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Biomedical subjects

R W Fuller

Publications and source records attributed to R W Fuller.

At least 73 records · Page 4Linked to original sources
PubMed1994

Effect of clonidine on induced cough and bronchoconstriction in guinea pigs and healthy humans.

We examined the effects of the alpha 2-receptor agonist clonidine, administered orally and by inhalation, on citric acid- and capsaicin-induced reflexes in guinea pigs and healthy human subjects. In groups (n = 8-10) of conscious guinea pigs, oral clonidine (10 and 100 micrograms/kg) was without effects, whereas inhaled clonidine (10-1,000 microM) caused a concentration-dependent inhibition of citric acid-induced cough (coughs during 3 min: control, 6.5 +/- 0.9; 1,000 microM clonidine, 1.7 +/- 1.0; P < 0.05) and reflex bronchoconstriction (time to onset of bronchoconstriction: control, 191 +/- 24 s; 1,000 microM clonidine, 317 +/- 33 s; P < 0.05). The inhibitory effect of inhaled clonidine on both reflexes was completely reversed by pretreatment with yohimbine but not with prazosin. In 12 healthy human volunteers, oral clonidine (150 mg) caused a significant fall in supine and erect systolic blood pressure and a significant increase in drowsiness as measured on a visual analogue scale 1 and 2 h after administration. Despite these effects, oral clonidine had no effect on capsaicin-induced cough or reflex bronchoconstriction in humans. In contrast to the effects in guinea pigs, inhaled clonidine (281 microM) had no effect on capsaicin-induced cough or reflex bronchoconstriction in humans. These data suggest that peripheral alpha 2-receptors exert an inhibitory effect on sensory neurotransmission in the guinea pig but not in the healthy human airway, indicating an important difference between the two species.

Administration, Inhalation↗
PubMed1994

Inhaled nicotine in humans: effect on the respiratory and cardiovascular systems.

Inhalation of nicotine (0-64 mg/ml) and capsaicin (2 x 10(-6)-2.5 x 10(-4) M) in 24 healthy nonsmoking subjects produced a concentration-dependent cough response. Two subjects coughed to capsaicin but not to nicotine. The mean (95% confidence interval) nicotine concentrations causing two and five coughs were 5.5 (3.5-8.7) and 15.8 (10.0-25.1) mg/ml, respectively, and were reproducible over 3 different days. Capsaicin inhalation did not alter the response to nicotine and vice versa. Both agents increased respiratory resistance, but the response was more rapid to capsaicin. Inhalation of nicotine (0-8 mg/ml) over 5 min caused increases in heart rate and blood pressure and a decrease in skin temperature. Inhaled ipratropium bromide (0.50 mg) had an antitussive effect and also inhibited the nicotine-induced bronchoconstriction, indicating a vagally mediated effect. Sodium cromoglycate (0.20 mg) did not affect cough or airway resistance changes caused by nicotine. This study shows that inhaled nicotine produces a concentration-dependent cough and airway obstruction in healthy subjects, probably because of stimulation of afferent nerve endings in the bronchial mucosa and mediated through parasympathetic cholinergic pathways. Respiratory reflexes evoked by nicotine are similar to those produced by capsaicin, but it is unclear whether these reflexes are mediated by the same type of sensory nerves.

Administration, Inhalation↗
PubMed1994

Capsaicin cough sensitivity decreases with successful treatment of chronic cough.

To assess the role of enhanced cough sensitivity in the pathogenesis of cough, we measured cough severity on a visual analogue scale (VAS) and capsaicin cough sensitivity (the concentration required to elicit two [C2] and five [C5] coughs) in 87 consecutive patients referred with chronic cough. Measurements were repeated after complete investigation and treatment, when patients were entered into one of four study groups: (1) treatment success (primary cause of cough successfully treated with elimination of the cough, n = 48); (2) primary treatment failure (treatment of potential primary cause of cough unsuccessful, n = 12); (3) cough treatment failure subgroup A (potential primary cause of cough identified and successfully treated but no improvement in cough, n = 8); and (4) cough treatment failure subgroup B (no potential primary cause of cough identified, n = 19). All patients in groups 3 and 4 were nonsmokers, had normal chest radiography and negative histamine challenge test, and failed to respond to intensive empirical treatment for rhinitis and gastroesophageal reflux. The VAS cough severity was lower and log C2 and C5 higher after treatment compared with initial values in the treatment success group but not in the other three groups. Enhanced sensitivity of airway nerves that mediate cough is important in the pathogenesis of nonproductive cough, and successful treatment is associated with a reduction in cough sensitivity. While enhanced sensitivity of airway nerves is usually present in patients with identifiable causes of chronic nonproductive cough, it is also found in other patients in whom the cause of cough is unknown.

Adult↗
PubMed1994

Nonbronchodilator effects of inhaled beta 2 agonists. Greater protection against adenosine monophosphate- than methacholine-induced bronchoconstriction in asthma.

There has been controversy about possible beneficial effects of beta agonists on airway function in asthma, in addition to their effects on airway smooth muscle. We compared the protective effects of terbutaline on bronchoconstrictor responses to methacholine, which constricts smooth muscle directly, adenosine 5'-monophosphate (AMP), which acts indirectly by mast cell activation, and sodium metabisulfite (MBS), which stimulates sensory nerves, in 15 mild asthmatic subjects in a randomized double-blind study carried out in two phases. In the first phase 12 subjects inhaled two doses of 0.5 and 2.5 mg terbutaline or placebo administered as a dry power (Tubohaler) 20 min before challenge with methacholine and AMP. Each subject received increasing doubling doses of methacholine and AMP nebulized from a dosimeter. Challenges were terminated when FEV1 fell by 20% from baseline (PC20). In the second phase 10 subjects (seven of whom had participated in Phase 1) inhaled 0.5 mg terbutaline or placebo before similar challenge with methacholine and MBS. In Phase 1 terbutaline inhibited the bronchoconstrictor response to methacholine by 2.1 and 3.3 doubling doses but caused a significantly greater inhibition of the response to AMP of 3.4 and 4.8 doubling doses after 0.5 and 2.5 mg, respectively. In the second phase 0.5 mg terbutaline had equivalent effects on responses to both methacholine and MBS of 2.6 and 2.2 doubling dilutions, respectively. This effect on methacholine and MBS implies functional antagonism of airway smooth muscle. The enhanced effect on AMP implies an additional non-smooth muscle action that may involve suppression of airway mast cell function.

Adenosine Monophosphate↗
PubMed1994

Effects of duloxetine, an antidepressant drug candidate, on concentrations of monoamines and their metabolites in rats and mice.

Duloxetine, (+)-N-methyl-3-(1-naphthalenyloxy)-2-thiophenepropanamine, is an inhibitor of the serotonin and norepinephrine neuronal transporters (Wong et al., 1993). In mice, duloxetine antagonized the depletion of brain serotonin by p-chloroamphetamine (ED50 = 2.5 mg/kg, i.p.) and the depletion of heart norepinephrine by 6-hydroxydopamine (ED50 = 1.1 mg/kg, i.p.). Brain concentrations of 5-hydroxyindoleacetic acid were decreased by duloxetine at 2 hr after doses of 1, 3 and 10 mg/kg and at 1 to 8 hr (but not 24 hr) after a 10 mg/kg i.p. dose of duloxetine. Duloxetine antagonized norepinephrine depletion in frontal cortex, but not dopamine depletion in striatum, after treatment of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. In rats, duloxetine decreased brain 5-hydroxyindoleacetic acid dose-dependently for up to 8 hr and decreased serotonin turnover measured by the accumulation of 5-hydroxytryptophan in rat hypothalamus after decarboxylase inhibition. In rats, duloxetine antagonized the depletion of brain serotonin by p-chloramphetamine and the depletion of norepinephrine and epinephrine in hypothalamus after i.c.v. injection of 6-hydroxydopamine. In vitro, duloxetine had little effect on either type A (serotonin as substrate) or type B (phenylethylamine as substrate) monoamine oxidase, IC50 concentrations being above 10(-5) M. These data extend evidence that duloxetine inhibits serotonin and norepinephrine transporters in vivo, actions that may lead to therapeutic efficacy in mental depression.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1994

Pharmacological characterization of LY293284: A 5-HT1A receptor agonist with high potency and selectivity.

(-)-LY293284, (-)-4R-6-acetyl-4-(di-n-propylamino)1,3,4,5- tetrahydrobenz[c,d]indole, is a conformationally restricted tryptamine derivative with an acetyl group serving as a protophilic substitution for the hydroxyl in serotonin (5-HT). In ligand displacement studies, LY293284 had a Ki of 0.07 nM for the 5-HT1A receptor but no affinity for other monoaminergic receptors within 3 orders of magnitude. LY293284 was evaluated in in vivo models, which have been used as markers for presynaptic and postsynaptic 5-HT1A receptor activity. LY293284 decreased hypothalamic 5-hydroxyindoleacetic acid levels (ED50, 2.9 micrograms/kg s.c.) and dorsal raphe serotonergic neuron firing rate (ED50, 0.08 micrograms/kg s.c.), which are accepted indices of presynaptic activity. LY293284 also induced a reduction in body temperature in rats (ED50, 3.6 micrograms/kg s.c.), which was blocked by pretreatment with (+/-)-pindolol. Hypothermic responses of rats to 5-HT1A agonists have had both pre- and postsynaptic characteristics in previous studies. The ED50 values for 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) in these tests were 15 to 45 times higher than those observed for LY293284. In models for postsynaptic activity, the ED50 for LY293284 for elevating serum corticosterone levels was 9.7 micrograms/kg s.c. and the minimum effective doses to induce lower lip retraction and flat posture were 3 micrograms/kg s.c. For comparison, the same indices obtained for 8-OH-DPAT were 222.4 and 100 micrograms/kg, respectively. The 5-HT syndrome responses induced by LY293284 were also attenuated by pretreatment with (+/-)-pindolol. LY293284 was 10 times more potent than 8-OH-DPAT in a drug discrimination test that used pigeons trained to identify 8-OH-DPAT. In sexual behavior tests with male rats, LY293284 induced a maximal reduction in ejaculatory latency at 0.01 micrograms/kg s.c., which was approximately 10 times higher potency than 8-OH-DPAT. In the pigeon conflict model for anxiolytic activity, LY293284 was 100 times more potent than 8-OH-DPAT in increasing punished responding. In the rat forced swim model for antidepressant-like activity, LY293284 was 30 and 35 times more potent than 8-OH-DPAT in decreasing immobility time and defecation rate. These studies have demonstrated that LY293284 is a highly selective and extremely potent 5-HT1A receptor agonist and represents a useful pharmacological tool for studying 5-HT1A receptor-mediated effects.

Animals↗
PubMed1994

The essential role of integrative biomedical sciences in protecting and contributing to the health and well-being of our nation.

The biomedical sciences in the United States are currently experiencing the effects of an increased emphasis on in vitro models of biological and disease processes. Advances in cellular and subcellular biology have been a driving force in the funding of new research, the training of new scientists, and new drug discovery and development. The importance of new findings at the cellular and subcellular levels is not disputed. However, the corresponding decline in funding and training opportunities for biologically relevant investigations at the level of the intact animal (including humans; hereafter designated as integrative biology) is a serious threat to continued biomedical advances. The lack of resources for integrative biology has far-reaching negative consequences in 1) the development and utilization of whole animal models of disease and dysfunction; 2) assessing the relevancy of in vitro studies to physiological mechanisms; 3) the evaluation of the scientific merit of whole animal investigations and their relevancy to the nation's scientific imperatives; 4) the instruction of young scientists in the technology and especially in the methods of integrative biology, including how to develop appropriate experimental hypotheses; 5) the instruction of graduate, medical, dental, pharmacy, and nursing students in drug and disease processes in the intact human; and 6) the ability of the pharmaceutical manufacturers, the FDA, the EPA and academia to hire scientists who can develop drugs and evaluate the effects of exogenous agents on the intact animal. These negative consequences can be alleviated in a variety of ways. These include 1) increasing the availability of funding for research in integrative biology, 2) increasing the opportunities for training in integrative biology, and 3) instituting grant reviews of integrative biomedical research by peers in integrative biomedical sciences. These measures can revitalize integrative biomedical research, help ensure the continued advancement of biomedical understanding, and consequently contribute to the alleviation of human suffering.

Animals↗
PubMed1994

Supersensitization of the oral response to SKF 38393 in neonatal 6-hydroxydopamine-lesioned rats is eliminated by neonatal 5,7-dihydroxytryptamine treatment.

5-Hydroxytryptamine (5-HT) 5-HT2c receptors mediate the enhanced oral activity response to the dopamine (DA) D1 agonist, (+/-)-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol (SKF 38393) in neonatal 6-hydroxydopamine (6-OHDA)-lesioned rats. To study the possible involvement of 5-HT fibers on this process, the effect of the 5-HT neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT) was determined. Rats were treated at 3 days after birth with desipramine (20 mg/kg i.p., base) 1 hr before intracerebroventricular vehicle, 6-OHDA (134 micrograms, base) and/or 5,7-DHT (50 micrograms, base). Oral activity was observed at 7 weeks and later. In neonatal 6-OHDA-lesioned rats oral activity dose-effect responses were increased by SKF 38393, 1-(3-chlorophenyl)-piperazine (m-CPP) and pilocarpine-respective DA D1, 5-HT2c and muscarinic receptor agonists. Rats treated neonatally with 5,7-DHT had agonist-induced responses resembling that of the saline control group. However, in rats treated neonatally with both 5,7-DHT and 6-OHDA, oral activity responses were reduced at nearly all doses of SKF 38393 and pilocarpine vs. that of the 6-OHDA group. The response of the 5,7-DHT + 6-OHDA group to m-CPP was reduced at only the 1.0 mg/kg dose. Of a variety of stereotyped behaviors that were observed in separate test sessions, m-CPP-induced grooming activity was less in the 5,7-DHT + 6-OHDA group vs. the 6-OHDA group.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Dose-related effects of a neonatal 6-OHDA lesion on SKF 38393- and m-chlorophenylpiperazine-induced oral activity responses of rats.

Neonatal 6-hydroxydopamine (6-OHDA) treatment of rats is associated with concurrent supersensitization of dopamine (DA) D1 and serotonin 5-HT1C receptors, for agonist-induced oral activity. The present study was conducted to determine if graded reduction of striatal DA content and/or graded elevation of striatal 5-HT content by 6-OHDA would alter sensitivity of either receptor type, and thereby influence oral activity responses to DA and 5-HT agonists. At 3 days after birth, groups of rats were pretreated with desipramine (20 mg/kg i.p.), 1 h before administration of a range of doses of 6-OHDA HBr (15, 30, 60, 100, 150 and 200 micrograms, i.c.v., salt form; half in each lateral ventricle) or the vehicle, saline (0.85%)-ascorbic acid (0.1%). Between 2 and 4 months, a series of challenge doses of SKF 38393 HCl (0.30 to 3.0 mg/kg i.p.) and m-chlorophenylpiperazine 2HCl (0.30 to 6.0 mg/kg i.p.; m-CPP 2HCl) were administered to each group of rats and oral activity was observed. Oral activity was determined for 1 min every 10 min during a 60-min period, starting 10 min after injection of agonist or vehicle. SKF 38393 dose-response curves demonstrated enhanced oral activity responses in rats lesioned neonatally with 150 or 200 micrograms of 6-OHDA. m-CPP dose-response curves demonstrated enhanced oral activity responses in these 2 groups of rats, as well as those lesioned neonatally with 100 micrograms of 6-OHDA. Striatal DA content was reduced by > 97% in these 3 groups of rats.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Ontogenetic SKF 38393 treatments sensitize dopamine D1 receptors in neonatal 6-OHDA-lesioned rats.

Neonatal 6-hydroxydopamine (6-OHDA) treatment of rats is associated with supersensitization of the dopamine (DA) D1 agonist induction of stereotyped and locomotor behaviors. The present study was conducted to determine whether ontogenetic treatments of these rats with the DA D1 receptor agonist, SKF 38393, would produce a maximal DA D1 receptor supersensitivity, as measured by locomotor behavior in adulthood. Rat pups were treated daily with SKF 38393-HCl (3.0 mg/kg per day, i.p.) or saline vehicle for 28 consecutive days from birth. These animals were additionally treated at 3 days after birth with 6-OHDA-HBr (100 micrograms, in each lateral ventricle, salt form) or its vehicle. Between 6 and 9 weeks locomotor activity or stereotyped behaviors were observed after weekly challenge doses of SKF 38393-HCl (3.0 mg/kg, i.p.). In the neonatal 6-OHDA group, successive SKF 38393 treatments produced progressively greater locomotor activity. In the group of rats treated during postnatal ontogeny with both 6-OHDA and SKF 38393 daily treatments, the first adult challenge dose of SKF 38393 produced an enhanced locomotor response, greater than that seen in other groups (P < 0.01). Subsequent SKF 38393 treatments of this group produced increasingly greater locomotor responses. SKF 38393-induced stereotyped behavioral effects were greater in the 6-OHDA-lesioned groups, whether or not SKF 38393 was administered ontogenetically. Profound reductions (> 99%) of DA and its metabolites were found in the striatum of neonatal 6-OHDA treated rats, regardless of whether SKF 38393 was co-administered ontogenetically.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Age-dependence of a 6-hydroxydopamine lesion on SKF 38393- and m-chlorophenylpiperazine-induced oral activity responses of rats.

Neonatal 6-hydroxydopamine (6-OHDA) treatment is associated with destruction of dopamine (DA) fibers and subsequent sprouting of serotonin (5-HT) fibers in the striatum of rats. Enhanced oral activity responses to SKF 38393 and m-chlorophenylpiperazine (m-CPP), respective agonists for the DA D1 receptor complex and 5-HT2C receptor complex, ensue. To study the ontogenetic nature of this effect, rats were treated at birth, 3 days, 7 days, 10 days or 14 days with 6-OHDA-HBr (200 micrograms i.c.v.; salt form), following desipramine-HCl pretreatment (20 mg/kg i.p., 1 h; base form). Another group of rats was treated at 35 days and again at 42 days with 6-OHDA-HBr (300 micrograms i.c.v.), following desipramine-HCl (20 mg/kg i.p., 1 h) and pargyline-HCl (50 mg/kg i.p., 30 min). In rats treated from birth to 10 days, 6-OHDA reduced striatal DA content at 5 months by > or = 94%. Striatal 5-HT content was elevated by 28% to 51%, but only in rats treated with 6-OHDA at 7 days from birth or earlier. An enhanced oral activity response to SKF 38393-HCl (0.03 to 1.0 mg/kg i.p.) was absent in rats treated 7 days or later, and the change in SKF 38393 effect was correlated with a change in striatal DA content. An enhanced response to m-CPP.2HCl (0.3 to 6.0 mg/kg i.p.) was absent after treatment at 14 or 35 days, when striatal DA content was reduced only 44% to 63% and 5-HT content was not changed.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Drug concentrations in mouse brain at pharmacologically active doses of fluoxetine enantiomers.

The i.p. injection of R-fluoxetine into mice at doses of 1-10 mg/kg led to higher concentrations of the desmethyl metabolite, R-norfluoxetine, in whole brain than was true for S-fluoxetine. R-Norfluoxetine, but not S-norfluoxetine, concentrations predominated over those of the parent drug at 7-24 hr after injection of the corresponding fluoxetine enantiomer. The more rapid N-demethylation of R-fluoxetine, and the relative inactivity of R-norfluoxetine as a serotonin uptake inhibitor compared with S-norfluoxetine, may explain the earlier report that R-fluoxetine is less potent than S-fluoxetine in antagonizing p-chloroamphetamine depletion of brain serotonin in mice. In the present study, a 10 mg/kg, i.p., dose of S-fluoxetine completely prevented p-chloroamphetamine given 24 hr later from depleting brain serotonin, whereas R-fluoxetine offered no protection at this time.

Animals↗
PubMed1993

Isoprenaline inhibits thromboxane B2 release from U937 cells.

The U937 monocytic cell line and its differentiated macrophage-like form have been well characterized, illustrating many similarities with their analogous in vivo cells. We examined the release of thromboxane B2 (TXB2) from undifferentiated and differentiated cells after stimulation with opsonized zymosan and investigated whether the release of this mediator could be modified by isoprenaline. After stimulation, the U937 cells released TXB2 in a dose-dependent manner, with the release greater from the differentiated cells. The TXB2 released was inhibited by flurbiprofen (> 10(-8) M; P < .01) and isoprenaline (> 10(-6) M; P < .01), and the inhibition was reversed by propranolol (10(-6) M; P < .02). Thus, it is clear that undifferentiated and differentiated U937 cells release TXB2, which can be inhibited by beta 2-adrenoceptor stimulation. These findings illustrate an important functional difference between the in vivo macrophages and differentiated U937 cells because beta 2-adrenoceptor stimulation does not inhibit mediator release from macrophages.

Cell Transformation, Neoplastic↗
PubMed1993

Evaluation of nefopam as a monoamine uptake inhibitor in vivo in mice.

Nefopam antagonized 6-hydroxydopamine-induced depletion of heart norepinephrine in mice with an ED50 value of 12 mg/kg. Nefopam was ineffective in antagonizing p-chloroamphetamine-induced depletion of brain serotonin in our standard assay in mice, apparently due to a short duration of action. Brain concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) were decreased after a 32 mg/kg, i.p., dose of nefopam at 1 and 2 hr but not at 4 hr. When nefopam was injected simultaneously with p-chloroamphetamine, it prevented brain serotonin depletion initially, but by 6 hr the protective effect was essentially lost, suggesting that p-chloroamphetamine persisted in mouse brain longer than did nefopam. Nefopam caused a dose-related antagonism of brain serotonin depletion at 2 hr after injection of a low dose of p-chloroamphetamine hydrochloride (10 mg/kg, i.p.), with a calculated ED50 value of 11 mg/kg. The lowering of brain 5-HIAA concentration 2 hr after nefopam injection occurred after a 32 mg/kg dose but not after a 3 or 10 mg/kg dose. These data suggest that nefopam is effective as an inhibitor of norepinephrine and serotonin uptake at doses previously shown to be analgesic in mice, consistent with uptake inhibition being a postulated mechanism important in its analgesic effect. Nonetheless, nefopam is a relatively weak inhibitor of monoamine uptake with a short duration of action in mice.

Animals↗
PubMed1993

Effect of inhaled corticosteroids on peripheral blood eosinophil counts and density profiles in asthma.

BACKGROUND: Inhaled corticosteroids are effective in the treatment of asthma and reduce bronchial hyperresponsiveness. We examined the effect of inhaled budesonide (1600 micrograms/day for 14 days) on the number and density profile of peripheral blood eosinophils in 10 patients with mild stable asthma in a double-blind, placebo-controlled, crossover trial. METHODS: At the end of each study period, blood was collected immediately before measurement of bronchial responsiveness calculated as the concentration of methacholine causing a 20% fall in forced expiratory volume in 1 second (PC20). Plasma leukocyte suspension obtained after sedimentation of blood with 46% dextran was layered on a Percoll continuous-density gradient. After centrifugation, 20 sequential aliquots of increasing density gradients were removed for differential counts. Eosinophils recovered from density of gradients less than 1.080 gm/ml were defined as hypodense. RESULTS: Budesonide treatment resulted in a fall in mean eosinophil count from 0.37 +/- 0.05 x 10(9) L-1 after placebo to 0.16 +/- 0.03 x 10(9) L-1 (p < 0.01). A significant reduction occurred in the hypodense eosinophil population from 51.6% +/- 4.3% after placebo to 38.1% +/- 3.1% after budesonide (p < 0.05). Mean log PC20 increased from -0.26 +/- 0.12 after placebo to -0.004 +/- 0.14 after budesonide (p < 0.01). CONCLUSION: We conclude that inhaled steroid therapy reduces the number of circulating hypodense eosinophils, which is an effect that may underlie the improvement in bronchial hyperresponsiveness.

Administration, Inhalation↗