[Influence of RGPU-207 compound and amiodarone on ion currents in shellfish neurons].

RGPU-207 compound and amiodarone in concentrations of 1, 10, 100 and 1000 microM produce dose-dependent and reversible effects on trans-membrane sodium, calcium, and potassium ion currents of neurons in pond snail and orb snail shellfish. In concentration of 1 microM, both compounds increased the amplitude of potassium ion currents, while not affecting the amplitude of sodium and calcium ion currents. In concentrations of 100 and 1000 microM, dose-dependent suppression of all currents (with predominant potassium ion current suppression) was observed. Under the action of RGPU-207 compound, the kinetics of activation and inactivation of sodium and calcium ion currents was not changed, but the kinetics of activation of the potassium slow current was slowing down. Amiodarone decelerated the inactivation of calcium ion current and accelerated the inactivation of potassium slow current. RGPU-207 compound, in comparison to amiodarone, produces a similar membranotropic effect on the shellfish neurons.

[Treatment of relapses of multiple sclerosis (a review)].

The most common clinical type of multiple sclerosis (MS), affecting up to 85% of patients living with this disease, is relapsing remitting(RRMS). Relapses are associated with significant functional impairment and decreased quality of life. Residual symptoms after MS relapses may persist and lead to sustained disability. Adequate management of MS relapses may help to shorten and lessen the symptoms and disability associated with their course. Systemic corticosteroids and adrenocorticotropic hormone (ACTH) have broad regulatory approval and remain the most established and validated treatment options for MS relapses. Recently, the direct anti-inflammatory effects and immunomodulatory activity of ACTH have been shown. Algorithms of using these medications for MS relapse treatment, data on plasmapheresis and perspectives of other therapeutic methods are reviewed.

[Afobazole effect on the electrical activity of neurons].

Changes in the membrane rest potential (RP), action potential (AP) and impulse activity (IA) in neurons of isolated central nervous system of Lymnaea stagnalis and Planorbarius corneus under the action of anxiolytic afobazole (2-mercaptobenzimidazole derivative) in 1, 10, 100 and 1000 microM concentrations have been studied using a microelectrode technique. It is established that afobazole produces a two-phase, dose-dependent and reversible effect on the electrical activity of neurons. Hyperpolarization by 5-8 mV in the first phase (1-100 microM) and depolarization by 8-10 mV in the second phase (1000 microM) have been observed. The corresponding changes in AP and IA parameters were due to the RP level changes related to their potential dependence and resulted from the direct activation-suppression action of afobazole on the neuron ionic currents.

[The new glutamic acid derivative RGPU-135 (glutaron, neuroglutamin) modulates ion currents in mollusk neurons].

The new glutamic acid derivative RGPU-135 (3-phenylglutamic acid hydrochloride, glutaron, neuroglutamin) produces dose-dependent and reversible modulation of transmembrane sodium, potassium and, to a greater extent, calcium ion currents in neurons of Lymnaea stagnalis and Planorbarius corneus mollusks at concentrations of 1, 10, 100, and 1000 microM. At concentrations within 1 - 10 microM micromole, Ca and K currents are activated rather insignificantly; at 100 pmole, the amplitude of calcium currents is increased by 5 - 10%; and at 1000 microM, the Na and K ion currents are suppressed by 5 - 12%. RGPU-135 does not influence the membrane surface charge potential and the gating of ion channels. The effects of RGPU-135 were quickly reversible, which indicated the relatively weak drug binding to the membrane structures and ion channels.

[Effect of migrepin on activity of trigeminal nucleus caudalis neurons].

Neurophysiological experiments on anesthetized rats were used to study the effects of various doses (12.5, 25, 37.5 mg/kg, i.v.) of drug composition migrepin (representing a combination of potassium-2,4-dichlorobenzoate, carbamazepine, and caffeine) on background firing of the trigeminal nucleus caudalis neurons and their responses to electrical stimulation of the dura mater. It was found that migrepin produces direct, dose-dependent inhibitory action on functional activity of TNC neurons. The results confirmed anti-migraine properties of the drug but did not exclude the necessity to study its action in clinical trials.

[Effect of GABA-positive drugs on the background and superior sagittalis sinus-electrostimulated activity of neurons in the nucleus trigeminalis caudalis of rats].

There is extensive clinical evidence for the high efficacy of GABA-ergic drugs in prophylactic and abortive treatment of migraine and cluster headache, while the mechanisms of anticephalgic drugs action are not clear, in particular, because of insufficient number of investigations on experimental headache models. In this study, the influence of baclofen (i.v.) in doses 2.5, 5, 10, and 15 mg/kg and valproate (i.v.) in doses 25, 50, 100, and 200 mg/kg on the background activity of the trigeminal nucleus caudalis neurons and that evoked by electrical stimulation of the superior sagittalis sinus was investigated in series of acute experiments on rats. It is established, that baclofen and valproate reduce both the background and evoked activity of trigeminal complex neurons in dose-dependent manner, thus determining the role of GABA-A and GABA-B receptors in realization of this effect. These results provide experimental basis for explanation of the clinical efficacy of the GABA-positive drugs in vascular headaches.

[Effects of digoxin and corglycon on ion currents in neuronal membrane of snail (Lymnaea stagnalis)].

The results of endocellular dialysis membrane potential monitoring show that cardiac glycosides digoxin and corglycon in concentration from 10(-12) to 10(-6) M influence the sodium, calcium and potassium ion currents in isolated snail (Lymnaea stagnalis) neurons in reversible and slightly dose-dependent manner. In low concentration (10(-12) - 10(-8) M) both substances increased all ionic currents by up to 5%, while in higher concentrations both drugs led to the suppression of ion currents. The most pronounced decrease (up to 26% relative to control) was observed for sodium ion current under the action of digoxin in a concentration of 10(-6) M. The process of slow potassium currents inactivation was accelerated by corglycon in a concentration of 10(-6) M. Digoxin caused a shift in the current - voltage curve maximum by 5 - 10 mV to the right on the potential axis. Generally, digoxin in comparison to corglycon produced less activating and more suppressing effect on the membrane ion currents studied.

[Strophanthin induced changes in the ion currents of Lymnaea stagnalis and Planorbis corneus neurons].

Experiments on isolated neurons of Lymnaea stagnalis and Planorbis corneus using the intracellular dialysis and fixed membrane potential techniques showed that strophanthin G in a concentration range from 10(-11) to 10(-6) M produce dolse-dependent reversible suppression of the ion currents in potassium, calcium, and sodium channels. At the maximum concentration (10(-6) M), the maximum suppression (up to 55% of that in the control) was observed for the calcium ion current. At the minimum concentration (10(-12) M), the drug did not influence the sodium ion current, but slightly (approximately by 5%) increased the calcium and potassium ion currents. In addition, strophanthin accelerated the inactivation of slow potassium ion currents.

[Antidepressants with different action mechanisms in the treatment of chronic daily headache].

Efficacy and safety of the following antidepressants: amitryptiline (tricyclic antidepressant), escitalopram (selective inhibitor of serotonin reuptake), milnacipran (selective inhibitor of serotonin and noradrenalin reuptake) and maprotiline (selective inhibitor of noradrenalin reuptake) have been compared during the treatment of 120 patients with chronic daily headache. A positive effect was found for all drugs, in particular in the presence of depressive and anxiety symptoms. Most effective proved to be milnacipran and amitryptiline. Escitalopram and milnacipran were more tolerable and had less side-effects. The authors suggested that the combination of noradrenergic and serotoninergic components appears to be most effective in treatment of chronic daily headache.

[The influence of ecdysteroid fraction from Serratula coronata on transmembrane ionic currents of snail neurons].

Changes of the transmembrane potassium, calcium, and sodium ion currents in isolated neurons of Lymnaea stagnalis snail under the action of ecdysteroid fraction (serpisten) from Serratula coronata L. applied from outside in 0.01 -1000 microg/ml concentrations have been studied using the voltage-clamp technique. It is established for the first time that serpisten non-selectively activates the potassium and calcium ion currents (the currents amplitude increases by 2 - 15%) and reduces nonspecific membrane leakage currents in the entire range of concentrations. The sodium ion current also increased by 4 - 7% under the action of Serpisten in low concentrations (0.01 -10 microg/ml) in comparison with control, but this current decreased by 5 -10% at serpisten concentrations of 100 and 1000 microg/ml. The effects were reversible. The kinetics of currents was not changed under the action of serpisten.

[Effect of afobazole on transmembrane ion currents in mollusk neurons].

The effect of anxiolytic afobazole (2-[2-morpholino)ethylthio]-5-ethoxybenzimidazole dihydrochloride) at concentrations of 1, 10, 100 and 1000 microM on transmembrane calcium, sodium, and potassium (slow and rapid) ion currents in isolated neurons of Lymnaea stagnalis mollusks have been investigated. Afobazole was found to produce a dose-dependent reversible action: the drug increased all ion currents at concentrations below 100 microM and inhibited all ion currents at concentrations from 100 to 1000 microM. Afobazole at high concentrations accelerated the inactivation of slow potassium ion current and reversibly inhibited the fast potassium ion current.

[A comparative study of the effect of brazidole, amiodarone, sotalol, and hydroxyzine on potassium ionic channels of mollusks neurons].

Intracellular dialysis and fixed membrane potential techniques were used to study the extracellular influence of antiarrhythmic drugs--brazidole (a new derivative of 2-mercaptobenzimidazole), amiodarone, sotalol, and hydroxyzine (a tranquilizer) in concentrations 1, 10, 100 and 1000 microM--on the slow potassium ionic transmembrane current in isolated neurons of Lymnnaea stagnalis mollusks. All drugs produced a doze-dependent and reversible suppression of the potassium ion current and accelerated the inactivation kinetics. With respect to the degree of current suppression at 100 microM concentration, the preparations under study can be arranged in the following order: brazidole = hydroxyzine > amiodarone > sotalol. The drugs influence the membrane stability by changing nonspecific leak currents. The antiarrhythmic action of bradizole can be related to its high membranotropic activity.

[Influence of He-Ne laser irradiation and local anesthetics on potassium channels in the snail neurons]. / Deistvie gelii-neonovogo lazernogo izlucheniia na kalievye kanaly neironov prudovika.

Using clamp method it had been shown that He-Ne laser irradiation of the snail neurons increases the amplitude of voltage-gated slow potassium currents in dose of 0.7 x 10(-4) (fluence 1.5 x 10(2) Wt/m2) and decreases it in dose 0.7 x 10(-3). Bupivacaine and lidocaine suppressed potassium currents. Laser irradiation in dose 0.7 x 10(-3) enhanced the inhibitory effect of bupivacaine (10 mcM) and in dose 0.7 x 10(-4) it decreased the inhibitory effect of bupivacaine. The results of the study suggest mechanisms of the He-Ne laser irradiation effect in combination with pharmacological substances on ion channels of electrically excitable cells.

[Response of the spinal trigeminal nucleus neurons to electric stimulation of the rat dura mater]. / Reaktsii neironov spinnomozgovogo iadra troinichnogo nerva na élektricheskoe razdrazhenie tverdoi mozgovoi obolochki golovnogo mozga krys.

Aseptic inflammation of tissues surrounding large meningeal blood vessels, e.g. the superior sagittal sinus, underlies pathogenesis of migraine. This inflammation develops due to antidromic activation of sensory trigeminal nerve endings and is followed by changes in responses of the spinal nucleus of the trigeminal nerve neurons to electrical stimulation of the superior sagittal sinus. However, characteristics of these reactions are still unclear. In experiments ou urethane-anesthetized rats, responses of 387 neurons of the spinal nucleus of the trigeminal nerve to electrical stimulation of the superior sagittal sinus, were recorded. It was tial discharge with the latency 7 to 19 ms (11.4 +/- 0.17 ms) and a subsequent long-lasting discharge with the latency 20 to 50 ms (34.2 +/- 0.8 ms). It is presumed that the first phase reflects orthodromic activation of prevascular A delta and C-fibers of the trigeminal nerve while the second phase is connected with activation of meningeal C-fibers which have low conduction velocity, and/or with a secondary activation of perivascular sensory endings of trigeminal nerve by releasing algogenic and vasoactive substances. These changes could be used as an indicator of efficacy of some antimigraine substances in animal experiments.

[On teaching surgery at the graduation course of a medical college according to a new curriculum]. / O prepodavanii khirurgii v meditsinskom vuze na vypusknom kurse po novomu uchebnomu planu.

Teaching surgery to students of the medical college represents a complex dynamic process based on the achievements and advantages of domestic medical education. The article presents an analysis of historical aspects of teaching surgery formed under the influence of N.I.Pirogov's ideas and shows the necessity of searching for new forms of organization of teaching surgery at the up-to-date stage of reorganization of higher professional school. Special attention is given to a compulsory preservation of traditional principles of the system of teaching surgery verified by almost two centuries of experience of using it.

[Current views on migraine and anti-migraine preparations]. / Sovremennye predstavleniia o migreni i mekhanizmakh deistviia sredstv dlia ee lecheniia i profilaktiki.

On the basis of comprehensive experimental and clinical research the authors defined a variety of migraine-related mechanisms and schemes of migraine-correction by drugs, which should be both of the vascular- and general-actions to ensure an effective medication.