ABSTRACT
Renal ischemia-reperfusion injury (IRI) is a common cause of renal dysfunction and renal failure. Histone/protein deacetylases (HDACs) regulate gene accessibility and higher order protein structures and may alter cellular responses to a variety of stresses. We investigated whether use of pan- and class-specific HDAC inhibitors (HDACi) could improve IRI tolerance in the kidney. Using a model of unilateral renal IRI, we investigated early renal function after IRI, and calculated fibrosis after IRI using an automated scoring system. We found that pan-HDAC inhibition using trichostatin (TSA) yielded significant renal functional benefit at 24-96 hours (p < 0.001). Treated mice developed significantly less fibrosis at 30 days (p < 0.0004). Class I HDAC inhibition with MS-275 yielded similar effects. Protection from fibrosis formation was also noted in a cold ischemia transplant model (p < 0.008) with a trend toward improved cold ischemic survival in TSA-treated mice. These effects were not accompanied by induction of typical ischemic tolerance pathways or by priming of heat shock protein expression. In fact, heat shock protein 70 deletion or overexpression did not alter renal ischemia tolerance. Micro-RNA 21, known to be enhanced in vitro in renal tubular cells that survive stress, was enhanced by treatment with HDACi, pointing to possible mechanism.
Subject(s)
Fibrosis/prevention & control , Histones/metabolism , Ischemia/prevention & control , Kidney/blood supply , Reperfusion Injury/prevention & control , Animals , Female , Histone Deacetylase Inhibitors/pharmacology , Mice , Mice, Inbred C57BLABSTRACT
BACKGROUND: Improving pregnancy outcomes for minorities is a major goal of health providers and policy makers. Since most strategies involve an intervention during pregnancy, it is important to know where minority women with various characteristics receive prenatal care and why. Our purpose was to evaluate services of prenatal care for white, African-American, Mexican-American, and Puerto Rican women. METHODS: The National Maternal and Infant Health Survey (1988) was used to ascertain age, income, marital status, education level, and source of funding of the study population of 21,000 women, who were assigned to an ethnic group based on self-indentification in the survey. The sources of prenatal care were classified as private (private physician, nurse-midwife, health maintenance organization) or public (state or local health department, community health center, hospital-based clinic). RESULTS: When categorized by ethnic group alone, 78 percent of white women received private care compared with 51 percent of Mexican-American women, 44 percent of African-American women, and 37 percent of Puerto Rican women. Private health insurance was held by 78 percent of white, 50 percent of African-American, 49 percent of Mexican-American, and 47 percent of Puerto Rican women. Of those with private insurance, 86, 62, 69, and 59 percent, respectively, received private care. Of white women with Medicaid funding, 52 percent received private care as opposed to a range of 20 to 42 percent for minority women. CONCLUSIONS: Substantial differences in sources of prenatal care exist between white and minority women and between different minority groups, suggesting that policy makers and health caregivers should tailor prenatal care intervention to the needs of specific minority populations.