bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contribution of Platelets to the Cardiovascular Effects of ADP in the Rat
Authors: Dejana Elisabetta , Castelli Maria Grazia , De Gaetano Giovanni , Bonaccorsi Aurora 
Published: July 2018

SummaryThe contribution of platelets to the cardiovascular effects of ADP was investigated in rats in different experimental conditions. Following rapid i. v. bolus injections of ADP (from 0.001 to 0.03 mg/kg b. w.) only a dose-related fall in blood pressure could be detected. Increasing the dose of ADP (up to 1 mg/kg b. w.), platelet fall and changes in cardiac rhythm (bradycardia, A. V. blocks and ectopic beats) became evident. All these phenomena were rapidly reversed. Inhibition of platelet aggregation by a pyrimido-pyrimidine compound (SH 869) or thrombocytopenia induced by Busulfan or antiplatelet antiserum did not significantly protect the animals from the cardiovascular effects of ADP. The fall in blood pressure, however, was reduced. Adenosine, at equimolar concentrations, caused ECG changes similar to those induced by ADP with no platelet aggregation and a less pronounced blood pressure fall.These results suggest that most of the cardiovascular modifications induced by rapid injection of ADP are largely independent of platelets. Platelets appeared to play a more important role when ADP was given for a longer period of time. A slow i. v. infusion of ADP (6 mg/kg b. w. for 10 min) was accompanied by platelet fall, cardiovascular collapse and ECG alterations typical of myocardial ischaemia. All these effects persisted throughout the ADP infusion but disappeared soon after its termination. They were almost completely inhibited in rats given SH 869 or made thrombocytopenic.In conclusion, platelets seem to contribute to the cardiovascular effects of ADP only in certain experimental conditions. In others, the nucleotide’s direct effects seem more important.
Effect of 1-Methyl-2-Mercapto-5-(3-Pyridyl)-Imidazole (KC-6141) on Rabbit Platelet Aggregation in Vitro and Rat Platelet Retention
Authors: Umetsu Teruhiko , Kato Tadakatsu 
Published: July 2018

SummaryEffect of l-methyl-2-mercapto-5-(3-pyridyl)-imidazole (KC-6141) on rabbit platelet aggregation in vitro and rat platelet retention were investigated.In the in vitro study, KC-6141 inhibited ADP-induced aggregation by 27% at 5× 10−4M, being more active than dipyridamole but much less than adenosine. Inhibition of arachidonic acid-and collagen-induced aggregation by KC-6141 was more effective than that of ADP-induced one and its ED50 was 2.1×10−5 and 8×10−5M, respectively. KC-6141 was 10 and 4 times more potent than aspirin in arachidonic acid-and collagen-induced aggregation, respectively. The dose-response curve of KC-6141 was parallel to that of aspirin, suggesting it is an aspirin-like compound.In the platelet retention study, a method for determining platelet retention in rats was devised so that platelet retention can be measured with a volume of blood as small as possible. By use of the method, effects of KC-6141, aspirin and dipyridamole were compared. When administered intraperitoneally at 100 mg/kg, KC-6141 indicated 54.8% inhibition of platelet retention, whereas aspirin and dipyridamole showed only 23.5 and 5.2% inhibition, respectively. On the oral administration at 200 mg/kg, KC-6141 inhibited by 60.8% and its ED50 was 125 mg/kg. The activity lasted over 32 hr.The above results demonstrated that KC-6141 is a compound with more potent action on the platelet aggregation, as well as on the platelet retention than aspirin and dipyridamole – a known antithrombotic drug.
The Effect of Mitomycin C on Platelet Aggregation and Adenosine 3′, 5′-Monophosphate Metabolism
Authors: Hashimoto Shuichi , Shibata Sachiko , Kobayashi Bonro 
Published: July 2018

SummaryThe effect of Mitomycin C on aggregation, adenosine 3′, 5′-monophosphate (cyclic AMP) metabolism and reactions induced by thrombin was studied in rabbit platelets. Mitomycin C inhibited the platelet aggregation induced by adenosine diphosphate or thrombin. The level of radioactive cyclic AMP derived from 8-14C adenine or 8-14C adenosine increased after incubating intact platelets with Mitomycin G. Formation of radioactive adenosine triphosphate also increased though mitochondrial oxidation was not stimulated. Similar effect was observed also in rabbit liver. Mitomycin C failed to stimulate platelet adenyl cyclase but inhibited cyclic AMP phosphodiesterase in the absence of theophylline. In the platelets preincubated with Mitomycin C, thrombin-induced inhibition of adenyl cyclase, stimulation of membrane-bound cyclic AMP phosphodiesterase, and release of 250,000 dalton protein from platelet membranes were prevented. These results suggest that Mitomycin C will affect cellular membrane structure and function, and this extranuclear effect of Mitomycin C will lead to inhibition of aggregation in blood platelets.
Effect on Platelet Functions of Derivatives of Cyclic Nucleotides
Authors: Pareti F I , Carrera D , Mannucci L , Mannucci P M 
Published: July 2018

SummaryDerivatives of cyclic nucleotides were evaluated for their ability to inhibit platelet aggregation and the release reaction. Derivatives substituted in position 8 (mainly 8-Br-cyclic GMP) were more active than 3’-5’ cyclic AMP, and their relative potency in inhibiting platelet aggregation and 14C-serotonin release was comparable to that of N62-0’-dibutyryl-cyclic AMP. Compounds substituted in position 6 or 2’-0 were not effective. The active compounds, which were also tested for their ability to stimulate platelet adenylate cyclase or to inhibit cyclic AMP phosphodiesterase, did not modify the intracellular levels of cyclic AMP. Since previous animal experiments have shown that these derivatives cause less side effects than cyclic AMP and its dibutyryl derivative in animals, it is suggested that modification of the cyclophosphate molecule might make it possible to find compounds active only on platelet function without interfering with other biological systems.
Ornithine Decarboxylase Activity in Cultured Endothelial Cells Stimulated by Serum, Thrombin and Serotonin
Authors: D’Amore P A , Hechtman H B , Shepro D 
Published: July 2018

SummaryOrnithine decarboxylase (ODC) activity, the rate-limiting step in the synthesis of polyamines, can be demonstrated in cultured, bovine, aortic endothelial cells (EC). Serum, serotonin and thrombin produce a rise in ODC activity. The serotonin-induced ODC activity is significantly blocked by imipramine (10-5 M) or Lilly 11 0140 (10-6M). Preincubation of EC with these blockers together almost completely depresses the 5-HT-stimulated ODC activity. These observations suggest a manner by which platelets may maintain EC structural and metabolic soundness.
Tissue Thromboplastin Activity of Isolated Human Monocytes
Authors: Prydz H , Allison A C 
Published: July 2018

SummaryCertain agents that induce spreading of or increased content or release of lysosomal enzymes from human monocytes also induce a dramatic increase in tissue thromboplastin content of the cells. The increase is inhibited by cycloheximide and actinomycin D and does not appear in granulocyte, lymphocyte or platelet populations treated in the same way. The effect of several other substances on the development of monocyte tissue thromboplastin activity is reported.
Treatment of Congenital Factor VII Deficiency with a New Concentrate
Authors: Mariani G , Mannucci P M , Mazzucconi M G , Capitanio A 
Published: July 2018

SummaryA new factor VII concentrate, made from ACD plasma by a process involving successive absorptions of cryoprecipitate supernatant on DEAE Sephadex and of the resulting supernatant on Al(OH)3, was administered to 10 patients with severe factor VII deficiency. 5 patients received only one dose for treatment of a single bleeding episode, the remaining 5 were given multiple infusions (47) for spontaneous hemorrhages or for the prevention of surgical bleeding. In vivo factor VII recovery ranged from 43 to 126% (average 88%) of the assayed in vitro activity of the concentrate. A dose of 0.5 u/kg was found to produce a 1% rise of the plasma factor VII levels. The mean half-life on injected factor VII as assessed in 7 kinetic studies was 205 min (range 168-234). Spontaneous bleeding was easily controlled by the concentrate and major surgical procedures (two tonsillectomies) could be performed without complications. 1 patient developed HBsAg positive hepatitis, but otherwise no serious side effects were observed. Factor VII concentrate reduces the risk of precipitating circulatory overload associated with the use of plasma and avoids the unnecessary rise of factor II, IX and X which follows prothrombin complex concentrates.
The Effects of an Increase in Endogenous Oestrogen on the Haemostatic Mechanism
Authors: Toy J L , Davies J A , Hancock K W , McNicol G P 
Published: July 2018

SummaryThe effects on the haemostatic mechanism of rises in circulating human oestrogen in a group of women being treated for infertility with pituitary hormones were studied. Despite large but brief rises in oestrogen levels no changes were found.
Platelet-Binding of the von Willebrand Factor
Authors: Green David , Muller Hendrik P 
Published: July 2018

SummaryThe aggregation of platelets by the antibiotic, ristocetin, requires a plasma cofactor (VIII:vWF) and one or more specific binding sites on the platelet membrane. The interaction between VIII:vWF and the platelet was examined using VIII:vWF labelled with 125 I. In the presence of ristocetin (1.5 mg/ml), from 70 to 90% of the 125 I-VIII:vWF became platelet- bound. By contrast, only 21% was bound with thrombin (2.5 u/ml), and 2.2% with buffer alone. Fractionation of the platelets revealed that peak radioactivity was present in the membrane fraction. Treatment of ristocetin-reacted platelets with either chymotrypsin, 100 ug/ml, or trypsin, 75 ug/ml, resulted in the partial release of the membrane-bound radioactivity. It is concluded that VIII:vWF binds to the platelet membrane in the presence of ristocetin.
Creatine Phosphate in Rat Blood Platelets
Authors: Shibata Sachiko 
Published: July 2018

SummaryCreatine phosphate (CP) was found in rat platelets by an assay method devised to increase the specificity and sensitivity. In this method, radioactivity of [14 C] ATP was measured after the reaction of CP with [14 C]ADP in the presence of creatine kinase. The mean value of the CP content in rat platelets was 24.8 nmoles per 109 platelets. Since the molar ratio of CP and ATP was 1:2.6, it is probable that CP plays a role in the energy metabolism of rat platelets.
Subcutaneous Ancrod after Operation for Fractured Hip - a Dose-Ranging and Feasibility Study
Authors: Lowe G D O , Morrice J J , Fulton A , Forbes C D , Prentice C R M , Barbenel J C 
Published: July 2018

SummaryWe have conducted a dose-ranging and feasibility study of daily subcutaneous injections of ancrod (Arvin) as a potential antithrombotic method in 28 patients following operation for fractured neck of femur. Sustained, predictable fibrinogen depletion during the first post-operative week was induced by four different regimes. A total dose of 10 units/kg weight, given in divided doses starting on the day of operation, is suggested as a possible antithrombotic regime. Ancrod treatment produced a rise in fibrinogen/fibrin degradation products, prolongation of the thrombin clotting time, and a fall in plasminogen, plasma viscosity, blood viscosity and haematocrit-corrected blood viscosity. A rise in plasma fibrinogen and corrected blood viscosity were observed in 14 control patients. Plasma fibrinogen was correlated with plasma viscosity and corrected blood viscosity. No adverse effects of treatment occurred. Subcutaneous ancrod appears to be a simple, safe, and feasible potential antithrombotic method, and merits trials of efficacy in the prevention of post-operative thromboembolism.
Evidence that Calcium Regulates Platelet Function
Authors: Detwiler Thomas C , Charo Israel F , Feinman Richard D 
Published: July 2018

SummaryIt is generally believed that calcium ions play a key role in regulation of platelet function.This is based on 3 types of evidence.1. Analogies with other cells. Calcium ions are known to trigger secretion and contraction in many cells, possibly reflecting a general role for calcium in all secretion and contraction.2. Indirect evidence. Platelet aggregation and secretion are induced by divalent cation ionophores. The response to the ionophore A23187 is identical to that induced by other potent stimuli.3. Direct evidence. Platelet activation can be blocked by drugs (e. g. certain local anesthetics) that block release of calcium ions from sarcoplasmic reticulum; the inhibition can be overcome by addition of extracellular calcium in the presence of a calcium ionophore. While this does not constitute definitive proof, the central role for calcium ions remains an attractive hypothesis that justifies attempts to further define calcium pools and fluxes in platelets.
Movement of Calcium Ions and their Role in the Activation of Platelets
Authors: Massini P , Käser-Glanzmann R , Lüscher E F 
Published: July 2018

SummaryThe increase of the cytoplasmic Ca-concentration plays a central role in the initiation of platelet activation. Four kinds of movements of Ca-ions are presumed to occur during this process: a) Ca-ions liberated from membranes induce the rapid shape change, b) Vesicular organelles release Ca-ions into the cytoplasm which initiate the release reaction, c) The storage organelles called dense bodies, secrete their contents including Ca-ions to the outside during the release reaction, d) At the same time a rearrangement of the plasma membrane occurs, resulting in an increase in its permeability for Ca-ions as well as in an increase in the number of Ca-binding sites.Since most processes occurring during platelet activation are reversible, the platelet must be equipped with a mechanism which removes Ca-ions from the cytoplasm. A vesicular fraction obtained from homogenized platelets indeed accumulates Ca actively. This Ca- pump is stimulated by cyclic AMP and protein kinase; it may be involved in the recovery of platelets after activation.It becomes increasingly clear that the various manifestations of platelet activation are triggered by a rise in the cytoplasmic Ca2+-concentration. The evidence for this and possible mechanisms involved are discussed in some detail in the contributions by Detwiler et al. and by Gerrard and White to this symposium. In this article we shall discuss four different types of mobilization of Ca-ions which occur in the course of the activation of platelets. In addition, at least one transport step involved in the removal of Ca2+ must occur during relaxation of activated platelets.
Dissociation of Factor VIII in the Presence of Proteolytic Inhibitors
Authors: Sussman Ira I , Weiss Harvey J 
Published: July 2018

SummaryWhen gel filtration of factor VIII is performed with buffers of high ionic strength (1.0 M NaCl or 0.25 M CaCl2), the procoagulant activity elutes with proteins of relatively low molecular weight. It has been suggested that in the presence of proteolytic inhibitors, the procoagulant activity would appear at the void volume. To test this hypothesis, chromatography with buffers of high ionic strength was performed in the presence of benzamidine hydrochloride, soy bean trypsin inhibitor, heparin, DFP, and aprotinin. Under all of these conditions, the procoagulant activity continued to elute with proteins of low molecular weight. Similar findings were obtained after chromatographing cryoprecipitate prepared from the plasma of a normal subject who had received heparin. Thus, at present there is no direct evidence to suggest that proteolysis is involved in the dissociation of factor VIII by buffers of high ionic strength.
The Abnormal Factor IX of Hemophilia B+ Variants
Authors: Bertina Rogier M , Veltkamp Jan J 
Published: July 2018

SummaryA rather large proportion of the hemophilia B patients can be characterized as hemophilia B+ because of the presence in their plasma of a protein which is immunologically identical with human factor IX. In a group of 33 hemophilia B patients we found 14 cases of hemophilia B+ belonging to 11 independent pedigrees. The variant factor IX molecules of these families have been compared with respect to the following properties: 1) factor IX activity and its dependence on phospholipid concentration; 2) factor IX antigen; 3) prolongation of prothrombin time with an ox brain thromboplastin; 4) electrophoretic mobility; 5) Ca2+ binding capacity; 6) affinity for binding to heparin and 7) susceptibility of the factor IX antigen to contact-induced activation. In the study of these parameters the use of a precipitating antibody against highly purified human factor IX showed to be of great value. According to our criteria at least 7 different factor IX variants were present in the 11 families with hemophilia B+ studied. Because of this rather high heterogeneity a suitable nomenclature for subclassification of hemophilia B+ variants is proposed.
The Binding of Calcium Ions to Bovine Factor X by Rate Dialysis
Authors: Yue Robert H , Gertler Menard M 
Published: July 2018

SummaryThe binding of Ca+2 to bovine factor X (molecular weight of 74,000) (Yue und Gertler 1977) was studied by the technique of rate dialysis and with the use of 45Ca+2. The binding data are consistent with a model of sequential mechanism. One mole of Ca+2 binds to the glycoprotein with a dissociation constant of 5.2 × 10-5 M and an additional 39 ± 4 moles of Ca+2 bind to this zymogen with a dissociation constant of 3.7 × 10-3M. The binding of the high affinity Ca+2 causes a functionally significant change in the zymogen, and (calcium) (factor X) complex is the real substrate in the activation process by the protease in Russell’s viper venom.
Identification of High Molecular Weight Derivatives of Plasmic Digests of Cross-Linked Human Fibrin
Authors: Regañon E , Vila V , Aznar J 
Published: July 2018

SummaryHighly cross-linked human fibrin was digested with plasmin and the nine main components (labelled initially 1 to 9) were detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The components of greater molecular weight, bands 1 and 2, which are identified with fragments Y dimer and Y-D (270,000 and 220,000) contain three subunits which are joined by disulphide bonds which originate from the α, β and γ-γ-chains of cross-linked fibrin. They show a reaction of partial identity against anti fibrinogen fragment D-sera and anti fibrinogen fragment E sera. Bands 3, 4 and 5 correspond to three species of fragment D-dimer and have molecular weights of 175,000,160,000 and 130,000. Each of these species differs in the size of the γ-γ-chain remnants, while all maintain the cross-link between the γ-γ-chains. The remnants of a and β-chains of cross-linked fibrin remain the same in all three species. The components of electrophoretic bands 6, 7 and 8 correspond to three fragments, each with a different molecular weight and with common antigenic components against anti fibrinogen fragment D-sera; these are called D6 (90,000), D7 (75,000) and D8 (65,000) and are formed by α- and β-chain remnants of equal molecular weight and by γ-chain remnants with a different molecular weight for each fragment. The last fragment to be identified, corresponding to electrophoretic band 9 (50,000 molecular weight) corresponds to fibrin fragment E. The present report is in agreement with previous studies of plasmin digestion of highly cross-linked fibrin, but differs from them in number of fragments D-dimer which appear during the digestion.
Alterations in the Coagulation and Fibrinolysis System in Pregnancy Labour and Puerperium, with Special Reference to a Possible Transitory State of Intravascular Coagulation during Labour
Authors: Gilabert J , Aznar J , Parrilla J J , Regañon E , Vila V , Estelles A 
Published: July 2018

SummaryVarious tests of hemostasis were carried out during pregnancy, labour and the puerperium in a group of 259 women. Determinations were carried out in the 1st, 2nd and 3rd trimesters, in the period of dilatation, the expulsion period, the period of expulsion of the placenta and the immediate postpartum period of labour and on each of the first 5 days of the puerperium. It was confirmed that during pregnancy there is an elevation of the fibrinogen degradation producs (FDP) levels with a proportional increase in the numbers of positive protamine sulfate and ethanol tests. The proportion of positive protamine sulfate and ethanol tests reaches a maximum in the expulsion of the placenta coinciding with the presence of soluble complexes heavier than fibrinogen as detected by polyacrylamide gel electrophoresis and by column chromatography.All this indicates that there is a transitory intravascular coagulation produced during labour reaching its maximum at the time of birth and tending to become normalized in the first few days of the puerperium.
The Effects of a Combined Alpha- and Beta-Blocking Drug, Labetalol, on Some Aspects of Platelet Function
Authors: Lote Knut , Svenson Birgit J , Ånstad Unni , Nordøy Arne 
Published: July 2018

SummaryThe effects of the combined alpha- and beta-adrenoreceptor blocking agent labetalol on human blood platelets as estimated by platelet aggregation, platelet count, bleeding time and platelet factor 3 activity were studied in 5 patients. The drug reduced adrenaline - induced platelet aggregation in vitro. However, it did not influence the above platelet function test in therapeutic plasma concentrations in vivo.
In Vitro and In Vivo Effects of Adrenaline and Phentolamine on Platelet Function
Authors: Ponari Oreste , Civardi Emilio , Megha Alessandro , Pini Mario , Poti’ Raffaele , Dettori Anton Giulio 
Published: July 2018

Summary
In vitro and in vivo effects of adrenaline (ADR) on platelet aggregation, on platelet factor 3 (PF3) availability and on platelet factor 4 (PF4) release were studied in man. Inhibitory action of an alpha-blocker, phentolamine (PHEN) was investigated in the same conditions.The threshold concentration (TC) of ADR inducing the typical two-phase response in aggregation tests when added to platelet-rich plasma (PRP) varied in different pools of plasma, but always induced an evident PF4 release and increased PF3 availability. A further increase in both parameters was obtained with higher concentrations but without any significant dose/response correlation.Adding PHEN alone to PRP did not induce platelet aggregation or modify PF4 release induced by stirring, but it reduced PF3 availability. On the other hand, PHEN prevented the effects of ADR in different platelet tests, at appropriate concentrations.Intravenous infusion of ADR lowered the TC, and increased PF3 availability and PF4 release. In vivo administration of PHEN, in contrast, increased TC and reduced PF3 availability, while PF4 remained unchanged.
Effect of Treatment with Activated Prothrombin Complex Concentrate (FEIBA) on Factor VIII-Antibody Level
Authors: Lechner K , Nowotny Ch , Krinninger B , Zegner M , Deutsch E 
Published: July 2018

SummaryThe influence of treatment with an activated prothrombin complex preparation (FEIBA) on the antibody level was studied in 10 haemophiliacs with an antibody to factor VIII. The antibody level was observed to rise at least once in five patients, while in the remaining five patients no rise occurred. In all, 6 out of 31 treatments were followed by an anamnestic rise of the antibody level, corresponding to 19.4%. A rise of the inhibitor level following FEIBA treatment is likely to occur in patients who show a marked antibody rise after factor VIII treatment (good responders), but have a low antibody level at the time of treatment. High doses of FEIBA and simultaneous transfusion of red cells may also enhance the likelihood of an anamnestic response. Stimulation of antibody production is probably due to the presence of small amounts of factor VIII in this preparation.