Polymyxin B, scavenger of endotoxin, enhances isolation yield and in vivo function of islets.

Collagenase purified from bacteria has been used to isolate islets for transplantation. However, collagenase is contaminated with small amounts of endotoxin, which induces dysfunction or apoptosis of islets. In this study, we investigated the effects of polymyxin B, endotoxin scavenger, on the yield and quality of isolated islets. It is revealed that polymyxin B neutralized endotoxin in vitro and inhibited endotoxin-mediated decreases of the glucose stimulation index. Additionally, adenosine triphosphate (ATP) quantitation, islet regression assay, and caspase-3 activation assay demonstrated that polymyxin B efficiently blocked the toxic effects induced by endotoxin. Thereafter, we isolated mouse islets both with and without polymyxin B and compared total islet equivalents (IEQs), glucose-stimulated insulin release, and ATP content. Polymyxin B enhanced islet recovery, and ATP content of islets, and glucose stimulation index, and reduced TNF-alpha expression of islets. Marginal transplantation (200 IEQs/mouse) under the kidney capsule of diabetic mice induced normoglycemia in 30% of the polymyxin B group, but not in any mouse of control group. This result suggests that islets isolated with polymyxin B more effectively lower blood glucose levels as compared with control islets. Thus, polymyxin B could serve as a useful agent in the protection of islets from endotoxin-induced inflammation and apoptosis.

Fat in liver/muscle correlates more strongly with insulin sensitivity in rats than abdominal fat.

Intrahepatic or intramuscular lipid (IHL/IML) content has been reported to be correlated with insulin resistance. Visceral fat has also been shown to be associated with insulin resistance. Thus, we investigated whether IHL/IML or visceral fat content is more closely associated with insulin resistance. Twenty Sprague-Dawley rats were divided into two groups based on regular chow diet (RCD) or high-fat diet (HFD; 40% fat). The insulin-sensitivity index (ISI) was determined by euglycemic glucose clamp study, the amount of visceral fat by computed tomography (CT), and the IHL/IML content by magnetic resonance spectroscopy (MRS). Weight, food, and water intake, physical activity, energy expenditure, lipid profile, adiponectin, and high-sensitivity C-reactive protein (hsCRP) levels were measured. At the study end point, visceral fat, and the IHL/IML content were higher in the HFD group than in the RCD group. The IHL/IML content was more highly correlated with ISI than was visceral fat amount. Stronger correlations were also found between adiponectin or hsCRP level and IML/IHL content than visceral fat, especially in the HFD group. Furthermore, the IHL/IML content was significantly associated with the ISI in the multiple regression models but visceral fat was not. There was clear discrimination between RCD and HFD groups in scatter plots of IML/IHL against the ISI, but substantial overlap in that of visceral fat against the ISI. This result suggests that IHL/IML contents are closely related with insulin resistance or atherosclerosis and is a better metabolic index of insulin sensitivity than the visceral fat.

Sclerosing hemangioma, presenting as a pneumonic pattern with mucinous adenomatous hyperplasia of the lung.

Pulmonary sclerosing hemangioma is generally considered a rare neoplasm presenting as a solitary benign nodule. During routine medical examination multiple abnormal nodular shadows were detected in the right lower lung field on chest X-ray in a 48-year-old asymptomatic woman. The patient underwent wedge resection for the pulmonary lesion. The resected lung had numerous scattered tiny nodules and small nodules congregated together, forming larger nodules. All of these lesions had typical features of sclerosing hemangioma. The authors call this unusual growth pattern of sclerosing hemangioma a 'pneumonic pattern'. Adjacent to the largest lesion, a relatively well-defined small mucinous lesion composed of mucinous tall columnar cells and basaloid squamous cells was detected. Because this lesion did not have expression of thyroid transcription factor-1, it is described as mucinous adenomatous hyperplasia.