BVT.2733, a Selective 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor, Attenuates Obesity and Inflammation in Diet-Induced Obese Mice

BACKGROUND: Inhibition of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is being pursued as a new therapeutic approach for the treatment of obesity and metabolic syndrome. Therefore, there is an urgent need to determine the effect of 11β-HSD1 inhibitor, which suppresses glucocorticoid action, on adipose tissue inflammation. The purpose of the present study was to examine the effect of BVT.2733, a selective 11β-HSD1 inhibitor, on expression of pro-inflammatory mediators and macrophage infiltration in adipose tissue in C57BL/6J mice. METHODOLOGY/PRINCIPAL FINDINGS: C57BL/6J mice were fed with a normal chow diet (NC) or high fat diet (HFD). HFD treated mice were then administrated with BVT.2733 (HFD+BVT) or vehicle (HFD) for four weeks. Mice receiving BVT.2733 treatment exhibited decreased body weight and enhanced glucose tolerance and insulin sensitivity compared to control mice. BVT.2733 also down-regulated the expression of inflammation-related genes including monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor alpha (TNF-α) and the number of infiltrated macrophages within the adipose tissue in vivo. Pharmacological inhibition of 11β-HSD1 and RNA interference against 11β-HSD1 reduced the mRNA levels of MCP-1 and interleukin-6 (IL-6) in cultured J774A.1 macrophages and 3T3-L1 preadipocyte in vitro. CONCLUSIONS/SIGNIFICANCE: These results suggest that BVT.2733 treatment could not only decrease body weight and improve metabolic homeostasis, but also suppress the inflammation of adipose tissue in diet-induced obese mice. 11β-HSD1 may be a very promising therapeutic target for obesity and associated disease

Non-Hispanic Black-White disparities in pain and pain management among newly admitted nursing home residents with cancer

Deborah S Mack,1 Jacob N Hunnicutt,1 Bill M Jesdale,2 Kate L Lapane2 1Department of Quantitative Health Sciences, Clinical and Population Health Research Program, Graduate School of Biomedical Sciences, University of Massachusetts Medical School, Worcester, MA, USA; 2Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, MA, USA Background: Racial disparities in pain management persist across health care settings and likely extend into nursing homes. No recent studies have evaluated racial disparities in pain management among residents with cancer in nursing homes at time of admission.Methods: Using a cross-sectional study design, we compared reported pain and pain management between non-Hispanic White and non-Hispanic Black newly admitted nursing home residents with cancer (n=342,920) using the de-identified Minimum Data Set version 3.0. Pain management strategies included the use of scheduled analgesics, pro re nata analgesics, and non-pharmacological methods. Presence of pain was based on self-report when residents were able, and staff report when unable. Robust Poisson models provided estimates of adjusted prevalence ratios (aPR) and 95% CIs for reported pain and pain management strategies.Results: Among nursing home residents with cancer, ~60% reported pain with non-Hispanic Blacks less likely to have both self-reported pain (aPR [Black versus White]: 0.98, 95% CI: 0.97–0.99) and staff-reported pain (aPR: 0.89, 95% CI: 0.86–0.93) documentation compared with Non-Hispanic Whites. While most residents received some pharmacologic pain management, Blacks were less likely to receive any compared with Whites (Blacks: 66.6%, Whites: 71.1%; aPR: 0.98, 95% CI: 0.97–0.99), consistent with differences in receipt of non-pharmacologic treatments (Blacks: 25.8%, Whites: 34.0%; aPR: 0.98, 95 CI%: 0.96–0.99).Conclusion: Less pain was reported for Black compared with White nursing home residents and White residents subsequently received more frequent pain management at admission. The extent to which unequal reporting and management of pain persists in nursing homes should be further explored. Keywords: nursing homes, cancer, pain, pain management, race&nbsp