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Biomedical subjects

Timothy R Koch

Publications and source records attributed to Timothy R Koch.

At least 19 recordsLinked to original sources
PubMed2005

Effects of esomeprazole magnesium on nonsteroidal anti-inflammatory drug gastropathy.

It has been proposed that tissue damage induced by nonsteroidal anti-inflammatory drugs is related to increased tissue free radical production with antioxidant depletion. We have shown that esomeprazole increases gastric total antioxidant capacity in mice and, therefore, hypothesized that the protective effect of esomeprazole during treatment with a nonsteroidal anti-inflammatory drug is related to increased gastric antioxidant capacity and decreased tissue free radical production. A/J mice received one of four treatments by daily gavage: saline in vehicle (control), indomethacin, esomeprazole, or indomethacin and esomeprazole. After 10 days, all mice were sacrificed and validated assays were used to measure gastric total antioxidant capacity, lipid peroxide levels, and myeloperoxidase activity. Indomethacin-treated mice developed weight loss and melena. No mice receiving indomethacin and esomeprazole died, but the death rate while receiving indomethacin was 38% (chi2, P = 0.05). Gastric lipid peroxide levels increased in mice receiving indomethacin treatment compared to treatment with esomeprazole and indomethacin (P = 0.03). There was a strong trend (P = 0.08) toward increased gastric total antioxidant capacity in mice receiving esomeprazole and indomethacin compared to mice receiving indomethacin. Gastric myeloperoxidase activities were not different among the four groups. Esomeprazole significantly improved survival in mice that received indomethacin, reduced free radical production, as estimated by lipid peroxide levels, and appeared to increase gastric total antioxidant capacity. The mechanisms for the beneficial effects of esomeprazole in the treatment of gastropathy are more complex than previously thought.

Animals↗
PubMed2005

Evaluation of chronic gastrointestinal symptoms following Persian Gulf War exposure.

This was a prospective study performed in a Department of Veterans Affairs Medical Center. The aim of this study was to use endoscopic and histological examinations to determine the potential diagnostic origins of chronic gastrointestinal symptoms among patients who were part of the deployment of troops to the Persian Gulf after August 1990. Twenty-four (8%) male patients (mean age, 42 years) of 308 patients in the Persian Gulf War Registry agreed to undergo endoscopic examination of chronic symptoms, including heartburn (29%), dyspepsia (33%), dysphagia (8%), diarrhea (63%), Hemoccult-positive stool (21%), and rectal bleeding (17%). There were 17 upper endoscopies, 18 colonoscopies, and 4 flexible sigmoidoscopies performed, all with biopsies. Five (33%) of 15 patients had positive serological findings for Helicobacter pylori. With upper endoscopy, major findings included esophagitis (12%), Schatzki's ring (12%), hiatal hernia (47%), antral erythema (59%), and duodenal erythema (29%). With lower endoscopy, major findings included ileitis (5%), lymphoid hyperplasia (9%), polyps (27%), diverticulosis (23%), and hemorrhoids (23%). Major histopathological findings included microscopic esophagitis (24%), gastritis with H. pylori (35%), gastritis without H. pylori (18%), Crohn's disease (5%), tubular adenoma (5%), hyperplastic polyps (18%), and melanosis coli (5%). Most patients with chronic heartburn or dyspepsia have evidence of esophagitis or H. pylori. Individuals with these chronic symptoms should undergo evaluation.

Adult↗
PubMed2004

Effect of the H, K-ATPase inhibitor, esomeprazole magnesium, on gut total antioxidant capacity in mice.

Antioxidant depletion is believed to be a mechanism involved in the pathophysiology of several upper gastrointestinal disorders, and H, K-ATPase inhibitors can alter free radical production by neutrophils. We hypothesized that the H, K-ATPase inhibitor esomeprazole magnesium would decrease gut free radical production with a concomitant increase in gut total antioxidant capacity. A/J mice (n = 10/group) received either vehicle (control) or one of three concentrations of esomeprazole magnesium in vehicle by once-daily gavage for 10 days. Using tissue extracts from stomach and colon, total antioxidant capacity, lipid peroxide levels, and constitutive Cu/Zn-superoxide dismutase were measured using validated assays. There was a dose-related increase in total antioxidant capacity (analysis of variance, P < 0.001) in stomach, but there was no change in the colon. In the assessment of free radical production, there was a trend toward decreased lipid peroxide levels in stomach from mice receiving esomeprazole. In stomach, Cu/Zn-superoxide dismutase activity was increased (ANOVA: p=.03) in mice receiving esomeprazole. In conclusion, gastric total antioxidant capacity and Cu/Zn-superoxide dismutase activity are increased by esomeprazole, and these changes may result in part from decreased free radical production. The present results support the notion that the pharmacological effects of this agent on upper intestinal tissue are more complex than previously thought, and appear to involve both enzymatic and nonenzymatic tissue antioxidants.

Animals↗
PubMed2004

Oxidative stress in nonalcoholic fatty liver disease: pathogenesis and antioxidant therapies.

Nonalcoholic fatty liver disease is a common cause of chronic liver disease, a common finding on liver biopsy in those patients with abnormal blood transaminase levels, and a common cause of cryptogenic cirrhosis in the United States. The prevalence of this disorder is expected to rise with the increase in obesity, and the clinical spectrum can range from simple steatosis (fatty liver) to cirrhosis of the liver. Insulin resistance is thought to be pivotal for the development of steatosis, and oxidative stress may be a potential factor that can promote hepatic necroinflammation and fibrosis. Preliminary studies have examined the role of oxidative stress and antioxidants in animal and human studies of this disorder. Efforts to improve the hepatic antioxidant system could be achieved by optimizing the patient's diet, by supplementation with precursors for antioxidants, or by supplementation with essential metals and/or antioxidants. Randomized, controlled trials are required to examine these potential approaches using patients with this disorder.

Animals↗
PubMed2003

Total antioxidant capacity following extrinsic denervation and small intestinal transplantation in the rat.

Transplantation of small intestine in a rat model has been shown to affect expression of neurochemicals within enteric inhibitory nerves. However, the mechanism for altered expression of inhibitory neurochemicals is uncertain. Based on our previous studies, we hypothesized that small intestinal transplantation would result in altered intestinal levels of antioxidant capacity. Glutathione, total antioxidant capacity, and lipid peroxide levels were measured at 3 months following (1) transection of rat small intestine, (2) transection and extrinsic denervation of rat intestine, and (3) isotransplantation of rat ileum or (4) allotransplantation of rat ileum with cyclosporine therapy to suppress rejection. Glutathione levels were not significantly different among the four groups. There were trends toward increased lipid peroxide levels following isografting and extrinsic denervation. Total antioxidant capacity was increased following extrinsic denervation (P=0.05). Increased intestinal total antioxidant capacity in response to extrinsic denervation may represent a compensatory mechanism for protection against oxidative stress. This result enhances our understanding of the relationship between tissue antioxidant levels and alteration of enteric nerves.

Animals↗
PubMed2003

The changing face of esophageal malignancy.

Concern has been expressed about the rapid increase in the incidence of esophageal carcinoma in the United States. This rise is due to an increase in the number of cases of adenocarcinoma of the esophagus. Because of the relatively small number of cases of esophageal carcinoma, the absolute risk of developing this cancer in the United States remains small. Potential origins for this increase in esophageal adenocarcinoma are examined in this review, including the risk induced by obesity, low dietary antioxidants, high dietary fat, family history of breast cancer, smoking, gastroesophageal reflux, and Barrett's esophagus. The risk of esophageal adenocarcinoma is inversely associated with infection by Helicobacter pylori organisms. A better understanding of risk factors involved in the increased incidence of esophageal adenocarcinoma is important for development of new preventive strategies for this serious disorder.

Adenocarcinoma↗