Morphological and Neurological Impairments Induced by Chronic Administration of Dimethyl Sulfoxide in Mice.

We studied the influence of DMSO administered ad libitum with drinking water in concentrations of 0.01, 0.1, and 1% for 4 and 6 weeks on pain sensitivity, motor coordination, and myelin content in the corpus callosum of C57BL/6 mice. After 6-week administration, DMSO in all studied concentrations decreased myelin content in the corpus callosum. Moreover, 4-week administration of 0.1% DMSO and 6-week administration of 1% DMSO increased the latency to fall in the rotarod test by 3.1 (p<0.05) and 5.1 (p<0.001) times, respectively. After 4-week administration of DMSO in concentrations of 0.01 and 0.1%, the latency of the tail flick response increased by 2.1 (p<0.05) and 1.8 times (p<0.001), respectively. Administration of DMSO in concentrations of 0.01 and 1% for 6 weeks led to a decrease of this parameter by 2.7 (p<0.05) and 3.8 times (p<0.01), respectively. Thus, DMSO in all studied concentrations decreased myelin content in the corpus callosum of C57BL/6 mice and modified motor coordination and pain sensitivity of animals.

Comparative Informativity of Computing Methods of Insulin Resistance Assessment.

We conducted a comparative study of the calculated indices of insulin resistance HOMA-R, Caro, FGIR, and QUICKI in 29 healthy volunteers (mean age 26.21±0.93 years) with normal body mass index (23.34±0.55 kg/m2). Among the used methods for insulin resistance assessment, QUICKI is the only method that has characteristics required for the diagnostic criterium: low variability coefficient, 100% reproducibility, and minimum coefficient of variation.

[Drug therapy of atrial fibrillation in elderly patients.]

Currently, studies of the causes of atrial fibrillation are actively conducted. However, molecular and cellular mechanisms of atrial fibrillation have not been precisely established so far. Great success in the treatment of atrial fibrillation was achieved thanks to the development of surgical methods. However, these approaches, unfortunately, are not always applicable to elderly and senile patients. Antiarrhythmic drugs used in atrial fibrillation, exhibit a large number of side effects. Much attention of researchers is now attracted by fundamentally new directions in the drug treatment of atrial fibrillation. These include predserdno-selective antifibrillatory funds. Drugs, the action of which is aimed at at atrial remodeling, inflammation and fibrosis, so is of interest. Effective suppression of atrial remodeling, inflammation and fibrosis prevents the formation of a permanent form of atrial fibrillation. A new approach to the treatment of atrial fibrillation, taking into account the vegetative status of the patient, will undoubtedly increase its effectiveness.

[Pharmaceutical aspects of medicated myopia control]. / Farmakologicheskie aspekty medikamentoznogo kontrolya miopii.

The article presents data on the mechanism of various approaches of drug-induced myopia control and their potential effectiveness, and analyses promising options for medicated correction of myopia.

The Behavioral and Neurochemical Aspects of the Interaction between Antidepressants and Unpredictable Chronic Mild Stress.

The behavioral and neurochemical effects of amitriptyline (10 mg/kg, i.p.) and fluoxetine (20 mg/kg, i.p.) after single and chronic administration in the setting of unpredictable mild stress in outbred ICR (CD-1) mice were studied. After a 28-day exposure to stress, we observed an increase in depressive reaction in a forced swim test in mice, as well as reduced hippocampal levels of serotonin (5-hydroxytryptamine, 5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) and an increased hypothalamic level of noradrenaline (NA). Single and chronic administration of amitriptyline and fluoxetine shortened the immobility period and increased the time corresponding to active swimming in the forced swim test. The antidepressant-like effect of fluoxetine - but not of amitriptyline - after a single injection coincided with an increase in the 5-HT turnover in the hippocampus. Chronic administration of the antidepressants increased the hypothalamic levels of NA. Thus, the antidepressant- like effect of amitriptyline and fluoxetine may result from an enhancement of the stress-dependent adaptive mechanisms depleted by chronic stress.

Metabolism of a New Antiaggregant, Indolinone Derivative.

Cytochrome p450-mediated metabolism of GRS (indolinone antiaggregant) and its effects on activities of cytochrome p450 isoenzymes were studied. Inhibition of 6 isomers of cytochrome p450 in human liver microsomes was studied with the use of specific substrates. It was found that human liver cytochrome p450 enzymes could not induce degradation of GRS and that GRS was not an inductor or inhibitor of cytochrome p450 family members 1A2, 2C9, 2C19, 2D6, 2C8, and 3A4. Hence, clinical use of the prospective antiaggregant would not involve the risk of uncontrolled fluctuations in GRS concentrations in the organism because of interactions between the drugs.

[Influence of amiodarone on the spectral analysis of heart rate variability in patients with atrial fibrillation elderly and senile age.]

Atrial fibrillation is more common among elderly patients. Number of comorbidities, such as heart failure, coronary heart disease, disorders of the conduction system of the heart increases with age. Atrial fibrillation is a health problem. In developed countries, there is a high prevalence of the disease. The disease affects more than 33 million people worldwide. Spectral analysis of heart rate variability can be successfully used to evaluate the effectiveness of therapy. The use of this method gives an idea of the role of the autonomic nervous system in the regulation of chronotropic function of the heart. These data help to define conditions of manifestation of efficiency of antiarrhythmic drugs. In this study, spectral analysis were studied in patients with different forms of atrial fibrillation. The effect of amiodarone class III antiarrhythmic drug were studied this study. It is shown that the structure of spectrum of heart rate variability in patients with newly diagnosed atrial fibrillation differs significantly from that in patients with disease duration from 6 months to several years on the background of amiodarone.

[Atropine use for the prevention of myopia progression]. / Primenenie atropina dlia kontrolia progressirovaniia miopii.

Given the prevalence of myopic refraction (from 50 to 84% in Asian countries and 35 to 49% in European countries and the United States in young people), the development of methods for monitoring and preventing myopia continues to be an urgent task. One of the directions of pharmacological intervention on the progression of myopia is associated with the use of a non-selective M-cholinoreceptors antagonist - atropine. The review presents the results of studies on various aspects of the potential for topical application of atropine to control the progression of myopia (experimental and clinical data on the mechanism of action, the effectiveness of clinical use, the possible side effects of various concentrations of the drug).The heterogeneity of the data presented does not yet lead to the conclusion that the long-term instillations of atropine are effective in prevention of progressive myopia. In addition, the wide application of this method, for example, in the territory of the Russian Federation, is limited by approved official instruction for the local application of the atropine solution in ophthalmology.

PROFESSOR MIKHAIL P. NIKOLAEV AND RUSSIAN PHARMACOLOGY.

Various stages of life, scientific research and pedagogical activity of Prof. Mikhail P. Nikolaev are considered. The importance of his works in drug evaluation, endocrinological pharmacology, pharmacology of heart and vessels, pathological pharmacology, and discovery of drugs for organotherapy is shown. Prof. M. P. Nikolaev's effort in training research staff and teachers in pharmacology and his own teaching experience in medical and pharmaceutical universities are summarized. The activity of Prof. M. P. Nikolaev in military pharmacology is analyzed. The role of Prof. M. P. Nikolaev in establishing Russian journal Farmakologiya i Toksikologiya (Parmacology and Toxicology) and creating All-Union Scientific Society of Pharmacologists in the USSR is emnhasized.

IMMUNOTHERAPY OF BLADDER CANCER. BCG VACCINE: PRINCIPLES OF ACTION, EFFICACY AND SAFETY.

Data on the principles of BCG vaccine action on the cancer of bladder are presented. Probable targets for BCG vaccine are estimated. Efficacy of BCG vaccine in non-muscle invasive cancer of bladder is analyzed. Side effects of BCG vaccine are examined. Possibilities of evaluating BCG vaccine usage at low (sub-therapeutical) doses are discussed. Various approaches to reducing the resistance of bladder cancer with respect to BCG vaccine are considered. The perspectives of bladder cancer immunotherapy are outlined.

[PROFESSOR A. A. SOKOLOVSKY AND EXPERIMENTAL PHARMACOLOGY IN RUSSIA.]

Various stages of the creative activity of Professor A. A. Sokolovsky have been analyzed. Sequential formation of his scientific outlook is shown and the history of creation of his basic hypotheses and ideas about the action of drugs is outlined. Manuals and textbooks on pharmacology, created by Prof. A. A. Sokolovsky, are considered. Peculiarities of teaching pharmacology introduced by Prof. A. A. Sokolovsky at the medical faculty of Imperial Moscow University are discussed.

[CLASSIFICATION AND PRINCIPLES OF ACTION OF ANTIARRHYTHMIC AGENTS.]

Data on the pathophysiological mechanisms of arrhythmias and the elecrophysiological mechanisms of antiarrhythmic drug action are reviewed. Development of the classification of antiarrhythmic drugs is analyzed.

[PROFESSOR VLADIMIR V. NIKOLAEV AND RUSSIAN PHARMACOLOGY.]

Various stages of scientific research activity of Prof. Vladimir V. Nikolaev are analyzed. The importance of Prof. Nikolaev's discovery of the two-neuron parasympathetic nervous system and some new methods of pharmacological substances evaluation is shown. Prof. Nikolaev is known as the editor of the first USSR Pharmacopoeia. Peculiarities of pharmacology teaching at the First Moscow Medical institute under conditions of changing social demands are described. Successful research of Prof. Nikolaev with colleagues in studying new mechanisms of drug action and developing original pharmacological substances is summarized.

[EFFICACY OF ANTIARRHYTHMIC AGENTS UNDER CONDITIONS OF STIMULATION OF THE SYMPATHETIC NERVOUS SYSTEM.]

The problem of weakening of the action of antiarrhythmic drugs under conditions of activation of the sympathetic nervous system draws increasing attention of researchers. These conditions are frequently encountered in clinical practice in cases of ischemia, myocardial infarction, and in patients with sustained ventricular arrhythmia. In addition, sympathetic, hyperactivity is a characteristic feature of serious cardiovascular diseases including heart failure. The beta-adrenergic stimulation can significantly modulate the electrophysiological action of antiarrhythmic drugs. There are significant differences in the ability of antiarrhythmic drugs to retain efficacy on the background of sympathetic stimulation. Additional administration of beta-blockers to patients with ventricular tachycardia, cardiac insufficiency, cardiomyopathy and patients after myocardial infarction is highly effective and is worth of addition al investigation. The search for drugs whose effect is not affected by sympathetic stimulation is still topical.

Studies of long-term noopept and afobazol treatment in rats with learned helplessness neurosis.

Long-lasting effects of new Russian psychotropic drugs Noopept and Afobazol on active avoidance conditioning and formation of learned helplessness neurosis were studied on an original experimental model in rats. Noopept eliminated the manifestations of learned helplessness after long-term (21-day) treatment by increasing the percent of trained animals. Afobazol was low effective in preventing manifestations of learned helplessness, but if used for a long time, it reduced the incidence of learned helplessness development by increasing the percent of untrained animals.

[Hepatotoxic effects of drugs from some pharmacological groups]. / Gepatotoksicheskoe deistvie lekarstvennykh preparatov nekotorykh farmakologicheskikh grupp.

The review presents the results of clinical-observations of side hepatotoxic effects of drugs from different pharmacological groups. Based on the data available in the literature, the authors systematized and supplemented the characteristic types of hepatic damages due to the use of drugs in different fields of medicine. The basic mechanisms responsible for the damaging effects of hepatotropic pharmacological agents are considered. The review places a particular emphasis on the major hepatic dysfunctions observed in oncological care when antitumor drugs having different mechanisms of action. This section of the review is supplemented with cases observed in the past years, wherein there are data on the hepatotoxicity of agents from the platin group, the nonsteroidal antiandrogen flutamide, topoisomerase II inhibitors in addition to the well-known alkylating drugs and antitumor antibiotics that have hepatotoxic properties.

Effect of noopept and afobazole on the development of neurosis of learned helplessness in rats.

We studied the effects of new psychotropic preparations noopept and afobazole on acquisition of the conditioned active avoidance response and development of neurosis of learned helplessness in rats. Noopept in doses of 0.05-0.10 mg/kg accelerated acquisition of conditioned active avoidance response and reduced the incidence of learned helplessness in rats. Afobazole in a dose of 5 mg/kg produced an opposite effect, which is probably related to high selective anxiolytic activity of this preparation.

[Effects of aminoglycoside antibiotics on various structures of the acoustic analyzer]. / Vliianie antibiotikov-aminoglikozidov na raznye struktury slukhovogo analizatora.

Aminoglycoside antibiotics decrease the microphone potential amplitude and the auditory nerve potential in response to acoustic stimulation. These drugs suppress the bioelectrical activity of medulla, cerebral cortex, and olivo-cochlear efferent system. The experiments on freely moving cats showed that cortical response to electric stimulation of thalamocortical fibers originating from medial geniculate body are more sensitive to aminoglycoside antibiotics than the microphone potential and the auditory nerve potential.

Neurochemical relationships in the action of opioid analgesics on cerebral cortex.

The experiments with unrestrained cats showed that opioid analgesics in near-analgesic doses decreased the amplitude of the primary test response recorded in the second sensorimotor zone of the cerebral cortex in 20-150-msec interval between the stimuli applied to thalamocortical fibers radiating from thalamic n. VPL. Application of test substances affecting certain neurotransmitter processes and microionophoretic application of drugs and neurotransmitters to cortical neurons showed that the inhibitory effect of opioid analgesics on cerebral cortex is probably realized through GABA-, serotonin-, beta-adreno-, and cholinergic structures. The excitatory amino acids are also involved into this process.