Previously, increased diameter and enhanced myogenic tone were seen after 2-week 45o head-up (HUT2) in the rat. We studied the reversibility and the effect of extended tilt on this phenomenon using two experimental groups: HUT2 plus 2-week horizontal (HUT2HOR2), and 4-week tilting (HUT4). 4-weeks in normal cages (NC4) served as control. Diameter of saphenous vein (SV) in 2-20 mm Hg pressure range, wall and media thickness, endothelial and smooth muscle cell densities, and cell proliferation were measured. The diameter of SV from HUT4 was significantly larger compared with HUT2HOR2 or NC4 within the whole pressure range both in Krebs-Ringer (870.4+/-21.3 vs. 778.2+/-24.9 and 771.6+/-28.1 microm at 10 mm Hg, respectively) and in Ca(2+)-free solution. Myogenic and norepinephrine-induced vascular tone, wall and media thickness did not differ among the three groups. Endothelial cell density decreased in HUT4 (10.7+/-1.2) vs. HUT2HOR2 (15.1+/-1.0) and NC4 (15.3+/-0.6), while that of smooth muscle was unchanged. No cell proliferation marker was seen. In conclusion, both increased diameter and enhanced myogenic tone of SV seen in HUT2 proved to be reversible. HUT4 resulted in increased SV diameter, similarly to HUT2, however, vascular tone was not amplified. This suggests that a prolonged orthostatic load may readjust the function of smooth muscle.

04B. Molecular and cellular biology (b) Biliary tract pathophysiology$121 liver, allowed to adhere in culture and submitted to a catalytic system, which reduces oxygen concentration to less than 1% within 30 minutes.Gene expressions were assessed by quantitative real-time RT-PCR.Results: In vivo, 24 hours after the onset of arterial liver ischemia in rats, cholestatic changes in serum were detected together with a decrease in bile flow and in bile acid and bicarbonate output in bile.No regurgitation of fluorescent ursodeoxycholic acid was detected, eliminating bile duct leakage as a major mechanism of cholestasis in this model.VEGF, a hypoxia-regulated gene, was induced in both hepatocytes and cholangiocytes, as ascertained by immunohistochemistry. Concomitantly, hepatic mRNA levels of ntcp, bsep and mrp2 were significantly reduced (by 70%, 50% and 70%, respectively), whereas Cftr mRNA levels were increased (by more than 4 fold), even though ductular reaction was not yet present at this time.In vitro, hypoxia caused a decrease in ntcp, bsep and mrp2 transcripts in hepatocytes (by 70%, 80% and 70%, respectively), and an increase in cftr transcripts (by 3 fold), associated with a rise in cAMP (by more than 10 fold) in cholangiocytes.Conclusion: These results demonstrate that hypoxia induces differential regulations in the expression of hepatobiliary transporters.The downregulation of transporters involved in bile salt-dependent and -independent secretion in hepatocytes may contribute to cholestasis.By contrast the upregulation of CFTR in cholangiocytes may, together with increased cAME a major regulator of CFTR expression and activity, and with subsequent ductular proliferation, provide a defense mechanism.

Introduction and Aim: Cell adhesion molecules play an important role in carcinogenesis, especially claudins, being part of tight junctions. The importance of certain claudins in development of several tumors has been shown, and some of them have even been suggested as a future therapeutic target. For this reason, the aim of our study was to analyse the expression of claudins in biliary cancers (BCs).

Endocrine tumours arising from the extrahepatic biliary ductal system are rare with a 0.2–2% frequency of all extrahepatic neoplasms. At this time, 34 cases of such endocrine tumours had been described. Among these neoplasms, only 17 cases were cancers. The most frequent clinical and biochemical signs of these cancers were jaundice, right subcostal pain and elevation in cholestatic liver enzyme levels. Preoperatively, cholangiography and CT-scan were found to be highly non-specific for the final diagnosis; however, these diagnostic procedures had been preformed in less than 6% of all cases. Percutaneous needle biopsy and endoscopic brush cytology provided the right preoperative diagnosis. With curative surgery the tumour-free survival can be ranged from 5 months up to 20 years, which suggests a more benign clinical course than in cholangiocancer.