Sex Differences in Experimentally Induced Colitis in Mice: a Role for Estrogens.

Sex differences have been found in the incidence and progression of inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease. The reported differences in observational studies are controversial, and the effects of sex hormones on the pathogenesis of IBD are not clear. The aim of this study was to analyze sex differences in the progression of experimentally induced colitis. Experimental colitis was induced in adult mice by adding 2% dextran sodium sulfate (DSS) into drinking water. Male and female mice were used as intact, gonadectomized, and supplemented with either estradiol or testosterone. In comparison to males, female mice with induced colitis had significantly longer colon (p < 0.05), lower decrease in body weight (p < 0.001), and lower stool consistency score (p < 0.05). Histopathological analysis showed less inflammatory infiltrates (p < 0.001) and crypt damage (p < 0.001) in female mice. Female mice with colitis had also lower concentration of TNF-α in colon homogenates (p < 0.01). Supplementation with estradiol in ovariectomized mice ameliorated the severity of colitis. Female mice are partially protected against chemically induced colitis. This protection seems to be mediated by estradiol.

Intracardiac ectopic thyroid (struma cordis).

A 67-year-old male with a history of gastrointestinal malignancy was found to have a tumor in the right ventricular outflow tract. The tumor was surgically removed, and the histological diagnosis was thyroid struma. We review the literature on this rare cardiac tumor.

Identification of expanded-criteria donor kidney grafts at lower risk of delayed graft function.

BACKGROUND: Organ shortage leads to the increased use of expanded-criteria donor (ECD) kidneys, which contribute to a higher risk of delayed graft function (DGF) after transplantation. The aim of this study was to determine factors that may better predict the risk of DGF. METHODS: Histologic assessments of donor renal biopsy were used with other clinical variables to predict the risk of DGF after kidney transplantation. The total Banff score equaled the sum of interstitial fibrosis (CI), tubular atrophy, arteriolar hyaline thickening, fibrous intimal thickening (CV), and fraction of sclerotized glomeruli. RESULTS: In total, 126 of 344 patients developed DGF after kidney transplantation. The histologic score for CI, tubular atrophy, and CV and the total Banff score were increased in patients with DGF. Only CI and CV were independent predictors of DGF (P<0.01). A CIV score (CI+CV; odds ratio, 2.68; 95% confidence interval, 1.55-4.66; P<0.001) was superior to the combination of the total Banff score (odds ratio, 1.48; 95% confidence interval, 0.85-2.55; P=NS). A CIV score≥1, donor age more than 51 years, and anoxia donor brain injury were associated with the highest risk of DGF. A CIV<1 identified a subgroup of ECDs at a lower risk of DGF comparable with standard-criteria donors (29.3% vs. 28.4%). CONCLUSIONS: Composite CIV score better identifies ECD kidneys with a lower risk of developing DGF. Morphologic evaluation of ECD kidneys and donor characteristics may improve kidney allocation.

Therapeutic DNA vaccination and RNA interference in inflammatory bowel disease.

Angiogenesis plays a significant role in numerous diseases. Recently, dysbalanced angiogenesis was found to be a component of pathogenesis of inflammatory bowel disease (IBD). Therefore, inhibition of angiogenesis is a novel therapeutic strategy that alleviates the inflammation and clinical outcomes of IBD. Bacteria act as vectors for the delivery of therapeutic sequences, a process that is particularly suitable in IBD, due to the natural occurrence of bacteria in gut. The main focus of the present study was the application of bacterial gene therapy in the modulation of angiogenesis in IBD. As a target molecule we used the main proangiogenic factor, vascular endothelial growth factor (VEGF). Bacterial strain Salmonella typhimurium SL7207 was used as a gene delivery vector for oral application. DNA vaccination and RNA interference were examined and their efficiency in improving the course of the disease in dextran sulfate sodium-induced colitis in mice was compared. The two approaches yielded similar beneficial results in evaluation of the disease activity parameters (stool consistency, weight loss and colon length) as well as VEGF expression and tumor necrosis factor-α (TNF-α). Improvement in all of the parameters compared with the control groups not treated by therapeutic bacterial strains was also observed. All the bacterial groups showed similar improvement in histopathological scoring. Results of this study are consistent with the literature and provide a basis for additional studies on the modulation of angiogenesis in IBD.