bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of Arachidonic Acid Metabolism in Human Endothelial Cells by Glucocorticoids
Authors: De Caterina Raffaele , Weksler Babette B 
Published: July 2018

SummaryTo learn whether glucocorticoids inhibit prostaglandin (PG) production in vascular endothelial cells, we investigated the effects of glucocorticoids on PG synthesis by cultured human umbilical vein endothelial cells (EC). Pretreatment of EC with dexamethasone (DX, 10-9 to 5 x 10-5 M) caused a dose-dependent inhibition of PGI2 production when PG synthesis from endogenous arachidonate was stimulated by human thrombin (0.25-2 U/ml) or ionophore A 23187 (1-5 μM). The inhibition was detectable at 10-7 M DX and maximal at 10-5 M (4.0 ± 0.7 vs. control: 7.7 ± 1.9 ng/ml, mean ± S.D., P <0.01). The production of PGE2 and the release of radiolabelled arachidonate (AA) from prelabelled cells were similarly inhibited. Prolonged incubation of EC with glucocorticoids was required to inhibit PG production or arachidonate release: ranging from 8% inhibition at 5 h to 44% at 38 h. In contrast, prostaglandin formation from exogenous AA was not altered by DX treatment. When thrombin or ionophore-stimulated EC were restimulated with exogenous AA (25 μM), DX-treated cells released more PGI2 than control cells (5.7 ± 0.5 vs. 4.1 ± 0.6 ng/ml, P <0.01). Both the decrease in PGI2 production after thrombin/ionophore and the increase after re-stimulation with AA were blunted in the presence of the protein synthesis inhibitor cycloheximide (0.1-0.2 μg/ml). Thus, incubation of EC with glucocorticoids inhibits PG production at the step of phospholipase activation. The time requirement for these steroid effects and their blunting by cycloheximide are consistent with the induction of regulatory proteins, possibly lipocortins, in endothelial cells.
A Comparison of the Antithrombotic and Haemorrhagic Effects of a Low Molecular Weight Heparin (LHN-1) and Conventional Heparin
Authors: Diness V , Nielsen J I , Pedersen P C , Wolffbrandt K H , Østergaard P B 
Published: July 2018

SummaryThe antithrombotic effects after intravenous administration of a low molecular weight heparin (LHN-1) and conventional heparin were compared in a rabbit model of experimental thrombosis, where thrombus formation was induced by a combination of endothelial damage and stasis. Both compounds were able to prevent thrombosis completely. However, LHN-1 was significantly less potent than conventional heparin, the ratio between doses with the same antithrombotic effect being 2.4:1 on a weight basis. Bleeding times after administration of LHN-1 and conventional heparin were determined by tail transsection in anaesthetized rats and by template bleeding in the ear of conscious pigs. Given intravenously at a dose ratio of 2.4:1 (w/w), LHN-1 affected APTT less than conventional heparin, whereas the effects on haemostasis were not significantly different. In conclusion, it was found that after intravenous administration LHN-1 prevented experimental thrombosis as effectively as conventional heparin. However, the correlation between antithrombotic and haemorrhagic effects of LHN-1 was the same as that of conventional heparin. The corresponding relation in man remains to be determined.
The Effects of Modulation of Prostanoid Metabolism on the Thoracic Platelet Accumulation Induced by Intravenous Administration of Collagen in the Guinea-Pig
Authors: Butler K D , Shand R A , Wallis R B 
Published: July 2018

SummaryThe effects of intravenously administered collagen on the circulatory platelet count, TxB2, 6-keto PGF1α and 51Cr-labelled platelet accumulation in the thorax have been evaluated in the guinea-pig. Administration of collagen induced a dose-related peripheral thrombocytopenia and a concomitant increase in 51Cr-labelled platelets in the thorax. There was also a transient dose-related increase in plasma TxB2 but no change in plasma 6-keto PGF1α levels.The thromboxane synthetase inhibitors tested, reduced the platelet accumulation, but only CGS 13080 significantly inhibited TxB2 production. In contrast all the cyclooxygenase inhibitors tested impaired the elevation of plasma TxB2 after collagen, but only diclofenac inhibited the 51Cr-labelled platelet accumulation.The greater effect of thromboxane synthetase inhibitors compared to cyclooxygenase inhibitors on platelet accumulation in this system cannot be completely explained by the changes measured in the circulating prostanoids.
Heparin-Induced Osteoporosis in Rats
Authors: Matzsch Thomas , Bergqvist David , Hedner Ulla , Nilsson Bo , Østergaard Per 
Published: July 2018

SummaryIn order to study the effect of heparin in inducing osteoporosis, 30 female rats were divided in two groups and treated with daily injections of 2 IU heparin/g body weight for 33 and 65 days and compared with the same number of rats acting as controls. The mineral bone mass in the femora of the animals was measured quantitatively. A significant (p <0.001) reduction in bone mineral mass was found in the heparin-treated animals. This effect was present to the same degree after 33 days as after 65 days of treatment. It is concluded that heparin in this dose causes osteoporosis in rats after 33 days and that the described method can be used as an experimental model for further studies on this topic.
Comparative Turn-Over of Heparin Cofactor II and Antithrombin III in Baboons Influence of Heparin and Pentosan Polysulfate Administration
Authors: Sié P , Lansen J , Lacheretz F , Verschuere B , Boneu B 
Published: July 2018

SummaryHeparin and pentosan polysulfate (PPS) interact in plasma with antithrombin III (AT III) and Heparin cofactor II (HC II) respectively. To assess the influence of heparin or PPS treatment on the metabolism of their respective cofactors, we performed a double tracer study in baboons receiving heparin or PPS. Purified AT III and HC II from human plasma were labelled with 131I and 125I respectively by the lactoperoxidase-glucose oxidase technique. The tracers had unchanged biological activities, were homogenous in SDS-PAGE, migrated as native proteins by crossed immunoelectrophoresis in the presence of heparin or PPS and virtually coeluted with endogenous baboon proteins from heparin-agarose. Nine animals were randomly allocated to receive, during the metabolic study, heparin (500 IU/kg/d, n = 3), PPS (5 mg/kg,d, n = 3) or a placebo (n = 3) given in 2 daily subcutaneous injections. Heparin levels and anticoagulant effects were similar in extent and duration to those usually achieved in man. The plasma concentrations of AT III and HC II did not vary under treatment. The half-life of the elimination phase in the placebo group ranged from 1.95 to 2.33 d for AT III and from 1.96 to 2.21 d for HC II. There was no significant difference in the half-lives of the 2 inhibitors between the placebo group and the animals receiving heparin or PPS. This suggests that clinical conditions associated with heparin treatment may be important for the effect of heparin on AT III metabolism previously reported in patients. When the data of the nine animals were pooled, a strong positive correlation (p <0.001) between the halflives of AT III and HC II was found, indicating similarities in the catabolic pathways of these two parent molecules.
Neutralization of a Low Molecular Weight Heparin (LHN-1) and Conventional Heparin by Protamine Sulfate in Rats
Authors: Diness V , Østergaard P B 
Published: July 2018

SummaryThe neutralization of a low molecular weight heparin (LHN-1) and conventional heparin (CH) by protamine sulfate has been studied in vitro and in vivo. In vitro, the APTT activity of CH was completely neutralized in parallel with the anti-Xa activity. The APTT activity of LHN-1 was almost completely neutralized in a way similar to the APTT activity of CH, whereas the anti-Xa activity of LHN-1 was only partially neutralized.In vivo, CH 3 mg/kg and LHN-1 7.2 mg/kg was given intravenously in rats. The APTT and anti-Xa activities, after neutralization by protamine sulfate in vivo, were similar to the results in vitro. In CH treated rats no haemorrhagic effect in the rat tail bleeding test and no antithrombotic effect in the rat stasis model was found at a protamine sulfate to heparin ratio of about 1, which neutralized APTT and anti-Xa activities. In LHN-1 treated rats the haemorrhagic effect was neutralized when APTT was close to normal whereas higher doses of protamine sulfate were required for neutralization of the antithrombotic effect. This probably reflects the fact that in most experimental models higher doses of heparin are needed to induce bleeding than to prevent thrombus formation. Our results demonstrate that even if complete neutralization of APTT and anti-Xa activities were not seen in LHN-1 treated rats, the in vivo effects of LHN-1 could be neutralized as efficiently as those of conventional heparin. The large fall in blood pressure caused by high doses of protamine sulfate alone was prevented by the prior injection of LHN-1.
Further Characterization of Wheat Germ Agglutinin Interaction with Human Platelets: Exposure of Fibrinogen Receptors
Authors: Lebret Marilyne , Rendu Francine 
Published: July 2018

SummaryIt was previously shown that (i) Wheat germ agglutinin, (WGA)-induced platelet activation occurred when only 17% of the lectin binding sites were occupied on the platelet surface and (ii) WGA caused the release of a platelet constituent which in turn participates in the observed effect. We now further define the platelet activation induced by WGA: the lectin induces a binding of fibrinogen to specific surface receptors. 125I-fibrinogen binding increases with the WGA concentration from 5 to 15 ug/ ml. Binding occurs without addition of exogenous calcium; its analysis demonstrated 54000 sites with a Ka = 0.8 × 106 M-1, Addition of 1 mM Ca2+ enhances the 125I-fibrinogen binding and reveals a second class of sites with higher affinity (9200 sites, Ka = 0.17 x 108 M-1). This 125I-fibrinogen binding is totally abolished by EDTA, ATP and arginine, and inhibited by 75% by CP/CPK; cyclooxygenase inhibitors and PGE1 also reduce the fibrinogen binding. Thus the WGA-induced fibrinogen binding is (1) release-dependent and (2) responsible for the aggregation process but not for the agglutinating effect of the lectin.
ADP-Induced Platelet Release Reaction in Acute Stroke
Authors: Mulley G P , Heptinstall S , Taylor P M , Mitchell J R A 
Published: July 2018

SummaryThe extent of the ADP-induced platelet release reaction has been determined in 107 patients admitted to hospital with acute stroke. In 43 of the patients a precise diagnosis was obtained and in those with proven thromboembolic stroke the mean extent of the release reaction was significantly higher than for those with either primary haemorrhagic stroke or those with subarachnoid haemorrhage. Enhanced platelet reactivity was also found in the patients in whom a precise diagnosis could not be obtained, most of whom probably had cerebral infarction. Comparison of the results obtained for patients with stroke with those obtained for individuals who had not experienced a stroke showed that thromboembolic stroke is associated with platelet hyperactivity while haemorrhagic stroke is associated with platelet hypoactivity. The part that abnormalities of platelet behaviour, whether causal or consequential, might play in occlusive stroke and intra-cranial haemorrhage is discussed and the need for large scale prospective studies is emphasised.
Contribution of Adrenaline to the Fibrinolytic Activity Evoked by E. Coli Endotoxin in the Rat
Authors: Fracasso J F , Rothschild A M 
Published: July 2018

SummaryIntravenous injection of E. coli endotoxin (ETX), of adrenaline (AD) or of carbamylcholine (CBCH), caused fibrinolytic activity (FA), directly detectable on plasminogen-rich fibrin plates, to appear in the plasma of the rat. Adrenodemedul- lation abolished responses to ETX or CBCH, but enhanced those to AD. Rats given ETX exhibited marked hypotension, followed by a compensatory phase of normotension abolished by adrenodemedullation and significantly attenuated by phenoxy- benzamine, an a-adrenergic blocking agent which however failed to block FA caused by either ETX or AD. Aspirin, but not indomethacin, inhibited FA evoked by ETX, AD or CBCH. These results suggest that FA evoked by ETX in the rat is caused by AD released from the adrenal gland and does involve the fatty acid cyclooxygenase system.
Decreased Antithrombin III Activity in Diabetes May Be Due to Non-Enzymatic Glycosylation – A Preliminary Report
Authors: Ceriello A , Russo P Dello , Zuccotti C , Florio A , Nazzaro S , Pietrantuono C , Rosato G B 
Published: July 2018

SummaryAntithrombin III activity was moderately but significantly decreased in insulin dependent diabetics (p <0.005), while no difference has been found between the diabetic (n = 25) and control groups (n = 22) in antithrombin III plasma concentration.Moreover, antithrombin III activity was inversely correlated with glycosylated plasma proteins (r = -0.57; p <0.01).These data show that in diabetes there is a depressed biological activity of antithrombin III and suggest that this reflects nonenzymatic
glycosylation of antithrombin III protein.
Shortening of Platelet Survival by Induced Hypercholesterolaemia In Rabbits and Its Prolongation by Anagrelide
Authors: Barrett P A , Butler K D 
Published: July 2018

SummaryInduction of atherosclerosis in rabbits by feeding a cholesterol enriched diet reduced the platelet half-life in male rabbits from 37.0 ± 4.1 hr to 30.1 ± 3.9 hr (mean ± S.D. p ≤0.01). Platelets from these animals exhibited increased sensitivity to arachidonic acid but decreased sensitivity to ADP. No significant change was found in aggregation to collagen or thrombin, or in the production of thomboxane B2 induced by collagen.The reduced platelet survival was dependent upon the recipient animal and not the platelet donor. Platelets from cholesterol- fed animals survived normally in normal animals, whereas platelets from normal animals in cholesterol-fed animals had a reduced platelet survival even compared to platelets from cholesterol-fed animals. This might suggest that some functional change had occurred in the cholesterol platelet in response to its altered environment.Anagrelide (1 mg/kg/day) normalised shortened platelet survival in both male and female rabbits fed the high cholesterol diet.
The Use of Evacuated Tubes for Blood Collection in Oral Anticoagulant Control
Authors: van den Besselaar A M H P , van Halem-Visser L P , Loeliger E A 
Published: July 2018

SummaryThe prothrombin time (PT) test is used to monitor oral anticoagulant therapy. Contact activation of patient blood samples in vitro may shorten the PT and thus lead to underestimation of the degree of anticoagulation. Commercial evacuated tubes for blood collection have been reported to induce shortening of the PT. The Thrombotest modification of the PT determination was used to investigate the properties of different brands of evacuated siliconized tubes. Two recently manufactured batches of such tubes did not induce appreciable shortening of the PT and can therefore be recommended for use in monitoring oral anticoagulant treatment.
The Novel Effect of a New Prostacyclin Analogue ZK36374 on the Aggregation of Human Platelets in Whole Blood
Authors: Saniabadi A R , Lowe G D O , Belch J J F , Forbes C D , Prentice C R M , Barbenel J C 
Published: July 2018

SummaryPlatelet aggregation was studied at 37° C in citrated whole human blood, using the Ultra Flo 100 Whole Blood Platelet Counter. Aggregation was measured as a fall in the number of single platelets following addition of an aggregating agent. At peak aggregation, the fall in the number of platelets induced by ADP (10 μM), collagen (1 μg/ml) or thrombin (0.2 U/ml) was about 90%. When blood was incubated with the prostacyclin- analogue ZK36374, the aggregation responses to ADP, collagen and thrombin were reduced with IC50’S = 0.5, 1.5 and 3 nM respectively and the corresponding IC100’S were: 1, 3 and 12 nM. When ZK36374 was added at peak aggregation, the number of single platelets increased significantly due to disaggregation of preformed platelet aggregates. It is concluded that the present technique represents a rapid, sensitive and more physiological approach for investigating the effects of pharmacological agents on platelet aggregation.
Investigation Including VIIIR: AG Multimeric Analysis of a Large Kindred with Type IIA von Willebrand’s Disease Showing a Dominant Inheritance and Similar Gene Expression in Four Generations
Authors: Hill F G H , Enayat M S , George A J 
Published: July 2018

SummaryForty-two members of a family have been studied with bleeding times, platelet aggregation, platelet retention in glass beads, measurement of factor VIII associated activity, 2-dimensional electrophoresis and multimeric analysis of factor VIII related antigen (VIIIR:AG). Eleven individuals with type IIA disease and one with asymptomatic and another with symptomatic type I disease have been studied. The degree of absence of high and intermediate multimers and the abnormal triplet configuration in the two remaining multimers was consistent in all affected family members. Multimeric analysis provides a unique and precise way of studying qualitative defects of VIIIR:AG and thereby the evaluation of gene expression in family studies.
Mepacrine Blockade of Arachidonate-lnduced Washed Platelet Aggregation: Relationship to Mepacrine Inhibition of Platelet Cyclooxygenase
Authors: Raz Amiram 
Published: July 2018

SummaryMepacrine, in addition to its established antilipolytic activity, was also found to inhibit the conversion of 14C-arachidonic acid to 14C-thromboxane B2 in human washed platelets. In the concentration range of 3.33-33 μM, mepacrine exerted a dose dependent inhibition of arachidonate conversion to thromboxane B2 in parallel to inhibition of arachidonate-induced platelet aggregation. Mepacrine inhibition of thromboxane formation was not accompanied by a concomitant increase in other cyclooxygenase products. Furthermore, mepacrine did not affect platelet transformation of added prostaglandin H2 to thromboxane A2 and other products. These results indicate that mepacrine inhibits the cyclooxygenase enzyme and not thromboxane synthase. In washed platelets, mepacrine inhibition of arachidonic acid conversion to thromboxane A2 appears to be a major factor in the overall inhibitory effect of the compound on the combined process of arachidonate release from cellular phospholipids and its conversion to proaggregatory products.
Fibrinolytic Activity and the Effects of Beta-Pyridylcarbinol (Ronicol) in Patients with Arteriosclerosis Obliterans
Authors: Grodzińska L , Basista M , Kȩdzior A , Korbut R , Kostka-Trąbka E , Gryglewski R 
Published: July 2018

SummaryTwenty-one patients with arteriosclerosis obliterans of lower extremities were treated with beta-pyridylcarbinol (Ronicol) for five weeks. The long-term therapy with beta-pyridylcarbinol did not influence platelet aggregability. Activation of the fibrinolytic system was observed. This fibrinolytic effect of Ronicol was abolished in patients treated with aspirin. In most cases a slight clinical improvement was seen, manifested by elongation of pain-free walking distance and increased blood flow in affected limbs. It is concluded that the therapeutic effect of Ronicol in humans may be partly mediated by the release of endogenous prostacyclin.
Non-Thrombogenicity of Clean Glass Revealed by Native Whole Blood Assay in Bead Columns
Authors: Bergeron J A , DiNovo J M , Razzano A F , Dodds W J 
Published: July 2018

SummaryThe previously described native whole blood assay for materials in solution or suspension has been adapted to materials in a bead column configuration. These experiments showed that the glass itself accounts for little or none of the high blood-reactivity observed with conventional glass bead columns. Columns composed solely of soft glass that was “cleaned” by heat treatment (500-595° C 18 hr, electric oven) were benign toward flowing native whole blood for all variables measured (platelet count and platelet-free plasma [C14]-serotonin content, platelet factor 3 and factor XII activities, and recalcification time) with the standard contact protocol. In addition, the effluent successfully maintained perfusion of the isolated kidney, a measure of the ability of platelets to support vascular integrity. Prolonged (30 min) normothermic contact with titrated whole blood increased the subsequent reactivity of initially clean glass toward whole blood albeit to a level much less than that of conventional glass bead columns.
Regulation of Thromboplastin Synthesis in Mouse Placental Cells In Vitro
Authors: Dalaker Knut , Prydz Hans 
Published: July 2018

SummaryMouse placental cells are probably constitutive producers of the thromboplastin apoprotein in vitro. The effect of cyclic AMP- elevating compounds on their expression of thromboplastin activity has been studied. Dibutyryl cyclic AMP, the phosphodiesterase inhibitor Ro 20-1724 and the adenyl cyclase stimulator forskolin all decrease the synthesis of thromboplastin. Prostaglandin E2 and the phosphodiesterase inhibitor butyl-methyl-xanthine have a biphasic dose dependent effect. A stimulation was observed at low concentrations, whereas higher doses decreased the synthesis of thromboplastin. Adrenaline had no effect. Combination of two compounds, each at maximally inhibiting concentration gave no significant additive inhibitory effect, showing that they probably act via the same pathway.
Homeopathic Treatment of Insomnia and Symptom Clusters Related to Cerebral Chemotoxicity in Oncology
Authors: Marechaud Natalia , Deana Nicolas , Wendling Julie , Bagot Jean-Lionel 
Published: July 2018

Background During chemotherapy, the correlation between insomnia and fatigue, anxiety, pain, depressed mood, and cognitive disorders makes these subjective complaints a ‘symptom cluster’ with common biological mechanisms. The theory of cerebral inflammation following the production of pro-inflammatory cytokines (high level of interleukin 1-β [IL1-β], IL6 and tumour necrosis factor-alpha) is currently the most generally accepted. Understanding these mechanisms should allow us to propose a chemoprotective homeopathic treatment of the nervous system.
Methods By retaining the inflammatory aetiology, we combined the rubrics ‘Inflammation of the brain’, ‘Inflammation of the meninges’, ‘Inflammation of the nerves’ with the symptom cluster: insomnia, fatigue, depressive state and memory disorders.
Results After repertorisation, we propose the following homeopathic protocol: Belladonna 15c, Phosphorus 15c, Cerebral cortex 4c and Nerves 4c, two pills of each medicine to be sucked together before breakfast, lunch and dinner, on each day of chemotherapy and for the following 2 days.
Conclusion This selected protocol, derived from a physiopathological knowledge of the symptoms, seems to be well suited to the prevention and treatment of post-chemotherapeutic cerebral inflammation. It is essential to start the homeopathic treatment before the chemotherapy session to anticipate the emergence of the ‘chemo-brain’ side effects. This proposed prevention protocol must be confirmed and quantified by randomised studies.
Cardiomyopathy Associated with Zinc Deficiency after Bariatric Surgery
Authors: Yahalom Malka , Koren Ofir , Rozner Ehud , Turgeman Yoav 
Published: July 2018

Noncompliance with vitamin and mineral supplement protocol after bariatric surgery may lead to true-elements deficiency. Among them, zinc and selenium deficiencies were closely related to cardiac complications, such as myocardial fibrosis, heart failure, and arrhythmias.We describe a 30-year-old female, 6 weeks after delivery and 5 years after bariatric surgery, who was admitted to the cardiology department because of dyspnea and clinical evidence of heart failure, as well as an echocardiogram that demonstrated reduced systolic left ventricular function. Standard antifailure regimen shows mild benefit. Zinc supplements added to treatment lead to significant clinical and echocardiographic improvement.