[Heat-shock protein enhances immunogenicity of E7 oncoprotein of human papillomavirus included in chimeric construction (E7 HPV-HSP70)].

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.

[Fibrinolytic and hypoglycemic effects of the Pro-Gly-Pro-Leu peptide during development of insulin-dependent diabetes in rats].

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.

[The protective effect of the arginine-heparin complex under simulation of insulin-dependent diabetes].

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.

[Antidiabetogenic action of Pro-Gly-Arg and Pro-Gly-Pro-Arg peptides after their intranasal chronic administration to animals].

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.

[Antiplatelet effect of adenosine triphosphate administration to animals under different experimental conditions].

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.

[Effect of chronic intramuscular administration of low molecular weight heparin-collagen complex on hemostatic indices and development of alloxan-induced diabetes].

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.

[Antidiabetic properties of high molecular weight heparin-adenosine triphosphate complex].

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.

[Effect of the heparin-lysine complex on the hemostatic and insular systems]. / Vliianie kampleksa geparin-lizin na gemostaticheskuiu i insuliarnuiu sistemu.

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.

[Antidiabetic and anticoagulant properties of the heparin-glutamic acid complex]. / Antidiabetogennye i protivosvertyvaiushchie svoistva soedineniia geparina s glutaminovoi kislotoi.

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.

[Insular system of animals in a chronic heparin deficiency]. / Insuliarnaia sistema zhivotnykh pri khronicheskom defitsite geparina.

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.

[Effect of a peony root preparation on the status of the insulin and hemostatic system in animals during development of alloxan diabetes]. / Vliianie preparata iz kornei piona na sostoianie insuliarnoi i gemostaticheskoi sistem zhivotnykh pri razvitii alloksanovogo diabeta.

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.

[Changes in the functional status of the hemostatic system with the administration of heparin combined with aspirin to animals with experimental diabetes]. / Izmenenie funktsional'nogo sostoianiia sistemy gemostaza pri vvedenii geparina v sochetanii s aspirinom zhivotnym s éksperimental'nym diabetom.

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.

[Antidiabetogenic action of heparin during its oral administration]. / Antidiabetogennoe deistvie geparina pri ego peroral'nom vvedenii.

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.

[Effect of heparin combined with aspirin upon intragastric administration on the state of the insulin system in animals with alloxan diabetes]. / Vliianie preparata geparina v sochetanii s aspirinom pri ego vnutrizheludochnom vvedenii na sostoianie insuliarnoi sistemy zhivotnykh pri alloksanovom diabete.

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.

[Prophylactic effect of vitamin A, neutralizing the development of experimental insulin-dependent diabetes in animals]. / Profilakticheskoe deistvie vitamina A, neitralizuiushchego razvitie vorganizme zhivotnykh éksperimental'nogo insulinzavisimogo diabeta.

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.

[Stable reduction of endogenous insulin production in the body in experimental insulin-dependent diabetes]. / Ustoichivoe vosstanovlenie produktsii éndogennogo insulina v organizme pri éksperimental'nom insulinzavisimom diabete.

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.

[The pancreas as a source of natural diabetogenic factor in alloxan diabetes]. / Podzheludochnaia zheleza kak istochnik estestvennogo diabetogennogo faktora pri alloksanovom diabete.

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.

[Recovery of the anticoagulation system function in patients with insulin-dependent diabetes by neutralization of the activity of diabetogenic factor]. / Vosstanovlenie funktsii protivosvertyvaiushchei sistemy u bol'nykh insulinzavisimym diabetom putem neitralizatsii v organizme aktivnosti estestvennogo diabetogennogo faktora.

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.

[C-peptide, diabetogenic factor and the blood anticoagulating system in patients with the insulin-dependent type of diabetes mellitus before and after heparin therapy]. / C-peptid, diabetogennyi faktor i protivosvertyvaiushchaia sistema krovi u bol'nykh insulinzavisimym tipom sakharnogo diabeta do i posle geparinoterapii.

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.

[The significance of an increased protein and fat content in the food ration of rats for the development of stable alloxan diabetes]. / Znachenie povyshennogo soderzhaniia belkov i zhirov v pishchevom ratsione krys dlia razvitiia ustoichivogo alloksanovogo diabeta.

An effective model of stable and prolonged alloxan diabetes in rats was described. For this purpose the rats were kept on a synthetic diet with the increased level of proteins and lipids during 1-2 mos. before i.v. injection of alloxan at a dose of 35-40 mg/kg with subsequent feeding by this ration during all the time of the experiment. This model of experimental diabetes ensures a high level of hyperglycemia and hypoinsulinemia as well as a high titer of activity of the diabetogenic factor, to the same extent, as in rats kept on the common laboratory ration.