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1.
Neurobiol Dis ; 62: 354-64, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24141021

ABSTRACT

There is currently a significant lack of therapeutic options for acute ischemic stroke, and no drug has been approved for treating patients at delayed time points (≥6h post-stroke). Afobazole, an anxiolytic currently used clinically in Russia, has been shown to reduce neuronal and glial cell injury in vitro following ischemia. Experiments using the permanent middle cerebral artery occlusion (MCAO) rat model were carried out to determine if afobazole can reduce ischemic stroke damage in vivo and expand the therapeutic window for stroke treatment. Post-stroke (24h) application of afobazole (0.3-3mg/kg) significantly decreased infarct volume at 96h post-surgery, as determined by Fluoro-Jade and NeuN staining of brain sections. Moreover, afobazole helped preserve both the levels and normal histological distribution of myelin basic protein, indicating a reduction in white matter injury. A time-dependence study showed that either pre-treatment or treatment started 6 to 48h post-stroke with the drug yields improved outcomes at 96h. The decrease in infarct volume produced by afobazole was blocked by the application of either a σ-1 (BD 1063, 30mg/kg) or a σ-2 (SM-21, 1mg/kg) antagonist, indicating that both receptor subtypes are involved in the effects of afobazole. Treatment with afobazole starting at 24h post-stroke resulted in enhanced survival one month following surgery. Behavioral testing of animals 28-32days post-surgery using the elevated body swing and forelimb grip-strength tests revealed that treatment with afobazole starting 24h post-stroke significantly reduces behavioral deficits caused by ischemic stroke. The increase in survival and improved functional outcomes are accompanied by a reduction in infarct volume, as determined by thionin staining of brain sections. Taken together, our data support the use of afobazole as a post-stroke pharmacological agent to expand the current therapeutic window.


Subject(s)
Benzimidazoles/therapeutic use , Brain Ischemia/drug therapy , Morpholines/therapeutic use , Stroke/drug therapy , Animals , Benzimidazoles/administration & dosage , Brain Ischemia/pathology , Hand Strength/physiology , Infarction, Middle Cerebral Artery/drug therapy , Infarction, Middle Cerebral Artery/pathology , Male , Morpholines/administration & dosage , Rats , Rats, Sprague-Dawley , Receptors, sigma/agonists , Stroke/pathology , Treatment Outcome
2.
Bioorg Khim ; 38(5): 545-54, 2012.
Article in Russian | MEDLINE | ID: mdl-23342488

ABSTRACT

In order to create an active pharmaceutical substance of the drug with prolonged action the modification of recombinant human granulocyte colony-stimulating factor GCSF (filgrastim) with polyethylene glycol (PEG, M 21.5 kDa) was conducted. A method for preparation of PEG-filgrastim designed for the development and scaling-up of the technological process of production was described. Modification of proteins with PEG was performed by selective covalent attachment of the molecule alpha-methyl-PEG-propionaldehyde to the alpha-amino group of the N-terminal methionine amino acid residue of the recombinant GCSF. The conditions of the reaction, which provide the desired product yield at least 85% of the total protein, also high protein concentration in the reaction mixture (more than 9 mg/mL) and reduce consumption of PEG in terms of terminal alpha-amino group of the protein was chosen. The data of RP HPLC and MALDI-mass spectrometry showed that the produced drug modified by the N-terminal residue and contains no more than 10% of products with a high degree of modification.


Subject(s)
Granulocyte Colony-Stimulating Factor/chemistry , Polyethylene Glycols/chemistry , Filgrastim , Humans , Recombinant Proteins/chemistry
3.
Antibiot Khimioter ; 55(1-2): 6-11, 2010.
Article in Russian | MEDLINE | ID: mdl-20583552

ABSTRACT

Efficacy of arbidol and ridostin in cupping postvaccinal complications due to variolation was studied by the clinico-virological, hematological and biochemical indices and it was shown that arbidol was efficient in cupping development of dermal complications, lowered the severity of the postvaccinal reaction and stimulated the cellular and humoral immune response. Ridostin, a high molecular interferon inductor, was highly efficient in cupping all the forms of the postvaccinal complications, including the neurological and cutaneous ones.


Subject(s)
Indoles/pharmacology , Interferon Inducers/pharmacology , RNA, Double-Stranded/pharmacology , RNA, Fungal/pharmacology , Smallpox Vaccine/adverse effects , Vaccinia virus , Animals , Cell Line , Chlorocebus aethiops , Indoles/immunology , Interferon Inducers/immunology , RNA, Double-Stranded/immunology , RNA, Fungal/immunology , Rabbits , Smallpox Vaccine/immunology , Smallpox Vaccine/pharmacology
4.
Probl Tuberk Bolezn Legk ; (4): 19-22, 2009.
Article in Russian | MEDLINE | ID: mdl-19514449

ABSTRACT

DST was ascertained to have a high sensitivity in virtually all patients with tuberculosis and a positive reaction was first noted in the infected. With stabilization and regression, the response to DST was much less pronounced than that in clinical and primary infection (that to the Mantoux test being more evident). DST showed its use as a marker of active tuberculosis not only in its local forms, but also in latent tuberculous infection. This makes it possible to apply DST when preventive treatment is performed. The agent may be used to monitor the progress of treatment. DST has a high specificity--healthy individuals had a negative response to DST while the Mantoux test was positive in many cases. The high specificity of DST was suggested by the fact that the persons vaccinated with (this caused BCG ostitis) had a negative reaction to DST while the Mantoux test was positive in all cases BCG-vaccinated BCG. The findings warrant the use of DST for the differential diagnosis of tuberculosis and BCG-associated complications and the possibility of differentiating postvaccinal and infection allergy in children and adolescents.


Subject(s)
Bacterial Proteins , Skin Tests/methods , Tuberculosis/diagnosis , Adolescent , Biomarkers , Child , Diagnosis, Differential , Follow-Up Studies , Humans , Mycobacterium tuberculosis/isolation & purification , Recombinant Proteins , Reproducibility of Results , Retrospective Studies , Tuberculosis/microbiology
5.
Probl Tuberk Bolezn Legk ; (2): 11-6, 2009.
Article in Russian | MEDLINE | ID: mdl-19382637

ABSTRACT

A new reagent for a skin test given the name Diaskintest has been designed for the screening diagnosis of tuberculosis and preclinical and clinical trials conducted. Preclinical trials were carried out on 315 laboratory animals (guinea-pigs, albino mice). The reagent Diaskintest was ascertained to be nontoxic, to have no sensitizing properties, to be safe and specific, and to induce no positive reactions in BCG-vaccinated animals and healthy guinea-pigs. Its specific activity was comparable with that of the national reference--purified tuberculin PPD-L-2. With progression of tuberculous lesions, the guinea-pigs showed higher responses to Diaskintest dilution and the BCG-vaccinated animals lacked responses to Diaskintest with increased delayed type hypersensitivity. The clinical trial was permitted by the Federal Service for Surveillance in Health Care and Social Development of the Russian Federation. Clinical trials were conducted in 150 persons. The safety, specificity, sensitivity of Diaskintest were first examined in the clinical studies and its action was compared with the results of tuberculin skin test (Mantoux test) with 2 TE of PPD L-2. Diaskintest was ascertained to be highly sensitive when given in a dose of 0.2 microg in 0.1 ml. In patients with active tuberculosis and new cases of Mycobacterium tuberculosis infection, the agent induced a positive skin reaction (a papule of more than 10 mm) in 98-100% of cases (p < 0.05). The agent caused no reaction associated with BCG vaccination. The specificity of the test was 93-100% with 95% significance. The rate of overexuberant reactions (vesicular necrotic changes, lymphangitis, and lymphadenitis) was 4-14% with 95% significance. Tuberculosis patients with significant immunopathological disorders might have no skin sensitivity to Diaskintest, as to PPD L-2 (a negative test). The findings substantiate the use of Diaskintest for mass epidemiological surveys for the differential diagnosis of tuberculosis and BCG vaccination-associated complications. The agent may be also used to evaluate the activity of the process in patients with tuberculosis and the efficiency of treatment in combination with other methods and to make a differential diagnosis of tuberculosis.


Subject(s)
Tuberculin Test/methods , Tuberculosis/diagnosis , Adolescent , Adult , Animals , Child , Diagnosis, Differential , Disease Models, Animal , Guinea Pigs , Humans , Mice , Middle Aged , Reproducibility of Results , Sensitivity and Specificity , Young Adult
6.
Vopr Virusol ; 53(4): 9-13, 2008.
Article in Russian | MEDLINE | ID: mdl-18756809

ABSTRACT

Experimental studies of arbidol and arbidol mesylate versus ribavirin suggest that insertion of these agents into the nutrient medium of the cultured cells GMK-AH-1 (D) after infection at concentrations of 50, 25, and 100 microg/ml, respectively, is effective in suppressing the reproduction of severe acute respiratory syndrome (SARS) virus. Arbidol and arbidol mesylate were shown to have a direct antiviral effect in early viral replication in the cultured cells. The promising antiviral agent is arbidol mesylate that is nearly 5 times as effective as arbidol in reducing the reproduction of SARS virus in the cultured cells. Insertion of arbidol, arbidol mesylate, and ribavirin into the nutrient medium 2 hours after infection of porcine embryonic renal cells caused a reduction in the accumulation of the pathogen by 2.5, 2.1, and 2.6 Ig, respectively.


Subject(s)
Antiviral Agents/pharmacology , Indoles/pharmacology , Severe acute respiratory syndrome-related coronavirus/drug effects , Animals , Cell Line , Chlorocebus aethiops , Dose-Response Relationship, Drug , Ribavirin/pharmacology , Severe acute respiratory syndrome-related coronavirus/physiology , Virus Replication/drug effects
7.
Vopr Virusol ; 52(2): 24-9, 2007.
Article in Russian | MEDLINE | ID: mdl-17500235

ABSTRACT

The study of the activity of arbidol against epidemic influenza A and B virus strains (2002-2005) in the cultured MDCK cells showed the higher sensitivity of enzyme immunoassay than that of hemagglutination test. The influenza A virus strains tested, including those resistant to rimantadine (5 microg/ml), were sensitive to arbidol (10 microg/ml). The population of influenza B virus strains was heterogeneous in this indicator, 43% of the strains being less sensitive to arbidol. There was an increase in the number of rimantadine-resistant influenza A(H3N2) virus strains (10-18%) in our country during 3 epidemic seasons. The sequencing analysis of protein M2-endoding gene revealed the amino acid replacement of serine by asparagine in position 31, which is characteristic of rimantadine-resistant strains. Arbidol in combination with rimantadine potentiated the effect of viral reproduction in the cultured cells, as compared with the effect produced by the same concentrations of the drugs used alone.


Subject(s)
Antiviral Agents/pharmacology , Indoles/pharmacology , Influenza A virus/drug effects , Influenza B virus/drug effects , Influenza, Human/virology , Rimantadine/pharmacology , Amino Acid Substitution , Animals , Cell Line , Disease Outbreaks , Drug Resistance, Viral , Drug Synergism , Humans , Influenza A virus/isolation & purification , Influenza B virus/isolation & purification , Influenza, Human/epidemiology , Microbial Sensitivity Tests , Russia/epidemiology , Seasons , Sequence Analysis, Protein , Viral Matrix Proteins/genetics
8.
Probl Endokrinol (Mosk) ; 53(2): 19-24, 2007 Apr 15.
Article in Russian | MEDLINE | ID: mdl-31627572

ABSTRACT

The development of modern pharmacology cannot be imagined without the use of genetic engineering methods (recombinant DNA technology). The success of medicine is increasingly based on the active use of protein preparations obtained using the technology of transferring hereditary information (genes) from one organism to another. The emergence of the ability to express foreign genes in the cells of various organisms (both eukaryotes and prokaryotes) has become one of the revolutionary events in the science of the last two decades of the 20th century and laid the foundations of modern biotechnology.

9.
Vopr Virusol ; 51(5): 4-7, 2006.
Article in Russian | MEDLINE | ID: mdl-17087058

ABSTRACT

The paper analyzes data of an experimental study of the efficacy of antiviral agents (amantadine, remantadine, ozeltamivir, zanamivir, arbidol, ribavirin) in the cultured cells and on a model of murine influenza pneumonia against influenza A viruses subtype H5N1. It also gives data on their use in the treatment of human beings during avian influenza outbreak. The mechanism of action of the agents, pharmacokinetics, adverse reactions, and their potential resistance are considered.


Subject(s)
Antiviral Agents/therapeutic use , Disease Models, Animal , Influenza A Virus, H5N1 Subtype/drug effects , Orthomyxoviridae Infections/drug therapy , Amantadine/therapeutic use , Animals , Cell Line , Humans , Indoles/therapeutic use , Influenza A Virus, H5N1 Subtype/physiology , Mice , Orthomyxoviridae Infections/virology , Oseltamivir/therapeutic use , Ribavirin/therapeutic use , Rimantadine/therapeutic use , Virus Replication/drug effects , Zanamivir/therapeutic use
10.
Vopr Virusol ; 50(6): 30-2, 2005.
Article in Russian | MEDLINE | ID: mdl-16408628

ABSTRACT

The antiviral effectiveness of the combined and single use of superlow-dose amixine and virasole on the course of experimental hemorrhagic fever with renal syndrome was studied in sucking albino mice parenterally infected with their virus Hantaan. The co-administration of virasole and amixine was shown to protect 52% of the infected animals from death, which is superior to the effect of their monotherapy. The combined use of the drugs substantially prolongs the survival of albino mice after their infection and the level of brain viral reproduction suppression ( delta = 3.21 g) in the experimental group as compared to the controls and to the mice given only one of the drugs.


Subject(s)
Antiviral Agents/therapeutic use , Hantaan virus , Hemorrhagic Fever with Renal Syndrome/drug therapy , Ribavirin/therapeutic use , Tilorone/therapeutic use , Animals , Animals, Suckling , Antiviral Agents/administration & dosage , Brain/virology , Drug Administration Schedule , Drug Evaluation, Preclinical , Drug Therapy, Combination , Hemorrhagic Fever with Renal Syndrome/virology , Ribavirin/administration & dosage , Tilorone/administration & dosage
11.
Vopr Virusol ; 50(6): 32-5, 2005.
Article in Russian | MEDLINE | ID: mdl-16408629

ABSTRACT

The effect of the antiviral drug arbidol on the reproduction of avian influenza A/H5 viruses was studied in in vitro experiments. The strains were isolated from the wild birds of Eastern Siberia and they were closely related to the 1997-2000 viruses from South-Eastern Asia. Arbidol was shown to exert a selective inhibiting effect on the reproduction of these viruses in the MDCH cell cultures.


Subject(s)
Antiviral Agents/pharmacology , Indoles/pharmacology , Influenza A Virus, H5N2 Subtype/drug effects , Animals , Animals, Wild/virology , Birds/virology , Cell Line , Dogs , Dose-Response Relationship, Drug , Influenza A Virus, H5N2 Subtype/physiology , Influenza in Birds/virology , Microbial Sensitivity Tests , Virus Replication/drug effects
12.
Voen Med Zh ; 325(9): 44-5, 80, 2004 Sep.
Article in Russian | MEDLINE | ID: mdl-15537102

ABSTRACT

The prophylactic action of arbidol to prevent the acute respiratory viral infections and their complications (extra-hospital pneumonia) was studied under conditions of two military collectives during winter and summer time. The data obtained confirm the prophylactic activity of the drug in respect of ARVI. Regardless of the degree of disease epidemic rise among the servicemen who didn't take arbitol the minimal threshold of grippe and other ARVI incidence (10-15%) remained in the experimental group. The incidence of pneumonia decreased. It was connected with decrease in viral-and-bacterial pneumonia. The number of patients with bacterial (generally pneumococcal) pneumonia didn't change.


Subject(s)
Antiviral Agents/therapeutic use , Indoles/therapeutic use , Military Personnel , Pneumonia, Viral/prevention & control , Respiratory Tract Infections/prevention & control , Virus Diseases/prevention & control , Acute Disease , Adolescent , Adult , Humans , Male , Pneumonia, Viral/etiology , Respiratory Tract Infections/complications , Respiratory Tract Infections/virology , Russia
13.
Vopr Virusol ; 49(2): 8-11, 2004.
Article in Russian | MEDLINE | ID: mdl-15106376

ABSTRACT

Experimental research was undertaken to investigate the use of amixin in prevention, emergency prevention schemes and treatment of mice infected with West Nile fever (WNF) agent, strain Eg-101; the results are indicative of the drug efficiency both in its peroral and subcutaneous administrations. Amixin was shown to be most effective in the former case when administered, 10 mg/kg, in 96 hours before mice were infected as well as during the entire incubation period: lethality protection--46%. In the latter case, the drug was effective, when 3 administration schemes were in use, 10 mg/kg. The maximum degree of protection efficiency was registered with amixin administration according to the emergency prevention scheme: lethality protection--33%. The drug suppresses effectively the WNF virus reproduction in cerebral tissues.


Subject(s)
Antiviral Agents/therapeutic use , Tilorone/therapeutic use , West Nile Fever/drug therapy , West Nile virus , Administration, Oral , Animals , Brain/virology , Disease Models, Animal , Injections, Subcutaneous , Interferons/blood , Mice , West Nile Fever/blood , West Nile virus/drug effects , West Nile virus/isolation & purification
14.
Voen Med Zh ; 323(9): 51-3, 96, 2002 Sep.
Article in Russian | MEDLINE | ID: mdl-12449757

ABSTRACT

The authors present the results of study of arbidolum therapeutic-and-prophylactic effectiveness in acute respiratory viral infections (ARVI) under conditions of military staff with determination of economic expediency. Coefficient of effectiveness of arbidolum prophylactic use was 25% and efficiency index--1.33. In experimental group the ARVI complicated forms were noted in 3% of the patients and in control group--in 5%. Due to decreased expenses on the treatment of non-complicated and complicated ARVI forms the cost of therapy of one servicemen in the first group was 290.6 rubles, in the second group--323 rubles, in the third group--336 rubles and in the fourth group--368 rubles. The results of investigation have shown the significant advantage of arbidolum therapeutic-and-prophylactic use compared with other variants. Its use permitted to decrease the febrile period, to reduce the manifestation of symptoms of intoxication and affection of upper respiratory tract.


Subject(s)
Antiviral Agents/therapeutic use , Indoles/therapeutic use , Military Personnel , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/prevention & control , Virus Diseases/drug therapy , Acute Disease , Adolescent , Adult , Humans , Male , Moscow , Respiratory Tract Infections/economics , Treatment Outcome , Virus Diseases/prevention & control
16.
Vopr Virusol ; 47(5): 25-9, 2002.
Article in Russian | MEDLINE | ID: mdl-12522965

ABSTRACT

The experimental studies conducted on 2-week suckling mice infected with Hantaan virus, Strain 76-118) treated with oral and subcutaneous amoxine showed its prophylactic, therapeutical-and-prophylactic, and therapeutical efficiencies. Oral amoxine exhibited the highest efficiency when used in a dose of 10 mg/kg-1 96 hours before infection and throughout the incubation period. The protective efficiency was 61%. Subcutaneously, the agent was effective when three schemes for injection in a dose of 1 mg/kg-1. Its maximum effect was observed when amoxine was given by the therapeutical-and-prophylactic scheme. The death protection rate was 65%. The agent is effective in suppressing the reproduction of Hantaan virus in the brain tissue.


Subject(s)
Antiviral Agents/therapeutic use , Hantavirus Infections/drug therapy , Hantavirus Infections/prevention & control , Tilorone/therapeutic use , Animals , Animals, Suckling , Antiviral Agents/pharmacology , Brain/virology , Dose-Response Relationship, Drug , Orthohantavirus/drug effects , Orthohantavirus/physiology , Mice , Tilorone/pharmacology , Virus Replication/drug effects
18.
Prikl Biokhim Mikrobiol ; 29(3): 354-61, 1993.
Article in Russian | MEDLINE | ID: mdl-8516277

ABSTRACT

A new immunochemical reagent is proposed which contains laccase, isolated from the culture liquid of the basidial fungus Coriolus hirsutus, as a marker enzyme. The feasibility of immunolaccase conjugates for different variants of immunoassay, i.e. "sandwich", competitive and indirect, is demonstrated. The comparison of immunolaccase and immunoperoxidase conjugates showed that the absolute sensitivity of laccase-antibody conjugates was 3 times higher than that of antibody-peroxidase conjugates (7.7 x 10(-11) M and 2.3 x 10(-10) M, respectively). The assay based on antibody-laccase conjugates is simpler than that employing antibody-peroxidase conjugates, since in the former case air oxygen in used as the second substrate of the enzymatic reaction.


Subject(s)
Basidiomycota/enzymology , Immunoenzyme Techniques , Oxidoreductases , Animals , Calibration , Evaluation Studies as Topic , Immunoglobulins/analysis , Indicators and Reagents , Insulin/analysis , Insulin Antibodies/analysis , Laccase , Ligands , Mice , Oxidoreductases/immunology , Oxidoreductases/isolation & purification , Sensitivity and Specificity
19.
Biokhimiia ; 58(2): 313-8, 1993 Feb.
Article in Russian | MEDLINE | ID: mdl-8485221

ABSTRACT

A method for purifying DNA-specific catalytic antibodies based on affinity chromatography on protein A Sepharose and on both modified and non-modified DNA-cellulose as well as HPLC has been developed. The elution conditions with high yields of DNA-hydrolyzing activity of antibodies have been optimized. The biochemical and immunological properties of catalytic antibodies have been examined. The kinetic parameters of the enzyme interaction with an oligonucleotide substrate have been determined. The influence of effectors on DNA hydrolysis by antibodies has been investigated.


Subject(s)
Antibodies, Antinuclear/isolation & purification , Antibodies, Catalytic/isolation & purification , Lupus Erythematosus, Systemic/immunology , Antibodies, Antinuclear/immunology , Antibodies, Catalytic/immunology , Base Sequence , Binding Sites, Antibody , Chromatography, Affinity , Humans , Hydrolysis , Molecular Sequence Data
20.
FEBS Lett ; 314(3): 259-63, 1992 Dec 21.
Article in English | MEDLINE | ID: mdl-1468555

ABSTRACT

Blood sera of patients with autoimmune diseases scleroderma (Scl), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA) have been shown to yield a specific immune response to topoisomerase I, the product of expression of a cDNA fragment cloned into lambda gt11 and monoclonal antibodies (MAB) to the enzyme. The 'topoisomerase test' is not absolutely specific for Scl. The stable positive response of autoimmune sera to anti-topoisomerase monoclonal antibodies has a specific character and is associated with the interaction of the Fab fragment of MAB with the IgG fraction of autoimmune serum. The response observed indicates the induction of anti-idiotypic antibodies against topoisomerase. The anti-idiotype, isolated by HPLC and affinity chromatography demonstrated the following functional activities: (i) the immunological reaction against DNA; (ii) high-affinity DNA-binding with topoisomerase-specific consensus; (iii) ability to compete with the native enzyme for binding with DNA and MAB to topoisomerase; (iv) immunological reaction against MAB to topoisomerase.


Subject(s)
Antibodies, Anti-Idiotypic/immunology , Autoantibodies/immunology , Autoimmune Diseases/immunology , DNA/immunology , Amino Acid Sequence , Antibodies, Monoclonal/immunology , Arthritis, Rheumatoid/immunology , Binding, Competitive , Chromatography, High Pressure Liquid , Humans , Lupus Erythematosus, Systemic/immunology , Molecular Sequence Data , Restriction Mapping , Scleroderma, Systemic/immunology
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