Eosinophil cationic protein in serum of corticosteroid-sensitive and resistant bronchial asthma.

Theories for the inflammatory basis of bronchial asthma are presented. The phenomenon of corticosteroid resistance (CR) in bronchial asthma is also discussed. Resistance to corticosteroids, which occurs in about 5% patients with moderate and severe asthma, presents still an important diagnostic and therapeutical problem. In addition, present opinions on the role of eosinophils in the allergic bronchial inflammation were analyzed. The aim of this study was to monitor serum eosinophil cationic protein (ECP) level in asthma patients, sensitive and resistant to glucocorticosteroids (GCS), before and after prednisolone treatment. The resistance to steroids was determined, based on the oral prednisolone test according to Carmichael and vasoconstriction assay according to Stoughton and McKenzie. In the group of corticosteroid-sensitive (CS) asthmatic patients a statistically significant decrease of ECP level was observed, after 10 day administration of prednisolone in a daily dose of 20 mg, which was associated with a meaningful increase of FEV1 value. On the other hand, the level of ECP in the serum of patients resistant to corticosteroids, although also decreased under influence of prednisolone, was not correlated with the increase of FEV1 value.

Pharmacological studies on new oncostatic acridine derivatives. I. Acute and subchronic action.

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.

Pharmacological studies on new oncostatic acridine derivatives. II. Chronic action.

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.

Pharmacological studies on 1-nitro-9-alkyl acridine derivatives. I. Acute and subchronic action.

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.

Pharmacological studies on 1-nitro-9-alkyl acridine derivatives. II. Chronic action.

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.

Comparative study between skin prick tests and TOP-CAST allergen leukocyte stimulation in diagnosis of allergic status.

A recently developed CAST-ELISA method was applied to determine allergen-induced leukocyte stimulation. This method is based on the measurement of sulfidoleukotriene secretion by peripheral blood leukocytes previously stimulated with specific allergen in the presence of interleukin 3. 24 patients allergic to different aeroallergens and some food allergens were included in this study. Subjects received no medication 2 weeks before the testing. Leukocytes were isolated by dextran sedimentation. After incubation with allergen at two concentrations, the cells were centrifuged and the concentration of sulfidoleukotrienes in supernatant was determined. The results were expressed in pg/ml after subtraction of values of spontaneous sulfidoleukotriene production in portions incubated without allergen. We observed a wide range of sulfidoleukotriene secretion upon allergen stimulation. Concentrations of leukotrienes ranged from 0 to 5780 pg/ml at lower allergen concentration and from 210 to 5680 at higher allergen concentration. On the basis of observed results, we conclude that the better allergen concentration is the higher one because there was no appearance of negative cell stimulation. In the lower allergen concentration we observed negative results in two cases. Sixteen healthy control subjects were also included in this study. Eleven subjects had negative skin prick tests (SPT) as well as CAST results. In 5 healthy subjects with positive SPT, we also observed positive CAST results in 4 persons. In 1 healthy person with positive SPT results, CAST results were negative. We conclude that TOP-CAST allergen is a valuable mixture of different aero and food allergens for determining the allergic status in patients with suspicious allergic status, although it cannot differentiate between health and disease states.

[Nedocromil sodium in treatment of bronchial asthma]. / Nedokromil sodu w leczeniu astmy oskrzelowej.

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.

[Validation of the Polish version of St. George's respiratory questionnaire in patients with bronchial asthma]. / Ocena polskiej wersji St. George's respiratory questionnaire u chorych na astme oskrzelowa.

St George's Respiratory Questionnaire (SGRQ) has been widely used in the assessment of health related quality of life (HRQOL) in patients with asthma and chronic obstructive pulmonary disease. Introduction of the new language version of the HRQOL questionnaire needs to be preceded by a highly structured process of validation. We aimed to validate the Polish version of SGRQ in the group of 83 patients with asthma. Following the comprehension study, we thus evaluated reliability, validity, reproducibility, responsiveness, and measurement equivalence of the Polish version of SGRQ. Disease severity and health status were also concurrently assessed. The reliability was good, with Cronbach's alpha coefficient exceeding 0.75 for global and all subscale scores. There have been highly significant correlations between spirometric parameters, intensity of symptoms, health status self-assessment, and the degree of depression, and quality of life scores. Reproducibility, stability and responsiveness were confirmed in the follow-up study. Minimal clinically important difference was found to be 5.3 points. Polish version of SGRQ was found to be psychometrically equivalent to four other versions of SGRQ, which underscores its validity in the population of Polish asthmatics.