scholarly journals Intragastric Application of Aspirin, Clopidogrel, Cilostazol, and BPC 157 in Rats: Platelet Aggregation and Blood Clot

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Sanja Konosic ◽  
Mate Petricevic ◽  
Visnja Ivancan ◽  
Lucija Konosic ◽  
Eleonora Goluza ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Blood Clot ◽  
Alpha Angle ◽  
Adenosine Diphosphate ◽  
Antithrombotic Agent ◽  
Bpc 157 ◽  
Multiple Electrode Aggregometry ◽  
Pentadecapeptide Bpc 157 ◽  
Clot Formation Time

We suggest that the stable gastric pentadecapeptide BPC 157 may rescue thrombocyte function. We focused on the antithrombotic agent aspirin, clopidogrel, and cilostazol application in rats; arachidonic acid, ADP, collagen, and arachidonic acid/PGE1 platelet aggregation (aggregometry) and blood clot viscoelastic properties (thromboelastometry); and the pentadecapeptide BPC 157. Rats received intragastrically for three days once daily treatment with antithrombotic agents—aspirin (10 mg/kg) or clopidogrel (10 mg/kg) or cilostazol (10 mg/kg). Medication (BPC 157 (10 μg/kg) or an equal volume of saline (5 ml/kg)) was given intragastrically, immediately after each antithrombotic agent application. For multiple electrode aggregometry and modified rotational thromboelastometry studies, blood sampling was at 2 h after last application. Adenosine diphosphate (ADP test 6.5 μM), arachidonic acid (ASPI test 0.5 mM), a combination of arachidonic acid and prostaglandin E1 (ASPI test 0.5 mM and PGE1-test 30 nM), and collagen (COL test 3.2 μg/ml) were used as aggregation agonists. Given with aspirin, clopidogrel, or cilostazol in rats, BPC 157 counteracted their inhibitory effects on aggregation activated by arachidonic acid, ADP, collagen, and arachidonic acid/PGE1. Specifically, this includes recovery of the aggregation induced by arachidonic acid (vs. aspirin, vs. clopidogrel, and vs. cilostazol), arachidonic acid/PGE1 (vs. cilostazol), ADP (vs. clopidogrel), or collagen (vs. clopidogrel). Contrarily, there is no effect on the used tests (extrinsic/intrinsic hemostasis system, the fibrin part of the clot) EXTEM, INTEM, and FIBTEM; clotting time; clot formation time; alpha-angle; maximum clot firmness; lysis index after 30 minutes; and maximum lysis. In conclusion, we revealed that BPC 157 largely rescues thrombocyte function.

The Essential Ectoenzyme SmNPP5 from the Human Intravascular Parasite Schistosoma mansoni is an ADPase and a Potent Inhibitor of Platelet Aggregation

2018 ◽  
Vol 118 (06) ◽  
pp. 979-989 ◽  
Author(s):  
Manal Elzoheiry ◽  
Akram Da'dara ◽  
Armelle deLaforcade ◽  
Samar El-Beshbishi ◽  
Patrick Skelly
Keyword(s):  
Platelet Aggregation ◽  
Schistosoma Mansoni ◽  
Thrombus Formation ◽  
Blood Clot ◽  
Adenosine Diphosphate ◽  
Dependent Manner ◽  
Multiple Electrode Aggregometry ◽  
Activity Measurements ◽  
Host Parasite

AbstractSchistosomes are intravascular parasitic platyhelminthes infecting > 200 million people globally and causing a debilitating disease, schistosomiasis. Despite the relatively large size of the adult worms and their disruption of blood flow, surprisingly, they do not appear to provoke thrombus formation around them in vivo. We hypothesize that proteins expressed at the host–parasite interface are key to this ability. Here, we functionally express an ectonucleotide pyrophosphatase/phosphodiesterase homologue, SmNPP5, that is expressed at the tegumental surface of intravascular Schistosoma mansoni. We report that SmNPP5, a known virulence factor for the worms, is a type one glycoprotein that cleaves the artificial substrate p-Nph-5′-TMP in a reaction that requires cations and at an optimal pH of 9. Using immunolocalization and enzyme activity measurements, we confirm that SmNPP5 is exclusively expressed at the host interactive surface of all intravascular life stages. SmNPP5 inhibits platelet aggregation in a dose-dependent manner, as measured by multiple electrode aggregometry (MEA) using whole blood. Inhibition is apparent when either collagen or adenosine diphosphate (ADP) is used as agonist but is lost following heat treatment of SmNPP5. Unlike its mammalian homologue, NPP5, the schistosome protein cleaves ADP and with a Km of 246 ± 34 µM. In sum, SmNPP5 is expressed in the intravascular environment where it can degrade ADP and act as an anticoagulant. In this manner, the protein likely helps limit blood clot formation around the worms in vivo to permit the parasites free movement within the vasculature.

scholarly journals Effect of alteplase on platelet function and receptor expression

2019 ◽  
Vol 47 (4) ◽  
pp. 1731-1739 ◽  
Author(s):  
Jun Lu ◽  
Peng Hu ◽  
Guangyu Wei ◽  
Qi Luo ◽  
Jianlin Qiao ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Platelet Activation ◽  
Platelet Function ◽  
Adenosine Diphosphate ◽  
Receptor Expression ◽  
Light Transmittance ◽  
Dependent Manner ◽  
Clot Retraction ◽  
Platelet Receptors

Objective To investigate the role of alteplase, a widely-used thrombolytic drug, in platelet function. Methods Human platelets were incubated with different concentrations of alteplase followed by analysis of platelet aggregation in response to adenosine diphosphate (ADP), collagen, ristocetin, arachidonic acid or epinephrine using light transmittance aggregometry. Platelet activation and surface levels of platelet receptors GPIbα, GPVI and αIIbβ3 were analysed using flow cytometry. The effect of alteplase on clot retraction was also examined. Results This study demonstrated that alteplase significantly inhibited platelet aggregation in response to ADP, collagen and epinephrine in a dose-dependent manner, but it did not affect ristocetin- or arachidonic acid-induced platelet aggregation. Alteplase did not affect platelet activation as demonstrated by no differences in P-selectin levels and PAC-1 binding being observed in collagen-stimulated platelets after alteplase treatment compared with vehicle. There were no changes in the surface levels of the platelet receptors GPIbα, GPVI and αIIbβ3 in alteplase-treated platelets. Alteplase treatment reduced thrombin-mediated clot retraction. Conclusions Alteplase inhibits platelet aggregation and clot retraction without affecting platelet activation and surface receptor levels.

A Study of Intravascular Platelet Aggregation in the Rat

1979 ◽  
Author(s):  
G. G. Duncan ◽  
G. M. Smith
Keyword(s):  
Arachidonic Acid ◽  
Platelet Count ◽  
Platelet Aggregation ◽  
Thromboxane A2 ◽  
Adenosine Diphosphate ◽  
Residual Response ◽  
Induced Aggregation ◽  
Anaesthetized Rat

Intravascular platelet aggregation can be studied by measuring the fall in the circulating platelet count induced by aggregating agents in anaesthetized animals. The Technicon Auto-counter was modified and connected via a double cannula to an anaesthetized rat to give a continuous count of the number of circulating platelets (1). Adenosine diphosphate (ADP), Collagen, Arachidonic acid (AA) and 5-Hydroxytryptamine (5-HT) were given at 15 minute intervals over a period of 2-3 hours. Aspirin (10 mg/Kg IV ) and Indomethacin (1-8 mg/Kg IV) partially inhibited collagen-induced aggregation and Indomethacin (2 mg/Kg IV) completely inhibited AA-induced aggregation. Adenosine (0.25 mg/min) inhibited the ADP-induced aggregation but did not inhibit aggregation produced by collagen or the residual response to collagen that remains after the addition of indomethacin.Reproducible responses to ADP and collagen were obtained but responses to AA and 5-HT were not reliable. Collagen-induced aggregation is thought to be mediated by the liberation of ADP, 5-HT and the formation of prostaglandin (PG ) endoperoxides and thromboxane A2. This study has shown that collagen-induced aggregation is reduced by inhibition of PG synthesis but the involvement of ADP or 5-HT could not be shown.

scholarly journals Platelet malondialdehyde production and aggregation responses induced by arachidonate, prostaglandin-G2, collagen, and epinephrine in 12 patients with storage pool deficiency

Blood ◽  
1981 ◽  
Vol 58 (1) ◽  
pp. 27-33
Author(s):  
HJ Weiss ◽  
B Lages
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Adenosine Diphosphate ◽  
Synthetic Pathway ◽  
Dense Granules ◽  
Storage Pool ◽  
Increased Sensitivity

We assessed the integrity of the prostaglandin synthetic pathway by measuring malondialdehyde (MDA) production and studied platelet aggregation responses to arachidonic acid and PGG2 in 12 patients with storage pool deficiency (SPD). Eight patients were deficient only in dense granules (delta-SPD) and four were deficient in both dense and alpha-granules (alpha delta-SPD). Production of MDA in response to arachidonic acid (AA), epinephrine, and collagen suggested that the transformation of AA to prostaglandin metabolites was normal in delta- SPD but abnormal in alpha delta-SPD and that the liberation of AA from phospholipids were abnormal in the majority of patients with SPD. Since the content of secretable adenosine diphosphate (ADP) is diminished in SPD platelets, the aggregation responses of these platelets to AA and PGG2 were studied to help answer the question whether these agents aggregate platelets directly or through release of endogenous ADP. Among patients with delta-SPD, aggregation by both AA and PGG2 was decreased in four albinos whose platelets were markedly deficient in ADP. In contrast, normal, or less strikingly abnormal, responses were observed in patients whose platelets either contained higher levels of platelet ADP or showed increased sensitivity to ADP. The more marked impaired responses to AA and PGG2 in patients with alpha delta-SPD suggest that substances derived from alpha-granules may also play a role in platelet aggregation by these agents. The aggregation responses in these patients with various types of SPD is consistent with a theory that granule-derived ADP mediates platelet aggregation by AA and PGG2.

scholarly journals Monitoring the entry of new platelets into the circulation after ingestion of aspirin

Blood ◽  
1983 ◽  
Vol 61 (6) ◽  
pp. 1081-1085
Author(s):  
G Di Minno ◽  
MJ Silver ◽  
S Murphy
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Adenosine Diphosphate ◽  
Normal Subjects ◽  
In Vitro Experiments ◽  
Early Entry ◽  
Cyclooxygenase Activity ◽  
Aspirin Ingestion ◽  
Thromboxane Formation

There have been reports of a 24–48-hr delay in the recovery of platelet cyclooxygenase activity and platelet function after the ingestion of aspirin. However, these studies employed a single aggregating agent to stimulate enzymatic or functional activity. We investigated the effects of some pairs of aggregating agents on 14 platelet-rich plasmas (PRP) from normal subjects 2 and 4 hr after ingestion of 650 mg aspirin and daily up to 72 hr. We studied platelet aggregation and secretion with a lumiaggregometer and thromboxane-B2 formation by radioimmunoassay. Aggregation and secretion occurred as early as 4 hr after aspirin ingestion in response to combinations of arachidonic acid with epinephrine, collagen, or adenosine diphosphate (ADP). Thromboxane formation was detected as early as 4 hr after ingestion of aspirin in response to 1 mM arachidonic acid in combination with 1 microgram/ml collagen. Up to 72 hr, there was a linear return of thromboxane formation stimulated by this combination, reflecting the entry of new platelets into the circulation. In vitro experiments with mixtures of aspirin-free and aspirin-treated platelets showed that the combination of collagen and arachidonic acid (AA) could produce full aggregation and secretion when only 2.5% of aspirin-free platelets were present. Use of the combination of collagen plus AA demonstrates the early entry into the circulation of platelets originating from megakaryocytes whose cyclooxygenase has not been completely acetylated.

scholarly journals Platelet malondialdehyde production and aggregation responses induced by arachidonate, prostaglandin-G2, collagen, and epinephrine in 12 patients with storage pool deficiency

Blood ◽  
1981 ◽  
Vol 58 (1) ◽  
pp. 27-33 ◽  
Author(s):  
HJ Weiss ◽  
B Lages
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Adenosine Diphosphate ◽  
Synthetic Pathway ◽  
Dense Granules ◽  
Storage Pool ◽  
Increased Sensitivity

Abstract We assessed the integrity of the prostaglandin synthetic pathway by measuring malondialdehyde (MDA) production and studied platelet aggregation responses to arachidonic acid and PGG2 in 12 patients with storage pool deficiency (SPD). Eight patients were deficient only in dense granules (delta-SPD) and four were deficient in both dense and alpha-granules (alpha delta-SPD). Production of MDA in response to arachidonic acid (AA), epinephrine, and collagen suggested that the transformation of AA to prostaglandin metabolites was normal in delta- SPD but abnormal in alpha delta-SPD and that the liberation of AA from phospholipids were abnormal in the majority of patients with SPD. Since the content of secretable adenosine diphosphate (ADP) is diminished in SPD platelets, the aggregation responses of these platelets to AA and PGG2 were studied to help answer the question whether these agents aggregate platelets directly or through release of endogenous ADP. Among patients with delta-SPD, aggregation by both AA and PGG2 was decreased in four albinos whose platelets were markedly deficient in ADP. In contrast, normal, or less strikingly abnormal, responses were observed in patients whose platelets either contained higher levels of platelet ADP or showed increased sensitivity to ADP. The more marked impaired responses to AA and PGG2 in patients with alpha delta-SPD suggest that substances derived from alpha-granules may also play a role in platelet aggregation by these agents. The aggregation responses in these patients with various types of SPD is consistent with a theory that granule-derived ADP mediates platelet aggregation by AA and PGG2.

Comparison of the effects of diltiazem and aspirin on platelet aggregation in cats

1996 ◽  
Vol 32 (1) ◽  
pp. 11-18 ◽  
Author(s):  
EN Behrend ◽  
GF Grauer ◽  
DS Greco ◽  
BJ Rose ◽  
MA Thrall
Keyword(s):  
Body Weight ◽  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Adenosine Triphosphate ◽  
Adenosine Diphosphate ◽  
Impedance Change ◽  
Collagen Secretion ◽  
Baseline Values

Platelet aggregation in response to collagen (1 or 3 micrograms/ml), arachidonic acid (10(-2) M), and adenosine diphosphate (ADP, 2 microM) was compared in healthy cats treated with diltiazem (approximately 2 mg/kg body weight, q 8 hrs for 10 doses), aspirin (approximately 21 mg/kg body weight [1 baby aspirin], q 72 hrs for three doses), or a combination of diltiazem and aspirin. Baseline values obtained prior to treatment served as controls. Addition of arachidonic acid to blood resulted in an impedance change (i.e., aggregation) with time in samples from the nontreated cats and the cats treated with diltiazem, but the addition had no effect in blood from cats treated with aspirin alone or with a combination of diltiazem and aspirin. Platelet aggregation in response to either concentration of collagen or to ADP was not altered by any treatment. Secretion of adenosine triphosphate (ATP) from the platelets was measured when the aggregating agent was 3 micrograms/ml collagen; secretion was not affected by any treatment.

ADP and arachidonic acid induced platelet aggregation in schizophrenia and atypical psychoses

1984 ◽  
Vol 14 (1) ◽  
pp. 207-211 ◽  
Author(s):  
L. J. Whalley ◽  
H. W. Reading ◽  
R. Rosie
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Adenosine Diphosphate ◽  
Healthy Controls ◽  
Chronic Schizophrenics ◽  
Nervous System Function ◽  
Aggregation And Disaggregation ◽  
The Difference ◽  
Drug Free

SynopsisPlatelet aggregatory responses to adenosine diphosphate (ADP) and arachidonic acid were examined in 6 drug-free schizophrenics, 5 other drug-free psychotics, 8 ‘acute-on-chronic’ schizophrenics (on long-term neuroleptic therapy) and 38 healthy controls. Platelet aggregation and disaggregation following ADP was significantly lower in ‘acute-on-chronic’ schizophrenics (on drugs) compared with healthy controls, and disaggregation following 1 µM ADP was significantly less in drug-free schizophrenics. The difference between maximum aggregation induced by ADP and that induced by arachidonic acid was significantly greater in schizophrenics (both on drugs and drug-free) than in controls. These findings are related to possible abnormalities of central nervous system function in schizophrenia.

Thiopental enhances human platelet aggregation by increasing arachidonic acid release

2001 ◽  
Vol 79 (10) ◽  
pp. 854-860 ◽  
Author(s):  
Rie Kitamura ◽  
Hideo Hirakata ◽  
Hiroto Okuda ◽  
Masami Sato ◽  
Hiroshi Toda ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
Cytosolic Calcium ◽  
Free Calcium ◽  
Human Platelet Aggregation ◽  
Low Concentrations ◽  
Acid Release ◽  
Control Study

Conflicting results have been reported regarding the effect of thiopental on aggregation and cytosolic calcium levels in platelets. The present study attempted to clarify these phenomena. Using platelet-rich plasma or washed suspensions, platelet aggregation, thromboxane (TX) B2 formation, arachidonic acid (AA) release, and cytosolic free calcium concentrations ([Ca2+]i) were measured in the presence or absence of thiopental (30–300 µM). Platelet activation was induced by adenosine diphosphate (ADP, 0.5–15 µM), epinephrine (0.1–20 µM) arachidonic acid (0.5–1.5 mM), or (+)-9,11-epithia-11,12-methano-TXA2 (STA2, 30–500 nM). Measurements of primary aggregation were performed in the presence of indomethacin (10 µM). Low concentrations of ADP and epinephrine, which did not induce secondary aggregation in a control study, induced strong secondary aggregation in the presence of thiopental ([Formula: see text]100 µM). Thiopental ([Formula: see text]100 µM) also increased the TXB2 formation induced by ADP and epinephrine. Thiopental (300 µM) increased ADP- and epinephrine-induced 3H-AA release. Thiopental (300 µM) also augmented the ADP- and epinephrine-induced increases in [Ca2+]i in the presence of indomethacin. Thiopental appears to enhance ADP- and epinephrine-induced secondary platelet aggregation by increasing AA release during primary aggregation, possibly by the activation of phospholipase A2.Key words: barbiturates, anesthetics, eicosanoids, phospholipase.

A polyphenol-rich diet is associated with decreased platelet aggregation in breast cancer patients

2019 ◽  
Vol 54 (2) ◽  
pp. 81-84
Author(s):  
Agnieszka Sut ◽  
Marcin Różalski ◽  
Jacek Golański ◽  
Maria Pytel ◽  
Marek Zadrożny
Keyword(s):  
Breast Cancer ◽  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Dietary Intake ◽  
Cancer Patients ◽  
Platelet Reactivity ◽  
Breast Cancer Patients ◽  
Plant Polyphenols ◽  
Multiple Electrode Aggregometry ◽  
Polyphenol Intake

It is well documented that plant polyphenols have both anti-cancer and anti-platelet effects. Hence, the aim of this work was to investigate a relationship between dietary intake of polyphenols and platelet aggregation in newly-diagnosed breast cancer patients. The nutritional value of a diet, including dietary intake of plant polyphenols was estimated. Platelet aggregation was induced with arachidonic acid (0.5 mmol/l), collagen (3.2 μg/ml) or ADP (6.4 μmol/l) and measured using multiple electrode aggregometry (Multiplate<sup>®</sup>) in whole blood. It was found that platelet aggregation was significantly higher in the low polyphenol intake group than the high intake group: the respective values (area under the aggregation curve recorded in units; U) were arachidonic acid: 84.8 vs. 65.3, P=0.003; ADP: 76.5 vs. 67.8, P=0.006; collagen 79.5 vs. 64.3, p=0.024 respectively. The study indicates, for the first time, an association between diet rich in polyphenols and reduced platelet reactivity in breast cancer patients.

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