bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence Of Cod Liver Oil And Corn Oil On Platelets And Vessel Wall In Man
Authors: Nordøy A , Brox J H , Killie J E 
Published: July 2018

Two groups of 10 healthy males were given dietary daily supplement of 25 ml cod liver oil (CLO) or corn oil (CO) for periods of 6 weeks in a blind crossover study. Between the two periods and after the last period there were 3 weeks and 4 months, respectively, without supplement. Plasma lipids, platelet lipids, prostaglandins and platelet functions were examined. Pieces of superficial forearm veins were excised after the two dietary periods and assayed for prostacyclins by bioassay and by GLC-MS.Collagen-induced platelet aggregation and TXB2 formation were significantly reduced in both the CLO and CO group. CLO was more potent than CO. The MDA production was not affected.In the total fatty acids of plasma and in the main platelet phospholipid fractions, CLO increased the amounts of fatty acids of the w-3 familiy whereas the w-6 fatty acids decreased. CO only moderately influenced the composition of these lipids. Cholesterol and triglycerides levels in serum were not affected. The vein biopsies showed no significant production of prostacyclin-like material in any of the dietary groups. In summary small amounts of CLO added to the diet gives significant changes in platelet lipids and reduced platelet aggregation and TXB2 production.
Kinetics Of Anticoagulant And Lipolytic Activity And Radiolabel After Intravenous Administration Of 35S-Heparin Fractions Of Different Molecular Weight
Authors: de Swart C A M , Sixma J J , Nijmeijer A , Holmer E , Andersson L O , Verschoor L 
Published: July 2018

Heparin fractions were prepared from commercial pig mucosal by affinity chromatography on antithrombin III, 35S- radiolabelling and gelchromatography. Three fractions were obtained with moLwt.of < 6.000, 6 - 35.000 and > 35.000 daltons. They were administered intravenous as a bolus into human volunteers. The anticoagulant activity was measured with the APTT and Xa inactivation, using standard curves. The lipolytic activity was as^ed as hepatic triglyceride lipase activity, and as extra-hepatic lipoprotein lipase activity by hydrolysis of tritiated triolein. Radioactivity data were corrected for degraded heparin fragments uncomplexed to protein by subtracting radiolabel with a mol.wt. < 10.000 passing through a filter.Low mol.wt. fractions induced neither of both lipase activity and had no effect on the APTT. Anti Xa activity and radioactivity disappeared in parallel with slightly concave curves in semilogarthmic plots. Heparin of intermediate and high mol.wt. induced both lipolytic and both anticoagulant activities. The elimination of radioactivity, hepatic triglyceride lipase activity and anti-Xa activity occurred parallel according to a convex curve in semilogarthmic plots. The extra-hepatic lipoprotein lipase activity disappeared following a slightly concave curve.These data indicate that relatively large heparin molecules are required for lipolytic and APTT activity. Hepatic triglyceride lipase activity might be present complexed to heparin, comparable to the antithrombin III-heparin complex. The elimination of anti Xa activity and hepatic triglyceride lipase activity might be determined by the heparin part of the complexes.
Anti-Platelet Therapy In Diabetic Patients With Retinopathy
Authors: Tindall H , Paton R C , McNicol G P 
Published: July 2018

The effect of a combination of aspirin at 2 dosage levels (330mg/day and 1gm/day) and dipyridamole 225mg/day on platelet lifespan and some haemostatic variables was investigated in 30 insulin-dependent diabetic patients with retinopathy. Platelet regeneration time using a modification of the Stuart technique was measured in 40 normal controls and all patients before therapy commenced. Treatment was then allocated in a double-blind manner using a Latin square design and haemostatic variables were measured at the end of each treatment period. Platelet survival by the standard Na51Cr radioisotopic technique was performed twice during treatment. The post-aspirin platelet regeneration time in normal subjects was 9.98 ± 0.22 days (mean ± SEM) and in diabetic patients was significantly (p<0.001) shorter at 7.16 ± 0.18 days. A similar result of 7.37 ± 0.20 days was obtained in the diabetic patients by Na51cr platelet survival (analysed by γ function). The aspirin/dipyridamole combination (330mg/75mg tds) resulted in significant (p<0.001) lengthening of platelet survival to 8.46 ± 0.13 days (as estimated by Na51Cr method). The postaspirin platelet regeneration time was significantly prolonged (p<0.01) in this group (9.75 ± 0.52 days).Although the lower dose aspirin - dipyridamole combination (110mg/75mg tds) caused a prolongation in regeneration time (8.29 ± 0.45 days) this time was not significantly different from placebo, and was significantly (p<0.01) shorter than the time taken on the higher aspirin dosage. No significant changes in haemostatic function were observed. These results support the hypothesis that platelets may be involved in the microvascular complications of diabetes mellitus. Treatment with Igm aspirin +225mg dipyridamole/day significantly lengthened platelet survival suggesting that long term trials at this aspirin dosage level are justified.
Human Platelet Age Correlates With Buoyant Density, But Not With Size
Authors: Mezzano D , Catalano P , Hwang K , Aster R H 
Published: July 2018

Following infusion of 51Cr-labelled autologous platelets into normal subjects, high density (HD) and low density (LD) platelet cohorts were isolated by centrifugation in isosmotic arabino- galactan (Stractan) . Specific radioactivity (SA) of LD platelets declined rapidly post-infusion (T1/2 =1.8 days) but SA of HD platelets remained constant or increased over a 3-4 day period and gradually declined for 6-7 days thereafter. These differences were exaggerated when platelet cohorts enriched in LD or HD cells by slow centrifugation in high density albumin were labelled and transfused. Mean survival of a platelet cohort enriched with HD cells was significantly (p < .02) shorter (7.73 days) than that of a cohort enriched with LD cells (9.33 days). In normal subjects treated with aspirin, capacity for thromboxane synthesis was regained more rapidly (p < .05) in LD than in HD platelets. HD and LD platelets differed only slightly in mean volume (HD platelets = 7.57 μ3, LD platelets = 6.87 μ3, 0.05 < p < 0.01).These findings imply that under normal conditions in man, newly formed platelets are less dense on the average than total platelets and become more dense as they age in the circulation. Thus, SA of LD platelets declines rapidly as these platelets move into a more dense compartment and are replaced by newly formed, unlabelled platelets; SA of HD platelets remains constant or increases as labelled platelets enter this compartment in numbers equal to or greater than the number leaving it at the end of their life span. The similarity in mean volumes of LD and HD platelets suggests that platelet size is unrelated to platelet age under normal conditions
Effect Of Age And Operations On Platelet Serotontin (5Ht) And Platelet Volume
Authors: Shuttleworth R D , O’Brien J R 
Published: July 2018

To pursue the concept that “activated” platelets (plats) in vivo might be deficient in 5HT (as well as being deficient in PF4 - Abstract submitted), we collected citrated blood from 39 “healthy” controls aged 15–50 yrs and from 14 patients (25–75 yrs), 2–8 days after major surgery. The plat 5HT, the 5HT uptake and plasma 5-hydroxyindoles (PPP 5HTs) were measured fluorometrically and the mean plat, volume (MFV) was measured using a Coulter S plus counter.In health (n = 39) with increasing age the MPV (correlation: r = 0.45, p<0.01), the plat 5HT (r = 0.62, p<0.001) and 5HT uptake (r = 0.45, p<0.0l) all decreased while the PPP 5HIs increased (r = 0.71, p<,0.00l). The plat 5HT was also positively correlated with 5HT uptake (r = 0.42, p<0.01) and with MPV (r = 0.45, p<0.01) and negatively with PPP 5HIs (r = 0.43, p<0.01).After operations (n = 14) irrespective of age the plat 5HT was lower than the controls' (p<.0.001) and the MPV and 5HT uptake were low, but not significantly so. The plat, count was significantly lower than the controls (p<0.001). Again the plat 5HT correlated with MPV and 5ê uptake.Differential centrifugation of normal PRP into platelet sub-populations with differing MPVs confirmed the correlation between MPV and plat 5HT.It is concluded that both operations and increasing age are associated with the appearance of small relatively empty plats “exhausted” of 5HT which cannot take up 5HT. Have these plats been partially activated and undergone release with a subsequent decrease in volume? Alternatively, are large platelets relatively full of 5HT removed from the circulation, or not produced? (These findings support and extend the findings of Shuttleworth et al, Blood March 1981: in press).
Factor VIII In Vessel Wall Influences Platelet Interaction With Subendothelium
Authors: Turitto V , Weiss H , Sussman I , Zimmerman T 
Published: July 2018

Immunological techniques have demonstrated the presence of factor VIII:AGN in both the endothelium and deeper layers of vessel wall. Since plasma factor VIII:VWF is known to mediate platelet adhesion to subendothelium, we investigated the influence of vessel wall factor VIII on platelet interaction with the vascular surface. Everted vessel segments (14 mm in length) from rabbit aorta, denuded of their endothelial lining by a balloon catheter technique, were incubated for 1 hr at 37°C in 1ml of either 0.2M Tris buffer (B), normal goat serum diluted 1/5 with B or goat serum containing an antibody to rabbit factor VIII:VWF diluted 1/5, 1/20 or 1/100 with B. The segments were exposed in an annular chamber to citrated huipn blood, flowing at 40ml/min (wall shear rate of 2600 sec-1 ) for 5 min. The percentage of subendothelial surface covered with adherent platelets (A) or platelet thrombi greater than 5μm in height (T) were determined morphometrically. Values of A were significantly decreased on vessels treated with serum containing antibody diluted 1/5 (A=30.4±5.9, p<0.0l) or 1/20 (A=31.7±5.0, p<0.0l) but not 1/100 (A=37.7±7.4, p=NS) compared to vessels incubated with either B(A=53.8±5.l) or normal serum (A=58.0±7.9). Thrombus formation (T) was not significantly decreased by treatment of the vessel wall with serum containing antibody. Similar results were obtained when the IgG fractions of serum were used instead of whole serum.Thus, it appears that factor VIII:AGN in the vessel wall may be important in the initial platelet events involved in hemostasis. The relative importance of vessel wall factor VIII versus that present in the plasma requires further study.
Effect Of An Arginine-Modifying Reagent On The Responses Of Rabbit Platelets To Agonists
Authors: Anderson E R , Foulks J G 
Published: July 2018

Arginyl groups participate at the active binding site of several enzymes with anionic substrates, particularly adenine nucleotides. Hence, such groups are reasonable candidates for the cationic groups at membrane surfaces which contribute to the binding of the phosphate groups of ADP to platelet receptors. To investigate the importance of surface arginyl residues to the aggregation responses of platelets, an impermeant analogue of the arginine-modifying reagent phenylglyoxal, p-sulfonyl phenylglyoxal (PSPG), was synthesized. Rabbit platelets were exposed to this reagent during an extra washing step inserted in the usual resuspension procedure. Pretreatment of resuspended rabbit platelets with 2-15 mM PSPG resulted in total inhibition of aggregation responses to ADP, and to 5-HT, and a concentration-dependent impairment of the preceding shape change responses. Aggregation responses to thrombin (which preferentially cleaves peptide bonds involving arginine and lysine) were inhibited in a concentration dependent manner. To determine whether the inhibition of ADP-induced aggregation by PSPG is non-specific or is a selective effect due to modification of arginyl groups at the active binding site for ADP, resuspended platelets were pretreated with inactive analogues of ADP during treatment with PSPG. The presence of either ATP or β,γ-methylene ATP during pretreatment with PSPG provided significant or complete protection against the inhibitory effects of PSPG on ADP responses, and also partial protection of the responses of platelets to thrombin. Neither of these agents was effective in protecting the ability of platelets to respond to 5-HT.These experiments indicate that intact arginine residues at the surface of rabbit platelets are necessary for their responsiveness to ADP, thrombin and 5-HT, and that these residues form part of the ADP receptor.
Human Platelet Aggregation In Response To Multiple Agonists In Plasma Anticoagulated With Heparin
Authors: Culliver H A , Ardlie N G 
Published: July 2018

The lowest concentrations at which epinephrine and vasopressin have been reported to interact positively in causing platelet aggregation in vitro are at least two orders of magnitude greater than the physiological concentrations of these hormones in blood. The aim of this study was to examine the interaction between several agonists of human platelet aggregation. The aggregating agents used were adenosine diphosphate (ADP), epinephrine, norepinephrine, 5-hydroxytryptamine and vasopressin. Platelet-rich plasma (PRP) was prepared from blood anticoagulated with minimal concentrations of heparin in an attempt to more closely reflect the in vivo situation.Aggregation caused by ADP was potentiated by epinephrine at a concentration exceeding the level obtained in circulating blood. When a third agonist (vasopressin) was used in combination with ADP and epinephrine, aggregation was enhanced at concentrations of vasopressin and epinephrine obtained in blood. When used as a fourth agonist norepinephrine and 5-hydroxytryptamine potentiated aggregation at physiological concentrations. The response to multiple agonists was greater in heparinized PRP than citrated PRP. Hirudin decreased the extent of aggregation in heparinized PRP caused by multiple agonists suggesting that thrombin may be involved.Since the concentrations of combined agonists required to induce in vitro platelet aggregation can be obtained in circulating blood these findings may explain why platelet activation occurs in certain pathological states.
Incidence Of Venous Thrombosis, Increased Platelet Release Reaction And Thromboxane Synthesis Following Tourniquet Ischaemia
Authors: Zahavi J , Price A J , Westwick J , Kakkar V V 
Published: July 2018

Deep vein thrombosis (DVT) was established by ascending phlebography in 121 meniscectomy (M) (mean age 34 years) and 27 total knee replacement (TKR) (mean age 62.9 years) patients, both procedures performed under ischaemia (by inflating a pneumatic tourniquet to 500 mm Hg). In 27 of the M, 10 TKR and another 10 patients undergoing herniorrhaphy (H) and served as controls plasma β-thromboglobu- lin (βTG) was measured by radioimmunoassay and in 22 M and 10 TKR patients plasma thromboxane B2 (TxB2) was also determined. The incidence of DVT was 29% in the M patients. It increased significantly with age reaching a level of 50% at 60 years. In the TKR group 49% developed DVT. There was also a positive correlation between the severity of of DVT and patient age in both groups. The mean plasma βTG and TxB2, rose sharply (p<0.001) 5 min after the release of the tourniquet and were positively correlated to each other. The high level returned to the pre-operative level after 48 hours. In the H patients βTG did not alter significantly pos toperativelyThe high incidence of DVT in the relatively young patients who underwent M (minor surgical trauma similar to that of H) reaching the incidence of TKR patients (major surgical trauma) at 60 years, suggests that tourniquet ischaemia may be an important factor in the development of venous thrombosis in these patients. The increased in-vivo platelet activation and thromboxane synthesis, indicated by the increased plasma βTG and TxB2 levels, which was not detected in the H patients, suggests that platelets may play an important role in the initiation of the DVT in tourniquet ischaemia patients.
Shortlasting Effects Of Acetylsalicylic Acid (ASA) And Dipyridamole On Spontaneous And Tissue Extract Induced Platelet Stimulation And On Platelet Retention
Authors: Breddin K , Kirchmaier C M , Trautmann K O , Sehrbrock M , Reinfelder G 
Published: July 2018

30 healthy individuals received single doses of 250,500 or 1000 mg ASA (Aspirin), 10 persons took 750 mg of an ASA preparation with retarded intestinal absorption.24 volunteers received 75 or 150 mg dipyridamole alone or together with 500 mg ASA.Spontaneous and tissue extract induced platelet stimulation were investigated using interference contrast microscopy. Collagen induced aggregation (1µg/mlPRP) was measured 30 - 45 minutes after blood sampling. Platelet retention was investigated using a modified Hellem test.Platelet stimulation and retention were inhibited for 8 - 10 hours after the intake of ASA. The higher doses had a more pronounced and longer lasting effect. The effect of 750 mg of the slowly absorbed form of ASA lasted longer than that of 1000 mg Aspirin. Platelet retention was inhibited in a similar way as platelet stimulation. No correlation between the long lasting inhibition of platelet aggregation and the shortlasting effects of ASA on platelet retention and platelet stimulation was found.It has to be established to which extent the shortlasting effects of ASA and Dipyridamole are essential for the antithrombotic effect of both drugs. If these effects are contributing to the antithrombotic effect of ASA, differences in the results of similar clinical trials as the AMIS and PARIS studies on patients with recent myocardial infarction could be explained by different dose regimens in these studies, e.g.the use of 2 × 500 against 3 × 330 mg ASA.
Lu 23051, A New Potent Inhibitor Of Platelet Aggregation
Authors: Lehmann H D , Gries J , Lenke D 
Published: July 2018

6- [p-(2-(Chiorpropionylamino)phenyl] -4.5-dihydro-5-methyl-3(2H)-pyridazinone, LU 23051, is primarily characterized by its strong inhibition of platelet aggregation under in vitro and in vivo conditions. In vitro there is a concentration-dependent inhibition of ADP and collagen induced aggregation in platelet rich plasma of man, rat and dog. The inhibitory concentration EC 33 % is 0.0010-0.030 mg/1 (man: ADP-0.030, col 1.-0.013 mg/l) depending on species and type of aggregation. When administered orally in ex vivo experiments on rats and dogs the substance is found to have a dose-dependent antiaggregatory effect in the range from 0.1-3.16 mg/kg. The ED 33 % is 0.27-0.63 mg/kg.-In addition after oral administration the substance has a good inhibitory effect in models being based on intravascular platelet aggregation. Thus, a dose of 1 mg/kg inhibits laser-induced aggregation in mesenteric venules of rats. Mortality after i.v. injection of collagen in mice is reduced by 50 % after a dose of 0.02 mg/kg. A dose of 0.039 mg/kg prolongs the bleeding time of rats by 50 %. The aggregation-inhibiting action is of long duration (0.1 mg/kg p.o.∼24 h). The substance does not interfere with clotting.Besides its effect on platelet aggregation LU 23051 acts as vasodilatator as well. Dilatation of coronary vessels by 100 % is seen in isolated guinea-pig hearts at a concentration of 0.1 mg/l. In spontaneously hypertensive rats the substance has an anti hypertensive effect. The ED 20 % is 0.36 mg/kg p.o.The combination of antiaggregatory and vasodilatatory effects opens up interesting aspects with respect to the pharmacotherapeutic use of the new substance
Effect Of Solvents On Indium-111 Oxine Transport In Human Platelets And On Platelet Function In Vitro
Authors: Tsukada T 
Published: July 2018

Mechanism of Indium-111 oxine(In) transport in human platelets in buffered saline and the effect of In-labeling on platelet function were studied using In dissolved in 25% of ethanol in saline (In-ES) or 0.01% of polysorbate 80 in HEPES buffer(In-PH). Increase in temperature up to 37° C progressively enhanced the transport of In-ES, while transport of In-PH reached to plateau at 15°C. A states of equilibrium was not reached during 2 hr incubation at 22°C in In-ES. Uptake of In-PH reached to plateau after only 15 min of incubation. Distribution of In taken up by platelets in InES was 57% in cytosol and 27% in stroma, while in In-PH 69% in stroma and 22% in cytosol. 88% of In in cytosol was bound to lipids(46% in cholesterol and 27% in PS+PI). 82% of In in stroma was found in PS+PI fraction.The fact that the ratio of free In between the platelet water space and the outside medium after 30 min of incubation at up to 0.1 uM of In exceeded unity, suggests satura- , ble component of In transport prevails at this concentration in In-ES and In-PH. Kinetic constant could be calculated, Kt= 2nM, Vmax= 2.5 pmol/min/ml in In-ES, and Kt= InM, Vmax=0.7 pmol/min/ml in In-PH.Elution of In from radiolableled platelets in autologous plasma incubated at 37°C for 5 hr was less than 10% in the case of In-ES and 56% in the case of In-PH. Less than 3% of labeled-In was eluated from platelets in collagen-induced aggregation and 4-7% of In was eluated in thrombin-induced aggregation.Although 0.3% of ethanol and/or 6nM of oxine have no inhibitory effect of platelet aggregation, collagen-induced aggregation and release reaction of In-labeled platelet was impaired. 0.003% of polysorbate 80 itself abolished completely the aggregability of platelets by collagen or thrombin.It is concluded In-PH is unsuitable for platelet labeling. In-111 oxine also seems to have problems which Cr-51 has, i.e. inhomogenous distribution of In in a platelet population, elution of In from labeled platelets in circulation.
Fibrinogen Induces Changes In Platelet Membrane Potential
Authors: Vainer H , Caprani A 
Published: July 2018

Changes in platelet membrane potential (MP) reflecting ion transmembrane transport accompany the platelet activation by various stimuli. We have studied the platelet MP and the effect of fibrinogen on its expression, using an electro-chemical method. The MP determination is based on the evaluation of the transmembrane partition coefficient (PC) (Ci/Ce) of an electroactive tracer, such as the ferro- cyanid anion. Washed human platelets are incubated with the tracer solution ; the amount of tracer in the supernatant (Ce) and in the acellular lysate of SDS-treated platelet pellet (Ci) is measured as the diffusion limiting current corresponding to the tracer oxidation at the surface of a rotating disc electrode. The kinetics for the PC evaluation have been studied in order to standardize the experimental conditions which allow to express the MP by the Nernst equation : Vi-Ve = RT/4F. Log Ci/Ce.The mean value ± SD (N = 9) of the platelet MP in saline is -5.5 ± 0.5 mV (PC = 0.445 ± 0.020). When fibrinogen replaces the saline, a MP of -8.83 mV (PC = 0.257) is observed. While it contrasts sharply with the MP of platelets in saline, it is comparable to the MP of platelets in plasma, which is : -8.63 mV (PC=0.266). We have also measured the effect of human albumin and gamma globulins on the MP ; both these plasmatic proteins cause a much smaller decrease of MP, as compared to fibrinogen (or plasma), all used at physiological concentrations in saline and without the platelet pretreatment with any agent.The results suggest that a relationship might exist between the marked decrease of platelet MP caused by fibrinogen - possibly via mediators of the transmembrane transport- and/or some of the platelet membrane glycoproteins which appear to function as binding sites for fibrinogen and must undergo (conformational) changes that allow fibrinogen to bind.