Balkan endemic nephropathy is a chronic tubulointerstitial disease frequently accompanied by urothelial cell carcinomas of the upper urinary tract. This disorder has recently been linked to exposure to aristolochic acid, a powerful nephrotoxin and human carcinogen. Following metabolic activation, aristolochic acid reacts with genomic DNA to form aristolactam-DNA adducts that generate a unique TP53 mutational spectrum in urothelium. The aristolactam-DNA adducts are concentrated in the renal cortex, thus serving as biomarkers of internal exposure to aristolochic acid. Here, we present molecular epidemiologic evidence relating carcinomas of the upper urinary tract to dietary exposure to aristolochic acid. DNA was extracted from the renal cortex and urothelial tumor tissue of 67 patients that underwent nephroureterectomy for carcinomas of the upper urinary tract and resided in regions of known endemic nephropathy. Ten patients from non-endemic regions with carcinomas of the upper urinary tract served as controls. Aristolactam-DNA adducts were quantified by 32P-post-labeling, the adduct was confirmed by mass spectroscopy, and TP53 mutations in tumor tissues were identified by chip-sequencing. Adducts were present in 70% of the endemic cohort and in 94% of patients with specific A:T to T:A mutations in TP53. In contrast, neither aristolactam-DNA adducts nor specific mutations were detected in tissues of patients residing in non-endemic regions. Thus, in genetically susceptible individuals, dietary exposure to aristolochic acid is causally related to endemic nephropathy and carcinomas of the upper urinary tract.
Background/Aims: An epidemiological survey of endemic nephropathy (EN) was performed in endemic Croatian areas and the current prevalence was compared to that reported for the same villages several decades ago. Methods: A total of 2,487 adult farmers from 6 endemic villages and 3 non-endemic villages were enrolled. An extensive epidemiological questionnaire, clinical examination and laboratory analyses of blood and urine were performed. According to the modified WHO criteria, participants were classified into diseased, suspected of having EN, and those at risk of developing EN. Results: The overall prevalence of EN in the Croatian areas was 1.0%, ranging between 0.3 and 2.3% in different villages. Those suspected of having EN amounted to 3.9%. In the endemic villages a decreasing trend in the prevalence of EN was observed comparable to the results obtained in previous surveys. It is interesting to note that no EN patients were recorded in the endemic village of Dubočac. Conclusion: The prevalence of EN in the endemic Croatian areas appears to be decreasing. For the first time, we failed to detect any EN patients in a village that was previously considered endemic, which might indicate that EN is diminishing.
Objective:The aim of our analysis is to determine how strong the relationship between hypertension and obesity.Design and method: Our study included a random sample of 1975 volunteers (1093 women and 882 men) aged 25-64 years, resident in Brno. Study participants were selected from the databases of Czech health insurance companies and examined as per protocol of the Czech Post-MONICA survey. The parameters determined included body height and weight, waist circumference, blood pressure, and body fat percentage using bioimpedance analysis with an InBody 370 device (Biospace, Seoul, Korea).Results: Using the body mass index (BMI), the prevalence of obesity and overweight in the study population was 17.42% and 34.68%, respectively. Another 22.11% of volunteers were found to have "normal weight obesity", i.e., increased amount of adipose tissue even in normal-weight individuals (term coined by Gallagher et al., 2000) whereas 31.59% were classified as obese by their waist circumference (central obesity). Based on their office blood pressure (mean of 2nd and 3rd measurements) or a history of hypertension, 39.39% were identified as hypertensives. As BMI increases (two-sample Z-test) so do the odds of developing hypertension both in the general population, and in women and men separately (except for a non-significant odds ratio in a subgroup of underweight men compared with normal-weight men). Obesity, as defined by waist circumference, was associated with a significant and marked increase in the odds of developing hypertension in all study participants (5.8-fold overall, 6-fold in females, and as high as 6.5-fold in males) compared with individuals with normal waist circumference. Conclusions:Obesity as defined using various methods is a major risk factors for the development of hypertension. The obese should have their blood pressure monitored more often than those with normal weight and waist circumference. Waist circumference is a simple screening tool for estimating the odds of developing hypertension. Obesity is thus an appropriate target for intervention designed to reduce the risk of developing hypertension. Objective:Relatively little is known about hypertension in underdeveloped countries, including Haiti, where a cross-sectional survey of hypertension and other common risk factors has not yet been conducted.Design and method: Residents of Fontaine in rural northern Haiti were interviewed by convenience sampling in their own homes by trained fieldworkers, (similar to U.S. NHANES III). After informed consent, a modified WHO STEPS demographic questionnaire assessed risk factors; anthropomorphic data and sitting oscillomet-ric blood pressures (Omron) were obtained. Hypertension was defined as systolic BP > 140 or diastolic > 90 mmHg or self-reported treatment.Objective: Data on prevalence of metabolic syndrome (MS) in rural regions are still inconclusive and several reports showed it to be higher in urban than in rural areas. The aim of this study was to determine the prevalence of MS in a rural, continental Croat...
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