Single-stage versus two-stage models to estimate creatinine corrected urinary analyte concentrations

The ability to detect 'known' differences in urinary analyte concentrations due to gender, age, and race/ethnicity when adjusted for similar differences in urinary creatinine concentrations were evaluated by a single-stage and a two-stage model by ten simulation studies. Log10 transformed values of observed urinary analyte concentration were used as the dependent variable and age, gender, and race/ethnicity were used as the categorical independent variables. In addition, while single-stage model used log10 transformed values of urinary creatinine as a covariate, two-stage model used a correction factor (CF) determined during the first stage of the model by fitting a secondary model for urinary creatinine. Single-stage model was almost always able to statistically significantly detect 'known' differences due to age, gender, and race/ethnicity. On the other hand, two-stage model was able to statistically significantly detect 'known' differences due to age, gender, and race/ethnicity a maximum of 87.2% of the times and as low as 10.6% of the times primarily because of the presence of multicollinearity between CF and urinary creatinine concentrations. Consequently, as long as the sole objective is to estimate the urinary analyte concentrations adjusted for the effect of all factors including urinary creatinine, single-stage models are the models of choice.     

家长吸烟对儿童尿中1-羟基芘的影响

为了解家长吸烟对小学生尿中１－羟基芘的影响,对４个地区小学生２３４份尿样中的１－羟基芘及其学校所在地空气中的苯并芘进行了同步采样分析,结果显示,学生尿中的１－羟基芘浓度与所在学校空气中苯并（ａ）芘的浓度有显著的正相关关系。家长吸烟组学生尿中１－羟基芘浓度均高于家长不吸烟组,但ｔ检验结果差别不显著,根据测定结果的分析,讨论了这种差别的意义。     

Animal models of fetal renal disease

Fetal models of urinary tract disease have been used for many years and have provided unique and important insights into the pathophysiology of these conditions. This review will summarize the principal model systems used and the current directions of investigation. These models (including rabbit, opossum, sheep and recently swine) have demonstrated that in utero obstruction of the urinary tract alters renal growth, differentiation and produces stereotypical patterns of tissue response, particularly fibrosis. New molecular understanding of these processes has identified specific mechanisms that may be key elements in the development of renal dysfunction due to obstruction. These factors include the renin–angiotensin system (RAS) and its interaction with TGF-β in altering growth regulation and tissue fibrosis. These factors offer the prospect of clinical utility as markers of disease progression as well as pharmacologic therapy. Gene knockout systems have opened a new horizon of molecular models of congenital obstructive uropathy with insights into the role of the RAS in particular. It remains to be defined how closely these knockouts represent the human conditions they resemble. Continued application of fetal models of urinary obstruction, integrating large animal and knockout systems offers promise for improved diagnosis and treatment in these challenging conditions. Copyright © 2001 John Wiley & Sons, Ltd.     

Fluoride in drinking water exacerbates glomerulonephritis and induces liver damage in ICR-derived glomerulonephritis mice

To evaluate the effects of fluoride on the kidney and the liver of ICR-derived glomerulonephritis (ICGN) mice by using laboratory tests and pathological examinations, fluoride was administered to the ICGN mice at 0, 25, 50, 100, and 150?ppm in drinking water for 4 weeks and to the ICR mice, which have normal kidney function at 0 and 150?ppm. The BUN, creatinine, GOT, and GPT in the serum of each mouse were determined. When a mouse died, the sample from the day closest to the death was assigned for the mean. Pathological changes in the kidney were examined after PAS (periodic acid-Schiff) staining. All of the ICGN mice in the 150?ppm group and one of seven in the 100?ppm group died before the end of week 4, but no ICR mice died. For ICGN mice, the mean value of body weight in the 150?ppm group was significantly lower than those in 0?ppm group and other fluoride-administered groups. The mean values of relative liver and kidney weights in the 100 and 150?ppm groups were significantly lower than those in the control. The mean values of BUN, creatinine, and GPT in the 150?ppm group were significantly higher than those in the control. The thickness of the glomerular capillary wall and the increased mesangial matrix in the kidney were prominent in the fluoride-administered ICGN mice. These results suggested that fluoride severely exacerbated glomerulonephritis and tublar-intestitial changes in ICGN mice.     

Urinary arsenic methylation profile in children exposed to low arsenic levels through drinking water

There is a lack of information on arsenic metabolism in children exposed chronically to low levels of arsenic (<50 µg L^?1). The objective of this study was to determine the methylation profile of urinary arsenic metabolites in children exposed to low-level concentrations of arsenic via their drinking water. A cross-sectional study was undertaken in 50 children from four towns in the Yaqui Valley, Sonora, with total arsenic values of 39.9, 16.8, 7.3, and 5.5 µg L^?1 in their drinking water, respectively. First morning void samples were analyzed for inorganic-As (InAs), mono and dimethyl arsenic (MMA and DMA). The total arsenic excreted in urine ranged from 23.1 to 99.1 µg L^?1 and these levels did not vary by sex. Children with the highest level of total arsenic in their drinking water excreted the highest amount in urine and the length of residence and age also had significant contribution. Children with a lower range of arsenic exposure (16.8–5.5 µg L^?1) had similar amounts of arsenic in urine with values of 23.1, 28.2, and 32.6 µg L^?1, respectively. DMA had the highest proportion in urine (52.1–74.7%), followed by InAs (16.3–34.9%) and MMA (4.4–8.4%). Compared to other reports, these children excreted a low %MMA (6.1%), and children from the towns with the lowest levels of arsenic had the highest %InAs and the lowest %DMA. This variability in arsenic methylation was partially explained by arsenic concentration in drinking water, years of residence and age, and may reflect genetic differences or more contribution from different exposure routes. In conclusion, our results show that at low levels of exposure the children's ability to metabolize InAs did not have a linear association with the levels of arsenic, and overall children from the Yaqui Valley excrete a lower %MMA than expected.     

Development of competitive immunoassays to hydroxyl containing fungicide metabolites

This paper describes the isolation of monoclonal antibodies and the development of competitive immunoassays to pesticide metabolites of the fungicides imazalil, carbendazim and thiabendazole. The metabolite specific hydroxyl residues were used as the reactive group with which to link the metabolite to the carrier proteins Keyhole Limpet Haemocyanin (KLH) and Bovine Serum Albumin (BSA). In each case immune responses in mice were raised and monoclonal antibodies were produced. Antibodies were developed into competitive ELISAs to the appropriate metabolite. The antibody raised to a metabolite of imazalil was optimised into a competitive ELISA format which had an assay IC50 of 7.5 μg/L and a limit of detection (LOD) of 1.1 μg/L. A single antibody isolated against the metabolite of carbendazim had assay IC50s of 3.2 and 2.7 μg/L for the metabolites of carbendazim and thiabendazole respectively with an LOD of 0.38 μg/L for both. These sensitive immunoassays may have application in the monitoring of human exposure to these fungicide residues either by occupational or non-occupational routes.     

Determination of urinary lead in school children in Manzini, Swaziland, Southern Africa

Two hundred and fifty-seven urine samples collected from school children living in the Manzini region, Swaziland, were analysed for lead (Pb), using a graphite furnace atomic absorption spectrometer. The mean urine lead concentration for the urban schools ranged from 0.038–0.040 gml^–1, while that for the rural schools ranged from 0.017–0.022 gml^–1. The observed range shown by the urban schools was above the normal (for healthy humans) urine lead concentration of 0.035 gml^–1. However, the mean urine lead concentration for the rural schools was found to be lower than this value. The mean urine lead concentration for the urban schools was significantly higher than that of the rural schools. The differences in the mean urine lead concentrations for boys and girls from both urban and rural schools were found not to be significant, despite the higher values shown by the girls. The difference in lead concentrations between urban and rural schools in Manzini was thought to be due to the traffic density within the urban area.     

Normal and abnormal development of the urogenital tract

An understanding of the normal development of the urogenital tract, at both the structural and molecular level, gives an insight into the mechanisms involved in renal pathology. In this review we will outline embryology of normal and abnormal renal development and discuss the function of some of the key regulatory molecules which have been described recently. Copyright © 2001 John Wiley & Sons, Ltd.