Biomedical subjects
Publications and source records attributed to B I Liubimov.
The use of a skin graft from the leg or back of mice or rats (10 X 20 mm) or rats (12 X 52 mm) with its further packing results in the 50 +/- 10% ruin of the distal part. The effect of different factors on necrosis change in size is quantitatively evaluated.
It was established in mouse experiments that tofranyl and ftoracizin promote rapid attainment of the maximum level of Li+ in tissues (rather than in blood) after their combined administration with LiCl. Haloperidol and to a less measure triphthazin, aminazin and phenazepam provide for Li+ accumulation in some of the organs at a higher level attainable by administering lithium chloride alone.
Rats were kept for one and six hours in a thermal chamber at a temperature of -4 degrees C under conditions of free choice between 5% ethanol and water. Study of the morphological picture of the supraoptic and paraventricular nuclei of the hypothalamus and neurohypophysis of rats that preferred alcohol or rejected it has shown an inverse relationship between marked initial preference of alcohol and resistance of the hypothalamohypophyseal neurosecretory system of the animals to hypothermal exposure that exhausts the neurosecretory function.
The new Soviet tranquilizer phenazepam given to rats intraperitoneally at a dose of 1 mg/kg daily was shown to be capable of suppressing ethanol addiction produced by 2-month intake of 5% ethanolic solution as the only source of liquid. The mechanism of this effect is likely to be related to the changes in the activity of the neurosecretory centers of the hypothalamus. The phenazepam in the treatment of chronic alcoholism.
It has been established in experiments on mini pigs of Siberian origin that phenazepam given at a dose of 1 mg/kg per os during organogenesis has no embryotoxic or teratogenic action. The drug content in the blood of pregnant animals was determined simultaneously. A conclusion is drawn about perspectiveness of using mini pigs for testing embryotoxic activity of drugs.
In experiments on rats it was shown that carbidine injected intramuscularly for two weeks does not effect gonadotropic action in a dose effective in experimental therapy of alcohol dependence (4 mg/kg). The drug neither potentiates adverse after-effects of chronic action of ethanol on ovo- and spermatogenesis nor slows down the course of the reparative processes in the gonads after ethanol is discontinued. However, further regressive changes in the gonadal generative elements were recorded in administering carbidine against the background of continued use of ethanol.
It was revealed in experiments on rats treated with a 5% ethanol solution with equal quantities of LiCl (experiment) and NaCl (control) for seven weeks as the only source of liquid that with li+ concentration in the blood plasma of approximately 0.6 meq/1 LiCl prevented the development of alcohol dependence. On studying the neurosecretory hypothalamic nuclei, hypophysis and adrenal cortex of the same animals a certain correlation has been demonstrated between the morphofunctional condition of the mentioned formations, the degree of ethanol preference development and the character of LiCl influence on the process.
Ethanol, used for 2 months in a 5% solution, disorganized the circadian cycle of the hystophysiologic activity of the rat epiphysis. During prolonged (course) administration in the doses close to those used at the clinic lithium chloride normalized the mentioned changes and also prevented their development in case of joint two-months use of ethanol and lithium salt. This effect of the drug correlates with the inhibition or prevention of the ethanol preference development observed under these perimental conditions. A possible interrelationship between the discovered capacity of lithium salt to normalize the chronobiological derangements of the epiphysis and clinical efficacy of these salts in alcoholism and other affective periodical disorders is discussed.
A selective uptake of ethanol by presenting its 5% solution as the only source of fluid was elaborated in rats for 2 months. It was found that lithium chloride injected intravenously in a dose of 35 mg/kg twice per 24 hours for 14 days depressed the ethanol preference causing a motivation inversion whose mechanism was associated with the changes in the activity of the hypothalamic centres of the neuroendocrine regulation. A possibility of lithium salts in the therapy of chronic alcoholism is discussed.
The influence of fluorophenazine on succinic-, citric acid-, NAD-H2-and NADP-H2-dehydrogenases in different structures of rat brain was investigated by histochemical methods. Three hours after a single subcutaneous injection of fluorophenazine (1 and 5 mg/kg) the enzymatic activity was the greatest in the limbic and the frontal regions of the cortex. The inhibitory effects of fluorophenazine in these structures were greater than those of the neuroleptics trifluoroperazine, chlorpromazine.
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Dynamics of nonachlazine, a new anti-anginal agent, distribution in organs following its single and repeated introduction in the form of a potion and aqueous solution was studied in tests with albino rats. It was ascertained that on introduction of a ready for use medicinal preparation (potion) the drug is absorbed by the blood and enters internal organs at a quicker pace than does its aqueous solution. The type of the medicinal preparation of the drug has no relevance to the rate of its elimination from the organism. With its repeated introduction (over a space of 12 days) the nonachlazine level in the heart and kidneys goes up, whereas its content in the blood and liver experiences but a slight change.
The psychotropic activity, the content in the organs and tissues, the acute and chronic toxicity of phthorphenazine-depot - (phthorphenazine-decanoate)-2-triphthormethyl-10-/3/1-(beta-caprionyl-oxyethyl)-piperazinyl-4/-propy/phenothiazine - were studied as contrasted against phthorphenazine dehydrochloride. Phthorphenazine-depot has been found to display a prolonged action, a single injection being sufficient to depress conditioned avoidance reflexes for a period of 45-50 days. The antagonism of the drug to phenamine is manifest for 30 days after its administration. After 17 days from the instant of its introduction phthorphenamine is capable of prolonging the anesthetic action of sodium thiopental. Upon a single administration phthorphenazine-depot continues to be in evidence in the tissues of organs and in the blood over a period of 4-5 weeks. The drug is little toxic, this having been ascertained in the course of acute and chronic experiments.
In tests set up on albino rats, guinea pigs and dogs chronic toxicity of aetmozine--a new antiarrhythmic drug used enterally in a dose of 35 mg/kg for periods of 1.3 and 6 months was studied. With different follow-up periods aetmozine was found not to lower the weight gain of the animals, nor to have any adverse effect on the blood and act as a local irritant. Histopathological changes occurring in the internal organs of the animals are of a reversible nature. Single oral administrations of the drug in a dose of 300 mg/kg at different terms of pregnancy did not produce any embryotoxic or teratogenous effects in rats.
Administration of ethanol (5 g/kg/day, per os) to the pregnant rats evoked delayed impairments of the learning and memory in the offspring. Prenatal alcoholization of the animals attenuated the habituation of the exploration behavior in open field, impaired acquisition and retention of active avoidance in a shuttle box, increased slow activity of the EEG spectrum power, disturbed the function of the serotoninergic system in the brain cortex and of the dopaminergic system in the hippocamp. The new nootropic drug nooglutyl (N-5/hydroxynicotinoyl/-L-glutamic acid) administered in a dose of 25 mg/kg/day from the 8th to the 20th day of life prevented the above-mentioned delayed disturbances of higher integrative functions and biochemical processes in rat brain.
A study was made of the effect of zixorin, an inductor of liver cytochrome P-450, on the intensity of the immediate type allergic reaction--active food anaphylaxis in response to ovalbumin in guinea-pigs. Intraperitoneal injection of zixorin in a dose of 50 mg/kh for 3 days before administration of the antigen resolution dose was found to lower 2,3-fold the level of lethal outcomes due to the anaphylactic shock. It is suggested that zixorin may be used in multimodality treatment of food allergy.
An attempt is made to elucidate the pathogenesis of polyuria arising consequent upon medication of affective states with lithium salts. Experiments conducted with 54 male-rats showed that changes in the neurosecretion of supraoptic nuclei of the hypothalamus and neurohypophysis that take place after a course-wise intraperitoneal administration in amounts of 200 mg/kg (2/9DL20) of lithium chloride per 24 hours for a duration of 6 days occur parallel with histochemical changes of renal acid muconpolysaccharides and they accord with the nature of diuresis disorders. By the 5th day of the experiment the compound perverts the antidiuretic effect of a single subcutaneous injection of pituitrin (10 U/kg). The authors infer therefrom that polyuria emerging after introduction of lithium salts is caused by a deranged synthesis and secretion of the diuretic hormone and also by the ability of lithium to mitigate the action of this hormone on the kidneys.
Experiments on rats with myocardial infarction induced by occlusion of the left coronary artery were made to explore the influence of calcium antagonists injected intraperitoneally for a long time (daily, for 21 days) on hemodynamics, contractile function and morphology of the heart muscle. It has been shown that verapamil (0.5 mg/kg), diltiazem (2 mg/kg) and nimodipine (20 micrograms/kg) do not exert under those conditions any noticeable effect on pump and contractile heart functions. Administration of verapamil in a doze of 2 mg/kg enhanced heart failure. The drugs under study normalized the response of contractile heart function to volumetric load, which is related to a considerable measure to the acceleration of reparative processes in the myocardium.