[Histamine receptors and their role in allergic diseases].
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Biomedical subjects
Publications and source records attributed to J Patkowski.
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Clinical study on efficiency of the nedocromil sodium (Tilade, Fisons) was performed in 20 patients with atopic and nonatopic bronchial asthma. The drug was administrated in dose of 8 mg per day for 2 months which allowed to renounce regular using of Beclocort forte after 7 days of the treatment. In both types of bronchial asthma the positive effect of nedocromil sodium was confirmed, causing increase of pulmonary ventilation and decrease of bronchial hyperactivity. Especially profitably effect was noticed in atopic bronchial asthma in which statistically important increase of peak expiratory flow (PEF) was obtained and decrease of bronchial hyperreactivity by PC20 for histamine was observed (p < 0.05). Mentioned above spirometric parameters did not differ in statistically important pattern in patients with nonatopic bronchial asthma, when Beclocort forte group with Tilade group compared. Neither important differences in general number of cells nor percentage composition of cell smears were observed in bronchoalveolar lavage fluid.
The genetic polymorphism of drug acetylation rate in man is an important determinant of the toxic and therapeutic response to certain drugs. This polymorphism can alter not only drug effects but may be a factor influencing the frequency of the occurrence of some disease states. The aim of our study was to establish whether there exists any correlation between the acetylator phenotype and the development of allergic diseases. In patients with allergic diseases and in healthy persons as a control group, the acetylation phenotype was determined by the sulfadimidinic method. In the group of patients with allergic diseases without infectional factor 76% slow and 24% rapid acetylators were found. This predominance of slow acetylators was statistically significant (by using chi 2 test) with comparison to the group of healthy persons, where 49% slow and 51% rapid acetylators were observed. Considerable predominance of slow acetylators in patients with allergic diseases suggest that phenotype of slow acetylation may be a factor playing some role in pathogenesis of allergic diseases and may be a factor predisposing to the development of these diseases.
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Preclinical pharmacological studies of two acridine derivatives, dihydrochloride N10-oxide 1-nitro-9-/3-dimethylaminopropylamino/-acridine (C-666) and dihydrochloride 1-nitro-9-[(2-dimethylamino)-1-methylethylamino]-acridine (C-829) are reported. Both compounds are characterized by biological activity, poor absorption from the gastrointestinal tract and local irritant action. Quality differences in an effect of both investigated acridine derivatives on the central nervous system were noted. C-666 proved to be deprived of the effect typical of the central component compounds while C-829 demonstrated mostly sedative activity. Clear dissociation in the effect of these both compounds was seen in in vitro experiments on isolated smooth muscle organs. C-666 acted spasmolytically on the motory action of intestine muscles while C-829 acted spastically. Both preparations had clearly hipotensic influence which can be due to the vascular effect and to their affinity with the intramyocardium transmitting system. Neither a distinctive effect on reproductivity of animals nor the teratogenic action were observed in the functional experiments.
Encouraging results of preclinical pharmacologic analysis prompted the following study on the chronic action of N10-oxide 1-nitro-9-/3-dimethylaminopropylamino/-acridine (C-666) and 1-nitro-9- [/2-dimethylamino/ -1-methylethylamino] -acridine (C-829). Toxic influence of both compounds on liver, kidneys, gonads and intestine epithelium was observed. These histological changes were not, however, followed by any disorders in functions of liver and gonads. Only administration of compound C-666 was followed by the decrease of filtration of renals glomuses. A slight involutional influence of acridine derivatives on lymphopoetic reproductive center of thymus and lymph nodes was observed. At the same time there were no disorders in the value of circular leukocyte system. It was stated that the investigated compounds had no effect on the system of the red cells of the blood; only blood clotting time was prolonged. Compounds C-666 and C-829 did not inhibit the growth of tested animals.
Preclinical pharmacologic studies of two further acridine derivatives, 1-nitro-9-(diethylaminopropylamino)-acridine (C-410) and 1-nitro-9-(diethylaminoethylamino)-acridine (C-516) are reported. Both compounds are characterized by high toxicity, especially when injected intravenously, poor absorption from the gastrointestinal tract, and local irritant action. Local irritation can be partly alleviated by using phosphate buffer of pH 7.0 as solvent. Both preparations caused hemodynamic changes (hypotension) due to stimulation of the parasympathetic system (in cats), and higher doses showed direct action on the myocardium. Both preparations acted directly on smooth muscles, predominantly spastically (blood vessels, intestines in vivo and in vitro), and spasmolytically only on the smooth muscle of the urinary bladder in cats. Compound C-410 is deprived of a central component, and compound C-516 in most tests exhibited sedative properties. Despite moderate impairment of spermato- and spermiogenesis, neither of the compounds depressed reproductivity of the animals and no teratogenic action was observed.
Encouraging results of preclinical pharmacologic analysis prompted the following study on the chronic action of 1-nitro-9-(diethylaminopropylamino)-acridine (compound C-410) and 1-nitro-9-(diethylaminoethylamino)-acridine (compound C-516). Neither compound had an appreciable effect on quantitative regeneration of peripheral formed blood elements. Liver and kidney function tests were not significantly affectd. Histopathologic studies showed involutive changes in the lymphatic tissues and slight degenerative lesions in parenchymal organs and nuclei. However, these changes were not severe enough to cause functional disturbances or to impair reproductivity.
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