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J Slapke

Publications and source records attributed to J Slapke.

47 records · Page 3Linked to original sources
PubMed1985

Nasal symptoms in pseudoallergic reactions.

In a retrospective investigation 469 pseudoallergic reactions (analgesics asthma reactions) that emerged in 197 patients with analgesics intolerance have been analysed. Besides mostly severe asthma-attacks 26.5% of the reactions were sneeze-attacks and in 37.5% nasal secretion was found. 86% of the reactions emerged within a maximum of 45 minutes after oral application of the analgesic. About a third of the analgesics-asthma reactions occurs together with reactions of the nose mucous membrane. So the connection of analgesics-asthma and chronic hyperplastical changes of the mucous membrane of the upper respiratory tract is also reflected in the course of the pseudoallergic intolerance reaction.

Analgesics↗
PubMed1984

[Experimental study on the significance of arachidonic acid metabolism in the pathogenesis of bronchial asthma with an in vivo model in the guinea pig].

In anaesthetized artificially ventilated guinea-pigs from two breeds were produced histamine-induced bronchoconstrictions after pretreatment with acetylsalicylic acid (ASS) and/or para-amino-methylbenzoic acid (PAMBA). It was detected a distinct but adverse action of ASS on the intensity of bronchoconstriction in both animal groups. PAMBA was without any effect alone but mostly inhibited ASS-action. Since PAMBA inhibits phospholipase-A2 and ASS inhibits cyclooxygenase--both key-enzymes of arachidonic acid metabolism--the findings are estimated as a hint to the role of arachidonic acid metabolism in our animal model of asthma.

Airway Resistance↗
PubMed1984

[Types of bronchial reaction to analgesics].

Bronchial reaction of asthma bronchiale patients (n = 102) to analgesics was tested by oral exposure to acetylsalicylic acid. 73 patients produced no changed bronchial response to the exposure test. Ventilation parameters improved in 12 patients. In cases in which analgesics intolerance had been recordable from case histories (n = 17), acetylsalicylic acid doses were carefully increased in a stepwise approach to identify the threshold dose required for inset of bronchoconstriction. The average triggering threshold dose was found to be 200 mg. In patients with normal analgesics tolerance products of arachidonic acid metabolism seem to have no effect on bronchial tonus. The observed dilating effect of analgesics may, possibly, be associated with elimination of a cyclooxygenase metabolite with relevance to bronchoconstriction. Inducer of analgesics intolerance is the shift of arachidonic acid metabolism in favour of the route of lipoxygenase. Of importance is possibly a free proteolytic activity (inhibitor deficiency) with increased basic release of arachidonic acid.

Aspirin↗
PubMed1983

Lung strips from guinea pigs as test system for lipoxygenase inhibitors. Inhibition of arachidonic acid-induced contractions by 3-t-butyl-4-hydroxyanisole and nordihydroguaiaretic acid.

Lung strips and tracheal spirals from guinea pigs and rats were compared as test systems for lipoxygenase inhibitors. The contraction of the smooth muscle was induced by addition of arachidonic acid. Lung strips of guinea pigs proved to be the most suitable in vitro model. Under basal conditions half-maximal contraction was produced by 13 microM arachidonic acid (AA) which was strongly inhibited by 50 microM nordihydroguaiaretic acid (NDGA) or 100 microM 3-t-butyl-4-hydroxyanisole (BHA). NDGA and BHA caused a shift of response towards higher concentrations of AA. BHA also produced pronounced dilatations of both basal tonus and carbachol-induced contractions of the preparations from the respiratory tract. It is concluded that the actions of NDGA and BHA on the airway preparations are due to inhibition of the lipoxygenase reaction and, therefore, of leukotriene synthesis. The assumption of the lipoxygenase inhibition is supported by their action on purified lipoxygenase from rabbit reticulocytes which was inhibited by 50% by 0.5 microM NDGA and 160 microM BHA. In contrast, the antioxidant 2,6-di-t-butyl-4-hydroxytoluene (BHT) did not inhibit at all at 1 mM. To the knowledge of the authors this is the first evidence so far reported for the bronchodilating action of BHA.

Animals↗
PubMed1979

[Salicylamide-- a potential pain-remedy alternative in the analgesic asthma syndrome].

Central pathogenetic mechanism of the analgesics-asthma-syndrome is very probably an analgesics-conditioned inhibition of the prostaglandin-biosynthesis (cyclooxygenase). Salicylamide, an analgesic without effect on the prostaglandin synthesis was in the oral exposition test of 18 patients with proved analgesics-asthma-syndrome in the dosage of 500 mg subjectively and objectively tolerated without reaction. Body-plethysmographically in consistent thoracic gas volume a slight decrease of the airways resistance could be registered. At the model of the isolated trachea of guinea-pigs salicylamide, in contrast to indomethacin and phenazone (prostaglandin-synthesis inhibitory substances) did not lead to an increase of the acetylcholine-induced spasm. Salcylamide can, after a tolerability test, be recommended as alternative analgesic in the analgesics-asthma-syndrome in a dosage of 500 mg.

Analgesics↗
PubMed1979

[Asthma caused by analgesics].

Asthma, caused by analgesics, a relatively frequent phenomenon in bronchial asthma conditioned by infection, often remains unrecognized and is then sometimes a danger of high degree for these patients. Pathogenetically, the asthma caused by analgesics perhaps does not underlie an immunological mechanism, but an induced by analgesics prostaglandin-E-synthesis inhibition. For this speak the results of skin tests, of the LTT with analgesics and of IgE concentration measurements. Concomitant phenomena of the asthma caused by analgesics are: initial rhinirrhoe, alcohol intolerance, polyposis nasi and NNH affections. Among the evoking noxae the pyrazolones (regard: pyrazolone containing asthma mixed preparations!) are of greatest importance. Since already the smallest doses of analgesics may evoke considerable asthmatic reactions the indication to the exposition test should be made cautiously. In an anamnestic suspicion on asthma caused by analgesics a strict avoidance of analgesics, antirheumatic drugs and antipyretic drugs is necessary. Salicyl amide does not cause in vitro a prostaglandin synthesis inhibition. Still further clinical examinations are necessary, whether it amy generally be recommended as a possible alternative of analgesics in asthma caused by analgesics.

Analgesics↗
PubMed1977

[Prostaglandins and bronchial asthma (author's transl)].

Prostaglandins (PG) show different effects on the bronchomotoric excitability depending on the fact to which group they certain. The best investigated PG are PGE1, PGE2 (bronchodilators) and PGF2a (bronchoconstrictor). It is possible that PG play a certain role in the pathogenesis of bronchial asthma. Among other hypotheses, the influence upon adenylate cyclase - cAMP systems (without affecting the adrenoreceptors) is evident. Probably, PG exert a regulatory function on bronchial tone. The pathogenetic imporatnce of PG metabolites for bronchial asthma is discussed. A therapeutical influence upon bronchial asthma is theoretically possible on four ways: by 1) stimulation of partial endogenous synthesis of PGE, 2) inhibition of the biotransformation of PGE, 3) exogenous application of PGE, i.e. development of PGE derivatives indifferent to bronchial mucosa, stable in solution and relatively resistant to biotransformation and 4) inhibition of biosynthesis of PGF2a. The development of synthetic PGE1 derivatives (15-methyl-11-desoxy-PGE1) appears to be of future importance. Summarizing we can say that, at the present stage of development, a directed therapeutic utilization of PG for bronchial asthma seems to be of low probability yet. The problem of aspirin-induced asthma including all its practical consequences is discussed.

Asthma↗
PubMedDate not supplied

A test hierarchy for anti-bronchoconstrictory lipoxygenase inhibitors: in vitro and in vivo experimental tests.

A test hierarchy for potential antiasthmatic lipoxygenase inhibitors was developed which includes besides molecular and cellular test systems, the arachidonic acid-(AA)-induced contraction of lung strips and ovalbumin-induced bronchoconstriction of sensitized guinea pigs. Nordihydroguaiaretic acid, butylated hydroxyanisole, benoxaprofen, BW 755C, salicylhydroxamic acid, FLM 5011 and other substances inhibit to a different extent the AA-induced contraction of lung strips and show anti-bronchoconstrictory activities in the ovalbumin-sensitized guinea pig.

Animals↗
PubMedDate not supplied

Influence of bilateral subnodular vagotomy and section of retrotracheal plexus on allergic bronchial constriction in guinea pigs.

A bilateral subnodular vagotomy and a tracheal dissection with immediate readaptation (n = 18) or one of both (n = 8) was performed on ovalbumin sensitized guinea pigs. Control animals got a shame operation (n = 13). About one week later the animals were narcotized by ethylurethane 1.3 g per kg b.w. intraperitoneally and received a tracheotomy with insertion of a tracheal cannula and an additional insertion of a flexible catheter into the right jugular vein. Then the animals were artificially ventilated in a tank respirator by rhythmical exposure to a negative chest wall pressure, the ventilator settings were f = 20 per min, I: E = 1: 1, and rectangular pressure = -2 kPa. Breathing parameters were measured pneumotachographically. Flow, tidal volume, ECG and ventilation pressure were recorded with a 12-channel UV-light recorder. After the recording of initial parameters an intratracheal bolus-instillation of 0.5 mg/kg b.w. ovalbumin was given and 5 min later, a second ovalbumin bolus i.v. of 1 mg/kg b.w. Mean minimal tidal volumes reached after i.t. OA-provocation were: 17.6 +/- 19 in controls, 39.7 +/- 30 after vagotomy and tracheotomy, 40.5 +/- 20 after vagotomy alone, and 27.6 +/- 18 after tracheotomy alone. We found a significant inhibition of allergic bronchial constriction by bilateral vagotomy. The dissection of the retrotracheal plexus by tracheotomy was without significant effect on the allergic response. The investigation could demonstrate the significance of vagotomy on asthmatic reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Serine esterase inhibitor reduces contractions with isolated trachea and lung strips from guinea pigs induced by phospholipase A2.

The regulation of the phospholipid metabolism (arachidonic acid (AA) cascade) plays a key role in the pathogenetic mechanisms of the various forms of bronchial asthma. This pathogenetic mechanism offers also important therapeutic implications. Since AA liberation is modulated by phospholipase A2 (PLP-A2) the authors studied the effects of PLP-A2 on guinea pig airways under in vitro conditions and their responses to action of protease inhibitor. Experiments were performed in organ bath with lung strips and tracheal spirals from male guinea pigs. PLP-A2 caused in both models dose-dependent contractions. Para-aminomethyl-benzoic acid reduced PLP-A2-induced contractions in lung strips and trachea in a similar way. This reduction is apparently due to inhibition of AA liberation. These experimental findings underline the relevance of AA cascade to pathogenesis of bronchoconstriction and bronchial hyperreactivity. They support the clinical effectiveness of para-aminomethylbenzoic acid demonstrated earlier. The search for new potential antiasthmatic drugs with the site of action on AA liberation from phospholipids requires in vitro test systems. Guinea pig airway preparations proved to be a suitable in vitro model. The inhibition of PLP-A2 by protease inhibitors seems to be a principal (corticosteroid-like) way for modulation of bronchoconstriction.

4-Aminobenzoic Acid↗