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Biomedical subjects

A Dufour

Publications and source records attributed to A Dufour.

At least 73 records · Page 4Linked to original sources
PubMed1992

Immunological alterations in cluster headache during remission and cluster period. Comparison with low back pain patients.

Cluster headache is a disorder of unknown origin. Some studies have focused their attention on neuroendocrine derangement, others on immunity. To probe central alterations in cluster headache (CH), immune parameters were investigated in cluster headache patients in comparison to low back pain patients and healthy controls. Increases in peripheral blood monocytes found in remission cluster headache patients may be attributable to chronic central nervous system (hypothalamic?) noradrenergic dysfunction or altered beta-endorphin. Alterations in NK+, CD3+ and CD4+ levels found in cluster period cluster headache and low back pain patients are probably pain or stress-related.

Adult↗
PubMed1992

Metabolism rate of oxodipine in rats and humans: comparison of in vivo and in vitro data.

The in vitro metabolism of oxodipine was studied with rat and human hepatic and intestinal microsomes. Rat liver, human liver and intestine were able to metabolize oxodipine in vitro to the main metabolites found in vivo, namely pyridine and deesterified derivatives; rat intestine did not produce any detectable metabolite. The Kms were found to be in the range of 30 to 60 microM. Human in vitro intestinal metabolism was negligible compared to that of liver and, taking into account the dose administered, it was predicted that the intestinal first-pass effect would also be negligible in vivo. The use of in vitro kinetic constants enabled us to evaluate the amount of oxodipine metabolized and to compare it to values found in vivo. Both results were on the same order of magnitude, indicating that it might be possible to evaluate the in vivo metabolism from in vitro data. Finally, we clearly showed, by substrate inhibition and immunoinhibition, that oxodipine was metabolized by the cytochrome P4503A subfamily both in intestine and in liver.

Administration, Oral↗
PubMed1991

Use of particle beam liquid chromatography-electron impact mass spectrometry for structure elucidation of oxodipine and three of its metabolites.

In order to test the analytical capabilities of the particle beam liquid chromatograph-mass spectrometer interface in structural identification in drug metabolism, a liquid chromatographic-mass spectrometric (LC MS) method using this new technique was developed for oxodipine and some of its expected metabolites. After two extraction steps at pH 9 and 1.5, the separation of the compounds, which have a wide polarity range, was carried out by an isocratic high-performance liquid chromatographic method with a 25-cm cyano-bonded column. The compounds were eluted with hexane-methanol-methylene chloride (76:12:12). Mass spectra were recorded after electron impact ionization (75 eV) with a source temperature of 150 degrees C. Under these conditions, comparison of the spectra with those obtained after gas chromatography or with a direct introduction probe showed identical fragmentation patterns when a sufficient amount of product was injected for LC-MS analysis.

Chromatography, Liquid↗
PubMed1991

Plasmid-encoded determinants for bacteriocin production and immunity in a Lactococcus lactis strain and purification of the inhibitory peptide.

Lactococcin, a bacteriocin produced by Lactococcus lactis subsp. lactis ADRIA 85LO30, was purified as a 2.3-2.4 kDa peptide. Six non-bacteriocin-producing (Bac-) and non-immune (Imm-) strains were isolated after curing experiments. These strains had in common the loss or modification of two plasmids: pOS4 (32 kb) and pOS5 (70 kb). By comparing pOS5 and several modified plasmids, a DNA region from pOS5 of about 10 kb, which was necessary for wild-type bacteriocin production and immunity, was identified.

Bacteriocins↗
PubMed1991

In vivo approach to determine the route of optimal drug absorption in rats.

The purpose of this paper is to describe the methodology to evaluate the optimal route of absorption in rats, avoiding the first pass effect of the liver (nasal, buccal and transdermal). These routes were investigated for a new benzamide, for which an absorption profile close to the intramuscular route is desired. Nasal route was investigated on anaesthetized rats by perfusion at a feeble flow rate of a recirculated solution through a tube from a reservoir, to the posterior part of the nasal cavity. Buccal absorption was evaluated by means of an original perfusion model adapted from the nasal recirculation model. Transdermal absorption was realized using a very simple "reservoir" system developed in our laboratory, which permits the application of the drug solution directly onto the skin. Action of some vehicles on nasal and transdermal drug absorption was studied. Absorption parameters, e.g. rate input and extent of drug input versus time were calculated by numerical deconvolution using the intramuscular route as reference. Results were evaluated and the most adequate route presenting absorption characteristics closest to those researched was further studied for application in man. In the present example, the drug was better absorbed when administered by nasal route.

Absorption↗
PubMed1991

Comparison of HPLC and RIA methods applied to the quantification of amisulpride in human plasma.

Quantification of amisulpride occurred up-till now using radioimmunoassay (RIA). A high performance liquid chromatographic (HPLC) assay with fluorimetric detection has been developed, which can be reproduced easily by any other laboratory. The aim of this paper is to compare amisulpride plasma levels (determined by RIA and HPLC) in 51 patients who received daily up to 800 mg of amisulpride in fractioned doses by IM or oral route, eventually together with other medications. Assay conditions and characteristics are briefly described and discussed. Results obtained with RIA and HPLC are compared and relative errors between both methods are calculated and examined as a function of the concentrations quantified. Correlation analysis using the concentrations (linear correlation) or their logarithm (logarithmic correlation) were realized for different concentration ranges. In fact, in the present case, logarithmic correlation was a more appropriate data processing method, which showed intercepts close to 0 and slopes close to 1. In conclusion, both methods are specific and sensitive enough to ensure the follow up of clinical studies. RIA may therefore be replaced whenever necessary by PHLC, without subsequent influence on the results.

Amisulpride↗
PubMed1991

An original intragastric delivery system for oral administration of solid formulations to fully conscious rats: its application to oxodipine studies.

The purpose of this paper is to describe an original intragastric delivery system for powders to conscious rats. This system is an administration cannula composed of a simple polypropylene tube, long enough to reach the stomach and an adapted metallic stem in the lumen of the tube. A finite dose of powder, set on the free extremity of the cannuly, is expulsed into the stomach. This delivery system is applied to study oxodipine absorption from oral solid forms containing appropriate vehicles. Different test formulations were administered to rats: solution by I.V. (1 mg/kg) and P.O. (2mg/kg) routes, and oral dry powders (2 ng/kg). Blood samples were collected until 12 hours post-dose. Oxodipine plasma levels are measured by a HPLC method. Results indicated that the rate and extent of absorption can be modulated by the administration of oxodipine in different formulations. The formulations studied can be classified as a function of the vehicles added to the solid formulation. In fact, the limiting factor of absorption in rats is the in vivo dissolution rate. Absolute bioavailability can be modulated by different formulations. The apparent elimination half-life was dependent on the dissolution rate of oxodipine from formulations.

Administration, Oral↗
PubMed1989

Cardiac electrophysiological effects of cibenzoline in the conscious dog: plasma concentration-response relationships.

The cardiac electrophysiological effects of cibenzoline were studied in the conscious dog. Sinus rate, corrected sinus recovery time (CSRT), and Wenckebach point (WP) were measured in six intact dogs. Atrial and ventricular rates, and atrial effective refractory period (AERP) were measured in seven atrioventricular (AV)-blocked dogs. In both groups, blood pressure and cibenzoline plasma concentrations were also monitored. Each dog received three intravenous injections of 0.75, 1.5, and 3 mg base/kg cibenzoline 30 min apart. Cibenzoline increased sinus and atrial rates from the second dose onward, and ventricular rate slightly at the third dose. It lengthened CSRT and decreased WP at the first two doses only, and increased AERP from the first dose onward. In both groups, cibenzoline increased mean blood pressure at each dose. Taken together, these results indicate that in the conscious dog, cibenzoline at low plasma concentrations exhibits electrophysiological effects (lengthening of CSRT and AERP, and decrease in WP) attributable to its antiarrhythmic properties, and that at increasing concentrations it produces effects (increase in sinus rate, no effect on CSRT nor WP) which reflect competition between the effects related to its antiarrhythmic properties and those resulting from its direct vagolytic effect.

Animals↗
PubMed1986

Electrophysiologic effects of cibenzoline in humans related to dose and plasma concentration.

The electrophysiologic effects of a new antiarrhythmic agent, cibenzoline, were investigated in 25 patients with an average age of 62 years. The compound was administered intravenously, as a bolus given over 2 minutes, then as a slow infusion over 40 minutes. Each subject was randomly allocated to receive one of the following four doses: 1.55 mg/kg (six patients), 1.8 mg/kg (six patients), 2.2 mg/kg (six patients), or 2.6 mg/kg (seven patients). Plasma cibenzoline concentrations at these doses were 378 +/- 80,525 +/- 194, 618 +/- 72, and 731 +/- 196 ng/ml, respectively. Administration of 1.55 mg/kg cibenzoline significantly shortened the sinus cycle (60 msec on average; p less than 0.025) and increased intraatrial (+8 msec; p less than 0.05) and His-Purkinje conduction times (HV interval + 13 msec; p less than 0.001). At 1.80 mg/kg, prolongation occurred in the HV interval (+9 msec; p less than 0.02), the duration of the QRS complex (+20 msec; p greater than 0.05), and the QT interval (+18 msec; p less than 0.025). At the higher doses these changes became more marked (maximum increase: HV = +16 msec, p less than 0.001; QRS + 25 msec; p less than 0.001; QT + 26 msec, p less than 0.05), and additional effects on atrioventricular nodal conduction time (AH interval + 17 msec; p less than 0.05) and atrial (+20 msec; p less than 0.05) and ventricular (+10 msec; p greater than 0.05) effective refractory periods were observed. Prolongation of the QRS duration was the effect that correlated best with plasma cibenzoline levels (r = 0.47; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Electrophysiologic effects, antiarrhythmic activity and pharmacokinetics of cibenzoline studied with programmed stimulation of the heart in patients with supraventricular reentrant tachycardias.

Cibenzoline, an imidazoline derivative is a new antiarrhythmic agent. Its electrophysiological effects and antiarrhythmic properties were studied with programmed electrical stimulation of the heart in 12 patients with recurrent episodes of reentrant supraventricular tachycardia; atrionodal (5 cases), circus movement tachycardia involving an accessory pathway (6 cases), intraatrial reentry (one case). Cibenzoline was infused intravenously at a dose of 1 mg kg-1 to 1.75 mg kg-1 during sustained episodes of tachycardia and over 9 to 15 min. Cibenzoline shortened the sinus cycle length, moderately increased the transnodal conduction time and markedly lengthened the HV interval. The refractory periods of the atrioventricular (A-V) node, the atrium and the ventricle did not change. The effects of cibenzoline on accessory pathways used in the anterograde direction were measurable in 4 cases. Complete blockade of the bypass was seen in every case. In the retrograde direction the refractory period of the bypass could be evaluated; in 5 patients it lengthened systematically. Infused intravenously during epidoses of tachycardia, the drug terminated the rhythm disorder in 9 out of 12 cases. Tachycardia could still be initiated in 8 patients after i.v. cibenzoline (2 out of 5 A-V nodal tachycardias, 6 out of 6 circus movement tachycardias). The distribution of the drug followed a bicompartment pharmacokinetic model. The plasma levels at the end of infusion ranged from 1.34 to 3.19 microgram ml-1. Cibenzoline, primarily has class I antiarrhythmic properties and its well-understood pharmacokinetics should be of help in tailoring the treatment to the individual needs of the patient.

Adolescent↗
PubMed1985

[Intravenous cibenzoline in the treatment of ventricular and supraventricular arrhythmias].

The efficacy of intravenous cibenzoline in the treatment of supraventricular and ventricular arrhythmias was demonstrated in a French trial of 212 patients including 40 in the acute phase of myocardial infarction. The minimal therapeutic plasma concentration was about 0.3 microgram/ml: this was obtained by a loading dose of 1 mg/kg relayed by a perfusion of 8 mg/kg/24 hours. The clinical tolerance was satisfactory in 96.2% of cases when the contra-indications were respected (severe cardiac failure, intraventricular conduction defects and non-paced 2nd and 3rd degree atrioventricular block). Local tolerance was excellent in all cases.

Anti-Arrhythmia Agents↗
PubMed1985

Renin angiotensin aldosterone system, urinary prostaglandins and kallikrein in pregnancy induced hypertension. Evidence for a disregulation of the renin-angiotensin-prostacyclin loop.

Plasma renin activity and aldosterone concentrations were measured simultaneously with urinary excretion of kallikrein and four prostaglandins (PGE2, PGF2 alpha, 6 keto PFG1 alpha and TXB2) in 23 patients with pregnancy induced hypertension (17 with permanent PIH and six with labile PIH, since in these latter their hypertension was controlled only by home bed rest) and in 16 normotensive pregnant women at the same stage of gestation (31 +/- 3 weeks). PRA was lower in permanent PIH than in controls and in labile PIH. No difference between the three groups was observed for plasma aldosterone and the urinary excretion of kallikrein and of the prostaglandins except that TXB2 was higher in labile PIH than in permanent PIH. Correlation studies of kallikrein disclosed correlations with most prostaglandin excretions, explained by the physiological stimulation of phospholipase A2 by kallidin. Correlation studies of PRA disclosed unexpected negative correlation with PGE2 and 6 keto PGF1 alpha in the permanent PIH group. In conclusion, labile PIH has a different biological profile than permanent PIH since they have higher PRA and higher TXB2 excretion, an association which suggests a more pronounced ureteral compression by the gravid uterus in this group. Permanent PIH has a disregulation of the renin angiotensin-prostacyclin loop since PRA and 6 keto PGF1 are negatively correlated. This suggests the role of an independent vasopressive substance which would stimulate PGI2 and suppress renin secretion.

Female↗
PubMed1984

Haemodynamic effects of intravenous cibenzoline in patients with coronary heart disease.

The effect of a single dose of cibenzoline ( (diphenyl 2,2 cyclopropyl)--2 imidazoline, Cipralan ), a new compound with antiarrhythmic properties was studied in 14 patients undergoing routine heart catheterization for suspected coronary artery disease. The effect of the drug on dP/dt, Vmax TP, Vce, negative dP/dt, heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), cardiac index (CI) and systemic vascular resistance (SVR) was measured before and after drug administration. A significant decrease in left ventricular isometric contraction parameters was manifested immediately after injection, with its maximal effect 2 to 5 min after injection. An increase in HR, a decrease in LVSP, a decrease in CI and an increase in SVR were observed; LVEDP was not significantly altered, nor was negative dP/dt. The effect of the drug on Vmax TP and LVEDP was also examined during two atrial pacing stress tests ( APST ) done before and 10 to 20 min after drug administration. Although the negative inotropic action of the drug was apparent during the second APST , the effect was less pronounced at higher paced heart rates. No difference in the two tests was found between the maximal paced heart rate, nor was there a difference in the angina threshold. Finally the plasma level of the drug and the changes in certain parameters were compared. A positive correlation was found between the plasma level and dP/dt, Vmax TP and cardiac index.

Adult↗
PubMed1984

Cardiac electrophysiological effects of cibenzoline by acute and chronic administration in the anesthetized dog.

The electrophysiological effects of cibenzoline on the myocardium of the anesthetized dog were studied by the endocavitary catheter method. Plasma cibenzoline levels were measured throughout. The cibenzoline effects on the sinus rate were negligible. The corrected sinus recovery time was significantly prolonged only following chronic oral administration. Atrial refractory periods were significantly increased only at the fifth minute following acute intravenous administration and after chronic oral treatment. The intranodal conduction time (AH) and the refractory periods in atrio-ventricular node were slightly modified or not at all. On the other hand, intraventricular and His-Purkinje (HV) conduction times, ventricular refractory periods and QRS duration were strongly increased following acute or chronic administration. This would imply a principal effect on the rapid kinetics sodium entry current. Nevertheless, the very marked effect upon this current could, under the experimental conditions adopted, have masked a lesser action upon other membrane permeabilities, involved in other myocardial structures.

Administration, Oral↗