Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: HUMANGGP:001400 (PRP)
 1,320 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the effect of temperature on platelets during storage for tests of platelet function. Aliquots of PRP were stored at constant pH at 37 degrees C, room temperature and 4 degrees C. At intervals up to five hours, samples were taken for estimation of platelet shape, plasma levels of beta-thromboglobulin and 14C-serotonin, and assessment of platelet aggregation in response to a range of concentrations of ADP and collagen. When PRP was stored at 37 degrees C there was a gradual decrease in the aggregation response during the period of storage. At room temperature the decrease was slower but the response to ADP often increased dramatically before decreasing; at this temperature there was pronounced liberation of beta TG while there was none at 37 degrees C. Platelets stored at 37 degrees C were smooth and elliptical when examined by electron microscopy, but those stored at room temperature showed partial loss of discoid shape and formation of some pseudopodia. Storage at 4 degrees C was associated with total loss of discoid shape and formation of many large pseudopodia. Light transmission studies also showed loss of discoid shape at room temperature and 4 degrees C. We conclude that storage at 4 degrees C or at room temperature causes platelet activation. To avoid this PRP should be stored at 37 degrees C prior to tests of platelet function.
 ...
PMID:Storage of platelets for tests of platelet function: effects of temperature on platelet aggregation, platelet morphology and liberation of beta-thromboglobulin. 294 93

The presence of platelets or platelet release products is known to augment the injury of endothelial cells caused by stimulated neutrophils (PMN leukocytes). In our in vitro studies, platelet-rich or platelet-poor plasma (PRP or PPP) was placed in one compartment and a PMN suspension in the other of a modified Boyden chamber divided by a dialysis membrane. The addition of the aggregating substance (ADP, collagen) to PRP but not to PPP was followed by PMN activation as shown by enzyme release and O-2 generation. The in vivo treatment with ASA completely prevented the platelets from triggering PMN activation. The in vitro addition of a thromboxane synthetase inhibitor (imidazole 10(-3) M) or a lipoxygenase inhibitor (NDGA 10(-6) M) did not show any effect on platelet-dependent PMN activation, thus suggesting that neither TxA2 nor lipoxygenase by-products are involved. Finally, in vitro and in vivo treatment with ticlopidine blunted the stimulating activity of the platelets on PMN. Our data further support the hypothesis that a sequential platelet-PMN interaction may occur, and that the therapeutic effect of some antiplatelet drugs may be partly due to a protective effect against platelet-dependent PMN-mediated vascular damage.
 ...
PMID:Platelet-dependent granulocyte activation in vitro: effect of ticlopidine. 299 67

Acquired von Willebrand disease (AVWD) has been described in two cases of nephroblastoma. We studied a patient with nephroblastoma who presented with a coagulopathy suggestive of AVWD. The subject had undetectable levels of F.VIIIR:Ag, diminished F.VIIIR:WF (16.3%), F.VIII:C activity (37%), and lack of platelet aggregation to ADP, epinephrine, collagen, and arachidonic acid. These results were associated with abnormally high serum levels (850 mg/dl) of hyaluronic acid (HA), which made the patient's serum hyperviscous. Examination of the neoplasm revealed HA in the tumor matrix. All abnormalities of coagulation resolved after chemotherapy and extirpation of the neoplasm, which produced normal serum HA levels. To study the effects of HA on platelet function, we added HA to normal platelet-poor plasma (NPP), which rendered F.VIIIR:Ag undetectable; treatment of HA with hyaluronidase eliminated F.VIIIR:Ag assay interference caused by HA. F.VIII:C activity decreased in vitro when HA was mixed with normal platelet-poor plasma (NPP). HA reduced the initial slope of normal platelet aggregation. Partial correction of platelet aggregation occurred after hyaluronidase treatment of HA-spiked PRP. Experiments in rabbits exposed to HA (serum level 400 mg/dl) demonstrated abnormalities similar to those noted in the patient. Shear rate studies of whole blood containing HA (500 mg/dl) yielded high shear stress, 27-136 dynes/cm2 over shear rates of 10-216 sec-1. We conclude that the coagulopathy demonstrated in this case is secondary to hyperviscosity produced by elevated levels of HA, which interferes with the assay for F.VIIIR:Ag. Thus the acquired coagulopathy associated with other cases of nephroblastoma may present as spurious von Willebrand disease.
 ...
PMID:Platelet dysfunction associated with Wilms tumor and hyaluronic acid. 303 95

Platelets from whole blood were separated into five density subpopulations using a discontinuous Percoll gradient. The content of diadenosine triphosphate (Ap3A), diadenosine tetraphosphate (Ap4A), ADP and ATP were determined in the subfractions. The dinucleotides were directly measured in neutralized, acid-soluble extracts of human platelets with a bioluminescence method not requiring any chromatographic step. When comparing the nucleotide contents of the density subpopulations it became evident that all nucleotides steadily increased with increasing density. Ap3A, Ap4A, ADP and ATP were present in 10-, 7-, 4- and 2-fold higher amounts in the heaviest platelets, respectively, as compared to the subfraction with the lowest density. This finding is practically relevant since the most dense platelet subpopulations may be lost during conventional centrifugation to obtain platelet-rich plasma. Therefore we compared a platelet population obtained from PRP with the platelet population, which had been prepared from whole blood by means of a continuous Percoll gradient. All the four nucleotides investigated were represented in 1.5- to 2-fold higher amounts in the whole blood platelet population. This indicates that PRP does not contain a representative population but lacks part of the large heavy platelets containing the highest amounts of nucleotides.
 ...
PMID:Unproportionally high concentrations of diadenosine triphosphate (Ap3A) and diadenosine tetraphosphate (Ap4A) in heavy platelets. Consequences for in vitro studies with human platelets. 303 Apr 68

The role of platelets in the sex difference observed in mouse thrombosis models was evaluated by examining platelet diminution in vivo after thrombotic challenge, and aggregation of mouse platelets in PRP. A fall in platelet count was observed in both sexes after i.v. injection of either arachidonic acid or the thromboxane agonist, U46619. Platelet diminution induced by high dose arachidonate (50 mg/kg) was significantly greater in males compared to female mice. Responses to U46619 were similar in both sexes. In PRP, male platelets exhibited a greater response than female platelets to both ADP (15 uM) and arachidonate (0.3 mM), but not to U46619 (4.6 and 6.9 uM). These results suggest that the gender difference in arachidonate-induced sudden death, in which males are more susceptible than females, is related to a sex difference in mouse platelet function.
 ...
PMID:Sex differences in mouse platelet aggregation. 308 59

SC 38249 [RS)-1-(2,3-bis-[(4-methoxyphenyl)methoxy]propyl)-1H-imidazole) caused dose-related inhibition of collagen-induced thromboxane A2 formation in human platelet rich plasma (IC50: 9.9 +/- 1.0 microM) accompanied by a dose-dependent increase in plasma PGE2. Broad inhibitory activity was evident against human platelet aggregatory and secretory responses in vitro. IC50 values of 11.9 +/- 1.9 microM (0.64 mM arachidonic acid), 18.3 +/- 3.8 microM (0.5 microgram ml-1 collagen) and 37.6 +/- 6.1 microM (25 nM Paf-acether) were obtained against maximum increase in PRP light transmission achieved by each agonist. Although less potent, SC 38249 retained significant inhibitory activity against PRP responses induced by a higher (3.0 micrograms ml-1) concentration of collagen (IC50: 272.5 +/- 24.6 microM), and against Paf-acether-induced responses in PRP pre-treated with 10 microM indomethacin (I.C.50: 192.0 +/- 16.1 microM). Experimental animal studies confirmed the in vitro anti-aggregatory efficacy of SC 38249, since significant inhibitory activity was observed against Paf-acether and ADP-induced responses in dog PRP ex vivo, anti-Forssman antibody-induced thrombocytopenia in anaesthetized guinea pigs, and collagen-induced intravascular aggregation in anaesthetized rabbits. Thus, SC 38249 is a novel thromboxane synthase inhibitor which possesses interesting anti-aggregatory properties which cannot wholly be attributed to prevention of platelet thromboxane A2 formation.
 ...
PMID:Effect of SC 38249, a novel substituted imidazole, on platelet aggregation in vitro and in vivo. 313 7

The effects of PGI2 and PGE1 on the ultrastructure of human platelets were studied by scanning (SEM) and transmission (TEM) electron microscopy in relation to the record of an optical aggregometer. Addition of PGI2 or PGE1 to citrated platelet-rich plasma (C-PRP) resulted in a permanent slight decrease in percent light transmission (%T) recorded by the aggregometer. SEM investigation of the platelets showed marginal pseudopods and occasional large stomata after application of prostaglandins. These alterations occurred within the initial 30 s and remained constant during the subsequent 20 min of incubation. TEM studies revealed morphological changes of alpha granules and moderately electron-dense material in the dilated profiles of the surface-connected canalicular system (SCCS). Addition of 10 microM ADP to C-PRP preincubated for 30 s with either 2 ng/ml (5 nmol/liter) PGI2 or 30 ng/ml (85 nmol/liter) PGE1 resulted in a further decrease of %T followed by a slight increase. The alterations of the aggregometer tracing were characterized in SEM by platelet shape change and the generation of primary aggregates. C-PRP samples preincubated with 3 and 9 ng/ml (8 nmol/liter and 24 nmol/liter) PGI2 or 40 and 120 ng/ml (113 nmol/liter and 338 nmol/liter) PGE1 did not produce additional changes in the aggregometer curves or in the ultrastructure of platelets in response to ADP. Our morphological study indicates that antiaggregatory prostaglandins induce an early phase of platelet activation but inhibit "shape change" and the formation of aggregates.
 ...
PMID:PGI2 and PGE1 induce morphological alterations in human platelets similar to those of the initial phase of activation. 330 81

An in vitro and ex vivo study has been made to determine the inhibition of platelet aggregation in human whole blood (WB) and platelet rich plasma by triflusal and its main metabolite HTB (2-hydroxy-4-trifluoromethylbenzoic acid). Triflusal was administered orally at 300 mg x 2/day, for 15 days, to 13 healthy volunteers (ex vivo tests). Triflusal and HTB, at concentrations lower than 1 mM, produced a significant inhibition of platelet aggregation induced by ADP (2.5 microM, final) and collagen (1 microgram/ml, final) in PRP, while about 50% inhibition was induced in WB samples at 0.12 mM. Ex vivo studies also revealed a stronger inhibitory effect of triflusal in WB samples against several inducers; differences were particularly pronounced against ADP (10.6 times more potent in WB). These results suggest an important role of red blood cells and/or leukocytes in the mechanism of action of triflusal. The antiplatelet effect of triflusal in WB was modified when incubated with HTB at therapeutic concentrations. The IC50 value against collagen increased from 82 to 140 microM with 37.5 microM HTB, but decreased in a dose-dependent manner when incubated with higher concentrations of HTB, suggesting that inhibition of platelet cyclooxygenase by HTB masks its negative interaction with triflusal.
 ...
PMID:Platelet antiaggregatory effect of triflusal in human whole blood. 338 35

Normal platelet sensitivity to in vitro ADP-induced aggregation (median 46, range 32-62% dT) and a normal antiaggregatory effect of prostacyclin (PGI2; ID50:0.65, range 0.18-2 ng PGI2/ml PRP) were found in a carefully selected group of 30 fairly well-controlled (average HbA1c 7.0%) Type 1 diabetic patients (14m/16f; median age 27.5, range 15-45 yr; duration of disease 7, range 1-24 yr) without macroangiopathy in comparison to 19 (9m/10f; age 26, range 17-40 yr) closely matched healthy controls (42, range 34-63% dT; 0.55, range 0.35-1 ng PGI2/ml PRP). By contrast, platelet malondialdehyde (MDA) release was significantly (p less than 0.001; Mann-Whitney, two-tailed, non-parametric test) increased in diabetics (6.55, range 0.91-18.94 nmol/10(9) platelets) in comparison to controls (3.9 range 2.6-6.9 nmol/10(9) platelets). Since MDA has been used as an indicator of platelet thromboxane formation (a potent stimulator of platelet aggregation), elevated platelet MDA in diabetics has been attributed to platelet activation. In the present study, for the first time increased platelet MDA release in diabetics has been shown to occur independently from enhanced platelet aggregation, even in well-controlled patients without evidence of either macroangiopathy or microangiopathy. This could be of clinical importance, since MDA is known to act on low density lipoprotein-uptake of human macrophages.
 ...
PMID:Increased platelet malondialdehyde, but normal platelet sensitivity to adenosine-5-diphosphate and prostacyclin in well-controlled type 1 diabetics without vascular complications. 354 22

Platelet count, aggregability and volume in the postoperative course of 20 patients were examined. Platelet count was decreased on the 1st postoperative d, and increased on the 7th and 14th d compared with the preoperative value. The maximal aggregation rate of platelets induced by ADP was decreased on the 3rd postoperative d, and then recovered to the preoperative level. In contrast, platelet volume was only slightly increased on the 3rd postoperative d. In this study, there was no correlation between platelet aggregability and platelet volume in PRP. We have proposed one parameter, 'platelet concentration ratio' (platelet concentration in PRP/platelet concentration in whole blood). In the postoperative course, this concentration ratio changed depending on platelet volume, and possibly on other conditions of blood such as hematocrit, viscosity and specific gravity. The concentration ratio influenced the subpopulations of platelets in PRP. Platelet aggregation tests may be performed using PRP in which platelet subpopulations differ from those in whole blood, especially in the postoperative state.
 ...
PMID:Platelet aggregability and platelet volume in the postoperative course: problems in the platelet aggregation test derived from the measurement of platelet volume. 365 71


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>