Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 40
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Clin Nutr ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31787367

RESUMO

BACKGROUND & AIMS: Epidemiological studies in school-age children are challenging, particularly those that aim to analyse metabolic markers on blood samples obtained via invasive and stressful procedures. The objective of this paper is to evaluate the use of saliva, as a non-invasive tool in epidemiological studies performed in school-age children, to capture metabolic changes associated with body mass index (BMI), dietary characteristics and physical activity in both boys and girls. METHODS: This is an observational study in which healthy children of ages between 8 and 12 years (n = 129, 60 girls and 69 boys) from three schools in a Mediterranean area of Spain were included. A panel of biomarkers was measured in serum and saliva and correlated with BMI, dietary characteristics and physical activity. RESULTS: Significant positive correlation between serum and salivary levels were detected for CRP (r = 0.770) in all included children, and boys (r = 0.805) and girls (r = 0.775) separately (P < 0.001, in all cases) and for insulin in girls (r = 0.442; P < 0.05). Among all studied salivary biomarkers, insulin was significantly correlated with the three factors studied: positively with BMI and negatively with dietary characteristics (intake and composition) and physical activity (P < 0.05). Obesity and diet composition were both positively associated to pro-inflammatory biomarkers, CRP and IL1b; while diet composition shared with physical activity levels the correlation with IL6 (positive with energy, fat, carbohydrate and saturated fatty acid intake, and negative with cholesterol intake and average physical activity in boys), NGF and glucose (in both cases correlations were negative with diet composition and physical activity variables) (P < 0.05, in all cases). Sex differences were detected in serum glucose and TNFα. CONCLUSIONS: Biomarkers in saliva are able to capture differences in BMI, dietary characteristics and physical activity levels in school-age children. Saliva may potentially constitute a useful non-invasive and stress-free tool to evaluate metabolic markers of inflammation and/or metabolism related to BMI and lifestyle in a sex-dependent manner.

2.
Front Immunol ; 10: 1880, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31440254

RESUMO

Mixed Connective Tissue Disease (MCTD) is a rare complex systemic autoimmune disease (SAD) characterized by the presence of increased levels of anti-U1 ribonucleoprotein autoantibodies and signs and symptoms that resemble other SADs such as systemic sclerosis (SSc), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Due to its low prevalence, this disease has been very poorly studied at the molecular level. We performed for the first time an epigenome-wide association study interrogating DNA methylation data obtained with the Infinium MethylationEPIC array from whole blood samples in 31 patients diagnosed with MCTD and 255 healthy subjects. We observed a pervasive hypomethylation involving 170 genes enriched for immune-related function such as those involved in type I interferon signaling pathways or in negative regulation of viral genome replication. We mostly identified epigenetic signals at genes previously implicated in other SADs, for example MX1, PARP9, DDX60, or IFI44L, for which we also observed that MCTD patients exhibit higher DNA methylation variability compared with controls, suggesting that these sites might be involved in plastic immune responses that are relevant to the disease. Through methylation quantitative trait locus (meQTL) analysis we identified widespread local genetic effects influencing DNA methylation variability at MCTD-associated sites. Interestingly, for IRF7, IFI44 genes, and the HLA region we have evidence that they could be exerting a genetic risk on MCTD mediated through DNA methylation changes. Comparison of MCTD-associated epigenome with patients diagnosed with SLE, or Sjögren's Syndrome, reveals a common interferon-related epigenetic signature, however we find substantial epigenetic differences when compared with patients diagnosed with rheumatoid arthritis and systemic sclerosis. Furthermore, we show that MCTD-associated CpGs are potential epigenetic biomarkers with high diagnostic value. Our study serves to reveal new genes and pathways involved in MCTD, to illustrate the important role of epigenetic modifications in MCTD pathology, in mediating the interaction between different genetic and environmental MCTD risk factors, and as potential biomarkers of SADs.

3.
Artigo em Inglês | MEDLINE | ID: mdl-30873579

RESUMO

INTRODUCTION: Mitochondrial DNA (mtDNA) is gaining increasing interest as a marker of cellular damage and could also act as an inflammatory mediator in cardiopulmonary bypass induced postoperative inflammatory response. Although minimally invasive heart valve surgery reportedly reduces inflammation, the mtDNA and cytokine profile in this context remains unclear. MATERIALS AND METHODS: Here, we report a prospective series of 40 elderly patients with aortic stenosis who underwent bioprosthetic aortic valve replacement (AVR) through upper ministernotomy with either a sutureless (n = 20) or a conventional (n = 20) valve. Primary end points included serial plasma levels of mtDNA (T1: at baseline; T2: 4 hours after surgery; and T3: 24s hour after surgery), cytokines (interleukin-6 [IL-6], tumor necrosis factor-α [TNF-α]), and myocardial necrosis biomarkers (MNBs), whereas secondary end points included clinical and echocardiographic data. RESULTS: Significant increases in the postoperative plasma levels (T2) of mtDNA, cytokines, and MNBs were observed in all patients. The postoperative plasma levels of mtDNA, TNF-α, and MNBs showed no significant differences between the treatment groups, although there was a trend toward lower levels in the sutureless group. The decreases in aortic cross-clamp and cardiopulmonary bypass times seen in the sutureless group were associated with significant lower postoperative levels (T2 and T3) of IL-6. CONCLUSION: AVR through upper ministernotomy was associated with a significant increase in postoperative plasma levels of mtDNA and cytokines. There was no difference in the mtDNA levels between the sutureless and conventional valve groups, suggesting a similar level of inflammation in both groups. However, the shorter operation time observed in the sutureless valve group was associated with significantly lower postoperative levels of IL-6, indicating potential clinical benefits.

4.
Artigo em Inglês | MEDLINE | ID: mdl-30889798

RESUMO

The present work analyses the traditional method of applying whitening products on Mediterranean greenhouses. Four commercial whitening products (agricultural solar protectors, ASPs), applied at four doses, were compared with a non-whitened cover. The traditional product "Blanco de España" with 99% calcium carbonate (CaCO3) and other three products with 97% CaCO3 that incorporate adhesives were tested. The use of adhesives in ASP did not influence the effect of the different products on the inside temperature, and at the same dose all four products show a similar behaviour. The findings support the maximum dose recommended by other authors of 0.50 kg L-1 (50/100), above which the transmissivity of the greenhouse cover decreases by over 50%. The effect of ASP on the transmissivity of the cover depends principally on the dose applied, but also on the climatic conditions (solar radiation, cloud cover, etc.) and on the time of year (solar elevation). The habitual use of a constant dose throughout the year does not seem to be the most adequate. Recommended doses should vary according to the time of year and the desired degree of transmissivity reduction. The adhesive components are shown to provide a high degree of protection against heavy rain. The study recommends a standardised method of ASP application, establishing a method that allows the grower to verify the concentration of the product that will remain on the greenhouse cover.


Assuntos
Agricultura/métodos , Ambiente Controlado , Luz Solar , Manufaturas , Temperatura Ambiente
6.
Asian Cardiovasc Thorac Ann ; 27(1): 5-10, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30409026

RESUMO

AIM: The underlying pathophysiologic mechanisms of aortic stenosis are not clear. Mitochondrial dysfunction plays a role in many pathological conditions including cardiac diseases. We aimed to analyze the mitochondrial DNA haplogroups in a group of patients undergoing valve replacement surgery due to severe aortic stenosis. METHODS: Mitochondrial DNA haplogroups were assessed in 176 patients with severe aortic stenosis and 308 control subjects. Cardiovascular risk factors and demographics were similar in both groups. RESULTS: Patients carrying haplogroup Uk had a lower risk of developing aortic stenosis, especially compared to patients carrying haplogroup H (odds ratio = 0.507; 95% confidence interval: 0.270-0.952, p = 0.035). CONCLUSIONS: Mitochondrial DNA haplogroups could be involved in the development of severe aortic stenosis. Specifically, haplogroup H could be a risk factor and Uk a protective factor for severe aortic stenosis in a population from Spain.


Assuntos
Estenose da Valva Aórtica/genética , DNA Mitocondrial/genética , Haplótipos , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/cirurgia , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Implante de Prótese de Valva Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Espanha
7.
Curr Rheumatol Rep ; 19(6): 32, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28470479

RESUMO

PURPOSE OF REVIEW: DNA methylation has emerged as an important contributing factor in the pathogenesis of systemic lupus erythematosus (SLE). Here, we describe the DNA methylation patterns identified in SLE and how these epigenetic changes can influence disease susceptibility, clinical heterogeneity, and disease flares. RECENT FINDINGS: Several genome-wide DNA methylation studies have been recently completed in SLE. Important observations include robust demethylation of interferon-regulated genes, which is consistent across all cell types studied to date, and is independent of disease activity. This interferon epigenetic signature was shown to precede interferon transcription signature in SLE, suggesting it might be an early event in the disease process. Recent studies also revealed DNA methylation changes specific for renal and skin involvement in SLE, providing a proof of principle for a value of DNA methylation studies in exploring mechanisms of specific disease manifestations, and potentially as prognostic biomarkers. Inherited ethnicity-specific DNA methylation patterns have also been shown to possibly contribute to differences in SLE susceptibility between populations. Finally, a recent study revealed that DNA methylation levels at IFI44L can accurately distinguish SLE patients from healthy controls, and from patients with other autoimmune diseases, promising to be the first epigenetic diagnostic marker for SLE. Genome-wide DNA methylation studies in SLE have provided novel insights into disease pathogenesis, clinical heterogeneity, and disease flares. Further studies promise to reveal novel diagnostic, prognostic, and therapeutic targets for SLE.


Assuntos
Metilação de DNA , Epigênese Genética , Lúpus Eritematoso Sistêmico/genética , Estudo de Associação Genômica Ampla , Humanos
9.
Rheumatology (Oxford) ; 56(suppl_1): i78-i87, 2017 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-28339517

RESUMO

Omics studies of systemic autoimmune diseases (SADs) in general, and SLE in particular, have delivered isolated information from transcriptome, epigenome, genome, cytokine and metabolome analyses. Such analyses have resulted in the identification of disease susceptibility genes and the description of IFN expression signatures, allowing extensive insight into the mechanisms of disease and the development of new therapies. Access to such technologies allows the recognition of patterns of disease at a pathway level, thereby, to reclassify SLE and other SADs and to develop new therapeutics from a personalized perspective. The use of omic information allows the discovery of correlative patterns involving drugs not currently suspected to be of value in SADs. In this review, we summarize the omics findings for SLE and propose ways of using the data for the identification of new biomarkers, finding new drugs and reclassifying patients not only with SLE, but also with other SADs.


Assuntos
Doenças Autoimunes/genética , Perfilação da Expressão Gênica , Genômica , Lúpus Eritematoso Sistêmico/genética , Metabolômica , Doenças Autoimunes/classificação , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia , Citocinas/imunologia , Descoberta de Drogas , Epigenômica , Predisposição Genética para Doença , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologia , MicroRNAs/genética
10.
J Autoimmun ; 74: 161-175, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27522116

RESUMO

The genome-wide association study is a free-hypothesis approach based on screening of thousands or even millions of genetic variants distributed throughout the whole human genome in relation to a phenotype. The relevant role of the genome-wide association studies in the last decade is undisputed because it has permitted to elucidate multiple risk genetic factors associated with the susceptibility to several human complex diseases. Regarding systemic lupus erythematosus (SLE) this approach has allowed to identify more than 60 risk loci for SLE susceptibility across populations to date, increasing our understanding on the pathogenesis of this disease. We present the latest findings in the genetic of SLE across populations using genome-wide approaches. These studies revealed that most of the genetic risk is shared across borders and ethnicities. Finally, we focus on describing the most important risk loci for SLE attempting to cover the genetic findings in relation to functional polymorphisms, such as missense single nucleotide polymorphisms (SNPs) or regulatory variants involved in the development of the disease. The functional studies try to identify the causality of some GWAS-associated variants, many of which fall in non-coding regions of the genome, suggesting a regulatory role. Many loci show an environmental interaction, another aspect revealed by the studies of epigenetic modifications and those associated with genetic variants. Finally, new-generation sequencing technologies can open other paths in the research on SLE genetics, the role of rare variants and the detailed identification of causal regulatory variation. The clinical relevance of the genetic factors will be shown when we are able to use them or in combination with other molecular measurements to re-classify a heterogeneous disease such as SLE.


Assuntos
Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/genética , Animais , Mapeamento Cromossômico , Epigênese Genética , Regulação da Expressão Gênica , Interação Gene-Ambiente , Estudos de Associação Genética , Variação Genética , Estudo de Associação Genômica Ampla , Genômica/métodos , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Locos de Características Quantitativas , Fatores de Risco
11.
Curr Opin Rheumatol ; 28(5): 506-14, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27227345

RESUMO

PURPOSE OF REVIEW: To describe the recent studies on the genetics of systemic lupus erythematosus (SLE) and Sjögren's syndrome. RECENT FINDINGS: We overview the most recent findings on the genetic susceptibility of the diseases and provide information on their genetic similarities and differences. SUMMARY: SLE and Sjögren's syndrome are two closely related systemic autoimmune diseases that share multiple clinical and molecular aspects, including a significant number of susceptibility genes. Several genome-wide association studies were recently published in different populations that provide a better picture of their molecular mechanisms. It is becoming clear that their genetic architecture is quite well established, but more information is required on expression quantitative trait loci, epigenetic genome-wide analyses, gene × gene interactions and the role of rare variants.


Assuntos
Antígenos de Histocompatibilidade Classe II/genética , Lúpus Eritematoso Sistêmico/genética , Síndrome de Sjogren/genética , Antígeno CD11b/genética , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Humanos , Fatores Reguladores de Interferon/genética , Lúpus Eritematoso Sistêmico/imunologia , Ligante OX40/genética , Fator de Transcrição STAT4/genética , Síndrome de Sjogren/imunologia , beta Carioferinas/genética
12.
Maturitas ; 86: 86-94, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26921934

RESUMO

BACKGROUND: Although multicomponent interventions are the gold standard for delirium management, few nurse-led interventions in Acute Geriatric Units (AGU) are described. OBJECTIVES: To analyze if a preventive multicomponent non-pharmacologic nurse-led intervention randomized clinical trial (MID-Nurse Study) is feasible (pilot study), and can reduce the incidence, duration, and severity of delirium in hospitalized older adults in an AGU. DESIGN: Parallel-group double-blind randomized clinical trial (pilot Study). SETTING: AGU Complejo Hospitalario Universitario, Albacete (Spain). PARTICIPANTS: 50 patients ≥65 years hospitalized in the AGU. Intervention group (IG) 21, control group (CG) 29. INTERVENTION: After risk factor analysis, all participants in the IG received a daily multicomponent non-pharmacologic intervention (orientation, sensorial deficit, sleep, mobilization, hydration, nutrition, drug chart review, elimination, oxygenation, pain) by the intervention nurses. The CG received usual care. MEASUREMENTS: Daily delirium presence with the Confusion Assessment Method (CAM), and severity with the Delirium Rating Scale-Revised-98 (DRS). Outcome measures were delirium incidence, prevalence, severity, and number of days with delirium, mortality, length of stay, use of physical restraint measures, and use of drugs for delirium control. RESULTS: Mean age 86.5 (48% women). 21 participants presented delirium during hospitalization (14CG and 7 IG). Process, resources, management, and scientific objectives were considered positive, making the study feasible. Delirium prevalence (33.3% vs 48.3%) and incidence (14.3% vs 41.4%; p=0.039) were reduced in the IG compared to CG. Total delirium severity was lower in the IG compared to the CG (35.0 vs 65.0; p=0.040). Mortality was not different between groups (CG 17.2% vs IG 19.0%). CONCLUSION: The MID-Nurse Study is feasible, and a multicomponent nurse-led intervention on patients with delirium in an AGU can reduce delirium prevalence, incidence, and severity. The clinical trial registration number ClinicalTrials.gov ID: NCT02558777.


Assuntos
Delírio/epidemiologia , Delírio/prevenção & controle , Padrões de Prática em Enfermagem , Idoso , Idoso de 80 Anos ou mais , Delírio/diagnóstico , Método Duplo-Cego , Estudos de Viabilidade , Feminino , Humanos , Incidência , Tempo de Internação , Masculino , Projetos Piloto , Prevalência , Medição de Risco , Índice de Gravidade de Doença , Espanha
13.
J Biomed Mater Res B Appl Biomater ; 104(7): 1366-73, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-26201533

RESUMO

Poly(glycerol sebacate) (PGS)/nanohydroxyapatite (nHA) composites were assessed to develop new materials for closure via tissue transport for nonhealing defects (e.g., cleft palate and large skin wounds). The elastic shape memory polymer, PGS, was reinforced with nHA at 3 and 5% loading to increase the mechanical properties compared with the undoped PGS. Differential scanning calorimetry (DSC) was utilized to identify a glass transition temperature (Tg ) of -25°C. X-ray diffraction demonstrated a reduction in the amorphous nature of the material. The Fourier transform infrared photoacoustic spectral (FTIR-PAS) data showed decreased CO bonding and increased hydrogen bonding with increased nHA incorporation. Composites exhibited Young's moduli in the range of 0.25-0.5 MPa and tensile strength of 1.5-3 N. No significant difference in extension to break (∼50 mm) with addition of nHA was observed. The elastic modulus significantly increased for 5% PGS/nHA compared to 0 and 3% PGS/nHA and tensile strength significantly increased for 3% PGS/nHA compared to 0 and 5% PGS/nHA. Degradation of 5% nHA/PGS significantly increased during the second week compared to PGS 0 and 3% PGS/nHA. The accelerated degradation for 5% PGS/nHA coupled with decreased flexibility and tensile strength implies an interruption in crosslinking. By maintaining flexibility and extension while increasing tensile strength, the 3% PGS/nHA doped satisfied the force range desired for closure of soft tissue defects. Based on this work, PGS with 3% nHA shape memory polymers should serve as a good candidate for closure of nonhealing soft tissues. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1366-1373, 2016.


Assuntos
Plásticos Biodegradáveis/química , Decanoatos/química , Durapatita/química , Glicerol/análogos & derivados , Nanocompostos/química , Polímeros/química , Glicerol/química
14.
Arthritis Rheumatol ; 67(11): 2978-89, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26200652

RESUMO

OBJECTIVE: Glycans attached to the Fc portion of IgG are important modulators of IgG effector functions. Interindividual differences in IgG glycome composition are large and they associate strongly with different inflammatory and autoimmune diseases. IKZF1, HLA-DQ2A/B, and BACH2 genetic loci that affect IgG glycome composition show pleiotropy with systemic lupus erythematosus (SLE), indicating a potentially causative role of aberrant IgG glycosylation in SLE. We undertook this large multicenter case-control study to determine whether SLE is associated with altered IgG glycosylation. METHODS: Using ultra-performance liquid chromatography analysis of released glycans, we analyzed the composition of the IgG glycome in 261 SLE patients and 247 matched controls of Latin American Mestizo origin (the discovery cohort) and in 2 independent replication cohorts of different ethnicity (108 SLE patients and 193 controls from Trinidad, and 106 SLE patients and 105 controls from China). RESULTS: Multiple statistically significant differences in IgG glycome composition were observed between patients and controls. The most significant changes included decreased galactosylation and sialylation of IgG (which regulate proinflammatory and antiinflammatory actions of IgG) as well as decreased core fucose and increased bisecting N-acetylglucosamine (which affect antibody-dependent cell-mediated cytotoxicity). CONCLUSION: The IgG glycome in SLE patients is significantly altered in a way that decreases immunosuppressive action of circulating immunoglobulins. The magnitude of observed changes is associated with the intensity of the disease, indicating that aberrant IgG glycome composition or changes in IgG glycosylation may be an important molecular mechanism in SLE.


Assuntos
Predisposição Genética para Doença , Imunoglobulina G/genética , Lúpus Eritematoso Sistêmico/imunologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/metabolismo , Masculino , Pessoa de Meia-Idade , Adulto Jovem
15.
J Food Sci ; 80(2): E349-58, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25619624

RESUMO

Air frying is being projected as an alternative to deep fat frying for producing snacks such as French fries. In air frying, the raw potato sections are essentially heated in hot air containing fine oil droplets, which dehydrates the potato and attempts to impart the characteristics of traditionally produced French fries, but with a substantially lower level of fat absorbed in the product. The aim of this research is to compare: (1) the process dynamics of air frying with conventional deep fat frying under otherwise similar operating conditions, and (2) the products formed by the 2 processes in terms of color, texture, microstructure, calorimetric properties, and sensory characteristics. Although, air frying produced products with a substantially lower fat content but with similar moisture contents and color characteristics, it required much longer processing times, typically 21 min in relation to 9 min in the case of deep fat frying. The slower evolution of temperature also resulted in lower rates of moisture loss and color development reactions. Differential scanning calorimetry (DSC) studies revealed that the extent of starch gelatinization was also lower in the case of air fried product. In addition, the 2 types of frying also resulted in products having significantly different texture and sensory characteristics.


Assuntos
Culinária/métodos , Solanum tuberosum/química , Varredura Diferencial de Calorimetria , Cor , Comportamento do Consumidor , Temperatura Alta , Humanos , Microscopia Eletrônica de Varredura , Odorantes , Paladar
16.
J Biomed Mater Res B Appl Biomater ; 103(2): 407-16, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24898435

RESUMO

Development of resorbable elastic composites as an alternative means to apply contractive forces for manipulating craniofacial bones is described herein. Composites made from the biodegradable elastomer, poly (1,8-octanediol co-citric acid) (POC), and hydroxyapatite (nHA) with a 200 nm diameter (0-20% loadings) were created to develop a material capable of applying continuous contractive forces. The composites were evaluated for variation in their mechanical properties, rate of degradation, and interaction of the hydroxyapatite nanoparticles with the polymer chains. First, an ex vivo porcine model of cleft palate was used to determine the rate of cleft closure with applied force. The closure rate was found to be 0.505 mm N(-1) . From this approximation, the ideal maximum load was calculated to be 19.82 N, and the elastic modulus calculated to be 1.98 MPa. The addition of nHA strengthens POC, but also reduces the degradation time by 45%, for 3% nHA loading, compared to POC without nHA. X-ray diffraction data indicates that the addition of nHA to amorphous POC results in the formation of a semicrystalline phase of the POC adjacent to the nHA crystals. Based on the data, we conclude that amongst the 0-20% nHA loadings, a 3% loading of nHA in POC may be an ideal material (1.21 MPa elastic modulus and 13.17 N maximum load) to induce contraction forces capable of facilitating osteogenesis and craniofacial bone repair.


Assuntos
Citratos , Fissura Palatina/terapia , Durapatita , Nanocompostos/química , Osteogênese , Polímeros , Animais , Citratos/química , Citratos/farmacologia , Fissura Palatina/patologia , Modelos Animais de Doenças , Durapatita/química , Durapatita/farmacologia , Elasticidade , Polímeros/química , Polímeros/farmacologia , Suínos
17.
Ann Rheum Dis ; 74(4): 762-8, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24336335

RESUMO

OBJECTIVE: Certain HLA-DRB1 alleles and single-nucleotide polymorphisms (SNPs) are associated with rheumatoid arthritis (RA). Our objective was to examine the combined effect of these associated variants, calculated as a cumulative genetic risk score (GRS) on RA predisposition, as well as the number of autoantibodies (none, one or two present). METHOD: We calculated four GRSs in 4956 patients and 4983 controls from four European countries. All four scores contained data on 22 non-HLA-risk SNPs, and three scores also contained HLA-DRB1 genotypes but had different HLA typing resolution. Most patients had data on both rheumatoid factor (RF) and anti-citrullinated proteins antibodies (ACPA). The GRSs were standardised (std.GRS) to account for population heterogeneity. Discrimination between patients and controls was examined by receiveroperating characteristics curves, and the four std.GRSs were compared across subgroups according to autoantibody status. RESULTS: The std.GRS improved its discriminatory ability between patients and controls when HLA-DRB1 data of higher resolution were added to the combined score. Patients had higher mean std.GRS than controls (p=7.9×10(-156)), and this score was significantly higher in patients with autoantibodies (shown for both RF and ACPA). Mean std.GRS was also higher in those with two versus one autoantibody (p=3.7×10(-23)) but was similar in patients without autoantibodies and controls (p=0.12). CONCLUSIONS: The GRS was associated with the number of autoantibodies and to both RF and ACPA positivity. ACPA play a more important role than RF with regards to the genetic risk profile, but stratification of patients according to both RF and ACPA may optimise future genetic studies.


Assuntos
Artrite Reumatoide/genética , Autoanticorpos/imunologia , Cadeias HLA-DRB1/genética , Alelos , Artrite Reumatoide/imunologia , Estudos de Casos e Controles , Grupo com Ancestrais do Continente Europeu , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Peptídeos Cíclicos/imunologia , Fator Reumatoide/imunologia , Medição de Risco , Fatores de Risco
18.
Ann Rheum Dis ; 74(3): e19, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24448344

RESUMO

OBJECTIVE: To evaluate the contribution of the SPP1 rs11439060 and rs9138 polymorphisms, previously reported as autoimmune risk variants, in the rheumatoid arthritis (RA) genetic background according to anti-citrullinated protein antibodies (ACPAs) status of RA individuals. METHODS: We analysed a total of 11,715 RA cases and 26,493 controls from nine independent cohorts; all individuals were genotyped or had imputed genotypes for SPP1 rs11439060 and rs9138. The effect of the SPP1 rs11439060 and rs9138 risk-allele combination on osteopontin (OPN) expression in macrophages and OPN serum levels was investigated. RESULTS: We provide evidence for a distinct contribution of SPP1 to RA susceptibility according to ACPA status: the combination of ≥3 SPP1 rs11439060 and rs9138 common alleles was associated mainly with ACPA negativity (p=1.29×10(-5), ORACPA-negative 1.257 (1.135 to 1.394)) and less with ACPA positivity (p=0.0148, ORACPA-positive 1.072 (1.014 to 1.134)). The ORs between these subgroups (ie, ACPA-positive and ACPA-negative) significantly differed (p=7.33×10(-3)). Expression quantitative trait locus analysis revealed an association of the SPP1 risk-allele combination with decreased SPP1 expression in peripheral macrophages from 599 individuals. To corroborate these findings, we found an association of the SPP1 risk-allele combination and low serum level of secreted OPN (p=0.0157), as well as serum level of secreted OPN correlated positively with ACPA production (p=0.005; r=0.483). CONCLUSIONS: We demonstrate a significant contribution of the combination of SPP1 rs11439060 and rs9138 frequent alleles to risk of RA, the magnitude of the association being greater in patients negative for ACPAs.


Assuntos
Artrite Reumatoide/genética , Autoanticorpos/imunologia , Citrulina/imunologia , Osteopontina/genética , Peptídeos/imunologia , Alelos , Artrite Reumatoide/imunologia , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Haplótipos , Humanos , Macrófagos/metabolismo , Masculino , Osteopontina/metabolismo , Polimorfismo de Nucleotídeo Único
19.
Am J Hum Genet ; 94(1): 47-61, 2014 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-24387989

RESUMO

In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci.


Assuntos
Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 3/genética , Loci Gênicos , Predisposição Genética para Doença , Escleroderma Sistêmico/genética , Alelos , Proteína 5 Relacionada à Autofagia , Proteínas de Transporte/genética , Estudos de Casos e Controles , RNA Helicases DEAD-box/genética , Endodesoxirribonucleases/genética , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Antígenos HLA/genética , Humanos , Subunidade p35 da Interleucina-12/genética , Desequilíbrio de Ligação , Modelos Logísticos , Masculino , Procedimentos Analíticos em Microchip , Proteínas Associadas aos Microtúbulos/genética , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas/genética , Fatores de Risco
20.
PLoS One ; 8(7): e68295, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23861880

RESUMO

Given the role of CD247 in the response of the T cells, its entailment in autoimmune diseases and in order to better clarify the role of this gene in RA susceptibility, we aimed to analyze CD247 gene variants previously associated with other autoimmune diseases (rs1052237, rs2056626 and rs864537) in a large independent European Caucasian population. However, no evidence of association was found for the analyzed CD247 single-nucleotide polymorphisms (SNPs) with RA and with the presence/absence of anti-cyclic citrullinated polypeptide. We performed a meta-analysis including previously published GWAS data from the rs864537 variant, revealing an overall genome-wide significant association between this CD247 SNP and RA with anti-CCP (OR = 0.90, CI 95% = 0.87-0.93, Poverall = 2.1×10(-10)). Our results show for first time a GWAS-level association between this CD247 polymorphism and RA risk.


Assuntos
Artrite Reumatoide/genética , Complexo CD3/genética , Estudos de Associação Genética , Polimorfismo de Nucleotídeo Único , Artrite Reumatoide/imunologia , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Razão de Chances
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA