Determination of adjusted reference intervals of urinary biomarkers of oxidative stress in healthy adults using GAMLSS models.

In this study we aimed at identifying main demographic, laboratory and environmental factors influencing the level of urinary biomarkers (DNA-derived 8-oxodG and lipid membrane-derived 8-isoprostane), and deriving their adjusted 95% reference intervals (RI) in a sample of healthy people from the general population. Data from 281 healthy subjects from the Gene Environment Interactions in Respiratory Diseases survey were used in this study. Generalized additive models for location, scale and shape (GAMLSS) were used to find determinants of the biomarkers among gender, age, season and distance from collection (DFC), and to predict their RI. The RI of the biomarkers stratified by season and adjusted for DFC showed a slight statistically significant decrease in the biomarkers at the increasing DFC in two seasons, except the 8-oxodG during the warm season: median levels at the min and max values of DFC were (ng/mgcreat) 7.0-1.1 in the cold and 3.9-3.9 in the warm seasons for 8-oxodG, 0.7-0.2 in the cold and 1.3-0.6 in the warm seasons for 8-isoprostane. Both the biomarkers should be evaluated in association with the DFC and season in large epidemiological studies. The (semi)parametric GAMLSS method is a useful and flexible technique, which makes it possible to estimate adjusted RI.

Increased microRNA 21 expression contributes to arsenic induced skin lesions, skin cancers and respiratory distress in chronically exposed individuals.

More than 26 million people in West Bengal, India, are exposed to arsenic through drinking water, leading to several deleterious endpoints including precancerous and cancerous skin lesions and other non-dermatological health effects. Here, our aim was to identify whether miR21 is associated with such dermatological and non-dermatological health outcomes in chronically exposed humans. A total of 123 subjects from West Bengal were recruited for this study (45 exposed individuals with skin lesions, 38 exposed individuals without skin lesions and 40 unexposed individuals). The miR21 expression patterns in the lymphocytes were studied by quantitative realtime PCR and the effects on downstream targets were validated by Western blotting. Associations between the miR21 expression patterns and non-dermatological health effects were determined from epidemiological survey data. In vitro studies were done with low dose (0.05ppm) of chronic arsenic exposure to HaCaT cells for 15 passages. Interestingly, within the exposed group, the skin lesion individuals showed almost 4.5 fold up-regulation of miR21 compared to the no skin lesion group. The expression of the downstream targets of miR21 (PTEN and PDCD4) varied inversely, while the expression of pAKT and PI3K varied proportionately with its expression levels. Results of in vitro studies showed similar trends. Again miR21 was 2.03 fold up-regulated in the exposed individuals with respiratory diseases compared to the individuals without the same. This study for the first time shows that miR21 plays an important role in contributing to arsenic induced dermatological and non-dermatological health outcomes in an exposed population.

[Clinical significance of urinary N-acetyl-beta-D-glucosaminidase activities in surgery].

Urinary N-acetyl-beta-D-glucosaminidase (U-NAG) activities were measured in 62 patients surgically treated in our clinic. The results obtained were as follows: The preoperative U-NAG activities were 9.53 +/- 8.63 IU/day in patients in elective operations, and 31.39 +/- 23.47 IU/day in cases in emergency surgery or exploratory laparotomies. The U-NAG activities were elevated slightly even in patients with no postoperative complications, suggesting there was significant damage to the renal tubular epithelium. In the patients with postoperative complications, the U-NAG activities were elevated markedly, especially in those with circulatory shock, suggesting severe damage to the renal tubular epithelium. Though the U-NAG showed abnormally high activities, the values of BUN, S-Cr, U-protein, UUN/BUN, FENa, Ccr, CH2O remained within the normal range. On the contrary, when they were abnormal, the U-NAG activities were not elevated. All patients, who showed high U-NAG activities with abnormal values of Ccr and/or CH2O, developed acute renal failure (ARF). In order to detect ARF in an early stage, Ccr and CH2O should be measured when U-NAG activities rose to over 50 IU/day.