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1.
J Surg Oncol ; 121(5): 901-905, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31858621

RESUMO

BACKGROUND AND OBJECTIVES: The prognosis of colorectal cancer (CRC) has improved in the last decades, however, a lower overall survival persists in the elderly. The understanding of immunity changes in the elderly with CRC will allow the emergence of new treatments with higher response rates. 4-1BB and CD40L, an immune checkpoint stimulator, play an important role in T-cell responses and platelets. Our aim was to characterize the soluble levels of CD40L and 4-1BB in CRC elderly patients. METHODS: A cross-sectional study was performed in 41 patients with CRC and 35 healthy elderly controls. Patients with CRC were divided into three groups according to staging: 13 patients with advanced tumor restricted to the organ (stages II); 16 patients with lymph node metastasis (stage III); and 12 patients with distant metastasis (stage IV). RESULTS: There were higher levels of soluble s4-1BB and sCD40L in CRC elderly stage II patients when compared with healthy controls (P = .0009 and P < .0001, respectively), stage III patients (P = .008 and P < .0001, respectively) and stage IV patients (P = .007 and P < .0001, respectively). CONCLUSIONS: We concluded that sCD40L and s4-1BB molecules may be prognostic biomarkers, since the reduction in plasma levels of these molecules was associated with disease progression.


Assuntos
Ligante de CD40/sangue , Neoplasias Colorretais/mortalidade , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/sangue , Idoso , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , Estudos Transversais , Feminino , Humanos , Metástase Linfática , Masculino , Metástase Neoplásica
2.
World Neurosurg ; 132: e630-e636, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31442656

RESUMO

BACKGROUND: Higher circulating soluble cluster of differentiation 40 ligand (sCD40L) levels at admission of an ischemic stroke have been found in nonsurvivor than in survivor patients. The objectives of this study were to determine whether serum sCD40L levels during the first week of a severe malignant middle cerebral artery infarction (MMCAI) are higher in nonsurvivor than in survivor patients and whether they could be used as biomarker of mortality prediction. METHODS: This multicenter study included patients with severe MMCAI (defined as Glasgow Coma Scale score <9). We determined serum sCD40L concentrations at days 1, 4, and 8 and performed receiver operating characteristic analyses to determine their capacity for 30-day mortality prediction. RESULTS: Nonsurvivors (n = 34) showed higher sCD40L levels on days 1 (P < 0.001), 4 (P = 0.004), and 8 (P < 0.001) than did survivor patients (n = 34). Areas under the curve of serum sCD40L concentrations at days 1, 4, and 8 of severe MMCAI for 30-day mortality prediction were 83% (P < 0.001), 89% (P < 0.001), and 87% (P < 0.001), respectively. CONCLUSIONS: The findings that nonsurvivors showed higher serum sCD40L levels during the first week of MMCAI than did survivors and that serum sCD40L levels during the first week of MMCAI could be used as a mortality predictor biomarker are 2 novel findings.


Assuntos
Biomarcadores/sangue , Ligante de CD40/sangue , Infarto da Artéria Cerebral Média/sangue , Infarto da Artéria Cerebral Média/mortalidade , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
3.
Transfus Clin Biol ; 26(3): 144-146, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31327557

RESUMO

Platelet transfusion is a safe process, but during or after the process the recipient may experience an adverse reaction and occasionally a serious adverse reaction (SAR). Platelet concentrate transfusion may be liable for significant absence of beneficial response. Danger may manifest clinically or biologically; in the latter case, manifestations are frequently an absence of the expected response to the blood component by the recipient. Blood platelets exert roles in inflammation, especially through the immunomodulator complex CD40/CD40L (sCD40L). In this review, we concentrate on the inflammatory potential of platelets and their participation to SARs in transfusion.


Assuntos
Citocinas/sangue , Inflamação/etiologia , Transfusão de Plaquetas/efeitos adversos , Plaquetas/metabolismo , Antígenos CD40/sangue , Ligante de CD40/sangue , Humanos , Inflamação/sangue
4.
Medicina (Kaunas) ; 55(7)2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31311177

RESUMO

Background and objectives: No-reflow (NR) phenomenon is defined as insufficient myocardial perfusion in coronary circulation in the absence of angiographic evidence of mechanical obstruction. The primary mechanisms of the NR occurrence are thought to be high platelet activity and thrombus burden. Soluble CD40 ligand (sCD40L), which is released into the plasma following platelet activation, accelerates the inflammatory process and causes further platelet activation. The aim of our study is to investigate the relationship between the NR phenomenon and sCD40L level in patients with ST-elevation myocardial infarction (STEMI). Methods: A total of 81 acute STEMI patients undergoing primary percutaneous coronary intervention and 40 healthy participants were included in this study. Acute STEMI patients were classified into two groups: 41 patients with the NR phenomenon (NR group) and 40 patients without the NR phenomenon (non-NR group). The serum sCD40L level was measured for all groups. Results: The serum sCD40L level was significantly higher in the NR group than in non-NR and control groups (379 ± 20 pg/mL, 200 ± 15 pg/mL and 108 ± 6.53 pg/mL, respectively; p < 0.001). Univariate regression analysis demonstrated that male sex, age, Gensini score and sCD40L level were the possible factors affecting the occurrence of the NR phenomenon. In multivariate regression analysis, age (odds ratio [OR], 1.091; 95% confidence interval [CI], 1.023-1.163; p < 0.008) and serum sCD40L (OR, 1.016; 95% CI, 1.008-1.024; p < 0.001) remained the independent predictor of the presence of NR. Conclusions: Our study showed that serum sCD40L level was an independent predictor of the NR phenomenon occurrence.


Assuntos
Ligante de CD40/análise , Fenômeno de não Refluxo/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Adulto , Idoso , Análise de Variância , Ligante de CD40/sangue , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fenômeno de não Refluxo/epidemiologia , Razão de Chances , Intervenção Coronária Percutânea/métodos , Estudos Prospectivos , Curva ROC , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia
5.
J Immunol Res ; 2019: 8063983, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31183392

RESUMO

Acute coronary syndrome (ACS) can be triggered by the presence of inflammatory factors which promote the activation of immune cells by costimulatory molecules such as CD40 and its ligand CD40L. Environmental and genetic factors are involved in the etiology of the ACS. The aim of this study was to explore the gene and protein expression associated with CD40 and CD40L genetic variants in ACS patients from the western Mexican population. A total of 620 individuals from western Mexico were recruited: 320 ACS patients and 300 individuals without a history of ischemic cardiopathy were evaluated. The genotype was determined using TaqMan SNP genotyping assays. CD40 and CD40L expressions at the mRNA level were quantified using TaqMan Gene Expression Assays. Soluble protein isoforms were measured by enzyme-linked immunosorbent assay. We did not find evidence of association between CD40 (rs1883832, rs4810485, and rs11086998) and CD40L (rs3092952 and rs3092920) genetic variants and susceptibility to ACS, although rs1883832 and rs4810485 were significantly associated with high sCD40 plasma levels. Plasma levels of sCD40L can be affected by gender and the clinical spectrum of acute coronary syndrome. Our results do not suggest a functional role of CD40 and CD40L genetic variants in ACS. However, they could reflect the inflammatory process and platelet activation in ACS patients, even when they are under pharmacological therapy. Due to the important roles of the CD40-CD40L system in the pathogenesis of ACS, longitudinal studies are required to determine if soluble levels of CD40 and CD40L could be clinically useful markers of a recurrent cardiovascular event after an ACS.


Assuntos
Síndrome Coronariana Aguda/genética , Antígenos CD40/genética , Ligante de CD40/genética , Genótipo , RNA Mensageiro/genética , Idoso , Biomarcadores , Antígenos CD40/sangue , Ligante de CD40/sangue , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Transcriptoma
6.
Mediators Inflamm ; 2019: 2473164, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30944545

RESUMO

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with the polyclonal activation of B lymphocytes and the production of autoantibodies that cause immune complex-related inflammation. Immunological factors derived from platelets modulate B cell function in SLE disease. However, platelets do not only modify the immune system by soluble factors. The binding of platelets to lymphocytes can modulate immune response. Thus, we speculate that the binding of platelets to lymphocytes in SLE patients may play a role in abnormal B lymphocyte response and the pathogenesis of SLE. We observed that levels of lymphocytes with bound platelets were higher in SLE patients than in healthy donors (HD). In SLE patients, the percentage of B lymphocytes with bound platelets positively correlated with plasmatic levels of IgG, IgA, IL-10, and soluble CD40L and negatively correlated with IgM levels, though not in HD. Preswitched memory B lymphocytes were the subpopulation with more bound platelets. Lymphocytes with bound platelets from both HD and SLE patients had major levels of CD86 and BAFFR and a greater production of IL-10 than lymphocytes without bound platelets. However, only B lymphocytes with bound platelets from SLE patients had increased levels of IgG and IgA on their surface. SLE patients with a suggestive renal manifestation had the highest levels of B and T lymphocytes with bound platelets. These results suggest that the binding of platelets to lymphocytes plays a role in SLE disease and that controlling this binding may be a promising therapeutic approach.


Assuntos
Linfócitos B/metabolismo , Linfócitos B/patologia , Plaquetas/metabolismo , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/patologia , Linfócitos/metabolismo , Linfócitos/patologia , Adulto , Ligante de CD40/sangue , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Interleucina-10/sangue , Masculino , Pessoa de Meia-Idade
7.
World Neurosurg ; 126: e1537-e1541, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30926559

RESUMO

BACKGROUND: Soluble cluster of differentiation 40 ligand (sCD40L) is a member of the tumor necrosis factor family with proinflamatory and procoagulant effects. A previous study found higher serum sCD40L levels at day 1 of traumatic brain injury (TBI) in nonsurviving than surviving patients. Thus the objective of this study was to compare serum sCD40L levels during the first week of a severe TBI between surviving and nonsurviving patients and to determine whether it could be used as a mortality predictor biomarker. METHODS: In this multicenter study severe TBI patients (with Glasgow Coma Scale score <9) with an Injury Severity Score in noncranial item <9 were included. Serum sCD40L concentrations at days 1, 4, and 8 of TBI were determined. We performed receiver operating characteristic analyses to determine the capacity of 30-day TBI mortality prediction by serum sCD40L levels at days 1, 4, and 8 of TBI. RESULTS: We found that nonsurviving (n = 34) patients in comparison with surviving (n = 90) patients had higher sCD40L levels on days 1 (P < 0.001), 4 (P = 0.004), and 8 (P < 0.001) of TBI. We also found that the areas under curve of serum sCD40L concentrations at days 1, 4, and 8 of TBI to 30-day mortality prediction were 82% (P < 0.001), 72% (P = 0.01) and 83% (P < 0.001), respectively. CONCLUSIONS: The existence of higher serum sCD40L levels in nonsurviving than surviving patients during the first week of TBI and fact that serum sCD40L levels during the first week of TBI can be used as a mortality predictor biomarker are the new findings of our study.


Assuntos
Lesões Encefálicas Traumáticas/sangue , Lesões Encefálicas Traumáticas/mortalidade , Ligante de CD40/sangue , Adulto , Idoso , Biomarcadores , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Análise de Sobrevida
8.
Int J Exp Pathol ; 100(1): 41-48, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30811756

RESUMO

Diabetes is associated with an increased risk of cardiovascular disease. This is partially attributed to an altered activation status of blood platelets in this disease. Previously, alterations have been shown in COX-1 and protease activated receptor (PAR)-3 receptor expression in platelets in two animal models of diabetes, there have not been studies which address expression of these proteins in mice with long-term streptozotocin (STZ)-induced diabetes. We have also addressed the effect of diabetes on platelet adhesion under flow conditions. With the use of flow cytometry, we have shown that certain markers of platelet basal activation, such as active form of αII b ß3 and of CD40L were increased in STZ-induced diabetic mice. Platelets from STZ-induced diabetic mice were also more reactive when stimulated with PAR-4 activating peptide as revealed by higher expression of active form of αII b ß3 , membrane-bound on vWillebrand Factor and binding of exogenous fluorescein isothyanate-labelled fibrinogen. Expression of COX-1 and production of thromboxane A2 in platelets of STZ-induced diabetic mice were higher than in control animals. We observed no effect of diabetes on ability of platelets to form stable adhesions with fibrinogen in flow conditions. We conclude that although certain similarities exist between patterns of activation of platelets in animal models of diabetes, the differences should also be taken into account.


Assuntos
Plaquetas/enzimologia , Ciclo-Oxigenase 1/sangue , Diabetes Mellitus Experimental/sangue , Proteínas de Membrana/sangue , Adesividade Plaquetária , Estreptozocina , Animais , Ligante de CD40/sangue , Vasos Coronários/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/enzimologia , Epoprostenol/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Receptores Ativados por Proteinase/sangue , Tromboxano A2/sangue , Fator de von Willebrand/metabolismo
9.
Microvasc Res ; 122: 85-93, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30502363

RESUMO

OBJECTIVES: Coronary microvascular dysfunction plays a major role in the pathogenesis of microvascular angina (MVA). Along with endothelial dysfunction, microvascular atherosclerosis and inflammation seem to contribute to the development of coronary microvascular dysfunction. Serum soluble ST2 (sST2) and serum soluble CD40 ligand (sCD40L) are two biomarkers associated with inflammation and atherosclerosis. The aim of this study was to investigate the role of these biomarkers in the pathogenesis of MVA and determine their possible association with coronary microvascular dysfunction. METHODS: A total of 152 patients were included in the study. Ninety-one patients with MVA {median age 56 years (40-79), of which 55 are women} and sixty-one controls {median age 52 (38-76), of which 29 are women} were included in the study. Serum concentration of sST2 and sCD40L were measured with a commercially available ELISA kit. RESULTS: Serum sST2 (median 13.6 ng/ml; interquartile range (IQR), 3.5-63.8 ng/ml vs median 10.6 ng/ml; IQR, 2.9-34.2 ng/ml, p < 0.0005) and sCD40L (median 5.3 ng/ml; IQR, 0.5-20.6 ng/ml vs median 2.2 ng/ml; IQR, 0.7-10.8 ng/ml, p < 0.0005) were significantly higher in patients with MVA compared to controls. Analysis of the associations between these biomarkers and potential contributors of MVA revealed that serum sST2 showed a positive correlation with LDL-cholesterol (r = 0.19, p = 0.016) and serum sCD40L concentrations correlated positively with hs-CRP (r = 0.22, p = 0.005). In logistic regression analysis, sCD40L and hs-CRP but not sST2 were found to be significantly associated with MVA. CONCLUSION: Higher serum concentrations of sST2 and sCD40L in MVA patients may be associated with inflammatory activation and coronary microvascular dysfunction. Larger studies are required for understanding their role in the pathogenesis of inflammatory and possibly fibrotic process in MVA patients.


Assuntos
Ligante de CD40/sangue , Mediadores da Inflamação/sangue , Proteína 1 Semelhante a Receptor de Interleucina-1/sangue , Angina Microvascular/sangue , Adulto , Idoso , Biomarcadores/sangue , Proteína C-Reativa/análise , Estudos de Casos e Controles , LDL-Colesterol/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Angina Microvascular/diagnóstico , Pessoa de Meia-Idade , Estudos Prospectivos , Regulação para Cima
10.
Cell Mol Biol (Noisy-le-grand) ; 64(14): 72-78, 2018 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-30511624

RESUMO

Migraine is a chronic neurological disease described by recurrent moderate to severe headaches often in association with neuro-inflammation. As cytokines are affect the immune response and migraine exacerbation, the current study aimed to investigate the possible associations between CD40 polymorphisms and level of soluble CD154 protein with migraine. In a prospective case-control study, we studied blood samples of 190 patients with migraine (migraineurs) and 200 healthy controls (HCs) from southeast Iran. Genotyping for the CD40 (rs4810485-intron, rs1883832-5´-UTR, and rs3765459-intron) gene variants were executed using PCR-RFLP and soluble CD154 protein levels were measured via ELISA method. Among CD40 gene variants, rs1883832 (TC genotype) was significantly associated with migraine (P = 0.007, OR = 2.326, 95% CI = 1.258-4.303).  No significant associations observed between the rs4810485 and rs3765459 SNPs with migraine. The most frequent genotypes for CD40 were GG in rs4810485 (51.5%) and rs3765459 (62.1%) as well as TC in rs1883832 (53.7%). There was no statistically relationship between these gene variants and different subclasses of migraine. Concentration of soluble CD40L among patients with rs1883832 (TC genotype) were significantly (P = 0.027, OR = 0.417, CI = 0.192-0.906) higher in compared to healthy controls. Our findings showed that in CD40 rs1883832, TC genotype may have a role in migraine susceptibility. Therefore, it suggested that in addition to other factors, CD40 rs1883832 (TC genotype) genetic variation may also play a critical role in the etiology of migraine.


Assuntos
Antígenos CD40/genética , Ligante de CD40/sangue , Estudos de Associação Genética , Predisposição Genética para Doença , Transtornos de Enxaqueca/sangue , Transtornos de Enxaqueca/genética , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Frequência do Gene/genética , Humanos , Irã (Geográfico) , Pessoa de Meia-Idade , Adulto Jovem
11.
J Neuroimmunol ; 325: 64-68, 2018 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-30408708

RESUMO

Currently, no data are available regarding the expression levels of CD40L on CD4+ T cells in patients with neuromyelitis optica spectrum disorders (NMOSD). The percentage of circulating CD40L+CD4+ T cells was measured by flow cytometry in 23 NMOSD patients and 10 healthy controls. The ratio of CD40L+CD4+ to CD4+ T cells in patients at acute phase (18.28 ±â€¯15.56%) was significantly higher than that in healthy controls (7.23 ±â€¯5.94%, P = .032) and was positively correlated with disease severity (r = 0.532, P = .041). Thus, our results suggest an important role of this molecule in acute attacks of NMOSD.


Assuntos
Aquaporina 4/sangue , Linfócitos T CD4-Positivos/metabolismo , Ligante de CD40/sangue , Imunoglobulina G/sangue , Neuromielite Óptica/sangue , Neuromielite Óptica/diagnóstico , Doença Aguda , Adulto , Biomarcadores/sangue , Ligante de CD40/biossíntese , Ligante de CD40/genética , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade
12.
Int J Biochem Cell Biol ; 105: 70-77, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30336263

RESUMO

Background Cluster of differentiation 40 ligand (CD40L) and rosuvastatin (RSV) affect atherosclerotic plaque stability, but little is known about their roles in extracellular matrix (ECM) production. We investigated the effects of CD40L and RSV on pre-existing advanced plaques. Methods and results Pre-existing advanced plaques were induced in apolipoprotein E-knockout (ApoE-/-) mice by the surgical placement of carotid constrictive silastic collars. Two weeks after surgery, mice were divided into the following treatment groups: control, empty adenovirus, CD40L adenovirus, CD40L adenovirus + RSV, and RSV. Mice received adenovirus via two tail-vein injections (2 × 109 pfu each) and/or RSV via intragastric administration (5 mg/kg; daily for 4 weeks). Mice in the CD40L adenovirus group exhibited increased plaque disruption rates, increased relative plaque macrophage and lipid content, reduced plaque collagen content, and increased local inflammation compared to the other treatment groups, but no significant differences in plaque area were observed among the groups. Notably, in the atherosclerotic plaques of the CD40L adenovirus group, both the mRNA and protein expression of prolyl-4-hydroxylase alpha 1 (P4Hα1) was significantly decreased, leading to a consequent decrease in the protein expression of collagen types I and III. Treatment with RSV decreased the serum levels of CD40L in a lipid-independent fashion and attenuated the effects of CD40L overexpression, particularly with respect to P4Hα1 downregulation. Conclusions CD40L destabilized advanced plaques in the carotid arteries of ApoE-/- mice, in part by decreasing P4Hα1 expression, and consequently collagen expression. These destabilizing effects were attenuated by RSV.


Assuntos
Apolipoproteínas E/deficiência , Ligante de CD40/genética , Placa Aterosclerótica/tratamento farmacológico , Pró-Colágeno-Prolina Dioxigenase/genética , Rosuvastatina Cálcica/farmacologia , Animais , Apolipoproteínas E/genética , Ligante de CD40/sangue , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Lipídeos/sangue , Masculino , Camundongos , Camundongos Knockout para ApoE , Placa Aterosclerótica/genética , Placa Aterosclerótica/patologia , Pró-Colágeno-Prolina Dioxigenase/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
13.
Am J Cardiol ; 122(9): 1477-1481, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30170691

RESUMO

Electronic cigarettes (E-cigarettes) have become popular as substitutes for conventional tobacco cigarettes or to aid quitting, but little is known about the potential risks to cardiovascular health for smokers and nonsmokers. We sought to compare the impact of E-cigarettes with conventional cigarettes on platelet function in healthy adult smokers and nonsmokers. A crossover single-blind study in 40 healthy participants (20 smokers, 20 nonsmokers, matched for age and sex) was conducted. Each participant smoked a conventional cigarette then returned 1 week later to vape a study E-cigarette with the same nominal nicotine content. Blood samples were drawn shortly before and 5 minutes after each episode and analyzed for platelet aggregation, soluble CD40-ligand (sCD40L) and soluble P-selectin (sP-selectin). At baseline, smokers had significantly higher levels of sCD40L and sP-selectin (all p ≤0.01) than nonsmokers. Within 5 minutes of using either a conventional cigarette or E-cigarette, changes in the levels of sCD40L, sP-selectin, and platelet aggregation (all p ≤0.01) were detectable in both smokers and nonsmokers. In smokers, there were no significant changes in sCD40L and sP-selectin but there was a significant increase in platelet aggregation. In nonsmokers, there was a significant increase in all markers of platelet activation following both cigarette and E-cigarette use. Both traditional and E-cigarettes have short-term effects on platelet activation, although in nonsmokers the use of E-cigarettes had a less important impact. In conclusion, we provide the first comparison data of the acute impact of Tobacco-cigarette and E-cigarette smoking on the platelet function in smokers and nonsmokers.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Agregação Plaquetária/efeitos dos fármacos , Fumar Tabaco/efeitos adversos , Vaping/efeitos adversos , Adulto , Biomarcadores/sangue , Ligante de CD40/sangue , Estudos Cross-Over , Feminino , Humanos , Masculino , não Fumantes , Selectina-P/sangue , Método Simples-Cego , Fumantes
14.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 40(4): 439-443, 2018 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-30193594

RESUMO

Objective To establish an animal model of transfusion-related acute lung injury (TRALI) and investigate the role of soluble CD40 ligand (sCD40L) in the development of TRALI. Methods The TRALI animal model established by trauma-hemorrhage-transfusion. Lung edema was evaluated by histopathological examination and the protein and Evans blue dye accumulation in bronchoalveolar lavage fluid. The concentration of sCD40L in storage packed red blood cell (PRBC) and rat's plasma was measured by enzyme-linked immunosorbent assay (ELISA). Results There were obvious epithelial hyperplasia and inflammatory cell infiltration in the lung tissue of 7 d-PRBC-treated group. The accumulation of protein in bronchoalveolar lavage fluid of 7 d-PRBC-treated group [(13.17±5.76)mg] was significantly higher than that in normal controls [(1.21±0.66)mg] and normal saline (NS)-treated group [(4.94±2.15) mg] (F=17.605,P<0.001). The leakage amount of Evans blue dye in 7 d-PRBC-treated group [(0.0109±0.0067)%/min] was significantly higher than that in NS-treated group [(0.0026±0.0006) %/min] (t=2.998,P=0.03). The concentration of sCD40L of the 7 d PRBC [(451.58±73.28) pg/ml] was significantly higher than 0 d PRBC [(277.94±98.18)pg/ml] (t=2.834,P=0.03). The concentration of sCD40L in the plasma of 7 d-PRBC-treated group [(878.21±125.30)pg/ml] was significantly higher than those in normal controls [(289.78±62.60)pg/ml] and NS-treated group [(418.07±47.68)pg/ml] (F=78.715,P<0.001). Conclusion The TRALI animal model was successfully established with trauma-hemorrhage-transfusion. The concentration of sCD40L in plasma of rats with massive transfusion is remarkably increased,suggesting sCD40L may play a role in the development of TRALI.


Assuntos
Ligante de CD40/sangue , Modelos Animais de Doenças , Transfusão de Eritrócitos , Lesão Pulmonar Aguda Relacionada à Transfusão , Animais , Ratos
15.
Am J Cardiovasc Drugs ; 18(6): 503-511, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30144017

RESUMO

BACKGROUND: The aim was to compare the peri-procedural biomarkers of coagulation and platelet activation in patients randomly allocated to intravenous enoxaparin or unfractionated heparin (UFH) in the ATOLL randomized trial (NCT00718471). METHODS AND RESULTS: A total of 129 patients (n = 58 enoxaparin and n = 71 UFH) admitted for ST-segment elevation myocardial infarction (STEMI) treated by percutaneous coronary intervention (PCI) were included in this substudy of the ATOLL trial. Activated partial thromboplastin time ratio, anti-Xa activity, von Willebrand factor antigen, prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complex (TAT), tissue factor pathway inhibitor and soluble CD40 ligand were measured at sheath insertion (T1) and at the end of the PCI (T2) and correlated with 1-month clinical outcomes. Target anticoagulation levels at T2 were more readily achieved in patients receiving enoxaparin compared to those receiving UFH (80.3 vs 18.2%, p < 0.0001). Increased levels of F1 + 2 and TAT measured at T2 were associated with the incidence of the composite ischemic endpoint (p = 0.04 and p = 0.03) and all-cause mortality (p < 0.0001 and p = 0.002). Release of F1 + 2 between T1 and T2 also predicted the composite ischemic endpoint (312 ± 513 vs 37 ± 292, p = 0.04) and net clinical outcome (185 ± 405 vs 3.2 ± 278, p = 0.03). CONCLUSIONS: During primary PCI, enoxaparin achieved therapeutic levels more frequently than UFH. Higher level of thrombin generation measured at the end of the PCI procedure was associated with more frequent ischemic events.


Assuntos
Anticoagulantes/uso terapêutico , Enoxaparina/uso terapêutico , Heparina/uso terapêutico , Intervenção Coronária Percutânea/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Antitrombina III , Biomarcadores , Ligante de CD40/sangue , Enoxaparina/administração & dosagem , Enoxaparina/efeitos adversos , Fator Xa/análise , Feminino , Heparina/administração & dosagem , Heparina/efeitos adversos , Humanos , Lipoproteínas/análise , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Peptídeo Hidrolases/sangue , Protrombina/análise , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Fator de von Willebrand/análise
16.
Viruses ; 10(7)2018 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-29976871

RESUMO

Platelets are considered as significant players in innate and adaptive immune responses. The adhesion molecules they express, including P-selectin, CD40L, and CD42b, facilitate interactions with many cellular effectors. Upon interacting with a pathogen, platelets rapidly express and enhance their adhesion molecules, and secrete cytokines and chemokines. A similar phenomenon occurs after exposure of platelets to thrombin, an agonist extensively used for in vitro activation of these cells. It was recently reported that the dengue virus not only interacts with platelets but possibly infects them, which triggers an increased expression of adhesion molecule P-selectin as well as secretion of IL-1ß. In the present study, surface molecules of platelets like CD40L, CD42b, CD62P, and MHC class I were evaluated at 4 h of interaction with dengue virus serotype 2 (DENV-2), finding that DENV-2 induced a sharp rise in the membrane expression of all these molecules. At 2 and 4 h of DENV-2 stimulation of platelets, a significantly greater secretion of soluble CD40L (sCD40L) was found (versus basal levels) as well as cytokines such as GM-CSF, IL-6, IL-8, IL-10, and TNF-α. Compared to basal, DENV-2 elicited more than two-fold increase in these cytokines. Compared to the thrombin-induced response, the level generated by DENV-2 was much higher for GM-CSF, IL-6, and TNF-α. All these events induced by DENV end up in conspicuous morphological changes observed in platelets by confocal microscopy and transmission electron microscopy, very different from those elicited by thrombin in a more physiological scenery.


Assuntos
Plaquetas/metabolismo , Ligante de CD40/metabolismo , Membrana Celular/metabolismo , Vírus da Dengue/fisiologia , Dengue/sangue , Dengue/virologia , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Plaquetas/imunologia , Ligante de CD40/sangue , Estudos de Casos e Controles , Moléculas de Adesão Celular/metabolismo , Citocinas/metabolismo , Citosol/metabolismo , Dengue/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Selectina-P/metabolismo , Adesividade Plaquetária , Agregação Plaquetária
17.
Biomed Res Int ; 2018: 7497314, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29780830

RESUMO

Sepsis is a severe and progressive disease characterized by systemic inflammatory response syndrome (SIRS). CD40 serves as a vital link between immune response and inflammation. This study was designed to investigate the potential association between a functional single-nucleotide polymorphism (SNP) of CD40 (rs1883832) and susceptibility to sepsis. We first performed a case-control study to explore the relationship between the CD40 rs1883832 polymorphism and sepsis. CD40 mRNA expression and protein expression were determined by real-time PCR and western blotting, respectively, in peripheral blood mononuclear cells (PBMCs) from sepsis patients and healthy controls. The plasma sCD40L levels in the two groups were measured by ELISA. The results showed that the frequencies of the TT genotype and the CD40 rs1883832 T allele were significantly higher in sepsis patients than in healthy controls. Plasma sCD40L levels were also significantly increased in sepsis patients. In addition, TT genotype carriers among sepsis patients displayed the highest CD40 expression at both the mRNA and protein levels, accompanied by the highest plasma sCD40L concentrations. In conclusion, the CD40 rs1883832 T allele acts as a risk factor for increased susceptibility to sepsis and may be involved in the process of sepsis through regulation of CD40 expression and plasma sCD40L levels.


Assuntos
Antígenos CD40 , Ligante de CD40 , Regulação da Expressão Gênica , Predisposição Genética para Doença , Polimorfismo Genético , Sepse , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Antígenos CD40/sangue , Antígenos CD40/genética , Ligante de CD40/sangue , Ligante de CD40/genética , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Sepse/sangue , Sepse/genética
18.
Front Immunol ; 9: 629, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29670618

RESUMO

Background: Notwithstanding its beneficial immunoprophylactic outcomes regarding leprosy and childhood TB, BCG vaccination may cause adverse events, particularly of the skin. However, this local hyper-immune reactivity cannot be predicted before vaccination, nor is its association with protection against leprosy known. In this study we investigated the occurrence of adverse events after BCG (re)vaccination in contacts of leprosy patients and analyzed whether the concomitant systemic anti-mycobacterial immunity was associated with these skin manifestations. Methods: Within a randomized controlled BCG vaccination trial in Bangladesh, 14,828 contacts of newly diagnosed leprosy patients received BCG vaccination between 2012 and 2017 and were examined for adverse events 8 to 12 weeks post-vaccination. From a selection of vaccinated contacts, venous blood was obtained at follow-up examination and stimulated with Mycobacterium leprae (M. leprae) antigens in overnight whole-blood assays (WBA). M. leprae phenolic glycolipid-I-specific antibodies and 32 cytokines were determined in WBAs of 13 individuals with and 13 individuals without adverse events after vaccination. Results: Out of the 14,828 contacts who received BCG vaccination, 50 (0.34%) presented with adverse events, mainly (80%) consisting of skin ulcers. Based on the presence of BCG scars, 30 of these contacts (60%) had received BCG in this study as a booster vaccination. Similar to the pathological T-cell immunity observed for tuberculoid leprosy patients, contacts with adverse events at the site of BCG vaccination showed elevated IFN-γ levels in response to M. leprae-specific proteins in WBA. However, decreased levels of sCD40L in serum and GRO (CXCL1) in response to M. leprae simultaneously indicated less T-cell regulation in these individuals, potentially causing uncontrolled T-cell immunity damaging the skin. Conclusion: Skin complications after BCG vaccination present surrogate markers for protective immunity against leprosy, but also indicate a higher risk of developing tuberculoid leprosy. Clinical Trial Registration: Netherlands Trial Register: NTR3087.


Assuntos
Hanseníase/imunologia , Mycobacterium bovis/imunologia , Mycobacterium leprae/fisiologia , Úlcera Cutânea/imunologia , Pele/imunologia , Linfócitos T/imunologia , Adolescente , Adulto , Anticorpos Antibacterianos/sangue , Bangladesh , Ligante de CD40/sangue , Quimiocina CXCL1/sangue , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Interferon gama/metabolismo , Hanseníase/complicações , Ativação Linfocitária , Masculino , Úlcera Cutânea/etiologia , Vacinação/efeitos adversos , Adulto Jovem
19.
Georgian Med News ; (274): 92-97, 2018 Jan.
Artigo em Russo | MEDLINE | ID: mdl-29461234

RESUMO

Aim of study‒ estimate the influence of the metformin therapy on the sCD40-ligand and sVE-cadherinlevels among patients with acute myocardial infarction and concomitant type 2 diabetes mellitus. The study included44patients with AMI and type 2 diabetes whichweredividedintotwo groupsdependingonthe glucose lowering drugs they have been taken: I group ‒ 21patients who have been taken metformin; II group ‒ 23patients, who have been taken short-acting insulin. Accordingtotheobtainedresults using of metformin as a glucose lowering drug in comparison with patients who have been taken short-acting insulin causes faster decreasing of the sCD40L level (-29,3% and -24,4% accordingly; р<0,05). Whereas there was no significant differencesin the dynamics of sVE-cadherinlevels (-22,4% and -19,2% accordingly; р>0,05). Positive influence of them et form in on thes CD40-ligand level probably is caused by the inhibition of the Akt-kinase phosphorylation responsible for the activation of the nuclear factor kappa-b which controls expression of the immune response genes, particulary CD40. It leads to the inhibition of the thrombocytes activation and differentiation of the monocytes to the macrophages able to product proatherogenic factors. It was established that metformin therapy among patients with acute myocardial infarction and diabetes mellitus type 2 leads to the faster decreasing of sCD40-ligand in comparison with insulin therapy, which can contribute to the improvemenet of the prognosis in this cohort.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Endotélio Vascular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Insulina de Ação Curta/uso terapêutico , Metformina/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Antígenos CD/sangue , Antígenos CD/genética , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Plaquetas/patologia , Ligante de CD40/sangue , Ligante de CD40/genética , Caderinas/sangue , Caderinas/genética , Diferenciação Celular/efeitos dos fármacos , Estudos de Coortes , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Feminino , Hemoglobina A Glicada/genética , Hemoglobina A Glicada/metabolismo , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Monócitos/patologia , Infarto do Miocárdio/sangue , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , NF-kappa B , Fosforilação/efeitos dos fármacos , Ativação Plaquetária/efeitos dos fármacos , Prognóstico , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
20.
Autism Res ; 11(3): 421-433, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29427532

RESUMO

Research has shown that a subset of the autism spectrum disorder (ASD) population presents with immune dysregulation. To explore this topic further, we investigated the efficacy and tolerability of intravenous immunoglobulin (IVIG) infusion in children with ASD. In this study, participants were recruited based on a diagnosis of autistic disorder, Asperger's disorder, or pervasive developmental disorder not otherwise specified. Participants also showed evidence of immune dysfunction based on abnormal levels of specific biomarkers, including CD40 ligand (CD154), lymphocyte stimulation, and T or B cell dysfunction. Of 17 screened patients, 14 completed the trial and received IVIG treatment (1 g/kg dose) for ten 21-day treatment cycles. The primary endpoint was disease improvement assessed using standardized cognitive and behavioral tests (Children's Communication Checklist [CCC-2], Social Responsiveness Scale [SRS], Aberrant Behavior Checklist [ABC], Clinical Global Impressions-Severity [CGI-S] and -Improvement [CGI-I], Autism Diagnostic Observation Schedule [ADOS], and Peabody Picture Vocabulary Test [PPVT]). Secondary endpoints included experimental biomarkers such as CD154, toll-like receptor-4, memory B cells, FOXP3, and lymphocyte stimulation. Significant improvements from baseline to study endpoint were observed in several subscales of the CCC-2, SRS, CGI-I, CGI-S, and ADOS, including Associated Maladaptive Behaviors (P ≤ .043), Reciprocal Social Interaction (P = .015), Communication (P < .001), and Stereotyped Behaviors and Repetitive Interests (P ≤ .013). Statistically significant reductions were also seen in numerous secondary outcomes of immunological biomarkers indicative of neuroinflammation. IVIG was well tolerated; no subjects withdrew due to an adverse event, and clinical data showed no evidence of thromboembolic events. Autism Res 2018, 11: 421-433. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Since research has demonstrated a link between autism spectrum disorder (ASD) and immune dysfunction, this study investigated the efficacy and tolerability of intravenous immunoglobulin (IVIG) infusion in children with ASD. Fourteen patients received IVIG treatment and were assessed using standardized cognitive and behavioral tests. Following treatment with IVIG, significant improvement was observed across several subscales of the clinical tests and significant reductions were seen in the markers of neuroinflammation. These data suggest that inflammatory etiologies may play a role in select cases of autism, and IVIG treatment may exert a positive impact on behaviors and markers of inflammation in ASD.


Assuntos
Transtorno do Espectro Autista/complicações , Doenças do Sistema Imunitário/complicações , Doenças do Sistema Imunitário/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Inflamação/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Adolescente , Transtorno do Espectro Autista/sangue , Linfócitos B/efeitos dos fármacos , Linfócitos B/metabolismo , Biomarcadores/sangue , Ligante de CD40/sangue , Ligante de CD40/efeitos dos fármacos , Criança , Pré-Escolar , Feminino , Fatores de Transcrição Forkhead/sangue , Fatores de Transcrição Forkhead/efeitos dos fármacos , Humanos , Doenças do Sistema Imunitário/sangue , Imunoglobulinas Intravenosas/sangue , Inflamação/sangue , Inflamação/prevenção & controle , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Masculino , Fármacos Neuroprotetores/sangue , Projetos Piloto , Receptor 4 Toll-Like/sangue , Receptor 4 Toll-Like/efeitos dos fármacos
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