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Plenary Talks

Abstract

The CH3NH3PbI3perovskite, is currently the most promising compound in photovoltaic (PV)technologies for making highly efficient solar cells due toits high efficiency in converting light into electricity, to itssimple fabrication procedure and low price. Several companies are already building perovskite-based PV devices for commercialization in the near future. Nevertheless, this material containsPb, and safety concerns during PV device fabrication and transportation have not yet been addressed. . Here we report an extensive toxicity study of the two most promising photovoltaic perovskitesCH3NH3PbI3and CH3NH3SnI3. The zoom-in in vitrostudies on epithelial and neuroblastoma cell cultures show severe toxic effects of both materials: modification of the genes upon perovskite exposure, biochemical and structural changes.The zoom-out in vivo studies on model living organisms (C-elegans and Drosophila) show changes in life cycle and early death even at low concentration of perovskite uptake. Acknowledgment: The work is performed in collaboration with Ines Benmessaoud, Anne-Laure Mahul, Hilal Lashuel, Massimo Spina, Bohumil Maco, B. Deplancke, and Endre Horvath and many others. The research of L.F. is supported by the ERC Advanced Grant Picoprop

Biography

László Forró obtained his B.S. at Eötvös Loránd University, Budapest and M.S. at Université Paris XI in physics. He received his PhD at the University of Zagreb in 1985. He was appointed at the Ecole Polytechnique Fédérale de Lausanne in1991 as senior research associate. He was promoted into a full professorship in 2002. Today he holds the chair of Nanostructures and Novel Electronic Materials.In his Laboratory of Physics of Complex Matter (http://lpmc.epfl.ch/) he is leading an interdisciplinary research activity. His honors and awards: Member of the Hungarian, Croatian,Serbian Academies of Sciences.

Speaker
Forro Laszlo / Laboratory of Physics of Complex Matter, Switzerland

Abstract

Despite extensive pre-clinical and clinical safety studies, multiple drugs have been withdrawn from the market, because of severe adverse drug reactions (ADRs). Which risk factors determine (variability in) the susceptibility of patients, notably also of rare and unpredictable “idiosyncratic” drug reactions (IDRs), are still incompletely understood. The fact that many drugs causing ADRs or IDRs are bio-activated to chemically reactive metabolites (CRMs) and/or that the protection against the CRMs is sometimes hampered, has led to the hypothesis that covalent binding of reactive drug metabolites (CRMs) to cellular proteins might initiate a cascade of events ultimately resulting in sometimes fatal ADRs or IDRs, for example by haptenizing proteins and related immune reactions. Certain HLA-alleles show a strong association with ADRs or IDRs of specific drugs. Alternatively, genetically determined polymorphisms or other causes of variability in the biotransformation enzymes involved in the bio-activation to and/or enzymatic protection against reactive drug metabolites (CRMs) are likely also risk factors for ADRs and IDRs. In this presentation, experimental approaches and molecular mechanisms leading to ADRs and IDRs will be illustrated and discussed using typical examples, such as Acetaminophen, Amodiaquine, Clozapine, Diclofenac and Nevirapine. Notably the activity as well as the inter-individual variability of biotransformation enzymes, such as Cytochromes P450 (CYPs), NAD(P)H Oxido-reductases (NQOs), Glutathione S-transferases (GSTs), Glucuronyl- and Sulfo-transferases (UGTs and STs) will be considered. Possible strategies for the translation of molecular mechanisms and inter-individual differences to ‘personalized drug safety and therapy’ will be illustrated and some related regulatory aspects will be touched upon briefly as well.

Biography

Nico P.E. Vermeulen (MSc in Chemistry (University of Nijmegen, 1975) and a PhD in Pharmacology (University of Leiden, 1980), was appointed professor of Molecular Toxicology in the Department of Chemistry and Pharmaceutical Sciences (CPS) at VU University Amsterdam, in 1985. Recently, he was Head of the Department of CPS (2009 - ‘15) and also Director of AIMMS (Amsterdam Institute of Molecules, Medicines and Systems; 2010 - ‘17) and, amongst others, coordinator of SafeSciMET, an IMI-JU consortium, and WP-Leader in two other IMI-JU projects: eTOX and MIP-DILI. He was awarded with the European ISSX Scientific Achievement Award (2006), an Honorary Doctorate (University of Copenhagen, 2011) and he is a Life Time Honorary Member of ISSX. He is author/co-author of more than 450 scientific publications in the fields of molecular toxicology/pharmacology, bioanalysis and medicinal chemistry. His general research interests are concerned with the roles molecular and computational toxicology can play in drug discovery, development and safety assessment. More specifically, he is interested in toxication/detoxication mechanisms, in silico and in vitro prediction and screening of ADME-Tox properties, (biocatalytic) metabolite production and profiling and translational biomarkers of adverse drug reactions (ADRs).

Speaker
Nico P.E. Vermeulen / VU University,Netherlands

Abstract

Biography

Prof. Dr. med. Helmut Greim was chairman of toxicology and director of the Institute of Toxicology and Environmental Hygiene at the Technical University in Munich from 1987 to 2003. He was head of the Institute of Toxicology, GSF-Forschungszentrum für Umwelt und Gesundheit in Neuherberg, Germany, from 1975 to 2000. After receiving M.D. degrees from medical schools in Freiburg and Berlin, Prof. Greim was associate professor of pharmacology and toxicology in the Department of Toxicology at the University of Tübingen and research associate professor of pathology at the Mount Sinai School of Medicine, New York, from 1970 to 1973. He has served on a number of committees, including the German Society of Pharmacology and Toxicology and the Board of Experts on the Environment for the German Federal Ministry of the Environment. He served as chairman of the Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK, 1992 - 2007), was chairman of the German Advisory Committee on Existing Chemicals (BUA, 1998 - 2007) of the Gesellschaft Deutscher Chemiker (GDCh), and was a member of the Enquète-Commission Environment and Health of the German Parliament (1992 – 1994). In 1998 he received the Arnold J. Lehman Award of the Society of Toxicology. He serves as chairman of the EU Scientific Committee on Health and Environmental Risks (SCHER) and is a member of the EU Scientific Committee on Occupational Exposure Limits (SCOEL) and of the Risk Assessment Committee of the European Chemicals Agency (ECHA). Prof. Greim has published over 300 papers in scientific journals

Speaker
Greim, Helmut / Technical university of munich, Germany

Keynote Talks

Abstract

BackgroundPrenatal phthalate chemicals may have adverse effects on brain development. However birth cohort findings have been conflicting and prospective data on autism is rare. MethodsAn Australian population-based birth cohort of 1064 women with prenatal recruitment. Maternal urine was collected at 36 weeks of pregnancy and phthalate metabolite concentrationsmeasured. A summed phthalate measures was derived from the daily intake values for DEP, DBP and DEHP. Parents completed questionnaires for doctor diagnosed autism spectrum disorder (ASD) (n=11), ASD traits (n=39)at four years. SNP data was generated using the Illumina GSA genotyping platform. Analyses include multiple linear and logistic regression. FindingsHigher prenatal summed phthalate levels were associated with subsequent ASD and ASD traits (AOR 2.25(95% CI 1.11 to 4.53); p=0.02 and 1.64 (1.14 to 2.36) p=0.008per SD unit increase respectively). Of the individual chemicals, the oxidised metabolites of DEHP had the strongest association with ASD. These findings did not differ materially by sex and persisted after extensive confounder adjustment and correction for potential selection bias. Gene-environment interaction was also evident. Interpretation Higher prenatal phthalate levelsare associated with a higher likelihood of ASD or ASD traits. Current recommendations and regulation on maternal phthalate exposure during pregnancy require re-evaluation.

Biography

Speaker
Ponsonby Anne-Louise / Murdoch Children's Research Institute, Royal Children's Hospital Melbourne, University of Melbourne, Victoria, Australia

Abstract

With rapid global advancement and an exponential growth rate in the EEE (electrical and electronic equipments) industries in the 21st century has come a corresponding change in consumer lifestyles, resulting in the generation of a huge amount of end-of-life electronics, known as electronic waste (e-waste). Moradabad, also known as “Brass City of India”, has become one of biggest informal e-waste recycling hubs in India because of cheapest labour cost and week legislations systems. Traders estimate about 80% circuit boards used in appliances end up in Moradabad. The objective of this study is to appraise the levels of heavy metal contamination within the vicinity of the Moradabad city. Surface dust samples were collected from various points near e-waste burning sites and its surrounding areas. Atomic absorption spectrophotometer preceded by acid digestion was used to evaluate the concentration of the heavy metals like Pb, Cd, Ar, Hg, Zn Cu, Cr, Ni etc. in the samples. Different soil indices like contamination factor (CF), Index of geo-accumulation (I-geo) and pollution load index (PLI) were calculated to determine the quality of the soil. All soil indices which were employed to determine the level of pollution, indicates extreme level of metals at all the study sites. The results show that the main sources of contamination are illegal e-waste recycling activities such as burning of PCB's, dismantling segregation, acid baths, grinding and washing etc. The risk of exposure to a particular toxicant i.e. the Hazard Quotient (HQ) was also calculated which indicate that children living around the scrap market and engaged in these activities face a very high risk of ingestion of toxic metals such as Pb, Cd, As and Hg. It was concluded that the exceedance of metal contamination imposed negative impact to the soil environment and human health.

Biography

Speaker
Anamika Tripathi / Hindu College, India

Abstract

Lindane (gamma-hexachlorocyclohexane) is organochloride extensively used in agriculture as insecticide and pesticide and medicine as scabicide, still widely used in undeveloped and developing countries. Due to frequent intoxications, adverse effects on numerous organ systems, as well as potential carcinogenicity, lindane usage has been limited in many countries. Seizures are one of the first and main manifestations of the lindane neurotoxic effects in humans and animals. These seizures are refractory to numerous classical and novel antiepileptic drugs. Lindane is documented to interact with the picrotoxin site within the GABAA receptor chloride channel and to suppress the chloride influx leading to repetitive epileptic activity, while other mechanisms of its proconvulsive activity are still unclear. We have characterized behavioral and EEG characteristics of seizure induced by lindane in rats which could be a suitable model of generalized seizures. Behavioral manifestations of seizure acitivity induced by lindane could be described by scale with following grades: 1 – head nodding, lower jaw twitching; 2 - myoclonic body jerks (hot plate reaction), bilateral forelimb clonus with full rearing (Kangaroo position); 3 – progression to generalized clonic convulsions followed by tonic extension of fore- and hind limbs and tail and 4 – prolonged severe tonic-clonic convulsions lasting over 10 sec (status epilepticus) or frequent repeated episodes of clonic convulsions for an extended period of time (over 5 min). By using this model, we examined the effects of different potential antiepileptic, as well as mechanisms of lindane action. We showed functional involvement of nitric-oxide signaling pathway in seizure initiation and development by lindane. We will discuss herein mechanisms of lindane neurotoxic effects with recommendation for further exploration of lindane model of generalized seizures.

Biography

Olivera Stanojlovic, MD, PhD is full professor of Medical Physiology, head of Laboratory of Neurophysiology at Belgrade University Faculty of Medicine. The topics of her research activities are neurophysisology, somnology, epileptology with focus on neurotoxicological aspects of different compounds. She published (author or coauthor) more than 80 scientific papers in international journals.

Speaker
Olivera Stanojlovic / University of Belgrade, Serbia
Sessions:

Abstract

Even though trace concentrations of some elements, such as copper, are essential for life in some species, they can harm others. Sub lethal effects ofAs, Cr, Cu, Cr, Ni, Pb, and Zn were determined in rotifers. Rotifers, ubiquitous and abundant fresh and brackish water micro invertebrates, have been used as indicators of water. Two experiments were designed to determine effects in rotifers population dynamics and at a molecular level (metallothionein like proteins presence). Neonate rotifers from the Plationuspatulus species were exposed to single and metal mixtures at different concentrations (10-150 μg/L) and monitored to determine effects on population growth, reproduction and morphology (flatness) among environments: absence, low and high concentration of elements in a mixture. MTLPs presence was determined in rotifers species (P. patulus, Euchlanisdilatata, and Epiphanes senta) exposed to Cu (20μg/L), reacted with metallothioneinantibody and fluorescein to be analyzed by confocal microscopy. No deformed rotifers (flat shape) were observed in controls, but in metal treatments. No differences were detected among environments, but trends were observed in population growth (decrease of) and reproduction (shift to sexual mode of). Rotifers exposed to Cu (50μg/L) did not reproduce and show high mortality (0.8) compared to the control population (<0.1). MTLPs experimental trends may indicate a decrease of these proteins in P.patulus and E.senta species exposed to Cu. As presented, concentrations in the range of 20 to 50μg/L are enough to study sub lethal effects of Cu.

Biography

Judith V. Ríos Arana completed her PhD (2003) and M.Sc. (1999) from the University of Texas at El Paso. She is a Full Time Researcher Professor at Chemical and Biological Sciences Department of the Universidad Autónoma de Ciudad Juárez since 2014. Research interest topics include environmental toxicology (aquatic ecotoxicology), limnology of arid zones, and environmental education. She was a Fulbright Fellow on 2010, and has published 13 papers in reputed journals and has been serving as an editorial board member of repute.

Speaker
Fiorentina Roviezzo / Universidad Autónoma de Ciudad Juárez, Chih., México

Abstract

Sphingosine-1-phosphate (S1P) levels significantly increase in bronchoalveolar lavage (BAL) of asthmatic patients following segmental allergen challenge and this increase well correlates with pulmonary inflammation. Epidemiological, genetic, clinical and experimental data indicate a potential for the Toll-like receptor 4 (TLR4) to initiate and exacerbate allergic airway disease. The aim of this study was to evaluate the contribute of TLR4 in S1P-dependent asthma-like disease in mice. BALB/c or TLR4 defective (C3H/HeJ) mice received S1P (10ng/mouse), LPS (0.1µg/mouse) or S1P+LPS. Furthermore, S1P-treated BALB/c mice were injected with the purified rabbit anti-TLR4 antibody (10µg/mouse). S1P administration induced airway hyperreactivity and pulmonary inflammation associated to an increase in the percentage of dendritic cells and macrophages into the lung of BALB/c mice. These effects were coupled to a reduction of dendritic cells in the mediastinic lymph node. All these S1P-mediated effects were absent in TLR4 defective mice or reversed by treatment with a purified rabbit anti-TLR4 antibody. Confocal analysis of pulmonary sections showed a significant increase in TLR4+ cells and a similar presence of S1P1 and TLR4 following S1P challenge. Accordingly, the immunoprecipitation evidenced an increased S1P1/TLR4 interaction. In conclusions, our findings suggest thata functional interaction between S1P1 and TLR4 leads to an enhanced allergic inflammatory response. Thus, S1P pathway contributes to the sentinel role played by innate immunity providing new targets for prevention and treatment of allergic airway diseases.

Biography

Speaker
Fiorentina Roviezzo / University of Naples Federico II, Italy

Abstract

The talk will be concerned with toxicology of cancer chemo or immune therapy. I have defined mathematical models of cancer growth and chemo or immune therapy. A three dimensional discrete dynamical system, i. e. a map, and an ordinary differential equations model in variables cancer, growth factors and growth inhibitors. So there is cancer and positive control and negative control. These mathematical models can predict how to give chemo or immune therapy optimally. See [1] and [9] below. There is an induced dynamical system, that describes the cancer growth with the optimal chemo or immune therapy. If time permits I shall explain fundamental mathematical concepts of dynamics applicable to problems in medicine.

Biography

Jens Christian Larsen graduated from The Technical University of Denmark in 1988 and got a Ph D degree from the Mathematics Institute of the Technical University of Denmark in 1991. After that he had post doc positions for six years and then an assistant professorship from The Royal Veterinary and Agricultural University of Denmark.

Speaker
Jens Christian Larsen / Denmark

Abstract

Glyphosate is rightly considered to be a once in 100 year herbicide and it has been a force for change agronomically, biologically, socially, financially, and psychologically for those that have used it. It was rapidly labeled for use by the US EPA, with full registration in less than three years. While many users consider it to be benign, this view is becoming challenged. The World Health Organization’s International Agency for Research on Cancer denoted glyphosate as a ”probable carcinogen to humans”. There have been several responses to this allegation and this presentation will focus on this important topic. The author conducted a literature review of the last five years of glyphosate toxicology data with respect to mammals. There is a huge body of evidence that has historically shown glyphosate is safe to use when label directions are properly followed, but in more recent years there have been studies with isolated experimental systems that introduced the idea of subtle chronic effects of glyphosate. Examples of test systems include the comet assay, long-term toxicity in rodents, shifts in microbial populations, activity-based protein profiling to map glyphosate targets in mice, plasmatic level determinations of glyphosate, neurotoxicity studies in mammals including axon development, and other research platforms. This presentation will discuss this body of knowledge on glyphosate and its effect on humans.

Biography

Thomas C. Mueller is a Professor in the Department of Plant Sciences at the University of Tennessee. He received his BS from the University of Illinois in Agronomy, his MS from the University of Kentucky in Crop Science, and his PhD from the University of Georgia in Crop Science. His primary research areas are environmental fate of pesticides (especially herbicides) in soils, water systems, and in the air (via drift), and the confirmation and subsequent control of herbicide-resistant weeds. He has published > 120 refereed articles in > 20 different journals. Dr. Mueller has served on an US-EPA Scientific Advisory Board, has served as an associate editor for Weed Science and Weed Technology, has served on the executive board for the Weed Science Society of America as Secretary, and was named a fellow of the WSSA in 2014.

Speaker
Thomas C Mueller / University of Tennessee, United States

Abstract

Glass ampoules are widely used in the packaging of injectable drug products. Many opening systems, such as CBR (Color-Break-Ring) or OPC (One-Point Cut) have been developed for the safe opening and reduced risk of contamination from glass microparticles. Lead (Pb) isa human toxicant and belongs to Class 1 of the ICH Q3D Guideline, which signifies higher toxicity and thus specific thresholds as per the daily intake (PDE) are set. In sample analysis of injectable drug products, Pb was detected ata concentration equal to 5.6% of the permitted concentration. Although the concentration was below the control threshold (30% of PDE), an investigation was conducted to determine whether the source of Pb present in an injectable solution could be attributed to the breaking ring color of the ampoule. In that sense, empty ampoules with CBR, ampoules with OPC and shattered glass without marks were analyzed. The validated methodology employed a sonication assisted extraction, usingan aqueous solution adjusted to pH 2.0. Analysis of the extracts was performed by using an ICP-MS instrumentation. Pb was found present at high concentrations in the samples with the breaking ring. On the contrary, Pb was not detected in the unmarked glass pieces or in the samples with the OPC. Finally, a comparison has been performed in drug products, by employinga customized opening procedure; the ampoules were opened by cutting the top of each ampoule, instead of using the breaking ring. A cleaner profile with regards to Pb was acquired. These results indicate that the presence of Pb is associated specifically with the white breaking ring of the glass ampoule.

Biography

Pharmacist with an MSc and PhD in Pharmaceutical Analysis.Author of 17 novel research papers in the international literature.Quality expert on chemical pharmaceutical products with integrated experience in the Pharmaceutical Quality System and products’ lifecycle management. Began his career as a Laboratory Manager in a company specialized in bioequivalence studies. In 2007 he joined the National Organization for Medicines, served as a Quality Assessor and as a member of the Laboratory of Human Medicines, a part of the OMCL network, conducting among others the post approval market surveillance. Since 2012, successively served all key positions in the field: as an RnD, Bioanalysis, Quality Control and Quality Assurance Senior Manager.

Speaker
Constantinos Kousoulos / Qualimetrix Analytical laboratories , Greece

Abstract

From 2010-2018 557 drugs gained market authorization; their risk evaluation was published in European Public Assessments Reports (EPAR) by the European Medicine Agency (EMA). These are the results of our analysis: No carcinogenicity studies have been performed for generic products (n=156), biosimilars (n=28), drugs with informed consent applications (n=31) or in compliance with EMA guideline for fixed combinations (n=52) and hybrid application (n=33). For 75 biotechnology-derived medicinal products (see ICH S6 (R1)) standard carcinogenicity bioassays are generally inappropriate, but evaluation of their neoplastic potential was needed in 9.6 % (n=7) due to concern. Finally there are 104 experiments for 229 drugs (45,4%) for which the sponsors conducted carcinogenicity bioassays with the active substance: In 57/104 cases (54.8 %) a traditional strategy (long-term carcinogenicity bioassay in rat & mice) was chosen; for 31/132 (26 %) compounds the ICHS1C alternative approach (1 long-term bioassay in rats & a short-medium-term study using transgenic mice) was performed. Until 2010 only in 5,5% (Friedrich et al., 2010). The preferred animal model for bioassays was the rat, 2 times hamsters; as transgenic rodent , mainly rasH2 mice. Final outcome of the studies: 39.4 % revealed a positive carcinogenic assessment in a least one species. In the majority of cases this positive result was assessed as “no hazard for humans”. Only 3 drugs, indicated for anti-cancer treatment, were identified as clearly carcinogenic (Dacogen, Lonsurf, Onivyde). In a minority of cases carcinogenicity potential could not be excluded or was low. Only in few cases post-marketing measures were required.

Biography

G. Bode has completed his PhD at the University of Duesseldorf and his habilitation at the University of Goettingen, Germany. He is board certified expert in Pathology, Neuropathology, Legal Medicine, Pharmacology and Toxicology. He was head of Drug Research Institutes in Germany and France. He has published more than 130 papers and has served as Topic Leader for Safety at the International Conferences on Harmonization for 16 years. Sandra Wagner completed her Master in Regulatory Affairs at the University of Bonn, Germany

Speaker
Gerd Bode / University of Goettingen, Germany

Abstract

There has been emerging interest in the application of cannabinoids in medicine, and several have been tested as drugs for a variety of disease processes. Synthetic cannabinoids (SCBs) are rapidly emerging drugs of abuse, which can result in extreme agitation, hallucinations, tachycardia, syncope, and seizures, and their use has exploded in many sections of the population including teenagers. However, the metabolism of classical and synthetic cannabinoids and the biological activity of their metabolites, produced by cytochrome P450s (P450s) and UDP-glucuronosyltransferases (UGTs), have not been thoroughly investigated. In the present studies, the oxidative and conjugative metabolic pathways of classical cannabinoids, such as ∆9-tetrahydrocannabinol (∆9-THC), and SCBs were compared. Cannabinoids underwent extensive metabolism by P450s and UGTs resulting in the biosynthesis of hydroxylated and carboxylated metabolites that were subsequently excreted in human urine, primarily as glucuronides. Steady-state kinetic analyses were performed, and rigorous metabolite identification was carried out using LC-MS/MS and HPLC-UV/Vis. Subsequent mechanistic studies involving binding and activation of cannabinoid receptors (CBRs) CB1 and CB2 showed that SCBs caused psychoactive effects similar to those of ∆9-THC. Moreover, CBRs were able to bind several hydroxylated and glucuronidated SCB metabolites with an affinity similar to that of the parent compound. Finally, our in vivo data demonstrated that SCB metabolites retained biological activity in mice. The fact that some hydroxylated derivatives and the glucuronides of SCBs are biologically active makes the study of these compounds essential for understanding their severe toxicity and pharmacokinetics/dynamics. Studies on the bioactivity of classical cannabinoid metabolites are underway. (NIH/NIDA DA039143 ARP & PLP).

Biography

Anna Radominska-Pandya, a Professor of Biochemistry and Molecular Biology at UAMS, is the Editor in Chief for Drug Metabolism Review. She received her Ph.D. from the Institute of Biochemistry and Biophysics, Polish Academy of Sciences in Warsaw, Poland. She published 175 papers in peer-reviewed journals and received thirteen R01 grants from NIH and DoD. Research interests include: regulation and suppression of human UGTs and their role as anti-proliferative agents in cancers, interactions between UGTs and cannabinoid receptors, delivery of UGT genes and drugs into cancers using nanomaterial, and the roles of UGTs in biotransformaing drugs including marijuana and synthetic cannabinoids.

Speaker
Anna Radominska Pandya / University of Arkansas for Medical Science, United States

Abstract

Aberrant DNA methylation of specific genes have been found in Hexavalent chromium [Cr (IV)] exposed populations. While little is known about genome-wide DNA methylation profiles in Cr (IV) exposed workers. In our study, We measured DNA methylation in blood samples from 94 electroplating workers and 94 matched controls using a combination of Infinium Methylation450K Chip and targeted-bisulfite sequencing. QuantiGene Plex 2.0 assay was used to detect the mRNA expression of differentially methylated genes. ICP-MS were used to detect the concentrations of metals in blood and urine samples. The findings in population study were furtherly detected in a human lymphoblastoid cell line. Our results indicated that the concentrations of three heavy metals (Cr, Cd and Pb) in both serum and urine samples from workers notably exceeded those from controls. A total of 131 differentially methylated CpG sites were found using Methylation450K Chip between 30 exposure samples and 30 control samples.,with 81 CpG sites hypermethylated and 50 hypomethylated. After being confirmed in targeted-bisulfite sequencing for DNA methylation alterations and in Quantigene for mRNA expression, two novel epigenetic markers (SEMA4B and CD44) were found to be associated with Cr (IV) exposure. The effects of Cr (IV) on DNA methylation and mRNA expression of SEMA4B and CD44 were furtherly determined in human lymphoblastoid cell line. Our findings indicated that DNA methylation of SEMA4B and CD44 genes may act as potential biomarkers for Cr (IV) exposure, motivating further study of these two genes in investigating the mechanisms of Cr (IV) induced carcinogenesis.

Biography

Jianlin Lou has completed his PhD from School of Public Health, Zhejiang University, P. R. China and postdoctoral studies from School of Medicine, Zhejiang University, P. R. China. He is the vice dean of Zhejiang Academy of Medical Sciences. He is also the Chairman of Occupational Health and Occupational Medicine Branch under Zhejiang Preventive Medicine Society. He has published more than 40 papers in reputed journals and has been serving as reviewer for more than 15 journals.

Speaker
Jianlin Lou / hejiang Academy of Medical Sciences, China

Abstract

Botulinum toxin (BTX) is considered to be the most lethal substance known to mankind. With LD50 of 1ng/Kg, only one gram of crystalline poison has the ability to kill one million people (Zhang, Sun et al. 2010). The fatal poison is formed by Clostridia botulinum which is an anaerobic, gram‐positive, spore‐ forming bacillus that exists in soil and aquatic sediments all over the world. Once absorbed into the systemic circulation, BTX targets the motor nerve endings where it works to attack SNARE proteins (specialized proteins responsible for neuromuscular transmission) resulting ultimately in blockade of A. choline release in the neuromuscular junction(Berliocchi, Fava et al. 2005). This in turn results in flaccid paralysis which involves quickly the diaphragm and respiratory muscles which ultimately results in respiratory arrest which is usually the cause of death (Witoonpanich, Vichayanrat et al. 2010). Owing to rarity of the disease, and overlap with other clinical presentations, botulism is considered a challenging clinical diagnosis. Moreover, botulinum toxin has a very long half‐life and the course of the disease may approach more than one month even with antidote therapy(Brook 2006). Herein, we are reviewing two cases of Foodborne Botulism following intake of traditionally made salted fish. Both cases were hospitalized, admitted into ICU, received trivalent botulinum antitoxin, and required mechanical ventilation for about two to three weeks. We tried to add adjuvant therapy to the antidote aiming at shortening of the mechanical ventilation‐ dependent duration in these patients. Higher doses of Hydroxycobalamin were used with concomitant observation of the clinical response and weaning ‐off mechanical ventilation. We hypothesis that Cobalamin antagonizes the delayed effect of BTX by attenuating the process of neuronal apoptosis via its possible inhibitory effect to caspases.

Biography

Speaker
Islam / Dr. Soliman Fakeeh Hospital, Egypt

Abstract

Endocrine disruptor chemicals (EDCs) are pollutants that pose risks for human health. Most of them, due to their ubiquity and lipophilic nature, give rise to phenomena of biomagnification and bioaccumulation. Exposure to EDCs has been linked to various diseases such as.chronic inflammations and endocrine dysfunctions. We carried out a pilot study to monitor 14 chemicals, belonging to different chemical classes, in the serum of people living in a polluted area of southern Italy. The study was aimed at identifying possible relationships between exposure to these substances and development of thyroid tumours. Indeed, it was hypothesized that higher incidence of differentiated thyroid carcinoma (DTC) was related to the exposure to environmental pollutants, even at low doses. Serums of 55 patients with nodular thyroid disease (27 with a diagnosis of benign thyroid nodule and 28 with DTC) were analysed by liquid chromatography to determine the levels of the pollutants (including some EDCs as bisphenol A and diethylhexylphthalate). Significant relationships between DTC onset and serum levels of bisphenol AF and diethylhexylphthalate were found. Furthermore, we found that DTC onset was dose independent and its incidence more than fourteen times with respect to controls, probably as the result of direct carcinogenic activity rather than inhibitory action exerted on the thyroid. Although these preliminary data need larger prospective studies to be confirmed, they suggest that exposure to chemical pollutants interfering on the endocrine system can play a role in the development of thyroid cancer.

Biography

Master’s degree in Pharmacy (1996) and in Biology (1987) at Federico II University of Naples - Italy – where, to date, she is researcher at the Department of Pharmacy. She is author or coauthor of more than 50 research papers and more than 60 communications at symposia. Her main scientific interests are in: i) development of analytical methods for analysis of xenobiotics in various matrices and ii) studies on drug absorption, metabolism and interactions with biological membranes mainly performed by chromatographic methods employing Immobilized Artificial Membrane, Human Serum Albumin and α-Acid Glycoprotein.

Speaker
Lucia Grumetto / University of Naples Federico II Session,Italy

Abstract

Botulinum toxin (BTX) is considered to be the most lethal substance known to mankind. With LD50 of 1ng/Kg, only one gram of crystalline poison has the ability to kill one million people (Zhang, Sun et al. 2010). The fatal poison is formed by Clostridia botulinum which is an anaerobic, gram‐positive, spore‐ forming bacillus that exists in soil and aquatic sediments all over the world. Once absorbed into the systemic circulation, BTX targets the motor nerve endings where it works to attack SNARE proteins (specialized proteins responsible for neuromuscular transmission) resulting ultimately in blockade of A. choline release in the neuromuscular junction(Berliocchi, Fava et al. 2005). This in turn results in flaccid paralysis which involves quickly the diaphragm and respiratory muscles which ultimately results in respiratory arrest which is usually the cause of death (Witoonpanich, Vichayanrat et al. 2010). Owing to rarity of the disease, and overlap with other clinical presentations, botulism is considered a challenging clinical diagnosis. Moreover, botulinum toxin has a very long half‐life and the course of the disease may approach more than one month even with antidote therapy(Brook 2006). Herein, we are reviewing two cases of Foodborne Botulism following intake of traditionally made salted fish. Both cases were hospitalized, admitted into ICU, received trivalent botulinum antitoxin, and required mechanical ventilation for about two to three weeks. We tried to add adjuvant therapy to the antidote aiming at shortening of the mechanical ventilation‐ dependent duration in these patients. Higher doses of Hydroxycobalamin were used with concomitant observation of the clinical response and weaning ‐off mechanical ventilation. We hypothesis that Cobalamin antagonizes the delayed effect of BTX by attenuating the process of neuronal apoptosis via its possible inhibitory effect to caspases.

Biography

Speaker
Islam Kotb / Dr. Samir Abbas hospital, Jeddah. Egypt

Abstract

Humans are exposed simultaneously or sequentially to large numbers of chemicals from various sources. Even so, the chronic toxicity evaluations for chemicals are still performed for a single chemical each time using animal models in order to set appropriate reference doses and regulatory limits. These evaluations are not always relevant for real-life exposure scenarios where concurrent exposure to other chemicals usually takes place, at doses around or well below the regulatory limits. The US-EPA published Guidelines for the Health Risk Assessment of Chemical Mixtures in 1986. This work was followed later by the efforts The Agency for Toxic Substances and Disease Registry, OECD, European Commission, EFSA and CLP Regulation (Regulation 1272/2008/EC, 2015) that gives the opportunity to Industry to perform animal testing in commercial mixtures as a last resort to prove a toxicological hazard. Advances in toxicological evaluation of chemical mixtures have raised deep concerns on how mixtures affect environment and human health, especially regarding low-level, long-term exposure to which humans are routinely encountered. Leading experts in the field of toxicology and related areas have developed several methodologies for long-term toxicity study of non- commercial chemical mixtures design to simultaneous investigate several key endpoints like target organ toxicity, genotoxicity, endocrine disruption and systemic mechanistic pathways like oxidative stress. All these associated with modern omics technologies can lead to evaluate long-term health effects of chemical mixtures. The presentation of the preliminary results of these kinds of studies that are settled in different laboratories around the world and solutions for the problems that could appear during these studies represents the novelty that could change the concept of toxicology safety evaluations. Validated and harmonized methods are needed to integrate the multiple streams of evidence relevant to mixture toxicity assessment, to predict the toxicity of mixtures consisting of chemicals of already known toxicity, and to elucidate mechanisms of possible interactions between the chemicals in the mixture. Linking xenobiotic chemical exposure to health effects has been the subject of many experimental and epidemiological studies but still remains a matter of permanent controversies. This issue is complicated by the multiple mechanisms of xenobiotic toxicity often involved, the uncertainties related to long term and low dose xenobiotic exposure. Aging is a complex senescence process that follows maturation, and is characterized by time-related functional decline due to genetic, biochemical, physiological and anatomical degeneration in tissues and organ systems. Loss of genome integrity is a key feature in senescence and the consequent development of aging-related diseases and cancer. Telomeres are repetitive tandem DNA sequences that cap chromosomal ends, protecting the integrity of information-carrying DNA. However, telomere length decreases with aging (and therefore its protective activity), as a result of repeated cell replication or environmental factors, namely those involving inflammation and oxidative stress. Consequently, shorter telomeres have been linked with shorter lifespan, and telomere length has been suggested as a biomarker of aging. Additionally, the genetics of telomeres, including TERT gene which encodes telomerase, is highly involved in many neoplasia including differentiated thyroid cancer. This lecture will provide a discussion on the environmental factors that may influence telomere dynamics, including obesity-related chronic low-grade inflammation and leptin resistance, and substance abuse, as well its consequences, with focus on thyroid neoplasia. It will be also highlighted the use of metabolomics as an important clinical and research tool in the development of biomarkers of senescence, in which the usefulness of telomere length measurement is becoming recognized. Our study with drugs of abuse user’s revealed that median of telomere length is about 1.000 base pairs lower than the median of healthy population. In addition the telomere length was conversely related on annual opiates use. Conclusively older biological age compared as fact with chronological age, based on telomere length in drugs of abuse users.Repeated measurements at a distance of 6 months or a year can reveal the rate of change of the short telomeres, and response of patients to treatments, lifestyle, diet, supplementation and exercise modifications. Within our in vitro experiments in cell cultures we’ve been able to discover a potent natural molecule that activates telomerase up to 1300% in relation to the control cells.

Biography

Aristides Tsatsakis is the Director of the Department of Toxicology and Forensic Sciences of the Medical School at the University of Crete and the University Hospital of Heraklion. Dr Tsatsakis has written over 1000 publications (books and abstracts proceedings), over 400 of them in ISI journals. He is holder of several patents and has an extensive array of citations and reads /downloads to his papers. Dr Tsatsakis has given numerous keynote and plenary lectures in international congresses and was the promoter and chair of noumerous Symposiums and workshops in International Forum. He has coordinated as a PI in over 50 scientific research and technology projects and has established worldwide collaborations. Aristides Tsatsakis was elected EUROTOX President-Elect in 2012 served as President (2014- 2016) of the Federation of European Toxicologists and European Societies of Toxicology. Dr. Tsatsakis has a long standing activitiy as Editor in toxicology journals. Prof. Tsatsakis is Emeritus Professor for the Federal Institute of Hygiene and Toxicology in Moscow (2014), Doctor Honoris Causa of the Mendeleev Moscow University (2016), of the Far East Federal University (FEFU), Vladivostok 2017 and of the Carol Davila, in Bucharest (2017). In 2016 was elected Foreign Member of the National Academy of Sciences of Russia (FMRAS) and in 2017 of Fellow Academy of Toxicological Sciences (FATS, USA). Aristides Tsatsakis is the inspirator, founder and chief scientific officer of the University of Crete spin-off Company ToxPlus S.A. The main research interests of Professor Tsatsakis are biomonitoring of various xenobiotics in a variety of biological samples and linking of chemical chronic exposure at low doses with health problems and diseases and risk assessments. He developed numerous biomarkers of exposure and of effects for the pesticide and chemical toxicology area uncovering the mechanistic understanding of the mode of actions and adverse outcome pathways and clinical effects.

Speaker
Aristides Tsatsakis / University of Crete, Greece

Abstract

In this study, we describe the changes associated with three months of intermittent fasting and probiotic yogurt consumption in a 72-year-old marathon runner with chronic lymphocytic leukemia for a number of years. Serum alpha-N-acetylgalactosaminidase (nagalase), a marker of inflammation and cancer cell proliferation, was significantly decreased at the end of a three-month observation. These results are consistent with immune modulating properties of certain probiotics based on the fermentation of milk and colostrum. Urinary excretion of non-metal toxicants that accumulate in adipose tissue such as Perchlorate, N-acetyl (2-hydroxypropyl) cysteine (NAHP), 2, 4-Dichlorophenoxyacetic acid, 3-Phenoxybenzoic acid (3PBA), N-acetyl phenyl cysteine (NAP), Phenylglycoxylic acid (PGO), Monoethylphthalate (MEP) and 2-Hydroxyisobutyric Acid (2HIB) was significantly increased. These results are consistent with the weight loss (5 Kg) associated with intermittent fasting and with the known features of probiotics as detoxification tools. Consistent with certain toxicants acting as endocrine disruptors, we observed an increased elimination of toxicants and a 33% decrease of serum Thyroid Stimulating Hormone (TSH), suggesting a trend toward normalization of thyroid function. These results support the hypothesis that a combination of intermittent fasting with the consumption of specific probiotic yogurts may lead to immune modulation, detoxification and other improvements

Biography

Dr. Jerry Blythe is a medical doctor and founder of a company in Polymer Research. He earned an undergraduate degree in science from Purdue University and a medical degree from Indiana University. Dr Blythe is a cancer survivor of many years and was invited to talk about his Case Report published in 2017, and what he did to reverse the course of the disease through the removal of toxins. Dr. Blythe served as director of an Industrial Medical Clinic, and holds memberships in the American Chemical Society, Medicinal & Fluorine Chemical Divisions, the American Association of Cancer Research, the International Society of Exercise Immunology, the CMT Association, and state and local medical organizations. Past memberships include the American College of Occupational and Environmental Medicine, the American Occupational Medical Association, and theAmerican College of Sports Medicine. He hasbeen aclinical lecturer at two medical schools, authored medical and technical articles, and has been featured in news media, radio and television including past mention in the German Frankfurther Zeitung and OTC Journal Aktuelles.

Speaker
Jerry E Blythe / Fybrinet Inc., US

Abstract

Although associated with a variety of toxic syndromes, silicone is widely used for cosmetic augmentation. Extravasation from implants is associated with autoimmunity. Injection of silicone oil as a dermal filler can cause nodules, and granulomas associated with hypercalcemia.Inadvertent injection of silicone oil or industrial grade silicone into vessels can result in the often fatal embolism syndrome, characterized by neurologic impairment and pulmonary hemorrhage. Diagnostic biopsy performed in a case of kidney injury has revealed a novel mechanism of toxicity. A 71-year old transgender woman presented with chronic kidney disease. History revealed extensive silicone injections andbreast augmentation with silicone implants; and subsequent surgical removal of ruptured implants andfiller. Urinalysis was negative for red and white blood cells, blood, and protein.Ultrasound showed normal sized kidneys with increased cortical echogenicity.Percutaneous kidney biopsy revealed black speckles on gross examination of cortex specimens. Light microscopy showed global (5/27 glomeruli), and segmental (7/27 glomeruli) glomerulosclerosis; unusually deformed capillary loops, resembling vacuoles of dried sessile droplets; moderate tubular atrophy and interstitial fibrosis; tubules with nonspecific proteinaceous casts. Immunofluorescence showed positive casts for IgA, kappa, and lambda; tubules, interstitium, and blood vessels were negative for antibodies. Electron microscopy showed moderate foot process effacement, with mild reactive changes; mesangial areas were normal in matrix and cellularity, without immune complex deposits. This is the first report of embolization of silicone to the kidney; involving spallation (fragmentation under stress) and microemboli to glomerular capillaries and stress deformation resulting in glomerulosclerosis, interstitial fibrosis and kidney injury.

Biography

Nikolas Harbord, MD completed his medical degree at Robert Wood Johnson Medical School (now Rutgers School of Medicine), USA and Internal Medicine residency and Nephrology fellowship training at Mount Sinai Beth Israel, USA. He is the Chief of the Division of Nephrology and Hypertension at Mount Sinai Beth Israel. He has written and published on the role of the nephrologist in the treatment of the poisoned patient.

Speaker
Nikolas Harbord / Mount Sinai Beth Israel/Icahn School of Medicine, USA

Abstract

In the Arab Muslim countries, Forensic medicine is practiced by the department of Forensic Medicine, under either the Ministry of Health or Ministry of Justice’s authority. In Egypt, the First Forensic Medicine department was established in 1890, in Cairo, whereas the Authority of Forensic Medicine was joined with the Ministry of Justice in 1932. Forensic medicine in Egypt is practiced as forensic pathology and clinical forensic medicine. The latter is taking an important role in all medical malpractice cases. In Egypt Forensic medicine is being taught in all the universities at undergraduate and postgraduate levels. The law in the Kingdom of Saudi Arabia (KSA) is entirely derived from Shari’ah law; this includes medical, and legal death investigations. This makes KSA unique, as other Islamic countries combine Islamic and other judiciary systems. Forensic medicine in KSA is affiliated to the Ministry of Health. Postgraduate Saudi board of forensic medicine was established by Saudi commission for health specialties since 2006. In Tunisia, Forensic Medicine has been practiced since the 1960s, under the authority of the Ministry of Public Health, as forensic pathology and clinical forensic medicine. There’s only one Forensic center present in Kuwait. It was established following a governmental decree in 1961. The center is known as the general department of criminal evidence and is under complete administrative control of the Ministry of Interior. Forensic medicine in the rest of Arab countries affiliated to either ministry of Justice or interior.

Biography

He founded Saudi board of forensic medicine&chairman exam committee.Compliant panel chairman DHCA, Dubai.Former president of Saudi society of forensic medicine and founder president of IALFS. He was nominated to representKSA in United Nations. FFFLM of the Royal College of Physicians,London, member of IALM andNAME.Prof. ofcollegeof medicine &forensic, Xi'an Jiaotonguniversity and ofcriminal justice college, east China university of political science &law, clinical Assoc. Prof. of faculty of medicine,IAU. He has authored and co-authored several articles and chapters in text books and supervised many PhD theses internationally.

Speaker
Osama Al Madani / Ministry of health, Saudi Arabia

Abstract

Cadmium is an extremely toxic metal and well known environmental pollutant that accumulates in many organs. The kidneys are recognized as a major target of cadmium-induced toxicity. However, all mechanisms that are involved in the early stages of cadmium nephrotoxicity, particularly considering low micromolarcadmium ions (Cd2+) concentrationsare still unknown. These low micromolarCd2 concentrations are concentrations observed within the range of extracellular concentrations following cadmium mild, chronic exposure.Therefore, the aim of this study was to investigate the effects of luminal and peritubular acute exposure to micromolar Cd2+ concentration (2.3 µmol/L)on luminal sodium-coupled transport of L-alanine in proximal tubular cells of frog kidney.We showed that acute peritubular exposure to extracellular low micromolarCd2+ concentration (2.3 µmol/L) led to a rapid, sustained, and reversible hyperpolarization of the peritubular cell membrane, paralleled by an increase in fractional K+ conductance. It is known that renal proximal tubule is epithelial tissue with low paracellular resistance, thus we alsoinvestigated the effect of peritubular acute exposure to micromolar Cd2+concentration on luminal sodium-coupled transport of L-alanine in proximal tubular cells of frog kidney.The results showed that the luminal application of L-alanine rapidly depolarized the peritubular membrane potential difference (PD) of - 42.00 ± 11.68 mV by 23.89 ± 4.15 mV with an average rate of slow repolarization of 5.64 ± 0.81 mV/min. Additionally, peritubular acute exposure to Cd2+ induced change in rapid depolarization of peritubular membrane PD of – 53.33 ± 13.01 mV by 18.78 ±3.31 mV (P< 0.01) after luminal application of L-alanine. Also, peritubular acute exposure to Cd2+ led to statistically significant decrease in the rate of slow repolarization of peritubular membrane PD (3.53 ± 0.35 mV/min; P< 0.05). Perfusing the lumen with 10 mmol/L L-alanine plus/minusCd2+ did not modify rapid depolarization and the rate of slow repolarization of the peritubular cell membrane potential. Each cell served as its own control. In conclusion, these results suggested that peritubular acute exposure to low micromolarCd2+ concentration reduced luminal sodium-coupled transport of L-alanine and this change may be one of possible mechanisms involved in early stages of Cd2+-induced nephrotoxicity.

Biography

Jelena Nesovic Ostojicreceived the M.D., M.Sc., and Ph.D. degrees from the University of Belgrade, Belgrade, Serbia, in 2000, 2005, and 2009. She is currently an Associate Professor of pathophysiology at the Medical Faculty, University of Belgrade. Over 15 years of experience in medical research. Performed basic science research in the field of electrophysiology; can apply appropriate techniques of conventional electrophysiology; research interests are physiology, biophysics and pharmacology of epithelial and excitable membranes. She has published 15 papers in reputed journals. Also large teaching experience in Serbian and English language. Currently engaged in three areas of research: electrophysiology (epithelial and excitable membranes),potassium channels in tubular cells of the kidney (animal models), pathogenesis of acute and chronic renal failure (animal models).

Speaker
Jelena Nesovic Ostojic / University of Belgrade, Serbia

Abstract

Inhibition of 5α-reductase has been widely accepted as a therapeutical approach in benign prostatic hyperplasia and alopecia. However, 5α-reductase is also present in the brain and is involved in neurosteroid synthesis. Neurosteroids contribute to the pathogenesis of hepatic encephalopathy (HE) by positive allosteric modulation of GABAA receptors, which indicates that inhibition of 5α-reductase may modulate the course of HE. This study aimed to investigate the effects of finasteride, 5α-reductase inhibitor, on motor, electroencephalographic (EEG), and cellular changes in the brain in thioacetamide-induced HE in rats. Male Wistar rats were divided into the groups: 1. control; 2. thioacetamide-treated, TAA (300 mg/kg daily); 3. finasteride-treated, FIN (50 mg/kg daily); 4. group treated with finasteride and thioacetamide (FIN+TAA). Daily doses of FIN and TAA were administered intraperitoneally during 3 days. Motor, EEG changes, expression of cellular markers, and oxidative stress parameters in the cortex, hippocampus, thalamus, and caudate nucleus were determined within 24h after treatment. Vital reflexes were significantly diminished in TAA vs. control (p<0.01), while these reflexes were preserved in all animals from FIN+TAA group. Motor activity and exploratory behavior were significantly lower in TAA vs. control (p<0.01) and significantly higher in FIN+TAA vs. TAA group (p<0.01). FIN pretreatment prevented TAA-induced decline in mean EEG voltage and caused a decrease in delta and an increase in theta relative power. Lipid peroxidation was significantly lower in the cortex (p<0.01) and higher in the thalamus (p<0.01) in FIN+TAA vs. TAA group and was found to correlate inversely with acetylcholinesterase activity in the thalamus. Antioxidative effect of FIN pretreatment in the cortex was associated with increased catalase activity, while prooxidative effect in the thalamus was associated with the reduction of glutathione peroxidase and glutathione reductase activities. FIN prevented TAA-induced increase in GFAP and reversed decline in NeuN expression in the hippocampus. Finasteride pretreatment improves motor and EEG changes in TAA-induced HE and prevents the development of hepatic coma. Inhibition of 5α-reductase exerts neuroprotective effects in HE and regionally selective effects on brain lipid peroxidation; prooxidant effects are evident in the thalamus and antioxidant in the cortex.

Biography

Dusan Mladenovic was born in 1980 in Belgrade, Serbia. He is employed as an Assistant Professor at the Institute of Pathophysiology, Faculty of Medicine, University of Belgrade. He has completed his PhD thesis in 2014. in the area of Molecular Medicine. In 2016 and 2017 he spent 10 months at Philipps University of Marburg, Germany, supported by the DAAD (Deutscher Akademischer Austauschdienst) Research Grant for Doctoral Candidates and Young Academics and Scientists. He is an author of 43 articles published in leading world papers, related to the efects of finasteride on the course of hepatic encephalopathy, to the pathogenesis of epilepsy and liver diseases.

Speaker
Dusan Mladenovic / University of Belgrade, Serbia

Abstract

In the past decade, nanotechnology has advanced rapidly, and many products containing nanoparticles are now essential for our daily lives. Although nanoparticles have many useful properties, there are concerns that these same properties may increase the toxicity of nanoparticles to human being compared with that of the bulk material. Despite our increasing exposure to nanoparticles, however, information regarding the ADMET of nanoparticles remains limited. Thus, safety information on nanoparticles has been collected as an urgent issue. From this viewpoint, we have performed lots of researches on the biological effects and toxicities of nanoparticles, which we broadly refer to as “nano-safety research”. In addition, our group is currently accumulating information about safe forms of nanoparticles such as elucidating the mechanisms underlying their biological effects. For example, we showed that injected silica nanoparticles were observed in the placenta, fetal liver, and fetal brain and that they induced greater intrauterine growth restriction and placental damage in mice than did silica particles larger than 100 nm. We also have found that neutrophils may protect against pregnancy complications—especially the silica nanoparticles-triggered breakdown of pregnancy maintenance. These information will be valuable for nanoparticle risk analyses and the development of more appropriate government regulations. We hope that our achievements in this field will promote the development of safe, sustainable nanotechnology. Thus, in this meeting, we will introduce our group’s ongoing research about “nano-safety research”, and discuss the current challenges of nanoparticle safety evaluation and the future with participants on this Congress.

Biography

Kazuma Higashisaka, Ph.D., has been an Lecturer at Osaka University since 2017. He graduated from Osaka University in 2009, and received his doctoral degree from Osaka University in 2016. He was a Research Fellow of the Japan Society for the Promotion of Science (2012) and was Assistant Professor at Osaka University from 2012 to 2017. He has published more than 20 papers in reputed journals and he was awarded the Best Poster Award of Safety of Engineered Nanoparticles and Nanotechnologies in 2012.

Speaker
Kazuma Higashisaka / Osaka University, Japan

Abstract

Trans fatty acids (TFA) are unsaturated fatty acids with at least one double bond in trans configuration. Trans fats in the diet are naturally occurring (ruminant) or TFA of industrial origin (iTFA). Majority of dietary iTFA comes from partially hydrogenated vegetable oils and products that contain these oils. Artificial TFA have adverse health effects, increase atherogenic lipoprotein(a), total and LDL-cholesterol, and decrease cardioprotective HDL-cholesterol. iTFA intake is connected with cardiovascular diseases (CVD), diabetes and various cancers. In order to reduce the incidence of non-communicable diseases, nutritional guidelines emphasize the importance of balanced diet, including a proper choice of fats. In line, World Health Organization has recommended that daily intake of TFA should not exceed 1% of daily energy intake. Thus, the content of TFA in foodstuffs of 2g/100g of total fats was set in EU countries with limiting legislation. Recent recommendations indicated that TFA dietary intake should be less than 0.5% energy for patients with CVD. There are worldwide efforts to meet these goals. The European Commission recognized two approaches to limiting iTFA in foodstuffs: legislative actions and voluntary restriction. Legislative limit of iTFA was confirmed as the most effective measure aimed to protect public health. However, only a minority of the European population, less than 50 million, is currently protected by the legislation. Differences in iTFA content among European countries have been reported. Despite increased extent of voluntary reductions by the food producers, the intake of TFA remains high in countries which have no legislative limitations on TFA levels.

Biography

Snjezana Petrovic, Molecular biologist and physiologist, has completed her MSc and PhD from Faculty of Biology, University of Belgrade, Serbia. Employed as Associate Research Professor at Centre of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, University of Belgrade. Current (2012-) topics of her research activities are nutrition and metabolism, dietary fats and fatty acids, fatty acid composition of different animal and human tissues. Previous field of work, neuroscience. She has published more than 30 papers in reputed international journals.

Speaker
Snjezana Petrovic / University of Belgrade, Serbia

Plenary Talks

Abstract

Humans are exposed simultaneously or sequentially to large numbers of chemicals from various sources. Even so, the chronic toxicity evaluations for chemicals are still performed for a single chemical each time using animal models in order to set appropriate reference doses and regulatory limits. These evaluations are not always relevant for real-life exposure scenarios where concurrent exposure to other chemicals usually takes place, at doses around or well below the regulatory limits. The US-EPA published Guidelines for the Health Risk Assessment of Chemical Mixtures in 1986. This work was followed later by the efforts The Agency for Toxic Substances and Disease Registry, OECD, European Commission, EFSA and CLP Regulation (Regulation 1272/2008/EC, 2015) that gives the opportunity to Industry to perform animal testing in commercial mixtures as a last resort to prove a toxicological hazard. Advances in toxicological evaluation of chemical mixtures have raised deep concerns on how mixtures affect environment and human health, especially regarding low-level, long-term exposure to which humans are routinely encountered. Leading experts in the field of toxicology and related areas have developed several methodologies for long-term toxicity study of non- commercial chemical mixtures design to simultaneous investigate several key endpoints like target organ toxicity, genotoxicity, endocrine disruption and systemic mechanistic pathways like oxidative stress. All these associated with modern omics technologies can lead to evaluate long-term health effects of chemical mixtures. The presentation of the preliminary results of these kinds of studies that are settled in different laboratories around the world and solutions for the problems that could appear during these studies represents the novelty that could change the concept of toxicology safety evaluations. Validated and harmonized methods are needed to integrate the multiple streams of evidence relevant to mixture toxicity assessment, to predict the toxicity of mixtures consisting of chemicals of already known toxicity, and to elucidate mechanisms of possible interactions between the chemicals in the mixture. Linking xenobiotic chemical exposure to health effects has been the subject of many experimental and epidemiological studies but still remains a matter of permanent controversies. This issue is complicated by the multiple mechanisms of xenobiotic toxicity often involved, the uncertainties related to long term and low dose xenobiotic exposure. Aging is a complex senescence process that follows maturation, and is characterized by time-related functional decline due to genetic, biochemical, physiological and anatomical degeneration in tissues and organ systems. Loss of genome integrity is a key feature in senescence and the consequent development of aging-related diseases and cancer. Telomeres are repetitive tandem DNA sequences that cap chromosomal ends, protecting the integrity of information-carrying DNA. However, telomere length decreases with aging (and therefore its protective activity), as a result of repeated cell replication or environmental factors, namely those involving inflammation and oxidative stress. Consequently, shorter telomeres have been linked with shorter lifespan, and telomere length has been suggested as a biomarker of aging. Additionally, the genetics of telomeres, including TERT gene which encodes telomerase, is highly involved in many neoplasia including differentiated thyroid cancer. This lecture will provide a discussion on the environmental factors that may influence telomere dynamics, including obesity-related chronic low-grade inflammation and leptin resistance, and substance abuse, as well its consequences, with focus on thyroid neoplasia. It will be also highlighted the use of metabolomics as an important clinical and research tool in the development of biomarkers of senescence, in which the usefulness of telomere length measurement is becoming recognized. Our study with drugs of abuse user’s revealed that median of telomere length is about 1.000 base pairs lower than the median of healthy population. In addition the telomere length was conversely related on annual opiates use. Conclusively older biological age compared as fact with chronological age, based on telomere length in drugs of abuse users.Repeated measurements at a distance of 6 months or a year can reveal the rate of change of the short telomeres, and response of patients to treatments, lifestyle, diet, supplementation and exercise modifications. Within our in vitro experiments in cell cultures we’ve been able to discover a potent natural molecule that activates telomerase up to 1300% in relation to the control cells.

Biography

Aristides Tsatsakis is the Director of the Department of Toxicology and Forensic Sciences of the Medical School at the University of Crete and the University Hospital of Heraklion. Dr Tsatsakis has written over 1000 publications (books and abstracts proceedings), over 400 of them in ISI journals. He is holder of several patents and has an extensive array of citations and reads /downloads to his papers. Dr Tsatsakis has given numerous keynote and plenary lectures in international congresses and was the promoter and chair of numerous Symposiums and workshops in International Forum. He has coordinated as a PI in over 50 scientific research and technology projects and has established worldwide collaborations. Aristides Tsatsakis was elected EUROTOX President-Elect in 2012 served as President (2014- 2016) of the Federation of European Toxicologists and European Societies of Toxicology. Dr. Tsatsakis has a long standing activity as Editor in toxicology journals. Prof. Tsatsakis is Emeritus Professor for the Federal Institute of Hygiene and Toxicology in Moscow (2014), Doctor Honoris Causa of the Mendeleev Moscow University (2016), of the Far East Federal University (FEFU), Vladivostok 2017 and of the Carol Davila, in Bucharest (2017). In 2016 was elected Foreign Member of the National Academy of Sciences of Russia (FMRAS) and in 2017 of Fellow Academy of Toxicological Sciences (FATS, USA). Aristides Tsatsakis is the inspirator, founder and chief scientific officer of the University of Crete spin-off Company ToxPlus S.A. The main research interests of Professor Tsatsakis are biomonitoring of various xenobiotics in a variety of biological samples and linking of chemical chronic exposure at low doses with health problems and diseases and risk assessments. He developed numerous biomarkers of exposure and of effects for the pesticide and chemical toxicology area uncovering the mechanistic understanding of the mode of actions and adverse outcome pathways and clinical effects.

Speaker
Aristides M Tsatsakis / University of Crete, Greece

Abstract

Biography

Zeliha Selamoglu is a Professor in Medical Biology department of Nigde Ömer Halisdemir University, Turkey. She earned her PhD in Biology from Inonu University, She has published over 100 peerreviewed journal articles with over 950 citations and many technical reports. She is a member of Society for Experimental Biology and Medicine: Associate Membership and European association for cancer research. She has served as Editorial Board member for many Journals.

Speaker
Zeliha Selamoglu / Nigde Ömer Halisdemir University, Turkey

Abstract

BACKGROUND: Although there are a number of reports concerning the occurrence of metal(loid)organic compounds in the environment, a systematic screening of gaseous, liquid, and solid samples for the presence of such compounds have not yet been reported. The same holds true for the toxicological evaluation of these mostly highly mobile and toxic species. METHODS: Concentrations of metal(loid)organic compounds were measured by instrumental techniques coupling chromatography on-line to elemental as well as organic mass spectrometry. Selected mammalian cell lines have been exposed to these species for evaluation of cellular cyto-, geno-, and neurotoxicity. RESULTS: Concentrations of metal(loid)organic compounds range over nine orders of magnitude in gas samples, over four orders of magnitude in waters, and over eight orders of magnitude in solids. There was a significant overlap between concentrations at environmental hot spots and concentrations causing toxic effects in exposed mammalian cells. CONCLUSIONS: The collected data suggest the existence of real and potential hot spots of metal(loid)organic compounds in the natural as well as the anthropogenic environment. A closer look at these hot spots with regard to the potentially associated health risks is recommended.

Biography

Elke Dopp is Professor for Hygiene and Environmental Medicine at the Medical Faculty of the University Duisburg-Essen. She has studied Agricultural and Environmental Sciences at the University of Rostock and got her doctoral degree (PhD) as well as the venialegendi (University teaching credentials)for Environmental Toxicology from the University of Rostock. In 2010 she became Professor at the University of Duisburg-Essen. She has published more than 100 papers in reputed journals, has published own book chapters and booksand has been serving as an editorial board member of repute. She was and is also member of national and international expert groups.

Speaker
Elke Dopp / University of Duisburg-Essen, Germany

Abstract

Biography

A. Wallace Hayes holds appointments at the University of Massachusetts, Institute of Integrated Toxicology, Michigan State University and the University of South Florida College of Public Health. Past positions include Corporate vice president, the Gillette Company; vice president, RJR Nabisco; director, Rohm & Hass; and professor at Alabama, Mississippi, and Wake Forest Universities. He holds degrees from Auburn and Emory Universities and was a National Science Foundation Fellow at Auburn, a National Institutes of Health (NIH) Individual Fellow at Vanderbilt, a North Atlantic Treaty Organization Senior Scientist in the UK, and an NIH Research Career Development awardee. He has served on committees for the National Academy of Sciences, the NIH, the Food and Drug Administration (FDA), the Environmental Protection Agency, and the Department of Defense. Hayes has authored 270 peer-reviewed publications, is editor of Hayes' Principles and Methods of Toxicology (CRC Press, 2014), co-author of Loomis’ Essentials of Toxicology and several toxicology journals. Other past positions include secretary general of the International Union of Toxicology; treasurer of the American Board of Toxicology; president of the American College of Toxicology, the Toxicology Education Foundation, and the Academy of Toxicological Sciences; and councilor of the Society of Toxicology. He is currently the vice president of the Toxicology Forum. He is a diplomat of the Academy of Toxicological Sciences and the American boards of Toxicology, Forensic Medicine, and Forensic Examiners; and a fellow of the Academy of Toxicological Sciences, Royal Society of Biology, the American College of Forensic Examiners, and the American College of Nutrition. He is a registered toxicologist in the European Union and a certified nutrition specialist. Hayes has won the Society of Toxicology's Merit Award, the Mid-Atlantic Society of Toxicology's Ambassador Award, the American College of Toxicology's Distinguished Scientist Award, and the International Dose-Response Society's Outstanding Leadership Award.

Speaker
A Wallace Hayes / University of South Florida College of Public Health, USA

Abstract

Biography

Dr Heinonen, Ph.D. in toxicology has adjunct professorships both at the University of Turku (biochemical toxicology) and at the University of Helsinki (biochemistry). She is European registered toxicologist. Dr Heinonen is the director of the Finnish Centre for Alternative Methods, FICAM. Her responsibility has been to set up and is to manage the GLP-grade centre, FICAM. Before FICAM Dr. Heinonen worked in pharma industry for 17 years in various positions such as Study director in in vivo and in vitro non-clinical regulatory (general toxicity and genotoxicity) and biological mechanistic studies, as laboratory head and department manager and also as R&D director. She set up several laboratories into GLP. She gained experience from clinical trials when acting as Clinical study director. Dr Heinonen has participated in several meetings with regulatory bodies (EMEA, FDA, national) with regard to various stages of pharmaceutical development including scientific advices on whole development plan. Before joining to pharmaceutical industry Dr. Heinonen worked at the Institute of Occupational Health performing animal toxicity and in vitro toxicity studies on chemical substances and using that data in carcinogenic risks assessments.

Speaker
Tuula Heinonen / University of Tampere, Finland

Keynote Talks

Abstract

Polyoxometalates are polyanionic oligomeric aggregates with a high density of negative charge, which contain transition metal ions held together by oxygen bridges. These metal based compounds were synthesized in order to be applied in catalysis, separations, analysis, and as electrondense imaging agents. Additionally, in vitro and in vivo studies has indicated that some of these complexes exhibit various biological activities such as anti-cancer, antibiotic, antiviral, and antidiabetic effects. However, their biological mechanism of action at the molecular level are not completely understood. Due to their anionic character and their high negative charge at physiologic pH values, they will hardly be able to penetrate cells. Therefore, it has been speculated that polyoxometalates are likely to act extracellularly inhibiting several different enzyme families such as phosphatases, kinases, sulfotransferases, sialyltransferases, and ecto-nucleotidases, which are mostly located on the plasma membrane with extracellular binding sites. However, the main limitation for their widespread application in biomedicine is the approved toxic action. For this reason, it is necessary to carry out toxicity evaluation of biologically active polyoxometalates as promising drug candidates. Accordingly, the results of in vitro oxidative stress and cell viability responses of a few selected polyoxotungstates are going to be presented using rat synaptosomes as a model system. Furthermore, in vitro interactions of the polyoxotungstates with physiologically important enzymes including acetylcholinesterase, Na,K-ATPase, and ecto-ATPases are going to be taken into account. These enzymes are targets for neurological and antitumorial drugs, and for toxins as well.

Biography

Dr. Mirjana B. Čolović, a research associate has been emoloyed at University of Belgrade, Serbia, from 2005. Her research activities are in the field of enzymology, toxicology, biosensors, physiologically active compounds and their interactions with biomolecules. She has published 38 papers in impacted international journals, 4 chapters in books, 3 articles in national scientific journals, and over 60 abstracts in international and national scientific meetings. She served as a reviewer in over 20 international journals and 9 foreign projects, and has been serving as an editorial board member in 2 international journals.

Speaker
Mirjana Colovic / University of Belgrade, Serbia

Abstract

Polyoxometalates (POMs) are negatively charged inorganic compounds which contain early transition metal ions such as tungsten, molybdenum, or vanadium, surrounded by oxygen atoms. Furthermore, POMs have been shown to exhibit biological activities in vitro as well as in vivo, including promising anticancer, antibacterial, antiviral, antidiabetic, and anti-Alzheimer effects. However, a toxic action of some POMs was confirmed which presents the main limitation for biomedicinal applications. Although the biological activity of POMs has been investigated for many years, reports of relevant toxicological studies are relatively rare. Toxicological studies of polyoxotungstates with different biological activities were performed using Wistar albino rats as a model system, in accordance with OECD Guidelines for the Testing of Chemicals. POM-induced toxic effects were followed after oral application of: 1) two Keggin-type POMs, {K-Ti2PW10} and {K-SiV3W9}, with different inhibitory potencies toward acetylcholinesterase activity; 2) donut-shaped POM {NaP5W30} and its Ag+-containing derivative {AgP5W30} with hypoglicemiant effect in rats with streptozotocin-induced diabetes; and 3) two organo-antimony-containing POMs (PhSb)4(GeW9)2 and (PhSb)4(PW9)2, which possess significant antimicrobial activity. The biochemical parameters of renal (serum urea and creatinine) and liver function (direct and total bilirubin, alanine transaminase, and aspartate aminotransferase) were determined. A histopathological analysis of kidney and liver tissue was carried out 14 days after the polyoxotungstate administration using light and transmission electron microscopy. The obtained results indicated that all investigated POMs cannot be considered highly toxic. There was no influence on the rat body mass and food intake. Biochemical studies demonstrated a similar impact of both anti-Alzheimer POMs on biochemical parameters, such as an increase of the hepatotoxicity parameters, ALT and AST. On the contrary, the results of biochemical analysis suggest a renal toxicity of POMs with hypoglicemiant effect. The obtained results were confirmed by histhopathological analysis.

Biography

Danijela Krstić obtained her BSc., MSc. and PhD in biochemistry from the Faculty of Chemistry, University of Belgrade, Serbia. Working as an Associate Professor in the Institute of Medical Chemistry, Faculty of Medicine, University of Belgrade. The topics of her research activities are enzymology, enzyme inhibition and toxic effects of different (organic or inorganic) pharmacologically and physiologically active compounds. She published (author or coauthor) more than 40 scientific papers in international journals.

Speaker
Danijela Krstic / University of Belgrade, Serbia

Sessions:

Abstract

Abstract: 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: 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 of Intelligence-second edition (WASI-II) questionnaire was used for each subject to evaluate the subtests of IQ. Results: A total of 419 subjects with the mean age of 12.51 ± 2.82 years had participated in this study. 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, functions 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 improvedby tuning up the lifestyles and economic conditions of the families in developing countries. Key words: Cranial Capacity Intelligence Quotient Adolescents Children Malaysia

Biography

Swamy K B, presently working as Professor& HOD of Clinical Anatomy, Lincoln University, Kuala Lumpur, MALAYSIA, has been awarded PhD by Andhra University, India. He has taken his Master’s Degree MS (in Clinical Anatomy) from Andhra Medical College, India, DMCh (Maternal & Child Health) from IGNOU, New Delhi, his Medical Degree (MBBS) in 1976, 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 (FRGS,,URGS) from Malaysian Government, 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 “9th Euro-Global Summit on Toxicology and Applied Pharmacology held through June 22-24, 2017 at Paris, France., 11th International Conference on Pharmacoepidemiology and Clinical Research October 02-03, 2017 Kuala Lumpur, Malaysia, Editor for many journals like "Novel Techniques in Nutrition and Food Science". Journal, Herald Scholarly Open Access Journals ( Annals Of anatomy & Physiology), Journal Anatomical Society Of India (JASI) and many more and also Manuscript reviewer for journals like “Food & Chemical Toxicology (Elsevier), "Novel Techniques in Nutrition and Food Science" and many more

Speaker
Swamy KB / Lincoln University College, Malaysia

Abstract

Gmelina arborea and Carissa edulis are medicinal plants worldwide used to manage various diseases, especially in Benin. This work was conducted to investigate the safety of the two plants extracts and fractions in two cell lines. Gmelina arborea and Carissa edulis leaves were collected, duly identified by the Botany department of the University, dried and extracted by water. The crude extracts were then fractionated using different polarity solvents (ethyl acetate and butanol).Caco-2 and HepG-2 cells were cultured in DMEM medium for 24 hours (h) and exposed to the extracts with concentrations range of 0.05 –7.5 mg/ml for 48h. The cell viability and cell growth tests were performed using the neutral red uptake test and MTT colorimetric assays. To evaluate cytotoxicity and necrotic cell death pathway lactate dehydrogenase (LDH) leakage was quantified in the extracellular medium. In addition the caspase-3/7 activation and DNA fragmentation assays were performed to figure out possible apoptosis cell death pathway. Both crude extracts and fractions from G. arborea and C. edulis reduced cell viability and inhibited the growth of the two cell lines. Furthermore, and importantly, lactate dehydrogenase leakage was observed with the extracts at the highest concentrations indicating that the major pathway of cell death was by necrosis since, neither caspases-3/7 activation nor DNA fragments showing ladder shapes were observed. Carissa edulis and Gmelina arborea reduced significantly cell viability concentration-dependently in the two cell lines in which the cell death pathway is by necrosis rather than by apoptosis. Keywords: Gmelina arborea, Carissa edulis, Cytotoxicity, Cell death pathway

Biography

OSSENI Razack has completed his PhD from University of Abomey-Calavi, Benin. He is a Pharmacist, Toxicologist in the laboratory of Pharmacology and Toxicology at the Faculty of Health Sciences of Cotonou, Benin. He has published more than 10 papers in reputed journals and has been serving as a reviewer in editorial board member of repute.

Speaker
Osseni Razack / University of Abomey-Calavi, Benin

Abstract

The main aim of this paper was chemical characterization and source apportionment of ambient PM2.5 associated oxidative potential in urban backgrounds of Athens, the capital of Greece. To this end, we collected the ambient PM2.5 samples during warm phase (i.e., June-September of 2017), and winter phase (i.e., February-March of 2018) at Global AtmosphereWatch (GAW) Demokritos station (DEM_Athens) in Athens. These samples were chemically analyzed for elemental and organic carbon (EC/OC), water-soluble organic carbon (WSOC), metals and trace elements, and levoglucosan. Moreover, the oxidative potential of PM2.5 was determined by the means of DCFH in vitro assay. Subsequently, we employed Spearman rank-order correlation analysis, principal component analysis (PCA), and multi linear regression (MLR) analysis to find out the major sources contributing to PM2.5 oxidative potential. Our results confirmed the significantly higher intrinsic (mass based), and extrinsic (volumetric) oxidative potential of ambient PM2.5 in urban background of Athens as opposed to many other metropolitan areas of the world. In addition according to MLR results, vehicular activities (characterized by EC) (44%), secondary organic aerosol (SOA) formation (characterized by WSOC) (16%), and biomass burning (characterized by levoglucosan) (9%) were the main sources of ambient PM2.5 oxidative potential. Eventually, our findings highlight the importance of vehicular and SOA sources on PM induced toxicity and can be used as a guideline by health authorities to adopt proper policies for mitigating the adverse health effects of exposure to ambient PM2.5.

Biography

Costantinous Sioutas is the Fred champion professor of civil and environmental engineering department at USC. His area of expertise includes development of several particle sampling technologies that have enabled the assessment of the relative toxicity of particulate matters using realistic atmospheres in in-vivo and in-vitro exposure studies funded by US EPA, NIH, and CARB in Southern California. Findings from his work have also been extensively used in the revision of US EPA national air quality standards on particulate matters.

Speaker
Constantinos Sioutas / University of Southern California, United States

Abstract

The strategy of price liberalisation and privatisation had been implemented in Sudan over the last decade, and has had a positive result on government deficit. The investment law approved recently has good statements and rules on the above strategy in particular to pharmacy regulations. Under the pressure of the new privatisation policy, the government introduced radical changes in the pharmacy regulations. To improve the effectiveness of the public pharmacy, resources should be switched towards areas of need, reducing inequalities and promoting better health conditions. Medicines are financed either through cost sharing or full private. The role of the private services is significant. A review of reform of financing medicines in Sudan is given in this article. Also, it highlights the current drug supply system in the public sector, which is currently responsibility of the Central Medical Supplies Public Corporation (CMS). In Sudan, the researchers did not identify any rigorous evaluations or quantitative studies about the impact of drug regulations on the quality of medicines and how to protect public health against counterfeit or low quality medicines, although it is practically possible. However, the regulations must be continually evaluated to ensure the public health is protected against by marketing high quality medicines rather than commercial interests, and the drug companies are held accountable for their conducts. Keywords: Sudan, Healthcare, Medicines, Regulatory authorities, Pharmacy Management.

Biography

Abdeen Mustafa Omer (BSc, MSc, PhD) is an Associate Researcher at Energy Research Institute (ERI). He obtained both his PhD degree in the Built Environment and Master of Philosophy degree in Renewable Energy Technologies from the University of Nottingham. He is qualified Mechanical Engineer with a proven track record within the water industry and renewable energy technologies. He has been graduated from University of El Menoufia, Egypt, BSc in Mechanical Engineering. His previous experience involved being a member of the research team at the National Council for Research/Energy Research Institute in Sudan and working director of research and development for National Water Equipment Manufacturing Co. Ltd., Sudan. He has been listed in the book WHO'S WHO in the World 2005, 2006, 2007 and 2010. He has published over 300 papers in peer-reviewed journals, 200 review articles, 7 books and 150 chapters in books

Speaker
Abdeen M. Omer / Ministry of Health, Sudan

Abstract

Chemical interactions have posed a big challenge to characterize mixture toxicity and human health risk assessment. The dilemma of lack of scientific information and research tools versus perception of high risks from exposures to chemical mixtures poses an enormous challenge for the toxicity assessment community. Therefore, there is an urge need to develop novel, integrated, and toxicology-focused methodologies and approaches for efficient analysis of toxicity pathways, biomarkers, and toxic mechanisms associated with exposure to chemical mixtures, and for accurate distinction of chemicals in the mixture that present little or no toxicity concern from those with the greatest likelihood of causing an adverse effect in the target species. High-throughput and high-content system biology methods especially applied to predictive toxicology provide opportunities for addressing these challenges. This presentation will focus on development and application of novel and quantitative system biology methods including genomic, proteomic, and metabolomic screening for distinct unique exposure and toxicity signatures for individual chemicals and mixtures. Statistical analysis for distinguishing critical components in mixtures, mathematical modeling for prediction of mixture toxicity and risk for unknown mixtures, and system biology approaches for identifying biological mechanisms underlying chemical interactions and mixture toxicity will also be presented in this presentation.

Biography

Yue received his Ph.D. in Proteomics in 2002 at the University of Michigan, Ann Arbor, USA, where he investigated pathological and physiological mechanisms of Duchenn Muscular Dystrophy (DMD) by identifying and characterizing disease targets, biomarkers, and toxicity pathways associated with the disease onset and progression using functional proteomic approaches. Prior to his Ph.D. studies, he had worked in Walther Oncology Center, Indiana University for four years, where he studied cytokine gene expression in human stem and progenitor cells and gene therapy. Following the completion of his Ph.D. study, Yue moved to Department of Proteomics at Invitrogen (Life Technology), where he worked as a lead scientist for a breast cancer research project focusing on identification of breast cancer biomarkers using Multiplexed Proteomics Technology Platform which was built within the research team. During this period, he also served as a project leader and worked on proteomic assay and technology development. His work resulted in two US patents and four new protein assays that have been widely used in current biomedical and human health research. In 2006, Yue took the position of Principal Investigator at the US Environmental Protection Agency (EPA) to work on the emerging field of toxicoproteomics. His research interests have been on the identification of toxic mechanisms and modes of action of chemical-induced carcinogenesis and identification of protein biomarkers of exposure, toxicity, and effect using improved toxicoproteomic technologies developed by his research team and others. He is currently leading an innovative research project on predictive proteomic risk assessment of chemical mixtures for chemical mixture identification, classification, screening, and prioritization. Yue has received EPA’s Scientific and Technological Achievement Award (STAA) twice. His research efforts and publications have led to the invitations to serve as conference chair, conference keynote speaker, and session chair for many national and international conferences, most notably SETAC, EUROTOX, AES, EPPH, and EOMICS. With regard to the service to the broader scientific community, Yue is currently serving as North America Regional Editor for Journal of Integrated OMICS, Associate Editor and Board Member for Environmental Health and Toxicology,Journal of Genomics and Proteomicsand other prestigious biological journals.

Speaker
Ge Yue / National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, USA

Abstract

Aberrant DNA methylation of specific genes have been found in Hexavalent chromium [Cr (IV)] exposed populations. While little is known about genome-wide DNA methylation profiles in Cr (IV) exposed workers. In our study, We measured DNA methylation in blood samples from 94 electroplating workers and 94 matched controls using a combination of Infinium Methylation450K Chip and targeted-bisulfite sequencing. QuantiGene Plex 2.0 assay was used to detect the mRNA expression of differentially methylated genes. ICP-MS were used to detect the concentrations of metals in blood and urine samples. The findings in population study were furtherly detected in a human lymphoblastoid cell line. Our results indicated that the concentrations of three heavy metals (Cr, Cd and Pb) in both serum and urine samples from workers notably exceeded those from controls. A total of 131 differentially methylated CpG sites were found using Methylation450K Chip between 30 exposure samples and 30 control samples.,with 81 CpG sites hypermethylated and 50 hypomethylated. After being confirmed in targeted-bisulfite sequencing for DNA methylation alterations and in Quantigene for mRNA expression, two novel epigenetic markers (SEMA4B and CD44) were found to be associated with Cr (IV) exposure. The effects of Cr (IV) on DNA methylation and mRNA expression of SEMA4B and CD44 were furtherly determined in human lymphoblastoid cell line. Our findings indicated that DNA methylation of SEMA4B and CD44 genes may act as potential biomarkers for Cr (IV) exposure, motivating further study of these two genes in investigating the mechanisms of Cr (IV) induced carcinogenesis.

Biography

Jianlin Lou has completed his PhD from School of Public Health, Zhejiang University, P. R. China and postdoctoral studies from School of Medicine, Zhejiang University, P. R. China. He is the vice dean of Zhejiang Academy of Medical Sciences. He is also the Chairman of Occupational Health and Occupational Medicine Branch under Zhejiang Preventive Medicine Society. He has published more than 40 papers in reputed journals and has been serving as reviewer for more than 15 journals.

Speaker
Jianlin Lou / Zhejiang university, China

Abstract

This study focused on the adsorption/absorption process of natural volcanic tuff, its application, kinetics, efficiency, velocity and selectivity order in removing heavy metals found in pharmaceutical wastewater. Series of experiments were conducted in batch-wise and fixed-bed columns to study the removal performance and selectivity sequence of mixed metal ions (Pb2+, Cr6+, Cu2+, Zn2+and Fe3+) in aqueous solution using natural volcanic tuff material as adsorbent. The main purpose of this study is to highlight the economical application of the method in treatment of pharmaceutical wastewater. Heavy metal salts were used to prepare synthetic pharmaceutical wastewater containing a mixture of different metal ions concentrations ranged from 1 to 20 mg/L were to be applied to columns packed with natural volcanic tuff rich in zeolite ranged between (0.50 – 3.50 mm ) in grain size. Photometric procedure was used for sample analysis. The absorption experiments were carried out under changing conditions, such as, different pH-values of solutions (2, 4, 6 and 7), initial solute concentrations ranging from (1, 5, and 10) mg/L, under different room temperatures (10, 20, and 30 Cº), and with use of varying tuff particle sizes (0.50 -3.50) mm. The results showed that Freundlich model described satisfactorily sorption of Cu2+ and Fe2+. Used volcanic tuff exhibit efficiency in removing heavy metals ranging from 45 – 99 % of the added Cr, Cu, Zn, Pb and Fe metal concentrations respectively. According to the percentage sorption and distribution coefficients values, the selectivity sequence of studied metals by volcanic tuff is strongly dependent of pH, however approximating all results a selectivity sequence can be given as Pb ≥ Fe > Cr > Zn > Cu at pH around 2 and a selectivity sequence as Fe > Cu > Cr > Zn > Pb at pH = 6-7 . The results confirms that natural volcanic tuff hold great potential to remove cationic heavy metal species from industrial wastewater. Keywords: heavy metal ions, absorption, pharmaceutical wastewater, Natural volcanic tuff

Biography

Speaker
Jamal A. AL RADIDEH / Al Balqa Applied University, Jordan

Abstract

Fast and accurate isocratic HPLC method was developed for determination of five active ingredients of Artemisia plant extract. The extract contains artemisinic acid, artemisitene, dihydroartemisinin, artemisinin and deoxyartemisinin. A solution of acetonitrile, water and methanol (50:30:20 % v/v) was found to be the best effective mobile phase for the HPLC analysis of Artemisia annua extracts, using high efficient reversed phase column Phenomenex Gemini 3 μm C18 (50 x 4.6 mm I.D ) column. The optimum baseline separation condition gives better peak shapes and resolution for all active ingredients in the extract of Artemisia anuua in less than 10 minutes. This extract is composed of more than one compound to be dissolved in the injection solvent so that profiling is more representative of the extracts. By applying the optimum separation condition, we quantitatively estimated the % of active ingredients in Artemisia extract as follows, artemisinic acid (10.089 %,), artemisinine (6.0%), dihydroartemisinin (23.94), artemisinin (55.999%) and deoxy artemisinin (3.969 %). The results revealed that the contents can be arranged according to their percentage artemisinin, followed by dihydroartemisinin, artemisinic acid, artemisitene and finally deoxyartemisinin. The purity of Artemisinin and amount in plant material to date has been marked by a considerable discrepancy in values. This is maybe due to the adoption of varied analytical procedures and use of inappropriate analytical techniques. In this paper, we are attempting to develop an artemisinin analysis to reach a universally acceptable method, which is dependable to the research and end-users communities. Thus, we have developed and validated an HPLC-UV method bearing in mind the limitations for its application scope. The recent results would help to give more reliable laboratory analysis data of artemisinin in both standard samples and in Artemisia annua extracts. This precise and accurate assay could be performed in the linear working range of 4.0-100 µg/ml for HPLC method. Keywords: quantitation of artemisinin's , HPLC–Uv methods, Artemisia extract

Biography

Speaker
Abdul-Wahab AWH Hamad / Al Balqa Applied University, Jordan

Abstract

Non-alcoholic steatohepatitis (NASH) is the most common chronic liver disease in the world, characterized by hepatic steatosis, inflammation, hepatocyte injury with or without fibrogenesis, which might lead to cirrhosis. Berberine (BBR) is a natural isoquinoline alkaloid with very impressive health benefits. The aim of this study is to evaluate the protective effect of BBR in experimental NASH induced by high fat/high-sucrose diet in male albino rats. Methods: 60 male albino rats divided randomly into four equal groups: group I (normal control group), group II (BBR treated control group), group III (NASH group) and group IV (BBR treated NASH group). Levels of PGC-1α in hepatic nuclear extract were measured by ELISA, while activity of cytosolic glycerol 3 phosphate dehydrogenase (GPDH1) in liver tissue homogenate, liver enzymes, lipid profile and plasma FRAP were measured spectrophotometrically. Results: There was a statistically significant decrease of hepatic PGC-1α, plasma FRAP, serum HDL-C along with significant increase in the activity of GPDH1, liver enzymes as well as hyperlipidemia in NASH group compared to both normal control and BBR treated control groups. These pathological disturbances were significantly ameliorated by BBR supplementation. In conclusion, the present study provided unequivocal evidence that disturbed hepatic PGC-1α and altered redox status acted as major contributing factors for the pathogenesis of high-fat/high-sucrose induced NASH in rats. It also shed some light on the potential therapeutic value of BBR in NASH; partly accredited to its hypolipidemic and antioxidant effects, in addition to upregulating the levels of PGC-1α in hepatic nuclear extracts.

Biography

Prof. HanaaGaballah is anassistant professor of Medical Biochemistry and molecular Biology, Faculty of Medicine, Tanta University, Egypt. Worked as Research Associate at Bioinformatics centre, Chemical Research Lab, Kyoto University, Japan: from 16/2/2013 -15/8/2013. She also has 16 publications. EmanElrefaei is an assistant lecturer of Medical Biochemistry and molecular Biology, Faculty of Medicine, Tanta University, Egypt.

Speaker
Eman Hashem Hashem Elrefaei / Tanta University, Egypt

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