RESUMEN
AIM: To study the effect of chimeric E7 protein of human papillomavirus type 18 on activation of adaptive immunity in absence of adjuvant. MATERIALS AND METHODS: Chimeric protein was genetically engineered and represents the protein molecule consisting of full-size E7 oncoprotein and heat-shock protein 70 (HSP70) of Mycobacterium tuberculosis in one polypeptide chain. Antibody titers as well as isotypes and subisotypes of immunoglobulins were measured by ELISA in sera of immunized animals. RESULTS: It was shown that studied construction E7 (HPV-18)-HSP70 significantly increases titers of antibodies to E7 protein of HPV type 18 and have cross-reactive antigenic activity with E7 protein of HPV type 16. Immunization with chimeric protein resulted in increase of IgG1 and IgG2b levels and decrease of IgG2a and IgM levels. CONCLUSION: . Oncoprotein E7 included in chimeric construction with HSP70 could be used for further studies on development of therapeutic vaccine for treatment of cervical cancer and precancerous lesions. Skew of immune response to Th2 type after intraperitoneal administration of the studied construction points to necessity for control of immunity during such studies.
Asunto(s)
Proteínas Bacterianas/inmunología , Proteínas de Unión al ADN/inmunología , Proteínas HSP70 de Choque Térmico/inmunología , Proteínas Oncogénicas Virales/inmunología , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/inmunología , Proteínas Recombinantes de Fusión/inmunología , Neoplasias del Cuello Uterino/prevención & control , Adyuvantes Inmunológicos/administración & dosificación , Animales , Anticuerpos Antivirales/sangre , Especificidad de Anticuerpos , Proteínas Bacterianas/administración & dosificación , Proteínas Bacterianas/genética , Proteínas de Unión al ADN/administración & dosificación , Proteínas de Unión al ADN/genética , Evaluación Preclínica de Medicamentos , Femenino , Proteínas HSP70 de Choque Térmico/administración & dosificación , Proteínas HSP70 de Choque Térmico/genética , Humanos , Inmunización , Esquemas de Inmunización , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Inyecciones Intraperitoneales , Masculino , Ratones , Proteínas Oncogénicas Virales/administración & dosificación , Proteínas Oncogénicas Virales/genética , Infecciones por Papillomavirus/sangre , Vacunas contra Papillomavirus/administración & dosificación , Vacunas contra Papillomavirus/genética , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/genética , Neoplasias del Cuello Uterino/inmunología , Neoplasias del Cuello Uterino/virologíaRESUMEN
Repeated (over 7 days) intranasal introduction of the Pro-Gly-Pro-Leu peptide into animals at a dose of 1 mg/kg before injection of the diabetogenic metabolite alloxan provided effective protection of an organism against development of insulin-dependent diabetes mellitus and prevented development of hypercoagulating alterations in the system of hemostasis. An increasing in the anticoagulating and fibrinolytic activities in rat blood plasma was detected. The peptide under study also showed antidiabetogenic action: repeated intranasal introduction of the Pro-Gly-Pro-Leu peptide into animals for 7 days inhibited development of diabetes symptoms in rats pretreated with alloxan.
Asunto(s)
Diabetes Mellitus Experimental/prevención & control , Diabetes Mellitus Tipo 1/prevención & control , Fibrinolíticos/uso terapéutico , Hipoglucemiantes/uso terapéutico , Oligopéptidos/uso terapéutico , Administración Intranasal , Aloxano , Animales , Glucemia/análisis , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/inducido químicamente , Fibrinólisis/efectos de los fármacos , Fibrinolíticos/administración & dosificación , Hipoglucemiantes/administración & dosificación , Masculino , Oligopéptidos/administración & dosificación , Ratas , Factores de TiempoRESUMEN
Daily intramuscular injections of the arginine-heparin complex for 5 days before injection of diabetogenic metabolite alloxan did not cause insulin-dependent diabetes in animals for 3 weeks. As a result of these injections, the anticoagulant fibrinolytic pattern of the anticoagulant system was activated and the platelet aggregation decreased. This effect held for 7 days after injection.
Asunto(s)
Anticoagulantes/farmacología , Arginina/farmacología , Diabetes Mellitus Experimental/prevención & control , Fibrinólisis/efectos de los fármacos , Heparina/farmacología , Activación Plaquetaria/efectos de los fármacos , Animales , Masculino , Ratas , Factores de TiempoRESUMEN
It was shown that chronic (over 7 days) intranasal injection of the Pro-Gly-Arg tripeptide to rats in the dose 1 mg/kg before the injection of a diabetogenic dose of alloxan, promotes effective defense against development of insulin dependent diabetes mellitus. At the same time, the tetra-peptide Pro-Gly-Pro-Arg did not show a hypoglycemic affect during diabetes mellitus provocation. Administration of Pro-Gly-Arg and Pro-Gly-Pro-Arg peptides also activates anticoagulation potential.
Asunto(s)
Diabetes Mellitus Experimental/prevención & control , Hipoglucemiantes/farmacología , Oligopéptidos/farmacología , Administración Intranasal , Animales , Coagulación Sanguínea/efectos de los fármacos , Masculino , Ratas , Factores de TiempoRESUMEN
A significant and considerable decrease in abnormally high platelet aggregation has been demonstrated after intramuscular administration of sodium adenosine triphosphate (ATP) to rats with depressed anti-coagulant system (in aging rats at the age of 11-12 months) and to rats with experimental diabetes both preliminarily and at the background of progressing diabetes. The elimination of one of thrombotic risk factors (decreasing elevated platelet aggregation) points to possible antithrombotic activity of ATP under these experimental conditions.
Asunto(s)
Adenosina Trifosfato/uso terapéutico , Envejecimiento/sangre , Diabetes Mellitus Experimental/sangre , Inhibidores de Agregación Plaquetaria/uso terapéutico , Agregación Plaquetaria/efectos de los fármacos , Adenosina Trifosfato/administración & dosificación , Adenosina Trifosfato/farmacología , Animales , Relación Dosis-Respuesta a Droga , Inyecciones Intramusculares , Inyecciones Intravenosas , Masculino , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/farmacología , RatasRESUMEN
Repeated intramuscular administration of low molecular weight heparin-collagen complex proved to increase fibrinolytic activity and to decrease platelet aggregation in the blood of rats (11 months) with depressed anticoagulant system. Administration of diabetogenic alloxan dose induced no diabetes mellitus in such animals.
Asunto(s)
Colágeno/administración & dosificación , Diabetes Mellitus Experimental , Fibrinólisis/efectos de los fármacos , Heparina de Bajo-Peso-Molecular/administración & dosificación , Agregación Plaquetaria/efectos de los fármacos , Aloxano/administración & dosificación , Aloxano/antagonistas & inhibidores , Aloxano/toxicidad , Animales , Colágeno/antagonistas & inhibidores , Diabetes Mellitus Experimental/inducido químicamente , Heparina de Bajo-Peso-Molecular/antagonistas & inhibidores , Inyecciones Intramusculares , RatasRESUMEN
Repeated intramuscular administration of the heparin-adenosine triphosphate (ATP) complex or ATP increased plasma anticoagulant and fibrinolytic activities and depressed the anticoagulation system in rats at the age of 10-11 months. Diabetogenic dose of alloxan induced no diabetes mellitus in such animals.
Asunto(s)
Adenosina Trifosfato/administración & dosificación , Anticoagulantes/administración & dosificación , Diabetes Mellitus Experimental/prevención & control , Heparina/administración & dosificación , Hipoglucemiantes/administración & dosificación , Aloxano/administración & dosificación , Animales , Fibrinólisis/efectos de los fármacos , Masculino , Peso Molecular , Ratas , Ratas MutantesRESUMEN
We studied the effect of chronic intraperitoneal administration of heparin-lysine complex on the state of the hemostatic and insular systems in young and senescent animals (rats). This complex exerted a positive effect on physiological function of the coagulant, anticoagulant, and fibrinolytic components of the hemostatic system in the norm and in developing experimental alloxan diabetes. In this case, both the complex and its components, lysine and heparin, had a pronounced antidiabetogenic effect.
Asunto(s)
Anticoagulantes/administración & dosificación , Diabetes Mellitus Experimental/fisiopatología , Hemostasis/efectos de los fármacos , Heparina/administración & dosificación , Lisina/administración & dosificación , Animales , Diabetes Mellitus Experimental/tratamiento farmacológico , Hemostasis/fisiología , Masculino , RatasRESUMEN
Natural heparin complexes proved to activate the anticoagulation system. The obtained experimental data convincingly confirm that glutamic acid alone, and particularly in a complex with heparin, has a considerable preventive potential and efficiently protects experimental animals with induced diabetes mellitus.
Asunto(s)
Anticoagulantes/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Ácido Glutámico/farmacología , Heparina/farmacología , Hipoglucemiantes/farmacología , Aloxano , Animales , Anticoagulantes/uso terapéutico , Glucemia/efectos de los fármacos , Plaquetas , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/metabolismo , Ácido Glutámico/química , Heparina/química , Hipoglucemiantes/uso terapéutico , Insulina/sangre , Masculino , RatasRESUMEN
The chronic heparin deficiency achieved by long-term treatment (for 3 weeks) with protamine-sulfate is accompanied by the development of stable hyperglycemia, decreased glucose tolerance, and the appearance of insulin resistance. Administration of exogenous heparin promotes the restoration of normoglycemia.
Asunto(s)
Heparina/deficiencia , Hiperglucemia/etiología , Resistencia a la Insulina , Animales , Prueba de Tolerancia a la Glucosa , Heparina/administración & dosificación , Heparina/uso terapéutico , Antagonistas de Heparina/administración & dosificación , Hiperglucemia/tratamiento farmacológico , Masculino , Protaminas/administración & dosificación , RatasRESUMEN
Administration of peony roots preparations provides the stable prophylactic effect against the development of experimental alloxan diabetes. This preparation and its complex with aspirin conserves the normal hemostatic system status and moderates the insular system disturbances. These preparations provide greater survival of animals.
Asunto(s)
Diabetes Mellitus Experimental/prevención & control , Hemostasis/efectos de los fármacos , Insulina/metabolismo , Extractos Vegetales/farmacología , Raíces de Plantas/química , Animales , Aspirina/farmacología , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatología , Masculino , RatasRESUMEN
It was shown that in the case of regular intragastric introduction of heparin combined with aspirin to rats with insulin-dependent experimental diabetes, enzymatic and nonenzymatic fibrinolysis of blood plasma was enhanced. The blood level of sugar was normalized in these animals.
Asunto(s)
Anticoagulantes/administración & dosificación , Aspirina/administración & dosificación , Diabetes Mellitus Experimental/sangre , Fibrinolíticos/administración & dosificación , Hemostasis/efectos de los fármacos , Heparina/administración & dosificación , Animales , Glucemia/análisis , Evaluación Preclínica de Medicamentos , Masculino , Ratas , Factores de TiempoRESUMEN
Oral heparin given to rats was found to neutralize the hyperglycemic and hypoinsulinemic effects of diabetogenic factor and to produce a protective action by preventing the animals from the diabetogenic action of alloxan. The chronic oral heparin use alleviated the course of severe alloxan diabetes in rats, by contributing to the reduction of hyperglycemic levels, to the elevation of blood insulin concentrations, thus promoting their higher survival.
Asunto(s)
Diabetes Mellitus Experimental/prevención & control , Heparina/farmacología , Hiperglucemia/prevención & control , Administración Oral , Animales , Hiperglucemia/etiología , Masculino , RatasRESUMEN
We studied the effect of heparin combined with aspirin on the development and course of experimental alloxan-induced diabetes mellitus. This drug produced a stable hypoglycemic action when it was regularly introduced intragastrically into rats with developing or chronic diabetes.
Asunto(s)
Aspirina/farmacología , Diabetes Mellitus Experimental/fisiopatología , Heparina/farmacología , Hipoglucemiantes/farmacología , Insulina/metabolismo , Aloxano , Animales , Aspirina/administración & dosificación , Glucemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Combinación de Medicamentos , Heparina/administración & dosificación , Hipoglucemiantes/administración & dosificación , Masculino , Ratas , EstómagoRESUMEN
Vitamin A deficiency contributed to higher incidence of abnormalities in experimental animals with insulin-dependent diabetes induced by alloxan. However, the similar doses of alloxan did not cause diabetes in the animals maintained on a diet containing adequate amounts of vitamin A used for prophylactic purposes for a long time. The natural diabetogenic factor specific to insulin-dependent diabetes was not found in the blood serum of these animals.
Asunto(s)
Diabetes Mellitus Experimental/prevención & control , Vitamina A/uso terapéutico , Aloxano , Animales , Glucemia/análisis , Masculino , RatasRESUMEN
Implantation of beta-cells allogenic culture into animals with alloxan diabetes did not produce persistent positive effect. The implanted beta-cells lost their viability as a result of toxic effect of natural diabetogenic factor occurring in blood plasma during insulin-dependent diabetes. Long-term administration of heparin into these animals within first 90 days of the experiment enabled to avoid the negative phenomenon and to neutralize the diabetogenic factor activity. Under these conditions the implanted beta-cells effectively produced endogenous insulin and the symptoms of diabetes disappeared within 14 months.
Asunto(s)
Diabetes Mellitus Experimental/metabolismo , Insulina/biosíntesis , Aloxano/farmacología , Animales , Glucemia/análisis , Trasplante de Islotes Pancreáticos , Masculino , Hormonas Hipofisarias/sangre , RatasRESUMEN
The results of experimental studies bear evidence that the pancreas of healthy animals produces a humoral factor which differs from insulin and prevents the development of alloxan diabetes. The pancreas of diabetic animals loses the above-mentioned activity and produces into the blood plasma a natural diabetogenic factor which promotes the development of alloxan diabetes.
Asunto(s)
Diabetes Mellitus Experimental/fisiopatología , Páncreas/metabolismo , Hormonas Hipofisarias/fisiología , Animales , Hormonas Hipofisarias/biosíntesisRESUMEN
Functions of the anticoagulation system were restored in patients with insulin-dependent diabetes after neutralization of the diabetogenic factor in blood of patients by repeated administration of heparin at low doses. Development of thrombosis was also prevented in these patients.
Asunto(s)
Coagulación Sanguínea , Diabetes Mellitus Tipo 1/sangre , Heparina/administración & dosificación , Hormonas Hipofisarias/antagonistas & inhibidores , Adolescente , Adulto , Coagulación Sanguínea/efectos de los fármacos , Femenino , Heparina/sangre , Humanos , Inyecciones Intramusculares , Masculino , Hormonas Hipofisarias/sangreRESUMEN
The authors analyzed the results of investigation of insulin residual secretion determined by the concentration of C-peptide in response to the stimulation of 1 mg of glucagon. The blood level of the diabetogenic factor (DGF) and activity of the anticoagulative system (ACS) were studied in parallel in patients with insulin-dependent type of diabetes mellitus before and after heparin therapy. The blood DGF disappeared, ACS function was restored, and the patient's body resistance to blood hypercoagulation developed against a background of heparin therapy. A decrease in insulin residual secretion was shown to be related to a duration of diabetes mellitus.
Asunto(s)
Coagulación Sanguínea/fisiología , Péptido C/sangre , Diabetes Mellitus Tipo 1/sangre , Heparina/uso terapéutico , Hormonas Hipofisarias/sangre , Adolescente , Adulto , Coagulación Sanguínea/efectos de los fármacos , Péptido C/efectos de los fármacos , Niño , Enfermedad Crónica , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Femenino , Glucagón , Humanos , Masculino , Factores de TiempoRESUMEN
Activity of risk factors responsible for experimental diabetes (alloxan and natural diabetogenic factor which is an albumin-like protein) was neutralized in healthy rats simultaneously with an increase of heparin concentration in circulation, which was observed 10 min after the anticoagulation system activation caused by thromboplastin.