Inhibition of platelet aggregation by monoclonal antibodies against glycoprotein IIb–IIIa complex

Monoclonal antibodies CRC64 are obtained against Ca²⁺-dependent glycoprotein IIb–IIIa complex of the platelet membrane which possess the ability to inhibit completely fibrinogen-dependent platelet aggregation. CRC64 is directed against the epitope formed by the glycoprotein IIb–IIIa complex and does not interact with proteins isolated after platelets are treated with ethylenediamine tetraacetate. Complete, reproducible blockade of platelet aggregation caused by 5 μM adenosine diphosphate is noted in an MCA concentration of 3 μg/ml, while in the case of a stronger inductor, namely 1 U/ml thrombin, platelet aggregation is inhibited in a concentration of 5 μg/ml. F(ab′)₂ fragments are also able to inhibit platelet aggregation completely and are usually effective in concentrations lower than native monoclonal antibodies. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 10, pp. 402–405, October, 1994 Presented by V. N. Smirnov, Member of the Russian Academy of Medical Sciences     

Influence of fibrinolysis system on ADP- and serotonin-induced aggregation of human platelets

Urokinase, a component of the fibrinolytic system, induces a time-dependent decrease in platelet aggregation activated by ADP and serotonin. Significant inhibition of ADP-induced aggregation was observed on the 30th–60th min and serotonin-induced on the 3th–10th min of preincubation with urokinase and depended on urokinase concentration. The plasmin inhibitor aprotinin partially abolished urokinase-induced reduction of the amplitude and rate of ADP-induced aggregation and had no effect on serotonin-induced aggregation. Our results favor multiple mechanisms of urokinase influence on platelet activity. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 2, pp. 158–161, February, 1998     

Antithrombogenic effect of urokinase bound to collagen substrate with bifunctional antibodies

In vitro experiments simulating collagen-induced thrombogenesis in arteries damaged during angioplasty demonstrate a marked inhibitory effect of surface-bound urokinase. In contrast to free urokinase, bound enzyme is more effective in preventing platelet aggregation on the collagen surface. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 5, pp. 504–507, May, 1994 Presented by V. N. Smirnov, Member of the Russian Academy of Medical Sciences     

Contribution of arachidonic acid cycle enzymes to platelet activation by low-density lipoproteins

The mechanism of platelet activation by low-density lipoproteins (LDL) was studied using inhibitors of arachidonic acid cycle enzymes. Lipoxygenase and cyclooxygenase inhibitors (indomethacin, acetylsalicylic acid, NDGA, and BW755C) inhibited LDL-induced platelet aggregation to a small extent, as was indicated by mere 20% to 30% decreases in the maximal rate of change in light transmission. 4-Bromophenacyl bromide inhibited LDL-induced platelet aggregation in a dose-dependent, manner, almost complete inhibition occurring at concentrations in excess of 20 μM. The results support the conclusion that enzymes to the arachidonic acid cycle do not contribute substantially to platelet activation by LDL. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 10, pp. 376–379, October, 1995 Presented by Yu. M. Lopukhin, Member of the Russian Academy of Medical Sciences     

Effect of human defensins on the cytoplasmic Ca2+ content in platelets

The effect of the total fraction of human defensins (HNP-1, HNP-2, and HNP-3) on the cytoplasmic Ca²⁺ content ([Ca²⁺]_i) in the platelets of healthy donors was studied. At concentrations of 0.1–40 μg/ml and an incubation time of 10 min defensins have no effect on [Ca²⁺]_i in platelets labeled with Fura-2AM. However, at higher concentrations (100 μg/ml) they increased platelet [Ca²⁺]_i. In addition, defensins (40 μg/ml) inhibited the Ca²⁺ increase in platelets induced by thrombin, adenosine diphosphate, and the lipopolysaccharide ofS. typhimurium endotoxin. The most pronounced inhibitory effect was observed in a suspension of thrombin-stimulated platelets. It is shown that the effect of human defensins on the functional activity of platelets is due to the alterations in the intracellular Ca²⁺. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 12, pp. 600–603, December, 1994     

Inhibition of platelet aggregation under the action of sodium hypochlorite. Effect of blood plasma components

The proteins fibrinogen and serum albumin and the amino acid alanine modified by sodium hypochlorite are shown to inhibit thrombin-induced aggregation of isolated platelets. The hypochlorite sodium-treated proteins and amino acids acquire the capacity to counter platelet aggregation as a result of the formation of chloramine derivatives. The aggregating capacity of hypochlorite sodium-inactivated platelets can be restored by native plasma and fibrinogen. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 5, pp. 488–490, May, 1995 Presented by Yu. M. Lopukhin, Member of the Russian Academy of Medical Sciences     

Effect of allicor on platelet aggregationin vitro andex vivo

An extract of garlic powder in isotonic phosphate buffer and adjoen (bioactive compound isolated from garlic powder) suppress human blood platelet aggregation induced by ADP and arachidonic acidin vitro. Adjoen more effectively than aspirin inhibits ADP-induced platelet aggregation but is inferior to aspirin if platelet aggregation is induced by arachidonic acid.Ex vivo oral intake of one Allicor tablet significantly decreases rabbit platelet aggregation induced with ADP. It is suggested that long-acting garlic powder tablets prevent thromboembolic complications and are recommended for correcting hemostasis parameters in patients with atherosclerotic involvement of blood vessels. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 7, pp. 79–100, July, 1997     

Effect of cortisol and pertussis toxin on the cAMP concentration in human lymphocytes

It is demonstrated that pertussis toxin and hydrocortisone potentiate the adenosine-induced rise of the cAMP concentration in lymphocytes. Hydrocortisone elicits an immediate (for the simultaneous addition of adenosine and cortisol) and reversible effect. The effect of pertussis toxin has a latency and is irreversible. Added together, these agents exert no cumulative effect. It is assumed that hydrocortisone and pertussis toxin have the same target — The inhibiting regulatory protein G_i. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 2, pp. 171–173, February, 1995 Presented by P. V. Sergeev, Member of the Russian Academy of Medical Sciences     

A soluble form of guanylate cyclase in the molecular mechanism of the physiological effects of nitrogen oxide and in the regulation of platelet aggregation

The articles is devoted to the role of heme in soluble guanylate cyclase functioning, the molecular mechanism of nitrogen oxide activation of guanylate cyclase, the role of guanylate cyclase in the process of platelet aggregation, and the mechanism of the antihypertensive and antiaggregative action of certain activators of the enzyme. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 3, pp. 230–235, March, 1995 Presented by I. P. Ashmarin, Member of the Russian Academy of Medical Sciences     

Effect of nimodipine on cell calcium concentration and platelet aggregation in patients with ischemic stroke

The rate of spontaneous platelet aggregation is 1.5-2-fold increased in patients with ischemic stroke in comparison with control values. Monotherapy with nimodipine lowers parameters of spontaneous platelet aggregation virtually to normal values. Nimodipine inhibits ADP-induced aggregation but does not affect the ADP affinity of platelet receptors. Experiments with a Fura 2-AM fluorescent probe show that the basal calcium level in platelets from patients with ischemic stroke reliably surpassed that in healthy donors. Nimodipine inhibits the ADP-induced rise of the cell calcium level. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny Vol. 121, N ^o 3, pp. 317–320, March, 1996 Presented by P. V. Sergeev, Member of the Russian Academy of Medical Sciences     

Proteoglycans and cells

Studies of proteoglycans for their capacity to perform the function of steric exclusion of cells are reviewed. The ability of the proteoglycans hyaluronic acid and protein-chrondroitinkeratosulfate and their aggregates to effect cell aggregation and steric exclusion is determined by the structure of glycosaminoglycan components and the amount of covalently bound protein in their macromolecules. These actions of proteoglycans, in which physicochemical processes predominate, can be stimulated or suppressed by protein substances and heparin fractions present in the medium. Results of model tests are fully consistent with those of animal experiments. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, N ^o 2, pp.124–127, February, 1996 Presented by D. S. Sarkisov, Member of the Russian Academy of Medical Sciences)     

Effect of high-density lipoproteins on ADP-induced platelet aggregation in plasma

Autooxidized high-density lipoproteins (HDL₂) inhibit ADP-induced platelet aggregation in platelet-rich plasma. Platelet aggregation in the presence of native HDL₂ and HDL₃ and autooxidized HDL₃ does not differ from the control (plasma with buffer). A conclusion is made on the important role of autooxidized HDL₂ as a thrombogenesis-inhibiting factor in atherosclerosis. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 8, pp. 160–163, August, 1998     

The murine toxin ofYersinia pestis: Some enzymatic activities

The phosphatase, phosphodiesterase, and phospholipase activities identified in this study in a highly purified preparation of theYersinia pestis murine toxin should shed light on the mechanism by which this toxin acts on the target cells of plague-sensitive animals Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 12, pp. 602–605, December, 1995 Presented by D. S. Sarkisov, Member of the Russian Academy of Medical Sciences     

Radiometric evaluation of the effect of xenobiotics on proliferation of bone marrow cells in mice

A radiometric method of evaluating the effect of chemical compounds on the proliferative activity of bone marrow cells is described which consists of measuring the incorporation of labeled³H-thymidine in DNA. Results are reported on a comparative study of the effect of known immunotropic substances on bone marrow cell proliferation using the present method and the method of evaluating endogenous colony formation. Analysis of the results obtained by two variants ofin vivo andin vitro experiments provides additional information regarding the mechanism of action of the substances. Translated fromByulleten Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 8, pp. 222–224, August, 1995 Presented by Yu. A. Romanov, Member of the Russian Academy of Medical Sciences     

Characterization of bacteriophages fromtox-containing, non-toxigenic isolates ofCorynebacterium diphtheriae

Non-toxigenic strains ofCorynebacterium diphtheriaecontinue to cause disease within immunized populations. A subset of these corynebacteria carry the diphtheria toxin gene but in a cryptic form. To determine whether such strains might contribute to the re-emergence of functional toxin genes, the phages andtoxmutations within three clone types were examined.tox-containing, β-related phages were isolated from two of the strain types. The third isolate appeared to harbour a defective prophage. One of thetox⁻phages encoded truncated, yet enzymatically-active, forms of diphtheria toxin, suggesting that it had sustained a point mutation within the latter half of its toxin gene. In contrast, the other mutant phage did not elicit the production of either a cross-reacting material or an ADP-ribosylating activity. Complementation tests employing a series of double lysogens confirmed that the mutations responsible for the non-toxigenic phenotype of all of the phages werecisdominant. Given these findings, it is reasonable to hypothesize thattox⁺genes can arise within human populations by either homologous recombination between two distincttox⁻phages or spontaneous reversion within a single mutant allele.     

Boosting the antitumor effect of doxorubicin by combined correction of hemostasis

The size of the primary tumor and number of metastases to the lungs in mice with Lewis pulmonary carcinoma treated with doxorubicin were, respectively, 3 and 2.2 times less than in the control. Injection of doxorubicin and heparin led to an 8-fold reduction of the tumor. The number of animals with detected metastases to the lungs and the mean number of metastases per animal were decreased. Supplementation of doxorubicin therapy with a complex of drugs correcting platelet aggregation and the antithrombogenic properties of the vascular wall resulted in a reduction of the number of metastases on the lung surface in comparison with the control and with the animals treated with doxorubicin alone. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 2, pp. 204–206, February, 1995 Presented by A. F. Tsyb. Member of the Russian Academy of Medical Sciences     

Effect of a micellar preparation of polyunsaturated phosphatidylcholine on platelet aggregationin vitro

Platelet aggregation was studied after incubation of cells with polyunsaturated phosphatidylcholine in platelet-rich plasma from healthy donors and coronary patients. The aggregation capacity of cells was found to be reduced after preincubation with the above drug. Statistical processing of the results using Student's and Van der Varden's tests showed more expressed effects of polyunsaturated phosphatidylcholine on cell aggregation in coronary patients than in donors. Translated fromByulleten's Eksperimental'noi Biologii i Meditsiny, Vol. 121, N ^o 2, pp. 199–203, February, 1996 Presented by Yu. M. Lopukhin, Member of the Russian Academy of Medical Sciences     

Effect of some lectins on the cholinergic structures of the frog heart

The effect of lectins (phytohemagglutinin — PHA, concanavalin A — ConA,Pisum sativum lectin — PSL,Ricinus communis lectin — RCL, and pokeweed mitogen — PWM) on the cardiac cholinoceptors is studied in experiments on isolated hearts of maleRana temporaria frogs. The test lectins in concentrations from 10⁻²³ to 10⁻³ are shown to exhibit cholinomimetic properties. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 9, pp. 252–255, September, 1994 Presented by A. D. Ado, Member of the Russian Academy of Medical Sciences     

Correlation between the inhibition of phosphorylation in platelet myosin light chains and the inhibition of platelet aggregation by a new calcium and calmodulin antagonist

The recently synthesized compound [1,2,5-trimethyl-4-phenyl-4-β-(N-methyl-N-4′-methoxybenzyl)-ethylamino]piperidine dihydrochloride (AR-3), which is a derivative of [1,2,5-trimethyl-4-phenyl-4-β-(N,N-disubstituted-ethylamino)]piperidines, was tested for its effects on platelet aggregation and phosphorylation of light myosin chains isolated from platelets. AR-3 caused 50% inhibition of platelet aggregation in concentrations of 25.5 to 32.2 μM (depending on the aggregation inducer used) and 50% inhibition of light myosin chain phosphorylation in a concentration of 70 μM or, when 1 μM calmodulin was added, 120 μM. The good correlation found between the inhibitory effects of AR-3 on platelet aggregation and the phosphorylation of light myosin chains from platelets indicates that this compound inhibits platelet aggregation largely by inhibiting the Ca²⁺-calmodulin-dependent phosphorylation of platelet myosin light chains, acting in this respect similarly to the well-known calmodulin antagonist W-7. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 7, pp. 40–42, July, 1996     

Effect of elementary proline-containing peptides on functional activity of anticoagulation system and primary homeostasis

Elementary proline-containing peptides being added to rat platelet-rich plasma or platelet suspension in concentrations of 10⁻¹–10⁻⁷ mg/ml elicit a considerable antiplatelet effect. Efficiency of inhibition of platelet aggregation increases in the following order: Pro-Gly>Pro-Gly-Pro>Gly-Pro-Gly-Gly. Intravenous injection of these peptides activates blood anticoagulation system in experimental animals. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 4, pp. 496–499, May, 1998