We previously demonstrated that acute inhibition of voltage-gated calcium channels (VGCCs) is a common mode of action for (sub)micromolar concentrations of chemicals, including insecticides. However, because human exposure to chemicals is usually chronic and repeated, we investigated if selected insecticides from different chemical classes (organochlorines, organophosphates, pyrethroids, carbamates, and neonicotinoids) also disturb calcium homeostasis after subchronic (24 h) exposure and after a subsequent (repeated) acute exposure. Effects on calcium homeostasis were investigated with single-cell fluorescence (Fura-2) imaging of PC12 cells. Cells were depolarized with high-K(+) saline to study effects of subchronic or repeated exposure on VGCC-mediated Ca(2+) influx. The results demonstrate that except for carbaryl and imidacloprid, all selected insecticides inhibited depolarization (K(+))-evoked Ca(2+) influx after subchronic exposure (IC50's: approximately 1-10 µM) in PC12 cells. These inhibitory effects were not or only slowly reversible. Moreover, repeated exposure augmented the inhibition of the K(+)-evoked increase in intracellular calcium concentration induced by subchronic exposure to cypermethrin, chlorpyrifos, chlorpyrifos-oxon, and endosulfan (IC50's: approximately 0.1-4 µM). In rat primary cortical cultures, acute and repeated chlorpyrifos exposure also augmented inhibition of VGCCs compared with subchronic exposure. In conclusion, compared with subchronic exposure, repeated exposure increases the potency of insecticides to inhibit VGCCs. However, the potency of insecticides to inhibit VGCCs upon repeated exposure was comparable with the inhibition previously observed following acute exposure, with the exception of chlorpyrifos. The data suggest that an acute exposure paradigm is sufficient for screening chemicals for effects on VGCCs and that PC12 cells are a sensitive model for detection of effects on VGCCs.
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http://dx.doi.org/10.1093/toxsci/kfv154 | DOI Listing |
PLOS Glob Public Health
January 2025
Department of International Public Health, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
Globally, one in five people in post-conflict areas are estimated to be living with a mental health condition. As a key public health issue, these conditions negatively affect individuals, communities, and societies to function after a conflict. Documenting the prevalence of mental health conditions amongst these populations is crucial to prioritise and guide future mental health interventions.
View Article and Find Full Text PDFPsychol Trauma
January 2025
Department of Psychology, Division of Clinical Psychology and Psychotherapy, Saarland University.
Objective: The way we interpret information shapes our perception of reality. Predictive processing frameworks propose that the ability to update interpretations based on disconfirming information is key to recovery from potentially traumatic events (PTEs). However, direct evidence for this assumption is scarce and comes from studies using paradigms with low ecological validity.
View Article and Find Full Text PDFAppl Biochem Biotechnol
January 2025
Department of Biotechnology-CBS, Metropolitan Autonomous University Iztapalapa, Av. Ferrocarril San Rafael Atlixco 186, 09310, Mexico City, Mexico.
The presence of antibiotics in wastewater discharges significantly affects the environment, mainly due to the generation of bacterial populations with multiple antibiotic resistances. The cometabolic capacity of nitrifying sludge to simultaneously remove ammonium (NH) and emerging organic contaminants (EOCs), including antibiotics, has been reported. In the present study, the removal capacity of 50 mg ampicillin (AMP)/L by nitrifying cultures associated with biosorption and biotransformation processes was evaluated in a sequencing batch reactor (SBR) system.
View Article and Find Full Text PDFBackground: Currently there is no way to determine if archived cerebrospinal fluid (CSF) specimens have been properly handled and can be considered suitable for research purposes. Transthyretin (TTR) is abundant in CSF and undergoes a redox reaction that shifts its native proteoform into an S-cysteinylated form. This reaction proceeds spontaneously ex vivo when CSF is thawed, but ceases at storage temperatures of -80°C.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Erasmus University Medical Center, Rotterdam, Zuid-Holland, Netherlands.
Background: Non-steroidal anti-inflammatory (NSAID) medication are suggested to have beneficial effects in the prevention of Alzheimer's disease, due to anti-inflammatory and possibly amyloid-lowering properties. However, the results of observational studies and randomized-controlled trials have been inconsistent, and duration and dose-response relationships are still unclear.
Method: We included 11,745 dementia-free participants from the prospective population-based Rotterdam Study (59.
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