bluuebunny/crossref_metadata_2025_split huggingface dataset:
SERUM PREPARED AFTER DAILY INTAKE OF FISH INHIBITS PGI-2 PRODUCTION BUT NOT PLATELET INHIBITORY ACTIVITY OF ENDOTHELIAL CELLS
Authors: Simonsen T , Vårtun Å , Lyngmo V , Hornstra G , Nordøy A 
Published: August 2018

Healthy males were given dietary supplement of 100 g mackerelpasta for six weeks. Controlls were given meatpasta. Blood were collected before and at the end of the dietary intervention. Fatty acid composition of total phospholipids in serum and free fatty acids were measured by GLCHuman endothelium cells were grown in medium supplemented with 10% serum prepared from blood of the mackerel and controll groups. The medium was then examined for PGI-2 by RIA of 6-Keto-PGFIα , and for platelet aggregation inhibitory activity (PAIA) measured as inhibition of collagen induced platelet aggregation in platelet rich plasma.Fatty acids of total phospholipids and FFA of serum showed a significant decrease in the ratio of Arachidonic acid (20:4 n-6) to Eicosapentaenoic acid (20:5 n-3) in the mackerel group.The 6-Keto-PGFlα was significantly lower in the medium added serum from the mackerel group at the end of the period than at start. PAIA was not reduced by serum collected after fish consumption.We conclude that dietary fish contribute to factors in serum, inhibiting PGI-2 production in endothelial cells in vitro. However, the ability of endothelial cells to inhibit platelet aggregation was not affected
TRYPTOPHAN PYROLYSIS PRODUCTS FOUND IN COOKED FOODS INHIBIT HUMAN PLATELET AGGREGATION BY INHIBITING CYCLOOXYGENASE
Authors: Manabe S , Yanagisawa H , Ishikawa S , Kitagawa Y , Tohyama K , Abe S , Wada O 
Published: August 2018

Humans are exposed to numerous toxic compounds in foods. During the past decade, several carcinogenic heterocyclic amines have been reported to be present in the cooked foods. Recently, we reported that some of the carcinogenic heterocyclic amines isolated from foods were present in human plasma. In order to know the effects of the carcinogens isolated from foods on the cell function, we investigated the effects of the carcinogenic heterocyclic amines including Trp-P-1(3-amino-l,4-dimethyl-5H-pyrido❘4,3-b❘indole) and Trp-P-2(3-amino-1-methyl-5H-pyrido❘4,3-b❘indole) on human platelet aggregation and polymorphonuclear leukocyte aggregation. Only tryptophan pyrolysis products, Trp-P-1 and Trp-P-2, had potent inhibitory effects on human platelet aggregation when platelets were preincubated with the carcinogens for 15 min. Other carcinogenic heterocyclic amines such as glutamic acid pyrolysates (Glu-P-1 and Glu-P-2) and 3H-imidazo ❘4,5-f❘quinoline-2-amines(IQ and MelQ) did show no effect on platelet aggregation even at 100 μM.The autoradiogram demonstrated that Tryptophan pyrolysis products, Trp-P-1 and Trp-P-2, dose-dependently inhibited the formation of HHT,PGD2,PGE2 and TXB2 induced by sodium arachidonate in human platelets labeled with ❘ 14c❘ arachidonic acid. Moreover, Trp-P-1 and Trp-P-2 did not show significant effects on leukocyte aggregation induced by sodium arachidonate (0.75mM) even at lOOnM. It is concluded that Trp-P-1 and Trp-P-2 isolated from cooked foodstuffs have potent inhibitory effects on the cyclo-oxygenase pathway of the platelet. Therefore, human platelet function might be affected with daily foods containing tryptophan pyrolysis products in vivo.
TRANSIENT AGGREGATION RESISTANCE OF HUMAN PLATELET-RICH PLASMA; A NEGLECTED IN VITRO PHENOMENON WITH PHYSIOLOGICAL IMPACT
Authors: Hardeman M R , Vreeken J 
Published: August 2018

Due to instability in the first in vitro period, platelet-aggregometry is usually deliberately postponed until ca. 1 hour after venepuncture (VP) . At that time aggregability is fairly constant for 1 hour or more. Investigation of the period immediately followed VP, hcwever, revealed a high aggregation resistance - measured as the threshold ADP-concentration which the platelets just could resist before they aggregate maximally and irreversibly - which subsequently decreased exponentially with time. This “Transient Aggregation Resistance” (TAR) appeared to be superimposed on a stable, so called Baseline Aggregation Resistance (BAR) .The latter, measurable 60 min or more after VP, yields the “classical” threshold ADP-concentration.Parallel aggregation-studies started 6 min after VP, subsequent studies were performed every 4 min. pH was controlled during storage of PRP at rocmtenperature. Extrapolation of the TAR-curve to t=0 (i.e. time of VP) yields the maximal value:TARmax Coefficients of variation for TARmax-method: 9.4% (n=6) ; intraindividial 15% (n=15, over 3 yrs); interindividual: 51% (n=16,wide range).This TAR-phencmenon which is proven to be caused by a plasma-factor, can be influenced by dietary n-3 fattty acids and can be also inhibited by ASA,suggesting a prostanoid nature. The physiological significance of TAIfoax can be illustrated by the following findings:1. Patients with myocardial infarction, hyperlipoproteinemia, sickle cell anemia (i.e. diseases with a high risk for thrombotic complications) have low TARmax-values. 2.Individuals with “spontaneous platelet aggregation” in vitro,but asymptomatic, have positive TARmax-values. 3.There is a clear,reciproke age-dependency of TARmax
It is concluded that a technique is available measuring the effect of circulating,labile platelet-aggregation influencing plasma factor(s). Furthermore, using this technique,it was found that normal fresh plasma contains a labile aggregation-inhibiting factor which is several orders of magnitude more potent than other stabile factors either present in plasma or associated with platelets. This factor is probably of prostanoid nature and might have significance as a reflection of the antithrcmbotic potential of the endothelium.
EFFECTS OF SIN 1 ON PLATELET ACTIVATION INDUCED BY THROMBIN IN HUMAN PLATELETS
Authors: SIMON M F , CHAP H , DOUSTE-BLAZY L 
Published: August 2018

The mechanism of platelet activation is well known. The interaction of agonist such as thrombin, on specific membrane receptor induces phosphatidylinositol-specific phospholipase C activation, with a concomitant formation of two second messengers (from PIP2): inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). IP3 is able to induce a rapid discharge of Ca2+ from internal stores and Ca2+ influx through plasma membrane by unidentified Ca2+ channels linked to receptor activation. The increase of cytoplasmic free calcium concentration leads to the activation of the calcium calmodulin dependent myosine light chain kinase which phosphoryla-tes 20 kD proteins (myosine light chain). DAG is a potent activator of protein kinase C, which phosphorylates 40 kD proteins. These different pathways act in synergism.Sin 1 is a platelet aggregating inhibitor. This compound is an active metabolite of molsidomine, which activates platelet guany-late cyclase, inducing a rapid rise in cyclic GMP level. The precise role of cyclic GMP in platelet activation is not yet known. In order to study the mechanism of action of this drug, we tried to determine the effect of Sin 1 on the different steps described above. We measured Ca2+ fluxes and phospholipase C activation in thrombin (0,5 U/ml) stimulated platelets in the presence of different doses of Sin 1 (10™7-10™3M). Serotonin secretion was inhibited by 30 % with Sin 1 (10™4M-10™5m). A parallel inhibition of phospholipase C was detected by measurement of [32P)-PA level. Platelets loaded with Quin 2 and stimulated by thrombin showed a 70 % inhibition of external Ca2+ influx as soon as a concentration of 10™7M of Sin 1 was added. A study on platelet loaded with [45Ca2+) and Quin 2 confirmed these results. On the contrary, discharge of internal Ca2+ store seemed to be unaffected.In conclusion, the major effect of Sin 1 on platelet phospholipase C pathway is an inhibition of Ca2+ influx through plasma membrane. Some further experiments are necessary to shown whether this inhibition is correlated with cyclic GMP formation (the major effect of Sin 1) and try to establish a relation between this inhibition and that exerted on phospholipase C.Sin 1 was a generous gift of Hoechst.
INHIBITORY EFFECT OF SIN 1 ON PLATELET FUNCTION:POSSIBLE INTEREFRENCE WITH PHOSPHOLIPASE C AND FIBRINOGEN BINDING
Authors: Levy-Toledano D , Weill D , Maclouf J , Rendu F , Soria C 
Published: August 2018

The mode of action of SIN 1, the main metabolite of an antianginal drug (Molsidomine) was investigated in vitro on huma platelet functions. SIN 1 inhibited dose dependently platelet activation as reflected by aggregation and release of serotonin induced by arachidonic acid, prostaglandin endoperoxydes analogues (U 46619, U 44069), collagen, and ADP (figst and second wave). The maximal inhibition was reached at 10−5 M. The thromboxane (TX) synthesis was inconsis^antly impaired even at high concentrations of SIN 1 (104 M) suggesting a discrepancy between the inhibitory effect on platelet activation and TX formation. The main cofactor of ADP-stimulated aggregation is fibrinogen ; SIN 1 dose-dependently inhibited the fibrinogen binding to platelets thereby explaining it antiaggregatory properties.In order to further investigate the mechanism of action of this drug on platelet activation we tested SIN 1 on the thrombin-induced phg^phosinositide metabolism and protein phosphorylation on 32P-prelabelled isolated platelets.P-phosphatidate (PA) formation was greatly inhibited. Phosphorylations of the myosin light chain (P20) and of 43 kDa protein (P43) were also reduced. These effects were accompanied by an inhibition of serotoninrelease, TXB2 synthsei^, and platelet aggregation.SIN rl_would seem to act on early biochemical events and more especially at thelevel of the membrane phospholipase C.
EFFECT OF FUROSEMIDE ON PLATELET AGGREGATION AND ON ALPHA-ADRENOCEPTOR-DENSITY IN MAN.
Authors: Kribben A , Fritschka E , Sibold M , Fassbender M , Distler A , Philipp Th 
Published: August 2018

Furosemide (FUR) reduces the ∝2-adrenoceptor- (∝2-R) mediated pressor effect of norepinephrine. Since it has been shown that FUR reduces platelet aggregation ( AGG) we studied the effect of FUR on α2-R as well as that on the ∝2-R-medi ated epinephrine ( EPI)-induced AGG a) ex vivo and b) in vitro. For comparison the effect of FUR on ADP-induced AGG was also studied. Methods: a) 8 normotensive men received FUR (30 mg b. i.d. ) for 3 weeks. EPI- (1 μmol/1) and ADP- (1 μmol/1) induced platelet AGG were measured before as well as after 3 weeks of FUR application with a semiautomatic device ( APACT) . Platelet ∝2-R-density was measured by 3H-yohimbine-binding and the fraction of high-affinity binding-sites was measured by competi tion of 3H-yohimbine with EPI. b) Platelet-rich plasma was incubated with FUR (1 mmol/1) for 10 min at 37 °C and AGG was measured (n=7) as described. Results: a) FUR decreased ∝2-R-densi ty from 293± 28 to 251±; 21 fmol/mg protein (p< 0.01) and high affinity binding sites from 64± 3 to 55± 5 % (p< 0.01). FUR inhibited ADP-induced AGG ex vivo while EPI-induced AGG did not change (table). b) In vitro FUR inhibited total ADP-induced AGG from 7 4 ± 4 to 45± 8 % (p< 0. 01) while again EPI-induced AGG did not change.Conclusions: The results suggest separate effects of FUR on α2 R-density and on platelet AGG. Although FUR decreased < r2-R, EPI-induced platelet AGG remained unchanged. Since FUR inhibited ADP-induced AGG ex vivo as well as in vitro FUR may interfere directly with the mechanism of ADP-induced platelet AGG.
PULMONARY MICROEMBOLISATION IN SURGICAL SHOCK: THE EFFECT OF CYCLO-OXYGENASE INHIBITION
Authors: Backhouse C M , Meek A C , Poskitt K R , McCollum C N 
Published: August 2018

Thromboxane release from platelet microemboli during major arterial surgery may mediate depression of cardio-pulmonary function. The effect of cyclo-oxygenase inhibition by aspirin has been studied in a porcine model of aortic surgery.Following autologous platelet labelling with 111-lndium, 24 pigs (20-25kg) were randomised to low dose (LD) aspirin (0.5mg/kg), high dose (HD) aspirin (10mg/kg) or placebo.Arterial and Swann Ganz catheters were inserted prior to surgery consisting of midline laparotomy, small bowel extériorisation, 1.5 hours of aortic clamping and 1 hour shock before resuscitation. On induction, during shock and at 3 days, platelet and leucocyte counts, lung platelet uptake (LPU), venous aggregates by screen filtration (SFP), mean arterial pressure (BP), cardiac output (CO), pulmonary shunt (PS) and alveolar-arterial pO2 difference (A-adO2) were measured.During shock following aortic declamping aspirin preserved blood pressure by increasing vascular resistance rather than CO. Venous aggregates by SFP tended to be lower on aspirin with significantly reduced LPU, subsequent pulmonary shunting and A-adO2. The improvement in PS but not A-adO2 remained significant at 3 days (p<0.05).Cyclo-oxygenase inhibition improved pulmonary function during surgical shock either by inhibiting platelet microemboli or by a direct effect on pulmonary arteriovenous shunts.
PREVENTION OF SYSTEMIC THROMBO-EMBOLISM IN PATIENTS WITH ATHEROSCLEROTIC INTERMITTENT CLAUDICATION
Authors: Boissel J P , Peyrieux J C , Destors J M , Lievre M , Moleur P 
Published: August 2018

Ticlopidine (TI), an anti-aggregating agent which inhibits the ADP-pathway has been tested in patients with intermittent claudication (IC) in 11 randomized clinical trials (RTCs).As expected, a significant reduction of cardio-vascular events (CVE) due to systemic thrombo-embolism was observed in the 2 larger. Reduction in the number of CVE due to systemic thromboembolism in any arterial bed was observed. This prompted us to confirm the hypothesis that TI was beneficial in preventing systemic thrombo-embolism in patients with IC. Four RCTs from the 11 were blindly selected on the basis on pre-set selection criteria : placebo controlled, more than 1 month duration, , less than 5 % lost-to-follow-up (index of quality), parallel groups, proven atherosclerotic disease. Meta-analysis was performed with 5 statistical methods which gave consistent findings : as compared to 311 patients on placebo, the 301 patients on TI have had a 66 % reduction in the number of CVE during the 6 months of follow-up (9.0 % to 3 % , p = 0.002). Walking distance, a secondary objective of meta-analysis, doubled in 42 % of the patients on TI as against 27 % (p = 0.0005).It was concluded that TI 250 mg b.i.d. prevents CVE in patients with atherosclerotic IC.
GEMFIBROZIL HAS ANTI-PLATELET EFFECTS IN PATIENTS WITH HYPERCHOLESTEROLAEMIA DURING PHYSICAL STRESS
Authors: Laustiola K , Lassila R , Koskinen P , Manninen V 
Published: August 2018

Earlier studies indicate an increased platelet reactivity in patients with hypercholesterolaemia. Physical and mental stress have also been reported to cause increased reactivity. The present study was undertaken to evaluate the effect of gemfibrozil (G) a new lipid lowering drug on platelet reactivity during physical stress. Ten otherwise healthy male subjects with serum cholesterol levels above 7 mmol/l were involved in a double-blind study. It consisted of two treatment periods of 8 weeks during which the patients were given either G (600 mg b.i.d.) or placebo (PI) and an 8 weeks wash-out period before the cross-over. At the end of the treatment periods an exercise test was carried out and platelet reactivity tested. Adrenaline, ADP and collagen were used to induce aggregation and 5-HT and T×B2 release measured. Plasma beta-TG and fibrinogen were also determined.The treshold concentration of adrenaline necessary to evoke secondary aggregation was increased in 8/10 patients during exercise after G treatment and in 2/10 after PI. When the lowest ADP concentration to cause secondary aggregation (2-4 uM) was used there was a significant decrease in the 5-HT (− 44%) and T×B2 (− 48%) secretion and a significant decrease in the area under the aggregation curve (− 28%). A decrease in 5-HT secretion was also seen after G treatment when a fixed ADP concentration of 10 uM was used. During collagen stimulation no changes were seen between the two groups. Beta-TG remained unchanged irrespective of treatment and fibrinogen showed a modest increase during exercise in both treatment groups. These results indicate a new anti-platelet effect of gemfibrozil which might be of importance in prevention of acute thrombotic events in hypercho1estero1aemic patients.
PLATELET TXA2 SYNTHETASE INHIBITION AND TXA2/PROSTAGLANDIN ENDOPEROXIDE RECEPTOR BLOCKADE COMBINED IN ONE MOLECULE (R 68070)
Authors: De Clerck F , Van de Wiele R , Xhonneux B , Van Gorp L , Somers Y , Loots W , Beetens J , Van Wauwe J , Freyne E , Janssen P A J 
Published: August 2018

F 68070, an oxime-alkane carboxylic acid derivative (Janssen Pharmaceutica), is a potent inhibitor of thromboxane A2 (TXA2) synthetase activity (IC50 in vitro against thrombin-stimulated human platelets in plasma : R 68070 : 2.9 x 10-8 M; CGS 13080 : 6 x 10-8 M; OKY-1581 : 8.2 x 10-8 M; dazmegrel : 2.6 x 10-8 M; dazoxiben : 2.3 x 10-8 M).The compound specifically inhibits platelet TXA2 synthetase activity (14C-arachidonic acid metabolism by washed human platelets) without effect on the cyclo-oxygenase, lipoxygenase (platelets, RBL cells) or prostacyclin synthetase activities (rat aortic rings).The inhibitory effect of R 68070 against human platelet TXA2 synthetase activity increases upon prolongation of the contact time (ICsg at 0.5 min of contact : 5.2 x 10-7 M; at 5 min : 8.3 x 10-8 M; at 30 min : 2.5 x 10-8 M) and is reversed by washing of the platelets.In vivo, the compound has a comparatively strong inhibitory effect on platelet TXA2 synthetase activity after oral administration to rats (ED50 - 2 h : R 68070 0.013 mg/kg; CGS-13080 : 0.8 mg/kg; OKY-1581 : 0.61 mg/kg; dazmegrel : 1 mg/kg; dazoxiben : 4.1 mg/kg) and a protracted duration of action in rats and dogs (inhibition 8 h after 1.25 mg/kg orally > 80 %).In vitro, R 68070 inhibits the aggregation of human platelets in plasma stimulated with collagen (IC50 : 4 x 10-6 M), but also with U 46619 (IC50 : 3.8 x 10-6 M) without affecting the primary aggregation reaction elicited by ADP, 5-HT or adrenaline. The compound thus also produces platelet TXA2/prostaglandin endoperoxide receptor blockade.In rats and in dogs R 68070 (1.25 mg/kg I.V.) potently prevents thrombus formation in carotid and coronary arteries damaged by electrical stimulation.The combination of platelet TXA2 synthetase inhibition with TXA2/prostaglandin endoperoxide blockade in one molecule thus might offer an improved anti-thrombotic effectiveness.
TREATMENT OF ADVANCED STAGES OF PERIPHERAL OBLITERATIVE DISEASE WITH THE THROMBOXANE RECEPTOR ANTAGONIST BM 13.177: A PLACEBOCONTROLLED DOUBLE BLIND STUDY
Authors: Hossmann V , Schäfer H J , Auel H , Etti H 
Published: August 2018

Twenty patients (67.2 ± 12.3 yrs; aged 39-86 yrs, 10 males, 10 females) with stage IV of peripheral obliterative arterial disease received at random either a) BM 13.177, a thromboxane receptor antagonist, at a dose of 6 g/24 hrs for 7 days i.v., followed by oral treatment of 6.4 g/day in four doses for 2 weeks and a subsequent placebo week, or b) placebo alone with the same protocol. The clinical course was followed by measurement of blood pressure (by Riva-Rocci on the left brachial artery and by Doppler of the ankle artries), blood flow at restand after 3 min of tourniquet ischemia (by venous occlusion plethysmography), TcpCf2 at the wrist of the affected limb, and by subjective estimation of pain with visual analog scale before, at the end of the infusion period, as well as on day 7 and 14 of oral treatment, and 7 days after treatment while patients of both groups were on placebo. In addition spontaneous platelet aggregation by PAT III, induced platelet aggregation in whole blood by collagen and in PRP by ADP at different doses on the same days were measured on the same days as described above.Results: BM 13.177 completely inhibited aggregation in whole blood induced by collagen 0.3 (ig/ml, however one week after treatment a rebound phenomenon was observed with 16.0 ± 3.8 OHM compared to pretreatment value of 11.0 ± 3.8 OHM (p < 0.01). At a higher dose of 1.2 |ig/ml the same inhibiting effect on platelet aggregation was observed. Spontaneous platelet aggregation as measured by PAT III was evident in only 2/10 pat. pre-treatment, was abolished in all patients on i.v. BM 13.177, returned in 1/10 pat. during oral treatment, but in 4/10 pat. on day 7 after treatment, while being on placebo, again indicating a rebound phenomenon (p < 0.03) ADP induced platelet aggregation was not significantly affected by BM 13.177. In the placebo group, too, no significant differences were observable between the different treatment regimens. Clinical data did not show any significant alteration in either verum or placebo group during the six week period, indicating no benificial effect of thromboxane receptor antagonists in advanced stages of peripheral obliterative arterial disease, although platelet inhibiting effects were clearly demonstable.
PLATELET FUNCTION AND LIPOPROTEINS IN PATIENTS WITH HYPOTHYROIDISM
Authors: Fujii S , Kariya T 
Published: August 2018

Platelet function and serum lipoprotein levels were studied in ten patients (two males and eight females) with hypothyroidism. Platelet aggregation and ATP release were determined by Lumi-aggregometer using ADP , collagen and epinephrine as stimulants. Platelet factor 4 (PF4) and thromboxane B2 (TXB2) were determined by radioimmunoassay. High density lipoproteincholesterol (HDL-C) was determined by heparin-manga-nese method. HDL subfractions were separated by gradient gel electrophoresis (PAA 4/30). Apolipopro-teins were measured by single radial immunodiffusion. Platelet aggregation increased in those patients at stimulating by epinephrine. ATP release also increased at stimulating by epinephrine. PF4 increased at stimulating by epinephrine. TXB2 increased at stimu-lating--by ADP or epinephrine significantly (p<0.05), respectively. Platelet aggregation was not correlated with thyroid hormones or total cholesterol levels.But it had a positive correlation tendency with HDL-C or HDL2-C and a negative one with HDL3-C levels.These results suggested some relationships between platelet function and HDL metabolism in patients with hypothyroidism.
REDUCED THRESHOLD FOR COLLAGEN INDUCED PLATELET AGGREGATION IN WHOLE BLOOD FROM PATIENTS WITH SYSTEMIC SCLEROSIS
Authors: Goodfield M J D , Orchard M A , Rowell N R 
Published: August 2018

Systemic sclerosis is a multi-system disorder characterised by skin lesions and narrowing of arterioles with reduction in blood supply to many organs. Previous reports have suggested that platelet aggregation is abnormal and could contribute to the pathogenesis. Platelet aggregation in whole blood was investigated in 10 patients with systemic sclerosis and 9 age matched controls. Subjects rested for 30 minutes before blood samples were taken without stasis, via a 19G needle into 3.8% trisodium citrate anti-coagulant. 0.5ml of blood was transferred to cuvettes, and equilibrated gt 22°C for 30 minutes, before being stirred at 750 r.p.m. at 37 C. Aggregation was induced by collagen (0.01 ug/1 to 1.0 ug/1), adrenaline (0,1,0.5 and 1.0 ug/1) and ADP (0.1,0.25 and 2.5 ug/1). Aliquots for counting free platelets were taken and assessed using the Ultraflow 100 particle counter.Platelet aggregation was significantly increased in patients with systemic sclerosis at all doses of collagen (p<0.01), and the mean dose giving 50% aggregation was significantly lower in the disease group (0.026+/-0.06mg/l) than in the controls (0.23+/-0.06mg/l, p<0.01). Aggregation was not significantly different with the other aggregating agents.Increased sensitivity of platelets to aggregation by collagen in whole blood may be of importance in the pathogenesis of the vascular and fibrotic lesions of this disease