The profile of spontaneous contractions as well as the influences of prostacyclin (PGI2) on the motility of human ovarian veins obtained during the estrogenic phase of the sex cycle were explored. The preparations exhibited a distinct phasic activity, which progressively decreased as isolation time progresses, dissapearing almost completely following more than two hours. PGI2 produced a biphasic influence on quiescent preparations. After the threshold is attained lower concentrations caused depression of tone whereas higher ones enhanced the basal tone and induced phasic contractile cycles. Phentolamine reduced markedly the stimulating influence of PGI2 but had no action on the inhibitory effects, whereas propranolol failed to alter either the excitatory of the depressive action. The results suggest a participation of alpha-adrenoceptive-mediated mechanisms in the stimulatory effect of PGI2. On the other hand, PGI2 may be of importance in the regulation of venous flow and the spontaneous or PGI2-induced contractions could play a role in the counter current mechanism between veins and arteries in the ovarian pedicle.
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http://dx.doi.org/10.1016/0090-6980(79)90120-5 | DOI Listing |
NPJ Syst Biol Appl
January 2025
United Therapeutics Corporation, Silver Spring, MD, USA.
Challenges in drug development for rare diseases such as pulmonary arterial hypertension can be addressed through the use of mathematical modeling. In this study, a quantitative systems pharmacology model of pulmonary arterial hypertension pathophysiology and pharmacology was used to predict changes in pulmonary vascular resistance and six-minute walk distance in the context of oral treprostinil clinical studies. We generated a virtual population that spanned the range of clinical observations and then calibrated virtual patient-specific weights to match clinical trials.
View Article and Find Full Text PDFCirc J
January 2025
Department of Echo-imaging Center, Aizawa Hospital.
Background: Selexipag, an oral prostacyclin (PGI) receptor agonist, is approved for adult patients with pulmonary arterial hypertension (PAH). This study evaluated the efficacy and safety of selexipag for Japanese pediatric patients with PAH.
Methods And Results: The study enrolled 6 patients who received selexipag twice daily at an individualized dose based on body weight; maintenance doses were determined for each patient by 12 weeks after starting administration.
Cells
December 2024
Biomedical Institute for Multimorbidity, Hull York Medical School, University of Hull, Hull HU6 7RX, UK.
Granule secretion is an essential platelet function that contributes not only to haemostasis but also to wound healing, inflammation, and atherosclerosis. Granule secretion from platelets is facilitated, at least in part, by Soluble N-ethylmaleimide-Sensitive Factor (NSF) Attachment Protein Receptor (SNARE) complex-mediated granule fusion. Although α-synuclein is a protein known to modulate the assembly of the SNARE complex in other cells, its role in platelet function remains poorly understood.
View Article and Find Full Text PDFActa Anaesthesiol Scand
January 2025
CAG Center for Endotheliomics, Department of Clinical Immunology, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
Background: Acute respiratory failure (ARF) is common in critically ill patients, and 50% of patients in intensive care units require mechanical ventilation [3, 4]. The COVID-19 pandemic revealed that COVID-19 infection induced ARF caused by damage to the microvascular pulmonary endothelium. In a randomized clinical trial, mechanically ventilated COVID-19 patients with severe endotheliopathy, as defined by soluble thrombomodulin (sTM) ≥ 4 ng/mL, were randomized to evaluate the effect of a 72-h infusion of low-dose prostacyclin 1 ng/kg/min or placebo.
View Article and Find Full Text PDFExpert Opin Drug Saf
December 2024
Department of Rheumatology, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing, China.
Background: Adverse drug events (ADEs) for endothelin receptor antagonists (ERAs) and prostacyclin-related drugs (PRDs) have been reported in clinical trials, but large-scale, real-world evaluations for respiratory, thoracic, and mediastinal disorders (RTMD) remain scarce.
Methods: A pharmacovigilance analysis of the FAERS database (Q1 2004~Q2 2024) used the reporting odds ratio (ROR) method for disproportionality analysis to assess the adverse drug events (ADEs) of ERAs and PRDs in pulmonary arterial hypertension, focusing on risks related to RTMD.
Results: Reports of ADEs for ERAs (bosentan, ambrisentan, and macitentan) were 15,286, 36795, and 17,497, respectively, and for PRDs (epoprostenol, treprostinil, iloprost, and selexipag) were 5,477, 57265, 3,247, and 5,504.
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