Day 3 :
- Track 11: Emerging In-vitro Models for the Toxicity Studies
Track 12: Developmental and Reproductive Toxicology
Track 13: Computational Toxicology
Location: Versailles - B
Inoviem Scientifi c, France
National Research Council, Italy
SRI International, USA
Time : 09:00-09:20
Travis Harrison received his graduate training at Virginia Commonwealth University in Immunology in 2001 with an emphasis in immunotoxicology. He has served as PI on multiple commercial and government contracts, and has managed several subcontracts for large government contracts. One of his areas of specialty has been development and GLP validation of immunoassays including nearly 100 assays to support GLP studies.
The CD28 antibody TGN1412, intended as a treatment for B cell chronic lymphocytic leukemia, caused systemic organ failure in initial human volunteers. This severe side effect was subsequently attributed to induction of a pro-inflammatory cytokine storm. Failure to detect this effect in animal studies underscores the need to supplement animal data with an evaluation of cytokine storm potential in human cells. We used human peripheral mononuclear cells (PBMCs) and monocyte-derived dendritic cells (DCs) to evaluate the cytokine storm potential of several siRNA compounds by measuring a panel of cytokines using Luminex. While some of the compounds elicited cytokines in PBMCs, the compounds failed to elicit cytokines in DCs. This finding demonstrates the value of an in vitro assay to evaluate potential immunostimulatory compounds and suggests that a robust evaluation may require examination of multiple cell types.
State University of New York, USA
Title: New methodology for Phenotyping P450 Polymorphisms and susceptibility to environmental toxicants using humanized budding Yeast
Time : 09:20-09:40
Michael Fasullo completed his Ph.D at the age of 28 years from the Department of Biochemistry at Stanford University School of Medicine and did a postdoctoral fellowship at Columbia University. He has been a faculty member at Loyola University of Chicago and The Albany Medical College, and is currently located at the College of Nanoscale College and Engineering, State University of New York. He has published more than 25 papers in reputed journals and has served as a reviewer for Genetics, Nucleic Acids Research, Cell Cycle, and for several National Institutes of Health grant review panels.
Human susceptibility to xenobiotics, such as pharmaceutical drugs and genotoxicants, is highly variable. Much variability is conferred by polymorphisms in P450 genes and in housekeeping genes involved in basic DNA repair and metabolism. Since humans express multiple P450 genes, it is often difficult to discern which variant P450 gene confers xenobiotic susceptibility. In addition, epidemiological studies are often limited due to small patient populations. As a model xenobiotic, we used the potent liver carcinogen aflatoxin B1 (AFB1), which is metabolically activated by CYP1A2 and CYP3A4. Since (budding yeast) do not express P450 genes that can metabolically activate AFB1, we were able to phenotype CYP1A2 variants and 2) profile the yeast genome for resistance to AFB1. We characterized AFB1 activation based on DNA adducts, Rad51 polymorphisms, cell survival, and genome instability. Considering that 31% of (Saccharomyces cerevisiae) budding yeast genes are very similar to human genes, we hypothesize that genes that confer AFB1 resistance in budding yeast will also confer resistance in humans. We introduced CYP1A2 into the diploid yeast collection containing ~5000 single gene deletions. Using state-of-the-art next generation DNA sequencing, we identified ~500 genes that confer AFB1 resistance, including genes that function in DNA repair, checkpoint response and adaptation, DNA damage tolerance, and oxidative stress. Future studies will be focused on identifying whether down-regulation of these human orthologs also confer AFB1 sensitivity. We are now profiling resistance to additional P450-activated xenobiotics and phenotyping CYP1A1 polymorphisms.
Inoviem Scientific, France
Title: Nematic protein organisation technology: A powerful tool to track drugs toxicity and side effects already at early preclinical development
Time : 09:40-10:00
Pierre Eftekhari has completed his PhD from Strasbourg University. He has more than 17 years of experience in drug development and is the Director of Inoviem Scientific, a company dedicated to cutting edge solutions in drug development as well as the head of exploratory pharmaco/toxicology team at ICT, CNRS UPR 3572 Strasbourg. He has published more than 28 papers in reputed journals and filed several patents.
Toxicity and lack of drug efficiency from preclinical to clinical phase, are two most important hinders for development of new therapies. These are mainly due to our lack of reliable knowledge at the early stage of drug development. Another major hinder is the drugs side effect after approval, which can lead to serious or life threatening conditions. Nematic protien organisation technology (NPOT) identifies both therapeutic target (ON) and toxic or side effect targets (OFF). NPOT is label free and works in physiological conditions, directly on human tissue. Where clinical relevance from genomics remains uncertain NPOT provides reliable toxicity profile identifies biomarkers and isolate success predictors. NPOT’s efficacy is shown by identifying OFF targets of two different drugs one from chloroquine family and one anti-TNFα therapy a biologic drug. They have led, at one hand to new molecule without any side effect yet improved clinical efficacy in Lupus as well as provided success predictors for anti-TNFα therapy in Inflammatory Bowel Disease (IBD). In additional thanks to NPOT we have improved our understanding on biological effects of a pharmacological active molecule at cellular and molecular levels. These findings explain the role of extracellular and intracellular matrix in expected beneficial or toxic effects. This knowledge redefines the modern pharmacology and toxicology, allowing the development of safer treatments. The author shall share these findings in detail, providing proofs and argument for the urgency to change our understanding and somehow dogmas in regard to the sciences of pharmacology and toxicology.
National Research Council, Italy
Time : 10:00-10:20
Alessandra Mezzelani has completed her Ph.D in “Veterinaty Biotechnologies” in 1995 from Milan University. She has been worked as associated researcher at the “National Tumor Institute of Milan” for 6 years. She is staff researcher at the Institute of Biomedical Technologies, National Research Council of Italy, responsible for the “Translational Bioinformatics Lab” since 2001. She has published 51 papers in reputed journals.
Autism is an increasing neurodevelopmental disorder that appears by 3 years of age, has a striking male prevalence and often shows comorbid situations, such as gastrointestinal (GI) disorders. Although some causative genetic variants have already been found, they affect only ~30% of cases and cannot explain the dramatic increase of autism in the last decades. As in other pathologies in which specific gene–environment interplay triggers the disease, the possible role of environmental factors, such as infections, xenobiotics and drugs in provoking autism in subjects with genetic susceptibility has been proposed. Among autism causative genes, we focused on neuroligine3 (NLGN3) and 4X (NLGN4X) because they play a key role in synaptic plasticity and, being located on X chromosome, are hemizygous in males. We analyzed some intronic and 3’UTR SNPS of NLGN3 and NLGN4X in 190 Italian autistic cases (male:female=4,4:1) by Sanger sequencing and High resolution Melting. Overall we found 3 SNPs haplotypes statistically significant in autistics comparing to the minor allele frequencies (MAF) from the 1000-Genomes Project CEU. Questioning bioinformatics predictive database it showed that some SNPs in the 3’UTR of NLGN4X may modify microRNA target sites. Interestingly, mining the literature we found, among xenobiotics, that ochratoxinA (OTA) and fumonisin B1, two of major food contaminating mycotoxins, provoke, in animal models, a neurological and immunological damage, especially in males. Moreover recent studies have also demonstrated that in in vitro and in in vivo experiments, these toxins modulated the level of some microRNAs. Surprisingly, OTA up-regulates some microRNA implicated in autism and in NLGN4X expression. In conclusion we speculate that a specific NLGN4X–mycotoxin interplay via 3’UTR SNPS- dysregulated microRNAs cross-talk could trigger autism in those patients suffering from gastrointestinal disorders and leaky gut. Further analyses are required to demonstrate this hypothesis and to define the effects of toxins on general population in order to establish the risk assessment and the daily tolerable intake.
The Goldberg Research Institute of Pharmacology, Russia
Time : 10:20-10:40
Tatyana Borovskaya has graduated from the Tomsk State Medical University got M.D. degree and completed her postdoctoral studies from the Goldberg Research Institute of Pharmacology. She is the head of Laboratory of Pharmacology. She has published 3 monographs, more than 160 papers in reputed journals and is the author of 14 patents. The field of interests covers toxicology, andrology and embryology.
Gonads as actively upgrading cell systems are targeted for action of cyto-static drugs. Severity of this side effect varies considerably. At the moment, due to the promising results of treating certain cancers, the number of patients who expects to recover fertility is significantly increased. The aim of this work is to study experimentally the severity of reproductive toxicity (at progenesis) of cyto-static influence of various types (adriamimin, pharmorubicin, platidiam, carboplatin, etoposide, irinotecan, paclitaxel), as well as finding ways to reduce it. Experiments were carried out with Wistar rats of reproductive age. The drugs were administered intravenously in a single minimum pyrogenic dose. Administration of drugs to female rats was found that earliest menopause can be expected under administration of anthracyclines. While maintaining the endocrine status, the partial infertility was detected after administration of doxorubicin. Ability to keep pregnancy was reduced more after administration of paclitaxel. After administration of drugs to male rats it was revealed that two of the drugs – pharmorubicin and paclitaxel – have damaging effect on spermatogonia that leads to sterility of the animals long after administration. Decrease of probability to keep fertility was found long after administration of etoposide and paclitaxel. It was found that busserelin, antioxidants, granulocyte colony-stimulating factor can reduce the toxic influence of cytostatics on gonads.
Sun Yat-Sen University, China
Time : 11:00-11:20
Ying Peng has completed his Ph.D at the age of 31 years from SunYat-Sen University School of Medicine, Guangzhou,China and postdoctoral studies fromNational Cancer Institute-at Frederick, NIH, MD, USA. He is the Director and Professor of Department of Neurology, Sun Yat-Sen Memorial Hospital, SunYat-Sen University. As a clinical neurologist,he has published more than 75 papers in reputed journals and serving as an Associate- Editor-in-Chief of “Chinese Journal of Nervous and Mental Disease” and Deputy- Chief of Neuro-pharmacological Association of Guangdong province, China.
Background: Astaxanthin (AST), known as a carotenoid pigment, is a strong antioxidant which protects membranous phospholipids and other lipids against peroxidation. Evidences showed that astaxanthin had up to several-fold stronger free radical antioxidant activity than vitamin E and carotene. In double-blind, randomized controlled trials, astaxanthin was found to lower oxidative stress in several human health conditions. Moreover, it is known that ROS up-regulate proinfalmmatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and IL-6. High levels of these cytokines are associated with neurotoxicity. Whereas, astaxanthin has been found to reduce makers of inflammation, e.g., TNF-α. Thus, astaxanthin has been deemed to be safe and has potential as a therapeutic antioxidant and anti-inflammation agent for further testing in human diseases. Objective: To explore the protective effect of astaxanthin on fetal alcohol spectrum disorder in mice, and to investigate the underlying mechanisms. Methods: The morphology, expression of neural marker genes, oxidative stress indexes, and inflammatory factors in mice model of fetal alcohol spectrum disorder with or without astaxanthin pretreatment were detected. Results: Results showed that astaxanthin blocked maternal ethanol induced retardation of embryonic growth, and the down-regulation of neural marker genes, Otx1 and Sox2. Moreover, astaxanthin also reversed the increase of MDA, H2O2, and the decrease of GPx in fetal alcohol spectrum disorder. In addiction, maternal ethanol induced up-regulation of TLR4, and the down-streaming MyD88, MyD88, NF-κB, TNF-α, and IL-1β in embryos, and this was inhibited by astaxanthin pretreatment. Conclusions: Results demonstrated a protective effect of astaxanthin on fetal alcohol spectrum disorder, and suggested that oxidative stress and toll-like receptor signaling associated inflammatory reaction were involved in this process.
University of Pretoria, South Africa
Title: The effects of veterinary growth stimulants from cattle feedlots in South Africa on reproductive and thyroid parameters in a rat model
Time : 11:20-11:40
Tiaan de Jager de Jager is Deputy Dean Research in the Faculty of Health Sciences, University of Pretoria (UP), South Africa. He is a Professor in Environmental Health in the School of Health Systems& Public Health (SHSPH) and an Extraordinary Professor in Andrology. He is also the Director of the UP Centre for Sustainable Malaria Control. His research focus is on environmental endocrine disrupting chemicals (EDCs) and health, with a special interest in malaria, water quality and male reproductive health. He was an expert peer reviewer of the 2002 WHO/PCS document on Global Assessment of the State-of-the-Science of Endocrine Disruptors. Since 2007, Tiaan published 20 peer-reviewed ISI papers, four research reports and 13 peer-reviewed conference proceedings. He is currently supervising six PhD students.
Introduction: In South Africa the cattle feedlot system is responsible for 75% of all bovine produced. Studies have revealed the presence of androgenic and estrogenic metabolites in water effluent from some of these feedlots. Veterinary growth stimulants (VGS) used in the feedlot industry are environmentally stable compounds, which may result in thyroid disruption and also affect fertility in wildlife and humans. Aims: a) To screen water sources from selected cattle feedlots for estrogenic activity using the Recombinant Yeast Screen (YES) and T47D-KBluc bioassays. b) To do a reproductive toxicology study, using the rat model on the identified mixture of VGS at environmentally relevant concentrations. c) To determine the effect of the identified mixture of VGS on the thyroid hormones, triiodothyronine (T3) and thyroxine (T4). Methods: Water samples were assessed in the selected bioassays for estrogenic activity and endocrine disrupting chemical (EDC) effects of the identified VGS on reproductive parameters in rats using the OECD 415 protocol. Three experimental groups were orally gavaged: Group 1 (control) with cottonseed oil; Group 2 with zilpaterol, diethylstilbestrol (DES) and α-zearalanol; Group 3 with β-trenbolone and methyltestosterone; and Group 4 with the mixture of compounds. Results: Nine samples had estrogenic activity ranging between 0.02(±0.004)-2.57(±0.39) ng/L and 3 had cytotoxicity. Statistically significant differences were found between Group 1 and 4 for the mean seminal vesicle (p=0.0074) and prostate mass (p=0.0151); Group 1 and 3 for total sperm count (p=0.0337) and anogenital distance (p=0.0117); Group1 and Groups 3 and 4 fortotal lumen diameter (p=0.0455 and p=0.0289 respectively). Statistically significant differences were found for T4 between Group 1 and Group 2 (p=0.0089) and 3 (p=0.0210) respectively. Conclusions: The bioassays confirmed estrogenic activity in cattle feedlot runoff water. VGS contribute to the complex aquatic environmental mixtures of EDCs. The results of the study indicate that growth stimulants may have an influence on the thyroid and reproductive health in maternally and direct exposed male rats. This highlights the contribution of growth stimulants to the complex environmental mixtures of EDCs and ultimately the potential effects on human reproductive health.
University of South China, China
Title: c-Jun N-terminal kinase is upregulated in the hypospadiac penis of fetal rats induced by maternal exposure to di-(2-ethylhexyl) phthalate
Time : 11:40-12:00
Ming Yong Li has completed his PhD at the age of 29 years from Children's Hospital of Chongqing Medical University. At present, he works at the first affiliated hospital of University of South China. His major study field is environmental toxicology with human reproductive health. He has published more than 10 papers in reputed journals in English and in Chinese.
Hypospadias is one of the most frequently occurring congenital anomalies, but its etiology is largely uncharacterized. Whole genome microarrays analysis of hypospadiac tissue from rats indicated a potential role for c-Jun N-terminal kinase (JNK) in the development of this anomaly. Therefore, the expression of JNK 1/2 in the hypospadiac penis of fetal rats induced by maternal exposure to di-(2-ethylhexyl) phthalate (DEHP), one important kind industrial plasticizer was investigated. 40 timed-pregnant rats were given DEHP by gastric intubation at doses of 0 (control), 750 mg/kg body weight/day from gestation day (GD) 12 to 19 to establish a hypospadiac rat model. In each group, half of them (10 rats) were raised to postnatal day 30 to observe hypospadias incidence. The left (10 rats) were caesarean delivered at GD 20, and fetal rats penis were collected for real-time quantitative polymerase chain reaction and immunochemistry to determine the mRNA expression and protein phosphorylation level of JNK1/2. The hypospadias incidence of DEHP maternal exposure group was 30.6%. Compared with controls, significantly decreased numbers of live male pups, body weight and AGD were observed (all P=0.000). JNK1 and JNK2 mRNA expressions in DEHP group increased significantly (P=0.018 and P=0.049, respectively). Subjects with DEHP exposured had increased phosphorylation protein expression of JNK1/2 in the mesenchymal cell layers of the preputial subcutaneous. Our findings suggest that DEHP produce reproductive and developmental toxicity, and JNK up-regulation may contribute to the development of hypospadias.
Gandhi Medical College, India
Time : 12:00-12:20
Neelam Shrivastava had completed MBBS in 1988 from Indore University India and LLB from Bhopal University in 1999. She has worked in Public Health Department as Assistance Surgeon till 1996 and since last 18 years she is working as a Medical Officer in Medico Legal Institute, Gandhi Medical College, Bhopal, India. There, she has done more than 5000 autopsies of different nature and expert opinions. She has also presented two international papers i.e. one in Istanbul, Turkey and another one in Goa, India.
One of the causes for suicide in young and unmarried females is illegal relationship which turns into pregnancy. To hide the shameful condition, female commits suicide and sometimes during autopsy, due to misdiagnosis of pregnancy parents have to face embarrassing condition. On the other hand if finding of pregnancy is not detected during autopsy and product of conception is not preserved for DNA test then accuse will exempted from punishment. Therefore, an accurate test of pregnancy is essential. The proposed method is easy and confirmatory test for the same which is done by examining urine for HCG (Human Chorionic Gonadotrophin) of deceased by HCG strip.
Lyon University, France
Time : 12:20-12:40
Nina Attik has completed her PhD (European PhD) with high honors from Nancy University (Pharmacy school) and Postdoctoral studies from Lyon University (Dental school). She is the winner of the Support Program for the Creation of Innovative Companies in the Mediterranean (PACEIM: 2011). She has published more than 15 papers in reputed journals and has participated as speaker in different conferences and meetings (national and international). She had also conducted many research European projects and manages many laboratory budgets.
It is generally accepted that in vitro cell material interaction is a useful criterion in the evaluation of dental material biocompatibility. The objective of this study was to use 3D CLSM time lapse confocal imaging to assess the in vitro biocompatibility of dental composites. This method provides an accurate and sensitive indication of viable cell rate in contact with dental composite extracts. The ELS extra low shrinkage, a dental composite used for direct restoration, has been taken as example. In vitro assessment was performed on cultured primary human gingival fibroblast cells using Live/Dead staining. Images were obtained with an FV10i confocal biological inverted system and analyzed with the FV10-ASW 3.1 Software. Image analysis showed a very slight cytotoxicity in the presence of the tested composite after 5 hours of time lapse. A slight decrease of cell viability was shown in contact with the tested composite extracts compared to control cells. The findings highlighted the use of 3D CLSM time lapse imaging as a sensitive method to qualitatively and quantitatively evaluate the biocompatibility behavior of dental composites.
- Track 14: Nanomaterials
Track 15: Particle and Fibre Toxicology
Track 16: Venomous Animals and Toxins
Track 17: Countersteps towards Toxicity
Location: Versailles - B
Lúcia Helena Faccioli
University of São Paulo, Brazil
All India Institute of Medical Sciences, India
University of Sao Paulo, Brazil
Title: Tityus serrulatus venom induces inflammation by mechanism dependent on lipid mediator release and lipid bodies’ formation
Time : 12:40-13:00
Lúcia Helena Faccioli has completed her PhD from São Paulo University (USP) and Postdoctoral studies from National Heart and Lung Institute, London in 1989-1990. She is full Professor in Immunology and Class 1A Researcher for the National Council for Scientific and Technological Development, since 2007; Head of the Laboratory of Inflammation and Immunology at School of Pharmaceutical Sciences of Ribeirao Preto-USP and member of Postgraduate Committee on Basic and Applied Immunology, at Ribeirão Preto School of Medicine-USP. She has published more than 130 papers in reputed journals and serving as an editorial board member of repute.
Tityus serrulatus venom (TsV) induces a severe systemic inflammatory reaction that can result in death. For this reason it is very important to understand the mechanisms responsible for the induction of inflammatory mediators release after envenomation. It was demonstrated that TLR2, TLR4 and CD14 receptors sense TsV and its major component, toxin 1 (Ts1), to mediate eicosanoids release and inflammation. Eicosanoids such as LTB4 and PGE2 are metabolites from arachidonic acid (AA) released from cell membranes after phospholipase A2 (PLA2) action. Consequently, the intracellular signaling cascade leading to production of eicosanoids, and the participation of lipid bodies (LBs) as functional organelles for LTB4 and PGE2 synthesis induced by TsV was investigated. Data revealed that TsV induced LBs formation on macrophages by mechanisms dependent on TLR2 and TLR4 recognition, and activation of the nuclear receptor PPARγ. Based on the data, it was suggested that during envenomation, LBs are the functional organelle for eicosanoids production andinduction of inflammatory reaction triggered by TsV. Finally, the term venom-associated molecular pattern (VAMP) was suggested to indicate molecules that are introduced into the host by stings and are recognized by PRRs, resulting in inflammation.
University of Calabar, Nigeria
Time : 13:00-13:20
Friday EUboh completed his Ph.D at the age of 35 from University of Calabar, Calabar, Nigeria, and is presently an Associate Professor of Biochemistry, with Toxicology as his area of research interest. He served as the acting Head of Biochemistry Department in the Department of Biochemistry University of Calabar, Calabar, Nigeria, from 2011 to 2013. Dr. Uboh is a member of Nigerian Society of Biochemistry and Molecular Biology, and Institute of Public Analysts of Nigeria. He has more than 60 papers published in reputable Journals, and is a reviewer and editorial board member of many Journals of repute. He has also presented many conference papers, locally and internationally.
Diesel fuel has been reported to cause hepatotoxicity in experimental animal models. This study assessed the protective effect of Vitamins A and E against diesel fuel-induced hepatotoxicity in rats. Vitamins A (retinol) and E(α-tocopherol), at prophylactic dosage (400 and 200 IU/kg/day, respectively) were orally administered, separately and as combined therapy, torats orally exposed to 4.0 ml/kg body weight of diesel fuel, once daily for 30 days. Serum lipid profile, including cholesterol, triglycerides, low density lipoproteins (LDL), very low density lipoproteins (VLDL) and high density lipoproteins (HDL); serum liver enzymes, including alanine and aspartate aminotransferases (ALT and AST), alkaline phosphatase (ALP) and gamma glutamyltransferase (GGT) activities; and liver tissue oxidative stress bioindicators, including malondialdehyde, catalase and superoxide dismutase (SOD) activities, were estimated using standard methods. A significant (p<0.05) increase in serum cholesterol, LDL, triglycerides, VLDL, liver tissue malondialdehyde levels, serum ALT, AST, ALP and GGT activities; and a significant decrease in serum HDL level,liver tissue catalase and SOD activities were recorded for rats orally exposure to diesel fuel, compared to control. Concomitant administration of vitamins A and E, respectively, to rats exposed to diesel fuel produced a significant (p<0.05) increase in serum HDL level, liver tissue catalase and SOD activities; decrease in serum cholesterol, triglycerides, LDL, VLDL, liver tissue malondialdehyde levels, serum ALT, AST, ALP and GGT activities; with vitamin E showing a higher potency than vitamin A. However, the effect of combined therapy of vitamins A and E was not significantly different (P>0.05) from that recorded for individual vitamins. The results of this study indicated that vitamins A and E provide protection against diesel fuel-induced hepatotoxicity; and that vitamin E is a more potent antioxidant than vitamin A in rats.
All India Institute of Medical Sciences, India
Title: Snake bite poisoning: A twelve years retrospective analysis of telephone calls reported to the National Poisons Information Centre, All India Institute of Medical Sciences
Time : 14:00-14:20
Amita Srivastava, working as Poison Information Consultant in the National Poisons Information Centre of AIIMS has completed her PhD degree at the age of 29 years from Indian Institute of Technology, Kanpur, India. She has published a number of papers in national and international journals. She is a life member of Society of Toxicology, India and also the member of Indian Society of Toxicology. She is in the panel of reviewing committee of Indian Journal of Pharmacology. She has been co-guide of many PhD students of AIIMS. She has a rich experience of handling sophisticated laboratory instruments like Inductively Coupled Plasma and Atomic Absorption Spectrophotometer.
Snake bite poisoning is a public health problem that takes a heavy toll of human lives in India. The exact incidence of morbidity and mortality is not available due to paucity of data. The present study was carried out to determine the incidence of snake bite envenomations reported to the National Poisons Information Centre, Department of Pharmacology, All India Institute of Medical Sciences, during a period of twelve years (April 1999-March 2011). Analysis of the data showed a total of two hundred and ninety cases. Majority of bites were due to elapids (82.77%) followed by viperids (5.24%), non-poisonous species (2.62%) and unidentified snakes (9.36%) respectively. Most of the bites occurred during the months of July to September (56.89%). The age group involved was between 18-40 years with a high incidence in males (73.12 %). The bites were mainly reported in lower extremity (50.18%) followed by upper extremity (31.85%). Bites over the face, ear, neck, abdomen, eyebrows comprised 9.73%. There were few cases where bite area was not identified (8.23%). Anti snake venom was administered to all patients but the optimal dose, frequency of administration and duration of therapy was variable. Poor health services, difficult transportation, and delay in the anti snake venom administration especially in rural areas are the important factors responsible for high mortality. The study highlights that awareness about early medical interventions is mandatory. Morbidity and mortality may be reduced if the National Protocol on snake bite management formulated by the Ministry of Health & Family Welfare, Government of India is followed by the health care facilities in the country.
Gachon University, Republic of Korea
Title: Assessment of ZnO and SiO2 nanoparticle permeability through blood–brain barrier and their toxicity using Evans blue and TEM
Time : 14:20-14:40
Seong Soo A An has completed his PhD from Carnegie Mellon University and Postdoctoral studies from Cornell University. He is the Associate Professor at Gachon University in the Department of Bionanotechnology and adjunct member at Gachon Medical Research Institute at Gachon University School of Medicine. He has published more than 100 papers in reputed journals and serving as an editorial board member of journals of following, Toxicology and Environmental Health Sciences, Molecular & Cellular Toxicology, and Rapid Communication in Photoscience.
Various nanoparticles (NPs) are being used in many products from paints, chemical processing, cosmetics and foods. Many of the toxicity studies with NPs suggested that their sizes alone cannot adequately explain the variety of gener¬ated toxic profiles. Recent studies with NPs have suggested that various sizes of NPs could determine in vitro toxicity, regardless of their chemical properties. In an attempt to address concerns regarding neurotoxicity of zinc oxide (ZnO) and silica oxide (SiO2) NPs, they were examined after exposing them via oral, dermal, and intravenous administrations of NPs and their toxicological effects on the brain over a prescribed period of time were assessed. Physiochemical profiles were determined on particle sizes at the beginning of the current toxicity investigations on ZnO and SiO2 NPs. After 28 days of repeated oral administrations of ZnO or SiO2 independently, damages to the blood–brain barrier (BBB), possibly due to neurotoxicity, were investigated by Evans blue technique. Next, in order to assess whether ZnO NPs could compromise the BBB, ZnO NPs were intravenously injected five times for 35 days, with 7 days terms in total of 90 days of termination. Deposition of SiO2 in brain from repeated dermal and oral administrations for 90 days were probed by transmission electron microscopy coupled with scanning energy-dispersive X-ray spectroscopy.
Cranfield University, United Kingdom
Time : 14:40-15:00
Claudia Moia obtained her First’s Degree in 2009 and her Master’s Degree in October 2011 in Biotechnology at the University of Pavia (Italy). As of May 2012 she is working as an Early Stage Researcher in Cranfield University (UK) as part of EU-funded Marie Curie ITN (initial training programme) network called NANODRUG, aiming to complete her PhD in Toxicology in May 2015.
Silica nanoparticles (SiNP) have been increasingly appliedin biomedical areas includingimaging and drug delivery. Although their bulk counterpartsare generally regarded safe, the safety of SiNP and submicron silica particles (SMP) is yet to be established. This study aimed to investigate the size relevance of silica particles (SiP) in toxicity using twohuman skin cellsin vitro. Since fetal bovine serum (FBS) is commonly used in cell culture to mimic in vivo environment, SiP toxicity is also investigated in the presence and absence of FBS to model the consequences of exposure via systemic and topical routes. SiPsof different size were assessed at 10-200 µg/ml for their effect on cell growth, viability, and ability to induce apoptosis. SiNP20 nm induced toxicity in keratinocyte HaCaT and melanoma A375 cells in the presence and absence of FBS, whilst SiNP 70 nm, SMP200 nm and SMP500 nmwere toxic only in HaCaT cells in the absence of FBS. The toxicity in both types of cells was associated with the reduction of cell viability and induction of apoptosis. This study demonstrated size-dependent toxicity of SiP in both cell lines, with HaCaT beingmore sensitive.SiPshowed higher toxicity in the absence of FBS than in the presence of FBS, suggesting that they could be more toxic via topical route than systemic route. As no blood supply can reach epidermis where keratinocytes and melanocytes are located, SiP can interact directly with these cells, leading to toxicity.
Daegu Gyeongbuk Institute of Science and Technology (DGIST), Republic of Korea
Title: Toxicity analysis of PbS nanoparticles using nano-sized vesicles (exosome) excreted from HEK293 cells
Time : 15:00-15:20
Eunjoo Kim finished her PhD in Environmental Toxicology in 2000 from Seoul National University. She has been worked as Principle Research Scientist at Daegu Gyeongbuk Institute of Science and Technology (DGIST) from 2005. Her major research field is toxicological pathology based on identification and analysis of biomarkers, and has been developed for biosensors to detect important biomarkers effectively. Recently, she has been started to focus on exosome studies for identification of serum biomarkers for disease and toxicology.
Tremendous research efforts have been devoted to fabricating high quality quantum dots (QDs) for applications in biology and medicine. However, a great deal of concern has been demonstrated about the potential hazards of QDs due to their heavy-metal content. In this work, we present the results of the cytotoxic study with PbS QDs modified with 3-mercaptopropionic acid (QD-MPA, ~10 nm). Small nucleotides known to participate in regulation of mRNA expression, miRNAs, were excreted into culture media following encapsulation by nano-sezed vesicles (~50 nm) called “exosome”. To investigate the pathological toxicity caused by QD-MPA, exosomes excreted from HEK293 cells were analyzed to see the genomic and proteomic biomarker changes. Exosome also contains proteins as a consequence of toxicological changes by environmental stressors. In this study, the change of exosome miRNA profiles was analyzed followed by an exposure of QD-MPA to HEK293 cells. As a result, 15 differentially expressed genes (DEG) were determined. A pathway analysis by IPA (Ingenuity Pathway Analysis) database showed that the DEGs caused by QD-MPA were primarily involved in cancer and organismal injury and abnormalities. A proteomic analysis in exoxomes also supported that the cancerous change was occurred by QD-MPA exposure. IRR23b and keratin 5 were identified as biomarkers for QD-MPA exposure identified in exosome proteomes. These proteins are also known as cancer biomarkers. When comet assay was performed whether DNA alteration was occurred, the results clearly showed that DNA fragmentation was occurred following the QD-MPA exposure. In conclusion, QD-MPA nanoparticles shows carcinogenic activities, and these pathological changes could be identified by genomic and proteomic analysis for secreted exosomes, which could provide an effective protocol to identify a possible pathological toxicity.
Award Ceremony for Best Posters