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Biomedical subjects

I P Baskova

Publications and source records attributed to I P Baskova.

At least 19 recordsLinked to original sources
PubMed1995

Arterial antithrombotic effect of piyavit, the novel pharmacological preparation from the medicinal leech, and of its components, prostanoids and enzyme destabilase.

Piyavit, the novel pharmacological preparation from the medicinal leech (Hirudo medicinalis) contained the leech saliva, produces the potent arterial antithrombotic effect examined on experimental of Laser Induced Thrombus formation. Administrated orally into rats or injected subcutaneously as water extract, non-diluted or in 1600 times diluted, it inhibits statistically significant comparing with control platelet thrombus stimulated by laser beams. Its components, prostanoid fraction and purified enzyme destabilase, endo-epsilon-(gamma-Glu)-Lys-isopeptidase, also inhibit thrombus formation in statistically different manner, comparing with control. All the tested preparations inhibit platelet aggregation induced by ADP. The dependence of arterial antithrombotic effect on the leech prostanoid is discussed.

Administration, Oral↗
PubMed1994

[Detection of nonspecific proteolytic activity in a destabilase--endo-epsilon-(gamma-glutamyl)-lysyl-isopeptidase in the presence of SDS].

The highly specific enzyme--destabilase [endo-epsilon-(gamma-glutamyl)- lysyl-isopeptidase]--similar to the true protease, acquires after incubation with sodium dodecyl sulfate a pronounced proteolytic activity towards certain proteins. At the same time, the amidolytic activity of the enzyme (substrate of p-nitroanilide gamma-glutamic acid) disappears, while its ability to catalyse the monomerization of the D-D dimer, a fragment of stabilized fibrin, is preserved. After SDS removal by gel filtration, the enzyme loses its nonspecific proteolytic activity, while its specific activity is fully reconstituted. Other detergents produce a more weak influence upon the enzyme. The putative mechanism providing the increase in the enzyme specificity in the presence of sodium dodecyl sulfate is discussed.

Amides↗
PubMed1992

Inhibition of plasma kallikrein. Kininase and kinin-like activities of preparations from the medicinal leeches.

The medicinal leech salivary gland secretion deprived of hirudin antithrombin activity inhibits amidolytic (substrate S-2302) and kininogenase (substrate kininogen) activities of plasma kallikrein, the main component of the intrinsic mechanism of blood coagulation. It therefore possesses high anticoagulant properties. Kininase (substrate bradykinin) activity of leech saliva and extracts from the medicinal leeches, as well as kinin-like effects of extracts heated at 100 degrees C have been detected. The last one is correlated with the hyperalgetic property of the heated extract. An analgetic effect was observed with the unheated extract but not with leech saliva after intranasal administration to rats.

Amino Acid Sequence↗
PubMed1992

Use of the medicinal leech in the treatment of ear diseases.

Medicinal leeches (Hirudo medicinalis) and the native secretion of their salivary glands diluted with saline (5 times) were successfully used for the treatment of some ear diseases: tinnitus caused by inner-ear affections, acute external otitis and chronic otitis media. The effect of diluted leech saliva injected into the region of the mastoid process by microelectrophoresis was 25-30% lower than that of the medicinal leeches.

Acute Disease↗
PubMed1992

[Monomerization of the fragment D dimer of stabilized fibrin by a secretion from the medicinal leech salivary gland].

The salivary gland secretion of the medicinal leech catalyzes the conversion into monomeric form of the fragment D dimer, the product of limited proteolysis of stabilized fibrin. Analysis of N-terminal sequences revealed identical fragments for the D-dimer gamma-gamma-chains and the D-monomer gamma-chains formed via this reaction and established the presence of only one N-terminal amino acid (Ser). These results provide evidence for the preservation of integrity of the polypeptide chains during monomerization of the D-dimer.

Amino Acid Sequence↗
PubMed1991

Destabilase, the novel epsilon-(gamma-Glu)-Lys isopeptidase with thrombolytic activity.

The salivary gland secretion of the leech Hirudo medicinalis contains the enzyme destabilase which hydrolyses epsilon-(gamma-Glu)-Lys cross-links in stabilized fibrin. Accumulation of Glu residues instead of the original Gln residues leads to spontaneous depolymerization of destabilized fibrin. L-gamma-Glu-p-nitroanilide; L-gamma-Glu-dansylcadaverine and isopeptide epsilon-(gamma-Glu)-Lys are low-molecular-weight substrates of destabilase. Destabilase probably exists in molecular forms of molecular weight 50,000, 25,000 and 12,300. The protein part of destabilase is covalently bound to a lipid component of molecular weight 390, which has little cross-reactivity to 6-keto-prostaglandin F1 alpha antiserum. The lipid component ensures the hydrophobic properties of destabilase, inhibition of platelet aggregation, protection from proteolysis and absorption from the intestine into blood during oral administration to experimental animals. It also ensures the protective antithrombotic effect. Almost total (80-100%) thrombolysis of preformed thrombus in the rat was achieved by destabilase 70-100 h after i.v. injection or oral administration.

Animals↗
PubMed1990

[Kinetics of L-gamma-Glu-pNA hydrolysis by destabilase, the enzyme from the medicinal leech Hirudo medicinalis].

The molecular mass of destabilase isolated from the medicinae leech Hirudo medicinalis was found to be equal to 12.3 kDa. A kinetic analysis of the sole presently known synthetic substrate, L-gamma-Glu-pNA, showed that the enzyme is relatively stable to heating (5 min, 70 degrees C); the pH optimum lies at 7.0-8.5. The enzyme has a specific activity of 0.15 x 10(-9) mol.s-1.mg-1; Km = 2.2 x 10(-4) M, kcat is 3.53 x 10(-3) s-1 (pH 8.0, 37 degrees C).

Animals↗
PubMed1990

[Hydrolysis of the isopeptide epsilon-(gamma-glutamyl)-lysine by destabilase from the medicinal leech Hirudo medicinalis].

Using amino acid analysis, the ability of destabilize to hydrolyze the epsilon-(gamma-Glu)-Lys isopeptide bond was demonstrated. Incubation of the epsilon-(gamma-Glu)-Lys isopeptide with the enzyme was accompanied by a decrease of the amount of the isopeptide and an increase of equimolar amounts of lysine and glutamic acid. Complete hydrolysis of the isopeptide was observed after 96 hour incubation with destabilize. It was supposed that the isopeptide is a less specific substrate for destabilize compared to L-gamma-Glu-pNA.

Amino Acids↗
PubMed1990

[The effect of preparations of Hirudo medicinalis leeches on DNA methylation in the rat liver].

The effect of the salivary gland secretion and dialysable part of the homogenate of the leeches Hirudo medicinalis on the methylation of DNA in the rat liver after the intraperitoneal injection and perfusion of isolated liver has been analysed. The maximum concentration of 5-methylcytosine is observed 1 h later the injection of preparations: for the salivary gland secretion the increase is 39%, for the dialysate of leech homogenate is 28%. The 5-methylcytosine content increases on 28% after the perfusion of isolated liver with the leech saliva and after the dialysate of the leech homogenate--on 20%. No other changes in DNA content is observed. It is suggested that the DNA-methylation of the liver cells is due to the penetration of biologically active substances produced by the medical leech into the cell-targets accompanied by the forming of corresponding ligand-receptor complexes.

5-Methylcytosine↗
PubMed1989

[Effect of medicinal leech preparations on indicators of atherogenesis].

Medicinal leech salivary gland secretion, administered intravenously to rats on an atherogenic diet, reduces fibrinogen level and plasma heparin tolerance and diminishes lipid deposits in the intima of large vessels. Long-term chronic oral administration of dried medicinal leech powder to rats, kept on an atherogenic diet, reduces the area of local edema in the intima of large vessels, although blood lipid composition, fibrinogen level and plasma heparin tolerance remain basically unchanged, as compared to respective values in the control animals. The salivary gland secretion reduces the 3H-thymidine incorporation into the human atherosclerotic intimal cell culture.

Administration, Oral↗
PubMed1988

Thrombolytic agents of the preparation from the medicinal leeches.

The thrombolytic effect of an extract from medicinal leeches orally administered to rats was shown. This effect depends on the number of administrations and on the concentration of extract. It is due to the leech prostaglandins and enzyme destabilase. After the extraction of prostaglandins by ethylacetate the thrombolytic effect diminished by 45%. It is supposed that the leech-prostaglandins, like prostacyclin and its stable analogous, induce the release of tissue plasminogen activator from vessel walls. The thrombolytic effect of destabilase was demonstrated in experiments in vitro. We observed the phenomenon of increasing of glutaminase activity of citrate blood and the appearance of amidolytic and destabilase activity.

Animals↗
PubMed1988

Antithrombotic effect of preparations from the leeches Hirudo medicinalis.

Antithrombotic effect of leech salivary gland secretion was maximal after intravenous administration into rats and was slightly decreased in cases of peroral administration. Blood from leech intestinal tract and leech homogenate exhibited less distinct antithrombotic action. Effect of these preparations was maintained after peroral administration. The antithrombotic effect of the leech preparations did not depend on their antithrombic activity caused by hirudin. These leech preparations appear to elongate a period of blood plasma recalcification caused by kallikrein inhibitor as well as apparently due to their capacity to inhibit aggregation of the thrombocytes.

Administration, Oral↗
PubMed1988

[Inhibition of kallikrein from human plasma by salivary gland secretion and extracts of the medicinal leech Hirudo medicinalis].

It has been shown for the first time that the salivary gland secretion of the medicinal leech (Hirudo medicinalis) contains a human blood plasma kallikrein inhibitor which is capable of blocking the amidolytic activity of the enzyme in an irreversible manner (with D-Pro-Phe-Arg-pNA as substrate) and which also suppresses the kininogenase activity of kallikrein. The inhibition of the amidolytic activity of highly purified kallikrein preparations from human blood plasma obeys the pseudo-first order kinetics. The experimental results suggest that in the salivary-gland secretion of H. medicinalis the inhibitor concentration exceeds by one order of magnitude that in whole leech homogenate extracts, which indicates that the inhibitor biosynthesis may be localized in leech salivary glands.

Animals↗
PubMed1987

[Mechanisms of inhibition of vascular-platelet hemostasis by salivary gland secretion of the medicinal leech Hirudo medicinalis].

The mechanism of inhibition of the vascular-platelet stage of hemostasis by medicinal leech salivary gland secretion was studied. It was shown that the secretion blocks platelet adhesion on the surface of collagens belonging to different genetic classes, inhibits the primary attachment of platelets and completely suppresses their spreading on collagen surface. Whatever its antithrombin activity, the leech secretion inhibits platelet aggregation stimulated by various inductors, e. g., ADP, prostaglandin endoperoxide analog U-46619, Ca2+ ionophore A23187, arachidonic acid. The secretion possessing the antithrombin activity causes a greater inhibition of the thrombin-stimulated aggregation than that devoid of this activity. Leech secretion stimulates adenylate cyclase of platelet membranes in a receptor-mediated fashion and increases the level of cAMP. The active substance is a low molecular weight, thermostable trypsin-resistant fraction of the secretion. Stimulation of adenylate cyclase is not mediated by adenosine receptors. It is supposed that the mechanism of this activating effect involves platelet prostaglandin receptors.

Adenylyl Cyclases↗