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Biomedical subjects

F Ruff

Publications and source records attributed to F Ruff.

At least 19 recordsLinked to original sources
PubMed1998

[Potential importance of antileukotrienes in the treatment of asthma and other inflammatory diseases: apropos of a new pharmacological class].

OBJECTIVES: Among the mediators involved in the asthma bronchoconstriction and inflammation mechanisms, there is now substantial evidence that the sulfidopeptide leukotrienes (LTs) are important. Antagonists of their receptors and inhibitors of their synthesis have been developed. IMPORTANT POINTS: Antagonists of LTs, as well as inhibitors of their synthesis, reduce the LTs actions: bronchoconstriction, bronchial hyperresponsiveness, hypersecretion and inflammation. They produce an acute bronchodilating effect in mild asthma, reduce the hyperresponsiveness responses due to allergens, aspirin and cold and dry air, and also cutaneous and gastrointestinal reactions. Oral administrations tested during 4 or 6 weeks diminish the use of the beta-agonists, decrease the asthma symptom scores and other inflammatory signs. PERSPECTIVES AND PROJECTS: More studies for longer periods, double blind trials and comparisons with classical treatments will be necessary to define the real place of LTs antagonists in the treatment of asthma. So their efficacy has to be confirmed as well as their good tolerance profile (particularly for hepatic functions). CONCLUSION: Antagonists of receptors and synthesis inhibitors of LTs have known a recent and important development. They constitute a new therapeutic class: further studies are needed to better define the place of these new drugs in the treatment of asthma and other inflammatory diseases.

Acetophenones↗
PubMed1991

Effect of temafloxacin on the pharmacokinetics of theophylline.

A number of fluoroquinolones have been shown to interact adversely with theophylline. We studied the influence of coadministration of temafloxacin, a new fluoroquinolone antimicrobial agent, on steady-state theophylline pharmacokinetics. Twelve healthy subjects (8 males, 4 females; average age and weight 34 years and 62 kg, respectively) were given oral controlled-release theophylline in an individualized dosage to achieve a target plasma level of 10 mg/L. Once steady state was achieved, temafloxacin 600 mg given orally twice daily was concomitantly administered for 4-5 days. Serial blood samples were collected before and during simultaneous temafloxacin administration and plasma assayed for theophylline using a high-performance liquid chromatography technique. Theophylline pharmacokinetic parameters were determined noncompartmentally, and results of single and combined administration were compared. Theophylline plasma concentrations did not differ significantly with temafloxacin coadministration, and similar area-under-the-curve (AUC) values were observed. Theophylline oral clearance increased from 2.67 +/- 1.01 L/hour to 2.69 +/- 0.93 L/hour, when given alone and with temafloxacin, respectively (p = 0.92). Only 2 of 12 subjects showed an appreciable decrease in clearance when theophylline and temafloxacin were administered together, while 2 subjects demonstrated increases greater than 15% and 8 showed no change. We conclude that temafloxacin does not interact significantly with theophylline and that these agents can be safely administered together.

Adult↗
PubMed1988

Beta-2 adrenergic responses to tulobuterol in airway smooth muscle, vascular smooth muscle and adrenergic nerves.

Experiments were designed to determine the mechanism of action of the bronchodilator drug tulobuterol. Tissues were suspended in organ chambers for isometric tension recording. Tulobuterol caused concentration-dependent relaxations of guinea pig tracheae, canine saphenous veins and canine bronchi; the compound relaxed canine coronary arteries only at high concentrations and did not affect spontaneously beating guinea pig atria. A metabolite of tulobuterol, 4-hydroxytulobuterol, was more potent in relaxing guinea pig tracheae than tulobuterol, salbutamol and isoproterenol. Other metabolites (3-hydroxy-, 5-hydroxy- and 4,5-dihydroxytulobuterol) were less efficacious than 4-hydroxytulobuterol. Both tulobuterol and 4-hydroxytulobuterol acted as partial agonists. The effects of tulobuterol in the saphenous vein (but not in the coronary artery) were antagonized by the selective beta-2 adrenergic blocker ICI 118,551 but were not affected by the selective beta-1 adrenergic inhibitor metoprolol. In bronchi, removal of the epithelium reduced the relaxations caused by tulobuterol. The drug did not inhibit responses of canine bronchi to electrical stimulation of the cholinergic nerves more than those to exogenous acetylcholine. Tulobuterol caused a moderate augmentation of the evoked release of [3H]norepinephrine in canine saphenous veins previously incubated with the labeled transmitter. Thus, tulobuterol is a selective beta-2 adrenergic agonist with minimal nonselective inhibitory effect on airway and vascular smooth muscle. It also facilitates adrenergic neurotransmission, which may help to explain its bronchodilator effect in the intact organism. Tulobuterol does not activate beta-1 adrenoceptors and has no direct positive chronotropic effect. A metabolite of tulobuterol, 4-hydroxytulobuterol, is more active than the parent compound.

Adrenergic Fibers↗
PubMed1988

[The H1 and H2 histamine receptors].

Histamine is a major mediator of the allergic reactions. Histamine have different actions: contraction of smooth muscles, vascular action, increase in gastric and adrenal medulla secretion. Effects on central or peripheral nervous system are discussed. The specific H1 or H2 activity explains the different configurations of histamine. The specificity of H1 receptors agonists is now well known: H1 activities have a positive charge on the side chain with an imidazole ring able to rotate around the axis of side chain. The contraction of smooth muscles is due to the action of H1 receptors agonists. Many doubts remain about the exact structures of the H2 receptors, and their agonists. Trough the H2 receptors occur dilatation of small arteries and capillaries, as well as an increase in gastric secretion. Subdivisions of H2 receptors have been, suggested. Recently H3 receptors have been described in the brain and in some peripheral tissues. Interrelations between H1 and H2 histamine receptors have been described as well as a feedback of synthesis and of histamine release.

Animals↗
PubMed1987

Comparison of once-daily evening versus morning sustained-release theophylline dosing for nocturnal asthma.

Eight diurnally active (approximately 0730-1100 hr) adults (41-61 yr) suffering from nocturnal asthma volunteered for a double-blind, cross-over randomized study of a once-daily dosing (600-900 mg/24 hr) of Armophylline (Rorer s.a., France), a sustained-release theophylline given either at 0800 hr or 2000 hr for 8-day durations. Study variables monitored daily were: (a) self-measured peak expiratory flow (PEF), heart rate, oral temperature and self-rated fatigue checked every 2 hr during the waking span as well as upon spontaneous nocturnal awakenings and (b) duration and subjective characteristics of sleep rated every morning. In addition, serum theophylline concentration (STC) plus the variables in (a) were sampled every 2 hr during the 24 hr of the eighth day of each timed treatment span. Rx at 0800 hr was associated with a nocturnal dip in PEF of 20 +/- 2.8% (X +/- S.E.M.) from the level achieved at the time of the diurnal crest; Rx at 2000 hr moderated the nocturnal fall; it was only 10 +/- 2.1% and within the physiologic limits of non-asthmatic persons. The STC peak height (Cmax) was greater (P less than 0.05) and time-to-peak (Tmax) shorter (P less than 0.005) with Rx at 0800 hr than at 2000 hr. With Rx at 2000 hr an STC plateau of approximately 12 hr resulted. A statistically significant correlation (r = 0.86; P less than 0.01) between PEF and the corresponding-in-time STC was observed with Rx at 2000 hr but not with Rx at 0800 hr. A small, but statistically significant, higher heart rate resulted from 2000 hr dosings in five out of eight subjects relative to the 0800 hr dosing. There were no differences in the sleep characteristics nor in oral temperature between dosing times. Once-daily (600-900 mg) SRT dosing at 2000 hr controlled the nocturnal dip of bronchial patency with no major side-effects in diurnally active adult patients with nocturnal allergic asthma.

Adult↗
PubMed1984

[Cromoglycic acid (disodium cromoglycate) and inhibitors of mast cell degranulation].

Cromoglycic acid (disodium cromoglycate) is a diacromone derived from khelline whose chief action in asthma is preventive, through inhibition of mastocyte degranulation. Since its digestive absorption is poor, it is given locally as a pulverulent aerosol. Cromoglycic acid is also used successfully in certain forms of ocular and nasal allergy. An oral preparation of cromoglycic acid is beginning to be used in food allergy and certain rectocolites. Trials are ongoing with several other substances, which have comparable properties and are active orally.

Animals↗
PubMed1984

[Serum histamine, osmolality and hemodynamics during aortography].

Translumbar aortic arteriography was carried out in sixteen patients by injecting 77 +/- 16 ml Télébrix 38 (sodium and meglumine ioxitalamate). Cardiac output was measured by thermodilution by means of a Swan-Ganz catheter. Anaesthesia was induced with thiopentone and fentanyl: the patients were under controlled ventilation. Arterial osmolalities at the 15th, 30th, 60th, 120th, 180th and 300th s showed a major increase, statistically significant from the 30th s on. Arterial and mixed venous histamine measured at the same time varied in parallel, showing a significant rise from the 30th s on for the arterial histamine level. The haemodynamic study of 29 injections showed a significant increase in the left and right ventricular systolic work indices, mostly due to an increase in the systolic index. These changes were similar to those seen during isovolaemic haemodilution. Two phenomena were therefore seen after translumbar aortic arteriography: an almost immediate histamine release, followed later by haemodilution.

Anesthesia, General↗
PubMed1983

[Continuous treatment of asthma in children with theophylline retard].

Continuous sustained-release theophylline therapy was used in 61 children with severe asthma, aged 5 to 16 years. Mean treatment duration was 5 months 8 days (range: 8 days-16 months). The necessary dosage to obtain correct blood theophylline levels was 18 +/- 3.6 mg/kg/day (range: 10-31 mg/kg/day). The adaptation of the doses to blood theophylline levels and regular check-ups confirmed intrapatient variability and the dose-dependent disposition of theophylline. In 35 of the 42 children (82%) who were observed for more than 3 months, theophylline induced a decrease of the frequency of the attacks and a better attendance to school. Nine times out of 30, oral steroid administration or sustained-release cosyntropin injections could be stopped and in 15, the dosages could be decreased by at least 50%. Evaluations of pulmonary function, performed several times in 12 children, showed that theophylline induces significant bronchodilatation, mostly of the large bronchi.

Adolescent↗
PubMed1982

The effects of atropine on anaphylactic shock in the guinea-pig.

The effects of atropine, 2 mg/kg i.v., on anaphylactic shock were studied in guinea-pigs sensitized to ovalbumin. Atropine only moderately reduced (--31%) the increase in pulmonary resistance observed and slightly prolonged (+26%) the survival time in pretreated animals compared with controls. These effects, however, were no statistically significant. The drug temporarily improved ventilation but had no influence on haematosis. On the other hand, atropine significantly reduced the amount of histamine released (--60%) and of GMPc synthetized in the lung (--21%). The levels of AMPc and prostaglandins E1, E2 and F2 alpha remained comparable to those of control animals. These results suggest that the reflex-induced action of the cholinergic system during anaphylaxis primarily affects large-calibre airways and that the role of acetylcholine in severe reactions is moderate when compared with the direct action of other mediators.

Airway Resistance↗
PubMed1981

Previous volume history of the lung and regional distribution of residual volume.

By use of 133Xe, the regional distribution of residual volume (RV) was measured in six seated healthy men, following a fast vital capacity (VC) expiration a) without and b) with a breath hold at residual volume of approximately 30 s and c) following a slow (greater than 30 s) VC expiration from total lung capacity (TLC) without a breath hold at RV. After the breath hold at RV, regional RV/TLC in the lower lung zones decreased significantly compared wih results obtained with fast expiratory VC and no breath hold at RV. At lung top the opposite was true. The distribution of regional RV/TLC was the same following the slow VC expiration with no breath hold at RV as with the fast expiration with the breath hold at RV. The different regional distribution of RV in b and c relative to a was probably due mainly to collateral ventilation, i.e., during the breath hold at RV and the slow expiration some of the gas that was trapped in the dependent lung zones behind closed airways escaped into the upper regions of the lung where the small airways had remained patent, leading to increased expansion of upper alveoli.

Adult↗
PubMed1979

[Measurement of blood theophylline levels in the child: will this affect methods of prescription? (author's transl)].

Twelve children aged between 2 and 13 years received an oral dose of 5 mg/kg of pure theophylline, and 28 children aged between 2 and 15 years were given 10 mg/kg/day of the same drug in 3 or 4 divided doses for 3 days. In the first group blood theophylline levels were higher than 10 microgram/ml, after 1 or 3 hours, in only 3 children, two of whom were receiving erythromycin at the same time. Six hours and 12 hours later, none of the serum levels were higher than 10 microgram/ml. In the second group, estimations were performed on the 4th day. At 8 a.m., when the last dose had been given 12 hours previously, blood theophylline levels were all less than 10 microgram/ml (mean: 4.03 +/- 0,88 microgram/ml). Two hours and four hours after the usual morning dose, serum levels of greater than 10 microgram/ml were found in respectively 35 and 25% of the children only. Since the bronchodilator effect of theophylline is optimal for serum levels of greater than 10 microgram/ml, the dose currently recommended in France (10 mg/kg/day) would thus appear to be insufficient in most instances. However, increase in individual doses must be guided by serum estimations, which make it possible to avoid complications related to overdosage.

Adolescent↗
PubMed1979

The effects of metiamide and H1 receptor blocking agents on anaphylactic response in guinea-pigs.

The effects of metiamide and of four H1 receptor blocking agents (mepyramine, promethazine, clemastine and ketotifene) on anaphylactic reaction were studied in the guinea-pig. The H1 blockers conferred partial protection which shows that with the experimental protocol utilized (challenge injection with high doses of antigen), histamine plays a lesser role than other mediators released or synthesized. Metiamide (30.0 mg/kg i.v.) noticeably enhanced the increase in pulmonary resistance observed during anaphylactic reaction and reduced the protective effect of the H1 antagonists on this parameter and on histamine release. These effects might be explained by an inhibition - at least partial - of the negative feed-back mechanism through which histamine controls its own release, or by a specific action of metiamide in high doses. The transient tachycardia initially observed in anaphylactic shock is partly related to stimulation of cardiac H2 receptors by the histamine released, since it is suppressed by metiamide.

Airway Resistance↗
PubMed1979

Influence of immersion to the neck in water on airway closure and distribution of perfusion in man.

We measured closing volume (CV), expiratory reserve volume (ERV) regional distribution of lung volume (Vr) and perfusion in 7 normal subjects in air and during immersion to the neck in water. In four subjects immersion resulted in a CV greater than ERV and the normal perfusion distribution became inverted. In the other subjects, ERV remained larger than CV and perfusion distribution during immersion was uniform, not inverted. In 5 subjects closing volume increased and in 3 of them, the ratio of apical/basal Vr increased significantly during immersion. One subject had nomeasurable CV and in the other it was not measured. The data suggest: (1) that when CV is greater than ERV during immersion there is an inversion of the normal perfusion distribution, caused by hypoxia and/or an increase in mean alveolar pressure in the alveoli beyond the closed airways, and (2) that an increase in pleural pressure gradient during immersion may contribute to the increase in C.V.

Adolescent↗