Electronic polymers in lipid membranes

Electrical interfaces between biological cells and man-made electrical devices exist in many forms, but it remains a challenge to bridge the different mechanical and chemical environments of electronic conductors (metals, semiconductors) and biosystems. Here we demonstrate soft electrical interfaces, by integrating the metallic polymer PEDOT-S into lipid membranes. By preparing complexes between alkyl-ammonium salts and PEDOT-S we were able to integrate PEDOT-S into both liposomes and in lipid bilayers on solid surfaces. This is a step towards efficient electronic conduction within lipid membranes. We also demonstrate that the PEDOT-S@alkyl-ammonium:lipid hybrid structures created in this work affect ion channels in the membrane of Xenopus oocytes, which shows the possibility to access and control cell membrane structures with conductive polyelectrolytes

Cadmium-induced oxidative cellular damage in human fetal lung fibroblasts (MRC-5 cells).

Epidemiological evidence suggests that cadmium (Cd) exposure causes pulmonary damage such as emphysema and lung cancer. However, relatively little is known about the mechanisms involved in Cd pulmonary toxicity. In the present study, the effects of Cd exposure on human fetal lung fibroblasts (MRC-5 cells) were evaluated by determination of lipid peroxidation, intra-cellular production of reactive oxygen species (ROS), and changes of mitochondrial membrane potential. A time- and dose-dependent increase of both lactate dehydrogenase leakage and malondialdehyde formation was observed in Cd-treated cells. A close correlation between these two events suggests that lipid peroxidation may be one of the main pathways causing its cytotoxicity. It was also noted that Cd-induced cell injury and lipid peroxidation were inhibited by catalase and superoxide dismutase, two antioxidant enzymes. By using the fluorescent probe 2',7'-dichlorofluorescin diacetate, a significant increase of ROS production in Cd-treated MRC-5 cells was detected. The inhibition of dichlorofluorescein fluorescence by catalase, not superoxide dismutase, suggests that hydrogen peroxide is the main ROS involved. Moreover, the significant dose-dependent changes of mitochondrial membrane potential in Cd-treated MRC-5 cells, demonstrated by increased fluorescence of rhodamine 123 examined using a laser-scanning confocal microscope, also indicate the involvement of mitochondrial damage in Cd cytotoxicity. These findings provide in vitro evidence that Cd causes oxidative cellular damage in human fetal lung fibroblasts, which may be closely associated with the pulmonary toxicity of Cd

Renal Morphology, Clinical Findings, and Progression Rate in Mesoamerican Nephropathy

BackgroundMesoamerican nephropathy (MeN) is a chronic kidney disease affecting rural inhabitants in Central America. We have previously described the renal morphology in 8 patients from El Salvador. To confirm the renal pathology, we have studied kidney biopsies from patients with MeN in Nicaragua. Follow-up urine and blood samples from both biopsy studies were collected to investigate the natural history

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

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

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