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Biomedical subjects

C Clerici

Publications and source records attributed to C Clerici.

At least 37 records · Page 2Linked to original sources
PubMed1997

A possible role for the cortisol/anticortisols imbalance in the progression of human immunodeficiency virus.

The progression of HIV infection is accompanied by complex alterations in the production of adrenal steroids. Cortisol levels are increased in HIV infection whereas those of dehydroepiandrosterone (DHEA), a physiologic antagonist of the immunoregulatory activities of cortisol, decrease. The progression of HIV infection to AIDS is also characterised by a shift from a type 1 to type 2 cytokine production. Thus, defective production of interferon gamma (IFN gamma), interleukin (IL)-2, and IL-12 as well as increased production of IL-4, IL-5, IL-6, and IL-10 are observed in HIV-seropositive individuals and are proposed to be in vitro immunologic marker of progression. Cortisol and pharmacological doses of glucocorticoids (GC) suppress IL-2 and IFN gamma production and favour the production of IL-4. Furthermore, GC and IL-4 stimulate the differentiation of B lymphocytes into IgE producing plasma cells, the concentration of which augments in HIV infection. Finally, GC induce programmed cell death (PCD) in a variety of different cells, including mature T lymphocytes, and type 2 cytokines were recently proposed to augment the susceptibility of T lymphocytes to PCD. It was suggested that the progressive shift from type 1 to type 2 cytokine production characteristic of HIV infection could be at least partially provoked by the increase in the production of cortisol and the reduction of DHEA. This hypothesis is discussed within the scenario of an endrocrinologic imbalance being responsible for HIV progression at least partially via increased susceptibility of HIV + CD4 lymphocyte to PCD.

Disease Progression↗
PubMed1997

Local and systemic effects of intraduodenal exposure to topical gallstone solvents ethyl propionate and methyl tert-butyl ether in the rabbit.

During topical dissolution of gallstones, solvent can escape to the duodenum causing toxic effects that have not yet been adequately quantified. We compared the local intestinal cytotoxic and systemic hepatotoxic effects of two gallstone solvents, methyl tert-butyl ether and ethyl propionate, on the rabbit's duodenum. Methyl tert-butyl ether, ethyl propionate, or saline (control) was infused intraduodenally for 3 hr in 32 male New Zealand rabbits. The solvents were infused either at a high infusion rate of 8.5 microl/min or at a low rate of 4.0 microl/min. Blood samples were collected for biochemical analysis from each animal before and after the 3-hr infusion period. A standardized histologic scoring system was used by a pathologist blinded to the treatments to quantify liver and intestinal tissue injury. None of the animals studied showed any significant changes in serum alkaline phosphatase, amylase, bilirubin, or their hepatic histology or histologic scoring for mucosal necrosis and ulceration. At the higher dose, methyl tert-butyl ether produced significantly more submucosal inflammation (P = 0.0017) and showed a trend of causing more submucosal edema than ethyl propionate, but ethyl propionate led to significantly higher elevations of aminotransferases than methyl tert-butyl ether as compared to saline. There were no detectable blood levels of methanol or ethanol in any of the animals studied. Ethyl propionate may be less damaging to the intestinal mucosa of the rabbit than methyl tert-butyl ether, but at the higher dose (equivalent to 60 ml/3 hr in a 70-kg human) it appears to produce more biochemical liver injury when administered intraduodenally.

Administration, Topical↗
PubMed1997

Alveolar epithelial cells in vitro produce gelatinases and tissue inhibitor of matrix metalloproteinase-2.

Type II pneumocytes are key cells of the alveolar epithelium. They lie on the alveolar basement membrane, which influences their phenotype and functions. We hypothesized that type II pneumocytes degrade basement membrane components by producing gelatinases, members of the matrix metalloproteinase family. To investigate this hypothesis, we used primary cultures of rat type II pneumocytes and cultures of the human A549 cell line. We found by zymography that 70-kDa gelatinase was present in media conditioned by these cells. This 70-kDa gelatinase was identified as gelatinase A by a Western blot, and the presence of its mRNA was demonstrated by reverse transcription-polymerase chain reaction. A 95-kDa gelatinase could be induced under certain conditions. Production of gelatinases may take place during the turnover of basement membranes, in physiological and in pathophysiological processes. This was suggested by the increase in production of both gelatinases that we observed after in vitro exposure to LPS or interleukin-1. The presence of tissue inhibitors of matrix metalloproteinase-1 and -2 was also demonstrated, suggesting that degradation of extracellular matrix by type II pneumocytes is tightly regulated.

Animals↗
PubMed1997

Hypoxia downregulates expression and activity of epithelial sodium channels in rat alveolar epithelial cells.

Decrease in alveolar oxygen tension may induce acute lung injury with pulmonary edema. We investigated whether, in alveolar epithelial cells, expression and activity of epithelial sodium (Na) channels and Na,K-adenosine triphosphatase, the major components of transepithelial Na transport, were regulated by hypoxia. Exposure of cultured rat alveolar cells to 3% and 0% O2 for 18 h reduced Na channel activity estimated by amiloride-sensitive 22Na influx by 32% and 67%, respectively, whereas 5% O2 was without effect. The decrease in Na channel activity induced by 0% O2 was time-dependent, significant at 3 h of exposure and maximal at 12 and 18 h. It was associated with a time-dependent decline in the amount of mRNAs encoding the alpha-, beta-, and gamma-subunits of the rat epithelial Na channel (rENaC) and with a 42% decrease in alpha-rENaC protein synthesis as evaluated by immunoprecipitation after 18 h of exposure. The 0% O2 hypoxia also caused a time-dependent decrease in (1) ouabain-sensitive 86Rubidium influx in intact cells, (2) the maximal velocity of Na,K-ATPase on crude homogenates, and (3) alpha1- and beta1-Na,K-ATPase mRNA levels. Levels of rENaC and alpha1-Na,K-ATPase mRNA returned to control values within 48 h of reoxygenation, and this was associated with complete functional recovery. We conclude that hypoxia induced a downregulation of expression and activity of epithelial Na channels and Na,K-ATPase in alveolar cells. Subsequent decrease in Na reabsorption by alveolar epithelium could participate in the maintenance of hypoxia-induced alveolar edema.

Animals↗
PubMed1997

Interferon plus ursodeoxycholic acid versus interferon in the treatment of chronic C viral hepatitis.

BACKGROUND: The aim of as study was to ascertain whether the association of interferon alpha-2a and ursodeoxycholic acid (IFN+UDCA) was more efficacious in ameliorating liver parameters than interferon (IFN) alone in patients with chronic hepatitis C. METHODS: Forty-one chronic hepatitis C patients, who had at least twice the normal value of one transaminase, were randomly assigned to treatment with IFN + UDCA (n = 21) or IFN alone (n = 20). IFN was administered subcutaneously at a dose of 3 MU thrice weekly, UDCA orally at 10 mg/kg bw/day. IFN therapy was terminated 6 months later and the responders (normalized transaminases) of both groups were treated with UDCA alone for a further 12 months. RESULTS: In the IFN + UDCA group there were 2 drop-outs from therapy and 11 responders, while in the IFN group they were, respectively, 3 and 10. Transaminases normalized after the first month of treatment in 7/11 responders with IFN + UDCA compared with 3/10 in the IFN responders group. The trend to normalization was more rapid with IFN + UDCA than with IFN alone (chi 2t = 3.95; p < 0.05). Disease relapse (defined as at least one transaminase > x 1.5 the normal value) was 3/11 in the IFN + UDCA group and 4/10 in the IFN group. 2/11 responders in the IFN + UDCA and 1/10 in the IFN group were HCV RNA negative by PCR. The total Knodell histological score decreased more in the IFN+UDCA than in the IFN group (-2.67 +/- 3.44. vs -1.67 +/- 2.16, mean +/- SD). CONCLUSIONS: The administration of UDCA determine an earlier normalization-time of transaminases in the patients responders to IFN therapy and could be useful to reduce the relapse into disease after the IFN therapy.

Adolescent↗
PubMed1996

Rat lung alveolar type II cell line maintains sodium transport characteristics of primary culture.

Culture of primary alveolar type II cells has been widely used to investigate the Na+ transport characteristics of alveolar epithelium. However, this model was restricted by early morphological and physiological dedifferentiation in culture. Recently, a cell line has been obtained by transfection of neonatal type II cells with the simian virus SV40 large T antigen gene (SV40-T2). SV40-T2 cells have retained proliferative characteristics of the primary type II cells (Clement et al., 1991, Exp. Cell Res., 196:198-205.) In the present study, we have characterized Na+ transport pathways in SV40-T2 cells. SV40-T2 cells retained most cardinal properties of the original alveolar epithelial cells. Na+ entry occurred, as in primary cultures, through both Na(+)-cotransporters and amiloride-sensitive Na+ channels. SV40-T2 cells expressed Na(+)-phosphate. Na(+)-amino acid and Na(+)-K(+)-Cl cotransports which are quantitatively similar to that of primary cultures. The existence of amiloride-sensitive Na+ channels was supported by molecular and functional data. SV40-T2 expressed the cloned alpha- and gamma-mRNAs for the rat epithelial Na+ channel (rENaC), whereas beta subunit was not detected, and 22Na+ influx was significantly inhibited by 10 microM amiloride. Na+, which enters SV40-T2 cells, is extruded through a Na+, K(+)-ATPase: mRNA for alpha 1 and beta 1 isoforms of Na+, K(+)-ATPase were present and Na+, K(+)-ATPase activity was evidenced either on intact cells by the presence of a ouabain-sensitive component of 86Rb+ influx or on cell homogenates by the measurement of ouabain-inhibitable ATP hydrolysis. These results indicate that SV40-T2 cell line displays most of the Na+ transport characteristics of well-differentiated primary cells in the first days of culture. We conclude that the SV40-T2 cell line provides a model of differentiated alveolar type II cells and may be a powerful tool to study, in vitro, the modulation of Na+ transport in pathophysiological conditions.

Amiloride↗
PubMed1996

Inhibition of Na-K-ATPase activity after prolonged hypoxia in an alveolar epithelial cell line.

Exposure to alveolar hypoxia may induce acute pulmonary edema. Because the vectorial sodium transport by alveolar epithelium represents an important mechanism for alveolar edema clearance, we examined whether hypoxia affects Na-K-ATPase activity in cultured SV40-transformed rat alveolar type II cells (SV40 ATII cells). Hypoxic exposures (O or 5% O2 for at least 12 h) induced a time- and O2 concentration-dependent decrease in ouabain-sensitive rubidium (osRb) influx. Neither the sensitivity of Rb influx to ouabain nor the maximum velocity of the enzyme measured on crude cell homogenates was affected by hypoxia. The osRb influx decrease was independent of hypoxia-induced ATP depletion. Na-K-ATPase inhibition was most likely related to impaired calcium homeostasis, because 1) calcium influx was increased in hypoxic cells, 2) hypoxia-induced osRb influx decrease was completely prevented by nifedipine (10-5 M), and 3) osRb influx decreased in normoxic cells incubated with ionomycin (10-6 M, 15 min). Furthermore, hypoxia-induced Na-K-ATPase impairment might be due, at least in part, to the endogenous release by hypoxic cells of a lipidic factor in extracellular medium, because incubation of normoxic cells with hypoxic cells conditioned medium (CM), or with the lipidic subphase from hypoxic cells CM, also induced a partial decrease in osRb influx. This decrease was associated with increased calcium influx into normoxic cells and was suppressed either by the removal of external calcium or by nifedipine, suggesting that the lipidic factor exerted its inhibitory action on Na-K-ATPase via an enhancement of calcium entry. These results indicate that prolonged hypoxic exposure impairs Na-K-ATPase activity in SV40 ATII cells and may therefore decrease the vectorial sodium transport by alveolar epithelium.

Adenosine Triphosphate↗
PubMed1996

Effect of ursodeoxycholic acid on hypertransaminasaemia and bile acid composition in patients undergoing bone marrow transplantation--a double-blind randomized control study.

A double-blind randomized placebo controlled trial of ursodeoxycholic acid was performed in 31 patients undergoing T-cell depleted allogeneic or autologous bone marrow transplantation to determine the effectiveness of this hydrophilic bile acid in improving the increase in serum liver enzymes that generally accompanies this procedure. Neither group showed any significant difference in magnitude of the increases in serum transaminases and gamma-glutamyltranspeptidase following the conditioning regimen that included chemotherapy and total body irradiation. In the 6 months after transplantation, serum enzymes decreased in both groups, but were consistently higher in the placebo treated patients, indicating that ursodeoxycholic enhances normalization of liver. Faecal bile acid showed that following chemotherapy and irradiation in which intestinal bacteria are ablated, secondary bile acid formation was practically abolished and faeces contained mainly cholic and chenodeoxycholic acids. During bile acid treatment, ursodeoxycholic acid accounted for 31.3 +/- 10.9% of faecal bile acids compared with 4.0 +/- 2.1% in the basal period. Serum and urinary ursodeoxycholic acid concentrations (mean +/- SD, 13.3 +/- 6.9 mumol/L and 2.65 +/- 0.84 mumol/L, respectively) were significantly higher in patients receiving bile acid than in thos on placebo (mean +/- SD, 0.15 +/- 0.12 mumol/L and 0.29 +/- 0.35 mumol/L, respectively) thus confirming compliance.

Administration, Oral↗
PubMed1995

Lipopolysaccharides stimulate Na-dependent transport in alveolar cells and protect against oxidant injury.

We have evaluated the effect of lipopolysaccharides (LPS), endotoxins from gram negative bacteria, on sodium-coupled amino acid and phosphate transport by alveolar epithelial type II cells and on their alteration induced by oxidants. Alveolar type II cells were obtained by enzymatic digestion of rat lung and grown for 24 h prior to incubation with LPS and then exposed or not exposed to H2O2 (2.5 mM; 20 min). LPS (10 micrograms/ml, 24 h) induced a significant increase in the Na-dependent component of alanine and phosphate uptake while they decreased Na,K-ATPase activity measured by ouabain-sensitive 86Rb influx. We showed that this stimulatory effect i) was independent from macrophage products since it was not mimicked either by supernatant of LPS-treated alveolar macrophages or by pretreatment with tumor necrosis factor and/or interleukin 1 and ii) was dependent on protein synthesis since it was abolished by protein synthesis inhibitors cycloheximide and actinomycin D. Moreover, LPS blunted H2O2-induced decrease of Na-dependent alanine and phosphate uptake. This protective effect of LPS against H2O2 injury i) was independent of macrophage products, ii) was abolished by cycloheximide, and iii) was not associated with either changes in extracellular H2O2 clearance or catalase and glutathione peroxidase activities. We conclude that, in alveolar type II cells, LPS stimulate sodium-coupled transport by a process involving protein synthesis and partially prevent H2O2-induced decrease of Na-coupled transport without discernible change in antioxidant activities.

Alanine↗
PubMed1995

Evidence for Na-K-Cl cotransport in alveolar epithelial cells: effect of phorbol ester and osmotic stress.

We have investigated the presence of Na-K-Cl cotransport in alveolar type II cells using uptake of 86Rb. Several data support the presence of a Na-K-Cl cotransport in these cells. First, a large fraction of ouabain-resistant 86Rb uptake was inhibited by bumetanide and furosemide. Second, bumetanide-sensitive 86Rb uptake required the presence of Na+ and Cl- in the incubation medium; dependency on extracellular Na+ and K+ was hyperbolic, with a Km of 14.6 mM and 8.3 mM, respectively, while dependency on extracellular Cl- was sigmoidal, which suggests a 1:1:2 stoichiometry. Third, a fraction of amiloride-insensitive 22Na influx was deeply inhibited by bumetanide. 22Na influx was dependent on the presence of extracellular K+ and Cl-. Since Na-K-Cl activity dramatically decreased with time in culture, further characterization of the cotransport on polarized cells could not be performed. The phorbol ester PMA inhibited Na-K-Cl cotransport in a time- and concentration-dependent manner. This inhibition was mimicked by oleoylacetylglycerol, dioctanoylglycerol, and the diacylglycerol kinase inhibitor R59022, and was reversed by an antagonist of PKC, staurosporine. Since the Na-K-Cl cotransport has been reported to be involved in cell volume regulation, we investigated its modulation by changes in extracellular osmolarity. Na-K-Cl activity was increased after a two-step procedure: swelling in hypotonic medium followed by shrinking in hypertonic medium. Under these conditions, cotransport activity increased whenever PKC activity was up- or downregulated, which suggests that the cell volume-induced modulation of the cotransport is independent from the PKC activity. Though we were not able to determine the polarity of the cotransport, it may also be involved in the absorptive function of alveolar type II cells, and would provide an alternate pathway for sodium entry.

Animals↗
PubMed1995

Cognitive event-related potential in hepatic encephalopathy.

A study of auditory P300 was performed on 24 patients with cirrhosis of the liver: 13 patients with hepatic encephalopathy (HE grade 1-2) and 11 patients without clinical encephalopathy (HE grade 0). The patients were also assessed using spontaneous EEG and neuropsychological methods: Mini Mental State, Digit Span and Number Connection Test. The P3 latency was found to be significantly increased in all patients (100%) with HE grade 1-2 and in 6 patients (54.5%) with HE grade 0. The clinical value of using the P300 latency in the hepatic encephalopathy is subsequently discussed.

Aged↗
PubMed1995

Oxygen metabolites modulate sodium transport in gerbil middle ear epithelium: involvement of PGE2.

The middle ear epithelium and respiratory epithelia share basic properties such as homeostasis of air-filled cavities and mucociliary clearance toward the pharynx. With the middle ear SV40-transformed (MESV) cell line, we used the short-circuit current (Isc) technique to investigate changes in ion transport induced by oxidants. Xanthine and xanthine oxidase on the basal side of the monolayers dramatically increased Isc up to 50%. This effect was not affected by superoxide dismutase or mannitol, but could be blunted by catalase or 1,3-dimethyl-2-thiourea. Increasing concentrations of H2O2 from 10(-5) to 5 x 10(-4) M produced a dose-dependent increase in Isc from 0.26 +/- 0.16 up to 4.21 +/- 0.43 microA/cm2 (P < 0.05, n = 5). Concentration of half-maximal stimulation (EC50) was 4.68 x 10(-5) M. This effect was inhibited by indomethacin and was related to a sodium transport, since the H2O2-induced increase in Isc could be prevented or abolished by 1) apical addition of benzamil (10(-6)M) and 2) substitution of sodium with N-methyl-glucamine. H2O2 exposure also induced indomethacin-sensitive increase in released prostaglandin (PG) E2 (EC50 = 5.62 x 10(-5) M) and in cAMP content (EC50 = 3.95 x 10(-5) M) with similar kinetics. These results suggest that exposure of MESV cells to oxidants stimulates the production of PGE2, which in turn increases the transepithelial sodium transport rate.

Animals↗
PubMed1994

Amino acid derivatives of 5-ASA as novel prodrugs for intestinal drug delivery.

In an attempt to obtain site-specific delivery of 5-ASA in the intestinal tract, we have determined the extent of absorption and metabolism of a number of novel 5-ASA derivatives, namely, (N-L-glutamyl)-amino-2-salicylic acid (1), (N-L-aspartyl)-amino-2-salicylic-acid (2), 5-aminosalicyl-L-proline-L-leucine (3), and 5-(N-L-glutamyl)-aminosalicyl-L-proline-L-leucine (4), which are selectively cleaved by intestinal brush border aminopeptidase A and carboxypeptidases. These novel prodrugs, 5-ASA, and sulfasalazine were administered to adult Fisher rats (N = 30) and to animals that had undergone prior colostomy (N = 30). Urine and feces were collected at timed intervals for 48 hr and the metabolites, 5-ASA, and N-acetyl-5-ASA were measured by high-performance liquid chromatography. The absorption and metabolism of all compounds were essentially identical in colostomized and normal animals. 5-ASA exhibited a rapid proximal intestinal absorption as evidenced by the high cumulative urinary excretion (> 65%) and low fecal excretion. Sulfasalazine, as expected, exhibited a lower urinary recovery (< 35%) and higher fecal excretion of 5-ASA and its metabolite. The novel glutamate and aspartate derivatives (1 and 2) behaved similarly to sulfasalazine, while administration of the proline-leucine derivative (3) resulted in urinary and fecal recovery values intermediate with respect to those observed with 5-ASA and sulfasalazine. 5-(N-L-Glutamyl)-aminosalicyl-L-proline-L-leucine yielded the highest fecal recovery of 5-ASA and its N-acetyl derivative, indicating a more efficient delivery to the distal bowel. Amino acid derivatives of 5-ASA appear to be potentially useful prodrugs for the site-specific delivery of 5-ASA to different regions of the intestinal tract.

Aminopeptidases↗
PubMed1993

Brush-border-enzyme-mediated intestine-specific drug delivery. Amino acid prodrugs of 5-aminosalicylic acid.

5-Aminosalicylic acid (5-ASA) is the active principle of a number of preparations aimed at the treatment of inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis, but its efficacy is limited by early absorption and metabolism. The possibility to exploit the selective hydrolytic activity of brush border enzymes such as aminopeptidase A and carboxypeptidases was studied by preparing the following four amino acid prodrugs of 5-ASA: 5-(N-L-aspartylamino)-2-salicylic acid, disodium salt (18), 5-(N-L-glutamylamino)-2-salicylic acid, disodium salt (19), [(5-aminosalicyl)-L-prolyl]-L-leucine, sodium salt (25), and [[5-(N-L-glutamylamino)salicyl]-L-prolyl]-L-leucine, disodium salt (28). In these compounds, the peptide bond is selectively split by the intestinal brush border aminopeptidase A (compounds 18, 19, and 28) and carboxypeptidases (compounds 25 and 28).

Amino Acids↗
PubMed1992

Effect of intraduodenal administration of 23-methyl-UDCA diastereoisomers on bile flow in hamsters.

3 alpha,7 beta-Dihydroxy-23-methyl-5 beta-cholan-24-oic acid (MUDCA) and its two diastereoisomers, alpha- and beta-MUDCA, were infused intraduodenally in biliary fistula hamsters in order to evaluate the effect on bile flow and their hepatic biotransformation processes compared with the natural analog ursodeoxycholic acid (UDCA). In addition, the corresponding glycine conjugates were compared. The bile acids were administered at different doses (0.7-6 mumol/min/kg) over periods of 90 min. The results indicate that the racemic mixture exhibits a potent choleretic effect at both low and high doses, while the two individual diastereoisomers show this effect only at high doses. The presence of a C-23 methyl group in the side chain prevents hepatic amidation and alternative conjugations occur, such as glucuronidation, in order to facilitate their biliary secretion. Biotransformation of the methyl derivatives of UDCA occurred mainly by conversion to more polar glucuronide conjugates. There was little alteration to the molecule and, unlike UDCA, very little amidation occurred. These data indicate that the presence of a C-23 methyl group prevents the usual side-chain amidation common to the most naturally occurring bile acids and that glucuronidation is a requisite for efficient biliary excretion.

Acute Disease↗
PubMed1992

Impairment of sodium-coupled uptakes by hydrogen peroxide in alveolar type II cells: protective effect of d-alpha-tocopherol.

Hydrogen peroxide (H2O2) is likely to play an important role in oxidant alveolar epithelium injury. We investigated the effect of H2O2 on uptake of phosphate, alanine in cultured rat alveolar type II cells. H2O2 induced inhibition of Na-dependent component of phosphate and alanine uptakes in time- and concentration-dependent manner. Twenty minutes exposure to 2.5 mM H2O2 decreased the maximum velocity (Vmax) of phosphate and alanine uptake by 50 and 62%, respectively, whereas Michaelis constant (Km) values were unchanged. H2O2 also decreased Na-K-ATPase activity, measured by ouabain-sensitive rubidium influx, and this effect was independent of H2O2-induced ATP depletion. A lipid-soluble antioxidant, d-alpha-tocopherol (20 microM, 24 h), prevented H2O2-induced decrease in Na-coupled uptake and Na-K-ATPase activity. These results indicate that H2O2 affects Na-dependent phosphate and alanine uptakes and suggest that this effect may be related at least, in part, to a decrease in Na transmembrane gradient, since H2O2 also affects Na-K-ATPase activity. The protective effect of d-alpha-tocopherol suggests that peroxidation of the membrane lipids is likely to be involved in the observed effects.

Adenosine Triphosphate↗
PubMed1992

Different effects of nasal and bronchial glucocorticosteroid administration on bronchial hyperresponsiveness in patients with allergic rhinitis.

Disorders of the upper respiratory tract, particularly allergic rhinitis, are commonly associated with bronchial hyperresponsiveness. The latter may be due to postnasal drip or to mediator or chemotactic factors into the lower airways that either directly alter airway reactivity or cause airway inflammation. The aim of this study was to compare the effect of an identical dose of nasal or bronchial corticosteroid administration on bronchial hyperresponsiveness in patients with allergic rhinitis. Eleven patients were studied. All of them were judged atopic on the basis of positive skin tests to common allergens. During control, spirometry, flow-volume curves, and specific airway conductance (SGaw) were measured. Bronchial challenges were then performed with increasing concentrations of carbachol, and dose-response curves were constructed. The concentration of carbachol that decreased SGaw by 35% from baseline (PD35) was determined by interpolating from the dose-response curve. Control measurements were repeated at 1-wk intervals to ensure that PD35 was stable in all the patients. Then the patients received for 2 wk, in a double-blind randomized crossover fashion, a topical administration of either an aerosol of 400 micrograms of beclamethasone dipropionate (B) into the nose (100 micrograms four times per day) or into the bronchi. During each trial period, identical sprays of placebo were used, the latter being administered into the nose when B was administered into the bronchi and vice versa. Measurements were then performed after 2 wk of intranasal administration and after 2 wk of intrabronchial administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗