[The mechanism of action of selenium substitution in inflammatory diseases. Modification of the activity of antioxidative enzymes in patients with acute pancreatitis]. / Untersuchungen zum Wirkungsmechanismus der Selen-Substitution bei entzündlichen Erkrankungen. Beeinflussung der Aktivität antioxidativer Enzyme bei Patienten mit akuter Pankreatitis.

From 20 patients with acute pancreatitis the activities of the antioxidative enzymes glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were estimated in the blood serum immediately before and during therapy with sodium selenite. The results demonstrate significant (p < 0.01 respectively < 0.05) enhanced activities of GSH-Px under the selenite therapy. Serum SOD activities were not significant influenced by the selenium treatment. The results obtained were not dependent on the reference basis (units/mg protein or U/l serum) used.

Specific activities of antioxidative enzymes in the cochlea of guinea pigs at different stages of development.

Significant activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were found in the cochleas of guinea pigs of different ages. The specific activities of SOD and GSH-Px (expressed as units/mg protein) increased significantly from fetal animals to animals 2 days old and then to 6-month-old animals.

5-Hydroxytryptamine releasing activity in culture supernatants of guinea pig lymphocytes.

5-Hydroxytryptamine (5-HT) is not only involved in anaphylactic reactions but also in delayed-type hypersensitivity (DTH) reactions. Supernatants of cultivated guinea pig spleen lymphocytes were investigated for possessing 5-HT releasing activity. Both fractionated supernatants of mixed lymphocytes unspecifically stimulated by Concanavalin A (Con A) and fractionated supernatants of non-stimulated mixed lymphocytes decrease the 5-HT content of rabbit thrombocytes. Fractions of a molecular weight smaller than 12,500 daltons are more effective than fractions of a higher molecular weight range. The 5-HT releasing activity of the supernatants is discussed in comparison to a cell migration stimulating activity.

Pharmacokinetics and immunotoxicity.

The possibilities of different actions of xenobiotics on the immunological system are described (different cells with immunocompetence in distinct stages of development, indirect action, pharmacokinetics and especially biotransformation). Results concerning the toxic action and biotransformation are given for DOTC. The atrophy of the thymus produced by DOTC was greater in the rat than in the mouse after intravenous, intramuscular and especially after oral administration. In vitro, the spontaneous movement of lymphocytes and macrophages in rats and mice was inhibited by similar concentrations of DOTC. In mice pretreated with SKF 525 A or CCl4 the atrophy of thymus was enhanced. Detection of DOTC in the thymus of rats and mice by means of electrothermal atomic absorption spectrophotometry showed a concentration of DOTC in the micromol range per Kilogram wet weight of the organ over a period of some days after administration of DOTC in doses producing atrophy of thymus. The possibilities of a direct or an indirect action of DOTC on the thymocytes were discussed.

[Effects of dialkyl tin salts on the immune system]. / Uber Wirkungen von Dialkylzinnsalzen auf das Immunsystem.

Single intravenous administration of 8 mg/kg of di-n-octyltin dichloride (DOTC) induced in mice a reversible decrease of thymus weight, thymocyte count and antibody titer against sheep red blood cells. After 14 days the values of treated animals were not lower than the values of control groups. The proportion of T and B lymphocytes in spleen and lymph nodes was found unchanged 4--5 days after administration of DOTC. concentrations of DOTC measured in thymus and spleen of treated mice were in the range of concentrations which are toxic for thymocytes and macrophages in vitro. The activity of di-n-alkyltin salts on the thymus of mice was independent of the length of the alkyl chains in the range of 4--8 C atoms.

Effect of histamine and stress on the gastric mucosal Ca2+ content during the development of gastric ulcers.

The influence of histamine, its triazole derivative (3-beta-aminoethyl-1,2,4-triazole) and immobilization stress on the gastric mucosal Ca2+ content during the development of gastric ulcers in guinea pigs and rats was investigated. A considerable fall in the concentration of Ca2+ in gastric tissues of guinea pigs after administration of histamine 0.25 mg/kg, down to 80% (8.0 mumol/g), its derivative (1 mg/kg) to 72% (7.2 mucol/g) and stress to 76% (7.6 mumol/g) was recorded by atomic absorption-spectrophotometric techniques, while the calcium level in the controls stood at 9.9 mumole/g. Similar changes (90-65%) were seen in the blood plasma. In rats, the Ca2+-decreasing effects of stress ran closely parallel with increasing ulceration, and depended on the duration of stress. The immobilization of rats evoked a slight rise in the Na+ content of the gastric tissues. After 4 h immobilization, the tissue concentration of Na+ was increased to 116% of control levels. Cimetidine (100 mumol kg-1 more than 50% inhibited the development of gastric ulcers and prevented the change in Ca2+ concentration ions. Thus, the data suggest that Ca2+ ions take part not only in the regulation of secretion, but also in stress tissue dystrophy.

[Biochemical mechanisms of the action of cimetidine on the development of experimental stomach ulcers in rats]. / Biokhimicheskie mekhanizmy deistviia tsimetidina na razvitie éksperimental'nykh iazv zheludka u krys.

In tests on rats with the use of the atom-absorption spectrophotometry a direct relation between the number of ulcerative lesion in the stomach, caused by immobilization, and the Ca2+ and Na+ content in the tissues of this organ was noted. The Ca2+ level declined propotrionally to the duration of the stress, viz. after a 1-hour long action-down to 76 per cent (9.9 micron/g) m after 4 hours-down to 65 per cent (7.7 micron/g) and with the calcium level in controls--11.8 micron/g. The Na+ content then increased, viz. after a 4-hour long immobilization is comprised 116 per cent (0.169 mM/g). The drug cimetidine prevented the development of lesions in the stomach and averted shifts in the content of ions in the tissues. The authors conclude that the fall of the Ca2+ ions in the tissues bears proof to a disturbed energy exchange in the cells and in this way contributes to the development of ulcerative lesions.

Estimation of the Ca2+ binding by microsomal membranes from pig coronary artery using a calcium ion selective electrode.

To estimate the Ca2+ binding of microsomal membranes from pig coronary artery a modified potentiometric method was used. With this method it was possible to follow directly changes in the Ca2+ ion activity of the incubation medium down to 10(-8) moles. Compared with the Ca45-filter technique the electrometrically measuring device built up was beside the obvious advantages of a directly indicating method more fast, simple and hightly sensitive.

Calcium uptake and calcium release by subcellular fractions of smooth muscle. II. Kinetics of calcium uptake by microsomes and mitochondria from pig coronary artery and guinea pig ileum.

Calcium uptake by the microsomal and mitochondrial fractions of pig coronary artery and guinea pig ileum was studied in the presence of ATP, ATP plus oxalate and without ATP and oxalate. Microsomes and mitochondria of both smooth muscles were found to be unable to accumulate appreciable amounts of calcium in the absence of ATP. Oxalate noticeably stimulated the calcium uptake of the mitochondrial fraction from pig coronary artery but had little effect on calcium uptake by the microsomal fraction of this smooth muscle. The calcium uptake of microsomes and mitochondria from guinea pig ileum was not or only slightly enhanced by oxalate. There are typical kinetics regarding the time course and the extent of calcium uptake by microsomes and mitochondria from pig coronary artery and guinea pig ileum. In comparison, considerable qualitative and quantitative differences between both smooth muscles are observed. The high ATP-dependent calcium uptake capacity of the mitochondria from pig coronary artery and guinea pig ileum are a further argument for the hypothesis that these organelles may play an important role in the contraction-relaxation mechanism of smooth muscle.