[A new Russian gestagen with anticancer activity].

The authors present results obtained in a complex study of 17alpha-acetoxy-3beta-butanoyloxy-6-methyl-pregna-4,6-dien-20-on (ABMP). ABMP was shown to differ from existing analogues by high gestagen activity and prolonged action. The substance does not possess androgenic or mineralocorticoid activity, is not toxic when used in high doses, and possesses significant cytostatic and chemiosensitizing activity. These properties of ABMP demonstrate that the substance should be studied in clinical setting as a gestagen with anticancer and chemiosensitizing activity for further application to therapy of hyperplastic processes in the female genital system and tumors that are sensitive to female sex hormones.

[Effects of ionic and non-ionic roentgen-contrast media upon ex vivo hemostasis in rabbits].

The influence of ionic and non-ionic contrast media on the ex vivo hemostasis in rabbits was studied for ionic urografin (76 %), non-ionic ultravist-300, and non-ionic omnipaque-300 intravenously injected in medium and high doses (1.5 ml/kg and 3.0 ml/kg, respectively). Ionic urografin (1.5 ml/kg) almost did not influence the level of hemostasis ex vivo. Non-ionic contrast media (ultravist and omnipaque) in the medium diagnostic dose (1.5 ml/kg) activated the hemostasis, the effect being much more pronounced in the case of omnipaque. Dose-dependent action was observed for both ionic and non-ionic contrast media.

The expression of esterase S gene of Drosophila virilis in Drosophila melanogaster.

Drosophila melanogaster was transformed with the esterase S gene from Drosophila virilis. This gene is strongly activated in ejaculatory bulbs of mature males of Drosophila virilis. The closely related gene from Drosophila melanogaster is activated in ejaculatory ducts. The tissue- and stage-specific expression of incomplete genomic copy of the esterase S gene integrated into the Drosophila melanogaster genome is the same as in Drosophila virilis. These data show that tissue and stage specificity is determined by relatively small 5' regulatory region of the esterase S gene. The comparison between deduced amino-acid sequences of the esterase S of Drosophila virilis and esterase 6 of Drosophila melanogaster was performed. These sequences revealed 50% homology.

[Interaction of steroids with human serum albumin by spin echo technique and paramagnetic sound methods]. / Issledovanie vzaimodeistviia steroidov s syvorotochnym al'buminom cheloveka metodom spinovoe ekho-paramagnitnyi zond.

The rate of water proton relaxation of the solutions of human serum albumin (HSA) modified by different spin labels has been investigated by spin echo technique. The rate of proton relaxation in the presence of the labeled HSA is higher than that in water solutions of spin labels. The proton relaxation data of the protein solutions can be explained by local properties of the water, bound with the protein (in the regions of spin labels) which seem to resemble those of water-glycerol solutions. The rate of proton relaxation was decreased in the presence of steroids that can be explained by a decrease of the local microviscosity of the water-protein matrix due to interaction of steroids with HSA.

[Primary structure of the esterase s gene from Drosophila virilis]. / Pervichnaia struktura gena ésterazy S Drosophila virilis.

Complete nucleotide sequence of the esterase S gene of Drosophila virilis has been determined. The length of the gene from the transcription initiation site down to the polyadenylation signal is about 1850 bp. Conceptual translation of the DNA sequence reveals a protein 549 amino acid residues long, its presumptive active site being highly similar to active sites of the known esterases of insects and mammals.

[Molecular stereopharmacology and the search for stereoselective drugs]. / Molekuliarnaia stereofarmakologiia i problema poiska novykh stereoselektivnykh lekarstvennykh sredstv.

Analyzing modern trends in stereopharmacology shows that its theoretical aspects are mainly associated with the studies of the steric parameters of active centers of drug receptors and enzymes by using compounds having a well-established stereostructure. Applied stereopharmacology underlines the vital necessity of selective production and use of drug eutomers and active modifications of polymorphic drugs. The creation of an information computer database of stereostructural parameters of drugs is considered to be basic for further design of new selective drugs.

[Dexamethasone and corticosterone binding by glucocorticoid-resistant and glucocorticoid-sensitive thymocytes in vitro and in vivo]. / Sviazyvanie gliukokortikoidochuvstvitel'nymi i gliukokortiko-rezistentnymi timotsitami deksametazona i kortikosterona in vitro i in vivo.

No correlation between the sensitivity of thymocytes to glucocorticoids and the number of glucocorticoid receptors has been revealed in studies carried out in vivo and in vitro. The micromedium of the thymus has been found capable of accumulating glucocorticoid hormones.

[Fenibut and fenazepam as potential protectors of pregnancy with a GABA-ergic mechanism of action]. / Fenibut i fenazepam kakpotentsial'nye gravidoprotektory GAMKergicheskogo mekhanizma deistviia.

It has been shown that the GABAergic system of the myometrium takes part in regulation of uterine contractility during the development of pregnancy Fenibut and phenazepam exhibit a specific uterotropic effect. The uterodepressant effect of fenibut is realized via the inhibiting GABA-receptors of the myometrium. The uteroinhibiting effect of phenazepam is mediated through the interaction with the postsynaptic GABA-benzodiazepin-C1-receptor complex of the myometrium.

[Serotonin receptors (results of the pharmacological study)]. / Retseptory serotonina (rezul'taty farmakologicheskogo analiza).

Information is presented on the classification of serotonin receptors which is based on the results of pharmacological and radioligand analysis. The genetic and biochemical characteristics of the types and subtypes of serotonin receptors are discussed. The role of serotonin receptors of the central and peripheral nervous system and the role of some effector cells and organs in the regulation of their functional activity is described.

[A comparative study of the interaction of steroid preparations with the lymphocytes]. / Sravnitel'noe izuchenie vzaimodeistviia steroidnykh preparatov s limfotsitami.

In in vivo and in vitro experiments, androgen anabolic steroid agents (testosterone, methandrostenolone) and dexamethasone showed a dose-dependent inhibition of PHA-stimulated proliferation of C57BL/6 mice thymocytes. The phytoecdysteroidal anabolic steroid ecdystene failed to inhibit thymocytic proliferation. The competitive radioligand analysis was used to show that testosterone and methandrostenolone displace the androgenic steroid mibolerone from lymphocytes. The findings provide evidence that lymphocytes have specific binding sites for androgen-anabolic steroids.

[The effect of x-ray contrast media on the amount of thromboxane and prostacyclin in the blood of man and rats in vivo and in vitro]. / Vliianie rentgenokontrastnykh sredstv na kolichestvo troboksana i prostatsiklina v krovi u cheloveka i krys in vivo i in vitro.

The in vivo and in vitro effects of radioopaque agents such as bilignost, iodamide, and triombrast on blood thromboxane B2 (TxB2) and prostacyclin levels were studied in man and rats. These radioopaque agents were demonstrated to increase prostacyclin levels and to decrease TxB2 in the plasma by 40%, as evidenced by urography when given in vivo (1-2 g/kg) and in vitro (2.5.10(-2) M and 2.5.10(-3) M).

[The effect of antioxidants on the fast burst of Fe2(+)-induced chemiluminescence]. / Vliianie antioksidantov na bystruiu vspyshku Fe2()-indutsirovannoi khemiliuminestsentsii.

A new micromethod for measuring the intensity of free radical oxidation reactions, based on an analysis of "fast flash" of iron-induced chemiluminescence parameters has been designed. The optimal concentration parameters of the reaction system have been determined. The effects of the antioxidants mexidol, probucol sodium dibunat and fenoxan have been examined in vitro.

[An experimental study of the cardiovascular activity of nistranol]. / Eksperimental'noe issledovanie serdechno-sosudistoi aktivnosti nistranola.

In concentrations of > or = 10(-5) mol/liter nistranol (11 beta-nitroxy-9 alpha-hydroxy-ethynylestradiol-diacetate) demonstrated cardiac and vascular activity in vitro. It caused concentration-dependent and reversible increase of the contractile parameters of an isolated atrial appendage of rats. A three-phase effect of nistranol on a isolated rat thoracic aorta was encountered: vasodilatation-vasoconstriction-vasodilatation. Anti-ischemic and antinecrotic effects of nistranol were noted in experimental myocardial infarction.

[The effect of iodine-containing x-ray contrast media on water status in the blood plasma]. / Vliianie iodsoderzhashchikh rentgenokontrastnykh sredstv na sostoianie vody v plazme krovi.

The impact of radio-opaque agents on human blood plasma water pool was studied by using relaxation proton magnetic resonance methods with a pulse gradient of magnetic field. The findings suggest that blood plasma water imbalance was induced by human serum albumin dehydration processes after RCN-HSA interaction.

[The effect of x-ray contrast media on the blast transformation of human peripheral blood T-lymphocytes in vitro]. / Vliianie rentgenokontrastnykh sredstv na blasttransformatsiiu T-limfotsitov perifericheskoi krovi cheloveka in vitro.

The effects of radiopaque agents on peripheral blood T-lymphocyte blast transformation were in vitro studied in healthy donors. It was shown that depending on the dose and type, radiopaque agents activated spontaneous proliferation of these cells and inhibited or activated PGA-induced proliferation. An individual sensitivity of peripheral blood lymphocytes to the radiopaque agents was revealed. There was a positive correlation between the functional response of peripheral blood lymphocytes to PGA and the degree of bilignost-induced inhibition of this reaction. There was also antagonism of some radiopaques in response to peripheral blood T-lymphocyte blast transformation.

[The mechanisms of the interaction of contrast media with serum albumin and gamma-globulin studied by means of fluorescence extinction and equilibrium dialysis]. / Issledovanie mekhanizmov vzaimodeistviia kontrastnykh sredstv s syvorotochnym al'buminom i gamma-globulinom metodami tusheniia fliuorestsentsii i ravnovesnogo dializa.

The mechanisms binding X-ray contrast media and magneto-resonance contrast media of various structure with human serum albumin and gamma-globulins were studied. Equilibrium dialysis showed that X-ray contrast media bind with blood plasma proteins, but magneto-resonance contrast media do not interact with these proteins. Electrostatic forces play a significant role in formation of complexes of X-ray contrast media with human blood serum albumin. With increase in the size of the molecule of the X-ray contrast media their affinity for the binding sites of this protein diminishes. The formation of complexes of X-ray contrast media with human blood plasma gamma-globulins occurs through hydrophobic interactions. Increase in the size of the molecules of these media reduces their affinity for the gamma-globulin binding sites.

[Antitumor activity of the new gestagen 17alpha-acetoxy-3beta-butanoyloxy-6-methyl-pregna-4,6-dien-20-one]. / Izuchenie protivoopukholevoi aktivnosti novogo gestagena 17 al'fa-atsetoksi-3 beta-butanoiloksi-6-metil-pregna-4,6-dien-20-ona.

Antitumor activity of a new highly active promising gestagen 17alpha-acetoxy-3beta-butanoyloxy-6-methyl-pregna-4,6-dien-20-one (butagest) was studied in mice with model cervical carcinoma (RShM-5). The reference drug was medroxyprogesteron acetate (MPA, Depo Provera) used in clinics. The new preparation introduced perorally in a dose of 1 mg per mice inhibited the model tumor growth by 73%, which was 18% (p < 0.01) more effective than the action of the reference drug MPA. The effect of the new gestagen was also studied in vitro with respect to human breast carcinoma of the MCF-7 line and human cervical carcinoma HeLa. The viability of the tumor cells was studied during a 6-day incubation with the drug at a concentration of 10(-7)-10(-5) M (MTT test). The reference compounds were progesterone and MPA. These drugs suppressed the growth of both MCF-7 and, in higher concentrations, of HeLa. Butagest inhibited the growth of HeLa in all concentrations. Thus, the new gestagen 17alpha-acetoxy-3beta-butanoyloxy-6-methyl-pregna-4,6-dien-20-one is capable of suppressing the viability of human breast carcinoma and human cervical carcinoma, being comparable or even more effective than the reference drugs.

[The effect of nitroglycerin on the Ca2+ ion level in the cytoplasm of human lymphocytes]. / Vliianie nitroglitserina na soderzhanie ionov Ca2+ v tsitoplazme limfotsitov cheloveka.

Fluorescence was used to examine the effects of nitroglycerin (60 microM) on basal and mitogen-induced (ConA, 25 micrograms/ml) Ca2+ levels in the human lymphocytic cytoplasm. Calcium-blocking effect of nitroglycerin was markedly shown in the medium containing 1 mM CaCl2 and virtually absent in calcium-free buffer. It is concluded that nitroglycerin affects cellular Ca2+ entry. A 120-minute preincubation led to a complete loss of the inhibitory effects of the drug on mitogen-induced Ca2+ responses of lymphocytes. Human lymphocytes are proposed as an experimental model for investigating the effects of nitrates and the mechanisms of their tolerance development.

[The biochemical and rheological properties of the blood during the performance of angiography using Ultravist]. / Biokhimicheskie i reologicheskie svoistva krovi pri provedenii angiografii s pomoshch'iu ul'travista.

It is shown that Ultravist makes it possible to receive clear visualization of vessel channel in the zone "of interest" without changing functional conditions of heart vascular system and biochemical blood parameters (level of erythrocytes, bilirubine, urine nitrogen, activity of aspartataminotransferase). In concentration 30 mg/ml in vitro and in vivo Ultravist decreases a viscosity limit not affecting other rheological properties of blood. A mechanism of the found Ultravist effect and prospects of its application in practice for children are considered.

[Estradiol binding and lipid metabolism in the plasma membrane of myometrial cells during tumor growth]. / Sviazyvanie éstradiola i metabolizm lipidov v plazmaticheskikh membranakh kletok miometriia pri opukholevom roste.

The study was concerned with evaluation of the parameters of specific binding of 17-beta-estradiol to myometrial plasma membrane in tumor growth versus lipid profile of the membrane and A2 and C phospholipase activity. Tumor growth was shown to involve an increase in the association constant of plasma membrane, changes in the lipid profile and activity of the enzymes. The role of these factors in myometrial carcinogenesis is discussed.