Factors associated with hysterectomy among older women from Latin America and the Caribbean.

To identify factors associated with hysterectomy, data collected from 1999-2000 were assessed from seven cities of the Health, Well-Being and Aging in Latin America and the Caribbean Study on 6,549 women, aged 60 years and older. Hysterectomy prevalence ranged from 12.8% in Buenos Aires (Argentina) to 30.4% in Bridgetown (Barbados). The median age for having had a hysterectomy ranged from 45 to 50 years across the cities and was 47 years in the pooled sample. Ethnic differences in hysterectomy rates were partially explained by differences across cities. Factors significantly associated with lower odds for hysterectomy included older age, household crowding conditions, and having public/military or no health insurance, compared to having private health insurance. Women who had three or more children were less likely to have had a hysterectomy, a finding that differs from most previous studies. Socioeconomic position related to rates of hysterectomy in late life rather than hysterectomies earlier in life. However, the nature of these differences varied across birth cohorts. The findings suggested that adverse socioeconomic factors were most likely related to hysterectomy risk by affecting access to health care, whereas parity was most likely acting through an effect on decision-making processes.

Adenosine monophosphate-activated protein kinase activation protects against sepsis-induced organ injury and inflammation.

BACKGROUND: Mortality in sepsis is most often attributed to the development of multiple organ failure. In sepsis, inflammation-mediated endothelial activation, defined as a proinflammatory and procoagulant state of the endothelial cells, has been associated with severity of disease. Thus, the objective of this study was to test the hypothesis that adenosine monophosphate-activated protein kinase (AMPK) activation limits inflammation and endothelium activation to protect against organ injury in sepsis. 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), which is an adenosine monophosphate analog, has been used to upregulate activity of AMPK. Compound C is a cell-permeable pyrrazolopyrimidine compound that inhibits AMPK activity. METHODS: Wild-type mice underwent cecal ligation and puncture (CLP) or sham surgery. Mice were randomized to vehicle, AICAR, or compound C. Mouse kidney endothelial cells were used for in vitro experiments. Renal and liver function were determined by serum cystatin C, blood urea nitrogen (BUN), creatinine, and alanine aminotransferase. Serum cytokines were measured by enzyme-linked immunosorbent assay. Microvascular injury was determined using Evans blue dye and electron microscopy. Immunohistochemistry was used to measure protein levels of phospho-AMPK (p-AMPK), microtubule-associated protein 1A/1B-light chain 3 (LC3), and intracellular adhesion molecule. LC3 levels were used as a measure of autophagosome formation. RESULTS: AICAR decreased liver and kidney injury induced by CLP and minimized cytokine elevation in vivo and in vitro. CLP increased renal and hepatic phosphorylation of AMPK and autophagic signaling as determined by LC3. Inhibition of AMPK with compound C prevented CLP-induced autophagy and exacerbated tissue injury. Additionally, CLP led to endothelial injury as determined by electron microscopy and Evans blue dye extravasation, and AICAR limited this injury. Furthermore, AICAR limited CLP and lipopolysaccharide (LPS)-induced upregulation of intracellular adhesion molecule in vivo and in vitro and decreased LPS-induced neutrophil adhesion in vitro. CONCLUSIONS: In this model, activation of AMPK was protective, and AICAR minimized organ injury by decreasing inflammatory cytokines and endothelial activation. These data suggest that AMPK signaling influences sepsis or LPS-induced endothelial activation and organ injury.

Augmenting autophagy to treat acute kidney injury during endotoxemia in mice.

OBJECTIVE: To determine that 1) an age-dependent loss of inducible autophagy underlies the failure to recover from AKI in older, adult animals during endotoxemia, and 2) pharmacologic induction of autophagy, even after established endotoxemia, is of therapeutic utility in facilitating renal recovery in aged mice. DESIGN: Murine model of endotoxemia and cecal ligation and puncture (CLP) induced acute kidney injury (AKI). SETTING: Academic research laboratory. SUBJECTS: C57Bl/6 mice of 8 (young) and 45 (adult) weeks of age. INTERVENTION: Lipopolysaccharide (1.5 mg/kg), Temsirolimus (5 mg/kg), AICAR (100 mg/kg). MEASUREMENTS AND MAIN RESULTS: Herein we report that diminished autophagy underlies the failure to recover renal function in older adult mice utilizing a murine model of LPS-induced AKI. The administration of the mTOR inhibitor temsirolimus, even after established endotoxemia, induced autophagy and protected against the development of AKI. CONCLUSIONS: These novel results demonstrate a role for autophagy in the context of LPS-induced AKI and support further investigation into like interventions that have potential to alter the natural history of disease.