Glomerular hyperfiltration with hyperglycemia in the spontaneously diabetic Torii (SDT) fatty rat, an obese type 2 diabetic model.

Glomerular hyperfiltration is observed in an early stage of kidney diseases including diabetic nephropathy. A better understanding of pathophysiological changes in glomerular hyperfiltration is essential for development of new therapies to prevent kidney disease progression. In this study, we investigated glomerular changes including glomerular filtration rate (GFR) and glomerular size in the Spontaneously Diabetic Torii (SDT) fatty rat, an obese type 2 diabetic model, and we also evaluated pharmacological effects of the sodium glucose cotransporter 2 inhibitor dapagliflozin on the renal lesions. Dapagliflozin was administered to SDT fatty rats from 5 to 17 weeks of age. Blood and urinary biochemical parameters were periodically measured. GFR was determined by transdermal GFR monitor at 16 weeks of age and histopathological analysis was performed at 17 weeks of age. SDT fatty rat developed severe hyperglycemia and exhibited pathophysiological abnormalities in the kidney, such as an increased GFR, glomerular hypertrophy and tissue lesions. Dapagliflozin achieved good glycemic control during the experimental period, inhibited the increase in GFR, and improved histopathological abnormalities in tubules. These results suggest that the SDT fatty rat is a useful model for analyzing the pathogenesis of diabetic nephropathy during its early stage and dapagliflozin improves not only hyperglycemia but also glomerular hyperfiltration and tubule lesions in SDT fatty rat.

Diabetic macular edema-like ocular lesions in male spontaneously diabetic torii fatty rats.

Diabetic macular edema (DME) is a major factor contributing to visual disabilities in diabetic patients, and the number of patients is increasing. Animal models play a key role in the development of novel therapies. In this study, pathophysiological analyses of ocular lesions in Spontaneously Diabetic Torii (SDT) fatty rats were performed. First, vascular endothelial growth factor (VEGF) concentrations in vitreous humor, retinal vascular permeability and retinal thickness were measured in SDT fatty rats (Experiment 1). Furthermore, the pharmacological effects of two anti-diabetic drugs, phlorizin and pioglitazone, on retinal lesions were evaluated (Experiment 2). As results, the SDT fatty rats exhibited VEGF increase in vitreous humor at 8 and 16 weeks of age, and both retinal vascular hyperpermeability and retinal thickening at 16 weeks of age. In particular, the layers between the retinal internal limiting membrane and the outer nuclear layer were thickened. Phlorizin treatment from 4 to 16 weeks of age improved hyperglycemia and normalized retinal thickness; however, the effect of pioglitazone on retinal thickness was not strong despite the normalization of hyperglycemia. These data demonstrate that the male SDT fatty rat is a useful model for developing new therapeutic approaches in DME.

[Current problems in the diagnosis of malignant pleural mesothelioma].

The diagnosis of malignant pleural mesothelioma (MPM) is challenging although MPM is highly aggressive tumor. The current diagnostic gold standard is principally based on light microscopic examination of hematoxylin-eosin and immunohistochemical stains of large tissue sections. However, pathological diagnosis of MPM and classification of histological findings into 1 of the 3 subtypes (epithelial, sarcomatoid, biphasic) are difficult. We studied correlation between initial and final histological diagnosis retrospectively from the records of 21 cases with MPM from 1989 to 2005. The diagnosis of MPM was confirmed by histopathological examination of pleural tissue samples obtained by closed biopsy under computed tomography (CT) or ultrasonography-guided (5 cases), by biopsy under thoracoscopy with local anesthesia (9), by open biopsy via thoracotomy (2), and by video-assisted thoracoscopic surgery (VATS) [5] . Pleural biopsy under those diagnostic methods led to initial diagnosis of MPM in 15 of 21 cases (71.4%) . In 6 cases (28.6%) , initial diagnosis of MPM were not confirmed because of missing malignant tissue (1 case) and relatively small and sarcomatous element (5). In 2 cases examined by closed biopsy and in 3 examined by thoracoscopy under local anesthesia, initial diagnosis of MPM were not confirmed. To get the accurate diagnosis of MPM, obtaining large tissue samples in the initial examination by less invasive thoracoscopy is recommended.

Rapid PCDD/PCDF screening method for fly ash with ion trap MS/MS.

A rapid screening method for the polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDF) in fly ash has been developed. The screening is done in two steps: (a) the extraction by the accelerated solvent extraction and (b) the quantitative measurement by ion trap tandem mass spectrometer (MS/MS). Anhydrous sodium sulfate was added to the fly ash containing activated carbon in order to increase the extraction efficiency. The selectivity of the ion trap MS/MS was confirmed with 13C-labelled internal standard. Then the results of the screening method were compared with those obtained by the conventional analytical method using high-resolution mass spectrometer (HRMS).