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1.
Cell Death Dis ; 12(1): 50, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33414384

RESUMO

Novel coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state, characterized by abnormal coagulation parameters and by increased incidence of cardiovascular complications. With this study, we aimed to investigate the activation state and the expression of transmembrane proteins in platelets of hospitalized COVID-19 patients. We investigated transmembrane proteins expression with a customized mass cytometry panel of 21 antibodies. Platelets of 8 hospitalized COVID-19 patients not requiring intensive care support and without pre-existing conditions were compared to platelets of healthy controls (11 donors) with and without in vitro stimulation with thrombin receptor-activating peptide (TRAP). Mass cytometry of non-stimulated platelets detected an increased surface expression of activation markers P-Selectin (0.67 vs. 1.87 median signal intensity for controls vs. patients, p = 0.0015) and LAMP-3 (CD63, 0.37 vs. 0.81, p = 0.0004), the GPIIb/IIIa complex (4.58 vs. 5.03, p < 0.0001) and other adhesion molecules involved in platelet activation and platelet-leukocyte interactions. Upon TRAP stimulation, mass cytometry detected a higher expression of P-selectin in COVID-19 samples compared to controls (p < 0.0001). However, we observed a significantly reduced capacity of COVID-19 platelets to increase the expression of activation markers LAMP-3 and P-Selectin upon stimulation with TRAP. We detected a hyperactivated phenotype in platelets during SARS-CoV-2 infection, consisting of highly expressed platelet activation markers, which might contribute to the hypercoagulopathy observed in COVID-19. In addition, several transmembrane proteins were more highly expressed compared to healthy controls. These findings support research projects investigating antithrombotic and antiplatelet treatment regimes in COVID-19 patients, and provide new insights on the phenotypical platelet expression during SARS-CoV-2 infection.


Assuntos
Plaquetas/patologia , Leucócitos/patologia , Trombose/epidemiologia , Adulto , Plaquetas/metabolismo , Plaquetas/virologia , /virologia , Estudos de Casos e Controles , Feminino , Alemanha/epidemiologia , Humanos , Leucócitos/metabolismo , Leucócitos/virologia , Masculino , Pessoa de Meia-Idade , Selectina-P/metabolismo , Fragmentos de Peptídeos/metabolismo , Fenótipo , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Trombose/virologia
2.
Medicine (Baltimore) ; 100(1): e24014, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33429764

RESUMO

INTRODUCTION: As a hematopoietic carcinogen, benzene induces human leukemia through its active metabolites such as benzoquinone, which may cause oxidative damage to cancer-related nuclear genes by increasing reactive oxygen species (ROS). Mitochondrion is the main regulatory organelle of ROS, genetic abnormality of mitochondrion can impede its regulation of ROS, leading to more severe oxidative damage. Mutations have been related to certain types of cancer in several mitochondrial genes, but they have never been completely analyzed genome-wide in leukemia. PATIENT CONCERNS: The patient was a 52-year-old female who had chronic exposure to benzene for several years. Her symptoms mainly included recurrent dizziness, fatigue, and they had lasted for nearly 8 years and exacerbated in recent weeks before diagnosis. DIAGNOSIS: Samples of peripheral blood were taken from the patient using evacuated tubes with EDTA anticoagulant on the second day of her hospitalization. At the same time blood routine and BCR/ABL genes of leukemic phenotype were tested. Platelets were isolated for mitochondrial DNA (mtDNA) extraction. The genetic analysis of ATP synthase Fo subunit 8 (complex V), ATP synthase Fo subunit 6 (complex V), cytochrome c oxidase subunit 1 (complex IV), cytochrome c oxidase subunit 2 (complex IV), cytochrome c oxidase subunit 3, Cytb, NADH dehydrogenase subunit 1 (complex I) (ND) 1, ND2, ND3, ND4, ND5, ND6, 12S-RNA, 16S-RNA, tRNA-Cysteine, A, N, tRNA-Leucine, E, displacement loop in platelet mtDNA were performed. All the detected gene mutations were validated using the conventional Sanger sequencing method. INTERVENTIONS: The patient received imatinib, a small molecule kinase inhibitor, and symptomatic treatments. OUTCOMES: After 3 months treatment her blood routine test indicators were restored to normal. CONCLUSION: A total of 98 mutations were found, and 25 mutations were frame shift. The ND6 gene mutation rate was the highest among all mutation points. Frame shifts were identified in benzene-induced leukemia for the first time. Many mutations in the platelet mitochondrial genome were identified and considered to be potentially pathogenic in the female patient with benzene-induced leukemia. The mutation rate of platelet mitochondrial genome in the benzene-induced leukemia patient is relatively high, and the complete genome analysis is helpful to fully comprehend the disease characteristics.


Assuntos
Plaquetas/patologia , Leucemia/etiologia , Leucemia/genética , Mitocôndrias/genética , Antineoplásicos/uso terapêutico , Benzeno/efeitos adversos , Exposição Ambiental/efeitos adversos , Feminino , Genoma Mitocondrial/genética , Genoma Mitocondrial/fisiologia , Humanos , Mesilato de Imatinib/uso terapêutico , Pessoa de Meia-Idade , Mitocôndrias/fisiologia
3.
Bratisl Lek Listy ; 122(1): 45-48, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33393320

RESUMO

AIM: To analyse the effect of systemic inflammatory status in patients with primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG) by calculating platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR). METHODS: This retrospective case-control study included 200 patients with POAG, 22 patients with PACG and 100 healthy subjects. The participants' white-blood-cell, lymphocyte, neutrophil, and platelet counts were recorded from previous blood assays. NLR and PLR were calculated manually. Results were compared among the groups. RESULTS: Both the POAG and PACG groups had higher platelet counts and PLR values than the control group (p=0.001 and p=0.001; respectively). The difference in NLR between POAG, PACG and control groups was not statistically significant (p=0.076). The POAG group had higher NLR values than the control (p=0.035). CONCLUSION: Both the POAG and the PACG groups exhibited higher platelet and PLR levels than the control. These results indicate a potential role of systemic inflammation in the pathogenesis of POAG and PACG (Tab. 4, Fig. 1, Ref. 35).


Assuntos
Glaucoma de Ângulo Fechado , Plaquetas , Estudos de Casos e Controles , Humanos , Inflamação , Pressão Intraocular , Linfócitos , Estudos Retrospectivos
4.
Cells ; 10(1)2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33430260

RESUMO

Sars-Cov-2 infection causes fever and cough that may rapidly lead to acute respiratory distress syndrome (ARDS). Few biomarkers have been identified but, unfortunately, these are individually poorly specific, and novel biomarkers are needed to better predict patient outcome. The aim of this study was to evaluate the diagnostic performance of circulating platelets (PLT)-derived extracellular vesicles (EVs) as biomarkers for Sars-Cov-2 infection, by setting a rapid and reliable test on unmanipulated blood samples. PLT-EVs were quantified by flow cytometry on two independent cohorts of Sars-CoV-2+ (n = 69), Sars-Cov-2- (n = 62) hospitalized patients, and healthy controls. Diagnostic performance of PLT-EVs was evaluated by receiver operating characteristic (ROC) curve. PLT-EVs count were higher in Sars-Cov-2+ compared to Sars-Cov-2- patients or HC. ROC analysis of the combined cohorts showed an AUC = 0.79 and an optimal cut-off value of 1472 EVs/µL, with 75% sensitivity and 74% specificity. These data suggest that PLT-EVs might be an interesting biomarker deserving further investigations to test their predictive power.


Assuntos
Plaquetas/metabolismo , Vesículas Extracelulares/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Plaquetas/patologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes
5.
Med Sci Monit ; 26: e927674, 2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33342993

RESUMO

BACKGROUND The aim of this study was to analyze the clinical features and laboratory indices of patients with coronavirus disease (COVID-19) and explore their association with the severity of the disease. MATERIAL AND METHODS A total of 61 patients with COVID-19 were divided into groups with common symptoms and with severe diseases, and clinical data were collected to analyze and compare the differences between them. RESULTS In patients with severe COVID-19, compared with the common group, lymphocyte count and albumin levels were lower, and aspartate aminotransferase (AST), blood urea, blood creatinine, lactate dehydrogenase (LDH), and C-reactive protein (CRP) levels, and prothrombin time (PT) were elevated (all P<0.05). The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume-to-lymphocyte ratio (MPVLR), and C-reactive protein-to-albumin ratio (CAR) were significantly elevated in the severe group compared with the group with common symptoms; however, the lymphocyte-to-monocyte ratio (LMR) was significantly reduced (P<0.05). Univariate logistic regression showed that lower lymphocyte count, prolonged PT, elevated CRP and LDH levels, and elevated NLR, PLR, MPVLR, and CAR were risk factors for COVID-19 severity (P<0.05). Multivariate logistic regression showed that elevated CRP levels (odds ratio [OR], 0.028; 95% confidence interval [CI]: 0.002-0.526; P=0.017), prolonged PT (OR, 0.014; 95% CI: 0.001-0.341; P=0.09), and an MPVLR >8.9 (OR, 0.026; 95% CI: 0.002-0.349; P=0.006) were independent risk factors for COVID-19 severity. CONCLUSIONS Elevated CRP and prolonged PT, and an MPVLR >8.9 were independent risk factors for COVID-19 severity.


Assuntos
/epidemiologia , Infecções por Coronavirus/diagnóstico , Adulto , Aspartato Aminotransferases/sangue , Plaquetas , Proteína C-Reativa/análise , China/epidemiologia , Coronavirus/patogenicidade , Infecções por Coronavirus/sangue , Creatinina/análise , Feminino , Humanos , Pacientes Internados , L-Lactato Desidrogenase/sangue , Contagem de Linfócitos , Linfócitos/química , Masculino , Volume Plaquetário Médio , Pessoa de Meia-Idade , Monócitos , Neutrófilos/química , Estudos Retrospectivos , Albumina Sérica/análise , Índice de Gravidade de Doença
6.
Int J Nanomedicine ; 15: 10151-10167, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33363371

RESUMO

Background: Traditional nanoparticle-based drug delivery systems suffer from several limitations, such as easy clearance from blood and inaccurate targeting. Materials and Methods: Here, we developed platelet membrane-coated nanoparticles (PM-NPs) to improve the precise delivery of drugs to tumor sites and enable a more efficient photothermal therapy (PTT) treatment. Results: Mimicking the natural platelet membrane, nanoparticles containing drugs and photothermal agents were not recognized and cleared by the immune system; they could circulate in the blood for a long time and accumulate more efficiently at the tumor site, thus releasing more antitumor drugs and achieving better PTT effects. It is worth mentioning that, in this study, we found that tumors in mice treated with the platelet-mimicking nanoparticles were completely eliminated without recurrence during the observation period (up to 18 days). Conclusion: This study provides a new strategy to design delivery systems of drugs or photothermal agents, whether in biotherapy or other fields.


Assuntos
Antineoplásicos/uso terapêutico , Plaquetas/metabolismo , Neoplasias da Mama/terapia , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Membrana Celular/ultraestrutura , Proliferação de Células/efeitos dos fármacos , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/administração & dosagem , Nanopartículas/ultraestrutura , Células RAW 264.7
7.
Zhonghua Shao Shang Za Zhi ; 36(12): 1167-1172, 2020 Dec 20.
Artigo em Chinês | MEDLINE | ID: mdl-33379853

RESUMO

Objective: To investigate the value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and blood platelet count (BPC) in judging the prognosis of adult patients with extensive burns. Methods: From January 2012 to December 2018, 99 adult patients with extensive burns who met the inclusion criteria were admitted to Union Hospital of Fujian Medical University, including 76 males and 23 females, aged 18 to 75 (43±13) years. According to the prognosis, the patients were divided into survival group of 79 cases and death group of 20 cases. Their clinical data were retrospectively analyzed by the method of case-control study. The gender, age, total burn area, inhalation injury, use of mechanical ventilation and white blood cell count, neutrophil count, lymphocyte count, and BPC on post injury day (PID) 1, 3, and 7 were collected, and the NLR, PLR, difference value of BPC on PID 3 and PID 1 (ΔBPC3), difference value of NLR on PID 3 and PID 1 (ΔNLR3), difference value of PLR on PID 3 and PID 1 (ΔPLR3), difference value of BPC on PID 7 and PID 1 (ΔBPC7), difference value of NLR on PID 7 and PID 1 (ΔNLR7), difference value of PLR on PID 7 and PID 1 (ΔPLR7) of patients in the two groups were calculated. Data were statistically analyzed with Mann-Whitney U test, independent sample t test, chi-square test to screen the death-related factors of patients. Binary classification single factor and multifactor logistic regression analysis were used to analyze the death-related factors of patients. The receiver's operating characteristic (ROC) curve of the independent risk factor of death of patients predicting the prognosis of adult patients with extensive burns was drawn, and the area under the curve, the optimal threshold and its sensitivity and specificity were calculated. Results: (1) There were statistically significant differences in total burn area and use of mechanical ventilation of patients between the two groups (Z=-2.615, χ(2)=7.282, P<0.01). (2) On PID 1, there was statistically significant difference in NLR of patients between the two groups (Z=-2.414, P<0.05). On PID 3, there were statistically significant differences in BPC and ΔNLR3 of patients between the two groups (Z=-2.048, -2.780, P<0.05 or P<0.01). On PID 7, there were statistically significant differences in lymphocyte count, BPC, NLR, and ΔNLR7 of patients between the two groups (Z=-2.248, -2.231, -2.641, -3.669, P<0.05 or P<0.01). (3) Binary classification single factor logistic regression analysis showed that the total burn area, mechanical ventilation, BPC and NLR on PID 7, and ΔNLR7 were related to death of patients (odds ratio=1.038, 0.193, 0.990, 1.086, 1.105, 95% confidence interval=1.010-1.067, 0.062-0.598, 0.982-0.998, 1.012-1.165, 1.037-1.178, P<0.05 or P<0.01). Binary classification multifactor logistic regression analysis showed that ΔNLR7 was the independent risk factor of death of adult patients with extensive burns (odds ratio=1.090, 95% confidence interval=1.008-1.178, P<0.05). (4) The optimal threshold of ROC curve of ΔNLR7 for predicting the prognostic death of 97 adult patients with extensive burns was -0.073 4. The sensitivity under the optimal threshold was 65.0%, and the specificity was 78.5%. The area under the ROC curve was 0.776 (95% confidence interval=0.650-0.882, P<0.01). Conclusions: Dynamic monitoring of NLR and BPC is of great significance to assist in judging the prognosis of adult patients with extensive burns. ΔNLR7 is an independent predictor of death in adult patients with extensive burns, while PLR can not predict the death of adult patients with extensive burns.


Assuntos
Queimaduras , Adolescente , Adulto , Idoso , Plaquetas , Estudos de Casos e Controles , Feminino , Humanos , Linfócitos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Adulto Jovem
8.
Medicine (Baltimore) ; 99(50): e23418, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327268

RESUMO

BACKGROUND: Triple negative breast cancer affects 10% to 20% of all women diagnosed with breast cancer. Due to its characteristics, treatment strategies are limited and metastatic recurrences are common in the first 5 years after treatment. However, not all patients affected by this disease develop metastases. Tumor-infiltrating lymphocytes have shown to be reliable predictive biomarkers of treatment response and metastatic recurrences. However, we need to develop simpler and faster ways to predict response to cytotoxic treatment and the possibility of eventual cancer relapse by identifying new biomarkers. Recently, new studies are emerging, suggesting a predictive role of circulating blood cells in different types of cancer. In this study, we will assess the correlation between tumor-infiltrating lymphocytes and different elements of the blood count in patients diagnosed with triple negative breast cancer. METHODS: The main objective of this study is to evaluate the correlation between the peripheral neutrophil-to-lymphocyte ratio and the amount of tumor-infiltrating lymphocytes, assessed in triple negative breast cancer patients at diagnosis. Secondary objectives include evaluation of the correlation between tumor-infiltrating lymphocytes at diagnosis and the baseline absolute neutrophil, lymphocyte, and platelet counts, as well as the platelet-to-lymphocyte ratio. The triple negative breast cancer patients will be enrolled in the PERCEPTION trial during the first year after the treatment completion. Two supplementary blood tests, at 12 months after the end of treatment and at the time of the first metastatic recurrence, will be performed. DISCUSSION: The discovery of new prognostic and predictive biomarkers is crucial for triple negative breast cancer. We set up the PERCEPTION clinical trial in order to evaluate certain blood counts as early biomarkers and to assess their correlation with tumor-infiltrating lymphocytes. Demonstration of comparative predictive and/or prognostic capacities of peripheral blood counts and tumor-infiltrating lymphocytes would allow introduction of the former as simple and cheap biomarkers in triple negative breast cancer patient management. TRIAL REGISTRATION: The PERCEPTION study has been registered in the French National Agency of Medical Security registry on the 2nd of July 2019 under the number 2019-A01861-56 and in the ClinicalTrials.org registry under the number NCT04068623.


Assuntos
Plaquetas/metabolismo , Neoplasias da Mama/sangue , Linfócitos do Interstício Tumoral/metabolismo , Neutrófilos/metabolismo , Neoplasias de Mama Triplo Negativas/sangue , Adolescente , Adulto , Biomarcadores Tumorais/sangue , Neoplasias da Mama/mortalidade , Feminino , Humanos , Contagem de Linfócitos , Linfócitos/metabolismo , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/mortalidade , Contagem de Plaquetas , Valor Preditivo dos Testes , Prognóstico , Neoplasias de Mama Triplo Negativas/mortalidade , Adulto Jovem
9.
Acta Cir Bras ; 35(10): e202001006, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33237177

RESUMO

PURPOSE: To evaluate and compare the effects of homologous and heterologous PRP (Platelet-Rich Plasma) on the quality and speed of skin wound healing, compared to Poor Platelet Plasma (PPP). METHODS: Twenty-one male adult rabbits were used; two for preparing homologous PRP, with the rest of them separated randomly in three groups, according to the treatment received: PPP - control (n=5), homologous PRP (n=7), heterologous (n=7). Excisional skin wounds were made on the back of the animals, for the application of homologous and heterologous PPP and PRP. At the 14th post-operative day (POD), the animals were subjected to a new wound, and the treatments were inverted. The wounds were evaluated macroscopically and histologically. RESULTS: A larger percentage of scar retraction was observed on the group treated with heterologous PRP, compared to homologous PRP, at the third POD, an increase of 25.03% (p=0.01). No other statistically significant differences among treatments were observed. Among every group, skin healing was efficient, without local adverse effects. CONCLUSIONS: Heterologous PRP contributed with more tissue retraction at the beginning of the wound healing process. After this, there were no differences on the wound healing skin process treated with PRP or PPP. However, our findings suggest the presence of others plasmatic factors, besides platelets, which could also contribute to the wound healing process, and thus, should be further investigated.


Assuntos
Plaquetas , Plasma Rico em Plaquetas , Animais , Masculino , Coelhos , Pele , Cicatrização
10.
Nat Commun ; 11(1): 5778, 2020 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-33188196

RESUMO

Breakdown of vascular barriers is a major complication of inflammatory diseases. Anucleate platelets form blood-clots during thrombosis, but also play a crucial role in inflammation. While spatio-temporal dynamics of clot formation are well characterized, the cell-biological mechanisms of platelet recruitment to inflammatory micro-environments remain incompletely understood. Here we identify Arp2/3-dependent lamellipodia formation as a prominent morphological feature of immune-responsive platelets. Platelets use lamellipodia to scan for fibrin(ogen) deposited on the inflamed vasculature and to directionally spread, to polarize and to govern haptotactic migration along gradients of the adhesive ligand. Platelet-specific abrogation of Arp2/3 interferes with haptotactic repositioning of platelets to microlesions, thus impairing vascular sealing and provoking inflammatory microbleeding. During infection, haptotaxis promotes capture of bacteria and prevents hematogenic dissemination, rendering platelets gate-keepers of the inflamed microvasculature. Consequently, these findings identify haptotaxis as a key effector function of immune-responsive platelets.


Assuntos
Plaquetas/patologia , Vasos Sanguíneos/patologia , Quimiotaxia , Inflamação/patologia , Pneumonia/sangue , Complexo 2-3 de Proteínas Relacionadas à Actina/metabolismo , Adulto , Animais , Movimento Celular , Microambiente Celular , Modelos Animais de Doenças , Fibrinogênio/metabolismo , Humanos , Lipopolissacarídeos , Lesão Pulmonar/microbiologia , Lesão Pulmonar/patologia , Staphylococcus aureus Resistente à Meticilina/fisiologia , Camundongos Endogâmicos C57BL , Microvasos/patologia , Pneumonia/microbiologia , Pseudópodes/metabolismo
12.
BMC Infect Dis ; 20(1): 864, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33213395

RESUMO

BACKGROUND: Routine blood parameters, such as the lymphocyte (LYM) count, platelet (PLT) count, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), lymphocytes multiplied by platelets (LYM*PLT) and mean platelet volume-to-platelet ratio (MPV/PLT), are widely used to predict the prognosis of infectious diseases. We aimed to explore the value of these parameters in the early identification of influenza virus infection in children. METHODS: We conducted a single-center, retrospective, observational study of fever with influenza-like symptoms in pediatric outpatients from different age groups and evaluated the predictive value of various routine blood parameters measured within 48 h of the onset of fever for influenza virus infection. RESULTS: The LYM count, PLT count, LMR and LYM*PLT were lower, and the NLR and MPV/PLT were higher in children with an influenza infection (PCR-confirmed and symptomatic). The LYM count, LMR and LYM*PLT in the influenza infection group were lower in the 1- to 6-year-old subgroup, and the LMR and LYM*PLT in the influenza infection group were lower in the > 6-year-old subgroup. In the 1- to 6-year-old subgroup, the cutoff value of the LMR for predicting influenza A virus infection was 3.75, the sensitivity was 81.87%, the specificity was 84.31%, and the area under the curve (AUC) was 0.886; the cutoff value of the LMR for predicting influenza B virus infection was 3.71, the sensitivity was 73.58%, the specificity was 84.31%, and the AUC was 0.843. In the > 6-year-old subgroup, the cutoff value of the LMR for predicting influenza A virus infection was 3.05, the sensitivity was 89.27%, the specificity was 89.61%, and the AUC was 0.949; the cutoff value of the LMR for predicting influenza B virus infection was 2.88, the sensitivity was 83.19%, the specificity was 92.21%, and the AUC was 0.924. CONCLUSIONS: Routine blood tests are simple, inexpensive and easy to perform, and they are useful for the early identification of influenza virus infection in children. The LMR had the strongest predictive value for influenza virus infection in children older than 1 year, particularly in children older than 6 years with influenza A virus infection.


Assuntos
Influenza Humana/diagnóstico , Área Sob a Curva , Contagem de Células Sanguíneas , Plaquetas/citologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Vírus da Influenza A/isolamento & purificação , Vírus da Influenza B/isolamento & purificação , Influenza Humana/sangue , Influenza Humana/virologia , Linfócitos/citologia , Masculino , Monócitos/citologia , Neutrófilos/citologia , RNA Viral/genética , RNA Viral/metabolismo , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade
14.
Int J Mol Sci ; 21(21)2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33153161

RESUMO

Progressive respiratory failure is seen as a major cause of death in severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection. Relatively little is known about the associated morphologic and molecular changes in the circulation of these patients. In particular, platelet and erythrocyte pathology might result in severe vascular issues, and the manifestations may include thrombotic complications. These thrombotic pathologies may be both extrapulmonary and intrapulmonary and may be central to respiratory failure. Previously, we reported the presence of amyloid microclots in the circulation of patients with coronavirus disease 2019 (COVID-19). Here, we investigate the presence of related circulating biomarkers, including C-reactive protein (CRP), serum ferritin, and P-selectin. These biomarkers are well-known to interact with, and cause pathology to, platelets and erythrocytes. We also study the structure of platelets and erythrocytes using fluorescence microscopy (using the markers PAC-1 and CD62PE) and scanning electron microscopy. Thromboelastography and viscometry were also used to study coagulation parameters and plasma viscosity. We conclude that structural pathologies found in platelets and erythrocytes, together with spontaneously formed amyloid microclots, may be central to vascular changes observed during COVID-19 progression, including thrombotic microangiopathy, diffuse intravascular coagulation, and large-vessel thrombosis, as well as ground-glass opacities in the lungs. Consequently, this clinical snapshot of COVID-19 strongly suggests that it is also a true vascular disease and considering it as such should form an essential part of a clinical treatment regime.


Assuntos
Plaquetas/patologia , Doenças Cardiovasculares/virologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/patologia , Eritrócitos/patologia , Ferritinas/sangue , Selectina-P/sangue , Pneumonia Viral/sangue , Pneumonia Viral/patologia , Betacoronavirus/isolamento & purificação , Coagulação Sanguínea/fisiologia , Plaquetas/virologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/patologia , Infecções por Coronavirus/virologia , Eritrócitos/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/virologia , Trombose/patologia , Trombose/virologia
15.
Medicine (Baltimore) ; 99(45): e23151, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33157998

RESUMO

During sepsis, platelets dysfunction contributes to organ dysfunction. Studies on platelets dysfunction in the long-term prognosis of sepsis are lacking. The aim of this study was to assess the role of platelets in the long-term prognosis of sepsis patients.A total of 4576 sepsis patients were extracted from MIMIC III Database. Survival was analyzed by the Kaplan-Meier method. Univariate and multivariate cox analyses were performed to identify prognostic factors. Significant prognostic factors were combined to build a nomogram to predict 1 year overall survival (OS). The discriminative ability and predictive accuracy of the nomogram were evaluated using the receiver operating characteristic curve (ROC) analysis and calibration curves used for sepsis.The more abnormal the platelet level, the worse prognosis of patients. After final regression analysis, age, blood urea nitrogen, platelets, international normalized ratio, partial thromboplastin time, potassium, hemoglobin, white blood cell count, organ failures were found to be independent predictors of 1 year OS of sepsis patient and were entered into a nomogram. The nomogram showed a robust discrimination, with an area under the receiver operating characteristic curve of 0.752. The calibration curves for the probability of the prognosis of sepsis patients showed optimal agreement between the probability as predicted by the nomogram and the actual probability.Platelet was an independent prognostic predictor of 1 year OS for patients with sepsis. Platelet-related nomogram that can predict the 1 year OS of sepsis patients. It revealed optimal discrimination and calibration, indicating that the nomogram may have clinical utility.


Assuntos
Plaquetas , Sepse/sangue , Sepse/mortalidade , Idoso , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nomogramas , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo
16.
Diagnosis (Berl) ; 7(4): 387-394, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33035183

RESUMO

Objectives The pandemic COVID-19 currently reached 213 countries worldwide with nearly 9 million infected people and more than 460,000 deaths. Although several Chinese studies, describing the laboratory findings characteristics of this illness have been reported, European data are still scarce. Furthermore, previous studies often analyzed the averaged laboratory findings collected during the entire hospitalization period, whereas monitoring their time-dependent variations should give more reliable prognostic information. Methods We analyzed the time-dependent variations of 14 laboratory parameters in two groups of COVID-19 patients with, respectively, a positive (40 patients) or a poor (42 patients) outcome, admitted to the San Raffaele Hospital (Milan, Italy). We focused mainly on laboratory parameters that are routinely tested, thus, prognostic information would be readily available even in low-resource settings. Results Statistically significant differences between the two groups were observed for most of the laboratory findings analyzed. We showed that some parameters can be considered as early prognostic indicators whereas others exhibit statistically significant differences only at a later stage of the disease. Among them, earliest indicators were: platelets, lymphocytes, lactate dehydrogenase, creatinine, alanine aminotransferase, C-reactive protein, white blood cells and neutrophils. Conclusions This longitudinal study represents, to the best of our knowledge, the first study describing the laboratory characteristics of Italian COVID-19 patients on a normalized time-scale. The time-dependent prognostic value of the laboratory parameters analyzed in this study can be used by clinicians for the effective treatment of the patients and for the proper management of intensive care beds, which becomes a critical issue during the pandemic peaks.


Assuntos
Betacoronavirus/genética , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Plaquetas/metabolismo , Proteína C-Reativa/análise , Infecções por Coronavirus/sangue , Infecções por Coronavirus/virologia , Creatinina/sangue , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Itália/epidemiologia , L-Lactato Desidrogenase/sangue , Estudos Longitudinais , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/virologia , Prognóstico
17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1694-1698, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067976

RESUMO

OBJECTIVE: To investigate the inducing effect of PKA inhibitor H89 of different concentrations on platelet apoptosis and its mechanism. METHODS: Platelets were isolated from peripheral venous blood of healthy volunteers. Different concentrations gradient PKA inhibitor H89 were co-incubated with washing platelets, and the effects of PKA inhibitor H89 at different concentrations on platelet mitochondrial membrane potential, phosphatidylserine and reactive oxygen species(ROS) were determined by ELISA and flow cytometry. RESULTS: Different concentration of PKA inhibitor H89 could induce the depolarization of mitochondrial membrane potential and PS exposure of platelet. However, high concentration(100 µmol/L) PKA inhibitor H89 could induce the production of ROS in platelets, but medium and low concentrations did not induce the production of ROS in platelets. And several ROS inhibitors could inhibit the apoptosis induced by high concentration PKA inhibitor H89. CONCLUSION: High concentration H89 can induce platelet apoptosis, however the mechanism of platelet apoptosis caused by H89 of high concentration is different from H89 at medium and low concentrations.


Assuntos
Plaquetas , Peptídeos e Proteínas de Sinalização Intracelular , Apoptose , Humanos , Potencial da Membrana Mitocondrial
18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1704-1709, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067978

RESUMO

OBJECTIVE: To investigate the role of mitochonaria in the regulation of platelet membrane protein GPIbα shedding and its mechanisms. METHODS: The washed platelets were obtained from peripheral blood in healthy volunteers and co-incubated with mitochondrial inhibitor carbonyl cyanide m-chlorophenyl hydrazone (CCCP), mitochondrial protector cyclosporin A (CsA) or matrix metalloproteinases inhibitor GM6001. After the platelets was stimulated, the effect of mitochondria to the shedding in platelet membrane protein GPIbα was detected by flow cytometry. RESULTS: Depolarization of mitochondrial membrane potential and the respiratory function of mitochondrial could be induced and destroyed by the uncoupling agent CCCP. At the same time, the shedding of GPIbα was detected out, and the result showed a statistical significance, which showed that the shedding of GPIbα could be activated by the damaged of mitochondrial in platelets. After the mitochondrial was protected by CsA, the shedding of GPIbα was inhibited significantly. GM6001 could only inhibited the shedding of GPIbα, but showed no inhibitation to the function of mitochondrial, which showed that the shedding of GPIbα was regulated at the mitochondrial, and the regulatory enzyme of receptor shedding (ADAM17) was located in the pathway of downstream of mitochondria. After the oxidative damage in cells was inhibited by NAC, and the changes of GPIbα shedding was detected, the result showed that the GPIbα shedding could be inhibited by NAC, which showed a dose-dependent manner. CONCLUSION: The GPIbα shedding could be caused by abnormality function of metabolic, and the metabolic imbalance of ROS is caused by the abnormallity function of mitochondria.


Assuntos
Plaquetas , Proteínas de Membrana , Humanos , Proteínas de Membrana/metabolismo , Mitocôndrias
19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1787-1790, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067991

RESUMO

The process of thrombus formation in vivo is complex, which is affected by the platelets, clotting system, and vessels, as well as blood flow. The previous research ways, which were either static or shear stress-mimicking ex vivo, could not reflect the condition in vivo completely. In recent years, The high resolution confocal microscope combined with bioluminescence system was developed which can be used to observe the animal thrombus formation in real time in vivo. By using this system, scientists have gotten a novel knowledge about the thrombus formation. In this review, the operating steps of this system, the hierarchical structure of thrombs revealed by this system and the related mechanism are sammrized briefly.


Assuntos
Trombose , Animais , Coagulação Sanguínea , Plaquetas , Microscopia
20.
Nat Commun ; 11(1): 4964, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009394

RESUMO

Thrombosis leads to platelet activation and subsequent degradation; therefore, replenishment of platelets from hematopoietic stem/progenitor cells (HSPCs) is needed to maintain the physiological level of circulating platelets. Platelet-derived microparticles (PMPs) are protein- and RNA-containing vesicles released from activated platelets. We hypothesized that factors carried by PMPs might influence the production of platelets from HSPCs, in a positive feedback fashion. Here we show that, during mouse acute liver injury, the density of megakaryocyte in the bone marrow increases following an increase in circulating PMPs, but without thrombopoietin (TPO) upregulation. In vitro, PMPs are internalized by HSPCs and drive them toward a megakaryocytic fate. Mechanistically, miR-1915-3p, a miRNA highly enriched in PMPs, is transported to target cells and suppresses the expression levels of Rho GTPase family member B, thereby inducing megakaryopoiesis. In addition, direct injection of PMPs into irradiated mice increases the number of megakaryocytes and platelets without affecting TPO levels. In conclusion, our data reveal that PMPs have a role in promoting megakaryocytic differentiation and platelet production.


Assuntos
Plaquetas/metabolismo , Diferenciação Celular , Micropartículas Derivadas de Células/metabolismo , Megacariócitos/citologia , MicroRNAs/metabolismo , Animais , Sequência de Bases , Linhagem Celular , Endocitose , Perfilação da Expressão Gênica , Humanos , Fígado/lesões , Fígado/patologia , Masculino , Megacariócitos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , MicroRNAs/genética , Poliploidia , Proteína rhoB de Ligação ao GTP/metabolismo
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