bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unfractionated Heparin and CY 216: Pharmacokinetics and Bioavailabilities of the Antifactor Xa and IIa Effects after lntravenous and Subcutaneous Injection in the Rabbit
Authors: Briant L , Caranobe C , Saivin S , Sié P , Bayrou B , Houin G , Boneu B 
Published: July 2018

SummaryThis report compares the pharmacokinetics and the bioavailabilities of the antifactor Xa and of the antifactor II a activities generated by intravenous (IV) and subcutaneous (SC) injections of increasing doses of unfractionated heparin (UH) and of a low molecular weight heparin (CY 216). Rabbits were injected with 500, 1,000, 2,500 and 5,000 antifactor Xa u/kg of both heparins and their biological activities were followed at various time intervals. After IV injection the clearance of the antifactor Xa activities was independent of the dose and the clearance of UH was significantly higher than that of CY 216; after SC injection the bioavailability estimated from the antifactor Xa effect was consistently over 100% for CY 216 while that of UH increased from 27% at the lowest dose to 93% at the highest dose. The pharmacokinetic parameters estimated by the antifactor IIa activity of UH were superimposable to those calculated with the antifactor Xa activity. For CY 216 no direct comparison between the two activities was made since the dose injected expressed in antifactor IIa units was 3.4 times lower. UH and CY 216 were therefore injected intravenously to other animals at equivalent and increasing doses expressed in antifactor IIa units (50-5,000 u/kg). The pharmacokinetic parameters calculated from the curves of the antifactor IIa activities were basically identical except at the two lower doses (50 and 100 u/kg) for which UH was cleared faster than CY 216. These results indicate that the antifactor IIa activity generated by an injection of CY 216 disappears faster than the corresponding antifactor Xa activity and therefore that the antifactor Xa/antifactor IIa activity ratio of CY 216 progressively increases after SC or IV injection.
Platelet and Shear Rate Promote Tumor Cell Adhesion to Human Endothelial Extracellular Matrix - Absence of a Role for Platelet Cyclooxygenase
Authors: Bastida Eva , Almirall Lourdes , Ordinas Antonio 
Published: July 2018

SummaryBlood platelets are thought to be involved in certain aspects of malignant dissemination. To study the role of platelets in tumor cell adherence to vascular endothelium we performed studies under static and flow conditions, measuring tumor cell adhesion in the absence or presence of platelets. We used highly metastatic human adenocarcinoma cells of the lung, cultured human umbilical vein endothelial cells (ECs) and extracellular matrices (ECM) prepared from confluent EC monolayers. Our results indicated that under static conditions platelets do not significantly increase tumor cell adhesion to either intact ECs or to exposed ECM. Conversely, the studies performed under flow conditions using the flat chamber perfusion system indicated that the presence of 2 × 105 pl/μl in the perfusate significantly increased the number of tumor cells adhered to ECM, and that this effect was shear rate dependent. The maximal values of tumor cell adhesion were obtained, in presence of platelets, at a shear rate of 1,300 sec-1. Furthermore, our results with ASA-treated platelets suggest that the role of platelets in enhancing tumor cell adhesion to ECM is independent of the activation of the platelet cyclooxygenase pathway.
ADP-Induced Platelet Aggregation as a Function of Age in Healthy Humans
Authors: Vilén L , Jacobsson S , Wadenvik H , Kutti J 
Published: July 2018

SummaryIn 120 healthy humans (58 males and 62 females) possible differences in platelet aggregability were investigated with respect to age and sex. By using a narrow range of final ADP concentrations (0.2-1.0 μM) primary and secondary aggregation were evaluated. The rate of primary aggregation was shown to be significantly related to increasing age and this was true for both sexes.As regards secondary aggregation the same pattern was seen in the group of male subjects. Thus, among the youngest (<34 years) the frequency of secondary waves was only one third of that encountered among the oldest (>50 years). No similar association was detectable among the female subjects.The present study calls attention to some important issues which should be considered in platelet aggregation studies; the interpretation of data obtained from such studies invariably requires a careful selection of appropriate age- as well as sex-matched control groups.
The Frequency of Bleeding and Height of Adolescent Haemophiliacs
Authors: Bem J L , Painter M J , Aronstam A , Patrick J H , Newcombe R E 
Published: July 2018

SummaryThe relation between the height of adolescent haemophiliacs and their bleeding frequency has been studied. 45 haemophiliacs aged 10-19 years were divided into 3 groups: small, medium and tall, using a Height Standard Deviation Score. The average bleeding frequency per 100 days in the group of small haemophiliacs was 8.71 ± SD 4.47, in the medium height group 10.18 ± SD 6.71, while the tall individuals bled in average 15.97 ± SD 3.15 every 100 days. There was no relationship between age and bleeding frequency.
Human Platelets Contain mRNA Transcripts for Platelet Factor 4 and Actin
Authors: Sottile Jane , Mosher Deane F , Fullenweider Jan , George James N 
Published: July 2018

SummaryRNAs from a number of cells, including platelets, were analyzed by Northern blotting for the presence of transcripts to four platelet proteins - actin, thrombospondin, fibronectin, and platelet factor 4. RNA from platelets contains considerable amounts of mRNA for platelet factor 4, easily detectable mRNA for actin, and traces of mRNA for thrombospondin. mRNA for platelet factor 4 was not detected in human lymphocytes or in any of 5 human cell lines.
Evaluation of the Binding to Fixed Platelets of Agonists and Antagonists of ADP-Induced Aggregation
Authors: Agarwal Ashok K , Tandon Narendra N , Greco Nicholas J , Cusack Noel J , Jamieson G A 
Published: July 2018

SummarySteady state binding of eleven different ADP analogues to formaldehyde-fixed platelets has been determined in a competitive binding assay using 3H-ADP. The compounds tested were the inactive analogues L-ADP and L-ATP; the agonists 2-chloroadenosine 5’-diphosphate, adenosine 5’-O-(2-thiodiphosphate)and the diastereoisomeric pair Sp-adenosine 5’-(1-thiodiphosphate) (Sp-ADP-α-S) and Rp-adenosine 5’-(1-thiodiphosphate) (Rp-ADP-α-S); and the antagonists adenosine 5’-O-thiomonophosphate, 2-chloroadenosine 5’-O-thiomonophosphate, 2-chloroadenosine 5’-triphoshate, and the diastereoisomeric pair 5’-(1-thiotriphosphate) (Sp-ATP-α-S) and Rp-adenosine 5’-(1-thiotriphosphate) (Rp-ATP-α-S). All compounds tested competed at the high affinity binding sites for ADP previously identified (Blood 1988; 71: 110-6) but in some cases competition could not be demonstrated at the low affinity sites because of the high nucleotide concentrations required. As a group, C2-substituted analogues bound less strongly (Ki >2 μM) than did the analogues without substituents in the purine ring (Ki <0.7 μM). With the pair of diastereoisomeric agonists Sp-ADP-α-S and Rp-ADP-α-S the Ki values at the high affinity site (210 nM and 560 nM) were of the same relative magnitude and in the same direction as their reported potencies as agonists (Ki 4 μM and 20 μM). With the diastereoisomeric antagonists Sp-ATP-α-S and Rp-ATP-α-S a similar relationship was seen between affinity (17 nM and 156 nM) and inhibitory potency (Ki 4 μM and 20 μM). These results may help to differentiate possible mechanisms in the interaction of ADP with its receptors.
Asialo von Willebrand Factor Enhances Platelet Adhesion to Vessel Subendothelium
Authors: Bastida Eva , Monteagudo Juan , Ordinas Antonio , Marco Luigi De , Castillo Ricardo 
Published: July 2018

SummaryNative von Willebrand factor (N-vWF) binds to platelets activated by thrombin, ADP or ristocetin. Asialo vWF (As-vWF) induces platelet aggregation in absence of platelet activators. N-vWF mediates platelet adhesion to vessel subendothelium at high shear rates. We have investigated the role of As-vWF in supporting platelet deposition to rabbit vessel subendothelium at a shear rate of 2,000 sec-1, using the Baumgartner perfusion system. We have studied the effects of the addition of As-vWF (from 2 to 12 μg/ml) to perfusates consisting of washed red blood cells, 4% human albumin and washed platelets. Our results show a significant increase in platelet deposition on subendothelium (p <0.01) in perfusions to which As-vWF had been added. Blockage of the platelet glycoproteins Ib and IIb/IIIa (GPIb and GPIIb/IIIa) by specific monoclonal antibodies (LJIb1 and LJCP8, respectively) resulted in a decrease of platelet deposition in both types of perfusates prepared with N-vWF and As-vWF. Our results indicate that As-vWF enhances platelet deposition to vessel subendothelium under flow conditions. Furthermore, they suggest that this effect is mediated by the binding of As-vWF to platelet membrane receptors, which in turn, promote platelet spreading and adhesion to the subendothelium.
Fibrinogen Nijmegen : Congenital Dysfibrinogenemia Associated with Impaired t-PA Mediated Plasminogen Activation and Decreased Binding of t-PA
Authors: Engesser Luzia , Koopman Jaap , Munk Gé de , Haverkate Frits , Novéková Irena , Verheijen Jan H , Briët Ernest , Brommer Emile J P 
Published: July 2018

SummaryCongenital dysfibrinogenemia was found in a patient with venous thrombosis. Blood clot lysis was prolonged and suggested an impairment of fibrinolysis. We investigated whether this was related to the fibrinogen abormality. Fibrinopeptide release was normal but fibrin polymerization was defective in the patient. The stimulating effect of the patient’s fibrin on t-PA mediated plasminogen activation was impaired. This could not be attributed to defective binding of plasminogen. However, the binding of t-PA to the patient’s fibrin was about 16% less than to normal fibrin. A variant t-PA (G K1 K2 P), which contained only one of the two fibrin binding sites, i.e. the kringle-2 domain, was bound to the abnormal fibrin for only 50% of normal.We conclude that the prolongation of blood clot lysis and the impaired stimulation of t-PA mediated plasminogen activation are related to the defective binding of the kringle-2 domain of t-PA onto the fibrin moiety of the abnormal fibrinogen. The impairment of fibrinolysis might explain the occurrence of throm-bosis in the patient.
The Active Serotonin Uptake and the Hypotonic Shock Response of Human Blood Platelets
Authors: Hardeman M. R , Heynens Carina J. L. 
Published: July 2018

SummaryThe present paper is part of a study on the evaluation of the active serotonin uptake and the response to hypotonic shock as in vitro viability tests for human blood platelets.The extraction and fluorometric assay of serotonin in plasma and in platelets were further automated by the introduction of a dialyzer in the earlier described system. Furthermore, the influences of some external factors on both tests were investigated.The serotonin uptake as well as the hypotonic shock response were pH dependent and especially the latter was rather sensitive to small pH changes. Changes in the Na+ : K+ ratio were also found to influence both criteria significantly.The serotonin uptake appeared to be linearly dependent on the platelet number while, within a range of 200 X 103 - 450 X 103 platelets per fxl, the slope of the hypotonic shock response was the same.
Sensitive Methods for the Detection and Characterization of Platelet Isoantibodies
Authors: Hirschman Richard J. , Yankee Ronald A. , Coller Barry S. , Gralnick Harvey R. 
Published: July 2018

SummaryTwo sensitive methods for the detection and characterization of platelet isoantibodies are presented in this paper. The methods involve incubating platelets with either radioactive serotonin or adenine, interaction of the platelets with serum antibody and finally detection of supernatant radioactivity. Both tests can be used for HL-A typing of platelets and both tests detect antibodies undetectable by complement fixation. The requirement of a heat labile serum component is variable in the serotonin test but absolute in the adenine test. Antibody activity was found to be in the 7S gamma globulin fraction on DEAE cellulose column chromatography.
On the Mechanism by which Bovine Fibrinogen Induces the Release and Availability Reaction of Human Blood Platelets
Authors: Kubisz P , Suranová J 
Published: July 2018

SummaryBovine fibrinogen can aggregate human blood platelets by a direct mechanism (first wave) and also indirectly by releasing endogenous ADP (second wave).A primarily non-altered surface structure of the thrombocytes is important for the induction of the first wave.Under certain conditions a second aggregation wave, concomitant with the release and the availability reaction is elicited.Besides the cells’ contact, the presence of ADP and calcium ions are necessary for the induction of the release reaction in human platelet rich plasma.The changes induced by bovine fibrinogen thus follow the same pattern as the irreversible phase of aggregation, linked to release as induced by ADP.
Platelet Thrombosis and Non-traumatic Intimal Injury in Mouse Aorta
Authors: Jørgensen Leif , Hærem Jørgen W. , Moe Narve 
Published: July 2018

SummaryAortas of mice, not exposed to any experimental injury, were examined by light and electron microscopy for the initial stages of mural thrombosis.Platelets in the lumen frequently formed groups or loose platelet aggregates. Individual platelets and platelet aggregates, both loose and dense, were often in contact with the inner vascular lining in focal areas. The underlying intimal tissue, including the endothelial cells, showed varying degrees of injury. Occasionally, however, platelet material was in contact even with structurally normal endothelial cells. The platelet- endothelial cell contact appeared to be an expression of adherence.Small mural thrombi were less frequently observed. They comprised platelets and fibrin and were mostly attached to subendothelial structures. Underneath the mural thrombi, the internal elastic membrane was often ruptured.The observed phenomena fit best with the theory that the primary event in mural thrombosis in aorta of mice is platelet aggregation under the influence of local flow irregularities. The next steps could be adherence of platelets to the vessel wall and injury of the intimai tissue through the release of vasodestructive agents from the platelets. Through this injury a focus of mural thrombosis could be established.
Clotting Mechanisms in Patients with Hypertriglyceridemia during Therapy with Anabolic or Progestational Drugs
Authors: Glueck Helen I. , Glueck Charles J. 
Published: July 2018

SummaryEffects of synthetic steroids with progestational and androgenic-anabolic activity (Norethindrone Acetate and Oxandrolone) on coagulation parameters and plasma lipids were studied in 20 patients with familial types III, IV and V hyperlipoproteinemia. Prior to therapy there was a relatively uniform elevation of fibrinogen (284 mg %) and esterase prothrombin (64 U/ml). On therapy mean fibrinogen fell sharply to 223 mg % (short-term) and 195 mg % long-term. There were no increments in other clotting factors, and levels of factor VII and X were decreased on drug in several patients who initially had abnormally high levels. The fall in fibrinogen on therapy did not correlate with concurrent decrements in cholesterol or triglyceride. In hypertriglyceridemic patients predisposed to coronary or peripheral vascular thrombosis, Norethindrone and Oxandrolone appear to ameliorate rather than potentiate any tendency to “hypercoagulability”.
Streptokinase Stability Pattern during Storage in Various Solvents and at Different Temperatures
Authors: Martin M , Auel Fräulein H ,   Technical assistance
Published: July 2018

SummaryThe activity drop of 5 u streptokinase was measured in 1 ml each of various solutions (0.9% NaCl solution, 5% glucose solution, 5% levulose solution, 10% dextran solution, gelatin solution, 3% albumin solution, Michaelis buffer, glucose (5%)-heparin (750 u/ml) solution) at different incubation temperatures (–20° c, 4° c, 20 c, 37 C), and over different observation periods (15 min, 30 min, 45 min, 60 min, 6 h, 12 h, 24 h, and 48 h). Solution media tested for streptokinase-protecting quality were broken down into three groups.Group I: Solvents displaying excellent stabilizing properties (gelatin and albumin solutions).Group II: Solvents displaying medium stabilizing properties (dextran and levulose solutions).Group III: Solvents displaying poor stabilizing properties (NaCl and glucose solutions, Michaelis buffer).In testing streptokinase concentrations as used for therapeutic purposes (1500 u/ml, 50,000 u/ml), no decay was found to take place over observation periods of up to 48 h, and no influence by different solvents (Group I, II or III) was traceable. Heparin stored with streptokinase at room temperature over a period of 48 h did not alter the streptokinase stability.Some mechanisms concerning the stability pattern of streptokinase are discussed. It appears that low streptokinase concentrations need negatively charged colloids to keep the protein structure intact. The streptokinase-protecting macro-molecules tested so far were albumin, gelatin, and streptokinase. Obviously, streptokinase by itself was able to preserve its own stability provided its concentration was of a certain order of magnitude (1500 u/ml, 50,000 u/ml).
Scanning Electron Microscopic and Electrophoretic Observations on Barium Sulphate Used to Adsorb Clotting Factors
Authors: Howell R. M , Deacon S. L. M 
Published: July 2018

SummaryElectron microscopy and particle electrophoresis were found to be complementary techniques with which to complete the physical data from an earlier study on barium sulphates used to adsorb clotting factors from serum. The differences revealed by scanning electron microscopy (S. E. M.) in the physical shape of low and high density grades of barium sulphate particles appear to be of greater significance than charge as expressed by electrophoretic mobility, in determining whether or not precursor or preformed factor Xa is eluted.This conclusion was based on the finding that at pH values close to 7, where the adsorption from serum occurs, all samples with the exception of natural barytes were uncharged. However as the high-density, or soil-grade, was found by S. E. M. to consist of large solid crystals it was suggested that this shape might induce activation of factor X as a result of partial denaturation and consequent unfolding of the adsorbed protein. In contrast, uptake of protein into the centre of the porous aggregates revealed by S. E. M. pictures of low-density or X-ray grade barium sulphate may afford protection against denaturation and exposure of the enzyme site.The porous nature of particles of low-density barium sulphate compared with the solid crystalline forms of other grades accounts not only for its lower bulk density but also for its greater surface/gram ratio which is reflected by an ability to adsorb more protein from serum.Neither technique produced evidence from any of the samples to indicate the presence of stabilising agents sometimes used to coat particles in barium meals.
Studies on Activator Formation in Human Plasma with Streptokinase
Authors: Martin M , Auel Miss H ,   Technical Assistance
Published: July 2018

SummaryA new method is presented for estimating the activator (plasminogen-streptokinase complex) concentration in native plasma of patients undergoing streptokinase infusion. The principle of the method is based on clot lysis time as recorded by the thromboelastograph. The test clot constituents were bovine fibrinogen, bovine plasminogen, EDTA, human plasma (with unknown activator concentrations), and thrombin. In order to obtain a standardization line, urokinase dissolved in NaCl solution was substituted for patients’ plasma. Thus, each lysis time could easily be converted into urokinase equivalent (CTA-u/ml). Streptokinase and plasminogen molecules in undiluted patients’ plasma were found to exist both in an activator-bound (equimolar plasminogen-streptokinase complex) and in a freely circulating form. This result is in agreement with earlier findings where the activator complex was demonstrated to be a widely dissociated complex in highly diluted plasma of patients, thus displaying an ample proportion of free streptokinase and plasminogen molecules. Streptokinase treatment using dosage schemes of 100,000 u SK/h, 150,000 u/h, and 200,000 u/h were monitored by quantitative activator, streptokinase, and plasminogen measurements. An average activator concentration of 50–100 CTA-u/ml and a SK-concentration of 7–16 u/ml were recorded during streptokinase infusion. Plasminogen values averaged 0.25%, independent of the amount of streptokinase infused. Each drop in streptokinase was accompanied by a drop in activator during the infusion, and each rise in streptokinase by a rise in activator. There was a strong correlation between streptokinase and activator concentrations in that, on the average, 1 u streptokinase equalled 8.4 CTA-u/ml activator (correlation coefficient r = 0.9). It is concluded that the activator concentration in the plasma of patients undergoing fibrinolytic treatment can easily be adjusted by regulating the hourly streptokinase influx.
The in Vitro Effects of Mithramycin on the Aggregation and the Calcium Uptake of Human Platelets
Authors: Chao Francis C. , Tullis James L. 
Published: July 2018

SummaryThe in vitro incubation of platelets with mithramycin caused a biphasic effect on ADP-induced aggregation. At a low dose of 10 [xg/ml, mithramycin caused an enhancement of aggregation whereas at high doses above 50 [μg/ml, it produced variable effects on aggregation with inhibition predominating. Effects on ADP-induced aggregation similar to those caused by mithramycin were produced by the simple addition of CaCl2 solution to the plasma medium. Mithramycin in the range which increased aggregation altered neither the whole blood clotting times nor the ionic calcium concentrations, but did increase the uptake of radioactive calcium by platelets. The results confirmed the in vivo observations that mithramycin treatment during tumor chemotherapy may directly alter the aggregation response of circulating platelets to ADP. The effects of mithramycin on aggregation may be mediated by alteration of calcium influx in normal platelets.