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Biomedical subjects

J Sassard

Publications and source records attributed to J Sassard.

At least 127 records · Page 7Linked to original sources
PubMed1988

Liquid-chromatographic determination of free and total 3,4-dihydroxyphenylglycol and 3-methoxy-4-hydroxyphenylglycol in urine.

We describe the conjoint measurement in urine of the alcoholic catecholamine metabolites 3,4-dihydroxyphenylglycol (DHPG) and 3-methoxy-4-hydroxyphenylglycol (MHPG). The method involves extraction with ethyl acetate and back-extraction into acetic acid (MHPG), followed by adsorption onto alumina (DHPG). The separation is performed by reversed-phase liquid chromatography with column switching and amperometric detection. Total (free plus conjugated) compounds are determined after a 24-h enzymatic hydrolysis. Twelve-hour excretion values for normal and hypertensive subjects are given, together with results obtained for patients with pheochromocytoma, chemodectoma, and congenital dopamine-beta-hydroxylase deficiency. The assay is sensitive, reproducible, and free of interferences, and may lead to a better understanding of overall catecholamine metabolism in health and disease.

Adrenal Gland Neoplasms↗
PubMed1988

Uric acid renal handling: spontaneous changes and influence of a thiazide alone or associated with triamterene.

The spontaneous changes in renal handling of uric acid, the consequences of methyclothiazide (M) and of a combination of M with three doses of triamterene (25, 50, 75 mg) were assessed in eight normal men, in a ten-week placebo controlled, double-blind study. In untreated subjects, significant correlations were found between blood uric acid (bUA) and UAV, between bUA and FeUA, between FeUA and plasma renin activity (PRA) and between bUA and PRA. Spontaneous variations in bUA and UAV were shown to be predominantly dependent on changes in sodium status. All diuretics significantly increased bUA and decreased FeUA. Under diuretics, bUA kept correlations with FeUA and PRA similar to that observed in untreated subjects indicating that the changes were dependent only on variations in renal transport induced by changes in sodium status. Addition of triamterene to methyclothiazide significantly lessened the thiazide induced abnormalities in UA.

Adult↗
PubMed1987

Determination of teicoplanin in human plasma and urine by affinity and reversed-phase high-performance liquid chromatography.

A sensitive, highly selective and simple high-performance liquid chromatographic method for the determination of teicoplanin, a novel glycopeptide antibiotic, composed of six components, in human plasma and urine is described. After an isolation step by affinity chromatography, the antibiotic substances were chromatographed on a Nucleosil C18 column with phosphate buffer-acetonitrile according to a gradient profile. All the components were detected by their UV absorption at 240 nm. The concentration of teicoplanin was determined by using the external standard procedure. This method was applied to the sum of the six major components as well as to each of them separately. The linearity of the method was checked between 0.5 and 50 micrograms/ml for plasma and between 2 and 50 micrograms/ml for urine. The limit of detection was 0.1 microgram/ml for both biological fluids. The coefficients of variation of the between-day assays did not exceed 8.6 and 8.9% in plasma and urine, respectively. The application of the method to a pharmacokinetic study of teicoplanin after a single intravenous therapeutic dose in a patient is reported. This rapid technique also appears to be suitable for drug monitoring.

Anti-Bacterial Agents↗
PubMed1987

Evidence for discrete alterations in central cardiovascular catecholamine and neuropeptide Y immunoreactive neurons in aged male rats and in genetically hypertensive male rats of the Lyon strain.

A computer-assisted morphometrical and microdensitometrical analysis has been performed on cardiovascular noradrenaline (NA), adrenaline (A) and neuropeptide (Y (NPY) neurons in adult and 24-month-old male rats and on hypotensive (LL), normotensive (LN) and hypertensive (LH) male rats of the Lyon strain using the indirect immunoperoxidase procedures. It was found that in NPY/phenylethanolamine-N-methyltransferase (PNMT) costoring neurons of the CI area of the rostral medulla oblongata NPY-like immunoreactivity showed a more marked reduction than the PNMT immunoreactivity. Furthermore, within the parvocellular part of the paraventricular hypothalamic nucleus. NPY immunoreactive nerve terminal profiles were much more affected than the PNMT immunoreactive profiles during aging as revealed by a marked reduction in the number of profiles and by a marked reduction of absorbency values in the microdensitometrical analysis. Thus, in the NPY/PNMT costoring neurons of the A C1 group of the ventrolateral medulla projecting, for example, to the hypothalamus, the peptide transmission line may have a special vulnerability to the aging processes which may contribute to the development of hypertension in old people in view of a vasodepressor role of many central NPY/PNMT neurons. An extensive morphometrical and microdensitometrical analysis of the various catecholamine (CA) cell groups of the medulla oblongata of the LL, LN and LH rats of the Lyon strain was performed. In a comparison between LL and LH rats the A2 cell group of the LH strain showed a trend for an increase in the mean tyrosine hydroxylase (TH) immunoreactive cell body area and the C3 group showed a significant increase in the number of PNMT immunoreactive profiles.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1987

Magnesuria induced by thiazides and the influence of triamterene.

The effects on magnesium excretion of 4 short-term diuretic treatments (methyclothiazide 2 mg either alone or associated with increasing doses of triamterene) were evaluated in 8 normal volunteers and compared to spontaneous variations during placebo administration. The thiazide exerted a small but significant magnesuric effect, which was prevented only by the lowest dose (25 mg) of triamterene. Larger doses had no protective effect on thiazide-induced magnesuria. Independently of their absolute effects on magnesium excretion, all diuretics impaired the normal ability of the kidneys to compensate fully for the expected changes in magnesium reabsorption induced by extracellular volume contraction.

Adult↗
PubMed1987

Pharmacokinetics of teicoplanin in renal failure.

By using a highly specific chromatographic technique, the effect of renal failure on the pharmacokinetics of the six main components of teicoplanin, taken individually or as a whole, was assessed for over 120 h after administration of a 3-mg/kg intravenous dose to healthy volunteers (group 1, n = 6) and to noninfected patients with moderate (group 2, n = 6) or severe (group 3, n = 7) renal failure. In subjects with normal renal function, total teicoplanin was mainly excreted in urine and its concentrations in plasma could be adequately fitted to a three-compartment model. Renal failure did not affect the model or the distribution of teicoplanin but strongly decreased its renal clearance (9.3, 3.2, and 0.6 ml/h per kg, respectively, for the three groups of subjects), in close relationship with the creatinine clearance (r = 0.973, n = 18, P less than 0.001). The cumulative urinary excretion of unchanged total teicoplanin was decreased (50, 21, and 5% of the given dose for groups 1 to 3) and the terminal half-life was enhanced (62, 96, and 111 h for groups 1 to 3) by renal impairment. The relative behavior of the six major components was only slightly affected by renal failure. Consequently, the dosage regimen adjustment could be based on the total teicoplanin concentration, and simulations with the mean estimated pharmacokinetic parameters suggest that the 6-mg/kg daily dose, known to be effective in patients with normal renal function, could be given every 2 and 3 days in patients with moderate and severe renal insufficiency, respectively.

Adult↗
PubMed1987

[Sensitivity of the cardiac baroreflex in genetically hypertensive rats of a Lyons strain].

To determine precisely the influence of high blood pressure and age on the baroreflex sensitivity (BRS), we measured it in conscious genetically hypertensive (LH), normotensive (LN) and low-blood pressure (LL) rats of the Lyon strains. Groups of male rats were studied at the age of 5, 9, 13, 21 and 40 weeks. Using our previously described technique, their blood pressure (BP) and heart period (HP) were recorded beat by beat, in the conscious unrestrained state. Each animal received 2 or 3 i.v. injections of phenylephrine (PHE, 5 micrograms/kg) and nitroglycerin (NG, 100 micrograms/kg). The BRS (msec/mmHg) was computed as the slope of the closest relationship found between systolic BP (SBP) and HP changes. Otherwise, in the 13-week-old rats, BRS had been measured in basal conditions, after vagal blockade (atropine: 2 mg/kg i.v.) and after beta-adrenergic blockade (propranolol: 2 mg/kg) so as to determine the relative importance of vagal and sympathetic components of the baroreflex. In LN and LL rats, the BRS measured with PHE and NG increased markedly between 5 and 9 weeks of age and then remained stable in LN rats or decreased between 21 and 40 weeks of age in LL rats. In LH rats, BRS remained stable between 5 and 9 weeks of age and increased slightly up to 21 weeks of age. Significant differences between LH and LN rats were observed starting from 9 weeks of age when BRS was measured with PHE and only at 9 weeks of age when it was measured with NG injections. In 13-week-old rats, the cardiac baroreflex response was estimated to depend for 82 p. 100 and 18 p. 100 upon vagal and sympathetic components respectively when BRS was measured with PHE injections and of 68 p. 100 and 32 p. 100 when it was measured with NG injections.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1987

[Circadian changes in the sensitivity of the baroreflex in the conscious rat].

The cardiac baroreflex sensitivity (BRS) was measured in quiet awake rats after phenylephrine injections. It was shown that BRS progressively increased during daytime (rest period) and decreased at the beginning of the night (activity period). These variations were independent from the levels of blood pressure and heart period recorded before the BRS measurements.

Animals↗
PubMed1987

Chronopharmacokinetics of indomethacin in rats.

In order to establish the origin of the circadian variations in the kinetics of indomethacin (Indocid) observed in humans, a chronopharmacokinetic study was developed in rats. In a first experiment, 3 groups of 24 h fasted rats each received a single i.v. dose of 0.25 or 0.5 or 1 mg/kg b.w. of indomethacin, respectively, at 8 h. Thus it could be demonstrated that the pharmacokinetics of indomethacin were linear in the dose range studied and obeyed a two-compartment model. In a second experiment, 3 other groups of rats from same strain received a single i.v. dose of 0.5 mg/kg b.w. of indomethacin at 2 h, 14 h and 20 h, respectively. In the 4 groups of rats having received 0.5 mg/kg b.w. of indomethacin, it was observed that only the pharmacokinetic parameters which reflected the distribution process exhibited significant circadian variations. When the animals were dosed at 2 h (physiological rest time for rats) the initial plasma concentration (Co = 4.2 +/- 0.08 micrograms/ml) and the area under the curve (AUC = 13.6 +/- 0.5 h micrograms/ml) was significantly lower while the distribution volume (Vd/b.w. = 120 +/- 2 ml/kg) and the total metabolic clearance (ClT/b.w. = 25 +/- 1.1 ml/h/kg) were higher than those observed in rats dosed at 20 h (period of activity). The apparent elimination half-life was not significantly altered by the time of administration. These results are in good agreement with those that we have previously reported in humans orally dosed with indomethacin, and suggest that the mechanisms of the circadian changes of the pharmacokinetics of indomethacin are mainly related to alterations in the drug distribution.

Animals↗
PubMed1986

Antihypertensive effects of S9490-3, a new converting enzyme inhibitor, in the conscious spontaneously hypertensive rat.

The acute and chronic cardiovascular effects of S9490-3, a new converting enzyme inhibitor, were studied by means of a computerized analysis of the intra-aortic blood pressure recorded for 48 consecutive hours, in the conscious, unrestrained adult spontaneously hypertensive rat (SHR). The software used allowed the simultaneous study of one control and one treated animal. A single intravenous dose of S9490-3 (2 mg/kg) induced a rapid fall in systolic and diastolic blood pressure, which remained significant for 11 h. This decrease was not associated with an elevation in heart rate. A chronic oral treatment with S9490-3 (1 mg/kg/24 h for 12 days) significantly lowered systolic and diastolic blood pressure and reduced the variability of systolic blood pressure. The heart rate was slightly increased at rest (day time) but significantly elevated in the freely exercising SHR (night time). However, it must be noted that this increase remained moderate. The baroreflex sensitivity of chronically treated animals was enhanced when measured after phenylephrine but not after nitroglycerine bolus. Chronically given S9490-3 significantly reduced the pressor effect of phenylephrine and decreased the left ventricle weight.

Administration, Oral↗
PubMed1986

Routine analysis of catecholamines and metabolites in urine by a liquid chromatographic column switching system.

A reversed-phase liquid chromatographic technique including a column switching system has been adapted for the routine measurement of catecholamines and their metabolites (14 compounds) in urine. From 1 ml of urine all the compounds and the internal standards were obtained according to combined extraction procedures involving organic solvent, anionic and weakly cationic resins. Finally four extracts (catecholamines, methoxamines, acidic and neutral derivatives) had to be chromatographed throughout a wholly automated apparatus. For each run, the column switching system determined the analytical columns to be used to obtain the separation of the compounds from interferences due to other co-extracted endogenous substances, while the analysis times remained between 20 and 40 min. Such a system allowed the rapid clean-up of columns (in direct- and back-flush mode) carried out between two consecutive injections. By coupling on-line fluorimetric and electrochemical detections the specificity of the technique could be checked, since the ratio of the responses of both detectors was an index of the purity of the peaks. Finally the advanced automation of the equipment allowed weekly the evaluation of catecholamines and the whole range of their known metabolites in 36 urine samples.

Catecholamines↗
PubMed1986

Swim training in genetically hypertensive rats of the Lyon strain: effects on plasma lipids and lipoproteins.

We studied the effects of training by forced swimming on plasma lipid and lipoprotein concentrations in the Lyon genetically hypertensive rats (LH), its normotensive (LN) and low blood pressure (LL) controls. Training was carried out 5 days a week for 5 weeks. The duration of daily training sessions was increased 15 min per day, from 2 to 6 h/day. Following training low density lipoprotein-cholesterol (LDL-C) was significantly lower (P less than 0.01) in LL, and the very low density lipoprotein (VLDL-C) was also lower in LN (P less than 0.01) and LH (P less than 0.05) rats compared with their sedentary controls. High density lipoprotein-cholesterol (HDL-C) was not significantly increased after training in all strains. Compared with controls, plasma total cholesterol, plasma triglycerides and phospholipids were not modified by training. The reduction of LDL-C, VLDL-C as well as the increase of the HDL-C:VLDL-C ratio suggest a beneficial effect of training on atherosclerosis and perhaps coronary heart disease risk.

Animals↗
PubMed1986

Pharmacokinetics of isoxicam in hepatic disease.

1 The pharmacokinetics of single and repeated oral doses of isoxicam, an extensively metabolized drug, were studied in patients with compensated and decompensated hepatic disease. 2 After a single oral dose, isoxicam was slowly absorbed and eliminated (half-life ranging from 10.5 to 53.9 h). Its pharmacokinetics did not differ from those observed in healthy volunteers and were not significantly influenced by the severity of hepatic disease. However, the t1/2 of isoxicam was found to be inversely (r = -0.700, P less than 0.05 n = 14) related to the log gamma-glutamyl transpeptidase plasma activity. 3 During chronic oral treatment in patients with compensated hepatic insufficiency, steady-state was achieved after 7-9 days of therapy. The mean elimination half-life of isoxicam in five patients was 42.6 +/- 4.5 h, a value which was not statistically different from that obtained in the single dose study. 4 It was concluded that patients with hepatic insufficiency do not require a systematic modification of drug dosage but that long-term treatment should be employed with caution in these patients.

Adult↗
PubMed1986

Blood pressure and baroreflex sensitivity in conscious hypertensive rats of Lyon strain.

The evolution with age of blood pressure (BP), heart rate (HR), and baroreflex sensitivity was studied in hypertensive (LH), normotensive (LN), and low blood pressure (LL) male rats of the Lyon strains. Intra-arterial BP was continuously recorded for 48 h in freely moving animals. On-line computer analysis of the BP curve allowed calculation of systolic (SBP), mean (MAP), and diastolic (DBP) blood pressure, HR, and their variability. At 5 wk of age, LH rats exhibited a higher BP than LN and LL controls, which, at 21 wk of age, was associated with significant bradycardia and a greater variability in DBP and HR. LL rats had a MAP similar to LN, which confirms that both strains are, in terms of BP, valid controls for LH animals. The baroreflex sensitivity measured after phenylephrine injections increased with age more markedly in LN and LL than in LH rats, whereas in the latter, it was significantly lower at the age of 9 and 21 wk. When measured after nitroglycerin injections, the baroreflex sensitivity was higher and more stable than that observed after phenylephrine administration. In addition, the baroreflex sensitivity in the different strains was inversely related to the level and the variability of DBP but not of HR.

Aging↗
PubMed1986

Surgical versus medical treatment in renovascular hypertension. Retrospective study of 166 cases.

A retrospective study of 166 cases of renovascular hypertension was performed. Before 1979, 114 patients were treated for renovascular hypertension. Forty underwent surgery. In this group, therapy resulted in cure or improvement in 45% of the patients. Seventy-four patients underwent medical therapy: 88% of these patients had improvement of blood pressure when beta-blockers were used, but only 41% when they were not. More recently (from 1979 to 1983), 52 patients were treated for renovascular hypertension, of which 31 patients have been operated for fibromuscular renal artery stenosis (62%) or atherosclerotic renal artery stenosis (32%). In this group, 90% of the patients were considered to be cured or improved with a mean follow-up of 36 months. Eighteen of thirty-one patients underwent autotransplantation with satisfactory results on blood pressure control. Twenty-one patients were treated by antihypertensive drugs: 86% of the patients were improved or cured (71.5% of the patients had atherosclerotic lesions) with a mean follow-up of 46.8 months.

Adult↗
PubMed1986

[Effect of the thymus on the development of genetic hypertension in the Lyons-strain rat (LH)].

The aim of this work was to determine the part played by the thymus in the development genetic hypertension. This study was conducted in the genetically hypertensive rats (LH) of the lyon strain and their two simultaneously selected controls: the normotensive (LN) and low blood pressure (LL) rats. Systolic blood pressure (SBP) and immunological characteristics were investigated in sham-operated and neonatally thymectomized rats of the 3 strains. At 5 weeks of age, sham-operated LH rats exhibited a higher SBP (122 +/- 4 mmHg) than LN (111 +/- 2 mmHg) and LL (100 +/- 2 mmHg) controls. White blood cell numbers and percentage of circulating lymphocytes, thymus histology as well as T cells and T subsets percentages in that organ did not significantly differ within the 3 strains. On the contrary, in the animals of the 3 strains, a positive relationship could be established between the SBP and the proliferative response of the splenocytes to Pokeweed-Mitogen (r = 0.93; N = 30; p less than 0.001) or to Concanavalin A (r = 0.42; n = 30; p less than 0.05). After neonatal thymectomy the SBP of LH rats was more markedly decrease than that of LN and LL rats and established as follows: 103 +/- 2 mmHg; 102 +/- 2 mmHg; 97 +/- 2 mmHg for LH, LN and LL respectively. 21 weeks after thymectomy the SBP remained significantly decrease in LH rats only 160 +/- 5 mmHg vs 177 +/- 6 mmHg in sham-operated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗