Chelerythrine, a potent inhibitor of protein kinase C (PKC), was evaluated for its effect on inositol phosphate (IP) metabolism in newborn rat cardiomyocytes in culture. In a first step, we evaluated ...the effect of chelerythrine on IP accumulation in basal conditions. For a 10–4 M dose, 5‐phosphatase activity (which dephosphorylates IP3 into IP2) was completely blocked and we observed a large increase in IP accumulation limited to IP2 without any increase in IP3, strongly suggesting that chelerythrine at this dose modifies IP metabolism. At a lower dose (10–5 M) of chelerythrine, which did not modify IP accumulation and 5‐phosphatase activity in basal conditions, the response to angiotensin II stimulation was completely abolished by the addition of chelerythrine. We conclude thus that chelerythrine, even at 10–5 M, interacts markedly with IP metabolism, and caution should be exerted when interpreting the results obtained with this drug, which is still currently used at this dose.
Thèse de doctorat : Biologie cellulaire et moléculaire : Paris 12 : 2006.
Titre provenant de l'écran-titre. Pagination : 224 f. Bibliogr. f. 193-221.
Heart failure, a progressive disorder characterized by deterioration of cardiac function and premature myocardial cell death, results from several common heart diseases such as coronary ...atherosclerosis, hypertension, and valvular diseases (1,2). With almost 550,000 new cases diagnosed each year, heart failure affects an estimated 4.7 million Americans, and costs associated with the disease range from $10 billion to $40 billion per year (3). The aggregate 5-year mortality of patients with heart failure is about 50%, while the 1-year mortality of patients with advanced disease may exceed 50% (3). To maintain adequate myocardial contractility in response to injury, the heart uses several mechanisms, including hypertrophy of myocardial cells, changing the energetics of myocardial cell contraction, and upregulating transcription of several genes (4,5).
Sleep apnoea syndrome and cardiac failure Badoual, T; d'Ortho, M P; Le Corvoisier, P ...
Archives des maladies du coeur et des vaisseaux
98, Številka:
3
Journal Article
Despite recent therapeutic advances, chronic cardiac failure is still associated with a significant morbidity and mortality. Sleep apnoea syndrome is common in this population, affecting almost half ...of these patients. However, it is rarely diagnosed and treated. There are two types of sleep apnoea syndrome, which can sometimes co-exist: the obstructive apnoea syndrome with collapse of the upper airways, and the central apnoea syndrome with cyclical Cheyne-Stokes respiration, linked with anomalies of central control. Apnoea leads to sympathetic stimulation and an increase in the left ventricular post-charge which can alter cardiac function and the prognosis. Diagnosis of sleep apnoea syndromes is now made with small ambulatory oxymeters which do not disturb sleep and which allow precise detection of episodes of desaturation. Treatment with positive pressure ventilation brings an improvement in daytime symptoms (fatigue, drowsiness) as well as an improvement in cardiac function. Screening for sleep apnoea is thus essential in patients with chronic heart failure, especially in those resistant to optimal drug treatment, in order to improve their management.