1. Among the phenolic metabolites of diclofenac in human plasma, an unknown compound (metabolite VI) was detected by h.p.l.c. and g.c. methods. This was also found in baboon plasma. 2. Metabolite VI was identified as 3'-hydroxy-4'-methoxy diclofenac by mass and n.m.r. spectroscopic analysis. Comparison with synthetic reference compound confirmed its structure. 3. In plasma, metabolite VI persists much longer than do unchanged diclofenac and the other phenolic metabolites. In urine, metabolite VI and its conjugates are excreted in trace amounts only. 4. A synthetic sample of metabolite VI was shown to be virtually inactive in animal models of inflammation and pain.
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http://dx.doi.org/10.3109/00498258809042242 | DOI Listing |
Trials
January 2025
Université Côte d'Azur, CNRS, LP2M, Nice, France.
Background: /aims. Pseudoxanthoma Elasticum (PXE, OMIM 264800) is an autosomal, recessive, metabolic disorder characterized by progressive ectopic calcification in the skin, the vasculature and Bruch's membrane. Variants in the ABCC6 gene are associated with low plasma pyrophosphate (PPi) concentration.
View Article and Find Full Text PDFMol Med
January 2025
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
Background: Lysinuric protein intolerance is a rare autosomal disorder caused by mutations in the Slc7a7 gene that lead to impaired transport of neutral and basic amino acids. The gold standard treatment for lysinuric protein intolerance involves a low-protein diet and citrulline supplementation. While this approach partially improves cationic amino acid plasma levels and alleviates some symptoms, long-term treatment is suggested to be detrimental and may lead to life-threatening complications characterized by a wide range of hematological and immunological abnormalities.
View Article and Find Full Text PDFBMC Nephrol
January 2025
Department of Nephrology, Japan Community Healthcare Organization Sendai Hospital, 981-3281, Sendai, Miyagi, Japan.
Background: Oliguric acute kidney injury (AKI) is one of the critical conditions which needs emergent treatment due to the lack of the capacity of excreting toxins and fluids, and plasma membrane bleb formation is considered as one of the characteristic morphologic alterations in ischemic AKI in both animal models and human. We present here an autopsy case with clear electron microscopy images capturing a definitive instance of blebbing in ischemic AKI.
Case Presentation: A 66-year-old man was admitted for oliguric AKI with nephrotic syndrome (NS).
Nat Commun
January 2025
Neurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, VU University Medical Center, Amsterdam UMC, Amsterdam, The Netherlands.
DOPA Decarboxylase (DDC) has been proposed as a cerebrospinal fluid (CSF) biomarker with increased concentrations in Lewy body disorders (LBDs) and highest levels in patients receiving dopaminergic treatment. Here we evaluate plasma DDC, measured by proximity extension assay, and the effect of dopaminergic treatment in three independent LBD (with a focus on dementia with Lewy bodies (DLB) and Parkinson's disease (PD)) cohorts: an autopsy-confirmed cohort (n = 71), a large multicenter, cross-dementia cohort (n = 1498) and a longitudinal cohort with detailed treatment information (n = 66, median follow-up time[IQR] = 4[4, 4] years). Plasma DDC was not altered between different LBDs and other disease groups or controls in absence of treatment.
View Article and Find Full Text PDFSci Rep
January 2025
Division of Human Nutrition and Health, Wageningen University, Stippeneng 4, 6708 WE, Wageningen, The Netherlands.
Cannabidiol (CBD), a specialized metabolite (phytocannabinoid) abundant in Cannabis sativa, is attracting increasing attention for its alleged health-promoting properties. The present study aimed to investigate the pharmacokinetics of CBD and its primary metabolite, 7-hydroxy-cannabidiol (7-OH-CBD), following a single oral dose of a CBD-rich Cannabis sativa extract, equivalent to 70 mg CBD, in healthy male (n=5) and female (n=6) participants. Using a randomized crossover design, the study evaluated the impact of a standardized high-fat meal compared to fasting on the oral bioavailability of CBD.
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