University of Texas Medical Branch

About: University of Texas Medical Branch is a education organization based out in Galveston, Texas, United States. It is known for research contribution in the topics: Population & Virus. The organization has 22033 authors who have published 38268 publications receiving 1517502 citations. The organization is also known as: The University of Texas Medical Branch at Galveston & UTMB.

Hydrogen sulfide replacement therapy protects the vascular endothelium in hyperglycemia by preserving mitochondrial function

Abstract: The goal of the present studies was to investigate the role of changes in hydrogen sulfide (H2S) homeostasis in the pathogenesis of hyperglycemic endothelial dysfunction. Exposure of bEnd3 microvascular endothelial cells to elevated extracellular glucose (in vitro “hyperglycemia”) induced the mitochondrial formation of reactive oxygen species (ROS), which resulted in an increased consumption of endogenous and exogenous H2S. Replacement of H2S or overexpression of the H2S-producing enzyme cystathionine-γ-lyase (CSE) attenuated the hyperglycemia-induced enhancement of ROS formation, attenuated nuclear DNA injury, reduced the activation of the nuclear enzyme poly(ADP-ribose) polymerase, and improved cellular viability. In vitro hyperglycemia resulted in a switch from oxidative phosphorylation to glycolysis, an effect that was partially corrected by H2S supplementation. Exposure of isolated vascular rings to high glucose in vitro induced an impairment of endothelium-dependent relaxations, which was prevented by CSE overexpression or H2S supplementation. siRNA silencing of CSE exacerbated ROS production in hyperglycemic endothelial cells. Vascular rings from CSE−/− mice exhibited an accelerated impairment of endothelium-dependent relaxations in response to in vitro hyperglycemia, compared with wild-type controls. Streptozotocin-induced diabetes in rats resulted in a decrease in the circulating level of H2S; replacement of H2S protected from the development of endothelial dysfunction ex vivo. In conclusion, endogenously produced H2S protects against the development of hyperglycemia-induced endothelial dysfunction. We hypothesize that, in hyperglycemic endothelial cells, mitochondrial ROS production and increased H2S catabolism form a positive feed-forward cycle. H2S replacement protects against these alterations, resulting in reduced ROS formation, improved endothelial metabolic state, and maintenance of normal endothelial function.

Induction of Covalent DNA Adducts in Rodents by Tamoxifen

Abstract: The antiestrogen tamoxifen, increasingly used as adjuvant treatment for breast cancer, has been found to covalently modify DNA of rodents. For instance, the liver DNA of female Sprague-Dawley rats treated with a single injection of tamoxifen contained two DNA adducts. Four additional DNA adducts were formed and adduct concentrations increased 5–7- and 10–15-fold after three and six tamoxifen injections, respectively, from levels observed after a single dose. The accumulation of DNA adducts with repeated administrations of tamoxifen to rodents may make this drug a poor choice for the chronic preventative treatment of breast cancer.

Handgrip Strength and Mortality in Older Mexican Americans

Abstract: OBJECTIVES: To examine the association between handgrip strength and mortality in older Mexican American men and women. DESIGN: A 5-year prospective cohort study. SETTING: Five southwestern states: Texas, New Mexico, Colorado, Arizona, and California. PARTICIPANTS: A population-based sample of 2,488 noninstitutionalized Mexican-American men and women aged 65 and older. MEASUREMENTS: Maximal handgrip strength, timed walk, and body mass index were assessed at baseline during 1993/94. Self-reports of functional disability, various medical conditions, and status at follow-up were obtained. RESULTS: Of the baseline sample with complete data, 507 persons were confirmed deceased 5 years later. Average handgrip strength ± standard deviation was significantly higher in men (28.4 kg ± 9.5) than in women (18.2 kg ± 6.5). Of men who had a handgrip strength less than 22.01 kg and women who had a handgrip strength less than 14 kg, 38.2% and 41.5%, respectively, were dead 5 years later. In men in the lowest handgrip strength quartile, the hazard ratio of death was 2.10 (95% confidence interval (CI) = 1.31–3.38) compared with those in the highest handgrip strength quartile, after controlling for sociodemographic variables, functional disability, timed walk, medical conditions, body mass index, and smoking status at baseline. In women in the lowest handgrip strength quartile, the hazard ratio of death was 1.76 (95% CI = 1.05–2.93) compared with those in the highest handgrip strength quartile. Poorer performance in the timed walk and the presence of diabetes mellitus, hypertension, and cancer were also significant predictors of mortality 5 years later. CONCLUSION: Handgrip strength is a strong predictor of mortality in older Mexican Americans, after controlling for relevant risk factors.

Serial MRI and neurobehavioural findings after mild to moderate closed head injury.

Abstract: Fifty patients who sustained mild to moderate closed head injury (CHI) underwent a CT scan, MRI, and neurobehavioural testing. At baseline 40 patients had intracranial hyperintensities detected by MRI which predominated in the frontal and temporal regions, whereas 10 patients had lesions detected by CT. Neurobehavioural data obtained during the first admission to hospital disclosed no distinctive pattern in subgroups of patients characterised by lesions confined to the frontal, temporal, or frontotemporal regions, whereas all three groups exhibited pervasive deficits in relation to normal control subjects. The size of extraparenchymal lesion was significantly related to the initial Glasgow Coma Scale score, whereas this relation was not present in parenchymal lesions. One and three month follow up MRI findings showed substantial resolution of lesion while neuropsychological data reflected impressive recovery. The follow up data disclosed a trend from pervasive deficits to more specific impairments which were inconsistently related to the site of brain lesion. These results corroborate and extend previous findings, indicating that intracranial lesions detected by MRI are present in most patients hospitalised after mild to moderate CHI. Individual differences in the relation between site of lesion and the pattern of neuropsychological findings, which persist over one to three months after mild to moderate CHI, remain unexplained.