Alberto Barbera

Inducible nitric oxide synthase knockout mice exhibit resistance to the multiple organ failure induced by zymosan

In the present study, by comparing the responses in wild-type mice (+/+) and mice lacking (-/-) the inducible (or type 2) nitric oxide synthase (iNOS), we investigated the role played by iNOS in the development of non-septic shock. A severe inflammatory response characterized by peritoneal exudation, high peritoneal levels of nitrate/nitrite, and leukocyte infiltration into peritoneal exudate was induced by zymosan administration in iNOS +/+ mice. This inflammatory process coincided with the damage of lung, liver, and small intestine, as assessed by histological examination. Lung, small intestine, and liver myeloperoxidase (MPO) activity, indicative of neutrophil infiltration and lipid peroxidation, were significantly increased in zymosan-treated iNOS +/+ mice. Peritoneal administration of zymosan in the iNOS +/+ mice induced also a significant increase in the plasma levels of nitrite/nitrate and in the levels of peroxynitrite at 18 h after zymosan challenge. Immunohistochemical examination demonstrated a marked increase in the immunoreactivity to nitrotyrosine and to poly ADP-ribose synthetase (PARS) in the lung, liver, and intestine of zymosan-treated iNOS +/+ mice. The intensity and degree of nitrotyrosine and PARS were markedly reduced in tissue section from zymosan-iNOS -/- mice. Zymosan-treated iNOS -/- mice showed a significantly decreased mortality and inhibition of the development of peritonitis. In addition, iNOS -/- mice showed a significant protection on the development of organ failure since tissue injury and MPO were reduced in lung, small intestine, and liver. Furthermore, a significant reduction of suppression of mitochondrial respiration, DNA strand breakage, and reduction of cellular levels of NAD+ was observed in ex vivo macrophages harvested from the peritoneal cavity of iNOS -/- mice subjected to zymosan-induced non-septic shock. In vivo treatment with aminoguanidine (300 mg/kg 1 and 6 h after zymosan administration) significantly prevents the inflammatory process. Taken together, our results clearly demonstrate that iNOS plays an important role in zymosan-induced non-septic shock.

Retromuscular sutured incisional hernia repair: a randomized controlled trial to compare open and laparoscopic approach.

To compare the early and intermediate results of the open and laparoscopic tension-free repair of incisional hernia, 24 patients were randomized prospectively to undergo laparoscopic or open repair of incisional hernia with retromuscular placement of the prosthesis using transabdominal sutures for mesh fixation. All the procedures were completed as planned. The mean duration of surgery was not significantly different between the 2 groups (P=0.15). Time to oral solid food intake was longer in the open group (P=0.002). The analgesic requirement was lower in the laparoscopic group (P=0.05). One patient after open surgery and 2 in the laparoscopic group suffered postoperative complications (P=0.71). Postoperative stay was shorter in the laparoscopic group (P=0.006). No readmission or recurrence was registered within 6 months from surgery in either group. Laparoscopic incisional hernia repair, based on the Rives-Stoppa technique, is a safe, feasible alternative to open techniques. However, larger studies and long-term follow-up are required to further evaluate the true effectiveness of this operation.

Effects of calpain inhibitor I on multiple organ failure induced by zymosan in the rat

ObjectiveZymosan enhances the formation of reactive oxygen species, which contributes to the pathophysiology of multiple organ failure. We investigated the effects of calpain inhibitor I (5, 10, or 20 mg/kg) on the multiple organ failure caused by zymosan (500 mg/kg, administered intraperitoneally as a suspension in saline) in rats. SettingUniversity research laboratory. SubjectsMale Sprague-Dawley rats. InterventionsMultiple organ failure in rats was assessed 18 hrs after administration of zymosan and/or calpain inhibitor I and was monitored for 12 days (for loss of body weight and mortality rate). Measurement and Main ResultsTreatment of rats with calpain inhibitor I (5, 10, or 20 mg/kg intraperitoneally, 1 and 6 hrs after zymosan) attenuated the peritoneal exudation and the migration of polymorphonuclear cells caused by zymosan in a dose-dependent fashion. Calpain inhibitor I also attenuated the lung, liver, and intestinal injury (histology) as well as the increase in myeloperoxidase activity and malondialdehyde concentrations caused by zymosan in the lung, liver, and intestine. Immunohistochemical analysis for nitrotyrosine and for poly(adenosine-disphosphate-ribose) revealed positive staining in lung, liver, and intestine from zymosan-treated rats. The degree of staining for nitrotyrosine and poly(adenosine-disphosphate-ribose) was reduced markedly in tissue sections obtained from zymosan-treated rats administered calpain inhibitor I (20 mg/kg intraperitoneally). Furthermore, treatment of rats with calpain inhibitor I significantly reduced the expression of inducible nitric oxide synthase and cyclooxygenase-2 in lung, liver, and intestine. ConclusionThis study provides the first evidence that calpain inhibitor I attenuates the degree of zymosan-induced multiple organ failure in the rat.

Ultrasound-guided radiofrequency-assisted segmental arterioportal vascular occlusion in laparoscopic segmental liver resection

BackgroundStudies have shown laparoscopic liver resection to be feasible and safe. Segmental hepatectomy is appealing because it allows a reduction of intraoperative blood loss and blood replacement by dividing tissues along the anatomic planes. However, an effective technique that allows the closure of segmental vessels during systematic segmentectomies before resection still is lacking in laparoscopic surgery.MethodsA simple technique guided by intraoperative ultrasound to facilitate laparoscopic liver segmentectomies is described. Coagulative desiccation of the vessels feeding the segment to be resected was induced by introduction of a “cooled-tip” radiofrequency electrode percutaneously under intraoperative ultrasound guidance at the level of the vessels. The intrahepatic parenchymal change induced by the radiofrequency was monitored using intraoperative ultrasound. After the application of energy to destroy the vessels feeding that segment, an area of marked discoloration on the surface of the liver became obvious. Liver parenchymal transection followed without any form of hepatic inflow occlusion.ResultsFor this study, 10 patients underwent a segmental resection using the described technique. The resection time ranged from 40 to 60 min including the time required to destroy the feeding vessels with radiofrequency. The intraoperative blood loss was less than 50 ml and did not necessitate intra- or postoperative blood transfusion. The surgical margins of the specimen were free of disease. There was no morbidity or mortality.ConclusionsThe preliminary experience shows that the reported technique is safe and effective, with the potential to make even difficult laparoscopic liver segmentectomies for segments such as VII and VIII, easier to manage.