Le prédicat

À partir des difficultés que présente l’analyse d’énoncés synonymiques tels que Ce gâteau est délicieux et Délicieux, ce gâteau en termes de « sujet » et « prédicat », cet article se propose de rappeler quelques tournants cruciaux dans l’histoire des deux notions. Le point de départ est le sens de base des termes grecs hypokeímenon et katêgórêma, leur emploi spécifique dans les Catégories d’Aristote, puis leur traduction latine dans les Boetii Commentarii, leur réemploi dans la Grammaire de Port-Royal, et, pour finir, le déplacement conceptuel introduit par J.W. Meiner (1781) et ses disciples, qui voient dans le prédicat l’élément central de la phrase, gouvernant des « arguments » parmi lesquels se trouve le sujet. Le dilemme didactique parait être le suivant : faire le bon choix entre ces conceptions incompatibles de la prédication ou abandonner le prédicat en tant que notion syntaxique.Synonymic utterances such as Ce gâteau est délicieux and Délicieux, ce gâteau, are difficult to analyse in terms of « subject » and « predicate ». Using this as a starting point, our paper aims at reminding the reader of some crucial turning points in the history of those two notions. We start by looking at the basic meaning of the Greek terms hypokeímenon and katêgórêma, their specific usage in Aristotle’s Categories on Interpretation, their latin translation in Boetii Commentarii, their reinvestment in Port-Royal Grammar. Finally, we place emphasis on the conceptual shift introduced by J. W. Meiner (1781) and his followers, who regard the predicate as the central element of the sentence, governing « arguments » amongst which the subject is to be found. The didactic dilemma seems to be the following : either we are forced to choose between these incompatible views on predication, or we give up the idea of the predicate as a syntactic notion

Patient adherence and the choice of antihypertensive drugs: focus on lercanidipine

Despite the development of many effective antihypertensive drugs, target blood pressures are reached in only a minority of patients in clinical practice. Poor adherence to drug therapy and the occurrence of side effects are among the main reasons commonly reported by patients and physicians to explain the poor results of actual antihypertensive therapies. The development of new effective antihypertensive agents with an improved tolerability profile might help to partly overcome these problems. Lercanidipine is an effective dihydropyridine calcium channel blocker of the third generation characterized by a long half-life and its lipophylicity. In contrast to first-generation dihydropyridines, lercanidipine does not induce reflex tachycardia and induces peripheral edema with a lower incidence. Recent data suggest that in addition to lowering blood pressure, lercanidipine might have some renal protective properties. In this review we shall discuss the problems of drug adherence in the management of hypertension with a special emphasis on lercanidipine

P-621: Metabolic determinants of proximal sodium reabsorption in healthy women

Increased reabsorption of sodium (Na) in the proximal segments of the nephron is present in hypertensive patients. Studies performed in men reported an association between proximal Na reabsorption and features of the metabolic syndrome. This study explores the relationship between metabolic variables and proximal Na reabsorption in healthy women. This study is population-based and cross-sectional examining 661 healthy women aged 40-75y. After 15 minutes rest, blood pressure was measured 3 times, blood was drawn and urine was collected. Fractional excretion of endogenous lithium (FELi) was used as an indirect marker of proximal sodium reabsorption, lithium being only reabsorbed in the proximal tubule. All women receiving blood pressure, blood glucose or lipid lowering therapy were excluded. Correlations: FELi was positively correlated with the fractional excretion of sodium (FENa, r=0.3, p<0.001). FELi was negatively associated with total cholesterol (r=-0.14, P<0.0001), LDL-cholesterol (r=-0.16, P<0.0001), BMI (r=-0.08, P<0.05) and weight (r=-0.09, P<0.05). Menopausal status or a family history of hypertension did not affect the associations. Simple linear regression analysis: age, waist circumference, waist/hip ratio, systolic blood pressure, diastolic blood pressure, Hdl cholesterol, triglycerides, serum uric acid or a family history of hypertension were not significant predictors of FELi. BMI was a significant predictor but the strongest relationships were found between FELi and total cholesterol, LDL-cholesterol and FENa. Multivariate linear regression model: When significant predictors of FELi were examined in a multivariate linear regression model also controlling for age, weight, systolic blood pressure and FENa, total cholesterol (p=0.003) or LDL-cholesterol (p=0.001) significantly and independently predicted FELi. In conclusion, these data suggest that metabolic parameters, in particular total cholesterol and LDL-cholesterol and to a lesser extent weight and BMI, are associated with increased proximal Na reabsorption in a healthy untreated women population. Considering the possible link between increased reabsorption of sodium and the development of hypertension, a major cardiovascular risk factor, this association may provide an additional hypothesis for the increased cardiovascular risk of subjects with the metabolic syndrom

The effect of pH-neutral peritoneal dialysis fluids on adipokine secretion from cultured adipocytes

Background. Adipokines are a group of fat-secreted hormones and cytokines, including leptin and adiponectin, with important functions in humans. Peritoneal dialysis (PD) is associated with markedly raised plasma adipokines, suggesting increased production in this setting. We have shown that low pH down-regulates leptin production. The current study was designed to test if novel pH-neutral PD fluids may regulate leptin and adiponectin secretion in vitro. Methods. We exposed 3T3-L1 adipocytes to a 50 : 50 mixture of dialysate and M199 containing 10% serum for upto 48 h. Dialysates were commercial PD fluids, i.e. conventional acidic, lactate-buffered solutions (PD-acid) and pH-neutral lactate-buffered (PD-Bal) or bicarbonate-buffered solutions (PD-Bic). Leptin and adiponectin concentrations in culture-cell media were measured by ELISA. Results. Compared with PD-acid, PD-Bal and PD-Bic produced a 25 and 43% increase, respectively, in leptin secretion at 48 h (P < 0.05). In contrast, adiponectin secretion was not affected. High glucose PD fluids (4.25%) specifically inhibited leptin secretion vs 1.5% glucose, buffer-matched solutions (P < 0.05). However, differences in leptin secretion due to pH and type of buffer remained significant. In further experiments, the pH of test media were extensively varied without the presence of dialysates. Leptin secretion was shown to increase in a parallel to pH, whereas large changes in pH did not affect adiponectin secretion. Conclusion. The pH-neutral PD solutions specifically induce leptin, but not adiponectin secretion from 3T3-L1 adipocytes. PD-Bic produced a greater leptin stimulation than PD-Bal, but this difference was attributable to pH per se, rather than the type of buffe

O-28: Molecular basis for the insurmountable AT-1 receptor antagonism of telmisartan

In vitro studies have shown that telmisartan is an insurmountable angiotensin II AT-1 receptor antagonist. In this study we have investigated the molecular basis of this insurmountable antagonism. The association and dissociation kinetics of telmisartan to angiotensin AT-1 receptors were measured using an in vitro radio-receptor binding assay. These radioligand binding studies were conducted either directly on rat vascular (aorta) smooth muscle cells (RVSMC) expressing solely the AT-1 receptor or on membrane preparation obtained from the same cells. The specific binding of3H-telmisartan to the surface of living RVSMC or membranes was saturable. From these data, a Kd value of 1.7 nM was estimated. Scatchard analysis of the3H-telmisartan binding on RVSMC indicated the existence of a single class of binding sites. The affinity of telmisartan for AT-1 receptor is only poorly affected by the presence of proteins (0.4% of rat plasma proteins) in the binding buffer, indicating that no great competition between telmisartan binding to its specific AT-1 receptor and to non-specific proteins binding sites occurs. In association experiments, the specific binding of3H-telmisartan increases quickly and reaches equilibrium within less than 1 hour, with an association rate constant calculated to be 0.006 min-1nM-1. Telmisartan dissociates very slowly from the AT-1 receptor, either in RVSMC membrane preparation or in living cells with a dissociation rate constant of ca. 0.01 min-1 resulting in a dissociation half-life (t1/2) of about 60 min, which is comparable to the previously published data for candesartan in bovine adrenal cortical membranes and almost 5 times slower than that of 125I-angiotensin II binding (t1/2=12 min). In contrast to candesartan that has been shown to re-associate with the AT-1 receptor, telmisartan does not appear to re-associate. Indeed, when the dissociation of labeled-telmisartan from AT-1 receptors was induced by washing the cells with cold-binding buffer, followed by addition of fresh binding buffer containing either cold telmisartan, Ang II or losartan, or nothing, no difference were observed in the dissociation rate constants measured with telmisartan whatever the composition of the binding buffer after removal of labeled-telmisartan. In conclusion, these results suggest that the insurmountable antagonism of telmisartan is due mainly to its very slow dissociation from angiotensin AT-1 receptor

P-440: Losartan but not irbesartan reduces serum uric acid in hypertensive patients with hyperuricemia and/or gout

Losartan has unique uricosuric properties and has been shown to decrease serum uric acid (SUA) levels in normal subjects as well as in hypertensive patients. The purpose of the present study was to compare the effects of losartan and irbesartan on serum uric acid in hypertensive hyperuricemic patients with or without gout. Twelve hyperuricemic (SUA>420mmol/L), hypertensive patients (mean age: 58 yr) participated in this randomized, double-blind, crossover study. After a 3-week run-in period during which patients received enalapril 20 mg o.d, patients were randomized to receive either losartan 50 mg o.d for 4 weeks followed by losartan 50 mg bid for another 4 week period or irbesartan 150 mg o.d followed by irbesartan 150 mg bid for 4 weeks. The losartan and irbesartan phases were separated by 3 weeks of the ACE inhibitor. All drugs were provided in an electronic pill container allowing to monitor compliance (MEMS system). Losartan decreased SUA significantly from 539±28 mmol/L to 490±22 mmol/L (p1 month). Hence, the uricosuric effect tends to decrease with time as SUA is reduced. Increasing the dose of losartan to 50 mg bid does not appear to induce a further decrease in serum uric aci

P-537: Pioglitazone blunts the blood pressure response to angiotensin II in insulin-resistant zucker rats

Thiazolidinediones are high-affinity agonists of peroxisome proliferator-activated receptors (PPAR)-γ which have been found to lower blood pressure (BP) in animal models of diabetes and reno-vascular hypertension. The mechanisms leading to this decrease in blood pressure are still unclear. Since the renin-angiotensin system is a main regulator of blood pressure, we investigated the effects of pioglitazone on blood pressure, plasma renin activity and on the blood pressure response to exogenous angiotensin II in insulin-resistant Zucker rats. Pioglitazone 20mg/kg/d or vehicle were administered for 4 weeks to 8-weeks old fa/fa Zucker rats. Pioglitazone-treated rats were heavier than vehicle-treated rats (respectively 481g±8g vs 437±5g, p=0.0002, mean±SEM) and ate more (35.6±0.5g/d vs 28.9±0.3, p<0.0001). The increase in blood sugar after an intra-venous glucose tolerance test was significantly attenuated in the pioglitazone treated rats at 10,15 and 30 minutes. Systolic (SBP), diastolic (DBP) blood pressure and heart rate (HR) were lower in pioglitazone-treated rats: SBP: 124±3 mmHg vs 144±3, p<0.001; DBP: 80±2 vs 94±2, p<0.001; HR: 369±6 vs 397±8, p<0.01. The BP response to exogenous angiotensin II was significantly attenuated in pioglitazone treated rats. With the 25 ng/kg Ang II dose the increase in BP was 27.8±2.4 mmHg with pioglitazone and 37.5±3.3 with the vehicle (p=0.04) and with the Ang II 100 ng/kg dose the increase in BP was respectively 36.1±2.7 mmHg and 49.2±2.3 (p=0.003). Plasma renin activity was comparable in both groups. In conclusion, these results show that pioglitazone blunts the BP response to angiotensin II in insulin-resistant Zucker rats. This effect may partially explain the blood pressure lowering effect of PPAR-γ agonist