Biomedical subjects

P Chitano

Publications and source records attributed to P Chitano.

28 records · Page 2Linked to original sources

PubMed1994

Mechanisms and pathology of occupational asthma.

Since the pathogenesis and the pathological features of occupational asthma are similar to those of nonoccupational asthma, the former represents a very useful model for the investigation of the pathogenesis of asthma in general. More than one mechanism may be operative in occupational asthma. Among the mechanisms proposed, immunological mechanisms and airway inflammation play an important role. There is evidence to confirm that T-lymphocyte activation and local accumulation in the bronchial wall of activated eosinophils occurs in asthma of diverse aetiology, i.e. immunoglobulin E (IgE)-mediated, occupational and intrinsic. Neurogenic pathways should be further investigated as a potential mechanism of modulation and amplification of airway inflammation in occupational asthma.

Adult↗

PubMed1993

The effect of compound 48/80 on contractions induced by toluene diisocyanate in isolated guinea-pig bronchus.

We have investigated the ability of compound 48/80 and of histamine H1 and H2 receptor antagonists to inhibit toluene diisocyanate-induced contractions in isolated guinea-pig bronchi. Compound 48/80 (100 micrograms/ml) significantly inhibited toluene diisocyanate-induced contractions. By contrast, the two histamine H1 and H2 receptor antagonists, chlorpheniramine (10 microM) and cimetidine, (10 microM) did not affect toluene diisocyanate-induced contractions, but significantly inhibited contractions induced by exogenously applied histamine (100 microM) and by 48/80. We investigated which mechanisms 48/80 used to inhibit toluene diisocyanate-induced contractions, paying particular attention to the possible involvement of capsaicin-sensitive primary afferents. In vitro capsaicin desensitization (10 microM for 30 min followed by washing) significantly reduced compound 48/80-induced contractions. A capsaicin-resistant component of contraction was also evident. Ruthenium red (3 microM), an inorganic dye which acts as a selective functional antagonist of capsaicin, did not affect 48/80-induced contraction. MEN 10,207 (Tyr5,D-Trp6,8,9,Arg10)-neurokinin A (4-10) (3 microM) a selective antagonist of NK2-tachykinin receptors significantly reduced 48/80-induced contractions. These results show that compound 48/80 inhibits toluene diisocyanate-induced contractions in isolated guinea-pig bronchi. It is likely that two mechanisms are involved in the inhibition: (1) the release of mediators other than histamine by mast cells, (2) an effect of 48/80 on sensory nerves.

Animals↗

PubMed1993

Relevance of classification by size to topographical differences in bronchial smooth muscle response.

To investigate heterogeneity of airway smooth muscle response, we studied strips of large and small branches from third- to sixth-generation bronchi obtained from ragweed antigen-sensitized and control dogs. The response to electrical field stimulation and carbamylcholine chloride was greater in strips from larger branches of the same generation when expressed as "tissue stress" (force per unit cross-sectional area of the whole tissue), whereas no difference emerged with use of the more appropriate "smooth muscle stress" (force per unit cross-sectional area of the muscle tissue). The response to histamine was significantly higher in small branches than in large ones, and histamine sensitivity [mean effective concentration (EC50)] was 7.79 x 10(-6) [geometric standard error of the mean (GSEM) 1.20] and 1.49 x 10(-5) M (GSEM 1.14), respectively (P < 0.01). Strips from control and sensitized animals at each site and strips from different generations did not show any significant difference. When we clustered our preparations according to dimensions, the response to histamine was significantly higher in small bronchi than in large ones and histamine EC50 was 8.95 x 10(-6) (GSEM 1.17) and 1.57 x 10(-5) M (GSEM 1.18), respectively (P < 0.05). We conclude that evaluation of muscle response in different tissues requires appropriate normalization. Furthermore, classification into generations is inadequate to study bronchial responsiveness, inasmuch as major differences originate from airway size.

Animals↗

PubMed1992

The products of the reaction between toluene diisocyanate and water contract isolated guinea pig bronchi.

We have investigated the ability of the products of the reaction between toluene diisocyanate (TDI) and water to contract bronchial smooth muscle. The experiments were performed in isolated guinea pig bronchi. TDI, both 2,4- and 2,6-toluenediamine (TDA) and mixtures of 2,4- and 2,6-TDA (ratio 80:20 and 20:80) caused concentration-dependent contraction in the isolated bronchi. The mixture of disubstituted urea and biuret also contracted the bronchi, but not in a concentration-dependent fashion. Our results provide evidence that all products of the reaction between toluene diisocyanate and water have the ability to contract isolated bronchial smooth muscle in guinea pigs. Whatever the role of toluenediamine in the adverse respiratory effects induced by exposure to isocyanates, our findings reveal the necessity of in vivo studies on the metabolism of inhaled toluene diisocyanate in humans to improve our understanding of the mechanism of action of isocyanates.

Animals↗

PubMed1992

The effect of phosphoramidon and epithelium removal on toluene diisocyanate-induced contractions in guinea-pig bronchi.

To evaluate the role of airway neutral endopeptidase 24.11 (NEP) and epithelium removal in the contraction of airway smooth muscle in response to toluene diisocyanate (TDI), we studied the effects of the NEP inhibitor, phosphoramidon, on TDI-induced contractions of guinea-pig bronchial rings with intact epithelium and without epithelium. In preparations with intact epithelium, phosphoramidon (10 microM) potentiated the contractile response to TDI (0.3 mM) (mean +/- SEM, 23.7 +/- 2.5% versus 67.9 +/- 10.3%, p less than 0.01). Phosphoramidon also increased TDI-induced contractions in tissues without epithelium (36.9 +/- 4.9% versus 52.5 +/- 7.1%, p less than 0.05). Removal of the epithelium increased the contractile response to TDI (23.7 +/- 2.5% versus 36.9 +/- 4.9%, p less than 0.05). These results demonstrate the response to TDI is increased in epithelium-free compared to intact bronchi and that NEP 24.11 modulates the effects of endogenously released tachykinins by TDI at all of the sites where NEP is found in the airways.

Animals↗

PubMed1991

Bronchial smooth muscle responses evoked by toluene diisocyanate are inhibited by ruthenium red and by indomethacin.

We have investigated the ability of ruthenium red, an inorganic dye with Ca2+ entry-blocking properties and a selective antagonist of capsaicin, and of indomethacin, a cyclooxygenase inhibitor, to inhibit bronchial smooth muscle responses evoked by toluene diisocyanate in guinea pigs. Previous exposure of isolated guinea pig bronchi to ruthenium red significantly decreased the response produced by toluene diisocyanate. Further, the response to toluene diisocyanate was significantly decreased by pretreatment with indomethacin. These findings provide evidence that toluene diisocyanate-induced contractions of guinea pig bronchi are produced indirectly by generation of a prostanoid that activates capsaicin-sensitive afferents via a ruthenium red-sensitive mechanism.

Animals↗

PubMed1990

Evidence that toluene diisocyanate activates the efferent function of capsaicin-sensitive primary afferents.

Isocyanates are an important cause of occupational asthma. The mechanism of isocyanate-induced asthma is still unknown. To determine whether toluene diisocyanate stimulates the 'efferent' function of peripheral endings of capsaicin-sensitive sensory nerves, we investigated the effect of toluene diisocyanate in the rat isolated urinary bladder, a preparation in which the action of capsaicin has been well characterized. Toluene diisocyanate (0.03-3 mM) produced a concentration-dependent contraction of the bladder strips. Its maximal effect was about 50% of the response to capsaicin (1 microM). Previous exposure of the strips to capsaicin followed by washing out produced complete unresponsiveness, both to the first exposure to toluene diisocyanate and to a second exposure of capsaicin. Further, the response to both toluene diisocyanate and capsaicin was completely prevented by extrinsic bladder denervation, achieved by bilateral removal of pelvic ganglia (72 h before). Repeated exposure of the rat bladder to toluene diisocyanate reduced the capsaicin-evoked release of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI), taken as biochemical marker of activation of these sensory nerves. These experiments provide the first evidence that toluene diisocyanate activates directly or indirectly the efferent function of capsaicin-sensitive primary sensory nerves.

Animals↗

PubMed1990

Pharmacological modulation of the contractile response to toluene diisocyanate in the rat isolated urinary bladder.

1. Toluene diisocyanate produced concentration-dependent contractions of the rat isolated urinary bladder. 2. The contractions were tetrodotoxin-resistant and were abolished by previous exposure of the strips to capsaicin. 3. Indomethacin (5 microM) and ruthenium red (30 microM) inhibited toluene diisocyanate-induced contractions. Responses expressed as a percentage of the response obtained with substance P, 30 nM, were respectively 141.6 +/- 24.8% and 20.1 +/- 5.1% in control and indomethacin-treated strips (P less than 0.005); 123.0 +/- 30.2% and 14.0 +/- 6.5% in control and ruthenium red-treated strips (0.01 less than P less than 0.05). 4. These results suggest that toluene diisocyanate-induced contractions of the rat isolated bladder are the result of the release of cyclo-oxygenase products which may act by activating the capsaicin receptor.

Animals↗

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

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↗