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A Papi

Publications and source records attributed to A Papi.

66 records · Page 4Linked to original sources
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

Effect of bumetanide on toluene diisocyanate induced contractions in guinea pig airways.

BACKGROUND: The loop diuretic frusemide has been shown to inhibit the bronchoconstrictor response to exercise, inhaled allergen, distilled water, adenosine, and sodium metabisulphite. Toluene diisocyanate contracts smooth muscle by activating capsaicin sensitive nerves and causes asthma that shares many features with allergen induced asthma. METHODS: The study was designed to assess the effect of two loop diuretics, bumetanide (10 and 100 microM) and frusemide (100 microM), on smooth muscle contraction induced by toluene diisocyanate (0.03-1000 microM) in guinea pig airways with and, in the case of bumetanide, without epithelium. The effect of bumetanide on the response to acetylcholine, neurokinin A, and electrical field stimulation in guinea pig bronchial smooth muscle rings was also examined. RESULTS: Bumetanide (10 and 100 microM) had no effect on toluene diisocyanate induced contraction whether airway epithelium was present or not. Frusemide (100 microM) caused no significant inhibition of toluene diisocyanate induced contraction (mean reduction on the entire curve 25%). Bumetanide inhibited non-adrenergic, non-cholinergic contraction induced by electrical field stimulation of bronchi pretreated with atropine (1 microM) and indomethacin (5 microM) and this inhibition was inversely related to the frequency of stimulation, suggesting that bumetanide may be inhibiting transmitter release at the prejunctional level. Bumetanide and frusemide did not inhibit the responses to exogenous acetylcholine (0.1 microM) or neurokinin A (1 nM). CONCLUSIONS: Bumetanide and frusemide in doses that are known to inhibit non-adrenergic, non-cholinergic contraction due to electrical field stimulation failed to inhibit the response to toluene diisocyanate in guinea pig airways.

Acetylcholine↗
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

Protection of erdosteine on smoke-induced peripheral neutrophil dysfunction both in healthy and in bronchitic smokers.

The purpose of the present study was to determine whether erdosteine and its metabolites (substances containing thiol groups) can prevent the alteration of the chemotactic function of polymorphonuclear cells (PMN) from peripheral blood induced by cigarette smoke of eight healthy non-smoking volunteers, when incubated in vitro before smoke exposure, and whether oral treatment with erdosteine (900 mg/day) for two weeks might restore the chemotaxis of PMN, either from eight healthy or from 16 chronic bronchitic smokers. The chemotactic stimuli in vitro were casein, lipopolysaccharides (LPS), and formyl-methionyl-leucyl-phenyalanine (FMLP). The results of the study in vitro have confirmed that PMN from non-smoking volunteers shows a reduced chemotactic responsiveness when exposed in vitro to smoke. This can be partially prevented in a dose-related manner by pre-incubation with erdosteine, its metabolites, cysteine, and glutathione (metabolites I and II being at least 10 times more active than the intact substance and the known biological standards also containing thiol groups). The experiment on PMN from healthy smokers (in a double-blind crossover design versus placebo) has indicated that the chemotaxis can be improved only after treatment with erdosteine. The same observation has been made in the experiment on PMN from smokers affected by chronic bronchitis (in a double-blind design versus placebo with two distinct groups). In these patients the phagocytic and bactericidal activities of PMN were not affected by the smoke and therefore, neither one was influenced by erdosteine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
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↗
PubMed1990

Increased bronchial responsiveness in primary and secondary Sjögren's syndrome.

We examined one group of 33 patients with primary Sjögren's syndrome, one group of 17 patients with secondary Sjögren's syndrome, i.e. associated with other connective tissue diseases, and one group of 14 patients with connective tissue diseases but without Sjögren's syndrome. In each patient we obtained chest radiographs and measured lung volumes, carbon monoxide diffusing capacity and airway responsiveness to methacholine. We observed no difference in chest radiograph abnormalities, in lung volumes and in carbon monoxide diffusing capacity among the three groups. However, we found a slight but significant increase of bronchial responsiveness in patients with primary and secondary Sjögren's syndrome compared with patients with connective tissue disorders but without Sjögren's syndrome. Thus PD20FEV1 methacholine was 1.07 mg (1.2) (geometric mean and GSEM) in primary Sjögren's syndrome, 0.91 mg (1.4) in secondary Sjögren's syndrome (NS), and 2.24 mg (1.09) in patients with connective tissue diseases but without Sjögren's syndrome (t = 2.59 and t = 2.8, both p less than 0.05, vs primary and secondary Sjögren's syndrome, respectively). These results show that some patients with Sjögren's syndrome have mild bronchial hyperresponsiveness, which may be related to the specific airway abnormalities of this disease.

Bronchial Provocation Tests↗
PubMedDate not supplied

Pulmonary blastoma: case report in an adult.

We present a case of biphasic pulmonary blastoma, a rare primary malignant lung neoplasm, in a 48 year old man. Despite its resection followed by postoperative chemotherapy, the neoplasm recurred and the patient survived only 41 months after the diagnosis.

Humans↗
PubMedDate not supplied

[Homologous intrauterine insemination: our experience].

Sixty-five couples with male infertility or unexplained infertility or infertility due to cervical factor underwent 156 cycles of homologue intrauterine insemination. The overall pregnancy rate was 16.5% with 2.4 mean value of insemination cycles for each couple. The highest pregnancy rate was observed in cases of cervical factor infertility. The mean age of patients who had pregnancy was 30 years (overall mean value 34 years) and the mean time of sterility was 3 years (overall mean value 4.4 years).

Adult↗
PubMedDate not supplied

A search for multidrug resistance modulators: the effects of retinoids in human colon carcinoma cells.

The development of multidrug resistance (MDR) is one of the major causes of failure in cancer therapy. The use of cell lines with acquired resistance to anticancer agents represents a very good tool for investigation into the possibility of reversal of MDR. In this study the ability of all-trans-retinoic acid (RA) and its derivative 6-OH-11-O-hydroxyphenanthrene (IIF; pat. WIPO W000 /117143) as antitumor agents was investigated in the human colon carcinoma cell line LoVo and in the counterpart resistant derivative LoVo/MDR cell line. Cell proliferation was measured by MTT assay, apoptosis was evaluated using DNA fragmentation and Annexin V detection assay. Retinoids suppressed cell proliferation in a time- and dose-dependent manner. Interestingly, IIF was significantly more effective than RA, particularly on LoVo/MDR cells. RA and IIF induced apoptosis in both cell lines, with IIF effect significantly higher than that of RA. Furthermore, on the basis that MDR phenotype is often caused by drug efflux due to overexpression of the membrane P-glycoprotein (P-gp), it was demonstrated that RA and IIF reduced P-gp synthesis in LoVo/MDR cells. Our results suggest that IIF could be a powerful tool in the development of colon carcinoma treatments, even when tumor cells present an MDR phenotype.

ATP Binding Cassette Transporter, Subfamily B, Mem↗