The transient K+ current (IK(A)) affects the rate of repetitive action potentials. The whole-cell patch-clamp technique was applied to cultured Drosophila neurons derived from embryonic neuroblasts. IK(A) was measured from neurons before and after application of 0.1 mM copper to the external saline. IK(A) was smaller in the copper-containing saline (12.0 +/- 1.6 pA) than in the control saline (37 +/- 6.5 pA). Activation and inactivation of IK(A) were unchanged by copper. These results suggest that copper can influence neuronal excitability and may affect neuronal function.
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http://dx.doi.org/10.1023/b:nere.0000018851.62617.36 | DOI Listing |
Cell Calcium
December 2024
Department of Physiology and Cell Biology, University of Nevada Reno School of Medicine, Reno, NV, 89557, USA. Electronic address:
Interstitial cells of Cajal in the plane of the myenteric plexus (ICC-MY) serve as electrical pacemakers in the stomach and small intestine. A similar population of cells is found in the colon, but these cells do not appear to generate regular slow wave potentials, as characteristic in more proximal gut regions. Ca handling mechanisms in ICC-MY of the mouse proximal colon were studied using confocal imaging of muscles from animals expressing GCaMP6f exclusively in ICC.
View Article and Find Full Text PDFInt J Toxicol
January 2025
Chemical and Preclinical Safety Department, Global Chemical and Preclinical Safety, Merck KGaA, Darmstadt, Germany.
The therapeutic window of antibody drug-conjugates (ADC) remains challenging due to safety issues such as interstitial lung disease (ILD) observed with specific deruxtecan-based ADCs. To avoid ILD, we designed M9140 by conjugating the maleimide-containing hydrophilic β-glucuronide linker to exatecan and our anti-CEACAM5 (CarcinoEmbryonic Antigen-related Cell Adhesion Molecule 5) specific antibody. Following repeated iv-infusion at 3 to 30 mg/kg of M9140 every 3 weeks, the pathological findings obtained in cynomolgus monkeys were confined to gastrointestinal and hematolymphoid tissues and resembled the toxicity of exatecan.
View Article and Find Full Text PDFCancer Immunol Immunother
January 2025
National Centre for Asbestos Related Diseases, The University of Western Australia, Perth, Australia.
Combination immune checkpoint inhibitors (nivolumab and ipilimumab) are currently a first-line treatment for mesothelioma; however, not all patients respond. The efficacy of treatment is influenced by the tumor microenvironment. Murine mesothelioma tumors were irritated with various radiotherapy doses.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by synapse and memory failure, and severe cognitive impairment. Physical exercise stimulates neuroprotective pathways, has pro-cognitive actions, and has been reported to alleviate memory impairment in AD. Irisin, an exercise-induced hormone, is secreted following proteolytic cleavage of fibronectin type-III-domain-containing 5 (FNDC5).
View Article and Find Full Text PDFAm J Gastroenterol
January 2025
Division of Endocrinology, Gerontology and Metabolism Stanford University School of Medicine.
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an important public health threat, potentially leading to chronic liver disease and liver cancer. Current guidelines recommend using the FIB-4 score for initial identification of subjects at risk of future complications. We formulate a novel population screening strategy based on the Steatosis-Associated Fibrosis Estimator (SAFE) score, recently developed for MASLD risk stratification in primary care.
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