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2.
Diabetes Metab Syndr ; 13(2): 1581-1589, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31336525

RESUMO

AIMS: S100A8 and S100A9 are myeloid-related damage-associated molecular patterns (DAMPs) primarily involved in the modulation of innate immune response to cellular injury. This study evaluated the correlation between circulating concentrations of S100A8 and S100A9 proteins with the severity of diabetic retinopathy (DR) in patients with type 2 diabetes (T2DM). METHODS: T2DM patients with HbA1c levels >7%, fasting blood glucose >126 mg/dl and history of diabetes were included in this study. DR severity was graded based on ETDRS and Gloucestershire classifications. Plasma samples were evaluated for S100A8 and S100A9 levels using ELISA. RESULTS: In this comparative study, DR patients (n = 89) had increased plasma S100A8 and S100A9 proteins compared to age-matched T2DM controls (n = 28), which was directly related to the severity of DR. Female DR subjects had increased S100A8 expression compared to their male counterparts. Substantial retention of S100A8 and S100A9 production was seen in DR patients above 50 years of age. Duration of T2DM was not found to affect protein levels, however T2DM onset at >50 years old significantly increased S100A8 and S100A9 concentrations. CONCLUSIONS: Our findings suggest that systemic circulation levels of S100A8 and S100A9 are correlated with the progression of DR in T2DM patients, indicating their potential role in DR pathogenesis.


Assuntos
Biomarcadores/sangue , Calgranulina A/sangue , Calgranulina B/sangue , Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/diagnóstico , Índice de Gravidade de Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/análise , Estudos de Casos e Controles , Retinopatia Diabética/sangue , Retinopatia Diabética/etiologia , Feminino , Seguimentos , Hemoglobina A Glicada/análise , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
3.
Talanta ; 204: 507-517, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31357327

RESUMO

Serum amyloid A (SAA) and S100 (S100A8, S100A9 and S100A12) proteins were previously identified as biomarkers of interest for rheumatoid arthritis (RA). Among SAA family, two closely related isoforms (SAA-1 and SAA-2) are linked to the acute-phase of inflammation. They respectively exist under the form of three (α, ß, and γ) and two (α and ß) allelic variants. We developed a single run quantitative method for these protein variants and investigated their clinical relevance in the context of RA. The method was developed and validated according to regulations before being applied on plasma coming from RA patients (n = 46), other related inflammatory pathologies (n = 116) and controls (n = 62). Depending on the activity score of RA, SAA1 isoforms (mainly of SAA1α and SAA1ß subtypes) were found to be differentially present in plasma revealing their dual role during the development of RA. In addition, the weight of SAA1α in the total SAA response varied from 32 to 80% depending on the pathology studied. A negative correlation between SAA1α and SAA1ß was also highlighted for RA early-onset (r = -0.41). SAA2 and S100A8/S100A9 proteins were significantly overexpressed compared to control samples regardless of RA stage. The pathophysiological relevance of these quantitative and qualitative characteristics of the SAA response remains unknown. However, the significant negative correlation observed between SAA1α and SAA1ß levels in RA early-onset suggests the existence of still unknown regulatory mechanisms in these diseases.


Assuntos
Alarminas/sangue , Artrite Reumatoide/sangue , Calgranulina A/sangue , Calgranulina B/sangue , Proteômica/métodos , Proteína Amiloide A Sérica/análise , Sequência de Aminoácidos , Biomarcadores/sangue , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Espectrometria de Massas em Tandem/métodos
4.
J Vet Diagn Invest ; 31(4): 645-651, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31170888

RESUMO

Pattern recognition receptors (e.g., S100A12 or S100A8/A9) hold promise as inflammatory biomarkers. We prospectively determined and compared serum S100A12 and S100A8/A9 concentrations in dogs with sepsis (n = 11) or systemic inflammatory response syndrome (SIRS; n = 8) over a 3-d period with each other, healthy controls (n = 50), and other clinical and clinicopathologic variables. Serum S100A12 and S100A8/A9 concentrations were significantly higher in dogs with sepsis or SIRS (all p < 0.05) at the time of hospital admission (day 1) compared to healthy controls, with no differences between patient groups. However, septic dogs had significantly lower serum S100A12 concentrations on day 2 and day 3 (both p < 0.05) compared to dogs with SIRS. Likewise, dogs with sepsis had significantly lower S100A8/A9 concentrations on day 2 (p < 0.05). Neither serum S100A12 nor S100A8/A9 concentrations were associated with survival to discharge. Our results suggest a differential expression of the S100/calgranulins between dogs with sepsis and those with SIRS. Serum S100A12 or S100A8/A9 concentration at the time of hospital admission did not differentiate dogs with sepsis from those with SIRS, but the trend of S100/calgranulin concentrations during the following 24-48 h may be a useful surrogate marker for differentiating sepsis from SIRS.


Assuntos
Doenças do Cão/sangue , Complexo Antígeno L1 Leucocitário/sangue , Proteína S100A12/sangue , Sepse/veterinária , Síndrome de Resposta Inflamatória Sistêmica/veterinária , Animais , Biomarcadores/sangue , Calgranulina A/sangue , Calgranulina B/sangue , Estudos de Casos e Controles , Cães , Regulação da Expressão Gênica , Masculino , Estudos Prospectivos , Sepse/sangue , Síndrome de Resposta Inflamatória Sistêmica/sangue
5.
Lupus ; 28(7): 826-833, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31068068

RESUMO

OBJECTIVES: We investigated the effect of hydroxychloroquine (HCQ) on S100A8 and S100A9 serum levels in systemic lupus erythematosus (SLE) patients with low disease activity receiving immunosuppressants. METHODS: SELENA-SLEDAI, Cutaneous Lupus Erythematous Disease Area and Severity Index (CLASI) and serum levels of complement factors, anti-dsDNA antibodies, and white blood cell, lymphocyte, and platelet counts were used to evaluate disease activity, cutaneous disease activity, and immunological activity, respectively. Serum S100A8 and S100A9 were measured at HCQ administration and after 3 or 6 months using ELISA. RESULTS: S100A8 and S100A9 serum levels were elevated at baseline and the magnitude of decrease from baseline at 3 and 6 months after HCQ administration was greater in patients with renal involvement than in those without (baseline: S100A8, p = 0.034; S100A9, p = 0.0084; decrease: S100A8, p = 0.049; S100A9, p = 0.023). S100 modulation was observed in patients with (n = 17; S100A8, p = 0.0011; S100A9, p = 0.0002) and without renal involvement (n = 20; S100A8, p = 0.0056; S100A9, p = 0.0012), and was more apparent in patients with improved CLASI activity scores (improved: S100A8, p = 0.013; S100A9, p = 0.0032; unimproved: S100A8, p = 0.055; S100A9, p = 0.055). No associations were observed for immunological biomarkers. CONCLUSION: HCQ may improve organ involvement in SLE by modulating S100 protein levels, especially in patients with renal or skin involvement.


Assuntos
Antirreumáticos/uso terapêutico , Calgranulina A/sangue , Calgranulina B/sangue , Hidroxicloroquina/uso terapêutico , Lúpus Eritematoso Cutâneo/tratamento farmacológico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Biomarcadores/sangue , Feminino , Humanos , Lúpus Eritematoso Cutâneo/sangue , Lúpus Eritematoso Sistêmico/sangue , Nefrite Lúpica/sangue , Nefrite Lúpica/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
6.
Lab Med ; 50(4): 370-380, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-30994906

RESUMO

BACKGROUND: The clinical significance of human S100A8/A9 (h-S100A8/A9) in patients with inflammatory bowel disease (IBD) is poorly understood. OBJECTIVE: To clarify whether serum S100A8/A9 is a sensitive biomarker for IBD. METHODS: Serum specimens from outpatients with IBD (n = 101) and healthy volunteers (HVs) (n = 101) were used in this study. Enzyme-linked immunosorbent assays for h-S100A8/A9 and inflammatory cytokines were performed using these specimens. Further, correlation analysis was performed to investigate the significance of h-S100A8/A9 fluctuation in patients with IBD. RESULTS: The average of serum h-S100A8/A9 concentration in outpatients with IBD was significantly higher than that in HVs. The concentration of h-S100A8/A9 in patients with IBD was barely correlated with that of CRP and inflammatory cytokines. Despite that finding, the serum level of h-S100A8/A9 in patients with ulcerative colitis (UC) was correlated with the severity of IBD, compared with other inflammatory proteins. CONCLUSION: Serum h-S100A8/A9 is superior to CRP as a sensitive biomarker for IBD.


Assuntos
Biomarcadores/sangue , Calgranulina A/sangue , Calgranulina B/sangue , Testes Diagnósticos de Rotina/métodos , Doenças Inflamatórias Intestinais/diagnóstico , Adulto , Idoso , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Doenças Inflamatórias Intestinais/patologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Soro/química , Adulto Jovem
7.
PLoS One ; 14(3): e0213344, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30865695

RESUMO

S100A8 and S100A9 proteins are highly upregulated in patients with psoriasis and have been proposed as potential biomarkers for psoriasis. The present study was designed to analyze the effect of narrowband ultraviolet B therapy on these proteins. S100A8, S100A9 gene expression and S100A8/A9 heterocomplex protein levels were analyzed in lesional and non-lesional skin before and after narrowband-UVB treatment in patients with chronic plaque type psoriasis. In addition, disease severity was measured by psoriasis area and severity index (PASI) and serum protein levels of S100A8/A9 were repeatedly analyzed. Narrowband-UVB treatment significantly reduced S100A8, S100A9 gene expression and S100A8/A9 protein levels in lesional skin while serum levels showed no significant change. No correlation between PASI and serum S100A8/A9 protein levels was found. These results implicate a role of S100A8/A9 in the anti-inflammatory effect of narrowband-UVB. Serum S100A8/A9 levels do not respond to treatment suggesting that serum S100A8/A9 does not originate from psoriasis skin keratinocytes. Serum S100A8/A9 levels do not correlate with PASI questioning serum S100A8/A9 as a biomarker for psoriasis skin activity. Trial Registration: DRKS 00014817.


Assuntos
Calgranulina A/metabolismo , Calgranulina B/metabolismo , Psoríase/metabolismo , Psoríase/radioterapia , Terapia Ultravioleta , Adulto , Biomarcadores/sangue , Biomarcadores/metabolismo , Calgranulina A/sangue , Calgranulina A/genética , Calgranulina B/sangue , Calgranulina B/genética , Regulação para Baixo/efeitos da radiação , Feminino , Expressão Gênica/efeitos da radiação , Humanos , Queratinócitos/metabolismo , Queratinócitos/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Psoríase/genética , Pele/metabolismo , Pele/efeitos da radiação , Suécia
8.
Biomark Med ; 13(3): 205-218, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30810341

RESUMO

AIM: We investigated whether plasma levels of the inflammation marker S100A8/A9, could predict acute kidney injury (AKI) onset in patients undergoing cardiac surgery necessitating cardiopulmonary bypass (CPB). PATIENTS & METHODS: Plasma levels of S100A8/A9 and other neutrophil cytosolic proteins were measured in 39 patients pre- and immediately post-CPB. RESULTS: All markers increased significantly post-CPB with S100A8/A9, S100A12 and myeloperoxidase levels significantly higher in patients who developed AKI within 7 days. S100A8/A9 had good prognostic utility for AKI, with an area under the receiver operating characteristic curve of 0.81 (95% CI: 0.676-0.949) and a cut-off value of 10.6 µg/ml (85.7% sensitivity and 75% specificity) irrespective of age. CONCLUSION: Plasma S100A8/A9 levels immediately after cardiac surgery, can predict onset of AKI, irrespective of age.


Assuntos
Lesão Renal Aguda/diagnóstico , Biomarcadores/sangue , Calgranulina A/sangue , Calgranulina B/sangue , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ponte Cardiopulmonar/efeitos adversos , Lesão Renal Aguda/sangue , Lesão Renal Aguda/etiologia , Idoso , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Curva ROC
9.
Arthritis Rheumatol ; 71(3): 451-459, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30225949

RESUMO

OBJECTIVE: To determine the relationship between serum levels of S100A8/A9 and S100A12 and the maintenance of clinically inactive disease during anti-tumor necrosis factor (anti-TNF) therapy and the occurrence of disease flare following withdrawal of anti-TNF therapy in patients with polyarticular forms of juvenile idiopathic arthritis (JIA). METHODS: In this prospective, multicenter study, 137 patients with polyarticular-course JIA whose disease was clinically inactive while receiving anti-TNF therapy were enrolled. Patients were observed for an initial 6-month phase during which anti-TNF treatment was continued. For those patients who maintained clinically inactive disease over the 6 months, anti-TNF was withdrawn and they were followed up for 8 months to assess for the occurrence of flare. Serum S100 levels were measured at baseline and at the time of anti-TNF withdrawal. Spearman's rank correlation test, Mann-Whitney U test, Kruskal-Wallis test, receiver operating characteristic (ROC) curve, and Kaplan-Meier survival analyses were used to assess the relationship between serum S100 levels and maintenance of clinically inactive disease and occurrence of disease flare after anti-TNF withdrawal. RESULTS: Over the 6-month initial phase with anti-TNF therapy, the disease state reverted from clinically inactive to clinically active in 24 (18%) of the 130 evaluable patients with polyarticular-course JIA; following anti-TNF withdrawal, 39 (37%) of the 106 evaluable patients experienced a flare. Serum levels of S100A8/A9 and S100A12 were elevated in up to 45% of patients. Results of the ROC analysis revealed that serum S100 levels did not predict maintenance of clinically inactive disease during anti-TNF therapy nor did they predict disease flare after treatment withdrawal. Elevated levels of S100A8/A9 were not predictive of the occurrence of a disease flare within 30 days, 60 days, 90 days, or 8 months following anti-TNF withdrawal, and elevated S100A12 levels had a modest predictive ability for determining the risk of flare within 30, 60, and 90 days after treatment withdrawal. Serum S100A12 levels at the time of anti-TNF withdrawal were inversely correlated with the time to disease flare (r = -0.36). CONCLUSION: Serum S100 levels did not predict maintenance of clinically inactive disease or occurrence of disease flare in patients with polyarticular-course JIA, and S100A12 levels were only moderately, and inversely, correlated with the time to disease flare.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Juvenil/sangue , Artrite Juvenil/tratamento farmacológico , Calgranulina A/sangue , Calgranulina B/sangue , Proteína S100A12/sangue , Adolescente , Biomarcadores/sangue , Criança , Pré-Escolar , Feminino , Humanos , Quimioterapia de Manutenção/métodos , Masculino , Exacerbação dos Sintomas , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Suspensão de Tratamento
10.
Rheumatol Int ; 39(3): 469-478, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30392117

RESUMO

S100 proteins are currently being investigated as potential diagnostic and prognostic biomarkers of several cancers and inflammatory diseases. The aims of this study were to analyse the plasma levels of S100A4, S100A8/9 and S100A12 in patients with incomplete systemic lupus erythematosus (iSLE), in patients with established SLE and in healthy controls (HCs) and to investigate the potential utility of the S100 proteins as diagnostic or activity-specific biomarkers in SLE. Plasma levels were measured by ELISA in a cross-sectional cohort study of 44 patients with SLE, 8 patients with iSLE and 43 HCs. Disease activity was assessed using the SLEDAI-2K. The mean levels of all S100 proteins were significantly higher in SLE patients compared to HCs. In iSLE patients, the levels of S100A4 and S100A12 but not S100A8/9 were also significantly higher compared to HCs. There were no significant differences in S100 levels between the iSLE and SLE patients. Plasma S100 proteins levels effectively discriminated between SLE patients and HCs. The area under the curve (AUC) for S100A4, S100A8/9 and S100A12 plasma levels was 0.989 (95% CI 0.976-1.000), 0.678 (95% CI 0.563-0.792) and 0.807 (95% CI 0.715-0.899), respectively. S100 levels did not differentiate between patients with high and low disease activity. Only the S100A12 levels were significantly associated with SLEDAI-2K and with cSLEDAI-2K. S100 proteins were significantly higher in SLE patients compared HCs and particularly S100A4 could be proposed as a potential diagnostic biomarker for SLE.


Assuntos
Lúpus Eritematoso Sistêmico/sangue , Proteínas S100/sangue , Adulto , Calgranulina A/sangue , Calgranulina B/sangue , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína A4 de Ligação a Cálcio da Família S100/sangue , Proteína S100A12/sangue , Adulto Jovem
11.
Clin Exp Rheumatol ; 36(6 Suppl 115): 90-96, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30582504

RESUMO

OBJECTIVES: The faecal calprotectin (FC) test is widely used as a non-invasive method for identifying intestinal inflammation. A recent study suggested FC may help to diagnose gastrointestinal involvement of Behçet's syndrome (GIBS). We aimed to determine whether FC helps to distinguish active from inactive intestinal involvement in GIBS. METHODS: We tried to contact 70 GIBS patients registered in our tertiary multidisciplinary clinic. We prospectively collected faecal specimens and serum from 39 GIBS patients who gave informed consent assessing calprotectin and CRP levels followed by a colonoscopy. We included 47 Crohn's disease (CD) patients as controls. Active disease was defined as having ulcer/s on colonoscopy. We filled the Disease Activity Index for Intestinal Behçet's Disease (DAIBD) and Crohn's Disease Activity Index (CDAI). The cut-off for positive FC was defined as ≥150 µg/g. RESULTS: Ulcers were detected in 12/39 GIBS patients. Sensitivity and specificity of the FC test for active disease was 91.7 (95%CI:61.5-99.8) and 74.1% (95%CI:53.7-88.9). Median FC and CRP levels and DAIBD scores were higher among patients with ulcers, whereas serum calprotectin and CDAI scores were not. A negative FC test was the only significant predictor of remission (OR:37.04, 95%CI:2.4-561.6; p=0.009) on multivariate analysis. Among CD patients, 16/25 active patients and 3/22 patients in endoscopic remission had a positive FC test (OR:11, 95%CI:11-49). CONCLUSIONS: FC, but not serum calprotectin seems to be a useful non-invasive tool for assessing disease activity in GIBS. Whether the presence of oral ulcers can cause false positive results remains to be studied.


Assuntos
Síndrome de Behçet/diagnóstico , Calgranulina A/metabolismo , Calgranulina B/metabolismo , Doenças do Colo/metabolismo , Fezes/química , Mediadores da Inflamação/metabolismo , Complexo Antígeno L1 Leucocitário/metabolismo , Úlcera/diagnóstico , Adulto , Síndrome de Behçet/sangue , Síndrome de Behçet/metabolismo , Biomarcadores/metabolismo , Calgranulina A/sangue , Calgranulina B/sangue , Doenças do Colo/sangue , Doenças do Colo/diagnóstico , Colonoscopia , Feminino , Humanos , Mediadores da Inflamação/sangue , Complexo Antígeno L1 Leucocitário/sangue , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Índice de Gravidade de Doença , Úlcera/sangue , Úlcera/metabolismo
12.
Med Sci Monit ; 24: 7673-7681, 2018 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-30367682

RESUMO

BACKGROUND The aim of this study was to determine the involvement of S100A8/A9 in the development of arterial thrombosis. MATERIAL AND METHODS A total of 303 patients were enrolled in this study, with 110 having acute coronary syndrome (ACS) and 110 having coronary heart disease (CHD), and 83 subjects served as healthy blood donors. The concentrations of Toll-like receptor 4 (TLR-4), cyclooxygenase-2 (COX-2), and S100A8/A9 protein were determined in the sera of the participants and in peripheral blood mononuclear cells (PBMCs) derived from a rat carotid artery thrombosis model and in human aortic endothelial cells (HAECs). The mitogen-activated protein kinase (MAPK) inhibitor SB203580 and the TLR-4 blocker CLI-095 were used to investigate the role of the TLR-4-MAPK-COX2 signaling axis in thrombosis. RESULTS The levels of COX-2, TLR-4, and S100A8/A9 in the sera of patients with ACS and CHD were significantly higher than in healthy controls (P<0.05). S100A8/A9 expression was significantly correlated with TLR-4 and COX-2 in the ACS group and with TLR-4 in the CHD group. In the rat carotid thrombosis model, the expressions of TLR-4, COX-2, and p-p38 MAPK significantly increased until 14 days after thrombosis induction, whereas S100A8/A9 expression increased until day 7, but then decreased. Administration of SB203580 to rats reduced COX-2 expression in PBMCs after thrombosis induction, and incubation of HAECs with CLI-095 reduced their p-p38 MAPK and COX-2 response to S100A8/A9 stimulation. CONCLUSIONS S100A8/A9 is upregulated after blood vessel injury and is enhanced in combination with TLR-4 COX-2 induction via p38 MAPK activation.


Assuntos
Calgranulina A/metabolismo , Calgranulina B/metabolismo , Trombose/metabolismo , Síndrome Coronariana Aguda/metabolismo , Idoso , Idoso de 80 Anos ou mais , Animais , Artérias/fisiopatologia , Calgranulina A/sangue , Calgranulina B/sangue , Linhagem Celular , Doença das Coronárias/metabolismo , Ciclo-Oxigenase 2/sangue , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Pessoa de Meia-Idade , Proteínas Quinases Ativadas por Mitógeno/sangue , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Trombose/fisiopatologia , Receptor 4 Toll-Like/sangue , Receptor 4 Toll-Like/metabolismo , Ativação Transcricional , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
13.
Front Immunol ; 9: 1773, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30105034

RESUMO

HLA-B27 is the allele most frequently associated with human anterior uveitis. The majority of HLA-B27-positive [acute anterior uveitis (AAU)] patients develop clinically distinct symptoms with acute symptomatic onset of flare and a recurrent disease course characterized by a massive cellular ocular infiltrate during uveitis relapse. By contrast, uveitis in HLA-B27-negative [idiopathic anterior uveitis (IAU)] patients tends to develop a clinically less fulminant, more chronic, and typically asymptomatic disease course. To analyze systemic immune responses in the different uveitis entities, we analyzed peripheral blood cells by flow cytometry. In addition, as a pro-inflammatory biomarker serum, S100A8/A9 levels were quantified by ELISA from patients with AAU (n = 27) and IAU (n = 21), and in healthy controls (n = 30). Data were obtained either during active uveitis flare or after 3 months of inactivity. IAU patients showed a transiently increased frequency of CD56- and CD163-positive monocytes and of both granulocytic myeloid-derived suppressor cells and Th17 cells during active uveitis. By contrast, AAU patients showed an elevated frequency of monocytes, activated T cells, and elevated S100A8/A9 serum levels during clinically quiescent disease. The differentially regulated response of both innate and adaptive immune cells in the blood may be related to the clinically distinct characteristics of the two different uveitis entities.


Assuntos
Antígeno HLA-B27/imunologia , Monócitos/imunologia , Monócitos/metabolismo , Uveíte Anterior/etiologia , Uveíte Anterior/metabolismo , Adulto , Autoimunidade , Biomarcadores , Calgranulina A/sangue , Calgranulina B/sangue , Estudos de Casos e Controles , Citocinas/metabolismo , Feminino , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Células Supressoras Mieloides/imunologia , Células Supressoras Mieloides/metabolismo , Fenótipo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Uveíte Anterior/diagnóstico , Adulto Jovem
14.
Dis Markers ; 2018: 6457347, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30057651

RESUMO

Study Design: This study was performed to investigate the diagnostic values of some inflammatory biomarkers in abdominal pain. Methods: Patients over 18 years of age with acute recent abdominal pain who presented to the Emergency Department were evaluated. Serum and urinary samples were taken and evaluated for serum and urine S100A8/A9 and serum amyloid A. All patients were referred to a surgeon and were followed up until the final diagnosis. In the end, the final diagnosis was compared with the levels of biomarkers. Results: Of a total of 181 patients, 71 underwent surgery and 110 patients did not need surgery after they were clinically diagnosed. Mean levels of serum and urine S100A8/A9 had a significant difference between two groups, but serum amyloid A did not show. The diagnostic accuracy of serum S100A8/A9, urine S100A8/A9, and serum amyloid A was 86%, 79%, and 50%, respectively, in anticipation of the need or no need for surgery in acute abdominal pain. Conclusions: Our study showed that in acute abdominal pain, serum and urine S100A8/A9 can be useful indicators of the need for surgery, but serum amyloid A had a low and nonsignificant diagnostic accuracy.


Assuntos
Abdome Agudo/sangue , Calgranulina A/sangue , Calgranulina B/sangue , Proteína Amiloide A Sérica/metabolismo , Abdome Agudo/cirurgia , Abdome Agudo/urina , Adulto , Biomarcadores/sangue , Biomarcadores/urina , Calgranulina B/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Proteína Amiloide A Sérica/normas , Proteína Amiloide A Sérica/urina
15.
Reprod Domest Anim ; 53(4): 1013-1015, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29604144

RESUMO

This study was carried out to examine the changes in plasma concentrations of the Ca-binding antimicrobial proteins S100A7 and S100A8 during pregnancy in dairy cows. Holstein Friesian cows (n = 19) were inseminated with Holstein Friesian semen. Blood was collected at days 30, 60, 90, 120, 150, 180, 210, 240 and 270 after insemination. Plasma was used for measuring the concentrations of S100A7 and S100A8. Both S100A7 and S100A8 concentrations showed similar patterns during gestation; they increased during the midgestation, between days 90 and 180, and then declined before calving. The findings indicated that plasma concentrations of S100A7 and S100A8 did not change significantly during pregnancy in cows. Further studies are required to determine the roles of S100A7 and S100A8 in physiological function during pregnancy in dairy cows.


Assuntos
Calgranulina A/sangue , Bovinos/sangue , Regulação da Expressão Gênica/fisiologia , Prenhez , Proteína A7 Ligante de Cálcio S100/sangue , Animais , Feminino , Gravidez , Prenhez/sangue
16.
Nutr Res ; 51: 57-66, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29673544

RESUMO

The study purpose was to evaluate the effectiveness of creatine monohydrate supplementation (20 grams/day for 1 week and then 5 grams/day for 11 weeks) on inflammation (C-reactive protein, interleukin-1ß, interleukin-6, s100 A8/A9, and tumor necrosis factor-α) and cartilage degradation (serum cartilage oligomeric matrix protein) in patients with knee osteoarthritis. We hypothesized that supplementing with creatine monohydrate for 12 weeks would lower biomarkers of inflammation and cartilage degradation in patients with knee osteoarthritis when compared to placebo. A total of 18 patients with mild to moderate knee osteoarthritis were recruited and randomized in a double blind fashion to either a creatine supplementation group (N = 9) or a placebo (N = 9). At baseline and after 12 weeks of supplementation patients had inflammatory and cartilage degradation biomarkers measured in the systemic blood. Further, patients completed the Knee injury and Osteoarthritis Outcome (KOOS) questionnaire as well as had their isometric thigh strength evaluated using an isokinetic dynamometer at both time points. Results indicated that there was no difference between the creatine and placebo groups at 12 week follow up in the inflammatory biomarkers measured nor was there any difference between the groups for cartilage degradation (all P>.05). No statistical differences were noted for the KOOS questionnaire subscales or total score (all P>.05). Muscle strength testing indicated a main effect of time for both groups where isometric thigh strength at 0° of knee flexion was lowered significantly (P=.047). No other significant differences were found in the strength data. We conclude that 12 weeks of supplementation with creatine monohydrate does not affect inflammatory biomarkers, cartilage degradation, KOOS scores, or muscle strength in patients with mild to moderate knee osteoarthritis.


Assuntos
Cartilagem/efeitos dos fármacos , Creatina/farmacologia , Suplementos Nutricionais , Inflamação/sangue , Articulação do Joelho/efeitos dos fármacos , Osteoartrite do Joelho/patologia , Idoso , Biomarcadores/metabolismo , Proteína C-Reativa/metabolismo , Calgranulina A/sangue , Cartilagem/metabolismo , Cartilagem/patologia , Proteína de Matriz Oligomérica de Cartilagem/metabolismo , Método Duplo-Cego , Feminino , Humanos , Interleucina-1beta/sangue , Interleucina-6/sangue , Articulação do Joelho/metabolismo , Articulação do Joelho/patologia , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/sangue
17.
APMIS ; 126(2): 152-159, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29700911

RESUMO

The dysregulation of inflammatory response to surgical injury affects outcomes. Alarmins, the earliest bioactive substances from damaged cells, play a crucial role in initiating the inflammation. We analyzed serum levels of alarmins (S100A8, S100A12, high mobility group box, and heat shock protein 70) after major abdominal surgery (MAS) in surgical (S) (n = 82) and nonsurgical (NS) groups (n = 35). The main objective was determining a role of selected alarmins in host response to MAS. The secondary objectives were (i) evaluation of the relationship among alarmins and selected biomarkers (C-reactive protein, interleukin-6), (ii) influence of the place of gastrointestinal resection, and (iii) role of alarmins in MAS for cancer. Except for HMGB1, the levels of all alarmins were higher in the S group compared with the NS group. In the S group, positive correlations were found between S100A8 and both IL-6 and CRP. Additionally, the S100A8 level was higher (p < 0.01) in patients who underwent upper gastrointestinal tract (GIT) surgery compared to middle and lower GIT resections. Alarmins levels did not differ between cancer and noncancer patients. MAS is able to elicit increase in alarmin levels. S100A8 can be considered a potential biomarker of surgical injury, especially in the upper part of the GIT.


Assuntos
Alarminas/sangue , Procedimentos Cirúrgicos do Sistema Digestório , Adulto , Idoso , Biomarcadores/sangue , Proteína C-Reativa/análise , Calgranulina A/sangue , Feminino , Proteína HMGB1/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos
18.
Anal Chem ; 90(5): 3366-3373, 2018 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-29420882

RESUMO

Circulating proteins are widely used as biomarkers in clinical applications for the diagnosis, prediction, and treatment of numerous diseases. Immunoassays are the most common technologies for quantification of protein biomarkers and exist in various formats. Traditional immunoassays offer sensitive and fast analyses but cannot differentiate between proteoforms. Protein microheterogeneity, mainly due to post-translational modification, has been recognized as a fingerprint for different pathologies, and knowledge about proteoforms is an important step toward personalized medicine. Mass spectrometry (MS) has emerged to be a powerful technique for the characterization and quantification of proteoforms. We have established a novel four-plex immunoassay based on Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight (MALDI-TOF) MS for the targeted quantification of the inflammatory markers C-reactive protein (CRP), serum amyloid A (SAA), and calprotectin (S100A8/9) and the kidney function marker cystatin C (CysC). Antibodies were covalently bound to superparamagnetic beads, which delivered robust and fast sample processing. Polyhistidine-tagged recombinant target proteins were used as internal standards for quantification. Our method identified a number of proteoforms for SAA ( n = 11), S100A8/9 ( n = 4) and CysC ( n = 4). The assay was characterized by low limits of detection (0.01-0.06 µg/mL) and low coefficients of variation (3.8-9.4%). Method validation demonstrated good between-assay agreement with immuno-turbidimetry ( R2 = 0.963 for CRP), ELISA ( R2 = 0.958 for SAA; R2 = 0.913 for S100A8/9), and nephelometry ( R2 = 0.963 for CysC). The low sample consumption of 20 µL and the high sample throughput of 384 samples per day make this targeted immuno-MALDI approach suited for assessment of inflammatory and renal status in large cohort studies based on precious biobanks samples.


Assuntos
Biomarcadores/análise , Proteínas Sanguíneas/análise , Imunoensaio/métodos , Isoformas de Proteínas/análise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Proteína C-Reativa/análise , Calgranulina A/sangue , Calgranulina B/sangue , Cistatina C/sangue , Humanos , Inflamação/metabolismo , Nefropatias/metabolismo , Proteína Amiloide A Sérica/análise
19.
Rheumatol Int ; 38(4): 623-630, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29196802

RESUMO

The aim of the study was to explore utility of serial serum myeloid-related protein 8/14 (MRP8/14) as a biomarker of clinical disease activity and angiographic progression in Takayasu arteritis (TA). Serum MRP8/14 levels were assayed by commercial ELISA for 85 TA patients and 24 healthy controls at baseline, and for 56 and 21 TA patients during follow-up visits R1 and R2, respectively. Disease was categorised as active, indeterminate and stable according to Indian Takayasu Arteritis score (ITAS 2010), ITAS-A(CRP) and angiography. Patients were divided into responders and non-responders/relapsers based on treatment response. Non-parametric tests were used for inter-group comparisons at baseline and during follow-up time points. Generalised Estimating Equation was used to study association between changes in serial MRP8/14 levels and disease activity. At baseline, median MRP8/14 levels were higher in patients with TA than healthy controls [7353 (4524 to11283) vs 4896 (3194 to 8474.5) ng/ml, p = 0.011]. Patients with active disease had higher levels [8552 (5463-12488)] than stable disease [5292.5 (3140.5-7310)], p = 0.002, and healthy controls [4896 (3194-8474.5)], p = 0.001. Changes in serial MRP8/14 level were associated with changes in disease activity, independent of steroid dose, p = 0.000. At R1, MRP 8/14 levels were lower than baseline in responders (n = 38) [9146.0 (6296.8-13693.8) vs 6501 (4314.8-8304.5), p = 0.004], but did not change in non-responders/relapsers (n = 14) [6693.5(4210.8-10516.3) vs 7755.0(5342-10741.0), p = 0.42]. Similar trend was observed at R2. MRP8/14 levels increased during follow-up in 66% and 26.3% of angiographic progressors and non-progressors, respectively. MRP8/14 in TA may act as a novel biomarker with prognostic implications.


Assuntos
Calgranulina A/sangue , Calgranulina B/sangue , Arterite de Takayasu/sangue , Adolescente , Adulto , Angiografia , Biomarcadores/sangue , Estudos de Casos e Controles , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Índia , Estudos Longitudinais , Masculino , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Esteroides/uso terapêutico , Arterite de Takayasu/diagnóstico por imagem , Arterite de Takayasu/tratamento farmacológico , Adulto Jovem
20.
Sci Rep ; 7(1): 17545, 2017 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-29235502

RESUMO

Psychological stress is thought to be an important trigger of cardiovascular events, yet the involved pathways and mediators are largely unknown. Elevated systemic levels of the pro-inflammatory alarmin S100A8/A9 correlate with poor prognosis in coronary artery disease (CAD) patients. Here, we investigated the links between S100A8/A9 release and parameters of anti-inflammatory glucocorticoid secretion in two different cohorts subjected to a psychological stress test. In the first cohort of 60 CAD patients, psychological stress induced a rapid increase of circulating S100A8/A9. This rapid S100A8/A9 response strongly correlated with elevated evening saliva cortisol levels, suggesting an association with a dysregulated hypothalamic-pituitary-adrenal (HPA) axis. In the second cohort of 27 CAD patients and 28 controls, elevated S100A8/A9 levels were still detectable 24 h after stress in 40% of patients and 36% of controls, with a tendency for higher levels in patients. The sustained S100A8/A9 response was associated with a poor rapid cortisol release after stress in patients, but not in the control group. Our findings reveal for the first time that acute psychological stress induces elevated levels of S100A8/A9. We also provide hypothesis-generating evidence that dysregulated cortisol secretion in CAD patients might be associated with an exaggerated pro-inflammatory S100A8/A9 response.


Assuntos
Calgranulina A/sangue , Calgranulina B/sangue , Doença da Artéria Coronariana/metabolismo , Hidrocortisona/metabolismo , Estresse Psicológico/metabolismo , Idoso , Biomarcadores/metabolismo , Estudos de Coortes , Doença da Artéria Coronariana/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Saliva/metabolismo
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