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Background. We investigated the efficacy of a 3C protease inhibitor (3CPI) in a murine coxsackievirus B3 (CVB3) myocarditis model. CVB3 is a primary cause of viral myocarditis. The CVB3 genome encodes a single polyprotein that undergoes a series of proteolytic events to produce several viral proteins. Most of this proteolysis is catalyzed by the 3C protease (3CP). Methods and Results. By way of a micro-osmotic pump, each mouse received 50 mM 3CPI in 100 [mu]L of 100% dimethyl sulfoxide (DMSO) during a 72-hour period. On the day of pump implantation, mice (n = 40) were infected intraperitoneally with 10(6) plaque-forming units of CVB3. For the infected controls (n = 50), the pump was filled with 100% DMSO without 3CPI. The 3-week survival rate of 3CPI-treated mice was significantly higher than that of controls (90% vs 22%; P < .01). Myocardial inflammation, viral titers, and viral RNA levels were also reduced significantly in the 3CPI-treated group compared with these measures in the controls. Conclusions. The protein-based drug 3CPI inhibited the activity of 3CP of CVB3, significantly inhibited viral proliferation, and attenuated myocardial inflammations, subsequent fibrosis, and CVB3-induced mortality in vivo. Thus, this CVB3 3CPI has the potential to be a novel therapeutic agent for the treatment of acute viral myocarditis during the viremic phase. [ABSTRACT FROM AUTHOR]

Background: The clinical application of natural orifice transluminal endoscopic surgery (NOTES) for sigmoidectomy is associated with several difficulties that need to be overcome before wider clinical application of the procedure. The purpose of this study was to evaluate the technical feasibility and safety of transgastric sigmoidectomy in a survival animal model, as well as to evaluate the safety and usability of a custom paired magnetic intraluminal device, which we developed for the NOTES procedure.Methods: Survival experiments were conducted on 24-33-kg dogs. After anesthesia, a gastrotomy was created using double-channel endoscope, and peritoneoscopy was performed. The sigmoid colon was retracted laterally using paired magnetic intraluminal device, the mesocolon was dissected, and the branch vessel was sealed. The anvil was placed into the descending colon through anus. A proximal and distal colonic transection was then performed. The circular stapler was passed through the anus and performed end-to-end anastomosis. Afterwards the specimen was removed through gastrotomy, and the gastric incision was closed. Postoperatively, all dogs were recovered and monitored for well-being during convalescence. Reexploration was practiced under anesthesia 2 weeks after surgery for evaluation of intra-abdominal complications, and intra-peritoneal cultures for microorganism.Results: The mean operative time was 141 (range, 122-157) min. There were no complications or physical evidence of sepsis or bowel obstruction during the observation period. Only one dog exhibited decreased body weight, decreasing to 20.4 kg from 22.4 kg after surgery; all of the other dogs exhibited increased body weight. We observed no evidence of peritonitis, intra-abdominal abscess, bleeding, or organ injury on reexploration conducted on day 14 after surgery.Conclusions: Transgastric NOTES sigmoidectomy is a safe operation technique as evaluated in a dog model. The paired magnetic intraluminal device that was used in this study was useful to avoid an abdominal incision for retracting the sigmoid colon. [ABSTRACT FROM AUTHOR]