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1.
Int J Mol Sci ; 22(5)2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33670905

RESUMO

Rheumatoid arthritis (RA) is a chronic autoimmune disease causing inflammation of joints, cartilage destruction and bone erosion. Biomarkers and new drug targets are actively sought and progressed to improve available options for patient treatment. The Collagen Triple Helix Repeat Containing 1 protein (CTHRC1) may have an important role as a biomarker for rheumatoid arthritis, as CTHRC1 protein concentration is significantly elevated in the peripheral blood of rheumatoid arthritis patients compared to osteoarthritis (OA) patients and healthy individuals. CTHRC1 is a secreted glycoprotein that promotes cell migration and has been implicated in arterial tissue-repair processes. Furthermore, high CTHRC1 expression is observed in many types of cancer and is associated with cancer metastasis to the bone and poor patient prognosis. However, the function of CTHRC1 in RA is still largely undefined. The aim of this review is to summarize recent findings on the role of CTHRC1 as a potential biomarker and pathogenic driver of RA progression. We will discuss emerging evidence linking CTHRC1 to the pathogenic behavior of fibroblast-like synoviocytes and to cartilage and bone erosion through modulation of the balance between bone resorption and repair.


Assuntos
Artrite Reumatoide/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Animais , Artrite Reumatoide/fisiopatologia , Biomarcadores , Proteínas da Matriz Extracelular/fisiologia , Humanos , Sinoviócitos/metabolismo , Sinoviócitos/fisiologia , Via de Sinalização Wnt
2.
Medicine (Baltimore) ; 100(13): e25019, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33787585

RESUMO

BACKGROUND: We aimed to assess the efficacy of resistance exercise in rheumatoid arthritis (RA) in randomized controlled trials (RCTs). METHOD: PubMed, the Cochrane Library, and Embase were searched according to the index words to identify eligible RCTs, and relevant literature sources were also searched. The latest search was done in August 2019. Odds ratios (OR), mean difference (MD), and 95% confidence interval (95% CI) were used to analyze the main outcomes. RESULT: Seventeen RCTs were included in the meta-analysis with 512 patients in the resistance exercise group and 498 patients in the control group. The results showed that compared with the control group, resistance exercise significantly decreased disease activity score in 28 joints (DAS-28) scores (standard mean difference [SMD]: -0.69, 95% CI: -1.26 to -0.11), reduced erythrocyte sedimentation rate (ESR) (SMD: -0.86, 95% CI: -1.65 to -0.07), and shortened the time of 50 ft. walking (SMD: -0.64, 95% CI: -0.99 to -0.28). No significant difference was observed in visual analog scale (VAS) scores (SMD: -0.61, 95% CI: -1.49-0.27) and health assessment questionnaire (HAQ) scores (weighted mean difference: -0.10, 95% CI: -0.26-0.06). CONCLUSION: Resistance exercise showed reducing DAS-28 score, ESR score, and the time of 50 ft. walking in RA patients compared with the control group. However, high quality multicenter RCTs with larger sample sizes to confirm the conclusion.


Assuntos
Artrite Reumatoide/terapia , Terapia por Exercício/métodos , Treinamento de Resistência/métodos , Adulto , Idoso , Artrite Reumatoide/sangue , Artrite Reumatoide/fisiopatologia , Sedimentação Sanguínea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Resultado do Tratamento , Velocidade de Caminhada
3.
Medicine (Baltimore) ; 100(5): e24562, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33592912

RESUMO

ABSTRACT: We previously identified E26 transformation specific sequence 1 (ETS1) rs73013527 single nucleotide polymorphism associated with RA susceptibility and disease activity. In the present study, we aims to further investigate the association between ETS1 rs73013527 and receptor activator of nuclear factor kappa B ligand (RANKL), an index related to bone destruction and was reported to elevate in RA.We determined genotypes of ETS1 rs73013527, serum RANKL concentration, clinical characteristics (disease duration, disease activity score for 28 painful/swollen joints), and laboratory markers (rheumatoid factor, anti-citrullinated protein antibody, anti-keratin antibody, c-reactive protein, erythrocyte sedimentation rate) of 254 RA cases. Univariate and multivariate analysis were employed to explore the association between ETS1 rs73013527 and serum RANKL levels in RA patients.Univariate and multivariate analysis indicated no association of serum RANKL levels with patient age, gender, clinical characteristics, and laboratory markers. Univariate analysis, not multivariate analysis indicated genotype CT/TT of ETS1 rs73013527 was significantly associated with elevated RANKL levels in RA patients.ETS1 rs73013527 is in relation to serum RANKL levels among patients with RA. ETS1 probably might be an indirect factors involved in RANKL regulation in RA.


Assuntos
Artrite Reumatoide/genética , Artrite Reumatoide/fisiopatologia , Proteína Proto-Oncogênica c-ets-1/genética , Ligante RANK/sangue , Adulto , Idoso , Artrite Reumatoide/sangue , Biomarcadores , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
4.
J Agric Food Chem ; 69(1): 259-266, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33372513

RESUMO

Rheumatoid arthritis (RA) is an autoimmune disease characterized by long duration and repeated relapse. This study explored the preventive effect of tangeretin (TAN) and 5-hydroxy-6,7,8,3',4'-pentamethoxyflavone (5-HPMF) on RA, and the underlying molecular mechanism based on a rat model stimulated by bovine type II collagen (BIIC). After the intervention of TAN or 5-HPMF (TAN/5-HPMF) for 5 weeks, the RA lesions and autophagy levels of the synovial tissue were significantly reduced, and the ROS content and HO-1 expression level were down-regulated simultaneously. The relative expression levels of p-AKT and p-mTOR were down-regulated after TAN/5-HPMF feeding. Meanwhile, the relative expression level of p62 increased by more than two-fold for TAN/5-HPMF treated rats at 200 mg/kg BW comparing with those in BIIC group. Results of immunofluorescence staining and Western blotting further confirmed that TAN/5-HPMF treatment reduced BIIC-induced conversion from LC3I to LC3II. Observations under transmission electron microscope also demonstrated that the autophagy level was reduced upon TAN/5-HPMF intervention. Collectively, these results revealed that TAN and 5-HPMF prevented the pathological process of BIIC-stimulated arthritis through inhibiting the autophagy of synovial cells, achieved via the ROS-AKT/mTOR signal axis. Thus, our findings confirmed the protective potential of TAN and 5-HPMF for RA disease.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/fisiopatologia , Flavonas/administração & dosagem , Substâncias Protetoras/administração & dosagem , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Apoptose/efeitos dos fármacos , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Autofagia/efeitos dos fármacos , Bovinos , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo II/efeitos adversos , Feminino , Humanos , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/metabolismo , Serina-Treonina Quinases TOR/genética
5.
Gene ; 765: 145070, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32898607

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is complex autoimmune system disease and significant impact on the health of population in our world. Numerous studies confirmed that genetic factors play a crucial role in the pathogenesis of RA. In this current study, we aimed to investigate IL-6 polymorphisms and RA risk in Chinese Han population. METHODS: 508 RA patients and 494 age- and gender- matched healthy controls were recruited, all subjects were genotyped with an Agena MassARRAY platform. Subsequently, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression after adjusting for age and gender. RESULTS: Our results suggested that IL-6 rs2243289 allele and genotype frequencies were associated with reduced RA risk under all genetic models (all p < 0.05). Stratification analysis revealed that IL-6 rs2243289 polymorphism was significant associated with decreased the risk of RA in the old groups (age > 54) (all p < 0.05). However, IL-6 rs2069837 and rs1800796 polymorphisms were associated with increased risk of RA among the young groups (age ≤ 54) (all p < 0.05). In addition, subgroup analysis by gender suggested that IL-6 rs2069837 and rs1800796 polymorphism were interacted with increased the risk of RA in males (all p < 0.05). Besides, IL-6 rs2243289 was associated with reduced RA risk in females. CONCLUSIONS: In conclusion, our results demonstrated the correlation between IL and 6 polymorphisms and RA susceptibility and confirmed for the first time that the relationship was restricted to age and gender in Chinese Han population.


Assuntos
Artrite Reumatoide/genética , Interleucina-6/genética , Adulto , Idoso , Alelos , Artrite Reumatoide/fisiopatologia , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China , Grupos Étnicos/genética , Feminino , Frequência do Gene/genética , Estudos de Associação Genética/métodos , Predisposição Genética para Doença/genética , Genótipo , Haplótipos , Humanos , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco
6.
J Ethnopharmacol ; 266: 113402, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32980481

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Lamiophlomisrotata (Benth.) Kudo. has been used to treat trauma bleeding, rheumatism, yellow water disease in traditional Chinese medicine. AIM: The aim of this work was to evaluate the anti-rheumatoid arthritis (RA) activities and underlying mechanisms of the total iridoid glucosides (TIG) from Lamiophlomisrotata (Benth.) Kudo. METHODS: The chemical constituents of TIG was analyzed by high-performance liquid chromatography (HPLC) with seven reference compounds (penstemonoside, chlorotuberside, shanzhiside methyl ester, phloyoside, 7-epliamalbide, phlorigidoside C and lamalbide). The anti-rheumatoid arthritis effects of TIG were investigated by arthritis indexes and paw swelling degrees, as well as histopathological and Micro-CT analysis in adjuvant-induced arthritis (AIA) rats. The impacts of TIG on the level of inflammatory cytokines (IL-1ß, TNF-α, IL-6, IFN-γ, IL-17 and IL-10), and the regulation of OPG/RANKL/NF-κB pathways were determined by the ELISA and western blot, respectively. RESULTS: TIG significantly reduced the arthritis indexes and paws swelling in AIA rats, attenuated the inflammation and bone destruction in joint tissues, reduced the generation of pro-inflammatory cytokines IL-1ß, TNF-α, IL-6, IFN-γ and IL-17, as well as increased the generation of anti-inflammatory cytokine IL-10 in serum. Moreover, TIG markedly inhibited the expression of p-IKK-α, p-IκB and p-p65, and decreased the ratio of OPG/RANKL in the synovial tissues. CONCLUSION: TIG possessed significant anti-RA activities on adjuvant-induced arthritis, which might be ascribed to the regulation of inflammatory cytokines IL-1ß, TNF-α, IL-6, IFN-γ IL-17 and IL-10, as well as inhibition of OPG/RANKL/NF-κB signaling pathways.


Assuntos
Antirreumáticos/farmacologia , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Glicosídeos Iridoides/farmacologia , Lamiaceae/química , Animais , Antirreumáticos/isolamento & purificação , Artrite Experimental/fisiopatologia , Artrite Reumatoide/fisiopatologia , Citocinas/metabolismo , Feminino , Inflamação/tratamento farmacológico , Inflamação/fisiopatologia , Glicosídeos Iridoides/isolamento & purificação , NF-kappa B/metabolismo , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
7.
J Ethnopharmacol ; 265: 113341, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32891814

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Solenostemma argel (Argel) is a traditional perennial edible herb that is commonly used in folkloric medicine for the treatment of rheumatic pain, inflammation, bronchitis, cold, diabetes, gastrointestinal cramps, and urinary tract infections. No previous reports traced the mechanistic activity of this plant for treatment of rheumatoid arthritis in relation to its chemical constituents. AIM OF THE STUDY: The present study was designed to substantiate the anti-arthritic potential of S. argel and identification of its secondary metabolites responsible for the action using ultra-performance liquid chromatography coupled to high resolution mass spectrometry (UPLC/HRMS). MATERIALS AND METHODS: The air-dried powder of S. argel was subjected to liquid-liquid fractionation method to yield polar metabolites fraction (PMF) and nonpolar metabolites fraction (NPMF) where the metabolites that represent each fraction were identified using UPLC/HRMS. The in-vitro anti-arthritic effects of both fractions were tested using protein denaturation, membrane stabilization and proteinase inhibition assays, in addition to in-vitro enzyme inhibition assays of COXs, LOX and collagenases. Adjuvant-induced arthritis (AIA) model was also established to evaluate their anti-arthritic effects in-vivo at two doses (200 and 400 mg/kg) in compared to the standard ibuprofen (5 mg/kg). Physical changes with hind paw edema and body weight gain as well as the assessment of serum rheumatoid biomarkers, inflammatory cytokines, oxidative stress markers, and the activity of hyaluronidase and ß-glucouronidase enzymes were studied. The histopathological study of ankle and knee joints and immunohistochemistry of caspase-3 and TNF-α in joint synovium were also examined. RESULTS: The PMF significantly (P < 0.05) reduced paw edema, serum rheumatoid markers, pro-inflammatory mediators, degeneration enzymes of cartilage and bone, and oxidative stress biomarkers. Interestingly, flavonoid glycosides and phenolic acids dominated the polar fraction, which showed the promising anti-arthritic activity of Argel compared to the NPMF which was dominated by pregnane glycosides. CONCLUSIONS: Since arthritis is a chronic disease and there are imperative needs for a lifelong treatment with desirable pharmacological action and lower cost than the currently approved synthetic drugs having severe side effects, the PMF of Argel could be used as a potent anti-rheumatic agent.


Assuntos
Antirreumáticos/farmacologia , Apocynaceae/química , Artrite Experimental/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antirreumáticos/isolamento & purificação , Artrite Experimental/fisiopatologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/fisiopatologia , Cromatografia Líquida de Alta Pressão , Edema/tratamento farmacológico , Mediadores da Inflamação/metabolismo , Masculino , Espectrometria de Massas , Extratos Vegetais/metabolismo , Ratos , Ratos Wistar , Metabolismo Secundário
8.
JAMA Netw Open ; 3(12): e2029917, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33315114

RESUMO

Importance: Patients with autoimmune disease and lung cancer pose a multidisciplinary treatment challenge, particularly with the advent of immunotherapy. However, the association between autoimmune disease and lung cancer survival is largely unknown. Objective: To determine the association between autoimmune disease and lung cancer survival. Design, Setting, and Participants: Retrospective cohort study between 2003 and 2019 at a single academic medical center (Northwestern University). A query of the Northwestern Medicine Enterprise Data Warehouse identified 349 patients with lung cancer and several autoimmune diseases. Types of lung cancers included small cell, adenocarcinoma, squamous cell carcinoma, non-small cell not otherwise specified, and large cell carcinoma. Autoimmune diseases included rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, mixed connective tissue disease, myositis, and Sjögren syndrome. Inclusion criteria were biopsy-confirmed lung cancer, autoimmune diagnosis confirmed by a rheumatologist, and death or an encounter listed in the electronic medical record within 2 years of study end. A control group of patients with biopsy-proven lung cancer but without autoimmune disease was identified. Data analysis was conducted from March to July 2020. Exposure: Presence of autoimmune disease. Main Outcomes and Measures: Overall survival and progression-free survival in patients with autoimmune disease. The hypothesis was that patients with autoimmune disease would have worse progression-free survival and overall survival compared with patients in the control group. Results: Of the original 349 patients, 177 met inclusion criteria. Mean (SD) age at lung cancer diagnosis was 67.0 (10.0) years and 136 (76.8%) were women. Most common autoimmune diseases were rheumatoid arthritis (97 [54.8%]), systemic sclerosis (43 [24.3%]), and systemic lupus erythematous (15 [8.5%]). Most common lung cancers were adenocarcinoma (99 [55.9%]), squamous cell carcinoma (29 [16.4%]), and small cell lung cancer (17 [9.6%]). A total of 219 patients (mean [SD] age at diagnosis, 65.9 [4.1] years; 173 [79.0%]) were identified as having lung cancer without autoimmune disease and included in the control cohort. Compared with patients in the control group, patients with autoimmune disease experienced no difference in overall survival (log-rank P = .69). A total of 126 patients (69.5%) with autoimmune disease received standard of care vs 213 patients (97.3%) in the control group (P < .001). No individual autoimmune disease was associated with worse prognosis, even among patients with underlying interstitial lung disease. Conclusions and Relevance: Compared with institutional controls, patients with autoimmune disease experienced no difference in survival despite the fact that fewer patients in this group received standard-of-care treatment. No individual autoimmune disease was associated with worse prognosis. Future multicenter prospective trials are needed to further evaluate autoimmune disease and lung cancer survival.


Assuntos
Neoplasias Pulmonares , Pulmão/patologia , Idoso , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/fisiopatologia , Artrite Reumatoide/terapia , Autoimunidade , Biópsia/métodos , Biópsia/estatística & dados numéricos , Comorbidade , Registros Eletrônicos de Saúde/estatística & dados numéricos , Feminino , Humanos , Pesquisa Interdisciplinar , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Estadiamento de Neoplasias , Noroeste dos Estados Unidos/epidemiologia , Prognóstico , Estudos Retrospectivos , Escleroderma Sistêmico/epidemiologia , Escleroderma Sistêmico/fisiopatologia , Escleroderma Sistêmico/terapia , Padrão de Cuidado/organização & administração , Padrão de Cuidado/estatística & dados numéricos , Análise de Sobrevida
9.
Molecules ; 25(22)2020 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-33202656

RESUMO

The rapid spread of the new Coronavirus Disease 2019 (COVID-19) has actually become the newest challenge for the healthcare system since, to date, there is not an effective treatment. Among all drugs tested, Hydroxychloroquine (HCQ) has attracted significant attention. This systematic review aims to analyze preclinical and clinical studies on HCQ potential use in viral infection and chronic diseases. A systematic search of Scopus and PubMed databases was performed to identify clinical and preclinical studies on this argument; 2463 papers were identified and 133 studies were included. Regarding HCQ activity against COVID-19, it was noticed that despite the first data were promising, the latest outcomes highlighted the ineffectiveness of HCQ in the treatment of viral infection. Several trials have seen that HCQ administration did not improve severe illness and did not prevent the infection outbreak after virus exposure. By contrast, HCQ arises as a first-line treatment in managing autoimmune diseases such as rheumatoid arthritis, lupus erythematosus, and Sjögren syndrome. It also improves glucose and lipid homeostasis and reveals significant antibacterial activity.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Síndrome de Sjogren/tratamento farmacológico , Artrite Reumatoide/imunologia , Artrite Reumatoide/fisiopatologia , Betacoronavirus/patogenicidade , Febre de Chikungunya/tratamento farmacológico , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/fisiopatologia , Febre de Chikungunya/virologia , Vírus Chikungunya/patogenicidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Esquema de Medicação , HIV/patogenicidade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/fisiopatologia , Infecções por HIV/virologia , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/fisiopatologia , Síndrome Respiratória Aguda Grave/virologia , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/fisiopatologia , Zika virus/patogenicidade , Infecção por Zika virus/tratamento farmacológico , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/fisiopatologia , Infecção por Zika virus/virologia
10.
Medicine (Baltimore) ; 99(44): e22892, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33126340

RESUMO

T cell immunoglobulin and mucin domain-3 (TIM-3) is a surface molecule expressed on immune cells which play a role in immune regulation. The aims of the present study were to determine whether circulating soluble T cell immunoglobulin domain and mucin-3 (sTIM-3) are elevated in rheumatoid arthritis (RA) patients, and investigate the relationships between sTIM-3 and clinical features of RA.The study included 116 patients with established RA and 27 healthy control subjects. Serum levels of sTIM-3 were measured via the enzyme-linked immunosorbent assays (ELISA). Correlations between serum sTIM-3 and a range of parameters including anti-citrullinated peptide antibody (ACPA) titer, erythrocyte sedimentation rate (ESR), and matrix metalloproteinase-3 (MMP-3) were assessed.Serum sTIM-3 was significantly elevated in RA patients compared with those in healthy subjects, and it was positively correlated with ACPA titer (r = 0.27 P = .005), ESR (r = 0.27, P = .004) and MMP-3 (r = 0.35, P < .001). In RA patients with high ACPA titers (≥200 U/mL), sTIM-3 was not correlated with ESR or MMP-3. Whereas, sTIM-3 was significantly correlated with ESR and MMP-3 in RA patients with low ACPA titers (<200 U/mL).Serum sTIM-3 was increased in RA patients, and it was associated with proinflammatory markers and disease activity in RA patients under a particular ACPA status. Our data suggest that circulating sTIM-3 may be a useful biomarker for the determination of disease activity in RA patients.


Assuntos
Anticorpos Anti-Proteína Citrulinada/sangue , Artrite Reumatoide , Receptor Celular 2 do Vírus da Hepatite A/sangue , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/fisiopatologia , Biomarcadores/sangue , Sedimentação Sanguínea , Correlação de Dados , Progressão da Doença , Feminino , Humanos , Articulações/imunologia , Articulações/patologia , Masculino , Metaloproteinase 3 da Matriz/sangue , Pessoa de Meia-Idade , Monitorização Imunológica/métodos , Gravidade do Paciente
11.
Isr Med Assoc J ; 9(22): 491-497, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32954695

RESUMO

BACKGROUND: Tocilizumab is an interleukin 6 (IL-6) receptor antagonist used treat moderate to severe active rheumatoid arthritis (RA). Both intravenous (IV) and subcutaneous (SC) routes are approved for the treatment of adults with RA. OBJECTIVES: To evaluate SC tocilizumab in a real-life clinical setting. METHODS: Our study was a multi-center, open-label, single-arm study. Participants were adults with a diagnosis of active RA, previously treated with disease-modifying antirheumatic drugs (DMARDs), with or without biologic agents. Participants received a weekly SC injection of tocilizumab 162 mg as monotherapy or in combination with methotrexate or DMARDs for 24 weeks. Efficacy, safety, and immunogenicity were assessed. RESULTS: Treatment of 100 patients over 24 weeks resulted in improvement in all efficacy parameters assessed: Clinical Disease Activity Index, Disease Activity Score using 28 joint counts and erythrocyte sedimentation rate, American College of Rheumatology response scores, Simplified Disease Activity Index, tender and swollen joint counts, and patient-reported outcomes including fatigue, global assessment of disease activity, pain, and Health Assessment Quality of Life Disease Index. Improvement was achieved as early as the second week of treatment. There were 473 adverse events (AEs)/100 patient-years (PY) and 16.66 serious AEs/100 PY. The most common AEs were neutropenia (12%), leukopenia (11%), and increased hepatic enzymes (11%). Of a total of 42 PY, the rates of serious infections and AEs leading to discontinuation were 4.8, and 11.9 events/100 PY, respectively. CONCLUSIONS: The safety, tolerability, and efficacy profile of tocilizumab SC were comparable to those reported in other studies evaluating the IV and SC routes of administration.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Qualidade de Vida , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/fisiopatologia , Quimioterapia Combinada , Feminino , Humanos , Injeções Subcutâneas , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento
13.
Life Sci ; 258: 118164, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32739467

RESUMO

High mobility group box-1 (HMGB1) protein is a diverse, single polypeptide moiety, present in mammalian eukaryotic cells. In response to stimuli, this nuclear protein is actively secreted in to the extracellular compartment or passively released by the necrotic cells, in order to mediate inflammatory responses, by forming complexes with IL-1α, IL-1ß, LPS and other moieties, and binding to RAGE, TLR and other receptor ligands, initiating downstream, signaling processes. This molecule acts as a proinflammatory cytokine and contributes to the progression of diseases like, acute lung injury, autoimmune liver damage, graft rejection immune response and arthritis. Small concentrations of HMGB1 are released during apoptosis, which facilitates oxidative regulation on Cys106, and propagates immune inactivating tolerogenic signals in the body. The review portrays the role of HMGB1 in rheumatoid arthritis, evidently supported by pre-clinical and clinical investigations, demonstrating extensive HMGB1 expression in synovial tissue and fluid as well as serum, excessive expression of transduction receptor signaling molecules, bone remodeling and uncontrolled expression of bone destroying osteoclastogenesis, resulting in destruction of articular cartilage, bone deformation and synovial proliferation, alleviating the pathogenesis in RA disease. Moreover, the review highlights the therapeutic regime targeting HMGB1, facilitating inhibition of its actions and release into the extracellular compartment, to ameliorate the destructive events that prevail in rheumatoid arthritis.


Assuntos
Artrite Reumatoide/patologia , Proteína HMGB1/metabolismo , Animais , Apoptose/efeitos dos fármacos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Artrite Reumatoide/fisiopatologia , Remodelação Óssea/efeitos dos fármacos , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Cartilagem Articular/fisiopatologia , Proteína HMGB1/análise , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Inflamação/fisiopatologia , Terapia de Alvo Molecular , Osteogênese/efeitos dos fármacos
14.
PLoS One ; 15(8): e0237072, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32745151

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is associated with an increased cardiovascular disease (CVD) risk which may start even before diagnosis. To explore this CVD risk prior to RA, we determined multiple risk factors and two 10-year clinical risk scores in a cohort of individuals at-risk of RA. We also analyzed associations with arthritis development and autoantibody status and compared a subset of at-risk individuals to an age and sex matched seronegative control group. METHODS: In a cohort of 555 consecutive arthralgia patients positive for rheumatoid factor (RF) and / or anti-citrullinated protein antibody (ACPA) we retrospectively identified patients with preclinical arthritis (i.e. those who developed arthritis), and non-arthritis patients (those without arthritis development during maximum 5 years follow up). Demographics, CVD risk factors and the 10-year cardiovascular risk according to the SCORE and QRISK3 system were determined at baseline. RESULTS: Preclinical arthritis patients (n = 188) had a higher heart rate (68 vs 63 bpm, p = 0.048) and lower cholesterol (5.2 mmol/l vs 5.5, p = 0.006), HDL (1.0 mmol/l vs 1.1, p0.003) and ApoB (0.85 g/l vs 0.91, p = 0.011) compared to non-arthritis patients (n = 367). Lipid levels were associated with ACPA status in both the preclinical arthritis and non-arthritis group. Ten-year CVD risk scores did not differ between preclinical arthritis and non-arthritis patients, in total, 7% (SCORE) and 8% (QRISK3) of seropositive arthralgia patients were classified as high risk. Seropositive at-risk patients (n = 71) had higher total cholesterol (5.4 vs 4.9, p<0.001), TC/HDL ratio (4.0 vs 3.0, p<0.001), triglycerides (1.4 vs 1.0, p = 0.001), ApoB (1.0 vs 0.9, p = 0.019) and 10-year risk scores (median SCORE 1.0 vs 0.0, p = 0.030 and median QRISK3 4.4 vs 3.1, p<0.001) compared to seronegative controls. CONCLUSION: Our results suggest that lipid changes commence prior to RA diagnosis and that ACPAs might play a role.


Assuntos
Artrite Reumatoide/complicações , Artrite Reumatoide/fisiopatologia , Doenças Cardiovasculares/etiologia , Adulto , Anticorpos Anti-Proteína Citrulinada , Artralgia , Artrite Reumatoide/imunologia , Autoanticorpos/imunologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/fisiopatologia , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fator Reumatoide/imunologia , Fatores de Risco
15.
Clin Rheumatol ; 39(11): 3195-3204, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32852623

RESUMO

INTRODUCTION: Covid-19 infection poses a serious challenge for immune-compromised patients with inflammatory autoimmune systemic diseases. We investigated the clinical-epidemiological findings of 1641 autoimmune systemic disease Italian patients during the Covid-19 pandemic. METHOD: This observational multicenter study included 1641 unselected patients with autoimmune systemic diseases from three Italian geographical areas with different prevalence of Covid-19 [high in north (Emilia Romagna), medium in central (Tuscany), and low in south (Calabria)] by means of telephone 6-week survey. Covid-19 was classified as (1) definite diagnosis of Covid-19 disease: presence of symptomatic Covid-19 infection, confirmed by positive oral/nasopharyngeal swabs; (2) highly suspected Covid-19 disease: presence of highly suggestive symptoms, in absence of a swab test. RESULTS: A significantly higher prevalence of patients with definite diagnosis of Covid-19 disease, or with highly suspected Covid-19 disease, or both the conditions together, was observed in the whole autoimmune systemic disease series, compared to "Italian general population" (p = .030, p = .001, p = .000, respectively); and for definite + highly suspected diagnosis of Covid-19 disease, in patients with autoimmune systemic diseases of the three regions (p = .000, for all comparisons with the respective regional general population). Moreover, significantly higher prevalence of definite + highly suspected diagnosis of Covid-19 disease was found either in patients with various "connective tissue diseases" compared to "inflammatory arthritis group" (p < .000), or in patients without ongoing conventional synthetic disease-modifying anti-rheumatic drugs treatments (p = .011). CONCLUSIONS: The finding of a higher prevalence of Covid-19 in patients with autoimmune systemic diseases is particularly important, suggesting the need to develop valuable prevention/management strategies, and stimulates in-depth investigations to verify the possible interactions between Covid-19 infection and impaired immune-system of autoimmune systemic diseases. Key Points • Significantly higher prevalence of Covid-19 is observed in a large series of patients with autoimmune systemic diseases compared to the Italian general population, mainly due to patients' increased susceptibility to infections and favored by the high exposure to the virus at medical facilities before the restriction measures on individual movement. • The actual prevalence of Covid-19 in autoimmune systemic diseases may be underestimated, possibly due to the wide clinical overlapping between the two conditions, the generally mild Covid-19 disease manifestations, and the limited availability of virological testing. • Patients with "connective tissue diseases" show a significantly higher prevalence of Covid-19, possibly due to deeper immune-system impairment, with respect to "inflammatory arthritis group". • Covid-19 is more frequent in the subgroup of autoimmune systemic diseases patients without ongoing conventional synthetic disease-modifying anti-rheumatic drugs, mainly hydroxyl-chloroquine and methotrexate, which might play some protective role against the most harmful manifestations of Covid-19.


Assuntos
Doenças Autoimunes/epidemiologia , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Doenças Reumáticas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/epidemiologia , Artrite Psoriásica/fisiopatologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/fisiopatologia , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/fisiopatologia , Betacoronavirus , Infecções por Coronavirus/fisiopatologia , Dermatomiosite/tratamento farmacológico , Dermatomiosite/epidemiologia , Dermatomiosite/fisiopatologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Itália/epidemiologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/fisiopatologia , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/fisiopatologia , Escleroderma Sistêmico/tratamento farmacológico , Escleroderma Sistêmico/epidemiologia , Escleroderma Sistêmico/fisiopatologia , Síndrome de Sjogren/tratamento farmacológico , Síndrome de Sjogren/epidemiologia , Síndrome de Sjogren/fisiopatologia , Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/epidemiologia , Espondilite Anquilosante/fisiopatologia , Doenças do Tecido Conjuntivo Indiferenciado/tratamento farmacológico , Doenças do Tecido Conjuntivo Indiferenciado/epidemiologia , Doenças do Tecido Conjuntivo Indiferenciado/fisiopatologia
17.
Health Qual Life Outcomes ; 18(1): 216, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32631349

RESUMO

Rheumatoid arthritis (RA) has a large and varied impact on the quality of life as associated with patient health including both physical and mental well-being. The aim of the study was to assess the factors that affect the assessment of the quality of life of RA patients depending on the prevalence of frailty syndrome. MATERIAL AND METHODS: The study involved 106 patients with RA (82 women; mean age 65.83 ± 5.01), who had been hospitalized in the Silesian Centre for Rheumatology, Rehabilitation and Disability Prevention in Ustron, Poland. The patients that were included in the study were divided into two groups depending on the incidence of frailty syndrome: Group 1 - robust patients and Group 2 - patients with frailty syndrome. RESULTS: Frailty syndrome was identified in 34.9% of the patients with recognized/diagnosed RA; in women, it was 36.14% and in men, it was 25.92%. The average TFI value was 4.11 ± 2.05; in the physical domain, it was 3.39 ± 1.66; in the mental domain, it was 0.41 ± 0.55 and in the social domain, it was 0.31 ± 0.48. The robust patients assessed their quality of life associated with sleep as being worse compared to patients with recognized frailty syndrome. CONCLUSION: Frailty syndrome has no significant impact on the assessment of the quality of life of patients with diagnosed RA. The factors that determine quality of life are different in robust patients and in patients with frailty syndrome. The assessment of the quality of life is affected by the degree of an individual's fitness regardless of the occurrence of frailty syndrome.


Assuntos
Artrite Reumatoide/fisiopatologia , Artrite Reumatoide/psicologia , Idoso Fragilizado/psicologia , Idoso Fragilizado/estatística & dados numéricos , Fragilidade/fisiopatologia , Qualidade de Vida/psicologia , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/epidemiologia , Feminino , Fragilidade/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Polônia/epidemiologia , Prevalência
18.
Microvasc Res ; 131: 104038, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32622695

RESUMO

BACKGROUND: The relationship between plasma arginine metabolites influencing vascular homeostasis and peripheral vasodilatory capacity in rheumatoid arthritis (RA) patients is not known. METHODS: l-arginine (Arg), monomethyl-l-arginine (MMA), l-homoarginine (hArg), asymmetric dimethyl-l-arginine (ADMA), symmetric dimethyl-l-arginine, and l-citrulline (Cit) were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) in 164 RA patients and 100 age- and sex-matched healthy controls without previous cardiovascular events. Log-transformed reactive hyperemia index (Ln-RHI) evaluated by flow-mediated pulse amplitude tonometry (PAT, EndoPAT2000 device) was assessed as surrogate measure of peripheral vasodilatory capacity in RA patients. Ln-RHI values <0.51 indicated peripheral endothelial dysfunction (ED). The relationship between plasma arginine metabolite concentrations, RA descriptors and peripheral vasodilatory capacity was evaluated by bivariate correlation and regression analyses. RESULTS: Plasma ADMA concentrations were significantly higher, and plasma hArg concentrations significantly lower, in RA patients than in controls (0.53 ± 0.09 vs 0.465 ± 0.07 µmol/L and 1.50 ± 0.60 vs 1.924 ± 0.78 µmol/L, respectively; p < 0.001 for both comparisons). Bivariate correlation analysis demonstrated no significant correlation between arginine metabolites and disease descriptors. In regression analysis in RA patients, higher plasma ADMA concentrations were independently associated with presence of ED [OR(95% CI) = 77.3(1.478-4050.005), p = 0.031] and lower Ln-RHI [B coefficient(95% CI) = -0.57(-1.09 to -0.05), p = 0.032]. CONCLUSIONS: ADMA was significantly, albeit weakly, associated with impaired microcirculatory vasodilatory capacity and peripheral endothelial dysfunction in RA. This suggests an important pathophysiological role of this metabolite in the vascular alterations observed in this patient group.


Assuntos
Arginina/análogos & derivados , Artrite Reumatoide/sangue , Artrite Reumatoide/fisiopatologia , Dedos/irrigação sanguínea , Metabolômica , Vasodilatação , Idoso , Idoso de 80 Anos ou mais , Arginina/sangue , Artrite Reumatoide/diagnóstico , Biomarcadores/sangue , Estudos de Casos e Controles , Citrulina/sangue , Estudos Transversais , Feminino , Homoarginina/sangue , Humanos , Itália , Masculino , Pessoa de Meia-Idade
19.
Autoimmun Rev ; 19(9): 102612, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32668290

RESUMO

"Rhupus" or "rhupus syndrome" is a poorly described and underdiagnosed disease in which features of both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) appear in the same patient, most often sequentially. The SLE-related involvement is usually mild, dominated by hematological abnormalities and skin, serosal and renal involvement. The natural history of rhupus arthritis follows an RA-like pattern and can progress towards typical inflammatory erosions, deformations and disability. Despite the lack of consensus on the definition of rhupus and on its place in the spectrum of autoimmunity, a growing number of studies are pointing towards a true overlap between RA and SLE. However, the inclusion criteria employed in the literature during the last 4 decades are heterogeneous, making the already rare cohorts and case reports difficult to analyze. Because of this heterogeneity and due to the rarity of the disease, the prevalence, pathophysiology and natural history as well as the radiological and immunological profiles of rhupus are poorly described. Moreover, since there is no validated therapeutic strategy, treatment is based on clinicians' experience and on the results of a few studies. We herein present a systematic literature review to analyze the clinical and laboratory data of all reported rhupus patients and to provide up-to-date information about recent advances in the understanding of the pathophysiological mechanisms, diagnostic tools and treatment options.


Assuntos
Artrite Reumatoide/complicações , Lúpus Eritematoso Sistêmico/complicações , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/fisiopatologia , Artrite Reumatoide/terapia , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/fisiopatologia , Lúpus Eritematoso Sistêmico/terapia , Prevalência , Síndrome
20.
PLoS One ; 15(6): e0234405, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32598346

RESUMO

Chronic pain is a complex experience that has now become a major public health issue. This has prompted many researchers to study attention, understanding it to be a crucial factor that allows altering the experience of pain, while attributing considerable importance to sustained attention. Accordingly, the main studies in this field stress the importance of emotion regulation processes and emotions on the perception of painful stimuli and attentional processes themselves. Nevertheless, only a handful of studies have been found that directly study the relationship between these variables. Within this context, this article sets out to analyse emotional regulation processes, emotional variables (depression and anxiety), the experience of pain, and age on the ability to maintain the vigilance response in a sample of patients with chronic pain. This involved selecting a sample of 49 patients with rheumatoid arthritis and examining their performance in an ad-hoc sustained attention test. With a view to complying with the study's main purpose, the participants were also assessed through the use of the following self-report measures: the Beck Depression Inventory (BDI-I); the Hospital Anxiety and Depression Scale (HADS); the McGill Pain Questionnaire, and the Difficulties in Emotion Regulation Scale (DERS). Linear regression analyses revealed a significant impact of the aging process on the performance times in the attention task. Likewise, age and depression recorded a significant correlation with the mistakes made during the task. These results suggest that higher depression levels and an older age might be related to a worse adaptation to pain management techniques based on attention processes, such as mindfulness.


Assuntos
Envelhecimento/psicologia , Atenção , Dor Crônica/psicologia , Depressão/psicologia , Emoções , Adulto , Idoso , Ansiedade/psicologia , Artrite Reumatoide/fisiopatologia , Artrite Reumatoide/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Percepção da Dor , Análise de Regressão , Autorrelato , Fatores Socioeconômicos , Espanha
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