Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 7th Euro-Global Summit on Toxicology and Applied Pharmacology Rome, Italy.

Day 2 :

Keynote Forum

Silvio De Flora

University of Genoa, Italy

Keynote: Modulation of cigarette smoke lung carcinogenesis. The experimental background

Time : 10:00-10:30

OMICS International Euro Toxicology 2016 International Conference Keynote Speaker Silvio De Flora photo
Biography:

Silvio De Flora, MD, PhD, was Assistant Professor (1966), full Professor and Chairman (1975), and Professor Emeritus (2012) at the School of Medicine of the University of Genoa (Italy), where he was director for 22 years of the Institute of Hygiene and Preventive Medicine (1986-1998) and of the Department of Health Sciences (1999-2005 and 2010-2012). Author of 460 full length papers, 308 of which available in PubMed. The overall impact factor is 1500. With almost 14,000 citations, the h-index is 58. He published in collaboration with 140 laboratories in European countries, China, Japan, India, New Zealand and USA. Member of the editorial board of 16 international journals. Principal investigator of a number of research projects, 10 of which awarded by the US NIH. He received several honors, among which the award from the Michigan State University (2002), the Sobels Award (Greece, 2005), and dedication of 10th ICMAA (Brazil, 2010).

Abstract:

Although cigarette smoke (CS) is recognized to play a dominant role in the epidemiology of lung cancer, cancer at other sites, and a variety of chronic degenerative diseases, it is difficult to reproduce its carcinogenicity in experimental test systems. We have developed an animal model that is suitable to detect the induction of lung tumours and other histopathological alterations induced by mainstream CS (MCS). This model, which involves the whole-body exposure of Swiss H mice to MCS during the first 4 months of life, followed by 3-4 months in filtered air, was validated by evaluating a number of dietary and pharmacological agents. The agents were administered orally, either individually or in combination, under conditions mimicking interventions either in current smokers or ex-smokers or even reproducing a transplacental chemoprevention. They included anti-inflammatory drugs, such as glucocorticoids (budesonide) and NSAIDs inhibiting COX-1, COX-2 and/or 5-LOH (celecoxib, aspirin, naproxen, licofelone), antidiabetic drugs (metformin, pioglitazone), antineoplastic agents (lapatinib, bexarotene, vorinostat), and natural products and dietary supplements (phenethyl isothiocyanate, myo-inositol, N-acetylcysteine, ascorbic acid, berry extracts). In addition, we evaluated a number of agents for the ability to affect molecular biomarkers in the same mouse model or in rats exposed either to MCS or to environmental CS (ECS). The results obtained provide evidence that experimental studies evaluating lung tumours and/or molecular alterations may be useful, together with epidemiological data, to assess modulation of lung carcinogenesis in smokers, to predict both safety and efficacy of putative lung cancer chemopreventive agents, and to explore their mechanisms of action.

Keynote Forum

Yiqun Deng

South China Agricultural University, China

Keynote: Mitochondrial biogenesis protects animal cells from T-2 toxin

Time : 08:55-09:20

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Biography:

Yiqun Deng completed his Doctorate degree in Biochemistry and Molecular Biology at Zhongshan School of Medicine, Sun Yat-Sen University in 2002. After five years’ Post-doctoral research at Weill Medical College, Cornell University, he is currently working as Professor, Dean of the College of Life Sciences, South China Agricultural University and Director of Guangdong Provincial Key Laboratory of protein function and regulation in agricultural organisms. He has authored 40 publications in peer-reviewed journals. He is an active member in five scientific societies and serves as an Editorial Board Member of several scientific journals.

Abstract:

T-2 toxin is one of the most toxic mycotoxins, which has broad toxic effects, like apoptosis, cell cycle arrestment and protein synthesis inhibition. However, the protective responses of the cells to T-2 toxin remain unclear. In our study, it was shown that T-2 toxin strongly induced the ROS accumulation, DNA damage and apoptosis in chicken primary hepatocytes. To further clarify the molecular mechanisms of the toxic and anti-toxic actions, the proteomic changes of chicken primary hepatocytes upon T-2 toxin treatment were investigated, and it was shown that the most abundant proteins regulated by T-2 toxin were associated with cell redox homeostasis, which explained its property of ROS accumulation. Surprisingly, 34% of the T-2 toxin regulated proteins were located in the mitochondrion, and particularly, most of them were up-regulated, which suggest that T-2 toxin potentially impacts on mitochondrial biogenesis. We confirmed experimentally that T-2 toxin enhanced the mitochondrial biogenesis and which generally occurred in different cells including HeLa, HepG2 and HEK 293-T, besides chicken primary hepatocytes. Subsequently, it is found that one of the key regulator of mitochondrial biogenesis, SIRT1, was upregulated under T-2 toxins treatment, and the enhancement of mitochondrial biogenesis and cell viability under T-2 toxin treatment were impaired by knocking-down SIRT1, and strengthened in SIRT1-overexpression cells. Interestingly, the promoter region of SIRT1 is not responsible for the up-regulation by T-2 toxin and further investigation is under way. In summary, our study suggested that the mitochondrial biogenesis enhancement via SIRT1 plays an important role in the protective response to T-2 toxin. This might provide a new direction in T-2 toxin defense.

Keynote Forum

Giovanni Pagano

Federico II Naples University, Italy

Keynote: Rare earth elements as novel environmental contaminants: current knowledge and research priorities

Time : 10:30-11:00

OMICS International Euro Toxicology 2016 International Conference Keynote Speaker Giovanni Pagano photo
Biography:

Giovanni Pagano graduated in Biological Sciences in 1971 at Naples University and at the International Institute of Genetics and Biophysics in Naples. He served the Italian National Cancer Institute in Naples up to retirement in 2005, with a major focus on environmental toxicology. In recent years GP has collaborated with a number of national and international institutions, and lecturing at several post-graduate courses. The current positions are Research Contractor at Federico II University, and Associate Researcher at the Stazione Zoologica Anton Dohrn. GP authored over 100 publications receiving over 2000 citations; ResearchGate Score 36.63.

Abstract:

Rare earth elements (REEs) are used in several industrial and medical applications. Relatively scarce information is available to date on REE-associated biological effects, including bioassays on animal models, and human health effects following occupational or environmental REE exposures. The literature is mostly confined to reports on cerium, lanthanum and gadolinium, whereas information gaps persist on the health effects of other REEs. An established action mechanism in REE-associated health effects relates to modulating oxidative stress, and adverse effects include a number of endpoints, such as growth inhibition, cytogenetic effects, embryonic arrest and malformations, and organ-specific toxicity. A major role for REE-associated effects relates to pH-dependent REE speciation, and environmental acidification enhances REE toxicity.

We have reported recently that a set of light REEs [Y(III), La(III), Ce(III), Nd(III), Sm(III) and Gd(III)] induce a number of adverse effects to early life stages in sea urchin sperm and embryos, including developmental defects, cytogenetic damage and redox anomalies. The current study is focused on some heavy REEs [Dy(III), Ho(III), Er(III), Yb(III) and Lu(III)], altogether pointing to more severe effects vs. light REEs. The likely environmental threats arising from REE exposures deserve a new line of research efforts. Research priorities should focus on elucidating the comparative toxicities of heavy vs. light REEs, which might provide warning about the use of most toxic REEs. Most relevant research lines should be designed in mammalian and human exposures, namely by performing life-long exposures in animal model and by undertaking appropriate epidemiologic investigations.

Keynote Forum

Wei Zheng

Purdue University, USA

Keynote: Role of altered adult neurogenesis in manganese-induced Parkinsonian disorder

Time : 09:30-10:00

OMICS International Euro Toxicology 2016 International Conference Keynote Speaker Wei Zheng photo
Biography:

Dr. Zheng received his Ph.D. from University of Arizona in Tucson. He was an assistant professor (1993-2000) and later associate professor (2000-2003) at Columbia University in New York city. Dr. Zheng joined Purdue University in 2003 and became a full professor in 2006. He has been serving as the Head of School of Sciences since 2008. Dr. Zheng has published one book, 161 peer-reviewed papers and more than 220 meeting proceedings and abstracts. He is a Fellow of the U.S. Academy of Toxicological Sciences and a frequet reviewer for NIH study sections and for more than 40 research journals.

Abstract:

Neural stem/progenitor cells (NSPCs) in the adult subventricular zone (SVZ) have the capability to self-renew and to migrate via the rostral migratory stream (RMS) to reach their final destination, the olfactory bulb (OB), where they mature and integrate into the local neuronal circuitry. Adult neurogenesis plays an important role in the etiology of neurodegeneratieve diseases. This study was designed to determine if exposure to toxic metal manganese (Mn) disturbed the proliferation, migration, survival and differentiation of NSPCs from SVZ via RMS to OB. Adult rats received a single ip-dose of BrdU at the end of 4-wk Mn exposure to label proliferating cells. Immunostaining and cell-counting showed a 48% increase of BrdU(+) cells in Mn-exposed SVZ than in controls (p<0.05). The BrdU(+) proliferating cells were identified as a mixed population of GFAP(+), Nestin(+) and DCX(+) cells, representing type-B neural stem cells, type-C transit progenitor cells, and migratory neuroblasts, respectively. Another group of adult rats received 3 daily ip-injections of BrdU followed by Mn exposure. By 4-wk post-BrdU labeling, most surviving BrdU(+) cells in the OB were differentiated into NeuN(+) matured neurons. However, survival rates of BrdU/NeuN/DAPI triple-labeled cells in the OB were 33% and 64% in Mn-exposed and control animals, respectively (p<0.01). These results suggest that Mn exposure initially enhances the cell proliferation in adult SVZ mainly by increasing type-B cells. In the OB, however, Mn exposure significantly reduces the surviving adult-born cells and markedly inhibits their differentiation into mature neurons, resulting in an overall decreased adult neurogenesis in the OB.  (Up to 250 words)

Keynote Forum

May Azzawi

Manchester Metropolitan University, UK

Keynote: The nanotoxicological influence of nanoparticles on vascular function

Time : 11:30-12:00

OMICS International Euro Toxicology 2016 International Conference Keynote Speaker May Azzawi photo
Biography:

Dr. May Azzawi is a Reader in Vascular Physiology at the Healthcare Science Research Institute (Faculty of Science and Engineering), Manchester Metropolitan University, United Kingdom. She received her PhD from the University of London (National Heart and Lung Institute, Royal Brompton Hospital, London) and has held postdoctoral and fellowship positions at the University of Manchester. She has over 20 years’ research experience in multidisciplinary fields, including Vascular Physiology and Nanomedicine, and has published widely (> 3,000 citations to date). Dr. Azzawi leads a ‘Nanovascular’ research group investigating the influence of nanoparticles on cellular and vascular function using ex vivo and 3D in vitro models. Her group focus on strategies (Nutraceutical and Nanotechnology) for the preservation and restoration of vascular function. She has authored over 50 publications, including peer reviewed articles and book chapters, and has secured over half a £million in research funding (Innovate UK, Erasmus Mundus, EPSRC). She is co- editor of the journal ‘Regenerative Nanomedicine’; editorial board member of ‘Applied Nanostructured Materials’; she co-chaired the 3rd International conference on Nanotechnology in Medicine; and acts as referee for a number of international journals in the fields of Nanomedicine and Vascular Science.

Abstract:

Silica nanoparticles (SiNPs) are attractive drug delivery platforms and diagnostic tools, however, recent reports suggest that they may be detrimental to arterial function. We aimed to examine whether SiNPs influence the function of small size arteries, which play an essential role in controlling blood perfusion into tissues. We show that while exposure to SiNPs under static conditions, attenuated dilator responses ex vivo, attenuation was only evident at lower agonist concentrations, when exposed under flow conditions or after intravenous injection, in vivo. Pharmacological inhibition studies suggest that SiNPs may interfere with the endothelial dependent hyperpolarising factor (EDHF) vasodilator pathway. The dosage dependent influence of SiNPs on arterial function, demonstrated in our study, will help identify strategies for their safe clinical administration in the future.

OMICS International Euro Toxicology 2016 International Conference Keynote Speaker Swamy KB photo
Biography:

Abstract:

Background: Diabetes Mellitus type 2 is a chronic metabolic disorder which is rapidly increasing in incidence globally. The International Diabetes Federation (IDF) reports that as of 2013 there were more than 382 million people living with diabetes. As the currently available anti-diabetic treatment modalities have not been meeting the requirements there is a dire need to identify a more number of safe and effective anti-diabetic agents. The aim of this study was to identify the effectiveness of Synsepalum dulcificum fruit (Miracle Fruit) extract in reducing blood glucose levels in Streptozotocin (STZ)-Nicotinamide (Nam) induced diabetic rats.
Methods: In this experimental research 29 Sprague-Dawley (SD) rats were divided into groups (G) 1. Normal controls -6 rats and group (G)2. Streptozotocin -Nicotinamide induced diabetic -23 rats. Again these 23 SD rats were divided into 4-groups as- G1.Diabetic controls-5, G2.Glibenclamide (600 µg/kg)-treated-6, G3. Medium dose fruit extract (250 mg/kg) treated-6 and G4. High dose fruit extract (500 mg/kg) treated-6.  All rats were assessed for fasting blood glucose and body weights every week during the span of 21 days period of study. Before starting the experimental research the body weights and fasting blood glucose were measured for all the rats. Then the toxicity of the fruit extract was tested with the highest dose of 5000 mg/kg on 12 SD rats and it showed that no adverse effects at all on the rats’ health.
Results: Eventually this study revealed that high dose fruit extract (500 mg/kg) only could significantly reduce fasting blood glucose levels (p<0.001) even though it caused a slight increase in body weight. Conclusion This study revealed that Synsepalum dulcificum fruit (Miracle Fruit) extract shows acceptable anti-hyperglycemic effects in rats. (Please refer to my article published: “The Clinical Effects of Synsepalum Dulcificum- A Review: J Med Food 17(11) 2014 1165 1169).

OMICS International Euro Toxicology 2016 International Conference Keynote Speaker Hemant Misra photo
Biography:

Dr. Hemant Misra received his PhD from Lucknow University in Medicinal and Pharmaceutical Chemistry and has published over 65 articles and a patent. He is VP Clinical Development for Prolong Pharmaceuticals. Dr. Misra has over 30 years of biopharmaceutical development, global clinical study management and corporate development experience. Dr. Misra has managed drug development, CGMP manufacturing, CTM, quality systems and multiple global clinical trials.

Abstract:

A 13-week study was conducted in Sprague Dawley rats and cynomolgus primates to assess the safety and pharmacokinetics of ANF-Rho as compared to Neulasta® (pegfilgrastim).  ANF-Rho is a novel polyethylene glycol-modified granulocyte colony stimulating factor that has biophysical and biological properties that produce a distinct pharmacokinetic and pharmacodynamic profile as compared to pegfilgrastim (Neulasta®).
The study design used 288 rats, divided into 5 dosage groups: control, 100, 300, 1000 (high) and 1000 (positive) µg/kg. A total of 58 monkeys were also divided into 5 dosage groups: control, 75, 250, 750 (high dose) and 750 (positive) µg/kg of ANF-Rho.   Doses were administered by weekly subcutaneous injections on Day 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85 and 92 at a dose volume of 5 mL/kg for rats and 2mL/kg for primates.  Genotoxicity assessments were evaluated using Salmonella typhimurium and Escherichia coli reverse mutation assay, rodent blood micronucleus assay and chromosomal aberration assay. Toxicology assessment included clinical observations, body weight change, food consumption, ophthalmic examination, function observational battery (motor activity, behavioral changes, coordination and sensory/motor reflex response), organ weight, bioanalytical and toxicokinetic analysis, immunogenicity, gross necropsy and histopathology.
No observed clinical signs seemed to be related to ANF-Rho administration.  There were no related effects in body weight changes or food consumption.  Observed ophthalmic effects were considered procedural-related due to the low incidence.  No biologically meaningful findings were noted during the function observational battery assessment.  Preliminary analysis showed a dose-related increase in spleen weight in rats and a dose-dependent decrease in kidney weight in primates.  Genotoxicity studies found no signs of mutagenicity, clastogenicity or cytotoxicity.
The results from this preliminary toxicology studies are unremarkable. These results are consistent with those of an earlier 28-day study.  Results from the 28-day rat neutropenia dosage model found that the blood pharmacodynamics parameters of ANF-Rho were significantly superior to Neulasta.  Both PK and PD data demonstrate relatively predictable systemic exposures and activity following SC or IV dose levels in both rat and primate. It is anticipated that this long terms 13-week study will provide evidence of safety sufficient to support advancement of ANF-Rho into Phase II clinical studies in chemotherapy-induced neutropenia.