Effect of chelating agents and stress factors on zinc content in paneth cells and prostate gland cells.

The effects of chelating agents dithizone and sodium diethyldithiocarbamate on zinc content in Paneth cells and prostate gland cells were studied on rats preliminary exposed to stress factors (exercise and immobilization). Dithizone induced irreversible triphasic and sodium diethyldithiocarbamate reversible biphasic changes in zinc metabolism in cells. Preliminary stress potentiated the damaging effect of dithizone.

[The effect of immunosuppressive substances on the zinc content in cells].

Decreases in zinc levels in the cells of various organs were observed in mice received cyclosporin A and sodium diethyldithiocarbamate. Glucocorticoid therapy induced a decrease of zinc levels in the granulocytes of human peripheral blood. The role of alterations in cell zinc metabolism in the mechanism of action of immunosuppressive agents is discussed in the paper.

[Epileptiform seizures induced by reagents selective for zinc].

The administration of reagents selectively responding to zinc to dogs, cats, rabbits, golden hamsters and mice induced epileptoid seizures. The convulsive action of these agents was due to zinc binding in the hippocampus.

[Diagnostic value of selective cytochemical reaction to zinc in peripheral blood granulocytes].

A method for cytochemical detection of zinc in peripheral blood granulocytes with selective reaction of 8-(p-toluenesulfonyl amino)-quinoline was developed. Zinc levels in granular leukocytes were found reduced in chronic myeloleukemia and elevated in leukemoid reactions. The method may be used for the differential diagnosis of these diseases.

[The significance of cytochemical studies of the metals in blood neutrophilic granulocytes in the diagnosis of lung diseases].

Peripheral blood smears from healthy persons and patients with pneumonia and pulmonary tuberculosis were used for a cytochemical study of metals in neutrophils with the help of dithisone and chlortetracycline. The content of metals in these cells was increased in pneumonia and active tuberculosis, but was normal or decreased in non-active pulmonary tuberculosis. It is concluded that cytochemical reactions for metals may be used in the diagnosis of pulmonary diseases.

[The effect of cyclosporin A on the islet cells of mice].

The action of immunosuppressive agent ciclosporin A on the insular apparatus was studied with an original method of cytochemical zinc detection in experiments on mice. The drug was found to lower zinc levels in pancreatic beta-cells. In ciclosporin A pretreatment the sensitivity of mice to zinc-binding diabetogenic agent enhanced.

[Zinc content of pancreatic islets in diabetes].

Content and distribution of zinc was studied in the pancreatic islets in human and rabbit diabetes. The diabetes development is followed by a decrease of zinc content in the insulin-producing cells in parallel with the severity of diabetes. The damage to the islet B-cells is the cause of zinc metabolism disturbance in the endocrine pancreas.

[Zinc contents of pancreatic islets in animals of various species after administration of diabetogenic agent, dithizone].

A decrease of zinc content in pancreatic islet was shown in animals which received diabetogenic agent dithizone. The changes of islet zinc content occurred mainly on account of insulin-producing cells and in coincidence with glycemia changes.

[Changes in lymph microcirculation in appendicular peritonitis].

When studied in experiment (63 dogs) and in clinical settings (116 patients), microlymphatic channel in appendicular peritonitis (AP) was found impaired, while lymphatic drainage of large-molecular substances and metabolites coming from the abdominal cavity appeared activated. Methods of correction of AP-induced abnormalities in microlymphocirculation have been developed which imply three levels of the impact: microcirculation, affected organ, lymphatic system. The clinical trial of the methods proved their efficacy even in the most severe AP forms.

[The dynamics of the Zn content in the pancreatic islets of rabbits after the administration of the diabetogenic agent dithizone].

The dynamics of changes of the Zn content in the pancreatic islets of rabbits after dithizon injection was studied. The amount of this metal in the islets reduced due to destruction of the cells and under the effect of high blood plasma glucose concentration. The insulin producing cells were devoid of zinc in diabetes of long duration with high hyperglycemia.

[The effect of diabetogenic substances on the zinc and calcium content in the pancreatic islet cells of rabbits].

The injections of diabetogenic drugs to rabbits induced a decrease in zinc and calcium content in B insulocytes dependent on the degree of these cells damage and hyperglycemia. The content of these metals in A insulocytes was not significantly altered due to a light injury of these cells. A high concentration of calcium in islet A cells is suggested to be a protective factor to the action of alteration agents.

The diabetogenic and acidotropic effects of chelators.

Diabetogenic and acidotropic effects of dithizone, 8-(p-toluenesulfonylamino)-quinoline and 8-(benzenesulfonylamino)-quinoline were studied in experiments on cats, rabbits, golden hamsters and mice. Selective damage of insulin producing cells, phase glycemic fluctuations and permanent diabetes development were shown to be connected with chelator zinc binding in the lysosome-segregation apparatus of these cells.

[Acidotropic effect of chelating agents on insulinocytes].

The acidotropic effect of chelates on insulocytes was demonstrated in experiments on dogs, cats, rabbits, rats, golden hamsters, and mice. On penetrating the cells these agents react with zinc and accumulate as complexes in the lysosome-segregation apparatus. The extent of damages occurring in the insulocytes in this case is determined by the amount of zinc bound by these agents.

[Effect of fasting, glucose load and dithizone injections on the zinc content in pancreatic islets of the rabbit].

The content of zinc in the pancreatic islets was increased in fasting animals and reduced after a glucose load and dithizone injection. A negative correlation between the blood sugar level and the zinc content in the pancreatic islets was encountered. A changed content of zinc in the islet cells may serve as a sensitive indicator of changes in the functional condition of the pancreatic insular apparatus.

Diabetogenic activity of chelators in some mammalian species.

The investigation of diabetogenic activity of chelators (dithizone and quinoline derivatives, was carried out in 6 mammalian species (dogs, cats, rabbits, rats, golden hamsters and mice). Rabbits are the most suitable animals for the production of diabetes with persistent hyperglycemia (permanent diabetes). The optimal conditions of such modelling are created by chelator injection of small doses to fasting rabbits.

[Mechanism of phasic fluctuations of glycemia after administration of diabetogenic substances].

Dithizone induces similar glycemic changes in rabbits, golden hamsters and mice (triphasic fluctuations resulting in diabetes). In rabbits who received 8-(p-toluenesulfonylamino)-quinoline, 8-(benzenesulfonylamino)-quinoline or alloxan, the glycemic reaction is similar to that observed after a dithizone injection. A degree of glycemic reaction to chromophiric chelants injected to animals, depends on their accumulation in the lysosome-segregation apparatus, of insulin producing cells (acidotropic action).

[Comparative histochemical study of insulinocytes and Paneth cells].

Histochemical reactions of insulocytes and Paneth cells of rabbits and rats were investigated following the injection of the agents selectively affecting the above cells, as well as of glucose, a specific stimulant of insulin secretion. The data obtained suggest a functional relation between the pancreatic islet cells and the intestinal cryptic basal regions, which is mediated by the mechanisms, involved in regulation of the glycemic level.

[Damaging action of dithizone on insulin-releasing cells].

Alterative action of dithizone was investigated in the experiments on various species of animals (fish, frogs, pigeons, mice, guinea pigs, golden hamsters, rats, rabbits, cats and dogs). The data received support the previously advanced suggestion that unsaturated (electrophilic) zinc complex formation is the basic mechanism of the alterative chelant's action.

[Toxic action of chelating agents on the animal hippocampus].

Injection of chelants into the animal body induces the development of the biphasic behavioral reaction. The first phase is marked by intensification of motor activity because of the direct chelant action on hippocampal synapses. The second phase is characterized by reduced motor activity due to the indirect chelant action on hippocampal synapses (via formation of toxic complexes with loosely bound zinc).

[Mechanism of the harmful action of chelating agents on pancreatic islet cells].

Injection of chelants into the body induces the development of intravital zinc histochemical reaction in the pancreatic islet cells. The relationship was noted between this reaction intensity, duration of zinc chelate sojourn in the cells and the degree of cell injury. It is concluded that basic to the mechanism of alterative action of chelants on the insulocytes is the formation in them of toxic complexes with zinc.

[Functional relationship between submaxillary gland and basal parts of intestinal cryptae and endocrine function of the pancreas].

The effect of fasting, glucose load and administration of the diabetogenic agent dithison on the cells of pancreatic islets, submaxillary glands and basal parts of intestinal cryptae was studied in rabbits by means of the histochemical dithison test. A potential relationship between these cells in realization of endocrine regulation of carbohydrate metabolism is suggested.