We have previously shown that the expression of nicotinamide N-methyltransferase (NNMT) is significantly increased in the brains of patients who have died of Parkinson’s disease (PD). In this study, we have compared the expression of NNMT in post-mortem medial temporal lobe, hippocampus and cerebellum of 10 Alzheimer’s disease (AD) and 9 non-disease control subjects using a combination of quantitative Western blotting, immunohistochemistry and dual-label confocal microscopy coupled with quantitative analysis of colocalisation. NNMT was detected as a single protein of 29 kDa in both AD and non-disease control brains, which was significantly increased in AD medial temporal lobe compared to non-disease controls (7.5-fold, P < 0.026). There was no significant difference in expression in the cerebellum (P = 0.91). NNMT expression in AD medial temporal lobe and hippocampus was present in cholinergic neurones with no glial localisation. Cell-type expression was identical in both non-disease control and AD tissues. These results are the first to show, in a proof-of-concept study using a small patient cohort, that NNMT protein expression is increased in the AD brain and is present in neurones which degenerate in AD. These results suggest that the elevation of NNMT may be a common feature of many neurodegenerative diseases. Confirmation of this overexpression using a larger AD patient cohort will drive the future development of NNMT-targetting therapeutics which may slow or stop the disease pathogenesis, in contrast to current therapies which solely address AD symptoms.

In this follow-up study, 526 persons were followed for almost 5 years to assess the reversibility and predictive value of four kidney biomarkers in a field epidemiology setting. This study examined (a) whether elevations in urinary albumin, N-acetyl-beta-D-glucosaminidase, retinol-binding protein, and alanine aminopeptidase remained elevated at follow-up and (b) whether these initial elevations were predictive of kidney disease (as measured by markers of kidney dysfunction: serum creatinine, serum cystatin C, creatinine clearance, and urine osmolality) at follow-up. Study participants were 8-76 years of age at baseline and were followed for an average of 4.5 years. Approximately 50% of adults who had an elevated biomarker did not have an elevation at followup. Youths with elevated biomarkers at baseline, but who completed adolescence by the time of the follow-up, no longer had any elevations in biomarkers at follow-up. Adult participants who had elevated biomarkers and selected health conditions at baseline (diabetes and, to a lesser extent, heart disease, hypertension, gout, and urinary tract disease) were more likely to show early indicators of kidney impairment at follow-up. Participants with these health conditions and normal kidney biomarker values at baseline had kidney test results at follow-up that were similar to results of study participants who did not have these health conditions at baseline. The presence or absence of elevated biomarkers at baseline among generally healthy participants was not associated with the development of early indicators of kidney impairment at follow-up. This longitudinal study confirmed the utility of these four kidney biomarker tests as markers of preclinical organ dysfunction among adults with certain preexisting medical conditions.

The Agency for Toxic Substances and Disease Registry (ATSDR) used a cross-sectional study to compare the serum dioxin toxic equivalent (TEQ) levels of a population-based representative sample of Calcasieu Parish residents aged 15 years and older to a similar group of residents of Lafayette Parish with less industrial facilities. Serum dioxins consisted of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and dioxin-like polychlorinated biphenyls. Overall, the mean and distribution of serum dioxin TEQ level in residents of both parishes were similar by age groups (15-29 years, 30-44 years, 45-59 years, and 60 year and older). When the Calcasieu Parish area was further divided based on distance to three industrial areas, the mean dioxin TEQ levels were similar. Serum dioxin TEQ levels in residents of both parishes increased with age. Calcasieu Parish residents who reported having eaten locally caught fish, smoked cigarettes, worked in an occupation with potential exposure, or used pesticides had dioxin levels similar to Lafayette Parish residents who reported these activities. African Americans had higher dioxin levels than Caucasians in Lafayette Parish and both races in Calcasieu Parish. The congener profiles were similar in residents of both parishes. When the combined Calcasieu and Lafayette Parish data were compared by age group to the National Health and Nutrition Examination Survey (NHANES) 2001-2002 data, the geometric means for the dioxin levels in the combined Parish data set were significantly lower than the NHANES data in all age groups (all P-values <0.0001), except the oldest age group where the significance level is marginal (P=0.067). The various percentiles of the youngest age group of the combined parish data were also significantly lower than those in NHANES. Since the combined parish dioxin levels were below a representative sampling of the US population, there is no increase in serum dioxin concentrations in both the parishes.

Agency for Toxic Substances and Disease Registry conducted a study to evaluate body burden levels of volatile organic compounds (VOCs) among residents of highly industrialized Calcasieu Parish, LA, USA, in 2002. Blood VOC levels in a representative sample of participants in Calcasieu Parish were compared with a similar group of participants in the less-industrialized Lafayette Parish. Participants' ages ranged from 15 to 91 years, 46% were men, and 89% were Caucasian. VOC levels in these two populations were also compared at the national levels. Solid-phase microextraction coupled with gas chromatography mass spectrometry was used to measure levels of 30 VOCs in blood samples collected from 283 self-described non-smoking study participants. Of the 30 VOCs, 6 had quantifiable levels in at least 25% of the blood samples analyzed. The frequency of detection was >95% for benzene and m-/p-xylene, >60% for 1,4-dichlorbenzene and toluene, 27% for ethylbenzene, and 39% for styrene. Calcasieu and Lafayette Parish participants had similar distributions for six VOCs in key percentiles and geometric means. When compared with a representative sampling of the 1999-2000 US general population, no significant differences were found between the parish data and the US general population.

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