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Pharmacology, Toxicology and Environmental Health Commons

Open Access. Powered by Scholars. Published by Universities.®

Department of Pharmacology and Toxicology

2009

Articles 1 - 10 of 10

Full-Text Articles in Pharmacology, Toxicology and Environmental Health

Effects Of Chlorpyrifos-Oxon On Prohormone Convertase Enzyme Activity, Sean William Harshman Jan 2009

Effects Of Chlorpyrifos-Oxon On Prohormone Convertase Enzyme Activity, Sean William Harshman

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Organophosphate (OP) compounds have been synthesized for various applications including medicine, pest control and weapons of terror. OPs irreversibly phosphorylate the active site of acetylcholinesterase, the primary target of toxicity, rendering it inactive causing a hypercholinergic state in the post synaptic cleft. However, very little is known about the effects of OPs on secondary targets of toxicity i.e. other serine hydrolases. The prohormone convertase (PC) enzymes, specifically PC1/3 and PC2, are serine hydrolases which are responsible for the processing of pro-opiomelanocortin in the anterior and intermediate lobes of the pituitary. To test the direct interaction between OPs and the PC …


Characterization Of Infectivity And Pathogenesis Of Partially Reconstructed 1918 And Highly Pathogenic Avian Influenza Viruses In The Balb/C Mouse Model, John Allen Pyles Jan 2009

Characterization Of Infectivity And Pathogenesis Of Partially Reconstructed 1918 And Highly Pathogenic Avian Influenza Viruses In The Balb/C Mouse Model, John Allen Pyles

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Influenza viruses are consistently responsible for an average of 20,000 deaths and 114,000 hospitalizations per year. To a great extent, these viruses always stay one step ahead of the available vaccines and people's immunity year after year because they have the ability to either mutate part of their genetic material, or to be transmitted from one species to another. That same genetic variability explains why highly pathogenic influenza viruses emerge that cause great mortality over several countries resulting in pandemics. Highly pathogenic strains of influenza A virus have emerged occasionally in recent history, producing pandemics such as the one in …


Identification Of Potential Protein Biomarkers Of Low Level Kidney Degradation, Christopher Lee Woolard Jan 2009

Identification Of Potential Protein Biomarkers Of Low Level Kidney Degradation, Christopher Lee Woolard

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The purpose of this research was the identification of potential dose-dependent and time-dependent serum protein biomarkers of low level kidney degradation in a rat model. Potential biomarkers were evaluated based on differential protein expression between control and dosed samples in rat serum. Proteins of interest demonstrated upregulation at a minimum 1.5 fold increase in protein concentration control versus dosed sample. In order to identify common biomarkers of kidney decrement, three nephrotoxins were chosen to target specific locations of the kidney: 1) D-Serine, which causes necrosis of the proximal straight tubules, 2) Puromycin, an antibiotic that degrades the Glomerular Basement Membrane …


Tcdd-Induced Modulation Of The Hs1,2 Enhancer Within The 3'Immunoglobulin Heavy Chain Regulatory Region, Tharu M. Fernando Jan 2009

Tcdd-Induced Modulation Of The Hs1,2 Enhancer Within The 3'Immunoglobulin Heavy Chain Regulatory Region, Tharu M. Fernando

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2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent environmental toxin that inhibits immunoglobulin (Ig) gene expression in mice. Transcriptional regulation of the Ig heavy chain (IgH) involves the 3'IgH regulatory region (3'IgH RR). The murine 3'IgH RR consists of four enhancers (hs3A, hs1,2, hs3B, and hs4), which are homologous to the human 3'IgH RR enhancers (hs3, hs1,2, and hs4). In humans, a polymorphism of the hs1,2 enhancer, resulting in a varying number of tandem repeats of a 53 bp sequence, has been correlated with autoimmune diseases like IgA nephropathy and Celiac disease. The repeated sequence contains a kB and DRE binding site. Previous …


Effects Of Direct Mechanical Ventricular Actuation On The Apoptotic Signaling Of A Failing Heart, Scott Kerns Jan 2009

Effects Of Direct Mechanical Ventricular Actuation On The Apoptotic Signaling Of A Failing Heart, Scott Kerns

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Cardiovascular disease accounts for more than 40% of all deaths in the United States (AHA-2004 report). A non blood contacting ventricular assist device (VAD) can be used to treat heart failure without the complications that arise from blood contacting VADs. This study used cellular markers of heart failure as indicators of heart function in an attempt to assess if direct mechanical ventricular actuation (DMVA) support lessened the impact of heart failure in rabbits. Cell signaling proteins were monitored using enzyme activity measurements and quantitative immunoblotting with antibodies against intrinsic and extrinsic apoptotic pathways during heart failure with and without DMVA …


Novel Neuroprotectants For Sarin Plus Cbdp Induced Convulsions, Kaushal V. Joshi Jan 2009

Novel Neuroprotectants For Sarin Plus Cbdp Induced Convulsions, Kaushal V. Joshi

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Sarin, also known as Sarin (German agent B) is classified as a weapon of mass destruction. Sarin (O-isopropyl methyl phosphonofluoridate) is a highly toxic nerve agent originally produced for chemical warfare and has been used in terrorist activities. Sarin is an extremely potent acetylcholinesterase inhibitor with high specificity and affinity for the enzyme. High sarin doses causes death due to anoxia resulting from airway obstruction, weakness of the muscles of respiration, respiratory failure and convulsions. Current treatments are still not effective at protecting against long term effects following exposure. A current approach aims to counteract the increased glutamatergic and cholinergic …


In-Vitro Biocompatibility Of Silver Nanoparticles Anchored On Multi-Walled Carbon Nanotubes, Alicia Brooks Castle Jan 2009

In-Vitro Biocompatibility Of Silver Nanoparticles Anchored On Multi-Walled Carbon Nanotubes, Alicia Brooks Castle

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Silver (Ag) nanoparticles were anchored on the surface of three different multi-walled carbon nanotubes (MWNTs): Ag-MWNTs (pure carbon), Ag-MWNT-COx (carbonyl and carboxyl doped), and Ag-MWNT-CNx (Nitrogen-doped). The chemical reactivity of the nanotubes was MWNTs< COx-MWNTs< CNx-MWNT. Ag-NP anchored on the MWNTs had an average size corresponding to MWNTs 6.64nm +/- 2.25nm; CNx-MWNTs, 13.24nm +/- 3.94nm, and COx-MWNT/Ag 11.75nm +/- 4.65nm. Cellular function and immune response were evaluated to determine biocompatibility of the synthesized nanomaterials (NM) on the human keratinocyte cell line (HaCaT). Cellular assays revealed toxicity after 24h however, full cellular recovery was observed at 48h. These results suggest Ag nanoparticles anchored on MWNTs have the ability to interact with cells without disrupting cellular function.


Ischemic Stroke In Type Ii Diabetic Mice: Deregulation Of Sdf-1a/Cxcr4 Axis, Avik Das Jan 2009

Ischemic Stroke In Type Ii Diabetic Mice: Deregulation Of Sdf-1a/Cxcr4 Axis, Avik Das

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Type 2 diabetes mellitus is a major risk factor for ischemic stroke. Also diabetes is associated with poor outcome after stroke. Underlying mechanisms are however not fully understood. Alteration in the expression of the SDF-1a/CXCR4 axis, which is important for ischemic tissue repair, can be a probable cause. In this study, we have determined the expression of SDF-1a/CXCR4 in the brains of type II diabetic mice at basal and in response to ischemic stroke and have investigated a method for overexpression of SDF-1a in the brains of the diabetic mice. Adult male C57BLKS/J mice (db/db) of age 8 weeks were …


Effect Of Low-Dose Sarin Exposure On The Neurochemistry Of Different Brain Structures In Mice, Dhawal Pravin Oswal Jan 2009

Effect Of Low-Dose Sarin Exposure On The Neurochemistry Of Different Brain Structures In Mice, Dhawal Pravin Oswal

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Sarin (GB) is a toxic organophosphate (OP) nerve agent that was released in the Gulf War and was used in terrorist attacks in Japan. People who survive such attacks exhibit various long-term effects including alterations in neuropsychological performances. It has also been hypothesized that the Gulf War Illness could be a result of low level exposure to OP's. In order to understand the effect of low dose exposure to GB on physiological and behavioral functions, we analyzed the levels of monoamines and their metabolites in different brain areas after exposure of mice to a sublethal dose of GB. Mice (male …


Impact Of Diabetes On Ace/Ace2 Balance And Angiotensin Ii Type 1 Receptor Expression In Db/Db Diabetic Mice, Malav Navinchandra Madhu Jan 2009

Impact Of Diabetes On Ace/Ace2 Balance And Angiotensin Ii Type 1 Receptor Expression In Db/Db Diabetic Mice, Malav Navinchandra Madhu

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Alterations in the renin-angiotensin system (RAS) are considered to be crucial for the development of diabetic complications like hypertension and nephropathy. Our previous work demonstrated role of AT1 receptors (AT1R) in the development of hypertension in db/db diabetic mice. The aim of this study was to test the hypothesis that there is upregulation of renal AT1R and imbalance in renal ACE/ACE2 homeostasis in db/db mice. In addition, we hypothesize that treatment with an anti-hyperglycemic or an AT1R blocker will correct this imbalance. Five week old control and db/db mice were housed in metabolic cages for 24 hour collection of urine. …