PubMed · 7724502
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
P Kardos, T Gebhardt, E Decot. 1995. [Chronic persistent cough: therapy].. https://pubmed.ncbi.nlm.nih.gov/7724502/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Disruption of mitochondria and free radical mediated tissue injury have been reported during cardiotoxicity induced by isoproterenol (ISO), a beta-adrenergic catecholamine. The present study was designed to investigate the effect of the combination of ferulic acid (FA) and ascorbic acid (AA) on the mitochondrial damage in ISO induced cardiotoxicity. Induction of rats with ISO (150 mg/kg b.wt., i.p.) for 2 days resulted in a significant decrease in the activities of respiratory chain enzymes (NADH dehydrogenase and cytochrome c-oxidase), tricarboxylic acid cycle enzymes (isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, alpha-ketoglutarate dehydrogenase), mitochondrial antioxidants (GPx, GST, SOD, CAT, GSH), cytochromes (b, c, c1, aa3) and in the level of mitochondrial phospholipids. A marked elevation in mitochondrial lipid peroxidation, mitochondrial levels of cholesterol, triglycerides and free fatty acids were also observed in ISO intoxicated rats. Pre-co-treatment with the combination of FA (20 mg/kg b.wt.) and AA (80 mg/kg b.wt.) orally for 6 days significantly enhanced the attenuation of these functional abnormalities and restored normal mitochondrial function when compared to individual drug treated groups. Mitigation of ISO induced biochemical and morphological changes in mitochondria were more pronounced with a combination of FA and AA rather than the individual drug treated groups. Transmission electron microscopic observations also correlated with these biochemical parameters. Hence, these findings demonstrate the synergistic ameliorative potential of FA and AA on mitochondrial function during beta-adrenergic catecholamine induced cardiotoxicity and associated oxidative stress in rats.
Most inhaled beta(2)-adrenergic agonist and anticholinergic bronchodilators have low lipid solubility because of their transient or permanent positive net charge at physiologic pH. Airway absorption of these cationic drugs is incompletely understood. We examined carrier-mediated mechanisms of cationic drug uptake by human airway epithelia. Airway tissues and epithelial cells, obtained from lung donors without preexisting lung disease, were evaluated for organic cation transporter expression by quantitative RT-PCR and immunofluorescence. For in vitro functional studies on primary airway epithelial cells, uptake of the cationic fluorophore 4-[4-(dimethylamino)-styryl]-N-methylpyridinium (ASP+) was characterized. Quantitative RT-PCR analysis demonstrated high mRNA levels for two polyspecific organic cation/carnitine transporters, OCTN1 and OCTN2, in human airway epithelia. Immunofluorescence of human airway sections confirmed OCTN1/2 protein expression, with a predominant localization to the apical portion of epithelial cells. Primary airway epithelial cells showed a carrier-mediated, temperature-sensitive and saturable uptake of ASP(+). Seventy-five to eighty percent of ASP(+) uptake was inhibited by L-carnitine, an OCTN2-carried zwitterion. The uptake was pH dependent, with approximately 3-fold lower rates at acidic (pH 5.7) than at alkaline (pH 8.2) extracellular pH. Albuterol and formoterol inhibited ASP(+) uptake, suggesting that all these molecules are carried by the same transport mechanism. These findings demonstrate the existence and functional role of a pH-dependent organic cation uptake machinery, namely OCTN1 and OCTN2, in human airway epithelia. We suggest that epithelial OCTN1/2 are involved in the delivery of inhaled cationic bronchodilators to the airway tissue.
Preterm labor (PTL) affects up to 25% of human pregnancies in developing countries, but there are few therapeutic options. Based on the key role of oxytocin (OXT) in labor and parturition, OXT antagonists are a potentially useful class of drugs for PTL. Barusiban is a new selective, potent, and long-acting OXT receptor antagonist. In this study barusiban was given by continuous i.v. infusion to monkeys during the last 3 wk of pregnancy; the monkeys were also given daily doses of OXT to induce uterine contractions and simulate PTL. Barusiban effectively suppressed OXT-induced PTL-like contractions and prevented early delivery. In contrast, fenoterol (a beta2-adrenoceptor [beta2-AR] agonist used as a comparative control) did not inhibit uterine contractions in this model. Barusiban was particularly effective in maintaining low intrauterine pressure (IUP) near the end of pregnancy, which is when IUP in both OXT controls and fenoterol-treated females increased substantially. Although barusiban delayed the onset of labor, it did not prevent normal delivery. These data demonstrate the safety and efficacy of barusiban in reducing uterine contractility in response to repeated OXT challenge, and suggest that barusiban may be therapeutically effective in long-term treatment of PTL.