Transforming growth factor-beta 1 (TGF-beta 1) is a primary determinant of the mesangial expansion observed in diabetic nephropathy. In this study, we quantitated the levels of intraglomerular TGF-beta 1 mRNA in patients with diabetes mellitus using a competitive polymerase chain reaction (PCR) method. Renal biopsy specimens were obtained from 29 patients with non-insulin-dependent diabetes mellitus. Total RNA was extracted from the glomeruli and reverse transcribed into cDNA with reverse transcriptase. To prepare samples containing identical amounts of beta-actin cDNA (8 pg), we performed competitive PCR by co-amplifying mutant templates of beta-actin with a unique EcoRI site. We also used this competitive PCR method to measure TGF-beta 1 cDNA by co-amplifying mutant templates of TGF-beta 1. We observed higher expression of TGF-beta 1 mRNA in glomeruli of patients with diabetic nephropathy as compared with normal glomeruli. Intraglomerular TGF-beta 1 mRNA was elevated, even in the early stage of diabetic nephropathy. Moreover, levels of intraglomerular TGF-beta 1 mRNA correlated with values of HbA1c. These data suggest that hyperglycemia induces intraglomerular TGF-beta 1 mRNA expression in vivo, and that TGF-beta 1 overproduction may be associated with the progression of diabetic nephropathy.

Background: Oxidative stress is an important pathogenetic factor in underlying diabetic complications. Recently, 8-hydroxy-2′-deoxyguanosine (8-OHdG) has been reported to serve as a new sensitive biomarker of the oxidative DNA damage in vivo. We studied the relationship between oxidative DNA damage and tubulointerstitial injury in patients with diabetic nephropathy. Methods: Type 2 diabetic patients (n = 25) and healthy control subjects (n = 20) were studied. The urine concentrations of 8-OHdG were measured by a competitive ELISA. The severity of the glomerular changes was graded using Gellman’s criteria, and the severity of the tubulointerstitial lesions was determined by a semiquantitative estimate of the space occupied by the fibrous tissue and/or interstitial infiltrates. Results: The urinary 8-OHdG excretion were significantly higher in the diabetics than in the healthy controls, and tended to increase with severity of the glomerular diffuse lesion, but it was not significant. The urinary 8-OHdG excretion significantly increased with severity of the tubulointerstitial lesion. Conclusions: Oxidative stress may contribute to the progression of tubulointerstitial injury in patients with diabetic nephropathy.

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Work-related Aggression and Violence Committed by Patients and Its PsychologicalInfluence on Doctors: Keigo Saeki, et al. Department of Community Health and Epidemiology, Nara Medical University School of Medicine-Objectives: To determine the incidence rate of work-related aggression and violence (WRAV) against doctors and investigate risk factors and psychological influences of WRAV doctors. Methods: We sent a self-administered questionnaire on WRAV committed by patients and their associates to 1,148 doctors in Nara Prefecture, Japan. We calculated the incidence rate of WRAV using the number of incidents encountered during the previous 12 mo and the doctor's average weekly working hours. Risk factors for the incidence WRAV were analyzed by Poisson regression, and the influence of WRAV on the symptoms of post-traumatic stress disorder (PTSD) was evaluated by multiple logistic regression analysis. Results: A total of 758 (66.0%) doctors returned the questionnaire. The incidence rate of WRAV was 0.20 [95% CI: 0.17-0.24]×10 -3 per practice hour. Adjusted incidence rate ratios of WRAV were significantly increased among doctors 1) with a shorter career (11.0; 95% CI: 5.0-24.2), 2) working in a region with the lowest average taxable income (1.6; 1.1-2.4), and 3) whose specialties were dermatology (3.8; 2.3-6.3), psychiatry (2.7; 1.3-5.6) and ophthalmology (1.9; 1.2-3.2). Of 289 subjects who had encountered WRAV at least once during their career, 26 doctors (8.2%) had symptoms suggestive of PTSD due to the most severe incident. Conclusions: Doctors encountered WRAV at an incidence rate of 0.20×10 -3 per practice hour, and some of them might develop PTSD. Countermeasures are required to maintain sound health and safe workplaces for doctors. (J Occup Health 2011; 53: 356-364)

Background/Aims: Advanced glycosylation end products (AGEs) are important pathogenetic factors underlying diabetic complications. Recently, a highly reliable new enzyme-linked immunosorbent assay for these metabolites has been established. We used the assay to correlate AGEs in serum with renal function categories and histopathology in patients with diabetic nephropathy. Methods: Type 2 diabetic patients (n = 71) and healthy control subjects (n = 35) were studied. The diabetic subjects were divided into two groups: normal renal function and chronic renal failure not requiring dialysis. In renal biopsy specimens from 22 diabetic subjects with a normal renal function, the severity of glomerular lesions was assessed morphometrically in terms of the ratio of the area of periodic acid-Schiff stained mesangium to total glomerular area. Results: The serum AGE concentrations were higher in both undialyzed diabetic groups, especially in those with renal failure, than in the controls. The serum AGE concentrations increased with the severity of glomerular lesions (morphometric ratio under 15%, 2.85 ± 0.73 mU/ml; 15–24%, 4.01 ± 0.71 mU/ml; 25% or more, 5.12 ± 0.64 mU/ml). Conclusions: The serum AGE levels measured by the new enzyme-linked immunosorbent assay reflected the severity of glomerulopathy, and, therefore, it may be a clinically useful tool for assessing diabetic renal complications.