Experimental Substantiation of Taurine Use in Prophylaxis of Isoniazid-Induced Neurotoxic Reactions.

The effect of taurine and vitamin B6 on the clinical process and mortality of experimental mice due to isoniazid was studied in an acute test. The use of taurine lowered the toxic effect of isoniazid, evident from delayed covulsions, their shorter time, rarer repeat and lower mortality of the animals due to tonoclonic spasm. The most significant decrease of the neurotoxic effect of isoniazid was observed with the use of taurine in a dose of 255 mg/kg. When taurine in the dose of 255 mg/kg was used in combination with vitamin B6 in prophylactic doses of 1.3 or 3.9 mg/kg, no death of the mice due to isoniazid in the acute test was recorded.

[Introduction of dinitrosyl iron complexes with thiol-containing ligands into animal organism by inhalation method].

The possibility of water-soluble dinitrosyl iron complexes (DNIC) with thiol-containing ligands introduction into lungs and other tissues of mice by free inhalation of little drops (2-3 microns diameter) of the solutions of these complexes was investigated. Little drops of 2-20 mM solutions of the complexes were obtained by using an inhalation apparatus (compressor nebulizer). A cloud of these little drops was then inhaled by animals in a closed chamber. A maximal amount of protein-bound DNICs formed in mouse lungs was 0.6 micromoles per kilogram of tissue weight. The amount of DNIC in lungs, liver and blood decreased to the undetected level within 2-3 hours after inhalation. No cytotoxic effect of DNIC formed in lungs on Mycobacterium tuberculosis was found in mice infected with these mycobacteria.

[Efficacy and tolerance of rezonizate in complex with fluoroquinolones or mycobutin on a model of experimental murine tuberculosis].

The efficacy of rezonizate, a novel antituberculosis drug, in combination with fluoroquinolones or mycobutin was studied in experiments on mice infected with Mycobacterium tuberculosis. By the pathomorphological and microbiological criteria, the highest therapeutic effect was observed when rezonizate was used in combination with levofloxacin, the lowest effect was produced by rezonizate combination with gatifloxacin.

[The effectiveness and safety of sparfloxacine in combined therapy for tuberculosis].

The effectiveness and safety of the difluoroquinolone sparflo (sparfloxacine) used in combined therapy for drug-sensitive and drug-resistant pulmonary tuberculosis were studied. Clinical trials were carried out in 60 patients with severe pulmonary tuberculosis. The more effective combinations of sparfo and other antituberculous drugs were determined. Data on the satisfactory tolerability of sparfo used in various combinations of first- and second-line agents are presented.

[Characterization of protection mechanisms in patients with drug-resistant pulmonary tuberculosis].

Examining the performance of the local protective system has indicated that patients with drug-resistant pulmonary tuberculosis in the presence of the higher count of cytotoxic lymphocytes had the diminished activation of lymphoid elements of bronchoalveolar lavage (BAL) and decreased alveolar macrophageal production of active oxygen forms. However, there was a drastically increased formation of active oxygen forms in the BAL macrophagues during mycobacterial phagocytosis, which may result to their death. At the same time, the decreased production of gamma-interferon in the BAL cells was found in patients with drug-resistant tuberculosis (8.0 +/- 3.0 U/ml versus 10.7 +/- 2.0 U/ml). In such patients, the generation of alpha-interferon was 105.0 +/- 38.0 U/ml versus 187.0 +/- 72 U/ml in patients with tuberculosis caused by drug-resistant Mycobacterium tuberculosis. In patients with drug-resistant tuberculosis, the lower production of alpha- and gamma-interferons in the BAL cells leads to their decreased regulatory effect on the mechanisms of local defense of the lung. The drastically enhanced production of active oxygen forms, which has been ascertained in patients with drug-resistant tuberculosis, is able to result in the death of macrophages, the release of lysing enzymes into the tissues surrounding the lung; the higher count of T cytotoxic lymphocytes, the lower levels of cells in apoptosis, and mycobacterial resistance to antibacterial drugs deteriorate the course of pulmonary tuberculosis in this category of patients.

[Comparative efficiency of treatment with moxyfloxacin and lomefloxacin for generalized murine tuberculosis caused by drug-resistant Mycobacterium strains].

The antituberculous efficacy of the new fluoroquinolone agent moxyfloxacin was studied on a model of generalized murine tuberculosis caused by a multidrug-resistant Mycobacterium strain. There was evidence for the high therapeutic effect of moxyfloxacin and its advantages over the antituberculous agent lomefloxacin.

[Optimization of tuberculosis complex chemotherapy with the use of moxifloxacin]. / Optimizatsiia komleksnoi chimioterapii tuberkuleza pri ispol'zovanii moksifloksatsina.

It was shown in vitro that moxifloxacin by its activity against Mycobacterium tuberculosis (susceptible and resistant to the main antituberculosis agents) was highly superior to lomefloxacin (by 2 to 4 times by the MIC and by 4 times by the MBC). In murine lung tissue culture the highest effect was observed with the use of moxifloxacin in combination with isoniazid and pirazinamide. The efficacy of the regimens with the use of moxifloxacin was estimated in the treatment of 152 patients with pulmonary tuberculosis diagnosticated for the first time. The use of moxifloxacin was shown to be most advantageous in complex therapy of patients with extended and progressive tuberculosis due to polyresistant Mycobacterium tuberculosis strains or patients with concomitant nonspecific inflammatory diseases of the respiratory tracts due to a great variety of grampositive and gramnegative organisms, acid fact bacteria, atypical bacteria and a great variety of anaerobes. The tolerance of the treatment regimens with the use of moxifloxacin was mainly satisfactory.

[Very high frequency electromagnetic irradiation in multimodal treatment of patients with disseminated infiltrative pulmonary tuberculosis]. / Elektromagnitnoe izluchenie kraine vysokoi chastoty v kompleksnom lechenii bol'nykh rasprostranennym infil'trativnym tuberkulezom legkikh.

Multimodality treatment involving very high-frequency electromagnetic radiation (VHFER) in combination with the antioxidants alpha-tocopherol and sodium thiosulfate, which had been performed in 27 patients with disseminated infiltrative pulmonary tuberculosis, was effective. As compared to patients receiving chemotherapy in combination with electromagnetic radiation (n = 29) and routine chemotherapy alone (n = 29), these patients had more benefits from the multimodality treatment in terms of bacterial isolation cessation and reduced hospital stay by 1.5-2 months, minimal pneumofibrotic changes occurred in 63% of the patients. Combined VHFER and antioxidative therapy were found to exert a normalizing effect on lipid peroxidation and immunity.

[Maxaquin in the combined treatment of tuberculosis]. / Maksakvin v kompleksnom lechenii tuberkuleza.

In the context of experimental and clinical pharmacology, the paper provides evidence for that use of Maxaquine, a fluoroquinolone agent, is effective in the combined therapy of tuberculosis. Indications for its clinical use, dosage, and administration rates have been defined. Treatment regimens for patients isolating drug-sensitive and drug-resistant Mycobacteria tuberculosis in the presence or absence of contaminant nonspecific respiratory infections are presented. The duration of combined therapy has been defined depending on the pattern of a process and comorbidity.

[Mechanism of action of lomefloxacin on Mycobacterium tuberculosis]. / Osobennosti mekhanizma deistviia lomefloksatsina na mikobakterii tuberkuleza.

The peculiarities of the mechanism of the lomefloxacin bactericidal action on Mycobacterium tuberculosis were studied. The electron microscopy of ultrathin sections of the cells of M.tuberculosis H37Rv exposed to 10 micrograms/ml of lomefloxacin for 24 hours revealed severe changes in their ultrastructure: exfoliation of the cell wall from the cytoplasmic membrane, loosening and fragmentation of the cytoplasmic membrane, lowering of the cytoplasm thickness, vacuolization and twisting of the mesosomes. The exposure of the cells to lomefloxacin for 72 hours resulted in their complete destruction: the cells proved to be a mass of unidentifiable fragments. Some destructions such as exfoliation of the intracytoplasmic membrane and the cytoplasm loosening and vacuolization were observed in the tubercle bacilli localized inside the phagosomes of the murine lung macrophages exposed to lomefloxacin. Such destructions were evident of the antibiotic good penetration not only into the macrophages but also through the phagosome walls as well as of the lomefloxacin intracellular bactericidal activity. In the experiments with the culture of the lung tissue from the tuberculosis foci of mice the basic mechanism fo the lomefloxacin action on M.tuberculosis was demonstrated: the lomefloxacin bactericidal effect was realized through the pathway of mechanism A of the antimicrobial action of fluoroquinolones.

[Bactericidal effects of maxaquin on mycobacterium tuberculosis]. / Bakteritsidnoe deistvie maksakvina na mikobakterii tuberkuleza.

Maxaquine is a fluoroquinolone agent that is effective against Mycobacterium tuberculosis (MBT). The drug was tested for effects on MBT growth in the infected lung tissue in relation to its concentration and exposure time. The bactericidal effect was found to be achieved no earlier than 72 hours of its administration. The minimum bactericidal concentration of maxaquine was 2 micrograms/ml.

[Effect of drugs of the fluoroquinolone series on morphokinetic parameters of the cellular elements of lung tissue]. / Vliianie preparatov ftorkhinolonovogo riada na morfokineticheskie parametry kletochnykh élementov legochnoi tkani.

The effect of various concentrations of ofloxacin, ciprofloxacin and lomefloxacin on the morphokinetic parameters of the cellular elements of the lung tissue of intact animals (mice, guinea pigs and dogs) was studied under the conditions of the tissue culture. It was shown that in a concentration of 100 micrograms/ml and the exposure time of 24 hours the drugs had no effect on the mobility and structure of the lung tissue cellular elements. When the drugs were used in a concentration of 100 micrograms/ml the mobility rate of the lymphocytes and macrophages proved to by markedly retarded by the end of the 24th hour. In a concentration of 1000 micrograms/ml the drugs killed the cell culture. There were detected no specific differences in the effect of the fluoroquinolones on the cellular elements of the lung tissue of the intact animals.

[Effect of lomefloxacin on the functional activity of the phagocytic system]. / Vliianie lomefloksatsina na funktsional'nuiu aktivnost' kletok fagotsitarnoi sistemy.

The in vitro effect of lomefloxacin on the absorption activity of macrophages with respect to Mycobacterium tuberculosis and chemiluminescence of the phagocytizing cells was studied with the use of a wide range of the antibiotic concentrations. Lomefloxacin was shown to have no inhibitory effect on the phagocytic activity of the pulmonary macrophages and on the formation of active oxygen in the phagocytizing cells for the realization of the bactericidal action on M. tuberculosis.

[Antitubercular activity of lomefloxacin in an experiment]. / Protivotuberkuleznaia aktivnost' lomefloksatsina v éksperimente.

The effect of lomefloxacin was studied on mice with experimental infection due to Mycobacterium tuberculosis. The antibiotic was administered in doses of 100 and 200 mg/kg. It was shown that the use of lomefloxacin for a month provided a lower death rate of the animals with progressing acute generalized tuberculosis, a lower level of the lesions in the internal organs and a lower number of the Mycobacterium isolates from them. The efficacy of the treatment depended on the drug dose. When lomefloxacin was used in a dose of 200 mg/kg, the survival rate was much higher and the number of the epithelial unicellular granulomas in the tissue of the lung and spleen was markedly decreased while with the lower dose the indices did not differ from those in the control.

[The state of the liver in rabbits during combination chemotherapy of experimental disseminated tuberculosis]. / Sostoianie pecheni krolikov pri kompleksnoi khimioterapii éksperimental'nogo disseminirovannogo tuberkuleza.

Functional and morphologic changes in the liver condition of experimental rabbits were studied in the process of the disseminated tuberculosis development and treatment. Medication of the animals was started 2 weeks after the infection at the peak of the process and continued for 60 days. In Group 1 of the rabbits, isoniazid and rifampicin were administered enterally in combination with intramuscular streptomycin, and in Group 2, isoniazid and rifampicin were given intravenously plus intramuscular streptomycin. The doses of the antibacterial drugs were adequate, as compared to the clinical ones. It was shown that an intravenous administration of isoniazid and rifampicin supplemented by intramuscular streptomycin resulted in more pronounced normalization of processes in the liver morphologic and functional changes caused by tuberculosis than an enteral route of administration of the drugs.

[Effectiveness of soluble rifampicin in combination with other antibacterial preparations in treating disseminated destructive pulmonary tuberculosis in an experiment]. / Effektivnost' rastvorimogo rifampitsina v komplekse s drugimi antibakterial'nymi preparatami pri lechenii rasprostranennogo destruktivnogo tuberkuleza legkikh v éksperimente.

Efficacy of a new rifampicin dosage form developed at the All-Union Research Institute of Antibiotics was studied on dogs with extensive destructive tuberculosis of the lungs. Intracavernous instillation and rapid intravenous administration (RIA) of the drug in combination with 10 per cent solution of isoniazid and intramuscular administration of streptomycin were used. Intracavernous instillation of rifampicin in combination with 10 per cent solution of isoniazid was performed under the control of an x-ray unit with an image converter tube or with the developed administration procedure through an indwelling catheter. Intracavernous administration of the drugs was alternated with their RIA: either one-stage administration of the antibiotic in daily half doses to each cavern followed by RIA every second day or RIA of a daily half dose in the morning followed by intracavernous instillation of the second half dose to one cavern in 5-6 hours and the second half dose to the other cavern on the next day. Intracavernous instillation of rifampicin in combination with isoniazid together with their RIA in treatment of extensive destructive tuberculosis of the lungs provided 100 per cent elimination of tubercle bacilli in the internal organs of all the dogs and closing of the caverns with cicatrization in 70 per cent of the dogs and formation of microcavities in 30 per cent of the dogs within 30 days.

[Complications and their elimination during the rapid intravenous administration of rifampicin in an experiment]. / Oslozhneniia i ikh ustranenie pri ékspressnom vnutrivennom vvedenii rifampitsina v éksperimente.

Reaction to rapid intravenous administration (RIA) of rifampicin in a dose of 10 mg/kg was studied on 173 healthy dogs. Immediately after the first RIA of rifampicin there were observed vomiting and ataxia of various levels in 5.2 per cent of the animals. After the drug administration their arterial pressure (AP) lowered to 50-60 mm Hg. By the 9th-11th minute it restored to the initial level. A collapse-like condition was recorded immediately after rifampicin RIA in 2.3 per cent of the dogs with marked decreasing of their AP up to 15-20 mm Hg. Its restoration to the initial level was slow and required 35-40 min. It was noted that after the third consecutive RIA of rifampicin the observed reaction disappeared. Probably this was due to adaptation of the host to rifampicin intravenous injections. Mezaton is an efficient agent rapidly arresting the reaction within 1-3 min.