bluuebunny/crossref_metadata_2025_split huggingface dataset:
PLATELET DEPOSITION AND PSEUDO-INTIMAL HYPERPLASIA IN PROSTHETIC VASCULAR GRAFTS
Authors: Harper R A , Lane I F , Backhouse C M , McCollum C N , Meek A C 
Published: August 2018

Platelet and fibrin accumulation in arterial grafts may cause pseudo-intimal hyperplasia and graft occlusion. The relationship between the rate of post-operative platelet accumulation and subsequent pseudo-intimal hyperplasia has been studied in prosthetic grafts implanted in greyhounds.The femoral artery in 30 greyhounds was replaced by a 6cm length of 6mm PTFE. Autologous 111In-platelet deposition over the graft was measured by probe and ratemeter for 7 days and radioactivity compared to the contralateral thigh. The daily increase in this ratio graft over reference was calculated as the Thrombogenicity Index (TI). Grafts were removed at 8 weeks and sectioned at 5, 30 and 55mm for measurement of pseudo-intimal thickening by grid microscopy.The animals subsequently developing occlusion or pseudo-intimal harrowing of greater than 50% of the lumen had a markedly greater TI of 0.22±0.027 compared to 0.03±0.019 in the 23 grafts maintaining wide patency (p<0.05). TI was highest in the 4 grafts which occluded at 0.3110.09 compared to 0.04±0.02 in the 26 that remained patent (p<0.01). There was a highly significant correlation (r=0.69) between post-operative TI and subsequent pseudo-intimal hyperplasia (p<0.001).Platelet deposition in the early post-operative period appears to promote the development of progressive pseudo-intimal thickening and ultimate occlusion
EFFECT OF DIPYRIDAMOLE + ASA ON THE RETINE VASCULAR PATTERN OF ESTREPTOZOTOCIN-DIABETIC RATS
Authors: Moreno A , de la Cruz J P , Garcia Campos J , Sanchez de la Cuesta F 
Published: August 2018

INTRODUCTIONWe have used an experimental model which allows the evaluation of the qualitative differences in the retinal vascular pattern by means of the labeling of the retine vascular tree with radish peroxidase (HRP) in estreptozotocin-diabetic rats. The aim of the study was to evaluate the effect of ASA and DIP + ASA on the vessels platelet behaviour of said retine pattern in a group of rats in t-hich the diabetes had 3 months of evolution.PROCEDURE22 Wistar male rats were divided into A groups; 1) control group, 2) diabetic rats without antiaggregant, 3) dietetic rats treated with 6 mg/day ASA p.o., 4) diabetic rats treated with 6 mg/day ASA +12 mg/day DIP p.o. For inducing diabetes 30 mg/Kg of i.v. estreptozotocine were administered. The animals were considered “diabetic” when glucemia was over 200 mg/100 ml. After 3 months of treatment with 4IU insuline and ASA, or ASA + DIP, the animals were sacrified. Samples of blood and rings of descending aorta were extracted. Platelet aggregation in IJB in front of 1 μg/ml of collagen and the prostacycline-like activity of the aorta ring were evaluated. The configuration of the retine vascular tree labeled with HRP was observed.RESULTS AND CONCLUSIONSMaximal aggregation intensity: 11.1 Ω in the control group,10.9Ω in the diabetic non-treated group, 4.8Ω in rats receiving ASA and 4.6Ω in rats treated with DIP + ASA. The incUbation during 10 min. of aorta rings in blood samples produced 38.7% inhibition in the control group, 12.8% in the non treated-diabetic group 0% in the ASA group and 49.3% in the group treated with DIP + ASA.The qualitative changes in the diabetic rats retinal vascular network non treated with antiaggregants showed a scarce visibility of capillars as well as large zones of tortuous vessels. The rats treated with ASA showed a continuous vascular bed and less tortuous vessels than the ones in the non treated group but the vascular diameters were smaller than the ones observed in non-diabetic rats; the rats treated with DIP + ASA showed a continuous vascular bed, scarce tortuous vessels and vascular diameters similar to the ones found in non-diabetic rats. Mortality rates: 0% in the control group, 50% in the non-treated diabetic group, 16% in the ASA group and 0% in the DIP + ASA group. The administration of DIP + ASA normalized the prostacycline-like activity and the retinal vascular pattern in estreptozotocin-diabetic rats.
HYPOGLYCEMIC EFFECT OF INDOBUFEN,AN ANTIAGGREGATING AGENT,IN ELDERLY DIABETIC PATIENTS
Authors: Barzizza F , Belloni G , Trespi E , Venturini A , Richichi I 
Published: August 2018

Inibition of platelet aggregation is of value in therapy for Transient Ischemic Attacks(TIA).We observed 2 consecutive elderly patients with type 2 diabetes mellitus(DM)and TIA,in whom chronic treatment with Indobufen(I) provoked a reduction of blood glucose levels; for this reason we started a cross-over study to assess the possible hypoglycemic effect of I in elderly patients with DM.Ten patients(5 males,mean age 75±5 years)with DM and TIA have been included in our study. After 1 month of diet treatment(1)all patients took either placebo tablets 2)or I 200mg every 12 hours for 4 weeks in a random cross-over fashion.After each period a daily blood glucose profile has been obteined. Results are the following:Indobufen in the dose of 200 mg every 12 hours has an hypoglycemic effect. This side effect can be dangerous in patients already treated with hypoglycemic agents, but can be usefull as a single drug therapy for aged patients with type 2 diabetes mellitus and atherosclerotic vascular disease.
ADHESION OF BLOOD PLATELETS FROM PATIENTS WITH DIABETES MELLITUS TYPE I, TO THE ENDOTHELIAL CELL MATRIX OF HUMAN VASCULAR ENDOTHELIAL CELLS, UNDER FLOW CONDITIONS
Authors: Nievelstein P F E M , Banga J D , Ottenhof-Rovers M , Zwaginga J J , de Groot P G , Sixma J J 
Published: August 2018

Platelet activation in diabetes mellitus may precede vasculopathy. We have studied platelet adhesion and thrombus formation in flowing blood of diabetic patients without macro-and microvascular complications. Platelet function and release, bleeding time, fibrinogen, FVIII:RAg, Ri:Co, Triglycerides, Cholesterol and HDL Cholesterol levels, Apo A, Apo B and TK values were in the normal range. Glucose levels and HBA1 were increased. The matrix of cultured human umbilical vein endothelial cells (ECM) was used for adhesion studies.In an adhesion model with citrated blood (3.1%) and an untreated ECM, three male and three female diabetics (mean age 29.6 y., range 20-32 y., average duration of diabetes 10.6 y., range 2-23 y.) were compared with six age and sex-matched corf-trols. No differences in platelet coverage (en face) was obtained at low (300 s™1 ) and high (1300 s™1 ) wall shear rates, and the time dependence (1-20 min) was the same.We also used a thrombosis model, consisting of the matrix of PMA-treated endothelial cells which induces tissue factor production, perfused with blood anticoagulated with low molecular weight heparin, which does not inhibit local thrombus formation. Four male and two female patients (mean age 25.4 y., range 22-40 y., average duration of diabetes 10 y., range 2-28 y.) were compared with six age and sex matched controls. Cross sections showed equal total adhesion at 300 s™1 and 1300 s™1 after 1, 3, 5 or 10 minutes perfusion. In the diabetics, spread platelets were significantly decreased at 300 s™1 after 1 and 3 min, and at 1300 s™1 after 5 min; small aggregates (< 5μM) were increased after 1 min at 300 s™1 . At 300 s™1 some patients (2 of 6) showed a faster and more extensive fibrin formation.We conclude that _ in this group of diabetics there is no difference in primary adhesion but that there is an enhanced tendency in thrombus formation and fibrin deposition.
ALCOHOL- AND TOBACCO CONSUMPTION IN PATIENTS WITH SUSPECTED DEEP VENOUS THROMBOSIS (DVT)
Authors: Lagerstedt C , Fagher B , Olsson C G , Ögvist B 
Published: August 2018

Alcohol has several effects on hemostasis that might predispose for thromboembolism. The association between alcohol consumption and venous thrombosis is sparesly documented and we have therefore conducted a prospective study.Methods: 395 consecutive patients with suspected DVT entered the study. The patients were questioned about consumption of beer, wine and liquor and the average weekly consumption of ethanol was estimated. The total weekly consumption of tobacco was also estimated. 302 of the patients (130 men and 172 women) underwent phlebography, which was classified either as normal or as fresh DVT or/and postthrombotic changes.Results: 31 of the 130 men reported a weekly consumption of 100 g ethanol or more. In men below 65 years of age (62 men, see table) there was a significant relationship between ethanol consumption and the presence of fresh DVT or/and postthrombotic changes at phlebographyIn men above 65 years of age the incidence of DVT/postthrombotic changes was not higher among those who consumed more than 100 g ethanol per week (9 of 14) than among them who consumed less than 100 g per week (35 of 54). Only 5 of the women admitted a consumption of at least 100 g ethanol per week, one of them had a DVT.Tobacco consumption was not related to the occurrence of DVTConclusion: Ethanol seems to be a risk factor for DVT in young and middle-aged men
DISCREPANCY IN FIBRINOLYTIC RESPONSE TO VARIOUS STIMULI IN HEALTHY MEN
Authors: Stegnar M , Keber I , Keber D , Vene N 
Published: August 2018

Absent or low fibrinolytic response to stimulation is believed to reflect thrombotic tendency. However, it has been observed, that poor response to one stimulus is not always associated with poor^ response to other stimuli. Therefore, correlation between fibrinolytic responses to various stimuli has been studied in two groups of healthy men. Nine volunteers of the first group were subjected to 20 min upper arm venous occlusion (VO) followed by vasopressin analogue (DDAVP) infusion (0,4 ug/kg body weight in 10 min). In the second group (16 volunteers) VO and physical exercise (EXER, discontinuous test on treadmill up to maximal heart rate) were applied successively in this order. Venous blood was sampled before stimulation and in the 20 min of VO in both groups. The third blood sample was obtained 20 min after start of DDAVP infusion in the first group and immediately after EXER in the second group. Fibrinolytic activity was determined by euglobulin clot lysis time and by specific tissue plasminogen activator (t-PA) activity assay and increase in activity above prestimulation value calculated. No significant correlation between fibrinolytic response to VO and DDAVP was observed in the first group. Also in the second group responses to V0 and EXER showed no correlation.The observed discrepancy in fibrinolytic responses to various stimuli rise an important question: Which fibrinolytic response is more relevant to development of thrombosis?
COMPARATIVE STUDY OF RADIOIMMUNOASSAYS FOR FRAGMENT E-NEOANTIGEN IN PLASMA AND E-ANTIGEN IN SERUM
Authors: Chen J P , Goldman M H , stegner M 
Published: August 2018

Fragment E-neoantigen (Eneo) is a specific marker of structual and conformational changes associated with the plasmic degradation of fibrinogen and fibrin. The Eneo radioimmunoassay (RIA) is capable of determining normal and pathological plasma levels of fibrin(ogen) degradation products (FDP). However, the detection of the minute quantity of E-related FDP present in the blood of a normal individual requires subjecting the Eneo RIA to a delayed (18 hr) addition of labeled ligand. This step increases the already lengthy period of incubation (48 hr) for the primary antigen-antibody complex to 66 hr. An additional incubation period (24 hr) is required to precipitate the primary complex with goat anti-rabbit IgG.In an attempt to simplify and speed up the diagnostic blood test for deep vein thrombosis (DVT), the serum fragment E-antigen (E:Ag) RIA has been compared with the Eneo RIA in plasma. Four patients with DVT were followed sequentially with respect to the pre- and post-operative change in response to vascular surgery. Both the Eneo RIA and E:Ag RIAs showed a gradation in plasma (132 - 463 ng/ml) and serum (171 - 1400 ng/ml) E-related FDP levels respectively. Significantly, the sequential measurements of plasma Eneo and serum E:Ag immunoreactivities for these patients appear to fluctuate in parallel with each other. Normal females gave higher plasma Eneo (15.2 ± 4.3 ng/ml) as well as serum E:Ag (42.7 ± 17.8 ng/ml) values than normal males (Eneo = 10.2 ± 5.5 ng/ml, E:Ag = 38.8 ± 19.5 ng/ml). Normal serum E:Ag levels represent the increase in Fg-E concentration, 3-4 times that of normal plasma Eneo levels.Considerably higher plasma Eneo (2.2 - 7.1 pg/ml of Fg-E equivalent) and serum E:Ag levels were observed in DVT patients under thrombolytic therapy with streptokinase. Western immuno-blotting of patients1 plasmas and sera revealed that the Fg-E antigenic sites of both pathological plasmas and sera showed a similar pattern with a major immunoreactive FDP at Mr-360,000.The serum E:Ag assay as currently practiced takes 24 hr to complete, but the time of the assay can be shortened considerably by adapting it to a solid-phase RIA.
A COMPARISON OF D-DIMER AND SERUM FIBRINOGEN/FIBRIN DEGRADATION PRODUCT LEVELS (F.D.P.’s) IN THE INVESTIGATION OF HYPERCOAGULABLE STATES
Authors: Wilde J T , Kitchen S , Freston F E , Greaves M 
Published: August 2018

D-Dimer assays measure specific breakdown products of crosslinked fibrin whereas FDP assays are not specific for these products. We have, therefore, measured D-Dimer levels (MabCo Dimer Test) semi-quantitatively in patients with clinical and laboratory evidence of disseminated intravascular coagulation, acute and chronic liver disease, acute leukaemia at presentation and acute venous thrombosis at diagnosis. We have also measured D-Dimer in the 3rd trimester of normal pregnancy and in pregnancies with complications. We compared these levels with F.D.P. levels measured by the Thrombo-Wellcotest. Patients with liver disease comprised mainly cirrhosis and acute viral hepatitis; those with venous thrombosis had this diagnosis confirmed by venography. Pregnancy complications included mainly pre-eclampsia, ante-partum haemorrhage and intra-uterine foetal death. D-Dimer levels were elevated ( 200ng/ml) in all 31 patients with D.I.C., in 34 of 40 with liver disease, in 13 of 16 with acute leukaemia, in all 10 patients with D.V.T., in 9 of 16 normal pregnancies and in 29 of 39 complicated pregnancies. Using a rank correlation method, there was correlation between D-Dimer and F.D.P. levels (Normal 8ug/ml) in the following groups of patients as follows (r is the correlation coefficient, levels of significance are shown in brackets):D.I.C. r=0.72(0.2%), liver disease r=0.56(0.2%), acute leukaemia r=0.72(0.2%), D.V.T. r=0.83(1%) and complicated pregnancy r=0.42(1)6). There was no correlation between D-Dimer and F.D.P. levels in normal pregnancy. Very rarely were D-Dimer levels elevated when F.D.P. levels were normal and vice-versa. We conclude that a close relationship does exist between D-Dimer and F.D.P. levels in the clinical conditions that we have studied. We note the high incidence of elevated D-Dimer levels and the close correlation with F.D.P. levels in patients with liver disease and the high incidence of elevated D-Dimer levels suggesting increased activity of the coagulation system in patients with acute leukaemia.
EFFECTIVENESS OF DEFIBROTIDE IN THE TREATMENT OF ACUTE MYOCARDIAL INFARCTION
Authors: Milazzotto F , Carelli M , Citone C , Di Macro Tullio G , Gambelli G C , Giampaolo P , Malinconico U , Polizzi C , Cornelli U 
Published: August 2018

Defibrotide (D) is an extractive polydesoxyribonucleotide. In preclinical studies the product was shown to be active as a pro -fibrinolytic, antithrombotic and thrombolytic agent while comply tely devoid of anticoagulant activity. In animal models, D was found to afford striking protection from the effects of acute lethal and non lethal myocardial ischemia as well as from myo -cardial injury following reperfusion. In this open single - blim trial, D was administered to patients with acute myocardial infaj ction (AMI) for the prevention of complicating arrhythmias; throy bus formation, pericarditis, etc.Sixty patients with AMI were divided randomly into two groups of 30 patients each. One group was treated with D by 6-hour drip infusion for 3 consecutive days (2.8 g on the first day, then 2.4 g daily). The other group was treated with equal volumes of physiological salt solution. All patients received conventional trea_t ment for AMI. The two trial groups were sufficiently homogeneous in terms of AMI type, age and sex distribution, PCT, Forrester index, Holter, and Peel index. D treatment proved effective in reducing the incidence of severe arrhythmia (p < 0.05), thrombus formation (p < 0.05), and pericarditis (p < 0.01). CPK, TT and PTT readings were not modified by the treatment; the incidence of post-AMI angina and the number of deaths (4 in each group) were similar in the two groups. The results of this pilot study are encouraging; further clinical trials are currently in progress to assess D activity in larger groups of patients treated with the product at higher dosages.
PROFIBRINOLYTIC ACTIVITY OF DEFIBROTIDE IS PTOSTACYCLIN-INDEFENDEMT
Authors: Porta R , Pescador R , Niada R , Mentavani M , Prino G 
Published: August 2018

The profibrinolytic, antithrombotic and thrombolytic activities of Defibrotide, a polydeoxyribonucleotide obtained from mammalian lungs, have been previously described. Defibrotide is also able to promote the generation and release into the circulation of prostacyclin and of plasminogen activator factor (tPA) from vascular walls. These two last activities, i.e., PGI2 and tPA stimulation, could be of importance in the profibrinolytic activity of Defibrotide. In an attempt to clarify the profibrinolytic mechanism/s of Defibrotide, the role of PGI2 generation in this activity was investigated in rabbits in which the cycloxygenase pathway was blocked with Indcmethacin. Male rabbits were treated with Indcmethacin, 10 ng/Kg, i.v., 20 minutes or 2 hours before Defibrotide administration. Defibrotide was injected i.v. into rabbits at two dose levels (16 or 64 rrg/Kg). Rabbits treated with Defibrotide only were used as controls. The profibrinolytic activity was evaluated measuring the lysed area of normal human fibrin plates induced by euglobulin fraction obtained from plasma. Results are reported in the Table.Indomethacin (Indo) administered 20 min (*) or 2h (**) before Defibrotide.AN3VA: N.S. vs. Vehicle + D 12.5 or D 50 ng/Kg i.v.; P< 0.01 vs. basal.The results reported here demonstrate that the profibrinolytic activity of Defibrotide is independent of PGI2 generation: Indcmethacin pro treatment was unable to suppress or to reduce the fibrinolytic response of the rabbit to Defibrotide.
PR0C0AGULANT ACTIVITIES IN HUMAN ALVEOLAR MACROPHAGES:
Authors: Nakstad Britt , Lyberg Torstein 
Published: August 2018

The coexistence of fibrin and tissue macrophages is a common finding in the histopathology of chronic inflammatory diseases of the lung.Fibrin deposition may occur as a result of activation of the extrinsic coagulation system,initiated by procoagulants generated by alveolar macrophages.In this study human alveolar macrophages (LAM) obtained by lavage of healthy donors were shown to express procoagulant factors,thromboplastin (tissue factor) and a direct factor X activator,probably a thromboplastin/ factor VII complex.In contrast to blood monocytes, LAM were only slightly susceptible for in vitro induction of thromboplastin activity (11,3 ± 2,6 (SEM)-fold and 1,3 t 0,2-fold activity increase after endotoxin stimulation).LAM were separated into four subpopulations by density gradient centrifugation.The specific thromboplastin activity of subpopulation cells varied inversely with their density (3,08 ± 0,42 U/mg cell protein for the least dense vs.0.49 ± 0.03 for the most dense subpopulation ).Low-density subpopulations of LAM released membrane material to the culture medium,which was sedimentable in the u1tracentrifuge and which expressed procoagulant activities with the same characteristics as the LAM procoagu1 ants.These findings suggest that alveolar macrophages and the membrane vesicles shed from their surface can contribute to local fibrin deposition in the lungs by expressing procoagulant factors.
MECHANISM OF ACTIVATION OF BLOOD COAGULATION BY LEUKOCYTE PROCOAGULANT ACTIVITY
Authors: Narahara N , Sadakata H , Uchiyama T , Andoh K , Tanaka H , Kobayashi N , Maekawa T 
Published: August 2018

To investigate the process of activation mechanism of blood coagulation by leukocytes, binding of radiolabelled Factor X and the activation of Factor X on the cell surface of leukocytes were studied by using cultured leukemia cell line, Molt-4 cells. Cells were cultured in RPMI 1640 medium with 10% inactivated fetal, calf serum at a concentration of 1x106cells/ml. After 6 hours' stimulation with 1 ug/ml of endotoxin(LPS: Escherichia coli 026:B6), cells were separated by centrifugation, washed three times with Tris containing NaCl buffer(pH 7.5, TBS), and then suspended in TBS containing 0.5% bovine serum albumin(TBS-BSA) to the concentration of 5x106 cells/ml. Factors X, VII and IX were purified from fresh-frozen human plasma by the method of Bajaj in a modified version. Factor VIII was purified from cryoprecipitate as starting material. Factor X labelled with 1-125 by the method of McFarlane showed a single band on autoradiography. Specific radioactivity was 0.3 mCi/mg. For the study on binding of Factor X, TBS-BSA solution containing 4 mM of CaClp, various amounts of radiolabelled Factor X with/without purified Factors VII, VIII and IX were added to the LPS-stimulated washed cell suspension and mixed well. N-butyl-phtalate was layered over the reaction mixture after incubation at room temperature for various minutes. Total amount of bound Factor X was calculated from the radioactivity of the cell pellet separated by centrifugation of the reaction mixture. The Xa activity generated in the supernatants was assayed using S2222.Results: Factor X bound specifically to the LPS-stimulated Molt-4 cells. Amount of bound Factor X and the dissociation constant was 1.0 ng/5x10bcells (5.2x103sites/cell) and 5x106M, respectively. More amounts of Factor X bound when Factors VIII and IX were present in the reaction mixture than their absence. Five times more Factor Xa was generated when Factors VII, VIII and IX were present in the reaction mixture as compared with presence of Factor VII, alone. These results suggest that blood coagulation cascade proceeds on the LPS-stimulated leukocyte surface.