Effects of Release-Active Antibodies to CD4 Receptor on the Level of lck-Kinase in Cultured Mononuclear Cells from Human Peripheral Blood.

For evaluation of effects of release-active antibodies to CD4 on cultured lymphocytes from human peripheral blood, we measured intracellular content of lck-kinase cell-based ELISA. In cells treated with release-active antibodies to CD4, the content of intracellular lck-kinase significantly (p<0.01) decreased in comparison with the control (purified water processed in a similar way). Phytohemagglutinin had no effect on the concentration of lck-kinase in cells. The decrease in the content of CD4-associated lck protein suggests that the preparation enhanced intracellular coupling of lck-kinase with T-cell receptor and potentiated T-cell immune response.

[The biomarkers in medicine: search, choice, study and validation].

The sphere of application of biomarkers is expanding every year and already comprises their using as indicator of presence or absence of disease, response to therapy, efficiency of medications or pre-clinical model of diagnostic parameter and even participant of process of search of mechanism of effect of medications. Hence, it is impossible to overestimate significance of studying of biomarkers. The article is dedicated to systematization and structuring of present information concerning biomarkers, starting from primary screening and completing with validation of chosen molecule or characteristic.

Antiviral Activity of Ergoferon against Group A Rotavirus.

Antiviral activity of Ergoferon was studied in vitro on an experimental model of rotavirus infection in MA-104 cell line. In infected cells treated with Ergoferon, rotavirus titer was shown to decrease by 83 and 90% in comparison with cells treated with solvent used for Ergoferon preparation (p<0.05) and distilled water (p<0.05), respectively. These findings demonstrate high anti-rotavirus activity of Ergoferon.

Preclinical Toxicological Study of Release-Active Preparations for Prediction of Their Pharmacological Activity and Side Effects.

We studied chronic toxicity of a few release-active preparations: Dietressa (release-active preparation of affinity-purified antibodies to type 1 cannabinoid receptor), Divasa (releaseactive preparation containing a combination of affinity-purified antibodies to brain-specific S-100 protein and endothelial NO-synthase), Cardostin (release-active preparation containing a combination of affinity-purified antibodies to C-terminal fragment of angiotensin II type 1 receptor and endothelial NO-synthase), and Bation (release-active preparation containing a combination of affinity-purified antibodies to IFN-γ and CD4). We evaluated not only side and toxic effects, but also the relationships between these effects and pharmacological activities of the preparations. The data of preclinical toxicological studies of the release-active preparations can be used for prediction of their pharmacological activity.

Mechanisms of Erythropoietin-Stimulating Action of Anti-Erythropoietin Release-Active Antibodies in Complex Treatment of Experimental Anemia during Gestation.

We studied the mechanisms of erythropoiesis stimulation and effectiveness of Poetam, a preparation containing release-active anti-erythropoietin antibodies as a supplement treatment for experimental iron deficiency anemia during gestation. The results confirmed potency of combined therapy to stimulate erythropoiesis, which was more efficacious in comparison with monotherapy as assessed by the count of erythrokaryocytes and erythroid progenitors in the hematopoietic tissue as well as by the content of erythrocytes and hemoglobin in the peripheral blood. Activation of erythropoiesis is related to the modulatory effect of Poetam on proliferative activity and differentiation of erythroid precursors, which in most aspects results from stimulatory action of Poetam on secretion of the hematopoietically active factors by adherent elements of the hematopoietic microenvironment.

Anxiolytic and Antidepressant Effects of Divaza and Brizantin.

The anxiolytic and antidepressant activities of complex preparations divaza and brizantin containing antibodies to brain-specific protein S100 were estimated using Vogel conflict test and Nomura forced swimming test. Course treatment (5 days) of brizantin in a dose of 2.5 ml/kg and divaza in a dose of 7.5 ml/kg significantly increased punished drinking in the Vogel conflict test in comparison with the control. Both drugs also improved general emotional behavior during training prior to the test procedure. Brizantin and divaza in a dose of 7.5 ml/kg increased the number of wheel revolutions in the Nomura forced swimming test in comparison with the control; the effect of divaza was more pronounced. High correlation coefficients between the number of wheel revolutions during the first and second 5-min sessions are also indicative of antidepressant action of divaza and brizantin.

Experimental study of the efficiency of Dietressa preparation on body weight reduction in mice feeding high-fat ration.

We studied the efficiency of Dietressa on body weight reduction in C57Bl/6 male mice feeding standard high-fat ration (24%). After 5-month daily intragastric administration of Dietressa, body weight gain was the lowest in comparison with other groups and did not differ from that in mice receiving the reference substance sibutramine for 5 months. In contrast to sibutramine, Dietressa did not increase motor activity of animals in the open field test and produced no anorectic effect. The mean body weight gain per each 1000 kcal of consumed food in the group of animals receiving Dietressa was lower than in the control group and mice receiving sibutramine.

[Immunotropic properties of anaferon and anaferon pediatric].

Anaferon and pediatric anaferon based on release-active antibodies to interferon-gamma (R-A antibodies to INF-gamma) proved to be efficient in the treatment of many viral infections. Immunomodulating (immunotropic) properties of the drugs were revealed in the preclinical studies at many Russian and foreign research medical institutions and are reviewed herein. Anaferon and pediatric anaferon stimulated the humoral and cellular immune responses and increased the neutrophil and macrophage activity. The crucial mechanism of the immunotropic action of R-A antibodies to INF-gamma was the effect on the system of interferons and in particular on INF-gamma and functionally conjugated cytokines, resulting in normalization of the functional activity of the innate factors of the immune defense and increasing of the antiviral action. The broad spectrum of the immunotropic activity provided the success of anaferon and anaferon pediatric for more than 10 years in the treatment and prophylaxis of the diseases associated with disorders in the immune system functional state.

[An experimental study of the effectiveness of the drug afalaza in chronic aseptic prostatitis].

A pilot study evaluated the efficacy of the drug afalaza (mixture of affinity purified antibodies to PSA and endothelial NO-synthase) compared with the Serenoa repens extract in a model of chronic abacterial prostatitis in Wistar rats caused by suturing of prostate tissue by silk thread. Except for the animals of intact group, rats (n = 13 in each group) underwent intraperitoneal injection of distilled water (10 ml/kg), afalaza (at a doses of 5, 7.5 and 10 ml/kg) or an Serenoa repens extract (50 mg/kg) 1 month after surgery for 45 days. After infusion, the mass, volume, and prostate weighting factor were evaluated, and prostate tissue was examined histologically. 2.5 months after surgery, development of chronic abacterial prostatitis was observed in the control group. Compared with intact group, significant increase in weight, weighting factor, and volume of prostate were detected in control group. Against the background of administration of Serenoa repens extract and afalaza, these parameters were not significantly different from control values. The use of Serenoa repens extract prevented the development of atrophic processes and slowed the development of sclerotic processes. Administration of afalaza at all studied doses prevented the development of sclerotic changes, and a dose of 7.5 ml/kg prevented the development of atrophic processes with the effectiveness matching to Serenoa repens extract. Taking into account the high safety of afalaza, this drug is a promising treatment for chronic prostatitis.

[Effect of kardostin on the generative function of female rats].

The effects of kardostin on the ovulatory cycle, conception, and sexual behavior of female rats have been experimentally studied. It is established that a two-week therapy with kardostin at a dose of 5 and 15 mg/kg changed phases of the estrous cycle (with the estrus phase being most prevalent) and led to ambiguous changes in the sexual behavior of female rats (a dose of 5 mg/kg increased sexual behavior, while a dose of 15 mg/kg inhibited it), activated fertility, and improved the quality of conception.

[Ergoferon and oseltamivir in treatment of influenza: results of multicentre randomized comparative clinical trial].

The narrow range of choice and virus resistance to the most common drugs require search and introduction of new drugs with proven efficacy and safety for the treatment of influenza. Ergoferon is a new combined medicine containing release active antibodies to interferon-gamma (anti-IFNgamma), CD4-coreceptor and histamine. The formulation influences various links of antiviral defense and provides antiinflammatory effect. The efficacy of the drug is related to its production process during which multiple reduction of the initial concentration of every component leads to release of special release activity. Previous experimental studies showed that anti-IFNgamma had antiviral activity against pandemic influenza virus A (H1N1) 2009 comparable to that ofoseltamivir (suppression of virus replication in the lung tissue, increase of the lifespan and reduction of the laboratory animals mortality). The aim of the multicentre randomized clinical trial was to compare (versus oseltamivir) the efficacy and safety of ergoferon in the treatment of influenza in adults. 213 patients with flu-like symptoms were examined in 8 medical centres of Russia during two epidemiological seasons (2010-11 and 2011-12). The inclusion criteria were: the first 48 hours after the onset; fever > or =37.8 degrees C, at least one common symptom and at least one respiratory symptom. Influenza was confirmed in 52 patients by QuickVue rapid diagnosis. 23 patients received ergoferon according to the treatment scheme and 29 received oseltamivir (daily dose 150 mg). Duration of the treatment was 5 days. The patients were followed up for 7 days. The primary endpoint was the percentage of the patients with the body temperature normalization for 2-5 days of the treatment. The maximum efficacy of ergoferon was observed on the second day of the treatment: almost half (48%) of the initially febrile patients had normal body temperature (versus 28% in the patients treated with oseltamivir). The comparison of the two groups of the patients by the morning and evening measurements of the body temperature every five days of the treatment by Cochran-Mantel-Haenszel revealed a significant difference between the two groups (chi2 = 7.1; p = 0.008). The average duration of the fever in the group of ergoferon was 2.3 +/- 1.2 days, in the group of oseltamivir--2.6 +/- 1.3 days (the efficacy of oseltamivir in the present study was comparable with the previously published data). The percentage of the patients treated with antipyretics because of hyperthermia on the second day of the treatment lowered 3 times and amounted to 17% (versus 41% in the oseltamivir group). The severity of common and respiratory symptoms (nose/throat/chest) significantly decreased on the third day of the treatment in both groups, the majority of the patients had either minimum severity or no signs of influenza. The clinical improvement was associated with positive changes in the life quality. No cases of the disease aggravation were recorded. Complications requiring antibiotic treatment or hospitalization were not observed during the followup. There were no adverse events recorded due to the drug use. No deviations in the laboratory indices were stated. Ergoferon is a new safe drug for the treatment of influenza. Its clinical efficacy was comparable to that of oseltamivir. The therapeutic effects of the drug were evident from: significant reduction of the disease severity, duration of febricity and general toxicity and respiratory flu symptoms, lower percentage of the patients with fever for 2 days. The febrile period in most of the patients did not exceed 2 days.

Study of the effects of preparation containing ultralow doses of antibodies to S-100 protein in experimental hemorrhagic stroke.

Ultralow doses of antibodies to S-100 protein increased rat survival, reduced neurological deficit, eliminated myorelaxation, and improved movement coordination and cognitive functions in rats with experimental hemorrhagic stroke; the efficiency of the preparation was not inferior to that of nimodipine. In contrast to nimodipine, ultralow doses of antibodies to S-100 protein exhibited pronounced anxiolytic properties.

Effect of ultralow doses of antibodies to S-100 protein in animals with impaired cognitive function and disturbed emotional and neurological status under conditions of experimental Alzheimer disease.

Course administration of ultralow doses of antibodies to S-100 protein restores cognitive functions and neurological status, improves emotional state, and reduces anxiety in animals with modeled Alzheimer disease based on cholinergic system deficiency caused by subchronic treatment with scopolamine.

Serotonin precursor 5-hydroxytryptophan disturbs the protective effect of low doses of antibodies to S100B protein during the formation of long-term sensitization.

We studied the effect of ultralow doses of antibodies to calcium-binding protein S-100B and 5-hydroxytryptophan, a metabolic precursor of serotonin, on the formation of long-term sensitization as a neurobiological model of anxiety and depression. Daily administration of antibodies to S-100B to edible snail before the formation of long-term sensitization prevents its development. 5-Hydroxytryptophan administered before the formation of long-term sensitization abolished the protective effect of antibodies to S-100B protein.

Application of ultralow doses of antibodies to interferon-gamma in complex therapy of bacterial infections and prophylaxis of bacterial complications.

Comparative placebo-controlled clinical trials on the efficiency and safety of ultralow doses of antibodies to human IFN-gamma (anaferon pediatric formulation and anaferon) and prophylaxis of bacterial complication showed that administration of these preparations in complex therapy of bacterial infection reduced the incidence of bacterial complications of viral infections and considerably decreased the duration of the main clinical symptoms of the disease.

Effect of impaza on cardiovascular system.

Experiment on ISIAH rats showed that antibodies to endothelial NO synthase in ultralow doses (impaza) produced a mild and progressive antihypertensive effect slightly inferior to that of losartan. The use of impaza is perspective in patients with erectile dysfunction and cardiovascular pathology.

Experimental study of hypotensive effect of kardos in rats with inherited hypertension.

Kardos, a preparation containing ultralow doses of antibodies to C-terminal fragment of type 1 receptor of angiotensin II, intragastrically administered to SHR rats with hereditary hypertension for 28 days reduced blood pressure by 14.8%. Kardos was not inferior to losartan and, in contrast to the latter reduced HR by 9.4%.

Antiaggressive activity of antibodies to S-100 protein in ultralow doses.

Experiments on rats demonstrated antiaggressive activity of ultralow doses of antibodies to S-100 protein in tests of motivated and unmotivated aggression. The effect of ultralow doses of antibodies to S-100 protein in single and course treatment was not inferior to that of benzodiazepine anxiolytic diazepam.

Evaluation of the efficiency and safety of combined treatment with impaza and nitrates in CHD patients with erectile dysfunction.

The safety of combined administration of ultralow doses of antigens to endothelial NO synthase (impaza) and nitrates for the treatment of erectile dysfunction in CHD patients was evaluated in an open non-comparative clinical trial. The efficiency and safety of impaza and the possibility of its administration to patients receiving nitrates were demonstrated.

Pharmacodynamics of kardos administered as monotherapy and in combination with hypothiazide and enalapril in grade I-II arterial hypertension.

Therapy with kardos produced an antiihypertensve effect in patients with grade I-II arterial hypertension. This antiihypertensve effect was considerably potentiated, when kardos was administered in combination with enalapril.