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Biomedical subjects

L Allegra

Publications and source records attributed to L Allegra.

At least 91 records · Page 5Linked to original sources
PubMed1992

Blood gas changes in nonasthmatic rhinitis during and after nonspecific airway challenge.

Noninvasive blood gas monitoring is a new, simple, and reliable method for assessing hyperreactivity associated with bronchial asthma. In this study, 104 atopic rhinitic subjects with no history of wheezing and 104 healthy volunteers were challenged with ultrasonically nebulized distilled water (UNDW). Blood gases were monitored transcutaneously (PtcO2 and PtcCO2) over 42 min (20 min for electrode stabilization, 3 min for monitoring a steady baseline, 5 min during UNDW, and 14 min after UNDW). Mean baseline PtcO2 and PtcCO2 values were comparable in the two groups. In rhinitic subjects only, a sudden decrease in PtcCO2 (starting immediately after the beginning of the challenge and maximal 34.7 +/- 0.4 mm Hg SEM versus baseline 41.8 +/- 0.2 SEM mm Hg at the third minute of UNDW exposure) was induced by the challenge and proved significant (p less than 0.001). In the same subjects, a slightly delayed decrease in PtcO2 (starting immediately after the end of UNDW inhalation and maximal 64.5 +/- 1.1 mm Hg SEM versus baseline 78.3 +/- 0.7 SEM mm Hg at 4 min post-UNDW) was also induced by the challenge and proved highly significant (p less than 0.001). The effects of UNDW inhalation on blood gases in normal subjects were negligible and nonsignificant. UNDW in nonasthmatic rhinitis but not in normal subjects gives rise to a sudden hyperventilation and to gas-exchange abnormalities presumably reflecting a ventilation-perfusion mismatching, which, however, is of shorter duration in rhinitic than in asthmatic subjects.

Adult↗
PubMed1992

Effects of salbutamol and bitolterol mesilate on pO2 levels in asthmatic patients and healthy volunteers.

The hypoxic effects of salbutamol 200 micrograms (CAS 18559-94-9) and bitolterol mesilate 740 micrograms (Biterol, CAS 30392-41-7), both administered by pressurized aerosol, were assessed by transcutaneous pO2 monitoring in 18 asthmatic subjects and in 12 normal volunteers. Unlike the latter, the asthmatics showed a highly significant difference in ptcO2 time course after the two drugs. After bitolterol mesylate the decrease in ptcO2 was much more gradual and the maximal decrease showed a 10-min time lag vs. salbutamol, which may partly explain the well known chronotropic effect of bitolterol. The clinical importance of the beta 2-induced hypoxemia may be related more to the dynamics of the ptcO2 decrease than to its absolute magnitude, which is usually fairly moderate.

Adult↗
PubMed1992

The influence of seaprose on erythromycin penetration into bronchial mucus in bronchopulmonary infections.

In bronchopulmonary infections antibiotics can be combined with other drugs, called mucoactive drugs, that act to reduce the abnormal viscoelasticity of the mucus enabling a deeper penetration of more antibiotic into the mucus. Seaprose is a protease that interacts with the polymeric fibrillar structure of the bronchial mucus to shorten the long chains of mucoproteins, DNA and other macromolecules, thus reducing the viscosity of the mucus. In order to assess whether the combination of seaprose (60 mg/8 h) plus erythromycin (500 mg/8 h) allows higher antibiotic levels in sputum than erythromycin (500 mg/8 h) plus placebo, the pharmacokinetic behaviour in sputum and in blood of these two treatments was investigated in a double-blind study in two groups of twenty patients each with bronchopulmonary infections. Serum and sputum levels were determined for each patient at the first and seventh day of the two drug regimens. Statistically significant differences for peak, AUC and MRT, were observed for erythromycin between the first and last dose in the group of patients treated with seaprose plus erythromycin; moreover significant differences for these parameters were observed between the two groups. These findings indicate the presence of a pharmacokinetic synergism between seaprose and erythromycin which allows erythromycin to penetrate bronchial secretion more easily and in higher amounts, performing a sterilizing action with therapeutic advantages.

Bronchial Diseases↗
PubMed1992

Thymomodulin increases release of granulocyte-macrophage colony stimulating factor and of tumour necrosis factor in vitro.

To evaluate the effects of thymomodulin (TMD), a thymic biological response modifier derived from calf thymus, on the release of various cytokines involved in the lung immune reactions, human alveolar macrophages (AM) and peripheral blood lymphocytes (PBL) were cultured either alone or in co-cultures. In co-cultures of AM with PBL, TMD did not induce any change in gamma-interferon (gamma-IFN) and interleukin-1 (IL-1) secretion, while it was able to increase the level, of tumour necrosis factor (TNF) (TMD 100 micrograms.m-1, p < 0.05 vs control cultures), and of granulocyte macrophage colony-stimulating factor (GM-CSF) (TMD 1, 10 and 100 micrograms.ml-1 p < 0.05, < 0.05 and < 0.01, respectively, vs control cultures). In cultures of AM alone, TMD did not induce changes in the levels of any of the tested cytokines, whilst in supernatants from PBL lymphocyte cultures, TMD at 1, 10 and 100 micrograms.ml-1 increased the amounts of GM-CSF (p < 0.01 each comparison vs control cultures). Thus, TMD seems to directly stimulate lymphocytes to secrete GM-CSF and to modulate macrophage-lymphocyte interactions, resulting in the release of TNF and GM-CSF.

Adult↗
PubMed1991

Ozone-induced impairment of mucociliary transport and its prevention with N-acetylcysteine.

The effects of an oxidizing gaseous pollutant on tracheal mucous velocity have been studied in conscious sheep. Acute (2 hours) exposure to 1.0 ppm of ozone showed an effect on tracheal mucous velocity that resulted in a significant decrease 40 minutes and 2 hours after exposure (35% and 40% of the baseline, respectively). Repeated exposure for longer periods (4 days, 5 hours/day) to 1.0 ppm of ozone also significantly decreased tracheal mucous velocity during the first and the second day (-47% and -70% of the baseline, respectively), but during the following days of exposure adaptation took place (tracheal mucous velocity ranging from -42% to -55% of baseline). The tracheal mucous velocity still significantly decreased 5 days after the last exposure. N-Acetylcysteine, known both for its mucolytic and antioxidizing properties, has been demonstrated to prevent significantly all of the immediate effects of either short-term or long-term ozone exposures on mucociliary functions.

Acetylcysteine↗
PubMed1991

Cellular and biochemical characteristics of bronchoalveolar lavage fluid in symptomatic nonallergic asthma.

We have undertaken cellular and biochemical examination of bronchoalveolar lavage fluid from nonallergic patients with asthma to determine the nature and degree of inflammatory process in symptomatic asthma. Six patients with asthma (mean methacholine provocative concentration causing a 20% fall in FEV1 was 0.26 mg/ml) and six control subjects underwent fiberoptic bronchoscopy with bronchoalveolar wash. The patients with asthma shed a higher number of epithelial cells into lavage fluid than normal control subjects (p less than 0.05). Their lavage fluid also contained increased numbers of neutrophils (p less than 0.025), eosinophils (p less than 0.025), and basophilic cells (p less than 0.025), and increased proportion of activated T cells (p less than 0.05). The basophilic cells were mast cells, as indicated by positive labeling with the monoclonal antibody MCG35. Biochemical analysis of lavage fluid demonstrated exudation of protein molecules in airways of patients with asthma with increased contents of albumin (p less than 0.05) and fibronectin (p less than 0.05). In the lavage fluid of patients with asthma, there were also increased amounts of interleukin-1-beta (IL-1-beta) (p less than 0.025), interleukin-6 (IL-6) (p less than 0.025), and granulocyte-macrophage, colony-stimulating factor (GM-CSF) (p less than 0.05), as compared with lavage fluid of normal control subjects. Immunocytochemical evaluation of lavage cells demonstrated that IL-1-beta, IL-6, and GM-CSF were mostly produced by nonciliated epithelial cells and/or monocytes. IL-1, IL-6, and GM-CSF can prime granulocytes to respond to other stimuli and can promote T cell activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Eicosanoid release from human bronchial epithelial cells upon exposure to toluene diisocyanate in vitro.

Epithelial injury and inflammation are involved in airway hyperresponsiveness and asthma induced by toluene diisocyanate. In that isocyanates are insoluble and highly reactive compounds, bronchial epithelial cells may represent the most important target cells of their toxic effect. We hypothesized that damage to airway epithelium by toluene diisocyanate may result in the release of metabolites of arachidonic acid, which are known to promote inflammation and to alter epithelial cell function and airway smooth muscle responsiveness. To test this hypothesis we examined eicosanoid products in the culture media of bronchial epithelial cells exposed in vitro to 8 and 18 ppb toluene diisocyanate. Epithelial cells derived from human bronchi obtained at surgery were cultured to confluency on collagen-coated microporous membranes. Those cells, which expressed differentiated characteristics of epithelial cells (they showed keratin-containing filaments and had a cobblestone appearance), were alternatively exposed to toluene diisocyanate or air for 30 min in a specially designed in vitro chamber. The production of metabolites of arachidonic acid was assessed by measuring the release of immunoreactive products into the cell medium at the end of the exposure and during a 2 hr period after exposure. This method revealed a predominant isocyanate-induced release of immunoreactive 15-hydroxyeicosatetraenoic acid. Release rate of this compound tended to be dose-related and was associated with cell damage as assessed by the release of lactate dehydrogenase in the medium.

Arachidonic Acid↗
PubMed1990

Bronchial epithelial cells exposed to isocyanates potentiate activation and proliferation of T-cells.

Bronchial epithelial cells release chemotactic factors for lymphocytes and express HLA-DR antigens. Thus they may contribute to the T-cell-mediated inflammatory responses involved in a number of pulmonary diseases such as asthma. In this study, the in vitro exposure of human bronchial epithelial cells to toluene 2,4-diisocyanate (TDI), an inflammatory and asthmogenic stimulus presumed to act at least in part through immunological mechanisms, provoked cell damage followed by proliferation of the cells that survived the injury. At the time of the proliferative response, epithelial cells released factors that upregulated the activation and proliferation of T lymphocytes presensitized by antigen receptor triggering. The T-cell activating factors were interleukin (IL) 1- and 6-like substances, as demonstrated by the ability of specific antisera to inhibit most of the biological effect, and by the ability of recombinant IL-1 and IL-6 to reproduce it. Appreciable amounts of immunoreactive IL-1 and IL-6 were indeed recovered in the supernatants of TDI-exposed epithelial cells. The release of these cytokines may represent an important mechanism by which epithelial cells respond to some environmental stimuli and contribute to the persistence of inflammatory responses in the airways.

Alkaline Phosphatase↗
PubMed1990

Long-lasting effects on rheology and clearance of bronchial mucus after short-term administration of high doses of carbocysteine-lysine to patients with chronic bronchitis.

The rheological behavior and clearance of bronchial mucus samples collected by protected expectoration from 24 out-patients with simple chronic bronchitis were investigated before, at the end of a short period of treatment (4 days) with a single oral dose of 2.7 g (sachet) of carbocysteine-lysine (evening meal), and on the 4th and 8th days after the end of treatment versus placebo. In the group treated with carbocysteine-lysine, there were significant reductions in viscosity (-67, -48, -62%) and increases in mucociliary transport (+41, +31, +34%) at the three times mentioned. The most striking finding was that the improvements were still present 8 days after cessation of treatment. The elasticity parameter was not affected in any statistically significant way (-10, -24, +65%). These findings suggest the presence of some type of 'post-mucoactive' effect.

Adult↗
PubMed1990

Nedocromil sodium prevents the release of 15-hydroxyeicosatetraenoic acid from human bronchial epithelial cells exposed to toluene diisocyanate in vitro.

The in vivo exposure to an asthmogenic stimulus, toluene diisocyanate (TDI), causes airway epithelial damage associated with inflammation and increased bronchial hyperresponsiveness. The latter mechanisms might partly be mediated by the release of eicosanoids from bronchial epithelial cells. We have previously demonstrated that the in vitro exposure of bronchial epithelial cells to TDI results in the release of immunoreactive 15-hydroxyeicosatetraenoic acid (15-HETE), a product of activation of the 15-lipoxygenase pathway with inflammatory properties. In the present study we show that TDI-induced release of 15-HETE from epithelial cells can be prevented by nedocromil sodium, an anti-asthmatic drug with anti-inflammatory properties. This mode of action of the compound may explain its clinical effectiveness in asthma.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1990

Specific binding of endothelin on human bronchial smooth muscle cells in culture and secretion of endothelin-like material from bronchial epithelial cells.

Endothelin, synthesized by endothelial cells, is the most potent vasoconstrictor and bronchoconstrictor agent known. We investigated endothelin release from human bronchial epithelial cells and the binding of the peptide to autologous bronchial smooth muscle cells in culture. Epithelial and smooth muscle cells were isolated by enzymatic digestion of bronchial tissue obtained on surgery, and cultured to confluency by standard methods. Epithelial cells stained positively for cytokeratin filaments. Smooth muscle cells stained uniformly for alpha-smooth muscle actin. Immunoreactive endothelin contents in the supernatants of epithelial cells extracted on C8 Amprep columns were evaluated by radioimmunoassay. Epithelial cells released appreciable amounts of immunoreactive endothelin into the culture medium (from 0.65 to 2.1 pmol/ml). A single specific binding site for [125I]endothelin 1 was identified on bronchial smooth muscle cells with an apparent Kd of 113 pM and a maximal binding capacity of 22.1 fmol/10(6) cells. At room temperature the binding was saturable, reached equilibrium at 120 min (25 pM endothelin 1), and was slowly and incompletely reversed by unlabeled endothelin over a period of 8 h. Conditioned medium from epithelial cells inhibited the [125I]endothelin 1 binding, dose dependently, and the effect was antagonized by monospecific antiserum. Thus, human bronchial smooth muscle cells possess specific binding sites for endothelin 1 and human bronchial epithelial cells secrete an endothelin-like material. This may have a role in the pathogenesis of asthma.

Binding Sites↗
PubMed1990

Human ciliated bronchial epithelial cells: expression of the HLA-DR antigens and of the HLA-DR alpha gene, modulation of the HLA-DR antigens by gamma-interferon and antigen-presenting function in the mixed leukocyte reaction.

HLA-DR class II molecules are expressed by a variety of nonlymphoid cells, including the respiratory epithelium. However, it is not known if ciliated bronchial epithelial cells express the HLA-DR genes, if the expression of class II molecules on their surface can be modulated by immune mediators and, finally, if these cells, like other HLA-DR-positive epithelial cells, have the potential to serve as antigen-presenting cells. To answer these questions, we collected ciliated bronchial epithelial cells by brushing and by suction during fiberoptic bronchoscopy and by scraping surgically resected bronchi. The number of cells recovered by brushing or suction during fiberoptic bronchoscopy was similar (P greater than 0.2), but lower than that obtained by scraping surgically resected bronchi (P less than 0.01); however, compared with brushing, suction of ciliated bronchial epithelial cells resulted in a better viability (P less than 0.05). HLA-DR antigens on ciliated bronchial epithelial cells were detected by immunofluorescence using the PTF 29.12 and the L243 monoclonal antibodies, both recognizing HLA-DR molecules on the vast majority of ciliated bronchial epithelial cells. Cytoplasmic dot blot analysis demonstrated that ciliated bronchial epithelial cells had mRNA HLA-DR transcripts, and Northern blot hybridizations showed that the size of the HLA-DR messages was the same observed in other HLA-DR-positive cells. Interestingly, ciliated bronchial epithelial cells showed a significant decline of HLA-DR expression after 5 days in culture, but the addition of gamma-interferon to the cell cultures was associated with the persistence of the expression of class II antigens on the cell surface (P less than 0.01 with control cultures at 5 days). Finally, while ciliated bronchial epithelial cells were ineffective in stimulating allogeneic T cell proliferation in a 6-day primary mixed leukocyte reaction (MLR), the addition of phorbol myristate acetate to the MLR was able to induce a significant T cell proliferation (P less than 0.001, all comparisons). Thus, human ciliated bronchial epithelial cells express HLA-DR surface antigens and have mRNA molecules for the HLA-DR genes, and the expression of the surface class II antigens can be modulated in vitro by immune mediators.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1990

Topical tolerability of salmon calcitonin assessed by mucociliary transport velocity investigation.

The topical tolerability of an intranasal salmon calcitonin spray preparation, of the excipients alone and of sodium taurocholate has been studied by assessment of the mucociliary transport velocity (MTV) on the frog's palate. The rate of mucus transport was investigated in 3 groups of animals (Rana esculenta; 6 frogs per group) in basal conditions and after a challenge with a salmon calcitonin intranasal spray preparation, with the excipients and with sodium taurocholate, respectively. The salmon calcitonin intranasal spray preparation and the excipients did not affect the mucociliary transport velocity on the frog's palate. On the contrary, sodium taurocholate produced severe impairments in the mucociliary transport velocity and histological lesions of the epithelial layer of the frog's palate. The comparison among the mean values of the mucociliary transport velocity before and after treatments showed a significant difference between controls and sodium taurocholate groups (p less than 0.05) as well as among the groups treated with sodium taurocholate versus salmon calcitonin and versus the excipients alone of the calcitonin preparation (p less than 0.05). These findings provide evidence that the salmon calcitonin intranasal spray preparation tested in the present ex vivo model does not affect the mucociliary transport velocity in the frog's palate, while this is markedly affected by sodium taurocholate. The use of sodium taurocholate as a promoter of absorption in intranasal preparations should thus be reconsidered.

Administration, Topical↗
PubMed1989

Response to acetylcholine and myosin content of isolated canine airways.

Contractility of tracheal smooth muscle strips and spiral strips of fourth to fifth generation bronchi was studied in organ baths. The relationship among contractility, airway smooth muscle myosin, and smooth muscle thickness was also examined. The trachea was divided into three segments, each consisting of 12-14 rings. Smooth muscle strips from each of the three regions (top, middle, and bottom of the trachea) and from fourth to fifth generation bronchi were studied. Acetylcholine (ACh) sensitivity (-log EC50) was 8.1, 7.1, 7.9, and 6.1 for the top, middle, and bottom of the trachea and the bronchi, respectively. At P = 0.01, the EC50 ACh value of the top of the trachea differed from the EC50 value of the bronchi. Maximal tension (Tmax) generated in bronchi (3.2 g) was lower (P less than 0.01) than in the top (10.4 g), middle (7.1 g), and bottom of the trachea (5.1 g). Differences between trachea and bronchi disappeared when Tmax was corrected for smooth muscle myosin content. Thickness of smooth muscle in bronchi was less (P less than 0.01) than in the three regions of trachea. Tmax was significantly correlated with airway smooth muscle thickness (r = 0.56; P less than 0.05). These results suggest that in mongrel dogs sensitivity to ACh shows a gradient from the top of the trachea to the bronchi and that Tmax is greater in the trachea than in the bronchi and is significantly correlated with thickness of smooth muscle.

Acetylcholine↗
PubMed1989

Blood gas changes during and after nonspecific airway challenge in asthmatic and normal subjects.

Twenty-eight asymptomatic asthmatics and 28 healthy volunteers were challenged with ultrasonically nebulized distilled water (UNDW). Blood gas composition was monitored transcutaneously (PtCO2 and PtcCO2) over 42 min (20 min for electrode stability, 3 min base line, 5 min during UNDW, and 14 min after UNDW). Flow-volume curves were recorded before and 15 min after UNDW. Forced expiratory volume in 1 s and expiratory flows decreased in asthmatics but not in normal subjects after UNDW. Mean base-line PtCO2 and PtcCO2 were comparable in the two groups. UNDW in normal subjects produced no significant changes in mean PtcCO2 and PtCO2. In asthmatics, the UNDW-induced decrease in mean PtcCO2 was greater and longer lasting, accompanied by a prolonged decrease in mean PtCO2. PtcCO2 and PtCO2 trends showed highly significant differences compared with healthy volunteers (P less than 0.001). Arterial blood gas measurements validated these changes. UNDW in asymptomatic asthmatics gives rise to a greater and more prolonged hyperventilation than in normal subjects and to gas-exchange abnormalities presumably reflecting a ventilation-perfusion mismatching.

Adolescent↗
PubMed1989

Ambroxol inhibits airway hyperresponsiveness induced by ozone in dogs.

To follow up previous observations that airway hyperresponsiveness induced by ozone is linked to airway inflammation and particularly to the release of arachidonic acid metabolites, we investigated the effect of ambroxol (a mucoactive and surfactant-stimulating drug that has recently been discovered to inhibit the release of arachidonic acid from cell membrane phospholipids) on airway hyperresponsiveness and bronchoalveolar neutrophilia induced by ozone in dogs. One group of 5 dogs was studied before treatment with nebulized saline and then after exposure to ozone (3 ppm, 1 h); another group of 6 dogs was studied before treatment with ambroxol (100 breaths of a 1% solution) and after exposure to ozone. On each occasion, we measured airway responsiveness to acetylcholine and counted the number of cells in bronchoalveolar lavage fluid. When the dogs were given the saline placebo, ozone induced a marked increase in airway responsiveness to acetylcholine and a marked influx of neutrophils in the airways. When the dogs were given ambroxol, ozone induced the same increase in the number of neutrophils in bronchoalveolar lavage, but did not increase the degree of airway responsiveness to acetylcholine. We conclude that ambroxol inhibits ozone-induced airway hyperresponsiveness in dogs, probably by inhibiting the formation and release of oxygenation products of arachidonic acid from neutrophils.

Acetylcholine↗