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Biomedical subjects

J Slapke

Publications and source records attributed to J Slapke.

At least 37 records · Page 2Linked to original sources
PubMed1988

[Bronchial hyperreactivity: state and perspective of drug intervention].

A decreased threshold of bronchial contractility under the influence of nonspecific and specific factors (bronchial hyperreactivity--BHR) is a disposing factor and precondition to the development of asthmatic disease. Probably the disturbance of the barrier function of the bronchial epithelium plays a central role in bronchial hyperreactivity. The release of phospholipid mediators from membrane phospholipids might be decisive for the establishment of bronchial hyperreactivity. This is documented, before all, by the decreasing effect of glucocorticosteroids upon the hyperreactivity since their pharmacologic efficacy is realized in first line by an inhibition of the release of arachidonic acid. We are arguing that an endogenously not compensated basical release of arachidonic acid and platelet activating factor is causally related to bronchial hyperreactivity. Prevention of asthma as well as therapy must aim at systematic reduction of bronchial hyperreactivity. Beside glucocorticosteroids and other inhibitors of phospholipase could prospectively be of therapeutic interest inhibitors of synthesis or antagonists of 5-lipoxygenase, of platelet activating factor, of leukotrienes or thromboxanes. There exist theoretical bases for practical measures of directed prevention of asthma in persons at risk. Their efficiency still awaits scientific evaluation.

Asthma↗
PubMed1988

[Possible significance of the lipoxygenase pathway of arachidonic acid metabolism for the pathogenesis of constrictive reactions of lung blood vessels].

Recent studies suggest a key role of lipoxygenase (LOX) pathway of arachidonic acid (AA) metabolism in the regulation of pulmonary artery tone. We investigated the influence of specific inhibition of leucotriene biosynthesis on constrictory reactions of isolated rabbit pulmonary arteries in the organ bath. The substance FLM 5,011 selectively inhibiting the LOX pathway leads at a bath concentration of 5 X 10(-5) M to an inhibition in the order of 75% of AA- and phospholipase (PLP) A2-induced contraction (cumulative measurement, 37 degrees C, pH 7.4, isotonic contraction). The inhibitory effect on calciumionophore A 53,712-induced contraction was only 31.4%. We compared these findings with actions of nordihydroguiaretic acid and PAMBA. Our findings suggest that in rabbit lung arteries receptors for AA-products must exist and that the activation of AA depends on calcium. The present investigations underline the relevance of LOX products to genesis of pulmonary hypertension in man.

Arachidonic Acid↗
PubMed1988

Antiinflammatory effect of a lipoxygenase inhibitor (FLM 5011) in severe active myocarditis.

FLM 5011 belongs to a group of chemical compounds with isolated lipoxygenase products in human polymorphonuclear leukocytes and alveolar macrophages. FLM 5011 has been shown to be protective against arachidonic acid-induced bronchoconstriction in vitro and in vivo. No severe side-effects were found in extensive tests on acute and subchronic toxicity in animals. In preliminary investigations on patients with severe active myocarditis impressive clinical and histological improvements after administration of FLM 5011 have been obtained, suggesting an antiinflammatory effect of the substance. A follow-up of more than 13 months compared with conventional immunosuppressive therapy indicates potential therapeutic value of this compound on the inflamed myocardium.

Adult↗
PubMed1988

[Therapy of asthma with theophylline preparations].

Theophylline, 1.3-dimethylpurindione-(2.6), is a common component as well of the basic treatment of obstructive lung disease as of the emergency therapy of asthma. Until now, the mode of action of the bronchodilating effect is not elucidated. Probably, the antagonistic action upon adenosine plays a central role. The clearance of theophylline is decisive for the serum level. It varies inter- and intraindividually, depending upon different factors, e. g. simultaneous application of other drugs, coexisting diseases, and circadian rhythms. Slow-release preparations are a progress in the basic treatment of bronchial asthma and chronic obstructive bronchitis. Among other items, they are especially advantageous in the treatment of bronchial obstructions during night-time. Theophylline-ethylendiamine (aminophylline) can be given intravenously and thus is the drug of choice in severe attacks of asthma. For optimal therapeutic effects, serum levels between 8 and 20 micrograms/ml are necessary. Side effects are observed mainly with serum levels above 15 micrograms/ml, concerning gastrointestinal tract, central nervous system, and cardiovascular system. Mild side effects are frequent. The most serious adverse reaction are epileptiform reactions. In perspective, by differentiation of adenosine-receptor-subtypes, the development of new xanthine-derivatives with most favourable action could be feasible.

Asthma↗
PubMed1988

[Clinical use of theophylline retard Oranienburg].

Theophylline retard "Oranienburg" has been applied in mild and intermediate forms of bronchial asthma as monotherapy (n = 40), and in severe forms of the disease in combination with other antiasthmatics (n = 21). With a dose of 560 mg twice daily the drug showed effective antiasthmatic activity which was especially evident from the possible reduction of corticosteroid requirement. The relative high rate of side effects from the drug can be lowered by stepwise increase and individual adjustment of the dose. In general, treatment should start with 2 tablets per day, given with 12 hours interval. To preserve the slow-release action, tablets should not be cut in half. In individual cases, determination of serum level of the drug may be required. The narrow therapeutic margin and the influence of numerous factors upon the clearance of theophylline require a thorough dosage and observation of the patients. Thus, the favourable properties of the preparation (lasting serum levels, improved compliance by patients) can be fully used.

Adrenal Cortex Hormones↗
PubMed1988

[Determination of bronchial reactivity by inhalation administration of cold air and pharmacologically active substances].

The indications for testing of nonspecific bronchial reactivity and the factors influencing the airway responsiveness are presented. In order to achieve a better quantification of airway responsiveness two new techniques are shortly reviewed: 1. Estimation of accumulative dose by using a combined method of bronchial provocation and simultaneous measurement of airway resistance and 2. Eucapnic cold airway hyperventilation, especially in suspected clinical cases of exercise-induced asthma.

Aerosols↗
PubMed1987

[Glucocorticosteroid therapy in bronchial asthma with special reference to the prevention of life-threatening bronchial obstruction in high-risk asthma].

The treatment of bronchial asthma with glucocorticosteroids requires consideration of unequivocal principles which include strong indication, considering the individual risk-benefit-relation. Glucocorticosteroids should be fitted in a medicamentous-therapeutic hierarchy. Inhalable glucocorticosteroids hardly cause systemic side effects, so they are very suitable for the continuous treatment, if the need in glucocorticosteroids is low. The indication for systemic application of glucocorticosteroid, their side effects, relative contraindications and pharmacological interactions are given. Careful analyses of cases of death, caused by bronchial asthma in accordance show that an inadequate glucocorticosteroid-therapy was the most important avoidable factor. The attention of the clinicians must be directed on a small group of patients characterised by high risk of death ("high-risk-asthma"). These patients, having certain clinical signs, need not only special intensive care, but also experienced, early and sufficient treatment with glucocorticosteroids to prevent life threatening situations.

Administration, Inhalation↗
PubMed1987

[Effect of antioxidants on the production of reactive oxygen metabolites by stimulated alveolar macrophages].

Reactive oxygen metabolites (ROM) (O2-, H2O2, 1O2, .OH, OX-) which are produced by stimulated alveolar macrophages (AM), neutrophils and eosinophils, play an important role in the pathogenesis of many acute and chronic lung diseases. With regard to a therapeutic application the influence of the antioxidants ascorbic acid (Vitamin C) and alpha-tocopheryl acetate (Vitamin E acetate) on the production of ROM by AM was investigated. The AM were isolated by bronchoalveolar lavage from patients with different lung disorders. The ROM were determined by means of chemiluminescence-measuring. alpha-Tocopheryl acetate solved in peanut oil causes a little increase of the yeast cell wall-induced chemiluminescence. Pure alpha-Tocopheryl acetate has no effect on the chemiluminescence. In contrast to alpha-Tocopheryl acetate the addition Vitamin C to the stimulated AM results in a strong diminution of the chemiluminescence signal. This result suggests that Vitamin C reduces the generation of ROM by AM. Therefore Vitamin C could be a suitable scavenger of radicals and oxidants in different lung diseases.

Antioxidants↗
PubMed1986

[Progress in drug treatment of bronchial asthma].

On the base of modern literature a statement is given on the actual situation of bronchial asthma treatment and its tendencies. It intends to be an instruction for the doctors daily practice and shell help all asthmatics getting the new possibilities of treatment in time. Furthermore these recommendations intend to support a reasonable and scientific prescription of new drugs.

Adrenal Cortex Hormones↗
PubMed1986

Pure enzymes in a test hierarchy for antibronchoconstrictory lipoxygenase inhibitors.

A test hierarchy for potential antibronchoconstrictive drugs acting as lipoxygenase inhibitors was developed which includes a purified mammalian lipoxygenase/leukotriene A4 synthase, purified cyclooxygenase, arachidonic acid metabolism of polymorphonuclear leukocytes, arachidonic acid-induced contraction of lung strips, isolated human bronchi, and ovalbumin-induced bronchoconstriction with sensitized guinea pigs. The lipoxygenase from rabbit reticulocytes turned out to be superior to a variety of other animal and plant lipoxygenases. Among the various test systems with respiratory tract preparations, the arachidonic acid-induced contraction of guinea pig lung strips gave the most reliable results in the search for new antiasthmatic drugs. The validity of the test hierarchy was ascertained in screening investigations. Novel classes of antibronchoconstrictory lipoxygenase inhibitors were found.

Animals↗
PubMed1986

Protease inhibitor prevents bronchoconstriction in man.

In order to assess the potential role of protease inhibitors in airways regulation in asthma, we have studied the effects of para-aminomethylbenzoic acid (PAMBA) in 74 patients with various forms of bronchial asthma. The effects were assessed in challenge tests by changes in PEF or FEV1 following oral administration of analgesics, exercise or allergen inhalation. PAMBA was used in a single blind manner with lactose as placebo. PAMBA administered orally (1.0 g) was found to reduce significantly the maximal change in FEV1, PEF following challenge in patients with analgesic-induced asthma (n = 30; p less than or equal to 0.01), exercise-induced asthma (n = 37; p less than or equal to 0.01) or allergen-induced asthma (n = 7; p less than or equal to 0.05). We suggest that PAMBA reduces the accumulation of bronchoconstrictory metabolites of arachidonic acid via inhibition of phospholipase A2.

4-Aminobenzoic Acid↗
PubMed1986

[Temperature dependence of bronchial and tracheal reactivity of isolated respiratory tract preparations of the guinea pig].

The intrapulmonary loss of heat due to hyperventilation may be considered as essential pathogenetic factor in producing exercise induced asthmatic response. The temperature dependence of smooth muscle contraction was investigated using isolated trachea and isolated lung strips of guinea pigs. The measurements of the contraction responses to cumulative dose administrations of acetylcholine (10(-9) to 10(-3) M) were made in thermostated organ baths (isotonic contraction, modified Krebs-Henseleit solution, pH 7.4, air gassing). The standardized measurement data were adjusted to a non-linear function with the aid of a computer. The reactivity of the isolated trachea remained unchanged with a change of the bath temperature (from 37 degrees C to 30 degrees C), whereas a markedly increased contraction response to acetylcholine was observed in the lung strips. The results indicate that the contraction induced by the drop in temperature is localized in the small airways. The stabilization of reactive oxygen metabolites as an asthma-inducing mechanism is discussed as a possible explanation of the temperature-dependent effects.

Airway Obstruction↗
PubMed1985

[Analgesic asthma].

Analgesics-induced asthma (AIA) is quite often unidentified and then is a severe danger to the patients affliced. In a case-control-study 1042 asthmatic patients selected by random were investigated. In 18.9% of patients the presence of AIA was recorded. Woman accounted for 71% of the AIA patients. Coincidence of AIA with nasal polyposis, paranasal sinus diseases, chronic rhinitis, alcohol intolerance and severe bronchial asthma was recorded with high significance. Chronic hyperplastic changes in the upper airways were exhibited by about 64% of the AIA patients. AIA is a non-allergic form of asthma, resembling immediate allergic type I reaction. Analgesics-based acute bronchoconstriction will typically develop within 45 min. following intake of the analgesic. Triggering threshold doses may differ strongly by individuals. Oral exposure test is connected with a high risk of complications. A case history usually is sufficient for save diagnosis. Analgesics without inhibiting action on cyclooxygenase usually are tolerated. The causes of AIA should be ascribed to changes in the release and conversion of arachidonic acid (Aa) from membrane phospholipids. The inhibition of Aa release (phospholipase-A2-reaction) by protease inhibitors or the inhibition of Aa transformation to bronchoconstrictive lipoxygenase products by lipoxygenase inhibitors were shown in vitro (isolated guinea pig lung strips and human bronchi). Paraaminomethylbenzoic acid also was found to be effective in clinical experiments preventing analgesics-induced bronchoconstriction. Both seem to be principal ways for modulation of bronchoconstriction.

Analgesics↗
PubMed1985

Nasal polyposis, bronchial asthma and analgesic intolerance.

A retrospective case-control study was conducted in 1042 arbitrarily selected bronchial asthma patients (197 patients with AIA and 845 controls with normal analgesic tolerance). Two thirds of all AIA patients reported one or more diseases in the region of the upper airways. Quite different from the control group, highly significant coincidence of AIA with nasal polyposis (42.6%), paranasal sinus diseases (39%), and chronic rhinitis (42,1%) was recorded in the AIA patients. AIA was characterized by stronger inclination to recurrence of nasal polyps and more frequent negative impact of polypectomy upon the course of asthma. The classical triad of "intrinsic asthma - nasal polyps - analgesic intolerance" was established in 39% of the AIA patients. The pathogenetic factors causing the association of asthma with polyps and the even more strongly association of AIA with polyps are still unknown. The presumed pathogenetic relationship between chronic hyperplastic alterations in the upper airways and the phenomenon of AIA might be caused by disorders in phospholid metabolism (liberation of arachidonic acid, lipoxygenase products, radical mechanisms).

Analgesics↗