A randomised controlled trial of bilateral dual transversus abdominis plane blockade for laparoscopic appendicectomy.

We investigated the effects of pre-operative ultrasound-guided bilateral dual transversus abdominis plane blocks on pain when sitting up and pain at rest after laparoscopic appendicectomy. We allocated 28 participants to injection with 60 ml ropivacaine 0.375% and 28 participants to 60 ml isotonic saline. The median (IQR [range]) cumulative pain scores during the first 12 postoperative hours were less after ropivacaine than saline (maximum 120): on sitting, 34 (19-46 [0-59]) vs 50 (30-59 [0-97]), respectively, p = 0.009; and at rest, 25 (10-33 [0-49]) vs 31 (24-43 [0-72]), respectively, p = 0.035. There were no differences in morphine consumption, nausea, vomiting, time in recovery or time to walk.

Nitric oxide contributes to cytokine-induced apoptosis in pancreatic beta cells via potentiation of JNK activity and inhibition of Akt.

AIMS/HYPOTHESIS: Pro-inflammatory cytokines cause beta cell secretory dysfunction and apoptosis--a process implicated in the pathogenesis of type 1 diabetes. Cytokines induce the expression of inducible nitric oxide (NO) synthase (iNOS) leading to NO production. NO contributes to cytokine-induced apoptosis, but the underlying mechanisms are unclear. The aim of this study was to investigate whether NO modulates signalling via mitogen-activated protein kinases (MAPKs) and Akt. MATERIALS AND METHODS: MAPK activities in INS-1 cells and isolated islets were determined by immunoblotting and in vitro kinase assay. Apoptosis was determined by ELISA measurement of histone-DNA complexes present in cytoplasm. RESULTS: Apoptosis in INS-1 cells induced by IL-1beta plus IFNgamma was dependent on NO production as demonstrated by the use of the NOS blocker NG-methyl-L-arginine. Accordingly, an NO donor (S-nitroso-N-acetyl-D, L-penicillamine, SNAP) dose-dependently caused apoptosis in INS-1 cells. SNAP activated c-Jun N-terminal kinase (JNK) and p38 MAPK, but suppressed the activity of extracellular signal-regulated kinase MAPK. In rat islets, NOS inhibition decreased JNK and p38 activities induced by a 6-h exposure to IL-1beta. Likewise, IL-1beta-induced JNK and p38 activities were lower in iNOS(-/-) mouse islets than in wild-type islets. In human islets, SNAP potentiated IL-1beta-induced JNK activation. The constitutive level of active, Ser473-phosphorylated Akt in INS-1 cells was suppressed by SNAP. IGF-I activated Akt and protected against SNAP-induced apoptosis. The anti-apoptotic effect of IGF-I was not associated with reduced JNK activation. CONCLUSIONS/INTERPRETATION: We suggest that NO contributes to cytokine-induced apoptosis via potentiation of JNK activity and suppression of Akt.