Day :
- Molecular and Clinical Pharmacology
Chair
Elza Nikoleishvili
The University of Georgia, Georgia
Session Introduction
Melanie Hermann
Evotec SE, Germany
Title: High content histology in drug discovery programs – A tool for target validation
Biography:
Melanie Hermann has completed her PhD at the German Cancer Research Center in Heidelberg, Germany by working on a Transgenic Mouse Model for Skin Cancer. Afterwards she was working as a Postdoc in the Department of Neurosurgery at UCSF, San Francisco, USA, where she did her studies on stroke and traumatic-brain-injury mouse models. Back in Germany, she continued her studies in the Department of Neuropathology at UKE, Hamburg,
Germany by working in the field of Prion disease and the rare Neurodegenerative disease FENIB (familial encephalopathy with neuroserpin inclusion bodies). Afterwards, she has started her carrier in industry and is now working as a Senior Research Scientist on different drug discovery programs at Evotec SE Hamburg by taking the Lead of high content histology approaches for target validation.
Abstract:
Targets arising from either disease relevant animal models, in vitro genetic experiments or the public domain need careful validation and confirmation, ideally prior to initiating a small molecule discovery program. Evotec has developed a number of in and ex vivo models across numerous therapeutic indications to help answer these questions. To maximize the efficiency and robustness of in vivo target modulation, Evotec has implemented an automated histology platform, which aims to identify, localize and validate targets within disease relevant tissues. Together with our in-house expertise in developing unbiased automated image analysis scripts for quantification, the high content histology platform is applied to quantify targets or other relevant factors and proteins within the tissue of choice. In addition, a stereotactic delivery of AAV-shRNA is routinely used to modulate in vivo expression levels and activity of target proteins, to investigate the effects this protein has on cell physiology and disease progression. Furthermore, after successful drug identification, high content histology readouts are used to confirm small molecule effects on disease progression.
Djebbar Atmani
Universite de Bejaia, Algerie
Title: Pistacia lentiscus as a source of bioactive compounds for human health
Biography:
Djebbar Atmani is a Senior Lecturer and Dean of the Faculty of Nature and Life Sciences, University of Bejaia (Algeria). He has obtained his Master of Science degree from California State University, Los Angeles (USA) in 1987 and his PhD from the University of Sétif (Algeria) in 2004. His research interest is Natural Products from Medicinal Plants. He has published over 50 papers in high impact scientific journals and attended several seminars and symposia worldwide and has been serving as Reviewer in several reputed journal.
Abstract:
Medicinal plants are believed to be an important source for the discovery of
potential antioxidant, anticancer, anti-inflammatory and anti-diabetic substances. The present study was designed to investigate the anti-inflammatory, antidiabetic and anticancer potential of Pistacia lentiscus (Anacardiaceae) extracts, as well as identification of active compounds, using appropriate methodology. Oral administration of the crude extracts of leaves and fruits (100 and 200 mg/kg) significantly decreased carrageenan-induced mice paw edema similar to the standard drug Diclofenac (50 mg/kg). Furthermore, Pistacia lentiscus leaf extract was effective in reducing the serum levels of IL-1β compared to acetylsalicylic acid. Blood glucose level was restored to normal values, for both concentrations (50 and 125 mg/kg) tested, in agreement with the in vitro antidiabetic effect. P. lentiscus extracts were also found to be significantly cytotoxic on melanoma B16F10 cell line and showed very good anti-hyperuricemic activity. Phytochemical analysis indicated the presence of copious amounts of flavonoids, tannins and phenolics in the extracts of this plant such as gallic acid, myricetinrhamnoside, quercetin 3-O-rhamnoside, synergic acid and ellagic acid, which could be responsible for the observed activity. Obtained results suggest that Pistacia lentiscus extracts exhibited strong biological effects and may be a candidate for the development of pharmacological agents that may be used in therapy against inflammatory-related disorders.
Wan-Ting Liao
Show Chwan Memorial Hospital, Taiwan
Title: Integrative traditional Chinese medicine therapy reduces risk of type 2 diabetes mellitus in patients with polycystic ovary syndrome
Biography:
Wan-Ting Liao is an Occupational Physician major in Herbalism. She has completed her MD from China Medical University. After finished several research of PCOS and the relationship of PCOS and Diabetes in her Master’s degree in China Medical University, she is now admitted to Institute of Medicine of Chung Shan Medical University for her MD/PhD program.
Abstract:
Polycystic ovary syndrome (PCOS) is a common condition in human beings,
affecting 5-10% of women of reproductive age worldwide. It might lead to a
variety of syndrome such as reproductive, metabolic and mood disorders. The
symptoms of PCOS are complex. The academic circles had made it clear that women with polycystic ovary syndrome have a higher proportion of insulin resistance and are expected to have an increased risk of developing type 2 diabetes in the future. Current treatment of PCOS mainly focuses on symptomatic treatment. This study aimed to understand whether the intervention of traditional Chinese medicine (TCM) in women with PCOS could reduce the risk of type 2 diabetes mellitus. Therefore, we selected the National Health Insurance Database as data source, and randomly selected 1 million enrollees. We identified 684 eligible patients who were newly diagnosed with PCOS in 1997-2010 and underwent blood test of serum testosterone or gynecologic ultrasound. All enrolled cases were 1:1 frequency-matched by age, and diagnosis of PCOS date and index days. Surprisingly, we found that the incidence of type 2 diabetes in TCM groups was significantly lower than in non- TCM group (HR=0.31, 95% CI=0.15-0.64, P=0.0014). Our study suggests that Chinese medicine may play a role in the prevention of subsequent complication of diabetes in patients with PCOS. It is expected that in the future, further clinical research and pharmacological analysis based on these findings.
Abdul Mannan Fateh
University of Malaya, Malaysia
Title: Study of morphogenesis and skeletal abnormalities from an aqueous extract of Verbena officinalis on developing SD embryos
Biography:
Abdul Mannan Fateh is currently studying PhD final year student in Pharmacology Department in the Faculty of Medicine in University Malaya in Malaysia. He has completed his Master’s degree (MSc) in Toxicology Department of Medical Elementology and Toxicology, Hamdard University (New –Delhi) India. He has worked in Medical College from 2008–2013 as a Lecturer in Toxicology in Yemen. He has published three Research Publications in well-reputed ISI journals Q1 and Q2 and high impact factor, participant in two international conferences at Oslo, Norway and Malaysia.
Abstract:
The safety of Verbena officinalis as a traditional herb remedy, in pregnancy and potential effects on foetal morphogenesis, embryo-toxicity and skeletal variations in pups of SD rats, has not yet been tested. This study carried out to
evaluate the potential effects of Verbena officinalis aqueous extract on pregnancy outcome in SD dams. Timed-pregnant of dams from sixth to the 20th day of gestation into five groups (n=10) SD dams received oral single daily of different doses of 3000, 2000, 1000, and 500 mg/kg/day V. officinalis aqueous crude extract of the (vehicle) control during organogenesis. The foetuses were inspected for external morphology and skeletal anomalies. Pups were stained with Alcian blue and Alizarin red. In the present study, the result demonstrated that Verbena officinalis cause embryo-toxicity abnormalities were observed difference with dams rats treated with 3000 and 2000 mg/kg as evidenced by the increased incidence in the post-implantation loss and low measure in the tail length, head cranium, and fetal weight. The total external foetal morphogenesis (stunted growth, micrognathia, subcutaneous hemorrhages and umbilical hernia) abnormalities were differences between all treated groups and control group, however, the higher incidence occurred at 3000 mg (36.2%), whereas some abnormalities of the skeleton such as incomplete ossification of skull and sternebrae, unossified metatarsal bones were observed in foetuses treated with V2000 (19.3%) and V3000 (42.9%) groups. The results of this prenatal study show that consumption of Verbena officinalis boiling tea appears to be unsafe to be used during pregnancy and high does have developmental toxicity on embryos.
Marwa M Safar
The British University, Egypt
Title: Venlafaxine ameliorates complete Freund's adjuvant-induced arthritis in rats via targeting STAT-3/IL-17/RANKL axis
Biography:
Marwa M Safar is an Associate Professor of Pharmacology. She has completed her PhD from Cairo University. Currently, she is the Head of Pharmacology & Biochemistry Department, at the Faculty of Pharmacy, The British University in Egypt. She has published more than 30 articles in reputed journals and supervised more than 15 Masters and PhD thesis.
Abstract:
Rheumatoid arthritis is usually accompanied by various comorbidities especially on the psychological side such as depression. This study aimed at revealing the potential curative effects of venlafaxine (VFX), a serotonin/norepinephrine reuptake inhibitor (SNRI), on experimentally-induced arthritis in rats. Arthritis was induced by injecting complete Freund's adjuvant (CFA, 0.1 ml, s.c.). One day thereafter, VFX (50 mg/kg, p.o.) was given for 21 days. Methotrexate was used as a standard disease modifying antirheumatic drug. CFA injection caused prominent arthritis evident by the increase in the hind paw and ankle diameter accompanied by elevating tumor necrosis factor-alpha, interleukin-6, interleukin-17 and matrix metalloproteinase-3 levels, effects that were diminished by VFX. Moreover, VFX down regulated gene expressions of receptor activator of nuclear factor kappa-B (NF-кB) ligand and signal transducer and activator of transcription-3 beside hampering immunohistochemical expression of vascular endothelial growth factor and NF-кB. This SNRI also improved the oxidant status of the hind limb as compared to the arthritic group. Nonetheless, MTX was better in amendment of arthritis authenticated by its effect on some inflammatory and oxidative stress biomarkers. This study provides a novel therapeutic use of VFX as a considerable anti-arthritic drug and offers an incentive
to expand its use in RA.
Noha F Abdelkader
Cairo University, Egypt
Title: Mechanisms underlying the gastroprotective effect of irbesartan aganist indomethacin-induced ulcer in rats
Time : 15:30-16:00
Biography:
Noha F Abdelkader has completed her PhD from the Faculty of Pharmacy, Cairo University, Egypt. She is an Associate Professor in Pharmacology and Toxicology Department, in the Faculty of Pharmacy, Cairo University. She has published 15 papers in reputed journals in addition to a number of conference proceedings. Her main research is focused on Neurodegenerative Disorders, Drug-Induced Toxicities, and Drug Repurposing. She has coordinated the Erasmus funded project IT-Based International Diploma and Professional Certificate in Clinical Toxicology. She is currently a Member of Egyptian Society of Pharmacology and Experimental Therapeutics, Pharmacology for AFRICA’ initiative and International Association of Therapeutic Drug Monitoring and Clinical Toxicology.
Abstract:
Recently, angiotensin II type 1 receptor blockers (ARBs) has emerged as a potential gastroprotective candidates. Thus, the aim of the current study was to investigate the gastroprotective potential of irbesartan in a rat model of gastric injury. Adult male Wistar rats were randomly allocated into five groups. Group I rats served as a control group. Group II rats were treated with irbesartan. Rats of groups III-V were treated with indomethacin. Wherase, groups IV and V were pretreated with ranitidine, as a reference anti-ulcer drug, and irbesartan; respectively. Irbesartan (50 mg/Kg, p.o) was administered once daily for two weeks; thereafter, gastric injury was induced by indomethacin (60 mg/Kg, p.o). Treatment with irbesartan mitigated indomethacin-induced elevation in gastric ulcer index and acidity, gastric mucosal apoptotic and inflammatory aberrations, as demonstrated by hampering caspase-3, prostaglandin E2 and tumor necrosis factor-alpha levels and cyclooxygenase-2 mRNA expression. Furthermore, irbesartan increased mucosal dimethylarginine dimethylaminohydrolase-1 (DDAH-1) gene expression and decreased elevated levels of matrix metalloproteinase-9, asymmetric dimethylarginine (ADMA), epidermal growth factor receptor (EGFR) mRNA and phosphorylated extracellular signal-regulated kinase 1 and 2 (pERK1/2). Morover, irbesartan ameliorated gastric histopathological alterations. Overall efficacy of irbesartan was comparable to ranitidine, the widely used H2 receptor blocker. In conclusion, irbesartan exhibited a significant gastroprotective effect against indomethacin-induced mucosal damage via acid-inhibitory, antiinflammatory, anti-apoptotic and extracellular matrix remodeling mechanisms that are probably mediated, at least partly, by down-regulating DDAH/ ADMA and EGFR/ERK1/2 signaling.
Naile Merve Guven
Ankara University, Turkey
Title: Role of oxidative stress and polycystic ovary syndrome
Time : 16:00-16:30
Biography:
Naile Merve Güven has been a Research Assistant at Ankara University, Faculty of Pharmacy, in the Department of Pharmaceutical Toxicology since 2018. She earned her Master's degree in the same Department in July 2019. She is currently a PhD student in the same Department. Her research interests cover CYP450 Enzymes, Diabetes Mellitus and Polycystic Ovary Syndrome. She has experience with microsome isolation from rat liver, protein determination by BCA, western blot, isolation of mononuclear cells from whole blood.
Abstract:
Polycystic ovary syndrome (PCOS), characterized by oligo-ovulation or anovulation, elevated androgens, and appearance of polycystic ovaries, is an endocrine disorder that affects women of childbearing age. Prevalence of PCOS varies between 6-15% according to different diagnostic criteria. Insulin resistance and related compensatory hyperinsulinemia play a critical role in the pathophysiology of PCOS. According to the results of various studies, up to 70% of women with PCOS have insulin resistance. Studies in adipocyte and skeletal muscle cells have reported that insulin resistance in PCOS is mediated by receptor-mediated signal transduction or post-receptor defect. Besides, defects in insulin signaling as a result of impaired insulin receptor tyrosine kinase activity in skin fibroblasts have been described. Although the underlying mechanism of oxidative stress in PCOS is not fully understood, it has been shown that insulin resistance promotes oxidative stress. Increased reactive oxygen species in case of oxidative stress are produced by mitochondria. The ovary, testis, and uterus are particularly affected by reactive
oxygen species because they are regions that require ATP and contain high levels of mitochondria. Oxidative stress has a harmful effect, which may influence the fertility of women negatively, on ovulation, fertilization, embryo development, and implantation. Oxidative stress plays a significant role in the process of ovulation by inducing apoptosis of luteal cells. Oxidative stress in the follicular fluid may cause inadequate oocyte and embryo development.