Effects of the nootropics piracetam and GVS-111 on voltage-dependent ion channels of neuronal membranes

The effect of two nootropics, piracetam and N-phenylacetyl-L-prolyglycine ethyl ester (GVS-111), is studied by measuring high-threshold K⁺ and Ca²⁺ currents in isolated snail neurons using a two-microelectrode patch-clamp technique. Piracetam and GVS-111 are shown to reduce the amplitude of both the K⁺ and the Ca²⁺ (to a lesser extent) current. The threshold concentrations for GVS-111 and piracetam are 10⁻⁹-10⁻⁸ M and 1–5×10⁻⁴ M, respectively. It is assumed that the antiamnestic effect of the nootropics is partially mediated by a blockade of ion channels of the neuronal membrane. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, N ^o 2, pp. 151–155, February, 1996 Presented by G. N. Kryzhanovskii, Member of the Russian Academy of Medical Sciences     

Modification of ethylmethane sulfonate-induced mytagenesis with adrenaline

Experiments withCrepis capillaris dry seeds show that pretreatment with adrenaline hydrochloride and adrenaline hydrotartrate significantly reduces the number of aberrations induced by the supermutagen ethylmethane sulfonate. The effective concentration ranges for adrenaline adrenaline hydrotartrate and hydrochloride are 10⁻¹–10⁻⁷ M and 10⁻³–10⁻⁷ M, respectively. Adrenaline hydrochloride is more effective than adrenaline hydrotartrate (79.1vs. 65%, respectively). Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 10, pp. 427–429, October, 1998     

In vitro effects of folic acid on γ-glutamyltransferase and glutathione reductase activities in malignant lung and thymus tumors

In vitro effects of folic acid (10⁻⁵, 10⁻⁴, and 10⁻³ M) on activities of γ-glutamyltransferase and glutathione reductase, the enzymes involved in glutathione metabolism, were studied in tissue samples obtained after surgical treatment of the lungs and thymus. Folic acid did not change γ-glutamyltransferase activity in lung cancer tissue, but in thymoma tissue this substance in a concentration of 10⁻³ M inhibited it by 16%. Folic acid had no effects on glutathione reductase activity in benign tumors and normal lung and thymus tissues, but increased this activity in thymoma and lung cancer tissues. Activation of glutathione reductase was probably related to binding of folic acid in the allosteric center of the enzyme, which probably induced conformational changes in the catalytic center, acceleration of electron transport from NADPH₂ to oxidized glutathione via flavin adenine nucleotide, and intense production of reduced glutathione. Translated fromByulleten', Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 10, pp. 422–425, October, 2000     

Effects of synthetic bis-β-chloroethylamine estrogen derivatives on proliferation of skin sarcoma cells

The effects of four new synthetic bis-β-chloroethylamine-containing estrogens and known cytostatic agents chlorophenacyl and estradiol mustard were compared on monolayer cultures of transformed L-929 fibroblasts (from murine skin sarcoma). The drugs within the concentration range of 10⁻⁵-5×10⁻⁷M inhibited proliferation of cultured cells by 67%. Chlorophenacyl displayed the least antiproliferative activity (15% inhibition at 10⁻⁵M). Steroid nucleus introduced into the molecule enhanced antiproliferative activity of test drug in comparison with chlorophenacyl, probably due to accumulation of the hormone-cytostatic molecules in cells. Estradiol had no effect on proliferative activity of L-929 cells, and no specific estrogen-binding sites were found in cultured transformed fibroblasts. The antiproliferative effect of hormone-cytostatics on this culture is not mediated via specific interactions with estrogen receptors. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 6, pp. 695–697, June, 2000     

Effect of amiridine and tacrine on the functional degeneration of the isolated neuron

Amiridine and tacrine are found to have a concentration-dependent effect on the spontaneous activity of an isolated neuron from crawfish. Amiridine in a concentration of 1 μM reliably prolongs the lifetime of the neuron, whereas lower concentrations are inactive and a high concentration (10 μM) reduces spontaneous activity. Tacrine is unable to prolong the lifetime of the neuron. It is suggested that, unlike tacrine, the therapeutic effect of amiridine stems from its ability to prolong neuronal functioning. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, N ^o 1, pp. 52–54, January, 1996 Presented by Yu. A. Romanov, Member of the Russian Academy of Medical Sciences     

Comparative study of the effect of amiridine on biological membranes

The effects of amiridine and of the comparable drugs tacrine and piracetam on synaptosomes and membranes of sarcoplasmic reticulum were studied by electron paramagnetic resonance; in addition, the effects of these drugs on the activity of Ca²⁺, Mg²⁺-dependent ATPase regulating calcium transport in neurons were investigated. In concentrations of 10⁻⁷ to 10⁻⁵ M the drugs did not affect the structure of synaptosomal membranes of rat brain. Amiridine and tacrine in a concentration of 0.1 mM reduced the rate of calcium ion transport across the sarcoplasmic reticulum membrane by inhibiting the function of Ca²⁺, Mg²⁺-dependent ATPase and induced marked changes of the structural rigidity of the protein part of the membrane. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N№ 11, pp. 503–505, November, 1995 Presented by Yu. A. Romanov, Member of the Russian Academy of Medical Sciences     

Effects of the anticonvulsant lamotrigine and carbamazepine on synaptic transmission in the CA1 area of rat hippocampal slices

Lamotrigine and carbamazepine (10⁻³ M) almost completely inhibit electrical activity of neurons in hippocampal slices. The effect of these drugs on signal transmission in the system of Schaffer collaterals/commissural fibers—CA1 hippocampal area pyramidal neurons shows that both anticonvulsants inhibit the excitability of the presynaptic axons and transmission efficiency in the glutamatergic synapses without any significant influence on signal transmission from a synapse to the spike generator region in the postsynaptic pyramidal neurons. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 9, pp. 307–310, September, 1998     

Effect of the phenol antioxidant katavidan on autooxidation of microsomes exposed to visible light

A study is performed of the effect of the phenol antioxidant katavidan on autooxidation of microsomes from rat liver exposed to visible light. It is shown that katavidan in a concentration of 10⁻³ M inhibits but in concentrations of 10⁻⁵–10⁻⁷ M stimulates autooxidation of microsomes. No stimulation is observed under conditions of dark incubation. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, № 10, pp. 393–394, October, 1994 Presented by I. P. Ashmarin, Member of the Russian Academy of Medical Sciences     

Effect of ultralow doses of thyroliberin on microviscosity of lipid components of biological membranes

Effects of the regulatory peptide thyroliberin on microviscosity of lipid components of endoplasmic reticulum biological membranes in mouse hepatocytes were studied by electron paramagnetic resonance. Thyroliberin in a concentration of 10⁻³–10⁻¹⁸ M decreased microviscosity of surface layers of membrane lipids. This decrease was the most pronounced (30%) under effects of 10⁻¹⁰ and 10⁻¹⁶ M thyroliberin. Physiological effects of thyroliberin corresponded to its influence on the membrane structure. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 1, pp. 38–40, January, 2000     

Effect of muscimol on the picrotoxinand bicuculline-induced delay in the desensitization of the GABA receptor/Cl− channel complex

Effects of picrotoxin and bicuculline on the muscimol-dependent³⁶Cl⁻ entry into synaptoneurosomes of the rat cerebral cortex are examined as well as desensitization of³⁶Cl⁻ entry at muscimol concentrations of 5 and 50 μM. At the 5 μM concentration (which is close to the muscimol IC₅₀), picrotoxin and bicuculline inhibited Cl⁻ entry into synaptoneurosomes and decreased the desensitization. At the 50 μM concentration, muscimol completely abolishes the bicuculline effects both on Cl⁻ entry and desensitization. Inhibition of Cl⁻ entry by picrotoxin is also abolished by 50 μM muscimol, whereas the picrotoxin-induced decrease in the desensitization rate is not. It is shown that both bicuculline effects result from inhibition of the GABA receptor, but the action of picrotoxin on the desensitization of Cl⁻ entry into synaptoneurosomes is not closely related to the functional activity of the GABA receptor/Cl⁻ channel complex. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 8, pp. 144–147, August, 1996     

Antioxidant properties of thiamine

Thiamine (10⁻⁴–10⁻⁶ M) inhibits lipid peroxidation in rat liver microsome and free radical oxidation of oleic acidin vitro. Thiamine interacts with free radicals and hydroperoxides and is oxidized to thiochrome and thiamine disulfide. The antioxidant effect of thiamine is probably related to sucessive transfer of 2H⁺ from the NH₂ group of the pyrimidine ring and H⁺ from the thiazole ring (after its opening) to reactive substrates. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 9, pp. 303–305, September, 2000     

Antioxidant properties of thiamine

Thiamine (10⁻⁴–10⁻⁶ M) inhibits lipid peroxidation in rat liver microsome and free radical oxidation of oleic acidin vitro. Thiamine interacts with free radicals and hydroperoxides and is oxidized to thiochrome and thiamine disulfide. The antioxidant effect of thiamine is probably related to sucessive transfer of 2H⁺ from the NH₂ group of the pyrimidine ring and H⁺ from the thiazole ring (after its opening) to reactive substrates. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 9, pp. 303–305, September, 2000     

Xymedon restores T-cell immune response inhibited by γ-irradiationin vivo: Interrelations with Ca2+-ATPase and DNA-relaxing activities

High radioprotective activity of xymedon was shown in mice. Radioprotective effects of this preparation were accompanied by restoration of the delayed-type hypersensitivity response and Ca²⁺-ATPase activity in splenocytes which were inhibited by γ-irradiation (3 Gy). At concentrations of 10⁻³ and 10⁻⁶ M xymedon stimulated the activity of DNA topoisomerase-I of splenocyte nuclei. Here we discuss a mechanism of radioprotective effects of pyrimidine derivatives associated with the inhibition of apoptosis of lymphoid cells and the stimulation of proliferation and differentiation of lymphoid precursor cells. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 1, pp. 66–70, January, 1999     

Effects of sex hormones and antihormones on the activity of redox system enzymes of human erythrocyte glutathione

Effects of estradiol and testosterone and of the antiandrogens cyproterone acetate, niftolide, and antiestrogen tamoxifen on the activities of human erythrocyte glutathione peroxidase and glutathione reductase were studiedin vitro. In contrast to hormone preperations, antihormones in high concentrations (10⁻⁴−5×10⁻⁴ M) modified the enzyme activities. Cyproterone acetate and tamoxifen increased the activity of glutathione reductase, while tamoxifen stimulated glutathione reductase and inhibited glutathione peroxidase. Niftolide inhibited both enzymes. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 8, pp. 185–187, August, 1997     

Interaction of bis-β-chlorethylamine estrogen derivatives with human ovarian adenocarcinoma cells

Antiproliferative effect of bis-β-chlorethylamine estrogen derivatives on human ovarian adenocarcinoma CaOV cells depends on the dose of the drug. In concentrations of 10⁻⁵ and 5×10⁻⁶ M they inhibit, while in a dose of 5×10⁻⁷ M stimulate cell proliferation. It is assumed that CaOV cells express estradiol receptors. The interaction of these cytostatics with estrogen-binding sites on CaOV cells is demonstrated. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 3, pp. 302–304, March, 1999     

cAMP-dependent inward rectifier current in neurons of the rat suprachiasmatic nucleus

Electrophysiological properties of the inward rectification of neurons in the rat suprachiasmatic nucleus (SCN) were examined by using the single-electrode voltage-clamp method, in vitro. Inward rectifier current (I _H) was produced by hyperpolarizing step command potentials to membrane potentials negative to approximately −60 mV in nominally zero-Ca²⁺ Krebs solution containing tetrodotoxin (1 μM), tetraethylammonium (40 mM), Cd²⁺ (500 μM) and 4-aminopyridine (1 mM).I _H developed during the hyperpolarizing step command potential with a duration of up to 5 s showing no inactivation with time.I _H was selectively blocked by extracellular Cs⁺ (1 mM). The activation of the H-channel conductance (G _H) ranged between −55 and −120 mV. TheG _H was 80–150 pS (n=4) at the half-activation voltage of −84±7 mV (n=4). The reversal potential ofI _H obtained by instantaneous current voltage (I/V) relations was −41±6mV (n=4); it shifted to −51±8mV (n=3) in low-Na⁺ (20 mM) solution and to −24±4 mV (n=4) in high-K⁺ (20 mM) solution. Forskolin (1–10 μM) produced an inward current and increased the amplitude ofI _H. Forskolin did not change the half-activation voltage ofG _H. 8-Bromo-adenosine 3′,5′-cyclic monophosphate (8-Br-cAMP, 0.1–1 mM) and dibutyryl-cAMP (0.1–1 mM) enhancedI _H. 3-Isobutyl-1-methylxanthine (IBMX, 1 mM) also enhancedI _H. The results suggest that the inward rectifier cation current is regulated by the basal activity of adenylate cyclase in neurons of the rat SCN.     

Modulation of the oxidative burst in mouse macrophages and human neutrophils by superlow concentrations of GM1 ganglioside

It is shown that ganglioside GM1 in picomolar concentrations stimulates the phorbol-12-myristate-13-acetate (PMA)-induced generation of active forms of oxygen by neutrophils and peritoneal macrophages. GM1 (10⁻¹¹ M) is found to enhance the luminol-dependent chemiluminescence induced by 10⁻⁸ M PMA in mouse macrophages in comparison with the effect of PMA alone. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 1, pp. 44–46, January, 1994 Presented by A. N. Klimov, Member of the Russian Academy of Medical Sciences     

Effects of calcium antagonists on serotonin-dependent aggregation and serotonin transport in platelets of patients with migraine

Flunarizine and cinnarizine (IC₅₀ 6.8×10⁻⁶ and 2.8×10⁻⁵ M, respectively) inhibited³H-serotonin uptake by platelets. In higher doses, they blocked serotonin-induced platelet aggregation and stimulated³H-serotonin release from these cells. Imipramine did not affect serotonin-releasing effects of preparations. In all patients cinnarizine was more potent in inhibiting serotonin uptake, and in half of the patients cinnarizine displayed higher activity as an inductor of serotonin release. Translated fromByulleten's Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 7, pp. 24–27, July, 2000     

Effects of calcium antagonists on serotonin-dependent aggregation and serotonin transport in platelets of patients with migraine

Flunarizine and cinnarizine (IC₅₀ 6.8×10⁻⁶ and 2.8×10⁻⁵ M, respectively) inhibited³H-serotonin uptake by platelets. In higher doses, they blocked serotonin-induced platelet aggregation and stimulated³H-serotonin release from these cells. Imipramine did not affect serotonin-releasing effects of preparations. In all patients cinnarizine was more potent in inhibiting serotonin uptake, and in half of the patients cinnarizine displayed higher activity as an inductor of serotonin release. Translated fromByulleten's Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 7, pp. 24–27, July, 2000     

Balysum-2 inhibitis evoked activity of the pyramidal neurons in hippocampus

The effects of Balysum-2 on the responsiveness of field CA1 hippocampal pyramidal neurons was studied in experiments with cultured cerebral slices. Addition to the medium of 10⁻⁴M Balysum-2 or its active ingredient (comenic acid) led to a reversible decrease in the peak amplitude of focal response (pop-spike) recorded in the pyramidal layer CA1 during stimulation of the radial layer. Perfusion of hippocampal slices with a solution containing the noncompetitive GABA_A-antagonist picrotoxin prevented the effects of Balysum-2 and comenic acid. Inhibition of hippocampal pyramids by Balysum-2 and comenic acid is probably caused by an incease in the inhibitory effect mediated by GABA_A-receptors. Translated fromByulleten' Eksperimental'noi Biologii I Meditsiny, Vol. 125, No. 1, pp. 63–65, January, 1998