World Congress on Pharmacology July 20-22, 2015 Brisbane, Australia

Biography:

Dr. He Li has completed his PhD from McGill University in 1994 and postdoctoral studies from NIH in 1998. He is the Director, Stress, Behavioral Studies and Neurobiology Laboratory. His laboratory has been working to discover novel therapeutic targets for treating neuronal disorders including epilepsy, traumatic brain injury as well as post traumatic stress disorder (PTSD) by studying the neurotransmitter systems in the amygdalaneuronal circuitry in the invitro brain slice and in vivo animal behaviors. He has published 69 peer reviewed articles, book chapters including Nature Neuroscience, Journal of Neuroscience, Neuropsychopharmacology, Molecular Psychiatry and Journal of Psychiatry Research.

Abstract:

Elevated startle response and hyperarousal are hallmarks of PTSD, and are generally considered to evince fear (DSM V). To further examine the efficacy of corticosterone in treating hyperarousal and elevated fear, the present study utilized a learned helplessness stress model in which rats are restrained and subjected to tail shock for three days. These stressed rats develop a delayed long-lasting exaggeration of the acoustic startle response (ASR) and retarded body weight growth, similar to symptoms of PTSD patients. We demonstrate that both pre-stress and post-stress administration of corticosterone mitigates a subsequent exaggeration of the ASR measured 14 days after cessation of the stress protocol. Furthermore, the mitigating efficacy of pre-stress administration of corticosterone (3 mg/kg/day for three days) appeared to last significantly longer, up to 21 days after the cessation of the stress protocol, in comparison to that of post-stress administration of corticosterone. However, pre-stress administration of corticosterone at 0.3 mg/kg/day for three days did not mitigate stress-induced exaggeration of the ASR measured at both 14 and 21 days after the cessation of the stress protocol. In addition, pre-stress administration of corticosterone mitigates the retardation of body weight growth otherwise resulting from the stress protocol. The relative efficacy of pre versus post administration of corticosterone and high versus low dose of corticosterone on stress induced exaggeration of innate fear response and stress-retarded body weight growth indicate that exogenous corticosterone administration within an appropriate time window and dosage are efficacious in diminishing traumatic stress induced pathophysiological processes.

Biography:

Xiang-Qun (Sean) Xie received his Pharmacy B. S. degree in 1982 from the Second Military Medical University in Shanghai, China; Ph.D. in Medicinal Chemistry from the School of Pharmacy, University of Connecticut, 1993; and followed by a Biophysics Post-doctoral training at MIT Francis Bitter National Magnet Laboratory. In addition, he obtained Executive MBA degree in 2003. Currently, Xie is a tenured Professor of Pharmaceutical Sciences and Drug Discovery Institute. He is the Principal Investigator of an integrated research laboratory, consisting of CompuGroup, BioGroup and ChemGroup (www.CBLigand.org/XieLab) and also a Founding Director of Computational Chemical Genomics Screening (CCGS) Center. He was co-PI of the NIH Pittsburgh Molecular Library Screening Center. He also holds joint faculty positions at the Departments of Computational Biology and Structural Biology, and Pitt Cancer Institute MT/DD Program. Before he joined Pitt, he was an Associate Professor and a Founding Director of Pharmacoinformatics Research Center in the College of Pharmacy at University of Houston Texas.

Abstract:

Alzheimer’s disease (AD) is one of the most complicated progressive neurodegeneration diseases that involve many genes, proteins, and their complex interactions. No effective medicines or treatments are available yet to stop or reverse the progression of the disease due to its polygenicnature. To facilitate discovery of new AD drugs and better understand the AD neurosignaling pathways involved, we have constructed an Alzheimer’s disease domain-specific chemo-genomics knowledgebase, AlzPlatform (www.cbligand.org/AD/)with cloud computing and sourcing functions. AlzPlatform is implemented with powerful computational algorithms, includ-ing our established TargetHunter, HTDocking, and BBB Predictor for target identification and polypharmacology analysis for AD research. The platform has assembled various AD-related chemogenomics data records, including 928genes and 320 proteinsrelated to AD, 194 AD drugs approved or in clinical trials, and 405 188 chemicals associated with 1 023 137 records of reportedbioactivities from 38 284 corresponding bioassays and 10 050 references. Furthermore, we have demonstrated the application of the AlzPlatform in three case studies for identification of multitargets and polypharmacology analysis of FDA-approved drugs and also for screening and prediction of new AD active small chemical molecules and potential novel AD drug targets by ourestablished TargetHunter and/or HTDocking programs. The predictions were confirmed by reported bioactivity data and our invitro experimental validation. Overall, AlzPlatform will enrich our knowledge for AD target identification, drug discovery, andpolypharmacology analyses and, also, facilitate the chemogenomics data sharing and information exchange/communications in aid of new anti-AD drug discovery and development.

Biography:

Ming-Chao Huang graduated from Taipei Medical University in 1984 and received Ph.D in Tokyo Women’s Medical University in 1997. The current position is Section Chief in the Neurological Institute of Taipei Veterans General Hospital and President of Taiwan Neurosurgical Society for Spine. Dr. Huang focuses on disease of spine, peripheral nerve, especially in brachial plexus injury, and brain tumor, both clinical and research. In brain tumor, he studies the effect and mechanism of anti-angiogenesis therapy. He also achieved success in the treatment brachial plexus injury and is now investigating its pain mechanism.

Abstract:

Neurotrophic factors are crucial for neuron survival and axon regeneration. Among them, acidic fibroblast growth factor (aFGF) is a normal constituent of the spinal cord and is expressed in motor neurons and primary sensory neurons. It is involved in repairing process after tissue damage. Our studies demonstrate that aFGF has beneficial effects in the treatment of cervical root injury, which is currently considered by most to be beyond surgical repair and medical treatment.In the last decade,we developed a repair technique by bridging severed nerve roots and the spinal cordwith autologous nerve graft and addingaFGFmixed infibrin glue. The fibrin glue not only acts as a tissue glue but also ensures slow-release of the aFGF. We achieved functional recovery in animal experiments as well as in clinical trial. In a series of animal experiments, the outcomeof both motor and sensory function was markedly improved.The improvement was related to the increase of both motor and sensory neuron survival, even in the worst clinical scenario, such as repairingin a chronic stage, or repairing ventral root only. In clinical trial, significant functional recovery were also observed, including muscle power and mechanical sensation.We believe that besides surgery, the addition of aFGF may play an important role not only in enhancing axonal regeneration but also in promoting neuronal survival; which arethe key factorsfor functional recovery.

Biography:

Alaa Abousetta has completed his MD " Doctorate of Audiological Medicine" at the age of 35 years from Ain Shams University, Cairo, Egypt. He is currently appointed as Associate Professor and the head of Audiovestibular unit at Faculty of Medicine Suez Canal University, Egypt. He has published around 20 papers in reputed journals and serving as editorial board member of repute. In addition, he has helped in inauguration of Audiovestibular units as well as academic degrees in Egypt and the Arab world.

Abstract:

This study was conducted to determine the injurious effects of noise on the hippocampus, and to show whether Ginkgo biloba (Gb) has any modulatory effect on hippocampal injury. Fifteen adult male albino rats were divided into three groups; control group, noise group and protected group. The noise group was exposed to 100 dB Sound pressure level (SPL) white noise, six hours/day for four consecutive weeks. The protected group was exposed to the same noise level with the administration of Gb extract to the animals (50 mg/kg daily) for 4 weeks. In the noise exposed group, both pyramidal cell layer and dentate gyrus (DG) granular cell layer showed a decrease in thickness with loss and degeneration of many cells. The protected group showed preservation of many parameters as compared to the noise group i.e. increase in thickness of Cornu Ammonis area3 (CA3)&DG; increase in surface area of cells and increased vascularity. In conclusion, noise had detrimental effects on cells of Cornu Ammonis area1 (CA1), CA3 & DG of the hippocampus. In view of this finding, the clinical auditory hazardous effects in people exposed to harmful noise such as tinnitus, as well as memory disturbances and learning disabilities might have a new dimension. The administration of Gb protected the hippocampus against the injurious effect of noise. The probable mechanism and usefulness of Gb in reducing the previously mentioned effects are discussed.

Biography:

He graduated from Medical Faculty of Istanbul (Capa) University in 1999. Ahmet Hacimuftuoglu has completed his Ph.D at the age of 27 years from Ataturk University and postdoctoral studies from Ohio State University School of Medicine. He set up the “in vivo voltammetry laboratory” in Ataturk University, in 2008. He is the head of the department of Medical Pharmacology in Ataturk University. He has published more than 50 papers in SCI journals and also has 4 patents and serving as an editorial board member of Turkish Journal of Biology and also serving as executive committee member of TUBITAK Biotechnology in Turkiye. He mainly works on glutamate and psychoneuropharmacology.

Abstract:

Neurotransmitters mediate communication between neurons and non-neuronal cells. Changings in neurotransmitter levels in the synaptic area can cause or aggravate central nervous system (CNS) disorders. In the past, detecting directly of these levels has been limited in its temporal and spatial resolution because of their nature of chemical signaling and their structures. Minimally invasive techniques for monitoring brain chemistry in vivo provided better understanding of neuropharmacology of CNS disorders. For monitoring and sampling brain chemistry; voltammetric electrodes, microdialysis and related analytical techniques had been used. Microdialysis, compared to voltammetry, offers lower temporal and spatial resolution. Glutamate is a principle neurotransmitter. But it also has neurotoxic effects. In our studies we used voltammetric electrodes for detecting glutamate activities in synaptic area. Different brain areas were chosen with stereotaxy three dimensionally for each experimental disease models. We used different glutamate transporter activator or inhibitor drugs to change glutamate levels in synaptic area in different animal models. To better understand the role of glutamate in neurodegenerative disease models, we used enzyme-based microelectrodes that were selective for glutamate and measures with fast temporal and high spatial resolution. Also our understanding on drugs and their action mechanisms are increasing by this method.

Biography:

Gisele Monteiro de Souza has completed her Ph.D at the age of 27 years from University de São Paulo and postdoctoral studies from the same University. Now, she is professor of Pharmaceutical Biotechnology at Faculty of Pharmaceutical Sciences (FCF/USP) andthe vice-coordinator of the Graduate Course in Biochemical-Pharmaceutical Technology. She has published more than 20 papers in reputed journals and serving as an associate editor of Brazilian Journal of Microbiology. She has received 10 scientific awards, including internationals. The main scientific interest is the study of molecular targets involved in cell response to antitumor drugs and the engineering of proteins used as biopharmaceuticals, such as asparaginase.

Abstract:

Carboplatin is a derivative of cisplatin, characterized by its ability to generate DNA lesions through the formation of adducts with platinum. Carboplatin was approved by the FDA in the 1980s and since then it has been widely used in the treatment of several types of tumors. In 2008, Hillenmeyeret al. published a wide toxicogenomic study of the yeast Saccharomyces cerevisiae, characterizing the fitness defect of this model cell when challenged against a large library of different chemical agents, including carboplatin. Using the results of this study as a preliminary guide, 53 yeast mutant strains from the Yeast Knockout (YKO) collection were selected and analyzed individually regarding their cell viability and growth ratio when carboplatin was present in the culture media. Thirty-four mutant strains were responsive to carboplatin treatment; among them 21 possess 88 human homolog genes. Focusing on the function of these human homologs, results showed an enrichment of proteins undertaking a physical interaction with cullins 1, 2 and 3 or regulated by HuR (ELAV1). Cullins are proteins that need to undertake a post-translation modification called NEDDylation to be active. Recent works have demonstrated that NEDDylation of HuR leads to its stabilization.HuR is a predictive marker of gemcitabine response and it has recently been demonstrated that cells treated with carboplatin possess an accumulation of cytoplasmic HuR. Additionally, inhibition of this pathway overcomes cisplatin resistance.The results suggest that HuR and cullins are involved in the cell response to carboplatinthrough theNEDDylation pathway. Upcoming experimentation with a NEDDylation inhibitor will be carried out on a human ovarian cancer cell line to further test this hypothesis.

Biography:

Dr. Naumenko became Head of the Department of Behavioral Neurogenomics at the Institute of Cytology and Genetics in 2014 followed by defense of doctoral (Dr.Sc.) thesis in physiology in 2012. He completed his Ph.D. in physiology at the Institute of Cytology and Genetics in 2006 after he graduated from Novosibirsk State University as molecular biologist in 2005. He joined the Department of Behavioral Neurogenomics while he was student in 2002 and began to study the role of different types of serotonin receptors in the regulation of genetically determined defensive behavior in animal models. Now he studies the molecular mechanisms of serotonin receptor interaction and their role in the mechanisms of aggressive behavior and depression. Dr. Naumenko is also studying the cross-talk between neurotrophic factors and brain neurotransmitters in the regulation of different kind of behavior.

Abstract:

The effect of glial cell line-derived neurotrophic factor (GDNF) on behavior and brain dopamine system in predisposed to depressive-like behavior ASC (Antidepressant Sensitive Cataleptics) mice in comparison with the parental “nondepressive” CBA mice was studied. In seven days after administration (800 ng, i.c.v.) GDNF decreased escape latency time and the path traveled to reach hidden platform in Morris water maze in ASC mice. GDNF enhanced depressive-like traits in both “nondepressive” CBA and “depressive” ASC mice. In CBA mice, GDNF decreased functional response to agonists of D1 (Chloro-APB hydrobromide) and D2 (Sumanirole maleate) receptors in tail suspension test, reduced D2 receptor gene expression in the substantianigra and increased monoamine oxydase A (MAO A) gene expression in the striatum. GDNF increased D1 and D2 receptor genes expression in the nucleus accumbens of ASC mice but failed to alter expression of catechol-O-methyltransferase, dopamine transporter, MAO B and tyrosine hydroxylase genes in both investigated mouse strains. Thus, GDNF produced long-term genotype-dependent effect on behavior and the brain dopamine system. GDNF pretreatment 1) reduced D1 and D2 receptors functional responses and D2 receptor gene expression in s. nigra of CBA mice; 2) increased D1 and D2 receptor genes expression in n. accumbens of ASC mice and 3) improved spatial learningin ASC mice. GDNF enhanced depressive-like behavior both in CBA and ASC mice. The data suggest that genetically defined variance in the cross-talk between GDNF and brain dopamine system contributes to the variability of GDNF-induced responses and might be responsible for controversial GDNF effects.

Biography:

Marta Ferreira has completed her PhD in Biomedical Sciences at the age of 31 years from Porto University and the postdoctoral studies from CIIMAR - Interdisciplinary Center for Marine and Environmental Research. Currently, she is a researcher at CIIMAR, a research and advanced training institution at University of Porto, studying the effects of classical and emergent contaminants to aquatic organisms. Marta Ferreira is an environmental toxicologist with more than 25 papers published in reputed journals in the area of expertise. She has also participated in several national and international research projects and students supervision.

Abstract:

Chemical compounds, including pharmaceuticals, are constantly released to the environment. The aquatic environments are final sinks for several compounds from natural or anthropogenic origins, thus the effects of these contaminants in organisms exposed to them have to be thoroughly investigated in order to ascertain their impacts to wild life and to the ecosystems. Pharmaceuticals are considered emerging contaminants because their toxic effects and risk to the environment may not be known. The widespread detection of pharmaceuticals in the environment has raised concern about the potential impact. The concern regarding the ecotoxicological effects of pharmaceuticals is based on the assumption of evolutionary conservation of the specific molecular targets, by acting in a specific mode, targeting human receptors or enzymes, they can elicit unwanted responses in non-target species at low concentrations. In fact, in the last decades several studies have reported the negative impacts of these contaminants to aquatic organisms. For example, psychopharmaceuticals (PP) that compensate the abnormal functioning of the neurotransmitter systems by targeting metabolism and secretion of neurotransmitters, can affect neurotransmitter systems in fish thereby impeding fitness and survival on a population scale. Pharmaceuticals can also interfere with efflux transporter proteins that have a role in elimination of pharmaceuticals, determining effective concentration of drugs administration in patients. These proteins are also relevant in bioavailability of contaminants in aquatic species and their inhibition in fish can increase toxicity of normally effluxed compounds. In conclusion, it is of extreme importance to wild and human life to investigate the real effects of pharmaceuticals to aquatic ecosystems.

Biography:

Abstract:

It has been established that mononuclear and binuclear dinitrosyl iron complexes (DNIC) with thiol-containing ligands (cysteine or glutathione – RS) (formulas {(RS-)2Fe+(NO+)2+ and (RS-)2Fe2+(NO+)42+}, respectively), produce miscellaneous physiological and biochemical effects on animal and human cells and tissues. Their biological action mimics that of nitrogen monoxide (NO), a universal endogenous regulator of metabolic processes, and its oxidized form, viz., nitrosonium ion (NO+), and is based on the ability of DNIC to act as NO and NO+ donors in biological systems. By acting as NO+ donors, DNIC with thiol-containing ligands initiate S-nitrosation of thiol-containing proteins responsible for programmed cell death. Intraperitoneal treatment of rats DNIC with glutathione (12.5 moles/kg, 10 injections in 10 days), beginning with day 4 after the surgical operation (model of peritoneal endometriosis), followed by 14-day keeping of animals on a standard feeding schedule without medication resulted in complete inhibition of the growth of endometrioid implants (EMI) in the majority of experimental animals. A comparison of effects of DNIC and GS-NO on the growth of EMI demonstrated their effects opposite on EMI; while DNIC effectively suppressed tumour growth, GS-NO failed to produce such an effect. General toxic effect of the latter was manifested in the uninterrupted growth of EMI and the appearance of peritoneal adhesions. An EPR study of EMI tissues of control rats established the presence of endogenous DNIC with thiol-containing ligands with a characteristic EPR peak at g = 2.04 resulting from enhanced generation of NO in cells and tissues of these animals. Another important finding of this study, viz., detection of an active form of ribonucleotide reductase (RNR) in EMI samples of control rats by a characteristic doublet EPR signal at g = 2.0 and splitting of 2.2 mT, provided additional evidence in favour of enhanced rates of proliferative processes in endometrial tissues of these animals. Very small concentration of RNR form was detected during EPR analysis of EMI samples of experimental rats.

Biography:

Prof. Dr. Maria Aparecida Marin-Morales is actually professor at the Universidade Estadual Paulista “Júlio de Mesquita Filho” (UNESP), campus of Rio Claro, São Paulo State, Brazil. Has graduation (1976), master (1983) and PhD (1992) in Biological Sciences in the Universidade Estadual Paulista “Júlio de Mesquita Filho” and post-doctorade in the Consejo Superior de Investigaciones Científicas (Spain) in 2011. Initiated her studies in mutagenesis in 1999 and the first articles in the area were published in 2004. Until now, she published 51 articles in renowned scientific journals and is an editorial board member of reputed journals.

Abstract:

Hymenoptera venoms are constituted by a complex mixture of chemically or pharmacologically bioactive agents and that may also contain substances capable of inhibiting and/or decreasing the genotoxic action of other compounds that are able to induce damages in the genetic material. In this study we evaluated the cytotoxic, genotoxic and antigenotoxic activities of the venoms of the bee Apis mellifera and of the wasp Polybia paulista using the HepG2 test system. We used 3 concentrations that were considered non cytotoxic to evaluate the genotoxic potential of the venoms (comet assay and micronucleus test). It was observed that these concentrations were genotoxic, therefore we used lowest concentrations to assess the antigenotoxic effects. These new concentrations showed that both venoms, instead of inhibiting and/or diminishing the genotoxic effect of methylmethane sulfonate (substance used as positive control), increased even more the damages caused by this compound. It was also observed that both venoms were able to induce lipid peroxidation and alter the activities of some antioxidant enzymes (CAT, SOD, GST). Thus, the genotoxicity of the venoms could be caused by the induction of reactive oxygen species (ROS) that interacted with biological membranes and with the DNA of the exposed cells. From this study, we can conclude that the use of Hymenoptera venoms for pharmacological purposes, for example in the treatments of cancer, should be done with extreme caution, since it was observed that even very low concentratins of these bioactive compounds can induce genotoxicity for human cells, as observed in the HepG2 cells.

Biography:

Dr. Xu Dan has completed her Ph.D in 2010 from Basic Medical School of Wuhan University. Her research work focus on xenobiotics developmental toxicology. She has published 12 papers in journals related to the field of toxicology.

Abstract:

The hypothalamic-pituitary-adrenal (HPA) axis is one of the most important neuroendocrine axes and plays an important role in stress defense responses before and after birth. Prenatal exposure to xenobiotics, including environmental toxins (such as smoke, sulfur dioxide and carbon monoxide), drugs (such as synthetic glucocorticoids), and foods and beverage categories (such as ethanol and caffeine), affects fetal development indirectly by changing the maternal status or damaging the placenta. Certain xenobiotics (such as caffeine, ethanol and dexamethasone) may also affect the fetus directly by crossing the placenta into the fetus due to their lipophilic properties and lower molecular weights. All of these factors probably result in intrauterine programming alteration of the HPA axis, which showed a low basal activity but hypersensitivity to chronic stress. These alterations will, therefore, increase the susceptibility to adult neuropsychiatric (such as depression and schizophrenia) and metabolic diseases (such as hypertension, diabetes and non-alcoholic fatty liver disease). The “over-exposure of fetuses to maternal glucocorticoids” may be the main initiation factor by which the fetal HPA axis programming is altered. Meantime, xenobiotics can directly induce abnormal epigenetic modifications and expression on the important fetal genes (such as hippocampal glucocorticoid receptor, adrenal steroidogenic acute regulatory protein, et al) or damage by in situ oxidative metabolism of fetal adrenals, which may also be contributed to the programming alteration of fetal HPA axis.

Biography:

Rekha Shenoy is currently working as an associate professor in the department of pharmacology at Manipal College of Pharmaceutical Sciences, Manipal University. She has been the recipient of three research grants funded by All India Council of Technical Education [AICTE] and Department of Biotechnology [DBT], New Delhi. Her areas of research interest are pharmacology of wound healing and role of antioxidants on healing status, inflammatory disorders and colon cancer. She has fifteen papers in impact factor journals to her credit. Dr Shenoy is happily married to Dr Arun T S, Manager- Quality Assurance, Ecron Acunova and is blessed with a son.

Abstract:

The general perception of herbal medicines as a safer alternative to allopathic drugs often leads to self-medication. Concomitant usage of herbal remedies (by chance or choice) with prescription medicines can lead to un-intended interactions modifying pharmacological properties of either drug, which could lead to potential treatment failure. We designed a study, where metformin [MET], an extensively prescribed anti-diabetic medication was evaluated with commonly used Indian herbal remedies, Sallaki (SAL) and Ashwagandha(ASH). Pharmacokinetic and pharmacodynamics profiles were determined under normal and insulin resistance conditions in rodents. A sensitive bioanalytical method was developed and validated in-house for the determination of metformin. Pharmacokinetic and pharmacodynamic evaluations were performed by using Winnonlin (v 5.3). The evaluations included estimation of Cmax, tmax, AUC0-t, AUC0-∞, Vd, Cl, t1/2 and Kel by non-compartmental pharmacokinetic analysis and estimation of plasma glucose concentrations at the scheduled time along with PK sampling. The data assessment involved plotting of response (plasma glucose) vs time and subsequent group wise comparison of the obtained data in both actual and percent-normalized form. The analysis of response vs time data was performed by non-compartmental pharmacodynamics analysis WinNonlin version 5.3. The PK-PD study demonstrated that increased obesity and associated pathological changes led to increased systemic exposure of metformin. In the absence of herbs, MET glucose profile was stable with a narrow range of plasma glucose variations. ASH does not affect metformin pharmacokinetics. The Cmaxwas reduced by 37% and AUC by 47%. Administration of SAL reduces the bioavailability of metformin. In presence of ongoing SAL treatment, higher doses of MET could be required to produce required effect. This study assumes greater importance considering the fact that the chosen herbal remedies and the drug are used for the treatment of chronic conditions.Notmany interactions are reported for metformin owing to its physico-chemical and metabolic characteristics. Our findings demonstrate that concomitant usage of metformin with sallaki may adversely affect the outcome or may result in needless increase in dosage.

Biography:

Dr.Joao Rocha has graduated in Pharmaceutical Sciences (PharmD), with a Masters (MSc) in Herbal Medicines and a PhD in Pharmacology&Pharmacotherapy at the Faculty of Pharmacy of the University of Lisbon. He is a Professor of Pharmacology&Pharmacotherapy in Pharmacy and Medicine Master Courses. Has published 16 full papers in international journals of Pharmacology, Medicine and Nutrition and has more than 60 communications at national and international congresses with focus on Pharmacology and Immunopharmacology. He is an editor and reviewer for international journals in the fields of Pharmacology and Toxicology. He also is a consultant for the Pharmaceutical Industry and National Drug Regulatory Agencies.

Abstract:

The drug discovery stage involves narrowing
down thousands of compounds to a few hundred promising possibilities that are ready for preclinical testing. Although preclinical studies only account for about 10% of the overall cost of development of an approved product, they precede the clinical and regulatory lifecycle of a given product and comprise the riskiest phase of new product development. It is estimated that only about 3–5% of all products graduate from the initial preclinical testing into the advanced clinical testing phase. Therefore, preclinical testing is widely considered as one of the crucial points in drug discovery and development. It is the point of the R&D process that can prematurely identify drug candidates with the potential to become “winners” and eliminate the “losers” prior to any significant expenditure (“fail early and cheap“). Recent strategies are being developed to change the paradigm in drug development, in order for the preclinical R&D phase to reduce high attrition rates in drug development today that led to increasingly cost in drug development yet a decline in the approval of new molecular entities. Some of those strategies involve Public-Private partnerships initiatives; translational approaches bridging the gap between preclinical and human testing that consists in a better crosstalk between basic science and clinical setting, fast-tracking patients’ acess to innovative medicines. These include the concept of repurposing/recycling new therapeutic uses from existing drugs and the development of efficacy/toxicological biomarkers able to predict, at early stages of development, the confidence in mechanism and safety of the investigational drug.

Biography:

He is a Doctor of Medicine in Pharmacology with 14 years experience in the specialty. He have been actively involved with pre-clinical drug research, clinical research, hospital administration and hospital logistics support system (Pharmacy management, Equipment procurement & maintenance, turnkey projects etc). In all, He have been a medical doctor for 24 years. His expertise revolves around the training of medical graduates & post graduates (inculcating interest in rational pharmacotherapeutics), so also in pre-clinical drug research involving in-vitro/in-vivo Pharmacokinetics & Pharmacodynamics. He has hands on experience in the traditional as well as the Problem Based Learning (PBL) types of medical curricula being followed in different medical schools all over the world. He has been an under-graduate and post-graduate examiner for many medical universities in India. Notably, He have initiated a mammoth toxicology & toxinology project for the Indian Armed Forces, involving the compilation & designing of a poisoning database & poisoning registry for the Indian Armed Forces Personnel & their families. On the administrative front, He has effectively controlled medical staff in 200-600 bedded hospitals.

Abstract:

Type-2 Diabetes Mellitus (T2DM) is a pandemic affecting the developed and developing countries. The global prevalence, as per an estimate in 2010, is 285 million people, which effectively translates into a total of 6% of the world’s adult population. Arguably, an effective and optimal treatment of this disease is the need of the hour. Till very recently the thrust of the treatment of this disorder was on insulin secretagogues and drugs which can reduce insulin resistance to some extent. Of late, this objective seems to have deviated into finding agents which can just reduce blood sugar levels, distancing themselves from the physiological mechanisms responsible for glycemic control. Drugs like α-glucosidase inhibitors and the SGLT-2 co-transport inhibitors facilitate the elimination of sugars in the feces and urine, respectively, with expected moderate to severe adverse effects. While these drugs may be useful in a specific category of patients, their general utility for all patients of T2DM may not be fully justified from a purely scientific perspective. The pathophysiology of T2DM mandates a reversal of all the processes which are impeding insulin action in spite of an almost normal secretion from the Islet-beta cells of the pancreas. The clinical limitations of agents like the biguanides and thiazolidinediones have probably initiated a race to come up with agents which just lower the blood sugar levels at any cost, especially the post-prandial levels. Active research is going on globally to come up with insulin analogs, novel insulin preparations and devices, novel insulin secretagogues, novel routes of administration including oral and nasal insulins etc, but adequate research in reversing insulin resistance seems to be lacking, which actually is the need of the hour for the optimal treatment of T2DM. In this talk we would focus very briefly on the insulin receptor, its physiological role, transduction mechanisms at the molecular level and the ongoing research on insulin receptors. This would be followed by a detailed discussion on potential targets for putative agents which can expectedly overcome the flaws in the affected receptors of T2DM, thereby facilitating an effective control of this dreaded disease.

Biography:

Anas Salem has completed his Ph.D at the age of 38 years from Assiut University and got grant from DAAD organization for doing academic researches in TUM, Munich, Germany. He has published more than 20 papers in reputed journals and serving as an member in many scientific journal.

Abstract:

Vitamin E (Vit. E) is needed for young rabbits to prevent reproductive abnormalities, abortion and poor survivability of kits. Also, exogenous progesterone (P4) is needed for rabbits to enhance early embryonic development because of inadequate corpus luteum (CL) development at this age. Hence, the aim of this study was to investigate the effect of injecting Vit. E and the combination Vit. E + P4 in young does on live body weight (LBW) gain, gestation length (GL), numbers of services/conception (NS), conception rate (CR), abortion rate (AR),litter size (LS), kit weight (KW), total litter weight (TLW), mortality rate (MR) and progesterone (P4) concentration. The group treated with Vit. E + P4 had a greater LBW gain and lesser AR at first and second pregnancy. Treatments did not have significant impact on GL and LS in the first two parities. Treatments resulted in a significantly lesser MR and greater TLW at the second parity. The Vit. E + P4 treatment resulted in a significantly lesser NS at the first parity, while Vit. E alone resulted in a significant reduction in NS at the second parity. Vit. E + P4 had a positive effect on CR at the first parity compared with controls. Vit. E alone increased CR at the second parity compared with that of the control group. The meanP4 concentration from mating to mid-pregnancy at first parity was significantly greater in the Vit. E + P4 than Vit. E and control groups. In conclusion, treatment with Vit. E + P4 at the first parity may be economically applied on rabbit farms because this treatment resulted in a greater maintenance of the first pregnancy and improved reproductive performance at the second parity as compared with results from the Vit. E treated and control groups. (up to 250 words)

Biography:

Huo Yan has completed his Ph.D at the age of 32 years from Shanghai Jiaotong University. Now he works at the Department of Pharmacy, Shanghai Jiao Tong University Affiliated Sixth People's Hospital. He focuses on natural bioactive compounds which exhibit anti-vascular disease activities. He has published more than 7 papers in reputed journals

Abstract:

Nur77 is an orphan nuclear receptor that belongs to the nuclear receptor 4A (NR4A) subfamily, which has been implicated in a variety of biological events, such as cell apoptosis, proliferation, inflammation, and metabolism. Activation of Nur77 has recently been shown to be beneficial for the treatment of cardiovascular and metabolic diseases. The purpose of this study is to identify novel natural Nur77 activators and investigate their roles in preventing vascular diseases. By measuring Nur77 expression using quantitative RT-PCR, we screened active ingredients extracted from Chinese herb medicines with beneficial cardiovascular effects. Hyperoside (quercetin 3-D-galactoside) was identified as one of the potent activators for inducingNur77 expression and activating its transcriptional activity in vascular smooth muscle cells (VSMCs). We demonstrated that hyperoside, in a time and dose dependent manner, markedly increased the expression of Nur77 in rat VSMCs, with an EC50 of ∼0.83μM. Mechanistically, we found that hyperoside significantly increased the phosphorylation of ERK1/2 MAP kinase and its downstream target cAMP response element-binding protein (CREB), both of which contributed to the hyperoside-induced Nur77 expression in rat VSMCs. Moreover, through activation of Nur77 receptor, hyperoside markedly inhibited both vascular smooth muscle cell proliferation in vitro and the carotid artery ligation-induced neointimal formation in vivo. These findings demonstrate that hyperoside is a potent natural activator of Nur77 receptor, which can be potentially used for prevention and treatment of occlusive vascular diseases.

Biography:

Abstract:

There are numerous reports in the literature about cognitive and neuroanatomicalabnormalities associated with prenatal exposure to ethanol (PEE). However, the literature is inconsistent with respect to the effects of small doses of ethanol (equivalent to one to two drinks a week) on the offspring. Furthermore, epidemiological studies testing foran association between PEE and the occurrence of symptoms that are characteristic of attentiondeficit hyperactivity disorder (ADHD) have yielded inconsistent results and attempts to verify the effects of prenatal alcohol exposure on attention in animal models are scarce. We investigated the role of dose of ethanol during pregnancy in relation to possible developmental and attentional impairments in the offspring of rats. By using liquid diets,we compared the effects of a standard (35% ethanol-derived calories - EDC) and a lower dose (10% EDC) of prenatal ethanol on developmental milestones - weight, negative geotaxis, grip strength- locomotor activity and attention in the offspring. Our results showed that PEE results in developmental impairment sand hyperactivity at the high – standard dose exposure. By using the Five choice reaction time task, a robust method to evaluate attention, we also demonstrated that prenatal ethanol can produce deficits associated with an increase in attentional demand in rodents, analogous to those observed in fetal alcohol syndrome and attentional deficit and hyperactivity disorders.

Biography:

Gopalan Kutty Nampurath PhD is a professor of pharmacology at Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, India. He has research experience of 25 years and has published 31 papers in reputed journals. His areas of research interest are inflammation, dyslipidemia and diabetes.He guided six PhDs and over 50 postgraduate students. He has peer-reviewed papers for international journals like European Journal of Medicinal Chemistry, Pharmaceutical Biology, Indian Journal of Pharmacology.

Abstract:

A recent report from our lab has claimed the remedial effect of three thiazolidin-4-ones against chemical mediated inflammation. Out of these molecules, [2-(4-chlorophenoxy)-N-(5-methyl-4-oxo-2(pyridin-2-yl)thiazolidin-3-yl)acetamide] (4C), corrected the inflammatory condition through inhibition of the major biomarkers of inflammation and pain such as cytokines (TNF-α and IL-6) and prostaglandin (PGE2) generation. This prompted the evaluation of its anti-inflammatory/antirheumatic effect in an experimental model of arthritis in the present study. After securing ethical clearance, experimental arthritis was induced in Sprague-Dawley rats using sub-plantar injection of complete Freund’s adjuvant (CFA). On Day 14 after CFA injection, animals were randomized and divided into different treatment groups (n=6) based upon the inflammation produced in contralateral paw (un-injected paw). Treatment with compound 4C inhibited the progression of chronic inflammation and reduced the associated pain sensation in rats. The compound was found effective against poly-arthritic condition in rats. In accordance with previous findings, 4C inhibited the generation of pro-inflammatory cytokines (TNF-α and IL-6) and PGE2 in the current experimental model of arthritis. In the earlier work on 4C, we reported the inhibition of COX-2 in vitro and inhibition of PGE2 generation in rat air pouch model. Thus, the mechansisms of anti-inflammatory and analgesic activities of the molecule have been established. In addition, results revealed that compound 4C was safer than diclofenac in terms of side effects such as gastric toxicity, renal toxicity, thrombocytopenia and hypertriglyceridemia that were observed in the current study. The results of study suggest the local and systemic ameliorative effect of oral 4C in arthritis condition.

Biography:

Dr C MallikarjunaRao, MPharm PhD is the Principal and professor of pharmacology at Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, India. He has research experience of 29 years and has published 83 papers in reputed journals. His areas of research interest are Pharmacology of inflammation, tissue repair,cancer and metabolic disorders. He guided seven PhDs and over 60 postgraduate students. He has peer-reviewed papers for international journals like Pharmaceutical Biology, Indian Journal of Pharmacology, Indian Drugs etc.

Abstract:

Extensive studies have been made for improving bioavailability of silymarin through various dosage forms, however not much information is availableto target hepatocytes and immune cells. Thus, the present study was designed to develop a formulation with a combination of liposomes and phytosomes. Conventional, PEGylated and charged liposomes (Dicetyl phosphate and Stearyl amine) of silymarin were prepared by film hydration method. Based on the entrapment of silymarin, 6:1lipid-cholesterol molar ratio was selected for development of various liposomal formulations. Formulations were optimised for their particle size using high-pressure homogenizer and stability during freeze drying using 5%w/v sucrose as cryoprotectant. Conventional, DP and PEGylated formulations showed better release profile at pH 1.2 and 7.4 compared to silymarin alone. These liposomes were screened in vitro on Chang liver cells and in vivo in Wistar rats against toxicities ofD-galactosamine and alcohol. Cell cycle analysis showed that the formulations were better in preventing D-galactosamine induced cell cycle arrest in S-Phase.Conventional and PEGylated liposomal formulations showed better protection in Chang liver cells and screened in vivo.Conventional liposomes of silymarin showed better hepatoprotection, and better anti-inflammatory effects when compared to silymarin suspension in both models. The pharmacokinetic results upon oral administration of silymarin and its conventional liposomes showed that conventional liposomes increased Cmax more than five times compared to silymarin suspension in normal rats and almost six times in alcohol induceddiseased rat.

Biography:

Dr. Sreedhara Ranganath Pai, M. Pharm.PhD is a professor and Head of pharmacology Department at Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, India. He has research experience of 17 years and has published 35 papers in reputed journals. His areas of research interest are Cancer biology and metabolic disorder. He guided two PhDs and over 28 postgraduate students. He has peer-reviewed papers for international journals like, Pharmaceutical Biology, Indian Journal of Pharmacology, Cytotechnology etc.

Abstract:

Orchids are widely known for their beauty and also for medicinal properties. Various studies reported that orchids, belonging to the genus Bulbophyllum have potential antitumor activity. Bulbophyllum sterile (Lam.)Suresh, (Orchidaceae), indigenous to southern India might possess antitumor activity. The present study was carried out to answer this question.Alcoholic extract of the leaves along with petroleum ether, dichloromethane and ethyl acetate fractions were all subjected to preliminary in vitro screening at a dose range of 50-500 µg/ml using MTT and SRB assay in HCT-116, MDA-MB-231 and A549 cell lines to determine the active fractions. The active fraction at its IC50 value was further evaluated under various anticancer screening protocols using acridine orange/ethidium bromide (AO/EB) staining, comet assay and cell cycle analysis. Further, in vivo studies were carried out in Ehrlich ascites carcinoma model. Dichloromethane fraction (DCM) was found to be most active in HCT-116 cell lines with IC50 value of 153.4 & 142.3 µg/ml using MTT and SRB assay respectively. Change in nuclear morphology was evident from AO/EB staining confirming apoptosis. Furthermore, increase in tail length and olive tail moment was evident from comet assay. Cell cycle analysis revealed G¬2/M phase blocking activity (29.9%) compared to (17.5%) of control. The fractions increased the mean life span in EAC inoculated mice and increased the hepatic antioxidant levels. We therefore conclude from in vitro and in vivo studies that leaves of Bulbophyllum sterile have potential antitumor activity.

Biography:

Dr. SrinivasMutalik has completed his Ph.D.in 2004 from ManipalUniversity and postdoctoral studies from University of Queensland, Australia. Heis working as Associate Professor in Manipal College of Pharmaceutical Sciences, Manipal University, India. He has good professional experience in academics and pharmaceutical industry at different capacities.DrMutalik has published more than 60 papers in reputed journals and has 4 patents.He has presented papers at various national and international conferences and delivered guest lectures. He has received several research grants from various funding agencies. DrMutalik’s research interests include development and evaluation of novel drug delivery systems.

Abstract:

The objective of the present work was to develop nanoparticulatesunscreen creams containing nanoparticles of a polyphenol along with classical sunscreen agents. Optimized nanoparticles exhibited desirable particle size, zeta potential and entrapment efficiency. FTIR and DSC studies revealed no interaction between polyphenol and excipients used. Transmission electron microscopy, scanning electron microscopy and atomic force microscopy revealed that the nanoparticles were spherical in shape. Optimized polyphenol nanoparticles showed excellent in vitro free radical scavenging activity. Nanoparticles did not exhibit cytotoxicity as indicated in MTT assay carried out using Vero and HaCaT cell lines. Skin permeation and skin deposition of morin from its nanoparticles was higher than from its plain form. Different sunscreen creams were formulated by incorporating nanoparticles along with zinc oxide and titanium dioxide in the cream base. Optimized creams showed excellent SPF values as determined by UV-2000S (Labsphere, USA). In in vitro skin permeation studies, skin permeation of polyphenol was considerably reduced and its skin deposition was substantially increased. In vivo skin permeation studies in rats indicated no transdermal permeation of polyphenol across the skin and excellent retention of polyphenol within the skin. Optimized sunscreen creams indicated excellent dermal safety. Optimized cream demonstrated exceptional in vivo antioxidant effect (estimation of catalase, superoxide dismutase, glutathione) in UV radiation exposed rats. The optimized sunscreen cream successfully demonstrated outstanding UV radiation protection as well as antioxidant properties.

Biography:

Dr. Usha Y Nayak has completed herPhD at the age of 28 years from Manipal University.She is working as Assistant Professor (Senior) at ManipalColleg of Pharmaceutical Sciences, Manipal University, India.She has published more than 25 papers in reputed journalsand presented papers at various conferences and received best paper awards. She has filed one Indian Patent.

Abstract:

Risperidone is widely used as an anti-psychotic drug to treat schizophrenia and bipolar disorder.It has significant first-pass metabolism with an oral bioavailability of 70% and a half-life of 3 hours. It produces extrapyramidal side effects dependent on dose. Hence in the present study surface modified liposomes of risperidone were prepared for brain targeting through nasal administration. Nasal administration will avoid the first pass metabolism also provides targeting to the receptor site and bypasses the blood–brain barrier thereby enhancing bioavailability. Liposomes were prepared by lipid film hydration followed by sonication using soyaphosphatidylcholine and cholesterol (molar ratio 8:1). The lipid/drug ratio was10:1. The formulation was modified in its composition by addition of a lipid DSPE-mPEG (2000) (0.05 to 0.2 molar ratio) for long time circulation. Liposomes were evaluated for Mean vesicle size, Poly dispersibility index (PDI), Zeta potential, Encapsulation Efficiency, in vitro release and plasma-brain pharmacokinetic studies. The average particle size and PDIwas found to be 98 to 115 nm and 0.17 to 0.19 respectively. The zeta potential was –28 to -36 indicating stable formulation.DSPE-mPEG (2000) containing liposomes showed higher entrapment (54%) compared to conventional liposomes (49.6%). Also DSPE-mPEG batch released maximum amount of drug 57.12 % at the end of 4 hrs following Korsmeyer-Peppas model and shows diffusion controlled release. The lower Tmax values for brain (0.25 h) when compared to blood (0.5 h) also may be due to nose to brain transport by passing the blood brain barrier. Cmax and AUC0-twere found to be significantly higher compared to pure drug, in particular DSPE-mPEG showed better performance compared to conventional liposomes.

Biography:

Dr. Sujit Nair is a Professor of Pharmaceutical Sciences and Director of the Cancer Discovery Biology Laboratory at Amrita University, India. He is also a member of the International Expert Panel of the National Medical Research Council, Government of Singapore; and a peer reviewer for several international journals. Prior to joining Amrita University, Sujit trained at the Ernest Mario School of Pharmacy and Center for Cancer Research at Rutgers, The State University of New Jersey, USA. His laboratory is funded by grants from the Government of India. He has published 25 manuscripts in peer-reviewed international journals and has authored two books. His current research interests include pharmacometrics, pharmacogenomics and systems pharmacology in discovery research and personalized medicine.

Abstract:

Exciting synergy between disciplines of pharmacokinetics, pharmacodynamics, pharmacogenomics, biostatistics and clinical pharmacology has translated into increased reliance on modeling and simulation strategies for better informing ‘go/no-go’ decisions, candidate optimization and biomarker validation in the discovery pipeline in pharmaceutical industry. With increasing practice of pharmacometrics in both the drug development and regulatory domains, we are moving away from empirical descriptions of exposure-response relationships towards more sophisticated pharmacometric models which we will exemplify and dissect. Strengths of model-based drug development and potential oversights will be discussed. With pharmacometrics fast occupying centre-stage in the translational medicine paradigm, unmet needs in modeling and simulation as well as future implications for personalized medicine will also be discussed.

Biography:

Dr. Arquimedes Gasparotto Junior has completed his Ph.D. at the age of 35 years from Federal University of Paraná and postdoctoral studies from Federal University of Santa Catarina. He is chief researcher in preclinical pharmacology and associate professor of medical school of the Federal University of Grande Dourados, Brazil. He has published three books and more than 25 papers in reputed journals and serving as an editorial board member of repute.

Abstract:

In this study was shown the cardioprotective effects of the methanolic extract obtained from Casearia sylvestris (MECS) using Swiss and C57BL/6 LDLr-null mice undergoing high fat diet (HFD). Dyslipidemia and atherogenesis were induced by the administration of HFD for 4 weeks. The MECS was administered orally at doses of 250 and 500 mg/kg, for two weeks, starting from the 2nd week of HFD. The gain in body weight and systolic blood pressure (SBP) were measured weekly over the four week study. At the end of the experiments the levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C) and very low-density lipoprotein (VLDL-C) were measured. Aldosterone, vasopressin and angiotensin converting enzyme (ACE) activity were also evaluated. The renal function, atherogenic index serum (AIS) and in vitro antiplatelet activity were investigated. Additionally, histopathological analyzes were performed to determine the intima-media thickness (IMT) and intima media ratio (IMR) in aorta samples. The HFD induced dyslipidemia and structural changes in the aortic wall, including raising of the systolic blood pressure in LDLr-null mice. In addition, we observed an increase in lipid peroxidation accompanied by a reduction of serum nitrite. The treatment with MECS was able to prevent the increase of SBP, TC, LDL-C, VLDL-C and triglycerides levels and increase HDL-C in Swiss and LDLr-null mice. These effects were accompanied by a significant reduction in oxidative stress. Moreover, AIS, IMT and IMR were significantly reduced in MECS-treated mice, and the extract was able to reduce platelet aggregation in vitro

Biography:

Dr Maria Inés Genovese is a Professor at the Department of Food Science and Experimental Nutrition of the University of São Paulo. Main research focus: Study of the bioactive compounds of phenolic nature, present in foods of the Brazilian biodiversity, in relation to chemical structure, biological activity, bioavailability and relationship maintenance/promotion of human health. Development of functional food ingredients through processes of extraction, concentration, purification, drying/microencapsulation. Evaluation of antioxidant, anti-inflammatory, antibacterial and anticancer potentials of food phenolic compounds and/or food functional ingredients/standardized extracts obtained therefrom. More than 80 papers published in reputed journals and participates in several international collaborative research projects on functional foods.

Abstract:

Proanthocyanidins, flavonoids and ellagic acid derivatives are polyphenols found in high concentrations in Brazilian native fruits such as jaboticaba (Myrciaria jaboticaba Vell. Berg), camu-camu (Myrciaria dubia (Kunth) McVaugh), and cupuassu (Theobroma grandiflorum (Willd. ex Spreng.) K. Schum). Those compounds are known due to their cancer chemopreventive, cardioprotective and antioxidant potential. However, little is known about their bioavailability and metabolites, which are the biologically active compounds indeed. Here, the aim is to investigate the metabolism of different classes of polyphenols present in native fruits, and the potentially health-beneficial biological activity, in both in vitro and in vivo assays. The metabolites formed from the jaboticaba polyphenols were identified in an in vitro fermentation model using human feces. In addition, the fate of a wide variety of metabolites was monitored after intragastric administration of jaboticaba extract (15 min – 8 h) in Wistar rats, using an UPLC-MS. The in vitro experiment showed that the ellagic acid derivatives were metabolized by the intestinal microbiota and degraded under testing conditions. Two compounds were identified after fermentation with fecal inoculum, p-hydroxybenzoic and p-hydroxyphenylacetic acids. In vivo, thirty eight metabolites were identified in plasma, stomach, liver, kidneys, brain, muscle and colon, and most of them were formed from ellagic acid derivatives. Further investigations are also made on the role of phenolic-rich extracts from those fruits upon oxidative stress and metabolic changes associated with a high fat (HFD) or a high-fat, high-sucrose (HFHS) diet in Wistar rats and C57BL/6J mice.

Biography:

Dr. Karen Mulkijanyan is the Head of the Department of Pharmacology at Tbilisi State Medical University Institute of Pharmacochemistry and Adviser on Technology Commercialization to aforesaid Institute’s Administration. He obtained his MS in Biochemistry in 1981 and PhD in Pharmacy in 2005. Dr. Mulkijanyan’s research interests include studying the pharmacology of anti-inflammatory and wound healing drugs and analysis and prediction of structure-activity relationship of natural, modified and synthesized compounds. He is the author and co-author of more than 90 papers in peer-reviewed journals, about 30 presentations at international scientific meetings, and 2 patents.

Abstract:

Extracts from the plants belonging to Boraginaceae family – Symphytum asperum, S.caucasicum and Anchusa italica have been used in folk medicine in the treatment of some kinds of disorders, mainly fractures and wounds. These extracts contain allantoin, claimed to be a cell proliferation-stimulating agent responsible for the wound-healing properties of Symphytum, and, on the other hand, hepatotoxic pyrrolizidine alkaloids, which strongly restrict internal use of comfrey extracts. Our research group succeeded in obtaining allantoin- and toxic pyrrolizidine alkaloids-free composition containing novel biopolymer from the roots of aforesaid plants – poly[oxy-1-carboxy-2-(3,4-dihydroxyphenyl)ethylene] (BP) and synthesis of its monomer (M-BP). BP and M-BP were studied to appraise their pharmacological properties. Different in vitro and in vivo experiments revealed that the investigated compounds exhibit: i) antioxidant activity and anticomplementary activity due to the inhibition of xantine oxidase and complement convertase, respectively; ii) burn and wound healing properties due to the shortening of the second phase of wound healing - the inflammatory response; iii) inhibition of androgen-dependent and -independent prostate cancer (PCA) cells growth in vitro. Consistent with in vitro results, in vivo study showed that BP strongly inhibited 22Rvl tumors growth without any toxicity; iv) abrogation of melanoma cells adhesion to tumor-conditioned medium- and VEGF-activated endothelial cells; v) significant stimulation of leucopoiesis in mice drug-induced leukopenia. Strong efficacy of BP and M-BP in different experimental models suggests its high therapeutic potential.

Biography:

Hamiyet Unal completed Ph.D in 2010 from Cleveland State University, USA under the supervision of Dr. Sadashiva Karnik, Professor, Department of Molecular Cardiology, Cleveland Clinic and Cleveland State University. She continued multi-disciplinary postdoctoral studies in Karnik Laboratory and has published several papers on angiotensin receptor structure and mechanism of signaling in reputed journals. Her seminal observations have contributed to basic concepts of GPCR activation mechanisms with emphasis on angiotensin receptor. She is currently an assistant professor in the Department of Pharmacology at Erciyes University, Turkey with continued affiliation with the Karnik Laboratory and Molecular Cardiology Department at Cleveland Clinic, USA.

Abstract:

The native angiotensin type 1 receptor (AT1R) displays low constitutive activity, which may contribute to pathologies such as cardiac hypertrophy in response to mechanical stress without requiring a natural or pharmacological agonist. Ligand-independent activation of the AT1R could arise in vivo due to factors such as the membrane environment, interaction with autoantibodies or interacting proteins, single nucleotide polymorphisms that increase expression and mechanical stretch. However, naturally occurring, disease causing gain-of-function mutations of AT1R are not known. Our lab engineered the first knowledge-based constitutively active mutant AT1R, by substituting Asn111:TM3 with a glycine that resulted in the highest basal activity of the receptor. We will discuss the structure-function basis of constitutive activation of AT1R and demonstrate a G-protein signaling bias in the N111G-AT1R mutant. We will provide mechanistic basis for transmembrane helical separation that leads to spontaneously active signaling conformation of AT1R based on our recent X-ray structure of human AT1R. We will describe a transgenic animal model expressing the N111G-AT1R mutant directed to endothelial cells. Our results demonstrate the usefulness of the N111G-AT1R mutant as a tool for elucidating physiological role of activated AT1R in different tissues. We will describe molecular mechanisms underlying inverse agonists of AT1R. Because the AT1R is a major therapeutic target in treating hypertension, cardiovascular and renal diseases, N111G-AT1R mutant is an invaluable resource for defining the pharmacology of this receptor. Finally, we will summarize independent studies that validate both mechanistic aspects of the N111G-AT1R mutant and its application in elucidating novel tissue-specific functions of AT1R.

Biography:

Clélia A. Hiruma-Lima has completed the Msc. in Chemistry and Pharmacology of Natural Products in the Lab. of Pharmaceutical Technology of Federal University of Paraíba, Brazil and she has their Ph.D. in Human Physiology from Institute of Biology in Campinas State University, Campinas, SP, Brazil. Actually she is professor and researcher in Department of Physiology, São Paulo State University, Botucatu, SP, Brazil. Her research group studies the effect of medicinal plant for treatment of digestive tract diseases such as peptic ulcer disease, diarrhea and inflammation. She published more than 90 papers in reputed journals from pharmacology and natural products area, 2 books and 30 chapters from medicinal plants theme.

Abstract:

The increase in human life expectancy has required the development of new drugs to treat several chronic diseases such as peptic ulcer disease (PUD). The PUD is a complex and multifactorial process including bacterial infections, the increase of acid secretion, generation of reactive oxygen species (ROS), inhibition of the endogenous PGs, and the degradation of the extracellular matrix. This disease has increasing in elderly people because the intrinsic weak mucosal barrier induced by aging and also the more frequent use of nonsteroidal anti-inflammatory drugs (NSAIDs). The last decade has offered new insights in the preventative therapy and also the healing of PUD and the synergistic efficiency of standardized herbal drugs could be the new perspective for treatment of this disease. In our project entitle "Standardized extracts for the treatment of chronic disease" (Biota/FAPESP) our research group realized integrative studies with multidisciplinary approach with phytochemical, pharmacological and toxicological assays. Based on this integrative studies we evaluated more than 20 medicinal species according the pharmacopeia standard and evaluated their ensure efficacy and safety of herbal medicines as antiulcer drug. The antiulcer studies of these extracts were investigated against different ulcerogenic agents including NSAID, HCl, pyloric ligature, absolute ethanol and ischemia–reperfusion procedure. We evaluated the gastroprotective effect of extracts by analyzing the gastric juice secretion, mucus, nitric oxide (NO), sulfhydryl compound, vanilloid receptor, glutathione (GSH) levels, and myeloperoxidase (MPO) activity in the gastric and duodenal mucosa. We also evaluated the gastric and duodenal healing effects of extracts and evaluated the effect of matrix metalloproteinase activity (MMP-2 and MMP-9) and roles of VEGF, PCNA, and COX-2 in cell proliferation.

Biography:

Rainbow Lai Ping LEE has just completed her Doctor of Health Science in the Hong Kong Polytechnic University. She is the Advanced Practice Nurse in the School of Nursing, the Hong Kong Polytechnic University. She teaches in both undergraduate and post-graduate nursing programmes and supervise student’s final year research project. Apart from teaching, she also actively involves in research. She is currently the board member of the World Federation of Chinese Medicine Societies in Nanjing and a member in the research themes of Gerontological Nursing and Infection Control in Hong Kong.

Abstract:

The essential oil derived from the leaves of Melaleuca atlernifolia by steam distillation is named as tea tree oil. Tea tree oil exhibits broad-spectrum of antimicrobial activity against a wide variety of micro-organism including bacteria, virus and fungus. It is believed that the antimicrobial properties of tea tree oil are due to the presence of its cyclic monoterpenes of which about 50% are oxygenated and about 50% are hydrocarbon. Monoterpenes acquire physicochemical characteristic of lipophilicity, which permits partitioning of lipophilic compounds into the lipid bilayer of the microbial cells. The interaction of tea tree oil lipophilic compounds with the lipid bilayer of the microbial cells causes dramatic changes in the structure of the bacterial cytoplasmic membrane leading to increase cell membrane permeability and damage cell function. Although the in vitro antimicrobial activity and in vivo efficacy of tea tree oil on Staphylococcus aureus have been reported, less is known about its efficacious in the decolonization of methicillin-resistant Staphylococcus aureus (MRSA) from wound colonized with MRSA. Since this wound has an implication for the control of the spreading of MRSA infection, we formulated and evaluated the efficacy of tea tree oil for MRSA clearing and wound healing. We have successfully to formulate a topical 10% tea tree oil preparation to clear around 88% MRSA from the chronic wounds within 28 days. All studied wounds treated with tea tree oil were completely healed.

Biography:

Gadagkar received his Ph.D from Dalhousie University, Canada in 1997. Subsequently, he did post-doctoral research in the field of computational biology at Arizona State University, USA. He is an Associate Professor at Midwestern University, Arizona, USA. He teaches Genetics and Statistics from a biomedical perspective, and his research is in the general area of molecular evolutionary biology. Dr. Gadagkar has published in journals such as Genetics, Molecular Biology and Evolution, BMC Evolutionary Biology, Journal of Molecular Evolution, and more recently in Fly and Journal of Pharmacological and Toxicological Methods. He is an Academic Editor for the journal, PLOS ONE.

Abstract:

Biological response curves commonly assume a sigmoidal shape that can be approximated well by means of the 4-parameter nonlinear logistic equation, also called the Hill equation. However, estimation of the Hill equation parameters typically requires access to commercial software or the ability to write computer code. Here we present two user-friendly and freely available computer programs to fit the Hill equation — a Solver-based Microsoft Excel template and a stand-alone “point and click” program, called HEPB. Both computer programs use the iterative method to estimate the Hill equation parameters, EC50 and the Hill slope, while constraining the values of the minimum and maximum asymptotes of the response variable. While the Excel template allows the user to work in the familiar Microsoft Office environment, HEPB, in addition to fitting the Hill equation, also computes the prediction band for the data at a user-defined level of confidence, and determines the EC50 value for each of the limits of this band to give boundary values that help objectively delineate sensitive, normal and resistant responses to the drug being tested. Furthermore, HEPB also has the option to simulate response values based on the original data and the fit of the Hill equation to that data. Both programs were tested by analyzing twelve datasets that varied widely in data values, sample size and slope, and were found to yield estimates of the Hill equation parameters that were essentially identical to those provided by GraphPad Prism and nls, the statistical package in the programming language R.

Biography:

He graduated from Medical Faculty of Istanbul (Capa) University in 1999. Ahmet Hacimuftuoglu has completed his Ph.D at the age of 27 years from Ataturk University and postdoctoral studies from Ohio State University School of Medicine. He set up the “in vivo voltammetry laboratory” in Ataturk University, in 2008. He is the head of the department of Medical Pharmacology in Ataturk University. He has published more than 50 papers in SCI journals and also has 4 patents and serving as an editorial board member of Turkish Journal of Biology and also serving as executive committee member of TUBITAK Biotechnology in Turkiye. He mainly works on glutamate and psychoneuropharmacology.

Abstract:

Neurotransmitters mediate communication between neurons and non-neuronal cells. Changings in neurotransmitter levels in the synaptic area can cause or aggravate central nervous system (CNS) disorders. In the past, detecting directly of these levels has been limited in its temporal and spatial resolution because of their nature of chemical signaling and their structures. Minimally invasive techniques for monitoring brain chemistry in vivo provided better understanding of neuropharmacology of CNS disorders. For monitoring and sampling brain chemistry; voltammetric electrodes, microdialysis and related analytical techniques had been used. Microdialysis, compared to voltammetry, offers lower temporal and spatial resolution. Glutamate is a principle neurotransmitter. But it also has neurotoxic effects. In our studies we used voltammetric electrodes for detecting glutamate activities in synaptic area. Different brain areas were chosen with stereotaxy three dimensionally for each experimental disease models. We used different glutamate transporter activator or inhibitor drugs to change glutamate levels in synaptic area in different animal models. To better understand the role of glutamate in neurodegenerative disease models, we used enzyme-based microelectrodes that were selective for glutamate and measures with fast temporal and high spatial resolution. Also our understanding on drugs and their action mechanisms are increasing by this method.

Biography:

Ming-Chao Huang graduated from Taipei Medical University in 1984 and received Ph.D in Tokyo Women’s Medical University in 1997. The current position is Section Chief in the Neurological Institute of Taipei Veterans General Hospital and President of Taiwan Neurosurgical Society for Spine. Dr. Huang focuses on disease of spine, peripheral nerve, especially in brachial plexus injury, and brain tumor, both clinical and research. In brain tumor, he studies the effect and mechanism of anti-angiogenesis therapy. He also achieved success in the treatment brachial plexus injury and is now investigating its pain mechanism.

Abstract:

Neurotrophic factors are crucial for neuron survival and axon regeneration. Among them, acidic fibroblast growth factor (aFGF) is a normal constituent of the spinal cord and is expressed in motor neurons and primary sensory neurons. It is involved in repairing process after tissue damage. Our studies demonstrate that aFGF has beneficial effects in the treatment of cervical root injury, which is currently considered by most to be beyond surgical repair and medical treatment.In the last decade,we developed a repair technique by bridging severed nerve roots and the spinal cordwith autologous nerve graft and addingaFGFmixed infibrin glue. The fibrin glue not only acts as a tissue glue but also ensures slow-release of the aFGF. We achieved functional recovery in animal experiments as well as in clinical trial. In a series of animal experiments, the outcomeof both motor and sensory function was markedly improved.The improvement was related to the increase of both motor and sensory neuron survival, even in the worst clinical scenario, such as repairingin a chronic stage, or repairing ventral root only. In clinical trial, significant functional recovery were also observed, including muscle power and mechanical sensation.We believe that besides surgery, the addition of aFGF may play an important role not only in enhancing axonal regeneration but also in promoting neuronal survival; which arethe key factorsfor functional recovery.

Biography:

Young Hyo Kim is an assistant professor at the Department of Otorhinolaryngology, Inha University, College of Medicine. His special research interests are allergy (clinical, basic and transitional research) and space medicine. He has published more than 35 papers in the international reputed journals (Science Citation Index journals).

Abstract:

To evaluate the antiallergic effects of oral benzaldehyde in a murine model of allergic asthma and rhinitis, we divided 20 female BALB/c mice aged 8–10 weeks into nonallergic (intraperitoneally sensitized and intranasally challenged to normal saline), allergic (intraperitoneally sensitized and intranasally challenged to ovalbumin), and 200- and 400-mg/kg benzaldehyde (allergic but treated) groups. The number of nose-scratching events in 10 min, levels of total and ovalbumin-specific IgE in serum, differential counts of inflammatory cells in bronchoalveolar lavage (BAL) fluid, titers of Th2 cytokines (IL-4, IL-5, IL-13) in BAL fluid, histopathologic findings of lung and nasal tissues, and expressions of proteins involved in apoptosis (Bcl-2, Bax, caspase-3), inflammation (COX-2), antioxidation (extracellular SOD, HO-1), and hypoxia (HIF-1α, VEGF) in lung tissue were evaluated. The treated mice had significantly fewer nose-scratching events, less inflammatory cell infiltration in lung and nasal tissues, and lower HIF-1α and VEGF expressions in lung tissue than the allergic group. The numbers of eosinophils and neutrophils and Th2 cytokine titers in BAL fluid significantly decreased after the treatment (P < 0.05). These results imply that oral benzaldehyde exerts antiallergic effects in murine allergic asthma and rhinitis, possibly through inhibition of HIF-1α and VEGF.

Biography:

Arquimedes Gasparotto Junior has completed his Ph.D. at the age of 35 years from Federal University of Paraná and postdoctoral studies from Federal University of Santa Catarina. He is chief researcher in preclinical pharmacology and associate professor of medical school of the Federal University of Grande Dourados, Brazil. He has published three books and more than 25 papers in reputed journals and serving as an editorial board member of repute.

Abstract:

In this study was shown the cardioprotective effects of the methanolic extract obtained from Casearia sylvestris (MECS) using Swiss and C57BL/6 LDLr-null mice undergoing high fat diet (HFD). Dyslipidemia and atherogenesis were induced by the administration of HFD for 4 weeks. The MECS was administered orally at doses of 250 and 500 mg/kg, for two weeks, starting from the 2nd week of HFD. The gain in body weight and systolic blood pressure (SBP) were measured weekly over the four week study. At the end of the experiments the levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C) and very low-density lipoprotein (VLDL-C) were measured. Aldosterone, vasopressin and angiotensin converting enzyme (ACE) activity were also evaluated. The renal function, atherogenic index serum (AIS) and in vitro antiplatelet activity were investigated. Additionally, histopathological analyzes were performed to determine the intima-media thickness (IMT) and intima media ratio (IMR) in aorta samples. The HFD induced dyslipidemia and structural changes in the aortic wall, including raising of the systolic blood pressure in LDLr-null mice. In addition, we observed an increase in lipid peroxidation accompanied by a reduction of serum nitrite. The treatment with MECS was able to prevent the increase of SBP, TC, LDL-C, VLDL-C and triglycerides levels and increase HDL-C in Swiss and LDLr-null mice. These effects were accompanied by a significant reduction in oxidative stress. Moreover, AIS, IMT and IMR were significantly reduced in MECS-treated mice, and the extract was able to reduce platelet aggregation in vitro.

Biography:

Dr. Naumenko became Head of the Department of Behavioral Neurogenomics at the Institute of Cytology and Genetics in 2014 followed by defense of doctoral (Dr.Sc.) thesis in physiology in 2012. He completed his Ph.D in physiology at the Institute of Cytology and Genetics in 2006 after he graduated from Novosibirsk State University as molecular biologist in 2005. He joined the Department of Behavioral Neurogenomics while he was student in 2002 and began to study the role of different types of serotonin receptors in the regulation of genetically determined defensive behavior in animal models. Now he studies the molecular mechanisms of serotonin receptor interaction and their role in the mechanisms of aggressive behavior and depression. Dr. Naumenko is also studying the cross-talk between neurotrophic factors and brain neurotransmitters in the regulation of different kind of behavior

Abstract:

Insufficient drug uptake by solid tumors remains the major problem for systemic chemotherapy. Although anticancer drug effects are dose-dependent, dose-escalationhas resulted in limited survival benefit with increased toxicities. Loco-regional treatments, offering dramatically higher drug concentrations in tumor tissues while minimizing systemic toxicity, thought to be a solution, but survival benefits are still not sufficient. We have proposed that the main obstacle preventing local drug extraction by the tumor cells is the hydrophilic nature of the drug formulations themselves, which prevents partitioning through membrane lipid bilayer. To overcome this obstacle we have developed an approach for drug hydrophobization in which the drug is linked to a hydrophobic moiety by highly labile chemical linkages [termed rapidly reversible hydrophobization (RRH)]

Biography:

Dr. Grzegorz Sawicki has completed his PhD in 1989 from Medical University in Wroclaw (Poland) and post-doctoral studies from University of Kentucky (USA) and University of Alberta (Canada). Currently he is Professor of Pharmacology at University of Saskatchewan (Canada). He has published more than 100 papers and book chapters.

Abstract:

Injury of the myocardium during ischemia/reperfusion (I/R) is a complex and multifactorial process including uncontrolled protein phosphorylation, increased production of reactive oxygen species such as nitric oxide and peroxynitrite and increased contractile protein degradation by matrix metalloproteinases (MMPs). It has been shown that inhibition of MMP-2, myosin light chain kinase (MLCK) or nitric oxide synthase (NOS) can protect the heart from contractile dysfunction triggered by I/R. In this study, we show that co-administration of a mixture of low (subthreshold) concentrations of inhibitors for MMP activity (doxycycline), MLC1 phoshorylation (ML-7 inhibitor of MLCK) and nitric oxide synthase (1400W or L-NAME) protects cardiomyocytes from hypoxia-reoxygenation (H-R) induced contractile dysfunction. Isolated cardiomyocytes were subjected to 2 min hypoxia and 20 min reoxygenation (H-R) in the presence or absence of the inhibitor cocktail. Contractility of cardiomyocytes was expressed as myocyte peak shortening. Inhibition of MMP-2 by doxycycline (25-100 µM), MLCK by ML-7 (0.5-5 µM) and NO synthase with L-NAME (25-100 µM) or 1400W (25-100 µM) protected myocyte contractility after H-R in a concentration dependent manner. This led to full recovery of contractile dysfunction induced by H-R. Mixture of NOS, MMP-2 and MLCK inhibitors in subthreshold or lower concentrations protected cardiomyocyte contractility and MLC1 from degradation by MMP-2. The results of this study suggest that administration of a mixture of low (subthreshold) concentrations of doxycycline, ML-7, and 1400W or L-NAME might to be a novel strategy for protecting cardiomyocyte contractility from oxidative stress induced by coronary revascularization during cardiopulmonary bypass.

Biography:

Ali Parlar has completed his Ph.Din 2001 from Ankara University. He iscurrently assistant professor at pharmacology department in Faculty of Medicine, Adıyaman University, Adıyaman, Turkey. He has research experience of 4 years and has 3 articles. His research areas are inflammation and ischemia/reperfusion.

Abstract:

The present study aimed to investigate the potential of anti-inflammatory effects of specific CB2 agonist, GW405833, in a rat model of acute inflammation, and along with effects on leukocyte recruitment, cytokines levels, and oxidative stress. The anti-inflammatory activities of GW405833 were assessed by measuring paw oedema induced by carrageenan, and capsaicin, myeloperoxidase (MPO) activity, peritonitis model and cytokine levels. Further, oxidative stress was evaluated by determining glutathione (GSH) levels and malondialdehyde (MDA) concentration. The results showed that GW405833 (3 mg/kg) significantly reduced carrageenan-induced paw oedema, and clearly inhibited capsaicin -induced paw oedema. It also inhibited the recruitment of total leukocytes and neutrophils, mieloperoxidase (MPO) activity, and reversed nearly to the normal levels the increased tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) levels, and malondialdehyde (MDA) concentration during carrageenan-induced acute inflammation. These results suggest that GW405833 suppresses the inflammatory response by inhibiting neutrophil migration that is partly mediated by reduction in IL-1β and TNF-α levels and oxidative stress. In conclusion, the activation of CB2 receptor, by specific agonist, has a major role in peripheral inflammations, and in the near future, maybe seen new pharmacologic approaches of peripheral cannabinoidergic system as a promising alternative to treat inflammation diseases.

Biography:

Rekha Shenoy is currently working as an associate professor in the Department of Pharmacology at Manipal College of Pharmaceutical Sciences, Manipal University. She has been the recipient of three research grants funded by All India Council of Technical Education [AICTE] and Department of Biotechnology [DBT], New Delhi. Her areas of research interest are pharmacology of wound healing and role of antioxidants on healing status, inflammatory disorders and colon cancer. She has fifteen papers in impact factor journals to her credit. Dr Shenoy is happily married to Dr Arun T S, Manager- Quality Assurance, Ecron Acunovaand blessed with a son.

Abstract:

The general perception of herbal medicines as a safer alternative to allopathic drugs often leads to self-medication. Concomitant usage of herbal remedies (by chance or choice) with prescription medicines can lead to un-intended interactions modifying pharmacological properties of either drug, which could lead to potential treatment failure. We designed a study, where metformin [MET], an extensively prescribed anti-diabetic medication was evaluated with commonly used Indian herbal remedies, Sallaki (SAL) and Ashwagandha(ASH). Pharmacokinetic and pharmacodynamics profiles were determined under normal and insulin resistance conditions in rodents. A sensitive bioanalytical method was developed and validated in-house for the determination of metformin. Pharmacokinetic and pharmacodynamic evaluations were performed by using Winnonlin (v 5.3). The evaluations included estimation of Cmax, tmax, AUC0-t, AUC0-∞, Vd, Cl, t1/2 and Kel by non-compartmental pharmacokinetic analysis and estimation of plasma glucose concentrations at the scheduled time along with PK sampling. The data assessment involved plotting of response (plasma glucose) vs time and subsequent group wise comparison of the obtained data in both actual and percent-normalized form. The analysis of response vs time data was performed by non-compartmental pharmacodynamics analysis WinNonlin version 5.3. The PK-PD study demonstrated that increased obesity and associated pathological changes led to increased systemic exposure of metformin. In the absence of herbs, MET glucose profile was stable with a narrow range of plasma glucose variations. ASH does not affect metformin pharmacokinetics. The Cmaxwas reduced by 37% and AUC by 47%. Administration of SAL reduces the bioavailability of metformin. In presence of ongoing SAL treatment, higher doses of MET could be required to produce required effect. This study assumes greater importance considering the fact that the chosen herbal remedies and the drug are used for the treatment of chronic conditions. Notmany interactions are reported for metformin owing to its physico-chemical and metabolic characteristics. Our findings demonstrate that concomitant usage of metformin with sallaki may adversely affect the outcome or may result in needless increase in dosage.

Biography:

Seyfullah Oktay ARSLAN has completed his Ph.D in 1995 from Istanbul University. He is the director of pharmacology at Faculty of Medicine, Yıldırım Beyazıt University, Ankara, Türkiye. He has research experience of 25 years and has published over 30 papers in reputed journals. His areas of research interest are inflammation, asthma, and ischemia/reperfusion. He performed the member of Drug Bioequivalence Commission of Health Ministry in 2004-2010 years. In addition he has GLP and GMP knowledge experiences.

Abstract:

In our previous studies, evaluations were made on some effects of the cannabinoid (CB)2 receptor activations’ during the inflammatory processes of peripheral tissues after intestinal ischemia/reperfusion . This study was designed to investigate the anti-inflammatory effects of selective CB2 receptor agonist, GW405833, in the carrageenan paw oedema test of rats. Mix type and neurogenic inflammation were induced by giving an intraplantar injection of carrageneen (50 µl, 1%) or capsaicin (50 µl, 0.1%) respectively, into the hind left paw. The study was designed in two series of groups: In the first group, plasma extravasations were measured via Evans blue dye method. The dye was injected in the tail vein 15 min before the end of the experiments. The anaesthetized animals were sacrificed by decapitation, and hind paws were incubated with formamide, and then the extracted dye was measured by spectrophotometry at 620 nm. In the second group, paw thickness was measured with electronic digital callipers, prior to and 4 h following carrageenan or 1 h following capsaicin administration, which corresponds to peak oedema. The anti-oedematous effects of GW405833 (3 mg/kg, i.v.) were compared to diclofenac (10 mg/kg, i.v.), a nonselective cyclooxygenase inhibitor, 15 min before these intraplantar injections of inflammatory agents. CB receptor involvement in the anti-inflammatory effects of GW405833 was evaluated by administration of the CB2 receptor antagonist, AM630 (1 mg/kg, i.v., 5 min before CB2 agonist injection). Pretreatment of rats with both GW405833 and diclofenac significantly attenuated carrageenan-induced paw oedema (P < 0.05) compared to vehicle-treated group. Likewise, GW405833 strongly inhibited capsaicin induced-oedema. In the second group, GW405833 significantly decreased the plasma extravasations in both carrageenan-induced mix type inflammation and capsaicin-induced neurogenic inflammation of rat paw. CB2 receptors mediate the anti-oedematous and anti-plasma extravasations effects of GW405833. The pretreatment with AM630 clearly reversed the all those effects of GW405833, which suggests a significant interaction between GW405833 and AM630. These results suggest that the GW405833 reduces inflammation through the activation of CB2 receptors when administered after carrageenan, and that effect seems to be related to the suppression of neurogenic inflammation.

Biography:

Alex Joseph has completed his Ph.D at the age of 35 years from Manipal University. He is presently working as Associate Professor in Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal University. He has published more than 35 papers in reputed journals and serving as an editorial board member of various journals

Abstract:

Thiazolidin-4-ones and coumarins are important pharmacodynamic heterocyclic scaffolds which have been reported to possess potent anti-inflammatory and anticancer properties. The combination of two pharmacophores on the same molecule is a well-established approach for the designing of potent molecules and further substitution on these scaffolds may further enhance their activity. Therefore a series of coumarin substituted thiazolidin-4-ones were synthesized and evaluated for their anticancer activity. Initially 3-acetylamiocoumarin was synthesized by cyclocondensation of salicyladehyde with N-acetylglycine. Acid hydrolysis of 3-acetylaminocoumarin afforded 3-aminocoumarin. Finally one pot reaction of 3-aminocoumarin and thioglycolic acid with different aldehydes in dry toluene yielded the corresponding coumarin substituted thiazolidin-4-ones. Structures of final compounds were confirmed by IR, NMR and Mass techniques. Among the fifteen coumarin substituted thiazolidin-4-ones screened for their in vitro cytotoxic effect on T47D and HeLa human cancer cell lines, compounds, 2-(3-fluorophenyl)-3-(2-oxo-2H-chromen-3-yl)thiazolidin-4-one (NKT-7), 2-(2-fluorophenyl)-3-(2-oxo-2H-chromen-3-yl)thiazolidin-4-one (NKT-8) and 2-(5-methylthiophen-2-yl)-3-(2-oxo-2H-chromen-3-yl) thiazolidin-4-one (NKT-14) exhibited maximum cytotoxicity with IC50 values below 2.5 µg/ml. Other moderately active compounds were NKT-4, NKT-5, NKT-6, NKT-7, NKT-13 and NKT-15 showing IC50 value between 3.45-14.67 µg/ml. The most active compounds NKT-7, NKT-8 and NKT-14 exhibited apoptosis mediated cell death as confirmed by Hoechst staining studies. Thiophen substituted thiazolidin-4-ones and fluoro/bromo/nitro phenyl substituted thiazolidin-4-ones were found to more cytotoxic than other thiazolidinones. These novel leads molecules can be further modified and screened to improve their anticancer activity.

Biography:

Alaa Abousetta has completed his MD " Doctorate of Audiological Medicine" at the age of 35 years from Ain Shams University, Cairo, Egypt. He is currently appointed as Associate Professor and the head of Audiovestibular unit at Faculty of Medicine Suez Canal University, Egypt. He has published around 20 papers in reputed journals and serving as editorial board member of repute. In addition, he has helped in inauguration of Audiovestibular units as well as academic degrees in Egypt and the Arab world.

Abstract:

This study was conducted to determine the injurious effects of noise on the hippocampus, and to show whether Ginkgo biloba (Gb) has any modulatory effect on hippocampal injury. Fifteen adult male albino rats were divided into three groups; control group, noise group and protected group. The noise group was exposed to 100 dB Sound pressure level (SPL) white noise, six hours/day for four consecutive weeks. The protected group was exposed to the same noise level with the administration of Gb extract to the animals (50 mg/kg daily) for 4 weeks. In the noise exposed group, both pyramidal cell layer and dentate gyrus (DG) granular cell layer showed a decrease in thickness with loss and degeneration of many cells. The protected group showed preservation of many parameters as compared to the noise group i.e. increase in thickness of Cornu Ammonis area3 (CA3)&DG; increase in surface area of cells and increased vascularity. In conclusion, noise had detrimental effects on cells of Cornu Ammonis area1 (CA1), CA3 & DG of the hippocampus. In view of this finding, the clinical auditory hazardous effects in people exposed to harmful noise such as tinnitus, as well as memory disturbances and learning disabilities might have a new dimension. The administration of Gb protected the hippocampus against the injurious effect of noise. The probable mechanism and usefulness of Gb in reducing the previously mentioned effects are discussed.

Biography:

SrinivasMutalik has completed his Ph.D.in 2004 from Manipal University and postdoctoral studies from University of Queensland, Australia. He is working as Associate Professor in Manipal College of Pharmaceutical Sciences, Manipal University, India. He has good professional experience in academics and pharmaceutical industry at different capacities.Dr. Mutalik has published more than 60 papers in reputed journals and has 4 patents. He has presented papers at various national and international conferences and delivered guest lectures. He has received several research grants from various funding agencies. Dr. Mutalik’s research interests include development and evaluation of novel drug delivery systems.

Abstract:

The objective of the present work was to develop nanoparticulate sunscreen creams containing nanoparticles of a polyphenol along with classical sunscreen agents. Optimized nanoparticles exhibited desirable particle size, zeta potential and entrapment efficiency. FTIR and DSC studies revealed no interaction between polyphenol and excipients used. Transmission electron microscopy, scanning electron microscopy and atomic force microscopy revealed that the nanoparticles were spherical in shape. Optimized polyphenol nanoparticles showed excellent in vitro free radical scavenging activity. Nanoparticles did not exhibit cytotoxicity as indicated in MTT assay carried out using Vero and HaCaT cell lines. Skin permeation and skin deposition of morin from its nanoparticles was higher than from its plain form. Different sunscreen creams were formulated by incorporating nanoparticles along with zinc oxide and titanium dioxide in the cream base. Optimized creams showed excellent SPF values as determined by UV-2000S (Labsphere, USA). In in vitro skin permeation studies, skin permeation of polyphenol was considerably reduced and its skin deposition was substantially increased. In vivo skin permeation studies in rats indicated no transdermal permeation of polyphenol across the skin and excellent retention of polyphenol within the skin. Optimized sunscreen creams indicated excellent dermal safety. Optimized cream demonstrated exceptional in vivo antioxidant effect (estimation of catalase, superoxide dismutase, glutathione) in UV radiation exposed rats. The optimized sunscreen cream successfully demonstrated outstanding UV radiation protection as well as antioxidant properties.

Biography:

Masako Nagashima received her medical degree at Dokkyo Medical University, Japan (2004). She was a resident from 2004 to 2009 and has been a research associate since 2009 in the Department of Pediatrics, Jichi Medical University in Tochigi, Japan. Also, she was the chief of inpatient medicine at the International University of Health and Welfare, Japan, from 2012 to 2013. Her research focuses on neuroimaging studies of neurodevelopmental disorders.

Abstract:

Attention deficit/hyperactivity disorder (ADHD) is among the most frequent neurodevelopmental disorders. Atomoxetine (ATX) and methylphenidate (MPH) have been recommended as primary medication choices to treat inhibition- and attention-related dysfunctions in ADHD children. This study used functional near-infrared spectroscopy (fNIRS) to explore the efficacy of both medications in school-aged children with ADHD for inhibitory and attention task performance. fNIRS is a promising tool, offering robust advantages such as its compactness, affordable price, tolerance to body motion and accessibility. We monitored the oxy-hemoglobin changes in ADHD children (6 to 14 years old) during go/nogo or oddball tasks before and 1.5 h after ATX, MPH or placebo administration, in a randomized, double-blind, placebo-controlled experiment. Age-, gender- and IQ-matched healthy controls, who did not receive medications or a placebo, were also monitored. In the control subjects, the go/nogo task modulated the right inferior and middle prefrontal gyri (IFG/MFG) and the oddball task modulated the right IFG/MFG and inferior parietal cortex (IPL). In ADHD children, these activations were absent in pre-medicated conditions. The reduction in the right IFG/MFG activation was normalized by both ATX and MPH for go/nogo and oddball tasks, but the right IPL was normalized only by ATX in the oddball task. These results led us to conclude that fNIRS could visualize the differential neuropharmacological effects of both substances in the inhibitory and attentional networks: ATX to up-regulate the noradrenergic system reflected in the right IFG/MFG and IPL activations, and MPH to up-regulate the dopamine system reflected in the IFG/MFG activations.

Biography:

Anas Salem has completed his Ph.D at the age of 38 years from Assiut University and got grant from DAAD organization for doing academic researches in TUM, Munich, Germany. He has published more than 20 papers in reputed journals and serving as an member in many scientific journal.

Abstract:

Vitamin E (Vit. E) is needed for young rabbits to prevent reproductive abnormalities, abortion and poor survivability of kits. Also, exogenous progesterone (P4) is needed for rabbits to enhance early embryonic development because of inadequate corpus luteum (CL) development at this age. Hence, the aim of this study was to investigate the effect of injecting Vit. E and the combination Vit. E + P4 in young does on live body weight (LBW) gain, gestation length (GL), numbers of services/conception (NS), conception rate (CR), abortion rate (AR),litter size (LS), kit weight (KW), total litter weight (TLW), mortality rate (MR) and progesterone (P4) concentration. The group treated with Vit. E + P4 had a greater LBW gain and lesser AR at first and second pregnancy. Treatments did not have significant impact on GL and LS in the first two parities. Treatments resulted in a significantly lesser MR and greater TLW at the second parity. The Vit. E + P4 treatment resulted in a significantly lesser NS at the first parity, while Vit. E alone resulted in a significant reduction in NS at the second parity. Vit. E + P4 had a positive effect on CR at the first parity compared with controls. Vit. E alone increased CR at the second parity compared with that of the control group. The meanP4 concentration from mating to mid-pregnancy at first parity was significantly greater in the Vit. E + P4 than Vit. E and control groups. In conclusion, treatment with Vit. E + P4 at the first parity may be economically applied on rabbit farms because this treatment resulted in a greater maintenance of the first pregnancy and improved reproductive performance at the second parity as compared with results from the Vit. E treated and control groups.

Biography:

Gisele Monteiro de Souza has completed her Ph.D at the age of 27 years from University de Sao Paulo and postdoctoral studies from the same University. Now, she is professor of Pharmaceutical Biotechnology at Faculty of Pharmaceutical Sciences (FCF/USP) andthe vice-coordinator of the Graduate Course in Biochemical-Pharmaceutical Technology. She has published more than 20 papers in reputed journals and serving as an associate editor of Brazilian Journal of Microbiology. She has received 10 scientific awards, including internationals. The main scientific interest is the study of molecular targets involved in cell response to antitumor drugs and the engineering of proteins used as biopharmaceuticals, such as asparaginase.

Abstract:

Carboplatin is a derivative of cisplatin, characterized by its ability to generate DNA lesions through the formation of adducts with platinum. Carboplatin was approved by the FDA in the 1980s and since then it has been widely used in the treatment of several types of tumors. In 2008, Hillenmeyeret al. published a wide toxicogenomic study of the yeast Saccharomyces cerevisiae, characterizing the fitness defect of this model cell when challenged against a large library of different chemical agents, including carboplatin. Using the results of this study as a preliminary guide, 53 yeast mutant strains from the Yeast Knockout (YKO) collection were selected and analyzed individually regarding their cell viability and growth ratio when carboplatin was present in the culture media. Thirty-four mutant strains were responsive to carboplatin treatment; among them 21 possess 88 human homolog genes. Focusing on the function of these human homologs, results showed an enrichment of proteins undertaking a physical interaction with cullins 1, 2 and 3 or regulated by HuR (ELAV1). Cullins are proteins that need to undertake a post-translation modification called NEDDylation to be active. Recent works have demonstrated that NEDDylation of HuR leads to its stabilization.HuR is a predictive marker of gemcitabine response and it has recently been demonstrated that cells treated with carboplatin possess an accumulation of cytoplasmic HuR. Additionally, inhibition of this pathway overcomes cisplatin resistance.The results suggest that HuR and cullins are involved in the cell response to carboplatinthrough theNEDDylation pathway. Upcoming experimentation with a NEDDylation inhibitor will be carried out on a human ovarian cancer cell line to further test this hypothesis.

Biography:

Karen Mulkijanyan is the Head of the Department of Pharmacology at Tbilisi State Medical University Institute of Pharmacochemistry and Adviser on Technology Commercialization to aforesaid Institute’s Administration. He obtained his MS in Biochemistry in 1981 and PhD in Pharmacy in 2005. Dr. Mulkijanyan’s research interests include studying the pharmacology of anti-inflammatory and wound healing drugs and analysis and prediction of structure-activity relationship of natural, modified and synthesized compounds. He is the author and co-author of more than 90 papers in peer-reviewed journals, about 30 presentations at international scientific meetings, and 2 patents.

Abstract:

Extracts from the plants belonging to Boraginaceae family – Symphytum asperum, S.caucasicum and Anchusa italica have been used in folk medicine in the treatment of some kinds of disorders, mainly fractures and wounds. These extracts contain allantoin, claimed to be a cell proliferation-stimulating agent responsible for the wound-healing properties of Symphytum, and, on the other hand, hepatotoxic pyrrolizidine alkaloids, which strongly restrict internal use of comfrey extracts. Our research group succeeded in obtaining allantoin- and toxic pyrrolizidine alkaloids-free composition containing novel biopolymer from the roots of aforesaid plants – poly[oxy-1-carboxy-2-(3,4-dihydroxyphenyl)ethylene] (BP) and synthesis of its monomer (M-BP). BP and M-BP were studied to appraise their pharmacological properties. Different in vitro and in vivo experiments revealed that the investigated compounds exhibit: i) antioxidant activity and anticomplementary activity due to the inhibition of xantine oxidase and complement convertase, respectively; ii) burn and wound healing properties due to the shortening of the second phase of wound healing - the inflammatory response; iii) inhibition of androgen-dependent and -independent prostate cancer (PCA) cells growth in vitro. Consistent with in vitro results, in vivo study showed that BP strongly inhibited 22Rvl tumors growth without any toxicity; iv) abrogation of melanoma cells adhesion to tumor-conditioned medium- and VEGF-activated endothelial cells; v) significant stimulation of leucopoiesis in mice drug-induced leukopenia. Strong efficacy of BP and M-BP in different experimental models suggests its high therapeutic potential.

Biography:

Afrianti, Leni Herliani was born in Bandung, West Java, Indonesia in 21 April, 1968. She get Bachelor of Engineering Degree from Food Technology Department, Pasundan University, Bandung, Indonesia, in 1986, and Master of Agriculture Degree in Post Harvest Agriculture of Padjadjaran University, Bandung, Indonesia in 2001, and Doctoral Degree of Pharmacology in School of Pharmacy Institute Technology Bandung in 2008, Indonesia. In 1995, she joined with Food Technology Department Faculty of Engineering Pasundan University, Bandung, Indonesia as lecturer. In 2012, she has become chairman of Food Technology Pasundan University Bandung, Indonesia until now. She presented a paper on several international conferences. She has published more than 40 papers in reputed journals and proceeding. She has received research funding from the National Strategic Grant Batch II of from 2009 to 2011 and Competence Grant 2014 to 2016 of the Ministry of Education (DP2M) Indonesia

Abstract:

The study was designed to evaluate the potential α-glucosidase, β-glucosidase, and α-amylase inhibitor activity of ethanol extract, 3-hydroxystigmastan-5(6)-en (terpenoid), and Pyrolle-2,4-dicarboxylic acid-methyl ester of the S.edulis for anti-diabetic agent.Type 2 diabetes mellitus (T2DM) or non-insulin dependent diabetes melitus are the most prevalent form of diabetes and tend to increase especially in the developing countries.Snake fruit, Salacca (Sallaca edulis reinw) variety. Bongkok is one of the tropical fruits that posses bioactivity. Two new compounds belong to pyrrole and terpenoid was found in the previous study. However the antidiabetic potential of ethanol extract and that two compound from S.edulis have not been well characterized.The inhibitor activity of α-glucosidase, β-glucosidase, and α-amylase was performed to test the antidiabetic potential of Salacca edulis ethanol extract and its pyrrole and terpenoid compounds. Ethanol extract, terpenoid and pyrrole from S.edulis have α-glucosidase inhibitory activity in a concentration dependent manner. Pyrrole and S.edulis ethanol extract was the most active in inhibiting β-glucosidase activity, however terpenoidwas the most active compound that inhibits α-amylase selectivity.

Biography:

Dr. Sreedhara Ranganath Pai, M. Pharm.PhD is a professor and Head of pharmacology Department at Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, India. He has research experience of 17 years and has published 35 papers in reputed journals. His areas of research interest are Cancer biology and metabolic disorder. He guided two PhDs and over 28 postgraduate students. He has peer-reviewed papers for international journals like, Pharmaceutical Biology, Indian Journal of Pharmacology, Cytotechnology etc.

Abstract:

Orchids are widely known for their beauty and also for medicinal properties. Various studies reported that orchids, belonging to the genus Bulbophyllum have potential antitumor activity. Bulbophyllum sterile (Lam.)Suresh, (Orchidaceae), indigenous to southern India might possess antitumor activity. The present study was carried out to answer this question. Alcoholic extract of the leaves along with petroleum ether, dichloromethane and ethyl acetate fractions were all subjected to preliminary in vitro screening at a dose range of 50-500 µg/ml using MTT and SRB assay in HCT-116, MDA-MB-231 and A549 cell lines to determine the active fractions. The active fraction at its IC50 value was further evaluated under various anticancer screening protocols using acridine orange/ethidium bromide (AO/EB) staining, comet assay and cell cycle analysis. Further, in vivo studies were carried out in Ehrlich ascites carcinoma model. Dichloromethane fraction (DCM) was found to be most active in HCT-116 cell lines with IC50 value of 153.4 & 142.3 µg/ml using MTT and SRB assay respectively. Change in nuclear morphology was evident from AO/EB staining confirming apoptosis. Furthermore, increase in tail length and olive tail moment was evident from comet assay. Cell cycle analysis revealed G¬2/M phase blocking activity (29.9%) compared to (17.5%) of control. The fractions increased the mean life span in EAC inoculated mice and increased the hepatic antioxidant levels. We therefore conclude from in vitro and in vivo studies that leaves of Bulbophyllum sterile have potential antitumor activity

Biography:

Gopalan Kutty Nampurath PhD is a professor of pharmacology at Manipal College of Pharmaceutical Sciences, Manipal University, India. He has research experience of 25 years and has published 31 papers in reputed journals. His areas of research interest are inflammation, dyslipidemia and diabetes.He guided six PhDs and over 50 postgraduate students. He has peer-reviewed papers for international journals like European Journal of Medicinal Chemistry, Pharmaceutical Biology, Indian Journal of Pharmacology etc.

Abstract:

The remedial effect of three thiazolidin-4-ones against chemical mediated inflammation. Out of these molecules, [2-(4-chlorophenoxy)-N-(5-methyl-4-oxo-2(pyridin-2-yl) thiazolidin-3-yl)acetamide] (4C), corrected the inflammatory condition through inhibition of the major biomarkers of inflammation and pain such as cytokines (TNF-α and IL-6) and prostaglandin (PGE2) generation. This prompted the evaluation of its anti-inflammatory/anti-rheumatic effect in an experimental model of arthritis in the present study. Experimental arthritis was induced in Sprague-Dawley rats using sub-plantar injection of complete Freund’s adjuvant (CFA). Treatment with compound 4C inhibited the progression of chronic inflammation and reduced the associated pain sensation in rats. The compound was found effective against poly-arthritic condition in rats. In accordance with previous findings, 4C inhibited the generation of pro-inflammatory cytokines (TNF-α and IL-6) and PGE2 in the current experimental model of arthritis. In the earlier work on 4C, we reported the inhibition of COX-2 in vitro and inhibition of PGE2 generation in rat air pouch model. The results revealed that compound 4C was safer than diclofenac in terms of side effects such as gastric toxicity, renal toxicity, thrombocytopenia and hypertriglyceridemia that were observed in the current study. The results of study suggest the local and systemic ameliorative effect of oral 4C in arthritis condition. Thus, the mechanisms of anti-inflammatory and analgesic activities of the molecule have been established.

Biography:

Adalberto Rezende Santos is Ph.D in Cellular and Molecular Biology from Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil. Actually, he is a Senior Investigator and Substitute Head of the Laboratory of Molecular Biology Applied to Mycobacteria of Oswaldo Cruz Institute, Supervisor at the post-graduation programs of Cellular, Molecular Biology, and Clinical Medicine from Fiocruz and Federal University of Rio de Janeiro respectively. He is ad hoc consultant of the Executive Secretariat of Science Technology and Environment and of the Ministry of Health, Brazil. He is also referee of the Journal of Infectious Diseases and Pharmacogenomics.

Abstract:

In humans, the enzyme N-acetyltransferase2 (NAT2), coded by NAT2 gene, is the main metabolizer of isoniazid, dapsone and hydralazine, used for the treatment of tuberculosis, leprosy and resistant hypertension, diseases highly incidents in Brazil. We studied NAT2 in different Brazilians populations for these three disease models. In the first study, we showed the predominance of NAT2 slow acetylation alleles in Rio and Goias states. However, population from Rio showed a higher heterogenesity in NAT2 allele distribution and significant higher frequency of intermediate phenotype. Six new SNPs were identified (29T>C, 152G>T, 203G>A, 228C>T, 458C>T e 600A>G) and seven new alleles were characterized. Further, we performed an in silico molecular modeling and structural protein analyses of NAT2. The new SNP (152G>T-Gly51Val) is directly involved in substrate recognition, SNP (203G>A-Cys68Tyr) modifies the catalytic site by the loss of a functional group and SNPs (458C>T, 578C>T, 683C>T and 838G>A) facilitate enzyme degradation, all of them alter the acetylation activity to slow acetylation. In a subsequent study to evaluate the influence of CYP2E1, GSTT1, GSTM1 and NAT2 genotypes on isoniazid-induced hepatitis in TB patients and found that only NAT2 slow acetylation phenotype represented a risk factor for the occurrence of this outcome during TB treatment. In a more recent study, the influence of the acetylation phenotypes in anti-hypertensive effect of hydralazine in patients with RH was evaluated. Again, the predominance of slow acetylation phenotype was observed and only slow acetylators had significant blood pressure reductions after hydralazine use, however, with a high incidence of ADRs.

Biography:

Dr. Usha Y Nayak has completed her PhD at the age of 28 years from Manipal University. She is working as Assistant Professor (Senior) at Manipal College of Pharmaceutical Sciences, Manipal University, India.She has published more than 25 papers in reputed journals and presented papers at various conferences and received best paper awards. She has filed one Indian Patent.

Abstract:

Risperidone is widely used as an anti-psychotic drug to treat schizophrenia and bipolar disorder. It has significant first-pass metabolism with an oral bioavailability of 70% and a half-life of 3 hours. It produces extrapyramidal side effects dependent on dose. Hence in the present study surface modified liposomes of risperidone were prepared for brain targeting through nasal administration. Nasal administration will avoid the first pass metabolism also provides targeting to the receptor site and bypasses the blood–brain barrier thereby enhancing bioavailability. Liposomes were prepared by lipid film hydration followed by sonication using soyaphosphatidylcholine and cholesterol (molar ratio 8:1). The lipid/drug ratio was10:1. The formulation was modified in its composition by addition of a lipid DSPE-mPEG (2000) (0.05 to 0.2 molar ratio) for long time circulation. Liposomes were evaluated for Mean vesicle size, Poly dispersibility index (PDI), Zeta potential, Encapsulation Efficiency, in vitro release and plasma-brain pharmacokinetic studies. The average particle size and PDIwas found to be 98 to 115 nm and 0.17 to 0.19 respectively. The zeta potential was –28 to -36 indicating stable formulation.DSPE-mPEG (2000) containing liposomes showed higher entrapment (54%) compared to conventional liposomes (49.6%). Also DSPE-mPEG batch released maximum amount of drug 57.12 % at the end of 4 hrs following Korsmeyer-Peppas model and shows diffusion controlled release. The lower Tmax values for brain (0.25 h) when compared to blood (0.5 h) also may be due to nose to brain transport by passing the blood brain barrier. Cmax and AUC0-twere found to be significantly higher compared to pure drug, in particular DSPE-mPEG showed better performance compared to conventional liposomes.

Biography:

Biography Dr C MallikarjunaRao, MPharm PhD is the Principal and professor of pharmacology at Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, India. He has research experience of 29 years and has published 83 papers in reputed journals. His areas of research interest are Pharmacology of inflammation, tissue repair,cancer and metabolic disorders. He guided seven PhDs and over 60 postgraduate students. He has peer-reviewed papers for international journals like Pharmaceutical Biology, Indian Journal of Pharmacology, Indian Drugs

Abstract:

Extensive studies have been made for improving bioavailability of silymarin through various dosage forms, however not much information is availableto target hepatocytes and immune cells. Thus, the present study was designed to develop a formulation with a combination of liposomes and phytosomes. Conventional, PEGylated and charged liposomes (Dicetyl phosphate and Stearyl amine) of silymarin were prepared by film hydration method. Based on the entrapment of silymarin, 6:1lipid-cholesterol molar ratio was selected for development of various liposomal formulations. Formulations were optimised for their particle size using high-pressure homogenizer and stability during freeze drying using 5%w/v sucrose as cryoprotectant. Conventional, DP and PEGylated formulations showed better release profile at pH 1.2 and 7.4 compared to silymarin alone. These liposomes were screened in vitro on Chang liver cells and in vivo in Wistar rats against toxicities ofD-galactosamine and alcohol. Cell cycle analysis showed that the formulations were better in preventing D-galactosamine induced cell cycle arrest in S-Phase.Conventional and PEGylated liposomal formulations showed better protection in Chang liver cells and screened in vivo. Conventional liposomes of silymarin showed better hepatoprotection, and better anti-inflammatory effects when compared to silymarin suspension in both models. The pharmacokinetic results upon oral administration of silymarin and its conventional liposomes showed that conventional liposomes increased Cmax more than five times compared to silymarin suspension in normal rats and almost six times in alcohol induceddiseased rat

Biography:

Marta Ferreira has completed her PhD in Biomedical Sciences at the age of 31 years from Porto University and the postdoctoral studies from CIIMAR - Interdisciplinary Center for Marine and Environmental Research. Currently, she is a researcher at CIIMAR, a research and advanced training institution at University of Porto, studying the effects of classical and emergent contaminants to aquatic organisms. Marta Ferreira is an environmental toxicologist with more than 25 papers published in reputed journals in the area of expertise. She has also participated in several national and international research projects and students supervision.

Abstract:

Chemical compounds, including pharmaceuticals, are constantly released to the environment. The aquatic environments are final sinks for several compounds from natural or anthropogenic origins, thus the effects of these contaminants in organisms exposed to them have to be thoroughly investigated in order to ascertain their impacts to wild life and to the ecosystems. Pharmaceuticals are considered emerging contaminants because their toxic effects and risk to the environment may not be known. The widespread detection of pharmaceuticals in the environment has raised concern about the potential impact. The concern regarding the ecotoxicological effects of pharmaceuticals is based on the assumption of evolutionary conservation of the specific molecular targets, by acting in a specific mode, targeting human receptors or enzymes, they can elicit unwanted responses in non-target species at low concentrations. In fact, in the last decades several studies have reported the negative impacts of these contaminants to aquatic organisms. For example, psychopharmaceuticals (PP) that compensate the abnormal functioning of the neurotransmitter systems by targeting metabolism and secretion of neurotransmitters, can affect neurotransmitter systems in fish thereby impeding fitness and survival on a population scale. Pharmaceuticals can also interfere with efflux transporter proteins that have a role in elimination of pharmaceuticals, determining effective concentration of drugs administration in patients. These proteins are also relevant in bioavailability of contaminants in aquatic species and their inhibition in fish can increase toxicity of normally effluxed compounds. In conclusion, it is of extreme importance to wild and human life to investigate the real effects of pharmaceuticals to aquatic ecosystems.

Biography:

Xu Dan has completed her PhD in 2010 from Basic Medical School of Wuhan University. Her research work focus on xenobiotics developmental toxicology. She has published 12 papers in journals related to the field of toxicology

Abstract:

The hypothalamic-pituitary-adrenal (HPA) axis is one of the most important neuroendocrine axes and plays an important role in stress defense responses before and after birth. Prenatal exposure to xenobiotics, including environmental toxins (such as smoke, sulfur dioxide and carbon monoxide), drugs (such as synthetic glucocorticoids), and foods and beverage categories (such as ethanol and caffeine), affects fetal development indirectly by changing the maternal status or damaging the placenta. Certain xenobiotics (such as caffeine, ethanol and dexamethasone) may also affect the fetus directly by crossing the placenta into the fetus due to their lipophilic properties and lower molecular weights. All of these factors probably result in intrauterine programming alteration of the HPA axis, which showed a low basal activity but hypersensitivity to chronic stress. These alterations will, therefore, increase the susceptibility to adult neuropsychiatric (such as depression and schizophrenia) and metabolic diseases (such as hypertension, diabetes and non-alcoholic fatty liver disease). The “over-exposure of fetuses to maternal glucocorticoids” may be the main initiation factor by which the fetal HPA axis programming is altered. Meantime, xenobiotics can directly induce abnormal epigenetic modifications and expression on the important fetal genes (such as hippocampal glucocorticoid receptor, adrenal steroidogenic acute regulatory protein, et al) or damage by in situ oxidative metabolism of fetal adrenals, which may also be contributed to the programming alteration of fetal HPA axis.

Biography:

Takuya Matsumoto has completed his Ph.D.from Tokyo University of Marine Science and Technology (TUMSAT) in 2008 and postdoctoral studies from TUMSAT in 2010 and Graduate School of Agricultural and Life Sciences, The University of Tokyo in 2012.He is now Assistant professor at Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima.He has conducted a series of studies about pharmacokinetics of marine pufferfish toxin, and published more than 17 papers in journals related to the field of toxinology and marine biochemistry.

Abstract:

Pufferfish, the family Tetraodontidae, generally contain a potent neurotoxin, tetrodotoxin (TTX) that selectively binds to voltage-gated sodium channels in muscle and nerve tissues. Pufferfish mainly acquire the toxin through the food chain associated with biological concentration.In wild adult pufferfish, TTX mainly localized in high levels in the liver and ovary, although the distribution and accumulation of TTX is species-specific.We previously examined the pharmacokinetics of TTX in pufferfish Takifugu rubripes adults following single intravenous and gastrointestinal administration, and observed thatTTX was well absorbed into the systemic circulation from the gastrointestinal tractandtransferred into the liver. In this study,we investigated the tissue distribution and biliary excretion of TTX inpufferfish T. rubripes juveniles (6-month-old) for 24 h after intramuscular administration. The blood concentration of TTX was 0.53±0.15 mg/mL at 1 h, and gradually decreased to 0.05±0.01 mg/mL at 24 h after administration. The TTX concentration in the liver declined from 1.59 ± 0.10 mg/g at 1 h to 0.48±0.21 mg/g at 24 h. In contrast, the concentration of TTX in the gallbladder bile remarkably increased from 0.08±0.03 mg/mL at 1 h to 0.39±0.05 mg/mL at 8 hand remained at almost the same level at 24 h. These findings indicate that juveniles may have less ability to accumulate TTX inliver or greater ability to excrete the toxin fromliver, while adults have greater ability to accumulate more TTX in liver or less ability to excrete TTX.

Biography:

Ahmet DOGRUL has completed his MD degree at the age of 24 years from Gulhane Academy of Medicine and got pharmacology specialist degree at 30 years at the same institute. He made postdoctoral studies at Arizona University. He is the director of Pharmacology Department and Pain Research Center of Gulhane Academy of Medicine. He has published more than 35 papers in peer reviewed international journals with 1200 citation.

Abstract:

5-HT7 receptors have been widely distributed in the brain and implicated in the pathogenesis of depression, anxiety, and pain. 5-HT7 receptors are expressed in dorsal horn of the spinal cord, mid brain, pons and medulla compatable with a role in the descending pain inhibitory mechanism. 5-HT7 receptor are also expressed in some part of gastrointestinal tissues. Using selective 5-HT7 receptor antagonist, SB 269970, we found that intrathecal administration of SB 269970, totally blocked systemically administered morphine, tramadol, cannabinoid and paracetamol-induced analgesia in tail flick test in mice. Other researcher reported the involvement of spinal 5-HT7 receptors in amitriptyline. and nefopam-induced analgesia. Opioid and nonopioid swim stress induced analgesia (SIA) are commonly used to evaluate pain inhibitory pathways. We observed that intrathecal SB 269970 injection blocked both opioid and non-opioid type SIA. Dorsolateral funiculus lesion or denervation of the spinal serotonergic neurons by 5, 7-DHT resulted in a marked decrease in 5-HT7 receptor expression in the dorsal lumbar spinal cord, accompanied by inhibition of opioid and non-opioid type stress-induced analgesia. We found that systemic and spinally administered 5-HT7 receptor agonists, LP 44 or AS 19 blocked acetic acid-induced writhing test, a visceral inflammatory pain model, reversed by SB 269970 pretreatment. In conclusion, clinically approved analgesic drugs including morphine, tramadol, cannabinoids, paracetamol, and amitriptyline produce antinociception involving, mimicking, at least in part, the 5-HT7 mediated brain circuitry responsible for SIA. Pharmacological targeting of 5-HT7 receptor mediated pain inhibitory mechanisms seems a new therapeutic alternatives for the treatment of inflammatory visceral pain.

Biography:

Dr. Sujit Nair is a Professor of Pharmaceutical Sciences and Director of the Cancer Discovery Biology Laboratory at Amrita University, India. He is also a member of the International Expert Panel of the National Medical Research Council, Government of Singapore; and a peer reviewer for several international journals. Prior to joining Amrita University, Sujit trained at the Ernest Mario School of Pharmacy and Center for Cancer Research at Rutgers, The State University of New Jersey, USA. His laboratory is funded by grants from the Government of India. He has published 25 manuscripts in peer-reviewed international journals and has authored two books. His current research interests include pharmacometrics, pharmacogenomics and systems pharmacology in discovery research and personalized medicine.

Abstract:

Exciting synergy between disciplines of pharmacokinetics, pharmacodynamics, pharmacogenomics, biostatistics and clinical pharmacology has translated into increased reliance on modeling and simulation strategies for better informing ‘go/no-go’ decisions, candidate optimization and biomarker validation in the discovery pipeline in pharmaceutical industry. With increasing practice of pharmacometrics in both the drug development and regulatory domains, we are moving away from empirical descriptions of exposure-response relationships towards more sophisticated pharmacometric models which we will exemplify and dissect. Strengths of model-based drug development and potential oversights will be discussed. With pharmacometrics fast occupying centre-stage in the translational medicine paradigm, unmet needs in modeling and simulation as well as future implications for personalized medicine will also be discussed.

Biography:

He is a Doctor of Medicine in Pharmacology with 14 years experience in the specialty. He have been actively involved with pre-clinical drug research, clinical research, hospital administration and hospital logistics support system (Pharmacy management, Equipment procurement & maintenance, turnkey projects etc). In all, He have been a medical doctor for 24 years. His expertise revolves around the training of medical graduates & post graduates (inculcating interest in rational pharmacotherapeutics), so also in pre-clinical drug research involving in-vitro/in-vivo Pharmacokinetics & Pharmacodynamics. He has hands on experience in the traditional as well as the Problem Based Learning (PBL) types of medical curricula being followed in different medical schools all over the world. He has been an under-graduate and post-graduate examiner for many medical universities in India. Notably, He have initiated a mammoth toxicology & toxinology project for the Indian Armed Forces, involving the compilation & designing of a poisoning database & poisoning registry for the Indian Armed Forces Personnel & their families. On the administrative front, He has effectively controlled medical staff in 200-600 bedded hospitals.

Abstract:

Type-2 Diabetes Mellitus (T2DM) is a pandemic affecting the developed and developing countries. The global prevalence, as per an estimate in 2010, is 285 million people, which effectively translates into a total of 6% of the world’s adult population. Arguably, an effective and optimal treatment of this disease is the need of the hour. Till very recently the thrust of the treatment of this disorder was on insulin secretagogues and drugs which can reduce insulin resistance to some extent. Of late, this objective seems to have deviated into finding agents which can just reduce blood sugar levels, distancing themselves from the physiological mechanisms responsible for glycemic control. Drugs like α-glucosidase inhibitors and the SGLT-2 co-transport inhibitors facilitate the elimination of sugars in the feces and urine, respectively, with expected moderate to severe adverse effects. While these drugs may be useful in a specific category of patients, their general utility for all patients of T2DM may not be fully justified from a purely scientific perspective. The pathophysiology of T2DM mandates a reversal of all the processes which are impeding insulin action in spite of an almost normal secretion from the Islet-beta cells of the pancreas. The clinical limitations of agents like the biguanides and thiazolidinediones have probably initiated a race to come up with agents which just lower the blood sugar levels at any cost, especially the post-prandial levels. Active research is going on globally to come up with insulin analogs, novel insulin preparations and devices, novel insulin secretagogues, novel routes of administration including oral and nasal insulins etc, but adequate research in reversing insulin resistance seems to be lacking, which actually is the need of the hour for the optimal treatment of T2DM. In this talk we would focus very briefly on the insulin receptor, its physiological role, transduction mechanisms at the molecular level and the ongoing research on insulin receptors. This would be followed by a detailed discussion on potential targets for putative agents which can expectedly overcome the flaws in the affected receptors of T2DM, thereby facilitating an effective control of this dreaded disease.

Biography:

Dr. SrinivasMutalik has completed his Ph.D.in 2004 from Manipal University and postdoctoral studies from University of Queensland, Australia. He is working as Associate Professor in Manipal College of Pharmaceutical Sciences, Manipal University, India. He has good professional experience in academics and pharmaceutical industry at different capacities.Dr. Mutalik has published more than 60 papers in reputed journals and has 4 patents. He has presented papers at various national and international conferences and delivered guest lectures. He has received several research grants from various funding agencies. Dr. Mutalik’s research interests include development and evaluation of novel drug delivery systems.

Abstract:

The objective of the present work was to develop nanoparticulate sunscreen creams containing nanoparticles of a polyphenol along with classical sunscreen agents. Optimized nanoparticles exhibited desirable particle size, zeta potential and entrapment efficiency. FTIR and DSC studies revealed no interaction between polyphenol and excipients used. Transmission electron microscopy, scanning electron microscopy and atomic force microscopy revealed that the nanoparticles were spherical in shape. Optimized polyphenol nanoparticles showed excellent in vitro free radical scavenging activity. Nanoparticles did not exhibit cytotoxicity as indicated in MTT assay carried out using Vero and HaCaT cell lines. Skin permeation and skin deposition of morin from its nanoparticles was higher than from its plain form. Different sunscreen creams were formulated by incorporating nanoparticles along with zinc oxide and titanium dioxide in the cream base. Optimized creams showed excellent SPF values as determined by UV-2000S (Labsphere, USA). In in vitro skin permeation studies, skin permeation of polyphenol was considerably reduced and its skin deposition was substantially increased. In vivo skin permeation studies in rats indicated no transdermal permeation of polyphenol across the skin and excellent retention of polyphenol within the skin. Optimized sunscreen creams indicated excellent dermal safety. Optimized cream demonstrated exceptional in vivo antioxidant effect (estimation of catalase, superoxide dismutase, glutathione) in UV radiation exposed rats. The optimized sunscreen cream successfully demonstrated outstanding UV radiation protection as well as antioxidant properties.

Biography:

Ramadan I. Al-Shdefat is an Assistant Professor of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Saudi Arabia. He is the director of the Research Centre, College of Pharmacy, from 2011 until date. Al-Shdefat received his B.Sc. degree in Pharmacy from Jordan University of Science and Technology, Jordan (1997) and his Ph.D. in Pharmaceutics from The State University of Medicine and Pharmacy, Republic of Moldova(2002). He has good experience in development of Novel drug delivery Systems and their in vitro and in vivo analytical and bio-analytical evaluations. He has very good knowledge of scientific and ethical aspects of pre-clinical and clinical research and observed a number of bioequivalence studies. He has done significant original work and published many research articles in national and international journals.

Abstract:

The objective of this study is to investigate the efficacy of nebulized Furosemide in children administered singly or combined with β-Cyclodextrins on asthma exacerbations. A blind randomized controlled experiment involving five groups of children with moderate attack of asthma. Twenty children were enrolled in each group, group 1 received nebulized Salbutamol, group 2 received nebulized Furosemide, group 3 received both Salbutamol and Furosemide, group 4 received a mixture of Furosemide/β-CD in a (1:0.5) molar ratio and group 5 received a mixture of Furosemide/β-CD in a (1:1) molar ratio. Pulmonary function parameters, peak flow rates, respiratory rate, oxygen saturation and clinical scores were obtained before and after treatment The study showed improvement in the primary outcome FEVl after drug administration in all five groups of patients. Complex of both Furosemide and Cyclodextrins led to a significant increase in peak flow rate and significantly improved of FEV1, FVC, respiratory rate, SaO2 and clinical scores as compared to other groups. The complex effect was nearly equal to Furosemide and Salbutamol combination. These results support the fact that Cyclodextrins are promising approach for improving efficacy of poorly water-soluble drugs administered by inhalation.

Biography:

He is a Doctor of Medicine in Pharmacology with 14 years experience in the specialty. He have been actively involved with pre-clinical drug research, clinical research, hospital administration and hospital logistics support system (Pharmacy management, Equipment procurement & maintenance, turnkey projects etc). In all, He have been a medical doctor for 24 years. His expertise revolves around the training of medical graduates & post graduates (inculcating interest in rational pharmacotherapeutics), so also in pre-clinical drug research involving in-vitro/in-vivo Pharmacokinetics & Pharmacodynamics. He has hands on experience in the traditional as well as the Problem Based Learning (PBL) types of medical curricula being followed in different medical schools all over the world. He has been an under-graduate and post-graduate examiner for many medical universities in India. Notably, He have initiated a mammoth toxicology & toxinology project for the Indian Armed Forces, involving the compilation & designing of a poisoning database & poisoning registry for the Indian Armed Forces Personnel & their families. On the administrative front, He has effectively controlled medical staff in 200-600 bedded hospitals.

Abstract:

Type-2 Diabetes Mellitus (T2DM) is a pandemic affecting the developed and developing countries. The global prevalence, as per an estimate in 2010, is 285 million people, which effectively translates into a total of 6% of the world’s adult population. Arguably, an effective and optimal treatment of this disease is the need of the hour. Till very recently the thrust of the treatment of this disorder was on insulin secretagogues and drugs which can reduce insulin resistance to some extent. Of late, this objective seems to have deviated into finding agents which can just reduce blood sugar levels, distancing themselves from the physiological mechanisms responsible for glycemic control. Drugs like α-glucosidase inhibitors and the SGLT-2 co-transport inhibitors facilitate the elimination of sugars in the feces and urine, respectively, with expected moderate to severe adverse effects. While these drugs may be useful in a specific category of patients, their general utility for all patients of T2DM may not be fully justified from a purely scientific perspective. The pathophysiology of T2DM mandates a reversal of all the processes which are impeding insulin action in spite of an almost normal secretion from the Islet-beta cells of the pancreas. The clinical limitations of agents like the biguanides and thiazolidinediones have probably initiated a race to come up with agents which just lower the blood sugar levels at any cost, especially the post-prandial levels. Active research is going on globally to come up with insulin analogs, novel insulin preparations and devices, novel insulin secretagogues, novel routes of administration including oral and nasal insulins etc, but adequate research in reversing insulin resistance seems to be lacking, which actually is the need of the hour for the optimal treatment of T2DM. In this talk we would focus very briefly on the insulin receptor, its physiological role, transduction mechanisms at the molecular level and the ongoing research on insulin receptors. This would be followed by a detailed discussion on potential targets for putative agents which can expectedly overcome the flaws in the affected receptors of T2DM, thereby facilitating an effective control of this dreaded disease.

Biography:

Rainbow Lai Ping LEE has just completed her Doctor of Health Science in the Hong Kong Polytechnic University. She is the Advanced Practice Nurse in the School of Nursing, the Hong Kong Polytechnic University. She teaches in both undergraduate and post-graduate nursing programmes and supervise student’s final year research project. Apart from teaching, she also actively involves in research. She is currently the board member of the World Federation of Chinese Medicine Societies in Nanjing and a member in the research themes of Gerontological Nursing and Infection Control in Hong Kong.

Abstract:

The essential oil derived from the leaves of Melaleuca atlernifolia by steam distillation is named as tea tree oil. Tea tree oil exhibits broad-spectrum of antimicrobial activity against a wide variety of micro-organism including bacteria, virus and fungus. It is believed that the antimicrobial properties of tea tree oil are due to the presence of its cyclic monoterpenes of which about 50% are oxygenated and about 50% are hydrocarbon. Monoterpenes acquire physicochemical characteristic of lipophilicity, which permits partitioning of lipophilic compounds into the lipid bilayer of the microbial cells. The interaction of tea tree oil lipophilic compounds with the lipid bilayer of the microbial cells causes dramatic changes in the structure of the bacterial cytoplasmic membrane leading to increase cell membrane permeability and damage cell function. Although the in vitro antimicrobial activity and in vivo efficacy of tea tree oil on Staphylococcus aureus have been reported, less is known about its efficacious in the decolonization of methicillin-resistant Staphylococcus aureus (MRSA) from wound colonized with MRSA. Since this wound has an implication for the control of the spreading of MRSA infection, we formulated and evaluated the efficacy of tea tree oil for MRSA clearing and wound healing. We have successfully to formulate a topical 10% tea tree oil preparation to clear around 88% MRSA from the chronic wounds within 28 days. All studied wounds treated with tea tree oil were completely healed.

Biography:

Illa Patel has completed her Ph.D in botany from Gujarat university, Gujarat, India. Presently she is Asst. professor in botany at the Department of life sciences, Hemchandracharya North Gujarat University (Patan), Gujarat, India. She is M. phil. and Ph.D guide and has specialization in plant physiology, biochemistry, Tissue culture, medicinal plants and phytochemistry. She has more than 40 publications in the reputed journals and presented more than 35 papers in national and international conferences. She is also having some funded research projects and she is member of many specific and academic bodies and rendering her services to many scientific journals.

Abstract:

Pterocarpusmarsupium Roxb. is an medicinally important plants belongs to the family Fabaceae commonly known as “Biyo” or “Indian Kino” distributed in forest of the Western Ghats of India.Plant contain various phytochemicals compounds likePhenol, flavonoids, alkaloids, Saponin, glycosides, stiroids etc. The main constituents arepterostilbene, triterpene alcohol, catechin, pterosuprin and marsupol which have medicinal properties to curing the different diseases likekapha and pitta, elephantiasis, erysipeals, rectalgia, dysentry, urinary discharge, piles and in diabetes. This plant urgently need to be conserve as it is highly exploited due to use of its heart wood and bark for obtaining many phytochemicals from it. Plant needed an ideal protocol for rapid multiplication and valid method of phytochemical analysis using atechniques of High Performance thin layer chromatography (HPTLC).This studies is aimed to developed in vitro callus and plants on MS media containing hormones viz.2,4-D, BAP, IAA individually at different concentration and in combination by using tissue culture techniques. The in vitro developed plant and callus were used to compare the phytochemicals constituent of it with in vivo plant parts through qualitative analysis in different extracts and quantify the amount of pterostilbene in eachpartwith using standard pterostilbene through HPTLC. Result of Priliminary analysis shows that in vitro developed callus contain many phytochemicals and HPTLC analysis shows it is a good source of pterostilbene. This study may be helpful for in vitro synthesis of phytoconstituents and give new resources to Pharma industry and also reduces pressure of natural plant population.

Biography:

Hamiyet Unal completed Ph.D in 2010 from Cleveland State University, USA under the supervision of Dr. Sadashiva Karnik, Professor, Department of Molecular Cardiology, Cleveland Clinic and Cleveland State University. She continued multi-disciplinary postdoctoral studies in Karnik Laboratory and has published several papers on angiotensin receptor structure and mechanism of signaling in reputed journals. Her seminal observations have contributed to basic concepts of GPCR activation mechanisms with emphasis on angiotensin receptor. She is currently an assistant professor in the Department of Pharmacology at Erciyes University, Turkey with continued affiliation with the Karnik Laboratory and Molecular Cardiology Department at Cleveland Clinic, USA.

Abstract:

The native angiotensin type 1 receptor (AT1R) displays low constitutive activity, which may contribute to pathologies such as cardiac hypertrophy in response to mechanical stress without requiring a natural or pharmacological agonist. Ligand-independent activation of the AT1R could arise in vivo due to factors such as the membrane environment, interaction with autoantibodies or interacting proteins, single nucleotide polymorphisms that increase expression and mechanical stretch. However, naturally occurring, disease causing gain-of-function mutations of AT1R are not known. Our lab engineered the first knowledge-based constitutively active mutant AT1R, by substituting Asn111:TM3 with a glycine that resulted in the highest basal activity of the receptor. We will discuss the structure-function basis of constitutive activation of AT1R and demonstrate a G-protein signaling bias in the N111G-AT1R mutant. We will provide mechanistic basis for transmembrane helical separation that leads to spontaneously active signaling conformation of AT1R based on our recent X-ray structure of human AT1R. We will describe a transgenic animal model expressing the N111G-AT1R mutant directed to endothelial cells. Our results demonstrate the usefulness of the N111G-AT1R mutant as a tool for elucidating physiological role of activated AT1R in different tissues. We will describe molecular mechanisms underlying inverse agonists of AT1R. Because the AT1R is a major therapeutic target in treating hypertension, cardiovascular and renal diseases, N111G-AT1R mutant is an invaluable resource for defining the pharmacology of this receptor. Finally, we will summarize independent studies that validate both mechanistic aspects of the N111G-AT1R mutant and its application in elucidating novel tissue-specific functions of AT1R.