Elevated IgG levels against specific bacterial antigens in obese patients with diabetes and in mice with diet-induced obesity and glucose intolerance

High fat diets increase the risk for insulin resistance by promoting inflammation. The cause of inflammation is unclear, but germfree mouse studies have implicated commensal gut bacteria. We tested whether diet-induced obesity, diabetes, and inflammation are associated with anti-bacterial IgG. Blood from lean and obese healthy volunteers or obese patients with diabetes were analyzed by ELISA for IgG against extracts of potentially pathogenic and pro-biotic strains of Escherichia coli (LF-82 and Nissle), Bacteroides thetaiotaomicron, and Lactobacillus acidophilus, and for circulating tumor necrosis factor α (TNFα). C57Bl/6 mice were fed low- or high-fat diets (10% or 60% kcal from fat) for 10 weeks and tested for anti-bacterial IgG, bodyweight, fasting glucose, and inflammation. Obese diabetic patients had significantly more IgG against extracts of E. coli LF-82 compared with lean controls, whereas IgG against extracts of the other bacteria was unchanged. Circulating TNFα was elevated and correlated with IgG against the LF-82 extract. Mice fed high-fat diets had increased fasting glucose levels, elevated TNFα and neutrophils, and significantly more IgG against the LF-82 extracts. Diabetes in obesity is characterized by increased IgG against specific bacterial antigens. Specific commensal bacteria may mediate inflammatory effects of high-fat diets.     

Morbidity related to defunctioning ileostomy closure after ileal pouch-anal anastomosis and low colonic anastomosis

Purpose  

Defunctioning ileostomies are widely performed in order to prevent or treat anastomotic leakage after colorectal surgery. The aim of the present study was to determine morbidity related to stoma closure and to identify predictive factors of a complicated postoperative course.     

The influence of the segmentation process on 3D measurements from cone beam computed tomography-derived surface models

To compare the accuracy of linear and angular measurements between cephalometric and anatomic landmarks on surface models derived from 3D cone beam computed tomography (CBCT) with two different segmentation protocols was the aim of this study. CBCT scans were made of cadaver heads and 3D surface models were created of the mandible using two different segmentation protocols. A high-resolution laser surface scanner was used to make a 3D model of the macerated mandibles. Twenty linear measurements at 15 anatomic and cephalometric landmarks between the laser surface scan and the 3D models generated from the two segmentation protocols (commercial segmentation (CS) and doctor’s segmentation (DS) groups) were measured. The interobserver agreement for all the measurements of the all three techniques was excellent (intraclass correlation coefficient 0.97–1.00). The results are for both groups very accurate, but only for the measurements on the condyle and lingual part of the mandible, the measurements in the CS group is slightly more accurate than the DS group. 3D surface models produced by CBCT are very accurate but slightly inferior to reality when threshold-based methods are used. Differences in the segmentation process resulted in significant clinical differences between the measurements. Care has to be taken when drawing conclusions from measurements and comparisons made from different segmentations, especially at the condylar region and the lingual side of the mandible.     

The cellular and molecular mechanisms for neutropenia in Barth syndrome

Barth syndrome (BTHS), a rare, X-linked, recessive disease, is characterized by neutropenia and cardiomyopathy. BTHS is caused by loss-of-function mutations of the tafazzin (TAZ) gene. We developed a model of BTHS by transfecting human HL60 myeloid progenitor cells with TAZ-specific shRNAs. Results demonstrate a significant downregulation in TAZ expression, mimicking the effects of naturally occurring truncation mutations in TAZ. Flow cytometry analyses of cells with TAZ-specific, but not scrambled, shRNAs demonstrate nearly twofold increase in the proportion of annexin V-positive cells and significantly increased dissipation of mitochondrial membrane potential as determined by DIOC6 staining. Transfection of TAZ-specific shRNA had similar effects in U937 myeloid cells but not in lymphoid cell lines. Further studies in HL60 myeloid progenitor cells revealed aberrant release of cytochrome c from mitochondria and significantly elevated levels of activated caspase-3 in response to TAZ knockdown. Treatment with caspase-specific inhibitor zVAD-fmk resulted in substantially reduced apoptosis to near-normal levels. These data suggest that neutropenia in BTHS is attributable to increased dissipation of mitochondrial membrane potential, aberrant release of cytochrome c, activation of caspase-3, and accelerated apoptosis of myeloid progenitor cells, and that this defect can be partially restored in vitro by treatment with caspase-specific inhibitors.