Day 2 :
Keynote Forum
Arie Regev
Eli Lilly, USA
Keynote: Hepatotoxicity due to Cancer Immunotherapy Targeting Immune Checkpoints
Time : 09:30-09:55 AM
Biography:
Dr. Regev received his M.D. degree from the Hebrew University in Jerusalem, Israel. He completed residency in Medicine and fellowship in gastroenterology at Rabin Medical Center and Tel Aviv University and clinical fellowship in Hepatology and Transplant Hepatology at the University of Miami (UM), Florida. He continued working at UM as Associate Professor of Medicine and director of the hepatology fellowship program until 2007. He joined Eli Lilly in 2007, and currently heads Eli Lilly’s Safety Advisory Hub and chairs Eli Lilly’s Liver and GI Safety Committee. Dr. Regev is the author of numerous publications in major medical Journals and several chapters in major medical textbooks. He is also an Associate Professor of Medicine at the Division of Gastroenterology and Hepatology of Indiana University School of Medicine.
Abstract:
Immunotherapy is a rapidly developing treatment modality for cancer. Of the broad range of immunotherapies presently in clinical development and clinical use those targeting T cell inhibitor receptors, referred to as “checkpointsâ€, are the most advanced. They include monoclonal antibodies directed against cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death‑1 (PD-1). Activation of the immune system by inhibiting T-cell checkpoints may cause immune-mediated toxicity, which may be serious and potentially fatal. Abnormal hepatic biochemical tests have been reported in as many as 8% of patients receiving immunotherapy, while clinically significant immune-mediate liver injury has been reported in about 1.5%. In some cases severe liver injury has occurred and cases of acute liver failure leading to death have been reported. Presently there is no reliable method to predict which patients will develop immune-mediated liver injury, and there is no dependable way to identify patients who will develop severe liver injury or liver failure. Although most patients respond to corticosteroid therapy, in some cases additional immunosuppressive agents have been used with varying results. Approaches to monitoring and therapy of such patients are still evolving, and may require studies of large cross-pharma databases, to enable better understanding of the natural history and response to therapy of this potentially lethal complication.
Keynote Forum
Hari Shanker Sharma
Uppsala University, Sweden
Keynote: Nanomedicine in Alzheimer’s Disease
Time : 10:30-11:00 AM
Biography:
Hari Shanker Sharma, Ph D (BHU), Dr Med Sci (UU) is the Director of International Experimental Central Nervous system (CNS) Injury & Repair (IECNSIR) at University Hospital, Uppsala University, Sweden. He is a qualified Neuroanatomist and experimental neurpathologist trained in Germany, Switzerland, Hungary, Sweden and USA. His main research interest is currently focused on neurotoxicity of nanoparticle and nanowired drug delivery of agents for enhanced neuroprotection in a variety of CNS insults or neurodegenerative diseases in relation to the blood-brain barrier (BBB) function. He has authored more than 250 original research papers and edited several book volumes or Progress in Brain Research series.
Abstract:
The pathophysiology of Alzheimer’s Disease (AD) and its modulating factors are still not well known. Recent evidences suggest that our military personnel are at high risk for developing AD following traumatic brain injury (TBI) and/or post-traumatic stress disorders (PTSD). Thus, further studies are needed in this area to unravel biological mechanisms of AD in order to explore suitable therapeutic strategies in clinics.rnNanoformulation enhances neurotherapeutic values of drugs or neurodiagnostic tools as compared to their parent compounds. Thus, role of nanomedicine is to enhance the drug availability within the central nervous system (CNS) for greater therapeutic successes. However, once the drug-nanoparticle complexes enter into the CNS, the fate of nanomaterial is largely unknown. There are evidences to suggest that neuroprotective agents if given either in double doses or administered through nontechnology, e.g., TiO2 nanowired delivery achieved better neuroprotection than the parent compound given alone. In our hands, cerebrolysin, a multimodal drug has superior neuroprotective effects in CNS trauma, hyperthermia and in pathogenesis of AD. These observations clearly indicate that nanomedicine is the need of the hour to induce clinical benefits in situations of AD and other neurodegenerative diseases. rnRecently, role of mesenchymal stem cells (MSCs) in reducing AD pathology is suggested. Thus, it would be interesting to investigate whether nanodelivery of MSCs alone or together with cerebrolysin could have an additive/synergistic effects in inducing neuroprotection in AD. We investigated the role of nanomedicine in Aï¢P induced brain pathology in AD. Furthermore co-administration of TiO2-nanowired MSCs and/or cerebrolysin in reducing AD pathology was also examined. A combination of nanowired MSCs and cerebrolysin potentiated neuroprotection in AD. The functional significance of tehse findings in relation to future clinical strategies in AD therapy will be discussed.rn
Keynote Forum
Sinerik Ayrapetyan
UNESCO Chair-Life Sciences International Postgraduate Educational Center Yerevan, Armenia
Keynote: The dysfunction of intracellular signaling system controlling cell hydration as a primary mechanism for cell pathology
Time : 10:00-10:30 AM
Biography:
Prof. Sinerik Ayrapetyan has completed his PhD in Cell Biophysics in the Institute of Physiology of Ukraine Academy of Sciences, Kiev. He is the head of Research Council and the coordinator of UNESCO Chair in Life Sciences at Life Sciences International Postgraduate Educational Center, Yerevan, Armenia. His current research interest is “Intracellular Signaling System in Norm and Pathology”. He has published 7 international books and 115 papers. He is an Editor in Chief of the journal “Bioavailability and Bioequivalence”, and a member of editorial board of the journals: "Electromagnetic Biology and Medicine", "Journal of International Dental and Medical Research", “ISRN Biophysics”, “Advances in Life Sciences", “Applied Pharmacy”, “European Journal of Biophysics”, “Biochimica et Biophysica Acta” etc. He is a member of International Coordination Council of WHO and number of professional international societies.
Abstract:
Cell hydration determines its functional activity via “folding-unfolding” mechanism of intracellular macro-molecules and cell surface-dependent changes of protein molecules’ activity, having enzymes, receptors and ionic channels forming properties. Therefore, the metabolically controlled cell hydration is of vital importance for living cells. The facts that intracellular osmotic pressure exceeds the extracellular one and that the membrane permeability for water is much higher than for ions, the osmotically driven water influx is balanced by metabolically generated water efflux from the cell. Our data have shown that net water influx and efflux through membrane activate and inactivate inward going ionic current in membrane. Therefore, this makes the ability of metabolic compensation of osmotically driven water influx as a marker for estimation of beneficial and harmful effects of any physical and chemical factors on cells and organisms. Among the number of metabolic mechanisms involved in regulation of cell hydration, Na+/K+-pump has a central role, which is due to both generations of Na+ gradients on membrane, serving as energy sources for a number of secondary ionic transporters in membrane, and water efflux from the cells. Our recent study has shown that the dysfunction of Na+/K+-ATPase a3 isoform-dependent signaling system controlling cell hydration is the common primary mechanism for cell pathology. In may talk the suggestion on the use of a3 isoform-dependent signaling system controlling cell hydration as a novel therapeutic target for treatment of different diseases will be discussed
- Biologic Drugs
Location: Hilton San Antonio Airport
Session Introduction
Lorella Ragni
Head of Formulation Department, Angelni S.p.A, Italy
Title: New And Old Technologies For The Cosmetic Innovation Learning From The Pharmaceutical World And Balancing Trhough The Regulatory Requiremnts
Biography:
Lorella Ragni graduated in Chemistry and Pharmaceutical Science at Bologna University Italy. Soon after the degree she attended the Master in Cosmetic Product Development at Ferrara University Italy.
After a short experience in 1988 as researcher in Synthetic Chemistry at Ancona University Italy, since 1989 she has been working in Angelini covering different positions in the Development Product Department. From 2001 to present she took over the position of Head of Formulation Department. During her working experience she has been the leader of several scientific groups of formulators and analysts for the development of solid, liquid, semisolid pharmaceutical products and new drug delivery systems. In the last five years she extended her range of activity in the formulation development of Food Supplements, Cosmetics and Medical Device for European Market. She constantly supports the Company in the research and evaluation of new technologies for the feeding of project pipeline and she was the author of several European and Worldwide Patents.
Abstract:
In the cosmetic field consumers are expecting the latest technology advances to be incorporated into innovative formulations, both in terms of active ingredients (entering the perimeter of cosmeceutics) and in terms of delivery technologies. The recent regulatory framework growing araound the cosmetic world, both in the EMA and FDA perimeters, is somewhat changing the way of pursuing innovation in this field. Cosmetics formulators today are looking more and more to mutuate technologies from the pharmaceutical world, looking both at the delivery sisthems and at the new functional ingredients. This cross-contamination between pharmaceutical and cosmeceutical technologies is very important to promote innovation in this field, and can also maximize the return of the research investment for companies that have a pipeline involving both types of products. However, the challenge is not only to respect regulatory requirements that are constantly evolving in the cosmetic and cosmeceutics world, but also to offer new, smart systems that are able to deliver the active ingredients to one or more skin layers minimizing the systemic adsorption.
Biography:
To be updated
Abstract:
To be updated
LÃvia Stocco Sanches Valentin
University of São Paulo School of Medicine, Brazil
Title: The Importance Of Dexamethasone Preoperatively For The Prevention Of Cognitive Dysfunction
Biography:
Livia Valentin has completed her PhD from University of São Paulo School of Medicine- FMUSP and postdoctoral from Harvard Medical School; David Geffen School of Medicine at UCLA; Cleveland Clinic Lerner College of Medicine of Case Werstern University; University of Copenhagen; Utrecht University; Max Planck Institute and Karolinska Institute as a multicenter study. She is the Principal Investigator of the RCT Evaluation of POCD through the MentalPlus® digital game. She has published papers in anesthesia and neuropsychology journals and has been serving as an editorial board member of a indexed journal and reviewer of journal about anesthesiology and neuroscience.
Abstract:
Background: Postoperative cognitive dysfunction (POCD) is a multifactorial adverse event most frequently in elderly patients or people aged over 60 years, neurological and psychiatric diseases. This study evaluated the effect of dexamethasone on POCD incidence after non-cardiac surgery and general anesthesia. Methods: One hundred and forty patients (ASA I–II; age 60–87 years) took part in a prospective randomized study involving the administration or not of 8 mg of IV dexamethasone before deep or superficial anesthesia according to bispectral index. Neuropsychological tests were applied preoperatively and at 3rd, 7th, 21st, 90th and 180th days after surgery and compared with normative data. S100β was evaluated before and 12 hours after induction of anesthesia. Linear regression with inference based on the generalized estimating equations (GEE) method was applied, followed by the post-hoc Bonferroni test considering P<0.05 as significant. Results: On the 3rd postoperative day, POCD was diagnosed in 25.2% of patients receiving dexamethasone plus deep anesthesia, 15.3% of the dexamethasone plus superficial anesthesia group, 68.2% of the deep anesthesia group and 27.2% of the superficial anesthesia group (p<0.0001). Neuropsychological tests showed that dexamethasone plus superficial anesthesia decreased the incidence of POCD, especially memory, attention and executive function. The administration of dexamethasone prevented the postoperative increase in S100β serum levels (p<0.002). Conclusion: Dexamethasone can minimize the incidence of POCD in elderly patients undergoing non-cardiac surgery, especially when associated with superficial anesthesia. The effect of dexamethasone on S100β levels might be related with some degree of neuroprotection.
Maysaa Ch Al Mohammedawi
Deakin University, Australia
Title: Nanoparticles loaded with 5-Fluorouracil, Leucovorin, and Bovine Lactoferrin, as drug delivery carriers
Biography:
Maysaa Ch Al Mohammedawi has completed her MSc and PhD in Medical Biotechnology from the Department of Biotechnology at Al Nahrain University, Baghdad, Iraq. She became a faculty member and group leader of Medical Biotechnology research over there. She worked on molecular analysis of infectious disease, studies on the virulence factors of the pathogens, and screening anticancer agents among bacterial components. In 2012, she was awarded MoHER (Iraq) career development fellowship. Recently, join the IIE-SRF (US) fellowship at School of Medicine, Deakin University, Australia. Her studies focus on improving the in vitro drug delivery system of antitumor agents toward colon cancer.
Abstract:
Encapsulation of drugs into nanoparticles (NPs) has become a promising approach for improving the efficacy of antitumor drugs. This study evaluates the cytotoxic effect of nanoformulated antitumor drug 5-fluorouracil (5-FU), alone and combined with leucovorin (LV) or iron saturated bovine lactoferrin (Fe-bLf) by, encapsulating into FDA approved biodegradable polymer poly-caprolactone (PCL) NPs. The spherical NPs were 200-300 ± 2.9 nm in size and had drug loading capacities of 90% (5-FU-PCL), 60% (5-FU-LV-PCL) and 80% (5-FU-Fe-bLf-PCL). Drug release of 5-FU and LV after 96 h reached 98.6 % and 99.89%, respectively; Fe-bLf release was 82.28% after 96 h. Both MTT and TUNEL assay results showed that the multi-combinatorial NPs had cytotoxicity as high as 97% and could induce apoptosis in human colon cancer cell lines (Coca-2 and SW480), but had no effect on normal FHs 74 Int cells. These findings highlight the novelty and promise of this drug delivery system, and the results warrant further evaluation in suitable animal model for its future clinical applications.
Mohammadreza Rouini
Tehran University of Medical Sciences, Iran
Title: Comparative bioequivalence study of two Rivaroxaban formulations in Iranian healthy volunteers
Biography:
Mohammad-Reza Rouini has completed his PhD from Tehran University of Medical Sciences and Post-doctoral studies from Ottawa University. He is the Director of Biopharmaceutics Lab at Faculty of Pharmacy. He has published more than 100 papers in reputed journals and has been serving as an Editorial Board Member of DARU.
Abstract:
It is a factor Xa inhibitor whose potent anticoagulant and antithrombotic effects have been demonstrated. This study was designed to evaluate the pharmacokinetics of a new generic formulation of rivaroxaban compared with a brand in healthy Iranian volunteers.
Twenty-eight healthy volunteers enrolled in this study. This study employed a randomized, single-dose, two-way crossover method using oral tablets of either Axabin® or Xarelto®, as the test drug and reference drug, respectively. Two tablets (2×10 mg) were administered with 240 ml water. Blood samples were gathered at the following times: 0 hour (predose), and 0.5, 1, 1.5, 2, 2.5, 3, 4,5, 6, 8, 10, 24, and 30 hours after drug administration. To provide an accurate analysis, rivaroxaban plasma concentrations were determined by an UHPLC-MS/MS. The optimum separation was performed with a C18 column using acetonitrile and 10mM ammonium acetate (pH = 3, 70:30, v/v) as a mobile phase, at a flow rate of 0.3 ml/min. Precipitation of proteins was employed for extraction of rivaroxaban from the plasma samples. The quantification range for rivaroxaban was 2.5–600 ng.ml-1. According to FDA guidelines, the bioequivalence assessment’s acceptable range is 80–125% at a 90% confidence interval (CI) for the mean ratios of test/reference formulation of the pharmacokinetic parameters. The 90% CI of parameters were AUC0-30 (82.02–98.31), AUC0-inf (82.4-100.34), and Cmax (82.7–104.49). Therefore, the results proved the claim that the two formulations of rivaroxaban are bioequivalent.
Omodamiro O D
Micheal Okpara University of Agriculture, Nigeria
Title: In vitro antioxidant activity and hypolipidemic effects of an ethanol extract of Amaranthus Viridis leaves on hyperlipidemic Wistar Albino rats
Biography:
Omodamiro O D holds a PhD in Pharmacology from College of Medicine and Health sciences, Abia State University Uturu Abia State Nigeria. He is currently a senior Lecturer in the Pharmacology Unit of Department of Biochemistry, Micheal Okpara University of Agriculture Umudike Abia State Nigeria. He has published over 30 research papers in international reputable journals. His areas of research are cardiovascular/endocrine pharmacology, ethnopharmacology, renal pharmacology and medicinal plants.
Abstract:
Amaranthus viridis Linn. (AV), commonly known as ‘Slender or Green Amaranth’ in English, is a multinational genus of herbs. Several species of are often considered as weeds, as leafy vegetables, cereals and ornamentals. Traditionally, an infusion of the plant (leaves and roots) is used to treat dysentery and epilepsy in children, purify blood, reduce inflammation, hemorrhoids, reduce labor pain and improve appetite in parts of Africa and India. The present study was designed to evaluate the In vitro antioxidant activity and hypolipidemic effect of an ethanol extract of AV leaves (EEAVL) in Wistar albino rats and mice as experimental models. Acute toxicity (LD50) of EEAVL was studied in mice using standard method. Th e result showed a LD50 of 353.6 mg/kg of the extract. Fourteen (14) Wistar albino rats of both sexes were divided randomly into seven (7) groups of two animals, each subjected to different treatment for 14 days. Group A was the non-high fat diet control; Group B was the high fat diet-induced control; Group C received 20 mg/kg of Simvastatin, a standard lipid lowering drug; Group D to G received 250 mg/kg, 125 mg/kg, 62.25 mg/kg and 31.13 mg/kg BW respectively of EEAVL of which all were still maintained on their induced diet. At the end of the treatment, the lipid profile and body weight were estimated and compared with the Simvastatin treated control group. The result showed a significant (p<0.05) decrease in T-Cholesterol, Triglyceride and LDL-C (p>0.05) while HDL-C was increased at the doses studied. EEAVL also caused a decrease in the rate of weight gain. In the in-vitro antioxidant test, there was a concentration dependent increase in the (%) scavenging activity when compared with the Vitamin C (control) for 1, 1-diphenyl-2-picrylhydrazyl (DPPH), Nitric oxide and anti-lipid peroxidation activity of AVL. Th e results showed no significant difference at higher concentrations when compared to the control. On a comparative basis, the measure of the antioxidant eff ectiveness of the extract showed better activity in quenching Nitric oxide radical with IC50 values of 72 mg/ml compared to Lipid peroxidation radicals (78mg/ml) and DPPH radicals (108 mg/ml). The result have shown that Amaranthus viridis L, a traditional folklore medicinal plant has in vitro antioxidant potentials and hypolipidemic effect which may provide therapeutic potentials in the management of Cardiovascular diseases, diabetes and their complications which might be caused by free radical generation and hyperlipidemia.
Noghayin Mega EHIGIE
University of Benin, Nigeria
Title: Comparative Testing And Pharmcovigilance Of Biosimilars
Biography:
Mega Ehigie born 16th February 1984 maried with 1 kid, Lecturer 1 in the department of pharmaceutical pharm technology obtain his Bachelor of pharmacy Degree (B. pharm )in year 2008 and Doctor of pharmacy (pharm D) and Master degree in pharmaceutic in 2012 all in university of Benin, have 3 publications 2 journal articles
Abstract:
Unlike traditional generic pharmaceuticals, Biosimilars (also known as biopharmaceuticals in the United States) aim to copy a complex recombinant, three dimensional protein structure with high molecular weight small changes in the manufacturing process can alter the poducts effect and safety. According to the guild lines of the European agency for evaluation of medicinal products (EMEA) extensive comparability testing will require to demonstrate that the Biosimilars has a comparable profile in terms of quality, safety and efficacy as the reference products. Various analytical assays are available to compare physiochemicals and biological properties between production batches of a potentially similar biopharmaceuticals (comparability) and in comparison with a reference products (similarity).It is important to recognise the limits of existing assay so that the results can be accurately interpreted for market authorisations. This work examines the quality and limits of such analytical tests to demonstrate comparability and similarity of a Biosimilars products to a reference drug with respect to protein content, activity, physio chemical integrity. Stability, impurities and additives, as well as immunogenicity are discussed. Although several assay are available, reliable tests for safety and efficacy still require development. Furthermore, international standards are missing and materials and methods differ from laboratories making the comparison of results very difficult. Clinical trials and post authorisations pharmacovigilance are essential to quarantee the products safety and efficacy over time. Pharmacovigilance, as part of a comprehensive risk management programme, will need to include regular testing for consistent manufacturing of the drugs.
Genet Minale
Addis Ababa University, Ethiopia
Title: Antimicrobial Anthrones From The Leaves Latex Of Aloe Sinana, Reynold
Biography:
Genet Minale is a lecturer in Ambo University in the department of pharmacy. She received a BSc. in chemistry from school of Natural Science in 2009 and MSc. in Pharmacognosy from school of Pharmacy in 2013 from Addis Ababa University, Ethiopia. In addition to teaching, Genet is one of the researchers on traditional medicine in Ethiopia. She conducts research on antimalarial and antimicrobial activities of some indigenous medicinal plant in Ethiopia and she collaborated on manuscript with her colleagues Dr. Kaleab Asres and Dr. Daniel Bisrat entitled in vitro antimicrobial activities of anthrones from the leaf latex of Aloe sinana in which she presented research compiled by Ethiopian Pharmaceutical Association. She currently founded to conduct a research on indigenous knowledge on traditional medicine and pharmacognostical evaluation of medicinal plant in Ethiopia by collaboration with Wondo Genet Agricultural research center.
Abstract:
Background: Aloe sinana Reynolds is endemic to Ethiopia where its leaf latex is traditionally used in and around the town of Debre Sina and other central highlands of the country for the treatment of various illnesses, including wound, snake bite and malaria. However, despite its use in traditional medicine, to date, there appears to have been no chemical or biological studies published on this plant. Aim: The aim of this study was to investigate the leaf latex of A. sinana for its antibacterial and antifungal activities, and to isolate and characterize the compounds that are responsible for the antimicrobial effect of the latex. Materials and Methods: The latex was extracted with methanol. Isolation of compounds was achieved by repeated preparative TLC, and spectroscopic techniques including 1H, 13C‑NMR and MS were used for characterization of the isolated compounds. Antimicrobial activity tests were performed against 21 bacterial and 4 fungal pathogens using the disc diffusion method. Results and Conclusion: Three compounds isolated from the leaf latex were identified as the anthrones, aloin, aloinoside and microdontin. Among the isolated compounds, aloinoside and microdontin were found to possess comparable activity (MIC 5 μg/ml) with that of ciprofloxacin against several Gram‑negative bacterial strains and Staphylococcus aureus. Additionally, microdontin showed potent and comparable activity with the standard antifungal drug griseofulvin against Penicillum spp. These findings support the traditional uses of the plant for the treatment of various infections and wound.