Scott T. Rehrig

Complement Inhibitor, Complement Receptor 1-Related Gene/Protein y-Ig Attenuates Intestinal Damage After the Onset of Mesenteric Ischemia/Reperfusion Injury in Mice

Complement receptor 1-related gene/protein y (Crry) is a murine membrane protein that regulates the activity of both classical and alternative complement pathways. We used a recombinant soluble form of Crry fused to the hinge, CH2, and CH3 domains of mouse IgG1 (Crry-Ig) to determine whether inhibition of complement activation prevents and/or reverses mesenteric ischemia/reperfusion-induced injury in mice. Mice were subjected to 30 min of ischemia, followed by 2 h of reperfusion. Crry-Ig was administered either 5 min before or 30 min after initiation of the reperfusion phase. Pretreatment with Crry-Ig reduced local intestinal mucosal injury and decreased generation of leukotriene B4 (LTB4). When given 30 min after the beginning of the reperfusion phase, Crry-Ig resulted in a decrease in ischemia/reperfusion-induced intestinal mucosal injury comparable to that occurring when it was given 5 min before initiation of the reperfusion phase. The beneficial effect of Crry-Ig administered 30 min after the initiation of reperfusion coincided with a decrease in PGE2 generation despite the fact that it did not prevent local infiltration of neutrophils and did not have a significant effect on LTB4 production. These data suggest that complement inhibition protects animals from reperfusion-induced intestinal damage even if administered as late as 30 min into reperfusion and that the mechanism of protection is independent of neutrophil infiltration or LTB4 inhibition.

Surgical Management of Metabolic Syndrome Related to Morbid Obesity.

Current treatment approaches in morbid obesity are multimodal in nature. Combination therapies include increases in moderate-intensity aerobic and resistance exercise; behavioral lifestyle changes to increase compliance with diet and activity recommendations; medical nutrition therapy; intensive medical therapy; and metabolic surgical procedures, such as gastric bypass and vertical sleeve gastrectomy. This article focuses on the preoperative evaluation and proper patient selection for metabolic surgery. The procedures are discussed relative to their anatomy, metabolic mechanism of action, and common adverse effects.

5-year qualitative results of isolated cryosurgical ablation for hepatic malignancy at Walter Reed Army Medical Center1

Cryosurgical ablation (CSA) is an established treatment for primary and metastatic liver malignancies. The study objective was to qualitatively define our patient CSA experience and compare it with the existing literature.A retrospective review was conducted of patients who underwent isolated CSA from September 1995 to April 2000. Data were collected on patient characteristics, tumor characteristics, sequential 12-hour laboratory data, transfusion requirements, and survival data. SPSS 9.0 (SPSS, Chicago, Illinois) was used for data analysis.Twenty-four patients (14 men, 10 women) were studied. Eighty-seven lesions (mean 3.8/patient) were treated. Six patients underwent treatment for primary liver tumors, whereas 16 were treated for metastatic disease. White blood cell count increased 1.7-fold, and platelet count decreased 2.0-fold. Aspartate aminotransferase and alanine aminotransferase increased significantly 42- and 29-fold, respectively. Seven out of 21 (33%) patients required blood transfusion. Our overall complication rate was 25%. Perioperative mortality was 0%. Kaplan-Meier survival analysis revealed an overall survival of 46% at a median follow-up of 33.7 +/- 6.8 months.CONCLUSIONS:Although isolated CSA of hepatic malignancies results in major and minor alterations in serologic parameters, they equate to little clinical significance. Blood product transfusions are necessary in 30% patients post-CSA. Significant perioperative complications occur in 25% of patients. Survival estimates suggest that nearly 50% of patients undergoing CSA can be expected to survive longer than 2 years post-CSA.

L-arginine prevents local and systemic injury induced by mesenteric ischemia/reperfusion

Cigarette smoking is closely associated with the ulcerogenic process in the stomach. During cigarette smoke exposure , there are gas and tar phases. Th is study was designed to investigate the effect of cigarette smok ing on apopto sis in the gastric mucosa and the roles of nitric oxide (NO) in the gas phase and the extracts in the tar phase in this pathological process. In this experiment, sodium nitroprusside (SNP) was used as a donor of NO, a main component in the gas phase , while the two types of extracts in the tar phase (chloroform and ethanol extracts) were isolated from the smoke of burning cigarettes. Male Sprague-Dawley rats (180-220 g) and human gastric epitheli al cell line AGS were used in the study. Programmed cell death was detected with the TUNEL method in the rat gastric mucosa and with the Acridin e Orange stain and measurement of DNA fragments in the AGS cell line. It was found that the apoptotic bodie s in the rat gastric mucosa were significantly elevated after exposure to cigarette smoking. However, neither filtered cigarette smoke, in which the most part of tar phase was blocked, nor oral administration of the two cigarette smoke extracts produced any effect on apoptosis in the rat gastric mucosa. Interestin gly, pretreatment with SNP , the chloroform extract could significantly increa se apoptosis. In vitro study, only the chloroform extract timeand dose-dependently induced DNA fragmentation in AGS cell line. Pretreatment with SNP, which by itself had no effec t on apoptosis , could further increase DNA fragmentation induced by the chloroform ext ract. These findings suggested that NO in the gas phase had synergic effect with the tar phase to induce programmed cell death in gastric cells both in vivo and in vitro .