Modulation of IL-2 expression after uptake of hepatitis C virus non-enveloped capsid-like particles: the role of p38 kinase.

Hepatitis C virus (HCV) has been shown to actively replicate in cells of the immune system, altering both their function and cytokine expression. Naked nucleocapsids have been reported in the serum of infected patients. We investigated interference of recombinant non-enveloped capsid-like particles with signaling pathways in T cells. HCV non-enveloped particles (HCVne) internalization was verified in Jurkat and Hut 78 T cells, as well as primary human peripheral blood and intrahepatic mononuclear cells. HCVne uptake leads to activation of the MAPKs-p38 signaling pathway. Using specific phosphoantibodies, signaling pathways inhibitors, and chemical agents, it was demonstrated that p38 activation in T cells correlated with IL-2 transcriptional activation and was accompanied by a parallel increase of IL-2 cytokine secretion. c-fos and egr-1, two transcription factors, essential for IL-2 promoter activity, were also found to be elevated. We propose that HCVne uptake by T lymphocytes results in increased MAPKs-p38 activity and IL-2 expression, thus altering the host immune response.

Laparoscopic cholecystectomy in cirrhotic patients with symptomatic gallstone disease.

BACKGROUND: The aim of this study was to evaluate the outcome in patients with liver cirrhosis who underwent laparoscopic cholecystectomy for symptomatic gallstone disease. METHODS: Retrospective analysis of prospectively collected data of 34 patients operated between March 1998 and April 2006. RESULTS: There were 19 male and 15 female patients with a median age of 62 years. Cirrhosis aetiology was viral hepatitis in 25 patients, alcohol in 6, primary biliary cirrhosis in 2 and in 1 patient the cause was not identified. Twenty-three were classified as Child-Pugh-Turcotte stage A and 11 as Child-Pugh-Turcotte stage B. The median Model For End-Stage Liver Disease score was 12. Median operating time was 96 min. In three patients there was conversion to open cholecystectomy. Postoperatively, one patient died and six more patients had complications. Median postoperative stay was 3 days. Patients with acute cholecystitis did not have increased morbidity, but had significantly longer hospital stay. CONCLUSION: Laparoscopic cholecystectomy can be carried out with acceptable morbidity in selected patients with well-compensated Child A and B stages liver cirrhosis. Patients with evidence of significant portal hypertension and severe coagulopathy should avoid surgery.

The use of spray electrocautery to control presacral bleeding: a report of four cases.

Bleeding originating from the presacral venous plexus during pelvic operations is difficult to control, constituting a potentially life-threatening complication. Although suture ligatures, packing, and placement of tacks are established hemostatic techniques, they are often proved to be ineffective. We report a simple novel technique using spray diathermy for managing this severe complication. We have applied our method in four patients, two undergoing low anterior resection, and the others undergoing abdominoperineal resection for rectal cancer, that manifested severe presacral bleeding during rectal mobilization. Electrocautery at spray setting was applied slightly above the target bleeders at the presacral fascia, delivering a high-frequency electrical current in combination with drainage suction. In all cases, the method resulted in successful hemostasis. Applying spray electrocautery is a simple and effective method for controlling presacral bleeding. The advantages of using such a method instead of conventional hemostatic techniques include the option of varying the degree of haemostatic effect by altering the frequency and the volume of electric current.