Effects of intracisternal administration of insulin on the time dynamics of behavior in rats.

The effects of intracisternal administration of insulin at doses of 2.5, 25, 50, and 200 ng on the behavior of rats in an open field test and elevated plus maze were studied at 45 min, 24 h, and nine days after single doses. On day 1, doses of 2.5 and 25 ng increased the probability of orientational-investigative behavior and locomotion in the open field, while doses of 50 and 200 ng, conversely, produced some tendency to decreases in investigative behavior (mainly at the dose of 50 ng). On day 2 after dosage with insulin, the tendency to increased investigative activity persisted only in rats given a dose of 25 ng of insulin, while on day 9 this was increased in all experimental animals independently of the insulin dose given. In the elevated plus maze, insulin doses of 2.5 and 200 ng decreased anxiety in rats during the first 5 min of testing on day one, while doses of 2.5 and 25 ng reduced anxiety in the second 5 min. On day 2, the level of anxiety increased (at doses of 50 and 200 ng) or tended to increase (at doses of 2.5 and 25 ng); on day 9, anxiety decreased in all experimental rats. Studies of the time dynamics of the behavior of rats showed that single doses of insulin had aftereffects in CNS structures, consisting of weakening of non-associative memory in the open field test on days 2 and 9 and increases in anxiety in the elevated plus maze on day 2, followed by weakening of anxiety on day 9.

[The influence of intracysternal insulin administration on the rat temporal behaviour dynamics].

Rat behaviour in the open field and elevated plus-maze was analyzed in rats after intracysternal administration of 2.5, 25, 50 and 200 ng of insulin in 45 min, 24 hrs and on the 9th day after single injection. Dose-dependent changes in 45 min occurred in both behavioural tests: insulin in low doses (2.5 and 25 ng) increased probability of locomotion and investigative activity in open field, while insulin in high doses (50 and 200 ng) did not alter locomotor activity and showed tendency to weakening of the investigative behavior (especially in the dose of 50 ng). Tendency was found in 24 hrs to increase probability of investigative behavior in open field after injection of 25 ng of insulin, although on the 9th day after insulin administration this behaviour increased in all experimental groups for all used doses. Insulin in the doses 2.5 and 200 ng decreased anxiety in elevated plus-maze in 45 min during the first five min; the doses 2.5 and 25 ng at the second five min exerted the same effect. In 24 hrs, the anxiety level increased for the doses 50 and 200 ng, and there was a tendency for an increase in the doses 2.5 and 25 ng; anxiety was decreased on the 9th day for all used doses of insulin. Thus, single insulin administration induced weakness of non-associative memory in open field on the day 2 and day 9 as well as increase of anxiety level on the day 2 and decrease of anxiety level on the day 9 in elevated plus-maze.

[Dose-dependent effects of intracisternally administered insulin on rat's behavior and glucose level].

Rat behavior in the open field and elevated plus-maze as well as glycaemia level were analyzed in rats after intracisternal administration of 2.5, 25, 50 and 200 ng of insulin. Dose-dependent changes were found in both behavioral tests: insulin in low doses (2.5 and 25 ng) increased probability of locomotion and investigative activity in open field, while insulin in high doses (50 and 200 ng) did not alter locomotor activity and showed tendency to weakening of the investigative behavior (especially in the dose of 50 ng). Significant decrease of rat anxiety level during the first 5 minutes of testing was found after administration of 2.5 and 200 ng of insulin and during the next 5 minutes after administration of 2.5 and 25 ng of insulin in elevated plus-maze. The glucose level in rats was increased in 1-2 hours after insulin administration, though glycaemia level did not exceed normal values. Thus revealed alterations of behavior are supposed to be the result of direct insulin influence on central mechanisms of activation and/or suppression of underlying behavioral characteristics of animals.

[Antioxidative defense and structural changes in the brain of rats with experimental diabetes mellitus].

The state of enzymatic and non-enzymatic components of the antioxidative defense system (ADS) and lipid peroxidation was studied in the homogenates of the brain of rats with diabetes melhtus (DM) on days 30, 60, and 90 after administration of alloxan. There was a decrease in the buffer capacity of ADS: reductions in the activities of superoxide dismutase (on DM days 60 and 90), glutathione peroxidase and antiradical activity (on day 90) and glutathione reductase (in all periods of DM). This was followed by the progressive enhancement of lipid peroxidation processes, achieving the maximum magnitude on day 90 of DM (as estimated by the level of malonic dialdehyde). Concurrent brain tissue ultrastructural analysis revealed slightly pronounced oxidative lesions of all cell elements, which enhanced by day 90 of DM. The most marked changes were found in the neuroglial cells, in astrocytes in particular, as compared with cerebral microvascular neurons and endotheliocytes. Administration of the a-lipoic acid agent espa-lipon to rats with DM produced a significant positive effect on the state of the ADS components, promoted the elimination of active manifestations of abnormal processes in the neuroglial cells and neurons and the development of compensatory and reducing processes.

[Characteristics of the rat behavior following single and multiple exposures of the hypoglycemic insulin doses]. / Osobennosti povedeniia krys posle odnokratnogo i mnogokratnykh vozdeistvii gipoglikemicheskikh doz insulina.

Rats behaviour in the "open field" changed in 2 hrs after a single episode of hypoglycaemia was abolished with glucose whereas no changes occurred in their stereotyped behaviour and intraspecies interaction. In 24 hrs quantitative parameters of the "open field" behaviour normalised although the behaviour still had an altered structure. At the same time, amphetamine-induced stereotyped behaviour's indices became reduced. These and other findings suggest some deeper behavioural changes in rats during their recovery from repeated hypoglycaemic episodes and absence of synchronisation of the insulin effects.

[Structural changes in platelets in alloxan diabetes as parameters of their activation in the vascular bed and morphologic features]. / Strukturnye izmeneniia trombotsitov pri alloksanovom diabete kak pokazateli ikh aktivizatsii v sosudistom rusle i osobennostei morfoobrazovaniia.

The present study shows that a stable level of blood platelet number persists in diabetic rats (following 15 and 60 days after experimental alloxan injection) Unusual platelet megaforms are seen accumulating (up to 36%), having no size analogs in control animals. A quantitative electron-microscopic analysis demonstrated that the enlargements of diabetic platelets was accompanied by their rounding in shape and by a more frequent (by 2.0-2.6 times) generation of surface pseudopodia. The share of platelets increased in two independent fractions, with considerable deflexion over the normal range limit variations in the number, size and general volume of their alpha-granules (cutting down) or dense (increase) bodies. At the same time a common decrease in these indexes for different types of grains in platelets of various dimensions occurred. The integral picture of the platelet granular apparatus (image of granular apparatus), that demonstrates quantitative proportions between the number and size indexes of different grain types, is found distorted in diabetic rats.

[The microcirculation in the mesentery of rats and thrombocyte aggregation during hypoglycemic coma]. / Mikrotsirkuliatsiia v bryzheike krys i agregatsiia trombotsitov pri gipoglikemicheskoi kome.

Sensitivity of the rat arterioles to epinephrine was not changed in hypoglycaemic coma (HC). However, a double threshold dose of epinephrine induced a faster and stronger vasoconstriction in the HC. The thrombocyte ADP-inducing aggregation was lowered in the HC. The data obtained can be useful for correction of severe hypoglycaemic cases.

[Lipid peroxidation in experimental arterial hypertension]. / Perekisnoe okislenie lipidov pri éksperimental'noi arterial'noi gipertenzii.

The studies were conducted on mature non-inbred male rats. Renovascular hypertension (RAH) was induced by aortic ligation between the renal arteries. The rats were included into the experiment following 14 days (acute PAH) and 1.5 months (chronic RAH) of ligation. The hypertensive rats displayed activated lipid peroxidation (LPO) processes, especially in rats with severe chronic PAH that had elevated serum levels of dienic conjugates and malonic dialdehyde as compared with control rats. Concurrently, the status of some antioxidative systems of the body was assessed--the concentration of tocopherol-like compounds and total sulfhydryl groups were measured. There were no changes in the levels of tocopherols in RAH rats as compared with the control, regardless of the duration of RAH. The content of total sulfhydryl groups declined in rats with acute RAH, in those with chronic RAH in particular, which is likely to be due to the depletion of reducing equivalents involved in the protection of cellular membranes from LPO metabolites excessively formed in RAH.

[The reactivity of the mesenteric arterioles to adrenaline in metabolic coma]. / Reaktivnost' arteriol bryzheiki k adrenalinu pri metabolicheskoi kome.

The reactivity of mesoappendix arterioles to applicated epinephrine application was investigated in 2 models of metabolic coma, hypoglycemic and acetonemic. Hypoglycemic coma (HC) was induced by insulin injection (20 IE/kg) i. m. to rats fasting for 18 hours. Acetonemic coma (AC) was induced by i. v. acetone injection (5.5 mmol). The sensitivity of arterioles to applicated epinephrine did not change in HC and increased twofold in AC vs. the control values (p < 0.01). The reaction of arterioles to injection of double threshold dose of epinephrine in HC developed sooner and the degree of vasoconstriction was 41% higher than in controls. In AC the reaction developed two times sooner and the degree of arterioles constriction was 1.5 times higher vs. the control (p < 0.01).

[Aggregation of blood platelets and their energetic status in acute arterial hypertension]. / Agregatsiia trombotsitov i ikh énergeticheskoe obespechenie pri ostroi arterial'noi gipertenzii.

The authors studied thrombin-induced aggregation of blood platelets washed clean of plasma and some parameters of their energetic status (content of ATP, ADP, and glycogen) in rats with acute vasorenal hypertension (AVH). Sensitivity of platelets to thrombin, the inductor of aggregation, was found to be increased and the initial aggregation in rats with AVN accelerated as compared to that in the controls. At the same time, the total adenine nucleotide content in platelets of rats with AVH was reduced--the ATP content by 33% and the glycogen content by 27%. The data obtained provide evidence that there is no correlation between the ATP and glycogen content in rat platelets and their ability for aggregation.

[Vasculo-thrombocyte hemostasis in arterial hypertension]. / Sosudisto-trombotsitarnyi gemostaz pri arterial'noi gipertenzii.

The components of the vascular-thrombocyte hemostasis were studied in two models of arterial hypertension: the genetically determined spontaneous (SAH) hypertension and the acute renovascular one (RAH). The reactivity of thrombocytes to the aggregation inductors was increased in hypertensive rats. Disaggregation was considerably accelerated in RAH which led to a shortening of the aggregation response. The contents of serotonin free adenine nucleotides and glycogen were decreased in the thrombocyte of hypertensive rats, the serotonin exchange was altered and the aorta antiaggregation activity was enhanced. The model of laser-induced thrombosis revealed an enhancement of thrombogenesis and a reduction of thromboresistance of the vessels in SAH. The prevalence of the thrombogenesis in vessels seems to be a potentiating factor for thrombosis in hypertension.

[Enzyme profile of exudate leukocytes from diabetic rabbits]. / Enzimaticheskii prophil leukotsitov eksudata pri diabete.

In leukocytes of exudate from diabetic rabbits, the activities of hexokinase, phosphoglucomutase and glucose-6-phosphate dehydrogenase are increased, and a tendency of adenylate kinase activity to decline is observable. The activities of UDP-pyrophosphatase, UDP-glycogentransferase, 6-phosphogluconate dehydrogenase and glutahione reductase in the exudate erythrocytes in diabetes are not essentially altered. The decrease of the key enzymes of glycolysis and pentose phosphate cycle, providing the leukocytes with energy and metabolites, reduces the functional activity of leukocytes from exudate in diabetes.

[UDPG pyrophosphorylase and phosphoglucomutase activity in the liver of rats with alloxan diabetes]. / Aktivnost' UDFG-prifosforilazy i fosfogliukomutazy v pecheni krys pri alloksanovom diabete.

The UDPH-pyrophosphatase and phosphomurase activity was determined in the liver homogenates of rats with manifest alloxan diabetes. In comparison with control animals, there was a statistically significant reduction of UDPH-pyrophosphorylase and phosphoglucomutase activity (by 29 and 33%, respectively) in diabetic rats. Decreased activity of the mentioned enzymes in the liver of rats with alloxan diabetes pointed to their participation in reduction of glycogen synthesis in the liver occurring in this disease.

[Enzymatic profile of the exudate leukocytes in diabetes mellitus]. / Enzimaticheskii profil' leikotsitov ekssudata pri diabete.

The activity of enzymes regulating the processes providing functional activity of leukocytes was studied in the exudate leukocytes of healthy rabbits and animals with alloxan diabetes. Rabbits with diabetes displayed a reduction of hexokinase, phosphoglucomutase, glucose-6-phosphate dehydrogenase and adenylate kinase activity. The activity of UDPH-pyrophosphorylase, UDPH-glycogentranspherase, 6-phosphogluconate dehydrogenase and glutathion reductase showed no significant changes in the exudate leukocytes in diabetes. A reduction of hexokinase and glucose-6-phosphate dehydrogenase limiting glycolysis and the pentose-phosphate cycle, respectively, providing energy for leukocytes and important in protein metabolism of these cells, is of great significance in the reduction of functional activity of leukocytes in the inflammatory focus in diabetes.

[Development of febrile and leukocytic responses in diabetic rabbits with aseptic inflammation]. / Razvitie likhoradochnoi i leikotsitarnoi reaktsii pri asepticheskom vospalenii u krolikov s diabetom.

Diabetic rabbits displayed a statistically significant reduction of the pyretic index in comparison with control. There was some delay in the development of leukocytic reaction, although no difference in leukocytosis was observed in the diabetic and control rabbits. Leukopenia, most pronounced in control animals 18 to 20 hours after the beginning of observation, was absent in some of the rabbits with diabetes. There were seen no significant differences in the intensity of leukocytic infiltration of the inflammatory focus in the diabetic and control rabbits. A diminished pyretic reaction during aseptic inflammation in rabbits with diabetes was apparently associated with the reduced capacity of leukocytes of the inflammatory focus to release pyrogens, determining the fever.

[2 forms of UDPG-glycogen transferase in leukocytes of rabbit exudate in diabetes]. / Dve formy UDGF-glikogentransferazy v leikotsitakh ékssudata krolikov pri diabete.

UDPG-glycogen transferase existed mainly as D-form, depending on glucose-6-phosphate, and in minority as E-form in leukocytes of exudate of rabbits with diabetes and of control animals. The total enzymatic activity as well as the activity of D-form were almost the same both in leukocytes under diabetes and in control. The E-form activity accounted for 18% of the total enzymatic activity in leukocytes of diabetic rabbits and for 14% in leukocytes of control animals. Preliminary incubation of leukocyte homogenates at 37 degrees for 30 min led to decrease in the relation between the enzyme forms both in control rabbits and in animals with diabetes.

[Concentration of components of the adenylate system in the liver during cholestasis]. / Soderzhanie komponentov adenilovoi sistemy v pecheni pri kholestaze

Content of adenyl system components, inorganic phosphate as well as the glucose-6-phosphate dehydrogenase activity were studied in rat liver tissue under extrahepatic cholestasis. Cholestasis was caused by ligation of the general biliary duct. The correlation was observed between the increase in total bilirubin in blood plasma and the decrease in content of inorganic phosphate. The glucose-6-phosphate dehydrogenase activity was unaltered.