Pharmacology Commons^™

Metformin, Glucotoxicity And Islet Dysfunction, Sartaj S. Baidwan

Wayne State University Theses

METFROMIN, GLUCOTOXICITY AND ISLET DYSFUNCTION

by

SARTAJ BAIDWAN

MAY 2017

Advisor: Dr. Anjaneyulu Kowluru

Major: Pharmaceutical Sciences

Degree: Master of Science

Glucotoxicity is the leading cause for β-cell dysfunction [e.g., defective glucose-stimulated insulin secretion] in Type 2 Diabetes [T2DM]. Recent studies from our lab have shown sustained Rac1 activation leading to the activation of downstream signaling steps including stress kinase [p53, p38MAPK] activation and mitochondrial dysregulation [caspase-3 activation] in pancreatic islet beta-cells exposed to glucotoxic [HG] conditions [20 mM; 24 hrs]. Metformin [MF] is an oral anti-diabetic drug that is being widely prescribed to T2DM. MF works by suppressing hepatic …

Endocrine-Disrupting Properties Of Pharmaceuticals And Personal Care Products (Ppcps): An Evaluation Using Aquatic Model Organisms, Manahil Monshi

Wayne State University Theses

Thousands of chemicals have introduced into the environment as a result of human activity since the industrial revolution, and the U.S. Government Accountability Office has estimated that as many as 1,500 new chemical entities are synthesized each year ("Key Issues: Toxic Chemicals - High Risk Issue," 2017). Many of these chemicals are now found in surface water and ground water and can have detrimental effects on environmental health and on human health. This anthropogenic contamination has resulted in the labeling of the diverse array of chemicals found in water, which are not routinely monitored or regulated, as contaminants of emerging …

Sex Differences In The Subjective Effects Of Oral Δ9-Thc In Cannabis Users, Jessica S. Fogel, Thomas H. Kelly, Philip M. Westgate, Joshua A. Lile

Behavioral Science Faculty Publications

Previous studies suggest that there are sex differences in endocannabinoid function and the response to exogenous cannabinoids, though data from clinical studies comparing acute cannabinoid effects in men and women under controlled laboratory conditions are limited. To further explore these potential differences, data from 30 cannabis users (N=18 M, 12 F) who completed previous Δ⁹-tetrahydrocannabinol (Δ⁹-THC) discrimination studies were combined for this retrospective analysis. In each study, subjects learned to discriminate between oral Δ⁹-THC and placebo and then received a range of Δ⁹-THC doses (0, 5, 15 and a “high” dose of …

Cellular And Molecular Mechanisms Underlying Alcohol-Induced Aggressiveness Of Breast Cancer, Yongchao Wang, Mei Xu, Zun-Ji Ke, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Breast cancer is a leading cause of morbidity and mortality in women. Both Epidemiological and experimental studies indicate a positive correlation between alcohol consumption and the risk of breast cancer. While alcohol exposure may promote the carcinogenesis or onset of breast cancer, it may as well enhance the progression and aggressiveness of existing mammary tumors. Recent progress in this line of research suggests that alcohol exposure is associated with invasive breast cancer and promotes the growth and metastasis of mammary tumors. There are multiple potential mechanisms involved in alcohol-stimulated progression and aggressiveness of breast cancer. Alcohol may increase the mobility …

The Role Of Progesterone Receptor Membrane Component 1 In Receptor Trafficking And Disease, Kaia K. Hampton

Theses and Dissertations--Pharmacology and Nutritional Sciences

The progesterone receptor membrane component 1 (PGRMC1) is a multifunctional protein with a heme-binding domain that promotes cellular signaling via receptor trafficking, and is essential for some elements of tumor growth and metastasis. PGRMC1 is upregulated in breast, colon, lung and thyroid tumors. We expanded the analysis of PGRMC1 in the clinical setting, and report the first analysis of PGRMC1 in human oral cavity and ovarian tumors and found PGRMC1 to correlate with lung and ovarian cancer patient survival. Furthermore, we discovered a specific role for PGRMC1 in cancer stem cell viability. PGRMC1 directly associates with the epidermal growth factor …

Immunotherapy Against Drugs Of Abuse, Gianna Raimondi (Class Of 2017)

Writing Across the Curriculum

Current treatments for drug addiction involve classical pharmacological therapy, involving the use of competitive or noncompetitive agonists (full, partial, or inverse) and antagonists. Drugs of abuse enter the brain after crossing the blood-brain barrier rapidly and binding to the proper receptor(s). They are able to do so because they are small and lipid soluble, and produce reinforcing effects by increasing levels of dopamine in brain areas associated with reward. This occurs in specific systems associated with addiction. In the mesolimbic system, neuron cell bodies originate in the ventral tegmental area (VTA) and project to the nucleus accumbens (NAc), amygdala, hippocampus, …

Determination Of Potency Of Tetanus Immunoglobulin Products By Commercial Tetanus Anti-Toxoid Test Kits, Wichuda Jariyapan, Kanitta Puwanardnaranuban, Saywarul Jadoonkittnan

The Thai Journal of Pharmaceutical Sciences

Replacement of using experimental animals in scientific research with alternative methods is encouraged, according to the ‘3Rs’ principles (replacement, reduction and refinement). This study presented results for determination of potency of tetanus i...

New Fluorinated Chalcone And Pyrazolines Analogues: Synthesis, Docking And Molecular Dynamic Studies As Anticancer Agents, Jasril Jasril

The Thai Journal of Pharmaceutical Sciences

Some of chalcones and pyrazolines analogues are known to have a good potency as anticancer agents. In this work, a fluorinated chalcone and two pyrazolines were successfully synthesized under microwave irradiation. Molecular docking and molecular dynamic.

Influence Of Disease-Related Knowledge And Personality Traits On Parkinson’S Patient Empowerment, Pramon Viwattanakulvanid, Tanattha Kittisopee

The Thai Journal of Pharmaceutical Sciences

Background: Parkinson’s disease (PD), a neurodegenerative disorder, has an impact on both the physical and mental functions of persons with Parkinson’s (PwP), who tend to lose their sense of empowerment, cognitive state of perceived competence and pe...

Stability Determination Of An Alternative Approach To Use Of Liquid Drug Substance As Oil Phase In Microemulsion Formulations: Methyl Salicylate, Warunee Leesajakul, Sunee Channarong, Pathamaporn Chuetee

The Thai Journal of Pharmaceutical Sciences

The objective of this study was to investigate the stability of microemulsions using methyl salicylate as oil phase in the presence and the absence of hydrophobic additives and/or drug after six-month storage at ambient temperature. The investigated addi.

G-Quadruplexes As Molecular Targets For Transcriptional Control, Rhianna Kyelle Morgan

Electronic Theses and Dissertations

DNA G-quadruplexes (G4s) have gained interest in modern drug discovery efforts. The majority of G4 research, including the mass of this research, heavily focuses on cancer therapeutic development, as G4s are more pronounced in oncogenic promoters compared to the rest of the genome, our efforts extend towards neuroprotection as well. In particular, this work covers G4s in the promoters of MYC, VEGF, kRAS, and Bcl-2. MYC and VEGF harbor the two most well described promoter G4s to date, and their stabilization cultivates transcriptional silencing. Downregulation of MYC reduces cell growth and alters cell energetics; it is promising for a variety …

The International Scientific Association For Probiotics And Prebiotics (Isapp) Consensus Statement On The Definition And Scope Of Prebiotics, Glenn R. Gibson, Robert W. Hutkins, Mary Ellen Sanders, Susan L. Prescott, Raylene A. Reimer, Seppo J. Salminen, Karen Scott, Catherine Stanton, Kelly S. Swanson, Patrice D. Cani, Kristin Verbeke, Gregor Reid

Department of Food Science and Technology: Faculty Publications

In December 2016, a panel of experts in microbiology, nutrition and clinical research was convened by the International Scientific Association for Probiotics and Prebiotics to review the definition and scope of prebiotics. Consistent with the original embodiment of prebiotics, but aware of the latest scientific and clinical developments, the panel updated the definition of a prebiotic: a substrate that is selectively utilized by host microorganisms conferring a health benefit. This definition expands the concept of prebiotics to possibly include non-carbohydrate substances, applications to body sites other than the gastrointestinal tract, and diverse categories other than food. The requirement for selective …

Ethanol Reversal Of Oxycodone Tolerances, Joanna C. Jacob

Theses and Dissertations

Oxycodone is a semi-synthetic opioid originally developed as a safer alternative to morphine. It is commonly prescribed for its pain-relieving effects, but has recently been implicated as a major underlying cause of the current opioid epidemic due to its clinical limitations that include tolerance, dependence and a high abuse liability. Simultaneous consumption of opioids and ethanol has been shown to increase the risk of overdose and death from opioids in opioid-tolerant individuals. We hypothesized that ethanol reversed opioid tolerance and previous studies showed that ethanol reversed morphine tolerance. This dissertation investigated whether ethanol reversed tolerance to other opioids in mice, …

Role Of Mitochondrial Beta-Oxidation In Ethanol Response: A Candidate Gene Study Using Caenorhabditis Elegans, Harini Pallikarana Tirumala

Theses and Dissertations

Alcohol use disorder (AUD) is the fourth leading cause of preventable death in the United States, and the fifth leading risk factor for premature death and disability, globally. There are currently very few treatment options for AUD and there is a need for effective preventive and treatment strategies for this condition. AUD risk has a significant hereditary component, with the contribution of genetic factors being estimated to be about 50%. The Davies-Bettinger laboratory uses C. elegans as a model organism to study the contribution of genetic factors in modulating neuronal responses to ethanol. In this project, we examined the role …

Knockout Of Sphingosine Kinase 1 Attenuates Renal Interstitial Fibrosis In Unilateral Ureteral Obstruction (Uuo) Model, Xiwen Zhang

Theses and Dissertations

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite and an important signaling molecule that plays a significant role in fibrosis. S1P synthesis is catalyzed by sphingosine kinases (SphKs), which phosphorylate sphingosine into S1P. The present study tested the hypothesis that SphK1-S1P signaling pathway participates in the kidney damage in unilateral ureteral obstruction (UUO) model. Wild type and SphK1 knockout mice were subjected to UUO for 7 days or 14 days and then four groups of kidneys were collected: wild type control group (WT-C), wild type UUO group (WT-UUO), SphK1-/- control group (KO-C) and SphK1-/- UUO group (KO-UUO). The mRNA level of …

The Effects Of The Hiv-1 Tat Protein And Morphine On The Structure And Function Of The Hippocampal Ca1 Subfield, William D. Marks

Theses and Dissertations

HIV is capable of causing a set of neurological diseases collectively termed the HIV Associated Neurocognitive Disorders (HAND). Worsening pathology is observed in HIV+ individuals who use opioid drugs. Memory problems are often observed in HAND, implicating HIV pathology in the hippocampus, and are also known to be exacerbated by morphine use. HIV-1 Tat was demonstrated to reduce spatial memory performance in multiple tasks, and individual subsets of CA1 interneurons were found to be selectively vulnerable to the effects of Tat, notably nNOS+/NPY- interneurons of the pyramidal layer and stratum radiatum, PV+ neurons of the pyramidal layer, and SST+ neurons …

Alpha6 Beta2 Subunit Containing Nicotinic Acetylcholine Receptor Contributions To Abuse-Related Effects Of Nicotine And Alcohol, Alexandra M. Stafford

Theses and Dissertations

Pharmacotherapies for tobacco and alcohol cessation are only modestly successful, so it is important to better understand mechanisms underlying their use and abuse. The overarching goal of this research is to assess a6b2 subunit containing nicotinic acetylcholine receptor (a6b2*nAChR; *denotes possible assembly with other subunits) contributions to abuse-related effects of nicotine and alcohol. In the absence of a6b2*nAChR-selective agonists, a6b2*nAChR gain-of-function (a6L9’S) mice provide a tool for selective activation of a6b2*nAChRs. Using the a6L9’S mice together with nicotine doses sub-threshold for stimulation of native nAChRs, these studies tested the hypothesis that activation of a6b2*nAChRs is sufficient to promote neurochemical and …

Salvianolic Acid B For Pulmonary Delivery Towards Reversal Of Emphysema, Sneha Dhapare

Theses and Dissertations

A new pathobiologic hypothesis has recently emerged that the alveolar structural destruction and loss in emphysema are caused by the deficiency of vascular endothelial growth factor (VEGF). Therefore, this project hypothesized that such pathobiologic VEGF deficiency of emphysematous lungs can be recovered with a natural caffeic acid tetramer, salvianolic acid B (SalB), through activation of signal transducer and activator of transcription 3 (STAT3), so that emphysema can be reversed as a result of inhibition of induced cell death, stimulation of cell proliferation and migration, and promotion of stem cell recruitment to the lungs.

SalB was first shown to be potently …

Investigating The Modulation And Mechanisms Of Α7 Nicotinic Acetylcholine Receptors In Nicotine Dependence, Asti Jackson

Theses and Dissertations

Tobacco dependence dramatically increases health burdens and financial costs. Limitations of current smoking cessation therapies indicate the need for improved molecular targets. Nicotine, the main addictive component of tobacco, exerts its dependency effects via nicotinic acetylcholine receptors (nAChRs). The homomeric α7 nAChR is one of the most abundant receptors found in the brain and has unique features in comparison to other nAChR subtypes such as high calcium permeability, low probability of channel opening, and a rapid desensitization rate. α7 nAChR agonists reduce nicotine's rewarding properties in the conditioned place preference (CPP) test and i.v. self-administration. Recently, the peroxisome proliferator-activated receptor …

Systematic Extraction And Characterization Of ?-Glucan From The Industrial Brewing Yeast (Saccharomyces Cerevisiae) Waste Material And The Immunomodulatory Studies On Tnf-? And Il-6 Cytokine Balance Of The Mouse Macrophage Cell Lines, Theeraya Krisdaphong

The Thai Journal of Pharmaceutical Sciences

Objectives: The aim of this investigation was to create value to the industrial waste production by systematic extraction and purification of ?-glucan from the industrial brewing yeast (Saccharomyces cerevisiae) waste material. In addition, the immunolo..