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  1. Thrombocyte counts in mice after the administration of papaya leaf suspension
    Sathasivam K, Ramanathan S, Mansor SM, Haris MR, Wernsdorfer WH
    Wien Klin Wochenschr, 2009 Oct;121 Suppl 3:19-22.
    PMID: 19915811 DOI: 10.1007/s00508-009-1229-0
    Following up a popular use of crude leaf preparations from Carica papaya for the treatment of dengue infections, a suspension of powdered Carica papaya leaves in palm oil has been investigated for its effect on thrombocyte counts in mice, administering by gavage 15 mg of powdered leaves per kg body weight to 5 mice. Equal numbers of animals received corresponding volumes of either palm oil alone or physiological saline solution. Thrombocyte counts before and at 1, 2, 4, 8, 10, 12, 24, 48 and 72 hours after dosing revealed significantly higher mean counts at 1, 2, 4, 8, 10 and 12 after dosing with the C. papaya leaf formulation as compared to the mean count at hour 0. There was only a non-significant rise of thrombocyte counts in the group having received saline solution, possibly the expression of a normal circadian rhythm in mice. The group having received palm oil only showed a protracted increase of platelet counts that was significant at hours 8 and 48 and obviously the result of a hitherto unknown stimulation of thrombocyte release. The results call for a dose-response investigation and for extending the studies to the isolation and identification of the C. papaya substances responsible for the release and/or production of thrombocytes.
    Matched MeSH terms: Blood Platelets/drug effects*
  2. The effect of CYP2C19 genetic polymorphism and non-genetic factors on clopidogrel platelets inhibition in East Asian coronary artery disease patients
    Amin AM, Sheau Chin L, Mohamed Noor DA, Mostafa H, Abdul Kader MASK, Kah Hay Y, et al.
    Thromb Res, 2017 10;158:22-24.
    PMID: 28802144 DOI: 10.1016/j.thromres.2017.07.032
    Matched MeSH terms: Blood Platelets/drug effects*
  3. Short-term estrogen replacement therapy reduces platelet marker levels in Malaysian postmenopausal women
    Sheikh SA, Roshan TM, Khattak MN, Baig AA, Noor SJ, Hassan R, et al.
    Menopause Int, 2011 Mar;17(1):6-10.
    PMID: 21427417 DOI: 10.1258/mi.2011.011001
    In healthy postmenopausal women (PMW) increased platelet activation has been associated with adverse cardiovascular events. There is much debate about the relationship between platelet function and serum estradiol level in PMW. This study assessed the effect of short-term oral estrogen replacement therapy (ERT) on platelet activation markers (CD62P and PAC-1) and its correlation with age and body mass index (BMI) among healthy PMW.
    Matched MeSH terms: Blood Platelets/drug effects*
  4. Fulltext Ruthenium-conjugated chrysin analogues modulate platelet activity, thrombus formation and haemostasis with enhanced efficacy
    Ravishankar D, Salamah M, Attina A, Pothi R, Vallance TM, Javed M, et al.
    Sci Rep, 2017 07 18;7(1):5738.
    PMID: 28720875 DOI: 10.1038/s41598-017-05936-3
    The constant increase in cardiovascular disease rate coupled with significant drawbacks of existing therapies emphasise the necessity to improve therapeutic strategies. Natural flavonoids exert innumerable pharmacological effects in humans. Here, we demonstrate the effects of chrysin, a natural flavonoid found largely in honey and passionflower on the modulation of platelet function, haemostasis and thrombosis. Chrysin displayed significant inhibitory effects on isolated platelets, however, its activity was substantially reduced under physiological conditions. In order to increase the efficacy of chrysin, a sulfur derivative (thio-chrysin), and ruthenium-complexes (Ru-chrysin and Ru-thio-chrysin) were synthesised and their effects on the modulation of platelet function were evaluated. Indeed, Ru-thio-chrysin displayed a 4-fold greater inhibition of platelet function and thrombus formation in vitro than chrysin under physiologically relevant conditions such as in platelet-rich plasma and whole blood. Notably, Ru-thio-chrysin exhibited similar efficacy to chrysin in the modulation of haemostasis in mice. Increased bioavailability and cell permeability of Ru-thio-chrysin compared to chrysin were found to be the basis for its enhanced activity. Together, these results demonstrate that Ru-thio-coupled natural compounds such as chrysin may serve as promising templates for the development of novel anti-thrombotic agents.
    Matched MeSH terms: Blood Platelets/drug effects*
  5. Fulltext Prevailing Knowledge on the Bioavailability and Biological Activities of Sulphur Compounds from Alliums: A Potential Drug Candidate
    Subramanian MS, Nandagopal Ms G, Amin Nordin S, Thilakavathy K, Joseph N
    Molecules, 2020 Sep 09;25(18).
    PMID: 32916777 DOI: 10.3390/molecules25184111
    Allium sativum (garlic) is widely known and is consumed as a natural prophylactic worldwide. It produces more than 200 identified chemical compounds, with more than 20 different kinds of sulfide compounds. The sulfide compounds particularly are proven to contribute to its various biological roles and pharmacological properties such as antimicrobial, antithrombotic, hypoglycemic, antitumour, and hypolipidemic. Therefore, it is often referred as disease-preventive food. Sulphur-containing compounds from A. sativum are derivatives of S-alkenyl-l-cysteine sulfoxides, ajoene molecules, thiosulfinates, sulfides, and S-allylcysteine. This review presents an overview of the water-soluble and oil-soluble sulphur based phytochemical compounds present in garlic, highlighting their mechanism of action in treating various health conditions. However, its role as a therapeutic agent should be extensively studied as it depends on factors such as the effective dosage and the suitable method of preparation.
    Matched MeSH terms: Blood Platelets/drug effects
  6. Platelet-activating factor (PAF) receptor binding antagonist activity of the methanol extracts and isolated flavonoids from Chromolaena odorata (L.) King and Robinson
    Ling SK, Pisar MM, Man S
    Biol Pharm Bull, 2007 Jun;30(6):1150-2.
    PMID: 17541171
    The leaf, stem and root extracts of Chromolaena odorata were evaluated for their effect on platelet-activating factor (PAF) receptor binding on rabbit platelets using 3H-PAF as a ligand. The leaf extract demonstrated high PAF receptor binding inhibitory activity of 79.2+/-2.1% at 18.2 microg/ml. A total of eleven flavonoids were subsequently isolated from the active leaf extract and evaluated for their effects on PAF receptor binding. Eight of the flavonoids exhibited >50% inhibition on the binding activity at 18.2 microg/ml. These flavonoids were identified as eriodictyol 7,4'-dimethyl ether, quercetin 7,4'-methyl ether, naringenin 4'-methyl ether, kaempferol 4'-methyl ether, kaempferol 3-O-rutinoside, taxifolin 4'-methyl ether, taxifolin 7-methyl ether and quercetin 4'-methyl ether. Their IC50 values ranged from 19.5 to 62.1 microM.
    Matched MeSH terms: Blood Platelets/drug effects
  7. Fulltext Platelet-activating factor (PAF) antagonistic activity of a new biflavonoid from Garcinia nervosa var. pubescens King
    Jalil J, Jantan I, Ghani AA, Murad S
    Molecules, 2012 Sep 10;17(9):10893-901.
    PMID: 22964504 DOI: 10.3390/molecules170910893
    The methanol extract of the leaves of Garcinia nervosa var. pubescens King, which showed strong inhibitory effects on platelet-activating factor (PAF) receptor binding, was subjected to bioassay-guided isolation to obtain a new biflavonoid, II-3,I-5, II-5,II-7,I-4',II-4'-hexahydroxy-(I-3,II-8)-flavonylflavanonol together with two known flavonoids, 6-methyl-4'-methoxyflavone and acacetin. The structures of the compounds were elucidated by spectroscopic methods. The compounds were evaluated for their ability to inhibit PAF receptor binding to rabbit platelets using ³H-PAF as a ligand. The biflavonoid and acacetin showed strong inhibition with IC₅₀ values of 28.0 and 20.4 µM, respectively. The results suggest that these compounds could be responsible for the strong PAF antagonistic activity of the plant.
    Matched MeSH terms: Blood Platelets/drug effects
  8. Platelet enhancement by Carica papaya L. leaf fractions in cyclophosphamide induced thrombocytopenic rats is due to elevated expression of CD110 receptor on megakaryocytes
    Nandini C, Madhunapantula SV, Bovilla VR, Ali M, Mruthunjaya K, Santhepete MN, et al.
    J Ethnopharmacol, 2021 Jul 15;275:114074.
    PMID: 33831466 DOI: 10.1016/j.jep.2021.114074
    ETHNOPHARMACOLOGICAL RELEVANCE: Carica papaya leaf juice/decoction has been in use in folk medicine in Srilanka, Malaysia and in few parts of India for enhancing the platelet counts in dengue. In Siddha medicine, a traditional form of medicine in India, papaya leaf juice has been used for increasing the platelet counts. Papaya leaf has been reported to enhance blood volume in ancient Ayurveda books in India. Carica papaya leaf is well known for its platelet enhancement activity. Although many preclinical and clinical studies have demonstrated the ability of papaya leaf juice for platelet enhancement, but the underlying mechanisms are still unclear.

    AIM OF THE STUDY: The study is aimed at identifying the key ingredients of papaya leaf extract and elucidate the mechanism (s) of action of the identified potent component in mitigating thrombocytopenia (Thp).

    MATERIALS AND METHODS: C. papaya leaf juice was subjected for sequential fractionation to identify the anti-thrombocytopenic phytochemicals. In vivo, stable thrombocytopenia was induced by subcutaneous injection of 70 mg/kg cyclophosphamide (Cyp). After induction, rats were treated with 200 and 400 mg/kg body weight papaya leaf juice and with identified fractions for 14 days. Serum thrombopoietin level was estimated using ELISA. CD110/cMpl, a receptor for thrombopoietin on platelets was measured by western blotting.

    RESULTS: Administration of cyclophosphamide for 6 days induced thrombocytopenia (210.4 ± 14.2 × 103 cells/μL) in rats. Treating thrombocytopenic rats with papaya leaf juice and butanol fraction for 14 days significantly increased the platelet count to 1073.50 ± 29.6 and 1189.80 ± 36.5 × 103 cells/μL, respectively. C.papaya extracts normalized the elevated bleeding and clotting time and decreased oxidative markers by increasing endogenous antioxidants. A marginal increase in the serum thrombopoietin (TPO) level was observed in Cyp treated group compared to normal and treatment groups. Low expression of CD110/cMpl receptor found in Cyp treated group was enhanced by C. papaya extracts (CPJ) and CPJ-BT. Furthermore, examination of the morphology of bone marrow megakaryocytes, histopathology of liver and kidneys revealed the ability of CPJ and fractions in mitigating Cyp-induced thrombocytopenia in rats.

    CONCLUSION: C. papaya leaf juice enhances the platelet count in chemotherapy-induced thrombocytopenia by increasing the expression of CD110 receptor on the megakaryocytes. Hence, activating CD110 receptor might be a viable strategy to increase the platelet production in individuals suffering from thrombocytopenia.

    Matched MeSH terms: Blood Platelets/drug effects*
  9. Physicochemical evaluation and in vitro hemocompatibility study on nanoporous hydroxyapatite
    Ooi CH, Ling YP, Abdullah WZ, Mustafa AZ, Pung SY, Yeoh FY
    J Mater Sci Mater Med, 2019 Mar 30;30(4):44.
    PMID: 30929088 DOI: 10.1007/s10856-019-6247-5
    Hydroxyapatite is an ideal biomaterial for bone tissue engineering due to its biocompatibility and hemocompatibility which have been widely studied by many researchers. The incorporation of nanoporosity into hydroxyapatite could transform the biomaterial into an effective adsorbent for uremic toxins removal especially in artificial kidney system. However, the effect of nanoporosity incorporation on the hemocompatibility of hydroxyapatite has yet to be answered. In this study, nanoporous hydroxyapatite was synthesized using hydrothermal technique and its hemocompatibility was determined. Non-ionic surfactants were used as soft templates to create porosity in the hydroxyapatite. The presence of pure hydroxyapatite phase in the synthesized samples is validated by X-ray diffraction analysis and Fourier transform infrared spectroscopy. The TEM images show that the hydroxyapatite formed rod-like particles with the length of 21-90 nm and diameter of 11-70 nm. The hydroxyapatite samples exhibit BET surface area of 33-45 m2 g-1 and pore volume of 0.35-0.44 cm3 g-1. The hemocompatibility of the hydroxyapatite was determined via hemolysis test, platelet adhesion, platelet activation and blood clotting time measurement. The nanoporous hydroxyapatite shows less than 5% hemolysis, suggesting that the sample is highly hemocompatible. There is no activation and morphological change observed on the platelets adhered onto the hydroxyapatite. The blood clotting time demonstrates that the blood incubated with the hydroxyapatite did not coagulate. This study summarizes that the synthesized nanoporous hydroxyapatite is a highly hemocompatible biomaterial and could potentially be utilized in biomedical applications.
    Matched MeSH terms: Blood Platelets/drug effects*
  10. Pharmacometabolomics analysis of plasma to phenotype clopidogrel high on treatment platelets reactivity in coronary artery disease patients
    Amin AM, Sheau Chin L, Teh CH, Mostafa H, Mohamed Noor DA, Abdul Kader MASK, et al.
    Eur J Pharm Sci, 2018 May 30;117:351-361.
    PMID: 29526765 DOI: 10.1016/j.ejps.2018.03.011
    Dual antiplatelet therapy (DAPT) of clopidogrel and aspirin is crucial for coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI). However, some patients may endure clopidogrel high on treatment platelets reactivity (HTPR) which may cause thromboembolic events. Clopidogrel HTPR is multifactorial with some genetic and non-genetic factors contributing to it. We aimed to use nuclear magnetic resonance (1H NMR) pharmacometabolomics analysis of plasma to investigate this multifactorial and identify metabolic phenotypes and pathways associated with clopidogrel HTPR. Blood samples were collected from 71 CAD patients planned for interventional angiographic procedure (IAP) before the administration of clopidogrel 600 mg loading dose (LD) and 6 h after the LD. Platelets function testing was done 6 h post-LD using VerifyNow® P2Y12 assay. Pre-dose and post-dose plasma samples were analysed using 1H NMR. Multivariate statistical analysis was used to indicate the discriminating metabolites. Two metabotypes, each with 34 metabolites (pre-dose and post-dose) were associated with clopidogrel HTPR. Pathway analysis of these metabotypes revealed that aminoacyl-tRNA biosynthesis, nitrogen metabolism and glycine-serine-threonine metabolism are the most perturbed metabolic pathways associated with clopidogrel HTPR. Furthermore, the identified biomarkers indicated that clopidogrel HTPR is multifactorial where the metabolic phenotypes of insulin resistance, type two diabetes mellitus, obesity, gut-microbiota and heart failure are associated with it. Pharmacometabolomics analysis of plasma revealed new insights on the implicated metabolic pathways and the predisposing factors of clopidogrel HTPR.
    Matched MeSH terms: Blood Platelets/drug effects*
  11. PXR, CAR and HNF4alpha genotypes and their association with pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin in Asian patients
    Hor SY, Lee SC, Wong CI, Lim YW, Lim RC, Wang LZ, et al.
    Pharmacogenomics J, 2008 Apr;8(2):139-46.
    PMID: 17876342
    Previously studied candidate genes have failed to account for inter-individual variability of docetaxel and doxorubicin disposition and effects. We genotyped the transcriptional regulators of CYP3A and ABCB1 in 101 breast cancer patients from 3 Asian ethnic groups, that is, Chinese, Malays and Indians, in correlation with the pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin. While there was no ethnic difference in docetaxel and doxorubicin pharmacokinetics, ethnic difference in docetaxel- (ANOVA, P=0.001) and doxorubicin-induced (ANOVA, P=0.003) leukocyte suppression was observed, with Chinese and Indians experiencing greater degree of docetaxel-induced myelosuppression than Malays (Bonferroni, P=0.002, P=0.042), and Chinese experiencing greater degree of doxorubicin-induced myelosuppression than Malays and Indians (post hoc Bonferroni, P=0.024 and 0.025). Genotyping revealed both PXR and CAR to be well conserved; only a PXR 5'-untranslated region polymorphism (-24381A>C) and a silent CAR variant (Pro180Pro) were found at allele frequencies of 26 and 53%, respectively. Two non-synonymous variants were identified in HNF4alpha (Met49Val and Thr130Ile) at allele frequencies of 55 and 1%, respectively, with the Met49Val variant associated with slower neutrophil recovery in docetaxel-treated patients (ANOVA, P=0.046). Interactions were observed between HNF4alpha Met49Val and CAR Pro180Pro, with patients who were wild type for both variants experiencing least docetaxel-induced neutropenia (ANOVA, P=0.030). No other significant genotypic associations with pharmacokinetics or pharmacodynamics of either drug were found. The PXR-24381A>C variants were significantly more common in Indians compared to Chinese or Malays (32/18/21%, P=0.035) Inter-individual and inter-ethnic variations of docetaxel and doxorubicin pharmacokinetics or pharmacodynamics exist, but genotypic variability of the transcriptional regulators PAR, CAR and HNF4alpha cannot account for this variability.
    Matched MeSH terms: Blood Platelets/drug effects
  12. Late stent thrombosis in a patient with CYP2C19*3/*17 genotype and clopidogrel high on-treatment platelet reactivity
    Tan SSN, Koh KT, Tiong LL, Ong TK, Fong AYY
    Pharmacogenomics, 2018 10;19(15):1151-1157.
    PMID: 30191759 DOI: 10.2217/pgs-2018-0082
    AIM: Recurrent thrombotic events still occur despite dual antiplatelet therapy in patient's post percutaneous coronary intervention (PCI) could be attributed to high on-treatment platelet reactivity.

    METHODS: A 44-year-old male, who had staged PCI to left anterior descending (LAD) 2 weeks after an anterior MI, with a drug-coated stent was readmitted with new anterior STEMI 35 days later. Coronary angiogram revealed mid-stent thrombus in situ. He had further uncomplicated PCI. Platelet function testing and genotyping showed clopidogrel high on-treatment platelet reactivity and CYP2C19*3/*17 genotype. Ticagrelor was commenced.

    RESULTS & CONCLUSION: This case study is the first reported in Malaysia to document a patient with a CYP2C19*3/*17 genotype presenting with a stent thrombosis after an uncomplicated index PCI procedure.

    Matched MeSH terms: Blood Platelets/drug effects*
  13. Isorhapontigenin, a resveratrol analogue selectively inhibits ADP-stimulated platelet activation
    Ravishankar D, Albadawi DAI, Chaggar V, Patra PH, Williams HF, Salamah M, et al.
    Eur J Pharmacol, 2019 Nov 05;862:172627.
    PMID: 31461638 DOI: 10.1016/j.ejphar.2019.172627
    Isorhapontigenin is a polyphenolic compound found in Chinese herbs and grapes. It is a methoxylated analogue of a stilbenoid, resveratrol, which is well-known for its various beneficial effects including anti-platelet activity. Isorhapontigenin possesses greater oral bioavailability than resveratrol and has also been identified to possess anti-cancer and anti-inflammatory properties. However, its effects on platelet function have not been reported previously. In this study, we report the effects of isorhapontigenin on the modulation of platelet function. Isorhapontigenin was found to selectively inhibit ADP-induced platelet aggregation with an IC50 of 1.85 μM although it displayed marginal inhibition on platelet aggregation induced by other platelet agonists at 100 μM. However, resveratrol exhibited weaker inhibition on ADP-induced platelet aggregation (IC50 > 100 μM) but inhibited collagen induced platelet aggregation at 50 μM and 100 μM. Isorhapontigenin also inhibited integrin αIIbβ3 mediated inside-out and outside-in signalling and dense granule secretion in ADP-induced platelet activation but interestingly, no effect was observed on α-granule secretion. Isorhapontigenin did not exert any cytotoxicity on platelets at the concentrations of up to 100 μM. Furthermore, it did not affect haemostasis in mice at the IC50 concentration (1.85 μM). In addition, the mechanistic studies demonstrated that isorhapontigenin increased cAMP levels and VASP phosphorylation at Ser157 and decreased Akt phosphorylation. This suggests that isorhapontigenin may interfere with cAMP and PI3K signalling pathways that are associated with the P2Y12 receptor. Molecular docking studies emphasised that isorhapontigenin has greater binding affinity to P2Y12 receptor than resveratrol. Our results demonstrate that isorhapontigenin has selective inhibitory effects on ADP-stimulated platelet activation possibly via P2Y12 receptor.
    Matched MeSH terms: Blood Platelets/drug effects*
  14. Inhibitory effects of compounds from Zingiberaceae species on platelet activating factor receptor binding
    Jantan I, Pisar M, Sirat HM, Basar N, Jamil S, Ali RM, et al.
    Phytother Res, 2004 Dec;18(12):1005-7.
    PMID: 15742349
    Ten compounds isolated from Alpinia mutica Roxb., Curcuma xanthorrhiza Roxb. and Kaempferia rotunda Linn. (Family: Zingiberaceae) were investigated for their platelet-activating factor (PAF) antagonistic activities on rabbit platelets using 3H-PAF as a ligand. Among them, four compounds showed significant inhibitory effects. Alpinetin and 5,6-dehydrokawain isolated from A. mutica exhibited IC50 values of 41.6 and 59.3 microM, respectively. The IC50 values of 3-deacetylcrotepoxide and 2-hydroxy-4,4',6'-trimethoxychalcone from K. rotunda were 45.6 and 57.4 microM, respectively. 1-Methoxy-2-methyl-5-(1',5'-dimethylhex-4'-enyl)-benzene, synthesized by methylation of xanthorrhizol which was obtained from C. xanthorrhiza, showed an IC50 value of 40.9 microM. The results indicated that these compounds were relatively strong PAF receptor binding inhibitors.
    Matched MeSH terms: Blood Platelets/drug effects*
  15. Fulltext Inhibitory effects of acetylmelodorinol, chrysin and polycarpol from Mitrella kentii on prostaglandin E₂ and Thromboxane B₂ production and platelet activating factor receptor binding
    Saadawi S, Jalil J, Jasamai M, Jantan I
    Molecules, 2012;17(5):4824-35.
    PMID: 22538486 DOI: 10.3390/molecules17054824
    Acetylmelodorinol, chrysin and polycarpol, together with benzoic acid, benzoquinone and stigmasterol were isolated from the leaves of Mitrella kentii (Bl.) Miq. The compounds were evaluated for their ability to inhibit prostaglandin E₂ (PGE₂) and thromboxane B₂ (TXB₂) production in human whole blood using a radioimmunoassay technique. Their inhibitory effect on platelet activating factor (PAF) receptor binding to rabbit platelet was determined using ³H-PAF as a ligand. Among the compounds tested, chrysin showed a strong dose-dependent inhibitory activity on PGE(2) production (IC₅₀ value of 25.5 µM), which might be due to direct inhibition of cyclooxygenase-2 (COX-2) enzymatic activity. Polycarpol, acetylmelodorinol and stigmasterol exhibited significant and concentration-dependent inhibitory effects on TXB₂ production with IC₅₀ values of 15.6, 19.1 and 19.4 µM, respectively, suggesting that they strongly inhibited COX-1 activity. Polycarpol and acetylmelodorinol showed strong dose-dependent inhibitory effects on PAF receptor binding with IC₅₀ values of 24.3 and 24.5 µM, respectively.
    Matched MeSH terms: Blood Platelets/drug effects*
  16. Inhibitory effect of compounds from Goniothalamus tapis Miq. and Goniothalamus uvaroides King on platelet-activating factor receptor binding
    Moharam BA, Jantan I, Jalil J, Ahmad F
    Phytother Res, 2012 May;26(5):687-91.
    PMID: 22002630 DOI: 10.1002/ptr.3620
    Phytochemical investigation on the bark of Goniothalamus tapis Miq. and G. uvaroides King has resulted in the isolation of eight styryl-lactones, (-)-cryptomeridiol, liriodenine, 3-methyl-1H-benz[f]indole-4,9-dione, (-)-stigmasterol and dimethyl terephthalate. The structures of the compounds were elucidated by spectroscopic techniques. The compounds were evaluated for their effect on platelet-activating factor (PAF) receptor binding on rabbit platelets using (3) H-PAF as a ligand. Among the compounds tested, (-)-cryptomeridiol, (+)-goniothalamin and (+)-isoaltholactone exhibited a significant and concentration-dependent inhibitory effect on PAF receptor binding, with inhibitory concentration (IC)(50) values of 17.5, 19.7 and 46.5 µm, respectively. The inhibitory effects of the first two compounds were comparable to that obtained from the positive control, cedrol. The results indicated that these compounds were strong PAF receptor binding inhibitors.
    Matched MeSH terms: Blood Platelets/drug effects
  17. Increased PAC-1 expression among patients with multiple myeloma on concurrent thalidomide and warfarin
    Abdullah WZ, Roshan TM, Hussin A, Zain WS, Abdullah D
    Blood Coagul Fibrinolysis, 2013 Dec;24(8):893-5.
    PMID: 24030118 DOI: 10.1097/MBC.0b013e3283642ee2
    Treatment with thalidomide is associated with vascular thrombosis. The effect of thalidomide on platelet activation is unclear, although the use of aspirin is justified for thromboprophylaxis. A study on platelet activation markers was done among multiple myeloma patients receiving thalidomide therapy with warfarin as thromboprophylaxis. Strict criteria and procedure were set to avoid misinterpretation of platelet activation other than due to the thalidomide's effect. Blood specimen pre and post thalidomide therapy were used for flow cytometric analysis. Platelet surface P-selectin, CD62P expression and PAC-1 (antibody that recognizes conformational change of the GPIIb/IIIa complex) were examined by using three-colour flowcytometer. Increased expression marker for PAC-1 was observed after 4 weeks of thalidomide treatment (P drug in future.
    Matched MeSH terms: Blood Platelets/drug effects
  18. Fulltext Impact of specific functional groups in flavonoids on the modulation of platelet activation
    Ravishankar D, Salamah M, Akimbaev A, Williams HF, Albadawi DAI, Vaiyapuri R, et al.
    Sci Rep, 2018 Jun 22;8(1):9528.
    PMID: 29934595 DOI: 10.1038/s41598-018-27809-z
    Flavonoids exert innumerable beneficial effects on cardiovascular health including the reduction of platelet activation, and thereby, thrombosis. Hence, flavonoids are deemed to be a molecular template for the design of novel therapeutic agents for various diseases including thrombotic conditions. However, the structure-activity relationships of flavonoids with platelets is not fully understood. Therefore, this study aims to advance the current knowledge on structure-activity relationships of flavonoids through a systematic analysis of structurally-related flavones. Here, we investigated a panel of 16 synthetic flavones containing hydroxy or methoxy groups at C-7,8 positions on the A-ring, with a phenyl group or its bioisosteres as the B-ring, along with their thio analogues possessing a sulfur molecule at the 4th carbon position of the C-ring. The antiplatelet efficacies of these compounds were analysed using human isolated platelets upon activation with cross-linked collagen-related peptide by optical aggregometry. The results demonstrate that the hydroxyl groups in flavonoids are important for optimum platelet inhibitory activities. In addition, the 4-C=O and B ring phenyl groups are less critical for the antiplatelet activity of these flavonoids. This structure-activity relationship of flavonoids with the modulation of platelet function may guide the design, optimisation and development of flavonoid scaffolds as antiplatelet agents.
    Matched MeSH terms: Blood Platelets/drug effects
  19. Fulltext Glycoprotein IIb/IIIa and P2Y12 induction by oligochitosan accelerates platelet aggregation
    Periayah MH, Halim AS, Yaacob NS, Saad AZ, Hussein AR, Rashid AH, et al.
    Biomed Res Int, 2014;2014:653149.
    PMID: 25247182 DOI: 10.1155/2014/653149
    Platelet membrane receptor glycoprotein IIb/IIIa (gpiibiiia) is a receptor detected on platelets. Adenosine diphosphate (ADP) activates gpiibiiia and P2Y12, causing platelet aggregation and thrombus stabilization during blood loss. Chitosan biomaterials were found to promote surface induced hemostasis and were capable of activating blood coagulation cascades by enhancing platelet aggregation. Our current findings show that the activation of the gpiibiiia complex and the major ADP receptor P2Y12 is required for platelet aggregation to reach hemostasis following the adherence of various concentrations of chitosan biomaterials [7% N,O-carboxymethylchitosan (NO-CMC) with 0.45 mL collagen, 8% NO-CMC, oligochitosan (O-C), and oligochitosan 53 (O-C 53)]. We studied gpiibiiia and P2Y12 through flow cytometric analysis and western blotting techniques. The highest expression of gpiibiiia was observed with Lyostypt (74.3 ± 7.82%), followed by O-C (65.5 ± 7.17%). Lyostypt and O-C resulted in gpiibiiia expression increases of 29.2% and 13.9%, respectively, compared with blood alone. Western blot analysis revealed that only O-C 53 upregulated the expression of P2Y12 (1.12 ± 0.03-fold) compared with blood alone. Our findings suggest that the regulation of gpiibiiia and P2Y12 levels could be clinically useful to activate platelets to reach hemostasis. Further, we show that the novel oligochitosan is able to induce the increased expression of gpiibiiia and P2Y12, thus accelerating platelet aggregation in vitro.
    Matched MeSH terms: Blood Platelets/drug effects
  20. Fulltext Efficacy and tolerability of celecoxib compared with diclofenac slow release in the treatment of acute ankle sprain in an Asian population
    Nadarajah A, Abrahan L, Lau FL, Hwang LJ, Fakir-Bolte C
    Singapore Med J, 2006 Jun;47(6):534-42.
    PMID: 16752024
    INTRODUCTION: Cyclooxygenase (COX)-2 selective inhibitors are attractive candidates for treatment of ankle sprain because of their efficacy as anti-inflammatory and analgesic agents and their overall safety, including lack of effect on platelet aggregation. The objective of this study was to assess the efficacy and tolerability of celecoxib compared with diclofenac slow release (SR) in the treatment of acute ankle sprain in an Asian population.
    METHODS: In this seven-day, multicentre, double-blind, randomised, parallel-group trial, 370 patients with first- or second-degree ankle sprain occurring at or less than 48 hours prior to the first dose of study medication were randomised to receive celecoxib 200 mg bid (189 patients) after a 400 mg loading dose or diclofenac SR 75 mg bid (181 patients). Patients were required to demonstrate moderate to severe ankle pain on weight bearing (45 mm or greater on a 100 mm visual analogue scale [VAS]) at baseline. The primary efficacy end point was the patient's assessment of ankle pain (VAS on full weight bearing) on day 4.
    RESULTS: Celecoxib was as effective as diclofenac SR in improving the signs and symptoms of ankle sprain. At day 4, mean VAS scores for celecoxib and diclofenac SR had decreased to 28 mm and 30 mm, respectively. Treatment differences were not statistically significant. Incidence of upper gastrointestinal adverse events was low in both treatment groups (0.5 percent versus 2.2 percent for celecoxib and diclofenac SR, respectively).
    CONCLUSION: Celecoxib, a COX-2 selective inhibitor, is as effective as diclofenac SR in treating ankle sprains. With its platelet-sparing properties, celecoxib may offer an advantage over diclofenac SR in managing musculoskeletal injuries.
    Matched MeSH terms: Blood Platelets/drug effects
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