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Regulation of Sperm Exocytosis
Exocytosis of the sperm acrosome is a prerequisite for fertilization. Exocytosis is a regulated process, and sperm develop the ability to undergo exocytosis slowly. This project investigates the role of sterols in the regulation of exocytosis.
Sponsor: National Institutes of Health
PI: Nicholas L. Cross
In Vitro Evaluation of Neurotoxic Plants
The application of in vitro tissue culture to the study of neurotoxins is being evaluated using pheochromocytoma cells and neurons. Extracts from neurotoxic plants (Asclepias) will be compared with commercially available neurotoxins.
Sponsors: Cantrell Hay Co., Kochia Industries, Charles Shipley, and College of Veterinary Medicine
PI: George E. Burrows
Pathophysiological Basis of Hypertension in Obesity
Obesity is a major risk factor for diabetes, hypertension, and cardiovascular disease. Almost 30% of the U.S. population is medically obese and approximately 53% of obese people are hypertensive. Obesity-associated hypertension is a major health problem in humans, but the mechanisms responsible for the genesis and maintenance of the disease are unknown. This project examines possible mechanisms explaining the coexistence of hypertension and obesity in sheep. The dietary obese sheep is a new and unique animal model that surpasses conventional models in rats because sheep express hyperinsulinemia, insulin resistance, hypertension, and obesity under experimentally defined conditions. The advent and use of this model will provide new knowledge on the cellular causes, prevention, and treatment of obesity-associated hypertension in humans.
Sponsor: Oklahoma Center for the Advancement of Science and Technology
PI: Joseph P. McCann
Development of New Polyvalent Antivenom for Snakebite
The objective of this research is to develop a better antivenom, which can be used to prevent all of the damaging actions of venoms of snakes found in the United States. There are two main problems with the antivenom now available for use. It is not very effective in preventing the local tissue-damaging action of the venoms, and its use often results in severe allergic reactions. This research will address both of these problems by first producing an antivenom that is capable of inhibiting venom components responsible for tissue damage and that has had the allergenic components removed.
Sponsor: National Institutes of Health
PI: Charlotte L. Ownby
The Effects of Various Levels of Lasalocid, Salinomycin, and Monensin Alone and in Combination on Toxicity in Broiler
Chickens
Ionophores (Lasalocid, Monensin, and Salinomycin) are feed additives used by poultry producers to prevent coccidial infections. Recently, a non-lethal, neurotoxic syndrome has been associated with the use of at least one of these ionophores. These investigators are attempting to define and describe the role of these feed additives in the neurotoxic syndrome.
Sponsor: Hoffman-La Roche
PIs: Subbiah Sangiah, Stanley VanHooser, and Joseph D. Roder
Influence of Dietary Sulphur-Containing Amino Acids on Cadmium-Induced Toxicity
Cadmium, a toxic mineral, can damage virtually every organ system in the body and is an environmental risk factor for human disease. Cadmium interacts with a variety of proteins. Metallothionein is a protein that is thought to aid in cadmium detoxification. This project is examining sulfur-containing amino acids and the effect on metallothionein and cadmium toxicity.
Sponsor: Dr. Frederick Radd (Ponca City, Oklahoma)
PIs: Subbiah Sangiah
Barbara Stoecker (Nutritional Sciences)
Toxicity Studies on Sophora nuttalliana and Kochia scoparia
Studies are in progress to evaluate the effects of the plants Sophora nuttalliana, Iva ciliata, and Baptisia australis on fetal development in rats. Plant extraction/alkaloid identification studies show sophocarpine to be the major alkaloid in S. nuttalliana and sinoacutane to be one of the many others present in lower concentrations. Based on preliminary experiments, S. nuttalliana should be considered a suspect teratogen. Direct toxic effects on pregnant rats are apparent only for B. australis. Additional studies on direct toxic effects in sheep are in progress for S. nuttalliana, Albizia julibrissin, and Erupatorium rugosum.
Sponsor: Oklahoma Agriculture Experiment Station
PI: George E. Burrows
Prediction on In Vivo Efficacy of Sarafloxacin Using In Vitro Antimicrobial Sensitivity Assays and Pharmacokinetic Data
Tests currently used to predict the effectiveness of antibiotics against bacteria causing disease are unreliable because they do not take into account the effect of host defense responses nor are they correlated with accurate pharmacokinetic information describing concentrations of antibiotics in animal tissues. The goal of this project is to develop a predictive in vitro susceptibility assay and use this, together with relevant tissue pharmacokinetic data, to estimate doses of sarafloxacin that are likely to achieve satisfactory antibacterial concentrations in chickens.
Sponsor: Oklahoma State Board of Agriculture
PI: Cyril R. Clarke
Neutrophil Chemotaxis in Response to Pasteurella haemolytica Infection
The objectives of this project were to investigate the chemotactic effects of various eicosanoids and cytokines and the role of Pasteurella haemolytica in stimulating release of these mediators. The role of intracellular calcium concentration in the response to P. haemolytica leukotoxin has been explored using the fluorescent calcium indicator, Fluo-3. A positive correlation between leukotoxin concentration, intracellular calcium concentration, and leukotriene B-4 synthesis has been confirmed. Partial inhibitory effects of the calcium channel antagonist, verapamil, suggested that calcium channels may be involved in the molecular pathogenesis of bovine pasteurellosis.
Sponsor: Oklahoma Agricultural Experiment Station
PI: Cyril R. Clarke
Endocrine Pancreas Control of Metabolism in Ruminants
Body condition and sex steroids affects the endocrine regulation of whole-body fuel metabolism and the regional distribution and metabolism of adipose tissue. The long-term goal of this work is to understand the interactive effects of insulin, growth hormone, and sex steroids on inter-organ fuel metabolism and adipose morphology in lean and obese animals.
Sponsor: Oklahoma Agricultural Experiment Station
PI: Joseph P. McCann
Pathophysiology of Heat StressÑBiochemical and Molecular Basis
High environmental temperature-relative humidity stress is a significant problem in the poultry industry. Heat stress affects various cellular structures and functions and causes changes in mitochondrial and nuclear structure, denaturing soluble, and membrane proteins. Experiments will be conducted to determine relative concentrations of mRNAs for Na+ K+ ATPase enzyme subunits in kidneys and intestinal (large and small) mucosa of broiler chickens exposed to both acute and chronic heat stress. Results of this inital study at the molecular level would enable us to design further studies in understanding various factors that control the expression of Na+ K+ ATPase pump in the kidneys and intestinal mcuosa of broiler chickens exposed to acute or chronic heat stress conditions.
Sponsor: Oklahoma State Board of Agriculture
PI: Subbiah Sangiah
Development of the Estrogen Response Network of the Bovine Reproductive Tract
Estrogens are key mediators of development, differentiation, and growth. The goal of research underway is to understand the regulation of gene expression in the uterus, to dissect the steroid-regulated network of genes, and to integrate this network with key mediators of the establishment and maintenance of pregnancy. Work is in progress to characterize the temporal and spatial appearance of the estrogen receptor during bovine fetal reproductive tract development and to characterize the appearance of a functional estrogenic hormone response in the fetal reproductive tract.
Sponsor: United States Department of Agriculture
PI: Jerry R. Malayer
Effects of Vitamin E on Water Pollutant Cadmium-Induced Toxicity in Rats
The major objective of the proposed study is to determine the effects of vitamin E pre-treatment on the water pollutant cadmium-induced changes in lipid peroxidation, hydroxyl free radicals generation, and glutothione in vital organs including liver, kidneys, and testes of rats. The results of the studies would provide us with information concerning some aspects of pathophysiological/biochemical mechanism(s) responsible for cadmium-induced toxicity. Additionally, the effectiveness of antioxidants such as vitamin E as one of the potential therapeutic agents for cadmium-induced toxicoses in rats could eventually be extended to treat human/farm animals.
Sponsor: OSU Environmental Institute Center for Water Research
PI: Subbiah Sangiah
Molecular Pathogenesis of Shipping Fever: Intracellular Calcium
Shipping fever pneumonia is characterized by massive influx of neutrophils into infected lung tissue. The hypothesis developed to explain the mechanism of this inflammatory response is that leukotoxin, a toxin produced by P. haemolytica, activates neutrophils by causing a sustained increase in intracellular Ca2+ concentration ([Ca2+]i), which results in uncontrolled synthesis of inflammatory mediators and disabling damage to neutrophil membranes. This hypothesis will be tested by characterizing the effects of leukotoxin on [Ca2+]i and will be used to identify the mechanisms of leukotoxin-induced increase in [Ca2+]i, cell damage, and synthesis of the inflammatory mediator, leukotriene B-4.
Sponsor: USDA (NRI)
PI: Cyril R. Clarke
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