Effect of GABA derivatives on the rate of thrombus formation, platelet aggregation, and plasma coagulation capacity in rats with experimental gestosis.

Experimental gestosis induced by replacement of drinking water with 1.8% NaCl promoted hypercoagulation, increased the rate and degree of platelet aggregation, and reduced clotting time in pregnant females. GABA derivatives, compounds RGPU-151, RGPU-152, and phenibut normalized parameters of hemostasis and platelet aggregation and the rate of thrombus formation in the animals. The efficiency of the test substances did not significantly differ from that of the reference drug sulodexide.

[Gravidaprotective action of phenibut in experimental pre-eclampsia].

It was established that the replacement of drinking water by 1.8% NaCl solution in female rats during pregnancy causes experimental pre-eclampsia (EP), as evidenced by an increase in the blood pressure, proteinuria, and edema in the control group as compared to pregnant female rats with normal drinking regime. Animals with EP exhibited disturbance of vasodilating endothelial function, microcirculation disorder, and increased coagulation and thrombogenic potential of blood. In addition, the group with EP showed evidence of the activation of lipid peroxidation (LPO) due to lower activity of antioxidant enzymes. Daily oral administration ofphenibut (25 mg/kg) in female rats with EP during pregnancy prevents the increase in blood pressure and the severity of proteinuria and edemation. Phenibut improves the vasodilator and antithrombotic endothelial functions, increases uterine blood flow, improves microcirculation, limits LPO, and increases the activity of antioxidant enzymes.

[Comparative study of the effects of new neuroactive amino acid derivatives on the postnatal development of the rat's offspring with experimental preeclampsia].

BACKGROUND: Our aim was to investigate the effect of derivatives of GABA and glutamate on the postnatal development of the offspring of rats with experimental preeclampsia. METHODS: The experiments were performed on 35 albino female rats aged 5-7 months, weighing 220-240 g, and their offspring in the amount of 284 individuals. Experimental preeclampsia was modeled by replacing the drinking water by 1.8% NaCl solution to pregnant females from 7 to 21 days ofgestation. Glutamic acid--compound RSPU-135 at a dose of26mg/kg, GABA derivative - compound RSPU-242 at a dose of 23 mg/kg and the reference drug sulodexide in a dose of 30 mg/kg administered to female orally daily, since the 7th day of gestation prior to delivery. Evaluated the physical development of offspring, sensory-motor reflexes, mental functions. RESULTS: It was found that the experimental preeclampsia causes a delay in physical development and maturation of sensory-motor reflexes in the offspring, as indicated by the later periods of eruption of the incisors and eye opening, response to the emergence of audio and olfactory stimuli, forming vestibular stability and coordination of movements compared to pups from females with physiological pregnancy. Offspring from females with experimental preeclampsia were noted for lagging behind in mental development, as evidenced by the decline of the orienting-exploratory activity, learning and memory, increase of anxiety level. Compound RSPU-135, to a greater extent, improves physical development, increases the rate of maturation of sensory-motor reflexes, RSPU-242--stimulation of cognitive functions, keeping the memory trace, orienting-exploratory, spontaneous locomotor activity, and reduce of anxiety level. CONCLUSION: The neuroactive amino acid derivatives limit the negative effects of experimental preeclampsia on the offspring.

[Effect of GABA derivative--RSMU-151 on the development of oxidative stress in rats with experimental gestosis].

Experimental gestosis induced in rats by drinking 1.8% sodium chloride solution instead of water during the entire period of pregnancy leads to activation of lipid peroxidation (LPO) process, as manifested by increased concentration of diene conjugates and malonic dialdehyde, decreased concentration of antioxidant enzymes (superoxide dismutase and glutathione peroxidase) in homogenates of rat brain, liver, uterus, and placenta. The GABA derivatives--RSMU-151 limits the damaging effect of gestosis, which is manifested by a decrease in the concentration of LPO products and by activation of the antioxidant system enzymes in all organs studied.

[Evolution of methodical approaches to solve problem of evaluating and predicting the thermal status of cosmonauts in the real flight]. / Evoliutsiia metodicheskikh podkhodov k resheniiu problemy otsenki i prognozirovaniia teplovogo sostoianiia kosmonavta v real'nom polete.

The problem of evaluating and predicting the thermal status of a cosmonaut in the long-term space mission is a pressing one and remains to be solved. The previous studies indicated that the best plan to be followed is to evaluate the thermal status of a cosmonaut during his egress into outer space with the use of the procedure of parotid thermometry of the mean body temperature.

[Conformational changes of spin-labeled native and modified phosphorylase B]. / Izuchenie konformatsionnykh izmenenii spin-mechenykh nativnoi i modifitsirovannoi fosforilazy B.

The phosphorylase B labelled with 2,2,6,6-tetramethyl-piperidine-1-oxyl-4-iodacetamide (phosphorylase I) and with 2,2,6,6-tetramethyl-piperidine-1-oxyl-4-ethylmaleinimide (phosphorylase II) was studied. It was shown that label I is characterized by a greater mobility with respect to the protein as compared to label II. In spin-labelled preparations of phosphorylase B the 1,5--2,0 SH-groups of the enzyme monomer having no effect on the enzyme activity were modified. The effects of AMP, glucose-1-phosphate and glucose-6-phosphate on the EPR spectrum of phosphorylase I were studied. The greatest changes in the spectrum (especially in the high field line) were found to occur in the presence of glucose-6-phosphate. These changes are due to the increase in the degree of anisotropic spin rotation. The experimental and theoretical spectra allowing to determine the correlation time for the protein moiety (tau b = 160 ns) were shown to be similar. The local conformation changes were found to occur in the vicinity of one of the two label-bound SH-groups of phosphorylase I. The EPR spectra demonstrate the S-shaped dependence of mobility of phosphorylase I label on concentration of glucose-6-phosphate (0,1--10 mM). In the presence of AMP no S-shaped dependence is observed. Reduced NaBH4 phosphorylase I does not reveal the S-shaped dependence of the label mobility on concentration of glucose-6-phosphate. The degree of the label immobilization in the apo-phosphorylase I--pyridoxal-5-chloromethylphosphonate complex in the presence of glucose-6-phosphate and AMP is the same as in cholophosphorylase I; however, in contrast to the choloenzyme it does not depend on glucose-6-phosphate (0,1--10,0 mM). The changes in the mobility of the spin label of apophosphorylase I and its complex with the AMP analog--adenosine-5'-chloromethylphosphonate--during the choloenzyme reconstruction by pyridoxalphosphate are indicative of participation of AMP and the phosphate group of AMP in the formation of the enzyme active center.

[Structural-functional analysis of the complex between phosphorylase B and adenosine-5'-chloromethylphosphonate]. / Strukturno-funktsional'nyi analiz kompleksa fosforilazy B s adenozin-5'-khlormentilfosfonatom.

A complex of phosphorylase B with a tritium-containing AMP analogue, adenosine-5'-chloromethylphosphonate, was obtained. It is found on the basis of the results of the determination of N- and C-terminal amino acids, amino acid composition and sequence, that the peptide 1, modified by adenosine-5'-chloromethylphosphonate, corresponds to the fragment 185-191 in the primary structure of phosphorylase B, and is probably located in the allosteric center of the enzyme. The peptide 2, which is bound with the AMP analogue and corresponds to the fragment 795-798, is suggested to be located at the site of binding the second AMP molecule. The arginine residue 184 is discussed as a possible functional amino acid protein interacting with 5'-phosphate AMP group.