THE ANTITHROMBOTIC EFFECT OF PALM OIL IS CORRELATED WITH ITS CONTENTS OF VITAMIN E

1987 ◽  
Author(s):  
E G Hornstra ◽  
A H Hennissen ◽  
R Kalafusz ◽  
D T S Tan
Keyword(s):  
Fatty Acid ◽  
Platelet Aggregation ◽  
Palm Oil ◽  
Whole Blood ◽  
Arterial Thrombosis ◽  
Edible Oils ◽  
Thrombus Formation ◽  
Saturated Fatty Acids ◽  
Atp Release ◽  
Significant Negative Correlation

Dietary saturated fatty acids are known to increase platelet aggregation and arterial thrombogenesis.We recently demonstrated, however, that palm oil, rich in saturated palmitic acid, has a distinct antithrombotic affect, which is associated with a decrease of the thromboxane-prostacyclin ratio in activated whole blood. To identify the antithrombotic component(s) of palm oil, seven palm oil fractions were prepared with comparable fatty acid compositions of the triglycerides but containing Various amounts of non-triglyceride material with different compositions.These fractions were fed to rats in amounts of 50 energy% for a period of 8 weeks, after which arterial thrombosis tendency was measured upon insertion of an aortic prosthesis, the aorta-loop. During loop insertion, 1 ml blood was collected in citrate for measuring platelet aggregation and ATP release in response to collagen, using the Chronolog whole blood lumi-aggregometer. Arterial thrombosis tendency was found to be negatively related to the total amount of non-triglyceride material in the various fractions (r = 0.78; p <0.05).No significant relationship was observed between arterial thrombus formation and the various sterols present in the non-triglyceride material.A significant negative correlation was found, however, with a-tocopherol (r = 0.86; p <.02). Collagen-induced platelet aggregation and ATP release in whole blood were not correlated to total amounts or α-tocopherol content of the non-triglyceride material.However, significant positive relationships were found between these platelet functions and the amountsof the various sterols (Campesterol: r = 0.70; P < 0.10 β-sitostero1 : r = 0.69; P <0.10. Cholesterol : r = 0.81; P < 0.05).These findings demonstrate that effects of edible oils on platelet function and arterial thrombogenesisare not only mediated by the fatty acid compostion of the triglycerides, but can also be determined by 'minor components', present in the non-triglyceride part of the oils.

Discrimination Between Prostglandin-Dependent And-Independent Functions Of Essential Fatty Acids In Arterial Throm- Bogenesis

1981 ◽  
Author(s):  
U M T Houtsmuller ◽  
G Hornstra ◽  
E Haddeman
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Linoleic Acid ◽  
Platelet Aggregation ◽  
Arterial Thrombosis ◽  
Thrombus Formation ◽  
Arterial Thrombus ◽  
Induced Aggregation

Arterial thrombus formation is reduced in essential fatty acid (EFA) deficiency. This goes together with an enhanced thrombin induced aggregation of platelets in vitro,whereas collagen-induced aggregation is definitely suppressed. A small amount of linoleic acid (18:2 (n-6)) is able to cure EFA-deficiency and to normalize arterial thrombogenesis. This latter effect may be due to either the structural function of this EFA or to its function as the ultimate dietary precursor of prostaglandins (PG). Columbinic acid, a stereo-isomer of γ-linolenic acid (18:3 (n-6)) was recently shown to possess all the structural functions of EFA, but not the PG-dependent ones. This fatty acid therefore presents a suitable tool to investigate the PG-dependence of arterial thrombogenesis and its underlying processes. We therefore compared the effect of small amounts of linoleic and columbinic acid (both as methylesters) on the water vapour release in vivo (which is a sensitive parameter for a non-PG dependent function of polyenoic fatty acids), arterial thrombosis tendency (time needed for the thrombotic obstruction of an aorta prosthesis) and platelet aggregation in vitro (aggregometry) induced by collagen and thrombin. In contrast to linoleic acid, columbinic acid did not normalize arterial thrombosis tendency and collagen induced platelet aggregation. Columbinic acid was equally effective as linoleic acid in the normalization of the water vapour release in vivo and of the thrombin-induced aggregation. We conclude that arterial thrombus formation and collagen- induced aggregation greatly depend on prostanoid formation, whereas thrombin-induced aggregation does not. The structural role of polyenoic fatty acids in thrombin-induced aggregation may provide a tool in the elucidation of factors determining the thrombin-sensitivity of blood platelets.

Platelet Aggregation in Finnish Men and Its Relation to Fatty Acids in Platelets, Plasma and Adipose Tissue

1985 ◽  
Vol 54 (03) ◽  
pp. 563-569 ◽  
Author(s):  
M K Salo ◽  
E Vartiainen ◽  
P Puska ◽  
T Nikkari
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Platelet Aggregation ◽  
Acid Composition ◽  
Saturated Fatty Acids ◽  
Free Living ◽  
Ω3 Fatty Acids ◽  
Induced Aggregation

SummaryPlatelet aggregation and its relation to fatty acid composition of platelets, plasma and adipose tissue was determined in 196 randomly selected, free-living, 40-49-year-old men in two regions of Finland (east and southwest) with a nearly twofold difference in the IHD rate.There were no significant east-southwest differences in platelet aggregation induced with ADP, thrombin or epinephrine. ADP-induced platelet secondary aggregation showed significant negative associations with all C20-C22 ω3-fatty acids in platelets (r = -0.26 - -0.40) and with the platelet 20: 5ω3/20: 4ω 6 and ω3/ ω6 ratios, but significant positive correlations with the contents of 18:2 in adipose tissue (r = 0.20) and plasma triglycerides (TG) (r = 0.29). Epinephrine-induced aggregation correlated negatively with 20: 5ω 3 in plasma cholesteryl esters (CE) (r = -0.23) and TG (r = -0.29), and positively with the total percentage of saturated fatty acids in platelets (r = 0.33), but had no significant correlations with any of the ω6-fatty acids. Thrombin-induced aggregation correlated negatively with the ω3/6ω ratio in adipose tissue (r = -0.25) and the 20: 3ω6/20: 4ω 6 ratio in plasma CE (r = -0.27) and free fatty acids (FFA) (r = -0.23), and positively with adipose tissue 18:2 (r = 0.23) and 20:4ω6 (r = 0.22) in plasma phospholipids (PL).The percentages of prostanoid precursors in platelet lipids, i. e. 20: 3ω 6, 20: 4ω 6 and 20 :5ω 3, correlated best with the same fatty acids in plasma CE (r = 0.32 - 0.77) and PL (r = 0.28 - 0.74). Platelet 20: 5ω 3 had highly significant negative correlations with the percentage of 18:2 in adipose tissue and all plasma lipid fractions (r = -0.35 - -0.44).These results suggest that, among a free-living population, relatively small changes in the fatty acid composition of plasma and platelets may be reflected in significant differences in platelet aggregation, and that an increase in linoleate-rich vegetable fat in the diet may not affect platelet function favourably unless it is accompanied by an adequate supply of ω3 fatty acids.

Dipyridamole Inhibits Platelet Aggregation in Whole Blood

1983 ◽  
Vol 50 (04) ◽  
pp. 852-856 ◽  
Author(s):  
P Gresele ◽  
C Zoja ◽  
H Deckmyn ◽  
J Arnout ◽  
J Vermylen ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Whole Blood ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
Significant Negative Correlation ◽  
Significant Inhibition ◽  
Oral Drug ◽  
Human Blood Samples ◽  
Induced Aggregation

SummaryDipyridamole possesses antithrombotic properties in the animal and in man but it does not inhibit platelet aggregation in plasma. We evaluated the effect of dipyridamole ex vivo and in vitro on platelet aggregation induced by collagen and adenosine- 5’-diphosphate (ADP) in human whole blood with an impedance aggregometer. Two hundred mg dipyridamole induced a significant inhibition of both ADP- and collagen-induced aggregation in human blood samples taken 2 hr after oral drug intake. Administration of the drug for four days, 400 mg/day, further increased the antiplatelet effect. A significant negative correlation was found between collagen-induced platelet aggregation in whole blood and dipyridamole levels in plasma (p <0.001). A statistically significant inhibition of both collagen (p <0.0025) and ADP-induced (p <0.005) platelet aggregation was also obtained by incubating whole blood in vitro for 2 min at 37° C with dipyridamole (3.9 μM). No such effects were seen in platelet-rich plasma, even after enrichment with leukocytes. Low-dose adenosine enhanced in vitro inhibition in whole blood.Our results demonstrate that dipyridamole impedes platelet aggregation in whole blood by an interaction with red blood cells, probably involving adenosine.

scholarly journals Effect of aspirin and sodium salicylate on thrombosis, fibrinolysis, prothrombin time, and platelet survival In rabbits with indwelling aortic catheters

Blood ◽  
1983 ◽  
Vol 61 (2) ◽  
pp. 353-361 ◽  
Author(s):  
M Cattaneo ◽  
A Chahil ◽  
D Somers ◽  
RL Kinlough-Rathbone ◽  
MA Packham ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Prothrombin Time ◽  
Whole Blood ◽  
Fibrinolytic Activity ◽  
Sodium Salicylate ◽  
Thrombus Formation ◽  
Significant Inhibition ◽  
Weak Inhibitor ◽  
Platelet Survival ◽  
High Doses

Abstract We have studied the effect of different doses of aspirin on platelet function, PGI2 formation, platelet survival, thrombosis, fibrinolysis, and prothrombin time in rabbits with indwelling aortic catheters. The thrombi formed around indwelling aortic catheters were found to have a large fibrin component, and their formation was inhibited by heparin administration. Thus, in these experiments we examined the effect of aspirin (a weak inhibitor of thrombin-mediated platelet aggregation) under conditions in which thrombin was a major factor in the initiation and growth of the thrombi. Only very high doses of aspirin tended to inhibit thrombus formation over the 5-day period of observation, and a statistically significant inhibition of thrombus formation was produced by equivalent concentrations of sodium salicylate. The failure of high doses of aspirin to achieve a significant inhibition of thrombosis under the conditions of these experiments (whereas an equivalent dose of sodium salicylate was inhibitory) could be due to aspirin inhibition of PGI2 formation. Shortened platelet survival was not affected by aspirin treatment or the dose sodium salicylate that inhibited thrombus formation. The tendency to inhibit thrombus formation appeared to be unrelated to an effect on platelets but was associated with prolongation of the one-stage prothrombin time and increased whole blood fibrinolytic activity; doses of aspirin that inhibited platelet aggregation in response to sodium arachidonate or collagen, and PGI2 formation by the vessel wall, did not have a significant effect on the amount of thrombus present at 5 days. However, the high doses of aspirin that inhibited PGI2 formation were associated with a tendency to increased thrombus formation during the first 3 hr after insertion of the catheter. The results of these experiments show that when thrombin is an important factor in the formation of thrombi, aspirin is a weak inhibitor of thrombosis unless doses are used that provide sufficient salicylate to interfere with blood coagulation and promote whole blood fibrinolytic activity. These results also show that thrombus formation can be inhibited without an apparent change in platelet survival.

Synergism Between Platelet Aggregating Agents: Possible Trigger Mechanisms During Hemostatic Plug And/Or Thrombus Formation

1981 ◽  
Author(s):  
S C Wong ◽  
G A Rock
Keyword(s):  
Platelet Aggregation ◽  
Serine Protease ◽  
Protease Inhibitors ◽  
Synergistic Effects ◽  
Thrombus Formation ◽  
Thrombotic Event ◽  
Atp Release ◽  
Serine Protease Inhibitors ◽  
Induce Platelet Aggregation

number of in-vitro studies have shown that various pair-combinations of aggregating agents such as ADP, epinephrine, collagen, thrombin, arachidonate and ionophore A 23187 can produce synergistic responses to induce platelet aggregation and release reactions. We have also produced synergistic effects by combining much lower doses of 3 or more aggregating agents and found markedly enhanced responses. It appears that the potential for synergistic effects is based both on the combination of the various agents and on the amount of each agent used for stimulation. Epinephrine is the most potent agent among them, although fibrinogen and Ca++ play a very important role. Indomethacin, ASA, PGE 1, and synthetic serine protease inhibitors (carboxylate and sulphonate analog) completely inhibit the platelet aggregation and release response. Of particular interest is the fact that addition of as little as 0.04% of the usual aggregating dose of epinephrine in the presence of 4% of collagen, 2% of thrombin and 10% of the normal plasma level of fibrinogen will initiate a marked response both of platelet aggregation and ATP release. This suggests a possible mechanism whereby acute insults such as stress or exercise, with release of epinephrine, can precipitate a thrombotic event in a patient who has normal or near-normal circulating levels of fibrinogen but who also has exposure of a very limited amount of the vascular endothelium (thereby exposing collagen). Since the effects of the acute insults of epinephrine secretion can be blocked by the presence of indomethacin, ASA, PGE 1 and specific serine protease inhibitors, prostaglandin synthesis must play a major role in this reaction.

Endotoxin-Induced Platelet Activation in Human Whole Blood In Vitro

1988 ◽  
Vol 59 (03) ◽  
pp. 378-382 ◽  
Author(s):  
Gyorgy Csako ◽  
Eva A Suba ◽  
Ronald J Elin
Keyword(s):  
Platelet Aggregation ◽  
Whole Blood ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Atp Release ◽  
Human Platelets ◽  
Lag Phase ◽  
Human Whole Blood ◽  
Dose Dependent

SummaryThe effect of purified bacterial endotoxin was studied on human platelets in vitro. In adding up to 1 μg/mL of a highly purified endotoxin, we found neither aggregation nor ATP release in heparinized or citrated human platelet-rich plasma. On the other hand, endotoxin at concentrations as low as a few ng/mL (as may be found in septic patients) caused platelet aggregation in both heparinized and citrated human whole blood, as monitored by change in impedance, free platelet count, and size. Unlike collagen, the platelet aggregation with endotoxin occurred after a long lag phase, developed slowly, and was rarely coupled with measurable release of ATP. The platelet aggregating effect of endotoxin was dose-dependent and modified by exposure of the endotoxin to ionizing radiation. Thus, the activation of human platelets by “solubilized” endotoxin in plasma requires the presence of other blood cells. We propose that the platelet effect is mediated by monocytes and/or neutrophils stimulated by endotoxin.

MEASURING WHOLE BLOOD PLATELET AGGREGATION AND ATP-RELEASE WITH A CHRONO-LOG WHOLE BLOOD LUMI-AGGREGOMETER: EFFECT OF STORAGE TIME OF BLOOD SAMPLES

1987 ◽  
Author(s):  
F C Sieders ◽  
A C v Houwelingen ◽  
G Hornstra
Keyword(s):  
Platelet Aggregation ◽  
Whole Blood ◽  
Storage Time ◽  
Bleeding Time ◽  
Atp Release ◽  
Blood Platelet ◽  
Blood Samples ◽  
Before And After ◽  
Positive Correlations ◽  
Blood Platelet Aggregation

The influence of storing blood for either one or two hours after blood sampling, on whole blood platelet aggregation and ATP-release was measured with a Chrono-log whole blood lumi-aggregometer, in 21 healthy male volunteers. Storage of blood samples, gently revolving at 37 °C in an incubator for one hour, caused a significant increase in aggregation and release as compared with results obtained immediately after sampling. After two hours' storage, the values had returned to their initial levels.Significant positive correlations were seen between values obtained before and after storage of blood, and between various aggregation and release parameters. In this study, bleeding time nor hematocrit values were significantly correlated with the aggregation and release parameters. The considerable influence of storage time on whole blood platelet aggregation and ATP-release underlines the importance of performing these determinations immediately after sampling, or possibly after a standardized storage time. Otherwise, comparison of results -obtained either in clinical situations or in trials - will increase variability as a result of which false conclusions may be obtained. This will be illustrated in a small trial using paracetamol.

INFLUENCE OF DIETARY FISH ON PLATELET FUNCTION AND THROMBOXANE FORMATION

1987 ◽  
Author(s):  
A C V Houwelingen ◽  
A Hennissen ◽  
F Verbeek-Schlppers ◽  
T Simonson ◽  
S Fischer ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Whole Blood ◽  
Bleeding Time ◽  
Fish Meal ◽  
International Association ◽  
Atp Release ◽  
Risk Indicators ◽  
Control Group ◽  
Dietary Fish ◽  
Heart Foundation

Many studies have been performed with respect to the effects of fish (products) on the possible prevention of ischemic cardiovascular disease in man. Most of the trials, however, were poorly designed without a proper control group, and their results are equivocal. We, therefore, performed a well- controlled intervention trial to investigate the effect of a reasonable amount of dietary fish on certain risk indicators of arterial thrombogenesis. In Tromstf, Maastricht and Zeist, healthy male volunteers were given a dietary supplement consisting of 135 g of canned mackerel (n=40) or meat paste (control, n=42) per day for a period of 6 weeks. Compliance was monitored on the basis of the urinary excretion of lithium, added to the supplements. Average compliance was about80% and decreased slightly with time. Bleeding time was significantly prolonged and platelet number decreased in the mackerel group.Platelet aggregation inPRP induced by thrombin decreased only at a low dose.Collagen-induced platelet aggregation in PRP decreased significantly. This was associated with a 50% reduction of the collagen-induced TxB2 formation in PRP(P < 0.001). TxB3 synthesis increased significantly in the mackerel group from 0.9 to 7.8% of the TxB2 production (GC/MS). Collagen- induced platelet aggregation and ATP release in whole blood were measured with the Chronolog whole blood lumiaggregometer (Maastricht only). In the same samples TxB2 formtion was measured (RIA) and although a significant reduction was seen in the mackerel group, platelet functionswere not significantly altered. However, platelet release (but not aggregation) was significantly related to the compliance and a decreasing effect of the mackerel supplement was observed in those 50% of the volunteers having the highest compliance. This demonstrates the necessity of monitoring compliance by objective means. Acknowledgements: Financial support was obtained from the Dutch Heart Foundation. The International Association of Fish Meal Manufactures (Potters Bar, Herts, England) provided the mackerel.

LPS Stimulates Platelet Secretion and Promotes Platelet Aggregation Via TLR4/MyD88 and the cGMP-Dependent Protein Kinase Pathway.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3658-3658
Author(s):  
Guoying Zhang ◽  
Emily Welch ◽  
Asrar B. Malik ◽  
Xiaoping Du ◽  
Zhenyu Li
Keyword(s):  
Platelet Aggregation ◽  
Protein Kinase ◽  
Platelet Activation ◽  
Thrombus Formation ◽  
Critical Role ◽  
Atp Release ◽  
Dependent Protein Kinase ◽  
Cgmp Dependent Protein Kinase ◽  
Dependent Protein ◽  
Platelet Secretion

Abstract Bacterial lipopolysaccharide (LPS) induces rapid thrombocytopenia, hypotension and sepsis. Although growing evidence suggests that platelet activation plays a critical role in LPS-induced thrombocytopenia and tissue damage, the mechanism of LPS-mediated platelet activation is unclear. Here we show that LPS stimulated platelet secretion of dense and alpha granules as indicated by ATP release and P-selectin expression, and thus enhanced platelet activation induced by low concentrations of platelet agonists. Platelets express components of the LPS receptor-signaling complex, including Toll-like receptor (TLR4), CD14, MD2, and MyD88. The effect of LPS on platelet activation was abolished by an anti-TLR4 blocking antibody or TLR4 knockout. Furthermore, LPS-induced potentiation of platelet aggregation and FeCl3-induced thrombus formation were abolished in MyD88 knockout mice. Importantly, TLR4 mediates LPS-induced cGMP elevation and the stimulatory effect of LPS on platelet aggregation was also abolished by inhibitors of nitric oxide synthase (NOS) and the cGMP-dependent protein kinase (PKG). Thus, LPS promotes platelet secretion and aggregation through a TLR4/MyD88 and cGMP/PKG-dependent pathway.

YM150, An Oral Direct Factor Xa Inhibitor: Combination with Aspirin or Clopidogrel In Arteriovenous Shunt Thrombosis In Rats

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3318-3318
Author(s):  
Yoshiyuki Iwatsuki ◽  
Chinatsu Sakata ◽  
Yumiko Moritani
Keyword(s):  
Platelet Aggregation ◽  
Arterial Thrombosis ◽  
Bleeding Time ◽  
Thrombus Formation ◽  
Control Level ◽  
Factor Xa ◽  
Antiplatelet Agents ◽  
Factor Xa Inhibitor ◽  
Direct Factor ◽  
Silk Thread

Abstract Abstract 3318 Background: YM150, an oral direct factor Xa inhibitor, is currently in clinical development for the prevention of venous thromboembolism in patients undergoing orthopedic surgery, prevention of stroke in patients with atrial fibrillation, and prevention of ischemic events after recent acute coronary syndrome (ACS). The antiplatelet agents aspirin or clopidogrel will likely be co-prescribed with YM150 in ACS. Here, we report the effects of YM150 in combination with aspirin or clopidogrel on thrombus formation, bleeding, platelet aggregation, and coagulation in rats. Methods: The antithrombotic effect was estimated in a rat arteriovenous shunt model. The shunt was formed by attaching a polyethylene tube containing a silk thread to the carotid artery and the contralateral carotid vein. Blood was allowed to circulate in this shunt for 15 min, and then the silk thread was withdrawn from the tube to assess the thrombus weight. YM150, aspirin, or clopidogrel was orally administered 0.5, 1, or 2 h before shunt formation, respectively. At the same time as shunt formation, an incision was made at the sole of the left foot using a template bleeding device (Surgicutt®) to measure bleeding time. To avoid interference with the thrombosis model, blood samples to assess platelet aggregation and prothrombin time were obtained from separate animals at the same time point as shunt formation in the thrombus study. Platelet aggregation was induced using 10 μg/mL of collagen and 5 μM of adenosine 5`-diphosphate (ADP) to assess the effects of aspirin and clopidogrel, respectively. Results: YM150 alone inhibited thrombus formation, with significance at 10 mg/kg and more (P < 0.05). Respective thrombus weights in the control, 3, 10, and 30 mg/kg groups of YM150 were 4.8, 3.6, 2.4, and 2.0 mg. Aspirin alone inhibited thrombus formation, with significance at 100 mg/kg and more (P < 0.01). Respective thrombus weights in the control, 30, 100, and 300 mg/kg group of aspirin were 6.2, 4.2, 2.8, and 1.5 mg. Clopidogrel alone inhibited thrombus formation, with significance at 1 mg/kg and more (P < 0.01). Respective thrombus weights in the control, 0.3, 1, and 3 mg/kg group of clopidogrel were 4.8, 3.6, 2.9, and 1.3 mg. When administered concomitantly with 100 mg/kg of aspirin, YM150 (3, 10, 30 mg/kg) further inhibited thrombogenesis, with significance at 30 mg/kg of YM150 (P < 0.05) and thrombus weights of 2.4, 1.5, and 1.3 mg, respectively. When administered concomitantly with 1 mg/kg of clopidogrel, YM150 (3, 10, 30 mg/kg) further inhibited thrombogenesis, with significance at 30 mg/kg of YM150 (P < 0.05) and thrombus weights of 3.0, 2.0, and 1.5 mg, respectively. Collagen-induced platelet aggregation was reduced to 16.7% of the control level by 100 mg/kg of aspirin, and ADP-induced platelet aggregation was reduced to 74.4% of the control level by 1 mg/kg of clopidogrel. These effects were not changed in the presence of YM150. Prothrombin time and bleeding time were not prolonged by any of the agents alone, and further, these parameters were not affected by combined use of YM150 with either aspirin or clopidogrel. Conclusions: The thrombosis study suggests that both the platelet aggregation and coagulation cascade participate in thrombus formation in this model since both antiplatelet agents and the anticoagulant YM150 were effective. Thus, the thrombosis induced in this model can be considered similar to arterial thrombosis in humans where both platelets and fibrin are involved. Taken together, YM150 is a promising antithrombotic agent that augments the effects of antiplatelet agents against arterial thrombosis without increasing bleeding risk. Disclosures: Iwatsuki: Astellas Phama Inc.: Employment. Sakata:Astellas Phama Inc.: Employment. Moritani:Astellas Phama Inc.: Employment.

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