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1.
J Agric Food Chem ; 68(6): 1571-1578, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-31927886

RESUMO

Diallyl trisulfide (DATS) is a secondary metabolite of allicin, a volatile organosulfur flavoring compound generated by the crushing of garlic. These compounds have various medicinal effects such as antiplatelet activity. In this study, we demonstrated for the first time the cellular mechanism involved in the inhibition of platelet aggregation by DATS and dipropyl trisulfide (DPTS), which is a saturated analogue of DATS. Washed murine platelets were incubated with these sulfides, and platelet aggregation was evaluated by light transmission aggregometry. The amount of reaction products produced by DATS, DPTS, and glutathione (GSH) was measured using liquid chromatography-mass spectrometry. Compared with DPTS, DATS potently inhibited platelet aggregation induced by thrombin, U46619, and collagen. N-Ethylmaleimide (NEM), which is commonly used to modify sulfhydryl groups, also suppressed platelet aggregation. The reactivity of DATS with GSH was higher than that of DPTS. These data suggested that DATS inhibited platelet aggregation through the reaction of sulfhydryl groups.


Assuntos
Compostos Alílicos/química , Compostos Alílicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Compostos de Sulfidrila/farmacologia , Sulfetos/química , Sulfetos/farmacologia , Animais , Plaquetas/efeitos dos fármacos , Plaquetas/fisiologia , Dissulfetos/química , Dissulfetos/farmacologia , Alho/química , Glutationa/química , Camundongos , Agregação Plaquetária/efeitos dos fármacos , Compostos de Sulfidrila/química
2.
J Med Life ; 12(3): 296-300, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31666834

RESUMO

During menstruation, endometrial hemostasis is achieved by platelet aggregation, fibrin deposition, and thrombus formation that interact with local endocrine and immunological factors which cause termination of menstrual bleeding. Interactions between steroidal sex hormones and platelet functions are not well understood. The aim of this study was to evaluate the effect of platelet function during the menstrual cycle and luteal phase in women of reproductive age. The cross-sectional study on women of reproductive age included 44 healthy women. Platelet function was assessed by PFA-100TM analyzer with collagen/epinephrine and collagen/ADP cartridges during the menstrual cycle and luteal phase. There were no significant differences in platelet function between menstruation and ovulatory phase. Platelet activity in Arab collagen/epinephrine cartridge increased during menstruation compared to non-Arab ethnic subjects and no significant differences in platelet function were found when using collagen/ADP cartridge. This study suggested modulation in platelet functions during menstruation and luteal phase in women of reproductive age. Further studies, including a large number of subjects, platelet genetic and progesterone factors change in platelet clotting associated to menstrual cycle should be conducted.


Assuntos
Plaquetas/fisiologia , Menstruação/fisiologia , Ovulação/fisiologia , Adulto , Colágeno/farmacologia , Estudos Transversais , Epinefrina/farmacologia , Feminino , Humanos , Pré-Menopausa/fisiologia
3.
Clin Lab ; 65(8)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31414765

RESUMO

BACKGROUND: Collective specific variegated alterations in the hemostatic system cast doubt on the uncritical usage of standard hemotherapy algorithms in patients with chronic liver disease. The aims of the present study were to examine the applicability of commonly used early viscoelastic parameters in this particular collective and to develop first-time thresholds for the early detection of clinically relevant platelet dysfunction. METHODS: Patients suffering from advanced chronic liver disease were enrolled in this prospective single-centre study and consecutively allocated to Group 1 (MELD (Model for End-Stage Liver Disease) score 6 - 11) or Group 2 (MELD score > 16). We performed conventional laboratory coagulation analyses, as well as viscoelastometry (ROTEM®, EXTEM test, and FIBTEM test) and aggregometry (Multiplate®, ASPItest, and ADPtest), in each patient to analyze their hemostatic capacity. We analyzed the association between the A10 values (clot firmness 10 minutes after the initiation of clot building) in the EXTEM and FIBTEM tests and the corresponding Maximum Clot Firmness (MCF) values and performed receiver operating characteristic (ROC) curve analyses to investigate the ability of early parameters from the ASPItest and ADPtest (Aggregation Units (AU) 1 minute (T1), 2 minutes (T2) and 3 minutes (T3) after induction of platelet aggregation) of the Multiplate® system to predict clinically relevant platelet dysfunction. RESULTS: In the complete study collective (n = 50) and in Group 1 and Group 2 (each n = 25), A10 values correlated highly significantly with corresponding MCF values. The bias between the A10 and the MCF values was 5.1 ± 2.4 mm and 1.2 ± 1.1 mm for the EXTEM test and FIBTEM test, respectively. The highest sensitivity and specificity values for the prediction of clinically relevant platelet dysfunction at measuring point T3 were analyzed to be the values 54.9 AU/min in the ASPItest and 50.1 AU/min in the ADPtest. CONCLUSIONS: The results of the study indicate that the basic principle of using the A10 values as so-called early vis-coelastic parameters for the estimation of MCF values is legitimate. The presumably divergent bias between the A10 and MCF values necessitates the development of collective specific thresholds in hemotherapy algorithms for coagulopathic patients suffering from advanced chronic liver disease.


Assuntos
Coagulação Sanguínea/fisiologia , Plaquetas/fisiologia , Hepatopatias/sangue , Agregação Plaquetária/fisiologia , Tromboelastografia/métodos , Idoso , Testes de Coagulação Sanguínea/métodos , Plaquetas/metabolismo , Viscosidade Sanguínea/fisiologia , Doença Crônica , Feminino , Humanos , Hepatopatias/diagnóstico , Hepatopatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC
4.
Int J Mol Sci ; 20(17)2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31461836

RESUMO

Platelets are megakaryocyte-derived fragments lacking nuclei and prepped to maintain primary hemostasis by initiating blood clots on injured vascular endothelia. Pathologically, platelets undergo the same physiological processes of activation, secretion, and aggregation yet with such pronouncedness that they orchestrate and make headway the progression of atherothrombotic diseases not only through clot formation but also via forcing a pro-inflammatory state. Indeed, nuclear factor-κB (NF-κB) is largely implicated in atherosclerosis and its pathological complication in atherothrombotic diseases due to its transcriptional role in maintaining pro-survival and pro-inflammatory states in vascular and blood cells. On the other hand, we know little on the functions of platelet NF-κB, which seems to function in other non-genomic ways to modulate atherothrombosis. Therein, this review will resemble a rich portfolio for NF-κB in platelets, specifically showing its implications at the levels of platelet survival and function. We will also share the knowledge thus far on the effects of active ingredients on NF-κB in general, as an extrapolative method to highlight the potential therapeutic targeting of NF-κB in coronary diseases. Finally, we will unzip a new horizon on a possible extra-platelet role of platelet NF-κB, which will better expand our knowledge on the etiology and pathophysiology of atherothrombosis.


Assuntos
Plaquetas/metabolismo , NF-kappa B/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Plaquetas/efeitos dos fármacos , Plaquetas/fisiologia , Humanos , NF-kappa B/genética , Ativação Plaquetária , Inibidores da Agregação de Plaquetas/farmacologia
5.
Biol Pharm Bull ; 42(8): 1253-1267, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366863

RESUMO

Systemic platelet behaviors in experimental animals are often assessed by infusion of isotope-labeled platelets and measuring them under anesthesia. However, such procedures alter, therefore may not reveal, real-life platelet behaviors. 5-Hydroxytryptamine (5HT or serotonin) is present within limited cell-types, including platelets. In our studies, by measuring 5HT as a platelet-marker in non-anesthetized mice, we identified stimulation- and time-dependent accumulations in liver, lung, and/or spleen as important systemic platelet behaviors. For example, intravenous, intraperitoneal, or intragingival injection of lipopolysaccharide (LPS, a cell-wall component of Gram-negative bacteria), interleukin (IL)-1, or tumor necrosis factor (TNF)-α induced hepatic platelet accumulation (HPA) and platelet translocation into the sinusoidal and perisinusoidal spaces or hepatocytes themselves. These events occurred "within a few hours" of the injection, caused hypoglycemia, and exhibited protective or causal effects on hepatitis. Intravenous injection of larger doses of LPS into normal mice, or intravenous antigen-challenge to sensitized mice, induced pulmonary platelet accumulation (PPA), as well as HPA. These reactions occurred "within a few min" of the LPS injection or antigen challenge and resulted in shock. Intravenous injection of 5HT or a catecholamine induced a rapid PPA "within 6 s." Intravenous LPS injection, within a minute, increased the pulmonary catecholamines that mediate the LPS-induced PPA. Macrophage-depletion from liver and spleen induced "day-scale" splenic platelet accumulation, suggesting the spleen is involved in clearing senescent platelets. These findings indicate the usefulness of 5HT as a marker of platelet behaviors, and provide a basis for a discussion of the roles of platelets as both "defenders" and "guardians."


Assuntos
Plaquetas/fisiologia , Fígado/fisiologia , Pulmão/fisiologia , Serotonina/fisiologia , Baço/fisiologia , Animais , Humanos , Camundongos
6.
Rev Assoc Med Bras (1992) ; 65(7): 988-992, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31389510

RESUMO

OBJECTIVE: The objective of this study was to investigate the effects of low triiodothyronine syndrome (LT3S) on platelet function and clotting factors in patients with nephrotic syndrome(NS). METHODS: Patients with primary nephrotic syndrome were divided into two groups, normal thyroid function (group A) and LT3S (group B), based on whether they had LT3S or not. Healthy subjects were selected as the control group (group C). Blood coagulation function was detected in each group. The platelet activation function (CD62P, CD63) was determined by flow cytometry. The platelet aggregation rate was detected by an optical method using adenosine diphosphate and arachidonic acid as inducers. RESULTS: The proportion of primary nephrotic syndrome with LT3S was 23.2% (69/298). Compared with group C, group A had higher CD62P and PAgTADP, and group B had higher CD62P, CD63, PAgTAA, and PAgTADP; the difference was statistically significant (all P < 0.05). There was no significant difference in renal pathology between group A and group B (X2 = 4.957, P = 0.421). Compared with group A, the 24-hour urine protein, CD63, PAgTAA, and PAgTADP were higher in group B, and APTT and Alb were lower. The difference was statistically significant (P < 0.05). Logistic regression analysis showed that LT3S was associated with CD36 (OR: 3.516; 95% CI: 1.742~8.186; P = 0.004) and PAgTAA (OR: 0.442; 95% CI: 1.001~1.251; P = 0.037). CONCLUSION: NS patients are prone to LT3S. Patients with LT3S may have abnormal platelet activation and increase of platelet aggregation.


Assuntos
Plaquetas/fisiologia , Síndromes do Eutireóideo Doente/sangue , Síndromes do Eutireóideo Doente/fisiopatologia , Síndrome Nefrótica/sangue , Síndrome Nefrótica/fisiopatologia , Tri-Iodotironina/sangue , Adulto , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome Nefrótica/complicações , Ativação Plaquetária/efeitos dos fármacos , Ativação Plaquetária/fisiologia , Agregação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/fisiologia , Contagem de Plaquetas , Testes de Função Plaquetária , Valores de Referência , Análise de Regressão , Tri-Iodotironina/deficiência
7.
Nord J Psychiatry ; 73(6): 372-379, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31304832

RESUMO

Background: Currently, increasing evidence supports the hypothesis that alterations in the immune-inflammatory system are critical for the pathophysiology of bipolar disorder (BD). Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), and mean platelet volume (MPV) have recently been investigated as inexpensive and simple inflammatory markers. Aims: The aim of this study is to compare NLR, PLR, MLR, and MPV in depressive, manic, and euthymic patients with BD and healthy controls, and to evaluate whether values of NLR, PLR, MLR, and MPV are possible state or trait biomarkers in BD. Methods: This retrospective study was conducted with 341 patients with BD (100 patients in a depressive state, 141 patients in a manic state, and 100 patients in a euthymic state) and 114 healthy controls. Results: We found that patients with BD in manic states had higher levels of MPV, NLR, and MLR, and patients with BD in depressive states had higher levels of MPV than the controls. Moreover, MPV predicted all states of BD, while NLR and MLR predicted the manic state of BD. Conclusions: NLR, MLR, and MPV obtained from simple and inexpensive blood tests were significantly higher in patients with BD than in healthy controls, which each imply low-grade inflammation. MPV may serve as a possible trait biomarker of BD, while NLR and MLR may both serve as possible state biomarkers of the manic state.


Assuntos
Transtorno Bipolar/sangue , Inflamação/sangue , Linfócitos/citologia , Volume Plaquetário Médio , Monócitos/citologia , Neutrófilos/citologia , Adulto , Biomarcadores/sangue , Plaquetas/citologia , Plaquetas/fisiologia , Feminino , Humanos , Masculino , Estudos Retrospectivos
8.
Cancer Treat Res ; 179: 37-54, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31317479

RESUMO

For over 100 years, a link has been recognized between thrombosis and cancer. However, whether this was a causal or correlational relationship was debated. It is now well established that cancer and thrombosis are mechanistically related in intricate ways and can directly fuel each other. Here, we present an historical perspective of platelets and how their physiological function in hemostasis can contribute to tumor development and metastasis. This emerging field has garnered great interest as aspirin therapy has been proposed as a prevention strategy for some malignancies. We highlight the advances that have been made, presenting platelets as a key component that supports many of the hallmarks of cancer that have been described and conclude with future directions and studies that are needed to clarify the role of platelets in cancer and solidify platelet modulating therapies within oncology.


Assuntos
Plaquetas/fisiologia , Hemostasia/fisiologia , Neoplasias/fisiopatologia , Trombose/fisiopatologia , Plaquetas/efeitos dos fármacos , Hemostasia/efeitos dos fármacos , Humanos , Neoplasias/complicações , Neoplasias/prevenção & controle , Trombose/etiologia , Trombose/prevenção & controle
9.
Blood ; 134(10): 826-835, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31300405

RESUMO

The stem cell leukemia (Scl or Tal1) protein forms part of a multimeric transcription factor complex required for normal megakaryopoiesis. However, unlike other members of this complex such as Gata1, Fli1, and Runx1, mutations of Scl have not been observed as a cause of inherited thrombocytopenia. We postulated that functional redundancy with its closely related family member, lymphoblastic leukemia 1 (Lyl1) might explain this observation. To determine whether Lyl1 can substitute for Scl in megakaryopoiesis, we examined the platelet phenotype of mice lacking 1 or both factors in megakaryocytes. Conditional Scl knockout (KO) mice crossed with transgenic mice expressing Cre recombinase under the control of the mouse platelet factor 4 (Pf4) promoter generated megakaryocytes with markedly reduced but not absent Scl These Pf4Sclc-KO mice had mild thrombocytopenia and subtle defects in platelet aggregation. However, Pf4Sclc-KO mice generated on an Lyl1-null background (double knockout [DKO] mice) had severe macrothrombocytopenia, abnormal megakaryocyte morphology, defective pro-platelet formation, and markedly impaired platelet aggregation. DKO megakaryocytes, but not single-knockout megakaryocytes, had reduced expression of Gata1, Fli1, Nfe2, and many other genes that cause inherited thrombocytopenia. These gene expression changes were significantly associated with shared Scl and Lyl1 E-box binding sites that were also enriched for Gata1, Ets, and Runx1 motifs. Thus, Scl and Lyl1 share functional roles in platelet production by regulating expression of partner proteins including Gata1. We propose that this functional redundancy provides one explanation for the absence of Scl and Lyl1 mutations in inherited thrombocytopenia.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/fisiologia , Plaquetas/fisiologia , Proteínas de Neoplasias/fisiologia , Proteína 1 de Leucemia Linfocítica Aguda de Células T/fisiologia , Trombopoese/genética , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fator de Transcrição GATA1/genética , Fator de Transcrição GATA1/metabolismo , Regulação da Expressão Gênica , Megacariócitos/patologia , Megacariócitos/fisiologia , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Proteínas de Neoplasias/genética , Proteína 1 de Leucemia Linfocítica Aguda de Células T/genética , Trombocitopenia/sangue , Trombocitopenia/genética
10.
Braz J Cardiovasc Surg ; 34(3): 297-304, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31310468

RESUMO

OBJECTIVES: To investigate the association between clinical hematologic parameters and saphenous vein graft failure after on-pump coronary artery bypass surgery. METHODS: A total of 1950 consecutive patients underwent isolated on-pump coronary artery surgery between November 2010 and February 2013. Of these, 284 patients met our inclusion criteria; their preoperative clinical hematological parameters were retrospectively obtained for this cohort study. And of them, 109 patients underwent conventional coronary angiography after graft failure was revealed by coronary computed tomography angiography. The primary endpoint was to catch at least one saphenous vein graft stenosis or occlusion following the coronary angiogram. We then analyzed risk factors for graft failure. In sequential or T grafts, each segment was analyzed as a separate graft. RESULTS: In logistic regression analysis, older age, platelet distribution width, and diabetes mellitus were identified as independent predictors of saphenous vein graft failure (P<0.). In contrast, preserved ejection fraction value favored graft patency (P<0.001). CONCLUSION: Increased platelet distribution width is easily measurable and can be used as a simple and valuable marker in the prediction of saphenous vein graft failure.


Assuntos
Plaquetas/fisiologia , Ponte de Artéria Coronária/efeitos adversos , Veia Safena/transplante , Grau de Desobstrução Vascular/fisiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Angiografia Coronária/métodos , Ponte de Artéria Coronária/métodos , Doença da Artéria Coronariana/etiologia , Ecocardiografia , Feminino , Testes Hematológicos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Valor Preditivo dos Testes , Curva ROC , Valores de Referência , Estudos Retrospectivos , Fatores de Risco , Veia Safena/fisiopatologia , Estatísticas não Paramétricas , Falha de Tratamento
11.
Asian Pac J Cancer Prev ; 20(7): 2079-2085, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31350969

RESUMO

Background: The prognosis and management of primary thrombocytosis (PT) and secondary thrombocytosis (ST) are different. This study aims to evaluate the role of platelet function tests by light transmission platelet aggregometry (LTA), plasma von Willebrand factor antigen (vWF:Ag), ristocetin cofactor activity (vWF:RCo) and inflammatory markers [erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)] for the differentiation between PT and ST. Methods: This prospective study was carried out in patients with platelet counts greater than 450 x 109/L. Primary outcomes were the sensitivity and specificity of platelet function tests by LTA for the differentiation of PT and ST. Secondary outcomes were sensitivity and specificity of ESR, CRP, vWF:Ag, and vWF:RCo for the differentiation of PT and ST. Results: Fifty-two patients were enrolled onto the study of which 26 (50%) had PT. The sensitivity and specificity of epinephrine, collagen, and arachidonic acid (AA) induced abnormal LTA for the differentiation of PT from ST were sensitivity of 50%, 38.5%, 26.9% and specificity of 88.5%, 100%, 100% respectively. The sensitivity and specificity of abnormal ESR, CRP, and either abnormal ESR or CRP in the differentiation of ST from PT were sensitivity of 88.5%, 80.8%, 100% and specificity of 65.4%, 61.5%, 46.2% respectively. The sensitivity and specificity of low vWF:Ag and vWF:RCo in the differentiation of PT from ST were sensitivity of 7.69%, 42.3% and specificity of 100%, 88.5% respectively. Conclusions: Abnormal platelet function determined by LTA with collagen, AA, epinephrine had high specificity ratings enabling the differentiation between PT and ST. vWF:RCo, ESR and CRP levels could be helpful in differentiating between PT and ST.


Assuntos
Biomarcadores/metabolismo , Plaquetas/fisiologia , Mediadores da Inflamação/metabolismo , Inflamação/metabolismo , Trombocitose/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , Feminino , Seguimentos , Hemorragia/etiologia , Hemorragia/metabolismo , Humanos , Inflamação/etiologia , Masculino , Pessoa de Meia-Idade , Testes de Função Plaquetária , Prognóstico , Estudos Prospectivos , Curva ROC , Trombocitose/classificação , Trombocitose/complicações , Trombocitose/metabolismo , Trombose/etiologia , Trombose/metabolismo , Adulto Jovem , Fator de von Willebrand/metabolismo
12.
Int J Mol Sci ; 20(11)2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31181592

RESUMO

Platelet interaction with collagens, via von Willebrand factor, is a potent trigger of shear-dependent thrombus formation mediated by subsequent engagement of the signaling collagen receptor glycoprotein (GP)VI, enforced by integrin α2ß1. Protein tyrosine kinase Syk is central in the GPVI-induced signaling pathway, leading to elevated cytosolic Ca2+. We aimed to determine the Syk-mediated thrombogenic activity of several collagen peptides and (fibrillar) type I and III collagens. High-shear perfusion of blood over microspots of these substances resulted in thrombus formation, which was assessed by eight parameters and was indicative of platelet adhesion, activation, aggregation, and contraction, which were affected by the Syk inhibitor PRT-060318. In platelet suspensions, only collagen peptides containing the consensus GPVI-activating sequence (GPO)n and Horm-type collagen evoked Syk-dependent Ca2+ rises. In whole blood under flow, Syk inhibition suppressed platelet activation and aggregation parameters for the collagen peptides with or without a (GPO)n sequence and for all of the collagens. Prediction models based on a regression analysis indicated a mixed role of GPVI in thrombus formation on fibrillar collagens, which was abolished by Syk inhibition. Together, these findings indicate that GPVI-dependent signaling through Syk supports platelet activation in thrombus formation on collagen-like structures regardless of the presence of a (GPO)n sequence.


Assuntos
Plaquetas/metabolismo , Colágeno/metabolismo , Glicoproteínas da Membrana de Plaquetas/metabolismo , Quinase Syk/metabolismo , Trombose/metabolismo , Plaquetas/efeitos dos fármacos , Plaquetas/fisiologia , Células Cultivadas , Colágeno/química , Cicloexilaminas/farmacologia , Humanos , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Agregação Plaquetária , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologia , Quinase Syk/antagonistas & inibidores
13.
Thromb Haemost ; 119(7): 1154-1161, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31154663

RESUMO

Several in vitro platelet function tests are available for the diagnosis of inherited platelet function disorders. Currently, the light transmission aggregometry (LTA) is recommended as one of the first-step tests. LTA is available in most specialized hemostasis laboratories. Although the LTA is accepted as a 'gold standard' assay for the evaluation of platelet function, its standardization in the clinical practice is still challenging. The GTH-based THROMKID-Plus Study Group has performed an inter-laboratory trial in Germany and Austria. Five different agonists were selected according to the Scientific and Standardization Committee/International Society on Thrombosis and Haemostasis recommendations and shipped in 3 different sets (one should represent a healthy control and two should simulate platelet function disorders) to 15 specialized laboratories in Germany and Austria. Agonists were analyzed by APACT or PAP4/8 aggregometer using platelet-rich plasma from healthy donors. In addition, laboratory-internal platelet agonists were tested in platelet-rich plasma from a healthy donor. All laboratories (9 used APACT, 6 used PAP4/PAP8) showed very consistent data regarding the maximum percentage of aggregation induced by the tested agonists and identified the differential diagnosis of the simulated platelet function disorders with one exception, which was due to technical problems. In contrast, there was a high variability of the laboratory-internal inductors regarding reagent type, concentrations and pathological cut-off values. Our study showed that the shipment of agonists is suitable for an inter-laboratory survey of LTA. However, there is still a remarkable need for standardization of agonist reagents and their concentration as well as for definition of reference ranges.


Assuntos
Transtornos Plaquetários/diagnóstico , Plaquetas/fisiologia , Testes de Função Plaquetária/métodos , Áustria , Alemanha , Voluntários Saudáveis , Hemostasia , Humanos , Agregação Plaquetária , Plasma Rico em Plaquetas/química , Garantia da Qualidade dos Cuidados de Saúde , Padrões de Referência , Valores de Referência
14.
Mediators Inflamm ; 2019: 9213074, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31148950

RESUMO

Platelet size has been demonstrated to reflect platelet activity and seems to be a useful predictive and prognostic biomarker of cardiovascular events. It is associated with a variety of prothrombotic and proinflammatory diseases. The aim is a review of literature reports concerning changes in the mean platelet volume (MPV) and its possible role as a biomarker in inflammatory processes and neoplastic diseases. PubMed database was searched for sources using the following keywords: platelet activation, platelet count, mean platelet volume and: inflammation, cancer/tumor, cardiovascular diseases, myocardial infarction, diabetes, lupus disease, rheumatoid arthritis, tuberculosis, ulcerative colitis, renal disease, pulmonary disease, influencing factors, age, gender, genetic factors, oral contraceptives, smoking, lifestyle, methods, standardization, and hematological analyzer. Preference was given to the sources which were published within the past 20 years. Increased MPV was observed in cardiovascular diseases, cerebral stroke, respiratory diseases, chronic renal failure, intestine diseases, rheumatoid diseases, diabetes, and various cancers. Decreased MPV was noted in tuberculosis during disease exacerbation, ulcerative colitis, SLE in adult, and different neoplastic diseases. The study of MPV can provide important information on the course and prognosis in many inflammatory conditions. Therefore, from the clinical point of view, it would be interesting to establish an MPV cut-off value indicating the intensity of inflammatory process, presence of the disease, increased risk of disease development, increased risk of thrombotic complications, increased risk of death, and patient's response on applied treatment. Nevertheless, this aspect of MPV evaluation allowing its use in clinical practice is limited and requires further studies.


Assuntos
Biomarcadores/metabolismo , Inflamação/metabolismo , Plaquetas/fisiologia , Diabetes Mellitus/metabolismo , Feminino , Humanos , Masculino , Volume Plaquetário Médio , Infarto do Miocárdio/metabolismo , Ativação Plaquetária/fisiologia , Contagem de Plaquetas
15.
Molecules ; 24(12)2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31200488

RESUMO

Platelets are an important component of the initial response to vascular endothelial injury; however, platelet dysfunction induces the acute clinical symptoms of thrombotic disorders, which trigger severe cardiovascular diseases such as myocardial infarction, ischemia, and stroke. In this study, we investigated the Dryopteris crassirhizoma's antiplatelet activity. A water extract of D. crassirhizoma (WDC) was partitioned into dichloromethane (DCM), ethyl acetate, n-butyl alcohol, and water. Among these four fractions, the DCM fraction potently inhibited the collagen-stimulated platelet aggregation in a concentration-dependent manner. From this fraction, five different acylphloroglucinol compounds and one flavonoid were isolated by activity-guided column chromatography. They were identified by comparing their mass, 1H-, and 13C-NMR spectral data with those reported in the literature. Quantifying the six compounds in WDC and its DCM fraction by high-performance liquid chromatography (HPLC) revealed that butyryl-3-methylphloroglucinol (compound 4) was the most abundant in these samples. Additionally, butyryl-3-methylphloroglucinol showed the strongest inhibitory activity in the collagen- and arachidonic acid (AA)-induced platelet aggregation, with inhibition ratios of 92.36% and 89.51% in the collagen and AA-induced platelet aggregation, respectively, without cytotoxicity. On the active concentrations, butyryl-3-methylphloroglucinol significantly suppressed the convulxin-induced platelet activation. Regarding the structure-activity relationships for the five acylphloroglucinol compounds, our results demonstrated that the functional butanonyl, methoxy, and hydroxy groups in butyryl-3-methylphloroglucinol play important roles in antiplatelet activity. The findings indicate that acylphloroglucinols, including butyryl-3-methylphloroglucinol from D. crassirhizom, possess an antiplatelet activity, supporting the use of this species for antiplatelet remedies.


Assuntos
Plaquetas/fisiologia , Dryopteris/química , Animais , Cromatografia Líquida de Alta Pressão , Masculino , Cloreto de Metileno/química , Estrutura Molecular , Extratos Vegetais/química , Ativação Plaquetária , Agregação Plaquetária , Coelhos
16.
BMC Endocr Disord ; 19(1): 62, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31200678

RESUMO

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) have accelerated atherosclerosis as a pro thrombotic state that is associated with the platelet activation priming. Platelets, which undergo the continuous mild stimulation, may lose their sensitivity to react to a strong stimulation. The present study aimed to investigate activation responses of platelets to mild and subsequent strong stimulations in patients with T2DM and healthy individuals. METHODS: Blood samples, which were taken from 40 patients with T2DM and 35 healthy individuals, were collected into the citrate containing tubes. The samples were subjected to the soft centrifugation to prepare the platelet rich plasma (PRP). Platelets in PRP samples were treated at a low (1 µM) concentration and then at a high (10 µM) concentration of ADP. Before and after stimulation with different doses of ADP, levels of CD62P expression and formation of platelet micro particles (PMPs) were measured using a flow cytometry method. RESULTS: The platelets from patients with T2DM had higher levels of CD62P expression before any stimulation (P = 0.003) than control samples. Platelets, which underwent the mild stimulation, indicated lower responses to CD62P expression, but higher PMPs formation after stimulation with high dose of ADP. Patients with T2DM had higher platelet micro particles in all states with the ADP stimulation. (P = 0.004, SD: ±74.52). CONCLUSIONS: The flow cytometry data indicated that platelets were pre-active and associated with metabolic conditions in patients with type 2 diabetes mellitus. The induction of desensitization state helped platelets to reduce the platelet activation and sensitivity to ADP in a diabetic environment. Furthermore, the production of platelets micro-particles was high in the patients; and desensitized platelets were more susceptible to shedding of micro-particles.


Assuntos
Difosfato de Adenosina/farmacologia , Plaquetas/fisiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Ativação Plaquetária/efeitos dos fármacos , Biomarcadores/análise , Plaquetas/efeitos dos fármacos , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Selectina-P/metabolismo , Prognóstico
17.
Asian Pac J Cancer Prev ; 20(6): 1879-1885, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31244313

RESUMO

Background: The aim of this study was to investigate the effect of platelet parameters before concurrent chemoradiotherapy (CCRT) on survival of patients with limited disease small cell lung cancer (LD-SCLC). Methods: This study consisted of patients who received CCRT due to LD-SCLC in the oncology clinic between 1997-2017. Examined platelet parameters included total platelet count (TPC), mean platelet volume, platelet distribution width, and platelet-lymphocyte ratio. The cut-off value for TPC was determined as 306x109/U (sensitivity: 62%, specificity: 75.5%), where patients below or equal to this level was classified as Group I, and those above as Group II. Results:The study included 90 patients whose mean age was 59 years (range: 42-83) and male ratio was 80.0% (n=72). Near three-fourths of patients (74.4%) were at clinical stage III. Among stage I-II patients, mOS was found as 126 months for Group I whereas it had not been reached in Group II (p=0.158). Stage III patients showed significantly lower mOS for Group 1 (16 [range: 14.1-17.8] months) compared to that in Group 2 (19.0 [range: 15.6-62.8] months; p=0.002). In multivariate analysis, Eastern Cooperative Oncology Group performance score (p=0.003), clinical stage (p<0.001), prophylactic cranial irradiation (p=0.004), and TPC (p=0.031) was determined as the most significant factors affecting survival. Conclusion: Our study suggests association of high baseline levels of TPC to improved survival in patients scheduled to undergo CCRT for LD-SCLC. Considering easiness and universal availability of TPC measurement, potential utilization of this biomarker may be promising to predict survival, albeit requiring validation by further well-designated prospective studies.


Assuntos
Plaquetas/fisiologia , Quimiorradioterapia/mortalidade , Neoplasias Pulmonares/mortalidade , Volume Plaquetário Médio , Recidiva Local de Neoplasia/mortalidade , Carcinoma de Pequenas Células do Pulmão/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Contagem de Plaquetas , Prognóstico , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/sangue , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/terapia , Taxa de Sobrevida
18.
Nat Rev Cardiol ; 16(9): 555-574, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31123340

RESUMO

Testosterone is the main male sex hormone and is essential for the maintenance of male secondary sexual characteristics and fertility. Androgen deficiency in young men owing to organic disease of the hypothalamus, pituitary gland or testes has been treated with testosterone replacement for decades without reports of increased cardiovascular events. In the past decade, the number of testosterone prescriptions issued for middle-aged or older men with either age-related or obesity-related decline in serum testosterone levels has increased exponentially even though these conditions are not approved indications for testosterone therapy. Some retrospective studies and randomized trials have suggested that testosterone replacement therapy increases the risk of cardiovascular disease, which has led the FDA to release a warning statement about the potential cardiovascular risks of testosterone replacement therapy. However, no trials of testosterone replacement therapy published to date were designed or adequately powered to assess cardiovascular events; therefore, the cardiovascular safety of this therapy remains unclear. In this Review, we provide an overview of epidemiological data on the association between serum levels of endogenous testosterone and cardiovascular disease, prescription database studies on the risk of cardiovascular disease in men receiving testosterone therapy, randomized trials and meta-analyses evaluating testosterone replacement therapy and its association with cardiovascular events and mechanistic studies on the effects of testosterone on the cardiovascular system. Our aim is to help clinicians to make informed decisions when considering testosterone replacement therapy in their patients.


Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Terapia de Reposição Hormonal , Testosterona/sangue , Testosterona/uso terapêutico , Animais , Aterosclerose/diagnóstico por imagem , Plaquetas/fisiologia , Débito Cardíaco/efeitos dos fármacos , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/mortalidade , Vasos Coronários , Progressão da Doença , Prescrições de Medicamentos/estatística & dados numéricos , Endotélio/fisiopatologia , Tolerância ao Exercício/efeitos dos fármacos , Glucose/metabolismo , Humanos , Metabolismo dos Lipídeos , Lipoproteínas/sangue , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Testosterona/farmacologia , Resistência Vascular/efeitos dos fármacos
19.
PLoS One ; 14(5): e0215386, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31042735

RESUMO

BACKGROUND: Novel crystalloid solutions containing polyethylene glycol polymers (PEG-20k) produce dramatic resuscitation effects but dose-dependently produce a hypocoagulative state. The objective of this study was to examine possible mechanisms of this effect. Based on previous thromboelastography data, we hypothesize the effect is largely due to platelet interactions with the polymers. METHODS: Whole citrated blood from healthy volunteers was diluted ex-vivo 10% with crystalloids and tested for coagulation and platelet function. The specific tests included prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and von Willebrand factor (vWf) activity, thrombin generation, thromboelastography with and without platelet mapping, platelet flow cytometry, and erythrocyte sedimentation rate. FINDINGS: Fibrinogen and vWF activities, PT, and aPTT were not affected by PEG-20k dilutions. Thrombin activity was mildly suppressed with PEG-20k (TTP- 20%). Platelet mapping demonstrated significantly greater % inhibition of both ADP and arachidonic acid-induced platelet aggregation with PEG-20k, but direct ADP-activated gpIIa/IIIb (PAC1) and P-selectin (CD62P) binding site expression was not altered. Mild dose-dependent suppression of TEG-MA was seen with PEG-20k using platelet poor plasma. Erythrocyte Sedimentation Rates (ESR) were dramatically accelerated after dilution with 10% PEG-20k, which was competitively blocked by smaller PEG polymers, suggesting nonspecific PEG-20k cell binding effects. CONCLUSIONS: PEG-20k creates a mild hypocoagulative state in whole blood at concentrations ≥10%, which may be due to platelet-PEG interactions at the IIb/IIIa interface with lesser effects on fibrin polymerization. This interaction may cause a functional thrombasthenia induced by nonspecific platelet surface passivation by the PEG polymer.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Soluções Cristaloides/farmacologia , Polietilenoglicóis/química , Adulto , Plaquetas/fisiologia , Soluções Cristaloides/química , Relação Dose-Resposta a Droga , Feminino , Fibrinogênio/metabolismo , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Plaquetária , Polietilenoglicóis/farmacologia , Ressuscitação , Tromboelastografia/efeitos dos fármacos , Adulto Jovem , Fator de von Willebrand/metabolismo
20.
Pan Afr Med J ; 32: 5, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31068998

RESUMO

Introduction: Haematological reference values are very important for diagnostic orientation and treatment decision. The aim of this study was to establish haematological reference values for Malian healthy adults. Methods: A cross-sectional study including 161 male Malians aged between 19 and 54 years old was performed. Median and reference ranges were calculated for haematological and biochemical parameters. Parametric student's t-test was used to determine any statistically significant differences by age, smoker status, body mass index (BMI) and occupation. Ranges were further compared with those reported for other African, Afro-American and Caucasian populations. Results: Increased levels of MCV, MCH, PLT and EOS were found in younger Malians who had abnormal BMI and altered platelets parameters. Notably, significantly lower eosinophil and monocyte counts were observed in Malians compared to Europeans The smoking status did not seem to directly affect RIs. Conclusion: This is the first study to determine normal laboratory parameters in Malian adult males. Our results underscore the necessity of establishing region-specific clinical reference ranges that would allow clinicians and practitioners to manage laboratory tests, diagnosis and therapies. These data are useful not only for the management of patients in Mali, but also to support European and American clinicians in the health management of asylum seekers and migrants from Mali.


Assuntos
Contagem de Células Sanguíneas/normas , Análise Química do Sangue , Plaquetas/fisiologia , Índice de Massa Corporal , Adulto , Fatores Etários , Estudos Transversais , Humanos , Masculino , Mali , Pessoa de Meia-Idade , Ocupações/estatística & dados numéricos , Valores de Referência , Fumar/epidemiologia , Adulto Jovem
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