Regional fat changes following weight reduction from laparoscopic Roux-en-Y gastric bypass surgery.

Fat accumulation in muscle (intermuscular, IM) and viscera plays a role in obesity comorbidities. This study examined the impact of Roux-en-Y gastric bypass (RYGB) surgery in morbid obesity on changes in regional fat and muscle depots, and these body composition markers were correlated with physical function. Women (n = 18) were assessed prior to (baseline) and 12 months following RYGB for regional body composition and physical function. Weight loss from baseline to 12 months was 33.7 (s.e.m. = 1.7)%; total body fat decreased from 86.8 (s.e.m. = 5.8) to 45.8 (s.e.m. = 3.9) kg during follow-up. Differential changes in regional body fat were apparent with a volume loss of 58.4% in visceral fat, 19.8% in abdomen IM fat and 50.7% in thigh IM fat. At baseline, abdomen IM fat volume was related to physical function. There was less loss of abdomen IM fat volume than other depots following surgery; furthermore its relationship with physical function is a novel finding.

Postoperative complications are not increased in super-super obese patients who undergo laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: It has been suggested that super-super obesity (body mass index [BMI] > or =60 kg/m2) increases the risk of complications after laparoscopic Roux-en-Y gastric bypass (LapRYGB). We hypothesized that a higher BMI does not increase risk the morbidity or mortality rate. METHODS: Complication rates for patients with a BMI > or =60 kg/m2 were compared to those for patients with a BMI <60 kg/m2 who underwent LapRYGB during the same time period. Differences between the groups were analyzed by Fisher's exact test, t-tests, and analysis of variance. RESULTS: Forty-five patients with a BMI > or =60 kg/m2 and 640 patients with a BMI <60 kg/m2 underwent LapRYGB. There were no statistically significant differences between the two groups in the complication or mortality rates. Excess weight loss was less, but actual weight lost was greater in the BMI > or =60 kg/m2 group. CONCLUSIONS: The complication and mortality rates are not increased in super-super obese patients who undergo LapRYGB. Acceptable weight loss can be achieved safely in these patients.

Experience with over 3,000 open and laparoscopic bariatric procedures: multivariate analysis of factors related to leak and resultant mortality.

BACKGROUND: Intestinal leak is a potentially lethal complication of Roux en-Y gastric bypass (GBP). Identification of patients at high risk for leak may reduce complication rates of surgeons early in the procedure learning curve. METHODS: A total of 3073 patients who underwent GBP were analyzed using univariate and multivariate logistic regression analyses of the following preoperative factors: hypertension (HTN), diabetes mellitus (DM), sleep apnea (SA), age, gender, weight, body mass index (BMI), and surgery type. Multivariate logistic regression analysis was performed for each procedure type. RESULTS: There were 48 (1.5%) deaths. Independent risk factors for death included leak, weight, procedure type, and HTN. A total of 102 (3.2%) leaks were found. Independent factors for leak included age, male gender, SA, and procedure type. CONCLUSION: The data suggests that older, heavier male patients with multiple comorbid conditions are at increased risk for leak and mortality. Surgeons early in their learning curve should avoid these high-risk patients to reduce complications.

Intravascular hemolysis increases atherogenicity of diet-induced hypercholesterolemia in rabbits in spite of heme oxygenase-1 gene and protein induction.

Free radical mediated oxidation of apoB lipoproteins in the arterial intima appears to contribute to atherogenicity of the entrapped particles. A plausible pathogenic mechanism for oxidation is the one induced by heme leaking from erythrocytes that is then carried into the arterial wall by its high affinity for lipoproteins. In the intima, in the presence of H(2)O(2) secreted by macrophages, heme can be a potent oxidant. To study the role of heme as a promoter of oxidative stress damage in vivo we used a model of intravascular hemolysis (IVH) caused by phenylhydrazine in rabbits with and without diet-induced moderate hypercholesterolemia (MHC). Evaluation of the antioxidant status of plasma indicated that at the end of the treatment period this was compromised by the MHC-IVH. After 10 weeks the animals with combined MHC-IVH showed more of the aorta surface covered by lesions (27%+/-8, mean (SD) than the animals with only MHC (11%+/-7), in spite of having similar plasma levels of VLDL+LDL lipoproteins. The animals with only IVH, as well as the controls, showed minimal lesions (<1%). Heme oxygenase (HO-1) expression in aorta and other tissues was markedly increased in the group with MHC-IVH and it was correlated with the extent of IVH. The data suggest that the oxidative stress associated with IVH potentiates the atherogenicity of moderate hypercholesterolemia and that in spite of a strong induction of HO-1 this is not sufficient to counteract the atherogenicity of the combined condition.

Draculin, the anticoagulant factor in vampire bat saliva, is a tight-binding, noncompetitive inhibitor of activated factor X.

The kinetic mechanism of action of Draculin on activated Factor X (FXa) is established. Draculin inhibits activated Factor X within seconds of incubation at near equimolar concentration (2-6 times on molar basis). Fitting the data to the equation for a tight-binding inhibitor gives a value for K(i)(K(d)) = 14.8+/-1.5 nM. The formation of the Draculin-FXa complex can be explained by a two-step mechanism, where for the first, reversible step, k(on) = 1.117 (+/- 0.169, S.E.M.) x 10(6) M(-1)s(-1) and k(off) = 15.388 (+/- 1.672) x 10(-3) s(-1), while for the second, irreversible step, which is concentration-independent, k(2) = 0.072 s(-1). K(d) obtained from k(off)/k(on) = 13.76 nM. Lineweaver-Burk plot shows a noncompetitive behavior. This noncompetitive mode of inhibition of Draculin is supported by the observation that Draculin, at concentrations giving complete inhibition, does not impair binding of p-aminobenzamidine to FXa. Moreover, under the same conditions, Draculin induces <14% decrease of the fluorescence intensity of the p-aminobenzamidine-FXa complex. We conclude that Draculin is a noncompetitive, tight-binding inhibitor of FXa, a characteristic so far unique amongst natural FXa inhibitors.

Expression of biological activity of draculin, the anticoagulant factor from vampire bat saliva, is strictly dependent on the appropriate glycosylation of the native molecule.

Draculin, a glycoprotein isolated from vampire bat (Desmodus rotundus) saliva, is a natural anticoagulant which inhibits activated coagulation factors IX (IXa) and X (Xa). The observation that under captivity conditions, the anticoagulant activity present in vampire bat saliva is dependent upon the salivation protocol, led us to investigate the possible relationship between the expression of biological activity of native draculin and the post-translational glycosylation of the protein backbone. Daily salivation of vampire bats yields a saliva that progressively decreases in anticoagulant activity, without any significant change in overall protein content, or in the amount of protein specifically recognized by a polyclonal anti-draculin antibody. Anticoagulant activity of the saliva is restored after a 4-day period of rest. Besides the marked difference in anticoagulant activity, purified native draculin, obtained from high- and low-activity saliva, shows significant differences in: (a) composition of the carbohydrate moiety, and (b) Glycosylation pattern. Furthermore, controlled chemical deglycosylation of native draculin, under conditions that do not affect the polypeptide backbone, progressively leads to complete loss of the biological activity. Our present results implicate that correct glycosylation of draculin is a seminal event for the expression of the biological activity of this glycoprotein.

Adenosine A2-receptor activation inhibits neutrophil-mediated injury to coronary endothelium.

Adenosine (ADO) attenuates polymorphonuclear neutrophil (PMN)-mediated damage, partly by inhibiting superoxide anion (O2-.) generation and PMN adherence to the coronary artery endothelium. This study tests the hypothesis that the antineutrophil effects of ADO are mediated by A2-receptor activation. Isolated canine PMN were activated by 100 nM platelet-activating factor (PAF). Compared with untreated activated PMN (100%), ADO attenuated O2-. production (46 +/- 9% of activated PMN), which was mimicked by the A2 agonist CGS-21680 (50 +/- 6% of activated PMN), unaltered by A1-selective antagonism with KW-3902 in the presence of ADO (40 +/- 7%), but blocked by combined A1-A2 blockade with 8-p-sulfophenyl theophylline (8-SPT, 94 +/- 14%). ADO reduced adherence of fluorescent PMN to endothelial surfaces of isolated canine coronary artery segments from 174 +/- 12 to 29 +/- 9/mm2 (P < 0.01), which was unaltered by A1 antagonism (35 +/- 7/mm2) but was reversed by 8-SPT (150 +/- 11/mm2). CGS-21680 inhibited adherence (48 +/- 8/mm2), comparable to that of ADO. Canine coronary artery rings were incubated with activated PMN to induce injury to the endothelium. The concentration of drug required to elicit 50% of maximal relaxation (-log M) derived from dose-relaxation responses to acetylcholine in PMN-damaged rings was significantly (P < 0.05) less in ADO-treated (6.88 +/- 0.08) and CGS-21680-treated (7.12 +/- 0.09) rings than untreated rings (6.54 +/- 0.10). This protection with ADO was reversed by inclusion of 8-SPT (6.49 +/- 0.12) but not KW-3902 (6.96 +/- 0.07). We conclude that ADO reduces PMN-induced coronary endothelial injury by A2-receptor-mediated inhibition of O2-. generation and adherence.