Day 1 :
Touro University, USA
Time : 10:00 - 10 :40 AM
Toxicology and identification of common syndromes plays a significant role in therapeutics.This is not limited to toxic substances and includes drug overdose, toxicity with drugs having a narrow therapeutic index, drugs of abuse, and other hazardous substances.While management of adverse effects include common approaches such as ionized diuresis, airway, breathing and circulation support, gastric lavage and hemodialysis, specific antidotes play a significant role. Identification of the offending agent is crucial which then determines management with an antidote and also symptomatic management. Antidotes do not exist for all toxic substances. Also of concern are substances that may have carcinogenic and teratogenic effects.Toxicology therefore involves the knowledge and practice of life saving modalities and therapeutic interventions that eradicate or reduce the levels of toxic substances. These interventions also have to take into account substances that produce delayed toxicity. Multi-organ involvement needs to be considered while coma and death often occurs due to cardiac, respiratory and renal failure, severe CNS depression and also vascular collapse.This presentation addresses common syndromes and therapeutic interventions and likely outcomes.
Umm Al Qura University, Saudi Arabia
Keynote: Fluticasone propionate attenuate induced nitric oxide synthase through dephosphorylation of p38 and Akt
Time : 10:40 - 11:20 AM
Mahdi Alsugoor obtained his BSc (Hons) in pharmaceutical science from King Saud University in Saudi Arabia and MSc in pharmacology from University of Hertfordshire and PhD in molecular and cardiovascular Pharmacology from the University of Hertfordshire in the United Kingdom. He is currently work at Umm Al-Qura university as the Vice Dean for Development and Entrepreneurship and the head of public health department in the Health Sciences college. He worked as a visiting lecturer in the University of Hertfordshire and has served on the reviewer Board of the several international journals. His research interest and expertise is in cell signalling, focusing on induced nitric oxide synthase and stem cell differentiation. He is also interested in antimicrobial resistance and stewardship.
Introduction:The upregulation of the inducible nitric oxide synthase (iNOS) and nitric oxide (NO) production have been implicated in inflammatory pathologies. Although research has revealed that non selective glucocorticoids (GCs) such as dexamethasone and hydrocortisone inhibit iNOS expression and NO production, the selective GCs , fluticasone propionate, action on iNOS expression and function remain to be investigated. In addition, investigations were performed to distinguish the GC and non-GC actions using receptor antagonists. Since the effects of GCs on upstream signalling pathways remain vague, further studies were conducted to investigate whether fluticasone regulates the p38 mitogen-activated protein kinases or protein kinase B (Akt) pathways, both of which have been reported to be critical for the induction of iNOS. Methodology: All experiments were conducted using primary cultures of rat aortic smooth muscle cells (RASMCs). The cells were activated with bacterial LPS (100 μg/mL) and interferon-gamma (IFN-γ, 100 U/mL) to induce iNOS and NO. Nitrite levels in cellular supernatants were quantified by the Griess assay, and expressions of iNOS , phospho-p38 (P-p38) and phospho-Akt (P-Akt) were investigated by western blotting. Results: Fluticasone (0.1 nM–3.0 µM) inhibited NO production and iNOS expression partially (~50%), and the effects were significant at 1 nM–3 µM. RU-486 (10 μM), a GC receptor (GCR) blocker, was able to reverse the inhibitions caused by fluticasone, though eplerenone (0.1–10.0 µM), the mineralocortocoid receptor blocker, had no effect. More importantly, fluticasone inhibited the phosphorylation of p38 and Akt in activated RASMCs. The inhibitions were reversed upon incubation with RU-486 (10 μM) for 1 h prior to the addition of fluticasone. Conclusion: fluticasone only partially inhibited iNOS expression and function. The inhibitions were reversed by RU-486, but not eplerenone, which strongly suggests a GC-mediated response to fluticasone and other receptors or pathways might be involved in regulation of iNOS expression and function. Mechanistic studies revealed that the GC can regulate key signalling pathways associated with the induction of iNOS. More specifically, fluticasone reduced the phosphorylation of p38, thereby suggesting that its actions can be mediated by suppressing these kinase pathways, which are widely reported to critically regulate iNOS expression and function.
University of Houston, USA
Time : 11:40 - 12:20 PM
Sivakumar Ganapathy is Professor of Molecular Plant Biotechnology at the Department of Engineering Technology at University of Houston. His primary research interest is engineering of commercially important plant alkaloids metabolic pathways to make medicines that can enhance human health. He is particularly interested in colchicine synthetic biotechnology and biomanufacturing of biopharmaceuticals. Sivakumar invented biorhizome technology for pharmaceutical colchicine manufacturing. Sivakumar's lab studies how gene circuits uniquely affect colchicine biosynthesis in Colchicaceae, uses genomic approaches to generate transcriptomes and microRNAomes in colchicine-producing biorhizomes and to identify and characterize the genes and gene elements controlling the colchicine biosynthetic pathway in Gloriosa superba. Other research focuses include computational mapping and electron crystallographic modeling of colchicine and its semisynthetics and developing potential anticancer medicines. He is internationally recognized in the field of plant-based natural products and is a pioneer in the unique biomanufacturing of biorhizome-based colchicine. He is also on the editorial board of several journals and serves as an expert of grant proposals and numerous scientific journals.
Plant-based drugs to treat human lethal diseases have been elicited with cutting-edge clinical research. Colchicine is an important alkaloid-based drug used to treat gout, cardiovascular disease, etc. However, plant-based biopharmaceuticals and industrial-scale development pose several challenges in biomanufacturing. Biorhizome is a new technology to enhance the colchicine biomanufacturing. Nevertheless, the biochemical pathways and regulatory networks in the biorhizomes that control colchicine biosynthesis are yet to be characterized, leaving a significant barrier to improving colchicine biomanufacturing. The presentation will emphasize the biomanufacturing of biopharmaceuticals and improving the commercial-scale biorhizome-based colchicine.