Effect of the H2 histamine receptor antagonist on oxygen metabolism in some morphotic blood elements in patients with ulcer disease.

BACKGROUND/AIMS: Our investigations was carried out in order to examine the effect of cimetidine, ranitidine and famotidine on the generation of free radicals, lipid peroxidation and enzymatic antioxidative defense in the blood of patients with peptic ulcer disease, clinically diagnosed as gastric or duodenal ulcer. METHODOLOGY: 124 non-smoking males (aged 20-51 years), were randomly divided into 4 groups: 28 patients received intravenously 200 mg of cimetidine; 26 patients intravenously 50 mg comprised of ranitidine; 25 patients received intravenously 20 mg of famotidine; and 45 healthy men served as the control group. Superoxide dismutase activity, malonyldialdehyde concentration in blood platelets and superoxide anion generation in granulocytes were determined in all examined men. An assay of superoxide dismutase activity and malonyldialdehyde concentration were performed before drug administration and after 2 and 72 hours. Superoxide anion generation was estimated before drug administration and after 2 hours. RESULTS: Our data indicate that all examined H2 receptor antagonists stimulate superoxide dismutase activity, but after 72 hours a distinct increase was observed, in addition to a decrease of malonyldialdehyde concentration. No differences have been observed in superoxide anion generation in patients with ulcer disease or in healthy subjects before and after ranitidine and famotidine administration. Only after 2 hours of cimetidine administration was a significant increase in superoxide anion generation observed. CONCLUSION: We concluded that H2 receptor antagonists have a beneficial effect on antioxidative processes.

Effect of perindopril therapy on fluidity and potential of erythrocyte membrane from individuals with coronary heart disease.

Erythrocyte membrane fluidity and membrane potential were measured in patients suffering from coronary heart disease (CHD) and treated with perindopril. Membrane fluidity was determined using electron paramagnetic resonance (EPR) spectroscopy, and membrane potential was evaluated using potential-sensitive fluorescent dyes. CHD does not change membrane fluidity at the depth of the 5 carbon in the fatty acid chain of membrane phospholipids. However the hydrophobic core of the membrane is altered in CHD. For 19 CHD patients, the correlation times tau B and tau C of a spin label 16DS were higher than for controls: tau B = (1.84 +/- 0.04) x 10(-9) s and tau C = (2.54 +/- 0.04) x 10(-9) s vs. tau B = (1.62 +/- 0.06) x 10(-9) s; and tau C = (2.24 +/- 0.07) x 10(-9) s (results given as mean +/- SEM). Such results indicate the increased microviscosity in hydrophobic regions of CHD erythrocyte membranes in comparison with controls. Perindopril therapy partly abolished these changes. The membrane potential of CHD red blood cells -17.89 +/- 1.36 mV was higher than the control value -9.83 +/- 0.59 mV. Perindopril treatment shifted the membrane potential value to -13.45 +/- 0.99 mV when measured after a single dose of the drug, or even depolarized the membrane after 7 days of therapy -4.95 +/- 0.73 mV. It is concluded that the erythrocyte membrane is more rigid and hyperpolarized in CHD, and perindopril therapy partly abolishes these changes as early as 3 h after administration.

Oxygen metabolism in blood of patients with gastric and duodenal ulcer disease.

Among multiagent mechanisms causing peptic ulcer disease, oxygen free radicals hypothesis is reasonable. Our investigation concerned the determination of oxygen free radicals generation lipid peroxidation and enzymatic antioxidative defense in blood of patients with peptic ulcer disease. The examinations were performed in 79 males, non-smokers, aged 20-51 with peptic ulcer disease, clinically diagnosed as gastric or duodenal ulcer. Biochemical investigations were carried out on blood platelets obtained from venous blood according to the centrifugation fractionation technique. Superoxide dismutase (CuZn-SOD) (EC 1.15.1.1.) activity and malonyl dialdehyde (MDA) concentration were determined according to Misra and Fridovich (1972) and Placer et al (1966) methods, respectively. Oxygen free radicals as the superoxide anion O2- generation in blood according to Bellavite et al. (1983) method was determined. The results indicate that patients with peptic ulcer disease have a higher level of malonyl dialdehyde in blood platelets, whereas the superoxide dismutase activity is significantly decreased in comparison with the control group. Oxygen free radicals generation both in patients with peptic ulcer disease as in healthy men is maintained at normal level. Our data suggest that in spite of similar range of oxygen free radicals generation both in patients with peptic ulcer disease and healthy men, the injury to patients by superoxide anion is more destructive and harmful to cells, because the enzymatic antioxidative defense is decreased. The increase of lipid peroxidation in patients with peptic ulcer disease also supports this conclusion.

[Clinical effectiveness of acipimox and fenofibrate in patients with hyperlipoproteinemia type II]. / Skutecznosc kliniczna acipimoxu i fenofibratu u osób z hiperlipoproteinemia typu II.

Hypolipaemic effectiveness and unfavourable effects of acipimox and fenofibrate were evaluated in patients with essential hyperlipoproteinaemia type II. The studies were carried out in two groups of 30 patients each. The studied patients were treated for three months with diet, and for another three months one group received acipimox (750 mg/day), and the other group was given fenofibrate (300 mg/day). After three months of pharmacological treatment in both groups a statistically significant decrease was seen of the concentrations of total cholesterol (by 13.8% and 19.3% respectively), LDL cholesterol (by 16.3% and 22.1%). TG (by 22.7% and 28.9%). The increase of HDL cholesterol concentration (twofold increase after fenofibrate) was non-significant. Desired LDL cholesterol values were achieved in eight patients (26.7%) treated with fenofibrate and in two patients (6.6%) receiving acipimox. Both drugs were well tolerated. Unfavourable effects were slight and did not require drug withdrawal.

Changes in antioxidant enzymes activities, aggregability and malonyldialdehyde concentration in blood platelets from patients with coronary heart disease.

In 41 patients with coronary heart disease (CHD) the concentrations of total blood platelet malonyldialdehyde (MDA: 2.11 +/- 0.25 nmol/10(9) platelets) and MDA corresponding to thromboxane A2 (TXA2 0.84 +/- 0.13 nmol/10(9) platelets) were increased in comparison with values in blood platelets of healthy subjects (1.19 +/- 0.09 and 0.71 +/- 0.05 nmol/10(9) platelets), respectively. The increased aggregability with ADP and thrombin of patient platelets was also observed. In relation to the blood platelets of healthy subjects, the antioxidant enzymes activities of patient blood platelets were significantly (P < 0.001) decreased. Platelet glutathione peroxidase (GSH-Px) activity of the patients (11.3 +/- 0.85 U/g protein) was significantly lower than controls (18.3 +/- 1.12 U/g protein). In patients with CHD the activities of the other antioxidative platelet enzymes: catalase (Cat, 7.37 +/- 1.38 U/g protein) and superoxide dismutase (SOD, 1529.4 +/- 167 U/g protein) were also significantly decreased in comparison with values for healthy subjects (Cat: 9.06 +/- 1.30 U/g protein and SOD: 1987 +/- 230 U/g protein, respectively). It is suggested that antioxidative defense in blood platelets may affect the haemostatic processes and lipid peroxidation in patients with CHD.

[Captopril treatment--2-year period of observation]. / Leczenie kaptoprylem--2-letni okres obserwacji.

Captopril was administered to 50 carefully selected patients with severe circulatory failure (18 patients classified as class III and 32 as class IV according to NYHA) in daily dose of 37.5-75 mg for two years. Patients were also given digoxin, diuretic agents and iso-dinitrosorbide. Clinical improvement increased with duration of captopril therapy. A significant improvement following the correction of therapy was achieved in 15% of patients, following one month in 28%, three months--in 70%, and after 1 and 2 years in 84% of the treated patients. All patients survived for one year, and 44--for two years (88%). Clinical improvement was manifested by: diminished of dyspnoea, edema, pulmonary and liver congestion, increase in left ventricle ejection fraction, change of disease staging by one or two NYHA classes, and reduced ventricular rate during atrial fibrillation (in 30% of patients within one year). More noticeable improvement was seen in patients with baseline ejection fraction > 40% than those with EF < 30%, in hypertensive patients than normotensive, and in patients classified to III NYHA class. Ejection fraction increased from 37.9 +/- 9.2% before the treatment to 54.6 +/- 7.7% after a two-year captopril therapy (p < .01). Captopril greatly contributes to the successful therapy of the chronic severe heart failure.

[The effect of suloctidil and acetylsalicylic acid on eicosanoid synthesis in human platelets]. / Wplyw syloktydylu i kwasu acetylosalicylowego na synteze prostanoidów w krwinkach plytkowych czlowieka.

The study aimed at comparing an effect of suloctidil and acetylsalicylic acid on malonyldialdehyde levels resulting from the arachidonic acid metabolism in blood platelets. It was shown that inhibitory effect of suloctidil is more potent than that of acetylsalicylic acid. Therefore the first is more inhibitor of an enzymatic metabolism of arachidonate in blood platelets than the latter.

Effect of cisapride and cimetidine on 24-hour intraesophageal pH monitoring in patients with gastroesophageal reflux disease.

In 16 patients with symptomatic gastroesophageal reflux disease (GERD) 24-h intraesophageal pH monitoring (Medilog 1010, Oxford) was carried out after placebo, cisapride (4 x 5 mg) and cimetidine (3 x 200 mg plus 400 mg at bedtime). The per cent time at which intraesophageal pH < 4.0 (refluxive time) was analysed. Cisapride shortened daytime and postprandial refluxive time from 16.1 +/- 14.5% and 12.6 +/- 9.2% to 5.1 +/- 4.4% and 7.5 +/- 6.5%, respectively (p < 0.01, p < 0.05). Whereas, cimetidine shortened particularly night refluxive time from 24.7 +/- 14.1% to 8.8 +/- 6.9% (p < 0.01) and total time from 20.4 +/- 12.8% to 12.0 +/- 6.4% (p < 0.05).

[Effect of cimetidine on the heart conduction system]. / Wplyw cymetydyny na uklad bodzcowo--przewodzacy serca.

An effect of cimetidine on ECG records has been investigated in a group of 40 patients with gastric or duodenal ulcers and coexisting circulatory disorders. For this purpose ECG has been recorded with Holter's technique (Medilog 2000) together with ECG-recording using high amplifying technique. An intravenous injection of 200 mg of cimetidine produced in some of patients inhibition of the sinus rhythm atrio-ventricular conduction disturbances as well as changes in the end phase of ECG ventricular image. The authors suggest, that intravenous administration of cimetidine to patients with cardiac diseases should be monitored with ECG recording.

Effect of submaximal physical exercise on antioxidative protection of human blood platelets.

The study was performed on healthy volunteers subjected to submaximal physical exercise (75% VO2max). Activities of catalase (CT) (EC 1.11.1.6), glutathione peroxidase (GPO) (EC 1.11.1.9), superoxide dismutase (ZnCu-SOD) (EC 1.15.1.1) and malonyldialdehyde (MDA) concentration in blood platelets before and after physical exercise were estimated. Physical exercise was found to induce a significant increase in the blood platelet enzymes activity accompanied by lowering platelet MDA concentration and platelet aggregability. The obtained results suggest that physical exercise has some effect on platelet reactivity and on platelet antioxidative enzymes.

[Platelet aggregation in patients with coronary disease treated with nifedipine]. / Agregacja krwinek plytkowych u osób z choroba wiencowa leczonych nifedypina.

The effect of nifedipine on the aggregation of blood platelets has been studied in patients with coronary heart disease. The study involved 78 males, aged between 36 and 64 years (mean age 51 years). The level of aggregation was evaluated before and after a single nifedipine dose of 10 mg (in 15 patients) and of 20 mg (in 34 patients) as well as before and after the treatment with nifedipine (of 29 patient) with a daily dose of 30 mg for two weeks. Aggregation of blood platelets induced by adenosine--diphosphate in of concentrations 1 microM/ml and of 5 microM/ml were estimated by the Born method. It was found that nifedipine reduces the aggregation of the blood platelets in patients with coronary heart disease following single and long-term treatment.

[Effectiveness of sucralfate in the treatment of gastric ulcer in women during menopause--comparison with cimetidine]. / Skutecznosc sukralfatu w leczeniu wrzodów zoladka u kobiet w okresie przekwitania--porównanie z cymetydyna.

The reported study was done in 60 women aged 44 to 60 years during menopause. In group I (n = 30) sucralfate was used (Venter, Krka) in doses of 1.0 g daily. The rate of symptom disappearance and ulcer healing and the frequency of recurrences were assessed. It was observed that the rate of ulcer healing after sucralfat was higher and recurrences were leas frequent.

[Superoxide dismutase activity and malonic dialdehyde level in blood platelets of patients with coronary disease]. / Aktywnosc dysmutazy ponadtlenkowej (SOD-1) oraz stezenie dialdehydu malonowego (MDA) w krwinkach plytkowych u osób z choroba niedokrwienna serca.

The investigations aimed at evaluating free superoxide radicals generation and the degree of blood platelets cell membrane lipids peroxidation on the base of superoxide dismutase activity and malonic dialdehyde level in patients with ischaemic heart disease. The obtained results have shown that blood platelets superoxide dismutase activity is markedly lower in patients with ischaemic heart disease than in healthy individuals whereas malonic dialdehyde levels are markedly higher.

[Effect of captopril on superoxide dismutase (SOD-1) activity and malondialdehyde (MDA) level in blood platelets in patients with arterial hypertension]. / Wplyw kaptoprylu na aktywnosc dysmutazy ponadtlenkowej (SOD-1) oraz stezenie dialdehydu malonowego (MDA) w krwinkach plytkowych u osob z nadcisnieniem tetniczym.

18 patients aged 40-50 with diagnosed hypertension (II class by WHO) underwent the study. SOD-1 activity, platelets MDA concentration and degree of platelets aggregation were estimated before and after 1.5 and 24 hours of administration of 12.5 mg captopril single dose. Values of evaluated parameters significantly changed after 1.5 hours of captopril administration: SOD-1 activity increased whereas MDA concentration and platelets aggregation decreased; after 24 hours of drug administration values returned to initial ones. It suggests inhibitory effect of captopril on lipids peroxidation and platelets reactivity.