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Biomedical subjects

C Advenier

Publications and source records attributed to C Advenier.

At least 181 records · Page 10Linked to original sources
PubMed1988

Comparison of the effects of epithelium removal and of an enkephalinase inhibitor on the neurokinin-induced contractions of guinea-pig isolated trachea.

1. The influence of epithelium removal and/or thiorphan on the effects of neurokinins (substance P (SP), neurokinin A (NKA), neurokinin B (NKB)) and related peptides on airway contractility was investigated on the guinea-pig isolated trachea. 2. Removing the tracheal epithelium significantly enhanced the sensitivity but not the maximum contractile responses to the peptides. 3. After removal of the epithelial layer, the shifts to the left of the log concentration response curves were greater for SP and SP-OMe (1.62 and 1.94 log units, respectively) than for two SP analogues substituted in position 9 namely [Pro9]SP sulfone and [beta-Ala4, Sar9]SP(4-11) sulfone (0.66 and 0.68 log units, respectively). The leftward shifts for compounds related to NKA or NKB lay between 0.58 and 0.73 log units. 4. The leftward shifts of the log concentration-response curves for SP, SP-OMe, [Pro9]SP sulfone, [beta-Ala4, Sar9]SP(4-11) sulfone and NKA were of similar magnitude after removal of the epithelium or after pretreatment with thiorphan (10(-5) M), an enkephalinase inhibitor, in the presence of epithelium. No significant additional shift of the curves to the left was observed with thiorphan plus epithelium removal. 5. The results obtained with the selective agonists for each of the three classes of neurokinin receptor (i.e NK1, NK2, NK3) suggest that the guinea-pig trachea contains receptors for SP and NKA but few if any for NKB. 6. It was concluded that neurokinins and related peptides (especially SP and analogues not substituted in position 9) are degraded by enkephalinase mainly located in the tracheal epithelium and that the addition of thiorphan or epithelium removal results in an inhibition or loss of enkephalinase activity, thereby increasing similarly the potencies of these peptides. It was, therefore, suggested that the supersensitivity to neurokinins produced by epithelium removal was due neither to the elimination of a permeability barrier nor to reduced production of a relaxant factor, but mainly to reduced peptide degradation.

Airway Resistance↗
PubMed1988

[Transcutaneous trinitrine. Calling into question the efficacy and innocousness of its use in facilitating venous approach].

Seven infants aged 6 days to 9 months were tested for the use by rubbing of a pomade containing 1 mg trinitrine. The study was interrupted because of high blood passage of trinitrine. The authors emphasize the difficulty of any comparison with the use of this drug in adults. They indicate that there was no clinically appreciable side-effect but they advise to delay, until further studies, the use of this technique, with the only objective of improving the technique of intravenous injections or sampling.

Administration, Cutaneous↗
PubMed1988

Effects of clonidine on bronchial responses to histamine in normal and asthmatic subjects.

Our aim was to examine the effects of clonidine (C), an agonist of central and peripheral alpha-2 adrenoceptors, on bronchomotor responsiveness to histamine (H). In a double-blind study, we compared on two different days the effects of pretreatment with placebo (P) and with 200 micrograms or 150 micrograms of C given orally, in ten normal (NS) and eight asymptomatic asthmatic subjects (AS) respectively, the response to inhalation of serially increasing doses of H. On each day, five doubling doses of H (first dose = 3.5 and 1.1 mumol in NS and AS, respectively) were administered every 5 min; forced expiratory volume in one second (FEV1) was measured after each dose. The dose-response curves were compared by an analysis of variance. Clonidine caused hypotension with bradycardia in all subjects. Baseline values and pre-challenge values of FEV1 after P and C were identical on the two study days. Compared to P, C did not modify the response to H in NS but significantly increased it in AS (p less than 0.01). Our results suggest that the neural control of the airways differs in AS compared to NS and could be explained either by a decrease in sympathetic inhibitory activity or a greater responsiveness of the airways to parasympathetic stimulation and/or a higher parasympathetic tone in AS.

Asthma↗
PubMed1987

Determination of theophylline and its metabolites in plasma and urine by reversed-phase liquid chromatography using an amine modifier.

A high-performance liquid chromatographic method for the determination of the concentrations of theophylline and its metabolites in plasma and urine samples is presented. The method uses the decylammonium ion, an N-alkylammonium modifier, and makes it possible to separate theophylline and its metabolites from other uric acid or xanthine derivatives, especially 1,7-dimethylxanthine, a metabolite of caffeine. The plasma and urine purification procedure is convenient, rapid and reproducible, and it can be used to determine low plasma and urine concentrations.

Acetonitriles↗
PubMed1987

Relative potencies of neurokinins in guinea pig trachea and human bronchus.

The three endogenous neurokinins, substance P (SP), neurokinin A (NKA) and neurokinin B (NKB), as well as NKA-(4-10), carbachol, acetylcholine and histamine, were tested in guinea pig tracheae and human bronchi in order to compare the activities of peptides and non-peptide agents and to characterize the neurokinin receptors by means of agonists. Neurokinin A and NKA-(4-10) were potent stimulants of the two preparations: pD2 values for NKA-(4-10) averaged 8.62 in the guinea pig trachea and 7.50 in the human bronchus. The rank order of potency of neurokinins was NKA-(4-10) greater than NKA greater than SP greater than NKB in the human bronchus and NKA-(4-10) greater than NKA greater than NKB greater than SP in the guinea pig trachea. SP was 2-3 orders of magnitude less active than NKA and appears to be a partial agonist. NKB is inactive on the human bronchus. Compared to non-peptide agents, NKA had an affinity 2-3 orders of magnitude greater than acetylcholine and histamine but produced only 75-80% of the maximal effect of acetylcholine. The present results indicate that neurokinins contract the human bronchus by activating a NK-A receptor type which is more sensitive to NKA than to SP and is insensitive to NKB. The guinea pig trachea appears to be a complex preparation containing not only NK-A but also other neurokinin receptors.

Animals↗
PubMed1987

Determination of clomipramine and its hydroxylated and demethylated metabolites in plasma and urine by liquid chromatography with electrochemical detection.

A procedure for the determination of clomipramine and its 8-hydroxy, demethyl, 8-hydroxydemethyl and didemethyl metabolites in plasma and urine by high-performance liquid chromatography with electrochemical detection is described. A 1-ml plasma or urine sample is made alkaline with a carbonate buffer (pH 9.8) and extracted with 20% ethyl acetate in n-heptane. After back-extraction into an acid phosphate buffer (pH 2.4), an aliquot is injected into a 5-microns ion-paired reversed-phase column and eluted with a mobile phase containing a phosphate buffer with tetramethylammonium chloride-acetonitrile (57:43). The detection is coulometric with a first cell at +0.40 V, a second at +0.73 V and a guard cell set at 0.75 V for oxidation of the mobile phase. The method provides recoveries in the general range of 80-110% and a day-to-day precision of 3.7-8.8%, depending on the compound. The minimum quantifiable level for all compounds was 0.2 ng/ml with a 20-microliters injection. Steady-state plasma concentration data and urinary levels are reported for 24 depressed patients receiving daily either 75-150 mg orally or 50-75 mg by infusion.

Chromatography, High Pressure Liquid↗
PubMed1987

Relaxant effect of the H2-receptor antagonist oxmetidine on guinea-pig and human airways.

The effects of three different H2-receptor antagonists (cimetidine, ranitidine and oxmetidine) were tested on isolated preparations of guinea-pig trachea and human bronchus against contractions induced by acetylcholine, histamine and potassium chloride (KCl). In addition, their influence on calcium concentration-response curves in guinea-pig tracheal spirals was examined in a potassium-rich solution (30 mM). Finally, their effects were studied in vivo against acetylcholine and histamine-induced bronchoconstriction in anaesthetized guinea-pigs. In guinea-pig isolated trachea, oxmetidine--in contrast to cimetidine and ranitidine, which were completely inactive--induced a concentration-dependent relaxation regardless of the excitatory stimulus: its--log EC50 values (i.e. the negative log concentration that caused a 50% relaxation) were 3.46 +/- 0.11, 4.61 +/- 0.09 and 4.20 +/- 0.12 against acetylcholine, histamine and KCl, respectively. In Ca2+-free, K+-enriched solution, the compound was able to inhibit Ca2+-induced contractions at concentrations close to those needed to counteract the spasmogenic effect of histamine in normal Krebs solution. Results obtained in the human bronchus preparation were similar to those observed in guinea-pig tracheal spirals. When tested against acetylcholine or histamine-induced bronchoconstriction in vivo, oxmetidine (10 and 30 mg Kg-1 intravenously) significantly reduced the increase in pulmonary airway resistance (Raw) induced by both agents. Once again, cimetidine and ranitidine were completely ineffective. In summary, oxmetidine displayed non-specific antispasmogenic activity on guinea-pig and human airways. This effect, which is independent of H2-receptor blockade, represents a side-effect of the drug which may be connected to its interference with Ca2+ influx and the action or release of intracellular Ca2+.

Acetylcholine↗
PubMed1986

Effects of Bay K 8644 on contraction of the human isolated bronchus and guinea-pig isolated trachea.

The effects of Bay K 8644, a dihydropyridine which increases calcium flux through the potential-operated channels were studied on the contractions induced by histamine, acetylcholine, KCl and Ca2+ on human isolated bronchial strips and the results were compared to those obtained on guinea-pig isolated tracheal spirals. Subsequently the contractant effects of Bay K 8644 in K+-enriched medium and in the presence of Ca2+ 0.03 mM were investigated. In Krebs normal calcium medium, Bay K 8644 did not significantly modify the EC50 of acetylcholine or histamine on the human bronchus, but in concentrations of 10(-7)-10(-6)M it potentiated the effects of KCl on that preparation. It did not modify the EC50 of acetylcholine, histamine or KCl on the guinea-pig trachea. In Ca2+-free Krebs medium with additional K+ (30 mM), Ca2+ concentration-response curves were displaced to the left by Bay K 8644 in the two preparations. Shifts were 0.52 +/- 0.11 and 0.72 +/- 0.16 log units respectively with Bay K 8644 10(-8) and 10(-7) M on human bronchus (n = 4) and 0.67 +/- 0.16 and 1.06 +/- 0.19 log units respectively with Bay K 8644 10(-7) and 10(-6) M on the guinea-pig trachea (n = 5). In Krebs medium with Ca2+ 0.03 mM and K+ 30 mM, Bay K 8644 (10(-8) to 10(-6) M) contracted both the human bronchus and the guinea-pig isolated trachea. This effect was competitively antagonized by nicardipine. 5 These results demonstrate the presence of dihydropyridine sites of action on human bronchus and confirm the minor role played by Ca2+ influx through potential-operated channels in the contractile effects of acetylcholine or histamine. They also demonstrate the similar reactivity of human bronchus and guinea-pig isolated trachea to Bay K 8644.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1986

[Diffusion of trimethoprim and sulfamethoxazole into the pleural fluid].

The level of Trimethoprim (TMP) and of Sulfamethoxazole (SMZ) in the fluid of both pleural effusion and plasma was determined in 7 patients on the first day of treatment consisting of two daily doses of 160 mg TMP and 800 mg SMZ. In 4 subjects, the levels were determined again on the third (J3) and fifth day of treatment (J5). Thus with TMP the ratio of pleural/plasma drug levels rose progressively from the first day of treatment to attain by 12 hours a mean value of 0.79 +/- 0.16; subsequently it stayed at about the same level for day 3 (J3) and day 5 (J5). As for SMZ, the ratio of the pleural plasma drug level reached a maximum at 8 hours on the first day of treatment (0.53 +/- 0.12) then rose progressively on day 3 (J3 0.58 +/- 0.06) and on day 5 to 0.71 (+/- 0.08). The levels of TMP in the pleural fluid were below those which are usually described in bronchial secretions. On the other hand those of SMZ are appreciably raised.

Drug Combinations↗
PubMed1985

Pharmacokinetics of the trimethoprim-sulphamethoxazole combination in the elderly.

The pharmacokinetics of a co-trimoxazole preparation (Bactrim Forte) containing trimethoprim (TMP) 160 mg and sulphamethoxazole (SMZ) 800 mg were determined in six young adults (29.3 +/- 4.4 s.d. years) and six elderly people (78.6 +/- 6.6 s.d. years). Following oral administration of a single dose, the pharmacokinetic parameters of SMZ and its N4-acetylated metabolite (N4SMZ) were similar in both groups. However Cmax of TMP was greater (2.06 +/- 0.29 s.d. vs 1.57 +/- 0.32 s.d. mg l-1; P less than 0.01) and its area under the curve was larger (34.30 +/- 6.98 s.d. vs 23.87 +/- 3.82 s.d. mg l-1 h; P less than 0.001) in elderly people than in younger subjects. Total clearance (CL/F) of TMP normalized to body weight was not significantly different in the two groups. There was no significant difference in serum protein binding of TMP and SMZ between the two groups. Urinary excretion of TMP, SMZ and N4SMZ was reduced by about 50% in the elderly compared to the young subjects. Renal clearance of TMP was significantly lower in the elderly group (19 +/- 10 s.d. vs 55 +/- 14 s.d. ml h-1 kg-1; P less than 0.001). Renal clearance of SMZ was not significantly different in the two groups. A study of plasma concentrations of TMP, SMZ and N4SMZ during continuous dosing in seven elderly patients treated for urinary or respiratory infections showed that steady state was reached after 3 days of treatment and that plasma drug concentrations were about two to three times higher than those observed after a single dose.

Acetylation↗
PubMed1985

Pharmacokinetics of ranitidine in acute upper gastrointestinal haemorrhage.

A pharmacokinetic study of ranitidine was performed in 14 patients with haematemesis divided into two groups according to the severity of blood loss. Pharmacokinetic values were calculated from plasma concentrations after the first of three daily injections (100 mg) and compared with those obtained in five healthy volunteers (50 mg i.v.). There were no significant differences between patients in the two haemorrhage groups and controls. The low, or even questionable, effectiveness of histamine H2-receptor antagonists in the treatment of upper gastrointestinal haemorrhage does not seem to be due to pharmacokinetic factors.

Acute Disease↗
PubMed1985

The guinea-pig isolated bronchus for the in vitro study of small calibre airway reactivity.

Small calibre airway reactivity to different contractile and relaxant agents was tested in vitro using small segments (about 1 mm long and 0.2 mm in internal diameter) of guinea-pig isolated intralobular bronchi. EC50 values of, and maximal contractile responses to contractile agents were as follows (mean +/- s.e.mean, n = 6): acetylcholine 13.6 +/- 2.6 microM and 1140 +/- 80 mg; histamine 5.2 +/- 0.7 microM and 1094 +/- 95 mg; 5-hydroxytryptamine (5-HT) 0.7 +/- 0.1 microM and 595 +/- 61 mg; prostaglandin F2 alpha (PGF2 alpha) 8.8 +/- 1.2 microM and 1100 +/- 88 mg; tetraethylammonium 2.9 +/- 0.3 mM and 1055 +/- 94 mg; KC1 14.6 +/- 0.5 mM and 965 +/- 81 mg. EC50 values of, and maximal relaxant responses to beta-adrenoceptor stimulants on preparations precontracted with acetylcholine (1.4 X 10(-4)M) were: isoprenaline 0.40 +/- 0.5 microM and 782 +/- 65 mg, n = 18; salbutamol 0.19 +/- 0.02 microM and 494 +/- 55 mg, n = 5; terbutaline 0.87 +/- 0.18 microM and 263 +/- 40 mg n = 5; fenoterol 0.06 +/- 0.02 microM and 722 +/- 47 mg, n = 5; adrenaline 0.71 +/- 0.13 microM and 653 +/- 62 mg, n = 5; noradrenaline 10.8 +/- 0.9 microM and 566 +/- 97 mg, n = 5. Differences in the maximal relaxant effects between the beta-adrenoceptor stimulants showed that the preparation utilized is a relevant model for assessment of the intrinsic activity of these drugs. 5 The high ratio (about 180) of the ECm for noradrenaline (beta-adrenoceptor agonist) to that for fenoterol (beta 2-adrenoceptor agonist), and the lack of effect of prenalterol (beta 1-adrenoceptor agonist) suggested that beta 2-adrenoceptors are preferentially involved in the relaxant activity of beta-adrenoceptor stimulants in this preparation.

Acetylcholine↗
PubMed1985

Interaction between clonidine and histamine on the guinea-pig isolated trachea.

In experiments on guinea-pig isolated tracheal spirals, clonidine, in concentrations of 10(-6) to 3 X 10(-4) M, had a contracting effect which was strongly inhibited by prazosin but not significantly modified by yohimbine. Moreover, clonidine (3 X 10(-5) to 3 X 10(-4) M) potentiated histamine-induced contractions; this latter effect was inhibited specifically by alpha 1-adrenoceptor antagonists (e.g. prazosin, AR-C 239) but unmodified by yohimbine, nicardipine or agents acting on the arachidonic acid cascade. It would therefore appear that clonidine in high concentrations contracts the guinea-pig trachea by stimulating alpha 1-adrenoceptors and that, contrary to what has been reported with other animal species, notably the dog, the guinea-pig trachea is devoid of alpha 2-adrenoceptors that mediate contractions.

Animals↗
PubMed1985

[Adrenergic and purinergic receptors and bronchial motoricity].

Numerous studies have been, and are being devoted to the nature of adrenergic and purinergic receptors in the bronchopulmonary system. Studies of beta-adrenoceptors performed with ligands (table I) have demonstrated the presence of two types of receptors, beta 1 and beta 2 in proportions of about 15 : 100 respectively; this proportion is approximately the same at all levels of the tracheobronchial tree. Beta-adrenoceptors (beta 1 + beta 2) are globally more numerous in peripheral organs which contain heterogeneous tissues. Their number can be modified in certain circumstances, notably in asthma, infection and after prolonged treatment with sympathomimetic amines. Functional studies using specific beta 1-adrenoceptor agonists (RO-363 or prenalterol) or determining the relative activities of beta 1 and/or beta 2 stimulants and their inhibition by selective beta-blockers have shown that stimulation of beta 1-adrenoceptors may produce partial relaxation of the isolated trachea but not of lung parenchyma, the latter being supposed to represent distal airways. Studies on isolated small bronchi, about 0.1 mm in diameter (fig. 1 and 2A) have confirmed that stimulation of beta 1-adrenoceptors has not effect on distal airways. They have also demonstrated that beta 2-stimulants have different intrinsic activities (fig. 2B). Studies of alpha-adrenergic receptors using ligands (table II) have shown that these receptors are in small number in the tracheobronchial tree of numerous animal species. Functional studies on the conscious guinea-pig have shown that clonidine can potentiate the bronchoconstrictor effects of acetylcholine, histamine and serotonin (fig. 3) and that this potentiating effect is specifically inhibited by yohimbine and piperoxan (fig. 4). This action of clonidine has been attributed to depression of the reflex sympathetic activity associated with bronchospasm. Alpha 1-adrenoceptor agonists (phenylephrine, methoxamine) induce contracture of the isolated bronchial smooth muscle (fig. 5) but may partially reduce the bronchoconstrictor effects of acetylcholine, histamine or serotonin (fig. 6). This last effect is partially inhibited by alpha 1-blockers (fig. 7) and seems to be due to shrinkage of the bronchial mucosa. Finally, studies of purinergic receptors in the bronchopulmonary system have shown that they probably are of the A2-P1 type (tables III and IV) and that they do not seem to be involved in the bronchodilator activity of theophylline.

Animals↗