Impaired coordination of nutrient intake and substrate oxidation in melanocortin-4 receptor knockout mice

Mutations in the melanocortin-4 receptor (MC4R) are associated with obesity. The obesity syndrome observed in humans with MC4R haploinsufficiency is similar to that observed in MC4R knockout mice: increased longitudinal growth, hyperphagia, and fasting hyperinsulinemia. For comparison with other commonly investigated models of obesity and insulin resistance, we have backcrossed Mc4r-/- mice into the C57BL/6J (B6) background. Female obese Mc4r-/- mice exhibit reduced energy expenditure and an attenuated increase in fatty acid oxidation following exposure to high fat diets compared to obese Lep ob/Lepob mice. The reduced energy expenditure and fatty acid oxidation correlates with changes in hepatic gene expression. The expression of genes involved in fatty acid oxidation increased in obese Lep ob/Lepob mice compared to wild type and obese Mc4r-/- mice. In contrast, a key lipogenic enzyme (fatty acid synthase) is increased in obese Mc4r-/- mice compared to obese Lepob/Lepob mice. Hyperinsulinemia, increased FAS mRNA expression and hepatic steatosis appear to be secondary to obesity in B6 Mc4r-/- mice. However, Mc4r-/- mice in a mixed genetic background develop severe hepatic steatosis at an early age. This might suggest an important role of the MC4R in regulating liver fatty acid metabolism this is masked on the B6 background. Interestingly, the 10- to 20-fold increase in liver triglyceride in this strain of Mc4r-/- mice is not always associated with fasting hyperinsulinemia or increased FAS mRNA expression. This observation suggests changes in liver secondary to triglyceride accumulation lead to hyperinsulinemia and increased hepatic FAS expression in Mc4r-/- mice

Adjuvant Chemoradiation Therapy for Pancreatic Adenocarcinoma: Who Really Benefits?

The role of adjuvant chemoradiation therapy (CRT) in pancreatic cancer remains controversial. The primary aim of this study was to determine if CRT improved survival in patients with resected pancreatic cancer in a large, multiinstitutional cohort of patients

Reversal of Flagellar Rotation Is Important in Initial Attachment of Escherichia coli to Glass in a Dynamic System with High- and Low-Ionic-Strength Buffers

The attachment rates of wild-type, smooth-swimming, tumbly, and paralyzed Escherichia coli to glass was measured at fluid velocities of 0.0044 and 0.044 cms(−1) (corresponding to shear rates of 0.34 and 3.4 s(−1), respectively), in 0.02 and 0.2 M buffer solutions. At the highest ionic strength, we did not observe a significant difference in the attachment rate of wild-type and paralyzed cells at either fluid velocity. However, when the ionic strength was reduced, paralyzed bacteria attached at rates 4 and 10 times lower than that of the wild type under fluid velocities of 0.0044 and 0.044 cms(−1), respectively. This suggested that the rotation of the flagella assisted in attachment. We then compared the attachment rates of smooth-swimming (counterclockwise rotation only) and tumbly (clockwise rotation only) cells to the wild type to determine whether the direction of rotation was important to cell attachment. At 0.0044 cms(−1), the smooth-swimming cells attached at rates similar to that of the wild type in both buffer solutions but significantly less at the higher fluid velocity. Tumbly cells attached at much lower rates under all conditions. Thus, the combination of clockwise and counterclockwise flagellar rotation and their coupling appeared to be important in cell attachment. We considered a number of hypotheses to interpret these observations, including a residence time analysis and a comparison of traditional Derjaguin-Landau-Verwey-Overbeek (DLVO) theory to soft-particle theory

Left-sided pancreatectomy: a multicenter comparison of laparoscopic and open approaches

To compare perioperative outcomes of laparoscopic left-sided pancreatectomy (LLP) with traditional open left-sided pancreatectomy (OLP) in a multicenter experience. LLP is being performed more commonly with limited data comparing results with outcomes from OLP. Data from 8 centers were combined for all cases performed between 2002-2006. OLP and LLP cohorts were matched by age, American Society of Anesthesiologists, resected pancreas length, tumor size, and diagnosis. Multivariate analysis was performed using binary logistic regression. Six hundred sixty-seven LPs were performed, with 159 (24%) attempted laparoscopically. Indications were solid lesion in 307 (46%), cystic in 295 (44%), and pancreatitis in 65 (10%) cases. Positive margins occurred in 51 (8%) cases, 335 (50%) had complications, and significant leaks occurred in 108 (16%). Conversion to OLP occurred in 20 (13%) of the LLPs. In the matched comparison, 200 OLPs were compared with 142 LLPs. There were no differences in positive margin rates (8% vs. 7%, P = 0.8), operative times (216 vs. 230 minutes, P = 0.3), or leak rates (18% vs. 11%, P = 0.1). LLP patients had lower average blood loss (357 vs. 588 mL, P < 0.01), fewer complications (40% vs. 57%, P < 0.01), and shorter hospital stays (5.9 vs. 9.0 days, P < 0.01). By MVA, LLP was an independent factor for shorter hospital stay (P < 0.01, odds ratio 0.33, 95% confidence interval 0.19-0.56). In selected patients, LLP is associated with less morbidity and shorter LOS than OLP. Pancreatic fistula rates are similar for OLP and LLP. LLP is appropriate for selected patients with left-sided pancreatic pathology