Pharmacology, Toxicology and Environmental Health Commons^™

Synthesis And Antihepatotoxic Activity Of Some New Xanthones Containing 1,4-Dioxane Ring System, Shah Alam Khan, Bahar Ahmed

The Thai Journal of Pharmaceutical Sciences

This study was aimed at the synthesis of few xanthone derivatives containing 1,4-dioxane ring system. The reaction of 3,4-dihydroxy xanthone derivatives (3a-c) with ethylene dibromide and epichlorohydrin under approriate reaction conditions afforded xant...

Effect Of Ocimum Sanctum Extract On Sodium Nitrite - Induced Experimental Amnesia In Mice, Manoj Dokania, Kamal Kishore, P.K. Sharma

The Thai Journal of Pharmaceutical Sciences

The present study investigated the antiamnesic effect of the extract of Ocimum sanctum (OS) on time induced amnesia and sodium nitrite-induced amnesia in mice by using two different rodent models of memory. The aqueous extract of OS was administered to m...

High Resolution Hybrid Mass Spectrometry For The Determination Of Marine Biotoxins, Azaspiracids, And Their Biotransformation Products., Zuzana Skrabakova

Theses

Azaspiracids (AZAs), polyether marine toxins, are produced by marine microalgae and accumulate in filter-feeding bivalve molluscs, such as mussels, clams, oysters and scallops, while grazing on phytoplankton, from which they derive nutrition. Although being discovered quite recently, AZAs have caused several human intoxication events and thus became a problem for health authorities and shellfish industries. The rapid development of highly sensitive liquid chromatography multiple tandem mass spectrometry (LC-MS/MS, LC-MS") methods enabled the identification of numerous AZA analogues and added to the control of shellfish contamination. Tandem mass spectrometry techniques, while being highly selective and sensitive for determination of AZAs in …

The Impact Of Tricaine Methanesulfonate, 2-Phenoxyethanol, And Carvone-Methyl Salicylate On The Innate Immune Response Of Zebrafish (Danio Rerio), Charles R. Wulff

Honors Theses

Anesthesia plays a vital role in the maintenance of aquaculture species, where it is used to minimize stress during complex handling tasks such as transport, assessment, and harvesting. However, anesthetics have been shown to suppress the innate immune response, which could impact immunity and increase risk of infection. Tricaine methanesulfonate (MS-222) and 2-Phenoxyethanol (2-PE) represent two of the most commonly used anesthetics in aquaculture, with R-(+)-carvone, in the form of carvone-methyl salicylate (CMS) has recently been proposed as an alternative anesthetic for food fish. These three anesthetics were used to assess the influence of anesthetics on the immune system of …

An Overview Of New Psychoactive Substances And The Outlets Supplying Them, Cathy Kelleher, Rachel Christie, Kevin Lalor, John Fox, Matt Bowden, Cora O'Donnell

Reports

This report represents the outcome of a review of new psychoactive substances2 within the Irish context, including a review of the outlets that supply these substances. The review was commissioned by the National Advisory Committee on Drugs (NACD) in accordance with Action 14 of the National Drugs Strategy (interim) 2009–2016. Action 14 provides for the monitoring of ‘head shops’3 and other outlets for the sale of psychoactive substances, under the Misuse of Drugs Act 1977 and the Misuse of Drugs (Amendment) Regulations 2007. Researchers at the Centre for Social and Educational Research (CSER) within the School of Social Sciences and …

Novel Inhibitors Of Lysine Specific Demethylase 1 As Epigenetic Modulators, Michael Crowley

Wayne State University Theses

The recently discovered enzyme lysine-specific demethylase 1 (LSD1) plays an important role in the epigenetic control of gene expression, and aberrant gene silencing secondary to LSD1 over expression is thought to contribute to the development of cancer. We recently reported a series of (bis)guanidines and (bis)biguanides that are potent inhibitors of LSD1, and induce the re-expression of aberrantly silenced tumor suppressor genes in tumor cells in vitro. We now report a new series of isosteres that are also potent inhibitors of LSD1. These compounds induce increases in methylation at the histone 3 lysine 4 (H3K4) chromatin mark, a specific target …

Gene And Environment Interactions Modulate Immune System Influences On Social Behavior, Yubin Zhang

Legacy Theses & Dissertations (2009 - 2024)

Autism is a neurodevelopmental disorder with unknown etiology, affecting about 1 in 110 children in the US. Here, we show that developmental exposure to anti-brain Abs impaired mouse social behaviors. BTBR mice, a mouse strain with high serum anti-brain Abs and behaviors that resemble autism, have more activated splenic B cells, CD4+ T cells (Th1, Th2 and Th17 subsets), and CD4+ T cells with expression of Vb6 chains than B6 mice (the control H-2 identical strain). Elevated numbers of activated (CD25+) CD4+Vb6+ cells also were detected in thymic preparations. All of the immunological and behavioral parameters of BTBR mice were …

The Role Of Androstane Neurosteroids In Alcohol-Mediated Social Behavior, Jason J. Paris

Legacy Theses & Dissertations (2009 - 2024)

Androgenic steroids, such as testosterone, may influence the propensity for aggression in both people and animals. Some of testosterone's effects on aggression may be due, in part, to its metabolic products that are 5á-reduced and 3á-hydroxylated to form, 3á-androstanediol (3á-diol), which can also enhance aggression in mice. Notably, alcohol (EtOH) consumption facilitates aggression in people and animals, particularly among those predisposed to act aggressively. In rats, EtOH can increase 3á-diol in prefrontal cortex, which may facilitate aggression. The present work aimed to elucidate the role of 3á-diol for EtOH-enhanced aggression. We hypothesized that EtOH would enhance inter-male aggression, social dominance, …

The Nasal Toxicity Of The Herbicide 2,6-Dichlorobenzonitrile : Mechanisms And Biomarkers, Fang Xie

Legacy Theses & Dissertations (2009 - 2024)

The overall goal of this study is to investigate mechanisms of the potent nasal specific toxicity of the herbicide 2,6-dichlorobenzonitrile (DCBN) in rodents, and to determine whether DCBN could induce similar nasal toxicity in humans. The central hypotheses are 1) that the nasal specific toxicity of DCBN in rodents is mediated by its electrophilic intermediates that are formed through metabolic activation catalyzed by target tissue cytochrome P450 enzymes (P450) and can interfere with stem cell regeneration and differentiation in the olfactory epithelium (OE); and 2) that human nasal tissues are also capable of catalyzing bioactivation of DCBN. The specific aims …

Regulation Of The Aryl Hydrocarbon Receptor And The Signal Transducer And Activator Of Transcription 1 By Long-Term Estrogen Exposure In Breast Carcinoma Cells, Neal Englert

Legacy Theses & Dissertations (2009 - 2024)

The risk of developing breast cancer is known to be associated with a woman's lifetime exposure to estrogens, both endogenous and exogenous. Increased exposure to estrogens stimulates cellular proliferation, which is a widely accepted theory of estrogen receptor positive mammary carcinogenesis. The molecular mechanisms of gene expression regulation in response to long-term estrogen exposure (LTEE) of MCF-7 breast cancer cells were addressed in this study, with a focus on the aryl hydrocarbon receptor (AHR) and signal transducer and activator of transcription 1 (STAT1).

In Vitro And In Vivo Pharmacodynamic Characterization Of The Novel Plasma Kallikrein Inhibitor Pf-04886847, Dhaval Sanjeev Kolte

Electronic Theses and Dissertations

Plasma kallikrein plays an important role in the pathogenesis of inflammation and thrombosis. Kallikrein cleaves high molecular weight kininogen (HK) to liberate the potent pro-inflammatory peptide bradykinin (BK). BK upon activation of its constitutive B2 receptors on endothelial cells leads to an increase in intracellular Ca2+ level and subsequent production of nitric oxide (NO) and prostacyclin (PGI2), ultimately leading to vasodilation, hypotension, increased vascular permeability and vascular leakage. Further, kallikrein activates the complement system and stimulates neutrophil chemotaxis, aggregation and elastase release. Furthermore, kallikrein mediates the conversion of factor XII (FXII) to activated factor XII (FXIIa) thereby potentiating the intrinsic …

Scoliosis: Comparative Analysis Of Surgery Vs. Brace Treatment, Jerry Frenkel

The Science Journal of the Lander College of Arts and Sciences

The following is the introduction of this article: The spine, or spinal column, as it is also called, is a complex structure made up of 33 vertebrae (bone segments) arranged vertically in succession from just below the skull to the tailbone. The entire column is broken up into various classes of vertebrae named, from superior to inferior, as cervical, thoracic, lumbar, sacral, and coccygeal. Different forms of spinal deformities that can occur include kyphosis, lordosis and scoliosis (Neuwirth and Osborn 2001). Scoliosis is defined simply in medical terms as a lateral three-dimensional irregular curvature of the spine. The curvature as …

Full Issue: Volume 5, Number 1, Fall 2011

The Science Journal of the Lander College of Arts and Sciences

No abstract provided.

Electro-Gene Transfer To Skin Using A Noninvasive Multielectrode Array, Siqi Guo, Amy Donate, Gaurav Basu, Cathryn Lundberg, Loree Heller, Richard Heller

Bioelectrics Publications

Because of its large surface area and easy access for both delivery and monitoring, the skin is an attractive target for gene therapy for cutaneous diseases, vaccinations and several metabolic disorders. The critical factors for DNA delivery to the skin by electroporation (EP) are effective expression levels and minimal or no tissue damage. Here, we evaluated the non-invasive multielectrode array (MEA) for gene electrotransfer. For these studies we utilized a guinea pig model, which has been shown to have a similar thickness and structure to human skin. Our results demonstrate significantly increased gene expression 2 to 3 logs above injection …

Preventing Mother-To-Child Transmission Of Human Immunodeficiency Virus-1 (Hiv-1): Effects Of Intrapartum And Neonatal Single-Dose Nevirapine Prophylaxis And Subsequent Hiv-1 Drug Resistance At Antiretroviral Treatment Initiation, Amanda L. Harmon

CMC Senior Theses

The prevention of mother-to-child transmission is one of the most powerful tools in human immunodeficiency virus type 1 (HIV-1) prevention and has huge potential to improve both maternal and child health. In the absence of any preventative measures, infants born to and breastfed by their HIV-positive mothers have roughly a one-in-three chance of acquiring the infection themselves. HIV can be passed on from mother-to-child during pregnancy, during labor and delivery, and even after during breastfeeding.

Intrapartum and neonatal single-dose nevirapine (sd-NVP) is the foundation of preventing mother-to-child transmission in lower resource settings where it has been used alone or as …

The Effects Of Protein Kinase C Inhibitors On Blood Nitric Oxide And Hydrogen Peroxide Release In Ischemia And Reperfusion Injury, Kyle D. Bartol

PCOM Biomedical Studies Student Scholarship

Vascular endothelial dysfunction is a key component initiating oxidative stress in ischemia/reperfusion (I/R). Endothelial dysfunction is characterized by an increase in hydrogen peroxide (H2O2) and a decrease in the bioavailability of nitric oxide (NO). Previous studies using protein kinase C (PKC) inhibitor Gö 6983 or PKC Beta (β) II inhibitor improved cardiac function in myocardial I/R, decreased leukocyte-endothelial interactions and leukocyte superoxide (SO) release and increased endothelial-derived NO release in vitro. This study examined the effects of Gö 6983 or PKC β II inhibitor on realtime H2O2 and NO release in femoral vein I/R in vivo. NO or H2O2 microsensors …

Synthesis, Evaluation And Structural Studies Of Antiproliferative Tubulin-Targeting Azetidin-2-Ones, Niamh O'Boyle, Lisa M. Greene, Orla Bergin, Jean-Baptiste Fichet, Thomas Mccabe, David G. Lloyd, Daniela M. Zisterer, Mary J. Meegan

Articles

A series of azetidin-2-ones substituted at positions 2, 3 and 4 of the azetidinone ring scaffold were synthesised and evaluated for antiproliferative, cytotoxic and tubulin binding activity. In these compounds, the cis double bond of the vascular targeting agent combretastatin A-4 is replaced with the azetidinone ring in order to enhance the antiproliferative effects displayed by combretastatin A-4 and prevent the cis/trans isomerization that is associated with inactivation of combretastatin A-4. The series of azetidinones was synthetically accessible via the Staudinger and Reformatsky reactions. Of a diverse range of heterocyclic derivatives, 3-(2-thienyl) analogue 28 and 3-(3-thienyl) analogue 29 displayed the …

Feedback From Malaysian Pharmacists Who Underwent A 3-Year Period Of Compulsory Service With The Government, Ong Aik Liang, Thomas Paraidathathu

The Thai Journal of Pharmaceutical Sciences

Since 2004, it is mandatory for all new pharmacy graduates in Malaysia to serve the government for a period of 4 years, before they are free to work as registered pharmacists in a sector of their choice, either public or private. With the enactment of th...

Sensitive, Selective And Extraction-Free Spectrophotometric Determination Of Lamotrigine In Pharmaceuticals Using Two Sulphonthalein Dyes, K. B. Vinay, H. O., N. Rajendraprasad, K. Basavaiah

The Thai Journal of Pharmaceutical Sciences

Two direct, simple, sensitive and rapid extraction-free spectrophotometric methods have been developed for the determination of lamotrigine (LMT) in pure form and in its dosage forms. The methods are based on formation of ion-pair complex between the dru...

Pharmacotherapy Safety And Efficacy In Adolescent Smoking Cessation, Jennifer Lincoln

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: To determine whether or not pharmacotherapy is a safe and effective treatment option for smoking cessation in adolescents