Prostate effect in dogs with the aldosterone receptor blocker eplerenone.

Eplerenone (Inspra) is an aldosterone receptor antagonist approved for the treatment of hypertension and heart failure after a myocardial infarction. In vitro receptor binding and transactivation studies showed eplerenone had high selectivity for the mineralocorticoid receptor over other steroid receptors (glucocorticoid, androgen, and progesterone). The most sensitive off-target effect of orally administered eplerenone preclinically was prostate atrophy in dogs. Dose-related prostate atrophy was observed at eplerenone dosages ≥15 mg/kg/day for 13 weeks or longer. The no observed adverse effect level (NOAEL) for the prostate effect in dogs was 5 mg/kg/day. The maximal effect was seen by 13 weeks and the atrophy was reversible even after 1 year of daily treatment. An additional study demonstrated dogs with eplerenone-induced prostate atrophy (confirmed by intrarectal ultrasound) had slightly decreased semen volume but no compound-related effects on libido, semen protein content, sperm motility, daily sperm production, or epididymal sperm transit time. Four possible mechanisms for prostate effect were investigated: (1) inhibition of testosterone synthesis and secretion; (2) inhibition of 5α-reductase, the enzyme within the prostate that converts testosterone into the more active growth factor dihydrotestosterone (DHT); (3) competitive antagonism of the androgen receptor; and (4) inhibition of 5α-reductase or competitive antagonism of the androgen receptor by aldosterone, which increased in dogs treated with eplerenone. Data from these studies supported blockade of androgen receptors at suprapharmacological concentrations of eplerenone. Another mineralocorticoid blocker, spironolactone, had greater antiandrogenic activity than eplerenone both in vivo and in vitro, and it has well known clinically significant antiandrogenic effects in humans, whereas eplerenone does not.

Predicting urban design effects on physical activity and public health: A case study.

With increasing global concerns about obesity and related health effects, tools to predict how urban form affects population physical activity and health are needed. However, such tools have not been well established. This article develops a computer simulation model for forecasting the health effects of urban features that promote walking. The article demonstrates the model using a proposed small-area plan for a neighborhood of 10,400 residents in Raleigh, North Carolina, one of the fastest-growing and most sprawling U.S. cities. The simulation model predicts that the plan would increase average daily time spent walking for transportation by 17 min. As a result, annual deaths from all causes are predicted to decrease by 5.5%. Annual new cases of diabetes, coronary heart disease, stroke, and hypertension are predicted to decline by 1.9%, 2.3%, 1.3%, and 1.6%, respectively. The present value of these health benefits is $21,000 per resident.

Value of an infection control practitioner in improving infection control practices at ambulatory sites.

Little information exists on the state of infection control (IC) practices in ambulatory sites. In preparation for a JCAHO survey, 62 ambulatory sites were visited to monitor and improve IC practices. A dedicated IC practitioner was instrumental in improving practices at ambulatory sites and in successfully completing a JCAHO survey.