Ectopic thymoma simulating a pericardial cyst.

We present a case of a 53 year old man with a thymoma near the pericardium, a rare ectopic localisation of thymoma. A round radiodensity found at the right cardiophrenic angle was initially suspected at the echocardiography to be a pericardial cyst. The diagnosis of thymoma was made only after histopathological examination of the surgically re-sected lesion.

Prostacyclin activates tachykinin release from capsaicin-sensitive afferents in guinea-pig bronchi through a ruthenium red-sensitive pathway.

1. We have investigated the ability of prostacyclin (PGI2) to contract guinea-pig isolated bronchi and the possible involvement of capsaicin-sensitive primary afferents in the response to PGI2. 2. PGI2 (0.1-100 microM) produced concentration-dependent contractions of the guinea-pig isolated bronchi. In vitro capsaicin desensitization (10 microM for 30 min followed by washing) significantly reduced the PGI2-induced contraction at all concentrations tested. A capsaicin-resistant component of contraction (40-60% of the overall response) was also evident. 3. Ruthenium red (3 microM), an inorganic dye which acts as a selective functional antagonist of capsaicin, significantly decreased PGI2-induced contractions, without affecting the response to substance P, neurokinin A or acetylcholine. 4. MEN 10, 207, (Tyr5, D-Trp6,8,9, Arg10)-neurokinin A (4-10) (3 microM), a selective antagonist of NK2-tachykinin receptors, significantly decreased PGI2-induced contractions and neurokinin A-induced contractions, without affecting the response to acetylcholine. 5. The effect of ruthenium red and MEN 10,207 on the one hand, and that of ruthenium red and capsaicin on the other was non additive. 6. These results indicate that PGI2-induced contraction of the guinea-pig isolated bronchi involves two distinct mechanisms, one of which involves transmitter (tachykinins) release from peripheral endings of capsaicin-sensitive primary afferents. In as much as PGI2-activation of primary afferents is sensitive to ruthenium red, we suggest that PGI2 shares a common mechanism of tachykinin release with that activated by capsaicin.

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.

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.

Toluene diisocyanate-stimulated release of arachidonic acid metabolites in the organ bath from guinea-pig airways.

This study was designed to evaluate whether metabolites of arachidonic acid play a role in the contractile response to toluene diisocyanate in isolated guinea pig airways. In control experiments we collected the supernatant from an organ bath over a time period of 2 h, after the addition of toluene diisocyanate (100 and 300 microM), and after the addition of toluene diisocyanate (300 microM) in the presence of indomethacin (5 microM). We measured prostaglandin E2, 6-keto-prostaglandin F1 alpha, prostaglandin F2 alpha, thromboxane B2, leukotriene B4, leukotriene C4/D4/E4/F4 by radioimmunoassays. Levels of prostaglandin F2 alpha and 6-keto-prostaglandin F1 alpha increased significantly after addition of toluene diisocyanate in the absence of indomethacin. These results suggest that prostaglandins are involved in toluene diisocyanate-induced contractions in guinea-pig airways.

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.

Toluene diisocyanate contracts guinea pig bronchial smooth muscle by activating capsaicin-sensitive sensory nerves.

This study was designed to evaluate the mechanism of action of toluene diisocyanate (TDI) and the role of endogenous neutral endopeptidase in modulating in vitro contractile responses to TDI in guinea pigs. TDI (0.01-1 mM) produced a concentration-dependent contraction of the guinea pig main bronchi. Sensory nerve desensitization with capsaicin greatly reduced and in some cases almost abolished TDI-induced contractions. The neutral endopeptidase inhibitor phosphoramidon significantly increased the contractile response to TDI. Pretreatment with the substance P antagonist (D-Arg1,D-Pro2,D-Trp7,9,Leu11)-substance P greatly reduced TDI-induced contractions. These results suggest that TDI activates the "efferent" function of capsaicin-sensitive sensory nerves and that neutral endopeptidase may play a role in modulating the response in guinea pigs.

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.

Does intravenous streptokinase therapy facilitate the formation of anti-heart antibodies in acute myocardial infarction?

Streptokinase (SK), a nonenzymatic protein produced by group C beta haemolytic streptococci, is a potent antigen. It is used worldwide as a thrombolytic agent in the treatment of acute myocardial infarction (AMI). Specific antiheart antibodies (AHA) have been found with a significantly high incidence in patients with AMI, and after streptococcal infection as a result of stimulation by constituents of the group A streptococci antigenically cross-reactive with sarcolemmal portion of the muscle fiber of the heart. Since there may be partial antigenic identity of group C streptococcal membranes with membranes isolated from group A streptococci, we have designed a prospective study to evaluate the incidence of serum AHA (and of other organ-specific and non-organ-specific antibodies) in 36 patients with AMI, 14 of whom treated with SK. AHA, of IgG class, were of the sarcolemmal-subsarcolemmal type, and did not fix complement. They were found in 4/36 patients already on admission; of the 32 patients negative, none developed AHA later, on days 7, 15 and 21 of hospitalization, also after treatment with SK (in 14 cases). There was no significant difference either within or between the two SK-treated and non-SK-treated groups also with regard to the incidence of organ-specific and non-organ-specific autoantibodies. These findings do suggest that the intravenous SK therapy does not facilitate the formation of AHA in AMI.

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.

Effect of subchronic in vivo exposure to nitrogen dioxide on lung tissue inflammation, airway microvascular leakage, and in vitro bronchial muscle responsiveness in rats.

OBJECTIVES: In a previous study on bronchoalveolar lavage fluid from rats exposed in vivo for seven days to 10 ppm nitrogen dioxide (NO2), it has been shown that there is an influx of macrophages into the airways. The present study investigated the effect of seven day exposure to 10 ppm NO2, on: (a) lung tissue inflammation and morphology; (b) airway microvascular leakage; (c) in vitro contractile response of main bronchi. METHODS: Lung tissue was studied by light microscopy, after fixing the lungs by inflation with 4% formalin at a pressure of 20 cm H2O. Microvascular leakage was measured by extravasation of Evans blue dye in the larynx, trachea, main bronchi, and intrapulmonary airways. Smooth muscle responsiveness was evaluated by concentration-responses curves to acetylcholine (10(-9)-10(-3) M), serotonin (10(-9)-10(-4) M), and voltage-response curves (12-28 V) to electrical field stimulation. RESULTS: Histology showed an increased total inflammation at the level of respiratory bronchioles and alveoli. No influx of inflammatory cells was found in the main bronchi. A loss of cilia in the epithelium of small airways and ectasia of alveolar capillaries was also found. By contrast, no alterations to microvascular permeability or modification of bronchial smooth muscle responsiveness was found. CONCLUSIONS: Subchronic exposure to 10 ppm NO2 causes airway inflammation and structural damage, but does not cause any persistent alteration to microvascular permeability or bronchial smooth muscle responsiveness in rats.