Effect of furosemide on transport of organic substances in the kidneys

The effect of furosemide on maximal reabsorption of glucose on the secretion of diodone, and on the excretion of urates was investigated in chronic experiments. After a single injection of furosemide the maximal reabsorption of glucose was found to be increased in dogs. The substance was found to have no effect on the secretory transport of diodone. Furosemide has an uricosuric action in rats and dogs.Department of Pharmacology, Altai Medical Institute, Barnaul. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 84, No. 10, pp. 436–438, October, 1977.     

Substrate stimulation of renal tubular secretion of penicillin and diodone in dogs

Chronic experiments on dogs showed that repeated (three times a day for 3 days) intramuscular injection of 40 mg/kg penicillin or 100 mg/kg diodone leads to an increase in the maximal rate of secretion of these substances in the kidneys. The results are regarded as direct proof of the existence of substrate stimulation of tubular secretion of organic substances.Department of Pharmacology, Altai Medical Institute, Barnaul. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 5, pp. 530–531, May, 1977.     

Interaction between renal transport of diodone,glucose, and urates in dogs

Interaction between the renal transport of diodone, glucose, and urates was investigated in chronic experiemtns on dogs. No changes were found in the maximal secretion of diodone and maximal reabsorption of glucose in response to the combined administration of these substances. It was also shown that with maximal saturation of renal secretory and reabsorption transport the excretion of urates was not significantly altered. The results indicate that combined administration of solutions of diodone and glucose can be used to enable the maximal secretion of diodone, the maximal reabsorption of glucose, and the excretion of urates to be determined simultaneously.Department of Pharmacology, Altai Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 2, pp. 164–166, February, 1977.     

Effect of retabolil on tubular secretion of the kidneys

The anabolic steroid retabolil, in chronic experiments on dogs (2 mg/kg for 7 days) and rats (5 mg/kg for 7 days) increased the renal tubular secretion of diodone. At the same time the concentration of protein and RNA in the renal cortex was increased, which could indicate the protein nature of the carrier taking part in renal secretory transport.Department of Pharmacology, Altai Medical Institute, Barnaul. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 3, pp. 312–313, March, 1976.     

Effect of prolonged administration of nitrazepam on sleep cycles in rats

The effect of nitrazepam given as a single dose or by prolonged intraperitoneal injection, on sleep cycles in male Wistar rats was studied. In a dose of 1 mg/kg nitrazepam had no significant effect on sleep cycles whether given as a single or by prolonged injection. In a dose of 10 mg/kg a single injection of nitrazepam reduced the duration of paradoxical sleep and the number of sleep cycles during 5 h of recording, whereas prolonged (7–14 days) administration of the drug led to an increase in these indices. Withholding the drug after its prolonged administration was followed by a further increase in the number of sleep cycles and the duration of paradoxical sleep. No correlation was found between the hypnotic and muscle-relaxing action of nitrazepam during its prolonged administration.Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. Institute of Pharmacology, Czechoslovak Academy of Sciences, Prague. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 81, No. 2, pp. 188–190, February, 1976.     

Effect of sodium succinate on some indices of carbohydrate metabolism of the ischemic myocardium

The effect of sodium succinate on the concentrations of lactic and pyruvic acids and of glucose in blood draining from the ischemic zone was investigated in experiments on dogs in which the coronary artery was ligated. After intracoronary injection of the compound in doses of 2 and 10 mg/kg the lactic acid concentration was lowered in blood flowing from the ischemic zone: In a dose of 10 mg/kg sodium succinate reduced the assimilation of glucose by the ischemic area of myocardium a little. After intravenous injection of sodium succinate in a dose of 100 mg/kg the lactic acid concentration also fell significantly and the utilization of glucose by the ischemic myocardium was inhibited and its concentration in the arterial blood rose considerably. The reduction in the blood lactic acid concentration may have been due to activation of the Krebs' cycle and increased utilization of oxygen in the ischemic region of the myocardium.Department of Pharmacology, Kursk Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 12, pp. 1439–1441, December, 1976.     

Prevention by curantil of damage to the myocardium by isoproterenol

Experiments on sexually mature albino rats showed that a single subcutaneous injection of isoproterenol caused electrocardiographic and ultrastructural changes in the myocardium characteristic of ischemia and necrosis of the heart muscle and disturbances of its contractile function. Preliminary administration of curantil for 3 days to sexually mature rats in a dose of 10 mg/kg had a marked protective action on the myocardium against damage produced by isoproterenol.Department of Human Anatomy and Department of Pharmacology, Ivano-Frankovsk Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR S. V. Anichkov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 11, pp. 546–548, November, 1978.     

Use of acetylcholinesterase reactivators and of central cholinolytics in the treatment of experimental tetanus

The therapeutic efficacy of acetylcholinesterase reactivators dipyroxime and isonitrozin, and also of the central cholinolytics benactyzine and adiphenine, was studied in experiments on rabbits with tetanus produced by intravenous injection of one lethal dose of tetanus toxin. Dipyroxime in a dose of 25 mg/kg had no therapeutic action, and in doses of up to 30–40 mg/kg caused death of the animals. Benactyzine and adiphenine, in a dose of 3–4 mg/kg, abolished tonic convulsions for 1.5–2 h, and isonitrozin in a dose of 25 mg/kg did so for 4–5 h. After combined administration of reactivators and cholinolytics, convulsions were abolished for 4–5 h.Central Research Laboratory, L'vov Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 7, pp. 40–42, July, 1978.     

Effect of lithium chloride on the neurosecretory system of the rat hypothalamus

The response of the hypothalamic-pituitary neurosecretory system (HPNS) of rats to a single and repeated injection (200 mg/kg each time) of lithium chloride was studied by quantitative cytochemical analysis. The response of the HPNS was found to depend directly on the dose of lithium given and to consist of activation of synthesis and liberation of neurosecretion after a single dose of LiCl or inhibition of hormone formation in the hypothalamus and exhaustion of the reserves of neurosecretion in the neurohypophysis after a course of injections. In the recovery period (7–30 days after stopping the course of injections of LiCl) the previous state of the HPNS was gradually restored.Laboratory of General Physiology, Institute of Pharamacology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 1, pp. 32–34, January, 1977.     

Role of GABA-ergic structures in the mechanism of action of haloperidol

The effect of haloperidol on convulsions induced in mice by bicuculline and thiosemicarbazide and on recovery cycles of the primary sensomotor cortical response in rats was studied. In a dose of 0.3–0.5 mg/kg, giving a tranquilizing effect, haloperidol had a protective action against convulsions induced by blockade of GABA receptors through the action of bicuculline, and potentiated depression of the testing response in the recovery cycle of the primary sensomotor cortical response in rats, i. e., within this dose range haloperidol potentiates GABA effects. With an increase in the dose of haloperidol to 1–2 mg/kg its effectiveness in both tests disappeared. On the basis of these results and data in the literature it is suggested that the postsynaptic GABA-positive effect plays an important role in the mechanism of the tranquilizing action of haloperidol and of other neurotropic agents.Laboratory of Pharmacology of the Nervous System, Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 3, pp. 313–315, March, 1980.     

Effect of intravenous diazepam on cortical unit activity in rabbits

Changes in single unit activity were studied by a microelectrode technique in the sensomotor cortex of rabbits at different times after a single intravenous injection of diazepam (1–5 mg/kg). A few seconds after the injection of diazepam marked depression of spontaneous activity and of activity evoked by sciatic nerve stimulation was observed, together with an increase in the duration of the inhibitory pause in responses of the neurons to afferent stimulation and to direct stimulation of the cortical surface. These changes were considerably reduced 15–60 min after injection of diazepam. The results were compared with those of other workers who studied the clinical and pharmacokinetic effects of the benzodiazepines. It is concluded that the depressant effect of diazepam on cortical activity is connected with its sedative, amnesic, and anticonvulsant effect, and also that GABA plays an important role in the mechanism of these effects.Laboratory of Pharmacology of the Nervous System, Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 1, pp. 41–45, January, 1978.     

Semisynthetic human insulin and purified pork insulin do not differ in their biological potency

Summary The biological potency of semisynthetic human insulin (Actrapid HM, Novo) and purified pork insulin (Actrapid MC, Novo) was assessed in normal and diabetic subjects. The blood glucose lowering effect and the related counter-regulatory response were initially tested in six healthy subjects who received an i.v. injection of 0.15 U/kg body weight of either insulin preparation. The attained insulin levels were very similar (peak at 15 min: HM 139±7, MC 129±7 µU/ml), as well as the resulting blood glucose curves. A prolonged suppression of C-peptide values was observed after injecting both preparations. The evoked counter-regulatory response [glucagon, growth hormone (GH), cortisol and catecholamines] showed minimal differences. Prolactin secretion was almost identical after HM and MC injection. A glucose clamp study was subsequently performed in six insulin-dependent diabetic (IDD) patients. Blood glucose levels were maintained at 80 mg/dl by the artificial pancreas during a 180 min infusion of MC or HM insulin (30 mU/kg/h). The amounts of dextrose infused during the last 60 min of the study were not significantly different (121±14 vs 137±11 mg/kg/h for MC and HM, respectively). It is clear from our results that at the dose levels used in this study, the biological potency of i.v. injected HM is very similar to that of MC.Abbreviations AUC area under the concentration: time curve - EDTA ethylene diamino tetraacetic acid - EGTA ethylene glycol tetraacetic acid - GCIIS glucose-controlled insulin infusion system - GH growth hormone - HM human semisynthetic insulin - IDD insulin-dependent diabetes - MBG mean blood glucose - MC monocomponent, highly purified pork insulin Supported by Landesversicherungsanstalt Württemberg and Dotation Herbert Weishaupt e.V.Fellow of the Deutscher Akademischer Austauschdienst 1982–1984Fellow of the Deutscher Akademischer Austauschdienst 1980–1982     

The effect of ganglion-blocking drugs on the conduction velocity of nervous excitation in the sympathetic ganglia

Summary Experiments were performed on cats under urethanechloralose anaesthesia. The author studied the effect of ganglioblocking drugs, novocain and barbamyl on the condition velocity (latency) of excitation in the superior cervical and stellate ganglia. Discharges from postganglionic fibers were recorded in response to a single supramaximal electric stimulation of the preganglionic trunk.All the preparations investigated viz. tetraethylammonium (0.5–10 mg/kg), hexonium (0.5–7 mg/kg) pentamine (0.5–10 mg/kg), mecamine (0.5–6 mg/kg), novocain (15–20 mg/kg) and barbamyl (10–20 mg/kg) provoked a lengthening of the interval between the artifact of the exciting stimulus and the response discharge by 0.5–4 milliseconds, which was parallelled by a decrease of the discharge amplitude. Reduction of the synaptic conduction velocity in the ganglia occuring under the effect of the substances under investigation is regarded as a consequence of decreased functional mobility of the ganglionic neurons; it is viewed as a general manifestation of the action of gangliotics, irrespective of the mechanism of their depressive effect.(Presented by Active Member AMN SSSR V. V. Zakusov) Translated from Byulleten' èksperimental' noi biologii i meditsiny Vol. 49 No. 3, pp. 61–64, March, 1960     

Effect of hydiphen on behavior and hemodynamic manifestations of emotional stress

Hydiphen is an original Soviet tranquilizer (diphenylphosphinylacetic acid hydrazide). In a dose of 120–150 mg/kg hydiphen restores the central baroreceptor reflex regulation of arterial pressure, when depressed in cats during an acute emotional-stress reaction (confrontation with a dog). The compound has an antihypertensive antiaggressive action, and does not induce ataxia. Behavior was investigated quantitatively in animals during group interaction, using a five-point system.Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. Department of Pharmacology, First Leningrad Medical Institute. Department of Pharmacology, S. V. Kurashov Kazan' Medical Institute, Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 3, pp. 310–312, March, 1980.     

Hypothalamic self-stimulation in morphine-dependent rats during the abstinence syndrome

Rats with lateral hypothalamic self-stimulation (SS) were given morphine injections twice a day for 15 days in doses rising from 20 to 120 mg/kg. Morphine facilitated SS starting with the 9th injection. Short-term (16–18 h) withdrawal of the narcotic from the rats or its discontinuation led to inhibition of SS. Complete suppression of SS was observed after injection of the morphine antagonist nalorphine in a dose of 5 mg/kg.Department of Pharmacology, Academician I. P. Pavlov First Leningrad Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR S. V. Anichkov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 3, pp. 304–307, March, 1978.     

Changes in large dense-core vesicles in sympathetic nerve endings caused by certain drugs

An electron-microscopic investigation of the large dense-core vesicles of adrenergic nerve endings in the middle cerebral arteries of vertebrates showed that 60–70 min after injection of iproniazid (3 mg/kg) and dopamine (40 mg/kg) significant changes (compared with the control) were observed in the vesicles, the number of which was increased statistically significantly. The participation of the large dense-core vesicles in the accumulation and conversion of noradrenalin and (or) its precursors is postulated.Department of Histology and Embryology, Vladivostok Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR, V. V. Kupriyanov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 6, pp. 700–701, June, 1977.     

Effect of nonachlazine and oxyfedrine on a focus of myocardial ischemia

Experiments on dogs, using the experimental model of angina pectoris developed by Szekeres et al. and modified by the writers, showed that nonachlazine in doses of 3 and 5 mg/kg reduce or even completely prevent the elevation of the ST segment on the epicardial ECG from a focus of myocardial ischemia. Oxyfedrine in doses of 0.05, 0.1, and 0.3 mg/kg had no such action. In doses of 0.1 and 0.3 mg/kg oxyfedrine worsened the epicardial ECG.Laboratory of Pharmacology of the Cardiovascular System, Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 12, pp. 691–694, December, 1978.     

Correlation between homovanillic acid concentration in the rat brain and sensitivity of dopamine receptors to the agonist after neuroleptic administration

Experiments on male Wistar rats showed that 6–12 h after a single injection of haloperidol in a dose of 1 mg/kg the intensity of apomorphine stereotypy increased gradually, to exceed the control level after 24 h. After injection of this neuroleptic the intensity of apomorphine stereotypy showed negative correlation with the homovanillic acid concentration in the rats' forebrain. It is suggested that the homovanillic acid concentration reflects the sensitivity of dopamine receptors to agonists.Laboratory of Psychopharmacology and Department of Pharmacology, Tartu University. (Presented by Academician of the Academy of Medical Sciences of the USSR, S. V. Anichkov). Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 87, No. 6, pp. 559–560, June, 1979.     

Insulin sensitivity of muscle tissue isolated from rats with manifest alloxan diabetes of varied duration

Sensitivity of muscle tissue to insulin was studied by measuring the intensity of its action on incorporation of labeled glucose into glycogen by the isolated diaphragm of 20 control rats and 27 rats with alloxan diabetes. If the duration of diabetes was 5–8 days the sensitivity of the muscle tissue to insulin was unchanged. After alloxan diabetes lasting 22–24 days, a significant decrease was found in the sensitivity of the muscle tissue to insulin. With an increase in the duration of decompensated alloxan diabetes to 5–8 months, a further decrease in incorporation of labeled glucose into glycogen by the diaphragm was observed. The results show that the sensitivity of muscle tissue to insulin is reduced by metabolic disturbances characteristic of diabetes mellitus.Laboratory of Physiology and Pathology of the Human Endocrine System. I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR V. G. Baranov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 10, pp. 412–414, October, 1979.     

Mechanism of action of eserine on DNA synthesis in the rat liver

Eserine, in a dose of 1–2 mg/kg, inhibits incorporation of radioactive precursors into rat liver DNA by 40–50%. Eserine has a direct action on DNA synthesis in the nuclei only in high concentrations (10^–5).In vitro experiments showed that DNA-synthetic activity of hepatocyte nuclei isolated from the liver of rats receiving a preliminary injection of eserine in a dose of 1 mg/kg is significantly reduced. It is concluded that the action of eserine on incorporation of radioactive precursors into rat liver DNAin vivo is localized at the level of DNA synthesis in the nuclei. A study of the action of acetylcholine on DNA-synthetic activity of isolated liver nuclei suggests that the inhibitory action of eserine on DNA synthesis is mediated through acetylcholine.Institute of Toxicology, Ministry of Health of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR, S. N. Golikov.) Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 87, No. 1, pp. 24–27, January, 1979.