Upregulation of clusterin occurs in several renal diseases and models of nephrotoxicity, but whether this promotes injury or is a protective reaction to injury is unknown. Here, in the mouse unilateral ureteral obstruction model, obstruction markedly increased the expression of clusterin, plasminogen activator inhibitor-1 (PAI-1), type I collagen, and fibronectin. Compared with wild-type mice, clusterin-deficient mice exhibited higher levels of PAI-1, type I collagen, and fibronectin and accelerated renal fibrosis in response to obstruction. In cultured rat tubular epithelium-like cells, adenovirus-mediated overexpression of clusterin inhibited the expression of TGF-b-stimulated PAI-1, type I collagen, and fibronectin. Clusterin inhibited TGF-b-stimulated Smad3 activity via inhibition of Smad3 phosphorylation and its nuclear translocation. Moreover, intrarenal delivery of adenovirus-expressing clusterin upregulated expression of clusterin in tubular epithelium-like cells and attenuated obstruction-induced renal fibrosis. In conclusion, clusterin attenuates renal fibrosis in obstructive nephropathy. These results suggest that upregulation of clusterin during renal injury is a protective response against the development of renal fibrosis.
BackgroundAdrenal incidentaloma is an adrenal neoplasm frequently encountered in clinical practice for which detection rates have recently increased. We describe here the clinical characteristics of adrenal incidentalomas.MethodsA retrospective study was performed examining the age, sex, location, size, function, and the histological findings for 348 patients with an adrenal mass discovered incidentally on computed tomography (CT) undertaken for health examination or nonadrenal disease from August 2005 to May 2012.ResultsPatients consisted of 156 males (44.8%) and 192 females (55.2%), aged between 20 and 86. Adrenal masses were most commonly found in patients in their sixth decade (32.5%). Regarding the location of the masses, 62.0% were found in the left adrenal gland, 30.2% were found in the right, and 7.8% were found bilaterally. Of all of the masses analyzed, 87.1% were 1 to 4 cm in size, and an adenoma-like appearance was the most common finding (75.3%) seen on CT scans. Hormonal analysis showed that 82.2% of the masses were nonfunctioning, 6.0% were diagnosed as subclinical Cushing's syndrome, 4.6% were aldosterone-producing adenomas, and 7.2% were pheochromocytomas. Adrenalectomy was performed in a total of 69 patients having adenoma (50.7%), pheochromocytoma (24.6%), and carcinoma (4.3%).ConclusionThe characteristics of benign, malignant, nonfunctional, and functional adrenal masses that were incidentally found at our hospital were similar to those presented in other studies.
BackgroundProprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating protein that promotes degradation of the low density lipoprotein receptor. PCSK9 has emerged as a target for lipid-lowering therapy, but the predictive value of the serum level of PCSK9 for the severity of coronary disease is largely unknown.MethodsFrom December 2009 to July 2012, 121 individuals who underwent coronary angiography (CAG) because of clinically suspected acute coronary syndrome were enrolled in this study. Serum levels of PCSK9 and metabolic parameters were measured. SYNTAX (SYNergy between percutaneous coronary intervention with [paclitaxel-eluting] TAXUS stent and cardiac surgery) and GRACE (Global Registry of Acute Coronary Events) scores were calculated.ResultsIndividuals with CAG lesions (n=100) had significantly higher levels of PCSK9 than those without lesions (n=21). The study population was stratified into three groups according to serum levels of PCSK9. The odds radio for occurrence of one or more CAG lesions was significantly higher in the group with the highest level of PCSK9 (odds ratio, 7.468; P=0.011) than in the group with the lowest level of PCSK9. Serum PCSK9 was positively associated with the number of involved coronary arteries. Multivariable linear regression indicated that levels of PCSK9 were positively correlated with GRACE risk scores and SYNTAX scores.ConclusionSerum PCSK9 concentrations are higher in patients with coronary artery lesions, and are associated with SYNTAX and GRACE scores, suggesting that PCSK9 is a potential biomarker of the severity of coronary artery disease.
BackgroundThe aim of the present study was to determine the population-based prevalence of diabetes mellitus (DM) and prediabetes in a rural district of Daegu City, Korea.MethodsBetween August and November 2003, a community-based health survey of adults aged 20 years and older was performed in the rural district of Dalseong-gun in Daegu City. A total of 1,806 of all eligible individuals agreed to participate. Fasting plasma glucose was measured in all participants. Two hour oral glucose tolerance was measured in the 1,773 participants for whom there was neither an established diagnosis of DM nor evidence of DM according to fasting glucose levels. The prevalence of DM and prediabetes was determined according to the 2003 criteria of the American Diabetes Association. Subjects with prediabetes were classified into one of three categories of glucose intolerance: isolated impaired fasting glucose (IFG); isolated impaired glucose tolerance (IGT); or combined IFG and IGT.ResultsThe prevalence of DM was 12.2%. The highest prevalence rates were observed in subjects in their seventies. A total of 34.7% of all subjects who were assigned a diagnosis of DM in the present study had not been diagnosed previously. The prevalence of prediabetes was 22.7%. The highest prevalence rates were observed in subjects in their fifties.ConclusionThe present study identified prevalence rates of 12.2% for DM (age-standardized prevalence rate [ASR], 6.8%), and 22.7% for prediabetes (ASR 18.5%). These results emphasize the need for community health promotion strategies to prevent or delay the onset of DM in individuals with prediabetes.
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