[Levels of carnitine and homocysteine in plasma of long-term hemodialysis patients with chronic renal failure]. / Stezenie karnityny i homocysteiny w osoczu u poddawanych hemodializie chorych na przewlekla niewydolnosc nerek.

Homocysteine and carnitine are the metabolic products of exogenous amino acids. Increased plasma concentration of homocysteine but decreased or normal carnitine concentration are usual findings in haemodialysis patients with chronic renal failure. This study aimed to evaluate the interrelationship (if any) between the above mentioned metabolites in haemodialysis uraemic patients. 44 haemodialyzed patients with chronic renal failure--HD (25 female, 19 male, mean age 47 +/- 12 years) were enrolled into this study. Blood samples for estimation of plasma glucose, cholesterol, triglycerides, albumin, folic acid, vitamin B12, homocysteine (HC), total (TC) and free (FC) carnitine were withdrawn after overnight fasting before subsequent haemodialysis session. In all subjects whole body total fat mass (TFM) and lean mass (TLM) were assessed by dual X-ray absorptiometry (DEXA). Hyperhomocysteinaemia was found in 90.9% patients, while carnitine deficiency in 22.7% of all analysed subjects. Both hyperhomocysteinaemia and carnitine deficiency was found in 18.2% of haemodialysis patients. Folic acid deficiency regardless of prescribed supplementation was observed in 9.5% patients. A significant positive correlation was found between plasma concentration of TC or FC and TLM (tau = 0.332, p < 0.001; tau = 0.298, p < 0.01 respectively). A negative correlation was observed between plasma concentration of folic acid and homocysteine (tau = -0.201, p < 0.05). No significant relationship was noted between homocysteinaemia, total and free plasma carnitine levels and anthropometrical parameters. In conclusion, plasma concentration of homocysteine and carnitine are independent indicators of abnormal amino acid metabolism in uraemic patients.

Treatment of steroid-dependent bronchial asthma with cyclosporin.

The treatment of chronic severe asthma is unsatisfactory for many patients. The aim of the study was to determine the effects of treatment of steroid-dependent asthma with cyclosporin. We performed a double-blind, placebo-controlled, randomized, parallel group trial on the effect of cyclosporin on pulmonary function, asthma severity and tapering of prednisone in 34 steroid-dependent asthmatics (mean oral prednisone dose: 16 mg.day-1). The study consisted of: 1) baseline period (12 weeks); 2) experimental period divided into two parts: Part I (12 weeks) cyclosporin or placebo treatment; Part II (22 weeks) cyclosporin or placebo treatment and oral prednisone reduction; and 3) follow-up observation (8 weeks). Asthma symptoms score, pulmonary function tests (daily peak expiratory flow (PEF) and bi-weekly forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and maximal mid-expiratory flow (MEF50), biochemical profile and blood cyclosporin levels were monitored throughout the study. Following cyclosporin administration, a slight beneficial effect on some subjective parameters of asthma severity was observed. At the same time, no beneficial effect on pulmonary function was noted. The time trends analysis of mean daily prednisone doses between the treatment groups revealed a statistically significant difference indicating that, during prednisone reduction, cyclosporin seemed to be slightly more efficient than placebo in reducing the requirement for systemic corticosteroid, even though the steroid reduction was accompanied by slight impairment of some pulmonary function. However, there was no significant difference in the final dose reduction between the treatment groups. These data and the known toxicity of the drug suggest a limited place for cyclosporin treatment in steroid-dependent bronchial asthma.

[Biological testing of the fibrogenic effect of dust from the "Sosnowiec" mine on the lung tissue]. / Biologiczny atest zwlókniajacego dzialania pylów z kopalni "Sosnowiec" na tkanke plucna.

In order to determine biological aggressiveness of settled dusts (mechanical, crumbled) and dusts collected using the gravimetric method, experimental studies were carried out, including: 1) evaluation of the physicochemical parameters (size of dust particles, content of silica, metals and other chemical compounds), 2) evaluation of the haemolytic activity, 3) experimental evaluation of fibrogenic potentials by means of: a) intraperitoneal test--to identity morphological type of reactive changes in the peritoneum and b) intratracheal test--to determine the level of hydroxyproline (collagen) in lungs and the morphological type of reactive changes. Albino rats were used for the experiment. The animals were divided into ten groups which received a single intratracheal injection of 50 mg of mining dust in 0.9% NaCl suspension. Comparative evaluation of biological aggressiveness of mining dusts was conducted basing on the findings of collagen levels in lungs. After the end of the experimental period (3 and 6 months, respectively) histopathological a examination of the lungs and mediastinal lymph nodes was made and the collagen levels in the pulmonary tissue (following Stegemann) were determined. As evidenced by the results of the pathomorphological examination and a statistical analysis: 1) after intratracheal injection the mining dusts induced changes within the respiratory system e.g. inflammatory process and emphysema. The exposure also brought about double increase of collagen level as compared to the control group, 2) histopathological study of the lungs and lymph nodes did not reveal progressive development of fibrogenic changes, 3) cytotoxic test showed differences in the haemolytic activity of settled dust and dusts collected by the gravimetric method.

[Comparative evaluation of the effects of detergents Emulkop and Rokafenol N-8 on the aggressiveness of coal mine dust in the aspect of prevention of its biological effect]. / Porównawcza ocena wplywu detergentów Emulkop i Rokafenol N-8 na agresywnosc pylów kopalnianych wegla w aspekcie biologicznej profilaktyki przeciwpylowej.

Comparative studies on the impact of the detergents Emulkop and Rokafenol N-8 upon the development and course of experimental pneumoconiosis caused by mine dusts were carried out. Albino rats and rabbits were used for the experiment. Methodological assumptions were based on the analogy with the conditions observed at the workplaces where some means of dust control were used. The acute toxicity evaluation was based on determination of the medial lethal dose (DL50) after intragastric administration of the detergents. Irritating action of the detergents on the skin was also evaluated. The effect of the detergents on the aggressiveness of selected dusts was estimated by means of the intratracheal and intraperitoneal tests. At the end of the experimental period (3 and 6 months, respectively) histopathological investigations of the lungs and mediastinal lymph nodes were carried out, and the hydroxyproline (collagen) levels in the pulmonary tissue were determined. According to Hodge and Sterner Chemical Substance Toxicity Classifications, Emulkop has been classified as non-toxic, and Rokafenol N-8 as a weakly toxic substance. On the basis of the investigation results obtained it has been established that: 1) Rokafenol N-8 does not qualify for use in coal mines as a formulation designed for dust control because it doesn't eliminate coniotic changes and causes a significant increase in the level of hydroxyproline (collagen) in pulmonary tissue, 2) in the case of Emulkop our studies have shown that this detergent can be used to prevent pneumoconiosis in coal mine workers.

[Evaluation of fibrotic effects from dusts originating from KWK "Brzeszcze" on lung tissue]. / Ocena zwlókniajacego dzialania pylów pochodzacych z KWK "Brzeszcze" na tkanke plucna.

In order to determine biological aggressiveness of settled dusts and dusts collected using the gravimetric method, experimental studies were carried out, including: 1) evaluation of the physicochemical parameters (size of dust particles, content of silica, metals and other chemical compounds); 2) evaluation of the haemolytic activity; 3) experimental of evaluation fibrogenic potentials by means of: a) intraperitoneal test--to identify morphological type of reactive changes in peritoneum and; b) intratracheal test--to determine the level of hydroxyproline (collagen) in lungs and the morphological type of reactive changes. Albino rats were used for the experiment. The animals were divided into ten groups which received a single intratracheal injection of 50 mg of mining dust in 0.9% NaCl suspension. Comparative evaluation of biological aggressiveness of mining dusts was conducted basing on findings of collagen levels in lungs. After the end of the experimental period (3 and 6 months) histopathological examination of the lungs and mediastinal lymph nodes was made and the collagen levels in the pulmonary tissue (following Stegeman) were determined. As evidenced by the results of the pathomorphological examination and statistical analysis: 1) after intratracheal injection the mining dusts induced changes within the respiratory system e.g. inflammatory process and emphysema.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclosporin for steroid-dependent asthma.

We used cyclosporin to treat 12 adult patients with severe bronchial asthma who had been on systemic steroids for an average of 16 years. During the baseline period, lasting 4-6 months, therapy with high doses of inhaled beclamethasone, aminophylline and salbutamol was standardized and a minimum necessary dose of systemic steroids was established. After 9 months' treatment with low-dose cyclosporin (average whole-blood trough levels of 105 ng/ml), in six patients the daily dose of oral prednisone could be reduced from mean 30 mg to mean 11 mg, while daily symptom scores and peak expiratory flows improved significantly. This was accompanied by a reduction in exacerbations of asthma. However, in six other patients attempts to taper the steroid doses were unsuccessful, and cyclosporin was stopped after 4 to 7 months. These preliminary results suggest that cyclosporin might be of benefit in some patients with steroid-dependent asthma.

Incides of lipid peroxidation in patients with hypercholesterolemia and hypertriglyceridemia.

Peroxidation of lipoproteins has received attention recently in connection with its possible initiation and propagation of atherosclerosis. We studied indices of lipid peroxidation in plasma of 30 patients with either hypercholesterolemia or both hypercholesterolemia and hypertriglyceridemia, and compared them with those of 19 healthy subjects. In the patients lipid hydroperoxides measured both iodometrically and as thiobarbituric acid-reactive substances (TBA-RS) were significantly increased, while concentrations of thiol groups remained unchanged. There was no correlation between concentrations of hydroperoxides and TBA-RS, possibly because the two methods assessed different breakdown products of lipid peroxidation. Lipid hydroperoxide levels, but not those of TBA-RS were correlated with LDL-cholesterol and triglyceride levels. In 6 patients administration of vitamin E at a daily dosage of 300 mg for 4 to 6 weeks depressed elevated hydroperoxides by 33%, and TBA-RS by 44% on average.

Dietary supplementation with vitamin E in hyperlipoproteinemias: effects on plasma lipid peroxides, antioxidant activity, prostacyclin generation and platelet aggregability.

In a placebo-controlled trial healthy volunteers and patients with hyperlipoproteinemias types II and IV received orally vitamin E at doses of 300 mg and 600 mg daily for 2 weeks. Serum tocopherol levels increased two-fold, but serum concentrations of total lipids, cholesterol, triglycerides, ceruloplasmin and transferrin remained unchanged. Dietary supplementation with vitamin E suppressed elevated concentrations of plasma lipid peroxides and this effect was correlated with an increase in serum antioxidant activity. In patients a mild platelet suppressant effect of vitamin E (600 mg daily) was observed. Feeding an atherogenic diet to rabbits for a week resulted in elevation of plasma lipid peroxides and a 90% decrease in arterial generation of prostacyclin. Enrichment of the atherogenic diet with 100 mg vitamin E daily prevented the increase in plasma lipid peroxides and protected the prostacyclin generating system in arteries. Thus, in hyperlipoproteinemias vitamin E corrects certain abnormalities of lipid metabolism which might predispose to atherosclerosis.

Serum lipoproteins, lipid peroxides and prostacyclin biosynthesis in patients with coronary heart disease.

Serum low-density lipoproteins (LDL) and high-density lipoproteins (HDL) were prepared by gradient ultracentrifugation and dialysis from 12 healthy subjects and 15 patients with coronary heart disease and hyperlipoproteinemia. In both lipoprotein fractions cholesterol and lipid peroxides were determined. The effect of these lipoproteins on spontaneous prostacyclin biosynthesis in rat aortic slices was studied. Serum lipoproteins were susceptible to peroxidation during the preparation procedure. LDL were more prone to peroxidation than HDL. Little lipid peroxides were formed in lipoproteins when calcium ions had been removed by EDTA, and when butylated hydroxytoluene (BHT) was present at all stages of their preparation. LDL when prepared without these precautions either from healthy subjects or from patients with coronary heart disease markedly suppressed prostacyclin generation by rat aortic slices. This inhibition was unrelated to LDL-cholesterol, but was due to LDL-lipid peroxides. Peroxide-low LDL prepared from most of the healthy subjects and patients with coronary heart disease and concomitant hyperlipoproteinemia, did not inhibit prostacyclin biosynthesis. However, in one quarter of the patients, LDL was inhibitory. Consequently, in some patients with coronary heart disease, there operate unknown mechanisms which are responsible for the inhibitory activity of LDL on prostacyclin generation.