Conference Schedule

Day 01 Schedule

Jun 15, 2020

Plenary Talks

Title: Timely concepts of Toxicology for Safety - Health and Well-being in our Modern World : Real Life Risks Simulations and Risk Assessments


Abstract


Risk and safety assessments for human protection is historically and up to nowadays based on some long-established practices and assumptions for hazard identification and characterization. These practices were considered useful for many decades, yet it is now globally recognized that they do not simulatereal life conditions. Real life risk comes from the exposure to complex mixtures of many different chemicals and their toxicity in mixtures might be altered in relation to their toxicity when studied in isolation. In addition, real life exposure is mainly exposure to low doses. However, the assumption that low dose�s toxicity can be explained by experimentation in high doses because all effects are following a linear and monotonic dose-response curve, is seriously challenged through a number ofstudies of the last three decades. As many of the technical drawbacks of the past are nowadays eliminated and new technologies and methodologies are available, we consider that it is time to go ahead with toxicology for Real Life Risk Simulation. As knowledge grows regarding real life combined exposure, we focus our research in an area with complete lack of data, i.e. the low-dose-long-term toxicity testing of complex chemicals� mixtures that simulates real life exposure. The Toxicology of the 21st century faces the challenge of explaining why epidemiological studies indicate that chemicals in doses considered safe are important factors that lead to the development of different chronic diseases. Precision medicine approach based on metabolome, genome, and microbiome relates data on the effect of toxic exposure to the phenotype. Toxic exposure inflicts damage at metabolic, genetic and microbiome levels,thus increasing cellular turnover, telomere attrition and the rate of aging. Data from our ongoing research in this direction will be presented.


Biography


Professor, Academician Aristidis Tsatsakis, PhD, ERT, DSc, FATS, DHonC, DHonC, DHonC, HonProf, FMRAS, FMWAS 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. Prof Tsatsakis has published well over 1000 works (articles in journals, books and abstracts proceedings), over 500 of them in ISI journals. He is the holder of several patents and has an extensive array of citations (over 12,000 GS) and reads /downloads (over 80,000 RG) of his papers. His current IF index is 54 (GS) and 43 (ISI). Prof Tsatsakis has given over 200 keynote and plenary lectures in international congresses and has been the promoter and chair of numerous Symposiums and workshops in International Forum. He has coordinated as a PI in over 60 scientific research and technology projects and has established worldwide collaborations. Prof. Tsatsakis has a long-standing activity as Editor in toxicology journals, he is currently Editor in chief of Toxicology Reports and editor of Food and Chemical Toxicology and has served as editor and guest editor in many other journals, such as Toxicology, Food and Chemical Toxicology, Toxicology Letters. 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. Prof. Tsatsakis is Emeritus Professor for the Federal Institute of Hygiene and Toxicology in Moscow (2014), Doctor Honorary 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 he was elected Foreign Member of the National Academy of Sciences of Russia (FMRAS), in 2017 Foreign Member of Fellow Academy of Toxicological Sciences (FATS, USA) and in 2018 Full Member of The World Academy of Sciences (FMWAS). In 2017 he was elected Honorary Member of Bulgarian Toxicology Society and in 2018 Honorary President of the European Institute of Nutritional Medicine (E.I.Nu.M.) and Honorary Member of EUROTOX. Aristides Tsatsakis is also the inspirator, founder and chief scientific leader of the University of Crete spin-off Company ToxPlus S.A. The main research interests of Professor Tsatsakis include biomonitoring and risk assessments of xenobiotics as well as links of chronic exposure to them at low doses with health problems and diseases. He developed numerous biomarkers of exposure and of effects for various chemicals, in particular pesticides, pharmaceuticals, etc., uncovering the mechanistic understanding of the mode of action and adverse outcome pathways leading to clinical effects and chronic diseases (metabolic, autoimmune, cancer etc.) Professor Tsatsakis� long-standing public activities in disseminating science for safety health and wellbeing of the society and the environment have often been endorsed and awarded by state and municipal authorities. His motivation and basic concept highlights the important role of academia involvement in social life problems. The postulation of real-life risks simulation based on low dose combined long term exposures related to health issues, is a crucial element and the central driving force for application of theory to practice on safety evaluations in 21 century.

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Aristidis Tsatsakis

University of Crete, Greece
H-index-57

Title: Protective role of Mesenchymal Stem Cell-Derived Exosomes in Toxicants-Induced Mitochondrial Dysfunction


Abstract


Cigarette smoke (CS)-induced lung inflammation and chronic obstructive pulmonary disease (COPD) involves mitochondrial dysfunction. Mesenchymal stem cells (MSC) and MSC-derived exosomes (EXO) are reported to show their therapeutic effects in animal models of inflammation/injury. We hypothesized that MSC and EXO combination (MSC+EXO) treatment may have protective effects against acute CS-induced lung inflammation and mitochondrial dysfunction compared to individual treatments (MSC or EXO alone). EXO were characterized by Western blotting, tunable resistive pulse sensing (qNano) and transmission electron microscopy. Mitochondria reporter mice (mt-Keima and mito-QC) were exposed to air or CS for 10 days. mt-Keima mice were treated with intraperitoneal injections of MSC or EXO or MSC+EXO for 10 days. Total cell counts and differential cell counts were analyzed using cellometer and flow cytometry respectively. Pro-inflammatory mediators in bronchoalveolar lavage fluid were measured by ELISA. Mitochondrial, DAMPs, inflammation and mitophagy markers were further analyzed by Western blot analysis, qPCR and confocal microscopy in acute CS exposed mouse lungs. Seahorse flux analyzer was used to measure the oxidative-phosphorylation (OXPHOS) in the BEAS2B cells and mMSC co-culture experiments. CS exposure increased the inflammatory cellular infiltrations in the lungs of the mt-Keima mice, while treatments showed varied degrees of protection. There were no changes in the mitophagy proteins like Pink1 and Parkin, which was also found using the mito-QC mice. Acute CS exposure increased the protein abundance of DRP1 (mitochondrial fission), S100A4 and S100A8, HMGB1, RAGE and AGE (DAMPs markers). MSC+EXO treatment increased the gene expression of mfn1, mfn2 and opa1 (mitochondrial fusion) and rhot1 (mitochondrial trafficking). BEAS2B+MSC co-culture showed protective response against the CSE-induced mitochondrial respiration (OXPHOS) confirming the beneficial effect of MSC to lung epithelial cells. MSC+EXO treatment showed attenuation of selected inflammatory and DAMPs markers such as MMP9, S100A4 and HMGB1. MSC+EXO treatment may act against these early events caused by CS exposure owing to its anti-inflammatory and other mitochondrial transfer mechanisms in COPD.


Biography


Irfan Rahman is an Associate Professor of Environmental Medicine and Pulmonary Medicine at the University of Rochester Medical Center, NY. His research is funded by the NIH via R01 mechanism. Dr. Rahman is an author of over two hundred (200) publications in peer-reviewed journals, and invited to write chapters in medical text books and editorials in journals. Dr. Rahman is an Associate Editor and a member of the editorial boards of several international journals. He has been serving on various NIH study section rosters since 2005. He is a full faculty member of F1000 Medicine team.

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Irfan Rahman

University of Rochester Medical Center, USA
H-index-96

Title: Translational Laboratory Research to Inform Cancer Risk Assessments


Abstract


Human epidemiological studies associating chemical exposures to cancer risk often areinconsistently validated across studies. Examples include the effect of smoking on cancer etiology other than the lung, such as urinary bladder and breast. Research findings from the laboratory have improved the understanding of arylamine carcinogen metabolism leading to improved design and interpretation of human molecular epidemiology investigations. Laboratory studies that infer and test biological plausibility, including cancer risks modified by differential metabolism of arylamine carcinogens in rapid and slow arylamine N-acetyltransferase (NAT2) acetylators, have been critical for investigating the role of smoking in the etiology of human cancers. This chapter will illustrate these concepts with an example of a cancer in which the role of smoking has largely been validated (urinary bladder cancer) and an example where a consensus has yet to be achieved (breast cancer).


Biography


Dr. Hein serves as Peter K. Knoefel Endowed Chair, Professor and Chair of the Department of Pharmacology & Toxicology, and Distinguished University Scholar at the University of Louisville (USA).Dr. Hein’s research program has been funded since 1983 by over 75 grants and contracts totaling over $50M from the National Institutes of Health and other federal and private foundations and industry. He has coauthored over 250 with over14,000 citations (h-index=60). He has presented about 150 invited research seminars in Australia, Austria, Canada, China, Czech Republic, Egypt, France, Germany, Greece, Italy, Norway, Switzerland, the United Kingdom and across the USA

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David W. Hein

University of Louisville School of Medicine, USA
H-index-60

Keynote Talks

Title: Cell Fate Control upon Genotoxic Damage: New Insights from the P53 Signalling Pathway


Abstract


The DNA damage response (DDR) is coordinated by an evolutionarily conserved signaling network governed byDNA damage-activated protein kinases, including ATM (ataxia telangiectasia mutated) and ATR (ataxia telangiectasia and Rad3-related), which coordinate the DDR and antagonize genomic instability and cancer. A detailed understanding of the players and the regulatory processes involved in controlling DNA damage-induced cell fate decisions might enable us to manipulate the DDR towards induction of cellular senescence and/or apoptosis to improve the efficacy of cancer therapies. A major downstream regulator of the DDR is the tumour suppressor protein p53, which is frequently mutated or functionally inactivated in cancer. Post-translational modification is a key regulatory principle for controlling p53 activity. In response to DNA damage, p53 is heavily phosphorylated and acetylated at multiple sites, which contributes to p53 stabilization, target gene selection and cell fate decision-making. Our previous work identified Homeodomain Interacting Protein Kinase 2 (HIPK2), as acentral cell fate regulator upon DNA damage. Upon severe DNA damage, HIPK2 forms a complex with p53, site specifically phosphorylates p53 at Ser46 and activates the cell death response. Accordingly, work from different labs demonstrated that HIPK2 is critical regulator ofcancer cell radio- and chemosensitivity. Our recent work shed light on the cellular pathways and mechanisms regulating HIPK2 activation and inactivation. Activation of HIPK2 is mediated by the DNA damage checkpoint kinases ATM and ATR, which control HIPK2 stabilization and activation through facilitating HIPK2 autophosphorylation and dissociation of its negative regulatory E3 ubiquitin ligase Siah-1.To gain deeper insight into HIPK2 regulation and function we screened for novel HIPK2 regulators. In our unpublished work we have characterized the role of novel HIPK2 regulators and thereby identified novel regulators of cancer cell chemosensitivity and –resistance.


Biography


Institute of Toxicology, University Medical Center Mainz, Johannes Gutenberg University, Mainz, Germany

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Thomas G Hofmann

University Medical Center Mainz, Germany

Title: A New Vision of Aristolochic Acid Nephropathy through NMR-Based Metabonomics


Abstract


The Balkan Endemic Nephropathy (BEN) is a kideney disease histologically characterized by an interstitial fibrosis, a proximal tubular atrophy and a high proteinuria. BEN shares some common symptoms with the aristolochic acid nephropathy (AAN) observed in Belgian patients who had consumed diet pills made of various chinese herbs contaminated with AA. Two hypotheses exist concerning the possible environmental factor of BEN, either an intoxication with ochratoxine A or with aristolochic acid. In this work, we compared by a metabonomic approach the nephrotoxicity of aristolochic acid with three prototypical renal toxicants (cisplatin, ifosfamide, and gentamicin). These molecules were chosen onthe basis of specific renal alterations. Cisplatin and ifosfamide are two antineoplastic agents, used in the treatment of solid tumors. Gentamicin is an aminoglycoside antibiotic, used in the treatment of bacterial infections. The metabonomics approach supplied a global view of the metabolic changes induced by exposure to the three prototypical molecules. Those characteristic metabolic signatures were obtained from the NMR-based spectroscopic analysis of collected biofluids (urine and blood) combined to multivariate data analysis. The results obtained in this study confirmed the proximal tubular damage for the three toxicants as evidenced by several markers of this particular injury (glucose, hippurate, organic acids, …) as well as the dose-dependent nature of the lesion. Although not completely definite, the comparison of the metabonomic signatures obtained with AA and the three prototypical molecules revealed some overlap with ifosfamide at late time points of the study, suggesting similar mode of actions between AAI and ifosfamide, at least partially.


Biography


Prof. Jean-Marie Colet has completed his PhD from University of Mons, Belgium and postdoctoral studies from University of Texas/Dallas, USA and King’s College London, UK. He is the director of the Laboratory of Human Biology & Toxicology at the University of Mons, Belgium. He has published more than 40 papers in reputed journals and has been serving as an editorial board member of repute. He has also worked as a toxicologist et Eli Lilly & Compagny as well as at Total Petrochemicals.

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Jean-Marie Colet

University of Mons, Belgium

Title: Addressing Challenges of Space Pharmacology for Long-Duration Exploration Missions


Abstract


Spaceflight-induced physiological changes and limited resources for rescue and medical care imposes unprecedented demands on the health and well-being of astronauts undertaking long-duration missions beyond Low Earth Orbit (LEO). Within almost a half-century of human spaceflight, space faring nations have learned to control astronaut’ health risks posed by exposure to the spaceflight environment. Pharmacological interventions have been routinely used in spaceflight missions to alleviate the immediate symptoms that impair crew function, as well as helping to minimize long-term physical and physiological damage to crew members.Because of the altered physiological status in astronauts caused by adaptation to low gravity, the response to terrestrial medications may be different from what we know from Earth-based medical practices. Prolonged exposure to spaceflight environmental factors including microgravity, solar and cosmic radiation, and cabin chemical factors may significantly change the drug therapeutic toxicity index, potency, and shelf life stability. Therefore, all efforts should be made to estimate and predict the individual efficacy-to-risk ratio of a particular drug therapy under medical emergency and common conditions.Preparing for future deep space missions to Mars and beyond brings new challenges to scientist, engineers and flight surgeons in an effort to have the ability to manage any plausible health problems which could occur when astronauts cannot rely on ground assistance. This presentation gives a broad overview of the multifaceted issues surrounding space pharmacology and further addresses specific challenges associated with future missions beyond LEO.


Biography


Yuri Griko has completed his PhD at the age of 32 years from Moscow Instituteof Physics and Technology in 1987 and postdoctoral studies from Johns Hopkins University. He is the director of Countermeasure Development Laboratory at NASA Ames Research Center. Hisresearch interests and research program management activities primarily lie in the areas of molecular biology, biophysics, protein-based drug design and delivery system, drug stability and formulation development. He has published more than 110 papers in reputed journals and is co-inventor on 4 US patents involving technology.He has been serving as an editorial board member of repute.

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Yuri Griko

NASA Ames Research Center, CA 94305, USA

Title: Polyoxometalates as Potential Drugs: Pharmacology and Toxicology Polyoxometalates as Potential Drugs: Pharmacology and Toxicology


Abstract


Polyoxometalates (POMs) are negatively charged metal-oxo clusters of early transition metal ions in high oxidation states (e.g. WVI, MoVI, VV). Numerous in vitro as well as in vivo studies have been demonstrated versatile biological activities of POMs such as anticancer, antibacterial, antiviral, as well as their capacity to regulate glycaemia, and possible applications in the therapy of some neurological and pulmonary diseases. Although the biological activity of POMs has been investigated for many years, there is a relative lack of relevant data related to the toxicity of these compounds in in vivo studies. Recently, different biological activities of the selected POMs have been investigated. The obtained results of in vitro acetycholinesterase inhibition induced by a series of Keggin heteropolytungstates suggest that POMs could act as promising therapeutic agents for Alzheimer's disease. Furthermore, a promising hypoglycemic effect of donut-shaped POM {NaP5W30} and its Ag+-containing derivative {AgP5W30} in Wistar rats with streptozotocin-induced diabetes was demonstrated. Moreover, a potent antileukemic effect of two newly synthesized polyoxopalladates against human acute promyelocytic cell line HL-60 was demonstrated. Additionally, toxicological studies of the investigated POMs were performed using Wistar albino rats as a model system, in accordance with OECD Guidelines for the Testing of Chemicals. The biochemical parameters of renal and liver function 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-AChE 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 hypoglycemic 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 has published more than 50 papers in impacted international journals. Her papers have been cited more than 1000 times.

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Danijela Z. Krstic

University of Belgrade, Serbia

Sessions:

Title: Mechanisms of Genomic Rearrangements: How Hexavalent Chromium, a Major Environmental Concern, Induces Chromosome Instability


Abstract


Particulate hexavalent chromium [Cr(VI)] is a known human lung carcinogen, but how it causes cancer is unknown. We hypothesize the carcinogenic mechanism involves the onset of chromosome instability mediated in part by the induction of DNA double strand breaks combined with the loss of DNA double strand break repair. Consistent with our hypothesis, we discovered using the comet assay, immunofluorescence, sister chromatid exchange assay, and DNA repair reporter constructs that particulate Cr(VI) both induces DNA double strand breaks and inhibits homologous recombination repair (HR) in human lung cells. For example, zinc chromate induces concentration-dependent increases in DNA double strand breaks and chromosome aberrations, which persist with longer exposure times; however, after 48 h zinc chromate simultaneously targets Rad51 and inhibits HR repair. Using immunoblotting, immunofluorescence and cryo-electron microscopy, we found zinc chromate inhibited Rad51 expression and repair foci formation, while also inducing cytoplasmic accumulation of Rad51 and loss of Rad51 filament formation on the DNA. Moreover, we found the loss of Rad51 response was a permanent phenotypic change; and successfully developed monoclonal cell lines expressing particulate Cr(VI)-induced loss of Rad51 response. Using great whale species, we discovered whales are exposed to Cr. Remarkably, comparing the effects in whale cells to those in human cells revealed whales may be more resistant to the genotoxic effects of Cr(VI). At the same level of Cr(VI)-induced DNA double strand breaks, whale cells were able to maintain their Rad51 response and consequently exhibited less chromosome damage. These outcomes support our hypothesis that the mechanism of particulate Cr(VI)-induced lung cancer involves loss of DNA repair and chromosome instability, which has important implications for Cr(VI)-induced cancer and lung cancer in general, and further suggest whales may have evolved mechanisms to protect against these outcomes.


Biography


Wise Laboratory of Environmental and Genetic Toxicology, Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky, USA

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John Pierce Wise

University of Louisville, USA

Title: A Novel LC-MS Column for Underivatized Amino Acids and Related Compounds


Abstract


There are four established methods for analyzing amino acids: pre-labeled, post-labeled, ion-pairing reversed-phase (RP), and normal-phase (NP), but each of these methods has disadvantages. The pre-labeled method has problems with derivatization efficiency and cost, while the post-labeled method is usually not compatible with LC-MS due to non-volatile mobile phases. The ion-pairing RP method has difficulty separating polar amino acids; on the other hand, the NP mode has problems separating all the compounds, especially the Leu and Ile isomers. We have developed a novel underivatized amino acid separation column for LC-MS which can separate all 20 amino acids using a mixed-mode stationary phase structure. We found that NP and ion-exchange (IEX) mixed-mode is much better than RP and IEX mixed-mode for polar amino acid retention and separation. We have estimated separation characteristics and applications using LC-MS instruments and got the following results: 1) isomers separation such as Leu/Ile, 2) applicable to MS, MS/MS and others, 3) 1min high-throughput analysis for selected amino acids, 4) various clinical metabolites and toxic compounds analysis. This novel underivatized LC-MS method will be a powerful tool for amino acid and related compiunds analysis in many different biochemistry applications.


Biography


Itaru Yazawa has co-founded a company, Imtakt Corporation in 1999 at Kyoto Japan to focus on separation technology providing his own desinged and manufactured HPLC columns to global market. He used to work for Shimadzu Corporation (intstument development) and YMC Co.Ltd (column development), and then he wanted to supply his own unique column products such as RP+AX+CX muli-mode ODS column "Scherzo C18 Family" and 2um Non-porous ODS column "Presto FF-C18" etc. which are based on his own technical idea. Now he will introduce a next generation novel amino acid analysis column for LC-MS "Intrada Amino Acid" for this conference.

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Itaru Yazawa

Imtakt Corporation, JAPAN

Title: Emerging Challenges in the Water Sector and Their Implications for Public Health


Abstract


Water is the most abundant compound on the surface of our planet earth. Its usefulness cuts across every facet of our existence, from domestic usage through to world economy and security. However, protection of this important resource has become a major global challenge especially amongst developing countries including South Africa. Even so, the problem of inadequate skilled manpower in the water sector is a recurring decimal suggesting the urgent need for collaboration between the water sector, government and academia. Also, the increasing incidences of emerging and re-emerging microbial pathogens in water; their survival strategies in conventional treatment processes; evidences suggesting increasing incidences of resistance to regular disinfection regimes; bioprospecting aquatic microbial diversity for new bioactive compounds in water treatment to replace current compounds that are being implicated in hazards; and the need for review of existing water quality guidelines to capture emerging trends such as wastewater effluents as reservoirs of antibiotic resistance determinants becomes imperative and will be discussed in this paper.


Biography


Prof Anthony Okoh is a Professor of Microbiology. He served as Head of the Department of Biochemistry and Microbiology at the University of Fort Hare (UFH) for 7 years. He is currently the Leader of the Water Research Niche Area of the university, and Director, SAMRC Microbial Water Quality Monitoring Centre in the same University. His research interests is in the area of Applied and Environmental Mirobiology. He has published over 360 journal articles and graduated 49 PhD and 66 Master’s degree students. He is a Fellow of the prestigious African Academy of Sciences amongst others.

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Anthony I Okoh

University of Fort Hare, South Africa

Title: Determination of -Methylphenethylamine and its Metabolites in Whole Blood (Wb) Of Rats Using Mixed Mode Solid Phase Extraction (Mmspe) And Uplc-Qtof-Ms


Abstract


Beta-Methylphenethylamine (BMP) is a recreational drug that was synthesized in the 1930s as an alternative analog of amphetamine (AMP); it is a positional isomer of AMP. Figure 9 shows the chemical structures of AMP and BMP. Pharmacologically, BMP acts as a DA-receptor agonist, facilitating DA release and inhibiting DA reuptake from the synaptic cleft, but to a lesser extent than AMP does. The metabolism of BMP is poorly understood, and the efficacy and safety of BMP have never been evaluated in humans. Hence, its use as an ingredient in weight loss products and dietary supplements has been banned by the FDA. To our knowledge, no pharmacokinetic study of BMP has been performed in animals. Therefore, one of the main goals of this project was to partially investigate the metabolic pathway of BMP in rats. In this study, our validated analytical assay for the identification and quantification of selected amphetamine-related drugs (ARDs) in WB by MMSPE and UPLC-qTOF-MS was used to determine BMP concentrations and to identify any of its metabolites in cardiac WB from rats exposed to BMP. There was one newly detected metabolite of BMP, which is proposed to be 1-amino-2- phenylpropan-2-ol. This proposed metabolite structure was determined through its fragmentation pattern by using the 〖MS〗^Eacquisition mode of qTOF-MS. Further experiments are required to confirm the proposed chemical structure of this newly detected metabolite of BMP.


Biography


Health Ministry, Poison Control and Chemistry Forensic Medicine Center, Saudi Arabia Laurentian University, Canada

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Ahmad Alamir

Saudi Health Ministry, Laurentian university canada

Title: Unusual Cases of Nervous System Damage: Diagnostic and Therapeutic Problems


Abstract


Introduction. Peripheral nervous system damage, or peripheral neuropathy, is a difficult clinical problem. The most common causes include traumatic injuries, inflammation, and metabolic disorders. Traumatic injuries, both acute and chronic, usually affect single nerves (mononeuropathies) while inflammation and metabolic disorders damage multiple nerves (polyneuropathies). The paper presents two rare cases of severe nervous system damage. Material: Case 1. The first part describes the clinical presentation of a female patient with yew needle extract poisoning. The predominant neurological symptom was severe spastic tetraparesis with a bilateral positive Babinski sign and total aphasia. After physical therapy and rehabilitation, the patient’s mental status and ability to maintain contact were considerably improved and further increases in muscle strength and physical function were seen, which helped the patient walk unassisted using a walking frame and perform the activities of daily living. Case 2. A quality inspector working at a gas station presented with distal paresis of both lower limbs after chronic, long-term, 20 years’ occupational exposure to gasoline fumes. He had memory gaps, psychomotor retardation, a gait with bilateral foot-dragging, diminished knee and ankle reflexes, and glove- and stocking-type superficial sensory disturbances. The patient underwent physical therapy and rehabilitation at the Department of Rehabilitation, including four-cell baths, electrical stimulation, low-frequency alternating magnetic fields, active exercises (non-weight bearing, with regulated resistance, improving the muscle strength of the extensors and flexors of both feet), exercises with regulated intensity on an ergometer, and gait training. The treatment resulted in partial improvements with respect to the weakened muscle groups. A further six months’ follow-up showed increasing central and peripheral nervous system deficits. Results and Conclusion. Toxic polyneuropathy and encephalopathy are irreversible in patients with chronic hydrocarbon poisoning caused by gasoline and result in permanent nervous system damage. Physical therapy and rehabilitation must be patient-specific. Key words: Taxusbaccata, gasoline poisoning, rehabilitation treatment.


Biography


Professor WłodzisławKulińskispecjalist in internal medicine , rehabilitation and physical medicine. Academic teacher , working in the Rehabilitation Clinic of the Military Medical Institute in Warsaw and the Faculty of Medicine at Jan Kochanowski University in Kielce. Author of more than 300 publications and more than 220soldies. Chief editor of ActaBalneologica quarterly and member of Polish and foreign societies.

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Wlodzislaw Kulinski

Military Institute of Medicine, Poland

Title: The Enterotoxic Activity of Sarcocystis Fayeri -15kDa Protein


Abstract


Genus Sarcocystis is a protozoa which has two-host life cycle. Herbivores are main intermediary hosts, and genus Sarcocystis forms sarcocysts in their muscle tissue. Sarcocystosis has been known as a problem of economic loss in cattle, but it also be known as a causative factor of food poisoning. The symptom of Sarcocystic food poisoning is mainly gastroenteritidis, but neurologic manifestation is also found. The pathogenic causing mechanism is not yet investigated in details, but we found a toxic candidate protein of 15 kDa molecular mass from the cysts of Sarcocystis fayeri. S. fayeri is identified a causative pathogen for food poisoning by eating raw horse meat (sashimi) in Japan. Now we tried to examine its function in more detail. First, we determined an amino acid sequence of the 15kDa size protein, and identified it as an actin depolymerizing factor (ADF). Then we synthesized a recombinant ADF protein. It showed an enterotoxic activity in a rabbit illeal loop test, but didn’t cause any damages on viability of L929, Raw264, and Caco-2 cells. For further examination of enterotoxic activity we tried cytokine assay of recombinant ADF. The culture supernatant of RAW264 cells treated with the recombinant ADF for 24 hrs was added into the medium for L929 fibroblast cells which are sensitive to TNF-alpha. After 24hr culture, the viability of the L929 cells was found to be dead, suggesting TNF-alpha production. In this study, we confirmed the enterotoxic activity of parasitic toxic candidate protein, but further research will be necessary to elucidate the mechanism of another species of Sarcocystis.


Biography


Akiko Yamazaki has completed PhD in 2011 at Institute of Tropical Medicine, Nagasaki University and worked at National Institute of Health Sciences Japan as a young researcher. She is an assistant professor of Iwate University from 2015. Her major areas of research is veterinary public health, food hygiene, and zoonosis.

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Akiko Yamazaki

Iwate University, Japan

Title: B[a]P Induced Repression of MMR and HR is Associated with Altered E2F1/E2F4 Signaling and Represents an Early Event During DNA Damage-Induced Senescence


Abstract


Genotoxic stress causes DNA damage and leads to the accumulation of mutations, carcinogenesis and/or cell death. To counteract these effects, DNA repair mechanisms have evolved in order to remove or tolerate DNA lesions. Thereby, the DNA repair is of central importance for maintaining genomic integrity and cell survival. Transcriptional regulation of DNA repair genes is an important regulatory mechanism contributing to the proper and coordinated function of the DNA repair. Previously we showed that exposure to benzo(a)pyrene (B[a]P), which represents the most important carcinogen formed by incomplete combustion during food preparation and smoking, causes an orchestrated upregulation of the DNA repair factors DDB2, XPC and POLH, enhancing repair activity and protecting cells, however at the cost of increased mutation frequency. Here we report, that at the same time transcriptional downregulation of the mismatch repair (MMR) factors MSH2, MSH6 and EXO1, as well as of the homologous recombination (HR) component RAD51 occurs, leading to diminished HR and MMR capacity. Transcriptional repression was caused by abrogated E2F1 signalling, which by itself was mediated by proteosomal degradation of E2F1. Furthermore, transcriptional repression of E2F1 and of the DNA repair factors was caused by activation of the DREAM complex. Abrogation of the E2F1-pathway was independent on cell death and autophagy but was associated with the induction of B[a]P-induced senescence, linking senescence induction and repression of DNA repair pathways.


Biography


Markus Christmann has completed his PhD at the Johannes Gutenberg University in Mainz, Germany and postdoctoral studies at the University Medical Center in Mainz, Germany. He is group leader at the Department of Toxicology, University Medical Center, Mainz, Germany. He has published more than 60 papers in reputed journals and has been serving as an editorial board member.

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Markus Christmann

University Medical Center Mainz, Germany

Title: Risk Assessment of Potentially Mutagenic Impurities in Drug Products Approved In Brazil


Abstract


The presence of impurities in drug products has been controlled according to international guidelines in the entire world. Impurities with mutagenic potential have their own guideline (ICH M7) sincelower limits are applied due to their greater toxicity. ICH M7 is not applicable for drug products which are already approved, however recently some mutagenic impurities have been found above the permitted limits in valsartanand other drug products which were already approved by regulatory agencies. The objective of this project is to identify the possible mutagenic impurities in anti-hypertensive drugs approved in Brazil and perform the risk assessment proposing control strategies for such impurities. The possible impurities in each drug substance were identified based on the drug master file, a document where the manufacturer describes the manufacturing process and potential impurities of the drug substance. For the mutagenicity prediction of the impurities, in silico systems were used, and to one inconclusive case the Ames test will be performed. For evaluation of the levels of the impurities in the drug substance, in silico tools such as the purge factor approach, as well as validated analytical procedures will be used. The preliminary results show that 23% of the evaluated impurities are mutagenic, however all impurities for which the risk assessment was concluded are below the acceptable limits. This shows how inevitable it is for mutagenic impurities to be present at low levels in drug substances, but it also suggests that the current manufacturing processes are adequate to keep the negligible risk.


Biography


Fernanda Waechter is a Drug Master File (DMF) Specialist at Ache Laboratorios, a Pharmaceutical company in Brazil. She is currently focused on toxicological evaluation of impurities for ICH M7 compliance, which is the subject of her Master’s studies in Toxicology at University of Sao Paulo (USP). She graduated in Pharmacy at the Federal University of Rio Grande do Sul (UFRGS). She has studied Biotechnology at Pitt Community College in 2008, andowned a scholarship from the Brazilian government in 2012 to study Pharmaceutical Sciences at University of California, Irvine (Science without Borders Program).

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Fernanda Waechter

University of Sao Paulo, Brazil

Title: Silicosis: The Pathogenic Mechanisms, Prevention and Potential Treatment


Abstract


Silicosis is an irreversible and incurable fibrotic lung disease, which is caused by occupational exposure to silicon dioxide or silica dust. The disease is characterized by interstitial lung inflammation during the early stages and the deposition of excessive collagen in later stages. The progressive pulmonary fibrosis results in breath difficulty and low blood oxygen levels and eventual death. Accumulating evidence indicated that multiple factors participate in this process. These include the induction of inflammatory cytokines and modulation of transcription factors or non-coding RNAs (ncRNAs). Other biological events, such as autoimmunity, angiogenesis, and epithelial-mesenchymal transition (EMT) are involved in different stages of silicosis. Great effort has been made in clinics and laboratory to develop treatment methods for this disease. Currently, there is no effective way to cure the disease, leaving the prevention being still the best way to avoid the disease. This talk reviews the recent progress in studying the pathogenic mechanisms of the disease, its prevention and potential treatment.


Biography


Dr Cheng Peng is currently working as a Senior Research Fellow at Queensland Alliance for Environmental Health Sciences (QAEHS), joint Research Fellow at UQ Centre for Clinical Research (UQCCR). He is also an adjunct Professor at Shandong Academy of Occupational Health and Occupational Medicine. His research interests include DNA repair proteins, molecular toxicities of environmental factors such as polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs), nano-particles and relevant health risk assessment. His also works on screening compounds with potential anti-leukemic and anti-silicosis effects.

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Cheng Peng

Shandong Academy of Occupational Health and Occupational Medicine, China

Title: Treat of the Blood is to the Treat of the Cancer


Abstract


Background: Blood is the only substance that exists throughout the human body. Blood is a source of life that feeds whole body and organs to function. According to this, if the blood is healthy; the whole body will be healthy. The aim of this article is to emphasize that blood is the most precursor substance that made a human healthy. At the same time, with drawing attention to the obligation that blood must be healthy, in the case of blood degeneration or loss its features, it is emphasizing carefully that whole body health will fail. Method: Examination of classical medical data and modern medical researches related to blood, an eclectic approach has been introduced which will fail human health with degeneration of blood. Moreover, treatment methods for solving the mentioned problems have been revealed in this study either. Result: It emphasized that the treatment of all the illnesses in the body, caused by degenerated blood, is possible by curing the blood. Because many diseases in the human body are caused by the degeneration of the blood. Cancer is also this kind of disease, and its treatment can only be understood by us, by means of blood treatment. Conclusion: With the degeneration of the blood, the whole body goes bad and diseases emerge. The treatment of this is to ensure that the degenerated blood is expurged and that the body can produce its own blood in a healthy manner. Key words: Human Health, Cancer, Blood, Treatment


Biography


Dr. Eda ALEMDAR was born in Erzurum-Turkey. Graduated from Erzurum High School. She started her university education at Selçuk University, Faculty of Science in Turkey, and she continued her studies and researches at University of GoceDelcev, Faculty of Medicine in Macedonia. Dr. Alemdar has two international patents in medicine. She has two inventions, one for cataract treatment and the other one for sinusitis treatment. She was involved in several international projects. These projects are about biological clock & biological rhythm and diseases related to environment. She is also involved in some research projects focused on the relationship between blood and health. According to these projects, blood is considered as the cause of large-scale diseases. When blood is clean and natural, many diseases can be cured, including cancer. She continues her studies and researches in collaboration with some universities and hospitals in Turkey.

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Eda Alemdar

Eda Alemdar, Goce Delchev University of Stip, Macedonia

Title: The Influence of Seasonal Factors on the Cytogenetic Activity of Cyclophosphamide and Zolendronic Acid


Abstract


Biological rhythms, being genetically fixed, are a universal form of adaptation to cyclically changing environmental factors.At the same time, seasonal biorhythms can modify the toxic effect of xenobiotics, chemicals, including pharmaceutical substances.Zoledronic acid is used as a drug for the treatment of osteoporosis, Paget's disease, and in the combined treatment of multiple myeloma.Cyclophosphamide is a cytostatic drug with a wide range of antitumor activity.In the literature, there are data on the mutagenic effect of zoledronic acid in human lymphocyte cell cultures and the renal epithelium of dogs and monkeys.Cyclophosphamide is a mutagen, which is confirmed by many studies, as well as data from the International Agency for research on cancer, which classified cyclophosphamide as an absolute carcinogen (1 category of carcinogens). The purpose of these scientific studies was to study the chronorectivity of cytogenetic (including mutagenic) effects of zolendronic acid and cyclophosphamide in chronic experiments on white rats with intranasal administration. Cytogenetic activity of pharmaceutical substances cyclophosphamide and zolendronic acid was studied in white rats.Intact animals that were not exposed to pharmaceutical substances were used as controls.The series of experiments included: the 1st experimental group, the exposure duration of 60 days, the 2nd experimental group-the exposure of 120 days, the 3rd experimental group-120 days of administration of substances and 30 days after the termination of their introduction (recovery period).Experimental animals were subjected to intranasal exposure of pharmaceutical substances in the following concentrations: 0.10, 0.05 and 0.01 mg/m3.At the end of the chronic experiments and the recovery period, washes were prepared from the lungs of white rats, in which cytogenetic damage to nuclear cells was taken into account using light microscopy. As a result of the experiment, we can conclude that the levels of cells with cytogenetic disorders in chronic inhalation intake of cyclophosphamide and zolendronic acid and in the recovery period are the result of direct and remote mutagenic action against the background of fluctuations in cell pools with different sensitivity to DNA damage, as well as the influence of seasonal and compensatory mechanisms of cell replacement repair. Comparison of spontaneous proliferative activity of cells of control and experimental animals at different times of the year indicates an increase in proliferative activity in the winter-spring period and a decrease in the autumn period, which should be taken into account when studying the cytogenetic activity and mutagenic properties of xenobiotics. The most pronounced cytogenetic disorders in the lung cells of experimental animals when exposed to zolendronic acid corresponded to a seasonal increase in the proliferative activity of cells against the background of a decrease in their resistance to DNA damage. The detected cytogenetic disorders in the cells of lung flushes caused by zoledronic acid do not allow us to unambiguously assert the presence of mutagenic activity in this pharmaceutical substance.


Biography


Republican Unitary Enterprise «Scientific Practical Centre of Hygiene», Laboratory of Industrial Toxicology, Minsk, Belarus

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Viktor Afonin

Respudlican unitary enerprise "SCIENTIFC PRACTICAL CENTRE OF HYGIENE

Title: Significance of toxicological interaction studies


Abstract


Risk assessment for mixtures of chemicals requires to investigate the presence of potential interactions between those chemicals. This is usually done by assessing how experimental toxicological mixture data depart from the model of Loewe additivity (Effect of combinations: mathematical basis of problem, Arch. Exp. Pathol. Pharmakol. 114, 1926). Several recent scientific studies propose to perform this task using an ad hoc method known as Model Deviation Ratio (MDR) method. More recently, the first official European regulatory document for the study combined exposures recommends the use of the MDR method (EFSA Scientific Committee et al. Guidance on harmonised methodologies for human health, animal health and ecological risk assessment of combined exposure to multiple chemicals. EFSA Journal, 2019). We show here that the MDR method is not calibrated, it leads to erroneous decisions and that the results reported lately in studies using the MDR are likely inaccurate. In contrast, we show that a classical statistical technique known as likelihood ratio test provides accurate results, including when sample size are close to the minimum required by OECD guidelines. We show also that the variance of the MDR can be evaluated by simulations and we explain how it allows us to use MDR when no other experimental are available, a situation typical of meta-analyses.


Biography


Gilles Guillot has completed his PhD at the University of Grenoble, France. He has been a faculty member at the Technical University of Denmark and a staff scientist at the European Food Safety Authority. He has been serving as Associate Editor Journal of the Royal Statistical Society. He is currently Vice President Biostatistics at IPRI.

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Gilles Guillot

International Prevention Research Institute, France

Title: Childhood TB in HIV Era- in Sub Saharan Africa


Abstract


Background- TB is surging much of the Africa because of HIV epidemic, it is observed that TB rate is much higher then what is reported it in public health system in developing country. In South Africa out of all TB case 16% are children. Objective- Childhood mortality is increasingly higher in sub-Saharan Africa. To know the reason of child mortality- is it because of TB or HIV or both? Method – TB & HIV infection in children in retrospective study was in our mind. WHO endorsed in 2010 new diagnostic tool to confirm TB, like Gene XPRT, MDR/RIP, PCR based test even in children. Presently it is not widely available in Sub Saharan Africa because of high cost. South Africa lucky to have Gene XPRT test kit available even in district hospital. BCG vaccine and Tuberculin skin test and its results interpitation helps for diagnosis and prognosis of childhood TB.In children, malnutrition, measles, and whooping cough increase the risk of progression to active TB disease. Results- Present deaths Worldwide, HIV: 6000/day, TB: 5000/day South Africa,-TB case Incidence: 4 th in the world, Childhood TB- 16% of all TB cases.In 2010, 8.8 million new TB cases globally, 1.1 million deaths (excluding HIV).1.1Million new HIV associated TB cases worldwide, Out of all 82% living in Sub Saharan-Africa. About 50-60% of all HIV patients when start with ART, had TB in their life time. Co-infection of TB &HIV – Globally- 13%, South Africa- are around 25- 60% of amongst children.It is observed that the patterns of TB symptoms are also changing to that of conventional one. Conclusion- Problem persists still on diagnosis of TB as 87% of the TB patients shows smear negative even with fluorescent microscope. It shows that smear negative TB patients have high mortality even with proper TB treatment. It also observed that HIV patients having low CD4 count had low TB organism in sputum. TB is a multisystem disease. TB is number one cause of death, in HIV infected patients specially children. TB and HIV are correlated with each other; if we can decrease the incidence of HIV we can decrease the incidence of TB both in morbidity and mortality, I will discuss all these issue and facts in this topic.


Biography


Dr Mir Anwar graduated Medicine from Bangladesh in 1975He did his post-graduation in Pediatrics from Ireland in 1982.Further he did his Public Health Post graduation- MPH (concentration Maternity and Child Health) from University of Massachusetts, USA in 2003. Then he joins in UN/ WHO and worked as a Pediatric Consultant & Public Health Specialist, around the world including Asia, Middle East, Africa, Pacific Island, Ireland and USA. Since 2007 he has been working in South Africa in different provinces of South Africa with the Department of Health. Presently he is working as a Clinical Medical Manager in Richmond Chest Hospital, KZN. South Africa. His main research interest presently is, Childhood TB with HIV in Sub-Saharan Africa. In his long carrier in Pediatric and Public Health he had attended several International Congress, Conferences, and Seminars and presented his original work. Some of them were published in International Journal Including American Child Neurology Journal, Japan Pediatric Neurology Journal, Pakistan Pediatric Journal, Bangladesh Child Medical Journal, and Nigerian Journal of Obstratics and Gynecology Etc. For his work he is honored by American Academy of Pediatrics, Royal College of Health, UK, and International College of Pediatrics. Etc. His Biography was published in Who’s Who in Medicine Cambridge, UK in 1985. He is an active member of different International and National Pediatric Organization, Association etc. Presently is one of the honorary Member of Editorial Board- Journal of Pediatrics & Neonatal Biology, Published from Texas, USA.

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Mir N Anwar

Stanger Hospital, South Africa

Title: Xenobiotics: A Screening Method Based on Immobilized Artificial Membrane Liquid Chromatography in Supporting Early Toxicity Assessment.


Abstract


The achievement of affinity indexes for phospholipids has been fruitfully performed by a Liquid Chromatography (LC) technique, the so called IAM- LC, the acronym of Immobilized Artificial Membranes, a chromatographic stationary phase consisting of phosphatidylcholine-like residues covalently bound to silica, the main biological component of cellular membranes. The scales of affinity of a xenobiotic, drugs or chemicals for phospholipids, achieved by IAM-LC, are able to measure not only the total membrane affinity of the analytes, but also the contribution of the different physico-chemical forces, polar/electrostatic and lipophilicity intermolecular interaction forces involved in membrane barrier passage. Being based on LC, this technique assures superior inter-laboratory reproducibility as compared to cellular or in vivo assays. These interactions were parametrized by ΔlogkWIAM values, i.e. the differences between experimental affinity values for phospholipids and the expected affinity values based on n-octanol lipophilicity. ΔlogkWIAM has been demonstrated able to describe and therefore predict the passage of xenobiotics though complex biological barriers and the related phenomena (e.g., intestinal absorption, skin permeation, blood-brain barrier passage), mirroring the interactions actually occurring in vivo. The IAM technique can be useful for a preliminary screening of drugs and chemicals for the evaluation of their pharmacokinetics/ toxicity properties to minimize animal testing.


Biography


Lucia Grumetto has completed her studies at Federico II University of Naples - Italy - master’s degree in Pharmacy (1996) and in Biology (1987). She is senior researcher working at the Department of Pharmacy Federico II University; she has published more than 52 papers in reputed international journals and has participated at several meeting communications. Main fields of scientific interests include development of analytical methods for the separation and quantification of xenobiotics (drugs, environmental pollutants) in complex matrices and elucidation of drug interaction mechanisms with biological membranes responsible for their absorption and metabolism, employing IAM-HPLC (Immobilized Artificial Membrane HPLC) technique.

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Lucia Grumetto

University of Naples Federico II, Italy

Day 02 Schedule

Jun 16, 2020

Plenary Talks

Title: Assessment of Toxicological and Pharmacokinetic Studies of The Promising Anticancer Agent, Methylglyoxal


Abstract


In vivo studies from several laboratories had found remarkable anticancer effect of methylglyoxal on cancer-bearing animals. However, many in vitro studies have assigned a toxic role for methylglyoxal. Our laboratory demonstrated that methylglyoxal is non toxic in vivo at its therapeutic dose. Four species of animals, both rodents (mouse, rat, rabbits) and non-rodent (dogs), were treated with different doses of methylglyoxal through oral, subcutaneous and intravenous routes. Acute (treatment for only 1 day) toxicity tests done with mouse and rat and chronic (treatment for around a month) toxicity test done with mouse, rat, rabbit and dog found that methylglyoxal had no deleterious effect on the physical and behavioral pattern of the treated animals. Fertility and teratogenecity studies established that animals produced healthy litters indicating no damage of the reproductive systems as well as no deleterious effect on the offspring. The biochemical and hematological parameters of methylglyoxal-treated rats and dogs and histological studies of several organs of methylglyoxal treated mouse indicated that methylglyoxal had no apparent deleterious effect on the vital organs of these animals. Additionally, pharmacokinetics of orally fed methylglyoxal in mice has indicated that the concentration of methylglyoxal reaches maximum at 4 h after administration and reaches its basal levels after another 4 h.


Biography


Manju Ray is an Indian scientist and has done notable work in the development of anticancer drug. Her interests cover tumor biochemistry and molecular enzymology. Ray graduated from the Calcutta University with degrees in M.Sc. in Physiology in 1969 and Ph.D in Biochemistry in 1975. She started her career in the Department of Biochemistry, Indian Association of Cultivation of Science, India, and became a professor. She is now a Hon. Visiting Scientist at Bose Institute, India and Distinguished Professor at GLA University, Mathura. Her research has, over a long span of her career in the department of biochemistry at the Indian Association for the Cultivation of Science (IACS), Jadavpur, in association with a team of scientists and doctors that has led to positive development of a drug for cancer treatment. She is an West Bengal Academy of Science fellow and Shanti Swarup Bhatnagar awardee.

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Manju. Ray

Bose Institute, India
H-index-47

Title: EFdA; A very excellent anti-HIV Modified Nucleoside, -From Design to the Current Clinical Results-


Abstract


EFdA (4’-ethynly-2-fluoro-2’-deoxyadenosine) prevents the emergence of resistant HIV mutants, and is over 400 times more active than AZT and several orders of magnitude more active than the other clinical reverse-transcriptase (RT) inhibitory 2’,3’-dideoxy nucleoside drugs, very low toxic, very long acting, and very useful for prophylaxis. EFdA is now under clinical trials by Merck & Co. as MK-8591. In the beginning of my talk, a general idea for the development of anti-viral modified nucleosides based on the mutation of viruses will be presented. Next, the development of EFdA is discussed and then the current results of the clinical trials of EFdA reporeted by Merck & CO. will be presented. For the design of the modified nucleoside that could solve the critical problems of the clinical drugs (1. Emergence of drug-resistant HIV mutants, 2. Adverse effects by drugs, 3. Necessity to take considerable amount of drugs), four working hypotheses were proposed. They are (1) the way to prevent the emergence of drug-resistant HIV mutants, (2) the way to decrease the toxicity of modified nucleosides, (3) the way to provide the modified nucleoside with the stability to both enzymatic and acidic cleavage of glycosyl linkage for long acting in the body, and (4) the difference of the substrate selectivity between RT and human DNA polymerses could make it possible to develop anti-HIV modified nucleosidex that is selectivly active to HIV and very low toxic to human beings. 4’-Substituded-2’-deoxynucleoside (4’SdN) which has 3’-OH was designed as the nucleoside that could satisfy these hypotheses. The study on 4’SdN has succcessfully developed EFdA [modified at the two positions (2 and 4’) of the physiologic 2’-deoxyadenosine] having very excellent anti-HIV activity.


Biography


Hiroshi Ohrui has completed his PhD from the University of Tokyo, and postdoctoral studies from Sloan-Ketteing Institute for Cancer Research and Syntex Research in U.S.A.. He is a Specifically Appointed Professor of Yokohama University of Pharmacy. He has published more than 250 papers in reputed journals and received several prizes including Japan Academy Prize.

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Hiroshi Ohrui

Yokohama University of Pharmacy, Japan

Title: Toxic Effects of Synthetic Cannabinoids, Relative To Δ9THC, are Associated with Atypical Metabolic Profiles and Properties at Cannabinoid Receptors CB1 and CB2


Abstract


Classical cannabinoid use is associated with few adverse effects as compared to synthetic cannabinoids (SCBs), which are rapidly emerging drugs of abuse, that can result in extreme agitation, hallucinations, tachycardia, syncope, and seizures. To potentially explain the higher toxicity associated with SCBs as compared to Δ9THC, we tested the hypothesis that SCBs exhibit disctinct metabolic profiles and atypical pharmacodynamic properties at CB1 and CB2 receptors. In the present studies SCBs and clasical cannabinoids were incubated with human liver microsomes (HLMs) as well as recombinant P450s in the presence of the NADPH regenerating system. Both classes of 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. Subsequent studies with recombinant P450s identified CYP3A4/5 and CYP2J2 as the major isoforms involved in the hydoxylation reactions. Steady-state kinetic analyses were performed, and rigorous metabolite identification was carried out using LC-MS/MS and HPLC-UV/Vis. 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. In conclusion, our study has shown that the atypical pharmacodynamic properties of SCBs at CB1 and CB2 relative to Δ9THC (higher potency/efficacy and greater production of desensitization) coupled with an unusual metabolic profile (production of metabolically stable, active Phase II metabolites) may contribute to the pronounced adverse effects observed with the abuse of SCBs when compased to marijuana. (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.

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Anna Radominska-Pandya

University of Arkansas, United States
H-index-47

Title:


Abstract



Biography


Balali-Mood (MD, Tehran Univ., 1968; PhD, Edinburgh Univ., 1981) is prof. of medicine and clinical toxicology; co-founder, Medical Toxicology Research Ctr (MTRC).and Clin Toxicol Dept (CTD), Mashhad Univ. of Medical Sciences (MUMS); clin. toxicol. adviser, OPCW and IPCS-WHO. His previous positions include: asst. prof. and dir. medical education, Ferdowsi Univ. Mashhad; res. fellow and lecturer, Edinburgh Univ.; dirs. MTRC and CTD, MUMS; and pres., Iranian Soc. of Toxicology and Asia Pacific Assoc. of Medi. Toxicol. He has received Int. and Nat. awards for teaching, research and medical care by Iranian authorities and Intl. organizations including Natl. Research Medal, Int Prof. Alireza Yalda Found. Award 2011 and The 2015 OPCW-The Hague Award. The National Elite Foundation recognized him as the Father of Toxicology of Iran and held commemoration in his birth place (Birjand, Mood) on 29 October 2016. Chief editor, JBUMS and assoc. editor of AJM. His membership includes: Iranian Medical Council; Iranian Acad. of Medical Sciences; Ir. Soc. Toxicology; Europ. Assoc. Poison Centr. Clin Toxicol; Asia pacific Association of Medical Toxicology and Program Advisory Committee, IPCS-WHO.

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Mahdi Balali-Mood

Mashhad University of Medical Sciences, Iran
H-index-32

Keynote Talks

Title: Optimization of Dispersive Liquid-Liquid Micro-Extraction Technique for Trace Tetermination of Pesticide Diazinon Before HPLC Analysis


Abstract


Measurement of pesticides in biological matrices is a serious challenge for researchers due to their very low concentration in different matrices. The aim of this study was to optimize a sample preparation procedure with high accuracy and validity for determination of diazinon. Dispersive Liquid-Liquid Micro-Extraction (DLLME) technique coupled with HPLC equipped with UV detector was developed for trace extraction and determination of diazinon in urine samples. One variable at a time method was used to optimize parameters affecting the diazinon extraction. Different parameters such as extraction solvent, disperser solvent, and volume of the extraction solvent, volume of the disperser solvent, centrifugation time and speed, salt addition, and sample pH were studied and optimized. Findings showed that optimal levels of these variables for diazinon were 150 μl of carbon tetrachloride as extraction solvent, 1.5 ml of methanol as dispersive solvent, pH of 6, 5 minutes centrifuge time at speed of 4000 rpm, 0% (w/v) salt addition. Correlation coefficient was 0.9965 indicating the linearity of a wide range of concentrations of the toxin. LOD and LOQ was calculated less than 0.7 and 5 μg L-1 respectively. The relative standard deviation for six replicate experiments in intra-day and inter-day at three selected concentrations (50, 200 and 1000 μg L-1) was less than 4% that indicates the accuracy and precision of the optimized method. Enrichment factor and extraction recovery for diazinon were 245 and 99% respectively. According to the results, dispersive liquid-liquid micro-extraction procedure was successfully developed for extraction of diazinon from urine samples.


Biography


Seyed Jamaleddin Shahtaheri has completed his PhD at the age of 38 years from Surrey University, England in 1992-1996. He was assigned as an academic member of Department of Occupational Health Engineering, Tehran University of Medical Sciences in 1996. Dr Shahtaheri achieved his Full Professorship in 2006. He has supervised 50 MSc and PhD theses and also published more than 160 scientific papers. He is now Editorial Member of 9 Journals. Dr Shahtaheri was the Persistent Organic Pollutant Review Committee (POPRC) Member under the Stockholm Convention, UNEP, UN during period of 2014-2018. He can be visited at: https://www.tums.ac.ir/faculties/shahtaheri

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Seyed J. Shahtaheri

Tehran University of Medical Sciences, Iran

Title: Influence of Acetyl-11-Keto-Beta-Boswellic Acid on Membrane Dynamics Following Benzo(a)pyrene Induced Lung Carcinogenesis


Abstract


Cancer is perceived as a deadliest disease of mankind is the second leading cause of deaths. Lung cancer incidences are increasing as a consequence of over exposure to environmental pollutants. Smoking remains the primary risk factor and is associated with many of the lung cancer cases. Further, dietary phytochemicals play a key role in chemoprevention of lung cancer. Membrane fluidity is the most important physiochemical property of cell membranes and governs its functional attributes. The current study was designed to understand the potential role of acetyl-11-keto-β-boswellic acid (AKBA), if any, on the regulation of membrane dynamics in conditions of Benzo(a)pyrene (BaP) induced lung carcinogenesis in female Sprague Dawley rats. The animals were divided into five groups which included I) Normal Control, II) Vehicle treated (olive oil), III) BaP treated, IV) AKBA treated and V) BaP + AKBA treated. To induce lung carcinogenesis, BaP was administered at a dose of 50mg/kg b.wt. in olive oil orally twice a week for 4 weeks. AKBA was supplemented to animals at a dose of 50mg/kg b.wt. in olive oil orally thrice a week for 24 weeks and the AKBA treatment started 4 weeks prior to BaP administration and continued thereafter till 24 weeks. Tumour incidence, multiplicity and tumour volume as well as tumour markers which included CEA, TSA and ALP were studied. Non-small cell lung carcinogenesis was confirmed by histological changes. Lipid profile and membrane fluidity related parameters were analysed in lung tissue samples obtained from rats belonging to different groups. Also, structural variations in lipids were analysed by FTIR. The results showed a significant increase in tumour markers in rats treated with Benzo(a)pyrene in comparison to normal controls. Histological changes, increased tumour incidence and tumour burden confirmed the development of lung carcinogenesis by BaP treatment. Total lipids, phospholipids contents, membrane fluidity, polarisation and membrane order parameters were significantly (p≤0.001) increased in BaP treated animals. However, a significant decrease was observed in the levels of glycolipids, cholesterol, micro-viscosity and anisotropy following BaP treatment in comparison to normal controls. Interestingly, an appreciable improvement in above indices was seen when AKBA was simultaneously administered to BaP treated animals. Furthermore, the structural variations observed in FTIR spectrum were also normalised in BaP treated rats upon AKBA supplementation. Hence, the study suggests that Boswellic acid can be used as a prophylactic intervention in containing the molecular events leading to BaP induced lung carcinogenesis.


Biography


Dr. D. K. Dhawan is presently working as a Professor in the department of Biophysics and also worked as chairman department of Biophysics, Coordinator of Centre for Nuclear Medicine as well as Centre for Medical Physics at Panjab University, Chandigarh, India. Professor Dhawan completed his M.Sc. (Honors) in Biophysics from P. U. in the year 1978 and Ph.D. from PGIMER, Chandigarh, in the year 1984. Prior to Ph.D., he worked as a trainee in Radiation Medicine Centre of Bhabha Atomic Research Centre, Mumbai and was awarded Post Graduate Diploma in Medical Radioisotopes Techniques. His research areas are neurodegeneration, cancer and toxicology. He has published 176 research articles, out of which 140 are cited in Scopus. Prof. Dhawan has supervised 33 Ph.D. and 42 M.Sc. theses during 30 years of his research career. He is a Fellow of Indian College of Nuclear Medicine and Indian Association of Biomedical Scientists.

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D. K .Dhawan

Panjab University, India

Title: Enzyme as Targets for Drugs and Toxins


Abstract


Enzymes are considered as common protein targets for many physiologically active agents. One of them is Na+/K+-ATPase that belongs to heterodimeric transmembrane enzymes whose primary physiological role is to maintain high internal K+ and low internal Na+ concentrations. Additionally, the critical role of this enzyme has been proven in regulation of cell growth, survival, migration, and adhesion. Modulations in its activity and expression, and relative subunit abundance were observed in carcinoma cell lines from different tissues. Other ATPase family enzymes, ecto-nucleoside triphosphate diphosphohydrolases, hydrolyze extracellular nucleotides and are included in purinergic signaling. Its inhibition may contribute or explain antidiabetic, antibiotic, and anticancer effects. Furthermore, acetylcholinesterase is a serine hydrolaze mainly found at neuromuscular junctions and cholinergic brain synapses, that hydrolases the neurotransmitter acetylcholine and terminates the nerve impulse transmission. It is the main toxic target for organophosphate and carbamate insecticide action, as well as the therapeutic target for neurological diseases (Alzheimer’s and Parkinson's disease) associated with loss of cholinergic neurons in the brain and the decreased level of acetylcholine. Consequently, many studies have been directed towards searching for the modulators of these enzymes for the purpose of developing selective and effective pharmacological agents in the treatment of cancer and neurological diseases. This presentation is focused on the inhibitory activity of some synthesized compounds against the selected enzymes, as promising pharmacologically active agents. Besides, their toxic effects as the main limitation in the potential biomedical application are considered.


Biography


Dr. Mirjana B. Čolović 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 published over 100 scientific contributions including 39 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. Her papers are cited over 1000 times.

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Mirjana B. Colovic

University of Belgrade, Serbia

Sessions:

Title: Progression of Diffuse Large B-Cell Lymphoma and their Survival Analysis


Abstract


The gene expression profiling data of 69 samples with diffuse large B cell lymphoma (DLBCL) condition from GEO database (GSE23501) was taken. This is a retrospective study included RNA and DNA extracted from 69 clinical samples.The gene expression data was obtained from the Affymetrix Human Genome U133 Plus 2.0 Array. Apart from the gene expression we also retrieved the clinical data for corresponding samples which includes age, gender, stage of the cancer (4-stages) and survival information.The survival times (in years)for progression-free survival (pfs) was recorded as dead (coded as 1, occurrence) oralive (coded as 0, non-occurrence).There are 4 main stages of DLBCL including stage1: one group of lymph nodes affected, stage 2: two or more groups of lymph nodes affected either above or below the diaphragm (muscle that separates the chest from the abdomen), stage3: lymph nodes affected on both sides of the diaphragm, and stage 4: lymphoma is found in organs outside the lymphatic system or in the bone marrow.The data was analyzed using Cox-Regression model which produces a survival function that predicts the probability that the event of interest has occurred at a given time‘t’ for given values of the predictor variables. The shape of the survival function and the regression coefficients for the predictors are estimated from observed data using maximum likelihood technique. The model can be applied to new cases that have measurements for the predictor variables. In this model, age and gender were considered as covariates and the data was analyzed to compare survival times of all the four stages. This procedure is useful for modeling the time to a specified event, based upon the values of given covariates. The model is based on survival function and baseline hazard. The value of the survival function is the probability that the given event has not occurred by time t. Again, the baseline hazard determines the shape of the survival function. The analysis revealed that there was higher risk to patients under stage3 and stage4 as compared to stage1 and stage2. At the end of one year, the progression-free survival for stage4 and stage3 were66% and 79% respectively and it was 84% for stage2 and 96% stage1. However, at the end of three years the survival drops drasticallyto 55% for stage4, 72% for stage3 and 77% for stage2. There was not much change in stage1 (92%) after 3 years. These data provide epigenetic evidence that the DLBCL stages are distinct and utilizes different oncogenic pathways. The heat maps were also drawn to study the distribution of genomic featuresof expression data.


Biography


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Suresh Kumar Sharma

Panjab University, India

Title: Nutraceutical vs. Pharmaceuticals in cancer treatment: Colon cancer as an example


Abstract


Colon cancer is the second most dangerous cancer leading to deaths worldwide. It is the number one classified cancer type in Egypt, owing to the unhealthy alimentary culture of Egyptians; acting as precursors to colon cancer. This made Egypt an efficient pool of biological data in terms of colon cancer. In general, surgical and chemical treatments have long been used, however; the cure percent were low, not to mention, the associated unbearable painful attacks. Carbon nano-tubes are nanostructured allotropes of carbon of remarkable thermal, mechanical, geometrical and electrical properties. In the present study, targeting legends were conjugated to strengthen targeting and anticancer properties of the carrier. Furthermore, carbon has been evaluated for its efficiency in treatment of colonic disorders. Cumin and Fenugreek are two of the most commonly used seeds in Middle East; namely in Egypt. They have been used as part of folk medicine in treatment of various intestinal infections and inflammation. They have been also reported for their anticancer activity. In this study, nutraceuticals were compared to chemical pharmaceuticals and evaluated for their anti-tumor effect. These were loaded to an oral carbon nanotube system designed for targeting colon tumor cells through interference with their cell cycle. The study was based on using colon cancer cell-lines from Egyptian patients at various stages of tumor and subjecting them to several drug combinations. Thus; the in-vivo data would be as relevant as possible for further clinical studies.


Biography


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Imane Muhammad Higazy

National Research Center, Egypt

Title: Modulatory Effect of Spirulina Platensis Extract Against UVA Toxicity on the African Catfish (Clarias Gariepinus)


Abstract


Ultraviolet-A radiation UVA (320-400 nm) is scattered rapidly in water with biologically useful amounts to at least 100 m deep in clear aquatic environments. The impact of UVA on the aquatic organism was widely investigated, but little is known about the putative role of antioxidants in alleviating its negative impacts. The present study aimed to elucidate the toxicity of UVA on the African catfish by investigate the impact of UVA on the haematological parameters, biochemical variables, and micronuclei and nuclear lesions formation. Also, the putative role of Spirulina platensis administration in alleviating these negative effects was evaluated. Fish were divided into four groups in triplicates as follows: group I was not exposed to UVA, group II was exposed to UVA only, group III was exposed to UVA with 100 ml ∕ L of Spirulina platensis extract, and group IV was exposed to UVR with 200 ml ∕ L of Spirulina platensis extract. At the end of this period, blood samples were collected, and the selected biomarkers were analysed. In the present result, a significant reduction was recorded in the total White Blood Cell count, Red Blood Cell counts, Haemoglobin concentration and Haematocrit value in the blood of fish exposed to UVA compared to the control one. The biochemical parameters (Aspartic Amino Transferase, Alanine Amino Transferase blood glucose, total protein, total lipid, creatinine, uric acid, and urea exhibited significant increases in the blood of fish exposed to UVA. The groups of fish exposed to UVA subjected to the Micronuclei (MN) and Nuclear Lesion (NL) tests showed statistically significant increase in the frequencies of MN and NL compared to the control. Treatment with Spirulina platensis attenuated the UVA-induced changes, and this improvement was more pronounced in fish received the high Spirulina platensis dose (200mg/L water). All the altered parameters were restored to be near the normal levels. The selected biomarkers could be effectively used as potential biomarkers in the field of environmental biomonitoring. The obtained results evoked that Spirulina platensis administration alleviated the destructive effects of UVA and reduced its toxicity effect on African catfish.


Biography


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Alaa G. M. Osman

Al-Azhar University, Egypt

Title: Risk Assessment Progress of Environmental Chemicals in China


Abstract


Since early 1980s, chemical pollution has become a serious environmental problem in rapidly developing China, and the environmental assessment of chemicals has garnered increased attention from the government. This study focuses on the history, current situation and the application of risk assessment for environmental chemicals in China. The related challenges and research needs are also discussed. The Chinese government promulgated “Provisions on the First Import of Chemicals and the Import and Export of Toxic Chemicals” in 1994, “Measures on Environmental Management of New Chemical Substances” came into force in 2003, and has revised from 2010. These indicated that the management pattern of new chemical substances was converted from hazard assessment to risk assessment. In China, current chemical risk assessment system includes qualitative ecological risk assessment, quantitative ecological risk assessment and qualitative health risk assessment. These three assessments are mainly composed by hazard assessment, exposure assessment and risk characterization. Meanwhile, “The Guideline for Risk Assessment of Chemical Substances” and “The Guideline for Hazard Identification of New Chemical Substances” have established to protect the ecologic environment and human health, and these two guidelines also provide the management concepts and techniques of risk assessment.Despite the progress on risk assessment of environmental chemicals has acquired, the basis of this work is still need be enhanced in China. Therefore, the human exposure parameters and environmental exposure parameters which based on Chinese peculiarity and suitable models applied to assess environmental risk should be developed. Such researches will effectively promote the integration strategy of chemical risk assessment.


Biography


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Zhengtao Liu

State Key Laboratory of Environmental Criteria and Risk Assessment,China

Title: Interaction of both Aluminum Exposure and ApoEε4 Gene on Cognitive Functions and ApoER2 Protein Expression in Al-exposed Workers


Abstract


1121 in-service workers in an aluminum factory were investigated. General information was collected using a self-designed questionnaire. Cognitive functions were assessed by MMSE, CDT, DST, FOM, and VFT. The plasma-Al mass concentrations were measured by ICP-MS as an internal exposure indicator. ApoE genotype was determined by LDR, and the content of ApoER2 (LRP8) protein in plasma was determined by ELISA. The multiplicative and additive models were fitted using non-conditional logistic regression to analyze the interaction between plasma-Al concentration and ApoEε4 gene. There was a dose-response relationship between aluminum exposure and cognitive impairment (p<0.05). Asaluminum exposure levels increased, the cognitive functions were gradually worsen, and the risk of cognitive impairment was gradually increasing.The ε4/ε4 genotype was not detected in normal cognitive function group. And the frequencies of ε2/ε3 and ε3/ε3genotype was much lower, but ε3/ε4 and ε4/ε4 genotypes were significantly higher in cognitive impairment group than in normal cognitive function group (χ2=26.863, P=<0.001). The ApoEε4 gene may be a risk factor for cognitive impairment.There is an additive interaction between aluminum exposure and ApoEε4 gene. When the two factors act together, the risk of cognitive impairment may be increased, and 44.2% of the risk can be attributed to the interaction of the two factors. Both aluminum exposure and ApoEε4 gene can decrease the expression of ApoER2 (LRP8) protein, andthe interaction of the two factors may further decrease the expression of ApoER2 (LRP8) protein. This research was supported by Natural Science Foundation of China (NSFC), Grant No. 81430078.


Biography


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Niu Qiao

Shanxi Medical University, China

Title: Protective Role of Antioxidants against Anticancer Drugs Induced Cytotoxicity


Abstract


Dietary modification is an important approach to cancer prevention and treatment. Hence, researchers have focused diet as the best way for cancer prevention and therapy. Chemoprevention is defined as the use of natural compounds to prevent or to inhibit (or) reverse the process of carcinogenesis. Some natural compounds like Curcumin, Piperine, Plumbagin and Nobiletin etc., are used as antioxidants for the treatment of many cancers induced by chemical carcinogens in experimental animals. These dietary nutrients are found to be very effective in minimizing the toxic side effects induced by the anticancer drugs during chemotherapy. The antioxidant and chemopreventive/chemotherapeutic efficacy of these natural antioxidants will be discussed.


Biography


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D. Sakthisekaran

University of Madras, India

Title: Mitochondria as a Selective Anticancer Therapeutic Target


Abstract


Mitochondria are organelles controlling production of adenosine triphosphate and mediate the homeostasis of redox state in the cells. These organelles are integrated in different signaling pathways including metabolic signaling and apoptotic pathways. The normal mitochondrial physiology is essential to cell survival. The disruption of mitochondrial function is a hallmark of Cancer. Mitochondria are extremely dynamic, and the balance of fission and fusion dictates their morphology. Imbalance of fission and fusion has been detected in cancerous cells. In these cells the fission activity is elevated and/or fusion is decreased resulting in a fragmented mitochondrial network. Importantly, restoration of this imbalance between mitochondrial fission and fusion impaired cancer cell growth. Mitochondrial network remodeling is considered as important therapeutic target. Cancer cells uniquely reprogram their cellular activities to support their rapid proliferation and migration, as well as to counteract metabolic and genotoxic stress during cancer progression. Solid tumors such as HCC nodules scavenge oxygen, therefore producing a hypoxic microenvironment. Hypoxia inducible factors (HIFs) mediate the activation of cell hypoxia response. HIFs actively promote glycolysis and enable tumor cell to survive in the hypoxic stress. Glycolysis metabolic pathway provides metabolic intermediates, such as pyruvate, for mitochondrial metabolism. Cancer mitochondria have the ability to flexibly switching between glycolysis and oxidative phosphorylation for their survival. Multiple strategies have been developed to target cancer cell mitochondria such as targeting mitochondrial metabolism and glycolysis enzymes. In addition, targeting hypoxia dependent signaling pathway such as HIF-alpha and its dependent dysregulated genes may be a selective target for cancer therapy.


Biography


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Sherin zakaria

Kaferelsheikh University, Egypt

Title: A Stepwise Approach in Implementing Pharmacogenomics in a Primary Care


Abstract


Pharmacogenenomic testing is proved to be useful in assisting the physicians to identify primary care patients at increased risk for medication toxicity, poor response or treatment failure and inform drug therapy. New testing are introduced and made available routinely, however the preparedness from the healthcare providers is lacking towards Pharmacogenenomic testing for clinical decision-making. Practical resources such as training, education are in demand which is necessary to overcome to implementation difficulties of these Pharmacogenenomic testing in primary care. Developing countries are employing practice network to implement genomics practice in primary health care, such as Implementing Genomics in Practice (IGNITE), the leading edge of genomic medicine implementation in USA. The preliminary foundation for implementation is exploring practice models, challenges and implementation barriers for clinical pharmacogenomics. Generally genomics researchers lack the knowledge of implementation; hence the initial step in enabling genomic medicine implementation is to assemble teams with the right expertise. A right combination this team will include genomic medicine researchers, implementation scientists, health services and outcomes researchers, patients from diverse demographic groups and members of the care delivery teams where implementation is to occur. This presentation focus on a stepwise approach Pharmacogenenomic testing in primary care: patient identification; Pharmacogenenomic test ordering; interpretation and application of test results, and patient education. We present clinical factors to consider, test-ordering processes and resources, and provide guidance to apply test results and counsel patients. Practice-based resources such as this stepwise approach to clinical decision-making are important resources to equip primary care providers to use Pharmacogenenomic testing.


Biography


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Satyajit Patra

American International Medical University, Saint Lucia

Title: High Doses of BPA and TCDD Alter the Differentiation Potential and Cell Function of Rat Adipose-Stem Cells


Abstract


Mesenchymal stem cells can differentiate into bone, cartilage, fat, and other tissues in vitro. Adipose-derived stem cells are an easy processing and isolation cell type, that are widely used for Regenerative Medicine purposes. There is a recent increase in the number of approved clinical trials regarding these cells. Although an important issue to consider when working with cell therapies are the possibility of chemical contamination, such as by endocrine disrupting chemicals (EDCs), which are lipophilic compounds that have high affinity for adipose tissue. Bisphenol A (BPA) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are among the most environmentally relevant EDCs recently studied. Accordingly, this study aimed to assess and quantify cell viability, apoptosis rate, DNA damage and the adipogenic or osteogenic differentiation potential of rat adipose-derived stem cells (rASCs) exposed to most studied doses of BPA and TCDD. Cells were characterized with standard assays. Results demonstrated that 10µM BPA and 10nM TCDD were able to significantly reduce cell viability, while all exposure levels did not increase the apoptosis rate but resulted in DNA damage. 1µM BPA caused significant oil droplet formation, while 10µM BPA and 10nM TCDD decreased adipocyte differentiation. Osteogenic differentiation did not significantly differ among the treatments. These results evidenced that 1µM BPA was responsible for increasing adipocyte differentiation. BPA and TCDD modified important processes in rASCs such as cell viability, adipogenic differentiation, and DNA damage. Together such findings evidenced that EDCs play an important role as contaminants, putatively interfering in cell differentiation and thus impairing the therapeutic use of ASCs.


Biography


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Helga CN. Holzhausen

Campinas State University (UNICAMP), Brazil