On the contrary, Graebe et al.[18] showed that chronic NOS inhibition by L-NAME led to marked increase in NHE3 exchanger and Na+ K+ ATPase protein levels in proximal convoluted tubules. This leads to sodium and water retention in the kidney and can worsen
ascites. In brief, RAD001 the use of nitrovasodilators can worsen systemic hemodynamics and probably lymphatic drainage. It is apparently a “catch-22” situation and much more needs to be learned about the two circulatory beds. In the current study, the use of L-NMMA led to suppression of the NO production in the LySECs and improved the lymphatic drainage with reduction in ascites. It is not known whether reduction in NO in the lymphatic system by L-NMMA is concurrently occurring in the portal circulation to the same degree and does it lead to increased vascular resistance and raised portal pressure.
If the data provided by the Spanish group stands the test of time in human studies, the drugs working in one area may not be suitable for Olaparib the other regional bed and we would need different strategies for the two circulatory beds (Fig. 1). Ribera et al. have resurrected the forgotten importance of lymphatic circulation in cirrhotic portal hypertension and also have rekindled the interest in NO and NO donors and inhibitors in the management of portal hypertension. They need to be complimented for having provided cellular and molecular insights into the pathophysiology of lymphatic dysfunction in portal hypertension by ascertaining a central role of NO to intrinsic lymphatic pump failure. Tacrolimus (FK506) It would be interesting to study the role of other vasodilatory molecules such as carbon monoxide and H2S in these two regional beds. The current study brings enthusiasm to the field of portal hypertension and has opened new vistas for further investigations and better therapeutic horizons. Shiv Kumar Sarin, M.D., D.M., F.N.A., D.Sc. Chandan Kumar, M.D. Department
of Hepatology Institute of Liver and Biliary Sciences New Delhi, India “
“Background and Aim: In an earlier study, we found that hepatitis C virus core protein, HCV-C, participated in the malignant transformation of HCV-C transfected normal human biliary epithelial (hBE) cells by activating telomerase. Here we further investigated the signaling of the malignant transformation. Methods: Reverse transcription-polymerase chain reaction (RT-PCR), western blotting and immunoprecipitation were used to analyze the expression of HCV-C, human telomerase reverse transcriptase (hTERT), nuclear factor-κB (NF-κB) and NF-κB inhibitor alpha (IκBα) genes and the phosphorylation level of IκBα protein. Electrophoretic mobility shift assays (EMSA) and NF-κB-linked luciferase reporter assays were carried out to measure NF-κB activity. Results: The expression of HCV-C and hTERT was detected only in HCV-C-transfected hBE (hBE-HCV-C) cells but not in vector-transfected or parental hBE cells.