[PHARMACOLOGICAL CORRECTION OF APOPTOSIS LEVEL OF CORTICAL NEURONS IN AGED HER2/NEU TRANSGENIC MICE].

Neurodegenerative changes and neuronal death are the basis for development of the nervous system aging. We investigated the mechanism of apoptosis of the sensorimotor cortex neurons of transgenic mice HER2/neu during aging, changes in the cortex function and the participation of exogenous neurometabolites (cytoflavin, piracetam) in regulation of neuronal death and locomotor and psycho-emotional status of mice. The level of apoptosis and expression of apoptosis markers (TUNEL, immunohistochemistry, Western blotting) in HER2/neu transgenic mice as compared to wild type mice (FBV line) were determined.

[Comparative experimental study of the influence of drugs that improve brain metabolism (angiogen, cytoflavin) on neuronal apoptosis and function of cerebral cortex during aging].

The safety of cortical neurons and their functional activity is essential for organism at all stages of ontogenesis. However, aging changes leading to an increase in apoptosis level may cause considerable damage to cerebral cortex function, including sensorimotor. We have studied the role of exogenous neurometabolites (angiogen, cytoflavin) in apoptosis regulation and correction of age-related motor and behavioral disturbances.

Pathways of apoptosis regulation in hepatocytes induced by first-line antitubercular drugs.

We studied pathways of apoptosis regulation during experimental hepatopathy caused by treatment with antitubercular drugs and involvement of some hepatoprotectors and immunomodulators in the regulation of hepatocyte apoptosis induced by antitubercular drugs. The intensity of apoptosis and expression of apoptosis-associated molecules were evaluated. It was shown that antitubercular drugs induce apoptosis in hepatocytes by triggering external signaling pathway and p53-dependent signaling pathway and simultaneously reducing the level of anti-apoptotic Bcl-2 protein.

[Pulmonary vasculitis as a clinical mask of HCV infection: efficiency of interferon-free antiviral therapy].

The paper describes a clinical case of pulmonary vasculitis caused by hepatitis C virus (HCV). Its diagnosis was established on the basis of in-depth laboratory testing and an investigation of the molecular biological markers of viremia (polymerase chain reaction--PCR--HCV RNA) in peripheral blood mononuclear cells. By taking into account of extrahepatic HCV replication and contraindications to interferon therapy, the female patient was given an interferon-free antiviral therapy cycle using an interferonogenic inductor in combination with ribavirin.

[Meglumine acridonacetate and complex therapy of patients with newly identified advanced pulmonary tuberculosis].

Clinical and immunological efficacy of meglumine acridonacetate (cycloferon) tablets was evaluated in complex treatment of patients with newly diagnosed advanced pulmonary tuberculosis. It was shown that the use of cycloferon according to our scheme increased the efficacy of the therapy (earlier disappearance of the disease symptoms and bacteria isolation, shorter-terms of cavern healing, more pronounced positive radiographic dynamics vs. the patients under the etiotropic therapy).

[The morphofunctional state of the liver and the possibilities of pharmacotherapy for its disease in small bowel obstruction].

Objective: To study the results of liver morphological studies in 40 Vietnamese pot belly pigs with simulated small bowel obstruction.

Materials And Methods: Liver morphofunctional changes in acute strangulation ileus were investigated in an experiment on 40 Vietnamese pot belly pigs weighing 15-20 kg. Five animals were used as a control.

[The hepatotropic activity of runihol and ademethionine against experimental liver damage caused by first-line antituberculosis drugs].

Experiments on 62 male albino outbred rats investigated the impact of 14-day use of the oral hepatotropic agents ademethionine and runihol in different doses in liver damage caused by a antituberculosis combination (HRZ). HRZ-induced liver damage was shown to be accompanied by the development of cytolysis and cholestasis. The test drugs in the doses under study had a mixed effect, by reducing the magnitude of biochemical manifestations of these syndromes.

[Pharmacological activity of runihol and S-adenosyl-L-methionine in rats with experimental liver damage by reserve antituberculosis drugs].

The hepatoprotective action of runihol and S-adenosyl-L-methionine (ademethionine) has been studied in a group of 47 white outbred male rats with model liver injury induced by reserve antituberculosis drugs (PAS, prothionamide, cycloserine). The ability of test drugs to correct structural and functional liver disorders is established. Both runihol and ademethionine favored decrease in the signs of structural and functional liver disorders induced by reserve antituberculosis drugs, Showing mixed type of action, the test drugs promoted recovery of the liver parenchyma and reduced manifestations of hepatocyte dystrophy to the same extent, without manifestations of necrobiotic processes and a mononuclear infiltration.

[Role of hepatoprotectors and immunomodulators in regulation of hepatocyte apoptosis induced by antituberculosis treatment].

Unlabelled: It was currently shown that hepatopathy due to drug toxicity is associated with increased apoptosis of hepatocytes. Therefore, development of drugs which regulate cell death is of great importance.

Aim: To involve some hepatoprotectors (ademethionine, reamberin, remaxol) and immunomodulators (cycloferon) into regulation of apoptosis in experimental models of liver first-line antituberculousis drugs (isoniazid, rifampicin, pyraztinamide).

[The hepatoprotective activity of remaxol and S-adenosyl-L-methionine for liver damage caused by reserve-series antituberculosis drugs].

Experiments on male albino outbred rats investigated the hepatoprotective activity of remaxol and ademethionine in liver damage caused by reserve-series antituberculosis drugs. The test drugs had a mixed action, by reducing the degree of cytolytic and cholestatic syndromes. Remaxol and ademethionine assist in diminishing the degree of liver structural and functional impairments occurring with reserve-series antituberculosis drugs, by restoring the girder structure of lobes and decreasing the magnitude of dystrophic changes to stimulate reparative processes.

[Hepato- and endothelioprotective action of runihol and ademetionine in experimental liver injury induced by TB drugs in combination with alcohol].

Hepato- and endothelioprotective action of runihol and ademetionine in 66 male rats with liver disease induced by essential and second-line antituberculosis drugs in combination with alcohol were studied. One-directed affirmative action study drugs, shown to reduce the level of biochemical markers of cytolysis and cholestasis in conjunction with a significant reduction in symptoms of fatty, hyaline droplet and hydropic degeneration. In this runihol had a more pronounced anticytolitic effect, while under the influence of ademethionine the normalization endothelial dysfunction was established.

[Immunotropic and antihypoxant therapy of experimental drug-sensitive and drug-resistant tuberculosis].

The results of pre-clinical research of cycloferon, remaxol and runihol on the model of experimental generalized tuberculosis, caused by the MBT with a different spectrum of drug sensitivity are presented. A considerable increase of the curative effect of the therapy with the used of cycloferon and remaxol. There was manifested the strengthening of lung clearance from the office, reducing the prevalence of specific inflammation in the lungs of the index of lung damage, stimulation of sorption and destructive ability of peritoneal macrophages, inhibited in the course of development of experimental tuberculosis infection.

[Antioxidant properties of remaxol, reamberin, and ademetionine in patients with drug-induced liver injury on the background of antituberculous therapy].

The antioxidant properties of remaxol, reamberin and ademetionine have been studied in comparison to 5 % glucose solution in a group of 120 patients with drug-induced liver injury. It is established that the inclusion of this drugs in the composition of complex therapy contributed to restoration of the antioxidant potential of the cells, which was manifested by increased activity of glutathione peroxidase and superoxide dismutase and integral indices of antioxidant protection (total antioxidant capacity and total antioxidant status) with a relative stabilization of the level of glutathione-S-transferase. Maximum pharmacotherapeutic effect with respect to all of the studiea indices has been achieved by the use of remaxol.

[The clinical efficacy of a succinate-containing infusion drug during pharmacotherapy for hepatic lesions of varying genesis: results of meta-analysis].

Aim: To pool the published results of trials of the new infusion hepatoprotector remaxol for the integral quantification of the magnitude of its clinical efficacy.

Subjects And Methods: The authors made a systematized review of the published results of randomized clinical trials of the succinate-containing infusion hepatoprotector remaxol in diseases associated with hepatic lesions (chronic hepatitis B and C, severe ethanol intoxication in the presence of alcohol dependence, drug-induced liver lesion during treatment of tuberculosis, and metabolic syndrome). The pooled database included information on 935 patients.

[Remaxol hepatoprotective therapy of patients with tuberculosis and HIV infection in day unit of tuberculosis dispensary].

To improve the treatment of hepatotoxic responses to antituberculosis polychemotherapy, the impact of remaxol on the biochemical indices and parameters of the antioxidant system in patients with tuberculosis and HIV infection was estimated. The use of remaxol having cytoprotective, anticholestatic, antihypoxitic and antioxidant effects in the treatment of patients with tuberculosis and HIV infection and liver drug damage due to tuberculosis polychemotherapy significantly improved the biochemical indices and lowered the level of the cytolytic and cholestatic syndromes. Remaxol increased the antioxidant system potential and had an antihypoxitic effect.

[The effect of runihol and exogenous S-adenosyl-L-methionine on the morphological pattern of the liver upon hepatotoxic exposure to reserve-series antituberculous drugs].

Experiments on 160 male albino outbred rats investigated the hepatoprotective activity of S-adenosyl-L-methionine (SAM) and runihol in liver damage caused by subtoxic doses of reserve-series antituberculous drugs (ATD) (PASA, cycloserine, prothionamide) and their combination. It was established that a combination of ATDs had the maximum hepatotoxic activity, cycloserine had the least. There was evidence that SAM versus runihol had a more pronounced ability to correct ATD-induced evolving cytolysis syndrome.

[Virus infections and interferon inducers in the complex therapy].

Interferon inductors of various chemical groups, belonging to antivirals, and induction of several types of endogenous interferon in blood serum are described. Cycloferon was shown efficient in the complex treatment of chronic hepatitis C, tuberculosis in HIV-infected subjects, arbovirus diseases, influenza and acute respiratory virus infections.

[Mechanism of hepatocyte apoptosis in experimental toxic liver injury].

One of the causes of drug hepatopathy is hepatocyte apoptosis, the mechanisms of which are still unclear. The experiments were performed in 24 Wistar rats to study the role of hepatoprotectors in the regulation of hepatocyte apoptosis in liver damage induced by administration of antituberculosis drugs (ATD). The level of apoptosis (TUNEL) was evaluated, and the expression of apoptosis-associated molecules was detected by immunohistochemistry and Western blotting.

[Comparative efficacy of clinical use of reamberin, remaxol and ademethionine in patients with tuberculosis of the respiratory organs and liver drug-injury].

The efficacy ofreamberin, remaxol, S-adenosyl-L-methionine (ademethionine) and 5% glucose solution was estimated in the treatment of patients with tuberculosis of the respiratory organs and drug hepatotoxicity signs confirmed by higher activity of liver indicative enzymes and nitrogen oxide levels. Remaxol showed a pronounced positive effect on the cytolytic syndrome signs, evident from lower activity of alanine aminotransferase and aspartate aminotransferase. At the same time ademethionine was superior to remaxol in the effect on the cholestatic signs and inferior in the effect on the cytolytic signs.

[Effectiveness of the hepatoprotective activity of reamberine, remaxol, and ademethionine and risk assessment in their use in patients with respiratory tuberculosis and drug-induced liver injury].

Aim: To comparatively evaluate the hepatoprotective activity of reamberine, remaxol, and exogenous ademethionine and a risk for unfavorable/favorable outcomes of their use in patients with liver injury during antituberculosis chemotherapy.

Subjects And Methods: One hundred and eighty patients with new-onset respiratory tuberculosis were examined and divided into 4 groups (45 patients in each group): Study Group 1 (SG1): patients who took reamberine; Study Group 2 (SG2): those who received remaxol; Study Group 3 (SG3): those who had ademethionine; and a Comparative Group (CG): those who received 5% glucose solution. The test drugs were intravenously administered in a dropwise manner once daily for 10 days.

[Antihypoxants in current clinical practice].

Hypoxia is a universal process accompanying and determining the development of various pathological conditions. In the most general form hypoxia can be defined as the incompatibility between energy requirements of the cell and energy production in the system of mitochondrial oxidative phosphorylation. The energetic status of the cell can be improved by such pharmacological products as antihypoxants of 5 groups: inhibitors of fatty acid oxidation, succinate-containing and succinate-producing agents, components of the natural respiratory chain, artificial redox-systems, and macroergic compounds.

[An experimental study of the efficiency of cycloferon in the complex chemotherapy of generalized drug-resistant tuberculosis].

The results of an experimental study of the efficiency of cycloferon included in a complex chemotherapy of generalized drug-resistant mycobacterium tuberculosis (MBT) are presented. It is established that cycloferon (3.6 mg/kg) produces a significant therapeutic effect, which is manifested by an increase in the lung clearance from MBT, a decrease in the spread of specific inflammation in the lungs, and the disappearance of MBT-induced alterations.

[Hepatotropic therapy in treatment of liver injury].

At present, the conception of the use, efficacy and safety of hepatotropic agents in treatment of drug-induced liver injury, in particular due to antituberculosis drugs is not yet final, which is conditioned by extremely rare clinical trials on the subject adequate to the up-to-date principles of the conclusive medicine. The review presents data on the hepatotoxic effect of antituberculosis drugs, analysis and systematization of the data on the use of hepatotropic agents in liver injury induced by antituberculosis drugs, the principles and characteristics of their clinical use. The mechanism of action of remaxol, a new original hepatotropic agent and the indications of its use are discussed.

[Relationship between the endogenous interferon IFN-gamma level and risk of hepatotoxic liver damage in tuberculosis patients].

Results of investigation in a group of 91 patients with infiltrative and disseminative forms of tuberculosis are presented. It is established that, at an initial level of IFN-gamma below 100 pg/ml, a higher frequency of development of the drug-induced liver injury takes place as manifested by increasing activity of the basic markers of cytolysis. Administration of the interferon inductor (cycloferon) favors positive clinical and laboratory dynamics of the tubercular process, increases the level of endogenous IFN-gamma (especially for an initial level below 100 pg/ml), and restricts the expression of drug-induced hepatotoxicity reactions.

[Spectral and functional properties of ceruloplasmin under UV irradiation].

During oxydase reaction spectral characteristics of ceruloplasmin at absorption of copper ions and protein part of the molecule are shown to change. It has been ascertained, that when irradiating ceruloplasmin by UV-light the functioning of intramolecular electron transport chain is broken, the degree of positive cooperativity (a Hill's constant) on substrate decreases. It is supposed, that these changes are caused by disturbance of interdomain interactions in a protein molecule.