Chemicals and Drugs Commons^™

Efficacy Of Deferasirox In Preventing Complications Of Iron Overload In The Iron Overloaded Gerbil, Rabaa M. Al-Rousan

Theses, Dissertations and Capstones

Iron overload is a significant, world-wide problem that results in several chronic diseases including cardiovascular, hepatic and pancreatic complications.The newly developed, orally effective, iron chelating agent deferasirox is thought to offer tremendous promise as an alternative to deferoxamine. However, the efficacy and safety profile of deferasirox is not yet clear. In the present study, the efficacy of deferasirox in removing iron from target tissues has been examined using the gerbil model of iron overload. Deferasirox administration resulted in a significant reduction of iron from cardiac and hepatic tissue. In addition deferasirox reduced iron induced increase in cardiac and hepatic oxidative …

A Mechanistic Study Of The Protective Effects Of S-Adenosyl-L-Methionine Against Hepatotoxicity Of Acetaminophen, Marcus V. Terneus Jr.

Theses, Dissertations and Capstones

Hepatic toxicity is known to be associated with excessive doses of the over-the-counter analgesic, acetaminophen (APAP). APAP overdose is the leading cause of drug-induced liver failure in the United States. APAP hepatotoxicity is dependent on the biotransformation of APAP by cytochrome P450 to the toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI). APAP, when taken in excessive doses, can lead to severe liver damage with the potential to progress to liver failure. Despite substantial efforts in past studies, the mechanism by which APAP induces such damaging effects is not completely understood. Recent discoveries suggest that glutathione (GSH) depletion, protein alkylation and reactive metabolite …

Antimicrobial And Spermicidal Activity Of Hydrogen Peroxide And Nonoxynol-9 Based Gel Preparations, Paul E. Grimmett

Theses, Dissertations and Capstones

Eighty gel formulations were prepared using five buffer systems (0.01M citrate, 0.02M citrate, 0.01M tartrate, 0.02M tartrate, and 0.01M citrate/0.01M tartrate), four hydrogen peroxide (H2O2) concentrations (0%, 0.3%, 0.9%, and 1.2%), and four nonoxynol-9 (N-9) concentrations (0%, 1%, 1.5%, and 2%). The eighty gel formulations were then tested for physio-chemical properties (viscosity and pH), antimicrobial effectiveness (Minimum Inhibitory Concentration Assay) against Candida albicans, Escherichia coli, and Streptococcus agalactiae, and finally, spermicidal effectiveness (Sander Cramer Assay). The gel formulation that contained the best combination of physio-chemical, antimicrobial, and spermicidal properties was a 0.01M citrate buffered hydrogel, which contained 0.9% H2O2 and …

Hk-2 Cells As A Human Model Of Glucuronide Transport, Eliza E. Robertson

Theses, Dissertations and Capstones

Glucuronidation is primarily a pathway of detoxification in most species, but many glucuronide conjugates are associated with toxicity. Numerous drugs are excreted in the urine as glucuronide conjugates. Being organic anions, it is likely that glucuronides are secreted into the urine by organic anion transporters found in renal proximal tubule cells (PTCs). Some drugs that are metabolized by glucuronidation have been shown to cause renal toxicity, yet little is known about the renal handling of glucuronide conjugates. It is hypothesized that glucuronides are transported into renal PTCs by an organic anion transporter (OAT) on the basolateral membrane of the cell. …

Phosphoproteomic Studies Of Smooth Muscle Contraction: Investigation Of Differential Phosphorylation In Relaxed/Contracted Rat Aortic Smooth Muscle Tissue Using Maldi-Tof Ms, Tonya M. Pekar

Theses, Dissertations and Capstones

Many human disorders are associated with the malfunction of smooth muscle tissue, or are related to the capabilities of its proper function—asthma, glaucoma, renal inefficiency, hypertension, and cardiovascular disease. Dysfunctional proteins are frequently implicated as the source of such disorders. As the second highest cause of death in the United States, the epidemic of cardiovascular disease makes the study of smooth muscle of utmost concern.

The capabilities of proteomics and mass spectrometry allow the entire proteome complement of a cell or tissue type to be analyzed at once. This investigation employs such techniques in an effort to better understand the …

A Mechanistic Study Of Myoglobin Nephrotoxicity, Jennifer L. Minigh

Theses, Dissertations and Capstones

Myoglobin is an endogenous protein that can become nephrotoxic under certain conditions such as crush injuries, drug overdose, and seizures where prolonged contraction of muscle leads to cell death and leakage of myoglobin. The mechanism of myoglobin-induced nephrotoxicity is not fully understood. The purpose of this study was to characterize the sequence and mechanistic events associated with the in vitro toxicity of myoglobin in renal cortical slices. Renal tissue was isolated from Fischer 344 rats. Slices of renal cortex were prepared by freehand. These slices were then incubated for 60-180 minutes with myoglobin (0-12 mg/mL) pretreated with 4 mM ascorbic …

Characterization Of Host-Bacteria Interactions Contributing To Group B Streptococcus Colonization, Jennifer Marie Smith

Theses, Dissertations and Capstones

Group B streptococcus (GBS) is the leading cause of life-threatening bacterial infections during the first three months of life. GBS is also a frequent cause of maternal postpartum infections. Both types of infections stem from maternal vaginal and/or rectal colonization with GBS in the perinatal period. Limited information is available concerning how the colonization process occurs and what role the host immune system may play in the establishment of persistent colonization by GBS. The complex interactions between the immune system and GBS normally should end in clearance of the bacteria. However, since colonization by GBS occurs in a large number …

Ritalin And The Child, Valerie Vickers

Theses, Dissertations and Capstones

This study focuses on Attention Deficit Hyperactivity Disorder (ADHD) the history of the disease, sufferers, individual accounts from sufferers, and both positive outcomes and negative repercussions of its treatment. Extensive secondary research and the collection of a personal account form the body of the work. The information focuses attention on key points regarding the historical background of ADHD, including: the discovery of the disease, change in categories of drugs used to control it, and the rate of evolution in thoughts on and treatment of the disease. Also researched are the various guidelines as well as ignored factors in the diagnosing …

Methods Development For The Identification Of Unknown Proteins, Laura Brumfield Neal

Theses, Dissertations and Capstones

The chemistry of transport, storage, energy production, and reproduction in physiological systems is controlled by the actions and interactions of proteins. A species full complement of these amazing machines is often referred to as its proteome. The new science of proteomics utilizes a set of powerful and evolving tools to characterize the nature of the proteome, and further to fully elucidate the functional attributes of the proteins and their associations.

A methodology was developed by combining several proteomic techniques, such as electrophoresis, RP-HPLC, and mass spectrometry, to correctly identity proteins. Three known proteins (myoglobin, albumin, and actin) were employed for …

An Open Label Study Of The Effects Of Levetiracetam In Children With Autism, Teresa C. Samsock

Theses, Dissertations and Capstones

This was an open-label study of levetiracetam in children with autism. Many anticonvulsant medications are used for management of externalizing behaviors and mood stability in autism; however, they are not consistently effective and adverse reactions limit their use. The objective of this study was to test the following research questions: (1) to determine whether levetiracetam reduces problematic externalizing behaviors in children with autism, and (2) to determine whether a nootropic effect from levetiracetam may be seen in cognition, memory, and/or language function in children with autism. Evaluations were gathered pre-treatment and during treatment using a battery of cognitive and behavioral …

Drug Of Choice As A Predictor Of Program Completion In A 12-Week Intensive Outpatient Program And Continuing Care Program, James R. Myers

Theses, Dissertations and Capstones

This study consisted of a one year examination of a twelve week Intensive Outpatient Program (IOP), followed by continuing care treatment, coupled with required attendance to a Twelve Step AA/NA Program. This study detailed the treatment plan available at a local Intensive Outpatient Program in Southern West Virginia. A sample, separating alcoholics from other substance abusers to obtain an estimated completion rate was used.

Tills thesis comprised a one-year history of subjects (6/30/98 -07/01/99). A total of 84 subjects entered into the Intensive Outpatient Program (IOP) within the above time frame. Determination of completion rates was based on a categorical …

Progestin Stimulation Of The Protooncogene C-̲M̲Y̲C In T47d Human Breast Cancer Cells, Kristy Ann Blankenship

Theses, Dissertations and Capstones

Moore and co-workers have previously demonstrated that progestins stimulate the growth of T47D human breast cancer cells. We now investigate the possibility that progestins might transactivate the protooncogcne c-myc as part of the mechanism for growth stimulation. Treatment of T47D cells with the synthetic progestin R5020 results in a rapid, dose-dependent increase in c-myc mRNA. This stimulation is evident as early as 5 minutes, increases up to 4-fold at 1 hour, and then returns toward basal levels. The optimal concentration of R5020 for induction of c-myc gene expression is 10 nM, which is within the physiologically relevant range of hormone …

Contradictions In Reported Side Effects And Paradoxical Effects With Diazepam (Valium), Wilfrid Reid Clement

Theses, Dissertations and Capstones

This study began with a request from the Hoffman LaRoche Company to collect data on one of their compounds, diazepam, which was being marketed under the trade name Valium.