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1.
Vopr Virusol ; 66(4): 279-288, 2021 09 18.
Article in Russian | MEDLINE | ID: mdl-34545720

ABSTRACT

INTRODUCTION: Combination antiretroviral therapy is currently the main component of treatment for human immunodeficiency virus (HIV) infected patients. At the same time, the high mutational potential of the virus and the frequency of side effects of existing drugs dictate the need for the development and preclinical study of new, more effective and safer compounds.The aim of the study is to evaluate the specific types of toxicity of a new non-nucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RNA-dependent DNA revertase) (NNRTI) based on the substance 1-[2-(2-benzoylphenoxy)ethyl]-6-methyluracil, a benzophenone derivative. MATERIAL AND METHODS: The study investigated reproductive toxicity, embryotoxicity, immunotoxicity, genotoxic (in micronucleus test in and comet assay) and allergenic properties of the test itemcompound. It was tested on three species of animals in two doses: the estimated therapeutic dose (1 TD) and its tenfold equivalent (10 TD). Taking into account the metabolic coefficients, the doses for rats (Rattus) were 9 and 90 mg/kg, for mice (Mus musculus), 21 and 210 mg/kg, and for guinea pigs (Cavia porcellus), 8 and 80 mg/kg, respectively. RESULTS AND DISCUSSION: According to the obtained results, a favorable safety profile of the tested compound was established. Negative effects on the immune system, reproductive function, the body of pregnant animals and the fetus were not observed, as well as the compound did not have genotoxic and allergenic properties. CONCLUSION: These data allows to consider the studied compound as a promising therapeutic candidate for the treatment of HIV-1 infection.


Subject(s)
Anti-HIV Agents , HIV Infections , HIV-1 , Animals , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/toxicity , Guinea Pigs , HIV Infections/drug therapy , HIV Reverse Transcriptase/genetics , HIV Reverse Transcriptase/pharmacology , HIV Reverse Transcriptase/therapeutic use , HIV-1/genetics , Humans , Lentivirus , Mice , RNA-Directed DNA Polymerase/pharmacology , RNA-Directed DNA Polymerase/therapeutic use , Rats , Retroviridae , Reverse Transcriptase Inhibitors/therapeutic use , Reverse Transcriptase Inhibitors/toxicity , Uracil/analogs & derivatives
2.
Eksp Klin Farmakol ; 77(11): 36-44, 2014.
Article in Russian | MEDLINE | ID: mdl-25668946

ABSTRACT

Central nervous system disorders are the leading cause of mortality and disability in the world. Unfortunately, the possibility of pathogenetic therapy is limited and it is important to search for new drugs with neuroprotective mechanism of action. One of the most promising groups of drugs are antioxidants--substances that can neutralize free radicals and reduce oxidative stress. This review focuses on preclinical and clinical studies of new antioxidants.


Subject(s)
Antioxidants/pharmacology , Brain Ischemia/drug therapy , Neurodegenerative Diseases/drug therapy , Neuroprotective Agents/pharmacology , Antioxidants/chemical synthesis , Antioxidants/classification , Brain Ischemia/metabolism , Brain Ischemia/physiopathology , Free Radicals/antagonists & inhibitors , Free Radicals/metabolism , Humans , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/physiopathology , Neuroprotective Agents/chemical synthesis , Neuroprotective Agents/classification , Oxidative Stress/drug effects
3.
Article in Russian | MEDLINE | ID: mdl-21666591

ABSTRACT

The diagnostic evaluation of brain activity disturbances using fractal EEG analysis was performed in 95 patients with different stages of epileptogenesis. The control group included 30 normals. Authors have shown the possibility to determine phases of the development of epileptic process according to the peculiarities of the dynamics of main EEG band power fluctuations with the spectrum in the form of 1/f(ß). The disturbances of alpha, theta, beta-1 and beta-2 band characteristics at the preclinical (initial) and clinical stages of epileptogenesis were revealed. There were topographical changes in indexes of fractal chaos linked with the growth of brain epileptization. The parameters of fractal fluctuations in alpha-band power proved to be the most informative for the objectification of the degree of intensity of epileptic disturbances. The method of fractal EEG analysis is concluded to be highly effective for diagnosis of all stages of epileptogenesis.


Subject(s)
Electroencephalography/methods , Epilepsy/diagnosis , Epilepsy/physiopathology , Adolescent , Adult , Female , Fractals , Humans , Male , Middle Aged , Young Adult
4.
Nord J Psychiatry ; 61(5): 339-42, 2007.
Article in English | MEDLINE | ID: mdl-17990194

ABSTRACT

The digitalization of EEGs (electroencephalogram) has showed new possibilities for analyzing electrical activity of brain. This has offered new methods, e.g. multifractal analysis of 1/f(beta) EEG rhythms fluctuations. It is one of highly mathematical methods feasible in routine practice now that modern personal computers (PCs) have reached sufficient computing power. In this study, we applied the multifractal analysis of 1/f(beta) EEG rhythms fluctuations in 33 patients suffering from schizophrenia and schizophrenia-like syndromes, and we had 23 healthy controls. Our results indicated that the patients suffering from schizophrenia have statistically different values compared with the controls. This method is rather easy and quick to perform when using a standard PC. It may have the potential to become an important tool in the diagnostics and analysis of the patients with schizophrenia and schizophreniformic psychoses. It can help to understand the quasi-chaotic processes in neural processing and narrow the gap between the phenomenological psychiatry and bio-psychiatry.


Subject(s)
Brain/physiopathology , Electroencephalography/statistics & numerical data , Fractals , Schizophrenia/diagnosis , Adult , Alpha Rhythm/statistics & numerical data , Beta Rhythm/statistics & numerical data , Diagnosis, Computer-Assisted , Female , Humans , Male , Models, Neurological , Nonlinear Dynamics , Psychotic Disorders/diagnosis , Psychotic Disorders/physiopathology , Schizophrenia/physiopathology
5.
Article in Russian | MEDLINE | ID: mdl-14763254

ABSTRACT

The peculiarities of immunologic processes and immunocorrecting potential of Cyclopheron were studied in 62 patients with preclinical epileptogenesis. Using clinical, EEG and biochemical examination, expression of epileptogenesis was estimated as regressed, compensated, increasing, decompensated. Preclinical stage of epilepsy was accompanied by disturbance of immunological brain reactivity the expression of which was correlated with a level of compensative epileptogenesis manifestation. The decrease of the latter is followed by intensive disintegration of neuroimmune interactions characterized by immunodeficiency of mixed type with significant presentation of neuroimmune disturbances. Therefore, a use of Cyclopheron, as a medication with multilevel immuno-correcting action, is expedient at initial stage of epilepsy.


Subject(s)
Acridines/therapeutic use , Adjuvants, Immunologic/therapeutic use , Epilepsy/drug therapy , Epilepsy/immunology , Neuroimmunomodulation , Adolescent , Adult , Antigens, CD/blood , Cytokines/blood , Electroencephalography , Epilepsy/blood , Fractals , Humans , Immunoglobulin E/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Lymphocytes/blood , Lymphocytes/drug effects , Lymphocytes/metabolism
7.
Biofizika ; 44(6): 1109-14, 1999.
Article in Russian | MEDLINE | ID: mdl-10707287

ABSTRACT

A new method for analyzing the chaotic component of EEG is proposed. The method is based on estimating the fractal dimension of fluctuations of alpha-rhythm power (the square of amplitude). It is shown that the dimensions of the background EEG fragments for epilepsy patients is significantly higher than that in norm, indicating a disbalance of cerebral mechanisms that control the alpha-activity in this disease. A tendency toward the disturbance of the normal fractal structure of EEG in a group of patients with initial signs of epilepsy was revealed. This suggests that the method is of considerable promise for setting the individual long-term prognosis of the development of the epileptic syndrome.


Subject(s)
Alpha Rhythm , Epilepsy/physiopathology , Fractals , Humans
9.
Ross Fiziol Zh Im I M Sechenova ; 83(11-12): 64-73, 1997.
Article in Russian | MEDLINE | ID: mdl-9541958

ABSTRACT

The data obtained revealed a significant augmentation of the EEG slow-wave activity following a 32-minute hyperventilation in neurologically healthy subjects. In 43% of the subjects, on the 8th minute of the hyperventilation a generalised paroxysm of the delta-activity occurred.


Subject(s)
Electroencephalography , Hyperventilation/physiopathology , Respiration/physiology , Adult , Alpha Rhythm , Delta Rhythm , Female , Humans , Male , Middle Aged , Theta Rhythm , Time Factors
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