Low Dose Ketoconazole is an Effective and a Relatively Safe Alternative in the Treatment of Hirsutism*

Summary: Efficacy, clinical and hormonal effect of ketoconazole in 400 mg/day dose was tested in a prospectively-designed study. Twenty four patients with hirsutism according to the Ferriman and Gallwey score (>8) and elevated blood androgen levels were administered 400 mg/day ketoconazole for 6 months. Basal and posttherapy early follicular phase androgens and biochemical parameters were evaluated. In 22 patients significant improvement and in 2 slight improvement was seen in subjective complaints. No side-effects were observed in these patients other than 2 cases of pruritus (transient), 2 mild gastric upset and 1 mastodynia. All patients completed the study. Low dose ketoconazole seems to be effective in the treatment of hirsutism with relatively few side-effects but still should be reserved as an alternative choice due to the potential for deleterious hepatic effects.     

Can angiotensin converting enzyme inhibitors prevent postoperative adhesions?

BACKGROUND: Peritoneal adhesions are pathological fibrotic bands developing after mesothelial damage. Transforming growth factor beta-1 (TGF-beta1) has mitogenic activities for macrophages and fibroblasts. Over-expression of TGF-beta1 has been implicated in the pathogenesis of several fibrotic disorders. Angiotensin II increases the expression of the TGF-beta1 in fibroblasts. The aim of the study was to investigate the effect of angiotensin converting enzyme inhibitor (ACE) on intraperitoneal adhesions. MATERIALS AND METHODS: Thirty male Wistar albino rats were divided into two groups. In the first procedure, laparotomy was performed through a 3-cm midline incision. Ileum was divided above 10 cm from ileocecal valve and a single-layer ileoileal anastomosis was performed. Although no treatment was given to rats in group 1, lisinopril (an ACE inhibitor) was given to rats in group 2 for postoperative 7 days in drinking water. Estimated amount of supplied lisinopril was 6.5 mg/kg/day. On postoperative 8th day, relaparotomy was performed and adhesions were evaluated. At the same time, blood samples were taken for TGF-beta1 measurements. RESULTS: Adhesion severity was significantly less in the ACE inhibitor group (P < 0.001). While mean TGF-beta1 level was 860.3 +/- 108.1 pg/dl (mean +/- SD) in control group, it was 335.8 +/- 52.4 pg/dl in ACE inhibitor group (P < 0.001). There was a significant correlation between serum TGF-beta1 levels and grade of adhesions (r = 0.948). CONCLUSION: It was concluded that ACE inhibitors might be useful for preventing peritoneal adhesions.     

Trefoil factor expression in biliary epithelium of graft-versus-host disease of the liver after allogeneic hematopoietic cell transplantation

BACKGROUND: The aims of this study were to determine the presence of trefoil factor family-3 (TFF3) expression in biliary epithelial cells (BECs) of chronic graft-versus-host disease (cGVHD) of the liver after allogeneic hematopoietic cell transplantation, to compare such expression in chronic liver diseases (CLD) with/without predominantly biliary disease, and to assess the effect of bile duct injury on the degree of TFF3 expression in BECs of cGVHD. METHODS: A total of 82 paraffin-embedded liver biopsy samples were reviewed. These samples were basically divided into two distinct groups according to the presence of ductal injury: group 1 with CLD and predominantly biliary disease (n=26: 17 cGVHD and 9 primary biliary cirrhosis [PBC]) and group 2 with CLD and predominantly parenchymal liver disease (n=56: 20 steatohepatitis and 36 chronic viral hepatitis). Group 2 was used as the controls. Immunohistochemistry was performed using a polyclonal anti-TFF3 antibody. Real-time quantitative PCR was used for the detection of TFF3 mRNA expression. RESULTS: Positive TFF3 immunohistochemical staining and the presence of TFF3 messenger RNA gene expression was demonstrably higher in group 1 than that in group 2 (P<0.0001 and P<0.05, respectively). No significant difference in terms of positive TFF3 stained BECs between GVHD and PBC samples was observed (P>0.05). The extent of TFF3 expression in GVHD samples with severe ductal injury were significantly more common than that of GVHD samples with mild/moderate ductal injury (P<0.0001). CONCLUSIONS: The expression of TFF3 in cGVHD of the liver is increased in response to bile duct damage and repair. Such expression seems to be related the severity of ductal injury.