Caspase-1-deficient (-/-) mice are protected against sepsis-induced hypotension and mortality. We investigated the role of caspase-1 and its associated cytokines in a nonhypotensive model of endotoxemic acute renal failure (ARF). Mice were injected intraperitoneally with 2.5 mg of LPS that induces endotoxemic ARF. On immunoblot analysis of whole kidney, there was an increase in caspase-1 protein in LPS-treated mice compared with vehicle-treated controls. In LPS-treated mice, the glomerular filtration rate (GFR) was significantly higher in caspase-1 -/- vs. wild-type mice at 16 and 36 h after LPS. To determine the mechanism of this protection, the caspase-1-activated cytokines IL-1beta and IL-18 were investigated. IL-1beta and IL-18 protein were significantly increased in the kidneys of LPS- vs. vehicle-treated mice. To determine the role of these cytokines, mice were treated with recombinant IL-1 receptor antagonist (IL-1Ra) or IL-18-neutralizing antiserum. In LPS-treated mice, GFR was not different in IL-1Ra-treated or IL-18-neutralizing antiserum-treated or combination therapy (IL-1Ra plus IL-18-neutralizing antiserum-treated) compared with control mice. In addition, tubular cell apoptosis, neutrophil infiltration, myeloperoxidase activity, caspase-3 activity, and calpain activity were not different between wild-type and caspase-1 -/- mice with endotoxemic ARF. In LPS- vs. vehicle-treated wild-type mice, renal IL-1alpha was significantly increased. In both LPS- and vehicle-treated caspase-1 -/- mice, renal IL-1alpha was very low. In summary, caspase-1 -/- mice are functionally protected against endotoxemic ARF. Neutralization of IL-1beta and IL-18 is not functionally protective. The role of the intracellular proinflammatory cytokine IL-1alpha in endotoxemic ARF merits further study.
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http://dx.doi.org/10.1152/ajprenal.00130.2004 | DOI Listing |
J Ultrasound Med
January 2025
State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, China.
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View Article and Find Full Text PDFARP Rheumatol
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Instituto de Medicina Molecular-João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Centro Académico de Medicina de Lisboa, Portugal.
Introduction - Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease, which causes local and systemic bone damage. The main goal of this work was to analyze, how treatment intervention with Ab501 (certolizumab mice equivalent) prevents the disturbances on bone structure and mechanics induced by arthritis. Methods - Thirty DBA/1 collagen-induced arthritis (CIA) mice were randomly housed in experimental groups, as follows: arthritic untreated (N=9), preventive intervention (N=10) and treatment intervention (N=11).
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
January 2025
Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Raebareli (NIPER-R), Transit Campus, Bijnor-Sisendi Road, Sarojini Nagar, Near CRPF Base Camp, Lucknow, UP, Lucknow, 226002, India.
Atopic dermatitis (AD) is a chronic skin inflammatory ailment commonly observed in young children and adults. Various therapeutic modalities are already explored for mitigation of AD but for prolong application very few modalities are recommended. Considering these challenges, we have successfully developed gliclazide-loaded hydrogels using the physical dispersion method.
View Article and Find Full Text PDFPsychopharmacology (Berl)
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Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Canada.
Rationale: Clinical literature indicates there may be a therapeutic use of cannabidiol (CBD) for stress-related disorders. Preclinical literature remains conflicted regarding the underlying neurobehavioral mechanisms, reporting mixed effects of CBD (increased, decreased, or no effect) on anxiety- and fear-related behaviors. Preclinical data demonstrated that CBD modulates hypothalamus-pituitary-adrenal (HPA) axis gene expression; it is unknown whether CBD changes HPA axis responsivity and how this relates to altered behavior.
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Department of Pharmacy, the Second Affiliated Hospital of Shaoyang University, Shaoyang, Hunan, China.
Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β (Aβ) plaques and the aggregation of tau protein, resulting in intense memory loss and dementia. Diabetes-associated cognitive dysfunction (DACD) is a complication of diabetes mellitus, which is associated with decreased cognitive function and impaired memory. A growing body of literature emphasize the involvement of microglia in AD and DACD.
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