Repin1 deficiency in adipose tissue improves whole-body insulin sensitivity, and lipid metabolism.

BACKGROUND/OBJECTIVES: Replication initiator 1 (Repin1) gene encodes for a zinc-finger protein and has been implicated in the regulation of adipocyte cell size and glucose transport in vitro. Here, we investigate the consequences of reduced adipose tissue (AT) Repin1 expression in vivo. SUBJECTS/METHODS: We have inactivated the Repin1 gene in adipose tissue (iARep-/-) at an age of 4 weeks using tamoxifen-inducible gene targeting strategies on the background of C57BL/6NTac mice. Furthermore, we differentiated human primary adipocytes derived from subcutaneous AT in vitro and knocked down REPIN1 using siRNA technique to measure glycerol release. RESULTS: Conditional Repin1 inactivation results in decreased AT mass, smaller adipocytes in both, subcutaneous and epigonadal AT compared to controls. Compared to controls, iARep-/- mice were more insulin sensitive, had better glucose tolerance and lower LDL-, HDL- and total cholesterol. Significantly lower AT expression of the Repin1 target genes Cd36 and Lcn2 may contribute to the phenotype of iARep-/- mice. Knockdown of REPIN1 in human in vitro differentiated adipocytes revealed an increased glycerol release. CONCLUSIONS: In conclusion, deficiency of Repin1 in AT causes alterations in AT morphology and function, which may underlay lower body weight and improved parameters of insulin sensitivity, glucose and lipid metabolism.

[Diarrhea as the initial manifestation of medullary thyroid gland carcinoma]. / Diarrhö als Erstmanifestation eines medullären Schilddrüsenkarzinoms.

BACKGROUND: With the differential diagnosis of a diarrhea a lot of causes has to be considered. In very rare cases diarrhea can be the first symptom of a medullary thyroid carcinoma (MTC). CASE REPORT: A 28-year-old patient came to the admission department because of persisting diarrhea. A computerized tomography revealed multiple hepatic and pulmonary metastases. A medullary thyreoid carcinoma was found as the cause of it. The serum calcitonin values were highly increased, later the carcinoembryonal antigen (CEA), too. Sandostatin, a radioimmune therapy (131J-anti-CEA antibody) and adriamycin were therapeutically applied. The patient died 24 months after the occurrence of the first symptoms. CONCLUSION: In case of persisting diarrhea the differential diagnosis of a medullary thyroid carcinoma must be taken into consideration and a calcitonin determination has to be arranged. Yet, typical symptoms like struma nodosa, swollen neck lymph nodes or a CEA increase can still be missing in the initial phase.

Ecstasy pimples - a new facial dermatosis.

Ecstasy (XTC) has become a popular drug in the rave, dance and techno scene. Several severe disorders due to drug addiction have been described but no dermatological symptoms. We report on 2 patients (20-year-old female, 21-year-old male) with medical problems after taking XTC. Both developed a facial rash with reddish pimples after oral intake of XTC. The distribution resembled either periorificial dermatosis or acneiform rash without white- or blackheads. The lesions cleared without specific treatment. We suggest that XTC pimples represent an acneiform dermatosis in young people taking designer drugs. Though the dermatosis itself seems to be mild, it may be a cutaneous marker for drug abuse.

Increased biliary secretion of cysteinyl-leukotrienes in human bile duct obstruction.

BACKGROUND/AIMS: The pathophysiological role of leukotrienes in liver disease is not well understood. Redistribution or enhanced formation in cholestatic states may result in increased hepatic concentrations that are expected to contribute to liver injury. To disclose the potential role of cysteinyl-leukotrienes in chronic liver diseases, we studied biliary and urinary secretion in the model situation of relief of bile duct obstruction. METHODS: Concentrations of cysteinyl-leukotrienes were determined in bile and urine of patients with extrahepatic biliary obstruction in the course of therapeutic decompression by endoscopic or transhepatic techniques. Leukotrienes were measured by radioimmunoassay after HPLC separation. Concentrations of bile acids in bile and serum were measured for comparison. RESULTS: Bile collected 2 h after decompression contained high concentrations of leukotrienes (57.5 +/- 22 microM). Biliary secretion decreased over 24 h reaching equilibrium values after 48-72 h (2.8 +/- 1.7 mM and 6.4 +/- 6.6 microM, respectively). Total bile acid concentration in serum followed a similar time course. In contrast, biliary bile acid concentration showed high interindividual variations. Bile contained all leukotriene C4, D4, E4 and NAc-LTE4, but LTC4 was predominant. Urinary leukotriene secretion in cholestasis (199.7 pmol/mmol creatinine) was less than 7% of maximal biliary secretion. It further decreased to 116.4 pmol/mmol creatinine within 72 h. Urine also contained all species of cysteinyl-leukotrienes, but the relative amounts of LTE4 and NAc-LTE4 were higher than in bile. CONCLUSIONS: Formation of cysteinyl-leukotrienes is increased in obstructive jaundice resulting in increased urinary excretion before and both biliary and urinary excretion after relief of the obstruction. Predominance of LTC4 suggests that the secreted leukotrienes are newly formed. Increased synthesis and retention of hepatic cysteinyl-leukotrienes may contribute to hepatic and extrahepatic consequences of cholestasis.