Joint toxicity of cadmium and ionizing radiation on zooplankton carbon incorporation, growth and mobility

The risk of exposure to radioactive elements is seldom assessed considering mixture toxicity, potentially over- or underestimating biological and ecological effects on ecosystems. This study investigated how three end points, carbon transfer between phytoplankton and Daphnia magna, D. magna mobility and growth, responded to exposure to γ-radiation in combination with the heavy metal cadmium (Cd), using the MIXTOX approach. Observed effects were compared with mixture effects predicted by concentration addition (CA) and independent action (IA) models and with deviations for synergistic/antagonistic (S/A), dose-level (DL), and dose-ratio (DR) dependency interactions. Several patterns of response were observed depending on the end point tested. DL-dependent deviation from the IA model was observed for carbon incorporation with antagonism switching to synergism at higher doses, while the CA model indicated synergism, mainly driven by effects at high doses of γ-radiation. CA detected antagonism regarding acute immobilization, while IA predicted DR-dependency. Both CA and IA also identified antagonism for daphnid growth. In general, effects of combinations of γ-radiation and Cd seem to be antagonistic at lower doses, but synergistic at the higher range of the doses tested. Our results highlight the importance of investigating the effects of exposure to γ-radiation in a multistressor context

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) and hypertension: a review of vasodilatory mechanisms of DHA and EPA

Hypertension is often characterised by impaired vasodilation involving dysfunction of multiple vasodilatory mechanisms. ω-3 polyunsaturated fatty acids (PUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) can reduce blood pressure, and vasodilation. In the endothelium, DHA and EPA improve function including increased nitric oxide bioavailability. However, animal studies show that DHA- and EPA-mediated vasodilation persists after endothelial removal, indicating a role for vascular smooth muscle cells (VSMCs). The vasodilatory effects of ω-3 PUFAs on VSMCs are mediated via opening of large conductance calcium-activated potassium channels (BK ), ATP-sensitive potassium channels (K ) and possibly members of the Kv7 family of voltage-activated potassium channels, resulting in hyperpolarisation and relaxation. ω-3 PUFA actions on BK and voltage-gated ion channels involve electrostatic interactions that are dependent on the polyunsaturated acyl tail, cis-geometry of these double bonds and negative charge of the carboxyl headgroup; suggesting structural manipulation of ω-3 PUFA could generate novel, targeted, therapeutic leads

Association between 24-Hour Urinary Cadmium and Pulmonary Function among Community-Exposed Men: The VA Normative Aging Study

Background: High levels of cadmium exposure are known to cause emphysema in occupationally exposed workers, but little has been reported to date on the association between chronic environmental cadmium exposure and pulmonary function. Objective: In this study we examined the association between pulmonary function and cadmium body burden in a subcohort of the Normative Aging Study, a community-based study of aging. Methods: We examined 96 men who had cadmium measured in single 24-hr urinary specimens collected in 1994–1995 and who had one to three tests of pulmonary function between 1994 and 2002 (a total of 222 observations). We used mixed-effect models to predict pulmonary function based on individual 24-hr urinary cadmium output, adjusted for age, height, time elapsed from the baseline, and smoking status. We assessed effect modification by smoking status. Results: Among all subjects, a single log-unit increase in baseline urinary cadmium was inversely associated with forced expiratory volume in 1 sec (FEV1) percent predicted [β = −7.56%; 95% confidence interval (CI) −13.59% to −1.53%]; forced vital capacity (FVC) percent predicted (β = −2.70%; 95% CI −7.39% to 1.99%), and FEV1/FVC ratio (β = −4.13%; 95% CI −7.61% to −0.66%). In models including an interaction between urinary cadmium and smoking status, there was a graded, statistically significant reduction in FEV1/FVC ratio across smoking status in association with urinary cadmium. Conclusions: This study suggests that chronic cadmium exposure is associated with reduced pulmonary function, and cigarette smoking modifies this association. These results should be interpreted with caution because the sample size is small, and further studies are needed to confirm our findings

Aluminum Bioavailability from Basic Sodium Aluminum Phosphate, an Approved Food Additive Emulsifying Agent, Incorporated in Cheese

Oral aluminum (Al) bioavailability from drinking water has been previously estimated, but there is little information on Al bioavailability from foods. It was suggested that oral Al bioavailability from drinking water is much greater than from foods. The objective was to further test this hypothesis. Oral Al bioavailability was determined in the rat from basic [26Al]-sodium aluminum phosphate (basic SALP) in a process cheese. Consumption of approximately 1g cheese containing 1.5% or 3% basic SALP resulted in oral Al bioavailability (F) of approximately 0.1% and 0.3%, respectively, and time to maximum serum 26Al concentration (Tmax) of 8-9h. These Al bioavailability results were intermediate to previously reported results from drinking water (F approximately 0.3%) and acidic-SALP incorporated into a biscuit (F approximately 0.1%), using the same methods. Considering the similar oral bioavailability of Al from food vs. water, and their contribution to the typical human\u27s daily Al intake ( approximately 95% and 1.5%, respectively), these results suggest food contributes much more Al to systemic circulation, and potential Al body burden, than does drinking water. These results do not support the hypothesis that drinking water provides a disproportionate contribution to total Al absorbed from the gastrointestinal tract

Monitoring Voltage-Dependent Charge Displacement of Shaker B-IR K+ Ion Channels Using Radio Frequency Interrogation

Here we introduce a new technique that probes voltage-dependent charge displacements of excitable membrane-bound proteins using extracellularly applied radio frequency (RF, 500 kHz) electric fields. Xenopus oocytes were used as a model cell for these experiments, and were injected with cRNA encoding Shaker B-IR (ShB-IR) K+ ion channels to express large densities of this protein in the oocyte membranes. Two-electrode voltage clamp (TEVC) was applied to command whole-cell membrane potential and to measure channel-dependent membrane currents. Simultaneously, RF electric fields were applied to perturb the membrane potential about the TEVC level and to measure voltage-dependent RF displacement currents. ShB-IR expressing oocytes showed significantly larger changes in RF displacement currents upon membrane depolarization than control oocytes. Voltage-dependent changes in RF displacement currents further increased in ShB-IR expressing oocytes after ∼120 µM Cu2+ addition to the external bath. Cu2+ is known to bind to the ShB-IR ion channel and inhibit Shaker K+ conductance, indicating that changes in the RF displacement current reported here were associated with RF vibration of the Cu2+-linked mobile domain of the ShB-IR protein. Results demonstrate the use of extracellular RF electrodes to interrogate voltage-dependent movement of charged mobile protein domains — capabilities that might enable detection of small changes in charge distribution associated with integral membrane protein conformation and/or drug–protein interactions

Metabolic profiling detects early effects of environmental and lifestyle exposure to cadmium in a human population

Background: The ‘exposome’ represents the accumulation of all environmental exposures across a lifetime. Topdown strategies are required to assess something this comprehensive, and could transform our understanding of how environmental factors affect human health. Metabolic profiling (metabonomics/metabolomics) defines an individual’s metabolic phenotype, which is influenced by genotype, diet, lifestyle, health and xenobiotic exposure, and could also reveal intermediate biomarkers for disease risk that reflect adaptive response to exposure. We investigated changes in metabolism in volunteers living near a point source of environmental pollution: a closed zinc smelter with associated elevated levels of environmental cadmium. Methods: High-resolution 1H NMR spectroscopy (metabonomics) was used to acquire urinary metabolic profiles from 178 human volunteers. The spectral data were subjected to multivariate and univariate analysis to identify metabolites that were correlated with lifestyle or biological factors. Urinary levels of 8-oxo-deoxyguanosine were also measured, using mass spectrometry, as a marker of systemic oxidative stress. Results: Six urinary metabolites, either associated with mitochondrial metabolism (citrate, 3-hydroxyisovalerate, 4- deoxy-erythronic acid) or one-carbon metabolism (dimethylglycine, creatinine, creatine), were associated with cadmium exposure. In particular, citrate levels retained a significant correlation to urinary cadmium and smoking status after controlling for age and sex. Oxidative stress (as determined by urinary 8-oxo-deoxyguanosine levels) was elevated in individuals with high cadmium exposure, supporting the hypothesis that heavy metal accumulation was causing mitochondrial dysfunction. Conclusions: This study shows evidence that an NMR-based metabolic profiling study in an uncontrolled human population is capable of identifying intermediate biomarkers of response to toxicants at true environmental concentrations, paving the way for exposome research. Keywords: metabonomics, cadmium, environmental health, exposome, metabolomics, molecular epidemiolog

Accuracy of GFR estimating equations based on creatinine, cystatin C or both in routine care.

peer reviewed[en] BACKGROUND: New equations to estimate glomerular filtration rate based on creatinine (eGFRcr), cystatin C (eGFRcys) or both (eGFRcr-cys) have been developed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and the European Kidney Function Consortium (EKFC). There is a need to evaluate the performance of these equations in diverse European settings to inform implementation decisions, especially among people with key comorbid conditions. METHODS: We performed a cross-sectional study including 6174 adults referred for single-point plasma clearance of iohexol in Stockholm, Sweden, with 9579 concurrent measurements of creatinine and cystatin C. We assessed the performance of the CKD-EPI 2009/2012/2021, EKFC 2021/2023, revised Lund-Malmö (RLM) 2011 and Caucasian, Asian, Pediatric and Adult (CAPA) 2014 equations against measured GFR (mGFR). RESULTS: Mean age was 56 years, median mGFR was 62 mL/min/1.73 m2 and 40% were female. Comorbid conditions were common: cardiovascular disease (30%), liver disease (28%), diabetes (26%) and cancer (26%). All eGFRcr-cys equations had small bias and P30 (the percentage of estimated values within 30% of mGFR) close to 90%, and performed better than eGFRcr or eGFRcys equations. Among eGFRcr equations, CKD-EPI 2009 and CKD-EPI 2021 showed larger bias and lower P30 than EKFC 2021 and RLM. There were no meaningful differences in performance across eGFRcys equations. Findings were consistent across comorbid conditions, and eGFRcr-cys equations showed good performance in patients with liver disease, cancer and heart failure. CONCLUSIONS: In conclusion, eGFRcr-cys equations performed best, with minimal variation among equations in this Swedish cohort. The lower performance of CKD-EPI eGFRcr equations compared with EKFC and RLM may reflect differences in population characteristics and mGFR methods. Implementing eGFRcr equations will require a trade-off between accuracy and uniformity across regions