Day 2 :
Keynote Forum
JÃrová Dagmar
National Institute of Public Health, Czech Republic
Keynote: Endocrine disruption and antimicrobials
Biography:
Dagmar Jírová, MD, PhD, graduated and received her PhD at the Charles University in Prague. Her professional specialization is dermatotoxicology and immunotoxicology, focused on safety assessment of cosmetics and other consumer products. She is holding the position of the Head of the Centre of Toxicology and Health Safety at the National Institute of Public Health, Prague, Czech Republic. She is the author of more than 200 publications in scientific journals, proceedings and monographs, posters or articles and publications for the public. She was the Principal Investigator in number of research projects in the field of alternative toxicological methods for evaluation of health risks of chemicals and consumer products.
Abstract:
Endocrine disruptors are hormonally active substances of natural or synthetic origin affecting the endocrine (hormonal) systems of humans. Such compounds can be found in chemical groups like steroids, cyclic hydrocarbons, phenols, flavonoids, phtalates, parabens or toxic metals. They are used as antimicrobials, biocides, plasticizers, surfactants, UV filters or fire retardants. They may be released from consumer products, e.g. cosmetics, toys, food packaging materials, household products, medical devices and other products of industry or agriculture. In the EU, they are banned for consumer products. Recently regulated CMR substances from the group of Antimicrobials/Preservatives (biocides) comprise: Chloracetamide (Reprotox. Cat. 2), Phenol (Mutagenic Cat. 2), Nonylphenol (Reprotox. Cat. 2), Parabens (pentyl-, phenyl-, benzyl- for absent data on reprotox.), Ketoconazole (Reprotox. Cat. 1B), Boron compounds (Reprotox. Cat. 1B), Formaldehyde (Carcinogenic Cat. 1B), Polyaminopropyl Biguanide-PHMB (Mutagenic Cat. 2). Significant reprotoxic effect has been proved in the past namely for distinct bisphenols (Reprotox. Cat. 2) or phthalates (Reprotox. Cat 1B or Cat. 2) which were subsequently banned. However, the production of analogous compounds is increasing underlining the necessity to test their safety including reprotoxicity. The European Commission's general policy is the use of alternative toxicological methods in vitro instead of conventional tests on vertebrates. Available methods in vitro to detect endocrine disruption are: OECD TG 455/457–Estrogen Receptor Transactivation Test Method, OECD TG 456–Effects on Steroidogenesis, OECD TG 236–ZFET, zebrafish embryo epigenetic assay, MCF-7 cell proliferation assay, Xenoscreen YES/YAS yeast assay.
Results of a pilot study to prove applicability of methods in vitro to detect reprotoxicity are presented.
Keynote Forum
Mukul Pore
Intox Pvt. Ltd., India
Keynote: Preclinical Development of Biopharmaceuticals (r-DNA Products)
Biography:
Mukul P Pore is one of the founders and is the Lifetime Director of INTOX Pvt. Ltd. which is a well known GLP Certified Contract research organization. He is a Diplomate of the American Board of Toxicology (DABT), European Registered Toxicologist (ERT) and Fellow of Indian Society of Toxicology (FST). He has designed and conducted number of toxicology studies for diverse kind of products - pharmaceuticals, agrochemicals, biotechnology products, speciality chemicals, vaccines, medical devices, industrial chemicals etc. during his experience of over 28 years in regulatory / descriptive toxicology. Since 1996, he has played an important role in establishing and bringing INTOX to international standard and repute. He is an Ad Hoc specialist for AAALAC International, USA (2010-2013; 2013-2016; 2016-2019). He is Member of many professional bodies/societies including Indian Society of Toxicology (STOX), Chinese Society of Toxicology, Japanese Society of Toxicology (JST), UK Registry of Toxicology and Laboratory Animal Scientists Association of India. He was nominated on ‘REACH Expert Committee” as “Expert in the field of Environment, Health and Safety” by Ministry of Chemicals & Fertilizers, Govt. of India (2015). He was nominated as Advisor of Editorial Board of “Toxicology International” Journal in 2009.
Abstract:
Biopharmaceuticals are an important component of pharma industry & have grown exponentially in the last decade. The growth is driven by factors such as growing pressure for affordable product development, advances in biochemical and molecular biology instrumentation, growing demand for biosimilar drugs to address ever growing chronic diseases, increasing number of off-patented therapeutics and monoclonals. Great successes were achieved and multiple life-altering therapies were developed for indications like cancer, rare genetic diseases, and immune disorders. Significant guidance has been released by regulatory agencies to help the rational and scientifically based development of these complex products. The goal of preclinical development of biosimilar is to demonstrate that, the drug is ‘highly similar’ to the reference biologic product in terms of ‘Safety, Efficacy and Quality’. Monitoring biopharmaceutical drug safety deserves special attention.
In this presentation, challenges in the preclinical development of biologicals (particularly ‘Biosimilars’) will discussed in short. Key features of biotechnology-derived molecules (Biosimilars including Vaccines), how they compare to traditional chemical drugs, and the impact these features on preclinical safety testing during their development will also be discussed.
- Young Research Forum
Location: Dubai, UAE
Session Introduction
Vincent Lal
The University of Queensland, Australia
Title: Determination of polycyclic aromatic hydrocarbon and its monohydroxilated metabolites in human liver cells using gas chromatography and high performance liquid chromatography with mass spectrometry
Biography:
Vincent Lal has his expertise in Environmental and Analytical Toxicology and passion in improving human health and wellbeing. His work is based on chemical risk assessment using in vitro technologies. He has several years of research, teaching, consultancy and administration experience in commercial and education institutions.
Abstract:
Human cell-based models can provide important information on exposure and risk from chemical contaminants. Measurement of the amount of chemical contaminant entering the cells and how effectively it is metabolised and removed can be useful towards our understanding of chemical health risk assessment. The aim for our study is to quantify intracellular uptake and metabolism of polycyclic aromatic hydrocarbons (PAHs) in a human liver carcinoma cell line (HepG2 cells) exposed to environmentally relevant concentrations of the pure model compound and contaminated soils. A number of PAH and their monohydroxilated metabolites, including 3-hydroxybenzo[a]pyrene, 1-naphthol and 1-hydroxypyrene were found in human liver cells following exposure. Biotransformation of PAHs in human liver cells increased with increasing dose. Cell exposure close to 0 h and to 24 h contact times was also investigated, both at low and high dosage. Benzo[a]pyrene was found to be toxic to cells; however, remaining PAHs in this study did not cause any significant changes in cell viability (or cytotoxicity) and their ability to recover. Chemical characterisation of PAHs and its metabolites was done using high performance liquid chromatography coupled to a high resolution mass spectrometer (HPLC-HRMS) and gas chromatography with mass spectrometry (GCMS). The ability to quantify chemical uptake and fate using human cell line based models will contribute to a more refined chemical risk assessment.
Gavrilă B I
Carol Davila University of Medicine and Pharmacy, Romania
Title: Could diagnostic biomarkers be used to predict the response to biologic therapy in Rheumatoid Arthritis?
Biography:
Gavrila Bogdan Ion completed his PhD in 2016 from University of Medicine and Pharmacy, Bucharest (Romania). Currently he is working as an Assistant Professor at Department of Internal Medicine and Rheumatology, Bucharest.
Abstract:
Background: Biologic therapies have revolutionized the treatment of rheumatoid arthritis (RA). Despite these advances, 20-40% of the patients are declared nonresponders to at least one of the therapies. The patient exposure to the potential side effects and high costs requires the discovery of a biomarker that could identify those who can benefit from the pretreatment of a certain therapy. We proposed to test the predictive role for the response to biologic therapy of diagnostic biomarkers used in RA: rheumatoid factor (RF) isotypes IgM and IgA, anti-cyclic citrullinated peptide (anti-CCP) and auto-antibodies against mutated citrullinated vimentin (anti-MCV). We also followed the evolution of serum levels of these biomarkers under biologic therapy.
Methods: prospective and observational study including 64 patients followed 12 months with active RA, uncontrolled by conventional synthetic DMARDs or declared non-responders to one of the biologic DMARDs.
Results: Lower baseline titres of RF type Ig M (51.36±95.359 U/ml, p=0.01629), Ig A (22.45±61.256 U/ml, p=0.03336) and anti-CCP (60.82±26.331ng/ml, p=0.00011) had predictive value for achieving a good EULAR response at 6 months. Regarding anti-MCV baseline titres, there were no differences between groups at 6 months (p=0.45914) or at 12 months (p=0.11354). Grouping patients in 2 categories (responders/non-responders), we identified significant differences between groups only for anti-CCP and response at 6 months (responders 96.04±50.355ng/ml, non-responders 146.16±41.68ng/ml, p=0.02834). For the EULAR response at 12 months, lower baseline titres for RF type Ig M (92.93±120.22 U/ml, p=0.01032) and Ig A (49.96±98.08 U/ml, p=0.00247) had predictive value for achieving a good response at 12 months. We didn’t obtain other information grouping patients in 2 categories. Regarding the evolution of serum levels, we noticed a reduction for all four biomarkers tested, statistically significant at 6 and / or 12 months from baseline.
Conclusion: Besides from their diagnostic role, these biomarkers could be used for other purposes in Rheumatoid Arthritis.
Sadhana Shrivastava
Jiwaji University, India
Title: Protective effects of caffeic acid on acrylamide induced toxicity in rats
Biography:
Sadhana Shrivastava has completed her PhD and Post-doctoral studies from Jiwaji University. She is currently working as a Scientist in DHR funded project. She has published more than 45 papers in reputed journals and books. She has been awarded many national awards and fellowships.
Abstract:
Statement of Problem: Studies concerning toxicity of acrylamide and its metabolite - glicydamide showed neurotoxic and genotoxic effect. Acrylamide (AA) is a synthetic chemical compound which is used in industry plastics, paints, cellulose-paper, cosmetic industries and its forms in some starchy foods during high-temperature cooking. Caffeic acid is a hydroxycinnamic acid found in barley grain and is an active antioxidant which scavenges free radicals. The present investigation was planned to investigate the therapeutic effect by caffeic acid against AA.
Methodology & Theoretical Orientation: AA was administered at the dose of 19.13 mg/kg, p.o. for 28 days to albino rats followed by therapy with 20 mg/kg, p.o. of caffeic acid for 7 days.
Findings: Significant increase in serum albumin, bilirubin, triglyceride, cholesterol, SALP, LDH, GGT, ALAD, ALAS was noted, as compared to the control group. Urea and creatinine was also increased, which indicated renal damage. Activity of acetylcholisterase and antioxidant defense system enzymes such as glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) were decreased in all tissues significantly after AA administration. Histopathological observation also supported biochemical studies as AA caused degeneration in the hepatocytes, hypercellularity in glomeruli and hypertrophy in epithelial cells and disorganization in the neurons.
Conclusion & Significance: This study has shown that caffeic acid protects against AA toxicity.
S Thilagavathi
Annamalai University, India
Title: 3, 3-Diindolylmethane inhibits RAS/PI3K/AKT signaling through GPR30 abrogate cell proliferation by BPA induced female Sprague Dawley rats
Biography:
S Thilagavathi is PhD Research Scholar working in cancer biology at in vivo model.
Abstract:
The present study was aimed to evaluate the antiestrogenic effect of 3, 3 –diindolylmethane (DIM) on bisphenol A (BPA) induced alteration in estrogen signaling pathway in mammary glands of female Sprague-Dawley rats. BPA (10 µg/kg/bw) administered rat mammary tissues western blot analysis shows an over expression of GPR30, Ras, Src, PI3K and Akt proteins and immunohistochemical analysis indicates an over expression of PCNA and no significant changes in ERs. Further, oral administration of DIM (5 mg/ kg/bw) to BPA treated rats alternative days for the period of 12 weeks reveals that significant decrease in the expression pattern of GPR30, Src, Ras, PI3K, Akt and PCNA as compared to BPA alone treated rats. The results of our study demonstrate that BPA induces rapid action via the over expression of proteins in nongenomic estrogen signaling pathway. Oral administration of DIM to BPA treated group inhibits rapid action of BPA by modulating the proteins of nongenomic estrogen signaling pathway.
- Special Session
Location: Dubai, UAE
Session Introduction
Swamy K B
Universiti Sultan Zainal Abidin, Malaysia
Title: The latest trends of IQ and Brain size and effects of Life style and Environmental Factors on Cranial Capacity
Biography:
Swamy K B has been awarded PhD by Andhra University, India. He has taken his Master’s Degree in Clinical Anatomy from Andhra Medical College, India, DMCh (Maternal & Child Health) and Medical Degree (MBBS) from IGNOU, New Delhi. He has expertise in Human Genetics, Reproductive & Developmental Anatomy and also in Herbal Medicine. He has been the Genetic Counselor for many institutions, with prestigious grants from Malaysia. He has conducted many researches on Herbal Medicine and Diabetes, on “Brain size and Intelligence Quotient (IQ)”. He has been the former Founder, Anatomist, Professor and Head of the Department for many Medical Schools in India as well as in Malaysia. He is an international Editorial Board Member for many reputed journals like Anatomical Society of India (ASI). Recently, he has been unanimously elected as an Executive Board Member for ASI and an Organizing Committee Member for the upcoming “9th Euro-Global Summit on Toxicology and Applied Pharmacology” to be held through June 22-24, 2017 at Paris, France.
Abstract:
Introduction:- Intelligence quotient (IQ) is widely used to assess different aspects of mental ability. Development in mental ability initiates from conception and continues through adulthood. Various environmental factors affect IQ.
Objectives:- The aim of this study was to assess the correlation between IQ and environmental characteristics on cranial capacity in children and adolescents in Malaysia.
Methods & Materials:- This cross sectional study was performed on primary and secondary school students in Kuala Terengganu, Malaysia. Students, who were aged between 6 to 16 years and did not have any mental or physical disabilities, participated in this study. Measurements including weight, height, body mass index and cephalometry were performed for each subject. The Wechsler Abbreviated Scale for Intelligence- Second Edition (WASI-II) questionnaire was used for each subject to evaluate the subtests of IQ. A total of 419 subjects with the mean age of 12.51 ± 2.82 years had participated in this study.
Results:- Boys were taller (p=0.04), had higher IQ (p=0.01) and cranial capacity (p<0.001) as well as block design score (p=0.02) when compared with girls. There was a significant mean effect for age (p=0.03), gender (p=0.04), paternal education (p=0.04), family income and block design (p=0.03) on cranial capacity.
Conclusions:- This study revealed different patterns of brain growth, function and IQ amongst male and female subjects as well as defining the environmental factors that can affect cranial capacity and that the IQ and cranial capacity may be improved by tuning up the lifestyles and economic conditions of the families in developing countries.
- Analytical Toxicology | Genotoxicity | Forensic Toxicology | Food Safety and Environmental Toxicology
Location: Dubai, UAE
Session Introduction
Sahar Y Issa
Alexandria University Faculty of Medicine, Egypt
Title: Clinical case study: Toxicity of dietary supplement used for weight reduction contaminated with adulterants
Biography:
Sahar Y Issa has completed her Doctorate degree in Clinical Toxicology & Forensic Medicine in 2008, from Faculty of Medicine, Alexandria University, Egypt and is a Lecturer of Clinical Toxicology & Forensic Medicine in the same University. She is currently a Consultant Toxicologist, and the Medical Director, supervising Emergency Toxicology, Molecular Toxicology and Therapeutic Drug Monitoring units in Dammam Poison Control Center, MOH - Saudi Arabia. She has published more than 25 papers in reputed journals and serving as an Editorial Board Member of repute.
Abstract:
Nowadays, dietary supplements’ consumption, especially those of plant origin, has been gaining more popularity among consumers owing to misbelieve that they are natural products posing no risks to human health. In many regions of the world including the European Union and the United States, dietary supplements are legally considered as special categories of food, thus are not popularly being submitted to any safety assessment prior to their commercialization. Among the safety issues, comes adulteration by the illegal addition of pharmaceutical substances or their analogues, since unscrupulous producers can falsify these products to provide for quick effects and to increase their profits and sales. This case study is about one product used locally as a dietary supplement, and was marketed for weight loss, muscle building, lead to several health complications in one user, who presented with renal impairment and also describes about several conventional and advanced analytical techniques used to detect and identify amphetamine-like adulterants in the dietary supplement.
Maria Walczak
Jagiellonian University, Poland
Title: The role of endothelial biomarkers in breast cancer metastasis
Biography:
Maria Walczak has graduated from the Faculty of Pharmacy Medical Academy in Krakow. She has obtained PhD degree from the Faculty of Pharmacy, Jagiellonian University Medical College (UJ CM), Krakow in 2001 and habilitation thesis in Pharmacokinetics in 2014. Since 2001 she worked at the Department of Pharmacokinetics and Physical Pharmacy UJ CM as a Lecturer, since 2010 at the Jagiellonian Centre for Experimental Therapeutics (JCET) as a Manager of the Laboratory of Analytics and Pharmacokinetics, and since 2015 as a head of Chair and Department of Toxicology, Faculty of Pharmacy UJ CM. Her scientific work refers to pharmacokinetic and toxicokinetic profiling, metabolite screening, assessment of protein binding of bioactive compounds and pharmacology of endothelium. She is keen in bioanalysis of novel compounds and biomarkers related to cancer metastasis using LC/MS/MS and CE techniques. She is a specialist in clinical pharmacy issues.
Abstract:
Statement of the Problem: Metastatic cancers are the main cause of cancer-related death in the world. For this reason identification of novel treatment targets is warranted. Study of breast cancer metastasis is limited due to poor knowledge in progression of breast tumor and varied heterogeneity. Breast cancer metastasis is a complicated process in which each step is modulated by a complex network of signaling pathways. In recent years attention is paid to the significance of vascular endothelium in cancer metastasis and abundant evidence suggests that endothelial inflammation plays an important pathogenetic role in the development of metastasis. The purpose of this study was to describe changes in endothelium in mouse model of 4T1 metastatic breast cancer at various stages of disease progression with the use of the multi-protein panel of endothelial biomarkers.
Methodology & Theoretical Orientation: The panel contains proteins of glycocalyx disruption: syndecan-1 (SDC-1) and endocan (ESM-1); pro-inflammatory molecules: soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1) and soluble form of E-selectin (sE-sel); pro-thrombotic molecule: von Willebrand factor (vWF); fibrinolytic molecules: plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (t-PA); pro-angiogenic molecules: the soluble form of the fms-like tyrosine kinase 1 (sFlt-1), angiopoietin 2 (Angpt-2) and adrenomedullin (ADM), and protein secreted by adipocytes - adiponectin (ADN). The biomarkers were determined using the liquid chromatography/mass spectrometry-multiple reaction monitoring-based method (LC/MS-MRM).
Findings: Some of these proteins altered during breast cancer progression. Using a panel of selected molecules was enabled to identify endothelial biomarkers for early and late metastatic phase.
Conclusion & Significance: Endothelial dysfunction in cancer confirms the hypothesis that condition of endothelium is a key step for disease development. The simultaneous analysis of many biomarkers in one sample enables for multidimensional screening of endothelial function in mouse 4T1 breast cancer.