Validated SNPs for eGFR and their associations with albuminuria

Albuminuria and reduced glomerular filtration rate are manifestations of chronic kidney disease (CKD) that predict end-stage renal disease, acute kidney injury, cardiovascular disease and death. We hypothesized that SNPs identified in association with the estimated glomerular filtration rate (eGFR) would also be associated with albuminuria. Within the CKDGen Consortium cohort (n= 31 580, European ancestry), we tested 16 eGFR-associated SNPs for association with the urinary albumin-to-creatinine ratio (UACR) and albuminuria [UACR >25 mg/g (women); 17 mg/g (men)]. In parallel, within the CARe Renal Consortium (n= 5569, African ancestry), we tested seven eGFR-associated SNPs for association with the UACR. We used a Bonferroni-corrected P-value of 0.003 (0.05/16) in CKDGen and 0.007 (0.05/7) in CARe. We also assessed whether the 16 eGFR SNPs were associated with the UACR in aggregate using a beta-weighted genotype score. In the CKDGen Consortium, the minor A allele of rs17319721 in the SHROOM3 gene, known to be associated with a lower eGFR, was associated with lower ln(UACR) levels (beta = -0.034, P-value = 0.0002). No additional eGFR-associated SNPs met the Bonferroni-corrected P-value threshold of 0.003 for either UACR or albuminuria. In the CARe Renal Consortium, there were no associations between SNPs and UACR with a P< 0.007. Although we found the genotype score to be associated with albuminuria (P= 0.0006), this result was driven almost entirely by the known SHROOM3 variant, rs17319721. Removal of rs17319721 resulted in a P-value 0.03, indicating a weak residual aggregate signal. No alleles, previously demonstrated to be associated with a lower eGFR, were associated with the UACR or albuminuria, suggesting that there may be distinct genetic components for these traits.     

Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects

In a previous clinical study, a probiotic formulation (PF) consisting of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 (PF) decreased stress-induced gastrointestinal discomfort. Emerging evidence of a role for gut microbiota on central nervous system functions therefore suggests that oral intake of probiotics may have beneficial consequences on mood and psychological distress. The aim of the present study was to investigate the anxiolytic-like activity of PF in rats, and its possible effects on anxiety, depression, stress and coping strategies in healthy human volunteers. In the preclinical study, rats were daily administered PF for 2 weeks and subsequently tested in the conditioned defensive burying test, a screening model for anti-anxiety agents. In the clinical trial, volunteers participated in a double-blind, placebo-controlled, randomised parallel group study with PF administered for 30?d and assessed with the Hopkins Symptom Checklist (HSCL-90), the Hospital Anxiety and Depression Scale (HADS), the Perceived Stress Scale, the Coping Checklist (CCL) and 24?h urinary free cortisol (UFC). Daily subchronic administration of PF significantly reduced anxiety-like behaviour in rats (P?相似文献   

Assessment of indoor environment in Paris child day care centers

Background

Children are sensitive to indoor environmental pollution. Up until now there has been a lack of data on air quality in child day care centers.

Objectives

The aim of this study is to document the indoor environment quality of Paris child day care centers by repeated measurements, and to compare pollutant levels in child day care centers with levels in Paris dwellings.

Methods

We selected 28 child day care centers frequented by a random sample of babies who participated in the PARIS birth cohort environmental investigation, and visited the child day care centers for one week twice in one year. Biological contaminants assessed were fungi, endotoxin, dust mite allergens, and chemical pollutants: aldehydes, volatile organic compounds and nitrogen dioxide (NO₂). Relative humidity, temperature, and carbon dioxide levels were measured simultaneously. A standardized questionnaire was used to gather information about the buildings and their inhabitants.

Results

Airborne endotoxin levels in child day care centers were higher than those found in Paris dwellings. Dust mite allergens in child day care centers were below the threshold level for sensitization in the majority of samples, and in common with dwelling samples. Penicillium and Cladosporium were the most commonly identified genera fungi. The child day care center indoor/outdoor ratio for most chemical pollutants was above unity except for NO₂, the levels for NO₂ being significantly higher than those measured in homes.

Conclusion

Chemical and biological contamination in child day care centers appears to be low, apart from endotoxin and NO₂. Failure to take child exposure in child day care centers into account could result in an overestimation of children's exposure to other pollutants.     

Brain-derived neurotrophic factor serum levels in alcohol-dependent subjects 6 months after alcohol withdrawal

Background: Diagnosing alcohol dependence is based on clinical signs and on the measured levels of biological markers of alcohol consumption. However, these markers are neither sufficiently sensitive and nor specific enough to definitively determine alcohol dependence. The neuroadaptive changes associated with alcohol dependence involve markers such as brain‐derived neurotrophic factor (BDNF), which regulate neuronal plasticity. Serum levels of BDNF have been reported to decrease during alcohol dependence and may be restored to normal soon after alcohol is withdrawn. However, the long‐term relationship between serum BDNF levels and abstinence status is unknown. Methods: We investigated serum BDNF levels in 101 abstinent and relapsing alcohol‐dependent subjects at the moment of hospitalization for alcohol withdrawal (M0) and 6 months later (M6) and compared them to the serum BDNF levels of 41 nondependent subjects. The BDNF levels of the alcohol‐dependent subjects were compared to their serum gamma glutamyl transferase (GGT) levels, mean corpuscular volume (MCV) values, and their score on the Beck Depression Inventory (BDI) questionnaire. Results: Forty‐four percent of the alcohol‐dependent participants remained abstinent during the 6 months following alcohol detoxification. Serum BDNF levels of the abstinent group at M6 were significantly higher than those of the original group of alcohol‐dependent subjects at M0 (p = 0.034). Only the abstinent group had higher BDNF levels than the control group (p < 0.001). Serum BDNF levels increased to a greater extent in the abstinent group than in the nonabstinent group (p = 0.016). No correlations were found between serum BDNF levels and GGT level, MCV value, or BDI score. Conclusions: Our data confirm that serum BDNF levels do not correlate with either chronic alcohol consumption or peripheral toxicity but may be linked to neuronal aspects of alcohol consumption and dependence. The increased serum levels of BDNF may reflect the concomitant activation of BDNF synthesis that accompanies the neuronal remodeling triggered by alcohol withdrawal and suggests that BDNF synthesis may have a role in the long‐term maintenance of abstinence. Monitoring the serum BDNF levels of alcoholics undergoing treatment could help to characterize alcohol dependence profiles and predict relapse.     

Comprehensive characterization of the peroxisome proliferator activated receptor-δ agonist GW501516 for horse doping control analysis

According to international sport institutions, the use of peroxisome proliferator activated receptor (PPAR)-δ agonists is forbidden at any time in athlete career due to their capabilities to increase physical and endurance performances. The (PPAR)-δ agonist GW501516 is prohibited for sale but is easily available on internet and can be used by cheaters. In the context of doping control, urine is the preferred matrix because of the non-invasive nature of sampling and providing broader exposure detection times to forbidden molecules but often not detected under its native form due to the organism's metabolism. Even if urinary metabolism of G501516 has been extensively studied in human subjects, knowledge on GW501516 metabolism in horses remains limited. To fight against doping practices in horses' races, GW501516 metabolism has to be studied in horse urine to identify and characterize the most relevant target metabolites to ensure an efficient doping control. In this article, in vitro and in vivo experiments have been conducted using horse S9 liver microsome fractions and horse oral administration route, respectively. These investigations determined that the detection of GW501516 must be performed in urine on its metabolites because the parent molecule was extremely metabolized. To maximize analytical method sensitivity, the extraction conditions have been optimized. In accordance with these results, a qualitative analytical method was validated to detect the abuse of GW501516 based on its most relevant metabolites in urine. This work enabled the Laboratoire des Courses Hippiques (LCH) to highlight two cases of illicit administration of this forbidden molecule in post-race samples.     

Long-term detection of clodronate in equine plasma by liquid chromatography–tandem mass spectrometry

Clodronate is a non-nitrogen-containing bisphosphonate drug approved in equine veterinary medicine. Clodronate is prohibited for use in competition horses; therefore, to set up an appropriate control, detection times and screening limits are required. The quantitative method in plasma consisted of addition of chloromethylene diphosphonic acid as internal standard. Automated sample preparation comprised a solid phase extraction with weak anion exchange properties on microplate. After methylation of the residue with trimethyl orthoacetate, analysis was conducted by high-performance liquid chromatography–tandem mass spectrometry. Using a weighting factor of 1/(concentration)², good linearity was observed in the range of 1 to 500 ng/ml, with low limits of detection and quantification of 0.5 and 1 ng/ml, respectively. Precision and accuracy determined at four concentrations were satisfactory, with an error percentage less than 15%. Absence of carry-over and good stability of clodronic acid in plasma after a long-term storage at −20°C were verified. The method was successfully applied to the quantification of clodronic acid in plasma samples from horses administered with a single intramuscular administration of Osphos® at a mean dose of 1.43 ± 0.07 mg/kg. The observed detection time will be verified in a clinical population study conducted in diseased horses.