Day 2 :
Cleveland Clinic Lerner College of Medicine, USA
Time : 09:00-09:25
Asha R Kallianpur is a physician-scientist and genetic epidemiologist with a background in Hematology and Public Health. She completed her medical degree at the University of North Carolina in Chapel Hill, N.C., and her Medicine residency, Hematology fellowship, and Master of Public Health degree at Vanderbilt University. She is Associate Professor of Molecular Medicine at Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, and Associate Staff at Cleveland Clinic in the Departments of Genomic Medicine and Medicine. Her research centers on the role of iron metabolism and mitochondrial genomic variation in chronic diseases.
HIV-associated neurocognitive disorders (HAND) occur in 40-50% of persons infected with HIV, including those with undetectable virus on antiretroviral therapy (ART). In contrast to HAND in the pre-ART era, frank dementia is now uncommon, but asymptomatic and mild forms of HAND remain common, owing to the intersection of aging-related changes with immune activation and antiretroviral drug toxicities. The neuropathogenesis of HAND is poorly understood, but intensive research over the past two decades has implicated persistent immune activation, neuro-inflammation, and monocyte-derived macrophages in the disease process. Candidate-gene studies have identified genetic variants as potential risk or protective factors in HAND, but due to many factors - study heterogeneity, diagnostic imprecision, low power, and changing epidemiology - only a few genetic variants have been replicated; nor have prior associations been replicated in the single, published genome-wide association study. Systems biology and machine learning approaches for analyzing high-throughput genetic, transcriptomic and epigenetic data, coupled with longitudinal studies that use consistent phenotypic definitions, tissue-based microarray studies, and genomic studies incorporating stable endophenotypes of HAND, hold promise for identifying fundamental biological pathways and gene networks that underlie this debilitating disease. Common themes including involvement of the mitochondrial genome, interferon-response and activation genes, and iron metabolism have emerged, suggesting that dysregulation of these processes may occur early in HIV infection and progress despite treatment. Correlation of multiple types of “omics” data with neuropathological and clinical disease features and longitudinal assessment are needed to elucidate patterns of altered pathways that promote HAND and develop treatment strategies.
National University of Singapore, Singapore
Keynote: Comprehensive metabolomic profiling of simulated combat trauma injury in a porcine model using NMR and LC-MS
Time : 09:25-09:50
Sam Li is a faculty member at the Department of Chemistry, National University of Singapore (NUS). He received his BSc, PhD and DSc degrees from Imperial College, UK. His research interests include environmental science and technology, metabolomics, biosensors and nanotechnology. He has authored/co-authored 325 publications in international peer review journals, more than 100 conference presentations and 10 US patents. He serves/served on editorial advisory boards of several international scientific journals, including Electrophoresis (Germany), Journal of Chromatographic Science (USA), LC-GC (Asia Pacific), and Biomedical Chromatography (UK)
The aim of this study is to use both nuclear magnetic resonance (NMR) and liquid chromatography-mass spectrometry (LC-MS) platforms to obtain a comprehensive profile of the metabolic changes occurring in an established porcine model of combat trauma injury, consisting of penetrating trauma with hemorrhagic shock (THS). The results obtained using NMR and LC-MS complemented the multi-faceted presentation of the physiological changes occurring after THS. The elevation of purine and pyrimidine metabolites clearly represent impaired energy metabolism, in particular the depletion of adenosine triphosphate (ATP). Increased levels of hydroxy fatty acids and the oxypurines, hypoxanthine and xanthosine, are indicative of oxidative stress. The reduced levels of lipoproteins, albumin and N-acetylglycoproteins indicate the activation of the acute phase of the inflammatory response. The elevation of several cysteine, methionine and methylated metabolites also indicates an activation of the inflammatory response. Lastly, accumulation of uremic retention solutes and toxins indicate acute renal failure. These results provide insights into possible strategies that can be implemented for the triage and treatment of combat trauma patients. Metabolite biomarker panels based on a combination of the identified metabolites that characterize energy depletion, oxidative stress, and inflammation can be developed to detect the onset and progression of traumatic hemorrhagic shock. Furthermore, knowledge of the affected pathways provides avenues for the development of supplementation strategies such as ATP supplementation to prevent energy depletion or the use of immune-modulating metabolites such as the sulfur-containing amino acids and the omega-3 fatty acids to prevent systemic inflammation.
Keynote: Metabolomics study of Ketosis-Associated Increases in FGF21 in Wild-type and PPAR alpha Knockout Mice.
Time : 09:50-10:15
Vladimir Tolstikov, Ph.D., is Scientist at Eli Lilly and Company. He received B.S. and M.S in Organic Chemistry in 1977 from M.V. Lomonosov Institute of Fine Chemical Technology, in Moscow, Russia. He received Ph.D. in Organic Chemistry in 1983 from the Institute of Chemical Means for Plant Protection, Moscow, Russia. He is a pioneer in HILIC separations development applied to Metabolomics. During his career he was working in leading research institutions in USA, Germany, Hungary and Russian Federation. He has joined Eli Lilly and Company in 2012. He is author, contributor and participant of 45 conferences, 5 book chapters, and 54 articles
Fibroblast growth factor 21 (FGF21) is a novel endocrine hormone that has a range of beneficial metabolic effects and consequently a number of exogenously administered FGF21-based therapeutics are under investigation. A potential alternative therapeutic strategy would be to increase endogenous production of FGF21, however an improved understanding of the metabolic factors involved in the regulation of FGF21 production is required. The ketotic state is one of the best described physiologic stressors associated with elevated FGF21 production and this regulation occurs, at least in part, via PPAR alpha. Eli Lilly and Company’s metabolomics platform, comprised of state-of-the-art instrumentation technologies, is capable of information delivery on hundreds of small molecules showing statistically significant biochemical alterations. Therefore, we applied a global metabolomics approach to examine the metabolic changes associated with FGF21 production in the livers of wild-type and PPAR alpha knockout mice in response to fasting or a ketogenic diet. Plasma FGF21 concentrations were increased by fasting and ketogenic diet in wild-type mice, but only by ketogenic diet in PPAR alpha KO mice and all increases correlated with increased FGF21 expression specifically in liver. Correlation analysis of metabolomics data detected a strong link between hepatic FGF21 expression and the glutathione-mercapturic acid pathway. Curve clustering analysis identified 2−dehydro−D−gluconate, deoxyribose−phosphate, and glycerol−3−phosphate\\\\\\\\r\\\\\\\\nas metabolites associated with FGF21 production independent of the regulation of PPAR alpha. The current metabolomics approach provides a novel means for furthering our understanding of the physiologic regulation of FGF21 production. \\\\\\\\r\\\\\\\\n
- Track 1: Metabolomics and Cancer Research
Track 4: Frontiers of Metabolomics Research
Track 5: Metabolic Syndrome
The Ohio State University, USA
Scott J Tebbutt
University of British Columbia, Canada
The University of Chicago, USA
Title: Preferential sequestration of a vanadyl chelate by cancer tissue facilitates 2-(fluorine-18)-2-deoxyglucose (FDG)
Time : 10:30-10:50
Marvin W Makinen has pursued research on the structural basis of enzyme action and enzyme mechanism using electron paramagnetic resonance and electron nuclear double resonance methods. The present research directed at cancer detection is derived from earlier research on inhibition of protein tyrosine phosphatase-1B by vanadyl (VO2+) chelates.
PET imaging with FDG as the tracer molecule for cancer detection is biochemically based and is associated with high specificity. However, FDG PET imaging relies on tumor size and the local metabolic characteristics of the type of cancer. Some breast cancer types characterized by low glucose uptake give rise to false negatives. Bis (acetylacetonato) oxidovana-dium (IV) [VO (acac)2] exhibits high stability in solution and displays a high capacity to enhance cellular glucose uptake. We observed that enhanced FDG uptake by MDA-MB-231 cultured human breast carcinoma cells was facilitated by VO(acac)2 over the 1–8 μM range in the presence of a background 5 mM glucose concentration, equivalent to the fasting level of blood glucose in a normal adult. Generating MDA-MB-231 xenograft tumors in SCID mice, we observed maximum FDG uptake approximately 4 hours post-VO(acac)2 injection. This observation closely correlates with the time of 3.5-4 hours for maximum preferential sequestration of the chelate by tumor tissue. Longer intervals between intraperitoneal injection of VO(acac)2 and the onset of FDG PET imaging showed decreased FDG uptake. We have observed up to 6-fold enhanced FDG uptake compared to controls with a two-fold higher dose of VO(acac)2. These preliminary results indicate that use of VO(acac)2 as a pharmacologic agent to enhance FDG uptake by malignant tissue has the potential to improve detection of both small tumors and tumors of low metabolic activity by FDG PET imaging.
University of British Columbia, Canada
Time : 10:50-11:10
Scott J Tebbutt is Associate Professor in the Department of Medicine, University of British Columbia, and Principal Investigator at the Centre for Heart Lung Innovation, St. Paul’s Hospital, Vancouver, Canada. His research program is focused on molecular signatures of complex respiratory disease, including the early and late reactions in atopic asthma and allergic rhinitis. He is also Chief Scientific Officer of the Prevention of Organ Failure (PROOF) Centre of Excellence - a not-for-profit organization dedicated to moving research findings into health care, and focused on non-invasive biomarkers that can diagnose and/or predict organ failure (heart, lung and kidney). His responsibilities include the evaluation of new, high-performance technologies to improve biomarker discovery, as well as computational biology approaches to better deal with cell type heterogeneity. He holds a BA in Biochemistry from the University of Oxford and a PhD in Molecular Genetics from the University of East Anglia (Cambridge Laboratory, John Innes Centre).
Some asthmatic individuals undergoing allergen inhalation challenge develop an isolated early response whereas others develop a dual response (early plus late response). The late response is associated with inflammation and chronic disease pathobiology, and it is important to develop biomarkers that can predict which individuals might be more susceptible to late phase responses. We are using transcriptomics (RNA-Seq) and metabolomics (mass spectrometry) of peripheral blood to identify molecular patterns that can discriminate allergen-induced isolated early from dual asthmatic responses. Peripheral blood was obtained prior to (pre-) and 2 hours post allergen inhalation challenge from 35 study participants. We are developing analytical tools such as sparse generalized canonical correlation discriminant analysis (SGCCDA) to derive classifier signatures that combine metabolite and RNA biomarkers of the late response
University of Oxford, UK
Time : 11:10-11:30
Khalid Al-Qahtani has completed his PhD at the age of 32 years from University Oxford. He was awarded the delegate’s choice prize for best young person’s poster presentation at the BMSS annual meeting, April 2014. He has published more than 9 papers in peer reviewed journals and is focussing on building a database for cancer metabolomics linking this with changes in metabolic pathways for studying regulation in cancer cells.
Introduction: The author will present highly selective and sensitive LC and GC methods for quantification of intracellular metabolites involved in tricarboxylic acid cycle (TCAs) metabolism including the configuration of the enantiomers of (L/D)-2-hydroxyglutaric (2-HG). These are applied to the analysis of brain cancer cells and tissues in order to look for metabolic differences between mutant and wild type cells. Method: The author has developed two novels LC-MS methods for studying changes in TCA cycle intermediates and their concentrations in cells. The first method focuses on the quantification of metabolites involved in TCA cycle metabolism and the second uses chiral separation for enantiomeric selectivity of (L/D)-2-HG and some amino acids associated with TCA reactions. In addition, third method for untargeted metabolites by using GC-MS for studying Fold changes on all brain metabolic profiles. Results: All isomers and enantiomeric forms of the metabolites were well separated with baseline resolution. Method validation provided limits of detection (LODs) for L/D-2HG ≤3μM (±2SD, Accuracy (%) ±4, %CV ±1.5, STD <5). calibration curves showed good linearity mainly over six orders of magnitude with a correlation coefficient R2 > 0.99. Conclusions: These methods were developed and applied to the analysis of brain cancer cells and tissues to investigate changes in TCA cycle intermediates identifying selected identifying selected enantionmer concentrations and studying isocitrate dehydrogenase (IDH) metabolon. We describe the methodology used and give examples from the analysis of selected wild-type and modified cancer cell lines which show highly specific enantiomeric changes in 2-hydroxyglutarate and 2-oxoglutarate taking place in mutant cell lines. There were statistically significant differences in TCAs metabolites (D-2HG, L-HG, 2-oxoglutarate, Oxaloacetate) levels between the IDHwt and IDH1R132H and IDH2R172K cells. There were significant differences in metabolite concentrations seen with IDH inhibition (shRNA, AGI-5198) and also when adding individual TCA cycle metabolites individually into culture media.
West Chester University,USA
Time : 11:30-11:50
John M. Pisciotta received his PhD from Johns Hopkins University for research on heme and lipid metabolism in malaria. Postdoctoral stints at the University of Maryland Center for Marine Biotechnology and then Pennsylvania State University College of Engineering focused on the development of novel bioelectrochemical systems (BESs) for production of bioenergtic products from waste. Dr. Pisciotta is currently an assistant professor in the Department of Biology at West Chester University in Pennsylvania where he teaches courses on Industrial Microbiology and Microbial Physiology.
At the metabolic level many organisms respond adaptively to changes in external stimuli such as exposure to toxins, drugs or radiation. For instance, high light exposure can induce up regulation of photo-protective metabolites and pigments in diverse plants and algae. Here we will focus on recent findings showing how application of electrical energy, alone or in combination with other stressors, may be used to guide and direct metabolism in microorganisms. Emerging bio-electrochemical tools and strategies for the targeted metabolomic analysis of useful electrically stimulated biological products including biofuels, antioxidants and pigments will be discussed. HPLC, GC and potentiostatic methodologies are used to study microbes as pure cultures or as syntrophic associations of bacteria, archaea and phototrophs such as cyanobaceria. Global profiling approaches useful for the discovery of novel electrically induced metabolites, proteins and response pathways will also be addressed.
Dr. Deliang Guo is Assistant Professor at Ohio State University Comprehensive Cancer Center. His major research interests are tumor metabolism, autophagy and oncogenic signaling. His research is supported by multiple grants from NIH, American Cancer Society and American Brain Tumor Association
Dysregulated lipid metabolism is emerging as a new hallmark in malignancies. Understanding lipid biology in cancer cells is important to identify the key player in regulating lipid reprogramming and develop an effective therapeutic strategy to treat cancer. Our studies have characterized that sterol regulatory element-binding protein (SREBP-1), an endoplasmic reticulum-bound transcription factor with central roles in lipid metabolism, is highly upregulated in glioblastoma (GBM), a most common primary brain tumor with a median survival only 12-15 months even after advanced therapies. Furthermore, we found that EGFR/PI3K/Akt signaling via SREBP-1 upregulates low-density lipoprotein receptor (LDLR) for elevated cholesterol uptake. These data demonstrate that SREBP-1 plays a central role in mediating oncogenic signaling-driven lipid metabolism reprogramming in cancer cells. Recently, we found that lipid droplets (LD) are prevalent in GBM and inversely correlated with patient overall survival. Blocking LD formation via inhibition of ACAT1 significantly suppressed GBM tumor growth via inhibition of SREBP-1-dependent de novo fatty acid synthesis. Taken together, our studies demonstrate that SREBP-1 is a central player in cancer lipid metabolism, and suggest that targeting SREBP-1 and LD formation is a promising therapeutic strategy to treat malignancies.
Tsinghua University School of Medicine, China
Time : 12:10-12:30
Ligong Chen has completed his PhD from University of California at Berkeley and Postdoctoral studies from UCSF School of Medicine and Pharmacy. He is the Principal Investigator in Pharmacology and Toxicology of Tsinghua University School of Medicine, a premier University in China. He has published more than 20 papers in reputed journals including Nature Genetics, PNAS, and JBC et al. He is an expert in Transporter Physiology and Pharmacology. His lab is working on various transporters’ role in human diseases, using metabolomics, genomics and proteomics as major tools.
Proliferating cancer cells require abundant energy, building blocks for macromolecules, as well as reducing power to counteract high oxidative stress. Glutamine is essential for the survival of cancer cells by providing carbon, nitrogen, NADPH and participating in regulatory pathways such as mTORC1 and MAPK signaling. Several transporters belonging to SLC1, 6, 7 and 38 families mediate absorption of glutamine across the plasma membrane. We focus on several members of the SLC38 family and have utilized metabolomics approach to analyze the effect of glutamine transporter on cancer cell metabolism. After overexpressing specific SLC38 transporters (SLC38A3 and SLC38A5) in pancreatic ductal adenocarcinoma cells, we analyzed alterations of metabolites with HILIC-LC/ESI-MS. We found that over expression of glutamine transporter indeed influenced TCA cycle, GSH production and nucleotide synthesis. Abundance of the intermediates of TCA cycle, glycolysis, GSH and nucleotide synthesis was changed. In addition, changes in the amount of urea cycle intermediates including citrulline and ornithine were observed, which introduces new perspective on the relationship between glutamine and ammonia metabolism in cancer cells. Intriguingly, significant rise of the amount of glutamine itself was not demonstrated in any analyzed cancer cell line, which suggests concomitant up-regulation of glutamine consumption through biosynthetic and regulatory pathways. Though more experiments are required to illuminate mechanisms contributing to the influence of glutamine transporter on relevant metabolites, metabolomics as a powerful tool strengthens our understanding of glutamine’s effect on key metabolic processes and helps to identify noncanonical metabolic pathways in glutamine metabolism.
Poster Presentations @ 13:30-14:30
West Chester University, USA
Time : 14:30-15:30
John M Pisciotta received his PhD from Johns Hopkins University for research on heme and lipid metabolism in malaria. Postdoctoral stints at the University of Maryland Center for Marine Biotechnology and then Pennsylvania State University College of Engineering focused on the development of novel bioelectrochemical systems (BESs) for production of bioenergtic products from waste. He is currently an Assistant Professor in the Department of Biology at West Chester University in Pennsylvania where he teaches courses on Industrial Microbiology and Microbial Physiology.
The metabolic profile of most species can be influenced by externally applied physicochemical factors. Electrical potentials have fairly recently been found to powerfully effect metabolite production profiles in diverse species. This workshop will explore the utility of a rapidly evolving class of bioreactor termed “Bioelectrochemical Systems” (BESs) as a research platform for conducting basic and applied metabolomic studies.
- Track 6: Metabolic Modelling
Track 7: Systems Biology and Computational Biology
Track 8: Bioinformatics and Advancements
Track 9: Data Analysis and Interpretation
John M Pisciotta
West Chester University, USA
University of Naples Federico II, Italy
Title: In silico identification of gene targets for bioethanol production from lignocellulosic hydrolysates using E. coli
Time : 15:30-15:50
Shireesh Srivastava has completed his PhD from Michigan State University and Postdoctoral studies from National Institute on Alcohol Abuse and Alcoholism, (NIAAA/NIH), Rockville, MD. He is a Team Leader in the DBT-ICGEB Center for Advanced Bioenergy Research, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India. He has published more than 15 papers in reputed journals and has won Fellows Award for Research Excellence at NIH as well as Sigma Xi award for excellence in graduate studies. His research interest is in metabolism and systems biology applications to solve challenging biomedical and biotechnological problems.
Hydrolysates of lignocellulosic biomass contain both hexoses and pentoses, with pentoses contributing to about 30% of the fermentable sugars. Thus, it is important to select an organism that can utilize both sugars effectively. E. coli has the advantage that it can utilize pentose and hexose sugars. However, in the course of its fermentation, it produces many by-products in addition to ethanol, such as acetate and formate. For efficient production of lignocellulosic biofuel, it is important to maximize product yield and minimize by-products formation. We employed in silico analyses on a recent genome-scale metabolic model of E. coli (iJO1366), to identify the knock-out targets to improve production of ethanol from glucose and xylose. Genetic Design through Local Search (GDLS) was employed to identify knock-out targets. GDLS involves reduction of the metabolic model to yield an equivalent Flux Balance Analysis model with fewer reactions and metabolites, followed by local search methodology to efficiently cover the space of genetic manipulations. Interestingly, similar knock-outs were identified for both glucose and xylose. Using these knock-outs, the ethanol was predicted to be over-90% of the theoretical yield on both glucose and xylose. The flux distribution in the mutant strain was identified through the Relative Change (RELATCH) method using available 13C-metabolic flux analysis data. The mutant strain had increased activity of Entner-Duodoroff pathway but reduced pentose-phosphate pathway and TCA cycle activity.
Embrapa Agroenergy, Brazil
Title: Metabolomics of xylose-fermenting yeast for increasing efficiency in the production of second generation ethanol
Time : 15:50-16:10
Patrícia has completed his PhD at the age of 27 years from State University of Campinas, performed a part of her PhD at Mass Spectrometry Research Center (MSRC), at Vanderbilt University.She is a researcher at Brazilian Enterprise for Agricultural Research, in the National Center for Agroenergy Research. She has published more than 20 papers in reputed journals and has been serving as a reviewer in scientific journals
The growing demand for alternative energy sources, adding value to products and utilization of residual biomass, as well as reducing the negative impacts on the environment, have encouraged the development of processes for producing ethanol from second generation (2G), ie, ethanol produced from lignocellulosic biomass. However, a bottleneck in the production of ethanol 2G is the inability of the yeast Saccharomyces cerevisiae, used in industry worldwide microorganism to produce ethanol, to convert pentoses such as xylose to ethanol (RUDOLF et al, 2009). Xylose is the second most abundant sugar on biomass, with about 33 % of fermentable sugars in the sugarcane bagasse (SASSNER et al, 2008). Given the importance of utilizing xylose to ethanol production, research have been done to identify yeast strains able to ferment pentose, highlighting two strategies: the identification of strains naturally capable of fermenting xylose and the development of recombinant strains of S. cerevisiae (WOHLBACH et al 2011; HÄGERDAL - HAHN et al, 2007).In this work, metabolomics approaches has been used to identify and quantify targets in the metabolic pathway for ethanol production from xylose. A method has been developed using UPLC-MS (Xevo TQD, Waters). ESI(+) and ESI(-)-MS, MS/MS and MRM experiments were performedin different conditions to obtain a sensitive and seletive method of targeted metabolomics. Finally, the metabolic pathways of four strains of yeast were compared and potential targets identified.
University of Naples Federico II, Italy
Title: Frontiers in comparative endocrinology: Challenges and opportunities of the “Program of Relevant National Interest
Time : 16:10-16:30
Giulia Guerriero is Associate Professor of Comparative Anatomy and Cytology, professor for the PhD School in Environmental Systems Analysis and the Advisory Board of the Center for Environmental Research (I.R.C.Env.) of the University of Naples Federico II. Her education is due to the PhD program in Evolutionary Biology and Comparative that followed the degree in Biological Sciences at the University Federico II and her research conducted in the United States of America (Thomas Jefferson University and Penn's Philadeplhia, Andrology Center of the Michael Reese Hospital in Chicago, Oregon Health Sciences University in Portland, Oregon). She’s a member of the Working Group of the Italian Society of Biological Biomarkers Marine Biology; of the Center of Research Bioactive Peptides (CIRPeB) of the University of Naples Federico II; the Young Investigator Awards Judging Annual Meeting of the Society for Free Radical Biology and Medicine, USA and Head of the Laboratory of Comparative Endocrinology (EClab) at the Department of Biology of the University of Naples Federico II. She is Associate Editor and member of the Editorial Board of international journals and member of several scientific societies. She collaborates with Italian and foreign researchers. Since 2011 she is representative of bilateral agreements between the University of Naples Federico II and Egyptians Universities and research centers of excellence. Her research papers, subject of wide dissemination and inviting as speaker at national and international conferences, have helped to define the correlation between oxidants and antioxidants in physiological defenses of embryonic and larval development of non-mammalian vertebrates and the role of steroidal neuroreceptors in the reproductive species and the importance of barcoding in the evaluation of species-specific responses. She is currently in charge of a scientific research project of national interest (PRIN) on the assessment of the health status of 'marine-coastal environment’, and an European applied research project (LIFE) for the development of protocols for the remediation of contaminated soils present in the Domitian-agro Aversa coast.
Comparative endocrinologists have important roles to play in many areas of the life sciences, such as the development of alternative animal model systems for discovery of novel hormones and hormone-signaling pathways; the discovery of new pharmaceuticals to treat human disease; the development of sensitive, representative and high-throughput endocrine-screening assays for EDCs; the analysis of the impact of global climatic change on animal populations; the elucidation of pathways and mechanisms of evolution through the study of endocrine genes and structures; and the development of more efficient means for the production of animal protein to feed the world's growing human population. Recently, the Italian Ministry of Education, University and Research has funded the project “Systems Biology”, aimed to provide a detailed picture of marine ecosystems subjected to high anthropogenic impact. The Project is articulated into two main phases: The study of the effects of toxic contaminants on “sea sentinels” and their strategic conservation; and the development and implementation of preservation and bioremediation strategies for the decontamination of marine water and sediments. Each phase is realized through a synergic collaboration among eight operative units. The unit from Federico II University of Naples (UniNA) assesses the environmental health status through the ecotoxicological impact on tissues involved in the reproductive events. UniNA defines the levels of reactive oxygen species and the antioxidants under steroid control; estimates xenobiotic effects on histones, sperm nuclear basic proteins, DNA damage and repair as well as qualitative and quantitative responses to stress of genes and proteins involved in the endocrine control of spermatogenesis. A full understanding of the capabilities of organisms to respond to environmental variation is necessary for understanding the impact of pollution on the viability of populations.
PGIMS ROHTAK, India
Title: Assessment of reproductive hormones and gynaecomastia in male CML patients with imatinib therapy
Time : 16:50-17:10
Veena Singh Ghalaut did her MBBS from J.N. Medical College Raipur, Madhya Pradesh and M.D Biochemistry from Pt. B.D.S PGIMS Rohtak. She is presently working as Senior Professor and Head in the Department of Biochemistry, Pt. B.D.S PGIMS Rohtak. She has teaching and research experience of approximately 35 years. There are more than 100 national and international publications and few biochemistry books to her credit. She has guided more than 50 MD/MS thesis projects. She is an active member of many associations and has been honored with several awards
It has been observed that decreased testosterone production and gynaecomastia may appear as adverse effects of imatinib therapy but vary sparse work is available in literature. In this study, we prospectively studied testosterone, LH and FSH levels at baseline and at 6 months of imatinib treatment in 34 newly diagnosed male BCR-ABL positive CML patients. While none of the patients had gynaecomastia at 6 months, the proportion of patients with low testosterone levels increased significantly from 11.8% at baseline to 58.8% (p<0.001) and those with high LH and FSH increased significantly from 26.4% and 23.5% to 82.4% and 76.4%, respectively (p<0.001 and p<0.001). Serum testosterone levels decreased significantly (p=0.002) and serum LH and FSH levels increased significantly at 6 months of imatinib therapy (p=0.001 and p=0.003) in comparison to baseline levels. The findings suggest that there may be decreasing effect of imatinib on testosterone levels in adult CML patients but there is need of further supporting studies.
PGIMS Rohtak, India
Time : 17:10-17:30
P S Ghalaut has completed his MD in Medicine 25 years ago from PGIMS Rohtak and also underwent advanced training in medical oncology at Tata Memorial Hospital Bombay and one year specially training in the field of management of leukaemias & lymphomas including Bone Marrow Transplantation at the University of Wales Cardiff (UK). He is the Director and Head of Department of medicine and hematology at PGIMS Rohtak. He has published more than 75 papers in reputed journals and has been training Postgraduate students since the past 25 years
Objectives: To evaluate and compare the levels of serum tryptase in patients of AML and CML before and after treatment and with controls. Methodology: The study included 25 newly diagnosed patients of AML and 20 newly diagnosed patients of CML and 40 age and sex matched healthy controls. Patients of renal failure, allergic reactions and those already taking chemotherapy were excluded. Serum tryptase levels were estimated in cases and controls by ELISA. Results: Mean age in AML and CML patients was 58.4±15.73 yrs and 51.4±13.27 yrs respectively. Severe anemia and low platelet count was observed in AML patients in comparison to controls while in CML patients, mild anemia and significantly raised TLC and Platelets was observed compared to controls. Mean value of percent of blast was 57.9±19.65 in AML patients and 7.95±5.90 in CML patients. The levels of uric acid in AML patients was (6.73±1.726 vs. 4.37±0.834), the difference in cases and control group is statistically significant (p<0.001). Serum tryptase levels were higher in AML and CML patients before Chemotherapy in comparison to controls (p value <0.001). Cases with high percentage of blasts were also found to have higher levels. Significant reduction in levels of tryptase was observed in AML and CML patients after chemotherapy (p value<0.003 and p value <0.017 respectively). Conclusion: Tryptase may be useful for diagnosis, assessment of severity of disease (leukemic cells burden), monitoring minimal residual disease and prognosis of both AML and CML patients.
Title: Isolation, Identification and Evaluation of Highly Cellulases Producing Trichoderma Isolates from Egypt
Time : 17:30-17:50
Fahmi A I received his Ph.D degree in molecular genetics from Texas A&M University in May 1992. He worked as assistant and associate professor in genetics department, Faculty of Agriculture, Menoufia University. Currently, He is working as a Professor in the same department. He is teaching genetic courses for undergraduate and graduate students. Also, he has supervised many graduate students who has worked for their master and doctorate degrees he is running research programs in the areas of molecular genetics and genetic mapping. Recently, he started a research project about using of Trichoderma sp. in hydrolyzing of organic wastes to produce compost for agriculture use. The first phase of this research program needs to isolate some Trichoderma highly producing of cellulases enzymes. Therefore, the topic of my abstract is Isolation, identification and evaluation of highly cellulases producing Trichoderma isolates from Egypt.
The objectives of this study were: 1) to characterize some Trichoderma isolates morphologically and molecularly, 2) to evaluate the best isolates for producing cellulases enzymes. 20 Trichodrma isolates were isolated from soil samples collected from six Egyptian governorates, in addition to seven provided isolates. According to morphological and molecular identification methods, they were divided into seven aggregate groups. Selected isolates that showed high ability to degrade cellulase were further evaluated. The result of submerged fermentation technique indicated that three isolates T44, T43 and T24 showed the highest activity for cellulases enzymes FPase, CMCase and -galactosidase, respectively. Also, the isolate T31 showed the highest production of free sugar, while the isolates T14, T19 and T44 demonstrated highest total protein concentrations. As for specific enzyme activity, isolates T17 and T24 were the highest for FPase enzyme, T17 was the highest for CMase enzyme and T24 was the best for -galactosidase. Furthermore, the result of solid state fermentation technique indicated that, isolates T14 was the best for producing FPase and -galactosidase and T20 was the highest for CMCase enzyme. Also, T20 was the best for producing free sugars while five isolates T1, T17, T20, T31 and T44 were the highest in producing protein. In addition, T17 showed the best hydrolysis percentage for rice straw. Moreover, extracellular proteins were analyzed by electrophoresis SDS-PAGE method. Most of highly producing cellulases isolates showed heavy band at around 65 KDa. Finally, it was concluded T14, T17, T19, T24, T31and T44 isolates could be recommended for biotechnological applications.