[Biochemical bases of ftorafur-potentiating effects of perfluorodecalin, inducer of cytochrome P-450 dependent microsomal monooxygenases]. / Biokhimicheskie osnovy ftorafurpotentsiruiushchikh éffektov perftordekalina induktora tsitokhrom P-450-zavisimykh mikrosomnykh monooksigenaz.

Activity of cytochrome P-450-dependent monooxygenase system is significantly lower in hepatoma H-2-73 and Lewis lung carcinoma-bearing mice as compared to that in control animals. An inhibition of the cytochrome P-450 system was observed after the injection of ftorafur. Treatment of the mice with perfluorodecalin markedly increased the antineoplastic activity of ftorafur determined by a loss of the leucocytes and of the weight hepatoma H-2-73- and Lewis lung carcinoma resistant to ftorafur alone.

[The effect of ziksorin on the development of experimental food anaphylaxis in guinea pigs]. / Vliianie ziksorina na razvitie éksperimental'noi pishchevoi anafilaksii u morskikh svinok.

A study was made of the effect of zixorin, an inductor of liver cytochrome P-450, on the intensity of the immediate type allergic reaction--active food anaphylaxis in response to ovalbumin in guinea-pigs. Intraperitoneal injection of zixorin in a dose of 50 mg/kh for 3 days before administration of the antigen resolution dose was found to lower 2,3-fold the level of lethal outcomes due to the anaphylactic shock. It is suggested that zixorin may be used in multimodality treatment of food allergy.

[The effect of the adamantylamides of 1,3-diphenylpyrazole-4-carboxylic acids on the cytochrome P-450 system of the liver]. / Vliianie adamantilamidov 1,3-difenilpirazol-4-karbonovykh kislot na sistemu tsitokhroma P-450 pecheni.

The effect of adamanthylamides of 1,3-diphenylptrazol-4-carbonic acids on the system of the liver microsomal monoxygenases was studied. A potent induction of the liver cytochrome P-450 by 1,3-diphenylpyrazol-5-methyl-4-carbonic acid, N-methyl-N-(adamant-1-il)amide was found. As a consequence of the induction of the liver cytochrome P-450, the compound reduced by 40% the degree of the delayed type hypersensitivity in mice.

[Effects of zixoryn on pharmacokinetics of antipyrine in intact and sensitized guinea pigs]. / Vliianie ziksorina na farmakokinetiku antipirina u intaktnykh i sensibilizirovannykh morskikh svinok.

The effect of zixoryn, a hepatic inductor of cytochrome P-450, on the pharmacokinetics of antipyrine in intact and sensibilized guinea-pigs was studied. It was found that sensibilization of albumin increased the half-time (T1/2), AUC and decreased the total body clearance (Clt) of antipyrine and the renal clearance (Clr) of metabolites in urine. The administration of zixoryn in sensibilized animals decreased T1/2 and AUC and increased the clearance of antipyrine and its metabolites.

[Post-stress correlation of the functional activity of macrophages by tuftsin and its derivatives]. / Poststressornaia korreliatsiia funktsional'noi aktivnosti makrofagov taftsinom i ego proizvodnymi.

The effect of 15 day programmed neurotization on the functional activity of the peritoneal macrophages has been studied. The NBT-test and the adhesion measurements were used. The experimental neurosis resulted in the decrease of the macrophage functional activity and in leukopenia. Tuftsin did not restore the stress induced depression of macrophage activity but led to additional rise of the adrenal glands weight and to pronounced granulocyte-monocytosis. Pentapeptide analog of tuftsin gave the additional inhibition of NBT-activity of the macrophage. Heptapeptide analog favoured the restoration of the macrophage activity after neurotization and stimulated lymphopoiesis.

[Effect of the induction of liver cytochrome P-450 by a chemically inert fluorocarbon on the reactions of immediate and delayed hypersensitivity]. / Vliianie induktsii tsitokhroma P-450 pecheni khimicheski inertnym ftoruglerodom na reaktsii giverchuvstvitel'nosti nemedlennogo i zamedlennogo tipov.

The effect of chemically inert perfluorodecalin (PFD) on the development of hypersensitive reactions of immediate and delayed types in guinea pigs and mice was studied. It was found that administration of PFD to animals both before sensitization (mice) and during the development of sensitization (guinea pigs) reduced the degree of the both types of hypersensitivity.

[Relation between the toxic killing of mouse small intestine enterocytes and the interval between the administration of the S-specific agent hydroxyurea]. / Zavisimost' toksicheskoi gibeli énterotsitov tonkoi kishki myshei ot intervala mezhdu vvedeniiami S-fazovo-spetsificheskogo agenta-oksimocheviny.

The dependence of small intestinal lesions on the interval between repeated regular injections of hydroxyurea was studied. The doses of 1 g/kg and 0.2 g/kg were used. To activate the enterocyte proliferation the mice were pre-irradiated at 2 Gy. 3-4 hours after the last hydroxyurea injection the two distinct minimum points of epithelial lesions were observed at interinjection intervals of 9 and 16.5 hours. The result was dose-independent.

[Relation of the survival of mouse hematopoietic stem cells to the interval between periodic injections of hydroxyurea]. / Zavisimost' vyzhivaniia stvolovykh krovetvornykh kletok mysh ot intervala mezhdu periodicheskimi vvedeniiami oksimocheviny.

The dependence was studied between the survival of proliferating hemopoietic stem cells (CFUs) on the interval between regular multiple injections of hydroxyurea (HU). Before HU injection mice were irradiated in a dose of 200 rad to trigger the proliferation of CFUs. The dependence obtained is resonance in character, with a maximum being attained during injections made with a 12-hour interval. Comparison with the mathematical model indicates that interval corresponding with the maximal survival should correlate with the mean time of the generation of proliferating CFUs.

[Mechanism of the effect of immobilized noradrenaline on the contact phase of blood coagulation]. / O mekhanizme vliianiia immobilizovannogo noradrenalina na kontaktnuiu fazu svertyvaniia krovi.

A deficiency in the contact phase of blood coagulation, depending on the specific isolation of Fletcher's factor (prekallikreins) from blood plasma, was observed after chromatography of blood plasma on a column with noradrenaline-Sepharose. Activation of kalliklein and dekinination of high-molecular kininogene occurred after the interaction between proenzymes of contact phase of blood coagulation (factor XII, prekallikreins, high-molecular kininogene).

[Kinin system components, free kinins and proteinase inhibitors in the edematous fluids of nephrotic syndrome patients]. / Komponenty kininovoi sistemy, svobodnye kininy i ingibitory proteinaz v otechnykh zhidkostiakh u bol'nykh s nefroticheskim sindromom.

Main components of the kinin system, free kinins, total arginine esterase activity content of alpha 1-antitrypsin and alpha 2-macroglobulin fractions were estimated in various edematous fluids (transduates of different localization, pleural exudates of the inflammatory type) of patients with nephrotic syndrome of various etiology. Noninflammatory edematous fluids (interstitial, abdominal and pleural transudates) were found to contain activated kallikrein and prekallikrein from blood plasma; 3-10 ng/ml of free kinins were present in interstitial edematous fluids and 30-60 ng/ml - in abdominal transudate. Kinins of abdominal transudate were identified with bradikinin by chromatographic properties; a single low-molecular form of kininogene was found, its content did not exceed 10% of the substance occurring in blood plasma of the patients. These edematous fluids practically did not exhibit the kininase activity and contained unsignificant amounts of proteinase inhibitors. Pleural exdates of the inflammatory type were distinctly different from transudates in content of the kinin system components. Depending on the higher content of protein (2.5% as compared with 0.3-0.7% in transudates) the exudates contained high-molecular kininogene and kininase I. Relative content of kallikrein in pleural exudates was lower and that of prekallikrein - higher as compared with transudates; acid kininogenases were not observed. Free kinins (30 ng/ml) were found in three samples of pleural exudates out of five samples studied. The inflammatory type of pleural exudates correlated with the high level of alpha 1-antitrypsin. As shown by comparative analysis of protein fractions from edematous fluids and corresponding samples of blood plasma of patients with nephrotic syndrome, diffusion is the main reason, which determines the course of protein transition from inter-into exovasal space, under conditions of increased vascular permeability. Kallikrein activation and extravasal formation of bradikinin were apparently the long-term affecting factors, supporting the state of increased vascular permeability in nephrotic syndrome; they had an aggravating role in pathogenesis of refractory nephrotic edema, nephrotic crises and cutaneous erythema.

[Effect of a polyvalent proteinase inhibitor from the lungs of a bull on the state of the kinin system in burn shock and acute burn toxemia]. / Vliianie polivalentnogo ingibitora proteinaz iz legkikh byka na sostoianie kininovoi sistemy pri ozhogovom shoke i ostroi ozhogovoi toksemii.

Effect of a polyvalent inhibitor of proteinases from bovine lungs (industrial preparation -- ingitrile, commercial grade -- conntrical) on the state of kinin system was studied in blood serum of patients with extensive burns at shock periods and in acute burn toxemia. Decrease in content of kallikreinogene, which is typical for shock and acute, toxemia and which reflects the activation of kallikrein-kinin system, was less distinct in patients, treated with the inhibitor, than in patients, which were not treated with ingitrile. The early and rapid restoration in kininogene content and distinct inhibition of the total arginine-esterase activity were observed in blood serum after treatment with the inhibitor. The inhibitor did not affect the phase alterations in the carboxypeptidase N activity within the first 3 days after the burns; the distinct decrease in the enzymatic activity was confirmed within the first period of the burn shock. Within 24-48 hrs after the burns content of alpha1-antitrypsin was distinctly increased in patients treated with ingitrile as compared with the untreated group. The data obtained suggest that the polyvalent proteinase inhibitor causes a decrease in activity of the kallikreinkinin system in blood plasma and affects the enzymes participating indirectly in formation of kinins in burned patients. The data obtained are in agreement with the distinct clinical effect of the inhibitor. The doses of the inhibitor used in these studies did not cause normalizing effect on the activity of the kinin system components and on the clinical state of patients only in extremely severe cases of burn shock and in acute burn toxemia with letal outcome within the few days after the injury.

[State of the kinin system and level of serum proteinase inhibitors in latent nephritis and the nephrotic syndrome of different etiology]. / Sostoianie kininovoi sistemy i uroven' ingibitorov proteinaz syvorotki krovi pri latentnom nefrite i nefroticheskom sindrome razlichnoi étiologii.

Main components of kinin system, the arginine-esterase activity and proteinase inhibitors were estimated in blood serum of patients with nephrotic syndrome of various etiology (glomerulonephritis, amyloidosis, systemic lupus erythematous) and also in patients with latent nephritis and in healthy donors. Content of all the kinin system components (kallikreinogen, kininogen and kininase 1) proved to be increased in all the forms of nephropathy studied. Free kallikrein was found in blood serum of patients with nephrotic syndrome as distinct from healthy persons and patients with latent nephritis. The arginine-esterase activity, which shows the level of trypsin-like proteinases, was altered dissimilarly, depending on the nephrotic syndrome etiology: it was maximally increased in nephrotic syndrome of amyloid genesis and decreased in patient with systemic lupus erythematosus. High content of kallikrein and kininase I with simultaneous decrease in kininogen was typical for patients with severe form of nephrotic syndrome. Impairment of kidney in nephrotic syndrome was also characterized by an increase in alpha1-antitrypsin and in the total antitryptic activity, which reached the maximal value in nephrotic syndrome of the I degree and decreased at the II degree of the disease. In nephrotic syndrome content of alpha2-macroglobulin was maximally increased at the II degree of nephrotic syndrome and decreased in severe form of the disease. The primary alteration in content of proteinase inhibitors and high level of kinin system components were assumed to determine the conditions for activation of kinin system in blood serum and to impair the nephrotic syndrome pathogenesis, which was complicated by systemic manifestations. High content of kinin system components was apparently determined by the increased synthesis in liver tissue in response to inflammation and massive proteinuria; kininase I and alpha2-macrolgobulin, as proteins with high molecular weight, were likely to be selectively retained in blood circulation when the capillary penetration was increased.

[Effect of trypsin inhibitor of a peptide-protein nature on kallikreins from human and rabbit blood stream]. / Deistzie Ingibitoroz Tripsina Peptidno-Belkozoi Prirody Na Kallikreiny Cyzorotiki Krozi Chelozeka I Krolika

The effect of three natural trypsin inhibitors--polyvalent Kunitz inhibitor (BPTI), the inhibitor from cow colostrum (CTI) and the inhibitor from soybean (SBTI)--on esterase and kininogenase action of partially purified kallikrein preparations from human and rabbit blood serum is studied. The effect of each inhibitor was estimated from Ki values. The latters show that BPTI, SBTI and CTI are strong inhibitors of both kallikreins. Ki values, as estimated from the hydrolysis rate of N-bensoyl-L-arginine ethyl ester, were found to be for human blood serum kallikrein and BPTI, SBTI and CTI 1,1-10(-9), 4,7-10(-9) and 3,6-10(-8) M respectively and for rabbit kallikrein--1,7-10(-9), 2,3-10(-8) and 2,3-10(-8) M. In the case of kallikrein catalysing more specific kininogenase reaction Ki value for complex of human serum kallikrein with BPTI was 4,8-10(-10) M, for SBTI--1,1-10(-10) M and for CTI--3,6-10(-8) M; for rabbit kallikrein--1,7-10(-9) M, 1,1-10(-9) and 2,3-10(-8) M respectively. The data obtained suggest the high sensitivity of human and rabbit serum kallikreins to the trypsin inhibitor of peptide-protein nature and a close similarity in composition of the active site for both serum kallikreins and trypsin, two spices different kininogenases--from human and rabbit serum had also similarity in molecule conformation and composition active site.