bluuebunny/crossref_metadata_2025_split huggingface dataset:
ASPIRIN FAILURE TO INHIBIT THE RELEASE OF PLASMINOGEN ACTIVATORS-INHIBITORS BY HUMAN PLATELETS
Authors: Woods A I , Lazzari M A 
Published: August 2018

Platelet-PA-Inhibitors can be released by thrombin, Col laaen( Col) and others.If they are physiologically important,inhibition of their release might facilitate thrombolysis.Intrinsic PA were tested in euclobulins (eug)of PPP and PPP+Washed platelets(WP) ,with and without aspirinf ASA) .treated with UK,SK and Col(20 atfd l2uo/ml) Results(mm2)were:euaPPP:232+78;+3×106WP/ul:217+71;+10%7ul:188+/5 +2×106MP/ul: 157+69:With UK:eugPPP:283+76;+3×l0517P/ul :234+69;+106 WP/ul :172+55;+2×l(PWP/ul :154+48; With SK:euoPPP:303+99;+3×l05WP/ul 252+65;+1067P/ul:203+68;+2×106UP/ul: 174+85;Wi th Col (20ug/ml) :eur PPP:234+97;+3×105WP/ul:160+63;+106WP/ul:141+73;+2×l06WP/ul:129+81; +2×106WP/ul+ASA: 105+31;Wi th Col uc/ml) :euaPPP:230+56;+3×l05NP/ul: 160+52;+106WP/ul:139+44;+2×106wp/ul:126+21;+2×106WP/ul+ASA:118+28. EugPPP+l/P showed lower lysis area.Col induced more decrease of lysis area in euc with WP.ASA did not modify this effect.UK and SK produced higher lysis area only in euoPPP.No difference was observed between high and low doses of Col-effect upon WP.Combined treatment of eucPPP+WP+Col, with UK and SK showed:(mm2):UK-treated eugPPP+2×106WP/ul+Col(29ug/ml):134+25;+ASA and Col(20ug/ml):115+65;+Col(2uc/ml):157+50;+ASA and Col(2uo/ml):133+49; SK-treated eupPPP+2×106WP/ul:+Col(20uo/ml):144+49;+ASA and Col(20ug/ml):128+ 60;+Co1(2ug/ml):173+66;+ASA and Col(2ug/ml):142+36.Col (20ug/ml) produced slight lower lysis area of UK and SK-treated eugPPP+WP. (p:ns). ASA did not modify this effect.Col (2uc/ml) did not produce changes in lysis area of UK and SK-treated eupPPP +WP. ASA produced slight lower lysis area(p:ns).Conclusion: high dosis of Col could release anti UK,anti SK and intrinsic PA-inhibitors from platelets;low dosis of Col could only release fntrinsic PA-inhibi tors. It suggests that anti UK and anti SK release might be triggered by stronger stimuli than intrinsic PA inhibitors.ASA could not inhibit any inhibitors release.We must consider that PA-inhibi tors could be released by different metabolic pathways other than cyclooxygenase pathway.
NORMAL FIBRINOPEPTTDE A (FPA) AND ELEVATED FIBRINOGEN DEGRADATION PRODUCTS AFTER LONG DISTANCE RUNNING
Authors: Bartsch P , Haeberli A , Straub P W 
Published: August 2018

Physical exercise leads to a shortening of activated partial thrcnboplastin time (PIT) and euglobulin lysis time (ELT). Whether this activation causes in-vivo thrombin and plasmin action remains controversial however. 19 well trained long distance runners were examined 25 min (range 5-53) after termination of a 100 km race (post-race values) run in 577 min (457-755) and 5 days later after at least one day without physical exercise (control values). FPA, platelet factors and fibrin (ogen) split products (fragment E and BB 15-42) were measured with radioimnunoassays. ELT was assessed before and after venous occlusion (VO). The table gives mean values ±SD:Thrombin time, platelet count, platelet factor 4 and haematocrit did not change significantly. FPA was normal in all post-race samples and did not correlate significantly with the time lag between arrival and blood sampling, indicating that activation of blood coagulation in exhaustive physical exercise of long duration does not lead to in-vivo fibrin formation. Activation of fibrinolysis, however, results in circulating plasmin activity as demonstrated by the elevation of the fibrin (ogen) degradation products fragment E and BB 15-42. Since the polyclonal antibodies used in the latter assay crossreact with BB 1-42, these results alone do not allow to jjdge whether plasmin degrades fibrin or fibrinogen. However, lack of fibrin formation suggests fibrinogenolysis rather than fibrinolysis.
PLASMA CROSSLINKED FIBRIN DEGRADATION PRODUCTS FRACTION D (D-DIMER) IN PATIENTS UNDERGOING ELECTIVE MAJOR ABDOMINAL SURGERY AND IN HEALTHY VOLUNTEERS
Authors: Hauch O , Nerstrøm H , Kølle T R , Jørgensen L N , Wille-Jørgensen P , Neerstand H 
Published: August 2018

An increased plasma level of D-dimer has been suggested as an indicator of postoperative thromboembolism (TE). We studied the D-dimer level in patients undergoing major elective abdominal surgery and in healthy volunteers to evaluate a possible value of D-dimer as a screening test for TE. 18 patients and 5 healthy volunteers were studied. The patients received low molecular weight heparin (Logiparin TM) subcutaneously once . daily for 7 days. The 125 I-fibrinogen uptake test (FUT) was done in all patients. Blood samples were taken preoperatively, postoperatively and on the postoperative day 1, 3, 4, 5 and 6. The volunteers had blood samples taken before and 4 hours after subcutaneous Logiparin injection. D-dimer was assayed by enzyme-immunoassay (Boehringer Mannheim, Elisa D-dimer, Cat.no. 998117). Results are given as median with 95% confidence limits in brackets.One patient developed deep venous thrombosis verified by phlebography. Two patients had abnormal FUT but normal phlebography. The plasma level for D-dimer in the 15 patients with normal FUT was 500 ng/ml (300-800) preoperatively. The D-dimer level increased postoperatively to 1700 ng/ml (900-3300) (p < 0.001). The following days the D-dimer level increased steadily to 4800 ng/ml (2600-6800) 6 days postoperatively. The plasma level of D-dimer in the volunteers were less than 110 ng/ml both before and after injection of Logiparin. The plasma level of D-dimer in the patient with deep venous thrombosis and the 2 patients with abnormal FUT were within the range of the patients with normal FUT.The postoperative D-dimer level was as high as that reported in patients with diagnosed thromboembolism.In conclusion, the D-dimer test does not seem to be a potential screening test for postoperative thromboembolism.
A MONITORING PARAMETER IN THROMBOLYSIS?
Authors: Roth R , Duckert F , Marbet G 
Published: August 2018

D-dimers are specific derivatives of cross-linked fibrin. Their concentration may be used to conduct thrombolysis and predict its outcome. In this investigation we studied the relationship between D-dimer plasma levels during thrombolysis of deep leg vein thrombosis (DVT) and the phlebographic success.METHODS: 17 patients (9 males, 8 females, age range 17-56 years) were studied. All patients had DVT and were treated with either an acylated streptokinaseplasminogen complex (n=lO) or streptokinase (n=5) or both drugs successively (n=2) for 4.6 days on average. The thrombolytic effect was assessed by ascending phlebography and the patients were divided into 3 groups: A complete clearance, B partial clearance, C no change. The D-dimers were measured by a non-competitive EIA assay with a monoclonal antibody against a conformational epitope on the plasmin-resistant D-dimer, fragment of cross-linked fibrin.RESULTS: The table gives the mean D-dimer levels in the 3 groups of patients at 12 hours intervals.The statistical analysis (Newman-Keuls multiple range test) suggests that low D-dimer levels, especially over the first 36 hours are related to treatment failures.CONCLUSIONS: Despite some overlapping between successful and non-successful cases and lack of absolute specificity of the assay the D-dimer concentration may predict treatment failure in the first two days.
CHRONIC ORAL DEFIBROTIDE STIMULATES VASCULAR PGI2 AND INHIBITS ATHEROSCLEROTIC PLAQUE FORMATION IN CHOLESTEROL-FED RABBITS
Authors: Lobel P , Palmer M , Schor K 
Published: August 2018

Defibrotide (DEF) is a polydeoxyribonucleotide fraction from bovine lung, possessing profibrinolytic and PGI2 stimulating properties. Male rabbits were fed for 4 months a standard laboratory diet (150 g/day) without (A) or with (B) DEF or a cholesterol (1%) supplemented diet without (C) or with (D) DEF (60 mg/kg x day) was administered orally (drinking water) and withdrawn 24-36 h prior to the acute experiments.DEF did not change the elevated serum cholesterol: 18 ± 2 (C) vs. 26 ± 5 (D) mM but significantly reduced the plaque formation in the aorta from 4.5 ± 0.3 (C) to 3.3 ± 0.2 (D) (subjective score). Collagen induced (0.6 pg/ml) thromboxane formation and ATP release was significantly reduced by DEF: 55+2 (C) vs. 42 ± 2 (D) ng/ml TXB2; 152 ± 11 (C) vs. 74±5 (D) AU ATP (platelet rTch plasma). DEF significantly increased the basal and bradykinin (Bk, 30 nM) stimulated PGI2 release from rabbit aorta preparations in Krebs buffer, while the PGI2 forming capacity (arachidonic acid, AA, 30 pg/ml) was unchanged Furthermore, the iloprost (30 nM) stimulated cAMP was significantly elevated by DEF in both control: 115 ± 10 (A) vs. 155 ± 18 (B) pmoles/1 and cholesterol-fed rabbits: 120 ± 14 (C) vs. 172 ± 9 (D). DEF, directly added to the platelets in vitro did not inhibit platelet activation up to 100 pg/ml.The data demonstrate a 2-3-fold stimulation of basal and hormone (Bk) induced PGI2 formation of control and sclerotic rabbit aorta after 4 months DEF treatment while the atherosclerosis per se does not significantly change these parameters. DEF treatment also significantly reduces platelet hyperreactivity at unchanged serum ch() lesterol. Both properties might be useful to prevent complication’s of atherosclerosis, such as myocardial infarction and stroke.
GRANULOCYTE ELASTASE RELEASE DURING BLOOD COAGULATION
Authors: Miura T , Inagaki M , Taki M , Saito N , Meguro T , Yamada K 
Published: August 2018

Granulocyte elastase (ELP) has a high-potency fibrinolytic activity. Hence, there is a possibility that ELP acts as a thrombolytic enzyme like plasmin in thrombolysis. We investigated the release of ELP from granulocytes, especially during blood coagulation.The biological activity of ELP was measured using a synthetic substrate, Suc-Ala-Tyr-Leu-Val-pNA. The immunological activity assayed as an alpha-l-antitrypsin-ELP complex was measured using an anti-ELP antibody (Merck), because more than 90% of ELP in blood forms alpha-l-antitrypsin-ELP complexes.The ELP activity in granulocytes extracted by 2 mol/1 KSCN was 10 mU/106 cells. This fibrinolytic activity corresponds to 1-2 U of plasmin in the fibrin plate method.The ELP release from separated granulocytes was observed by adding Ca2+, and the release was increased by Ca ionophore A 23187. The release was dose-dependent as far as 10 mM Ca2+ (final concentration) and the maximum release was obtained within 15 minutes. However, the ELP release was not produced by thrombin.The level of alpha-l-antitrypsin-ELP complex in serum was twice higher and that in heparinized plasma was 1.5 times higher than that in sodium citrated plasma. ELP was not released from granulocytes incubated in both prekallikrein deficient plasma and Factor XII deficient plasma containing 10 mM Ca2+. But addition of normal plasma (about 10%) resulted in ELP releaseThese results suggest that the ELP release from granulocytes is dependent on Ca2+ and the release is relevant to the blood coagulation system, especially to contact factors.
THE EFFECT OF PHYSICAL EXERCISE ON MONOCYTE FUNCTION, COAGULATION FACTORS, FIBRINOLYSIS AND PLATELETS
Authors: Ûsterud B , Hansen J B , Olsen J O , Wilsgård L 
Published: August 2018

Over a 2 years period, the Norwegian national team of cross country skiers, have been tested after strenous championships as well as before and after regular training.Finishing a 50 km race generated a rise of white cells from 5.4 ± 1.0 to 19.3 ± 3.7 × 109 /I (n=14). The mobilization of new and more sensitive white cells may explain the resultant rise in monocyte response to stimuli in vitro after the race. Thus, monocytes from blood incubated with 2 ng/ml blood, drawn from the athletes just after finishing the 50 km race, possessed 6-7 fold higher specific activity of thromboplastin than monocytes from blood drawn and stimulated in a rest-period. There was a positive correlation between the inverse level of F. VII in plasma of the skiers after the race and the monocyte response to stimuli in vitro as expressed by the level of thromboplastin. Activated monocytes with exposed thromboplastin are probably pulling out F. VII from the circulation just as seen in patients with gram negative septicaemia.A group of long distance runners were also tested after strenous jogging. High monocyte response to stimuli in vitro was associated with extremely active platelets that aggregated spontaneously after drawing the blood into heparin and tested it in a whole blood aggregometer. Those individuals with very active monocytes and platelets had also an extremely activation of their fibrinolytic system as judged by whole blood clot lysis. In contrast, everyone with low cell activation had hardly any change in their fibrinolytic activity after strenous running.The clear trend in this study was that almost everyone of our top athletes had a very depressed blood-cell activation system as compared to non athletes. Low blood cell activation in vivo was also associated with a low induction of the fibrinolytic system.
CYCLIC THROMBUS FORMATION IN RABBIT AORTA: A NEW MODEL OF ACUTE ARTERIAL THROMBOSIS
Authors: Kuhn M , Müller T H , Eisert W G 
Published: August 2018

Existing models of arterial thrombosis either require extensive surgical intervention or are limited by the short period of observation. Therefore we developed a new model in rabbits to monitor cyclic flow reductions (CFR) due to thrombus formation in a partially denuded and stenosed aorta.An electromagnetic flowprobe was positioned proximally to a stenosis of the abdominal aorta in anesthetized New Zealand rabbits after limited denudation of the vessel using a hemostat. The aortic blood flow was spontaneously reduced due to formation of thrombi. It returned to the basal level after gently shaking the occluder. The 'free flow' (defined as mean area under the flow curve) as well as the frequency of CFR were monitored. CFR persisted in all control animals for 3 to 4 hours. Prostacyclin at an infusion rate of 100 to 250 ng/kg/min completely abolished CFR in 16 of 20 animals. I.v. application of nitroglycerine (0.7 mg/kg/h) or papaverine (2 mg/kg/h) did not affect CFR. This as well as histology indicates strong involvement of platelet aggregation rather than vasospasm. CFR were also reduced by the following drugs: phosphodiesterase inhibitors (AHP 719, 1 mg/kg/h, i.v.; UDCG 212, 5 ug/kg/min., i.v.), a cyclooxigenase inhibitor (sulphinpyrazone, 30 mg/kg, i.v.) or a thromboxane synthetase inhibitor (dazoxiben, 1 mg/kg, i.v.) as well as an alpha2 antagonist (yohimbine, 1 mg/kg, i.v.). Heparin (800 U/kg, i.v.) reduced CFR suggesting significant contribution of the coagulation system.This new approach opens an avenue to long term observations of antithrombotic therapy in a fairly simple and highly reproducible model.
A NEW PAN SPECIES MODEL FOR THE MEASUREMENT OF IN VIVO THROMBOLYSIS
Authors: Hotchkiss A , Refino C , DeGuzman L , Rigter B , Eisert W 
Published: August 2018

A new model suitable for the quantitation of Li vivo thrombolytic efficacy was developed which has significant advantages over currently available models. This model allows animals to be used repeatedly and produces data that are less variable.This is a species-independent model utilizing an arterio-venous shunt (AVS). This model was used in rabbits (3 kg) and beagle dogs (13 kg). Each animal was used repeatedly during a 7 day experimental period without evidence of antibody formation. Clot lysis data are less variable than the rabbit jugular vein clot lysis model (RJV). The average coefficient of variation at all doses ([SD/Mean]×l00) with the AVS model was 13±9 and 21±6 for dogs and rabbits, respectively, compared to 25±11 for the RJV model. The rate of data accunulation with the AVS is 3-fold greater than the RJV.In the dog, catheters (25 cm long, 1.6 mm ID) were placed in the jugular vein and the carotid artery, tunneled under the skin to the back of the neck, exteriorized and plugged with a heparin lock. Thrombi were made from a donor dog by placing 0.7 ml of whole blood in a 1 cc plastic syringe barrel containing a cotton thread. The blood was clotted for 2 hr at 37.5 deg C, in vitro. The thrombus was rinsed and the syringe barrel was connected into the circulation by silicone tubing for a 90 min test period. Clot lysis was determined by weight. The flow rate across the thrombus was regulated to 60 ml/min by placing a teflon capillary tube (30 cm, o.7 mm OD) on the venous side. The procedure for the rabbit study differed as follows: Rabbit blood made larger clots therefore the blood was diluted with saline (4 to 1). Clots were incubated 90 min in vitro. The flow rate was 40 ml/min. Clot lysis was measured by the loss of 125-1 fibrinogen.The dose of reccminant t-PA (ActivaseR, Actilyse™) that achieved 40% lysis (ED40) was determined to be 180 ugAg in the dog and 660 ugAg in the rabbit AVS model. Using the RJV model the ED40 was 340 ug/kg.
QUANTITATIVE DETERMINATION OF ENDOGENOUS PGI2 RELEASE IN ANAESTHETIZED BEAGLE DOGS
Authors: Hermán F , Hadházy P , Magyar K 
Published: August 2018

A 30μm diameter pore size screen was inserted into an arteriovenous bypass system in anaesthetized, heparin-treated beagle dogs. The arterial blood was directed through the screen by a roller pump at a constant rate. As a result, the pressure proximal to the filter continuously increased (F.Hermdn et al.Thromb. Res.44 /1986/,575). The concentration of proximally infused PGI2 that stabilized the filtration pressure curve (pressure stabilizing concentration= PSC) was determined. If it was low enough (between 0.4 and 1.5 nmol/1) we administered the PGI2-releaser bradykinin (1/ug/kg), angiotensin II (0.5/ug/kg) or ADP (20/ug/kg) in bolus dose intravenously. Together with the cnanges in blood pressure, we observed a transient decrease in filtration pressure. From the pressure changes, based on the previously determined PGI2 concentration-res-ponse relationship, we estimated the amounts of released PGI2 as well as the time course of this release. Indomethacin (2 mg/kg i.v.) significantly decreased the PSC for exogenous PGI2 thereby increasing the sensitivity of the method; the release of PGI2 was abolished. The sensitivity of the method could also be increased by infusing BM.13.177 - an endoperoxide, thromboxane receptor antagonist - proximal to the filter (final concentration: 1-10/ug/ml). This substance did not affect the release of PGI2.We conclude that by using this technique the endogenous release of prostacyclin can be continuously determined provided that PGI2 level exceeds 50 pg/ml.
PLASMINOGEN ACTIVATORS (t-PA and u-PA) IN HUMAN NEOPLASTIC CELL LINES AND THEIR MODULATION BY BASEMENT MEMBRANE COMPONENTS
Authors: Arnoux D , Boutière B , Pourreau-Schneider N , Martin P , Sampol J 
Published: August 2018

Plasminogen activators (PA)may play an important role in the regulation of enzyme activation relative to basement membrane degradation associated with the invasive growth of tumors. In order to acquire a better understanding of the complex cascade reactions leading to the formation of plasmin, we have undertaken a comparative study of urokinase-type (u-PA) and tissue-type (t-PA) plasminogen activators in cellular extracts of 20 human cancer cell lines (13 malignant melanomas, 6 breast adenocarcinomas and 1 vulvar carcinoma). Four malignant cell lines,showing various t-PA or u-PA activity levels, were selected to study the modulation of proteolytic activity by laminin and fibronectin, major components of basal membrane. This study was performed in cellular extracts and conditioned medium. Our results showed that melanoma cells have high t-PA activity preferentially released into the culture medium. On the vulvar cell line, A 431, u-PA activity predominates and is also secreted into the medium. In contrast, breast cancer cells MCF-7 and MDA show u-PA activity, mostly recovered in the cellular extracts. An enhancement of respective PA activities occurs when cells are cultured on fibronectin or laminin, varying with the nature of the cell line.Additional studies are needed to precise interrelation between tumor cells, basement membrane components and PA activities and the potential significance of proteolytic activities as markers of malignancy and invasive capacity.
INFRACLINIC ACTIVATION OF PLATELETS AND FIBRIN FORMATION IN CANCER PATIENTS
Authors: David J L , Lambrichts M , Closon M T 
Published: August 2018

Thromboembolism has been frequently reported in cancer patients, mainly in cases with solid tumors. Besides in several animal models, fibrin deposition around the tumor and platelet aggre gates appear to be involved in invasion and metastasis. This study was aimed at evaluating the extent of in vivo platelet activation and fibrin formation in several kinds of human cancer. We excluded from this study patients whose blood was sampled with difficulty as well as those having clinical evidence of thrombosis or embolism, those with thrombocytopenia, increased fibrinogen degradation products or biological pattern of disseminated intravascular coagulation. Fibrinopeptide A (fpA) and β-thrombo-globulin (β-tg) were determined by RIA. Free platelet count ratio (PCR) was determined on whole blood samples as an index of circulating aggregates. Usual coagulation tests, antithrombin III activity, protein C plasma level, F VIII related antigen (F VIII RAG), F VIII Ristocetin cofactor (F VIII RCF) and F VIII procoagulant activity (F VIII C) were also determined.It was found that in more than fifty percent of patients, fpA was significantly increased above the upper reference limit. Cases with increased B-tg were less frequent. Separate increases in β-tg or fpA levels were often observed. PCR remained within the reference values in almost all patients. F VIII RAG, RCF and C were usually above 150 % of the reference mean.We conclude that platelet release and fibrinoformation frequently occur in cancer patients showing no sign of thrombotic process. Increased level of fpA with normal plasma β-tg level suggests that thrombin generation occurs only in the extravascular compart ment, probably next to the tumoral tissues. Increased levels of plasma β-tg with normal fpA levels may result from platelet activation by other stimuli than thrombin. It must be emphasized that normal PCR does not exclude the presence of fibrinous circulating aggregates which cannot be dispersed by EDTA. High F VIII activities may be due to the release of the von Willebrand factor from tumoral vessels.
ALPHA-2-ANTIPLASMIN (α2AP) IN ACUTE NONLYMPHOBLASTIC LEUKAEMIA AS A MARKER OF DISEASE ACTIVITY
Authors: Cofrancesco E , Poliani E , Salvatore M , Boschetti C , Moreo G , Cortellaro M 
Published: August 2018

α2AP (Coatest Antiplasmin Kit, Ortho Diagnostic Systems), antithrombin III (Atlll, Coatest Antithrombin Kit, Ortho Diagnostic Systems) and plasminogen (S2251) were assayed in 21 patients with acute nonlymphoblastic leukaemia (ANLL: 5M2 5M4 5M5) before and after chemotherapy and during bone marrow cellularity recovery. The aim of the work was to investigated disturbances of coagulation and fibrinolysis with special reference to proteases inhibitors and to evaluate the prognostic value of changes in these parameters in ANLL patients. Low α2AP levels were observed in the initial phase of the disease: Ul.5 ± 2k.79 SD in 10 DIC patients versus 6U.10 !± 20.70 SD in patients without DIC (p < 0.05). α2AP normalized only in the 11 patients who achieved haematological remission (71.63 ± 13.13 SD) and remained low in those who did not respond to chemotherapy (6l.88 ± 17.86 SD, p < 0.01). No significant modification of Atlll and plasminogen levels were observed during the course of the illness.It may be postulated that proteolytic cleavage of α2AP by granulocyte proteases contributes to the low levels of the inhibitor in ANLL, and suggested that α2AP may represent a marker of leu-kaemic disease activity. In fact the mean α2AP level of all patients at diagnosis plus those who did not respond to chemotherapy was significantly lower than that of patients in haematological remission (55.93 ± 23.13 versus 71.63 ± 13.13, p < 0.05).