Biomarkers of oxidative stress and its association with the urinary reducing capacity in bus maintenance workers.

BACKGROUND: Exposure to particles (PM) induces adverse health effects (cancer, cardiovascular and pulmonary diseases). A key-role in these adverse effects seems to be played by oxidative stress, which is an excess of reactive oxygen species relative to the amount of reducing species (including antioxidants), the first line of defense against reactive oxygen species. The aim of this study was to document the oxidative stress caused by exposure to respirable particles in vivo, and to test whether exposed workers presented changes in their urinary levels for reducing species.METHODS: Bus depot workers (n = 32) exposed to particles and pollutants (respirable PM4, organic and elemental carbon, particulate metal content, polycyclic aromatic hydrocarbons, NOx, O3) were surveyed over two consecutive days. We collected urine samples before and after each shift, and quantified an oxidative stress biomarker (8-hydroxy-2'-deoxyguanosine), the reducing capacity and a biomarker of PAH exposure (1-hydroxypyrene). We used a linear mixed model to test for associations between the oxidative stress status of the workers and their particle exposure as well as with their urinary level of reducing species.RESULTS: Workers were exposed to low levels of respirable PM4 (range 25-71 μg/m3). However, urinary levels of 8-hydroxy-2'-deoxyguanosine increased significantly within each shift and between both days for non-smokers. The between-day increase was significantly correlated (p < 0.001) with the concentrations of organic carbon, NOx, and the particulate copper content. The within-shift increase in 8OHdG was highly correlated to an increase of the urinary reducing capacity (Spearman ρ = 0.59, p < 0.0001).CONCLUSIONS: These findings confirm that exposure to components associated to respirable particulate matter causes a systemic oxidative stress, as measured with the urinary 8OHdG. The strong association observed between urinary 8OHdG with the reducing capacity is suggestive of protective or other mechanisms, including circadian effects. Additional investigations should be performed to understand these observations.

Artificial muscle for end-stage heart failure.

We describe a device made of artificial muscle for the treatment of end-stage heart failure as an alternative to current heart assist devices. The key component is a matrix of nitinol wires and aramidic fibers called Biometal muscle (BM). When heated electrically, it produces a motorless, smooth, and lifelike motion. The BM is connected to a carbon fiber scaffold, tightening the heart and providing simultaneous assistance to the left and right ventricles. A pacemaker-like microprocessor drives the contraction of the BM. We tested the device in a dedicated bench model of diseased heart. It generated a systolic pressure of 75 mm Hg and ejected a maximum of 330 ml/min, with an ejection fraction of 12%. The device required a power supply of 6 V, 250 mA. This could be the beginning of an era in which BMs integrate or replace the mechanical function of natural muscles.

Common variants in UMOD associate with urinary uromodulin levels: a meta-analysis.

Uromodulin is expressed exclusively in the thick ascending limb and is the most abundant protein excreted in normal urine. Variants in UMOD, which encodes uromodulin, are associated with renal function, and urinary uromodulin levels may be a biomarker for kidney disease. However, the genetic factors regulating uromodulin excretion are unknown. We conducted a meta-analysis of urinary uromodulin levels to identify associated common genetic variants in the general population. We included 10,884 individuals of European descent from three genetic isolates and three urban cohorts. Each study measured uromodulin indexed to creatinine and conducted linear regression analysis of approximately 2.5 million single nucleotide polymorphisms using an additive model. We also tested whether variants in genes expressed in the thick ascending limb associate with uromodulin levels. rs12917707, located near UMOD and previously associated with renal function and CKD, had the strongest association with urinary uromodulin levels (P<0.001). In all cohorts, carriers of a G allele of this variant had higher uromodulin levels than noncarriers did (geometric means 10.24, 14.05, and 17.67 μg/g creatinine for zero, one, or two copies of the G allele). rs12446492 in the adjacent gene PDILT (protein disulfide isomerase-like, testis expressed) also reached genome-wide significance (P<0.001). Regarding genes expressed in the thick ascending limb, variants in KCNJ1, SORL1, and CAB39 associated with urinary uromodulin levels. These data indicate that common variants in the UMOD promoter region may influence urinary uromodulin levels. They also provide insights into uromodulin biology and the association of UMOD variants with renal function.

Rapid sample pre-treatment prior to GC-MS and GC-MS/MS urinary toxicological screening.

Drug screening is an important issue in clinical and forensic toxicology. Gas chromatography coupled to mass spectrometry (GC-MS) remains the gold standard technique for the screening of unknown compounds in urine samples. However, this technique requires substantial sample preparation, which is time consuming. Moreover, some common drugs such as cannabis cannot be easily detected in urine using general procedures. In this work, a sample preparation protocol for treating 200 μL of urine in less than 30 min is described. The enzymatic hydrolysis of glucuro-conjugates was performed in 5 min thanks to the use of microwaves. The use of a deconvolution software allowed reducing the GC-MS run to 10 min, without impairing the quality of the compound identifications. Comparing the results from 139 authentic urine samples to those obtained using the current routine analysis indicated this method performed well. Moreover, additional 5-min GC-MS/MS programs are described, enabling a very sensitive target screening of 54 drugs, including THC-COOH or buprenorphine, without further sample preparation. These methods appeared as an interesting alternative to immuno-assays based screening. The analytical strategy presented in this article proved to be a promising approach for systematic toxicological analysis (STA) of drugs in urine.

Associations of ambulatory blood pressure with urinary caffeine and caffeine metabolite excretions.

Intake of caffeinated beverages might be associated with reduced cardiovascular mortality possibly via the lowering of blood pressure. We estimated the association of ambulatory blood pressure with urinary caffeine and caffeine metabolites in a population-based sample. Families were randomly selected from the general population of Swiss cities. Ambulatory blood pressure monitoring was conducted using validated devices. Urinary caffeine, paraxanthine, theophylline, and theobromine excretions were measured in 24 hours urine using ultrahigh performance liquid chromatography tandem mass spectrometry. We used mixed models to explore the associations of urinary excretions with blood pressure although adjusting for major confounders. The 836 participants (48.9% men) included in this analysis had mean age of 47.8 and mean 24-hour systolic and diastolic blood pressure of 120.1 and 78.0 mm Hg. For each doubling of caffeine excretion, 24-hour and night-time systolic blood pressure decreased by 0.642 and 1.107 mm Hg (both P values <0.040). Similar inverse associations were observed for paraxanthine and theophylline. Adjusted night-time systolic blood pressure in the first (lowest), second, third, and fourth (highest) quartile of paraxanthine urinary excretions were 110.3, 107.3, 107.3, and 105.1 mm Hg, respectively (P trend <0.05). No associations of urinary excretions with diastolic blood pressure were generally found, and theobromine excretion was not associated with blood pressure. Anti-hypertensive therapy, diabetes mellitus, and alcohol consumption modify the association of caffeine urinary excretion with systolic blood pressure. Ambulatory systolic blood pressure was inversely associated with urinary excretions of caffeine and other caffeine metabolites. Our results are compatible with a potential protective effect of caffeine on blood pressure.

Atmospheric deposition and migration of artificial radionuclides in Alpine soils (Val Piora, Switzerland) compared to the distribution of selected major and trace elements.

Artificial radionuclides ((137)Cs, (90)Sr, Pu, and (241)Am) are present in soils because of Nuclear Weapon Tests and accidents in nuclear facilities. Their distribution in soil depth varies according to soil characteristics, their own chemical properties, and their deposition history. For this project, we studied the atmospheric deposition of (137)Cs, (90)Sr, Pu, (241)Am, (210)Pb, and stable Pb. We compared the distribution of these elements in soil profiles from different soil types from an alpine Valley (Val Piora, Switzerland) with the distribution of selected major and trace elements in the same soils. Our goals were to explain the distribution of the radioisotopes as a function of soil parameters and to identify stable elements with analogous behaviors. We found that Pu and (241)Am are relatively immobile and accumulate in the topsoil. In all soils, (90)Sr is more mobile and shows some accumulations at depth into Fe-Al rich horizons. This behavior is also observed for Cu and Zn, indicating that these elements may be used as chemical analogues for the migration of (90)Sr into the soil.

Mineralocorticoid effects in the kidney: correlation between alphaENaC, GILZ, and Sgk-1 mRNA expression and urinary excretion of Na+ and K+.

Aldosterone exerts its effects through interactions with two types of binding sites, the mineralocorticoid (MR) and the glucocorticoid (GR) receptors. Although both receptors are known to be involved in the anti-natriuretic response to aldosterone, the mechanisms of signal transduction leading to modulation of electrolyte transport are not yet fully understood. This study measured the Na(+) and K(+) urinary excretion and the mRNA levels of three known aldosterone-induced transcripts, the serum and glucocorticoid-induced kinase (Sgk-1), the alpha subunit of the epithelial Na(+) channel (alphaENaC), and the glucocorticoid-induced-leucine-zipper protein (GILZ) in the whole kidney and in isolated cortical collecting tubules of adrenalectomized rats treated with low doses of aldosterone and/or dexamethasone. The resulting plasma concentrations of both steroids were close to 1 nmol/L. Aldosterone, given with or without dexamethasone, induced anti-natriuresis and kaliuresis, whereas dexamethasone alone did not. GILZ and alphaENaC transcripts were higher after treatment with either or both hormones, whereas the mRNA abundance of Sgk-1 was increased in the cortical collecting tubule by aldosterone but not by dexamethasone. We conclude the increased expression of Sgk-1 in the cortical collecting tubules is a primary event in the early antinatriuretic and kaliuretic responses to physiologic concentrations of aldosterone. Induction of alphaENaC and/or GILZ mRNAs may play a permissive role in the enhancement of the early and/or late responses; these effects may be necessary for a full response but do not by themselves promote early changes in urinary Na(+) and K(+) excretion.

L'incontinence urinaire chez des personnes âgées hospitalisées en unité de gériatrie: est-ce vraiment une priorité pour les infirmières [Urinary incontinence in hospitalized geriatric patients : is it really a priority for nurses?].

INTRODUCTION: urinary incontinence (UI) is a phenomenon with high prevalence in hospitalized elderly patients, effecting up to 70% of patients requiring long term care. However, despite the discomfort it causes and its association with functional decline, it seems to be given insufficient attention by nurses in geriatric care. OBJECTIVES: to assess the prevalence of urinary incontinence in geriatric patients at admission and the level of nurse involvement as characterized by the explicit documentation of UI diagnosis in the patient's record, prescription of nursing intervention, or nursing actions related to UI. METHODS: cross-sectional retrospective chart review. One hundred cases were randomly selected from those patients 65 years or older admitted to the geriatric ward of a university hospital. The variables examined included: total and continence scores on the Measure of Functional Independence (MIF), socio-demographic variables, presence of a nursing diagnosis in the medical record, prescription of or documentation of a nursing intervention related to UI. RESULTS: the prevalence of urinary incontinence was 72 % and UI was positively correlated with a low MIF score, age and status of awaiting placement. Of the examined cases, nursing diagnosis of UI was only documented in 1.4 % of cases, nursing interventions were prescribed in 54 % of cases, and at least one nursing intervention was performed in 72 % of cases. The vast majority of the interventions were palliative. DISCUSSION: the results on the prevalence of IU are similar to those reported in several other studies. This is also the case in relation to nursing interventions. In this study, people with UI were given the same care regardless of their MIF score MIF, age or gender. One limitation of this study is that it is retrospective and therefore dependent on the quality of the nursing documentation. CONCLUSIONS: this study is novel because it examines UI in relation to nursing interventions. It demonstrates that despite a high prevalence of UI, the general level of concern for nurses remains relatively low. Individualized care is desirable and clinical innovations must be developed for primary and secondary prevention of UI during hospitalization.

Independent relations of left ventricular structure with the 24-h urinary excretion of sodium and aldosterone

Objective: Previous studies reported on the association of left ventricular mass index (LVMI) with urinary sodium or with circulating or urinary aldosterone.We investigated the independent associations of LVMI with the urinary excretion of both sodium and aldosterone. Design and method: We randomly recruited 317 untreated subjects from a White population (45.1%women; mean age 48.2 years).Measurements included echocardiographic left ventricular (LV) properties, the 24 h urinary excretion of sodium and aldosterone, plasma renin activity (PRA), and proximal (RNaprox) and distal (RNadist) renal sodium reabsorption, assessed fromthe endogenous lithium clearance. Inmultivariable-adjusted models,we expressed changes in LVMI per 1 SD increase in the explanatory variables, while accounting for sex, age, systolic blood pressure and the waist-to-hip ratio. Results: LVMI increased independentlywith the urinary excretion of both sodium (+2.48 g/m2; P=0.005) and aldosterone (+2.63 g/m2; P=0.004). Higher sodium excretion was associated with increased mean wall thickness (MWT: +0.126 mm, P=0.054), but with no change in LV end-diastolic diameter (LVID: +0.12mm, P=0.64). In contrast, higher aldosterone excretion was associated with higher LVID (+0.54 mm; P=0.017), but with no change in MWT (+0.070mm; P=0.28).Higher RNadistwas associatedwith lower relativewall thickness (−0.81×10−2, P=0.017), because of opposite trends in LVID(+0.33 mm; P=0.13) and MWT (−0.130mm; P=0.040). LVMI was not associated with PRA or RNaprox. Conclusions: LVMI independently increased with both urinary sodium and aldosterone excretion. IncreasedMWT explained the association of LVMI with urinary sodium and increased LVID the association of LVMI with urinary aldosterone.