RESUMO
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.
Assuntos
Anticorpos/farmacologia , Antígenos CD4/genética , Linfócitos T CD4-Positivos/efeitos dos fármacos , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/genética , Adulto , Antígenos CD4/imunologia , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Regulação da Expressão Gênica , Humanos , Ativação Linfocitária/efeitos dos fármacos , Proteína Tirosina Quinase p56(lck) Linfócito-Específica/imunologia , Masculino , Fito-Hemaglutininas/farmacologia , Cultura Primária de CélulasRESUMO
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.
Assuntos
Biomarcadores Farmacológicos/sangue , Biomarcadores/sangue , Diagnóstico Precoce , Humanos , Programas de RastreamentoRESUMO
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.
Assuntos
Anticorpos/farmacologia , Antivirais/farmacologia , Rotavirus/efeitos dos fármacos , Carga Viral/efeitos dos fármacos , Animais , Antígenos CD4/imunologia , Linhagem Celular , Embrião de Mamíferos , Histamina/imunologia , Interações Hospedeiro-Patógeno , Interferon gama/antagonistas & inibidores , Rim/efeitos dos fármacos , Rim/patologia , Rim/virologia , Macaca mulatta , Testes de Sensibilidade Microbiana , Rotavirus/fisiologiaRESUMO
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.
Assuntos
Anticorpos/farmacologia , Depressores do Apetite/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Feminino , Masculino , Atividade Motora/efeitos dos fármacos , RatosRESUMO
Antibodies to 5100 proteins (anti-5100) in release-active form (RA anti-5100) are an active component of some domestic drugs(tenoten, tenoten for children, divaza, brizantin, kolofort and proproten-100). The authors present the results of preclinical and clinical trials (with detailed consideration of experimental data) which demonstrated a wide spectrum of specific pharmacological activity and safety as well as mechanisms of anti-5100 action.
Assuntos
Anticorpos/farmacologia , Proteínas S100/antagonistas & inibidores , Proteínas S100/imunologia , Estresse Psicológico/terapia , Anticorpos/efeitos adversos , Anticorpos/uso terapêutico , Estudos Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Humanos , Estresse Psicológico/imunologiaRESUMO
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.
Assuntos
Anemia Ferropriva/tratamento farmacológico , Anticorpos/farmacologia , Complicações na Gravidez/tratamento farmacológico , Anemia Ferropriva/sangue , Animais , Anticorpos/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Contagem de Eritrócitos , Células Eritroides/efeitos dos fármacos , Eritropoese/efeitos dos fármacos , Feminino , Camundongos Endogâmicos C57BL , Gravidez , Complicações na Gravidez/sangueRESUMO
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.
Assuntos
Ansiolíticos/farmacologia , Anticorpos/farmacologia , Antidepressivos/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Diazepam/farmacologia , Combinação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Ratos , Estresse Psicológico/patologia , Natação/psicologiaRESUMO
The present paper reviews preclinical research of divaza, the combination of release-active antibodies to brain-specific 5100 protein and release-active antibodies to endothelial NO-synthase. Preclinical studies have revealed that the specific pharmacological activity of the compounds is retained in the combination, and the components mutually potentiate each other's effects. The previous research have demonstrated high efficacy of divaza in the experimental models of cerebral ischemia and neurodegenerative diseases. Divaza also displays the antihypoxant and antioxidant activity in the animal models of hypoxia by reducing the pathological changes of brain tissue. Significant reduction of the lipid peroxidation process in the affected brain regions can be one of the mechanisms of this effect. In standard experimental models of anxiety and depression, divaza positively influences the psycho-emotional state of animals.
Assuntos
Anticorpos/uso terapêutico , Antioxidantes/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Proteínas S100/imunologia , Animais , Modelos Animais de Doenças , Peroxidação de Lipídeos/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Proteínas S100/metabolismoRESUMO
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.
Assuntos
Fármacos Antiobesidade/farmacologia , Anticorpos/farmacologia , Antagonistas de Receptores de Canabinoides/farmacologia , Obesidade/tratamento farmacológico , Redução de Peso/efeitos dos fármacos , Animais , Depressores do Apetite/farmacologia , Ciclobutanos/farmacologia , Dieta Hiperlipídica , Gorduras na Dieta/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/fisiopatologia , Receptor CB1 de Canabinoide/antagonistas & inibidores , Receptor CB1 de Canabinoide/metabolismoRESUMO
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.
Assuntos
Anticorpos/farmacologia , Prostatite/tratamento farmacológico , Animais , Doença Crônica , Avaliação Pré-Clínica de Medicamentos , Masculino , Extratos Vegetais/farmacologia , Prostatite/patologia , Ratos , Ratos Wistar , Esclerose/patologia , Esclerose/prevenção & controle , SerenoaRESUMO
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.
Assuntos
Anticorpos/farmacologia , Antivirais/farmacologia , Imunidade Celular/efeitos dos fármacos , Imunidade Humoral/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Indutores de Interferon/farmacologia , Adulto , Animais , Linfócitos B/citologia , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Criança , Feminino , Humanos , Interferon gama/antagonistas & inibidores , Interferon gama/imunologia , Células Matadoras Naturais/citologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos CBA , Neutrófilos/citologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologiaRESUMO
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.
Assuntos
Bloqueadores do Receptor Tipo 2 de Angiotensina II/farmacologia , Anticorpos Monoclonais/farmacologia , Fertilidade/efeitos dos fármacos , Fertilização/efeitos dos fármacos , Comportamento Sexual Animal/efeitos dos fármacos , Animais , Ciclo Estral/efeitos dos fármacos , Feminino , Masculino , Ciclo Menstrual/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , Óxido Nítrico Sintase Tipo III/metabolismo , Gravidez , Ratos , Receptor Tipo 2 de Angiotensina/metabolismoRESUMO
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.
Assuntos
Antivirais/uso terapêutico , Influenza Humana/tratamento farmacológico , Oseltamivir/uso terapêutico , Adolescente , Adulto , Antipiréticos/uso terapêutico , Temperatura Corporal , Antígenos CD4/imunologia , Feminino , Febre/tratamento farmacológico , Histamina/imunologia , Humanos , Influenza Humana/etiologia , Interferon gama/imunologia , Masculino , Pessoa de Meia-Idade , Federação Russa , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
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.
Assuntos
Anticorpos/imunologia , Anticorpos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Interferon gama/imunologia , Antivirais/uso terapêutico , Humanos , Indutores de Interferon/uso terapêutico , Resultado do TratamentoRESUMO
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).
Assuntos
Anticorpos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Hiperplasia Prostática/tratamento farmacológico , Adulto , Idoso , Anticorpos/efeitos adversos , Anticorpos/farmacologia , Humanos , Fatores Imunológicos/farmacologia , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/patologia , Qualidade de Vida , Resultado do Tratamento , Urodinâmica/efeitos dos fármacosRESUMO
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.
Assuntos
Anticorpos/uso terapêutico , Doença das Coronárias/complicações , Disfunção Erétil/tratamento farmacológico , Nitratos/uso terapêutico , Anticorpos/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Nitratos/efeitos adversos , Resultado do Tratamento , Vasodilatadores/uso terapêuticoRESUMO
Kardos monotherapy allows attaining the target levels of systolic and diastolic blood pressure in patients with high-risk and very-high-risk hypertension. We demonstrated excellent tolerability of the preparation in combination with reliable blood pressure decrease over 24 h, during day and night hours.
Assuntos
Anticorpos/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Receptores de Angiotensina/química , Receptores de Angiotensina/imunologia , Adolescente , Adulto , Idoso , Anticorpos/administração & dosagem , Anticorpos/imunologia , Anticorpos/farmacologia , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/imunologia , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
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.
Assuntos
Anti-Hipertensivos/farmacocinética , Anti-Hipertensivos/uso terapêutico , Enalapril/uso terapêutico , Hidroclorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Anticorpos/sangue , Anticorpos/imunologia , Anticorpos/uso terapêutico , Anti-Hipertensivos/sangue , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Quimioterapia Combinada , Enalapril/sangue , Enalapril/farmacocinética , Enalapril/farmacologia , Feminino , Humanos , Hidroclorotiazida/sangue , Hidroclorotiazida/farmacocinética , Hidroclorotiazida/farmacologia , Masculino , Pessoa de Meia-Idade , Receptor Tipo 1 de Angiotensina/química , Receptor Tipo 1 de Angiotensina/imunologia , Resultado do TratamentoRESUMO
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.
Assuntos
Anticorpos/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Sistema Cardiovascular/efeitos dos fármacos , Animais , Anticorpos/imunologia , Anti-Hipertensivos/imunologia , Disfunção Erétil/tratamento farmacológico , Hipertensão/tratamento farmacológico , Losartan/uso terapêutico , Masculino , Óxido Nítrico Sintase/imunologia , Distribuição Aleatória , Ratos , Resultado do TratamentoRESUMO
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%.