[PHYSICAL AND BEHAVIORAL DEVELOPMENT OF THE OFFSPRING OF FEMALE RATS TREATED WITH AFOBAZOLE DURING PREGNANCY.]

It is experimentally established that afobazole produces no damaging action on the organogenesis and fetogenic processes registered in the postnatal period of rat offspring development. It was noted that, in rat babies in lactation age, the dynamics of body weight gain was lower on average by 7.4% (p < 0.05) in males and 17.0% (p < 0.001) in females; the rate of muscular force maturing was lower by 2.7% (p < 0.05); and the locomotive activity was lower (by 19.4% for ver- tical standings and by 50% for looking into floor holes, p < 0.05) compared to control values. For the same offspring passed to definitive food, the body weight gain and behavioral activity did not differ from control indicators, while the terms of sexual development were delayed in females and did not change in males. By two-month age, the physical development of rat offspring was completely created and met physiological standards.

Modification of sulpiride model of benign prostatic hyperplasia for evaluation of the effectiveness of drug therapy.

Specific effects of ultra-low doses of antibodies to prostate-specific antigen obtained from laboratory rats of late reproductive age with sulpiride model of benign prostatic hyperplasia were compared with the results of clinical application of the preparation. Clinical reproducibility of experimental data was proven, which suggests that the developed model is adequate for pilot testing of the effects of pharmacotherapy of this disease.

Clinical study of the efficiency and safety of afala in patients with benign prostatic hyperplasia.

The use of afala in patients with benign prostatic hyperplasia and moderate urination disturbances reduced the symptoms of the disease, improved urodynamic parameters, and increased quality of life. Clinical efficiency of afala was comparable with the efficiency of Serenoa repens extract (reference preparation).

Experimental study of ultralow-dose antibodies to cyclophosphamide on cyclophosphamide myelotoxicity.

The possibility of using ultralow-dose cyclophosphamide for reducing the myelotoxicity of cyclophosphamide, injected in the maximum permissible dose, was studied in mice. Combined treatment by the cytostatic and its ultralow-dose preparation led to a lesser suppression of the erythroid, lymphocytic, and particularly granulocytic hemopoiesis stems. This effect is explained by stimulation of the secretory activity of hemopoiesis-inducing microenvironment and hence, of the functional activity of granulocytopoiesis under the effect of ultralow-dose cyclophosphamide.

Effect of combination of anticytokine preparations anaferon and artrofoon on immune inflammation in rheumatoid arthritis.

Treatment with a combination of artrofoon and anaferon significantly reduced clinical and laboratory parameters of rheumatoid inflammation and significantly decreased the content of antiinflammatory cytokines in the blood. These findings attest to antiinflammatory and immunomodulating effects of these preparations.

Experimental and clinical study of the effect of artrofoon on proinflammatory cytokine production.

The effect of Artrofoon on the production of proinflammatory cytokines was evaluated in experiments on mice with collagen-induced arthritis and in a clinical study on patients with rheumatoid arthritis. Artrofoon produced an antiinflammatory effect on animals with collagen-induced arthritis and reduced clinical signs of inflammation in patients with rheumatoid arthritis. These changes were accompanied by a significant decrease in the production of tumor necrosis factor-alpha and interleukin-1beta.

Comparative study of pharmacological activity of afala on the model of hormone-induced prostatitis in rats.

Afala (ultralow-dose antibodies to prostate-specific antigen) injected for 60 days to rats with hormone-induced prostatitis caused by sulpiride prevented the development of prostatic hyperplasia and reduced the severity of histological changes. The effect of Afala was superior to that of the reference drug (Serenoa repens extract).

Mechanisms of regulation of hemopoiesis during experimental cytostatic myelosuppression induced by carboplatin.

The mechanisms of suppression and recovery of the bone marrow erythroid stem were studied on the model of myelosuppression induced by administration of carboplatin in the maximum tolerated dose. Single administration of the cytostatic led to the development of long-term hypoplasia of hemopoiesis. Despite enhanced proliferation of erythroid precursor caused by increased erythropoietic activity of blood plasma and bone marrow cells, inhibition of cell maturation prevented recovery of the content of morphologically recognizable erythrokaryocytes in the bone marrow.

Specific activities of poetam preparation (superlow-doses of antibodies to erythropoietin) and recombinant erythropoietin.

We compared the capacity of superlow-dose of antibodies to erythropoietin (Poetam) and recombinant erythropoietin (Recormon) to stimulate the recovery of adriamycin-suppressed erythropoiesis in mice. Both preparations exhibited high erythron activation capacity and considerably increased the content of erythrocytes and reticulocytes in the peripheral blood and content of erythrokaryocytes and erythroid precursors in the hemopoietic tissue of experimental animals. The effect of Recormon manifested immediately after injection, while the effect of Poetam was somewhat delayed, but more lasting (due to activation of host erythropoietin system).

A randomized, open-label, comparative, 6-month trial of oral ultra-low doses of antibodies to tumor necrosis factor-alpha and diclofenac in rheumatoid arthritis.

Artrofoon (oral ultra-low doses of antibodies to TNF-alpha is a novel drug approved by the Russian Ministry of Health for the treatment of rheumatoid arthritis (RA). The aim of this study was to assess clinical efficacy and safety of artrofoon in RA compared with diclofenac. In a 6-month, randomized, open-label, comparative trial, 60 patients with active RA (eight men and 52 women aged 23 to 62, mean disease duration 10 years) received artrofoon (8 tablets daily, n = 30) or diclofenac (100 mg daily, n = 30). RA signs and symptoms as well as serum levels of inflammatory markers were evaluated before treatment and at months 1, 3 and 6. Most patients in the artrofoon group showed a 20% improvement in major RA symptoms by the end of the study. The clinical effect rose gradually reaching maximum at month 6. In the artrofoon group, 57% of the patients achieved an American College of Rheumatology (ACR) 20% criteria (ACR20) by month 6 versus 20% of those receiving diclofenac. In some patients in the artrofoon arm, serum proinflammatory cytokine levels significantly decreased (> or = 25% reduction). Diclofenac produced a less pronounced clinical effect, and no changes in cytokine profile. Unlike conventional nonsteroidal anti-inflammatory drugs, artrofoon produced no adverse effects and the overall tolerability and safety were excellent. A half-dose treatment with artrofoon (4 tablets daily) was able to sustain clinical improvements over a 6-month follow-up period. To conclude, artrofoon is a safe and effective treatment for rheumatoid arthritis that acts by influencing the inflammatory process.

Pharmacological regulation of functional activity of stem cells in restoration of the myocardium during the postinfarction period.

The effect of granulocytic CSF on myocardial tissue recovery after acute myocardial infarction was studied on rats. A course of granulocytic CSF after ligation of the left coronary artery normalized ECG parameters and morphological picture of the myocardium 1 month after treatment. It was shown on mouse model of myocardial infarction that this process was associated with more intensive mobilization and homing of mesenchymal stem cells in the heart.

Mechanisms of hepatoprotective effect of preparation containing superlow doses of antibodies to granulocytic colony-stimulating factor.

The hepatoprotective effects of superlow dose preparation of antibodies to granulocytic CSF were studied on a model of CCl4-induced hepatitis. The preparation exhibited high antiinflammatory and antisclerotic activities determined by stimulation, mobilization, and determined homing of mesenchymal stem cells into damaged liver with subsequent differentiation of these cells into mature hepatocytes.

Mechanisms of the effects of granulocytic CSF on tissue reparation during chronic CCl4-induced damage to the liver.

Hepatoprotective effects of granulocytic CSF were studied using experimental model of CCl4-induced hepatitis. It was found that treatment with granulocytic CSF increased the content of stromal precursors and mesenchymal stem cells in the bone marrow and peripheral blood with subsequent increase in the number of hepatic precursor cells in the liver. These findings attest to mobilization of progenitor mesenchymal cells and their migration into damages liver tissue, which accelerates its regeneration related to changes in the parenchyma, but not connective tissue development.

Dose-dependent effects and specificity of action of antibodies to endogenous regulators in ultralow doses.

We studied the effects of antibodies against interferon-gamma, erythropoietin, and tumor necrosis factor-alpha in ultralow doses on the production of endogenous interferon-gamma. Course peroral treatment with potentiated antibodies to interferon-gamma in various dilutions produced similar changes in experimental animals. The treatment stimulated spontaneous production of endogenous interferon-gamma by mouse lymphocytes. It should be emphasized that antibodies to other cytokines in ultralow doses did not stimulate interferon-gamma production. These data illustrate the specificity of action of antibodies to endogenous regulators in ultralow doses.

Cytogenetic effects of antibodies to gamma-interferon in ultralow doses.

Single and course administration of ultralow doses of antibodies gamma-interferon did not increase the incidence of cytogenetic abnormalities in bone marrow cells from BALB/c mice and produced no genotoxic effect on Drosophila melanogaster wing cells in the test of somatic mosaicism.

Effects of ultralow doses of antibodies to prostate-specific antigen on morphological and functional state of rat prostate.

Morphological and morphometric assays showed that administration of antibodies to the prostate-specific antigen in ultralow doses for 1.5 months delayed the development of atrophic and sclerotic processes in rats with chronic aseptic prostatitis. The concentration of zinc ions playing an important role in binding of androgens increased in the prostate of rats receiving the preparation. Studies of copulatory behavior showed that male rats with chronic prostatitis receiving antibodies to the prostate-specific antigen displayed increased sexual activity compared to control and intact animals.

Efficiency of potentiated antibodies to tumor necrosis factor-alpha (Artrofoon) in the therapy of patients with rheumatoid arthritis.

Antiinflammatory activity of a new preparation Artrofoon (antibodies against tumor necrosis factor-alpha in ultralow doses) and nonsteroid antiinflammatory drug diclofenac in patients with rheumatoid arthritis was compared in an open randomized trial. The course of treatment with Artrofoon more significantly improved clinical and laboratory signs in patients with the articular form of rheumatoid arthritis than diclofenac.

Repair of radiation induced DNA damages in unicellular green algae.

Two cell repair systems--photoreactivation and repair of single-strand DNA breaks have been studied using unicellular green algae as a test-system. Effects of the genotype and the intensity of pico/second UV-laser irradiation on the degree of the photoreactivation have been investigated. It has been shown that the lower intensity (I = 8.10(6) W/cm2) effects less the inactivation of living cells comparing with I = 30.10(6) W/cm2, regardless of the genotype. The clearly expressed higher potentials of strains LARG-1 and 260 to produce and repair alterations of the cyclobutane-pyrimidine dimers type have been established. An analysis of DNA degradation during gamma rays irradiation and after incubation has been carried out for investigation the relationship between strains radioresistance and repair of single-strand break. It has been shown that high efficiency of the repair system is characteristic of the resistant strain obtained from chronically irradiated population.