RESUMO
BACKGROUND: Molecular biomarkers are promising tools to be routinely used in clinical psychiatry. Among psychiatric diseases, major depression disorder (MDD) has gotten attention due to its growing prevalence and morbidity. METHODS: We tested some peripheral molecular parameters such as serum mature Brain-Derived Neurotrophic Factor (mBDNF), plasma C-Reactive Protein (CRP), serum cortisol (SC), and the salivary Cortisol Awakening Response (CAR), as well as the Pittsburgh sleep quality inventory (PSQI), as part of a multibiomarker panel for potential use in MDD diagnosis and evaluation of disease's chronicity using regression models, and ROC curve. RESULTS: For diagnosis model, two groups were analyzed: patients in the first episode of major depression (MD: n = 30) and a healthy control (CG: n = 32). None of those diagnosis models tested had greater power than Hamilton Depression Rating Scale-6. For MDD chronicity, a group of patients with treatment-resistant major depression (TRD: n = 28) was tested across the MD group. The best chronicity model (p < 0.05) that discriminated between MD and TRD included four parameters, namely PSQI, CAR, SC, and mBDNF (AUC ROC = 0.99), with 96% of sensitivity and 93% of specificity. CONCLUSION: These results indicate that changes in specific biomarkers (CAR, SC, mBDNF and PSQI) have potential on the evaluation of MDD chronicity, but not for its diagnosis. Therefore, these findings can contribute for further studies aiming the development of a stronger model to be commercially available and used in psychiatry clinical practice.
Assuntos
Biomarcadores/metabolismo , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/diagnóstico , Adulto , Algoritmos , Área Sob a Curva , Fator Neurotrófico Derivado do Encéfalo/sangue , Proteína C-Reativa/biossíntese , Estudos de Casos e Controles , Feminino , Humanos , Hidrocortisona/sangue , Hidrocortisona/metabolismo , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Prevalência , Escalas de Graduação Psiquiátrica , Psiquiatria/normas , Psicometria , Curva ROC , Análise de Regressão , Saliva/metabolismo , Sono , Fatores de Tempo , Adulto JovemRESUMO
Cardiovascular diseases (CVD) are highly prevalent non-communicable diseases worldwide. Periodontitis may act as a non-traditional cardiovascular risk (CVR) factor, linked by a low-grade systemic inflammation mediated by C-reactive protein (CRP). Patients with periodontitis reported higher serum CRP levels; however, a CRP systemic and periodontal correlation in gingival crevicular fluid (GCF) and its CVR impact have been barely studied. We aimed to assess the association between periodontal diseases and CVR in a group of adult women, based on serum high-sensitivity CRP (hs-CRP) levels; and secondly, to determine the association between serum and GCF CRP levels. Gingival crevicular fluid and blood samples were obtained from women with periodontitis, gingivitis, and healthy controls. Serum and GCF CRP were determined by turbidimetric method and Luminex technology, respectively. Data were analyzed and adjusted by CVR factors. All women presented moderate CVR, without an evident association between serum hs-CRP levels and periodontal diseases. While serum hs-CRP concentrations did not significantly differ between groups, patients with gingivitis and periodontitis showed higher CRP levels in GCF, which positively correlated to CRP detection in serum.
Assuntos
Proteína C-Reativa/biossíntese , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/complicações , Doenças Periodontais/sangue , Doenças Periodontais/complicações , Adolescente , Adulto , Estudos Transversais , Feminino , Gengiva/metabolismo , Líquido do Sulco Gengival/metabolismo , Gengivite/sangue , Gengivite/complicações , Humanos , Nefelometria e Turbidimetria , Periodontite/sangue , Periodontite/complicações , Medição de Risco , Fatores de RiscoRESUMO
The pathogenesis of Rheumatoid Arthritis (RA) is not fully understood, probably influenced by genetic and environmental factors. Interstitial Lung Disease (ILD) is an extra-articular manifestation of RA, which contributes significantly to morbidity and mortality. The identification of anti-HLA antibodies has been useful in the transplantation field; however, its contribution to autoimmune diseases as RA has not been fully studied. We aimed to determine the presence of anti-HLA antibodies in RA patients with and without ILD and its possible association with clinical and biochemical markers. One-hundred and forty-seven RA patients, of which 65 had ILD (RA-ILD group), were included. Sera samples for Anti-HLA Class II LABScreen panel-reactive antibodies (PRA) were analyzed. In both groups, women predominated, and lung function was worse in patients with ILD. The anti-CCP+ (UI/mL) was higher in the RA group in comparison to RA-ILD (p < 0.001). Expositional risk factors (tobacco smoking and biomass-burning smoke) were higher in RA-ILD patients. PRA+ was identified in ~25% RA-ILD patients, while ~29% in the RA group. The CRP levels have a positive correlation with the percentage of reactivity (%PRA, p = 0.02, r2 = 0.60) in the RA-ILD group. In conclusion, anti-HLA antibodies correlate with C-reactive protein levels in RA patients with ILD.
Assuntos
Artrite Reumatoide/imunologia , Autoanticorpos/sangue , Proteína C-Reativa/biossíntese , Doenças Pulmonares Intersticiais/imunologia , Adulto , Artrite Reumatoide/complicações , Biomarcadores/sangue , Feminino , Humanos , Doenças Pulmonares Intersticiais/complicações , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
AIM: To characterize the potential of human periodontal ligament fibroblasts (HPLF) to synthesize CRP and Th-related cytokines in response to IL-6 in periodontal health and apical inflammation. METHODOLOGY: Primary HPLF stimulated with IL-6, soluble(s) IL-6 receptor (R) and controls were assayed for CRP, Th1, Th2, Th17 and Treg-related cytokines by quantitative real-time PCR and ELISA, respectively. IL-6R mRNA expression and its soluble protein levels were screened in HPLF cultures, and ex vivo samples of healthy periodontal ligaments (n = 5) and apical lesions (n = 13). Data were analysed with ANOVA or unpaired t-test. RESULTS: 0.5 ng mL-1 IL-6 plus 1 ng mL-1 of its soluble receptor (sIL-6R) for 24 h was effective in inducing CRP production. IL-6 alone had a mild dose-dependent effect; co-stimulation with sIL-6R significantly enhanced this effect, whereas it was completely abolished by the addition of IL-6R blocking antibody (P < 0.05). Similarly, higher mRNA expression and protein levels of Th1, Th17 and partially Treg-related cytokines were found for IL-6 combined with its soluble receptor versus the nonstimulated group and IL-6R antibody (P < 0.05). IL-6R mRNA expression was slightly induced by IL-6 compared to THP-1 cells, but sILR-6 protein could not be detected in HPLF. High sIL-6R levels were detected in apical lesions and were immunolocalized to mononuclear inflammatory cells and proliferating epithelium. CONCLUSION: IL-6 trans-signalling induced Th1 and Th17-related cytokines and represents an extra-hepatic mechanism for PCR synthesis in human periodontal ligament fibroblasts, contributing to explain the bone-destructive phenotype of apical lesions and eventually its systemic complications.
Assuntos
Proteína C-Reativa/biossíntese , Fibroblastos/metabolismo , Interleucina-17/biossíntese , Interleucina-1/biossíntese , Interleucina-2/biossíntese , Interleucina-6/farmacologia , Ligamento Periodontal/citologia , Receptores de Interleucina-6/fisiologia , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Humanos , Mediadores da Inflamação/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transdução de SinaisRESUMO
INTRODUCTION: C-reactive protein (CRP) is the prototype component of acute-phase proteins induced ultimately by interleukin (IL)-6 in the liver, but it is unknown whether periradicular tissues locally express CRP. The present study aimed to identify whether CRP messenger RNA synthesis occurs in situ within apical lesions of endodontic origin (ALEOs) and healthy periodontal ligament and its association with IL-6 and to determine their protein levels and tissue localization. METHODS: Patients with asymptomatic apical periodontitis and healthy volunteers presenting at the School of Dentistry, University of Chile, Santiago, Chile, were enrolled. ALEOs and healthy teeth were obtained and processed for either immunohistochemistry and double immunofluorescence to assess IL-6 and CRP tissue localization, whereas healthy periodontal ligaments were processed as controls for real-time reverse-transcription polymerase chain reaction for their RNA expression levels and multiplex assay to determine their protein levels. Statistic analysis was performed using the unpaired t test or Mann-Whitney test according to data distribution and Pearson correlation. RESULTS: IL-6 and CRP were synthesized in ALEOs, whereas their RNA expression and protein levels were significantly higher when compared with healthy periodontal ligament. IL-6 and CRP immunolocalized to the inflammatory cells, vascular endothelial cells, and mesenchymal cells. Both, IL-6 and CRP colocalized in ALEOs, and a positive correlation was found between their expression levels (P < .05). CONCLUSIONS: IL-6 and CRP messenger RNA are constitutively expressed in periodontal ligament and up-regulated in ALEOs along with higher protein levels. Given their pleiotropic effects, IL-6 and CRP protein levels in apical tissues might partially explain the development and progression of ALEOs as well as potentially asymptomatic apical periodontitis-associated systemic low-grade inflammation.
Assuntos
Proteína C-Reativa/biossíntese , Interleucina-6/biossíntese , Periodontite/metabolismo , Regulação para Cima , Adolescente , Proteína C-Reativa/genética , Feminino , Humanos , Interleucina-6/genética , Masculino , Pessoa de Meia-Idade , Periodontite/genética , Periodontite/patologia , RNA Mensageiro/metabolismoRESUMO
PURPOSE: Obesity is a major risk factor for several cancers, including female cancers. Endogenous hormones and inflammatory factors may mediate the association between anthropometric measures and cancer risk, although these associations have been studied mainly in Caucasians. The aim of the current study was to explore the association of circulating hormones, adipokines, and inflammatory factors with obesity and overweight in premenopausal Mexican women. METHODS: We conducted a cross-sectional analysis of 504 premenopausal women from the large Mexican Teachers' Cohort (MTC, ESMaestras) study to determine the association of insulin-like growth factor I (IGF-I), its major circulating binding protein (IGFBP-3), leptin, adiponectin, C-peptide, and C-reactive protein with comprehensive measures of body size. Biomarkers were measured by immunoassays. Multivariate regression analyses were performed to compare geometric mean biomarker concentrations with measured markers of body size and adiposity. RESULTS: Mean IGF-I and IGFBP-3 concentrations significantly increased with increasing height and leg length. Concentrations of IGF-I, adiponectin, and the IGF-I/IGFBP-3 ratio strongly decreased with increasing BMI, weight, waist and hip circumferences, waist-to-hip ratio (WHpR), and waist-to-height ratio (WHtR), while CRP, leptin, C-peptide concentrations, and the leptin/adiponectin ratio strongly increased. Adiponectin and the leptin/adiponectin ratio remained significantly related to measures of central adiposity (waist circumference, WHpR, and WHtR) after adjustment by body mass index. CONCLUSIONS: The results of our study suggest a strong relation between biomarkers and body size in this study population and suggest that different fat depots may have different metabolic properties.
Assuntos
Tamanho Corporal , Inflamação/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/biossíntese , Adiposidade , Adulto , Biomarcadores , Índice de Massa Corporal , Peso Corporal , Peptídeo C/sangue , Proteína C-Reativa/biossíntese , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Imunoensaio , Leptina/sangue , México , Pessoa de Meia-Idade , Análise Multivariada , Obesidade/sangue , Sobrepeso/sangue , Pré-Menopausa , Circunferência da Cintura , Relação Cintura-QuadrilRESUMO
Markers of fetal inflammatory response syndrome (FIRS) can influence the morphologic alterations in liver of autopsied neonates. The IL-6, TNF-α, and C-reactive protein (CRP) expression in liver fragments were marked by immunohistochemistry and the intensity of steatosis, percentage of fibrosis, and the number of foci of extramedullary erythropoiesis were evaluated. The degree of steatosis correlated positively with IL-6 (p = 0.06), positively with CRP (p ≤ 0.001), and negatively with TNF-α (p = 0.06). The collagen percentage correlated positively with IL-6 (p = 0.055) and positively with TNF-α (p ≤ 0.001). Erythropoiesis correlated positively with IL-6 (p ≤ 0.001) and negatively with CRP (p = 0.00754). The analyzed markers of FIRS have an important role in triggering hepatic morphologic alterations.
Assuntos
Doenças do Recém-Nascido/metabolismo , Doenças do Recém-Nascido/patologia , Fígado/metabolismo , Fígado/patologia , Autopsia , Biomarcadores/análise , Proteína C-Reativa/análise , Proteína C-Reativa/biossíntese , Feminino , Humanos , Recém-Nascido , Interleucina-6/análise , Interleucina-6/biossíntese , Masculino , Gravidez , Complicações na Gravidez/metabolismo , Complicações na Gravidez/patologia , Síndrome , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/biossínteseRESUMO
BACKGROUND: The aim of this study is to evaluate the link between C-reactive protein (CRP) and Alzheimer's disease (AD) and mild cognitive impairment (MCI) among Mexican Americans. METHODS: Non-fasting serum CRP levels, Mini-Mental State Examination scores, and Clinical Dementia Rating scale (CDR) scores were analyzed from 1,066 participants (Mexican American n = 471; non-Hispanic n = 595) of the Texas Alzheimer's Research & Care Consortium. RESULTS: Among the total cohort, CRP levels among AD cases were significantly decreased as compared to normal controls (p < 0.001) and MCI cases (p = 0.002). CRP levels among MCI cases were decreased relative to controls (p = 0.03). Among Mexican American and non-Hispanic AD cases, CRP levels were significantly decreased among AD cases as compared to controls. CRP levels were only associated with disease severity (CDR scores) among non-Hispanics (p = 0.03) AD cases. CONCLUSIONS: These results show that while CRP levels are decreased among Mexican American AD cases, CRP does not appear to be related to clinical variables as it is among non-Hispanic whites.
Assuntos
Doença de Alzheimer/etnologia , Proteína C-Reativa/metabolismo , Disfunção Cognitiva/etnologia , Americanos Mexicanos/etnologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/sangue , Doença de Alzheimer/diagnóstico , Biomarcadores/sangue , Proteína C-Reativa/antagonistas & inibidores , Proteína C-Reativa/biossíntese , Disfunção Cognitiva/sangue , Disfunção Cognitiva/diagnóstico , Estudos de Coortes , Regulação para Baixo/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , População Branca/etnologiaRESUMO
In this study we evaluated the onset and resolution of inflammation in control and streptozotocin-induced diabetic rats subjected to a single session of intense exercise. The following measurements were carried out prior to, immediately after, and 2 and 24 hours after exercise: plasma levels of proinflammatory cytokines (TNF-α, IL-1ß, IL-6, CINC-2α/ß, MIP-3α, and IL-6), immunoglobulins (IgA and IgM), acute phase proteins (CRP and C3), and creatine kinase (CK) activity. We also examined the occurrence of macrophage death by measurements of macrophages necrosis (loss of membrane integrity) and DNA fragmentation. An increase was observed in the concentration of IL-1ß (3.3-fold) and TNF-α (2.0-fold) and in the proportion of necrotic macrophages (4.5-fold) in diabetic rats 24 hours after exercise, while the control group showed basal measurements. Twenty-four hours after the exercise, serum CK activity was elevated in diabetic rats but not in control animals. We concluded that lesion and inflammations resulting from intense exercise were greater and lasted longer in diabetic animals than in nondiabetic control rats.