Pharmacology, Toxicology and Environmental Health Commons^™

Influence Of Ephx1 Polymorphism And Clinical Factors On Carbamazepine Resistant Epilepsy, Khanistha Tuanthaisong, Yotin Chinvarun, Mayuree H. Tantisira, Pornpimol Kijsanayotin

The Thai Journal of Pharmaceutical Sciences

The treatment outcomes of carbamazepine (CBZ) vary widely among patients. Single nucleotide polymorphisms (SNPs) in genes involved in pharmacokinetics and pharmacodynamics of CBZ may influence patients’ response to CBZ. We aimed to investigate the asso...

Simultaneous Estimation Of Cefixime And Cloxacillin In Human Plasma By Reversed Phase-Hplc With Uv Detection, Sommath D. Bhinge, Sharangouda M. Malipatil, Lalit V. Sonawane

The Thai Journal of Pharmaceutical Sciences

An accurate, rapid and simple reversed-phase high performance liquid chromatography (RP-HPLC) method was developed and validated for simultaneous estimation of cefixime, cloxacillin and for chloramphenicol (internal standard) in human plasma. Chromatographic separation was accomplished using CAPCELL PAK C8 (4.6 mm Ó 250 mm, 5 μm) analytical column using phosphate buffer, methanol and acetonitrile (40:45:15) as eluent. Detection and quantification were performed by UV/Vis detection at 225 nm. The lower limit of detection and quantification were 0.01 μg†mL-1 and 0.25 μg†mL-1 for cefixime, 0.03 μg†mL-1 and 0.39 μg†mL-1 for cloxacillin. The calibration curves were linear over the concentration range 0.5 to …

Sterol Lipid Metabolism In Down Syndrome Revisited: Down Syndrome Is Associated With A Selective Reduction In Serum Brassicasterol Levels, Gavin Tansley, Daniel T. Holmes, Dieter Lütjohann, Elizabeth Head, Cheryl L. Wellington

Pharmacology and Nutritional Sciences Faculty Publications

Over the past 15 years, insights into sterol metabolism have improved our understanding of the relationship between lipids and common conditions such as atherosclerosis and Alzheimer's Disease (AD). A better understanding of sterol lipid metabolism in individuals with Down Syndrome (DS) may help elucidate how this population's unique metabolic characteristics influence their risks for atherosclerosis and AD. To revisit the question of whether sterol lipid parameters may be altered in DS subjects, we performed a pilot study to assess traditional serum sterol lipids and lipoproteins, as well as markers of sterol biosynthesis, metabolites, and plant sterols in 20 subjects with …

Aging And Down Syndrome, Elizabeth Head, Wayne Silverman, David Patterson, Ira T. Lott

Pharmacology and Nutritional Sciences Faculty Publications

No abstract provided.

The Effects Of Extended Access To Methamphetamine Self-Administration On Dopaminergic Markers In The Striatum, Joe Luevano

Open Access Theses & Dissertations

Methamphetamine (METH) abuse is a persistent problem in the U.S. and abroad. Escalation of METH use among independent users occurs for a variety of physiological and psychological reasons. Methamphetamine dependence may be attributed to the rewarding effect of this drug via the dopaminergic systems of the central nervous system (CNS). The presence of METH in the CNS increases synaptic release of dopamine. This increase in dopaminergic neurotransmission is thought to be directly attributed to the rewarding effects of METH. Following METH use, compensatory changes have been found to occur in the dopaminergic system during various periods of abstinence. It is …

A Survey Of Selected Pharmaceuticals And Personal Care Products In A Binational River And Their Effects On A Member Of Its Zooplankton Community, Plationus Patulus (Rotifera), Diana Angelica Martinez Gomez

Open Access Theses & Dissertations

The presence of 9 selected PPCPs (acetaminophen, caffeine, cotinine, codeine, fluoxetine, erythromycin, ciprofloxacin, sulfamethazine, and trimethoprim) was surveyed in water samples collected at four sites along the middle Rio Grande during two flow regimes (irrigation and non-irrigation). Water collection for PPCPs analyses were conducted from August 2010 through September 2011. Three of the sites were located upstream, in, and downstream of the El Paso, TX/Ciudad Juárez, MX metroplex. Site selection was based on their proximity to the metroplex and due to the fact that the Rio Grande in this region is an effluent receiver water system (IBWC, 2011). The fourth …

Role Of Na+K+2cl- Co-Transporters In Insulin Secretion, Saeed Alshahrani

Browse all Theses and Dissertations

The objective of this study is to investigate the role of intracellular chloride concentration ([Cl^-]i) in insulin secretion in vivo and in vitro.

The maintenance of high [Cl^-]i in insulin-secreting pancreatic β-cells plays an important role in glucose-induced depolarization and insulin secretion. Insulinotropic glucose concentrations i.e., >6 mM induces electrical activity in β-cells which results in insulin secretion. This electrical activity is mainly due to electrogenic efflux of Cl^- from β-cells through volume-regulated anion channels (VRAC). The solute carrier family 12 group A member 1 (Slc12a1) and 2 (Slc12a2) encode several splice variants of the …

The Proton-Coupled Folate Transporter: Biology And Therapeutic Applications To Cancer, Sita Desmoulin

Wayne State University Dissertations

Folates are essential cofactors of tumor cell proliferation and survival required for nucleotide biosynthesis and amino acid metabolism. In cancer therapy, inhibition of folate-dependent metabolic pathways has been achieved through the use of antifolates. Unfortunately, the efficacy of many clinically approved antifolates is limited by a lack of tumor selectivity. Facilitative transport of folates into mammalian cells is achieved by the reduced folate carrier (RFC) and proton-coupled folate transporter (PCFT). As PCFT is a folate-proton symporter with an acidic pH optimum, PCFT may provide a mechanism for targeting cytotoxic antifolates to tumors, based on their acidic microenvironments. To establish the …

Investigation Of The Absorptive Potential Of Polymeric Nanoparticles Across The Lungs And Their Development For Efficient Systemic Delivery Following Pulmonary Administration, Abdul Khader Mohammad

Wayne State University Dissertations

The lungs are an attractive route for drug delivery due to their high epithelial surface area available for absorption, a thin epithelium and extensive vasculature to name a few. Accordingly, a vast number of small molecule drugs, peptides, and proteins have been used to investigate their translocation across the lungs with many of the tested candidates showing excellent pharmacokinetics following pulmonary administration. Findings from all these studies over the years have strongly established the lungs as a route for drug delivery of small molecules and proteins. Nanoparticles on the other hand have gained increasing interest in drug delivery due to …

Multifunctional Bioreducible Nanoparticles For Gene Therapy, Jing Li

Wayne State University Dissertations

Gene therapy is a promising therapeutic strategy to treat diseases caused by single or multiple gene mutations. Non-viral gene delivery vectors exhibit many advantages over viral vectors, including enhanced safety, versatility in choosing different types of therapeutic nucleic acids, and ease of formulation. However, low transgene efficiency and lack of targeting ability remain major challenges. Bioreducible polyplexes (polyelectrolyte complexes of disulfide-containing polycations and nucleic acids) utilize the redox potential gradient existing between extracellular space and intracellular environment as a physiological stimulus to enhance delivery of therapeutic nucleic acids to the subcellular space. Bioreducible containing polyplexes undergo intracellular reduction mediated GSH, …

Valproic Acid-Induced Teratogenesis In Japanese Rice Fish (Oryzias Latipes) Embryogenesis, Mengmeng Wu

Electronic Theses and Dissertations

Valproic acid (VPA) was introduced as an antiepileptic in 1967 in France and it has become the most prescribed anticonvulsive drug therapy worldwide since then. In the clinic, valproic acid is selected to treat absence seizures, myoclonic seizures, generalized tonic-clonic seizures, atonic attacks and partial seizures. Epilepsy is the second most comneurologic disorder that affects pregnant women (0.5%–1%). Approximately 1 out of 250 pregnant women are taking antiepileptic drugs. Valproic acid is designated as a human teratogen, which induces major congenital anomalies, facial dysmorphic features, and autistic-like behaviors, which affect verbal, cognitive, communicative, and social abilities of affected children. We …

Compositional Determinants Of The Pharmacological Actions Of Heparins, Angel Lee Gray-Shah

Dissertations

This dissertation primarily focuses on how differences in molecular weight (MW) and structural composition affect the pharmacological activity of heparin and its derivatives. Heparins are a mixture of glycosaminoglycans chains which are used to prevent thrombosis in a number of clinical indications. Heparins promote the inhibition of blood coagulation via their plasmatic cofactors antithrombin (AT) and heparin cofactor II (HCII).

In these studies, various heparins with molecular weights ranging from 2.6 to 16.5 kDa were investigated. Not only the molecular weight but also the oligosaccharide composition greatly varied in these agents. One of the major objectives of this research was …

Elucidating Transcription Factor Regulation By Tcdd Within The Hs1,2 Enhancer, Sharon D. Ochs

Browse all Theses and Dissertations

Immunoglobulin heavy chain (IgH) expression and Ig secretion is inhibited by the environmental contaminant 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD). Within the IgH gene, the 3' IgH regulatory region (3'IgH RR) has been identified as a transcriptional target of TCDD. The 3'IgH RR, which in part regulates transcription of the IgH gene, is composed of four enhancers in the mouse: hs3a; hs1,2; h3b; hs4 and three enhancers in the human: hs3a; hs1,2; hs4. In humans the hs1,2 enhancer has an invariant sequence (IS) containing a DRE, NF-κB, NF1 and AP-1 binding site. Also, the enhancer has an AP1.ETS and Oct …

Evaluation Of Cm-2,525 As A Neuroprotectant Against Sarin: A Comparison With 8-Oh-Dpat, Amanda R. Furman

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Exposure to the chemical warfare agent sarin produces long term neurological deficits. The long term medical consequences could be averted with the development of neuroprotectants to preserve brain function. In our mouse model, the combination of the carboxylesterase inhibitor 2-(o-cresyl)-4H-1:3:2-benzodioxaphosphorin-2-oxide (CBDP) with the organophosphorus (OP) nerve agent sarin was used to render mice more sensitive to poisoning and reduce the amount of hydrogen fluoride cleaved from sarin during binding to esterases. Since carboxylesterase acts as a scavenger, reducing the levels causes sarin to have a greater inhibition effect on acetylcholinesterase. These smaller doses permitted the use of doses similar to …

Use Of Phage Display Libraries To Select For B-Cell Receptor-Specific Peptides Of Chronic Lymphocytic Leukemia Cells, Richard M. Chou

Browse all Theses and Dissertations

Peptides with high affinity to the B-cell receptor (BCR) fused to a toxin could be an effective therapy for Chronic Lymphocytic Leukemia (CLL) patients. We screened captured BCR of a CLL patient with peptides from 7 and 12-mer phage display libraries, using two strategies. Lymphocytes from two patients diagnosed with CLL expressing two different unmutated VH genes (VH 1-3 and VH4-34, respectively) were used. Membrane BCRs were obtained from patient CLL cells by lysis, identified by western blot, semi-quantified and screened with phage libraries. The first strategy involved using patient VH4-34 BCRs which were captured using goat anti-human IgM to …

Light-Limited Access To Fructose Alters Metabolic Function And Adipose Tissue Catecholaminergic Activity In Mice, Naima Salem Rodwan

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Consumption of high levels of fructose produces glucose intolerance, sympathetic nervous system activation, and renal dysfunction. A diet high in fructose may play a role in the worldwide epidemic of obesity and diabetes. The aim of this study was to test the hypothesis that time (light/dark) limited access to fructose influences body fat, metabolic function, and adipose tissue catecholaminergic activity in mice. Male C57BL/6 mice were given standard chow and assigned to one of three groups: Control (n=10, water 24h); FL (n=11, 10% fructose solution during 12h light period); and FD (n=10, 10% fructose solution during 12h dark period). Metabolic …

Enhanced Angiotensin Ii-Induced Cardiac And Aortic Remodeling In Ace2 Knockout Mice, Mahmoud Alghamri

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Activation of the renin angiotensin system (RAS) is a well-known driving force, governing the aggravation and progression of CVD and associated target organ damage. Angiotensin (Ang) converting enzyme 2 (ACE2), a new member within the RAS family, was first cloned from the ventricle of patient with heart failure. ACE2 was shown to be upregulated under pathological conditions. We hypothesize that loss of ACE2 negatively affects cardiac function and exacerbates hypertrophic cardiomyopathy and aortic remodeling in response to Ang II. Eight weeks old ACE2 knock out (KO) and wild type (WT) mice were infused with Ang II s.c. (1000 ng/kg/min for …

Studies On Waterborne Cadmium Exposure To Lymnaea Stagnalis In Varying Water Qualities And The Development Of A Novel Tissue Residue Approach, Nish M. Pais

Theses and Dissertations (Comprehensive)

Recent studies have shown that the use of bioaccumulation (tissue residues) as a predictor for toxic effects for metals is a flawed concept.Adams et al. (2010) suggested a novel tissue residue approach (TRA) in which bioaccumulation in resistant organismsis related to toxic effects in sensitive organisms. The goal of this thesis was to test these assumptions in relation to Cd exposure using the great pond snail, Lymnaea stagnalis by developing and improving the understanding of Cd accumulationin aquatic invertebrates.

The relationship between Cd bioaccumulation and its toxicity was studied in L. stagnalisusing acute (96h) and chronic (one month) …

Combretazet-3 A Novel Synthetic Cis-Stable Combretastatin-A4-Azetidinone Hybrid With Enhanced Stabilityand Therapeutic Efficacy In Colon Cancer, Lisa M. Greene, Shu Wang, Niamh O'Boyle, Sandra A. Bright, Jane E. Reid, Patrick Kelly, Mary J. Meegan, Daniela M. Zisterer

Articles

In recent years an extensive series of synthetic combretastatin A-4 (CA-4)-azetidinone (β-lactam) hybrids were designed and synthesised with a view to improve the stability, therapeutic efficacy and aqueous solubility of CA-4. Lead compounds containing a 3,4,5-trimethoxy aromatic ring at position 1 and a variety of substitution patterns at positions 3 and 4 of the β-lactam ring were screened in three adenocarcinoma-derived colon cancer cell lines (CT-26, Caco-2 and the CA-4 resistant cell line, HT-29). In both CT-26 and Caco-2 cells all β-lactam analogues analysed displayed potent therapeutic efficacy within the nanomolar range. Substitution of the ethylene bridge of CA-4 with …

Bioavailability, Bioaccumulation, And Trophic Transfer Of Trace Metals In The Tims Branch-Steed Pond Tributary, Paul Gethyn Edwards

Masters Theses

The Department of Energy's (DOE) Savannah River Site (SRS) is a 777 km² former nuclear weapon material production and current research facility located along the Savannah River in west-central South Carolina. In 1954, direct environmental discharges were released from "M-Area", a fuel and aluminum-clad Uranium (U) nuclear reactor target manufacturing facility through a drainage ditch into the Tims Branch-Steed Pond water system. The wastewater discharges released into Tims Branch contained large volumes of inorganic wastes including depleted and natural U, aluminum (Al), and Nickel (Ni) along with smaller quantities of mercury (Hg), lead (Pb), copper (Cu), chromium (Cr), and …