Scientific Program

Day 1

KEYNOTE SPEAKERS
  • Drugs of misuse and therapeutics a deadly combination

    University of Toronto, Canada
    Canada
    Biography

    Manuela G Neuman is Adjunct Professor of Pharmacology and Toxicology, Associated Global Health at the University of Toronto, and a Professor at the Carol Davila University of Medicine and Pharmacy (UMF), Bucharest. She is the Founder and CEO of In Vitro Drug Safety and Biotechnology, Toronto. She holds an MSc in Biology from University of Bucharest, a Post-doctoral Fellowship from the Institute of Inframicrobiology, Faculty of Medicine, Bucharest, PhD in Physiology and Pharmacology from Tel-Aviv University. She also completed her Post-doctoral fellowship in Clinical Chemistry, Hepatology, Immunology, Gastroenterology and Clinical Pharmacology at the University of Toronto, Toronto, Canada. Her research was in the Department of Biochemistry and in the Chemotherapy Institute, while she acted as a Biochemist at the "Victor Babes" Hospital in Bucharest. In these positions of pharmaceuticals, she had "hands on" daily routine, as well as, acting as a Laboratory Scientific Director making liaison between the laboratory and drug discovery platforms and translational research. She has published extensively in the areas of therapeutic and drug of (use and misuse) monitoring, new biologic and their monitoring in clinical practice, pharmacogenetic and immunopharmacogentic clinical applications, drug-induced liver and skin adverse reactions, liver immunology, hepatocellular carcinoma and inflammatory bowel disease. Since 1992, she is a member of the IATDMCT.

    Abstract

    Alcohol consumption remains a significant risk factor for the development of liver damage in patients being treated with pegylated interferon (PEG-IFN-?), in the presence or absence of ribavirin as well the protease inhibitors for viral hepatitis B, C (HBV, HCV) and human immunodeficiency viral infections (HIV) or HCV-HIV. The daily alcohol consumption of >60 mg/day provides a significant risk factor for the development of cirrhosis, hepatocellular carcinoma and the increased risk of mortality. This applies to treatments that used a variety of the non-nucleoside reverse transcriptase inhibitor class. Severe hepatotoxicity [defined as AST or ALT being at >5 upper limit of normal] is also seen in patients who are co-infected HIV/HCV and are being treated with indinavir, nelfinavir, ritonavir, saquinavir, or ritonavir plus saquinavir. In highly active antiretroviral therapies (HAART) that included PI-based, NNRTI-based, and PI- plus NNRTI-based therapies, alcohol abuse is an identified risk factor for the drug-induced liver injury (DILI). Alcohol misuse and over the counter drugs (sulphonamides, antipyreticsor anti-inflammatory) may lead to DILI and liver transplant. Also misuse of illicit drugs in the presence or absence of alcohol lead to drug-induced liver injury.

  • Assessment of inhibitory effects of Ficin-hydrolyzed gelatin derived from squid (Uroteuthis duvauceli) on breast cancer cell lines and animal model

    Tehran University of Medical Sciences
    Iran
    Biography

    M Reza Khorramizadeh, is a Full Professor at Tehran University of Medical Sciences (TUMS), directs Biosensor Research Center and newly instituted Zebra fish Core Lab at Endocrinology and Metabolic Molecular-Cellular Sciences Institute. Concurrently, he is a 2nd affiliation to the Dept. of Medical Biotechnology, School of Advanced Technology in Medicine, TUMS.

    Abstract

    Marine novel natural products have been applied for cancer therapies. Enzyme-digested gelatin hydrolysates have proven to serve as promising sources of potent biologically active peptides. Potential anti-breast cancer properties of the extracted Ficin-digested gelatin hydrolysate from Indian squid (Uroteuthis duvauceli) extensively characterized by cellular and animal models. Gelatin was extracted from squid skin, hydrolyzed by Ficin, and characterized by standard physio-chemical methods. Ficin-digested gelatin hydrolysate was used at various doses of 0-0.1 mg/mL for treatments of MCF-7 and MDA-MB-231 breast cancer cells versus HUVEC normal cells. Cytotoxicity, phase-contrast morphological examination, apoptosis/necrosis, clonal-growth, cell-migration, Matrix-metalloproteinases (MMPs) zymography, and Western blotting were used for cellular assessments. For animal studies, breast tumor-induced BALB/c mice received hydrolyzed gelatin regimen, followed by tumor size/growth and immune-histochemical analyses. Significant inhibition of MCF-7 and MDA-MB-231 with no cytotoxicity on HUVEC cells was detected. Apoptosis was increased in cancer cells, as revealed by elevated ratio of cleaved caspase-3 and PARP. MMP-2 and MMP-9 activities in both cancer cells were dramatically diminished. In mice, gelatin hydrolysate prevented weight loss, decreased tumor size, induced p53, and down-regulated Ki67 levels. These findings suggest that Ficin-digested gelatin hydrolysate could be a beneficial candidate for novel breast cancer therapies.

Exhibitor Hosted Session
Speaker
  • Corina T Bot
    Short and long-term cytotoxicity investigations in stem cells for primary and secondary assays with an all- inclusive approach
    Time: 11:20 - 12:50
    Speaker
    Corina T Bot
    Nanion Technologies
    Germany
    Biography

    Corina T Bot has obtained her PhD in Applied Physics from New Jersey Institute of Technology in 2010. Next, she worked for two years as a Post-doctoral Associate in Cardiology, at Cornell University, Weill Cornell Medical College. In her current position as a Senior Scientist at Nanion Technologies, she provides technical and scientific support for cell-based electrophysiology and toxicology assays, and automated patch clamp screening. Together with her colleagues at Nanion, she is participating in the FDA-directed Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative, which aims to replace the preclinical hERG current assay required under the ICH S7B safety pharmacology guidelines and clinical TQT study.

    Abstract

    In recent years, human stem cell-derived cardiomyocytes (hiPSC-CMs) have proven to represent a relevant human in-vitro system for modeling and interrogating complex biological processes, phenotypic profiles and disease models. Chip-based approaches allow parallel patch clamp recordings without compromising data quality or technical sophistication. We present high-throughput ion channel recordings in hiPSC-CMs using Nanion’s automated patch clamping systems. The CardioExcyte 96 is a hybrid screening instrument that combines impedance with MEA-like extracellular field potential (EFP) recordings. In the light of the new Comprehensive in-vitro Proarrhythmia Assay (CiPA), a FDA directed initiative to improve guidelines and standardize assays and protocols, the use of hiPSC-CMs may become critical in determining the proarrhythmic risk of potential drug candidates. In accordance with the CiPA guidelines, we present pharmacological investigations of short- and long-term effects of compounds from each risk category, in hiPSC-CMs. This approach strengthens the importance of testing compounds in assays complementary to patch clamp electrophysiology, to provide a more complete safety profile.

Toxicology | Pharmacology
Chair
Co-Chair
Speaker
  • Denis Gris
    Endogenous negative regulators of inflammation preserve neuronal survival
    Time: 13:50-14:15
    Speaker
    Denis Gris
    Université de Sherbrooke
    Canada
    Biography

    Dr. Denis Gris has started his scientific career with the Master's and Ph.D. in Neuroscience at Dr. Lynn Weaver's laboratory at the University of Western Ontario. He studied the role of inflammation in spinal cord injury. He discovered that the influx of neutrophils is detrimental for recovering after spinal cord injury. Using anti CD11d antibody as a treatment, he demonstrated that animals recovered faster and better after the treatment. Also, he showed that sever spinal cord injury results in massive inflammatory reactions throughout the body leading to syndrome similar to multiple organ dysfunction syndrome. Dr. Denis Gris continued his education in Dr. Jenny P-Y Ting's laboratory as a post doctoral fellow at the University of North Carolina at Chapel Hill. There he studied in detail mechanism of activation of innate and adoptive immune responses. In collaboration with Dr. Wen, Dr. Eitas, Dr. Allen, and other members of the laboratory, Dr. Gris studied inflammation during obesity which leads to insulin resistance; innate and adoptive responses during multiple sclerosis. In summary, his role in this laboratory was to define the role of novel family of immuno regulatory proteins (NLRs) in different human diseases. Currently, Dr. Denis Gris is a member of Immunology Program at the University of Sherbrooke and he is studying neuro-immune interactions during healthy state and disease.

    Abstract

    Cyanotoxins have been shown to be highly toxic for mammalian cells, including brain cells. However, little is known about their effect on inflammatory pathways. Our study investigated whether mammalian brain and immune cells can be a target of certain cyanotoxins, at doses approximating those in the guideline levels for drinking water. We examined the effects on cellular viability, apoptosis, and inflammation signaling of several toxins on murine macrophage-like RAW264.7, microglial BV-2, and neuroblastoma N2a cell lines. We have tested cylindrospermopsin (CYN), microcystin-LR (MC-LR), and anatoxin-a (ATXa), individually as well as in mixture. Searching into protective mechanism against cyanotoxins, we found that Nlrx1, a protein localized to mitochondria, ameliorates toxin effects. Decreased expression of Nlrx1 correlated with increased vulnerability of all cell types to toxin exposure. Our results demonstrate that CYN, MC-LR, and ATX-a, at low doses individually and in mixture, have potent effect inducing apoptosis and inflammation. Further research of the neuroinflammatory effects of these compounds in-vivo is needed to improve safety limit levels for cyanotoxins in drinking water and food.

  • Olga Anne
    A risk of exposure to noise and air pollution to human health
    Time: 14:40-15:05
    Speaker
    Olga Anne
    Klaipeda University
    Lithuania
    Biography

    Olga Anne has completed her PhD at the age of 37 years from Moscow Chemical Technological University, Russian. She is the senior researcher/professor of Klaipeda University, Lithuania. She has over 60 publications in pre-reviewed journals and 17of them are in ISI WOS journals that have been cited over 45 times.

    Abstract

    The World Health Organization (WHO) pays attention to the evidence highlighting the necessity of sustainable approach of health, environment and transport interaction. Frequently, the influence of physical or chemical pollution that are associated with a certain risk to human health, are evaluated separately. The cumulative effect of both could have significant impact to human health, for instance, to cause cardiovascular diseases. The intention of the study is to determine the risk of the cumulative effect of city traffic noise and air pollution on population health and to propose measures to reduce the risk. The measurements of the transport equivalent noise level, particulate matter (PM10) and nitrogen dioxide (NO2) emissions were carried out at the most noisy and polluted areas of the city. At the same time the citizens opinion poll regarding their health state was organized. The evaluation of noise levels as well as certain pollutants concentrations in the ambient air and their possible cumulative risk to human health was fulfilled. The suggestions on how to reduce the negative health risk of transport noise and air pollution were proposed. The results of the measurements performed and the questionnaire survey suggest that the inhabitants of the city are exposed to the interaction of noise and certain air pollutants. The assessments of the state of the health submitted by the respondents were correct and in accordance with vehicles noise and outdoor air pollution levels. As a consequence, people are at risk of cardiovascular and respiratory diseases. The most sensitive population group of transport impact caused by noise and air pollution is elderly people.

  • Yong-Yeon Cho
    Molecular targeting of ERKs-RSK2 signaling axis in human cancer
    Time: 15:30-15:55
    Speaker
    Yong-Yeon Cho
    The Catholic University of Korea
    South Korea
    Biography

    Yong-Yeon Cho, PhD, is an Associate Professor and Director for Integrated Research Institute of Pharmacutical Sciences at the College of Pharmacy, The Catholic University of Korea. He earned his PhD degree at the Tohoku University (Applied Genetic Engineering) under the supervision of Professor Tokuo T Yamamoto in Sendai, Japan in 2000. He then joined Zigang Dong as a Post-Doc at the Hormel Institute, University of Minnesota, in Dec-2001. He brought with him his expertise in Molecular Biology and Genetic Engineering, which was integral to the research of protein-protein interactions, signaling networks and molecular targeting of small molecules. Based on his scientific achievements, he became Research Assistant Professor at the Hormel Institute, University of Minnesota in 2005. His efforts resulted in the breakthrough that the post-translational modification of stem cell factors plays an important role to regulate stemness of ES cells and reprogramming efficiency. He came back and started a new endeavor in Korea in 2011. Currently, he continues his research on molecular mechanisms of novel signaling pathways regulating protein stability regulation in cancer development and chemoresistance.

    Abstract

    Receptor tyrosine kinases (RTKs) which are activated by diverse stimuli, such as growth factors, cytokines and environmental stresses, play a key role in cell proliferation, transformation and cancer development in humans. Since constitutive active mutations in Ras and Raf are frequently observed with high percentage in many solid tumors, including colon, pancreas, ovarian, melanoma, non-small cell lung and other cancers, Ras-mediated Rafs/MEK/ERKs/RSK2 signaling axis plays a key role in the regulation of cell proliferation, transformation and cancer development. Thus, Ras/Rafs/MEKs/ERKs/RSKs signaling pathway has become an important target to develop/identify chemopreventive and therapeutic agents. Recently, our results demonstrated that RSK2, a downstream kinase of ERKs, is an important proof-of-concept on the human cancer development. Ectopic expression of RSK2 induced anchorage-independent cell transformation without stimulation of tumor promoters such as epidermal growth factor. Moreover, human skin cancer tissue array demonstrated that total- and phospho-RSK2 protein levels were higher in skin cancer tissues compared with normal skin tissues. Utilizing cutting edge molecular and computational research tools, we provided evidences that kaempferol and eriodictyol were natural compounds which target and inhibit RSK2 activity. Moreover, we found that magnolin, a natural compound abundantly found in magnolia flos, targeted ERK1 and ERK2 and inhibited ERK1 and ERK2’s activities with 68 nM and 16.5 nM of IC50 values. Moreover, magnolin suppressed cell migration and invasion in cancer cells by inhibition of epithelial-to-mesenchymal transition of cancer cells. Taken together, our results provide strong evidences that ERKs and RSK2 are key kinases regulating cell proliferation and transformation, and are important targets to develop/identify small molecules as chemopreventive and/or therapeutic agents.

  • Manveen Bhardwaj
    Neuropotential role of Taurine: role of neurotransmitters, oxidative stress, mitochondrial dysfunctioning and histopathological evidences
    Time: 16:15-16:40
    Speaker
    Manveen Bhardwaj
    Panjab university
    India
    Biography

    Manveen Bhardwaj is a Doctoral Research Fellow at Panjab University, India

    Abstract

    Rationale: Alterations in neurotransmitters levels is the main culprit of the epilepsy. With the antioxidant effects, taurine cause the alterations in the Glutamate and GABA levels. But its mechanism of action in epilepsy is still undeciphered. Thus, there exists rationale in preventing the glutamate excitotoxicity by taurine as neuroprotective strategy in pentylenetetrazole (PTZ) induced kindling epilepsy. Objective: Aim of present study is to investigate the neuroprotective role of taurine and its modulation by minocycline (Mino) in the kindling epilepsy. Method: PTZ (40 mg/kg, i.p.) was administered alternatively for 29 days until animal exhibited full motor seizures. Taurine was given orally at a dose of 25, 50 and 100 mg/kg by dissolving it in distilled water once a day 1 h prior to PTZ treatment and minocycline at the dose of 50 and 100 mg/kg and its combination (Taurine 50 mg/kg + Mino50 mg/kg) and (Taurine 100 mg/kg + Mino100 mg/kg) for the period of 29 days. Various neurobehavioral parameters followed by biochemical, mitochondrial respiratory enzyme complexes (I-IV), neurotransmitter examinations (Glutamate, GABA, Serotonin, Dopamine and Norepinephrine) by HPLC and histopathological alterations by haematoxylin and eosin stain were assessed. Results: PTZ administration significantly impaired the cognitive performance in the morris water maze (MWM) performance test, increased the seizure score, caused oxidative stress, mitochondrial dysfunctioning and also caused alterations in the neurotransmitter levels and in the histopathology of hippocampus and cortex. Treatment with the taurine (25, 50 and 100 mg/kg), minocycline (50 and 100 mg/kg) for 29 days significantly improved the seizure score, reduced AChE activity, oxidative damage (reduced LPO, nitrite level and elevate the SOD, catalase and GSH levels) and also restored the mitochondrial complexes (Complex I, II and IV) and improved the neurotransmitter levels (Glutamate, GABA, Serotonin, Dopamine and Norepinephrine). Combination of taurine with minocycline showed more significant effects as compared to the per se effect. Further, histopathological alterations showed the significant improvement effects in the combination of taurine with minocycline. Conclusion: Taurine when combined with minocycline show the neuroprotection by decreasing the glutamate excitotoxicity against the PTZ induced kindling epilepsy.

  • M Reza Khorramizadeh
    Functionalization of ZnO nanoparticles by 3-mercaptopropionic acid for aqueous curcumin delivery: synthesis, characterization, and anticancer assessment
    Time: 16:40-17:05
    Speaker
    M Reza Khorramizadeh
    Tehran University of Medical Sciences
    Iran
    Biography

    M Reza Khorramizadeh, is a Full Professor at Tehran University of Medical Sciences (TUMS), directs Biosensor Research Center and newly instituted Zebra fish Core Lab at Endocrinology and Metabolic Molecular-Cellular Sciences Institute. Concurrently, he is a 2nd affiliation to the Dept. of Medical Biotechnology, School of Advanced Technology in Medicine, TUMS.

    Abstract

    Inherent biocompatibility and stability of zinc oxide nanoparticles (ZnO-NPs) and their biomedical potentials make them an emerging candidate for drug delivery. The aim of this study was to develop and assess a simple procedure for surface functionalization of ZnO-NPs by 3-mercaptopropionic acid (MPA) for water-soluble curcumin delivery. Carboxyl-terminated ZnO nanoparticles were successfully made using ZnCl2 and NaOH in the presence of MPA. The functional groups were activated by 1, 1’-Carbonyldiimidazole (CDI) and the curcumin bonding was carried out at room temperature for 24 h. The core-shell nanocomposite had a significant better solubility versus free curcumin, as characterized by XRD, FTIR, UV-Vis spectrophotometry, DLS, and TEM, p<0.005. In addition, MTT cytotoxicity assessment on MDA-MB-231 breast cancer cells revealed a drop of IC50 values from 5 ?g/mL to 3.3 ?g/mL for free curcumin and ZnO-MPA-curcumin complex, respectively. This result showed an augmented cancer-inhibitory effect of nanoconjugate complex. In conclusion, the presented improved solubility and elevated functionality of novel ZnO-MPA-curcumin nanoformula is promising, and could be considered for new therapeutic endeavors.

  • Yuguo Song
    Novel toxicity related to nanomaterials? Silica nanoparticles cause pleural effusion and pericardial effusion in workers and in rats
    Time: 17:05-17:30
    Speaker
    Yuguo Song
    Capital Medical University
    China
    Biography

    Yuguo Song works as a Chief-physician and the Deputy Director at the Department of Occupational Medicine & Clinical Toxicology, Beijing Chaoyang Hospital, Capital Medical University (Beijing, China). He received his BS degree in Clinical Medicine from the University of Tsingdao Medical College, Shandong Province in 1990, and then he got his MD and PhD degree in Capital Medical University. He is the recipient of several research achievement awards including Wu Zhizhong Prize in Occupational Medicine (China) and International Travel Award from the American Academy of Clinical Toxicology. He worked as a Visiting Scholar in 2010 at West Virginia University, USA. His research focus is on occupational lung disease, clinical toxicology and nanotoxicology.

    Abstract

    Nanomaterials introduce novel risk factors and potentially lead to novel hazards within the workplace or through environmental contamination. Here, we introduce our study in the nanoexposed workers and animal experiments. Further information on the novel toxicity related to the silica nanoparticles was collected and the potential mechanisms were discussed. With the rapid development of nanotechnology and the extensive use of nanoproducts, the potential hazards of nanomaterials to the environment and human health were widely concerned. Nanomaterials introduce novel risk factors and potentially lead to novel hazards within the workplace or through environmental contamination. In vitro and in vivo studies show that the toxicities nanomaterials posed include damage to lungs, heart, liver, kidney and nerve, as well as reproductive and immune systems and they also have carcinogenicity. Additionally, some studies reported the specific toxicity of nanomaterials which appears due to their unique physicochemical properties. However, it is still controversy in regarding to the nano-specific toxicity, and some scientists regard that there is no evidence of novel ‘nano-specific hazard’ comparing to micro –materials. We previously reported that a group of patients exposed to nanomaterials presented with an unusual disease with pleural and pericardial effusion, pulmonary fibrosis and granuloma. And our further rodent study shows that silica nanoparticles that were isolated in patients can also cause pleural effusion and pericardial effusion- a rare and unusual symptom- which may be the novel toxicity related to nanomaterials. Here, we introduce our study in the nanoexposed workers and animal experiment, further information on the novel toxicity related to the silica nanoparticles was collected and the potential mechanisms will be discussed.

Day 2

KEYNOTE SPEAKERS
  • First-in-human studies – an examination of the evolving regulatory and clinical practices to ensure subject safety

    University of Toronto, Canada
    Canada
    Biography

    Beatrice Setnik has been working in the area of CNS research, clinical drug development and abuse potential assessment for over 16 years and is an expert in the area of abuse liability evaluation. She is currently the Vice President of Scientific and Medical Affairs at INC Early Phase and an Adjunct Professor with the Department of Pharmacology and Toxicology at the University of Toronto. She earned her Doctorate degree in Pharmacology and the Collaborative Program in Neuroscience from the University of Toronto in 2005.

    Abstract

    First-in-human studies are a key milestone in drug development. In such studies, a drug already tested in a preclinical setting (in vitro, animals) is tested in humans for the first time. Study participants, who are often healthy volunteers, face an element of risk as the ability to predict the effects in humans is limited. In recent history, albeit in rare cases, study subjects have experienced serious harm in such trials. Regulatory guidelines have evolved following such events to ensure the safety and well-being of study subjects, and most recently in 2017 the European Medicines Agency (EMA) has revised its guidance on first-in-human trials. The revised guidance includes additional strategies to mitigate and mange risks for study subjects, including guidance for the calculation of the starting dose, rules for subsequent dose escalation and the criteria for establishing the maximum dose. The guidance also provides criteria to stop a study, review emerging data and handling of adverse events in relation to the study stopping rules. Over recent years, first-in-human studies have become increasingly complex and include multiple parts such as single-dose ascension, multiple-dose ascension, food interactions, different age groups or gender, proof of concept, or relative bioavailability of different formulations. As such data generated during the course of the trial should be carefully reviewed and used to inform the decision to initiate a subsequent study part or to inform the selection of the doses to be evaluated. This session will discuss the evolving requirements for conducting first-in-human studies and will focus on the key regulatory and clinical considerations in ensuring subject safety.

  • To live or to die – H2S causes the both

    Laurentian University
    Canada
    Biography

    Rui Wang has completed his MD in China and PhD in Canada. He was the Vice-President of Research of Lake Head University, Canada from 2004-2014. He has served Laurentian University as Vice-President Research since 2015. He has published 267 peer-reviewed papers on the studies of gasotransmitters, including hydrogen sulfide and carbon monoxide that have been cited over 20,100 times. He has also served on the expert panel for toxicological profile for hydrogen sulfide and carbonyl sulfide for US Department of Health and Human Services, Public Health Service, and Agency for Toxic Substances and Disease Registry in 2013.

    Abstract

    Known as a rotten egg gas, hydrogen sulfide (H2S) can cause human intoxication and death at high concentrations, which is a major life-threatening risk for oilers or city sewage workers. Catastrophically accumulated H2S gas was also responsible for the biggest life extinction on Earth that killed 95% of all life species on Earth, the end-Permian extinction. Research conducted by my team as well as others over last decades has revealed, however, the critical importance of H2S to the homeostatic regulation of human health. In this talk, I will highlight some most promising and intriguing discoveries in H2S toxicology and biology, including the toxicological profile of H2S, the roles of H2S in the regulation of blood pressure, ion channel functions, and mitochondrial bioenergetics. H2S is a silent killer whereas in the meantime we cannot live without it.

Workshop Session
Speaker
  • Workshop Session
    Impedance and extracellular field potential for cardiac safety assays: A combined approach for non-invasive screening of iPS cells
    Time: 11:20-12:50
    Speaker
    Corina T Bot
    Nanion Technologies
    Germany
    Biography

    Corina T Bot has obtained her PhD in Applied Physics from New Jersey Institute of Technology in 2010. Next, she worked for two years as a Post-doctoral Associate in Cardiology, at Cornell University, Weill Cornell Medical College. In her current position as a Senior Scientist at Nanion Technologies, she provides technical and scientific support for cell-based electrophysiology and toxicology assays, and automated patch clamp screening. Together with her colleagues at Nanion, she is participating in the FDA-directed Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative, which aims to replace the preclinical hERG current assay required under the ICH S7B safety pharmacology guidelines and clinical TQT study.

    Abstract

    The CardioExcyte 96 is a hybrid screening instrument that combines impedance with MEA-like extracellular field potential (EFP) recordings. Changes in the impedance signal indicate effects on cell contractility and overall shape, whereas the field potential parameters provide information about the electrophysiological activity of the beating network of cells. The ongoing Comprehensive in-vitro Proarrhythmia Assay (CiPA) is a FDA directed initiative to improve guidelines and standardize assays for determining the proarrhythmic risk of potential drug candidates. In agreement with the CiPA initiative, standard protocols and SOPs were created for the CardioExcyte96, as well as automated data analysis on required endpoints. Workshop presents the workflow of utilizing the CardioExcyte96 for the assessment of acute /chronic cardiotoxicity in cultured iPSC cardiomyocytes. Cytotoxic responses of cell monolayers involve metabolic or biochemical changes that affect the morphology of the cells, or reduce their overall viability. In that regard, effects of reference compounds tested for long-term cytotoxicity in hepatocyte-like cells will be presented.

Poster Presentations
Speaker
  • Jain Jeong
    Lin28a expression protects against streptozotocin-induced ?-cell destruction and prevents diabetes in mice
    Speaker
    Jain Jeong
    Kyungpook National University
    South Korea
    Biography

    Jain Jeong is currently studying for PhD at Kyungpook National University in Korea. His current laboratory research work is focusing on elucidating gene function and their relation to diseases using various transgenic mice models.

    Abstract

    Lin28a is a highly conserved RNA-binding protein that represses the miRNA let-7. Lin28a is highly expressed in embryonic stem cells (ESCs) and is involved in ESC differentiation. Lin28a also functions as a reprogramming factor for induced pluripotent stem (iPS) cells. A previous study showed that Lin28a modulates glucose metabolism, insulin sensitivity, and promotes cancer cell proliferation. Lin28a overexpression enhances cell proliferation and facilitates glucose transport in the mouse pancreatic ?-cell line Min6. To investigate the effect of Lin28a expression on ?-cells, cells were treated with the appropriate streptozotocin (STZ) concentrations. Pancreatic ?-cells overexpressing Lin28a showed higher survival than mock cells. Furthermore, Lin28a was found to promote proliferation and inhibit apoptosis in STZ-treated cells. In addition, Lin28a-overexpressing cells show enhanced glucose transport. Lin28a inhibits let-7 expression and activates the PI3K/Akt signaling pathway. In addition, this study aimed to identify the relationship between Lin28a and type 1 diabetes in vivo using Lin28a-overexpressing transgenic (Tg) mice. Lin28a Tg mice showed enhanced glucose transport and increased insulin secretion. We performed STZ experiments to mimic diabetes in vivo. Lin28a-overexpressing mice were found to have lower blood glucose levels and higher survival following STZ treatment of pancreatic ?-cells. The islet of Langerhans in Lin28a-overexpressing mice secretes more insulin than in WT mice when subjected to STZ treatment. In conclusion, Lin28a expression protects against STZ-induced pancreatic ?-cell destruction and promotes cell proliferation in pancreatic ?-cells. The results indicate that Lin28a improves the function of the islet of Langerhans in mice.

  • Périco L L
    Hydroalcoholic extract obtained from Eugenia punicifolia leaves and its effect in improving injury induced by gastric ischemia- reperfusion in male and female rats
    Speaker
    Périco L L
    University of São Francisco
    Brazil
    Biography

    Périco L L possess a Bachelor's degree in Pharmacy from the Faculdades Adamantinenses Integradas (2010), a Master's degree in Biological Sciences (Pharmacology) from the Institute of Biosciences of Botucatu at the São Paulo State University (UNESP) (2014). She is currently a Doctoral student in Pharmacology and Biotechnology at Institute of Biosciences of Botucatu (UNESP), where she works on the following topics: Pharmacology of Natural Products, with an emphasis on medicinal plants with antiulcerogenic, anti-inflammatory, antinociceptive and antidiarrheal activity. She participates in the thematic project: "Standardized herbal medicines for the treatment of chronic diseases". During the Master's degree, she worked with animal models for gastroprotection. She currently works with animal models for the evaluation of hormonal effects on gastric ulcer healing. Her current project is titled: The role of the hydroalcoholic extract from the leaves of Eugenia punicifolia in experimental peptic ulcer disease: characterization of anti-inflammatory, healing and antiapoptotic mechanisms of action.

    Abstract

    Introduction: Eugenia punicifolia (Kunth) DC. (Myrtaceae), popularly known as “murta”, is a shrub largely distributed in the Amazon region and Savanna biome. The leaves of this medicinal plant are popularly used as a natural therapeutic agent to treat inflammation, wounds and infections. Aim: The aim of this study was to evaluate the gastric healing effect against ulcer induced by ischemia and reperfusion (I/R). Material & Methods: The gastric ulcers were induced by I/R in male and female (intact and ovariectomized) Wistar rats, according to the method described by Ueda et al. Hydroalcoholic extract from Eugenia punicifolia leaves (HEEP - 125 mg/kg – lower effective dose of previous assays, dose-response curve), lansoprazole (30 mg/kg) or vehicle (saline – 0.9%; 10 mL/kg) were administered during 6 days to determine the healing effects of the subacute treatment. After treatments, the rats were killed and the stomach removed for analysis of lesions areas (mm2) and biochemical parameters such as: superoxide dismutase (SOD - antioxidant), myeloperoxidase (MPO - inflammation marker), malondialdehyde (MDA - lipid peroxidation marker), catalase (CAT - antioxidant) and reduced glutathione (GSH - antioxidant). The results are expressed as mean ± standard error of the mean and statistical significance was determined by ANOVA followed by Dunnett's test (p<0.05). Animal Research Ethical Committee n. 675. Results & Discussion: The results show that the treatment with lansoprazole and HEEP during 6 consecutive days significantly healed the gastric ulcers decreasing the lesion area (males [63.43% and 73.68%]; intact females [68.80% and 52.83%]; ovariectomized females [50.39% and 43.13%]; respectively) when compared with their control group treated with vehicle. There are no significant changes between healing area of ovariectomized females and males rats treated with HEEP for 6 days (p>0.05). But when compared intact females with males, our results showed that the latter presents decrease in the lesion area after the treatment with the HEEP (p<0.01). Our results indicate that HEEP administered for 6 days presents curative effects against the I/R induced lesions increasing GSH levels (p<0.0001) in intact females. The biochemical parameters evaluated in this study are not related to the healing of the gastric mucosa of males and ovariectomized females. Conclusion: Treatment with HEEP administered during 6 consecutive days in male and female rats (intact and ovariectomized) after gastric injury induced by I/R, could heal the mucosa with a significant increase in GSH levels, acting as antioxidant.

  • Mathias Oulé
    In vitro assessment of the toxic effects of an AKWATON based-disinfectant on human tissues
    Speaker
    Mathias Oulé
    Université de Saint-Boniface
    Canada
    Biography

    Mathias Oulé holds a Bachelor's degree in Mathematics, a Master's degree in Biochemistry from the University of Abidjan (Côte d'Ivoire), a Master's degree in Microbiology and a Doctorate in Microbiology from Laval University (Québec). Since 2000, he is Professor of Microbiology at Saint-Boniface University (Winnipeg, MB); Head of the Department of Biological Sciences from 2006 to 2010. For several years, he has been researching on AKWATON, a microbicidal polymer with high solubility in water, odorless, colorless, non-corrosive and harmless, to fight nosocomial infections and superbugs. In 2012, the Society for General Microbiology (SGM) issued press release on his studies on AKWATON's sporicidal activity, published in the Journal of Medical Microbiology (JMM).

    Abstract

    The purpose of this study is to prove the potential safe use of AKWATON as a new antimicrobial product. Many service products are often removed from the market due to their toxic effects on the human body or to their aggressiveness towards the environment. Antimicrobial products such as disinfectants may contain harmful ingredients that can cause disease. Some disinfecting products are corrosive or irritating; others produce strong odors, which in the long run can cause real health problems. AKWATON is a new disinfectant, member of the family of guanidine polymers. Its bactericidal, fungicidal and sporicidal properties have been demonstrated and widely documented. In this study, the toxic effects of AKWATON and of three well known commercial antimicrobial products currently on market, were evaluated and compared on various human tissues including eyes, lung, skin and liver cells. The testing were performed using the TB (Trypan blue) and MTT (3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) methods. Cell-cultures and the different tests done, showed that the AKWATON based-disinfectant was much less toxic, killing many fewer cells than the commercial disinfectants. It spared more than 64% of skin cells; 65% of lung (IMR-90) cells; 66% of eye cells (ARPE-19) and 64% of liver (Hep-G2) cells while some well-known disinfectants currently marketed killed 100% of cells. This study demonstrated that AKWATON can be used as an odorless, colorless, non-corrosive and harmless disinfectant for hospital, agriculture industry, farming, food service and household facilities or as antiseptic.

  • Nuris Ledon
    Safety and biosimilarity of ior®LeukoCIM compared to Neupogen® based on toxicity, pharmacodynamic and pharmacokinetic studies in the Sprague-Dawley rat
    Speaker
    Nuris Ledon
    Centre of Molecular Immunology
    Cuba
    Biography

    Nuris Ledon has a PhD in Pharmaceutical Sciences since 2000. She is also an Auxiliary Professor and Senior Researcher at Molecular Immunology Center, La Havana, Cuba with 25 years of experience. She counts with two Master´s degrees, one in Pharmacology and other in Business Administration. She has published more than 50 articles on subjects like Pharmacology and Toxicology of different drugs. She has participated in numerous congress and summits and has tutored several theses

    Abstract

    This study examined the safety, pharmacodynamic and pharmacokinetic biosimilarity of the human recombinant filgrastim products iorRLeukoCIM and NeupogenR following a 28-day repeated subcutaneous dose administration in male and female Sprague-Dawley rats with a 14- day recovery period. Safety profiling was based on clinical observations, clinical pathology and pathology findings for control rats dosed with vehicle and rats dosed either with 15, 75 and 150 ?g/kg of iorRLeukocim or 150 ?g/kg of NeupogenR. Adverse clinical findings for both iorRLeukoCIM and NeupogenR were similar and consisted of mild to moderate forelimb alopecia; skin lesions (scab formation on the shaved dorsal region) and mild to severe swelling of the hock-joint (tarsal joint) and hind limb, alone or accompanied with lameness in high dose group animals which was more prominent in males. All adverse findings were fully reversible. As expected, iorLeukoCIMR and NeupogenR both increased white blood cell and neutrophil levels in rats and to a similar extent for high dose iorRLeukoCIM and NeupogenR. The pharmacokinetics of filgrastim following dosing with iorRLeukoCIM was well behaved and comparable for high dose iorRLeukoCIM and NeupogenR. The results of this study imply that iorRLeukoCIM and NeupogenR had safety profiles, pharmacodynamic responses and toxicokinetic profiles that were biosimilar.

  • Sun-Mi Yoo
    Inhibition of ERKs/RSK2/I?B? signaling axis by magnolin suppresses cancer cell invasion and migration
    Speaker
    Sun-Mi Yoo
    The Catholic University of Korea
    South Korea
    Biography

    Sun-Mi Yoo is an Ph. D. course sudent at the College of Pharrmacy, The Catholic University of Korea. Ms Yoo graduated B. S. degree at the Yonsei University (Life science) and entered graduate school of M. S./Ph. D. joint program on major of Pharmecutical Biochemistry in 2014 supervised by professor Yong-Yeon Cho. Ms. Yoo has studied on the protein-protein interaction and signaling network involved in cell transformation, cancer metastasis anc chemoresistance. Ms. Yoo found that ERKs/RSK2 signaling pathway plays a key role in cancer cell metastasis and molecular targeting of ERKs using magnolin, a natural compound abendently found in magnolia flos, strongly suppressed cancer cell migration and invasion. Moreover, During the M. S./Ph. D. course, she has identified a novel signaling pathway involved in chemoresistance through p90RSKs.

    Abstract

    Previously, our study demonstrated that I?B? phosphorylation at Ser32 by RSK2, a kinase regulated their activity by ERK1 and 2, induced NF-?B transactivation activity through I?B??destabilization, and magnolin inhibited ERK1 and 2 activities by targeting of the ERK active pocket. However, the role of magnolin in cell migration has not been clearly elucidated. Here, we found that magnolin inhibited NF-?B transactivation activity by suppression of ERK1/2/RSK2 signaling pathway. We demonstrated that magnolin abrogated increase of EGF-induced COX-2 protein level and wound healing in a dose dependent manner. In human lung cancer cells such as A549 and H1975 which harbor constitutive active Ras and EGFR mutants, respectively, we found that magnolin suppressed wound healing and cell invasion in Boyden chamber assay in a dose dependent manner. Importantly, gene expressions and activities of MMP-2 and -9 were inhibited by magnolin treatment. Notably, E-cadherin levels, an epithelial marker, was elevated by magnolin treatment and N-cadherin, Snail, Vimentin levels, mesenchymal markers, were suppressed by magnolin treatment in a dose dependent manner. In addition, the knockdown or knockout of RSK2 in A549 lung cancer cells or MEFs revealed that magnolin targeting ERKs/RSK2 signaling suppressed epithelial-mesenchymal transition. These results demonstrated that magnolin is beneficial for the anti-invasion and -migration in cancer metastasis.

  • Wookbong Kwon
    Tet1 overexpression leads to anxiety-like behavior and enhanced fear memories via the activation of calcium-dependent cascade through Egr1 expression in mice
    Speaker
    Wookbong Kwon
    Kyungpook National University
    South Korea
    Biography

    Wookbong Kwon is currently studying for PhD at Kyungpook National University in Korea. His current laboratory is focusing on elucidating gene function and their relation to diseases using various transgenic mice models.

    Abstract

    Ten-eleven translocation methylcytosine dioxygenase 1 (Tet1) initiates DNA demethylation by converting 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) at CpG-rich regions of genes, which plays a key role in adult neurogenesis and memory. In addition, the overexpression of Tet1 with 5-hmC alteration in patients with psychosis has also been reported, for instance in schizophrenia and bipolar disorders. The mechanism underlying Tet1 overexpression in the brain, however, is still elusive. In the present study, we found that Tet1-transgenic (Tet1-TG) mice displayed abnormal behaviors involving elevated anxiety and enhanced fear memories. We confirmed that Tet1 overexpression affected adult neurogenesis with oligodendrocyte differentiation in the hippocampal dentate gyrus of Tet1-TG mice. In addition, Tet1 overexpression induced the elevated expression of immediate early genes (IEGs), such as Egr1, c-fos, Arc, and Bdnf followed by the activation of intracellular calcium signals (i.e., CamKII, ERK, and CREB) in prefrontal and hippocampal neurons. The expression of gamma-aminobutyric acid (GABA) receptor subunits (Gabra2 and Gabra4) fluctuated in the prefrontal cortex (PFC) and hippocampus. We evaluated the effects of Tet1 overexpression on intracellular calcium-dependent cascades by activating the Egr1 promoter in vitro. Tet1 enhanced Egr1 expression, which may have led to alterations in Gabra2 and Gabra4 expression in neurons. Taken together, we suggest that the Tet1 overexpression in our Tet1-TG mice can be applied as an effective model to study various stress-related diseases that show hyperactivation of intracellular calcium-dependent cascades in the brain.

  • M Reza Khorramizadeh
    Characterization of methionine oxidized human recombinant erythropoietin by nano LC-ESI-MSMS; isoform distribution and biological activity
    Speaker
    M R Khorramizadeh
    Tehran University of Medical Sciences
    Iran
    Biography

    M Reza Khorramizadeh, is a full Professor at Tehran University of Medical Sciences (TUMS), directs Biosensor Research Center and newly instituted Zebra Fish Core Lab at Endocrinology and Metabolic Molecular-Cellular Sciences Institute. Concurrently, he is a 2nd affiliation to the Dept. of Medical Biotechnology, School of Advanced Technology in Medicine, TUMS.

    Abstract

    Methionine (Met) oxidation is a significant form of protein damage caused by endogenous or environmental oxidizing agents. In this study we examined the effect of increasing levels of Methionine-54 oxidation on the isoform distribution and biological activity of the human recombinant erythropoietin. Mass spectrometry was applied to determine and compare the Met oxidation level of three batches of human recombinant erythropoietin. Isofrom distribution of the analyzed products was assessed by capillary zone electrophoresis (CZE) method. The calculated area percent of isoforms 2-4 which belongs to more acidic glycoforms, were decreased with increasing the level of methionine oxidation in all samples. Also, the results showed that the percent of isoforms 5-8 (more basic) were increased in all samples along with the elevating Met oxidation level. The in vivo biological activity of proteins was decreased by increasing the level of oxidation. In conclusion, Met oxidation level in human recombinant erythropoietin showed significant association with the net charge and isoform distribution of the glycoprotein and could be applied for monitoring and validation of production processes and quality control assessments.

Toxicology | Pharmacology
Chair
Co-Chair
Speaker
  • Xavier Ortiz
    A high throughput targeted and non-targeted method for the analysis of microcystins and anatoxin-A using on-line solid phase extraction coupled to liquid chromatography - quadrupole time-of-flight high resolution mass spectrometry
    Time: 14:55-15:20
    Speaker
    Xavier Ortiz
    Ontario Ministry of the Environment and Climate Change
    Canada
    Biography

    Xavier Ortiz obtained his PhD degree at IQS-Barcelona (Spain), where he developed methods for the analysis of Persistent Organic Pollutants in food using GC-HRMS technology. Before coming to Canada, he worked in the pharmaceutical and biotechnology private sectors as Analytical Lab Manager; characterizing, isolating and purifying natural products from microalgae by preparative LC. Currently, he is a Research Scientist at the Ontario Ministry of the Environment and Climate Change, developing new methods for the analysis of emerging pollutants in the Canadian Environment using chromatography and mass spectrometry. He is the Ministry’s Lead Scientist in cyanotoxins analysis, specializing in lab automation to increase productivity and non-targeted analysis of previously unknown toxins.

    Abstract

    Microcystins are cyclic heptapeptide hepatotoxins produced by cyanobacteria in freshwater. Sample preparation for the analysis of these cyanotoxins in water from algal blooms can take up to several days due to the matrix complexity and the low detection limits required complying with current legislation. Moreover, there is a large number of unknown microcystins that could potentially exist in the environment resulting from different amino acid substitutions into the microcystin skeletal structure. To tackle these problems, the present study involved the development of a high throughput method based on on-line solid phase extraction coupled to liquid chromatography that can provide quantitative results for 12 microcystin variants (LR, YR, RR, HtyR, HilR, WR, LW, LA, LF, LY, Dha7-LR and Dha7-RR) and anatoxin-A in less than three hours with detection limits between 0.004-0.01 µgL-1 and uncertainty between 4-14%. Data dependent acquisition was employed for the non-targeted analysis of these cyanotoxins. Filtering the data based on structure diagnostic fragments, two unknown microcystin variants not previously reported in the literature were detected. The structures Leu1-microcystin-Met(O)R and Leu1-microcystin-LY were fully characterized by accurate mass measurement, collision induced dissociation and fragmentation prediction software.

  • Tracy A Kimmel
    Developing new approaches to the health hazard assessment of potent pharmaceuticals
    Time: 15:20-15:45
    Speaker
    Tracy A Kimmel
    SafeBridge Consultants, Inc.
    Canada
    Biography

    Tracy A Kimmel has received her PhD in Environmental Health Sciences from New York University, and is a Diplomate of the American Board of Toxicology. She has almost 25 years’ experience in the pharmaceuticals industry, including 12 years working with Corporate EH&S groups. She is currently Senior Manager of Toxicology at SafeBridge Consultants, Inc. Her primary responsibilities include performing health hazard assessments of pharmaceutical and industrial compounds, predicting the toxicity of compounds using computational modeling software and qualitative analyses, evaluation of pharmaceutical impurities and synthetic intermediates, and assisting with environmental risk assessments. She is a former Chair of the Occupational Alliance for Risk Science (OARS) Workplace Environmental Exposure Level (WEEL) Committee, and now serves on the ACGIH Threshold Limit Value (TLV®) Committee. She has contributed to peer-reviewed journal articles and publications, has prepared white papers on occupational hazard assessment, and has delivered presentations and workshops at worldwide locations.

    Abstract

    The current approach to setting “safe” levels of exposure to potent pharmaceutical compounds has remained fundamentally unchanged for over 50 years. This approach has been applied to both worker setting (through the setting of Occupational Exposure Limits) and, more recently, patient and/or product safety (through the setting of Permitted Daily Exposures). New developments in pharmaceutical technology (i.e., antibody-drug conjugates, nanodrugs, viral vectors and other biologicals, and emerging immunotherapy targets) have combined with ever-increasing drug potency present challenges to the paradigm of hazard assessment, and have spurred advances and adaptations by which robust evaluations of these compounds can be performed. The purpose of this presentation is to deliver an overview of the hazard assessment process and its applicability to both work and patient/product safety, which will include a description of what constitutes a “potent” pharmaceutical agent. Application of hazard assessment methodologies to novel drug candidates and drug delivery technologies, which stretch the boundaries of established approaches to hazard assessment, will then be discussed.

Video Presentations
Speaker
  • Rama Krishna Pedada
    An analytical study of deaths due to poisoning in Visakhapatnam
    Time: 16:05-16:20
    Speaker
    Rama Krishna Pedada
    Andhra Medical College- King George Hospital
    India
    Biography

    Prof Rama Krishna Pedada works at Andhra Medical College, Visakhapatnam, Andhra Pradesh, India.

    Abstract

    Objective: To determine and classify the various types of poisoning deaths as seen at Andhra Medical College Mortuary, Visakhapatnam city. Materials & Methods: This is a retrospective study of all the deaths due to poisoning seen in the Department of Forensic Medicine and Toxicology, Andhra Medical College, Visakhapatnam City over a 15-year period (January 2001?December 2015) as recorded in the autopsy registers and postmortem reports of the department. Observations: Poisoning is one of the commonest methods of committing suicide especially in developing countries like India. A total of 22475 autopsies were done during the period. 2074 cases representing 9.23% of all bodies received by the mortuary were deaths due to poisoning. Organophosphate compounds were the most commonly 78.98% abused substance. The common motive of poisoning was suicidal 93.43% with male to female ratio 6.69:1. Peak incidence was observed in the age group 21-40 years. Type of poison consumed, socioeconomic status and place of household are also ascertained. Conclusion: This study shows the pattern of poisoning deaths in Visakhapatnam and this preliminary data will provide a baseline for future research and help in formulating policies to prevent deaths due to poisoning.

  • Shahnawaz Ahmad Wani
    Ameliorative potential of Eugenol and Carvacrol in cobalt mediated hypercontraction in isolated Wistar rat aorta
    Time: 16:20-16:35
    Speaker
    Shahnawaz Ahmad Wani
    Jamia Millia Islamia
    India
    Biography

    Shahnawaz Ahmad Wani did his MSc Biochemistry from Jamia Millia Islamia (JMI), New Delhi India. He is pursuing PhD from Department of Bioscience, JMI and is working on topic titled as “Effect of Metal Pollutants on Cardiovascular System”. He has presented four conference paper in various national and international seminars. He has one publication on titled mechanism of flavonoids in smooth muscle relaxation.

    Abstract

    Cobalt is a very important element that is naturally present in biochemically important compounds like cyanocobalamin (Vit B12). But occupational exposure of cobalt is reported to cause various diseases like lung cancer, cardiovascular diseases like cardiomyopathy and gastrointestinal diseases. Cobalt is reported to augment vascular contractility in spontaneously hypertensive rats. So, we have planned this study to check contractile effect of cobalt in toxic range on Wistar rat aortic rings, and to study the ameliorative potential of eugenol and carvacrol which are plant derived terpenoids and possess antioxidant activities using organ bath system (Ad instruments). In our study, a hyper-contractile response was seen at all the various concentrations of cobalt used, i.e. 800 nM, 10 µM, and 50 µM and the hypercontractile response in case of cobalt incubated aortic rings were 132%, 128%, 108% respectively with respect to control taken as 100% with Phenylephrine induced contraction. Eugenol and carvacrol could act as possible ameliorators of hypercontraction. We have noticed that at saturating concentration of 100 µM eugenol and 10 µM carvacrol caused 38% and 42% relaxation in cobalt unexposed aortic rings; while 40% and 48% relaxation was observed when cobalt exposed aortic rings were co-incubated with eugenol and carvacrol. In our study, we have found that the relaxation caused by both the natural compounds is due to the quenching of ROS and by enhancing nitric oxide release from endothelium of aorta. To conclude, acute exposure of cobalt to aortic rings causes increase in hypercontractile response by generating oxidative stress, which is effectively lessened by eugenol and carvacrol.

  • Christie M Sayes
    Nanomaterial drug products: manufacturing and analytical perspectives
    Time: 16:.35-16:50
    Speaker
    Christie M Sayes
    Baylor University
    USA
    Biography

    Christie M Sayes is an Associate Professor of Environmental Science and Toxicology at Baylor University. She is a Subject Matter Expert in nanomaterial-related toxicology and exposure. Her activities include working with partners, collaborators, and clients in designing and directing studies and training and advising facility staff. She possesses a working knowledge of laboratory science and US regulatory climates. Her routine activities include data collection, analyses, and interpretation as well as results documentation and reporting. She functions as point of contact for study control.

    Abstract

    The increasing use of nanotechnology, including nanoparticles, in the preparation of drug products requires both manufacturing and analytical considerations in order to establish the quality metrics suitable for performance and risk assessment. A range of different nanoparticle systems exists including (but not limited to) nano-drugs, nano-additives and nano-carriers. These systems generally require more complex production and characterization strategies than conventional pharmaceutical dosage forms. The advantage of using nanoparticle systems in pharmaceutical science is that the effective and desired function of the material can be designed through modern manufacturing processes. The systematic nomenclature allows for greater understanding of the drug product under evaluation based on available data from other nanoparticle reports. Analytical considerations of nano-drugs, nano-additives and nano-carriers and the way in which they are measured are directly connected to quality control. Ultimately the objective is to consider the entire nano-drugs, nano-additives and nano-carriers product life cycle with respect to its manufacture, use, and eventual fate. The tools and approaches to address the needs of these products exist; it should be the task of the pharmaceutical scientists and those in related disciplines to increase their understanding of nanomedicine and its novel products.

  • Bhanu P S Sagar
    Safety and toxicity evaluations of Xanthium strumarium Linn
    Time: 16:50-17:05
    Speaker
    Bhanu P S Sagar
    IEC College of Engineering & Technology- IEC Group of Institutions
    India
    Biography

    Bhanu P S Sagar had completed his PhD from Jamia Hamdard, Post-doc from National Institute of Immunology and DSc in Alternative Medicine. He is presently the Director of Pharmacy College at IEC-GI & Former Vice-Chancellor of IEC University and has published 47 papers and presented 30 papers. He has presented two papers in “AAPS 2006 National Biotechnology Conference” in Boston, USA. He is evaluator for various international journals and also selected for “Marquis Who’s Who in Asia” and “Marquis Who’s Who in World”. He has received many awards and prime areas of research include Plant Tissue Culture, Phytochemical & Pharmacological investigations of natural products.

    Abstract

    Xanthium strumarium L. is poisonous to mammals due its toxic principle which is a diterpenoid glycoside i.e. atractyloside found in the roots and seeds. It was thought worthwhile to carry out the hepatotoxic assessments and safety and toxicity evaluations of oral administration of atractyloside and methanolic extracts of X. strumarium L. in Albino Wistar rats. So, present investigation was undertaken with following objectives: To develop standardized protocols for Extraction, isolation, purification, characterization and quantitative estimation of Atractyloside; Hepatotoxic assessments of oral administration of atractyloside in Albino Wistar rats and; To study the safety and toxicity evaluation of methanolic extract in Albino Wistar rats. Xanthium strumarium Linn. root and seeds were found to contain alkaloids, anthraquinones, flavonoids, atractyloside, phenolics, steroids, terpenoids, and resin etc. In the present investigation, attempt was made to separate the atractyloside by using instant preparative thin layer chromatography (IPTLC) technique. Purified atractyloside was chemically characterized by IR, Mass and NMR spectral analysis. Atractyloside concentrations were found to be 2.9 and 4.3 mg/ml in plant root and seeds respectively using HPLC techniques. During hepatotoxic assessment, atractyloside produced severe hepatotoxicity in Albino Wistar rats. Observations of the sub-acute and acute toxicity studies had indicated that methanolic extract of X. strumarium had shown a narrow safety margin in animals. On the basis of sub-acute and acute toxicity evaluation studies, it was established that both atractyloside and methanolic extract of X. strumarium L. possess a narrow safety margin in rats used in in-vivo experimental and preclinical pharmacological studies.

Toxicology | Pharmacology Session Continues
Chair
Co-Chair
Speaker
  • Beatrice Setnik
    Evaluating the abuse potential of CNS active drugs: regulatory and methodological considerations
    Time: 17:05-17:30
    Speaker
    Beatrice Setnik
    University of Toronto, Canada
    Canada
    Biography

    Beatrice Setnik has been working in the area of CNS research, clinical drug development and abuse potential assessment for over 16 years and is an expert in the area of abuse liability evaluation. She is currently the Vice President of Scientific and Medical Affairs at INC Early Phase and an Adjunct Professor with the Department of Pharmacology and Toxicology at the University of Toronto. She earned her Doctorate degree in Pharmacology and the Collaborative Program in Neuroscience from the University of Toronto in 2005.

    Abstract

    Prescription drug abuse continues to be a great concern and regulatory agencies such as the FDA and Health Canada require abuse potential evaluation to inform appropriate drug scheduling for novel CNS-active drugs at the time of drug approval. One of the required studies includes the human abuse potential study (HAP). HAP studies are a type of clinical study evaluating subjective and objective drug effects related to abuse potential and drug impairing effects. The preferred design is a randomized, double-blind, placebo- and positive-controlled crossover study. The studies are generally conducted in drug-experienced, non-dependent recreational drug users who have a past and recent history of using a drug in the pharmaceutical class of the test drug. Generally, these studies are considerably distinct compared to healthy volunteer and patient studies, and host their own complexities and challenges. The drug using population represents a unique subgroup requiring adaptions to clinical trial methodology. Challenges with these populations include, but are not limited to, compliance with restrictions around concomitant medication and drug use, risk-taking behavior, and prior addictive disorders. The population needs to be carefully selected and screened to ensure that safety is not compromised, eligibility requirements are met, appropriate discrimination between the active control versus placebo is established, and that subjects are able to comply with the study requirements. Furthermore, a population using drugs by a specific route (e.g. intranasal, intravenous) may be needed if the clinical trial intends to study unintended routes of administration, as is often the case in studies evaluating abuse-deterrent formulations. Understanding the profile and nature of the population and the study requirements ensures appropriate rigidity in the methods and conduct of such studies. This session will provide an overview of the key regulatory and clinical methodological considerations in conducting HAP studies.

  • H Shirkhanloo
    Speciation of inorganic and organic selenium in human serum samples based on isopropyl 2-[(isopropoxycarbothiolyl) disulfanyl] ethane/ionic liquid by ultrasound-assisted dispersive liquid-liquid microextraction
    Time: 17:30-17:55
    Speaker
    H Shirkhanloo
    Research Institute of Petroleum Industry
    Iran
    Biography

    H Shirkhanloo is an Associate Professor of Analytical Chemistry, Department of Chemistry, Environment and Occupational Health at Research Institute of Petroleum Industry, Iran.

    Abstract

    A simple in-vitro speciation of inorganic selenium (SeIV and SeVI) and organic selenium (Se-Cys, Se-T, Se-Alb Se-M) in human biological samples based on isopropyl 2- [(isopropoxycarbothiolyl) disulfanyl] ethane thioate (IICDET) as a complexing agent were studied by ultrasound-assisted dispersive liquid-liquid bio-microextraction (USA-DLLMBE). In first stage, 100 ?L (?0.1 g) of hydrophobic ionic liquid of C8MIM [PF6] were only added to organic selenium (Se-Cys, Se-M, and Se-ALB) in 10 mL of standard solution and human serum, urine and plasma samples that were thermally extracted into IL phase at human biological pH in 10 min and after dilution with 100 ?L of acetone, directly determined by electro thermal atomic absorption spectrometry (ET-AAS). In second stage, after separation IL from sample, inorganic selenium (Se IV) in remained samples was com plexed by IICDET and extracted to IL at pH=4 (R-S2Se-R). After reduction Se (VI) to Se (IV) by HCl with temperature 130 ?, inorganic Se speciation was obtained based on total Se determination. After optimized conditions, the enrichment factor (EF), Linear range and limit of detection (LOD) for inorganic selenium were obtained 25.2, 0.02- 1.35 ?g L-1 and 5 ng L-1 in human biological samples respectively. The validation of methodology was achieved by certified reference material (CRM) and ICP-MS.

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