Efficacy of the bovine antimicrobial peptide indolicidin combined with piperacillin/tazobactam in experimental rat models of polymicrobial peritonitis.

OBJECTIVE: To investigate the efficacy of piperacillin/tazobactam combined with indolicidin in the prevention of lethality in two rat models of polymicrobial peritonitis. DESIGN: Prospective, randomized, controlled animal study. SETTING: Research laboratory in a university hospital. SUBJECTS: Adult male Wistar rats. INTERVENTIONS: Adult male Wistar rats were given an intraperitoneal injection of 1 mg of Escherichia coli 0111:B4 lipopolysaccharide or had intraabdominal sepsis induced by cecal ligation and puncture. For each model, all animals were randomized to receive isotonic sodium chloride solution intraperitoneally, 1 mg/kg indolicidin, 120 mg/kg piperacillin/tazobactam, and 1 mg/kg indolicidin combined with 120 mg/kg piperacillin/tazobactam. Each group included 20 animals. MEASUREMENTS AND MAIN RESULTS: Main outcome measures were: bacterial growth in blood, peritoneum, spleen, liver, and mesenteric lymph nodes; endotoxin, interleukin-6, and tumor necrosis factor-alpha concentrations in plasma; and lethality. All compounds reduced significantly bacterial growth and lethality compared with saline treatment. Treatment with indolicidin resulted in significant decrease in plasma endotoxin and cytokine levels, whereas piperacillin/tazobactam exerted the opposite effect. The combination between indolicidin and piperacillin/tazobactam proved to be the most effective treatment in reducing all variables measured. CONCLUSION: Indolicidin may have potential therapeutic usefulness alone and when associated with piperacillin/tazobactam in polymicrobial peritonitis.

Tachyplesin III and granulocyte-colony stimulating factor enhance the efficacy of tazobactam/piperacillin in a neutropenic mouse model of polymicrobial peritonitis.

We investigated the efficacy of tazobactam/piperacillin (TZP), tachyplesin III and granulocyte-colony stimulating factor (G-CSF) in an experimental murine neutropenic intraabdominal infection. BALB/c male mice were rendered neutropenic by intraperitoneal administration of cyclophosphamide on days -4 and -2 pre-infection. Septic shock was induced by cecal ligation and puncture. Animals received intravenously isotonic sodium chloride solution (control group C1), 1mg/kg of tachyplesin III, 120 mg/kg of TZP, 0.1mg/kg of G-CSF, tachyplesin III plus TZP, G-CSF plus TZP and finally tachyplesin III plus G-CSF plus TZP, respectively. Lethality, bacterial growth in blood, peritoneum, spleen, liver, and mesenteric lymph nodes, endotoxin, IL-6 and TNF-alpha concentrations in plasma were evaluated. All compounds reduced the lethality when compared to controls. Endotoxin and cytokine plasma levels were significantly higher in TZP-treated animals compared to tachyplesin III-treated animals. Finally, all drug combinations showed to be the most effective treatment in reducing all variables measured. Interestingly, the strongest results concerning the bacterial growth inhibition, lethality and endotoxemia were obtained when the three compounds were contemporaneously administered. The presence of their positive interaction makes tachyplesin III and G-CSF potentially valuable as an adjuvant for antimicrobial chemotherapy of sepsis.

Adjustable totally implantable intragastric prosthesis (ATIIP)-Endogast for treatment of morbid obesity: one-year follow-up of a multicenter prospective clinical survey.

BACKGROUND: The Adjustable Totally Implantable Intragastric Prosthesis (ATIIP)-Endogas is a new mini-invasive technique for the treatment of morbid obesity. The ATIIP is conducted using a surgical and endoscopic procedure. The permanent presence of an air-inflated prosthesis inside the gastric corpus-fundus area and the fixation of the stomach to the abdominal wall are the two main principles in the technique. The prosthesis is connected to a subcutaneous totally implantable system. The aim of the ATIIP is to induce early satiety and reduction of meal intake. This study presents the preliminary results of 1-year follow-up of a multicenter prospective clinical survey. METHODS: From November 2004 to March 2007, 57 patients underwent ATIIP: 28 males (49%) and 29 females (51%), with mean age 43.6 years (18-69) and mean BMI 48.9 (33.7-81.2). Follow-up was 1-28 months. RESULTS: Feasibility was 100%, reproducibility 100%, and acceptability found no vomitting. Mean volume of the prosthesis was 210 ml of air (first 3 months, 40 patients). Mean %EWL was 22.3% (3 mos, 40 pts), 28.7% (6 mos, 38 pts), and 39.2% (12 mos, 20 pts). Early postoperative complication was local subcutaneous infection in 7 pts (12.2%). In 16 pts who had a subcutaneous drain and empirical antibiotic therapy until the 4th postoperative day, local infection occurred in 1 patient (6.2%). Late postoperative complications occurred in 3 pts (5.2%) who developed port erosion. CONCLUSIONS: Preliminary results indicate that the ATIIP is feasible, reproducible, safe with low risk of complications and has encouraging results in weight loss. Morbidly obese patients >60 years old and the super-obese (BMI>50) are specific indications.

Efficacy of tachyplesin III, colistin, and imipenem against a multiresistant Pseudomonas aeruginosa strain.

An experimental study has been performed to compare the in vitro activity and the in vivo efficacy of tachyplesin III, colistin, and imipenem against a multiresistant Pseudomonas aeruginosa strain. In vitro experiments included MIC determination, time-kill, and synergy studies. For in vivo studies, a mouse model of sepsis has been used. The main outcome measures were bacterial lethality, quantitative blood cultures, and plasma levels of lipopolysaccharide, tumor necrosis factor alpha, and interleukin-6. The combination of tachyplesin III or colistin with imipenem showed in vitro synergistic interaction. A significant increase in efficacy was also observed in vivo: combination-treated groups had significantly lower levels of bacteremia than did groups treated with a single agent. Tachyplesin III combined with imipenem exhibited the highest efficacy on all main outcome measurements. These results highlight the potential usefulness of these combinations and provide therapeutic alternatives for serious infections caused by gram-negative bacteria in the coming years.

[Bariatric pacing. A new frontier for the treatment of severe obesity]. / Pacing gastrico. Una nuova frontiera nel trattamento dell'obesità grave.

A new bariatric procedure, gastric myo-electrical stimulation, has been developed. The Implantable Gastric Stimulator (IGS) induces satiety while avoiding the morbidity and mortality of the common restrictive malabsorptive or combination restrictive or malabsorptive procedure. The procedure does not alter normal anatomy. Advantages of IGS therapy are simplicity, a more rapid procedure, a safer procedure and the absence of nutritional side effects associated with some bariatric operations. The devices consists of a stimulation lead implanted in the gastric wall, connected to an electronic pulse generator (Transcend IGS, Transneuronix Inc, Mt. Arlington, NJ, SA) implanted subcutaneously into the abdominal wall. The lead is implanted by laparoscopy into the muscular layer of the lesser curvature of the stomach at the end of the pes anserinus area. The generator is connected (proper connection, was confirmed via radio frequency programming), and implanted subcutaneously. The mechanism of action of the IGS therapy requires a concomitant program of diet and lifestyle modifications in order to optimise the results.