is combined the human monoclonal antibody Nimotuzumab with conventional oncologic therapies in intrinsic tumors of cerebral stalk and other localizations. The results show that female sex, astrocytoma (histologic variety) and infratentorial (topographically) prevail, in agreement with the literature. 50 % of treated patients have a satisfactory response, whereas 50 % remaining disease progression. The best response is obtained for Infratentorial tumors. In conclusion, Nimotuzumab, as immunotherapy, is feasible for pediatric patients with brain tumors and therefore may constitute another therapeutic option for them.

Biography:

Sushil Suri has completed his MD Medicine from Kanpur University and special training in Allergy and Immunology from CSIR and VPChest Institute Delhi. Elected Life Member of the IndianCollege of Allergy & Applied Immunology: CONFERENCES Year Conference Venue 1995 Indo-US conference on Recent New Delhi, India Advances in Pediatric Pulmonology & Tuberculosis National Conference on Sleep AIIMS, New Delhi, India. Research. He is the Ex Associate Profesor Medicine, Malaka Manipal Medical College,Malaka ,Malaysia.Presently Consultant Allergist, Suri Medical Foundation Hospital, Lucknow,U.P.India and is faculty at Career Institute of Medical Sciences and Hospitals, Lucknow He has published more than 6 papers in reputed journals.

Abstract:

The work of Kasliwas et al(1959) and Shivpuri et al(1971) have proved beyond doubt that there is a definite correlation between pollen peaks and symptomatology of the patients of respiratoty allergy. With these factors in mind the present study was conducted with the aims - to clinically evaluate the cases of bronchial asthma, to know the spectrum of allergens by skin testing in these cases(intradermal skin tests) and to find out seasonal and climatic variations in these cases. The patients were prepared for intradermal skin test as per Shivpuri et al (1964)The intradermal skin tests were performed by means of a tuberculin syringe and 26 gauge (1”length)short bevelled needle.A negative control test was done in the similar manner with 0.01ml of buffer saline ( the diluent of the antigen)and marked as “C’. A positive control test was done by Histamine phosphate solution(100 microgram/ml) and marked as “H”.Interpretation was done as per Shivpuri’s criteria(Shivpuri1962,1969)The 2 to 4 reactions were taken as “markedly positive”.This study showed that the prevalance of allergic manifestations were higher in first degree relatives(50%)than the second degree relatives(8%)of the patients . In this study the pollen antigens which gave “significant positive reactions”(and there clinical correlation with the patient’s history)in the descending order of significance were as Cassiasiamea, Adhantoda, Morus, Parthenium, Artemesia, Argemonemaxicana, Cannabisoccidentalis, Rumex, Asphodelous, Gynandropsis, Amaranthus, Cenchrusalbum, Ricinuscommunis, Crataeva nurvuala, Melia, Kigelia, Prosopsis, Pennisetum, Dodonaea, Azadirechta, Putranjiva rox-burghii.The extensive botanical and aero-biological surveys with clinical evaluation of a very largre number of cases of alleric bronchial asthma should be carried out in future in order to draw the exact polen calender of this region.

Biography:

Nathali Kaushansky, PhD, is a staff scientist in the Neurobiology Department at the Weizmann Institute of Science. She received her BSc in Chemistry and MSc in Biomedical Engineering from the Technion – Israel Institute of Technology, Haifa, Israel. She completed her PhD studies and post-doctoral training in the Immunology Department in The Weizmann Institute of Science. In the last 10 years her work has focused on characterization of autoimmune T- and B-cells against myelin and neuronal target antigensin Multiple Sclerosis (MS). Her study aims to establish a highly specific “multi – targeting” immunomodulatory approach via co-antagonizing of most known and potentially pathogenic T-cell autoreactivities in MS. The primary goals of her recent research were 1: studying mechanisms underlying immunomodulation by this multi epitope targeting agent (specifically designed artificial multi-epitope protein (Y-MSPc)-recently published) and 2: Studying immunogenetics of susceptibility to MS, mainly at defining HLA-DR2-related epitopes of the different most important myelin target antigens in MS.

Abstract:

Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS, associated with complex anti-myelin autoimmunity. Among all approaches proposed for MS therapy, an approach that neutralizes only the pathogenic T cells reacting against myelin, while leaving the innocent immune cells intact, is the ultimate goal in the immune-specific therapy for MS. The multiplicity of primary target antigens, along side the dynamic nature of autoimmunity in MS, whereby the specificity of anti-myelin pathogenic autoreactivities may shift or expand in the same patient with disease progression, impose major difficulties in devising immune-specific therapy to MS. To overcome this multiplicity and the potential complexity of pathogenic autoreactivities in MS, we have put forward the concept of concomitant multi-antigen/multi-epitope targeting as, a conceivably more effective approach to immunotherapy of MS. We constructed an EAE/MS-related synthetic human Target Autoantigen Gene (MS-shMultiTAG) designed to encode in tandem only EAE/MS related epitopes of all known encephalitogenic proteins. The MS–related protein product (designated Y-MSPc) was immunofunctional and upon tolerogenic administration, it effectively suppressed and reversed EAE induced by a single encephalitogenic protein. Furthermore, Y-MSPc also fully abrogated the development of “complex EAE” induced by a mixture of five encephalitogenic T-cell lines, each specific for a different encephalitogenic epitope of MBP, MOG, PLP, MOBP and OSP. Strikingly, Y-MSPc was consistently more effective than treatment with the single disease-specific peptide or with the peptide cocktail, both in suppressing the development of “classical” or “complex” EAE and in ameliorating ongoing disease. Overall, the modulation of EAE by Y-MSPc was associated with energizing the pathogenic autoreactive T-cells, downregulation of Th1/Th17 cytokine secretion and upregulation of TGF-b secretion. Moreover, we show that both suppression and treatment of ongoing EAE by tolerogenic administration of Y-MSPc is associated also with a remarkable increase in a unique subset of dendritic-cells (DCs), CD11c+CD11b+Gr1+-myeloid derived DCs in both spleen and CNS of treated mice. These DCs, which are with strong immunoregulatory characteristics and are functional in down-modulation of MS-like-disease displayed increased production of IL-4, IL-10 and TGF-b and low IL-12. Functionally, these myeloid DCs suppress the in-vitro proliferation of myelin-specific T-cells and more importantly, the cells were functional in-vivo, as their adoptive transfer into EAE induced mice resulted in strong suppression of the disease, associated with a remarkable induction of CD4+FoxP3+ regulatory cells. These results, which highlight the efficacy of “multi-epitope-targeting” agent in induction of functional regulatory CD11c+CD11b+Gr1+myeloid DCs, further indicate the potential role of these DCs in maintaining peripheral tolerance and their involvement in downregulation of MS-like-disease.

Biography:

Abstract:

Context
- Treatment in antibody mediated rejection of kidney allografts - responders and non responders. Objective - Antibody mediated ( C4d positive and or DSA by luminex positive ) rejection vs T cell mediated rejection in 81 graft biopsies done over 3 year in 138 kidney transplant recipients - comparison for treatment outcomes Data Source - Authors experience , histopathology slides, DSA testing by luminex Reports, Treatment and follow up records of kidney transplant between 2008 and 2011 in kamalnayan Bajaj Hospital, Aurangabad

Observations:
Definative diagnosis of antibody mediated rejection was made if some of the following 3 observations were noted but not all were present 1. morphological evidence of tissue injury existed in 79 /81 biopsies, 2 biopsies were reported as essentialy normal. 2. C4d positivity - immunopathologic evidence for antibody action was noted in 18/79, 22 /79 had T cell mediated acute rejections, 11 of these with borderline changes, remaining were CNI toxicity and nonspecific IFTA 3. serologic evidence for circulating donor specific antibody was positive in 14/79 (MFI values > 3000 in either anti class 1 or class 2 IgG antibody ) . Effective treatment given was methylprednisolone 500 mg daily for 3 days started on suspician of rejection , sending for graft biopsy with c4d staining in all before first dose of pulse steroids . C4d staining positive cases with positive DSA in 3 first 30 post-operative day period cases recd. rabbit thymoglobulin 3 mg/kg over 3 days and 5 mg/kg over 5 days in one case. All these patients recovered. late onset after 3 months of transplant to 3 year - 5/14 DSA +, C4d positive recipients were treated by 4 sessions of daily Plasmapheresis removing 2 litre each time and , low dose ivig ( 100 mg/kg/day after TPE ) with 1 gm of rituximab after last plasmapheresis . Bortezomib 1.2 mg/m2 on day 1,4,7,11 and repeat courses with dsa titres follow up were used in 5 chronic humoral denovo antibody mediated rejections with beneficial effects in 2 cases - DSA dropped to MFI < 1000 Class 1 and class 2 IgG with improvements in proteinuria and stabilisation of creatinine

Conclusion
Antibody mediated rejections with dsa positivity behaved differently to treatment in immdte post-operative period (4/14recovered) , late onset acute rejections ( 5/14 did not respond - 1 died, 4 progressed to end stage ) and chronic ,denovo antibody mediated rejection (5/14 had creeping creatinine -progressing very slowly ) Treatment responders and nonresponders were analysed for clinical presentations, dsa titres, side effects of intervention, and histopathological details

Biography:

Abstract:

A case–control and trio-families study was performed to establish a potential association between TNF-alpha gene promoter SNPs at -308 and -238, and occurrence of CAD in a Pakistani population. In the first phase, 150 patients and 150 controls were enrolled in the case–control association study. In the second phase, heritability of susceptible alleles was investigated from 88 trio-families with CAD affected offspring. Biochemical analysis of lipids and hs-CRP was carried out spectrophotometrically, while serum TNF-alpha concentrations were determined by enzyme-linked immunosorbent assay. Genotyping of the TNF-alpha SNPs were determined by PCR-RFLP method. Elevated serum TNF-alpha and hs-CRP was observed from CAD vs. controls (P < 0.0001; for both). The evaluation of TNFalpha-308G>A polymorphism in case – control studies revealed that the said SNP was significantly associated with the increased risk of CAD. The findings demonstrated a significant link between the TNF-alpha variant allele A at -308 and CAD (P = 0.0035), whereas the -238 SNP was not associated with the disease. Haplotype A–G of the TNF-alpha gene at -308G>A and -238G>A showed higher frequency in the patient group compared with controls (P < 0.05). Moreover, the data showed preferential transmission of the disease susceptible allele A at TNF-alpha-308 from parent to affected offspring in a trio-family study (P < 0.0001). The current research leads to conclusion that the TNF-alpha-308G>A polymorphism is associated with CAD in the study population. Furthermore, for the first time, we showed that the TNF-alpha-308A allele was significantly associated with the familial CAD in our high risk population.

Biography:

Angel A Justiz Vaillant is a medical doctor who has completed his PhD at the age of 35 and has more than 20 publications in reputed journals.

Abstract:

The Human Papilloma Virus (HPV) and Human Immunodeficiency Virus (HIV) are both sexually transmitted infections, which have impacted the prevalence of cervical dysplasia and cancer in women. Infections with one of these viruses can facilitate infection with the other. In Jamaica cervical cancer is seen in 27.5 per 100, 000 women making it the second leading cause of cancer death in this population only to breast cancer as a cause of death in women with cancer. Our study investigates the sero prevalence of anti-HIV antibodies in women with abnormal pap smears in Jamaica to determine the influence of HIV on cervical dysplasia. Only patients with positive confirmatory tests were classified as HIV positive. Enzyme-Linked Immunosorbent Assay (ELISA) was used for screening while the Western blot was used for confirmation. Sero-prevalence of anti-HIV antibodies in women with abnormal pap smears was 0.85%. The preliminary results of HIV sero prevalence in women with abnormal pap smears may be low in Jamaica because of the success of the HIV/AIDS programme. A larger study can be done in the future and be representative of the Jamaica population, since the present study has as a limitation a smaller number of controls in comparison to cases. The findings reported do not support the hypothesis that HPV infection facilitates HIV infection in the studied population. It is the first study of its class reported in the Caribbean. It has been postulated that HPV infections may account for the cervical dysplasia despite the low prevalence of HIV association in the women with abnormal pap smears and that persistent HPV and to a lesser extent the HIV is responsible for the prevalence of abnormal pap smears in Jamaica. A limitation of the study was that the control group was smaller than that expected for 3 million’s population but a larger study can be done in the future.

Biography:

Michelle completed both her Bachelor and Master Science degrees in Biology and she is finishing up her PhD in the Health Sciences program. Michelle currently holds the Technical Director position responsible for clinical diagnostics, clinical trials and R & D groups at the Amerimmune Immunology Laboratory. Previously, she has worked in the pre-clinical and clinical studies of different therapeutic areas at Hoffmann La-Roche, Inc. and Merck & Co. Inc. She utilizes her expertise in different technologies as the basis not only to study the biologics and mechanisms of immune cells in different diseases but to develop assays that support major clinical decisions and impact lives. With more understanding in how immune cells function or not function in immu-nodeficiencies patients, our lab strives to contribute in this field and achieve a new milestone in medicine.

Abstract:

Primary immune deficiencies (PIDs) affect approximately 1 in 1200 persons in the United States. Despite attempts to increase awareness and detection of PID, diagnosis is delayed over 10 years in 45% of the cases. In addition, the traditional diagnosis of immune disorders is taught as a step-wise approach and there are no clear guidelines on which step comes first or how far to progress the evaluation. We hypothesized that physicians lack understanding of immune disorders, the components of an immune deficiency evaluation and its interpretation as being the three main obstacles in identifying PIDs. We designed a diagnostic method called “curbside consultation” and offered it to physicians in Northern Virginia. We then calculated the prevalence of PID before and after our intervention by surveying 328 primary care providers (PCPs) and specialists asking the number of PID patients they have diagnosed. We provided them with the 10 warning signs of immunodeficiency and offered to perform the curbside consultation in patients they suspected of having an immunodeficiency. Patients’ clinical history and pertinent findings were reported to us and a blood sample to perform the immunological assays. Laboratory results were interpreted by an immunologist based on the supporting clinical data provided. A total of 9,265 patients were involved in the study over a two-year period. Prevalence of PID was 5.3:100,000 before the curbside consultation was implemented and increased to 33:100,000 afterwards (P<0.01). The most significant change in prevalence was observed in otolaryngology, pulmonary and pediatric gastroenterology patients. The addition of a qualitative assay and immune profiling, each by itself had a statistically significant impact on identifying additional cases of PID. Furthermore, the value each one of these immune tests differed between specialties. For example, T and NK cell abnormalities are more common in pediatric cardiology patients whereas B cell abnormalities are more predominant in pulmonary, primary care, and otolaryngology referrals. Hereby, we demonstrate the need for a complete assessment of the immune system, in a quantitative and qualitative manner. There is a statistically significant impact in improving accurate diagnosis of immune disorders. We believe that our approach saves healthcare costs by reducing patient referrals, decreasing exhaustive diagnostic evaluations and interventions and likely lessening morbidity by shortening delays in diagnosis.

Biography:

Ricardo Rosales has completely a PhD from Louis Pasteur University-France and Post-doctoral studies at the NIH (National Institutes of Health)-USA. He is a Full Professor at the México University. He is the President of Virolab S de RL de CV. He has published more than 30 papers in reputed journals.

Abstract:

Vaccinia virus was developed and tested as a safe smallpox vaccine. It was also found to be avirulent for normal or immunosuppressed individuals, and not to have negative side effects in all human tested up to now. The approach of expressing a foreign protein via vaccinia virus vectors has already been used to protect animals from other virus infections. Also, it is well known that Human papilloma viruses can induce warts, condylomas, and other intraepithelial cervical lesions that can progress to cancer. Cervical cancer is a serious problem in developing countries because early detection is difficult, and thus proper early treatment is many times missing. Based on this, we evaluate the potential of the MVA E2 recombinant MVA-Virus Vaccine in Phase I, II and III clinical trials to eliminate all types of papillomavirus lesions. 89.3% female patients showed complete elimination of lesions after treatment with MVA E2. In men, all lesions were completely eliminated. All MVA E2-treated patients developed antibodies against the MVA E2 vaccine and generated a specific cytotoxic response against papilloma–transformed cells. Papillomavirus DNA was not detected after treatment in 83% of total patients treated. MVA E2 did not generate any apparent side effects. These data suggest that therapeutic vaccination with MVA E2 vaccine is an excellent candidate to stimulate the immune system and generate regression in intraepithelial lesions when applied locally.

Biography:

Tatiana Barichello concluded her Master degree in 2002 and PhD in 2007 in Biological Sciences-Biochemistry in the Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil. She received the award Brazilian Academy of Sciences/L´Oreal/UNESCO for Women in Science in 2011. At the UT Health she is Assistant Professor at the Department of Psychiatric and Behavioral Sciences and at UNESC is Professor of Post-Graduate Program in Health Sciences University of Southern Santa Catarina, Brazil. She is author of 80 research papers (H-index=17, Thompson Reuters).

Abstract:

Bacterial meningitis is a life threatening infection associated with cognitive impairment in many survivors. The pathogen invades the central nervous system (CNS) by penetrating through the luminal side of the cerebral endothelium, which is an integral part of the blood-brain barrier (BBB). The replication of bacteria within the subarachnoid space occurs concomitantly with the release of their compounds that are highly immunogenic. These compounds known as pathogen-associated molecular patterns (PAMPs) are recognized by antigen-presenting cells through the binding of Toll-like receptors, triggering an inflammatory cascade. This in turn produces cytokines and chemokines, increases adhesion molecule expression and attracts leukocytes from the blood. This cascade leads to lipid peroxidation, mitochondrial damage and blood-brain barrier permeability. In spite of effective antibacterial treatments, approximately one third of survivors suffer from long-term sequelae, such as hearing loss, cerebral palsy, seizures, hydrocephaly or cognitive impairment. Our understanding of the pathophysiology of bacterial meningitis is mostly based on observations of human cases and studies in rodent experimental models. In experimental bacterial meningitis the levels of tumour necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, and cytokine-induced neutrophil chemoattractant-1 (CINC-1) were detectable in the brain in the first 24 hours post-infection. These cytokines were increased simultaneously with a decrease of enzymatic defence, an increase of oxidative stress production, and the BBB disruption. The rodents also showed long-term cognitive impairment, depressive-like, and anxiety-like behaviours however, the imipramine treatment reversed depressive-like and anxiety-like behaviours, re-established hippocampal brain-derived neurotropic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) expression, and normalized adrenocorticotropic hormone(ACTH) levels in the blood. In an attempt to minimise the long-term cognitive impairment, rodents that were subjected to bacterial meningitis were exposed to different adjuvant treatments: N-acetylcysteine and deferoxamine, inhibition of matrix metalloproteinases, complex B vitamins, erythropoietin, and tryptophan pathway inhibition. These compounds presented neuro-protective properties and prevented long-term cognitive impairment in experimental bacterial meningitis.

Biography:

Xiubo Fan has completed her PhD from Dalian University of Technology in 2008 and worked as Research Scientist in Singapore General Hospital, Singapore since then. She has published 14 papers in international peer reviewed journals and has been serving as an Editorial Board Member of Autoimmune Diseases and Therapeutic Approaches.

Abstract:

In vitro, the effect of mesenchymal stromal cell (MSC) on immune suppression has been well studied. However, in vivo, questions regarding MSC optimal therapeutic strategy, homing, survival, and timing for immune suppression are still elusive. To address these questions for systemic lupus erythematosus (SLE), autoimmune lymphoproliferative syndrome (ALPS) and Sjogren’s syndrome, a MLR/MpJ-Faslpr/J (Faslpr) mice model was employed. Multipotency of bone marrow derived MSC (BM-MSC) was determined by phenotypic analysis and multipotential differentiation assay. Four- to six-month-old Faslpr mice showed onset of autoimmune disease with lymphoproliferation. Optimal infusion dose was determined by serial dilution. Homing and survival of MSC were monitored by fluorescent microscopy. Infusion frequency was deduced from immunomodulatory kinetics study. BM-MSC with passage number less than 10 could properly maintain multi-lineage differentiation capacity and stem cell phenotypes. Eight rounds administration of 10×106 cells/kg BM-MSC improved mouse survival from 62.5% to 92.9% and reversed lymphoproliferation to normal levels at day-21 post-transplantation (PT) (p=0.189). BM-MSC mainly and eventually homed to immune organs at four months PT. Immunomodulatory kinetics showed that the optimal immunosuppression period of BM-MSC occurred from day-7 to day-21 PT in immune organs, lung, and kidney; hence, optimal infusion frequency was deduced as 21 days. In conclusion, an appropriate therapeutic strategy in a pre-clinical autoimmune disease mouse model was established with a defined MSC source as well as optimal infusion dose, frequency, and administration number. It will help to standardize cell preparation, characterization and administration protocol, and minimize the outcome discrepancies between different centers worldwide.

Biography:

Ahmad G Hegazi worked as a Professor of Microbiology & Immunology, National Research Center National Research Center, Dept. Parasitology, 1997-2000, Chair of Faculty of Medicine, Zagazig University, 1981-1997, part-time Professor and Supervisor of Immunology Section, National Research Center, 1990- up till now. He is also Prof. of Microbiology & Immunology, African Federation of Apiculture Associations (AFAA), 2001- up till now, Standing Commission on Apitherapy (APIMONDIA), 1999 - up till now, Member of Standing Scientific Committee, National Research Center, 1998 –up till now. He was awarded the Excellent Medal of the First Class, 1995, received the Senior Scientist Prize of National Research Center, 1996, and won The Second Best Research Paper award from International Congress of Propolis, Argentina, 2000. He has published in Egyptian Journal of Immunology, 1995, was in the Editorial Board of The Egyptian Association of Immunologists, 1992 –1997, Secretary General, Referee in 37 international journals patents: 4 Patents Educational Activities. He has published 193 articles in national and international scientific journals, 6 books in English and 7 books in Arabic.

Abstract:

Bee venom acupuncture (BVA) from honeybee (Apis mellifera) was potentially used as complementary modality for treatment of many diseases. The aim of this study is to evaluate the efficacy of bee venom acupuncture as alternative medicine therapy for the long term treatment of rheumatoid arthritis (RA). This study is a randomized, controlled clinical trial with two parallel arms. The study intend to compare the effects of BVA by bee sting or bee venom collected by the electric shock device and p with pharmacotherapy only in patients with RA. Forty patients with Rheumatoid arthritis disease are allocated to group of patients with RA are treated with BVA (bee sting) therapy or bee venom collected by the electric shock device at apiacupoints twice a week with convention drug therapy. While other group of patient with Rheumatoid arthritis disease on convention drug therapy. Tender joint count, swollen joint count, morning stiffness, visal analog scal (VAS), health assessment Q, ESR, CRP, Tumor Necrosis Factor (TNF), Interleukin 1(IL1) Interleukin 6,(IL6), Nuclear Factor and Kappa B (NF-KB). All these parameters will be assessed before and after treatment. The results revealed that the bee venom apiacupuncture showed significant improvement in patients received bee venom group compare to patients received pharmacotherapy only. It is concluded that both modes of treatment for RA gave improvement regarding pain intensity, disability and quality of life being more evident in bee venom group supported with improved serum TNF, IL1. IL6 and NF-KB.

Biography:

Paulo R Z Antas has completed his PhD from Fiocruz and Post-doctoral studies from Vanderbilt University Medical Center. He is the Vice-Head of Clinical Immunology Laboratory, Oswaldo Cruz Institute-Fiocruz, a public health organization in Brazil. He has published more than 30 papers in reputed journals and has been serving as an Editorial Board Member of repute.

Abstract:

The inflammatory response plays an important role during the induction of several neonatal diseases. Previous studies have shown that during newborn infections, the natural imbalance between pro- and anti-inflammatory responses shifts towards the production of pro-inflammatory cytokines. In this study, we employed an array system to detect 9 pro- and anti-inflammatory cytokines and performed ELISA for 6 other cytokines. We then compared the immune response profiling in umbilical cord blood (UV) plasma samples with circulating levels in otherwise healthy donors (HD). Concentrations of ex vivo monokine levels, such as interleukins (IL)-18, IL-23 and IL-27, were profoundly reduced in the UV in relation to the HD group (p-values of 0.003, 0.009 and <0.0001, respectively). Conversely, UV-plasmatic TGF-1 levels displayed marked enhancement (p-value=0.005) in relation to HD. Several factors may be implicated in these neonatal alterations and additional characterization of a broader cytokine panel is warranted to reveal other possible candidates.

Biography:

Praveena T is currently pursuing her PhD under the supervision of Prof. Jamie Rossjohn, Department of Biochemistry and Molecular Biology, Monash University. She has been awarded Monash Graduate Scholarship (MGS) and Faculty of Medicine International Post-graduate Scholarship (MIPS) for undertaking her Doctoral studies in Australia. Her PhD work presented in the abstract has contributed to a paper that is currently under re-review in Nature Communications journal.

Abstract:

Natural killer T cells (NKT) are an innate-like population of T lymphocytes that recognize lipid antigens presented on the major histocompatibility complex (MHC)-like molecule CD1d. Upon activation, NKT cells release an array of Th1 and Th2 cytokines that confers ability to influence immune outcomes in a broad range of diseases, including cancer, tumor immunity, autoimmunity, allergy and infection.Thus their immunomodulatory potential enables them to be of important therapeutic targets. NKT cells are widely studied in mice and humans and possess two main subsets, type I and type II. Type I NKT cells typically express an invariant α-chain (Vα14-Jα18 in mice, Vα24-Jα18 in humans) paired with a broad spectrum of β-chains (Vβ8.2, Vβ7 and Vβ2 in mice and Vβ11 in humans) and recognize α-Galactosylceramide (α-Galcer) and termed as ‘semi-invariant’ (iNKT) cells. Type II NKT cells express a diverse TCR repertoire and do not recognize α-Galcer. We have identified a new subset of NKT cells in humans that do recognize α-Galcer presented by CD1d but express different TCRs from that of Inkt cells and termed as ‘Vα24- or non-canonical TCRs’. It is important to note, the prototypical NKT cell antigen, α-Galcer is undergoing phase I/II clinical trials. In our study, we have solved the crystal structure of a non-canonical NKT TCR-CD1d/α-Galcer complex and investigated the structural and molecular basis of glycolipid recognition. Thus, our results shed light in understanding the mechanism of lipid antigen recognition and would aid in designing new immunotherapeutic agents to modulate immune responses in various clinical settings.

Biography:

Hana Zelenková has been active in Dermatovenerology since 1973. Since 2000 she has been directing her own Private Clinic of Dermatovenereology. Orientation: Psoriasis vulgaris, atopic dermatitis, mycosis, aesthetic dermatology (anti aging medicine, keloid and scar). She has given more than 650 expert lectures in Slovak Republic as well as abroad, and has 420 scientific publications. She is the Founder and President of the Slovak Society for Aesthetic and Cosmetic Dermatology President of the traditional international DERMAPARTY congress.

Abstract:

Cyclosporine A is an immunosuppressant cyclic polypeptide isolated from the Tolypocladium inflatum fungus. Indications: organ transplantations (kidney, liver, heart, lungs, pancreas, skin), bone marrow transplantations, autoimmune disorders, and selected dermatoses such as psoriasis or AD. The indication window is opening wider and wider. In most indications the recommended administration form is oral. Transplanted patients require routine monitoring of CyA levels in blood. In non-transplantation indications the monitoring of CyA levels in blood is of limited importance, only. In dermatology, Cyclosporine A is administered in three groups of indications: Group I – dermatoses treated with maximum efficacy drugs, where CyA represents an extraordinarily effective first choice drug. Group II - dermatoses with the possibility to administer an alternative systemic drug based on the therapist’s choice, however, with CyA still being the best choice. Group III - other dermatoses (with individual therapy assessment due to presumed disease development and possible relapses). The window of indications is still widening (chronic urticaria, vitiligo). The commencement of CyA therapy in line I – III requires erudition and experience. In patients with severe dermatoses CyA therapy rapidly improves the local finding and radically improves the quality of patients’ life. Cyclosporine A must be only administered according to evidence based medicine!!!

Biography:

S Catherine Alexander is an Associate Professor in Research Centre and PG Department of Zoology, Jayaraj Annapackiam College for Women (Autonomous), Periyakulam, India. She has completed her PhD in Fish Immunology from Madural Kamaraj University, India and has 23 years of teaching and research experience in immunology. She is the Principal Investigator in major research project funded by University Grants Commission, Government of India. She has published research articles in reputed journals with high impact factor and guiding PhD scholars.

Abstract:

Immunotoxicity is simply defined as the study of the interaction of xenobiotics with the immune system, a definition which incorporates the ability of chemicals both to compromise immune function and to produce specific tissue damage or allergy. The immune responses to chronic exposures to specific immunotoxicological contaminants can be monitored and correlated to disease resistance and overall health. Even very low sub lethal doses of contaminants can have profound effects upon the structure and/or function of the immune system that could be almost as harmful as direct toxic doses, when a disease outbreak occurs. Fish and their immune system may also represent an important scientific tool in the monitoring of environmental quality, particularly immunotoxic environmental pollution. Only in the last few years environmental toxicologists have started to consider effects of aquatic pollution on the immune competence of fish. The impact of contaminants and other environmental factors on the immune system of fish and shellfish is an issue of ecological and economical concern, because it may result in clinical pathology and disease, by increasing the susceptibility of affected organisms to pathogens. Hence, the present study is aimed at investigating the direct effect of sub lethal concentrations of industrial effluents in the nearby areas (tannery industry, coffee industry and electroplating industry) on the specific immune response in terms of antibody level and nonspecific immune mechanisms in terms of serum lysozyme activity, anti protease activity and myeloperoxidase activity and disease resistance against live virulent fish pathogens in selected fin fish species. The results of this study re-emphasize the importance of integration of immunological assays into environmental monitoring with reference to industrial effluents. It also demonstrates the sensitivity of immune mechanisms in relation to environmental contamination, indicating their possible use as immunological indicators.

Biography:

Sadaf Hasan completed her PhD in November 2013 from Interdisciplinary Biotechnology Unit, Aligarh Muslim University, India. She was a recipient of Doctoral Fellowship award (UGC-MANF). She worked on oral biofilms and is currently working as a Research Associate studying antibiotic resistance. She has participated in several national and international conferences. She has published her work in 5 journals of international repute viz., PLoS One, BMC Microbiology and Future Medicine. She is a member of Biochemical Society, UK and has been serving as a reviewer for some international journals.

Abstract:

Antibiotics have revolutionized medicine in many respects and their discovery was a turning point in human history. Unfortunately, the use of these wonder drugs has been accompanied by the rapid appearance of resistance. The acquisition of Extended-spectrum-β lactamases (ESBLs) and Metallo-β lactamases (MBLs) by bacteria confer resistance against the majority of available antibiotics. The outbreak of such multi drug-resistant bacteria has posed a serious concern globally, by jeopardizing the optimism of therapeutic success against future infectious diseases. Monotherapy has been a choice to treat invasive infections since ages. Neverthe¬less, combination therapy has proved to be a promising substitute over monotherapy for infections that do not respond to standard treatments, such as infections occurring by MDR species. Infact, combination therapy is persistently recommended as empirical treatment for bacterial infections in intensive care units, where mono¬therapy fails to combat infections. Hence, we have conducted a study to explore the potential synergistic combinations of different antibiotics against extended-spectrum β-lactamase and metallo β-lactamase producers. The MICs were determined against 12 strains, harboring different resistant markers (blaNDM, blaCTX-M, blaTEM, blaSHV, blaOXA and armA), followed by in vitro synergy testing using microdilution, chequerboard and time-kill assays against different antibiotics. Results suggested that, of all the tested combinations, cefoxitin gave highest rate of synergy when paired with streptomycin and cefotaxime, thus forming effective synergistic combination against multidrug-resistant bacteria. Interestingly, the combination of cefotaxime/cefoxitin showed synergistic activity even against the atrocious NDM-1 producing strains. Therefore, this novel synergistic combination can be used against different resistant strains, including NDM-1 producers.

Biography:

Postdoctoral Research at Mayo Clinic, Rochester, USA (2014-2015), University of Illinois at Chicago, USA (2010-2014), Indian Institute of Toxicology Research, Lucknow, India (2009-2010). His research interests focus on the role of macrophages in the initiation, progression and resolution of inflammatory processes. The long term research interest is to elucidate the inflammatory signaling in macrophages during chronic and acute inflammation. Macrophage recruitment and plasticity are key components of several inflammatory diseases including asthma, fibrosis/cirrhosis, rheumatoid arthritis and atherosclerosis. Understanding the mechanisms that regulate macrophage phenotypic plasticity in tissues is critical for the identification and validation of markers and therapeutic targets in inflammatory diseases.
Awards 2010: Ramanujan Fellowship Award
2014: Ramalinga Swami Fellowship Award
2013: Mirus Research Award, Mirus Bio LLC, USA
2009: Research Bursary Award, UK
2008: FEBS Pre Doctoral Award , Greece
e Cheminfo Award, USA
2007: EMBL International Ph.D Fellow Award
2007: Research Travel Grant Award, USA

Abstract:

Nitric oxide synthases are a family of enzymes that catalyze the production of nitric oxide (NO) from L-arginine. NO is an important cellular signaling molecule, having essential roles in many biological processes including the control of blood pressure, regulation of neuronal activity and immune responses. NOS3 (endothelial NOS or e NOS) and NOS2 (inducible NOS or I NOS) have been appreciated as mediators of inflammatory processes. However, considerably less is known about the role of NOS1 (neuronal NOS or n NOS) in inflammation. We have uncovered an important role for this enzyme in regulating TLR4 signaling. We demonstrate that in contrast to the enhanced susceptibility of NOS2-/- and NOS3-/- mice to LPS, NOS1-/- mice are, in fact, more resistant to LPS-induced lethality and tissue injury. We demonstrate that the loss of NOS1 attenuates TLR4-stimulated cytokine production and NF-κB activity in vivo and in vitro. Macrophages from NOS1-/- animals demonstrate an LPS-induced decrease in protein levels of the p65 subunit of NF-κB. This decrease in p65 protein correlates with an increase in protein levels of suppressor of cytokine signaling-1 (SOCS1) and increased physical association between SOCS1 and p65. On studying the mechanism of NOS1-regulation of inflammation we found that an early pulse of NOS1-derived NO was required to stabilize p65 in the nucleus of macrophages via the inhibitory S-nitrosation of suppressor of Cytokine Signaling-1 (SOCS1). NOS1-derived NO through nitrosation of Cys147 and Cys179 on SOCS1 permits p65-mediated pro-inflammatory gene transcription and is essential for the mechanism of inflammation. Taken together, our results demonstrate that NOS1 is a fundamental early regulator of gene transcription of the inflammatory response thereby heavily impacting the course, type and duration of the inflammatory process.

Biography:

Mehmet Sen has completed his PhD from theUniversity of Houston, Department of Biology and Biochemistry with Glen Legge, M.D., Ph.D., and postdoctoral studies from Harvard Medical School, Department of Biological Chemistry and Molecular Pharmacology with Timothy Alan Springer, Ph.D.He is currently establishing his lab at the University of Houston. His research interests lie in the structural and functional basis of receptor/ligand interactions, which are relevant to human health and disease.

Abstract:

The 2 integrins, which are expressed only on leukocytes, must be activated rapidly to restrict integrin-dependent firm adhesion and emigration of leukocytes from the bloodstream only to sites where cues for inflammation or homing are locally displayed. All 2 integrin subunits contain I domains that bind ligand. Here, we describe two 2 integrin structures: a cocked, metastable state of the leukocyte integrin X2 ectodomain that primes it for rapid conformational change, and reveals how allostery is relayed to activate the I domain, and a closed state of the leukocyte integrin L2 headpiece. The X2 crystal structure reveals the X2 ectodomainin a bent conformation; however, its ligand-binding XI domain is in a high affinity, open conformation. Compared to the closed conformation, much of the I 7-helix unwinds, loses contact with the I domain, and reshapes to form an internal ligand that binds to a hydrophobic and metal ion-containing pocket at the interface with the X -propeller and 2I domains. An analogous pocket binds external ligand in integrins that lack I domains. In comparison of the the2 subunits of the cocked X2 and the closed L2 structures, I domain undergoes unexpected conformational change which reveals ratchet-like changes in positions of conserved hydrophobic residues located in the both N- and C-terminals of the 1-helix, despite absence of change in the neighboring I domain 7-helix, which pistons in integrin headpiece opening. Mutations of these residues demonstrate a key role for ratchet residues in stabilizing active and inactive 2 integrin states Comparisons to other integrins suggest that the cocked state is a specialization of the 2 integrin subunit. My two structures together with mutational analysis demonstrate the metastability of the cocked state, and suggest that it potentially catalyze rapid equilibrium between bent-closed, extended-closed, and extended-open states for rapid upregulation of leukocyte adhesiveness in 2 integrins.

Biography:

Rundk Ahmed Hwaiz is PhD student at Lund University. She was a Lecturer at Hawler Medical University at Erbil/ Kurdistan, Iraq. She has 10 published papers. She will defend her thesis in April 2015.

Abstract:

Accumulating evidence suggest that platelets play an important role in regulating neutrophil recruitment in septic lung injury. Herein, we hypothesized that platelet-derived CCL5 might facilitate sepsis-induced neutrophil accumulation in the lung. Abdominal sepsis was induced by cecal ligation and puncture (CLP) in C57/BL6 mice. CLP increased plasma levels of CCL5. Platelet depletion and treatment with the Rac1 inhibitor NSC23766 markedly reduced CCL5 in the plasma of septic mice. Moreover, Rac1 inhibition completely inhibited proteinase-activated receptor4-induced secretion of CCL5 in isolated platelets. Immunoneutralization of CCL5 decreased CLP-induced neutrophil infiltration, edema formation and tissue injury in the lung. However, inhibition of CCL5 function had no effect on CLP-induced expression of Mac-1 on neutrophils. Blocking CCL5 decreased plasma and lung levels of CXCL1 and CXCL2 in septic animals. CCL5 had no effect on neutrophil chemotaxis in vitro, suggesting an indirect effect of CCL5 on neutrophil recruitment. Intratracheal challenge with CCL5 increased accumulation of neutrophils and formation of CXCL2 in the lung. Administration of the CXCR2 antagonist SB225002 abolished CCL5-induced pulmonary recruitment of neutrophils. Isolated alveolar macrophages expressed significant levels of the CCL5 receptors CCR1 and CCR5. In addition, CCL5 triggered significant secretion of CXCL2 from isolated alveolar macrophages. Notably, intratracheal administration of clodronate not only depleted mice of alveolar macrophages but also abolished CCL5-induced formation of CXCL2 in the lung. Taken together, our findings suggest that Rac1 regulates platelet secretion of CCL5 and that CCL5 is a potent inducer of neutrophil recruitment in septic lung injury via formation of CXCL2 in alveolar macrophages.

Biography:

Mohammed Yousif Merza is a PhD student and permanent staff at Hawler Medical University, Kurdistan. He has graduated from Salahadin University, Hawler in 2003 and completed a Master’s degree at Glasgow University, UK in 2008. He has published 5 papers in reputed journals.

Abstract:

Leukocyte infiltration and acinar cell necrosis are hallmarks of severe acute pancreatitis (AP) but the signaling pathways regulating inflammation and organ injury in the pancreas remain elusive. In the present study, we investigated the role of CXCL4 in AP. Male C57BL/6 mice were treated with an anti CXCL4 antibody (20 µ/kg) prior to induction of pancreatitis by infusion of taurocholate into the pancreatic duct. Pretreatment with anti CXCL4 Ab reduced blood amylase levels, pancreatic neutrophil recruitment and hemorrhage and edema formation in taurocholate-evoked pancreatitis. Moreover, administration of anti CXCL4 Ab decreased the taurocholate-induced increase of myeloperoxidase activity in the pancreas and lung. Treatment with anti CXCL4 Ab markedly reduced levels of CXCL2 in the pancreas and IL-6 in the plasma in response to taurocholate challenge. Notably, inhibition of CXCL4 had no direct effect on secretagogue-induced activation of trypsinogen in pancreatic acinar cells in vitro. A significant role of CXCL4 was confirmed in an alternate model of AP induced by L-arginine challenge. Our findings show that CXCL4 regulates neutrophil accumulation and tissue damage via CXCL2 formation in AP. Thus, these results reveal new signaling mechanisms in pancreatitis and indicate that targeting CXCL4 might be an effective way to ameliorate severe AP.

Biography:

Abdel-Azeem M El-Mazary has completed his MBBCH and MD degree a from Minia University, Egypt. He did Post-doctoral workshops and training courses in Pediatrics in both Cairo and Mansoura Universities, Egypt. He is the Director of Neonatology Unit Clinic of Minia University Hospital. He is working as Associate Professor in Pediatrics, Pediatric Department, Minia University. He has published more than 16 papers in reputed journals and has been serving as an Editorial Board Member of (Science Research Journal) and as a Reviewer in (European Journal of Clinical Nutrition).

Abstract:

Background: Fever is one of the most frequently encountered pediatric problems, accounting for 25% of visits to pediatric emergency room. The vast majority of young children with fever have an infectious etiology, like cold, upper respiratory tract infections (ear infection, croup, bronchiolitis and pneumonia), gastroenteritis, UTI and other infections, but there are also other important causes of fever in children under five years as immunization reaction, collagen vascular disease, chronic inflammatory disease, metabolic disease, transfusion reaction, drug fever, or poisoning. The cause of fever in young children can be a diagnostic challenge because it is often difficult to identify the exact cause as in most cases the acute illness is due to self - limiting viral infection however; fever may also be the presenting feature of serious bacterial infections such as meningitis or severe pneumonia. Objective: This study aimed to compare between two different approaches; the standardized approach of IMCI (Integrated Management of Childhood Illness) versus the traditional approach in management of fever in children less than five years old. Methods: This is a prospective study carried out on 50 children less than five years old represented with fever attended the outpatient clinic of Minia University Hospital for children during the period from September 2012 to January 2014. These 50 children were divided into 2 main groups: Group 1: Included 25 children subjected to standardized (IMCI) approach of management which designed with limited diagnostic tools, limited medications and opportunities to practice complicated clinical procedures to reach a classification rather than diagnosis, and group II: Included 25 children subjected to traditional approach of management which designed to use serial investigations and procedures with many medications to reach to a specific cause or diagnosis. Results: Most of children in standardized approach (64%) were diagnosed at 1st day, while most of children in traditional approach were diagnosed at 4th (34%) or 5th day (20%), these differences were statistically significant, and 60% of children treated with the standard approach was improved compared to only 12% of children treated with traditional approach, 40% of treated with traditional approach had worse outcome compared to 16% of treated with the standard approach and these differences were statistically significant. Conclusions: This study showed that the standardized approach of IMCI designed to reach a classification and/or a diagnosis earlier with much better outcome than the traditional approach in majority of cases which is better for practical applications especially in developing countries.

Biography:

Yongxin zhang is currently doing his research work at Zyxell Inc., headquartered in Carrollton, Texas, USA. It is a cell science- and technology-based company.

Abstract:

Antigen-specific T immunocyte in vitro expansion provides effective cells in cancer therapy, but a successful expansion partially depends on the activity of the harvested cells. Ideally, the cells should be harvested at the point of maximum function. However, the activities of most, if not all, immunocytes decline when the cells are cultured in vitro. Therefore, the determination of the peak time point is critical for the efficient expansion of effective antigen-specific T immunocytes. Our previous studies demonstrated that hematopoietic stem cells reduce their engraftment potency during ex vivo expansion due to non-specific differentiation and has a optimal harvest time point for their highest engraftment potency during the expansion. Similar to hematopoietic stem cells, lymphocytes also cannot keep the activity at their highest level following in vitro culture. Antigen-specific cytotoxic T lymphocyte (asCTL) is a typical example, in which the total cytotoxicity increases for a certain period as cell number increases at the early expansion stage, but decreases at late stage because individual cell-based killing function always gradually declines and drops very fast at the late stage. In this study, CMV asCTLs and cancer cell-induced asCTLs were expanded in ZYX bioreactor, the correlation between cell number and their total antigen-specific cytotoxicity was established, and the peak time point of total antigen-specific cytotoxicity was determined. From this data, a computer program was used to predict the peak time point of total antigen-specific cytotoxicity by real-time monitoring the cell number changing in the CTL expansion. The results showed that our system could determine the optimal time point for the asCTL harvest without needing a series of CTL assays.

Biography:

Hadeel Faisal Gad has graduated from faculty of Veterinary Medicine, University of Khartoum in 2002 and earned her PhD degree in Immunology in 2013 from Institute of Endemic Diseases, studying the cellular immunology of Pulmonary Tuberculosis and Visceral Leishmaniasis co-infection. She investigates the role of gene mutations as a susceptibility to the two diseases co-infection. She worked as a part time Lecturer and Researcher at King Saud University.

Abstract:

Background: Leishmaniasis-tuberculosis co-infection has been reported many times mainly in the east region of Africa, but little is known about the immunological interactions of the co-infection. A case control study was carried out to analyze in-vitro cytokines responses in visceral leishmaniasis (VL) patients and pulmonary tuberculosis (TB) patients. Method: The cytokine profiles of 30 leishmaniasis patients, 30 tuberculosis patients and 10 healthy individuals were compared after stimulation with live Leishmania Promastigotes and BCG. Th-1 (IFN-γ and TNF-α), Th-2 (IL-10) and inflammatory cytokine IL-15 were measured in the supernatants of stimulated whole blood samples whole blood using ELISA. Results: The concentration of Th-1 cytokines (IFN-γ and TNF-α) were significantly higher in the supernatants of stimulated whole blood of VL patients compared with TB patients mainly when stimulated by L.donovani antigen. Th-2 cytokine IL-10 was significantly produced by whole blood of TB patients particularly stimulated with BCG. A significant concentration was detected in stimulated whole blood of VL and TB patients compared by healthy controls. Conclusion: The Th-1 cytokines expressions to the homologous antigen stimulation in visceral leishmaniasis patients were higher compared to the non-stimulated which suggests a strong adaptive response. Meanwhile, the Th-2 cytokine IL-10 expression to the homologous antigen stimulation in TB patients was higher than the non-stimulated which led to strong suppression the protective Th-1 cytokines expression. This finding suggests that a re-occurring TB infection may generate a weak protective immune response which could lead to a more persistent infection.

Biography:

Christian Pasquali has completed his Master and PhD between the Vienna IMP Institute and Compiegne University respectively. He was Director of Operational Research and Technology Transfer at xigen Pharmaceutical and is now Directing the unit of Preclinical Research at vifor Pharma, Geneva. He has published more than 35 papers in peer reviewed journals and has been serving as an chairs and speakers in various scientific congress.

Abstract:

Secondary bacterial infections following influenza infection are a pressing problem facing respiratory medicine. Although antibiotic treatment has been highly successful over recent decades, fatalities due to secondary bacterial infections remain one of the leading causes of death associated with influenza.We have assessed whether administration of a bacter-ial extract alone is sufficient to potentiate immune responses and protect against primary infection with influenza, and secondary infections with either Streptococcus pneumoniae or Klebsiella pneumoniae in mice.We show that oral administration with the bacterial extract, OM-85 (Broncho Vaxom), leads to a maturation of dendritic cells and B-cells characterized by increases in MHC II, CD86, and CD40, and a reduction in ICOSL. Improved immune responsiveness against influenza virus reduced the threshold of susceptibility to secondary bacterial infec-tions, and thus protected the mice.The protectionwas associated with enhanced polyclonal B-cell activation and release of antibodies thatwere effective at neutralizing the virus. Taken together, these data show that oral administration of bacterial extracts provides sufficient mucosal immune stimulation. Further to these findings and to potentiate the various mechanistic means by which OM-85 can modulate the host immune response, a general overview on other recent findings including other therapeutic indication such as asthma will be discussed.

Biography:

I am a post-doctoral researcher working in the laboratory of Dr. Richard Simpson at the University of Houston. I joined Dr. Simpson’s lab in 2009 and was funded his first two years as a teaching fellow and the last three years as a research assistant working on NASA grant NNX12AB48G. I am interested in cancer immunotherapy using NK-cells, especially how exercise and Cytomegalovirus (CMV) infection modulate NK-cell activity against hematologic malignancies. My goal is to understand the mechanisms underlying the effects of exercise and CMV infection on the phenotype, cytotoxicity, proliferative capacity, and persistence of NK-cells with an eye toward developing adjuvants for allogeneic adoptive transfer of NK-cells. My research thus far has been funded by a NASA grant awarded to Dr. Richard Simpson and he will continue to have access to these resources if awarded this fellowship. Through this collaboration with NASA, I have acquired expertise in cell culture techniques, cytotoxicity assays, and flow cytometry methods that have led to multiple publications in prestigious peer-reviewed journals.

Abstract:

We showed previously that acute exercise is associated with a preferential redeployment of highly-differentiated NK-cells and increased cytotoxicity against HLA-expressing tumor cell lines during exercise recovery. In this part II study, we retrospectively analyzed these findings in the context of latent cytomegalovirus (CMV) infection and performed additional experiments to explore potential mechanisms underpinning the marked reduction in NK-cell redeployment with exercise in CMV-seropositive individuals. We show here that latent CMV infection impairs NK-cell mobilization with exercise, only when the intensity of the exercise bout exceeds the individual blood lactate threshold (BLT). This impaired mobilization is associated with increased proportions of poorly exercise-responsive NK-cell subsets (NKG2C+/KIR-, NKG2C+/NKG2A-, and NKG2C+/CD57+) and decreased NK-cell β2-adrenergic receptor (AR) expression in those with CMV. As a result, NK-cell production of cyclic AMP (cAMP) in response to in vitro isoproterenol (synthetic β-agonist) stimulation was drastically lower in those with CMV (6.0 vs. 20.3 pmol/mL, p<0.001) and correlated highly with the proportion of NKG2C+/CD57+ NK-cells (R2 = 0.97). Moreover, NK-cell cytotoxic activity (NKCA) against the K562 (36.6% vs. 22.7%, p<0.05), U266 (23.6% vs. 15.9%, p<0.05), and 221.AEH (41.3% vs. 13.3%, p<0.001) cell lines was increased at baseline in those infected with CMV; however, latent CMV infection abated the post-exercise increase in NKCA as a result of decreased NK-cell mobilization. Additionally, NKCA per cell against the U266 (0.24 vs. 0.12, p<0.01), RPMI-8226 (0.17 vs. 0.11, p<0.05), and 221.AEH (0.18 vs. 0.11, p<0.05) cell lines was increased 1h post-exercise (relative to baseline) in CMV-seronegative subjects, but not in those infected with CMV. Collectively, these data indicate that CMV may compromise NK-cell mediated immunosurveillance after acute exercise due to an increased proportion of “CMV-specific” NK-cell subsets with impaired β-adrenergic receptor signaling pathways.

Biography:

Abstract:

Heavy metals like arsenic and lead are toxic to humans and animals. Arsenic is carcinogenic and plays its role through drinking water and by entering the food chain via the water bodies. There are numerous reports of the toxic effects of arsenic and with time, research on arsenic has only gained impetus. In this study we tried to address the immunotoxicological effects of arsenic contamination and subsequent effect of its oxidative stress-induced dysfunction of both the critical defences viz. the antioxidant mechanisms as well as innate immunity in the fish Channa punctatus Bloch. Fish were treated with sub-lethal doses of sodium arsenite solution (0.24 mg/L) for 4 days and when analysed for its effect on the intestinal macrophages, it was observed that it altered the bacterial phagocytosis and the intracellular killing activity which correlated with the decrease in the release of the antimicrobials viz, nitric oxide and myeloperoxidase and the inflammatory cytokines, thus rendering the fish prone to infections. Severe damages in terms of disarrangement and fragmentation of the mucosal epithelial lining of the intestine, as observed by transmission electron microscopy emphasizes on arsenic-induced oxidative stress. While the decrease in pro-inflammatory cytokines suggests the involvement of MAPK and NFκ pathways in the portrayal of immune dysfunction, loss of antioxidant homeostasis could be a result of direct inhibition of enzymes by arsenic. We therefore, conclude that arsenic affects the fish C. punctatus Bloch. by suppressing its immune system and antioxidant defences due to an increase of the oxidative stress, making it more susceptible to microbial attack.

Biography:

Haleh Talaie has completed her MD at the age of 28 years from Shahid Beheshti University of Medical Sciences and Research fellow, Division of Clinical Pharmacology & Toxicology, University of Toronto, Canada (2004). she is the director of Iranian Healing Oriented Integrative Medicine Institute.she has published more than 30 papers in reputed journals. Spring/Autumn 2014 : Accepted as postdoctoral integrative medicine fellowship in Arizona Center for Integrative Medicine University of Arizona ,USA(financial support not yet approved) March 2011- up to present: Integrative Medicine self education in Toxicological Research Center (TRC) and in Taleghani General Hospital,SBMU. April 2009 – Feb 2011: Integrative Medicine Courses in Clinical Excellence Center of SBMU. Oct. 2005- Nov 2005: Participation in Toxicology Rounds of Toronto, Canada poison center and Clinical pharmacology and toxicology of HSC of university of Toronto. Oct. 2003- May 2004: Research fellow, Division of Clinical Pharmacology & Toxicology by supervision of Dr Gideon Koren, M.D., A.B.M.T., F.R.C.P.C The Hospital for Sick Children, University of Toronto, Canada March 1997- 2003: Trainer & coordinator of Medical Education, Shahid Beheshti University (formerly Melli University) Medical Sciences & Health Services (SBUM), Tehran, Iran 1994 -1997: Board of Infectious Diseases specialty (SBUM) 1995-1997: Master in Public Health, Tehran University of Medical Sciences, Tehran, Iran 1987-1994: Training in Emergency ward & Outpatient clinic, Gillan Medical university,Iran 1978-1987: Shahid Beheshti University of Medical Sciences, (SBUM), Tehran, Iran

Abstract:

Background: Ventilator-associated pneumonia (VAP) is the main cause of acquired infections in ICUs. Every year, millions of people suffer from poisoning by various substances. Our aim was to determine the association between VAP incidence and different kinds of toxicity among Toxicological ICU (TICU) patients. Materials and Methods: Poisoned patients with diagnosis of VAP were enrolled to our retrospective study at TICU of Loghman Hakim Hospital. Data was collected through the medical records. The statistical analysis was performed with SPSS (version 16, Chicago, IL, USA). Results: Among 675 patients with MV > 48 h, 150 patients had the diagnosis of VAP. Mean age was 36.6 years. 74.7% were males. Intentional poisoning was 70.3%. The incidence of VAP was 22%. The higher incidence of VAP was recorded in anti depressants and opioid toxicities. The majority of bacterial isolates (81.3%) were multi drug resistance. MRSA accounted for 50.7% of VAP cases. Non survivors' hospital length of stay (mean = 18.7days) was significantly higher than survivors (12.8). The hospital length of stay in VAP patients was highest in the Acinetobacter spp (mean > 20 days). Mortality rate of VAP cases was 18.6%. Conclusion: No specific association was detected between incidence of VAP and different kinds of toxicity, while Anti Depressants and opioids had high VAP incidence, in a Quarter of this population. It is noticeable that pesticide had the lowest incidence for its short hospitalization. In our TICU, MRSA and Acinetobacter spp were the main agents leading to VAP and prolonged ICU stay, respectively.

Biography:

Abstract:

Hermansky-Pudlak Syndrome (HPS) comprises a group of inherited disorders caused by mutations that alter the function of lysosome-related organelles. Pulmonary fibrosis is the major cause of morbidity and mortality in BLOC-3 mutant HPS-1 and HPS-4 patients. Chitinase 3-like-1 (CHI3L1), a prototypic chitinase-like protein, plays a protective role by ameliorating cell death and stimulating fibroproliferative repair. Here we demonstrate that circulating CHI3L1 levels are higher in HPS patients with pulmonary fibrosis compared to those that remain fibrosis-free, and that these levels associate with disease severity. Using murine models we also demonstrate that a defect in CHI3L1 inhibition of epithelial apoptosis and exaggerated CHI3L1-driven fibroproliferation play important roles in HPS fibrosis. Lastly we demonstrate that these divergent responses are mediated by differences in the trafficking and effector functions of two CHI3L1 receptors. Specifically, the enhanced sensitivity to apoptosis is due to the BLOC-3 dependent, and thus abnormal, trafficking of IL-13Ra2. In contrast, the fibrosis is due to interactions of CHI3L1 and CRTH2, which traffics normally in BLOC-3 HPS.

Biography:

Abstract:

Introduction: A better understanding of the impacts of malaria control interventions on Anopheles mosquito vector and Plasmodium falciparum parasite populations, acquired immunity, and burden of the disease, is needed to guide malaria elimination strategies. Therefore the impacts of implemented strategies need to be monitored overtime to anticipate the consequences of changing malaria epidemiology. To gain insights on the impact of malaria control interventions on anti-malarial antibodies responses, we closely investigated the dynamics of IgG antibodies responses to P. falciparum antigens in relation to decrease malaria transmission resulting from successful control interventions in a West African setting. Methods: A total of 1235 sera obtained in 2000 (n=218), 2002 (n=186), 2008 (n=269), 2010 (n=288) and 2012 (n=274) from inhabitants of Dielmo (Senegal) aged 3.4 to 90.9 years old were tested by ELISA to investigate the prevalence and magnitude of antibody responses to crude schizont extracts obtained from a locally adapted P. falciparum strain (Pf0703). The threshold for positivity was defined as an OD ratio >2. Statistical analyses were performed using R software and threshold of significance was set at 0.05 Results: The prevalence of anti-sch0703 antibodies progressively decreased from 97.25% in 2000 to 57.3% in 2012. When categorized between various age groups, the seroprevalence increased significantly (P<0.5) with age from 47.19% in children <7 years old to 89.45% in >=15 years old. The seroprevalence within age groups through the different periods significantly dropped after the implementation of insecticides nets in 2008. Similarly, the magnitude of IgG antibody responses in positive responders decreased progressively from 2000 to 2012 despite limited variation in the different age groups. Mean levels of IgG antibodies fluctuated from 2002 to 2012 indicating a moderate to no relationship between the magnitude of IgG antibodies responses and malaria interventions. Discussion and conclusion: While the data suggest that all implemented control strategies (rapid diagnostic test, ACT treatment and LLINs use) contributed to the decrease of immune responses to P. falciparum antigens, the role of LLINS was the most pronounced as revealed by the significant decline in seroprevalence and magnitude of antibodies responses observed after 2008. Implementation of LLINS was reported associated with a substantial reduction of Anopheles mosquitos and a decreased of the entomological inoculation rates to its lowest value in 2012 when parasite carriage almost disappeared in Dielmo villagers. The rapid decrease of protective immunity allows new infections to be rapidly detected and treated, but also favors the re-establishment of human-vector contacts contributed in boosting immune responses to P. falciparum malaria antigens.

Biography:

Hana Zelenková has been active in Dermatovenerology since 1973. Since 2000 she has been directing her own Private Clinic of Dermatovenereology. Orientation: Psoriasis vulgaris, atopic dermatitis, mycosis, aesthetic dermatology (anti aging medicine, keloid and scar). She has given more than 650 expert lectures in Slovak Republic as well as abroad, and has 420 scientific publications. She is the Founder and President of the Slovak Society for Aesthetic and Cosmetic Dermatology President of the traditional international DERMAPARTY congress.

Abstract:

Cyclosporine A is an immunosuppressant cyclic polypeptide isolated from the Tolypocladium inflatum fungus. Indications: organ transplantations (kidney, liver, heart, lungs, pancreas, skin), bone marrow transplantations, autoimmune disorders, and selected dermatoses such as psoriasis or AD. The indication window is opening wider and wider. In most indications the recommended administration form is oral. Transplanted patients require routine monitoring of CyA levels in blood. In non-transplantation indications the monitoring of CyA levels in blood is of limited importance, only. In dermatology, Cyclosporine A is administered in three groups of indications: Group I – dermatoses treated with maximum efficacy drugs, where CyA represents an extraordinarily effective first choice drug. Group II - dermatoses with the possibility to administer an alternative systemic drug based on the therapist’s choice, however, with CyA still being the best choice. Group III - other dermatoses (with individual therapy assessment due to presumed disease development and possible relapses). The window of indications is still widening (chronic urticaria, vitiligo). The commencement of CyA therapy in line I – III requires erudition and experience. In patients with severe dermatoses CyA therapy rapidly improves the local finding and radically improves the quality of patients’ life. Cyclosporine A must be only administered according to evidence based medicine!!!

Biography:

Arnie Berk is a virologist and cell biologist in the Molecular Biology Institute and Department of Microbiology, Immunology and Molecular Genetics at UCLA. As a postdoctoral fellow, his analysis of adenovirus mRNA synthesis led to the initial discovery of RNA processing of spliced mRNAs from pre-mRNA precursors containing introns, and his analysis of early SV40 mRNA lead to the initial discovery of alternatively spliced mRNA isoforms encoding distinct, but related proteins. At UCLA his research has focused on the mechanisms of transcriptional activation and control of the cell cycle by the adenovirus E1A and E1B proteins. Work from his laboratory demonstrated that the tumor suppressor activity of p53 depends on its activity as a transcriptional activator. His laboratory discovered that activation of transcription by the adenovirus large E1A protein results from its interaction with the human mediator of transcription complex, and that this promotes assembly of pre-initiation complexes on promoter DNA and stimulation of elongation by promoter proximal paused RNA polymerase II. The small E1A protein was shown to regulate host cell transcription and cell cycle progression through modifications of chromatin structure. He is a Fellow of the American Academy of Arts and Sciences and holds the UCLA Presidential Chair in Molecular Cell Biology.

Abstract:

To analyze control of host cell gene expression by adenovirus small E1A protein, we performed experiments with structure-based e1a mutants completely defective for binding to either p300/CBP or RB-family proteins. RNA-seq and ChIP-seq for e1a, RB1, RBL1 (p107), RBL2 (p130), p300, pol2, H3K9ac, H3K18ac, H3K27ac and H3K4me1 revealed that p300/CBP acetylation of RB1 K873/K874 (1) in a trimeric p300/CBP-e1a-RB complex (2) inhibits RB phosphorylation by cyclin/CDKs, thereby locking RB1 in a repressing conformation (1,3) that interacts with repressive chromatin modifying enzymes (3). e1a then delivers these repressing p300/CBP-e1a-RB complexes to host cell genes that have unusually high p300 association within the gene body and are highly enriched for cytokine signaling pathway genes, repressing their transcription. The p300/CBP-e1a-RB complex condenses chromatin as assayed by confocal microscopy of an amplified lacO array (4). e1a-induced chromatin condensation requires simultaneous binding of e1a to an RB and p300/CBP, e1a-binding to the chromatin remodeler p400 (5), HDAC activity, p300 KAT activity, the p300 bromo-ring-PHD domain (6), and acetylation of RB1 K873/K874 (2) and e1a K239 (7). Our data suggests a model for how the p300/CBP-e1a-RB complex spreads over repressed genes. 1. Chan HM doi:10.1038/ 35083062 2. Wang HG PMID 8416379 3. Dick FA, Rubin SM doi:10.1038/nrm3567 4. Verschure PJ doi: 10.1128 /MCB.25.11.4552-4564 5. Fuchs M doi:10.1016/S0092-8674(01) 00450-0 6. Delvecchio M doi:10.1038/nsmb.2642 7. Zhang Q doi: 10.1073/pnas.011283598

Biography:

Rongtuan Lin is an Associate Professor in the Department of Medicine, McGill University and a Senior Investigator at the Lady Davis Institute for Medical Research. Dr. Lin received his Ph.D. degree from Concordia University and he completed Post-doctoral training at the Lady Davis Institute for Medical Research. He have published more than 120peer-reviewedpapers,which have been cited for more than 10,000 times. He made important contributions in the fields ofinnate antiviral immunity.

Abstract:

The innate immune response to virus infection plays a critical role in limiting virus multiplication and pathogenesis. Central to the innate antiviral response is the rapid induction of type I interferon (IFN) expression; IFN gene expression is tightly regulated by the recognition of extra- and intra-cellular signals, generated during primary infection.The viral genome or viral replicative intermediates containing 5’triphosphate (5’ppp) RNA binds to RIG-I and ultimately leads to the production of pro-inflammatory cytokines and anti-viral factors, as well as type I interferons (IFNs) that amplifies the antiviral immune response.Given that viral RNA-RIG-I interaction is the initial trigger of the innate and adaptive immune response, an attractive strategy for the development of an efficient and broad spectrumantiviral therapy to inhibit virus infection involves the use of RIG-I agonist that mimic viral RNA to activate the host defense. Our previous study demonstrated that treatment of various cell lines and primary cells with 5’pppRNA in vitro led to protection against infection and replication of a broad range of RNA and DNA viruses. In vivo, intravenous administration of 5’pppRNA protected mice from a challenge with H1N1 and H5N1 Influenza virus. Our recent study shown that5’pppRNA has the ability to counteract Ebola virus infectivity in vitro. We identified STING among a plethora of differentially expressed genes induced by the RIG-I agonist 5’ppp RNA. STING has been identified as an RIG-I signaling cofactor and a critical adaptor protein required for cytosolic DNA and cyclic dinucleotides (CDNs) triggered immune responses.We further detailthe mechanism of STING regulation.Furthermore, our results also unveiled an essential contribution of STING in the establishment of the 5’pppRNA induced antiviral responses during HSV1 infection.Taken together, these observations demonstrate that the STING is induced via RIG-I signaling and up-regulated STING is essential for 5’ppp RNA mediated HSV restriction.

Biography:

Kimihiko Okazaki graduated from Kyoto University, Faculty of Medicine in 1959. He was then engaged in medical chemical research till 1981 and started working as an internist as of July 16, 1981. His main achievements are discoveries of (1) A novel coenzyme in Baker’s yeast, (2) Initiator of rat liver regeneration, and (3) A radical cure method of immune diseases.

Abstract:

It has long been taken for granted that all of antibody molecules rigidly combine with their receptors. On the other hand, it is well established that an equilibrium state exists among antibody molecules in the vicinity of their receptors. These two concepts obviously disagree with each other. Namely, either one of these two concepts ought to be wrong. However, the concept of existence of equilibrium can't be wrong since it has been established more recently than the other one, which used to be believed presumptively. Apparently, contemporary immunologists should be aware of the contradiction. Unfortunately, they don't seem to be so. It seems to me that authoritative immunologists, at least, are aware of it because they must not be stupid enough not to be aware of the contradiction. I'm afraid that they are just too egocentric to admit the irrelevancy. For them, it is more important to keep their research problems unfinished than to heal autoimmune diseases. In my opinion, purpose of medical research is to save sick people applying the best treatment for their diseases. Applying the relevant concept, the pathogenic antibodies can easily be replaced from the responsible cells, i.e., cytolytic T lymphocytes, by accumulating non- pathogenic antibodies in the body of the patient. The latter can be accomplished by repeating intradermal injections with non-specific antigens. I do have numerous cases of successful healing of autoimmune and allergic diseases. I have no case of failure. In conclusion, it is about time for authoritative contemporary immunologists to admit my idea.

Biography:

Abstract:

This work has been presented in several national and international ENT meetings and has been awarded "Prof. Dr. Juan Carlos Arauz " First Prize for "A new technique for treating recurrent respiratory papillomatosis using chromoendoscopy associated with Endoscopic Laryngotracheal Surgery (ELS)" research paper. It was granted by the Argentine Society of Otolaryngology and Children Phonoaudiology at the IX Argentinian Congress of Pediatric Otolaryngology and Children Phonoaudiology during the III IAPO Regional Meeting, Córdoba, May 24, 2007

Introduction
Chromoendoscopy is an endoscopic technique which uses acontrast stain to paint the aerodigestive tractmucosal liningfollowed by an optical assessment to highlightingany epithelial abnormalities. Detailed and high-definition magnified views achieved with the aid of rigid endoscopes can often allow for identification of the tissue type or pathology based upon the pattern uncovered.According to the literature we reviewed, we may have been the first ones to use indigo carminein the field of otolaryngology.Tiny lesionsthat usually go overlooked with conventional microlaryngoscopy become visible upon the instillation of indigo carmine and further decreasing the chances of an early lesion postoperativerecurrence. Chromoendoscopy, in recurrent respiratory papillomatosis (RRP), helpsidentify unsuspected intraoperative lesions byclearly enhancing the view of their boundaries and surface type. It is also suitable to assess the presence of residual lesions, if any, after theirsurgical removal.

Objectives:
To demonstrate the usefulness of chromoendoscopy in RRP in laryngotracheal surgery. Material and Methods: We used indigo carmine associated with endoscopic laryngeal surgery. Before staining, the mucosa may need to be treated with a mucolytic agent to get rid of excess mucus to boost staining. Rigid suspension laryngoscopes of different proximal and distal diameters were used with chromoendoscopy. Patients underwent chromoendoscopy associated with endoscopic laryngeal surgery under general anesthesia in the O.R.

Results:
In this second phase of our research work, this diagnostic technique was applied toeighteen patients with recurrent laryngeal papillomatosis and two patients with suspected carcinoma of the larynx. We were able to optimize the intraoperative diagnosis and reduce the likelihood of the relapse risk in all patients.

Conclusion:
Chromoendoscopy associated with endoscopic laryngeal surgery is an excellent low-cost intraoperative diagnostic method for the treatment of invasive diseases of the larynx such as laryngeal papillomatosis

Keywords:
larynx, papillomatosis, chromoendoscopy, respiratory, surgery, diagnosis, intraoperative, rigid endoscope, RRP.

Biography:

Rajiv Mahendru possessed Post-Graduate Degree in Obstetrics and Gynaecology from Himachal Pradesh University at the age of 29 years and became one of the youngest Professors. Presently, Head of the Department in the only second women medical college of India. He has 41 Publications in reputed journals and is the recipient of a prestigious Award for excellence in Medical field. Appointed as the Chief-editor of the Special issue of an international journal of repute and has numerous presentations to his credit at international arena as an invited Guest Speaker. He is the member of editorial board of international journals, Academic Board of many universities, member of recruitment for medical teachers, and assessor for establishing Medical colleges. He has chaired numerous sessions in the National and International conferences

Abstract:

Thyroid autoimmunity is the most common autoimmune disorder in women of reproductive age, with a prevalence varying between 5 and 15%. Many studies show a significant association between the presence of thyroid autoantibodies, infertility and recurrent pregnancy loss. The aim of study was to find out an association between anti-TPO-Ab, TSH and infertility among female patients attending the Gynaenecologycal OPD for the management of infertility. A cross-Sectional study was conducted for the period of six months from Jan. 2011 to June 2011 in the Department of Obstetrics and Gynaecology in collaboration with the Department of Biochemistry in a rural medical Institute of India. Fifty infertile females of reproductive age group with both primary and secondary infertility were selected for the study and fifty age-matched non pregnant healthy females who had no problem of infertility were taken as controls. Serum anti-TPO Ab, TSH levels were evaluated by Enzyme linked Immunosorbant assay method. The results obtained from the study showed statistical significance between anti-TPO Ab levels, TSH levels, age and infertility in both the groups. The parameters observed may be considered as a valuable aid in investigation and diagnosis of autoimmune thyroid disease in patients with unexplained infertility.

Biography:

Yong Li is an Associate Professor within the Department of Pediatric Surgery at the University of Texas, School of Medicine at Houston. He is also appointed as an Associate Professor in the Center Stem Cell for Regenerative Medicine at the Brown Foundation Institute of Molecular Medicine (IMM), UTHealth. He accomplished his MD and PhD training in China, and was a general surgeon before he went to London of UK in 1997. His first research career as a Post-Doctor fellow trained in Imperial College School of Medicine in UK (1998-1999), and later as a Post-doctoral Research Associate in Children’s Hospital of Pittsburgh of UPMC. He was promoted to a research Assistant Professor in 2002, Assistant Professor in 2004 (within tenure track system in 2006), and lead his research team approach success in the field of stem cell, anti-fibrosis in regeneration medicine. These projects also include the enlargement and application of adult stem cells (muscle and skin) to repair traumatic injury (muscle, tendon, spinal cord and brain) and congenital diseases. As in 2011, he has published over 66 refereed journal articles and review papers, and five book chapters. He has won twenty more international awards for his scientific advances, including most recently, he has won the Michael Miller Young Investigator Award at Children’s Hospital of UPMC.

Abstract:

Totipotent and pluripotent stem cells (e.g. ESCs or iPSCs) and adult tissue derived stem cells have been studied for many years. Stem cell transplantation has been considered a top priority for use to treat a variety of disease states and for various tissue regeneration regimes. Various autologous stem cells have been successfully used in clinical trials, though the scarcity of stem cells has limited their application. Allogeneic derived stem cells are a potential stem cell source; however, this remains a major challenge due to their potential to trigger an immune response or rejection after transplantation. Through several years of investigation, we have discovered and isolated a novel type of muscle derived small-size stem cells (Mu3SCs) from both mice and human tissues. These Mu3SCs have been characterized as being small in size, capable of multipotent differentiation and demonstrate a naturally aggressive migration capacity. We discovered that Mu3SCs were able to survive, proliferate and differentiate within a variety of tissues and are capable of engrafting throughout the skeletal muscles of mdx mice, a dystrophic mouse model of human Duchenne muscular dystrophy, via intravenous injection. We also demonstrated that GFP pre-labeled Mu3SCs remained in the blood stream for up to three weeks. We thus hypothesized that a percentage of small in size stem cells within the general stem cell populations that are “immune-privileged”, since the Mu3SCs have the ability to escape immunological recognition in the transplanted host, which is essential for inducing immunological tolerance.

Biography:

Kamalakannan Rajasekaran is a Research Scientist at Blood Research Institute, Milwaukee, WI. He obtained his PhD in Immunology from Madurai Kamaraj University. His studies are aimed at deciphering the signaling events that are responsible for NK cell-mediated cytotoxicity and pro-inflammatory cytokine production. His studies have led to the understanding of the role of signaling molecules such as Adap, Carma1 and TAK1 in the production of pro-inflammatory cytokines. His work, published in reputed scientific journals, including Nature Immunology, has paved the way for drafting a molecular ‘blueprint’ for targeting unique signaling molecules to regulate the production of inflammatory cytokines following cell-mediated immunotherapy.

Abstract:

Introduction: A strategy to contain the production of pro-inflammatory cytokines without affecting the cytotoxicity of Natural Killer (NK) or T cells will pave the way for preventing deleterious side effects of cellular immunotherapy to treat tumors. Our earlier studies have defined an essential role of the Carma1-Bcl-10-Malt1 signalosome for cytokine production. Cytotoxicity of NK cells that are deficient in Carma1 or Bcl-10 was moderately reduced. Following its activation by the Src family tyrosine kinase Fyn, the adapter protein ADAP plays a critical role in organizing this signalosome. Hence, we hypothesize that loss of ADAP in NK cells will result in a significant reduction in pro-inflammatory cytokine production without affecting its cytotoxic potential. Objective: 1. Analyze the tumoricidal and pro-inflammatory cytokine production efficiency of NK cells deficient in ADAP or its upstream activator Fyn. 2. Biochemical analysis of the signaling events associated with these effectors functions. Methods: NK cells derived from wild type, Fyn-/- and Adap-/- mice were analyzed for: 1. Tumoricidal activity using tumor cells labeled with 51Cr. 2.Pro-inflammatory cytokine production following stimulation with plate-bound mAbs to activate NK cell receptors 3. Phosphorylation of signaling molecules and 4.Nuclear translocation of transcription factors using western blot Results: In the Fyn-/- NK cells, cytotoxicity was significantly reduced where as cytokine production was significantly increased compared to wild type NK cells. In the Adap-/- NK cells cytotoxicity was unaffected while cytokine production was significantly decreased. In the absence of Fyn, phosphorylation of PI (3)-K-p85α and ERK1/2, events associated with cytotoxic granule mobilization were decreased. In the Adap-/- NK cells, while the phosphorylation of PI (3)-K-p85α was unaffected, phosphorylation of ERK1/2 was increased compared to wild type. In the Adap-/- NK cells, despite an increased phosphorylation of ERK1/2, there is a defect in its nuclear translocation, which may in turn account for a reduced nuclear translocation of c-Fos. Conclusions: The role of ADAP is redundant for NK cell-mediated cytotoxicity whereas, it is essential for pro-inflammatory cytokine production. Our analysis indicates that ADAP is essential for the nuclear translocation of ERK1/2 which is important for the activation of c-Fos and the induction of pro-inflammatory cytokines. In the absence of Fyn, cytotoxicity is reduced while cytokine production is significantly increased. Significance: Regulating the production of pro-inflammatory cytokines without affecting the cytotoxicity of the effectors cells by blocking the ADAP signaling module might help prevent the deleterious side effects such as ‘Cytokine Release Syndrome’ and improve the efficacy of cellular immunotherapy.

Biography:

Kristin Schmidt studied transcription factors involved in the development of the retina in a neurobiology lab at UCLA\'s Jules Stein Eye Institute. There, she became familiar with assorted tissue preparation techniques, IHC, IF, microscopy, and laser capture microdissection/microgenomics. In 2005 she joined Arcturus Bioscience and provided tech support for LCM instruments and reagents, troubleshooting issues ranging from harvesting tissue to biomolecule extraction and analysis via microarray, real-time PCR, or next-generation sequencing. In 2006 she moved into a global Field Applications Scientist role with Molecular Devices and in 2010 with Life Technologies where she trained LCM users and distributors all around the world. In 2015 she joined PerkinElmer Inc. as a Field Applications Scientist specializing in Phenoptics – multiplex staining in FFPE tissue, multispectral imaging, and image analysis

Abstract:

There has been a rapid growth in the field of tumor immunobiology in recent years as a result of recent successes in cancer immunotherapies, and it is becoming clear that immune cells play many sometimes conflicting roles in the tumor microenvironment. However, obtaining phenotypic information about the various immune cells that play these roles in and around the tumor has been a challenge. Existing methods can either deliver phenotypic information on homogenous samples (e.g., flow cytometry or PCR) or morphologic information on single immunomarkers (standard IHC). We present here a methodology for delivering quantitative per-cell marker expression and phenotyping, analogous to that obtained from flow cytometry, but from cells imaged in situ in FFPE tissue sections. This methodology combines: The sequential multi-marker labeling of up to 8 antigens using antibodies all of the same species in a single section; automated multispectral imaging (MSI) to remove the typically problematic FFPE tissue auto fluorescence and correct cross-talk between fluorescent channels; and an automated analysis that can quantitate the per-cell marker expression, determine the cellular phenotype, count these cells separately in the tumor compartment and in the stroma and provide high-resolution images of their distributions. We present here examples of this new methodology: The simultaneous labeling, analysis and validation of CD4, CD8, CD20, PD-L1, Foxp3, cytokeratin and DAPI in breast cancer; and CD8, CD34, PD-L1, FOXP3 and DAPI in head and neck squamous cell carcinoma. Each example will show the application of the multiplexed staining, per-cell quantitation and cellular phenotyping from multispectral images of FFPE tissue sections, as well as methods to explore the spatial distributions of the phenotype cells in and around the tumor.

Biography:

Takahiro Yamada graduated from Hokkaido University School of Medicine, Japan. He has completed his PhD from the same university and Post-doctoral studies from Nagasaki University School of Medicine, Japan and The Hospital for Sick Children, Toronto, Canada. Currently, he is the Lecturer of Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine and is the Chief Obstetrician of Obstetrics Clinic of Hokkaido University Hospital. He has published more than 90 papers in reputed journals.

Abstract:

Although, there were no mortalities from the pandemic (H1N1) 2009 among pregnant Japanese women, pregnant women with flu are at higher risk of hospitalization and mortality compared to general population. During the pandemic (H1N1) 2009, it is estimated that more than 60% of pregnant Japanese women were vaccinated against the novel virus. However, as we had no data regarding vaccination coverage rate for seasonal flu in pregnant Japanese women, we conducted a multi-center study to determine vaccination coverage against 2013 – 2014 seasonal flu and the prevalence rate of flu infection among pregnant Japanese women. In that study, 51% of participants reported having received vaccination in or after October 2013. The women aged <25 years had a lower vaccination rate than those aged ≥25 years (P=0.0000). Interestingly, although experience of prior birth did not affect vaccination coverage rate, multiparous women had a higher rate of contracting influenza than primiparous women irresp ective of vaccination status (P=0.0216 and P=0.0003 for women with and without vaccination, respectively). These results raised a question why multiparous pregnant women are more susceptible to flu than primiparous pregnant women. We conducted a study to address this issue during 2014-2015 flu season and results of this study will be presented.

Biography:

Igor Malyshev is a Head of the Department of Pathophysiology and Head of the Laboratory of Cell Biotechnology, Medical School at the Moscow State University of Medicine and Dentistry. He is also the Head of the Laboratory of Stress at the Institute of General Pathology and Pathophysiology, Moscow and Adjunct Professor of Biomedical Sciences at University of North Texas Health Science Center, USA. He is a Member of the Board of directors of the International Society for Adaptive Medicine and an Editorial Board Member of Journal of Biosciences and Medicines. He has published 3 books and monographs and 146 full length articles.

Abstract:

Introduction: An important factor of antitumor immune defence is macrophage NO. We hypothesized that the tumor vulnerability can be predetermined by genetic features of NO generating systems. Methods: The content of NO in tumor was changed by the iNOS inhibitor ITU, NO traps c-PTIO and NO donor. NO production was evaluated by nitrites. Macrophage phenotype was assessed by iNOS and CD markers. Results: The lifespan of mice C57BL/6N with carcinoma was 25% more than C57BL/6J. NO content reduction decreased lifespan of high-resistant to tumor subline C57BL/6N by 23%. NO content rise increased lifespan of low-resistant subline C57BL/6J by 26%. C57BL/6N M1 macrophages had a higher NO production, than C57BL/6J M2 macrophages. Discussion: Thus, the carcinoma vulnerability is determined by genetic features of macrophage NO generating systems. C57BL/6J and C57BL/6N have differences in SNP and NNT (nicotinamide nucleotide transhydrogenase) gene. NO, NNT and SNP deserve attention in developing methods for anticancer therapy.

Biography:

Francis Mussai is a Senior Clinical Lecturer at the University of Birmingham, UK and leads a research group investigating the immunosuppressive microenvironment created by both paediatric and adult malignancies. The group has identified key aspects of how arginine catabolism by both tumour cells and tumour associated myeloid cells can alter anti-cancer immunity. He is also a Consultant Paediatric Oncologist and is involved in the development of early phase clinical trials for paediatric malignancies in the UK and Europe.

Abstract:

Arginine is a semi-essential amino acid whose physiological levels are maintained principally from dietary intake and through intestinal-renal recycling of citrulline. At the cellular level, arginine metabolism is essential for cell division, protein synthesis and as a precursor for nitric oxide and polyamines. The role of arginine processing in the tumour microenvironment to impair anti-tumour immunity has become increasingly apparent. T cells, which provide the corner stone of the anti-cancer immune response, are notably arginine dependent. Tumour associated macrophages (TAMs) and the induction of Myeloid-derived suppressor cells (MDSCs) can decrease local and systemic arginine concentrations, through increased arginase 1 expression, suppressing T cell proliferation. TAM and MDSC derived reactive nitric oxide species production via expression of iNOS, may further inactivate T cell responses. More recently the malignant cells of some haematological and solid tumours have been recognised to be arginine addicted, due to the loss of critical arginine recycling enzymes – a state known as arginine auxotrophism. The resulting dependence on extracellular arginine from the blood and tumour microenvironment further suppresses both antigen-specific and non-specific T cell responses. The importance of these findings and their translational consequences will be presented in this meeting.

Biography:

C C Yin has received her MD from Beijing Medical University and PhD from the University of Wisconsin-Madison. She is currently an Associate Professor in the Department of Hematopathology at the University of Texas MD Anderson Cancer Center. In addition to clinical responsibilities on the leukemia, lymphoma and molecular diagnostic services, she has been actively participating in multiple research projects in the molecular genetic abnormalities in leukemia and lymphoma, which has led to over 100 research papers and over 20 book chapters.

Abstract:

Expression of immunoglobulin (Ig), a marker characteristic of B-cells, has been reported in epithelial cells and has been suggested to play a role in their survival and growth. We assessed the frequency and level of Ig gamma heavy chain (IgG) expression in acute myeloid leukemia (AML) and found that IgG was expressed at a high frequency and level in AML cell lines and primary myeloblasts, but not in monocytes or neutrophils from patients with non-hematopoietic neoplasms or healthy controls. AML-derived IgG had the same molecular weight as B-cell-derived IgG and was secreted. We further detected IgG VHDJH transcripts in AML cell lines and sorted primary myeloblasts, confirming that IgG expression was indeed produced by AML cells. AML-derived IgG gene rearrangements showed evidence of somatic hyper mutation of the variable (V) gene segments and restricted (AML cell lines) or biased (primary myeloblasts) V usage. Anti-human IgG reduced cell viability and induced apoptosis in AML cell lines. Although the function of the AML-derived IgG is unclear, our findings suggest that AML-derived IgG may be a novel AML-related gene that contributes to leukemogenesis and AML progression. AML-derived IgG may serve as a useful molecular marker for monitoring minimal residual disease or designing target therapy.

Biography:

Nurieva Roza Insafetdinovna has completed her PhD from Pushchino State University, Russia and Post-doctoral studies from University of Washington, Seattle, USA. Currently, she is the Assistant Professor in Immunology Department at MD Anderson Cancer Center. She has published more than 50 papers in reputed journals and has been serving as an Editorial Board Member of repute.

Abstract:

Apart from T helper (Th)-2 cells, T follicular helper (Tfh) cells are a major class of IL-4 producing T cells, required for regulation of type 2 humoral immunity. Although the transcriptional control of IL-4 has been an area of extensive investigation, the precise regulation mechanism of IL-4 production in Tfh cells remains mainly unknown. In the current study, we found that the transcription factor BATF, a member of the AP-1/Jun family is essential for IL-4 expression in Tfh cells rather than in canonical Th2 cells. Functionally, BATF in cooperation with Interferon regulatory factor (IRF) 4 along with Stat3 and Stat6 trigger IL-4 production in Tfh cells by directly binding to and activation of the CNS2 region in the IL-4 locus. In addition, Batf-to-c-Maf signaling is an important determinant of IL-4 expression in Tfh cells. BATF deficiency impairs the generation of IL-4 producing Tfh cells that results in protection against allergic asthma. IL-4 acts as an autocrine factor in controlling BATF-mediated IL-4 expression in Tfh cells. Our results thus indicate a critical role of BATF in promoting the generation of pro-allergic IL-4 producing Tfh cells.

Biography:

Navin K Verma completed his PhD and Post-doctoral training in Clinical Medicine at Trinity College Dublin, Ireland. In 2013, he joined Lee Kong Chan School of Medicine, Nanyang Technological University, Singapore, where he is currently an Assistant Professor of Immunology and Cell Biology. His research is focused on molecular processes involved in T-cell motility. In particular, he is investigating biological roles and functional significance of the integrin LFA-1 signalling for T-cell migration in health and immune-medicated diseases.

Abstract:

Introduction: The T-cell integrin LFA-1 interacts with the ligand ICAM-1 expressed on endothelium and this interaction is important in T-cell motility. But downstream signalling pathways triggered by LFA-1/ICAM-1 ligation in T-cells are not clear. Here, we show that LFA-1-signalling for T-cell migration modulates gene expression, induces notch and TGF-β pathways and influences T-cell differentiation. Methods: Primary human T-cells or T-cell line Hut78 were stimulated via LFA-1 by incubating on immobilised recombinant ICAM-1. Standard molecular, biochemical and imaging techniques including Affymetrix Gene Chip® microarrays, real-time PCR, Western-immunoblotting, siRNA, confocal microscopy and high content analysis were utilized. Results: LFA-1/ICAM-1 ligation in T-cells induced genomic signatures associated with Notch and TGF-β pathways. We verified the activation of notch signalling by nuclear translocation of its cleaved intracellular domain and up-regulation of target genes Hey1 and Hes1. Moreover, a subset of molecules associated with reduced TGF-β responsiveness including Smad7, Smurf2 and Ski were found to be up-regulated, which was dependent of Stat3 and/or JNK activation. While LFA-1/ICAM-1 promoted Notch-dependent Tbet+ Th1 polarization, LFA-1-stimulated T-cells were refractory to TGF-β-mediated induction of Foxp3+ iTreg or RORγt+ Th17 differentiation. Pre-treatment of cells with blocking anti-LFA-1 antibody, specific inhibitors or siRNA against identified molecules substantially suppressed LFA-1-mediated modulation of T-cell functional phenotypes. Conclusion: We demonstrate a novel mechanism by which LFA-1/ICAM-1 ligation regulates immune response through notch and TGF-β pathways concurrent with its role in T-cell migration. These new findings have implications for normal immunologic functions and may also have therapeutic relevance for immune-mediated diseases.

Biography:

Robert H Schiestl has obtained his PhD from the University of Vienna. He was a Post-doctoral fellow at Edmonton, Alberta, Rochester, NY, and Chapel Hill, NC before working as a Professor at Harvard, where he stayed for 10 years. Since 15 years, he is working as a Professor at UCLA with 190 publications, 6 press releases, 10 patents and 2 startup companies.

Abstract:

To determine susceptibility of subpopulations of cells in the peripheral blood as well as of peripheral lymphoid organs to several types of DNA damage in genetic mouse models of spontaneous chronic intestinal inflammation and to determine the sufficiency of tumor necrosis factor α (TNF-α) in inducing this genotoxicity. By determining correlations of DNA damage to disease activity, we hope to substantiate systemic genotoxicity as a biomarker of inflammatory activity in intestinal inflammation. Peripheral blood subpopulations were isolated via magnetic bead sorting and cells from peripheral lymphoid organs were isolated incolitic IL-10 mice of various disease activity (3 and 6 months of age), Gαi2 mice (3 months of age) and in wild-type mice with no intestinal inflammation. DNA strand breaks were measured in cells with the alkaline comet assay with hOGG1 incubation to determine oxidative base damage and DNA double strand breaks specifically were quantified by γH2AX foci immune-staining. Recombinant mouse TNF-α or saline was injected (500 ng/mouse) into the tail vein of wild-type mice and peripheral blood was analyzed for DNA damage at several time points post injection. DNA single and double strand breaks were found in subpopulations of cells in the peripheral blood as well as in the peripheral lymphoid organs, which correlated to disease activity of mice with intestinal inflammation. CD4 and CD8 T-cells seemed most sensitive to DNA damage. TNF-α was sufficient to induce DNA damage in wild-type mice. Chronic intestinal inflammation induces systemic DNA damage, in which CD4 and CD8 T-cells are the most sensitive. TNF-α plays a role in inducing this damage though further mechanisms remain investigated. Levels of DNA damage in the peripheral blood correlated strongly to inflammatory activity and severity of disease, making DNA damage to leukocytes a good biomarker to diagnose and monitor disease in inflammatory bowel disease patients.

Biography:

Xiao-Xia Jiang has completed her PhD from Institute of Basic Medical Sciences. She is an Associate Professor in the Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences. She has published more than 40 papers in reputed journals.

Abstract:

B1 cells are the dominant population of B cells in the pleural and peritoneal cavities. They are a significant source of serum antibody, and they make a dominant contribution to low-affinity IgM antibodies that are present in serum of unimmunized mice. B1 cells in the mouse are thought to be derived from precursors in fetal liver rather than from adult bone marrow. They are believed to maintain their cell numbers in adult mice by longevity and homeostatic proliferation. Unlike conventional B cells (B2 cells) and despite the importance of B1 cells in protection from infections and their association with autoimmunity, the mechanism of B1 cell proliferation and function remained poorly understood. Mysm1 is a histone de-ubiquitinase and has been shown to play an essential role in hematopoiesis and lymphocyte development. Our previous study has demonstrated that in Mysm1 deficient mice, B2 cell development is blocked and B2 cell number is significantly lower compared with their counterpart. In this study we found that, in contrast to the dramatically decreased level of B2 cells, the percentage of B1 cells in the spleen and peritoneal cavity of Mysm1 deficient mice was increased compared with that in wild type mice. Mechanistic study has demonstrated that miR150 expression is compromised in B1 cells from Mysm1 deficient mice. Mysm1 controls the transcription of miR150 through regulating the chromatin state of miR150 locus. What’s more, forced expression of miR150 in B1 cells from Mysm1 mice can partly rescue the phenotype. Overall, our study, for the first time, reveals the important role of histone H2A de-ubiquitinase in B1 cell proliferation and development.

Biography:

Omar E Franco completed his MD at the “Universidad Nacional de Asunción”. After four years of medical training, he received a scholarship from the Japanese Government for a clinical fellowship, and then did his PhD at Mie University in Japan. Then he did a Post-doctoral training with Dr. Simon Hayward Lab at Vanderbilt University. More recently he was promoted to Research Assistant Professor and moved to North Shore University Health System as a Senior Research Scientist. He has more than 40 publications and is a member of the Society of Basic Urological Research. His main interest is in the tumor microenvironment.

Abstract:

Prostate cancer cells are surrounded by a complex tumor microenvironment. The stromal cells present in the vicinity of cancer cells and the extracellular matrix they deposit, play a key role in restraining or promoting tumorigenesis. We and others have shown that carcinoma associated fibroblasts (also known as CAF or reactive stroma) populations seen in human tumors are not, in fact, homogeneous, but, rather are mixed cell populations. Observations of human prostate tumors suggested that impaired TGFβ signaling in a proportion of normal human prostatic stromal cells is responsible for the pro-tumorigenic phenotype described in CAF. Our research was performed using fibroblasts derived from patient samples undergoing radical prostatectomy. Primary cell lines representing normal prostate fibroblasts (NPF) or CAF were generated. The non-malignant but initiated prostate epithelial cell line BPH1 was used to assess for paracrine tumor-inducing activity related to the fibroblasts. To evaluate the role of stromal TGFβ signaling we generated fibroblasts expressing the dominant negative TGFβR2 (DN) using a lentiviral system. Tissue recombinants composed of combinations of different stromal cells in the presence of epithelium were grafted beneath the renal capsule of SCID mice for 6-8 weeks. Macroscopical and histological analysis of the architecture as well as characterization of relevant downstream pathways was performed. Recombinants of NPF and BPH1 cells gave rise to small grafts composed of small, non-invasive cords. Stromal mixtures lacking at least 50% of proper TGFβ signaling were able to promote malignant transformation of the reporter prostate epithelial cell line. There was a robust infiltration of inflammatory cells correlated with the occurrence of tumors in our in vivo system. Tissue samples from prostate cancer patients and CAF/BPH1 recombinants showed mosaic TGFβ signaling activation depicted by phospho-Smad2 staining; supporting the notion of a mixed tumor microenvironment. In vitro studies showed that normal-looking fibroblasts cooperate with the impaired stroma in the secretion of factors commonly disregulated in cancer such as the chemokine SDF1α, little is known about the cross-talk between subpopulations of stromal cells in the tumor microenvironment. Our data supports the idea that heterogeneity (in this study TGFβ signaling) within fibroblastic populations can elicit local changes in paracrine signaling resulting in malignant changes in benign prostatic epithelial cells. A clear understanding of the role of the normal stroma and the complex interactions between different stromal cell types during carcinogenesis is required to develop better therapeutic strategies.

Biography:

Pieter Rousseau Fourie has completed his BSc in Electrical Engineering, MB ChB and PhD in Medical Physiology and Pediatric Specialty (MMed), all from the Stellenbosch University, South Africa. He holds an Associate Professorship in the Department of Critical Care and Anesthesiology, Faculty of Health Sciences, Stellenbosch University and runs a pediatric practice at Cape Gate Med clinic, Bracken fell, South Africa. He has published more than 35 papers in reputed journals.

Abstract:

Immune deficiencies in South Africa can be divided into two categories, primary and secondary immune deficiencies. In the private Paediatric clinic, children often present with a number of problems that can be traced to selective primary immune deficiencies. Not all children are eligible for intravenous immunoglobulin therapy, either due to costs or non-IgG immune deficiencies such as selective IgA or T-cell deficiencies. Intramuscular and sub dermal options are equally expensive and more uncomfortable. The use of oral immune modulators, such as the erythromycin derivatives, has raised some concern, mainly because of the potential risk of bacterial resistance. Other so called immune boosters, e.g. echinaceas, are being advertised as potential solutions but have yet to prove to be effective. A practical approach to immune modulation will be presented that has a direct beneficial effect on the health outcome of the children.

Biography:

Estibalitz Laresgoiti-Servitje is a Researcher at the Tecnológico de Monterrey. She received her Medical Doctorate in 1996. Her Post-graduate studies include a Master’s in Immunology, a Master’s in Neurosciences and a PhD in Health Psychology. Her research interests include the neuroendocrine regulation of the immune system and the modulation of the immune system during normal pregnancy and preeclampsia.

Abstract:

Introduction: The placenta is a complex organ that mediates maternal-fetal exchange. Placental perfusion models have shown that there is minimal transfer of certain inflammatory cytokines to the fetal circulation, but bidirectional transfer of cytokines also exists. Objective: This study evaluated if cytokine concentrations in normal and overweight mothers may be similar to the ones of their newborn babies. Methods: Thirty-four pregnant women were included in this study after being admitted to the labor and delivery unit of the National Institute of Perinatology. All participants had single non-complicated pregnancies and did not receive any medication at least three weeks prior to pregnancy termination. Immediately after delivery, maternal blood was obtained by venipuncture and fetal blood was obtained from the umbilical artery. Clinical and demographic data was obtained from clinical records. Cytokine concentrations were measured in maternal and umbilical blood serum using a 27 plex-panel cytokine assay from Bio-Plex (BioRad). Results: Related t-test of all the participants’ samples revealed significant differences between mother and baby’s concentrations of IL1-RA, IL-4, IL-6, IL-7, IL-12, IL-13, IL-17, Eotaxin, G-CSF, GM-CSF, IP-10, MCP, MIP-1, RANTES and VEGF. MANOVA results showed higher but non-significant concentrations of IL-10 in normal weight women and their babies, compared to those in overweight women. No significant differences were found for any cytokine among weight groups. Conclusion: The placenta is an important mediator of maternal-fetal cytokine exchange because it exerts control over the cytokines that are transferred to the fetal circulation. Cytokine transfer appears to be similar in normal and overweight women. However, the effect of co-variables was not evaluated.

Biography:

Ebtesam H M Al-Ali has completed her BSc degree at 1993 from Kuwait University and joined the work as Scientific Researcher at Kuwait Institute for Scientific Research with the molecular genetics group. She led 5 completed projects and has published more than 7 papers in reputed journals and international conferences.

Abstract:

Mycoplasma has a wide distribution in nature, they lack the cell wall and they include important pathogens of animals, plants insects and human. It is difficult to diagnose the Mycoplasma infection based on symptoms alone, therefore a faster and more specific method is needed because of the difficulties of culturing them in laboratory. The objective of this work was to detect avian Mycoplasmosis using PCR diagnostic kit (VenoMGs) and Enzyme Linked Immunosorbant Assay (ELISA) diagnostic kit (ProFLOK) in comparison to culture method. Two advanced techniques were applied: The results obtained from Polymerase Chain Reaction (PCR) technique were compared with serological detection method using ELISA, to study the spread of this disease in sample from broiler and layer flocks. Fifty bird samples were tested for Mycoplamosis. 25 positives (50%) were from ELISA test and 29 positives (58%) from PCR, where only 7 were positive (14%) with culture methods. Swab samples obtained from the choanal cleft gave more positive (60%) with PCR than tracheal samples (56%) and cultures were grown in broth media with a pH indicator. Rapid, sensitive and specific tests that detect nucleic acid from pathogenic Mycoplamas are very attractive for the laboratory detection of infected flocks, and methods reported here are of high sensitivity and specificity for Mycoplasma. The use of these methods for surveillance of the disease will establish data concerning the predominant Mycoplasmosis diseases in Kuwait and improves the veterinary medical service in Kuwait.

Biography:

Eman H Abdel-Rahman is currently working as a Professor in National Research Center, Egypt since 2005. In 1990, she was appointed as Assistant Researcher, in 1995, as a Researcher and in 2000, as an Associate Professor at the National Research Center, Egypt. She received her BSc degree in Zoology in 1981 at Cairo University, Egypt. She completed her MSc in Immunoparasitology in 1990 from Cairo University, Egypt. She obtained PhD from Cairo University, Egypt in 1995 in Immunoparasitology. Her current research interests are immunoparasitology, biological control, DNA technology, glycoprotein antigens and parasitology.

Abstract:

Cystic echinococcosis is a worldwide zoonotic disease caused by larval stages of Echinococcus granulosus. The persistence of cysts in the intermediate hosts as sheep, camels and humans is of interest since, once fully formed, cysts are apparently unaffected by the host’s immune response. Moreover, E. granulosus larval stages possess various molecules which modulate the host immune response and promote parasite survival and development as antigen B and antigen 5 of hydatid cyst fluid. The advent of proteomic analysis of the larval stages proteins has significantly improved the identification and characterization of proteins to use as potential new diagnostics as heat shock protein 20. During cystic echinococcosis, host immune responses switch from Immunoglobulin G1 and interferon gamma to IgG4, IgE, Interleukin 4, IL-5, IL- 6, IL-10 and tumor necrosis factor. Despite of this humoral and cellular immune responses evoked by the host, the parasite not only escape but impair the response and survive for a long time in the host. Among the immunologic tests for assessing the host-parasite relationship, assays of immunoglobulin isotypes detection with the use of distinct parasite antigens, circulating antigens detection and detection of Th1/Th2 cytokine expression. Enzyme Linked Immunosorbent Assay is the most commonly used in the immunodiagnosis of cystic echinococcosis. Accurate serological diagnosis of the cystic echinococcosis, as other helminthiasis, requires highly specific and sensitive antigens to be used in the assays. The choice of an appropriate source of antigenic material is a crucial point in the improvement of the diagnostic features of tests, and must be based on the developmental stage of the parasite. The current review emphasizes recent advances in the identification and characterization of novel antigens with potential for the immunodiagnosis of cystic echinococcosis. The need to search for new antigenic components with high diagnostic sensitivity and specificity remains a crucial task in the improvement of immunodiagnosis of the disease.

Biography:

Gregory Lee received his Ph. D from the California Institute of Technology and completed his postdoctoral studies at the University of California, San Diego. He became a full Professor at the University of British Columbia in 1989, and retired in 2012 with the title of Professor Emeritus. He is the co-founder of Vancouver Biotech Ltd. He has published more than 200 papers, including 30 papers in cancer research. He has been serving as an editorial board member of the Journal of Carcinogenesis and Mutagenesis, and the Journal of Cancer Science and Therapy since 2012.

Abstract:

RP215 is a monoclonal antibody generated against ovarian cancer cell extract and has been shown to react with a carbohydrate-associated epitope located mainly on the heavy chains of immunoglobulins expressed on the surface of most cancer cells. In contrast, these cancerous immunoglobulins, designated in general as CA215, are not found on normal human B cells. Upon isolation from the shed medium of cultured cancer cells, CA215 was found to recognize numerous human serum protein components or fragments, of which both anti- and pro-cancer activities have been identified. These observations strongly support the hypothesis of cancerous immunoglobulins possessing dual functions in cancer cells. Through decades of investigations, it was also revealed that apoptosis and complement-dependent cytotoxicity can be induced by RP215 or its humanized forms, as well as by antibodies against antigen receptors, such those against immunoglobulins or T cell receptors. For example, RP215 and these anti-antigen receptors were found to demonstrate a high degree of correlation in terms of the regulations of many genes involved in the growth and proliferation of cancer cells (EX: NFκB-1, IgG, P21, cyclin D1, ribosomal P1, and c-fos), as well as for toll-like receptors. Furthermore, significant dose-dependent reductions of implanted tumors were also observed following treatment with RP215 in nude mouse animal models. RP215-based immunodiagnostics were also developed for monitoring of the serum levels of CA215 among cancer patients. Judging from these experimental observations, humanized RP215 may be a suitable candidate for antibody-based anti-cancer drug development as it targets cancerous immunoglobulins which are widely expressed on the surface of most cancer cells in humans.

Biography:

Born in 1959 in Brussels, Pierre van der Bruggen completed in 1982 studies in the Faculty of Agronomy at the Université catholique de Louvain and, in 1987, a Ph.D in Agronomical Sciences on a fungus pathogenic for cassava. In 1988, he joined the research group of Thierry Boon at the Ludwig Institute for Cancer Research. He became Associate Professor in 2000 at the Medical Faculty of the Université catholique de Louvain, where is is now Full Professor. Pierre van der Bruggen identified in 1991 the first human gene, MAGE-1, coding for a tumor antigen recognized by cytolytic T lymphocytes. He and his group identified over the years several other cancer germline genes and defined a large number of antigenic peptides, which are encoded by these genes and recognized on tumors by CD8 or CD4 T lymphocytes. Efforts have then been devoted to set up assays that accurately monitor CD4+ T cell responses to cancer vaccines. The group is currently involved in the study of MAGE-3-specific regulatory T cells and anergy of human tumor-infiltrating lymphocytes. Together with Nathalie Demotte, a Ph.D. student in his group, Pierre van der Bruggen identified a novel mechanism causing anergy of CD8 T lymphocytes, including human tumor-infiltrating lymphocytes. Their observations indicate that human tumor-infiltrating lymphocytes, which are very often anergic, can recover ex vivo their effector functions with galectin antagonists. A clinical trial with cancer patients started recently on the basis of these results. Pierre van der Bruggen received the Prize of the "Fondation Maggy et Robert de Hovre" in 1995, the Prize of the "Fondation Alexandre et Gaston Tytgat" in 1998, and the Prize "Wivine et Jacques Allard-Janssen" in 2009. He is the author of 98 research articles (40 as first or last author, 58 as co-author) and 31 review articles.

Abstract:

Freshly collected human tumor-infiltrating CD8 T lymphocytes (TILs) are often defective for the secretion of cytokines and lytic enzymes. We reported previously that these functions could be restored with agents that release the galectin present at the TIL surface. We show here that the non-secreting TILs nevertheless produce normal amounts of intracellular cytokines. We observed poor LFA-1 recruitment and defective actin rearrangement at the TIL secretory synapse. These defects were relieved by galectin removal. Mild LFA-1 blockade by antibodies on normal CD8 blood T cells also blocked actin rearrangement and abolished cytokine secretion but not production. We conclude that galectin prevents the formation of a functional secretory immunological synapse by preventing optimal LFA-1 recruitment. This is the first observation of uncoupled cytokine production and secretion, a defect which is not revealed by intracellular cytokine immunomonitoring assays.

Biography:

I have completed philosophy degree in Biochemistry from Awadhes Pratap Singh University, Rewa, Madhya Pradesh, India. Recently working as a Senior Research Fellow at Immunology Division, NIMR, and Delhi, India. Working on Stem cells therapy to explore scientific knowledge and its future prospectus.

Abstract:

Introduction: Malaria is vector born diseases caused by plasmodium species, survive and replicated into two (Human and Mosquito) host systems. In human, malaria parasite escapes immune response and replicate. In our experiments we found that, accumulation of mesenchymal stem cells in the secondary lymphoid organ using the mouse model of malaria with Plasmodium berghei and imbalance of immune cells during malaria infection. We used rodent malaria parasite to understand host systems. Surprisingly we found that imbalanced numbers of immune cells with the infection were unable to protect. A part from these cells types, increased number of mesenchymal stem cells were unable to protect during malaria infection. Mesenchymal stromal cells or mesenchymal stem cells (MSCs) are multipotent in nature and able to differentiate into different cell types. These differentiating cells were able to express Notch1 may underline mechanism of action of mesenchymal stem cells by production of soluble factors such as IL6 and MIP1a. We also found that these Sca-1+ cells were able to modulate immune response by modulating regulatory T cells with disease progression. Regulatory T cells modulation also dependent upon expression of Notch-1+ cells. Sca-1+ mesenchymal stem cells able to express Notch-1+ during infection, may suggesting that partially Sca-1+Notch-1+ mesenchymal stem cell dependent protection during malaria infection.

Biography:

Manhal Khuder Hasso is a Associate Professor in Duhok Polytechnic University, Iraq

Abstract:

Introduction
Liver X receptors (LXRα and LXRβ) are members of the nuclear receptor superfamily of ligand-activated transcription factors that regulate many biological and physiological processes. LXRs are important regulators of cholesterol and lipid metabolism and this is mediated by regulating a wide range of genes such as ABCA1 and ABCG1 that are involved in lipogenesis, cholesterol efflux and absorption, and bile acid synthesis. Since there is a relationship between chronic inflammatory diseases and lipid metabolic dysfunction, the role of LXRs has been investigated in different inflammatory diseases and disease models. Generally, LXRs have an anti-inflammatory effector function, however occasionally pro-inflammatory effects have also been reported. MicroRNAs (MiRNAs) are small, evolutionary conserved, single-stranded, non-coding RNA molecules with 20- 22 nucleotide base pairs. They regulate mRNA translation by fine tuning the production of proteins involved in the initiation or maintenance of inflammation. MiR-155 is one of the most studied members of miRNAs, and it has a regulatory role in certain inflammatory diseases such as collagen induced arthritis, lung fibrosis, and cardiovascular diseases. Idiopathic pulmonary fibrosis (IPF) is a devastating inflammatory disease of unknown aetiopathogenesis characterised by progressive breathlessness. IPF is characterised by approximately 50% survival of around 3 years after diagnosis, and there is no effective treatment. The main imperative for pulmonary fibrosis research is to identify potential causal inflammatory and remodelling pathways that contribute to IPF initiation and progression in order to determine possible candidate pathways for therapeutic intervention.

Hypothesis:
LXRs play an important role in lipid metabolism and cholesterol homeostasis and because there is a strong relationship between metabolic disease and chronic inflammatory and fibrotic diseases, e.g. LXR agonists may be beneficial for the treatment of RA. We proposed the following hypothesis ‘’ Liver X Receptors can modulate bleomycin-induced pulmonary fibrosis and therapeutic intervention with LXR agonists may be beneficial for the treatment of pulmonary fibrosis.

Methods & Results:
Administration of the LXR agonist GW3965 to LXR-/--/- or LXRwild type mice given bleomycin to induce pulmonary fibrosis significantly exacerbated the severity of the disease only in LXRwild type mice. The worsening of disease was seen as enhanced loss of body weight, increased inflammatory and fibrotic pathomorphological changes in the lung, increased inflammatory cells in the bronchoalveolar lavage, increased concentrations of several pro-inflammatory and pro-fibrotic mediators, and increased expression of genes that regulate inflammation and fibrosis, such as collagen and TGF, increased lung collagen content, and finally up-regulation of the expression of the alternative activated macrophages (M2)markers arginase 2 and IL-13 receptor The effect of the LXR agonist was mediated specifically by LXRs because the severity of disease did not change in LXR-/--/- mice given bleomycin and treated with GW3965, nor on similarly treated single LXRα or LXRβ gene-deleted mice. Furthermore, similar activation of LXRs in primary human or murine fibroblasts demonstrated up-regulation of the expression of collagen. The function of LXR agonist was directly on collagen gene expression and did not require de novo protein synthesis as demonstrated by the addition of cycloheximide as a translation inhibitor to murine primary fibroblasts activated with LXR agonist. This suggested that the LXR may have acted directly on the promoter region of the collagen gene. Also I investigated if the collagen genes have response elements for LXR in their promoter regions using a cell reporter system. I demonstrated that the collagen genes have response elements for LXR in their promoter regions. In a parallel set of experiments, administration of bleomycin or PBS to miR-155-/- and miR-155 wild type mice demonstrated a significantly stronger inflammatory and fibrotic process in the miR-155 gene-deleted mice. This worsening of disease was seen as an enhanced loss of body weight, increased inflammatory and fibrotic pathomorphological changes in the lung, increased inflammatory cells in the bronchoalveolar lavage, increased concentration of several pro-inflammatory and pro-fibrotic mediators, and increased expression of genes that regulate inflammation and fibrosis; such as collagen and TGFincreased lung collagen content, and finally up-regulation of the expression of the alternative activated macrophages (M2) markers arginase 2 and IL-13 receptor. The effect was mediated specifically by miR-155 because the severity of disease was increased in miR-155-/- mice compared with miR-155 wild type mice given bleomycin. Also no differences were observed in miR-155-/- and miR-155 wild type mice given PBS.

Conclusion:
My results demonstrate that both the LXR and miR-155 have an important impact on the progression and extent of murine pulmonary fibrosis. Since completing the work for this thesis some of my additional pilot work has shown that LXR is a target for miR-155 and therefore both may have an important role in lung homeostasis. My results suggest the therapeutic approaches for IPF might include targeting the LXRs or LXR-regulated pathways, including potential fine tuning levels of LXR with miR-155 antagonists. The aim would be to prevent excessive remodelling. Furthermore, any such therapeutic intervention would need to be done in a very careful way because LXRs are involved in many other physiological processes. Therefore, more targeted therapy perhaps controlling miR-155 may be of clinical relevance for therapeutic strategies.

Biography:

Dr. Kiran Sharma is presently working as post doc fellow in the Department of Biochemistry and Medical Genetics, University of Manitoba from May 2013 till present. She received her MSc (2007) from Guru Nanak Dev University, Punjab, India and BSc (2004) from the Himachal Pradesh University, Shimla, India. Dr. Sharma received her Ph.D. from Dept. of Surgical Oncology, King George Medical University, Lucknow, India in 2013. Her thesis work was entitled as “Role of Genetic Variants of Hormonal, Inflammatory and Xenobiotic metabolism pathway genes to Gallbladder cancer susceptibility”.

Abstract:

Gallbladder cancer (GBC) is a violent neoplasm associated with late diagnosis, unsatisfactory treatment, and poor prognosis. The disease shows complex interplay between multiple genetic variants associated inflammation and tumorigenesis. We analyzed 15 polymorphisms in nine genes involved in various pathways to find out combinations of genetic variants contributing to GBC risk. The genes included in the study were (matrix etallopeptidase-2, MMP-7, MMP-9), tissue inhibitor of metalloproteinases (TIMP-2), cytochrome P450 (CYP)1A1, CYP1B1, phospholipase C epsilon 1 (PLCE1), liver X receptor (LXR)-alpha and LXR-beta. Genotypes were determined by PCR-RFLP andTaqMan probes. Statistical analysis was done by SPSS version 16.Multilocus analysis was performed by Classification and RegressionTree (CART) analysis and multifactor dimensionality reduction(MDR) to gene–gene interactions in modifying GBC risk. In silicoanalysis was done using various bioinformatics tools (F-SNP,FAST-SNP). Single locus analysis showed association of MMP-2(−735 C > T, −1306 C > T), MP-7 − 181 A > G, MMP-9 (P574R,R668Q), TIMP-2 − 418 G > C, CYP1A1-MspI, CYP1A1-Ile462Val,PLCE1 (rs2274223 A > G, rs7922612 T > C) and LXR-beta T > C(rs3546355 G > A, rs2695121 T > C) polymorphisms with GBC risk (p < 0.05) whereas CYP1B1 and LXR-α variants were not associatedwith GBC risk. Multidimensional reduction analysis revealed LXR-β(rs3546355 G > A, rs2695121 T > C), MMP-2 (−1306 C > T), MMP-9(R668Q), and PLCE1 rs2274223 A > G to be key players in GBCcausation (p < 0.001, CVC = 7/10). The results were further supportedby independent CART analysis (p < 0.001). In-silico analysis ofassociated variants suggested change in splicing or transcriptionalregulation. Interactome and STRING analysis showed network ofassociated genes. The study found PLCE1 and LXR-β networkinteractions as important contributory factors for geneticpredisposition in gallbladder cancer.

Biography:

Assistant Professor of Molecular Microbiology and Immunology (Research) My primary research interests are directed towards understanding the immunopathogenesis of lung injury and repair. I have interrogated the roles of a chitinase-like protein and its receptors in a variety of lung diseases including asthma, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis. My future research plans are aimed at dissecting the common mechanisms that underlie the pathogenesis of pulmonary fibrosis, specifically the role of intracellular receptor trafficking pathways in disease progress. My long-range research goals are to identify the immune and cellular responses that mediate lung injury and repair responses and to identify specific molecular targets that can be targeted in the treatment of related disorders.

Abstract:

Rationale:
Tissue injury and repair are juxtaposed inlungs from patients with Idiopathic Pulmonary Fibrosis (IPF). IPF is characterized by epithelial apoptosis, aberrant fibroblast and myofibroblast proliferation, and matrix deposition.Studies from our laboratory and others have demonstrated that injury and fibroproliferative repair are essential events in the pathogenesis of IPF. They also demonstrated that interventions that abrogate injury also prevent excessive fibroproliferative repair. Chitinase 3-like 1(CHI3L1) (also called YKL-40 in man and BRP-39 in mouse) is a prototypic chitinase-like protein that has been retained over species and evolutionary time. Dysregualted expression of CHI3L1has been noted in a variety of human diseases characterized by inflammation, tissue remodeling, and fibrosis.Previous studies from our laboratory demonstrated that CHI3L1 mediates aeroallergen-induced adaptive Th2 inflammation and IL-13-induced pulmonary fibrosis, while itinhibits apoptosis and confers tissue cytoprotection in the setting of a variety of pulmonary injuries including Streptococcus pneumoniae infection, and oxidant injury. However, the ability of CHI3L1 to regulate injury and/or fibroproliferative repair and the regulation of CHI3L1 in IPF have not been adequately defined.
Hypothesis:

We hypothesized that (a) CHI3L1 is differentially regulated and has distinct effects on the injury and repair phases of PF; (b) CHI3L1 is expressed in an exaggerated manner and is a useful biomarker in IPF.
Methods:

We characterized the expression of CHI3L1 afterbleomycin administration and used CHI3L1-/- and YKL-40 transgenic miceto define the roles of CHI3L1 in bleomycin-induced injury and repair. We also characterized the levels of CHI3L1 in plasma fromIPF patients and the relationships between the levels of CHI3L1 and disease progression.

Results:
CHI3L1 expression was acutely and transiently decreased during the injury phase and returned to normal or super normal levels during the fibrotic phase following bleomycin administration. Overexpression of CHI3L1during “injury” significantly amelioratedbleomycin-induced inflammation and cell death. In contrast, overexpression of CHI3L1 solely during fibroproliferative repair enhanced tissue fibrosis andaugmented extracellular matrix gene expression, TGF-β production, and alternative macrophage activation. The levels of circulating CHI3L1 were elevated in IPF patients compared to normal controls. Importantly,high levels ofCHI3L1were associated with increased risk of disease progression.
Conclusions:

CHI3L1 plays a protective role in the injury phase and a pro-fibrotic role in the repair phase of pulmonary fibrosis. CHI3L1 is increased in the circulation of patients with IPF where it likely represents an attempt on the part of the host to diminish injury and induce repair which correlates with disease progression.

Biography:

Abdul-Rahman Mubarak studied Bachelor of Science Molecular Biology and Biotechnology at University of Cape Coast and M.PHIL. In Clinical Immunology at University of Ghana Medical School.

Abstract:

Introduction
Human leukocyte antigen G (HLA-G) is a non-classical major histocompatibility complex (MHC) class Ib antigen characterized by a limited polymorphism. The expression of HLA-G at immune privileged sites and its ability to inhibit the effectors functions of immune cells has set HLA-G as a molecule of immune tolerance. This expression pattern is unique among HLA genes and suggests that HLA-G may be involved in interactions that are critical in establishing and/or maintaining pregnancy.

Methods
The study participants include women undergoing spontaneous abortion, non-pregnant women, males and an archive sample of women who had normal vaginal deliveries without any complications and any history of malaria infection from gestation to delivery. The sHLA-G level was measured using BiovendersHLA-G ELISA kit following the manufacturer’s protocol.

Results
sHLA-G levels was found to be higher in women undergoing spontaneous abortion as compared to women who had normal vaginal delivery and non-pregnant women. sHLA-G level was also found to be higher in second trimester as compared to first trimester in both women who had spontaneous abortions and women who had normal delivery.

Conclusion
Although sHLA-G level was found to be higher in women undergoing spontaneous abortion as compared to non-pregnant women and women who had normal delivery, it may not be playing any role in implantation rather playing a role in the maintenance of maternal immune tolerance to foetal antigen after implantation because plasma sHLA-G levels was found to increase with increasing trimester in both women who had normal delivery and women undergoing spontaneous abortion

Biography:

Sthiti Porna Dutta has joined as Ph.D scholar in the Department of Biochemistry in the immunology laboratory of North Eastern Hill University in 2012. She has completed her Msc in Biochemistry at an age of 23 from Annamalai University, Tamilnadu in 2012 .She has attended several national conferences and workshops and participated as young scientist in the National Seminar organised by NORTH EAST BIOLOGICAL CONSORTIUM .She has done dissertation projects on Protein analysis of kumal rice and Production of Bio-Electricity from organic and sewage waste and the antibiotic sensivity test of the micro organisms isolated and identified from them.

Abstract:

Effects of N-Nitrosodibutylamine on the expression of the liver mitochondrial membrane surface proteins in mice: N-Nitrosodibutylamine (DBN) is an established hepatocarcinogen in rodents and its effects on liver mitochondria in Swiss albino mice have been examined. In the present investigation, DBN at a dosage of 10 mg kg-1 body weight was used to induce carcinogenesis in male mice by intravenous administration of the carcinogen at weekly intervals for a period of 16 weeks. This protocol triggered the initiation of carcinogenesis. Cancer induction was followed by monitoring the activities of marker enzymes such as acetylcholine esterase (AChE), glutathione-S-transferase (GST) and gamma-glutamyl transpeptidase(GGT), which was further supported by the histological examination of liver tissue of DBN exposed mice. The observed alteration in marker enzymes activities indicate hepatic dysfunction and damage to liver caused by DBN-treatment in mice. Whether, the DBN exposure also affect on mitochondrial membrane surface protein was of great concern to us. Hence liver mitochondria are chosen as our target of interest. Our preliminary observations indicate a drastic distortion in shape and size of liver mitochondria in mice upon DBN exposure. The membrane was highly disrupted and mitochondria contained large vacuoles or enlarged cristae compartments in comparison to the normal control mice. The proteomic analysis of the liver mitochondrial membrane surface proteins showed differential expression in DEN-treated mouse compared to that of the normal control. These results suggest that specific mitochondrial proteins are uniquely susceptible to alterations in expression and carry implications for the further investigation of their potential as therapeutic and prognostic markers.

Biography:

Kanga Rani Selvaduray is a Assistant Professor, International Medical University, Malaysia

Abstract:

Several mechanisms have been postulated for the anti-cancer effects of tocotrienols. In this study, the anti-cancer mechanism of tocotrienols is for the first time linked to increased expression of interleukin-24 (IL-24) mRNA, a cytokine reported to have anti-tumor effects in many cancer models. The anti-proliferative effects of tocotrienol-rich fraction (TRF) from palm oil, γ- and δ-tocotrienol (γ-T3 and δ-T3) and α-tocopherol (α-T) were studied on 4T1 murine mammary cancer cells. TRF, γ-T3 and δ-T3 significantly inhibited the growth of the 4T1 cells with IC50 values of 8.99, 4.79 and 3.73μg/ml respectively. Tumor incidence and tumor load in BALB/c mice were decreased by 57.1% and 93.6% respectively (p<0.05) with TRF supplementation. Tumourigenesis was examined and compared against control in both nude and BALB/c mice models. The mice were injected with MDA-MB-231 and 4T1 cells respectively for the different models, and were fed with TRF by oral gavage. This study shows that palm tocotrienols have strong inhibitory effects on the growth of both MDA-MB-231 and 4T1 cells both in vitro and in vivo. In addition the immune modulatory effects of tocotrienols were also investigated and it was found that TRF enhanced production of NK cells (P < 0.05) as well as IFN-γ (P < 0.05), which in turn regulate the immune protection against cancer cells. These observations were recorded in both mice models. The 4T1 cells treated with TRF, δ-T3 and α-T exhibited highest levels of IL-24 mRNA in δ-T3 treated cells, followed by TRF and α-T. The IL-24 mRNA levels in tumor tissues of BALB/c mice supplemented with TRF increased two-fold as compared to control mice. Increased levels of IL-24 have been associated with inhibition of tumor growth and angiogenesis. TRF and δ-T3 treated 4T1 cells significantly decreased IL-8 and vascular endothelial growth factor (VEGF) mRNA levels. We hereby report that the anti-tumor including the anti-angiogenic effects of tocotrienols are associated with increased levels of IL-24 mRNA.

Biography:

Divocha Valentina in 1967 she graduated from I. I. Mechnikov Odessa State University, Faculty of Biology (Department of Virology). In 1973 continued her postgraduate study ate Odessa Institute of Virology and Epidemiology (specialty virology). In 1974 she was awarded her candidate degree with the thesis "Interaction of Coxsackie B viruses with sensitive cell cultures and their antigenic relationships." In 2009 she was awarded her doctoral degree with the thesis entitled "Biological basis antiprotease therapy of influenza." Under her leadership performed a doctoral and two master's theses. Scientific experience is 35 years. I have more than 180 scientific publications, 2011 monograph, textbook "Virology" (2012), 10 patents, 3 innovations. I am currently working as the head of the Laboratory of Experimental and Clinical Pathology for Ukrainian Research Institute of Transport Medicine, is the supervisor of the nine research programs in virology and biochemistry.

Abstract:

Introduction:
Interaction of virus and cell in the pathogenesis of viral diseases is insufficiently studied. The main point here is penetration of virus into a healthy cell with an obligatory virus’ deproteinization. However the deproteinization of viruses is studied insufficiently. First of all it refers to the mechanisms of introduction of flu virus in the cells of mammals, including humans. In this regard in 1983 we offered the new theory of flu pathogenesis with participation of proteinazno-inhibitory system.

Objective:
To study the state and role antiproteinasis systems of the virus and recipient in the development of an influenzal infection for receiving essentially new medical preparations on the basis of inhibitors of trypsin-like proteinases.

Methods:
In work presented we used flu viruses, A/PR/8/34 (H1N1), AO/32(H1N1) strains, white mice, chicken embryos, white rats, waste of γ-globulin and albumin manufacturing, human interferon and immunoglobulin, herpetic, gonococcus and tularemia vaccines and medicines: Influvac, Fluarix, Vaxigrip – anti-influenzal vaccines, Avaxim – vaccine for hepatitis A and blood preparations - Fraxiparine, Solcoseryl.

Results:
It has been established that cleaning and concentration of influenzal virus A by different methods doesn't exempt virus from cellular enzymes – trypsin-like proteinases and their inhibitors. Both domestic (human immunoglobulin and interferon, anti-influenzal and herpetic vaccines), and foreign preparations (Influvac, Fluarix, Vaxigrip, Avaxim, Fraxiparine and Solcoseryl) had trypsin-like proteinase and its inhibitor in their structure. In the experiments on the white mice at infection with flu A virus there was a violation of proteinase - inhibitory balance, especially during the first hours after contamination. From the lungs of healthy mice six isoforms of trypsin-like proteinase have been allocated and antiproteinase immune serums were received to them. At the treatment of the animals infected with a lethal dose of flu A virus, only one serum (to the third isoform) has protected white mice from death. From the waste of γ-globulin manufacture of donor blood, inhibitor of trypsin - like proteinases which protected for 80% of white mice from death, was emitted.

Conclusions:
Endogenous inhibitors of human blood proteinases are perspective preparations in the fight with flu in humans.

Biography:

Assi Flaviurs is a Public Health researcher in Cameroon. He is participating in PhD program of School of Medicine, University of Buea- Cameroon. His research concentrates on transmission, knowledge, attitude and sex behaviors among female sex workers in Cameroon. Before the PhD program, Assi taught and studied in Public Health and Health Promotion for 5 years with a number of researches and projects in health prevention field.

Abstract:

Female sex workers (FSWs) are at heightened risk of sexually transmitted infections (STIs) and HIV. The purpose of this systematic literature review of STI/HIV prevalence for FSWs in central African is to appraise and understand the burden of STIs and HIV. Electronic databases searched included PubMed (MEDLINE), Embase, Global Health, MeSH, Cochrane Library, Health Reference Centre, Pro Quest, Psyc INFO, Science Direct, Social Services Abstracts, SCOPUS, CINAHL, Web of Science, and POP Line. Relevant articles published from 2007 to 2012 were identified. The findings of this multi-country regional review provided reliable evidence that despite prevention efforts, FSWs remain one of the main populations most affected by HIV/STIs. The review reveals that the prevalence of HIV/STIs among FSWs in a number of African countries is high, especially in Cameroon and Nigeria, two countries with the highest HIV and STI prevalence. Furthermore, FSWs who work on the street, or freelance, or use multiple venues are significantly more likely to be infected with HIV/STIs than those who work from a single venue.

Biography:

Place and date of birth: Yerevan, Armenia, April 29, 1953 Education: MD, Yerevan State Medical Institute, Armenia, 1976.Scientific degrees: Candidate of Medical sciences (PhD): Leningrad Military-Medical Academy, 1984. Doctor of Medical Sciences (DSci): Leningrad Military-Medical Academy, 1988. Research interests: Gastroenterology, Immunology, Bacteriology. Publications: over 80 peer-reviewed journal papers, 1 monography (book) “The Functional Blocks And The Problems Of Clinical Medicine”, Moscow-Leningrad, 1990, 360 pp. 4 Patents regarding new methods of treatment. Memberships in professional societies: Academician of the Academy of Natural Sciences of Russia Academician of the Academy of Ecology (Russia) Member of the editorial board of “Russian Journal of Gastroente rology, Hepatology, Coloproctology” (Moscow).

Abstract:

Background:
The mechanism of bloodstream bacteria clearing is unknown. Bloodstream high velocity prevents bacteria recognition and phagocytosis by leukocytes, besides, erythrocytes are 99.9% of blood cells and leukocyte chance to get in contact with bacteria is extremely low. Many bacterial species that enter bloodstream and are resistant to blood humoral bactericidal factors nevertheless are rapidly cleared from bloodstream. Till now there is no reasonable explanation how blood bacteria clearing really happens.

Methods:
Phase-contrast immersion vital microscopy with high speed video camera registration and standard microbiologic laboratory research methods in patients with bacteremia and sepsis. Results: It was revealed that bacteria cannot grow and proliferate in bloodsream because they become triboelectrically charged and this electric charge stops trans membrane inflow of nutrients and outflow of metabolites. Interaction of both bacteria and erythrocyte electric charge provides bacteria attraction and fixation on erythrocyte surface that stimulate erythrocyte membrane receptors and causes oxygen release and bacteria killing by oxidation. Killed bacteria lose zeta potential and cannot be kept on the surface of erythrocyte and are released back to plasma and then are digested in the liver and spleen by local macrophages. Bacteria that are resistant to released oxygen concentration on the surface of erythrocyte may penetrate erythrocyte membrane producing variety of enzymes (hemolysins, hyaluronidases, kinases, exfoliatins, lipases, etc.) and enter erythrocyte. Inside erythrocyte bacteria are killed by reactive oxygen species (ROS) and are released back to plasma. Very few bacteria resist ROS and survive inside erythrocyte by means of catalase production and metabolism slowing down. Erythrocyte with bacteria inside may continue to function for a while but usually it is decomposed during passing the spleen and released bacteria are digested by local macrophages. Conclusion: From bacteria elimination point of view human body consists of two separate but interacting compartments: (a) compartment of blood circulation (pulmonary circulation and systemic circulation); (b) compartment out of blood circulation (the tissues that get oxygen from blood circulation, lymphatic vessels, lymph nodes, etc.). The liver and spleen are some special kind of interface between these compartments. In bloodstream bacteria clearing is performed by erythrocyte: bacteria attraction and fixation is an electric charge interaction phenomenon whereas bacteria killing are provided by bacteria oxidation on the surface or inside erythrocyte. Erythrocytes in arterial blood have maximal bactericidal activity whereas in venous blood erythrocytes attract and fix or engulf bacteria but cannot kill them because of lack of oxygen (oxyhemoglobin). Venous blood erythrocytes kill fixed or engulfed bacteria during blood oxygenation in the lungs. Compartment out of circulation is the realm of leukocytes and bacteria killing occurs by means of phagocytosis and production of different humoral factors.

Biography:

Stefano D’Errico is a Professor in Department of Legal Medicine,Ospedale Campo di Marte, Italy

Abstract:

Learning objective:
After attending this presentation, attendees will understand the relevance of a complete methodological approach in fatal cases of anaphylactic shock and the opportunity of a complete immunoserological investigation. Synopsis of content: The most frequent reactions to cephalosporins are non pruritic, non-urticarial rashes which occur in 1.0% to 3% of patients for most, the mechanism is considered idiopathic and not a contraindication for future use. Anaphylactic reactions from cephalosporins are extremely rare with the risk estimated at 0.0001% to 0.1%. Several studies suggest that cephalosporin-induced anaphylaxis occurs no more frequently among patients with known penicillin allergy than among those without such allergy. Allergic reaction to cephalosporins may occur because of sensitization to unique cephalosporin haptens or to determinants shared with penicillins, although the different epitopes have not been defined. Lack of knowledge of the exact chemical structure of cephalosporin antigen determinants has hindered clinical interpretation of allergic reactions and cross-reactivity. In patients with a primary response to cephalosporins, selective recognition of the R1 side chain has been observed with some degree of cross-reactivity between different cephalosporins, which almost always concerned cephalosporins with identical or similar R1 side chains. Authors present the case of a 79 y.o. man who suddenly died after i.m. administration of ceftriaxone. Dyspnoea, cyanosis and cardiac arrest occurred immediately after administration. Resuscitation manoeuvres were unsuccessful. In the history coronary by-pass and multiple administration of different antibiotics were recorded in the last ten years from general practitioner, without symptoms. Lipotimic crisis after administration of cefepime occurred few month before death. A complete post-mortem examination was performed. Gross examination was unremarkable except for mild pulmonary oedema. Histological examination revealed polivisceral stasis, mild cerebral oedema and acute pulmonary oedema mixed to acute pulmonary emphysema. Myocardial interstitial oedema was also detected. An immunohistochemical technique was used to estimate mast-cell population, using the anti-tryptase antibody as a mast-cell specific marker. Pulmonary mast cells were identified and a great number of degranulating mast cell with tryptase-positive material outside were observed. Toxicological analysis on blood specimens was unremarkable. Serum dosage of mast cell tryptase from femoral blood detected serum values of 93.5 kUA/ml. Research of total and specific IgE was performed showing that the subject was sensible for penicillins, amoxicillin, cephalosporins and also for the most common allergens. Death was due to anaphylactic shock; past administrations of cefepime sensitized the man to cephalosporins and a fatal cross reactivity of ceftriaxone with cefepime occurred due to the identical 7 position side chain structure in both molecules.

Paper’s proposition:
This presentation will impact the forensic community by alerting on the cross reactivity between cephalosporins as a potential cause of malpractice claim in general practice and by advising on the importance of collecting more evidence as possible in fatal cases of anaphylaxis.

Keywords:
cephalosporins, anaphylactic shock, tryptase.

Biography:

Rebekah Diamond will complete her MD at the Icahn School of Medicine at Mount Sinai in New York, NY in May 2015. Her paper “Elucidating the novel finding of an increased incidence of hypertension in patients with biliary atresia” was just accepted in the Journal of Pediatric Gastroenterology and Nutrition. She is currently applying for a residency program in Pediatrics.

Abstract:

Introduction:
Chimeric antigen receptor therapy (CART) is a decades old approach to cancer immunotherapy that has gained recent attention as clinical trials show its efficacy in treating chemotherapy resistant leukemia. This technology is a powerful, targeted immunotherapy therapy. Given the rapid advances in CART and increasingly efficient production techniques, it follows that this therapy could be used for other disease processes with targetable molecules for engineered immune cells. This study evaluated current scientific investigation into the uses of chimeric antigen receptor therapy in treating non-oncological disease.

Methods:
A literature database review was conducted using Pubmed.com. The phrase “chimeric antigen receptor” was typed into the database search engine. All resulting titles were assessed and those relating to CART or chimeric antigen receptors in non-oncological disease were noted and reviewed.

Results:
The Pubmed.com search returned 2706 results with the above-described parameters. Of these, approximately one half resulted from the individual search words and deemed irrelevant. Of the remaining, only 16 papers meeting the description of non-oncological chimeric antigen receptors (N=11 infectious disease, N=4 autoimmune, N=1 allergy).

Conclusion:
The investigation into non-oncological uses of CAR therapy is extremely limited but early studies show promise. The majority of research is in preclinical investigation. This technology should emerge as an important therapy as CART research continues to show efficacy cancer treatment.

Biography:

Nashwa Khairat Abousamra received her MD in Clinical Pathology, Hematology, April 2004 , Mansoura University, Egypt. Masters Degree in Clinical Pathology (Hematology), May 1997, Mansoura University, Egypt. She has many international publications. She has experienced as an internship house officer in Mansoura University hospital from 1 March 1993 to 28 February 1994. General practitioner in Egyptian Ministry of Health, Mansoura from 1 March 1994 to 15 May 1994. Resident in Clinical Pathology, Clinical Pathology Department, Mansoura University from 17 May 1994 to 28 May 1998. Demonstrator of Clinical Pathology, Clinical Pathology Department, Mansoura University from 28 May 1998 to 28 July 1998. Assistant lecturer in Clinical Pathology, Clinical Pathology Department, Mansoura University from 28 July 1998 to 28 September 2004. Lecturer in Clinical Pathology, Hematology Unit, Clinical Pathology Department, Mansoura University from 28 September 2004 to 22 November 2009. She is continuing as Assistant Prof of Clinical Pathology, Hematology Unit and as Professor of Clinical Pathology, Hematology Unit, Clinical Pathology Department, Mansoura University

Abstract:

B-cell chronic lymphocytic leukemia (B-CLL) is a heterogeneous disease with a wide variability in patients' clinical course. Numerous prognostic markers were introduced to screen for patients likely to have progressive course of B-CLL bearing the potential to facilitate risk-adapted treatment strategies. Extracellular ATP functions as a "natural adjuvant" that boosts immune responses in the tumor micro environment but might also contribute directly to cancer cell death. CD39/ENTPD1 is the dominant ecto nucleotidase catalyzes the sequential hydrolysis of ATP to AMP that is further degraded to adenosine. The present study was conducted to analyze CD39 expression in T cells and B-CLL cells by flow cytometry to evaluate its impact on the clinical course of 68 unselected B-CLL patients and correlate it with well-established risk factors. CD39 expression in T cells was increased in the peripheral blood of B-CLL patients compared to healthy controls. The higher levels were associated with the advanced stage of disease. CD39 expression in T cells negatively interacted with patients' time to first treatment (TFT). Although our results revealed CD39 expression in B-CLL cells as a marker of less aggressive disease, our attempt to correlate its level with TFT failed to give any prognostic relevance. Overall, our data indicate that T-cell CD39 expression may identify subsets of B-CLL patients with unfavorable clinical outcome in term of therapeutic need. Moreover, it can be incorporated into prognostic schema to improve the prediction of disease progression in CLL. CD39 may find utility as a future target for the development of novel therapies with immune-modulating antitumor agents in CLL.

Biography:

Iulia Popescu is a Senior Scientist in University of Pittsburgh, USA

Abstract:

CMV remains an important opportunistic pathogen in solid organ transplantation, particularly in lung transplant recipients (LTRs). LTRs mismatched for CMV (donor+/recipient-; D+R-) are at high-risk for active CMV infection and increased mortality; however the immune correlates of viral control remain incompletely understood. We prospectively studied 23 D+R- LTRs during primary CMV infection to determine whether acute CD8+ T-cell parameters differentiated the capacity for viral control in early chronic infection. T-box transcription factors expression patterns of T-bet >Eomes differentiated LTR controllers from viremicrelapsers, and reciprocally correlated with granzyme B loading, and CMV phosphoprotein 65 (pp65)-specific CD8+IFN-+ and CD107a+ frequencies. LTR relapsers demonstrated reduced CD8+Ki67+ cells ex vivo and substantially impaired CD8+pp65-specific in vitro proliferative responses at 6 days, with concomitantly lower pp65-specific CD4+IL-2+ frequencies, as compared to LTR controllers. However, CMV-specific in vitro proliferative responses could be significantly rescued, most effectively with pp65 antigen and exogenous IL-2, resulting in an increased T-bet:Eomes balance, and enhanced effector function. Using class I CMV tetramers, we observed similar frequencies between relapsers and controllers, though reduced T-bet: Eomes balance in tetramer+ cells from relapsers, along with impaired CD8+ effector responses to tetramer-peptide re-stimulation. Together, these data show impaired CMV-specific CD8+ effector responses is not for complete lack of CMV-specific cells, but rather, underscores the importance of the T-bet:Eomes balance, with CMV-specific proliferation a key factor driving early T-bet expression and effector function in CD8+ T cells during primary infection, and differentiating the capacity of high-risk LTRs to establish immune control during early chronic infection.

Biography:

Rajesh K. Sharma is Assistant Professor at University of Louisville. He completed his Ph.D. in immunology at Banaras Hindu University in India. Dr. Sharma pursued his postdoctoral studies in cancer immunology and immunotherapy at the University of Louisville. Dr. Sharma serves as reviewer for various journals. His research interests are in the area of cancer vaccines, cancer immunotherapies, particularly development of combinatorial therapeutic approaches for cancer. Dr. Sharma is also involved in understanding the role of chemokine and its receptors in cancer-immune interplay and if these chemokine networks could be exploited to enhance the therapeutic efficacy of immunotherapies.

Abstract:

Cancer immunotherapy has recently emerged as a viable alternative to standard of care therapies and many FDA approved immunotherapies are in clinic. Several new forms of immunotherapies targeting cytotoxic-T-lymphocytes (CTLs) such as adoptive cell therapies and vaccines are in advanced clinical trials. In all of these, trafficking of CTLs to tumor is a critical step for achieving therapeutic efficacy. However, inefficient infiltration of activated CTLs into tumors is increasingly being recognized as one of the major hurdles limiting efficacy. We herein investigated the roles of chemokine receptors in regulation of CTL migration to tumor. Using tumor studies in receptor knockout mice, depletion of CTLs, adoptive transfer in Rag2-/- mice, we have demonstrated the critical role of BLT1 in controlling the migration of CTLs to tumor in cervical cancer model. Furthermore B16 melanoma model was used for validation of this notion and evaluation of the involvement of another chemokine receptor CXCR3 that has been widely implicated in migration of CTLs in context of infection or autoimmunity. We herein demonstrate that BLT1 and CXCR3 both receptor play a critical and combinatorial role in controling the CTL traficking to tumor. We finally showed that anti-PD-1 antibody immunotherapy failed in BLT1-/- and CXCR3-/- mice suggesting the indisapansable requirement of these receptor during therapy. These studies provides further insights in CTL migration to tumor during tumor development as well as the course of cancer immunotherapies. The findings may have translational implications for improving inharent as well as immunotherapy induced CTL responses in cancer patients.

Biography:

Award: "Prof. Dr. Juan Carlos Arauz " First Prize for “A new technique for treating recurrent respiratory papillomatosis using chromoendoscopy associated with Endoscopic Laryngotracheal Surgery (ELS)” research paper

Abstract:

Introduction:
Chromo endoscopy is an endoscopic technique which uses a contrast stain to paint the aero digestive tract mucosal lining followed by an optical assessment to highlighting any epithelial abnormalities. Detailed and high-definition magnified views achieved with the aid of rigid endoscopes can often allow for identification of the tissue type or pathology based upon the pattern uncovered. According to the literature we reviewed, we may have been the first ones to use indigo carmine in the field of otolaryngology. Tiny lesions that usually go overlooked with conventional micro laryngoscopy become visible upon the instillation of indigo carmine and further decreasing the chances of an early lesion post-operative recurrence. Chromo endoscopy, in recurrent respiratory papillomatosis (RRP), helps identify unsuspected intraoperative lesions by clearly enhancing the view of their boundaries and surface type. It is also suitable to assess the presence of residual lesions, if any, after their surgical removal.

Objectives:
To demonstrate the usefulness of chromo endoscopy in RRP in laryngotracheal surgery.

Material & Methods:
We used indigo carmine associated with endoscopic laryngeal surgery. Before staining, the mucosa may need to be treated with a mucolytic agent to get rid of excess mucus to boost staining. Rigid suspension laryngoscopes of different proximal and distal diameters were used with chromo endoscopy. Patients underwent chromo endoscopy associated with endoscopic laryngeal surgery under general anesthesia in the O.R.

Results:
In this second phase of our research work, this diagnostic technique was applied to eighteen patients with recurrent laryngeal papillomatosis and two patients with suspected carcinoma of the larynx. We were able to optimize the intraoperative diagnosis and reduce the likelihood of the relapse risk in all patients.

Conclusion:
Chromo endoscopy associated with endoscopic laryngeal surgery is an excellent low-cost intraoperative diagnostic method for the treatment of invasive diseases of the larynx such as laryngeal papillomatosis.

Biography:

Dharmendra Jain, Asst Prof Of Cardiology, Ims, Banarasi Hindu University, , Varanasi, India

Abstract:

Introduction & Aim:
Donor-specific complement-fixing alloantibody identification is known to play a major role in antibody-mediated renal transplantation rejection and management. Specifically, the deposition of C4d in the peritubular capillaries in a kidney biopsy is a valuable marker of antibody-mediated rejection (AMR). Various methods have been reported for the detection of allo-antibodies in recipient sera. These antibodies can be HLA or non-HLA, complement-fixing or non-complement fixing, donor T and/or B cell specific. The C4d Flow-PRA is one of the screening methods to identify the HLA specific complement fixing antibodies. However, the results are limited by the lack of donor specificity in this method.

Method:
We hereby report a novel method christened Donor-specific-Flow-C4d (DFC) of identifying donor-specific (T and/or B cell), C4d-fixing alloantibodies. The test was validated using pooled reference serums and comparing the results with immunohistochemistry findings.

Results:
In present report we have discussed a series of cases representing a variety of cases in renal transplants wherein the newer method i.e. DFC was beneficial. Some of the prototype cases cited was of AMR, where initially there was a dilemma of AMR versus ACR as the result of histopathological finding of allograft biopsy and FCXM were not sufficient to confirm it as complement mediated rejections. The positivity on the DFC method confirmed the diagnosis of AMR due to donor B cell specific, complement fixing, alloantibodies for both of these cases. An another case was of a deferred pre-transplant donor, wherein the recipient serum was confirmed to be positive for donor T and B cell specific; complement fixing, HLA alloantibodies without using an invasive procedure of allograft biopsy. This was helpful in pre- transplant prediction of a possibility of an AMR. There were also a few cases with a clear indication of correlation of the DFC and the histopathological findings. The patients were managed with the therapeutic protocols used for an ACR.

Conclusion:
With the added advantage of being non-invasive and Donor T and B cell specificity, this newer method provides information pre-transplant; whereas kidney biopsy based C4d evaluation can only be done post-transplant. It helps in decision of donor deferral, which is important in Asian countries like India, where most of the transplants are live related. We postulate that this method incorporates the best features of all the available modalities (i.e. FCXM, C4d-FlowPRA and NIH-CDC).

Biography:

Dr. S.C.K. Tay earned his MPH in Veterinary Public health, Parasitology, Zoonoses, Epidemiology and Clinical Microbiology from the University of Minnesota, Minneapolis St. Paul, U.S.A and his MSc. Vet, Med., D.V.M from the Central University of Timisoara, Romania. He obtained his BSc. from the University of California Davis. Presently, he is a professor in the department of Clinical Microbiology School of Medical Sciences, KNUST. He joined the department in 1989 and served as the head of the department for three years. Committee member special Primary Interest Group for Veterinary Public Health of America Public Health Association for three years. He has published more than twenty (20) papers. He is currently the coordinator for KNUST QWeCI Project, Impact of Climate variability on Human and Animal Health, EU funded project

Abstract:

Lympatic filariasis(LF) is a parasitic disease of public health concern in Northern Ghana. Since mass drug administration of ivermectin and albendazole began in 2000 with Kassena-Nankana district as one of the implementing units, no studies has been conducted among pre-school and school-age children on the prevalence of W. bancrofti antigenaemia in spite of 3.5% prevalence reported among adults in 2008. This study was therefore carried out in four communities in the Kassena-Nankana district between December 2010 and May 2012 where mass drug administration has been administered and continued to be administered to investigate the prevalence of W.bancrofti antigenaemia among school children to aid advocacy for more comprehensive treatment coverage for children. The study was a cross sectional analytical survey, restricted to school children between the ages of 2-10 years. Four hundred(400) school children aged 2-10 years were randomly selected from a list of compounds in the communities. About 3-5 mls of blood was collected into heparinized test tube and tested during immunochromatographic test to detect W.bancrofti antigen(ICT-Filariasis card test). Of the 200 children tested before MDA, 25(12.5%) children tested positive for filarial antigen and of the 200 school children tested after MDA, 13(6.5%) children tested positive for circulating filarial W.bancrofti antigen. The microfilaria antigen prevalence among the communities after MDA ranged from 0% in Bui to 4.0% in Manyoro and 22% in Gumongo. This study has demonstrated that community variations in the prevalence of filarial antigen exist in Kassena-Nankana district. There is the need for regular surveillance thatwill inform treatment coverage and effectiveness.

Biography:

Abstract:

Abstract Background: Bacterial pathogens isolated from dacryocystitis patients are diverse and complex in terms of their distribution, prevalence, and antimicrobial susceptibility pattern. The clinical importance of microbial causes of dacryocystitis and pattern of drug resistance has not been reported in northwest Ethiopia. Moreover, the management of dacryocystitis is based on only clinical observation Therefore, this study attempted to identify and define clinical and microbiological characteristics of microbial agents of dacryocystitis and its antibiotic susceptibility patterns. Methods: A cross sectional study was conducted from January 2011-January 2012 among dacryocystitis patients attending ophthalmology outpatient department of Gondar University teaching Hospital. Socio demographic and clinical data collection, microbiological analysis and antibiotic susceptibility test patterns were done following standard procedures. Results: From the total of 51 dacryocystitis cases, bacterial origins were isolated among 31(60.8%) cases. The dominant isolates were Coagulase negative Staphylococci (CNS) 9(29.0%), Staphylococcus aureus (S. aureus) 6(19.4%), and Pseudomonas species 3(9.7%). S. pneumoniae, Entrobacter species, K. pnemoniae and H. influenzae were each accounted 6.5% isolation rate. Among the commonly prescribed antimicrobials tested for susceptibility pattern; amoxicillin 38.7%, ciprofloxacin 25.8%, chloramphinicol 25.8%, co-trimoxazole 25.8%, and ampicillin 19.4% were resistant to the overall bacterial isolates identified. Only Citrobacter species were sensitive to all antibiotics tested but the rest bacterial isolates were resistant for at least to one, two, three, four and more antibiotics tested. Overall, 9(29.0%) of the bacterial isolates were resistant to only one antibiotics and resistance to two, three and four antibiotics each accounted 5(16.1%) rate. Conclusions: Though the information derived from this study was very meaningful, further studies encompassing viral, fungal, parasitic and anaerobic bacterial origin are important to better define the spectrum and relative incidence of pathogens causing dacryocystitis. Microbiological analysis and antimicrobial susceptibility pattern is mandatory for the selection of a specific antimicrobial therapy and to the control of further resistance development of bacterial strains.

Biography:

Abstract:

Hermansky-Pudlak Syndrome (HPS) comprises a group of inherited disorders caused by mutations that alter the function of lysosome-related organelles. Pulmonary fibrosis is the major cause of morbidity and mortality in BLOC-3 mutant HPS-1 and HPS-4 patients. Chitinase 3-like-1 (CHI3L1), a prototypic chitinase-like protein, plays a protective role by ameliorating cell death and stimulating fibroproliferative repair. Here we demonstrate that circulating CHI3L1 levels are higher in HPS patients with pulmonary fibrosis compared to those that remain fibrosis-free, and that these levels associate with disease severity. Using murine models we also demonstrate that a defect in CHI3L1 inhibition of epithelial apoptosis and exaggerated CHI3L1-driven fibroproliferation play important roles in HPS fibrosis. Lastly we demonstrate that these divergent responses are mediated by differences in the trafficking and effector functions of two CHI3L1 receptors. Specifically, the enhanced sensitivity to apoptosis is due to the BLOC-3 dependent, and thus abnormal, trafficking of IL-13Ra2. In contrast, the fibrosis is due to interactions of CHI3L1 and CRTH2, which traffics normally in BLOC-3 HPS.

Biography:

ppointments 2007-present:Lecturer (Pharmacology), School of Biomedical and Biomolecular Science, UCD 2004-2007: Principal Investigator, SMMS, UCD 2003-2004: Research Manager/Research Fellow, RCSI, Dublin 2001-2003: Locum Lecturer, Clinical Pharmacology, RCSI, Dublin 1999-2003 Postdoctoral Research Fellow, RCSI, Dublin 1995-1999: Postgraduate student, Department of Clinical Pharmacology, RCSI, Dublin 1994-1995: Research Assistant, Cell and Molecular Biology Group, NUIG, Galway

Abstract:

Conjugated linoleic acid (CLA) has the unique property of inducing regression of pre-established murine atherosclerosis despite a continuing high cholesterol challenge. Our previous findings and those of others cumulatively point to the monocyte/macrophage as the cellular target through which CLA mediates its effect. Understanding the mechanism(s) involved may help identify pathways that limit human disease. In this study, we aimed to define and validate potential mechanisms through which CLA alters monocyte function and confers an atheroprotective phenotype. Transcriptomic analysis of aortic tissue during CLA-induced regression of atherosclerosis identified an enrichment of the IL-10 signalling pathway coincident with increased circulating IL-10 serum levels. Interestingly, we found significantly increased IL-10 production in bone marrow derived macrophages from CLA fed mice. Importantly, CLA supplementation regulated immune cell infiltration of the aorta with increased numbers of Ly6C lo monocytes evident. In addition, we identified increased numbers of Ly6Clo monocytes in the spleen of CLA fed mice and furthermore showed that bone-marrow progenitor cells differentiate to an M2 phenotype during regression of atherosclerosis. As chronic recruitment of monocytes and their subsequent migration through the activated endothelium contributes to atherosclerotic plaque development we next investigated the effect of CLA on monocyte adhesion in vitro and in vivo. We showed that CLA inhibits human peripheral blood monocyte cell (HPBMC) adhesion to activated endothelial cells via loss of CD18 expression, the β2 chain of LFA-1 and Mac-1 integrins. In addition, using a static adhesion assay, we identified that CLA prevents monocytes from binding to ICAM-1 and subsequently reduces the capacity of these cells to polarise. CXCL12-CXCR4 interactions induce a conformational change in β2 integrins, facilitating leukocyte adhesion. We found that CLA inhibits CXCR4 expression, resulting in a failure of monocytes to directionally migrate towards CXCL12. Finally, using intravital microscopy we showed that during CLA induced regression of pre-established atherosclerosis in apoE-/- mice there is reduced leukocyte adhesion and decreased CD18 expression on Gr1+/CD115+ pro-inflammatory monocytes. In summary, the data presented describe a novel immunoregulatory role for CLA in atherosclerosis regression specifically in the alteration of the circulating phenotype of monocytes and in the regulation of monocyte adhesion, polarisation and migration. Overview of Current Research Programmes: The current focus of my research group is the identification ofmechanisms governing the regression of atherosclerosis. My laboratory has established a novel model of atherosclerosis regression in vivo, achieved by administration of conjugated linoleic acid (CLA) in theapoE knockout mouse model of atherosclerosis.We have previously shown that dietary CLAinduces resolution of pre-established lesions in vivo. Importantly we have identified that the monocyte/macrophage is the cellular target through which CLA mediates this effect. Our recent research efforts have focused on the identification of distinct genes/pathways regulated by CLA that may yield further information as to how atherosclerosis can be reversed. To do this we employ an approach that involves confirmation of a phenotypic change in vivo by en face analysis and intravital microscopy. Using a transcriptomic and proteomic approach we then construct networks associated with the altered phenotype, followed by identification of central or “hub” genes which regulate the network. Using cellular models and functional assays we validate a functional role for these hub genes in vitro examining the effect of gene deletion or over expression on, monocyte-endothelial interactions, integrin regulation, adhesion, migration and foam cell formation. We then extend this study into human patients to seek evidence for regulation of the target genes in atherosclerotic disease progression. Through this approach we have identified novel pathways. Some have complimentarity with pathways associated with atherosclerosis susceptibility for example we have recently characterized and ascribed a functional role forSorLA in monocyte migration and have confirmed its regulation in human disease (McCarthy et al 2010). Furthermore, we identified the nuclear receptor co-activator PGC-1as a nexus gene in a network regulated by CLA. In collaboration with Christopher Glass and colleagues at UCSD, we have recently identified that macrophage specific deletion of PGC-1α increases atherosclerosis in vivo. Importantly, we showed that PGC1α is expressed in the plaques of patients where its expression is inversely related to disease progression, raising the possibility that this is a regulatory pathway in human atherosclerosis. Our other research goals arise from our findings that that CLA functions as an anti-inflammatory lipid mediator in vivo, by modifying its Ly6Clo infiltration of the aorta and M2 macrophage polarisation. We have shown that bone-marrow progenitor cells from CLA fed mice differentiate to an M2 phenotype suggesting that the cells derived from these sources may be pre-programmed towards an anti-inflammatory profile before entering established plaques. Thus, CLA may modulate the phenotype of macrophages in vascular lesions that in turn impacts on the progression of atherosclerosis (McCarthy et al., 2013).

Biography:

Eitan Rubin received PhD from The Weizmann Insitute of Science. Upon graduation, he worked in the bioinformatics company Compugen and managed the bioinformatics core facilities for the Wezimann Institute of Science and for Harvard University. He joined Ben-Gurion University in 2005, and have been exploring various avenues of computaional medicine since then. Starting in 2011, his lab is now compeltly focused on the computational investigation of cancer care. He has published more than 30 papers in reputed journals and edited one book.

Abstract:

The move toward precision cancer medicine challenges traditional approaches both in terms of cancer medicine and in terms of clincal trial designs. The WIN consortium was established to promote translational cancer research by facilitating the translation of innovative methodologies to cancer care via collaborative and create clinical trials. The consortium has launched the Winter trial, in which mutations profiling and expression profiling are used to prioritize therapeutic approaches in advanced cancer patients. We are also launching two additional trials, Spring and Summer, which gradually attempt to benefit earlier stages of specific cancers. In this presentation the 3 trials will be briefly described, both in terms of the unique trial designs and in terms of the prioritization principles. I will then show the results we have recently obtained that show that exploring the immune system in situ in the tumor is feasible, and that immune monitoring is useful for predicting treatment efficacy. Altogether we will present exampels of modern, personalized clinical trials and propose that adding immune-monitoring to such trials could strengthen our ability to utilize immunological breakthroughs at the bedside.

Biography:

Faten Ismail Mohammed has studied rhematology and autoimmune diseases for more than 25 years, during which he has authored many international papers. He has served as the head of rheumatology and rehabilitation department at El Minia University hospitals and a reviewer for many international journals as clinical rheumatology. He is a member of the scientific advisory committees for Upper Egypt, Rheumatology and Immunology Society.

Abstract:

Introduction:
Primary Sjögren's syndrome (pSS) is associated with increased risk of lympho proliferative malignancy, B- cell Non Hodgkin lymphoma (B-NHL) is the most frequent type.

Objective:
To evaluate CD4+ T lymphocytes distributions in patients with (pSS) and the association of CD4+T lymphocytopenia with the development of (B-NHL).

Patients & Methods:
This study included 8 (pSS) patients associated with B-NHL (group l), 50 (pSS) patients without B-NHL (group ll), and 30 Healthy volunteers served as controls. The frequency of circulating CD4+and CD8+ T lymphocytes distributions and CD4+/CD8+T cell ratio was assessed using Flowcytometry Coulter EPICS-XL and compared between patients groups and controls.

Results:
There was statistically significant CD4+ T lymphocytopenia in (pSS) patients with B-NHL than those without lymphoma and controls (p0.001), moreover, a significant low CD4+/CD8+T cell ratio 0.8 in group1 than group II and controls (p0.001) was found. Significant positive correlations of CD4+T lymphocytopenia with other risk factors (parotid swelling, vasculitis, rheumatoid factors, low complement, cryoglobulinemia were detected.

Conclusion:
CD4+T lymphocytopenia is associated with B-NHL developed in patients with pSS and can be considered as an important predictor of lymphoma

Biography:

H Al-Khalaifa holds a PhD in immuno-nutrition from the University of Reading- United Kingdom and MSc in medical immunology from the University of Manchester. She has been working in Kuwait Institute for Scientific Research since 1996. She participated in many research projects and activities. She gained skills and experience in immunological techniques, immunonutrition approaches, biodiversity monitoring and assessment techniques, poultry production research, production of added-value products, analysis techniques including gas chromatography, proximate analysis, flow cytometry, etc. She published more than 20 scientific papers in refereed journals and conferences.

Abstract:

The main immune organs in poultry are the thymus, spleen and bursa of Fabricius. During an immune response, mature lymphocytes and other immune cells interact with antigens in these tissues. Consequently, the mass of these organs can in some cases indicate immune status. It was observed that feeding laying chickens on diets rich in PUFA, especially n-3 PUFA, promoted the growth of the thymus, spleen and bursa up to 4 weeks of age. From the age of 4 weeks onwards, the immune tissue weight started to be suppressed and the bursa was degenerated in the course of 4 to 8 weeks of age. The objective of the current study is to investigate the effect of feeding flaxseed on immune tissue weights. Cobb 500 broiler chickens were fed flaxseed at 15%, the control diet did not contain any flaxseed. Values are presented as a percentage of body weight to account for differences in weights between different birds. Results showed that dietary supplementation with flaxseed did not affect the weights of the spleens of broiler chickens. However, it significantly lowered bursa weights (p<0.01), compared to the control diet. In addition, the bursae were thinner in appearance compared with bursii from chickens fed the control diets. In conclusion, dietary supplementation with flaxseed did not affect the growth of the spleen of the chickens. Conversely, it was reported in some studies that feeding PUFA to chickens and mice results in increased spleen weights. However, chickens fed a diet containing flaxseed had smaller and thinner bursii than chickens fed the control diets (P=0.001). This modulation in the weight of immune organs may indicate immunomodulation effect of fatty acids in flaxseed. More investigation studies need to be applied to shed light on the mechanism behind this immunomodulation.

Biography:

Kim Do Won is Assistant Professor - Hallym University, South Korea

Abstract:

Cholesterol is one of the important components for necessary to maintain the body. It is related to function as a component of cell membranes and it is also an important raw material of sex hormone and cortical hormone. For function of cholesterol, it needs movement through blood. Because cholesterol does not dissolve in water, it moves through lipoprotein in blood. The lipoproteins can be divided into LDL (Low Density Lipoprotein) and HDL (High Density Lipoprotein) depending on the density. When LDL-cholesterol is present in high amount in blood, wall of blood vessels will be covered with lipid component. Therefore, it is important to measure value of LDL-cholesterol and diagnose diseases such as Cardiovascular Disease (CVD), obesity, diabetes, atherosclerosis, hypertension and stroke. In this paper, it shows that measuring the LDL-cholesterol in blood through an immunological method. The paper suggests double bio marker, using two types of immunological measuring methods. One is streptolysin O (SLO) recombinant protein that it can specifically combine with cholesterol because carboxyl-terminal of SLO has tryptophan-rich. The other is a monoclonal antibody about Apolipoproetin B-100 existing in surface of LDL particle. The experimental results show that measuring LDL-cholesterol is dependent concentration and LDL- cholesterol of 2㎍/ml recognize the value of O.D. 630nm <0.77. Also, the method recognized concentration of cholesterol until 125 to 250ng/ml. For those reasons, this method can consider measuring LDL- cholesterol in serum.

Biography:

Abstract:

The net outcome of the battle between the anti-tumor and the tumor promoting immune cells and their associated cytokines within the tumor environment will determine the ultimate fate of the affected tumors. Th17 cells and their effector cytokines have emerged as important mediators in inflammatory and autoimmune diseases and serve as an ambitious field in current immunology research. Recent studies suggest a potential impact of Th17 cells on solid tumors but relatively little is known about their contribution in hematological malignancies. The current study was designed to investigate the possible involvement and clinical significance of circulating Th17 cells in acute leukemia patients. Compared with healthy controls, acute leukemia patients had a higher proportion of circulating Th17 cells accompanied with increased serum concentrations of IL-17 and IL-21. Circulating Th17 cells were reduced in patients achieved complete remission (CR) after chemotherapy, suggesting that circulating Th17 cells can be used to evaluate therapeutic efficacy in acute leukemia patients. Notably, the increased prevalence of initial Th17 cells was significantly associated with probability of achieving CR as well as with longer overall survival of acute leukemia patients. These results strongly suggest that Th17 cells may be a powerful new prognostic determinant which could serve as a potential therapeutic target to modulate anti-tumor response in acute leukemia patients. Mechanisms by which Th17 cells influence acute leukemia, and whether these mechanisms mediate direct or indirect effects need to be determined.

Biography:

Shimelis Dagnachew is Asst.Professor of Addis Ababa University, Ethiopia

Abstract:

Immune reactions do not always lead to protection in trypanosomoses, though they appear to be involved in immunopathological processes. Therefore, the objective of this experimental study was to determine cytokine responses upon infection with tsetse-adapted and mechanically transmitted Trypanosoma vivax in cattle of Northwest Ethiopia. Eighteen trypanosome-naïve Bos indicus cattle were assigned randomly into three groups of six (group TT= infected with a T. vivax isolate from tsetse infested area, group NT = infected with a T. vivax isolate from non-tsetse infested area and group C=non-infected control). Each infected animal received approximately 3x106 trypanosomes intravenously. Blood samples were collected in a week interval for parasitological examination, packed cell volume (PCV) determination and cytokine assay. The experimental infection caused an acute disease with detectable parasitaemia from 5 and 12 days and peak parasitaemia 8 and 14 days post infection for NT and TT infected cattle, respectively. There were significant reduction (P<0.05) after the infection in mean PCV value with 21.861.56% (TT), 22.760.90% (NT) and 30.670.64 (control). Significant increases were observed for all cytokines (P<0.05) in both the infected groups and no significant differences (P>0.05) between TT and NT groups. Interferon gamma, tumor necrosis factor alpha and interleukin-12 increased quickly at the first peak parasitaemia and persists with a steady pattern whereas an increase of interleukin-10 appeared only at the second peak parasitaemia. In conclusion, the magnitude and secretion patterns of cytokines responses were similar in TT and NT infected groups of cattle, although the responses occurred one week earlier in the later group.

Biography:

Haleh Talaie has completed her MD at the age of 28 years from Shahid Beheshti University of Medical Sciences and Research fellow, Division of Clinical Pharmacology & Toxicology, University of Toronto, Canada (2004). she is the director of Iranian Healing Oriented Integrative Medicine Institute.she has published more than 30 papers in reputed journals. Spring/Autumn 2014 : Accepted as postdoctoral integrative medicine fellowship in Arizona Center for Integrative Medicine University of Arizona ,USA(financial support not yet approved) March 2011- up to present: Integrative Medicine self education in Toxicological Research Center (TRC) and in Taleghani General Hospital,SBMU. April 2009 – Feb 2011: Integrative Medicine Courses in Clinical Excellence Center of SBMU. Oct. 2005- Nov 2005: Participation in Toxicology Rounds of Toronto, Canada poison center and Clinical pharmacology and toxicology of HSC of university of Toronto. Oct. 2003- May 2004: Research fellow, Division of Clinical Pharmacology & Toxicology by supervision of Dr Gideon Koren, M.D., A.B.M.T., F.R.C.P.C The Hospital for Sick Children, University of Toronto, Canada March 1997- 2003: Trainer & coordinator of Medical Education, Shahid Beheshti University (formerly Melli University) Medical Sciences & Health Services (SBUM), Tehran, Iran 1994 -1997: Board of Infectious Diseases specialty (SBUM) 1995-1997: Master in Public Health, Tehran University of Medical Sciences, Tehran, Iran 1987-1994: Training in Emergency ward & Outpatient clinic, Gillan Medical university,Iran 1978-1987: Shahid Beheshti University of Medical Sciences, (SBUM), Tehran, Iran

Abstract:

Background
Acinetobacter baumannii is an important opportunistic pathogen which causes complications in hospitalized patients, especially those in ICU. The aim of this study was to determine the frequency of class 1 and 2 integrons in multi-drug resistance A. baumannii and to investigate the association between the presence of integrons and antibiotic resistance patterns.

Methods:
A total of 40 A. baumannii strains were isolated from 372 ICU patients from June to Oct 2012. A. baumannii was detected in 50% of tracheal cultures, 15% in blood, 15% in urine samples, and 22.5% in other locations. In accordance with CLSI 2011, 12 antibiotics were used through disc diffusion method. Existence of integron classes was investigated by PCR assay with the amplification of integrase genes.

Results:
The most effective antibiotic against Acinetobacter baumannii was polymyxin B with 100% susceptibility, followed by meropenem, piperacillin, cotrimoxazole, ceftazidime with 100% resistance; this was followed by ciprofloxacin 97.5%, tetracycline, 92.5%, imipenem 62.5%, and gentamicin 60% resistance. The presence of integron class 1 was 7.5%, class 2 was 67.5%, and non-integron was 20%.

Conclusion:
The association between multidrug resistance and class 2 integron was not statistically significant. Other factors accounting for the lack of significance of the findings may be the impact of other resistance determinants such as transposons or plasmids, not investigated in the current study. Considering the increasing trend of MDR infections among ICU patients with critical problems in follow up, the use of appropriate infection control strategy and a regular surveillance system is necessary in our hospital.

Keywords:
Acinetobacter Baumannii, Class 1 Integron, Class 2 Integron, Multidrug Resistance, and PCR Assay.

Biography:

Mahsa Sedighi completed her MD degree at the of 32 years from Shiraz Medical School. She was among the founders of Shiraz Medical College Research Club. She has been invited as Editorial Board Member and Reviewer from international journals. She is currently an independent researcher.

Abstract:

Background: Vitamin D receptors have been identified in the spinal cord, nerve roots, dorsal root ganglia and glial cells, and its genetic polymorphism association with the development of lumbar disc degeneration and herniation has been documented. Metabolic effects of active vitamin D metabolites in the nucleus pulposus and annulus fibrosus cells have been studied. Lumbar disc herniation is a process that involves immune and inflammatory cells and processes that are targets for immune regulatory actions of vitamin D as a neurosteroid hormone. In additionto vitamin D’s immune modulatory properties, its receptors have been identified in skeletal muscles. It also affects sensory neurons to modulate pain. Aim: In this study, we aim to study the role of vitamin D3 in discogenic pain andrelated sensory deficits. Additionally, we will address how post-treatment 25-hydroxy vitamin D3 level influences pain and sensory deficits severity. The cut-off value for serum 25-hydroxy vitamin D3 that would be efficacious in improving pain and sensory deficits in lumbar disc herniation will also be studied. Methods/Design: We will conduct a randomized, placebo-controlled, double-blind clinical trial. Our study population will include 380 cases with one-level and unilateral lumbar disc herniation with duration of discogenic pain less than 8 weeks. Individuals who do not have any contraindications, will be divided into three groups based on serum 25-hydroxy vitamin D3 level, and each group will be randomized to receive either a single-dose 300,000-IU intramuscular injection of vitamin D3 or placebo. All patients will be under conservative treatment. Pre-treatment and post-treatment assessments will be performed with the McGill Pain Questionnaire and a visual analogue scale. For the 15-day duration of this study, questionnaires will be filled out during telephone interviews every 3 days (a total of five times). The initial and final interviews will be scheduled at our clinic. After 15 days, serum 25-hydroxy vitamin D3 levels will be measured for those who have received vitamin D3 (190 individuals).

Biography:

Shailasree S is Asst Professor University of Mysore, India

Abstract:

Systematic screening of chemical libraries for small molecules revealed limited studies involving promising small molecules (lacking details on studies inferring drug-target interactions) with a capacity to kill cancer cells in-vitro. In the present study, myricetin was evaluated for its capacity to induce cytotoxic effect to neuroblastoma N2a cell and have listed the multi-target paradigm leading to its growth inhibition, apoptosis/autophagy. Toxic pathway, especially the upstream network of responses happening in toxicant-treated cancer cells prior to their programmed cell death is reported to provide an unbiased approach in unraveling changes deciding on the final fate of the cell. Studies preceding cell death by probe sets strongly pointed to changes in cluster related to genes with a role in chromosomal stability, eg., heterogeneous nuclear ribonucleoprotein (HNRNPM), that was down regulated. Those involved in adaptive carbon metabolism eg., argininosuccinate synthase (ASS1) were upregulated identified as intermediate response upon exposure to toxicant. Consumption of phosphocreatine and a parallel accumulation of creatine indicated exhaustion of cellular energy buffer. The prominent role of GSH to counter increasing cell stress as early adaptation before breakdown of cellular homeostatis was observed. Direct data substantiating cell death by apoptosis with p38 MAP kinase mediated p53 activated upregulation of caspase 3 is reported and will be discussed. Our data report on autophagy, representing an additional mechanism inducing cell death detected by accumulation of LC3-II protein and acridine-orange stained autophagosomes is included.

Biography:

Ahmed G Hegazi worked as a Professor of Microbiology & Immunology, National Research Center National Research Center, Dept. Parasitology, 1997-2000, Chair of Faculty of Medicine, Zagazig University, 1981-1997, part-time Professor and Supervisor of Immunology Section, National Research Center, 1990- up till now. He is also Prof. of Microbiology & Immunology, African Federation of Apiculture Associations (AFAA), 2001- up till now, Standing Commission on Apitherapy (APIMONDIA), 1999 - up till now, Member of Standing Scientific Committee, National Research Center, 1998 –up till now. He was awarded the Excellent Medal of the First Class, 1995, received the Senior Scientist Prize of National Research Center, 1996, and won The Second Best Research Paper award from International Congress of Propolis, Argentina, 2000. He has published in Egyptian Journal of Immunology, 1995, was in the Editorial Board of The Egyptian Association of Immunologists, 1992 –1997, Secretary General, Referee in 37 international journals patents: 4 Patents Educational Activities. He has published 193 articles in national and international scientific journals, 6 books in English and 7 books in Arabic.

Abstract:

Apitherapy (the term comes from the Latin apis, which means "bee."), or bee therapy, is the use of honey bee products for therapeutic purposes. Bee venom, bee pollen, raw honey, royal jelly, and propolis are products from bees that are generally considered to have medicinal effects. Now days the apitherapy has great interest of biologist, medical doctors and scientist due to their biological and phytochemical as well as pharmacological activities, so the aim of this review was to through more light on the role of bee products and their influence on cytokines. The term cytokine encompasses a large and diverse family of polypeptide regulators that are produced widely throughout the body by cells of diverse embryological origin. Cytokines participate in many physiological processes including the regulation of immune and inflammatory responses. Cytokines include chemokines, interferons, interleukins, lymphokines, tumor necrosis factor but generally not hormones or growth factors. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B lymphocytes, T lymphocytes and mast cells, as well as endothelial cells, fibroblasts, and various stromal cells; a given cytokine may be produced by more than one type of cells. They act through receptors, and are especially important in the immune system; cytokines modulate the balance between humoral and cell-based immune responses, and they regulate the maturation, growth, and responsiveness of particular cell populations. Some cytokines enhance or inhibit the action of other cytokines in complex ways. Bee products contain physiologically active substances from floral origin of honey bee and plants origin. Bee products act upon both innate and adaptive immune response. At different levels, in the human innate response, these compounds suppress DNA synthesis, decrease proinflammatory cytokine synthesis (IL-2, IL-12 and IL-4), inactivate both the classical and alternative complement pathway, and decrease superoxide anion production in rabbit neutrophils. In adaptive immune response, propolis and honey induce the increase of antibody production by plasma cells, enhance the secretion of TGF-β after the activation of T regulatory cells.

Biography:

Amber Rose, PhD., L. Ac. (Board Certified-NCCAOM), LMSW, is an expert, pioneer, and maverick in the field of immunology. Her approach to healing is unlike anything you have ever seen before. Her Bee Venom research goes back 22 years and she also has 30 years of experience as an acupuncturist. Dr. Rose has treated over 55,000 patients with Lyme, MS, HIV/AIDS, CFS, Fibromyalgia, Lupus, ALS, Parkinson’s, Arthritis, and chronic pain. She had a free clinic in Bethesda, MD for four years. Her NEW book, Pioneers: Healing Lyme with Bee Venom Therapy was released in August 2015.

Abstract:

Objective: Examine Effects of Bee Venom Therapy on 60 Lyme Patients. Methods: 60 patients with Lyme, their ages ranging between 25-68 were divided into two groups. Group 1 (40 patients) were treated with the Bee Venom Therapy (BVT) protocol for Lyme. Some of these patients were on antibiotics when they began BVT, but weaned themselves off. They received 3000 mg of Vitamin C every day and were treated with Bee Venom (BV), three times per week. On alternate days they followed a detox protocol (drinking apple cider vinegar in water and soaking for 10 minutes in an Epsom salt bath mixed with 32 ounces of hydrogen peroxide). Group 2 (the Control Group - 20 patients) did not receive any BV. They continued their regular medical care without BVT intervention. Results: Results revealed 2 patients fully recovered after 2.5 years. All symptoms disappeared and all blood work was normal with no signs of Lyme nor any co-infections present. 8 patients had 85%-90% recovery at the 1 year mark. Their energy increased, their minds were clear; they showed very few Lyme symptoms, with much improved blood work. 30 patients showed lessening of symptoms between 1 week and 9 months of BVT. 20 patients (control group) did antibiotics only and no BVT. Their Lyme symptoms worsened. Conclusion: Bee Venom Therapy has made a significant difference in the quality of life of all Lyme patients treated with Bee Venom. BVT combined with a detox protocol is a safe treatment for Lyme patients. BVT is also effective in conjunction with antibiotic treatments. More research is needed to replicate the study done at Rocky Mountain Laboratory, by Lubke and Garon (1997) where a component of bee venom, melittin, was shown to effectively kill the Lyme spirochete.

Biography:

Aliaa El Gendy graduated from Faculty of Medicine, Cairo University. She completed her MSc in Rheumatology and Rehabilitation from Cairo University in 2003 and PhD in Application of laser in internal medicine from Cairo University in 2013. Her domains of interest are application of laser in medicine, medical nutrition and apitherapy.

Abstract:

The objective of this study was to determine the therapeutic modality employing bee venom acupuncture (BVA) for controlling of chronic low back pain (CLBP). This study is a randomized, controlled clinical trial with two parallel arms. We intend to compare between the effects of BVA by bee sting in patients with CLBP and patients with chronic LBP on pharmacotherapy only. We recruited with a target sample size of 40 participants. The study was under taken for six months. Inclusion criteria age 28:65 history of back pain more than 3 months .The curative effect was measured by scoring of visual analog scale (VAS) of LBP at the time of screening and Oswestry low back pain disability questionnaire. The results revealed that the bee venom acupuncture showed significant improvement in patients who received bee venom group when compared to patients who received pharmacotherapy only. It is concluded that both modes of treatment for CLBP gave improvement regarding pain intensity, disability and quality of life being more evident in bee venom group supported with improved serum (IL1 and NF-KB)

Biography:

Maha M Saber is currently the Head of Complementary Medicine Department in the National Research Centre, Egypt. She is also the Professor of child health, consultant of Pediatrics and consultant of therapeutic nutrition. She received her MB Bch degree in 1985 from the Faculty of Medicine, Ain Shams University and her Master’s degree in Pediatrics in 1990. She received her PhD in Child health in 1995. Her research work has been focused lately on therapeutic nutrition, complementary medicine and bee products and their therapeutic effects. She organized and contributed to national and international research projects since 1998 and up till now; she has been the Principal Investigator and Member of multiple research projects within the National Research Center. She has published many scientific papers and articles in national and international journals. She is also the Head of the field of complementary medicine, Head of the field of management of regional obesity at the Center of Excellence, National Research Center, and the President of the Arabic Society of Therapeutic Nutrition and Complementary Medicine.

Abstract:

In most ancient cultures, honey has been used for both nutritional purposes and for medicine. The belief, that honey is a nutrient, drug and an ointment has been carried into our days. For a long time in human history it was the only known sweetener, until industrial sugar production began to replace it after 1800. In the long human history, honey has been not only as a nutrient but also as a medicine. A medicine branch, called apitherapy, has developed in recent years, offering treatments for many diseases by honey and the other bee products. Main sugars are the monosaccharide, fructose and glucose. Beyond the two monosaccharides, about 25 different oligosaccharides have been detected. Honey contains about 0.5% proteins, mainly enzymes and amino acids. The amount of vitamins and minerals is small and the contribution of honey to the recommended daily intake (RDI) of the different trace substances is marginal. Honey contains a number of other trace elements. From the nutritional point of view, the minerals chrome, manganese and selenium are of nutritional importance, especially for children of the age of 1 to 15 years. The elements sulphur, boron, cobalt, fluorine, iodine, molybdenum and silicon can be important in human nutrition too, although there are no RDI values proposed for these elements. Honey contains 0.3-25 mg/kg choline and 0.06 to 5 mg/kg acetylcholine. Choline is essential for cardiovascular and brain function and for cellular membrane composition and repair, while acetylcholine acts as a neurotransmitter.

Biography:

Magdy I Al-Shourbagi is currently working as the Head of Hyperbaric Oxygen therapy Unit at Sharm El Sheikh International Hospital, Egypt. He is the Consultant of Ear, Nose and Throat, in the same hospital. He received his MB Bch degree in 1983 from Faculty of Medicine, Ain Shams University and his Master’s degree in ENT in 1989 from Diploma of Healthcare Quality, National Institute of training of Physician and Hyper Baric Oxygen therapy, Army Navy Academy, Alexandria. His interest has been focused lately on hyperbaric oxygen therapy and bee products and their therapeutic effects. He is also the Head of Quality Department in Sharm International Hospital.

Abstract:

Allergic rhinitis (AR) is characterized by nasal mucosal inflammation resulting from immunoglobulin E (IgE) mediated hypersensitivity reaction. Allergen exposures stimulate infiltration of inflammatory cells within the nasal mucosa, including basophils, eosinophils, mast cells and mononuclear cells. These inflammatory cells release several allergic mediators, such as histamine, cysteinyl leukotrienes and prostaglandins, which sustain the inflammatory reaction and produce characteristic nasal symptoms of sneezing, itching, rhinorrhea and nasal congestion. Bee venom (BV) consists of various biologically active amines, peptides and nonpeptide components and has radio protective, anti-mutagenic, anti-inflammatory, anti-nociceptive and anticancer activities. Two main components of BV, melittin and adolapin, have anti-inflammatory activity that involve inhibition of cycloxygease-2 and phospholipase-A expression and decrease levels of tumour necrosis factor-α interleukin (IL)-1, IL-6 and nitric oxide. The anti-allergic activity is associated with marked inhibition of OVA-induced tracheal contraction and histamine release from lung tissue. The mast-cell degranulating peptide binds to the mast cell receptors and inhibits the binding of IgE and production of histamine. BV also inhibits the release of inflammatory mediators similar to non-steroidal anti-inflammatory drugs.

Biography:

Mona Mostafa graduated from Faculty of Medicine, Cairo University holding a degree of M B BCh in 2003, Master’s degree in Neuropsychiatry at Cairo University, 2009 and Doctorate degree in Neurology from the same university in 2015. Her research activities include \"Sleep apnea and cognitive dysfunction in myasthenia gravis\" and \"Vitamin D and its receptor gene polymorphism in ischemic vascular dementia\". Her recent projects are “Effect of low level laser on diabetic peripheral neuritis” and “Effect of low level laser on carpal tunnel syndrome”. Her domains of interest are cognitive functions – Apitherapy.

Abstract:

Venom therapy in particular that involves bee venom was practiced in ancient Egypt, Greece and China. Venom components have been widely used in oriental medicine to relieve pain and to treat inflammatory diseases, while other potential venom-related treatments for immune-related diseases, neurological diseases, infections and tumor therapies are currently under investigation. Several proteins, neurotransmitters and peptides comprise the main components of the venoms. Some peptides are exclusive related to bee, namely melittin, apamin and mast cell degranulating (MCD) peptide. Apamin is a peptide neurotoxin that selectively blocks the small conductance of Ca2+ dependent K+ channels (SK channels) expressed in the central nervous system (CNS). Increased activity of these channels may be related to decrease in plasticity and memory deficit that is seen with aging, so bee venom therapy may be helpful in protecting cognitive functions and learning deficit. Moreover it was observed that apamin protects dopamine neurons from degeneration, also it restores the function of silent neurons, so it may be hypothesized that apamin would be helpful in Parkinson’s disease (PD) and neurodegenerative disorders. Not only learning deficit, PD or neurodegenerative disorders would be responding to bee venom therapy but also it was claimed that chronic pain syndrome, multiple sclerosis, Bell’s palsy, post-herpetic neuralgia, guillain-barre syndrome, neuritis, sciatica, diabetic neuropathy and carpal tunnel syndrome also would be responded to bee venom therapy through different mechanisms of action of the other venom component. Therefore, research work focusing on studying the effect of different bee venom components in neurological disorder is inevitable in correlation with its immune modulation.

Biography:

Ehab Kamal is currently Lecturer of Tropical Medicine and Complementary Medicine in the National Research Centre. He got his Master’s degree from Ain Shams University 2009 and his MD degree from Azhar University 2014. He participated in the research on ozone therapy in the treatment of hepatitis C virus and in the dietary management of non-alcoholic steatohepatitis as fields of complementary medicine applications.

Abstract:

Apitherapy, or “bee therapy” (from the Latin apis which means bee) is the medicinal use of products made by honey bees. Products of the honey bee include bee venom, honey, pollen, royal jelly, propolis and beeswax. The exact origin of Apitherapy is difficult to pinpoint and can be traced back, in a general sense, to ancient Egypt, Greece and China. Use of honey and other bee products can be traced back thousands of years and healing properties are included in many religious texts including the Veda, Bible, and Quran. These are mostly attributed to nutritional benefits of consumption of bee-products and not use of bee venom. Honey bee venom contains at least 18 active substances. Melittin, the most prevalent substance, is one of the most potent anti-inflammatory agents. Adolapin is another strong anti-inflammatory substance and inhibits cyclo-oxygenase; it thus has analgesic activity as well. Apamin inhibits complement C3 activity and blocks calcium-dependent potassium channels, thus enhancing nerve transmission. Other substances, such as Compound X, hyaluronidase, phospholipase A2, histamine and Mast Cell Degranulating Protein (MSDP), are involved in the inflammatory response of venom. Thus the trial of Apitherapy in a range of immune mediated disorders such as IBD is a promising field to control such chronic gastrointestinal disorders that need long-term and medications with multiple side effects and as a trial to keep the patients in a remission state to control their life disabling symptoms and signs.

Biography:

Walid M. A. Sadek is currently a Researcher of Animal Husbandry in Sheep and Goats Research Department, Animal Production Research Institute, Agricultural Research Center, Dokki, Giza. From 2001 till now. He has a master degree in 2004, and his PhD in 2011. He lectured at the Faculty of Agriculture, Mansoura University for the academic year 2008-2009. Participated in the accomplishment 18 scientific research and published 6 scientific papers. Member in the Egyptian Society of sheep and goats and Egyptian Society of Nutrition and Feeds.

Abstract:

Different sources of forage protein fed twenty lactating goats in 2nd and 3rd season were used in this study. Immune response, hematological pattern and milk production were determined. The feeding trails lasted for 14 weeks. The results revealed that was non-significant effect of the tested silages on most hematological and biochemical parameters. Results indicated also that improving of the average daily gain and milk yield g/h by G1, G2 and G3 respectively. The economic efficiency was better with G3 compared with the other groups. The cellular and biochemical changes in the blood especially the increased gamma globulins and the hepatoprotective effect.

Biography:

Eitedal Mahmoud Daoud is currently a Professor of Child-Health in the National Research Centre, Cairo, Egypt. She received her Master’s degree in Pediatrics in 1989 at Cairo University and her PhD in Child-Health in 1996 from Ain Shams University and Diploma in Clinical Nutrition from National Institute of Nutrition in 2014. She organized and contributed to national research projects since 1997 and up till now. She has been the Principal or Co –PI or Member Investigator on research projects within the National Research Centre. She has published many scientific papers and articles in national and international journals. She is interested in studies related to clinical nutrition and bee.

Abstract:

The antioxidant activity of honey was not influenced after digestion. There is a significant correlation between the antioxidant activity, the phenolic content of honey and the inhibition of the in vitro lipoprotein oxidation of human serum. Honey intake caused a higher antioxidative effect in blood than the intake of black tea, although its in vitro effect measured as ORAC activity was five times smaller than that of black tea. Darker the honey, the higher is the phenolic content and its antioxidant power. Further, in a lipid peroxidation model system buckwheat honey showed a similar antioxidant activity as 1 mM α-tocopherol. Also, the influence of honey ingestion on the antioxidative capacity of plasma was also tested. In the first study, the trial persons were given maize syrup or buckwheat honeys with a different antioxidant capacity in a dose of 1.5 g/kg body weight. In comparison to the sugar control honey caused an increase of both the antioxidant and the reducing serum capacity. In the second study humans received a diet supplemented with a daily honey consumption of 1.2 g/kg body weight. Honey increased the body antioxidant agents: Blood vitamin C concentration by 47%, β-carotene by 3% and uric acid by 12% and glutathione reductase by 7%. It should be kept in mind that the antioxidant activity depends on the botanical origin of honey and has remarkable variations in honey from different sources. The antioxidant activity of honey is probably the reason of the protective effect of honey against damage and oxidative stress induced by CS in rat testis. Manuka honey protects middle-aged rats from oxidative damage. Ingested honey resulted in different antioxidant effects: the level of DNA damage was reduced, as well as the malondialdehyde level and the glutathione peroxidase activity in the liver of both the young and middle-aged groups. The glutathione peroxidase activity was increased in the erythrocytes and the catalase activity was reduced in the liver and erythrocytes of both young and middle-aged rats given supplementation.

Biography:

Amgad Hazzaa is currently Lecturer of alternative medicine in Arab Moroccan academy- Algeria- from 2010 till now, he got his Bachelors’ Degree in Physical Medicine, Cairo University, Diploma in Microbiology, Banha University, High Studies in alternative Medicine, Clinical Doctorate in Physiotherapy- Cairo University

Abstract:

Background
Bee venom (BV) has been used in the treatment of muscloskeletal and rheumatic problems in the clinical field, the use of honey and other bee products in human treatments traced back thousands of years and healing properties are included in religious texts. Apitherapy is the use of honey bee products for medical purposes, this include bee venom, raw honey, royal jelly, pollen, propolis, and beeswax. Whereas bee venom therapy is the use of live bee stings (or injectable venom solutions with different degrees of dilutions) to treat various diseases such as arthritis, rheumatoid arthritis, multiple sclerosis (MS), lupus, sciatica, low back pain, and tennis elbow. Objectives: To assess the clinical evidence for bee venom therapy (BVT) with or without physiotherapy modalities in cases with rheumatoid arthritis.

Setting:
Dar Elshefaa Medical center for Physiotherapy in Damas, Meet Ghammr, Dakahlia.
Time: 3 months From 3 Jan, 2015 to 5 April, 2015 Participants: Patients with Rheumatoid arthritis and suffer from back pain , a total of 38 patients had been enrolled in the previous study, and 8 of these were excluded from the current study, Thirty patients who had been treated, they were divided randomly into two groups, Group (A) with combined BVA and physiotherapy, group (B) treated by physiotherapy with injection of normal Saline Nacl and considered as a control group.

Intervention:
Physiotherapy program with or without using of bee venom therapy (BVT), Physiotherapy program involved (Infrared, Wax, ultrasound, Tens & Therapeutic exercises), BVT involved injecting purified & graduated diluted BV (1gm-500 ml normal serum saline concentration which was doubled every month at 3 months therapy).

Main Outcome Measures:
Four outcomes assessed at baseline for three months intervention to measure pain and patient satisfaction, lumbar range of motion was measured by Inclinometer and functional disability was measured by oswestry disability scale & Erythrocyte sedimentation rate (ESR), Measurements were taken at two intervals pre-treatment and post-treatment. Results: Bee venom therapy (BVT) was associated with clinically significant improvement at 3-month follow-up, the group A whom were treated by traditional therapy with bee venom therapy in the involved muscles showed significantly improvement of pain intensity, functional disability & Lumbar range of motion (P< 0.0001), Also a significant improvement for ESR.

Conclusion: There is a good scientific clinical evidence for bee venom therapy (BVT) more than control group treated by physical therapy only at 3-month therapy in pain, ROM , functional disability and ESR , also the BVT group showed significantly greater satisfaction compared with the control group.

Keywords:
honey bees, apitherapy, bee venom, bee sting, back pain, physiotherapy, and rheumatoid arthritis.

Biography:

Eman Hussien Abdel-Rahman is currently working as Professor in National Research Center, Dokki, Cairo, Egypt since 2005. In 1990, she was appointed as Assistant Researcher at the National Research Center, Dokki, Cairo, Egypt. In 1995, she was appointed as Researcher at the National Research Center, Dokki, Cairo, Egypt. In 2000, she was appointed as Associate Professor at the National Research Center, Dokki, Cairo, Egypt. In 2005, she was appointed as Professor at the National Research Center, Dokki, Cairo, Egypt. Eman Hussien Abdel-Rahman received her B.Sc. in Zoology in 1981 at Cairo University, Egypt. She got M.Sc. in Immunoparasitology in 1990 from Cairo University, Egypt. Dr. Eman Hussien Abdel-Rahman obtained Ph.D. from Cairo University, Egypt in 1995 in Immunoparasitology. Eman Hussien Abdel-Rahman’s current research interests are Immunoparasitology, Biological Control, DNA Technology, Glycoprotein Antigens, Parasitology.

Abstract:

Cystic echinococcosis is a worldwide zoonotic disease caused by larval stages of Echinococcus granulosus. The persistence of cysts in the intermediate hosts as sheep, camels and humans is of interest since, once fully formed, cysts are apparently unaffected by the host’s immune response. Moreover, E.granulosus larval stages possess various molecules which modulate the host immune response and promote parasite survival and development as antigen B and antigen 5 of hydatid cyst fluid. The advent of proteomic analysis of the larval stages proteins has significantly improved the identification and characterization of proteins to use as potential new diagnostics as heat shock protein 20. During cystic echinococcosis, host immune responses switch from Immunoglobulin G1 and interferon gamma to IgG4, IgE, Interleukin 4, IL-5, IL- 6, IL-10 and tumor necrosis factor. Despite of this humoral and cellular immune responses evoked by the host, the parasite not only escape but impair the response and survive for a long time in the host. Among the immunologic tests for assessing the host-parasite relationship, assays of immunoglobulin isotypes detection with the use of distinct parasite antigens, circulating antigens detection and detection of Th1/Th2 cytokine expression. Enzyme Linked Immunosorbent Assay is the most commonly used in the immunodignosis of cystic echinococcosis. Accurate serological diagnosis of the cystic echinococcosis, as other helminthiasis, requires highly specific and sensitive antigens to be used in the assays. The choice of an appropriate source of antigenic material is a crucial point in the improvement of the diagnostic features of tests, and must be based on the developmental stage of the parasite. The current review emphasizes recent advances in the identification and characterization of novel antigens with potential for the immunodiagnosis of cystic echinococcosis. The need to search for new antigenic components with high diagnostic sensitivity and specificity remains a crucial task in the improvement of immunodiagnosis of the disease.