L’acylation des protéines : une fonction cellulaire importante des acides gras saturés

Fatty acid acylation of proteins corresponds to the co- or post-translational covalent linkage of a fatty acid, activated in the form of acyl-CoA, to an amino acid residue of the substrate protein. The cellular fatty acids which are involved in protein acylation are mainly saturated fatty acids. Palmitoylation (S-acylation) corresponds to the reversible attachment of palmitic acid (C16:0) to the side chain of a cysteine residue via a thioester bond. N-terminal myristoylation refers to the covalent attachment of myristic acid (C14:0) by an amide bond to the N-terminal glycine of many eukaryotic and viral proteins. Octanoylation (O-acylation) typically concerns the formation of an ester bond between octanoic acid (caprylic acid, C8:0) and the side chain of a serine residue of the gut and brain peptide ghrelin. An increasing number of proteins (enzymes, receptors, oncogenes, tumor suppressors, proteins involved in signal transduction, eukaryotic and viral structural proteins) have been shown to undergo fatty acid acylation. The acyl moiety can mediate protein subcellular localization, protein–protein interaction or protein–membrane interaction. Therefore, through the covalent modification of proteins, saturated fatty acids exhibit emerging specific and important roles in modulating protein functions. This review provides an overview of the recent findings on the various classes of protein acylation leading to the biological ability of saturated fatty acids to regulate many pathways. Finally, the links between these elucidated biochemical mechanisms and the physiological roles of dietary saturated fatty acids are discussed.     

Patients souffrant de schizophrénie en EHPAD et objectifs de prise en charge par l’équipe de psychiatrie de secteur ?

Old people's home welcomes old subjects presenting more and more numerous psychic and organic pathologies with the headway in age. What are the difficulties met in establishment and which tracks of solutions can be envisaged? What are coverages proposed for the residents living in establishment and who suffer from psychiatric chronic pathologies like the schizophrenia? What role then for the team of Psychiatry of sector?     

Left main coronary dissection after mild chest trauma. Favorable evolution with fibrinolytic and surgical therapies

A 32-year-old woman had acute anterior myocardial infarction after a mild chest trauma (automobile accident). Unstable angina recurred shortly after admission, and extensive dissection of the left coronary artery was demonstrated. Medical therapy including systemic fibrinolysis was started but clinical stabilization and good long-term result was achieved only by aortocoronary bypass grafting.     

Spontaneous arrhythmias in various models of cardiac hypertrophy and senescence of rats. A Holter monitoring study.

OBJECTIVE: The aim was to define experimental models of spontaneous arrhythmias in various models of cardiac hypertrophy in rats. METHODS: Cardiac hypertrophy was induced by several methods and 24 h Holter monitoring was recorded in conscious rats to quantify spontaneous arrhythmias in hypertrophied hearts. Male Wistar rats were studied. A group of young controls 1-2 months old (n = 16) was compared to four groups of animals with cardiac hypertrophy: (1) thyrotoxic rats which received a daily intraperitoneal injection of L-thyroxine for 7 d (n = 6); (2) rats subjected to abdominal suprarenal aortic stenosis (n = 11); (3) senescent rats 22-24 month old (n = 6); and (4) S-DOCA-salt (senescent animals rendered hypertensive by uninephrectomy and DOCA-salt treatment, n = 8). RESULTS: (1) Thyroxine resulted in 20% cardiac hypertrophy, with normal arterial tension, sinus tachycardia, a shorter P wave length and PR interval, and frequent (5/6) atrioventricular block. No premature beats were seen. (2) In aortic stenosis, atria and left ventricle were hypertrophied by 53% and systolic carotid pressure increased by 63%. The incidence of supraventricular premature beats was increased [frequency = 0.70 (SEM 0.3) per 24 h in control v 99(61) in aortic stenosis, p < 0.05]. Ventricular premature beats remained as rare as in control. (3) In senescent and S-DOCA-salt rats all types of spontaneous arrhythmias, but specially supraventricular arrhythmias and atrioventricular block, were frequent. Cardiac hypertrophy produced by DOCA-salt treatment in senescent rats had no effect on the incidence and nature of arrhythmias, but resulted in an increased QTc interval. CONCLUSIONS: Senescent rats and rats with aortic stenosis represent valid models of spontaneous arrhythmias occurring in the absence of ischaemia or toxic insult. Spontaneous arrhythmias in rats are mainly of supraventricular origin. Hyperthyroidism in rats is a model of atrioventricular block probably related to tachycardia. Holter monitoring in rats may have several potential pathophysiological and pharmacological applications.     

Opposite central cardiovascular effects of nifedipine and BAY k 8644 in anesthetized rats

The central cardiovascular effects of the calcium channel blocker nifedipine and the calcium channel activator BAY k 8644 were studied in anesthetized and ventilated normotensive Wistar-Kyoto (WKY) or spontaneously hypertensive rats (SHR). Both drugs were administered in a 1.5-microliter volume into the lateral ventricle of the brain (i.c.v.) or into the cisterna magna (i.c.). The injection of vehicle alone (i.c. or i.c.v.) did not significantly change mean arterial pressure (MAP) or heart rate. Nifedipine (5 and 50 micrograms/kg) and BAY k 8644 (5 and 50 micrograms/kg) induced opposite effects on MAP when centrally injected. Nifedipine decreased MAP and induced a bradycardia (i.c.v.) or no change in heart rate (i.c.), and BAY k 8644 increased MAP without any significant change in heart rate (i.c. or i.c.v.). These effects were more marked with the highest dose of either drug. These effects seemed to be of central origin, since they were suppressed by ganglionic blockade by hexamethonium (100 mg/kg i.v.), whereas after hexamethonium the hypotensive and the hypertensive responses to intravenously injected nifedipine and BAY k 8644, respectively, were preserved. Bilateral vagotomy suppressed the bradycardia induced by i.c.v. administered nifedipine. Previously i.c.v. administered nifedipine (5 micrograms/kg) antagonized the pressor response to BAY k 8644 (5 micrograms/kg i.c.v.). Changes in MAP and heart rate were significantly more marked in SHR than in WKY. These results indicate that a calcium channel inhibitor and a calcium channel activator can modulate in opposite fashion central mechanisms involved in blood pressure control.     

Long-term fluvastatin reduces the hazardous effect of renal impairment on four-year atherosclerotic outcomes (a LIPS substudy)

Mild renal impairment is an important risk factor for late cardiovascular complications. This substudy of the Lescol Intervention Prevention Study (LIPS) assessed the effect of fluvastatin on outcome of patients who had renal dysfunction and those who did not. Complete data for creatinine clearance calculation (Cockcroft-Gault formula) were available for 1,558 patients (92.9% of the LIPS population). Patients were randomized to fluvastatin or placebo after successful completion of a first percutaneous coronary intervention. Follow-up time was 3 to 4 years. The effect of baseline creatinine clearance on coronary atherosclerotic events (cardiac death, nonfatal myocardial infarction, and coronary reinterventions not related to restenosis) was evaluated. Baseline creatinine clearance (logarithmic transformation) was inversely associated with an incidence of adverse events among patients who received placebo (hazard ratio 0.99, 95% confidence interval 0.982 to 0.998, p = 0.01). However, no association was noted between creatinine clearance and the incidence of adverse events among patients who received fluvastatin (hazard ratio 1.0, 95% confidence interval 0.99 to 1.0, p = 0.63). No further deterioration in creatinine clearance was observed during follow-up, regardless of baseline renal function or allocated treatment. Occurrence of adverse events was not related to changes in renal function during follow-up. Fluvastatin therapy markedly decreased the risk of coronary atherosclerotic events after percutaneous intervention in patients who had lower values of creatinine clearance at baseline. The benefit of fluvastatin was unrelated to any effect on renal function.     

Complementary role of thallium-201 scintigraphy to predischarge exercise electrocardiography for patients stratification after a first myocardial infarction

The value of a predischarge exercise test combined with thallium-201 myocardial scintigraphy in detecting patients with severe multivessel disease (MVD) was studied in 58 consecutive patients discharged after a first acute myocardial infarction. Twelve electrocardiographic, clinical and scintigraphic variables were analysed. Angiography at one month revealed MVD (greater than 70% narrowing in vessels unrelated to infarction) in 26 patients (45%). ST segment depression of 1mm or greater, thallium defects in multiple vascular distributions (MVTL), and reversible thallium defects in a vascular distribution different from the infarct related vessel predicted patients at risk for MVD (predictive value respectively of 68%, 65% and 75%). The other variables were not significantly associated with the presence of MVD. Only ST segment depression and thallium defects in multiple vascular distributions emerged as independent predictors of MVD. Their combination yielded a 77% sensitivity and a 59% specificity for MVD. Combination of thallium imaging with the predischarge exercise ECG significantly improved the stratification provided by the exercise test alone (P less than 0.05). A positive thallium scan (MVTl defects) associated with a positive ECG (ST depression) carried a risk for MVD of 80% in the population studied. When both tests were negative, MVD was infrequent (risk 22%). Because improvement in the stratification of patients is not as clear as expected from studies performed at a later stage, it appears that exercise thallium scintigraphy at a submaximal level one or two weeks after infarction does not provide optimal information. Predischarge exercise thallium-201 scintigraphy, however, is superior to an exercise tolerance test alone in separating patients into those with high and low risk of MVD.     

Combined treatment of liver failure and hepatorenal syndrome with orthotopic liver transplantation.

Hepatorenal syndrome (HRS) is a severe complication of liver failure with high mortality. The pathogenesis of this reversible functional renal failure is not yet clearly understood. Diagnosis is based upon the association of clinical and biological criteria. A patient was admitted to our institution for severe liver failure secondary to an exacerbation of cirrhosis, where he developed a fulminant hepatorenal syndrome. Both, the renal and hepatic failure were successfully treated by orthotopic liver transplantation. Special attention was paid to the immunosuppressive treatment with Cyclosporine whose use, we believe, should be delayed until function has partially recovered.