Day 2 :
- Track 6: Forensic Pharmacology, Toxicology and Toxinology
Track 7: Theoritical Pharmacology
Track 12: Latest Trends in Pharmacological Drug Developments
Track 13: Pharmacological Drug Discovery
Chair
Vladimir S Naumenko
Institute of Cytology and Genetics, Russia
Co-Chair
Ramadan Al-Shdefat
Prince Sattam Bin Abdulaziz University, Kingdom of Saudi Arabia
Session Introduction
Gisele Monteiro de Souza
University de Sao Paulo, Brazil
Title: A toxicogenomic study of Carboplatin in Saccharomyces cerevisiae : The involvement of HuR and Cullins in response to this antitumor drug
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.
K Mulkijanyan
Tbilisi State Medical University, USA
Title: Plant biopolymers from Boraginaceae family species and their synthetic derivatives: Prospective pharmacological agents
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.
Leni Herliani Afrianti
Universitas Pasundan, Indonesia
Title: Potent -Glucosidase, -Amylase, and -glucosidase Inhibitor Activity of Ethanol Extract,3-hydroxystigmastan-5(6)-en (terpenoid), and Pyrolle-2,4- dicarboxylic acid-methyl ester from Salacca edulis Reinw variety Bongkok for antidiabetic agent
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
Gopalan Kutty Nampurath
Manipal University, India
Title: A Preclinical Profiling of a Promising Drug Candidate for Rheumatoid Arthritis
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.
Adalberto Rezende Santos
Oswaldo Cruz Institute
Title: Pharmacogenetics research in different disease models: our experience in Brazilian population
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.
Usha Y Nayak
Manipal University, India
Title: Nanoparticulate novel sunscreen creams: Development and evaluation
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.
C MallikarjunaRao
Manipal University, India
Title: Hepatoprotective and Pharmacokinetic studies of silymarin liposomes in alcohol and D-galactosamine induced toxic models
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
Marta Ferreira
CIIMAR – Interdisciplinary Center for Marine and Environmental Research, Portugal
Title: Marta Ferreira
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.
Xu Dan
Wuhan University, China
Title: Prenatal xenobiotic exposure and intrauterine hypothalamus-pituitary-adrenal axis programming alteration
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.
Takuya Matsumoto
Prefectural University of Hiroshima, Japan
Title: Distribution and biliary excretion of tetrodotoxin in the marine pufferfish Takifugu rubripes juvenile after an intramuscular administration
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.
Ahmet Dogrul
Gulhane Academy of Medicine,Turkey
Title: The central role of 5-HT7 receptors in the mechanism of clinically important analgesic drugs, endogenous pain inhibiton and visceral pain modulation
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.
Sujit Nair
Amrita Vishwa Vidyapeetham University, India
Title: Pharmacometrics in the translational pharmacology paradigm
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.
Vivek Lal
King Faisal University, KSA
Title: New Drug Development in Type-2 Diabetes Mellitus : Current and Future Trends – An Overview
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.
Ramadan Ibrahim Al-Shdefat
Prince Sattam Bin Abdulaziz University, Saudi Arabia
Title: New complexes of inhaled furosemide and cyclodextrin: assessment of the bronchodilator effect
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.