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At least 1,531 records · Page 85Linked to original sources
PubMed1986

A method for production of N2 microbubbles in platelet-rich plasma in an aggregometer-like apparatus, and effect on the platelet density in vitro.

The mechanisms involved in the interactions between microgasbubbles and platelets are not clear. The platelet aggregatory response to agonist-induced, receptor-mediated stimuli has been studied extensively. As a direct in vitro approach to elucidate the interaction between gas bubbles and platelets, N2 microbubbles were used as a platelet agonist in an experimental apparatus similar to an ordinary aggregometer. N2 microbubbles of varying number and size were produced in platelet-rich plasma (PRP) and incubated at 37 degrees C. The gas-liquid interface of the gas bubbles consists of plasma proteins and lipids. In stirred PRP a considerable decrease occurred in the platelet density, which could not be attributed to formation of citrate complexes with calcium and/or the corresponding reduction in the concentration of free calcium. Gas bubbles with a diameter in the range of 40-120 micron caused the greatest reduction in the platelet density. The platelet movements in PRP and the curvature of the N2 microbubble surface seemed more important for the interaction than the total gas bubble surface available for contact.

Analysis of Variance↗
PubMed1985

Human platelet aggregation and release reaction induced by platelet activating factor (PAF-acether)--effects of acetylsalicylic acid and external ionized calcium.

The effects of the cyclo-oxygenase inhibition on PAF-acether-induced human platelet aggregation and secretion are controversial. We studied the above parameters on citrated platelet-rich plasma of 12 normal subjects before and after the in vivo administration of acetylsalicylic acid (ASA). Individual sensitivities to PAF-acether were highly variable. ASA completely inhibited the platelet secretion induced by low concentrations of PAF-acether, but caused only partial inhibition when platelets were exposed to high concentrations of PAF-acether. The concentration of PAF-acether which overcame the cyclo-oxygenase inhibition varied substantially, depending on the individual sensitivity of the platelets to it. The addition of CaCl2 2 mM to the samples did not affect the extent of the platelet secretion, but increased irreversible aggregation in samples taken both before and after the ASA administration. These data suggest that low concentrations of PAF-acether stimulate the human platelet secretion by activating the cyclo-oxygenase pathway, whereas higher concentrations also trigger other mechanism(s) that suffice to induce human platelet secretion and full aggregation.

Aspirin↗
PubMed1984

[Platelet aggregation and coenzyme Q10 content in platelets in cancer patients].

Platelet aggregation, plasma beta-thromboglobulin (beta-TG) concentration and coenzyme Q10 content in serum and platelets were measured in 45 patients with unresectable carcinoma of the lung and in 7 patients with metastatic pulmonary tumor before and after receiving chemotherapy. A significant increase in the plasma beta-TG concentration in cancer patients (47.4 +/- 18.7 ng/ml) was observed (p less than 0.001) compared to the controls (30.3 +/- 9.2 ng/ml). Serum coenzyme Q10 content was lower in cancer patients (0.42 +/- 0.19 micrograms/ml) (p less than 0.05) compared to the controls (0.57 +/- 0.24 micrograms/ml). The reason of decrease in serum coenzyme Q10 content in cancer patients was difficult to explain. No significant difference of the coenzyme Q10 content in platelets (1 X 10(8) cells) was observed either cancer patients (12.5 +/- 2.8 ng) or the controls (12.6 +/- 2.1 ng). No significant correlation was noted among platelet aggregation, plasma beta-TG concentration and coenzyme Q10 content in serum and platelets. Administration of either vindesine or KW2083 did not influence the coenzyme Q10 content in platelets. These results suggest that ATP synthetic pathway by oxidative phosphorylation in platelet be maintained in cancer patients, although a significant increase of plasma beta-TG concentration appears to be associated with an acceleration in the metabolic turnover of platelet.

Adult↗
PubMed1984

Isolation of a platelet membrane protein which binds the platelet-activating factor 1-0-hexadecyl-2-acetyl-SN-glycero-3-phosphorylcholine.

The phospholipid platelet-activating factor 1-0-hexadecyl-2-acetyl-SN-glycero-3-phosphorylcholine (AGEPC) initiates platelet function by interacting specifically with 1399 +/- 498 (mean +/- SD) high-affinity membrane receptors per platelet. In studies designated to characterize the high affinity binding site, AGEPC-human serum albumin-Sepharose was employed to isolate a 180,000 mol. wt. protein from human platelet plasma membranes. Platelet plasma membranes were isolated by adsorption of sonicated human platelets to a column of wheat germ agglutinin-Sepharose and elution with N-acetyl-glucosamine. The plasma membranes were solubilized in 5% sodium dodecyl sulphate and applied to a column of AGEPC-human serum albumin-Sepharose. After washing the column extensively, the specifically bound material was eluted with a five-fold molar excess of AGEPC. Sodium dodecyl sulphate polyacrylamide gel electrophoresis of the eluted material revealed a single protein with an apparent molecular weight of 180,000. This protein was not recovered from solubilized platelet membranes when chromatography was performed with a column of human serum albumin-Sepharose lacking AGEPC. The capacity of this protein to bind AGEPC suggests that it represents a constituent of the human platelet receptor for AGEPC.

Adult↗
PubMed1984

Quantitative assessment of platelet morphology by light scattering: a potential method for the evaluation of platelets for transfusion.

Normal fresh platelets are discoid, and platelets that have been stored become spherical. Discoid morphology correlates with normal viability and imparts to a platelet suspension a "streaming" appearance when agitated. We developed a device that quantitates the percent of discoid cells in a suspension by means of laser light scattering at low angles. It performs this assay within 3 minutes on platelets contained in a plastic blood bag. The ability of the device to quantitate discoid platelets was demonstrated in the following ways: (1) comparison of percentage discs calculated from light-scattering data with visually observed optical streaming; (2) correlation of percentage discs from light scattering with the percentage determined by phase microscopy; and (3) observation of changes during room temperature storage. Platelet suspensions containing extreme (dendritic and balloon) forms were examined, and we conclude that these forms do not significantly affect the light-scattering assay. The optical measurements were also used to accurately approximate the total platelet counts of the suspensions. This device may have a role in the evaluation of platelets for transfusion.

Blood Platelets↗
PubMed1983

Platelet-activating factor and analogues: comparative studies with human neutrophils and rabbit platelets.

Platelet-activating factor and 12 structural analogues stimulated rabbit platelets to aggregate and release [14C]-serotonin. They likewise caused human neutrophils to aggregate, degranulate, and take up [3H]-deoxyglucose. Their respective potencies, which varied by 4-5 orders of magnitude, correlated highly (r greater than or equal to 0.93) in all assays. These compounds also selectively desensitized neutrophils to the degranulating actions of platelet-activating factor but not to C5a or a formylated oligopeptide. Three other analogues with structures quite similar to platelet-activating factor were unable to activate or desensitize the cells. Hence, the structure-activity relations of the analogues in several assays of platelet and neutrophil function were similar and they stimulated neutrophils by a common activation mechanism that differed from those used by C5a or formylated oligopeptides. These data are consistent with the notion that platelet-activating factor activates and desensitizes various target cells through stereospecific receptors. Apparently, these putative receptors on neutrophils and platelets have similar structural specificities for platelet-activating factor and its analogues.

Animals↗
PubMed1982

Degranulation of rabbit platelets with PAF-acether: a new procedure for unravelling the mode of action of platelet-activating substances.

Aggregation and secretion of ATP induced by thrombin, collagen, the snake venom component convulxin and platelet-activating factor (PAF-acether) were studied after the exposure of rabbit platelets to 1 microM of PAF-acether. This concentration, which is around 6 orders of magnitude above the concentration needed to induce full aggregation, was required to remove most of the releasable ATP from the platelets. The depleted platelets aggregated to PAF-acether, to thrombin and to convulxin under conditions where only very low amounts of ATP were secreted, confirming that these agents do not require the release of dense body components to trigger aggregation. Furthermore, when exposure to PAF-acether was associated to inactivation of platelet cyclooxygenase with aspirin, aggregation to thrombin persisted, validating the claim that thrombin induces aggregation by a third pathway unrelated to ADP and to thromboxane A2. Aggregation by collagen was markedly reduced by exposure of the platelets to PAF-acether or to aspirin; when both procedures were associated, aggregation was suppressed. Failure to desensitize the rabbit platelets to PAF-acether upon exposure to high amounts of it indicates the absence of irreversible membrane changes due to PAF-acether, and allows its use as a depleting procedure for the dense body materials, which does not affect platelet membrane components as is the case for thrombin.

Adenosine Triphosphate↗
PubMed1980

Human platelet acetylcholinesterase: the effects of anticholinesterases on platelet function.

Platelet acetylcholinesterase (AChE) activity was measured in gel-filtered platelet preparations. Three different anticholinesteratic agents (eserine, neostigmine, and diisopropylphosphorofluoridate) at final concentrations of 10 muM caused complete inhibition of AChE activity after 30 min incubation at room temperature with either platelet-rich plasma or gel-filtered platelets. Complete inhibition of platelet AChE had no effect on platelet aggregation, factor-3 availability, and plasma clot retraction. We conclude that platelet membrane AChE activity is not required for normal platelet function as measured by these in vitro parameters.

Acetylcholinesterase↗
PubMed1995

Relaxin depresses platelet aggregation: in vitro studies on isolated human and rabbit platelets.

BACKGROUND: Relaxin, a peptide hormone of ovarian origin, has been shown to cause a striking dilatory action on microvessels in different organs. In our recent studies, relaxin has been shown to stimulate the production of nitric oxide, a powerful vasodilatory agent, in several targets. Nitric oxide also inhibits platelet aggregation. This prompted us to search for a role of relaxin in platelet function. EXPERIMENTAL DESIGN: The effect of relaxin on platelet aggregation was studied in isolated human and rabbit platelets. The samples were incubated with relaxin at different concentrations and then stimulated with collagen or thrombin. Aggregation and intracellular levels of cGMP and Ca2+ were determined. In some experiments, inhibitors or potentiators of nitric oxide activity were also used to clarify whether the mechanism of action of relaxin involves the L-arginine-nitric-oxide pathway. Electron microscopy of platelets treated and not treated with relaxin was also carried out. RESULTS: Preincubation of the platelets with relaxin before stimulation with proaggregants resulted in a significant, concentration-dependent inhibition of platelet aggregation, accompanied by an elevation of intraplatelet cGMP and a decrease in the rise of cytosolic Ca2+ levels. The effect of relaxin appeared to be mediated through nitric oxide. Ultrastructurally, relaxin was shown to hinder the conformational changes and granule exocytosis usually occurring in platelets during aggregation. CONCLUSIONS: This newly recognized antiaggregatory property of relaxin, together with the vasodilatory and hypotensive activities of the peptide demonstrated in previous studies, allows for this hormone to be regarded as a protective agent against thrombotic and hypertensive disorders of pregnancy and cardiovascular diseases.

Adult↗
PubMed1995

Exhibition of anti-platelet effect of isocarbacyclin methyl ester and its free acid via an increase in cAMP in platelets.

Isocarbacyclin methyl ester (CAS 88931-51-5, TEI-9090) and its free acid (CAS 88911-35-7, TEI-7165) are chemically stable analogues of prostaglandin (PG) I2. The cAMP increasing activities of TEI-9090 and TEI-7165 were investigated. TEI-9090, TEI-7165, PGI2, and PGE1 caused the accumulation of cAMP in rabbit and human platelets. The effects of TEI-9090, TEI-7165, and PGE1 were longer lasting than the effect of PGI2. Each drug concentration-dependently increased the cAMP level in rabbit and human platelets. The order of cAMP-increasing activity was PGI2 > PGE1 = TEI-9090 = TEI-7165 in rabbit platelets and PGI2 > TEI-9090 = TEI-7165 > PGE1 in human platelets. The antiplatelet aggregation activity of TEI-9090 in rabbit and human platelets was remarkably decreased by the addition of an esterase inhibitor, diisopropyl fluorophosphate (DFP). However, this activity of TEI-7165 was not affected by the inhibitor. In the presence of DFP, the cAMP accumulation by TEI-9090 in rabbit platelets was almost completely inhibited but that by TEI-7165 was not inhibited. These results suggest that TEI-9090 is deesterified to TEI-7165 and that this free acid then inhibits platelet aggregation via an increase in the cAMP level in the platelets.

Alprostadil↗
PubMed1995

Indirect allorecognition of platelets by T helper cells during platelet transfusions correlates with anti-major histocompatibility complex antibody and cytotoxic T lymphocyte formation.

To study the cellular immunology of platelet-induced alloimmunization, a murine transfusion model was developed. BALB/c (H-2d) recipient mice were transfused weekly with 2 x 10(8) platelets or 10(3) leukocytes from C57BL/6 (H-2b) donor mice. Recipient antidonor major histocompatibility complex (MHC) class I alloantibodies could be detected in flow cytometric assays by the fifth platelet transfusion. In contrast, when leukocytes only were transfused, alloantibodies were not detected. In vitro assays demonstrated that murine H-2b platelets were positive for MHC class I expression but lacked MHC class II molecules on their membranes and were unable to stimulate proliferation or cytokine production when incubated with naive H-2d spleen cells. In vivo, however, platelet transfusions induced two distinct patterns of cell-mediated reactivity. First, during the initial transfusions and before alloantibody formation, there was induction of T-cell anergy, characterized by the inability of recipient T cells to respond to Concanavalin A (ConA) or to proliferate in an antidonor mixed lymphocyte reaction (MLR), together with suppressed natural killer (NK) cell activity. This unresponsiveness was associated with a transient increase in nitric oxide (NO)-dependent cytotoxicity and interleukin-1 (IL-1) production. Second, once alloantibodies developed, significantly increased antidonor CD8+ cytotoxic T lymphocyte (CTL) and NK cell responses were observed. At this time, when recipient spleen cells were depleted of CD8+ T cells and incubated with only donor platelets in 7-day antigen-presenting cell (APC) assays, enhanced proliferation and IL-2 production occurred. These cellular responses were not seen when 10(3) allogeneic leukocytes were transfused. Thus, the results suggest that leukoreduced platelet transfusions induce antidonor MHC antibodies and CD8+ CTL responses in recipient mice. At the same time, the transfusions induced recipient CD4+ T-cell activation when incubated with donor platelets in the presence of syngeneic APCs, an indirect recognition pathway that correlates with the time of alloantibody production.

Animals↗
PubMed1994

Monoclonal antibodies to platelet glycoproteins Ib and IIb/IIIa inhibit adhesion of platelets to purified solid-phase von Willebrand factor.

Platelet membrane glycoproteins Ib (GPIb) and IIb/IIIa (GPIIb/IIIa) bind soluble von Willebrand factor (vWf) after stimulation with ristocetin (GPIb) or with thrombin or ADP (GPIIb/IIIa). In fluid-phase, vWf does not bind to these platelet receptors without stimulation. In contrast, platelets adhere to solid-phase vWf without stimulation by ristocetin, adenosine diphosphate (ADP), or thrombin, and adhesion increases after stimulation by these agonists. The effect of monoclonal antibodies specific for GPIb (6D1) and GPIIb/IIIa (10E5 and HP1-1D) on platelet adhesion to solid-phase vWF was studied. Adhesion of radiolabeled, washed platelets (with washed red blood cells) aspirated at a constant wall shear rate of 1000 sec-1 through glass capillary tubes coated with purified human vWf was quantified. Unstimulated platelet adhesion was decreased 80% to 90% by blocking either the GPIb site or the GPIIb/IIIa site with 6D1 or 10E5, respectively, or with 6D1 and 10E5 together. Adhesion was not reduced significantly by HP1-1D (anti-GPIIb/IIIa). After stimulation with ADP or thrombin, the platelet adhesion was reduced by prior incubation with saturating concentrations of either 6D1 (61% reduction) or 10E5 (80% reduction), as well as with both 6D1 and 10E5 (80% reduction). After stimulation with ristocetin, the adhesion was reduced with either 6D1 (90% reduction) or 10E5 (90% reduction) or both 6D1 and 10E5 (90% reduction). Prior incubation with HP1-1D had minimal effect on platelet adhesion to vWF after stimulation with thrombin, ADP, or ristocetin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMedDate not supplied

Morphological alterations of blood platelets induced by platelet activating factor (PAF) and partial inhibition by ketoprofen in calves.

The influence of platelet activating factor (PAF) was investigated in vivo on the ultrastructure of bovine platelets, and on the platelet count. The effect of an intravenous administration of ketoprofen (a non-steroidal anti-inflammatory drug) pretreatment followed by PAF infusion was also observed in a group of six healthy male Friesian calves. PAF infusion alone caused a moderate thrombocytopenia, which peaked one minute post challenge and returned to levels not significantly different from control after 30 min. Electron microscopy revealed that after PAF infusion, platelets lost their lentiform shape and became irregular, with many pseudopods. Their microtubules became impossible to distinguish. The numbers of alpha granules and dense bodies were significantly decreased. Glycogen particles became rare or even disappeared. Giant platelets occasionally appeared. The Golgi apparatus was more often visible and the number of mitochondria was significantly increased. Ketoprofen pretreatment lowered PAF-induced thrombocytopenia and decrease in the number of dense bodies. Under these conditions, the Golgi apparatus was rarely visible and giant platelets were not observed. These results showed that the morphological ultrastructure of blood platelets in bovines were modified following PAF infusion and that ketoprofen pretreatment before PAF infusion provided partial protection, limiting the extent of the morphological alterations and maintaining a normal platelet count.

Animals↗
PubMed2004

Variable inhibition of high-shear-induced platelet plug formation by eptifibatide and tirofiban under conditions of platelet activation and high von Willebrand release: a randomized, placebo-controlled, clinical trial.

BACKGROUND: Glycoprotein (GP) IIb/IIIa antagonists have become a mainstay for the treatment of acute coronary syndromes. Yet, they have rarely been evaluated under relevant pathophysiologic conditions, for example, high shear rates in the presence of physiologic calcium concentrations. We compared the efficacy of eptifibatide and tirofiban versus placebo on high shear-induced platelet plug formation in a model in which healthy subjects exhibit von Willebrand factor concentrations and platelet activation comparable to patients with acute coronary syndromes. METHODS: Thirty male volunteers received 2 ng/kg endotoxin and standard doses of eptifibatide, tirofiban, or placebo over a period of 5 hours in a randomized, double-blinded, placebo-controlled, double-dummy parallel-group trial. Platelet inhibition was measured with the Platelet Function Analyzer-100 (PFA-100) and the Ultegra method. RESULTS: Although bolus infusion of both GPIIb/IIIa antagonists inhibited high shear-induced platelet plug formation, continuous infusion of eptifibatide prolonged closure times more effectively than did tirofiban (P <.008). Interestingly, tirofiban had only placebo-like effects on platelet plug formation after 2 hours. However, when additional drug was exogenously added, closure time values were maximally prolonged in all cases. CONCLUSIONS: Standard doses, particularly of tirofiban, have limited impact on high shear-induced platelet plug formation at physiologic Ca(2+) concentrations.

Adolescent↗
PubMed1999

Evaluation of platelet function with the PFA-100 system in patients with congenital defects of platelet secretion.

The template bleeding time is still the screening test for defects of platelet function, although it is an invasive and poorly reproducible technique. The PFA-100 measures platelet function at high shear. Whole blood is aspirated through a capillary to an aperture of a membrane coated with platelet agonists. The system measures the time required to obtain occlusion of the aperture by a platelet plug (closure time). We measured the closure times in the PFA-100 system and the bleeding time in seven patients with delta-storage pool deficiency, 10 patients with "primary secretion defect" (not due to abnormalities of platelet granules or the arachidonate pathway), and 40 controls. Measurements were repeated I and 4 hours after intravenous infusion of desmopressin in six delta-storage pool deficiency and eight primary secretion defect patients. Baseline bleeding time and closure times with the collagen/epinephrine cartridge were longer in delta-storage pool deficiency and primary secretion defect patients than in controls. In contrast, closure times with the collagen/adenosine diphosphate cartridge were normal in both delta-storage pool deficiency and primary secretion defect patients. Treatment with desmopressin increased the plasma von Willebrand Factor levels, shortened the prolonged bleeding time, shortened the closure times with the collagen/adenosine diphosphate cartridge, and normalized the closure times with the collagen/ epinephrine cartridge. Therefore, the PFA-100 test may be a less invasive alternative to the bleeding time in the diagnosis and therapeutic monitoring of patients with platelet secretion defects. The collagen/epinephrine cartridge is more sensitive than the collagen/adenosine diphosphate cartridge to defects of platelet secretion.

Adult↗