We suggest testing for elevated androgen levels in all women with an abnormal hirsutism score. We suggest against testing for elevated androgen levels in eumenorrheic women with unwanted local hair growth (i.e., in the absence of an abnormal hirsutism score). For most women with patient-important hirsutism despite cosmetic measures (shaving, plucking, waxing), we suggest starting with pharmacological therapy and adding direct hair removal methods (electrolysis, photoepilation) for those who desire additional cosmetic benefit. For women with mild hirsutism and no evidence of an endocrine disorder, we suggest either pharmacological therapy or direct hair removal methods. For pharmacological therapy, we suggest oral combined estrogen-progestin contraceptives for the majority of women, adding an antiandrogen after 6 months if the response is suboptimal. We recommend against antiandrogen monotherapy unless adequate contraception is used. We suggest against using insulin-lowering drugs. For most women who choose hair removal therapy, we suggest laser/photoepilation.
Precision-cut liver slices (PCLS) are increasingly used as a model to investigate anti-fibrotic therapies. However, many studies use PCLS from healthy animals treated with pro-fibrotic stimuli in culture, which reflects only the early stages of fibrosis. The performance of PCLS from cirrhotic animals has not been well characterized and there is no consensus on optimal culture conditions. In this study, we report a method for the collection and culture of cirrhotic PCLS and compare the effect of common culture conditions on viability, function, and gene expression. Additionally, we compared three methods of RNA isolation and identified a protocol with high yield and purity. We observed significantly increased albumin production when cultured with insulin and dexamethasone, and when incubated on a rocking platform. Culturing with insulin and dexamethasone maintained gene expression closer to the levels in fresh slices. However, despite stable viability and function up to 4 days, we found significant changes in expression by day 2. Due to the influence of matrix stiffness on fibrosis and hepatocellular function, it is important to evaluate prospective anti-fibrotic therapies in a platform that preserves tissue biomechanics. PCLS from cirrhotic animals represent a promising tool for the development of treatments for chronic liver disease.
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