1,283 research outputs found
Bone Resorption and Environmental Exposure to Cadmium in Women: A Population Study
BACKGROUND: Environmental exposure to cadmium decreases bone density indirectly through hypercalciuria resulting from renal tubular dysfunction.
OBJECTIVE: We sought evidence for a direct osteotoxic effect of cadmium in women.
METHODS: We randomly recruited 294 women (mean age, 49.2 years) from a Flemish population with environmental cadmium exposure. We measured 24-hr urinary cadmium and blood cadmium as indexes of lifetime and recent exposure, respectively. We assessed the multivariate-adjusted association of exposure with specific markers of bone resorption, urinary hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP), as well as with calcium excretion, various calciotropic hormones, and forearm bone density.
RESULTS: In all women, the effect sizes associated with a doubling of lifetime exposure were 8.4% (p = 0.009) for HP, 6.9% (p = 0.10) for LP, 0.77 mmol/day (p = 0.003) for urinary calcium, -0.009 g/cm(2) (p = 0.055) for proximal forearm bone density, and -16.8% (p = 0.065) for serum parathyroid hormone. In 144 postmenopausal women, the corresponding effect sizes were -0.01223 g/cm(2) (p = 0.008) for distal forearm bone density, 4.7% (p = 0.064) for serum calcitonin, and 10.2% for bone-specific alkaline phosphatase. In all women, the effect sizes associated with a doubling of recent exposure were 7.2% (p = 0.001) for urinary HP, 7.2% (p = 0.021) for urinary LP, -9.0% (p = 0.097) for serum parathyroid hormone, and 5.5% (p = 0.008) for serum calcitonin. Only one woman had renal tubular dysfunction (urinary retinol-binding protein > 338 mu g/day).
CONCLUSIONS: In the absence of renal tubular dysfunction, environmental exposure to cadmium increases bone resorption in women, suggesting a direct osteotoxic effect with increased calciuria and reactive changes in calciotropic hormones
Biomarkers to assess right heart pressures in recipients of a heart transplant: a proof-of-concept study
Background: This proof-of-concept study investigated the feasibility of using biomarkers to monitor right heart pressures (RHP) in heart transplanted (HTx) patients.
Methods: In 298 patients, we measured 7.6 years post-HTx mean pressures in the right atrium (mRAP) and pulmonary artery (mPAP) and capillaries (mPCWP) along with plasma high-sensitivity troponin T (hsTnT), a marker of cardiomyocyte injury, and the multidimensional urinary classifiers HF1 and HF2, mainly consisting of dysregulated collagen fragments.
Results: In multivariable models, mRAP and mPAP increased with hsTnT (per 1-SD, +0.91 and +1.26 mm Hg; P < 0.0001) and with HF2 (+0.42 and +0.62 mm Hg; P ≤ 0.035), but not with HF1. mPCWP increased with hsTnT (+1.16 mm Hg; P < 0.0001), but not with HF1 or HF2. The adjusted odds ratios for having elevated RHP (mRAP, mPAP or mPCWP ≥10, ≥24, ≥17 mm Hg, respectively) were 1.99 for hsTnT and 1.56 for HF2 (P ≤ 0.005). In detecting elevated RHPs, areas under the curve were similar for hsTnT and HF2 (0.63 vs 0.65; P = 0.66). Adding hsTnT continuous or per threshold or HF2 continuous to a basic model including all covariables did not increase diagnostic accuracy (P ≥ 0.11), whereas adding HF2 per optimized threshold increased both the integrated discrimination (+1.92%; P = 0.023) and net reclassification (+30.3%; P = 0.010) improvement.
Conclusions: Correlating RHPs with noninvasive biomarkers in HTx patients is feasible. However, further refinement and validation of such biomarkers is required before their clinical application can be considered
Blood pressure and urinary sodium excretion in relation to the A-1984G adrenomedullin polymorphism in a Chinese population
Adrenomedullin (ADM) is a vasodilator and inhibits salt appetite. An A-to-G substitution at position -1984 in the promoter region of the ADM gene likely increases transcription. We therefore investigated this polymorphism in relation to blood pressure and urinary sodium in a Chinese population. We genotyped 427 Chinese enrolled in a family-based population study. We measured blood pressure by conventional sphygmomanometry and ambulatory monitoring. The frequencies of the ADM AA, AG, and GG genotypes were 50.6, 38.2, and 11.2%, respectively. In adjusted analyses, G allele carriers, compared to AA homozygotes, had significantly lower conventional (45.3 versus 48.5 mm Hg, P=0.004) and 24-h (42.6 versus 44.3 mm Hg, P=0.03) pulse pressures and urinary sodium excretion (143.8 versus 159.4 mmol/day, P=0.03). In parents, but not offspring, both systolic pressure and pulse pressure were significantly (P<0.01) lower in G allele carriers. The genotypic difference in sodium excretion was consistent across the age range. In 68 informative offspring, transmission of the G allele was associated with lower urinary sodium excretion (effect size, 40.1 mmol/day, P=0.01). In 81 healthy volunteers, the plasma ADM concentration was 15.2% higher in GG homozygotes than in sex- and age-matched AA subjects (11.4 versus 9.9 pmol/l, P=0.10). In conclusion, in Chinese, the ADM -1984G allele is associated with lower sodium excretion and in older subjects also with lower systolic pressure and narrower pulse pressure
Ethnic differences in proximal and distal tubular sodium reabsorption are heritable in black and white populations.
BACKGROUND: Segmental handling of sodium along the proximal and distal nephron might be heritable and different between black and white participants.
METHODS: We randomly recruited 95 nuclear families of black South African ancestry and 103 nuclear families of white Belgian ancestry. We measured the (FENa) and estimated the fractional renal sodium reabsorption in the proximal (RNaprox) and distal (RNadist) tubules from the clearances of endogenous lithium and creatinine. In multivariable analyses, we studied the relation of RNaprox and RNadist with FENa and estimated the heritability (h) of RNaprox and RNadist.
RESULTS: Independent of urinary sodium excretion, South Africans (n = 240) had higher RNaprox (unadjusted median, 93.9% vs. 81.0%; P < 0.001) than Belgians (n = 737), but lower RNadist (91.2% vs. 95.1%; P < 0.001). The slope of RNaprox on FENa was steeper in Belgians than in South Africans (-5.40 +/- 0.58 vs. -0.78 +/- 0.58 units; P < 0.001), whereas the opposite was true for the slope of RNadist on FENa (-3.84 +/- 0.19 vs. -13.71 +/- 1.30 units; P < 0.001). h of RNaprox and RNadist was high and significant (P < 0.001) in both countries. h was higher in South Africans than in Belgians for RNaprox (0.82 vs. 0.56; P < 0.001), but was similar for RNadist (0.68 vs. 0.50; P = 0.17). Of the filtered sodium load, black participants reabsorb more than white participants in the proximal nephron and less postproximally.
CONCLUSION: Segmental sodium reabsorption along the nephron is highly heritable, but the capacity for regulation in the proximal and postproximal tubules differs between whites and blacks
Cadmium accumulation and interactions with zinc, copper, and manganese, analysed by ICP-MS in a long-term Caco-2 TC7 cell model
The influence of long-term exposure to cadmium (Cd) on essential minerals was investigated using a Caco-2
TC7 cells and a multi-analytical tool: microwave digestion and inductively coupled plasma mass spectrometry.
Intracellular levels, effects on cadmium accumulation, distribution, and reference concentration
ranges of the following elements were determined: Na, Mg, Ca, Cr, Fe, Mn, Co, Ni, Cu, Zn, Mo, and Cd.
Results showed that Caco-2 TC7 cells incubated long-term with cadmium concentrations ranging from 0 to
10 lmol Cd/l for 5 weeks exhibited a significant increase in cadmium accumulation. Furthermore, this
accumulation was more marked in cells exposed long-term to cadmium compared with controls, and that
this exposure resulted in a significant accumulation of copper and zinc but not of the other elements
measured. Interactions of Cd with three elements: zinc, copper, and manganese were particularly studied.
Exposed to 30 lmol/l of the element, manganese showed the highest inhibition and copper the lowest on
cadmium intracellular accumulation but Zn, Cu, and Mn behave differently in terms of their mutual
competition with Cd. Indeed, increasing cadmium in the culture medium resulted in a gradual and significant
increase in the accumulation of zinc. There was a significant decrease in manganese from 5 lmol
Cd/l exposure, and no variation was observed with copper.
Abbreviation: AAS – Atomic absorption spectrometry; CRM– Certified reference material; PBS – Phosphate
buffered saline without calcium and magnesium; DMEM – Dubelcco’s modified Eagle’s medium
Haematological phenotypes in relation to the C1797T beta-adducin polymorphism in a Caucasian population
beta-Adducin plays a role in maintaining the structural integrity of the red blood cell (erythrocyte) membrane. Moreover, beta-adducin-deficient knock-out mice show a phenotype characterized by mild anaemia and compensated haemolysis. We therefore investigated whether, in humans, common haematological phenotypes of red blood cells were associated with a polymorphism in exon 15 of the human beta-adducin gene (C1797T). We studied 802 unrelated individuals and 294 families (459 parents and 609 offspring) randomly selected from a Caucasian population. We employed generalized estimating equations to allow for the non-independence of the observations within families, while controlling for co-variables. In 917 men, with adjustments applied for age, body mass index, serum total cholesterol, smoking and alcohol intake, CC homozygotes had significantly ( P =0.02) lower values for red blood cell count (4.93 x 10(12)/l compared with 4.86 x 10(12)/l), haemoglobin level (9.30 compared with 9.18 mmol/l) and haematocrit (45.0% compared with 44.4%) than T allele carriers. In the 329 men who consumed alcohol, the differences between CC homozygotes and T allele carriers were 0.13 x 10(12)/l ( P =0.02) for red blood cell count, 0.23 mmol/l ( P =0.005) for haemoglobin and 1.08% ( P =0.02) for haematocrit. In 953 women, none of these associations was significant ( P >/=0.06), regardless of alcohol intake [13.3% of women ( n =127) consmued alcohol]. In conclusion, in men consuming alcohol, the beta-adducin CC genotype was associated with lower red blood cell count, haemoglobin level and haematocrit. We hypothesize that, in CC homozygotes, alcohol consumption may unveil the greater fragility of the red blood cell membrane. This genotype may slightly potentiate the structural and functional haematological disturbances associated with alcohol intake
Catch-up growth in the first two years of life in Extremely Low Birth Weight (ELBW) infants is associated with lower body fat in young adolescence
Aim To investigate growth patterns and anthropometrics in former extremely low birth weight (ELBW, <1000 g) children and link these outcomes to neurocognition and body
Blood pressure changes after renal denervation at 10 European expert centers
We did a subject-level meta-analysis of the changes (Δ) in blood pressure (BP) observed 3 and 6 months after renal denervation (RDN) at 10 European centers. Recruited patients (n=109; 46.8% women; mean age 58.2 years) had essential hypertension confirmed by ambulatory BP. From baseline to 6 months, treatment score declined slightly from 4.7 to 4.4 drugs per day. Systolic/diastolic BP fell by 17.6/7.1 mm Hg for office BP, and by 5.9/3.5, 6.2/3.4, and 4.4/2.5 mm Hg for 24-h, daytime and nighttime BP (P0.03 for all). In 47 patients with 3- and 6-month ambulatory measurements, systolic BP did not change between these two time points (P0.08). Normalization was a systolic BP of <140 mm Hg on office measurement or <130 mm Hg on 24-h monitoring and improvement was a fall of 10 mm Hg, irrespective of measurement technique. For office BP, at 6 months, normalization, improvement or no decrease occurred in 22.9, 59.6 and 22.9% of patients, respectively; for 24-h BP, these proportions were 14.7, 31.2 and 34.9%, respectively. Higher baseline BP predicted greater BP fall at follow-up; higher baseline serum creatinine was associated with lower probability of improvement of 24-h BP (odds ratio for 20-μmol l(-1) increase, 0.60; P=0.05) and higher probability of experiencing no BP decrease (OR, 1.66; P=0.01). In conclusion, BP responses to RDN include regression-to-the-mean and remain to be consolidated in randomized trials based on ambulatory BP monitoring. For now, RDN should remain the last resort in patients in whom all other ways to control BP failed, and it must be cautiously used in patients with renal impairment
Blood pressure response to renal denervation is correlated with baseline blood pressure variability: a patient-level meta-analysis
Background: Sympathetic tone is one of the main
determinants of blood pressure (BP) variability and
treatment-resistant hypertension. The aim of our study was
to assess changes in BP variability after renal denervation
(RDN). In addition, on an exploratory basis, we investigated
whether baseline BP variability predicted the BP changes
after RDN.
Methods: We analyzed 24-h BP recordings obtained at
baseline and 6 months after RDN in 167 treatmentresistant
hypertension patients (40% women; age, 56.7
years; mean 24-h BP, 152/90 mmHg) recruited at 11 expert
centers. BP variability was assessed by weighted SD [SD
over time weighted for the time interval between
consecutive readings (SDiw)], average real variability (ARV),
coefficient of variation, and variability independent of the
mean (VIM).
Results: Mean office and 24-h BP fell by 15.4/6.6 and 5.5/
3.7 mmHg, respectively (P < 0.001). In multivariable-adjusted
analyses, systolic/diastolic SDiw and VIM for 24-h
SBP/DBP decreased by 1.18/0.63 mmHg (P 0.01) and
0.86/0.42 mmHg (P 0.05), respectively, whereas no
significant changes in ARV or coefficient of variation
occurred. Furthermore, baseline SDiw (P ¼ 0.0006), ARV
(P ¼ 0.01), and VIM (P ¼ 0.04) predicted the decrease in
24-h DBP but not 24-h SBP after RDN.
Conclusion: RDN was associated with a decrease in BP
variability independent of the BP level, suggesting that
responders may derive benefits from the reduction in BP
variability as well. Furthermore, baseline DBP variability
estimates significantly correlated with mean DBP decrease
after RDN. If confirmed in younger patients with less
arterial damage, in the absence of the confounding effect
of drugs and drug adherence, baseline BP variability may
prove a good predictor of BP response to RDN
Immunologic biomarkers in relation to exposure markers of PCBs and dioxins in Flemish adolescents (Belgium).
In this study, we investigated 17- to 18-year-old boys and girls to determine whether changes in humoral or cellular immunity or respiratory complaints were related to blood serum levels of polychlorinated biphenyls (PCBs) and dioxin-like compounds after lifetime exposure in Flanders (Belgium). We obtained blood samples from and administered questionnaires to 200 adolescents recruited from a rural area and two urban suburbs. Physicians recorded medical history and respiratory diseases. We measured immunologic biomarkers such as differential blood cell counts, lymphocyte phenotypes, and serum immunoglobulins. As biomarkers of exposure, we determined the serum concentrations of PCBs (PCB 138, PCB 153, and PCB 180) and dioxin-like compounds [chemical-activated luciferase expression (CALUX) bioassay]. The percentages of eosinophils and natural killer cells in blood were negatively correlated with CALUX toxic equivalents (TEQs) in serum (p = 0.009 and p = 0.05, respectively). Increased serum CALUX TEQs resulted in an increase in serum IgA levels (p = 0.05). Furthermore, levels of specific IgEs (measured by radioallergosorbent tests) of cat dander, house dust mite, and grass pollen were also significantly and negatively associated with the CALUX TEQ, with odds ratios (ORs) equal to 0.63 [95% confidence interval (CI), 0.42-0.96], 0.68 (0.5-0.93), and 0.70 (0.52-0.95), respectively. In addition, reported allergies of the upper airways and past use of antiallergic drugs were negatively associated with CALUX TEQs, with ORs equal to 0.66 (0.47-0.93) and 0.58 (0.39-0.85), respectively. We found a negative association between IgGs and marker PCBs in serum (p = 0.009). This study shows that immunologic measurements and respiratory complaints in adolescents were associated with environmental exposure to polyhalogenated aromatic hydrocarbons (PHAHs). The negative correlation between PHAHs and allergic responses in adolescents suggested that exposure may entail alterations in the immune status
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