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The effects of corticotropin-releasing factor (CRF) and urocortins on the noradrenaline (NA) released from the locus coeruleus (LC).
Peptides
December 2024
Department of Pathophysiology, Faculty of Medicine, University of Szeged, Hungary.
Corticotropin-releasing factor (CRF) activates the hypothalamic-pituitary-adrenal (HPA) axis and stimulates the noradrenergic neurotransmission, both processes being implicated in the pathogenesis of anxiety and depression, but the intimate site and mechanism of interaction of CRF and CRF-related peptides, named urocortins (UCN1, UCN2, UCN3), with noradrenaline (NA) was not fully elucidated yet. Therefore, the aim of the present study was to investigate the actions of CRF and urocortins on the NA released from the rat locus coeruleus (LC), the primary source of NA in the brain, and the participation of CRF receptors (CRF1 and CRF2) in these actions. In order to do so, male Wistar rats were used, their LC were isolated and dissected, and the LC slices were incubated with tritium-labelled NA, superfused and stimulated electrically.
View Article and Find Full Text PDFWhole cell affinity for 4-amino-5-hydroxymethyl-2-methylpyrimidine (HMP) in the marine bacterium Candidatus Pelagibacter st. HTCC7211 explains marine dissolved HMP concentrations.
Environ Microbiol Rep
October 2024
Department of Microbiology, Oregon State University, Corvallis, Oregon, USA.
Article Synopsis
- Vitamin B1 (thiamin) is essential for marine microorganisms, but many cannot synthesize it and must obtain it from their environment, particularly its pyrimidine precursor, HMP.
- HMP auxotrophy is common in marine plankton, and the low dissolved levels indicate that specialized uptake systems are needed to maintain these low concentrations.
- Research on the SAR11 clade, particularly Candidatus Pelagibacter st. HTCC7211, identified a sodium solute symporter called ThiV as the main transporter for HMP, with evidence showing its uptake is highly selective and regulated by environmental factors.
Monomethyl auristatin E (MMAE), a payload for multiple antibody drug conjugates (ADCs), demonstrates differential red blood cell partitioning across human and animal species.
Xenobiotica
August 2024
Preclinical and Translational Pharmacokinetics and Pharmacodynamics, Genentech Inc, South San Francisco, CA, USA.
Monomethyl auristatin E (MMAE) has been used as a payload for several Food and Drug Administration (FDA) approved antibody-drug conjugates (ADCs). It is known that MMAE is released from the ADC following binding, internalisation and proteolytic degradation in target tissues. A striking discrepancy in systemic MMAE levels has been observed across species with 50-fold higher MMAE levels in human than that in rodents when normalised by ADC dose with unknown mechanism.
View Article and Find Full Text PDFAltered lipid metabolism in synovial fibroblasts of individuals at risk of developing rheumatoid arthritis.
J Autoimmun
January 2023
Department of Rheumatology & Clinical Immunology and Department of Experimental Immunology, Amsterdam UMC Location University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Infection and Immunity Institute, Amsterdam, the Netherlands; Amsterdam Rheumatology & Immunology Center (ARC), Academic Medical Center, Amsterdam, the Netherlands. Electronic address:
Objective: Fibroblast-like synoviocytes (FLS) can augment the inflammatory process observed in synovium of patients with rheumatoid arthritis (RA). A recent transcriptomic study in synovial biopsies revealed changes in metabolic pathways before disease onset in absence of synovial tissue inflammation. This raises the question whether alterations in cellular metabolism in tissue resident FLS underlie disease pathogenesis.
View Article and Find Full Text PDFAbsorption, metabolism and excretion of once-weekly somapacitan, a long-acting growth hormone derivative, after single subcutaneous dosing in human subjects.
Eur J Pharm Sci
December 2021
Stem Cell Development, Novo Nordisk A/S, Måløv, Denmark; Clinical Drug Development, Novo Nordisk A/S, Søborg, Denmark. Electronic address:
Somapacitan is a reversible albumin-binding growth hormone (GH) derivative in clinical development for once-weekly administration in patients with adult GH deficiency (AGHD) and children with GH deficiency (GHD). To date, the use of somapacitan in AGHD or severe AGHD has been approved in the USA and Japan, respectively. This study (ClinicalTrials.
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