The active form of human immunodeficiency virus type 1 protease (HIV-1 PR) is a homodimeric structure in which two subunits are linked through a two-stranded antiparallel beta-sheet consisting of the N- and C-termini of each monomer. To inhibit the dimerization process or disrupt the dimeric interface leading to inactive enzyme, conformationally constrained "molecular tongs" have been designed and synthesized to interfere with one monomer end in a beta-sheet fashion. These molecules are based on two peptidic strands attached to an aromatic scaffold. Inhibitions (submicromolar range) were obtained with molecular tongs containing tripeptidic or tetrapeptidic arms attached to a pyridinediol- or naphthalenediol-based scaffold (Kid = 0.56-4.5 microM at pH 4.7 and 30 degrees C). Kinetic studies are in agreement with an interface inhibition mechanism.
SUMMARY BackgroundIleocaecal resection for penetrating Crohn's disease is still challenging with a high rate of post-operative morbidity and faecal diversion.
Laparoscopic resection of HCC in patients with chronic liver disease has similar results to open resection in terms of postoperative outcomes, surgical margins, and long-term survival.
Hepatic artery (HA) rupture after liver transplantation is a rare complication with high mortality. This study aimed to review the different managements of HA rupture and their results. From 1997 to 2007, data from six transplant centers were reviewed. Of 2649 recipients, 17 (0.64%) presented with HA rupture 29 days (2-92) after transplantation. Initial management was HA ligation in 10 patients, reanastomosis in three, aorto-hepatic grafting in two and percutaneous arterial embolization in one. One patient died before any treatment could be initiated. Concomitant biliary leak was present in seven patients and could be subsequently treated by percutaneous and/or endoscopic approaches in four patients. Early mortality was not observed in patients with HA ligation and occurred in 83% of patients receiving any other treatment. After a median follow-up of 70 months, 10 patients died (4 after retransplantation), and 7 patients were alive without retransplantation (including 6 with HA ligation). HA ligation was associated with better 3-year survival (80% vs. 14%; p = 0.002). Despite its potential consequences on the biliary tract, HA ligation should be considered as a reasonable option in the initial management for HA rupture after liver transplantation.Unexpectedly, retransplantation was not always necessary after HA ligation in this series.
In a methodologically robust trial in the first cohort reported up to date, the regenerative response in obese patients was comparatively slower based on their initial TLV or body weight.
Pancreas-preserving surgical management of the PR after LTPOPF can be performed with acceptable mortality and morbidity. These data suggest that CP should have a more precisely specified role in the management algorithm and should not be performed systematically.
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