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Biomedical subjects

N Frossard

Publications and source records attributed to N Frossard.

At least 37 records · Page 2Linked to original sources
PubMed2001

Local increase in the number of mast cells and expression of nerve growth factor in the bronchus of asthmatic patients after repeated inhalation of allergen at low-dose.

BACKGROUND: Repeated inhalation of allergen at low-dose induces an increase in bronchial hyper-responsiveness, without any associated symptom. The concomitant events in the bronchus have not been described. OBJECTIVE: We have studied the dynamic number of mast cells in the airways of patients with mild asthma before and after repeated inhalation of allergen at low-dose and the expression of nerve growth factor (NGF), which is reported to promote growth and survival of mast cells. METHODS: Twelve patients with mild asthma to cat allergen were enrolled at random in a blind placebo-controlled study, and submitted to repeated low-dose allergen exposure (1/5 of the provocative dose). Mast cells were immunolocalized using an antibody against mast cell tryptase. NGF and its high affinity receptor, TrkA, were immunolocalized using anti-NGF and anti-TrkA antibodies, respectively. NGF mRNA was quantified by competitive polymerase chain reaction (PCR) after reverse transcription of total RNA extracted from bronchial biopsy. NGF protein levels were measured by ELISA in bronchoalveolar lavage (BAL) fluid. RESULTS: Bronchial mast cell number was increased significantly after allergen exposure as compared with before. NGF expression in the bronchus was immunolocalized mainly to epithelial cells, but also to fibroblasts, blood vessels, and a few infiltrated cells. NGF mRNA levels in bronchial biopsies were increased significantly after allergen exposure. The high affinity receptor for NGF, TrkA, was immunolocalized to the infiltrated mast cell membrane. CONCLUSION: Our study shows that the increase in the number of mast cells and in the expression of NGF induced by allergen exposure in the bronchus of asthmatic patients is occurring before the onset of symptoms. In addition, our finding of the presence of the TrkA receptor on the membrane of the infiltrated mast cell in situ brings evidence of the mast cell as a target cell for the growth factor activity of NGF in the airways in asthma.

Administration, Inhalation↗
PubMed2001

Difference in exposure to airborne major rat allergen (Rat n 1) and to endotoxin in rat quarters according to tasks.

UNLABELLED: Endotoxins found in occupational settings constitute a risk factor in the severity of respiratory allergic symptoms. OBJECTIVES: To assess the airborne concentrations of major rat allergen (Rat n 1) and endotoxin under various circumstances. METHODS: We took 483 airborne samples from 12 sites: 114 individual samples for endotoxin measurements and 113 for Rat n 1, from 38 workers (nine animal technicians, nine laboratory technicians, nine scientists and 11 students); and 256 static samples in rat rooms and experimental rooms, with or without disturbance, for simultaneous endotoxin and Rat n 1 measurements. Rat n 1 was measured with a two-site monoclonal ELISA and endotoxins with the Limulus method. RESULTS: Airborne Rat n 1 and endotoxin were significantly higher in rat rooms than in experimental rooms. Animal technicians had the greatest exposure to both Rat n 1 and endotoxin. Cage cleaning and rat feeding induced the highest exposure to Rat n 1 and endotoxin. Furthermore, we observed no significant difference in endotoxin exposure between researchers with or without rat contact during the sample period. There was no correlation between the number of rats present and airborne endotoxin concentrations. CONCLUSIONS: Exposure to airborne Rat n 1 and endotoxin is higher during cleaning and feeding tasks than during any other task, we feel that a major source of both is contaminated bedding that becomes airborne during disturbance.

Air Pollutants, Occupational↗
PubMed2001

Human lung fibroblasts secrete nerve growth factor: effect of inflammatory cytokines and glucocorticoids.

Nerve growth factor (NGF) has recently been suggested to contribute to inflammation and bronchial hyperresponsiveness in asthma. However, the cell types capable of NGF production in the human lung and airways, as well as the regulatory role of pro-inflammatory cytokines and of glucocorticoids on NGF secretion in pulmonary cells, have not been described. Human pulmonary fibroblasts were cultured in the presence or absence of either interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha) and/or glucocorticoids. NGF secretion was measured by enzyme-linked immunosorbent assay. The human pulmonary fibroblasts constitutively secreted NGF in vitro. The rate of NGF secretion was shown to be cell density-dependent, since higher NGF secretion was detected in preconfluent cells, i.e. ones with less established cell-to-cell contact (41.0+/-5.0 pg x 10(-6) cells at 80% confluence), than cells in higher densities (8.2 +/- 3.4 pg x 10(-6) cells at 100% confluence). Stimulation with the pro-inflammatory cytokines IL-1beta (0.3-30 U x mL(-1)) or TNF-alpha (0.1-30 ng x mL(-1)) dose- and time-dependently (8-72 h) elevated the NGF secretion (effective concentration causing 50% of the maximum response (EC50)=2.9 U x mL(-1) and 1.0 ng x mL(-1), respectively). Treatment with the glucocorticoid budesonide (10(-7) M) markedly reduced the constitutive secretion of NGF by 42%, and attenuated the cytokine-stimulated NGF secretion to the same level. In conclusion, human lung fibroblasts may serve as a source of nerve growth factor in the lung, positively regulated by the asthma-associated and pro-inflammatory cytokines interleukin-1beta and tumour necrosis factor-alpha, and negatively regulated by the anti-inflammatory glucocorticoids.

Budesonide↗
PubMed2001

New insights into the second generation antihistamines.

Second generation antihistamines are recognised as being highly effective treatments for allergy-based disease and are among the most frequently prescribed and safest drugs in the world. However, consideration of the therapeutic index or the benefit/risk ratio of the H1 receptor antagonists is of paramount importance when prescribing this class of compounds as they are used to treat non-life threatening conditions. There are many second generation antihistamines available and at first examination these appear to be comparable in terms of safety and efficacy. However, the newer antihistamines in fact represent a heterogeneous group of compounds, having markedly differing chemical structures, adverse effects, half-life, tissue distribution and metabolism, spectrum of antihistaminic properties, and varying degrees of anti-inflammatory effects. With regard to the latter, there is growing awareness that some of these compounds might represent useful adjunct medications in asthma therapy. In terms of safety issues, the current second generation grouping includes compounds with proven cardiotoxic effects and others with the potential for adverse drug interactions. Moreover, some of the second generation H1 antagonists have given cause for concern regarding their potential to cause a degree of somnolence in some individuals. It can be argued, therefore, that the present second generation grouping is too large and indistinct since this was based primarily on the concept of separating the first generation sedating compounds from nonsedating H1 antagonists. Although it is too early to talk about a third generation grouping of antihistamines, future membership of such a classification could be based on a low volume of distribution coupled with a lack of sedating effects, drug interactions and cardiotoxicity.

Anti-Asthmatic Agents↗
PubMed2000

Inhalation of toluene diisocyanate affects cytochrome P450 2B1 expression in rat lung.

In the lung the expression of xenobiotic-metabolizing enzymes such as cytochromes P450 (CYP) and glutathione S-transferases (GST) may be affected by inhaled pollutants. Toluene diisocyanate (TDI) is a highly volatile chemical compound known to induce a wide array of diseases in workers exposed to vapors or sprays, including respiratory allergy and asthma. We investigated the effect of inhaled TDI on expression of CYP 1A1, 2B1, 2E1, and 3A1 and of alpha-, mu-, and pi-GST in rat lung. Animals were exposed to targeted concentrations of 0.01, 0.1, or 1 ppm TDI vapors or to cleaned filtered air for 8 h. Expression of CYP and GST was analyzed 18 24 h after the end of exposure using western blotting, northern blotting, and immunohistochemistry. Constitutive levels of CYP 2B1 and 3A1 proteins were found in lung tissue from control rats, whereas CYP 1A1 and 2E1 proteins were not detectable. Animal exposure to TDI vapors neither modified CYP 3A1 protein expression, nor led to any detectable expression of CYP 1A1 or 2E1. In contrast, exposure to 1 ppm TDI induced a 40% reduction in CYP 2B1 protein levels. This decrease was associated with a 33% decrease in CYP 2B1 mRNA levels. Additionally, CYP 2B1 immunolabeling localized to ciliated epithelial cells, Clara cells, and type II alveolar cells in the lung tissue of control rats was markedly decreased in animals exposed to 1 ppm TDI. Constitutive levels of alpha-, mu-, and pi-GST proteins were found in lung tissue from control rats. Exposure to TDI had no effect on lung expression of either of the GST. In conclusion, this study clearly shows a selective decrease in CYP 2B1 expression by TDI vapors in rat lung. The contribution of CYP 2B1 to metabolize further xenobiotics is therefore altered.

Administration, Inhalation↗
PubMed2000

[Role of bronchial smooth muscle in inflammation].

We now have to consider the airway smooth muscle as an actor of the bronchial inflammation in asthma. In addition to its bronchoconstricting role in response to mediators secreted by the adjacent cells and tissues, that may be considered as to be passive regarding the airway inflammation, the airway smooth muscle may now be considered as pro-inflammatory, since it has the potential of synthesizing and secreting a variety of chemokines and growth factors that will favor cell proliferation, and attraction of inflammatory cells. The airway smooth muscle may modify its phenotype from a contractile to a secretory or a proliferative phenotype. These differentiation states of the bronchial smooth muscle may be studied experimentally by culturing the airway smooth muscle. The demonstration of the occurrence and/or coexistence of such differentiation states in vivo will help understand the exact role of the bronchial smooth muscle in the airway inflammation in asthma.

Animals↗
PubMed1999

Consistency and efficacy of cetirizine (10 mg) versus ebastine (20 mg) at 4 h on skin reactivity.

OBJECTIVE: We compared the consistency and efficacy of the two antihistamines, cetirizine (10 mg) and ebastine (20 mg) on histamine skin reactivity 4 h after treatment. METHODS: Twenty-four healthy volunteers participated in a randomised double-blind cross-over study. The areas of wheals and flares induced by increasing (0, 5, 10, 50, 100, 200, 300 mg/ml) histamine concentrations, administered by prick tests, were measured before and 4 h after intake of cetirizine or ebastine. RESULTS: Before treatment, concentration-response curves were similar and threshold concentrations identical (0.57 mg/ml and 0.57 mg/ml for cetirizine and ebastine, respectively). Both treatments exerted a significant effect. However, cetirizine was significantly more efficient than ebastine 20 mg (P < 0.01 both for wheals and flares). After cetirizine, the threshold concentration inducing a 3-mm(2 )wheal was significantly higher (266 mg/ml) than after ebastine (77 mg/ml) (P < 0.01), and total inhibition of the wheal was obtained in 18 of 24 patients for cetirizine and in 4 of 24 for ebastine (P < 0.001). The variation coefficient for the wheal reaction was 31% for cetirizine and 159% for ebastine, indicating a much lower variability after cetirizine. CONCLUSION: Our study shows clearly that the efficacy of a single therapeutic dosage of cetirizine is greater and consistently better than that of ebastine for suppression of cutaneous reactivity to histamine 4 h after treatment in healthy volunteers. The need for ebastine to metabolise into the active carebastine might explain this difference.

Adolescent↗
PubMed1999

Effect of toluene diisocyanate and its corresponding amines on viability and growth of human lung fibroblasts in culture.

Toluene diisocyanate (TDI) is a highly volatile chemical known to cause occupational asthma in exposed workers. TDI-induced asthma is associated with airway epithelium injury and repair, and subepithelial fibrosis. We investigated the effect of TDI and its hydrolysis products, the 2,4- and 2,6-toluenediamines (TDA), on viability and growth of human lung fibroblasts (HLFs) in culture, using a tetrazolium-based cell viability assay. The effects of increasing concentrations of each of these chemicals were evaluated on quiescent cells seeded at two densities (2500 and 5000 cells/well) and treated for 24 or 48 h. TDI (10(-4)-10(-5) mol/L, as a mixture of 80% 2,4-TDI and 20% 2,6-TDI) exhibited a partial but significant cytotoxic effect (10-24%, p<0.05) on HLFs. This effect was observed at both cell densities, and was time- and concentration-dependent. 2,4-TDA, at lower concentrations (10(-8)-10(-6) mol/L) applied for 48 h, also partially reduced HLF viability (10-15%, p<0.05), whereas it tended to trigger cell growth at concentrations higher than 10(-5) mol/L. 2,6-TDA exhibited both a cytotoxic and a proliferative effect on HLFs that depended on concentration, time of exposure and cell culture density. Significant cytotoxicity was only observed after 24 h of treatment with 10(-7)-10(-6) mol/L 2,6-TDA, and reached greater intensity in cells cultured at the highest density. In contrast, 2,6-TDA stimulated HLF growth only after 48 h of incubation at 10(-4) mol/L on cells cultured at the lowest density. Taken together, our results showed that TDI and 2,4-TDA somewhat decreased HLF viability, whereas 2,6-TDA appeared to exhibit both a cytotoxic and a growth stimulatory effect on these cells. TDI and 2,4-TDA are thus suggested to contribute to airway epithelium damage associated with TDI-induced asthma, whereas 2,6-TDA might either trigger epithelial damage or induce cell proliferation that could contribute to epithelium repair or subepithelial fibrosis.

Asthma↗
PubMed1999

Human bronchial smooth muscle cells in culture produce stem cell factor.

A mast cell infiltration of the bronchial smooth muscle layer has been reported in patients sensitized to common allergens. Stem cell factor (SCF) is a chemotactic and survival factor for mast cells. SCF is expressed as a soluble (sSCF) and a membrane-bound (mSCF) form, after alternative splicing of the exon encoding the proteolytic cleavage site. SCF expression by human bronchial smooth muscle cells in culture was evaluated, comparing it to that of human lung fibroblasts in culture. sSCF released in the culture supernatant was assessed by an enzyme-linked immunosorbent assay. Total SCF messenger ribonucleic acid (mRNA) was measured by competitive polymerase chain reaction (PCR) after reverse transcription. Expression of the two forms of SCF mRNA was assessed by PCR, with primers spanning the alternatively spliced exon. Smooth muscle cells produced sSCF (21.9+/-2.6 pg x mL(-1)), although at lower levels than fibroblasts (35.9+/-3.5 pg x mL(-1)); the expression of total SCF mRNA was also at lower levels than in fibroblasts (8.6+/-0.2 and 19.0+/-2.0 amol x fmol glyceraldehyde 3-phosphate dehydrogenase complementary deoxyribonucleic acid(-1), respectively). However, smooth muscle cells expressed proportionally more (1.7-fold) mSCF mRNA than did fibroblasts. In conclusion, this study shows that bronchial smooth muscle cells express stem cell factor, with a relatively high expression of membrane-bound stem cell factor. This might be related to the presence of mast cells within the bronchial smooth muscle layer, i.e. at the site of bronchoconstriction, with possible implications in the pathophysiology of asthma.

Bronchi↗
PubMed1999

Evidence for in vitro expression of B1 receptor in the mouse trachea and urinary bladder.

1. Motor responses to des-Arg9-bradykinin and bradykinin were studied in the isolated mouse trachea (precontracted with carbachol, 10 microM) and the urinary bladder of either Swiss, C57B1/6J or bradykinin B2 receptor knockout (Bk2r(-/-)) mice after 1-6 h in vitro. The expression of mRNA for the mouse B1 receptor in tracheal and urinary bladder tissues was also studied by using Northern blot analysis. 2. In isolated tracheae, des-Arg9-bradykinin produced a relaxant response that increased over time: no response was observed after 1 h of incubation, whereas after 6 h the maximum response (1 microM) was 68-84% of the relaxation produced by isoproterenol (1 microM) in the three mouse strains. The relaxant response to bradykinin (1 microM) observed at 1 h (38-51% of isoproterenol) was increased (62-65% of isoproterenol) after 6 h in Swiss and C57B1/6J mice, but was absent in Bk2r(-/-) mice. In the presence of cycloheximide, des-Arg9-bradykinin did not cause any response at 6 h. 3. Similar findings were obtained in the urinary bladder: at 1 h des-Arg9-bradykinin (1 microM) did not cause any motor effect, whereas at 6 h it caused a contraction that was 28-59% of that produced by carbachol (1 microM) in the three mouse strains. Cycloheximide blocked the response to des-Arg9-bradykinin. Bradykinin (1 microM) contracted urinary bladders at 1 h (34-35% of carbachol), as well as at 6 h (66-77% of carbachol) in Swiss and C57B1/6J strains, but was without effect in Bk2r(-/-) mice. 4. Northern blot hybridization with a specific cDNA probe against mouse B1 receptor mRNA using total RNA extracted from tracheae and urinary bladders freshly removed from Swiss and Bk2r(-/-) mice revealed minimal expression. However, marked hybridization was detected 150 min after in vitro exposure in both tissues. 5. Evidence is provided that in vitro exposure of mouse trachea and urinary bladder causes a time-dependent induction of B1 receptors that cause relaxation and contraction, respectively.

Animals↗
PubMed1999

Repeated inhalation of low doses of cat allergen that do not induce clinical symptoms increases bronchial hyperresponsiveness and eosinophil cationic protein levels.

The aim of this study was to investigate whether repeated exposure to subclinical doses of cat allergens, not inducing asthma symptoms, could affect eosinophil cationic protein (ECP) levels in bronchoalveolar lavage (BAL) or in peripheral blood, without the appearance of clinical symptoms. Twelve patients with mild asthma, all sensitized to cats and not exposed to cat allergen at home, underwent a series of inhalations of cat allergen or placebo for 8 days over 2 weeks. A methacholine challenge was performed before and after the allergen and saline exposures, and BAL and blood were sampled for ECP measurements and eosinophil counts. No patients experienced asthma symptoms. However, PD20 methacholine (geometric mean) decreased significantly from 263 microg before to 126 microg after inhalation of allergen. Inhalation of saline did not induce any significant change in PD20. The change in log PD20 before and after cat allergen exposure was statistically different from the change in log PD20 before and after saline. Median ECP levels in BAL and serum increased significantly after allergen exposure, from 0.8 to 3.1 microg/l (p<0.02) and from 15.9 to 31.4 microg/l (p<0.05), respectively. No change was observed after saline inhalations. The change in BAL and serum ECP levels was statistically significant compared to that in the control group. The number of eosinophils did not change, however, nor did IL-5 and RANTES levels in BAL and serum. In conclusion, our results show that (1) exposure of asthma patients to repeated low doses of allergen, which did not provoke any clinical symptoms, is capable of inducing a local eosinophil activation associated with an increase in nonspecific bronchial hyperresponsiveness and (2) the increase in serum ECP levels due to eosinophil activation precedes the occurrence of asthma symptoms and may thus be a marker of allergen exposure in allergic asthma.

Administration, Inhalation↗
PubMed1999

Calcitonin gene-related peptide-immunoreactive nerves and neuroendocrine cells after lung transplantation in the rat.

Bronchial innervation is interrupted at lung transplantation. Nerve fibers with cell bodies above the section, such as sensory C fibers, should degenerate. Using histofluorescence, we evaluated calcitonin gene-related peptide (CGRP) immunoreactivity in syngeneic Lewis rats 1 and 5 mo after unilateral lung transplantation and in controls. CGRP-immunoreactive (IR) neuroendocrine cells were located within the epithelium of large and small bronchi. At 1 mo after transplantation, their number had significantly increased in large bronchi and had normalized 5 mo after transplantation. The density of CGRP-IR fibers in control lungs gradually decreased from large (0. 35 +/- 0.02 micron/micron basal lamina) to small (0.23 +/- 0.02) and peripheral bronchi (0.12 +/- 0.01). At 1 mo after lung transplantation, few CGRP-IR fibers were observed in large bronchi (0.17 +/- 0.02), fewer in small bronchi (0.04 +/- 0.01) (P < 0.01), and none in peripheral bronchi. At 5 mo after lung transplantation, transplanted lungs still had fewer CGRP-IR fibers in large (0.22 +/- 0.02) and small (0.11 +/- 0.02) bronchi (P < 0.02) than did controls, but there were, nonetheless, more in the small bronchi than at 1 mo after transplantation (P < 0.01). Additionally, few CGRP fibers were present in the peripheral bronchi (0.03 +/- 0.01) (P < 0.01). These results clearly demonstrate the occurrence of denervation followed by partial reinnervation with CGRP-IR fibers after transplantation in rat lung.

Animals↗
PubMed1999

[The bronchorelaxant effect of helicidine, a Helix pomatia extract, interferes with prostaglandin E2].

Helicidine is a biological extract prepared from the snail Helix pomatia L. and used in man as an anti-tussive agent. However, its mechanisms of action are not fully defined. In this study, we have investigated a possible relaxant effect of helicidine on guinea-pig airway smooth muscle and evaluated the role of prostanoids and airway epithelium in this relaxation. H. pomatia extract (0.001-1 mg/ml) induced a dose-dependent relaxation of guinea-pig trachea pre-contracted with histamine both in the presence and absence of tracheal epithelium. No significant difference in dose-dependency or magnitude of the relaxation was observed between tracheal segments with or without epithelium (maximal relaxant response of 35 +/- 7 and 25 +/- 7.5%, respectively). Relaxation of the trachea induced by H. pomatia extract (0.001-1 mg/ml) was inhibited by pre-treatment with the cyclooxygenase inhibitor, indomethacin, both in the presence or absence of tracheal epithelium. H. pomatia extract (1 mg/ml) induced a marked and significant increase in prostaglandin E2 release in tracheal segments with and without epithelium. These results indicate that helicidine possesses a broncho-relaxant activity which is independent of epithelium integrity and which is partly mediated by the release of the relaxant prostanoid, prostaglandin E2. The origin of prostaglandin E2 production in the airways remains to be defined.

Animals↗
PubMed1998

Increase in non-specific bronchial hyperresponsiveness without specific response to isocyanate in isocyanate-induced asthma: a pilot study.

Increased non-specific bronchial hyperresponsiveness (BHR) has been reported after positive reaction to isocyanates in patients with isocyanate-sensitive asthma. The increased responsiveness may, however, also precede the asthma attack. We therefore compared non-specific BHR to a cholinergic agent before and after exposure to toluene-diisocyanate (TDI) that induced no asthma symptoms in 11 workers with isocyanate-related asthma. Patients were exposed for 3 consecutive days to progressively increasing doses of TDI (5, 10, and 20 ppb min-1 for 20 min) in an exposure chamber with continuous TDI monitoring. No immediate nor late asthmatic bronchial reaction was observed in any patient after any dose of TDI during or after challenge. A significant increase in non-specific BHR was noted 24 h after the last dose of TDI challenge, however. This increase was at least one doubling dose for seven of 11 patients. In conclusion, our study shows that, in patients with isocyanate-induced asthma, exposure to TDI induces a slight but significant increase in non-specific BHR in the absence of any immediate or late bronchial response to isocyanate. This result, which requires further confirmation, may justify a proposal to measure non-specific BHR, even after a negative specific inhalation test to TDI, as an additional diagnostic element for TDI-induced occupational asthma, to help lower the percentage of the undetected occupational asthma cases.

Adult↗
PubMed1998

Consistency of the efficacy of cetirizine and ebastine on skin reactivity.

BACKGROUND: At therapeutic dosage, cetirizine and ebastine induce significant inhibition of skin reactivity to histamine. The consistency of their efficacy, that is, efficacy with the least interindividual variability among subjects, has not been carefully assessed, however. OBJECTIVE: To compare the consistency and efficacy of these antihistamines on skin reactivity. METHODS: Twenty-four healthy volunteers participated in a randomized double-blind crossover study. The areas of wheals and flares induced by increasing (0, 5, 10, 50, 100, 200, and 300 mg/mL) histamine concentrations, administered by prick tests, were measured before and four hours after intake of 10 mg of each antihistamine, allowing concentration-response curves to be established. The threshold histamine concentrations inducing wheal areas of 3 mm2 (positivity) were calculated by interpolation. The coefficient of variation (SD/mean %) was used to evaluate the consistency of the response. RESULTS: Pretreatment concentration-response curves were similar, and threshold concentrations identical (0.29 mg/mL and 0.34 mg/mL for cetirizine and ebastine, respectively). For both, curves were lower after treatment than before. After cetirizine, the threshold concentration was significantly higher (217 mg/mL) than after ebastine (0.82 mg/mL) (P < .001), and total inhibition of the wheal reaction was observed in 21 of 24 patients at the lowest histamine concentration and in 17 of 24 at the highest. Ebastine never totally inhibited reaction, even to 5 mg/mL of histamine. Over the entire concentration-response curve, the coefficient of variation for the wheal reaction was 6.3% for cetirizine and 72.6% for ebastine, and, for flares, 11.0% and 83.7%, respectively. Hence, variability was much lower after cetirizine. CONCLUSION: Our study shows clearly that the efficacy of a single therapeutic dosage of cetirizine is consistently good for suppression of cutaneous reactivity to histamine in healthy volunteers. The need for ebastine to metabolize into the active carebastine might explain its lesser consistency.

Adult↗
PubMed1998

Nasal effect of cetirizine and loratadine at 24 hours in patients with allergic rhinitis.

Numerous studies have compared the duration of the cutaneous effect of cetirizine and loratadine. We assessed their nasal effects 24 hours after administration in patients with allergic rhinitis, using a randomized, double-blind, crossover, placebo-controlled trial. Nasal challenge was performed by nebulization of increasing doubling dosages of histamine (0.04-1.28 mg/nostril) in 12 patients (seven males, five females, aged 31 +/- 7 years). Nasal airway resistance was measured by posterior rhinomanometry 24 hours after intake of cetirizine (10 mg), loratadine (10 mg), or placebo. Baseline nasal airway resistance was identical on all study days (2.86 +/- 0.10 cm H2 O/L per second). Twenty-four hours after intake, the dose-response curve of nasal obstruction to histamine was significantly lower after treatment with cetirizine compared with placebo (P < 0.05). However, although the curve was lower on loratadine than on placebo, the curves did not differ significantly. In conclusion, our study shows significant efficacy of cetirizine, but not of loratadine, in the nose at 24 hours after a single dose. This suggests that the nasal action of cetirizine is longer lasting than that of loratadine in patients with allergic rhinitis.

Adult↗
PubMed1998

Up- and down-regulation by glucocorticoids of the constitutive expression of the mast cell growth factor stem cell factor by human lung fibroblasts in culture.

Stem cell factor (SCF) is a major mast cell growth factor that promotes differentiation and chemotaxis of mast cells and inhibits their apoptosis. SCF therefore may be involved in diseases associated with an increased number of tissue mast cells such as asthma, for which the major treatment is glucocorticoids. In this study, we evaluated the effect of the glucocorticoid budesonide on the constitutive expression of SCF by human lung fibroblasts in primary culture. Budesonide (0.1 microM) induced a time-dependent biphasic effect on SCF mRNA and protein production. A short treatment (2.5-10 hr) induced an inhibition of SCF protein accumulation (-58% at 2.5 hr) and mRNA expression (-69% at 2.5 hr), associated with an accelerated decay of SCF mRNA and with a decrease in SCF gene transcription observed by nuclear run-on assay. Longer treatment (24-72 hr) led to increases in SCF protein accumulation (+64% at 48 hr) and mRNA expression (+125% at 24 hr) as a consequence of transcriptional activation. Similar effects of a decrease followed by an increase in SCF production were observed using another glucocorticoid, dexamethasone. Overall, our results show that glucocorticoids potently regulate SCF expression in human lung fibroblasts, successively decreasing and increasing SCF mRNA levels according to treatment duration. Such time-dependent modulation of SCF levels may explain some current discrepant findings about the effects of glucocorticoids on SCF production and may have functional consequences during glucocorticoid treatment, such as asthma therapy.

Budesonide↗