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Biomedical subjects

M Robuschi

Publications and source records attributed to M Robuschi.

At least 37 records · Page 2Linked to original sources
PubMed1992

Protective activity of inhaled frusemide against immunological respiratory changes and mediator release in guinea-pigs.

The antianaphylactic activity of inhaled frusemide was studied in ovalbumin-sensitized guinea-pigs. The exposure of the animals to frusemide aerosol (1% solution for 20 min) attenuated the respiratory response to ovalbumin challenge (aerosol 1% solution) and was associated with a significant reduction of blood histamine (70%; P less than 0.01) and thromboxane-B2 (35%; P less than 0.01) compared to control animals. Similar results were obtained in isolated lungs perfused via the trachea excised from ovalbumin-sensitized guinea-pigs exposed to frusemide aerosol (1% solution for 20 min). In this series of experiments frusemide significantly prevented the increase in tracheal perfusion pressure (45%; P less than 0.01) and the concomitant release into the pulmonary effluent of both histamine (75%; P less than 0.01) and thromboxane-B2 (39%; P less than 0.01). In another series of experiments, frusemide (1 x 10(-4) M) significantly reduced the immune release of histamine from mast cells of ovalbumin-sensitized rats. The inhibitory activity of frusemide was in the same range of potency (66%; P less than 0.01) as that of disodium cromoglycate (1 x 10(-4) M). These data taken together indicate that frusemide when given by inhalation prevents histamine release secondary to antigen-antibody reaction.

Administration, Inhalation↗
PubMed1992

Prevention of exercise-induced bronchoconstriction by a new leukotriene antagonist (SK&F 104353). A double-blind study versus disodium cromoglycate and placebo.

The effects of 800 micrograms of inhaled SK&F 104353, a peptidoleukotriene receptor antagonist, and of 20 mg disodium cromoglycate (DSCG) on exercise-induced bronchoconstriction were compared in 18 asthmatic patients. The study was conducted according to a double-blind, crossover, randomized, placebo-controlled design. Two baseline exercise tests were carried out, and pulmonary function tests were done before and at 1, 5, 10, 15, 20, and 30 min after completion of the exercise. Patients showing a 20% or greater decrease in FEV1 in both exercise challenges entered the blinded portion of the study. When placebo was administered before exercise, FEV1 fell to the same extent as during the baseline phase. After SK&F 104353 and DSCG, the bronchoconstriction was attenuated. The mean maximal percentage fall in FEV1 after exercise was 29% after placebo and 20% after SK&F 104353 and DSCG. The differences between the two active treatments did not reach the 5% level of statistical significance, though at 20 min SK&F 104353 showed a more pronounced effect than DSCG. The protective effect suggests an important role of leukotrienes in the pathogenesis of exercise-induced bronchoconstriction.

Adult↗
PubMed1991

Hyperreactivity and bronchial obstruction.

The main obstructive components in bronchial asthma and chronic obstructive pulmonary disease (COPD) are discussed. It is underscored that bronchospasm plays a significant role also in COPD, and that it merits specific treatment (beta 2-stimulants, antimuscarinics, theophylline) even when, in some cases, obstruction appears to be 'irreversible'. The majority of COPD patients react positively, although to a lower degree than asthmatics, not only to chemical agents (histamine, methacholine), but also to 'osmotic' stimuli, such as ultrasonically nebulized distilled water. Geometric factors seem to be in part responsible for the anomalous response. Considering the potent antireactive activity of bronchodilators (beta 2-stimulants in particular), this finding is a further indication for a regular bronchodilator treatment in COPD. Whether such a therapy serves also to improve the prognosis of COPD in the long run has not yet been established.

Asthma↗
PubMed1991

Bronchodilating activity of broxaterol transdermal patch and its protective effect on bronchial constriction induced by inhaled distilled water mist.

The bronchodilating activity and the ability of broxaterol transdermal patch to inhibit bronchial constriction in response to distilled water mist (UNH2O) inhalation were assessed. The study was performed in 10 asthmatic patients in clinical remission according to a placebo-controlled, double-blind, randomized crossover design. Test medications were broxaterol patch (size = 1.75 cm2; programmed delivery = 105 mcg/h) and a matched placebo patch. A spirometric examination was performed before patch application (at 8:30-9:00 a.m.) and 24 hours later. Immediately afterwards, the UNH2O inhalation test was made, consisting of 3 bronchial exposures lasting 30, 60 and 120 s respectively with 3-minute intervals between challenges. Immediately after each exposure, a spirometric examination and specific airway resistance measurements were made. The results obtained show that broxaterol patch exerts a statistically significant bronchodilating effect and has a better protective effect than placebo patch on UNH2O-induced bronchial constriction. The local tolerability of patches was very good. Slight tremors were observed in some subjects.

Administration, Cutaneous↗
PubMed1990

Prevention of antigen-induced early obstructive reaction by inhaled furosemide in (atopic) subjects with asthma and (actively sensitized) guinea pigs.

The present study was undertaken to determine the effect of furosemide on antigen-induced bronchoconstriction. Ten patients with stable asthma (eight men and two women), aged 17 to 48 years, were challenged with the same dose of allergen (Dermatophagoides pteronissinus, Parietaria, and grass mix) that had induced an FEV1 fall of at least 20% in a preliminary study on two occasions: immediately after placebo and furosemide (approximately 28 mg) administered by inhalation in random order and double-blind. Furosemide did not demonstrate any direct bronchodilator effect but markedly attenuated allergen-induced bronchoconstriction. The mean (95% confidence interval) maximum fall in FEV1 was 31.5% (40.2% to 22.8%) after placebo and 8.4% (11.8% to 4.9%) after furosemide administration. Furosemide, administered by aerosol to anesthetized guinea pigs actively sensitized to ovalbumin, dose dependently protected the animals from anaphylactic reaction. Infusion of furosemide (10 mg/kg for 10 minutes) failed to protect the animals from the anaphylactic response. In nonsensitized guinea pigs, the cardiovascular and pulmonary changes induced by histamine (10 micrograms/kg intravenously [i.v.]), leukotriene C4 (1 micrograms/kg i.v.), and platelet-activating factor (0.1 microgram/kg i.v.) were not modified by aerosol administration of furosemide (10 mg/ml for 10 minutes). In conclusion, inhaled furosemide induces a clear-cut protection against immediate obstructive reaction caused by areoallergerns and ovalbumin, both in subjects with asthma and actively sensitized guinea pigs, respectively.

Administration, Inhalation↗
PubMed1990

Antianaphylactic and antihistaminic activity of the non-steroidal anti-inflammatory compound nimesulide in guinea-pig.

Nimesulide (4-nitro-2-phenoxymethane sulfonanilide, Aulin, Mesulid) is a non-steroidal anti-inflammatory compound which shows antihistaminic activity and inhibits the immune release of histamine. The antihistaminic activity of this compound is specific for H1-receptor and has been demonstrated on isolated strips of guinea-pig trachea and on histamine-induced multiphasic inotropic response in left atria of guinea pig electrically driven. The effect of nimesulide is of non competitive type and, at the concentration of 1 x 10(-5) mol/l, is nearly 2 time less potent than pyrilamine (mepyramine) at 1 x 10(-6) mol/l. Nimesulide (1.6 mumol/kg i.v.) inhibits both bronchoconstriction (69%) and TXB2 formation (93%) induced by histamine (0.05 mumol/kg i.v.) in anaesthetized guinea-pigs. In contrast indomethacin (1.6 mumol/kg i.v.) decreases the generation of TXB2 (89%) without affecting the enhancement in tracheal insufflation pressure induced by histamine. In actively sensitized guinea-pigs both nimesulide and indomethacin protect the animals from deadly anaphylactic crisis. The rise in tracheal pressure induced by the antigenic challenge is inhibited of 80% and 63% respectively by nimesulide and indomethacin (6.4 mumol/kg i.v.). At this dose the two compounds reduced of 90% approximately the immunological release of TXB2 in the circulation. The release of histamine, induced by the anaphylactic reaction caused in perfused lungs obtained from actively sensitized guinea-pigs, is lessened by nimesulide (EC50 = 3.06; fid. lim. 2.59-3.63 mumol/l) and potentiated by indomethacin (EC50 = 0.89; fid. lim. 0.67-1.17 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗
PubMed1989

Inhaled frusemide is highly effective in preventing ultrasonically nebulised water bronchoconstriction.

A decrease in the osmolarity of the periciliary fluid of central airways is supposed to be the initiating mechanism by which ultrasonically nebulised distilled water (UNH2O) induces bronchoconstriction in asthmatics. It is therefore possible that substances, such as frusemide (F), which, in vitro, interfere with ions and water translocation across the tracheo-bronchial epithelium, can also modify such response. To test this hypothesis, 16 adult asthmatics were challenged with UNH2O after being pretreated with either inhaled F (approximately 28 mg delivered into the mouth) or placebo (the diluent) administered in random order and double-blind by means of a jet nebuliser. F did not modify baseline FEV1 and sRaw but attenuated markedly their changes after UNH2O. Mean max % (95% CI) sRaw increases after placebo and F were 293% (168-419) and 63% (21-104), respectively; mean max % falls in FEV1 were 26% (20-32) and 6% (-1-12). Thus inhaled F is highly effective in preventing UNH2O-induced bronchoconstriction and this unexpected property could have therapeutic implications.

Administration, Inhalation↗
PubMed1988

Prevention of exercise-induced bronchoconstriction by inhaled frusemide.

To determine whether inhaled frusemide, a diuretic able to interfere with ion and water movement across airway epithelium, can modify exercise-induced bronchoconstriction, a three-part randomised, double-blind, placebo-controlled study was done in asthmatic patients who had a fall in FEV1 of at least 20% after running up and down a corridor. In the first part the effect of approximately 28 mg frusemide given as an aerosol was compared with that of a placebo. In the second part two doses of inhaled frusemide (approximately 14 mg and 28 mg) were examined. In the third part the effect of 20 mg oral frusemide was tested. Inhaled frusemide had a good and dose-related protective effect, whereas oral frusemide was ineffective. The mean (95% CI) maximum percentage falls in the FEV1 were: 11.5 (14.3-8.7) with frusemide and 33.8 (39.1-28.5) with placebo in the first part of the study; 13.6 (21.6-6.0) with 28 mg frusemide, 19.7 (28.2-11.3) with 14 mg frusemide, and 34.6 (39.4-30.0) with placebo in the second part of the study; and 15.2 (19.9-10.5) with inhaled frusemide, 38.2 (47.1-29.3) with oral frusemide, and 35.3 (45.9-24.7) with placebo in the last part of the study. The findings lend support to the hyperosmolarity hypothesis of exercise-induced asthma and may have therapeutic implications.

Administration, Inhalation↗
PubMed1988

Intolerance to tartrazine in aspirin-induced asthma: results of a multicenter study.

One hundred and fifty-six German, Italian and Polish patients with confirmed aspirin-induced asthma underwent open oral challenges with increasing doses of tartrazine up to 25 mg. All positive challenges were repeated under double-blind conditions. Only 4 of 156 patients (all Polish) had positive reactions in a double-blind test, as evidenced by a fall in FEV1 greater than 25% from baseline and corresponding clinical symptoms. Sixty-five patients who tolerated 25 mg tartrazine well received 50-3,000 mg tartrazine and none showed adverse reactions. Thus, intolerance to tartrazine appears to be rare among Central-European and South-European patients with aspirin-induced asthma, its frequency amounting to about 2.6%.

Administration, Oral↗
PubMed1988

Control of the bronchial tone.

The tone of airway smooth muscle is the functional expression of a dynamic equilibrium between various excitatory and inhibitory mechanisms. On the excitatory side, the vagal reflex mechanism, mainly activated by central airway irritant receptors, is the most important. Bronchial epithelium plays a pivotal role in the regulation of the responsiveness of these receptors. Cholinergic responses of the bronchial muscle are mediated by muscarinic (M2) receptors. On the inhibitory side, the main mechanism is the adrenergic one: beta 2-receptors are mainly stimulated by circulating adrenaline. A dense population of beta 2-receptors has recently been observed in bronchial epithelium. Nonadrenergic-noncholinergic mechanisms--both excitatory and inhibitory--participate in the regulation of bronchial motor tone, but their role in man is still to be defined. Nonsteroidal anti-inflammatory drugs do not modify bronchial motor tone; thus, in this respect, at least in physiological conditions, a modulatory function of the prostaglandin system can be excluded. Probably the same applies to leukotrienes, but for a definite answer, specific antagonists are needed.

Asthma↗
PubMed1987

Prevention of fog-induced bronchospasm by nedocromil sodium.

A single dose double-blind crossover study was performed to compare the efficacy of nedocromil sodium (4 mg) and placebo administered from pressurized aerosols against bronchoconstriction induced by the inhalation of ultrasonically nebulized distilled water (fog) in twelve asthmatic subjects. Neither active nor placebo pre-treatment produced any significant change in baseline FEV1 and SRaw. Nedocromil sodium significantly attenuated fog-induced falls in FEV1 (P less than 0.001) and increased specific airways resistance (SRaw, P less than 0.01). The results provide further evidence of the potential therapeutic usefulness of nedocromil sodium in the management of chronic obstructive airways disease.

Adolescent↗
PubMed1987

Evaluation of a new bronchodilating compound (broxaterol) administered as a pressurized aerosol.

The bronchodilating activity and the tolerability of a new beta 2-agonist, broxaterol hydrochloride, administered in single doses of 200 and 400 micrograms as pressurized aerosol were studied in 12 adult patients with reversible airway obstruction, taking placebo as a control. A double-blind three-way cross-over design using a series of randomly chosen latin squares was employed. FVC, FEV1, MMEF, heart rate, and blood pressure were measured immediately before and 7.5, 15, 30, 60, 120, 180, and 240 min after each treatment. Our results show that broxaterol is an effective bronchodilating drug with a dose-related activity. The areas under the curves of the changes in FVC, FEV1, and MMEF after the 400 micrograms dose were found to be significantly greater as compared to the 200 micrograms dose. Both broxaterol doses produced significant increases in all the spirometric indices already at the first measurement, i.e., 7.5 min after treatment. Broxaterol 400 micrograms induced significant increases in FVC, FEV1, and MMEF through at least 4 h. The tolerability of the new compound was good.

Administration, Inhalation↗
PubMed1986

Prevention of fog-induced bronchospasm by Duovent and its components (fenoterol, ipratropium bromide) in asthmatics.

16 hyperreactive asthmatics were challenged with an ultrasonic mist of H2O at the same time of day on 4 usually consecutive days 2 h after premedication with placebo, fenoterol (200 micrograms), ipratropium bromide (80 micrograms) and Duovent (fenoterol 200 micrograms + ipratropium bromide 80 micrograms), given in random order and double-blind conditions. The challenge test consisted of 3 exposures of 30, 60 and 120 s with 4-min intervals. Specific airway resistance (sRaw) was measured under basal conditions and 1, 2 and 3 min after each exposure. FEV1 was measured under basal conditions and immediately after the last sRaw measurement. Fenoterol afforded a good protection; ipratropium bromide alone was ineffective but enhanced the protective effect of fenoterol when the two drugs were given in combination (Duovent). A similar effect was also observed after a second challenge performed 1 h (9 patients) or 3 h (6 patients) after the first one, which was performed 2 h after premedication.

Adolescent↗
PubMed1986

Prevention of fog-induced bronchospasm by high doses of ipratropium bromide in asthmatics.

In 12 adult asymptomatic, relatively stable adult asthmatics the protective effect of 3 doses (200, 1,000 and 2,000 micrograms) of ipratropium bromide against bronchospasm induced by an ultrasonic mist of distilled water was functionally (sRaw, FEV1) assessed. Ipratropium bromide and placebo were administered as an inhalation powder via a special inhaler in random order and under double-blind conditions at the same time on 4 usually consecutive days 90 min prior to the challenge. A considerable protective effect (clearly inferior, in any case, to that previously observed by us with fenoterol) was demonstrated (% protection approximately equal to 50) without any striking difference among the 3 doses. Mouth dryness (dose-related) was the sole complaint in some patients.

Adult↗
PubMed1985

Tolerance of carprofen in patients with asthma caused by non-steroidal anti-inflammatory drugs.

Eight asthmatics with respiratory intolerance to NSAIDs and two subjects (one asthmatic, one healthy) only sensitive (asthma) to pyrazolone drugs were challenged under single-blind conditions with a new NSAID, carprofen. No adverse effects were observed in patients sensitive to pyrazolones. Among the other patients, only three developed considerable bronchial obstruction which was rapidly reversed by inhalation of a beta 2-stimulant (fenoterol: 2 puffs). Two subjects developed nasal obstruction with rhinorrhoea: in conjunction with bronchoconstriction in one patient and alone in the other. In conclusion, acute administration of carprofen in patients with respiratory intolerance to NSAIDs, in contrast to most other NSAIDs, never creates a situation of real danger even though in some patients it may considerably increase nasal and bronchial resistance.

Adult↗
PubMed1983

Drug effect on bronchial response to PGF2 alpha and water inhalation.

A new method of challenge with H2O is described after summarizing the results of previous studies concerning the pharmacological prevention of bronchoconstriction induced by PGF2 alpha and by ultrasonic mist of distilled water (H2O). This provides a simple, rapid and reproducible way of obtaining linear dose-response curves by plotting times of exposures against absolute or percent increases in sRaw. The preventive activity of several drugs against this type of bronchospasm has been tested. Beta 2-stimulants (fenoterol) were the most effective, both in terms of intensity and duration of action (more than 6 hours). DSCG, tiaramide and nifedipine were also efficient. Oxitropium bromide was almost ineffective, in spite of the comparatively high doses used. The H1 and H2 antihistamines chlorpheniramine and ranitidine were ineffective. The possible implications of these results are discussed, mainly in order to try to understand the mechanism of H2O bronchospasms, for which airways cooling does not seem at work.

Albuterol↗