Pharmacology, Toxicology and Environmental Health Commons^™

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 …

Transferrin Receptor Targeted Delivery Of Sirna For Gene Therapy, Yuran Xie

Wayne State University Dissertations

Gene therapy is thought to be a solution for various difficult to treat diseases such as cancer. Small interfering RNA (siRNA) as a promising anti-sense molecule can specifically silence disease related gene have been exploit in different diseases. However, lack of safe and efficient siRNA delivery systems limits the application of siRNA therapy in clinic. Transferrin receptor (TfR) is an essential transmembrane receptor involved in iron uptake. TfR universally express in most cells/ tissues but upregulated in certain cells, for example, many cancer cells and activated T cells (ATCs). To overcome the biological barriers and increase siRNA delivery efficiency, in …

Protein Phosphatase 2a Interactions In Islet And Human Skeletal Muscle In Diabetes, Divyasri Damacharla

Wayne State University Dissertations

Type 2 Diabetes is a metabolic disorder associated with insulin resistance and consequent high blood glucose levels. Under normal conditions, in response to high blood glucose levels, pancreatic beta cells produce insulin. The secreted insulin is dis-tributed to tissues thereby stimulating insulin stimulated glucose uptake. However, maximum glucose disposal takes place in skeletal muscle. Thus, studying beta cells and skeletal muscle in respect to diabetes is crucial. Protein Phosphatase 2A (PP2A) is one of the major serine/threonine phosphatases belonging to PhosphoProteinPhospha-tase (PPP) family. It constitutes about 80% of all serine/threonine phosphatases. It is regulated by numerous regulatory subunits as well …

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..

Extra Precision Docking Studies Of Novel Luteolin Analogues For The Inhibition Of Tankyrase Ii- “A Theoretical Based Approach Towards Novel Cancer Target, Aravinda Pai, Jayashree B.S., Sanchari Basu-Mallik, Richard Lobo

The Thai Journal of Pharmaceutical Sciences

Luteolin, a natural bio-flavonoid is known to possess variety of pharmacological activity, particularly tumour growth inhibition. Reports are available to substantiate the interaction of luteolin with Tankyrase II, one of the key enzymes responsible for .

Clinical Outcomes Of A Pharmaceutical Care Service In Lithium Clinic Adjunct To Standard Care Compared With Standard Care Alone In Patients With Bipolar Disorder: 10 Years Naturalistic Retrospective Cohort Study, Orabhorn Suanchang, Vithaya Kulsomboon, Yupadee Sirisinsuk, Norrawee Phoomchan, Charnwit Skawatananont

The Thai Journal of Pharmaceutical Sciences

Objective: To compare the long-term clinical outcomes of bipolar patients following lithium maintenance therapy between patients who received standard care plus pharmaceutical care service (lithium clinic group) and patients who received standard care al.

Isocratic Ultra-Performance Liquid Chromatographic Assay Of Quetiapine Fumarate In Pharmaceuticals, N Rajendra Prasad, Kanakapura Basavaiah

The Thai Journal of Pharmaceutical Sciences

An isocratic and reversed phase ultra-performance liquid chromatographic (RP-UPLC) method has been developed for the determination of quetiapine fumarate (QTF)) in bulk drug and in its tablets. The method was developed using AQUITY UPLC HSS T3 (2.1 x 50.

Stability-Indicating Method To Determine Bioactive Nucleosides In Crude Drugs, Extracts, And Products From Cordyceps Sinensis And Cordyceps Militaris, Boonta Chutvirasakul

The Thai Journal of Pharmaceutical Sciences

The aim of this study was to develop a stability indicating method to determine bioactive nucleosides including uridine, guanosine, adenosine, and cordycepin in crude drugs, extracts, and products from Cordyceps Sinensis and Cordyceps Militaris by gradie.

A Medicines Terminology Governance Model For Thailand, Anuchai Theeraroungchaisri, Ratsapan Phuksaritanon, Boonchai Kijsanayotin

The Thai Journal of Pharmaceutical Sciences

At present, Thailand does not have a national governance system for developing a health data standard and coding system, especially drug codes and medicine terminology. There is no single responsible organization and also no mechanism for cooperation amo.

From Yosemite To A Global Market: How Patagonia, Inc. Has Created An Environmentally Sustainable And Socially Equitable Model Of Supply-Chain Management, Mary-Clare Bosco

Pomona Senior Theses

There is an urgent pressure of the time (2016) to re-evaluate our patterns of consumption to adapt to changing climates and reduce waste and pollution. Because an immediate restructuring of global production strategies is not likely any time soon, industrial innovators are finding new ways of redesigning supply-chain management in efforts to move towards environmentally sustainable business in which all manufacturing practices are transparent. Patagonia, Inc. is a testament to the often-debated question of economic value in green business practices, and this thesis acts as an outline as to how they arrived at such an impressive presence in the business …

Identification Of “Kratom” (Mitragyna Speciosa) Alkaloids In Commercially Available Products, Julia Grzymkowski, Michelle R. Peace, Justin Poklis

UROP Posters

“Kratom” is the common name for the botanical mitragyna speciosa. It is a tree native to Southeast Asia in which leaves contain the psychoactive alkaloids mitragynine and 7-hydroxymitragynine. Kratom is often ingested as teas, chewed, or smoked. It acts as a stimulant in small doses and as an opioid in large doses. Overdoses can result in vomiting, seizures, and death. Recently the Drug Enforcement Agency (DEA) placed Kratom on Schedule 1, but, due to public outcry, it was almost immediately removed.

Eleven kratom based products were obtained from various tobacco shops, “headshops” and via the internet including: Choice brand …

Dredging Land Reclamation Causing Mucus Development In Massive Spherical Corals In The Spratly Islands, South China Sea: The Effects On China’S Fishing Industry, Tiffany K. Ho

UROP Posters

Images from Asia Maritime Transparency Initiative depicted huge masses of white coral mucus secreted from coral reefs in the Spratly Islands of the South China Sea, an area where several land reclamation projects are occurring. The purpose of this research was to understand how increased sedimentation levels from the dredging land reclamation method affects mucus development in massive corals, such as Acropora, located in these reefs. Journal articles that focused on the biology of coral mucus, bacterial communities associated with coral tissue, mucus, and seawater, coral mortality from different environment impacts, coral coverage of reefs in Spratly Islands, and symbiotic …

Characterization Of Sex Differences In The Reinforcing Effects Of Nicotine, Rodolfo Jesus Flores Garcia

Open Access Theses & Dissertations

It is presently unclear whether ovarian hormones, such as estradiol (E2) promote the reinforcing effects of nicotine in females. Thus, we compared extended access to nicotine intravenous self-administration (IVSA) in intact male, intact female, and OVX female rats (Study 1) as well as OVX females that received vehicle or E2 supplementation (Study 2). The E2 supplementation procedure involved a 4-day procedure involving 2 days of vehicle administration and 2 days of E2 administration. Two doses of E2 (25 or 250 ug) were assessed in separate groups of OVX females in order to examine the dose-dependent effects of this hormone on …

Integration Of Biological Effects, Fish Histopathology And Contaminant Measurements For The Assessment Of Fish Health: A Pilot Application In Irish Marine Waters, Michelle Giltrap, Jenny Ronan, John Bignell, Brett Lyons, Evelyn Collins, Heather Rochford, Brendan Mchugh, Evin Mcgovern, Lorraine Bull, James Wilson

Articles

This study investigates the use of a weight of evidence (WOE) approach to evaluate fish health status and biological effects (BEs) of contaminants for assessment of ecosystem health and discusses its potential application in support of the Marine Strategy Framework Directive (MSFD). External fish disease, liver histopathology and several BEs of contaminant exposure including 7-ethoxy resorufin O-de-ethylase (EROD), acetylcholinesterase (AChE), bile metabolites, vitellogenin (VTG) and alkali labile phosphates (ALP) were measured in two flatfish species from four locations in Ireland. Contaminant levels in fish were generally low with PCBs in fish liver below OSPAR environmental assessment criteria (EAC). There were …

From Disposable Culture To Disposable People: Teaching About The Unintended Consequences Of Plastics, Sasha Adkins

Antioch University Dissertations & Theses

Plastics, the epitome of disposable culture, pose both a toxicological and a spiritual problem. This dissertation examines plastics at a molecular level using the discourse of endocrine disruption, and at a sociological level using the discourses of eco-theology and environmental justice. Adding to the literature on the adsorption of toxicants to plastic marine debris, I demonstrate that certain types of plastic -- those containing mercaptans, such as styrene butadiene block copolymer -- efficiently concentrate methyl mercury from seawater. Further, samples of polycarbonate contributed mercury to seawater. I propose the term plastic-mediated magnification to describe the phenomenon that plastics, along with …

Bioanalysis For Cocaine, Opiates, Methadone And Amphetamines Exposure Detection During Pregnancy, Marta Concheiro, Elena Lendoiro, Ana De Castro, Eva Gonzalez-Colmenero, Ana Concheiro-Guisan, Patricia Penas-Silva, Manuel Macias-Cortina, Angelines Cruz-Landeira, Manuel Lopez-Rivadulla

Publications and Research

Drug exposure during pregnancy constitutes a major legal issue and public health concern. Drug and metabolite determination in biological matrices from mother and newborn is an objective indication of prenatal drug exposure. However, limited data are available regarding the interpretation of these analytical results in terms of window of detection and degree of exposure. We collected paired maternal hair, meconium, placenta and umbilical cord from 727 mother-newborn dyads. We analyzed these specimens by liquid chromatography tandem mass spectrometry for the determination of cocaine, opioids, methadone and amphetamines, and compared the analytical results from the four different matrices. The cases were …