bluuebunny/crossref_metadata_2025_split huggingface dataset:
DIFFERENT LOW MOLECULAR WEIGHT HEPARINS (LMWHs) ARE NOT IDENTICAL IN THE IN VITRO SCREENING REGARDLESS OF POTENCY ADJUSTMENT
Authors: Hoppensteadt D , Fareed J , Walenga J M , Emnuele R M , Racanelli A 
Published: August 2018

There is considerable controversy in the standardization and potency evaluation of low molecular weight heparins (LMWHs).Since these agents are produced by fractionation or depolymerization procedures, the resulting material shows marked compositional variations regardless of the similarity in molecular weight. In order to address the question “are different LMWHs the same?”, we utilized a uniform multiparametric in vitro test battery. Seven commercial LMWHs Choay Fraxiparine (CY 216), Choay CY 222, Novo LHN, Kabi Fragmin, Opocrin 2123 (OP), Hepar RD 11885 (RD), Pharmuka Enoxaparine (PK) and an unfractionated porcine mucosal heparin (PMH) were studied at equigravimetric amounts in established assays. PMH and LMWHs were ranked acdording to the dose-dependent effects and the results are summarized in the following:As evident from the above data, each of the agents studied showed a distinct profile in the in vitro test system studied. This data suggests that LMWHs are individual drugs with marked differences in in vitro actions, which may not be the true determinants of the relative safety/efficacy in clinical settings.
SUBCUTANEOUS ADMINISTRATION OF A LOW MOLECULAR WEIGHT HEPARIN (CY 222) COMPARED WITH SUBCUTANEOUS ADMINISTRATION OF STANDARD HEPARIN IN PATIENTS WITH ACUTE DEEP VEIN THROMBOSIS
Authors: FAIVRE R , NEUHART E , KIEFFER Y , TOULEMONDE F , BASSAND J P , MAURAT J P 
Published: August 2018

68 patients (pts) with acute deep vein thrombosis (DVT) were randomized to either CY 222 (Choay Institut, Cl, France) (n=33) in a dose of 750 u anti-Xa Cl/kg/day or standard heparin (SH) (n=35), 500 ui/kg/day, both given by 2 daily subcutaneous (sc) injections for 10 days. In SH group, dose was monitored by daily activated partial thromboplastin time to maintain a prolongation between 2 to 3 times the control value ; in CY 222 group dose remained unchanged during the 10-day treatment. Venography was repeated at day 10. Initial DVT localization and derived Marder’s score was similar in both groups (14.1 ± 11.7 in CY 222 group and 14.3 ± 10.6 in SH group, p = NS).The results show that : 1/ no bleeding complication was observed in CY 222 pts, but large hematoma occured in 3 SH pts, 1 patient in each group developed a recurrent pulmonary embolism and 2 others pts (1 in each group) did not undergo control phlebography ; 2/ in CY 222 group, 8 pts obtained complete lysis (CL, thrombolysis more than 90%), 11 partial lysis (PL, thrombolysis between 30% and 90%), and 11 no change (NC, less than 30%) ; 3/ in SH group, 4 pts obtained CL, 15 PL, 8 NC and extension was seen in 2 pts. Thus, phlebographic improvement (thrombolysis more than 30%) was observed in 65% in both groups.In conclusion, these preliminary results suggested that sc administration of CY 222 and SH, both given by 2 daily injections, was equally effective in pts with acute DVT, and CY 222 seemed to be safer than SH.
TREATEMENT OF PULMONARY EMBOLISM BY A VERY LOW MOLECULAR WEIGHT HEPARIN FRAGMENT (CY 222), A DOSE RANGE STUDY
Authors: Quilliet L , Charbbonnier B , Raynaud PH , Delahousse B , Toulemonade F , Brochier M L 
Published: August 2018

Experimental studies showed that CY 222 (MW 2500 - 250 U AXAIC/ mg - 25 Ul/mg) kept the profibrinolytic properties of heparin with a considerable reduction of bleeding risk and that the optimal dose was about 1 000 U AXAIC/kg/day in rabbits. We have tested the dose related effectiveness and tolerance of this drug in 47 patients (pts) with acute pulmonary embolism (PE) less than 5 days. Pts were divided into 3 groups receiving : Group I : 500 (n = 16), Group II : 750 (n = 17), Group III : 1 000 (n = 14) U AXAIC/kg/day by continuous intravenous infusion for ten days. Effectiveness was appreciated by Miller’ s index with pulmonary angiography (PA) performed before, on the 5th day and on the 10 th day of treatment. The decrease of Miller’ s index mean value was comparable in the 3 groups. But the improvement was faster in the group IIIWe noticed 5 recurrent PE (2 in Group I, 1 in Group II and 2 in Group III) of which one was fatal (Group I), and 2 hematoma at the venous punction site in Group III.In conclusion, CY 222 is a safe treatment of PE and the most effective dose seems to be 1 000 U AXA IC/kg/day in spite of minor bleeding.
KINETICS OF EXPERIMENTAL ANTITHROMBOTIC ACTIVITY OF MF 701 DERMATAN SULFATE
Authors: Morani A , Gianese F , Bianchini P 
Published: August 2018

In order to evaluate the intensity and duration of the prophylactic activity of dermatan sulfate against thrombosis induced by ligature of the inferior vena cava (Reyers'model), we treated 6 groups of rats at increasing intervals of time before ligature (1 min, 30 min, 45 min, 2 h, 16 h). Within each group the rats were injected subcutaneously with saline solution (controls) or increasing doses (2.5, 5, 10 and 20 mg/kg) of MF 701, dermatan sulfate (Mediolanum Farmaceutici, Milan, Italy). Two hours after ligature the presence of thrombi and their weight were recorded.A significant, dose-dependent antithrombotic effect was observed for all the treatment times. The maximum effect occured when the compound was administered 45 min before ligature (total abolition of thrombosis at the dose of 5 or more mg/kg). Total inhibition was also observed at 2 h (with 10 mg/kg) and at 4 h (with the same dose). A significant antithrombotic effect, over 50% com pared with the controls, was still found at 16 h at the dose of 20 mg/kg.These results confirm the experimental antithrombotic efficacy of dermatan sulfate already reported in a different animal model by F. Fernandez et al. (Br J. Haematol. 64, 309, 1986) and demonstrate the long duration of the prophylactic effect of the compound.
ANTITHROMBIN III, PLASMINOGEN, α2 ANTIPLASMIN, PREKALLIKREIN AND HEPARIN ASSAYS ON AN AUTOMATED COAGULATION LABORATORY (ACL 810) ANALYZER
Authors: Mammen E F , Farag A M , Sachs R J , Brown J M 
Published: August 2018

A recently introduced automated, microcomputer controlled centrifugal analyzer ACL 810 (Instrumentation Laboratories, IL) performs both clot based and chromogenic substrate based assays. We compared the performance characteristics of this new instrument with the Multistat III Centrifugal Analyzer (MCA, Instrumentation Laboratories) and the Protopath system (American Dade). Antithrombin III (AT) and plasminogen (PLG) were assayed on the ACL 810 using II kits, on the MCA using Kabi kits, S-2238 and S-2251, and on the protopath Dade reagents. 02 Antiplasmin (AP) was determined on the ACL with kits from General Diagnostics and on the MCA with the Kabi kits S-2251. On the protopath we used Dade reagents. Prekallikrein (PK) was analyzed on the ACL and MCA using Kabi kits S-2302. We adapted the plasminogen channel of the ACL for this assay. The correlation data for these four assays were as follows:AT and PLG assays on the ACL using Kabi kits correlated equally high.We also compared heparin assays, both anti IIa and anti Xa, on the ACL (anti IIa, II kits, anti Xa, Stago kits) with the MCA (anti Xa) and a spectrophotometer (anti IIa). The data are summarized below:These data suggest excellent correlations between the new ACL 810 and other instruments for these assays.
COMPUTER PREDICTION OF ANTICOAGULATION STATUS AND WARFARIN DOSE FOLLOWING CARDIAC SURGERY
Authors: Crow M J , Latif A B , Critchley A I , Stainton C , Nealon P , Rajah S M 
Published: August 2018

Fluctuations are freguently seen in the anticoagulant status of patients in the immediate post operative period following prosthetic heart valve replacement. These patients are at high risk of haemorrhage or thromboembolism. We have used a pharmokinetic model of warfarin metabolism to develop a computer programme to predict the maintenance dose of warfarin from early prothrombin activity determinations. This will enable controlled anticoagulation to be achieved. The expression for warfarin kinetics employs 4 constants determined by the residual sum of the sguares, which are used immediately to redefine dosage predictions. In a pilot study data obtained from 16 patients post operation 3, 5 and 7 days after commencing treatment, has been used to predict the reguired maintenance dose at 21 days. These predicted doses were then compared with the maintenance dose achieved by clinical practice. The programme was told to optimise its dose to achieve a PT ratio of 3 whereas clinically the ratio was allowed to vary in the therapeutic range of 2 to 4. Predicted doses at 21 days are shown.in the table:Correlation between predicted and clinical maintenance doses after 3 and 5 days treatment was poor but had improved significantly by 7 days, despite similar levels of prothrombin activity. Predicted prothrombin activity never exceeded the upper limit of the therapeutic range, and the predicted dose can be uprated on addition of further data within 2 minutes.After 7 days computer predicted warfarin dose has produced a good correlation with the clinical maintenance dose (the doses of only 3 patients varying by more than 1 mg/day). The significant fluctuations seen in the prothrombin ratio during clinical dosage were not observed with computer dosing and we now feel it is safe to use this programme to anticoagulate patients post operatively.
FIBRINOGENS NEW YORK II, III, AND IV : RELATIONSHIP BETWEEN ABNORMAL FIBRIN MONOMER POLYMERIZATION, BLEEDING TENDENCY, AND THROMBOTIC TENDENCY
Authors: Karp George , Liu Chung Y 
Published: August 2018

It has been proposed that a normal fibrin monomer polymerization is required for a normal fibrin potentiation of tPA-induced plasminogen activation. Accordingly, an abnormal fibrin moncmer polymerization may contribute to a thrombotic tendency. To investigate this possibility, three abnormal plasma fibrinogens (dysfibrinogenemia) have been studied and tentatively designated New York II (NY-II), New York III (NY-III), and New York IV (NY-IV) after the city where they were described.Each of these patients has a long thrombin clotting time (TCT), a long Reptilase clotxing time, and an abnormal fibrin monomer polymerization. The abnormal fibrin moncmer polymerization can be corrected by addition of Ca2+. NY-II is characterized by a normal level of plasma fibrinogen, but delayed fibrino-peptide release and marked prolongation of the TCI; NY-III, by a normal level of plasma fibrinogen and a normal fibririopeptide release; and NY-IV, by a low level of plasma fibrinogen, a normal fibrinopeptide release, and marked prolongation of the TCT. Each of these cases appears to be congenital, not acquired although the absence of data on relatives prevents definite conclusions. SDS-PAGE analysis of the mobility of the reduced abnormal fibrinogens shows no detectable abnormality, indicating no significantly altered molecular size of Aα, Bβ, and γ chains.No patient appears to be associated with either a bleeding or a thrombotic tendency. Thus, no direct association is observed between an abnormal fibrin monomer polymerization and a thrombotic tendency. Accordingly, fibrin monomer polymerization is not a function absolutly required for potentiation of plasminogen activation. However, based on the present observations and the observations previously described of abnormal fibrinogens with abnormal fibrin monomer polymerization from patients associated with bleeding and/or thrombotic tendency, a bleeding tendency seems to be correlated with a condition in which both a long TCT and an abnormal fibrin moncmer polymerization can not be normalized by addition of Ca2+.
MICROCARRIER CULTURE OF HUMAN ENDOTHELIAL CELL TYPES - A SOURCE OF METABOLITES
Authors: Hunter N R , MacGregor I R , Dawes J , Pepper D S 
Published: August 2018

The production of human endothelial cell secretory products in amounts sufficient for biochemical studies is largely restricted by the culture growth area. Conventional flat bed systems yield at best 20-30 x 106 cells per 180cm2 culture flask. To overcome this problem, cells may be grown on Cytodex 3 microcarriers allowing large numbers of cells to be grown and conditioned in small culture volumes. A typical microcarrier unit will contain 200-300 x 106 cells and may be expanded in excess of 1000 x 106 cells at confluence. High viability (95%) and recovery (70-80%) in sub-culturing of microcarrier to microcarrier culture can be achieved with careful management of culture conditions and brief exposure to enzymes.Human umbilical artery and vein, and saphenous vein endothelial cells were prepared and grogn on microcarrier cultures to cell populations of 200-450 x 106 cells and conditioned for 14 day periods in serum-free media.The production profiles of several endothelial cell proteins including thrombospondin (TSP), von Willebrand Factor (vWF) and issue plasminogen activator (t-PA) were measured by radioimmunoassay under these conditions, and demonstrate the use of microcarrier cultures in producing milligram quantities of engothelial cell protein. For example, a HUVEC culture of 200 x 106 cells conditioned with serum-free media for 14 days yielded a total of 6.9mg TSP, 0.7mg vWF and 48.9ug t-PA. In this laboratory one such application of the system was the purification of endothelial proteins in amounts sufficient for immunisation of mice prior to the production of monoclonal antibodies and for subsequent characterisation.
CHANGES IN ENZYMATIC ACTIVITIES IN BRAIN CAPILLARY ENDOTHELIAL CELLS INJURED BY PLATELET AGGREGATION IN VIVO
Authors: Fujimoto T , Djuricic B , Tanoue K , Fukushima Y , Yamazaki H 
Published: August 2018

We have reported cerebrovascular injuries induced by platelet aggregation in vivo. Appearance of vacuoles in endothelial cells and eventual deendothelialization are characteristic in large cerebral arteries (Stroke, 16:245, 1985). Minor changes are observed in brain capillaries, but disturbances of blood-brain barrier (BBB) are seen. To analyse changes in BBB, enzymatic activities in capillary endothelial cells before and after ADP-induced platelet aggregation in vivo were investigated.80 mg/kg of ADP was injected through a catheter into the right internal carotid artery of 32 rabbits. One hr later, right and left cortexes freed from pial membranes were homogenized and microvessels were isolated using discontinuous sucrose gradient ultracentrifugation. Purity of microvessel fraction was ascertained microscopically. The follwing enzymatic activities in these samples were measured.; cytochrome C oxydase (CCO), monoamine oxidase (MAO), p-nitrophenyl-phosphatase transferase (pNPPase, K-dependent component of Na, K-ATPase), gamma-glutamyl transferase (GT) and adenylate cyclase (AC). The enzymatic activities did not change after a vehicle-injection and did not show any differences between capillaries of both the cortexes before the ADP-injection. One hr after the ADP, GT and CCO activities decreased significantly in the capillaries of injection side. MAO activity also reduced without significance. The other enzymes did not show significant changes in their activities. Although pNPPase and AC which are associated with inner surface of plasma membrane were preserved well, activity of GT which is associated with outer portion of the membrane decreased significantly. It suggests superficial luminal injury and that plasma membrane might be affected from the side of vascular lumen. Reduced CCO activity suggests that disturbance in BBB is probably related to the increase in vesicular transportation and/or energy failure. Reduction of MAO activity indicates that damages to mitochondria exist in the capillaries. Cerebral blood vessels are prone to damage by released substances from activated platelet in vivo.
EICOSANOIDS AND VASOSPASM
Authors: Wilkinson D , Vowden P , Latif A B , Rajah S M , Kester R C 
Published: August 2018

To investigate the hypothesis that abnormalities in prostanoid metabolism may be an aetiological factor in Raynaud's syndrome (RS) we have measured the stable metabolites 6-keto-prostaglandin F1α (6-keto-PGF1α ) and thromboxane B2 (TXB2), using a radioimmunoassay. The table gives their levels (in ng/ml) and ratio (mean±SD) in healthy volunteers and in a group of patients with RS.In the control group there was no significant correlation between prostanoid levels and age, sex or smoking habit. In primary Raynaud's TXB2- levels and the ratio tend to be elevated from our control values. Patients with Vibration White Finger Disease (VWF) have a similar eicosanoid profile to that of the primary Raynaud's group with elevated TXB2 levels. One patient in this group had markedly raised 6-keto-PGF1α and TXB2 levels and later proved to have a circulating auto-antibody. Menstruating females in our study showed both elevated TXB and ratios similar to the primary group. It is interesting to note that menstruating females have an increased sensitivity to cold with abnormal cold stress tests. Patients with Raynaud's syndrome secondary to a systemic disorder have markedly elevated 6-keto-PGF1α and TXB2 levels although the ratio of the two remains within our normal range. There is a significant difference between secondary Raynaud's and all other groups investigated in the study (Mann-Whitney U test p = 0.04). Further research into prostanoid metabolism may yield a greater understanding of the pathophysiology of Raynaud's syndrome. Therapy may best be aimed at altering the levels of these important local hormones.
THE RECOVERY OF ENDOTHELIAL CELL AND PLATELET PROSTAGLANDIN SYNTHESES AFTER ADMINISTRATION OF ASPIRIN AND INDOBUFEN
Authors: Sheehan S J , Latif A B , Bibby S R , Kester R C , Rajah S M 
Published: August 2018

Suppression of endothelial prostacyclin (PGI2) by cyclooxygenase inhibition may contribute to the formation of neointimal hyperplasia. While aspirin (ASA) inhibits platelet function for several days, it returns to normal within 24 hours after indobufen (IDB), a reversible cyclooxygenase inhibitor, suggesting that prostacyclin may recover at an even faster rate. In a randomised, controlled study, recovery of platelet and endothelial cell prostaglandin synthesis was compared in 49 New Zealand white rabbits following indobufen (3.5 mg/kg) or aspirin (5 mg/kg). Prostacyclin in arterial incubates and platelet thromboxane A2 (TXA2) production in serum were measured by radioimmunoassay of their meta-bolities, 6Keto PGF1 and thromboxane B2. Platelet prostaglandin synthesis was also monitored by changes in serum malondiealdehyde (MDA).At one hour, both ASA and IDB significantly inhibited PGI2 (p<0.005). TXA2 (p<0.005), and MDA (p<0.02). After IDB, TXA2 and MDA levels returned to normal by 24 hours while inhibition continued in the ASA group (p<0.01). PGI2 synthesis following IDB recovered at 8 hours against 24 hours in the ASA group. We conclude that while both drugs inhibit platelet and endothelial prostaglandins, the earlier recovery of prostacyclin synthesis following indobufen may allow the endothelium to resume its physiological function.
FATTY ACIDS AND PLATELET FUNCTION IN A SOUTH AMERICAN INDIAN GROUP WITH A HIGH DIETARY CONSUMPTION OF DOCOSAHEXAENOIC ACID
Authors: Bosch V , Bosch N , Valles M , Ortíz N , Gómez R 
Published: August 2018

The effect of dietary polyunsaturated fatty acids on hemostasis has elicited much interest. We studied indians from the Orinoco river shore, whose main animal protein intake derives from river fishes with a high confceqt of 22:6n-3 (0.2g/100g)r We determined in 50 indians plasma phospholipid fatty acids (FApl) by gas/liq chromatography and bleeding time by Symplate I divice (BT), in 15 were analyzed platelet count, aggregation with collagen and ADP, platelet factor 3 availability (PF3), platelet phospolipid fatty acids (FApt) and plasma vWFAg.RA from human milk was also determined. Subjets from the city of Caracas served as control. Data on BT, FAlp and FApt are shown in table (X±SD).FA Composition of milk showed that indians have 3 times more 22: 6n-3 than controls. Platelet studies shewed normal number and morphology. Percent platelet aggregation with collagen (4ug/ml) was below 50% in 4 of indians, 2 of them with a BT within the control range. Maximum slope of aggregation with ADP (4uM) was diminished in 2 cases. Diference in PF3 was not significant, VWFAg range from 50 to 100% and control from 53 to 127%. In conclusion we have found a population that shows an increased plasma and platelet 22:6n-3 and a prolonged BT most likely of dietary origen. Mechanism by wich n-3 FA modifies BT needs fur ther investigation.
SEX DIFFERENCE IN THE INHIBITORY EFFECT OF ASPIRIN UPON THE DEVELOPMENT OF OCCLUSIVE ARTERIAL THROMBOSIS IN RATS
Authors: Uzunova A 
Published: August 2018

The aim of the study was to investigate the effect of aspirin upon the development of occlusive arterial thrombosis in rats of either sex. For this purpose 3 months old male and female Wistar rats were pretreated with three different doses of aspirin: 10, 30 and 60 mg/kg b.w., orally by stomach tube, 3 hours before the thrombosis procedure. Occlusive arterial thrombosis was induced by the method of Hornstra and Vendel-mans-Starrenburg (1973). The dry thrombus weight (TW) and the obstruction time (OT) of the bypass-cannula served as criteria for the degree of the development of thrombosis.The results showed a dose-dependent statistically significant inhibition of arterial thrombosis in male rats by all doses of aspirin studied. TW was decreased 2, 2.5 and 9 times by 10, 30 and 60 mg/kg aspirin respectively. OT was significantly prolonged in male rats by all doses of aspirin studied. Inhibition of arterial thrombosis in female rats was achieved only by the largest dose of aspirin tested - 60 mg/kg: TW was decreased and OT was prolonged. Paradoxically, female rats treated with 10 mg/kg aspirin showed a tendency for augmentation of arterial thrombosis which contrasted to the significantly decreased TW and prolonged OT of male rats given 10 mg/kg aspirin. Female rats treated with 30 mg/kg aspirin showed only a tendency for inhibition of arterial thrombosis without any significant difference for both, TW and OT. The results were interpreted as suggestive the existance of sex differences in cyclooxygenase inhibition by aspirin and/or the prostaglandin system in rats. The data obtained were in agreement with epidemiological observation of uneffectiveness of aspirin treatment of female patients with stroke. They also showed the need for the most appropriate dose of aspirin for clinical purposes which might be effective in females too.