Targeting S100A9 Reduces Neutrophil Recruitment, Inflammation and Lung Damage in Abdominal Sepsis.

S100A9, a pro-inflammatory alarmin, is up-regulated in inflamed tissues. However, the role of S100A9 in regulating neutrophil activation, inflammation and lung damage in sepsis is not known. Herein, we hypothesized that blocking S100A9 function may attenuate neutrophil recruitment in septic lung injury. Male C57BL/6 mice were pretreated with the S100A9 inhibitor ABR-238901 (10 mg/kg), prior to cercal ligation and puncture (CLP). Bronchoalveolar lavage fluid (BALF) and lung tissue were harvested for analysis of neutrophil infiltration as well as edema and CXC chemokine production. Blood was collected for analysis of membrane-activated complex-1 (Mac-1) expression on neutrophils as well as CXC chemokines and IL-6 in plasma. Induction of CLP markedly increased plasma levels of S100A9. ABR-238901 decreased CLP-induced neutrophil infiltration and edema formation in the lung. In addition, inhibition of S100A9 decreased the CLP-induced up-regulation of Mac-1 on neutrophils. Administration of ABR-238901 also inhibited the CLP-induced increase of CXCL-1, CXCL-2 and IL-6 in plasma and lungs. Our results suggest that S100A9 promotes neutrophil activation and pulmonary accumulation in sepsis. Targeting S100A9 function decreased formation of CXC chemokines in circulation and lungs and attenuated sepsis-induced lung damage. These novel findings suggest that S100A9 plays an important pro-inflammatory role in sepsis and could be a useful target to protect against the excessive inflammation and lung damage associated with the disease.

[Implementation of endoscopic sleeve gastroplasty in Sweden]. / Endoskopisk sleeve-gastroplastik behandlingsalternativ vid obesitas.

Obesity is a growing health problem and challenge to the health care systems in the western world. Available treatment is limited to lifestyle modifications, cognitive therapy, drugs and bariatric surgery. On one hand, lifestyle changes and pharmacological treatment have very limited long-term effects on obesity. On the other hand, bariatric surgery is effective to maintain long-term weigh reduction but is associated with complications and reaches less than 2 % of patients with indication for surgery. Thus, there is a gap in the management of patients with obesity, and endoscopic bariatric therapies might fill that gap by providing effective, repeatable and reversible alternatives for selected patients with obesity. This article introduces endoscopic methods to achieve weight loss with special focus on endoscopic sleeve gastroplasty (ESG). Data in the literature demonstrates that ESG is effective in reducing total and excessive body weight up to two years after the procedure as well as reducing obesity-related co-morbidity. The challenge is that ESG requires advanced endoscopic skills and is not yet available at many centres. A structured training program is needed to disseminate ESG and offer selected patients with obesity an alternative to bariatric surgery in Europe.

Anastomotic healing in the rat colon: comparison between a radiological method, breaking strength and bursting pressure.

BACKGROUND AND AIMS: While mechanical parameters (breaking strength, bursting pressure) are used to measure colonic anastomotic healing, reported values are inconsistent. This study developed a novel approach to study colonic anastomotic repair and compared it with mechanical methods. METHODS AND MATERIALS: We created standardized four- and eight-suture colonic anastomoses and performed contrast enemas in rats. RESULTS: All eight-suture anastomoses were tight at completion. In contrast, all four-suture anastomoses leaked immediately after the operation, but the integrity increased progressively, and at 12 h all were closed. No changes in breaking strength were observed up to 3 days postoperatively, in contrast to anastomotic bursting pressure which increased progressively over the same period. Integrity and bursting pressure increased in parallel to the anastomotic content of myeloperoxidase (MPO), indicating that neutrophil infiltration is not detrimental in normal healing. Moreover, local irradiation, which enhanced MPO activity, did not increase leakage, suggesting that neutrophil accumulation per se has no effect on the integrity of colonic anastomosis. In addition, administration of 5-fluorouracil, which decreased anastomotic MPO levels, increased anastomotic leakage. CONCLUSION: We present a novel approach to study anastomotic healing using radiological examination. While bursting pressure appears to be suitable for measuring early anastomotic healing in the colon, we demonstrate that breaking strength is not sufficiently sensitive to be used in examination of early healing. Moreover, our data suggest that the acute inflammatory response and associated neutrophil recruitment in the anastomosis does not negatively affect healing in the rat colon.