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1.
PLoS Negl Trop Dis ; 14(3): e0007327, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32163420

RESUMO

BACKGROUND: The chikungunya virus (CHIKV) is a re-emerging alphavirus that can cause chronic and potentially incapacitating rheumatic musculoskeletal disorders known as chronic chikungunya arthritis (CCA). We conducted a prospective cohort study of CHIKV-infected subjects during the 2013 chikungunya outbreak in Martinique. The aim of this study was to assess the prevalence of CCA at 12 months and to search for acute phase factors significantly associated with chronicity. METHODOLOGY/PRINCIPAL FINDINGS: A total of 193 patients who tested positive for CHIKV RNA via qRT-PCR underwent clinical investigations in the acute phase (<21 days), and then 3, 6, and 12 months after inclusion. The Asian lineage was identified as the circulating genotype. A total of 167 participants were classified as either with or without CCA, and were analyzed using logistic regression models. The overall prevalence of CCA at 12 months was 52.1% (95%CI: 44.5-59.7). In univariate analysis, age (RD 9.62, 95% CI, 4.87;14.38, p<0.0001), female sex (RD 15.5, 95% CI, 1.03;30.0, p = 0.04), headache (RD 15.42, 95% CI, 0.65;30.18 p = 0.04), vertigo (RD 15.33, 95% CI, 1.47;29.19, p = 0.03), vomiting (RD 12.89, 95% CI, 1.54;24.24, p = 0.03), dyspnea (RD 13.53, 95% CI, 0.73;26.33, p = 0.04), intravenous rehydration (RD -16.12, 95% CI, -31.58; -0.66 p = 0.04) and urea (RD 0.66, 95% CI, 0.12;1.20, p = 0.02) were significantly associated with the development of CCA. For the subpopulation with data on joint involvement in the acute phase, the risk factors significantly associated with CCA were at least one 1 enthesitis (RD 16.7, 95%CI, 2.8; 30.7, p = 0.02) and at least one tenosynovitis (RD 16.8, 95% CI, 1.4-32.2, p = 0.04). CONCLUSIONS: This cohort study conducted in Martinique confirms that CCA is a common complication of acute chikungunya disease. Our analysis emphasized the importance of age and female sex for CCA occurrence, and highlighted the aggravating role of dehydration during the acute phase. Early and adequate hydration were found to reduce the risk chronic chikungunya disorders. TRIAL REGISTRATION: clinicaltrials.gov (NCT01099852).


Assuntos
Artrite/epidemiologia , Artrite/patologia , Febre de Chikungunya/epidemiologia , Febre de Chikungunya/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Vírus Chikungunya/classificação , Vírus Chikungunya/genética , Vírus Chikungunya/isolamento & purificação , Doença Crônica , Feminino , Seguimentos , Genótipo , Humanos , Masculino , Martinica/epidemiologia , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Prospectivos , RNA Viral/genética , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , Adulto Jovem
2.
BMC Med Genet ; 21(1): 27, 2020 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-32039712

RESUMO

BACKGROUND: Stickler syndrome is the most common genetic cause of rhegmatogenous retinal detachment (RRD) in children, and has a high risk of blindness. Type I (STL1) is the most common subtype, caused by COL2A1 mutations. This study aims to analyze the mutation spectrum of COL2A1 and further elucidate the genotype-phenotype relationships in the East Asian populations with STL1, which is poorly studied at present. METHODS: By searching MEDLINE, Web of Science, CNKI, Wanfang Data, HGMD and Clinvar, all publications associated with STL1 were collected. Then, they were carefully screened to obtain all reported STL1-related variants in COL2A1 and clinical features in East Asian patients with STL1. RESULTS: There were 274 COL2A1 variants identified in 999 patients with STL1 from 466 unrelated families, and more than half of them were truncation mutations. Of the 107 STL1 patients reported in the East Asian population, it was found that patients with truncation mutations had milder systemic phenotypes, whereas patients with splicing mutations had severer phenotypes. In addition, several recurrent variants (c.3106C > T, c.1833 + 1G > A, c.2710C > T and c.1693C > T) were found. CONCLUSIONS: Genotype-phenotype correlations should certainly be studied carefully, contributed to making personalized follow-up plans and predicting prognosis of this disorder. Genome editing holds great potential for treating inherited diseases caused by pathogenic mutations. In this study, several recurrent variants were found, providing potential candidate targets for genetic manipulation in the future.


Assuntos
Artrite/genética , Doenças do Tecido Conjuntivo/genética , Análise Mutacional de DNA , Perda Auditiva Neurossensorial/genética , Mutação/genética , Descolamento Retiniano/genética , Artrite/epidemiologia , Artrite/patologia , Doenças do Tecido Conjuntivo/epidemiologia , Doenças do Tecido Conjuntivo/patologia , Oftalmopatias Hereditárias , Estudos de Associação Genética , Perda Auditiva Neurossensorial/epidemiologia , Perda Auditiva Neurossensorial/patologia , Humanos , Fenótipo , Descolamento Retiniano/epidemiologia , Descolamento Retiniano/patologia
3.
J S Afr Vet Assoc ; 90(0): e1-e5, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31793309

RESUMO

Infectious arthritis or tenosynovitis in broiler and breeder chickens results in major loss of productivity because of reduced growth and downgrading at processing plants. The most common causative agents of avian infectious arthritis are the bacterium Mycoplasma synoviae and avian reoviruses (ARVs) (family Reoviridae, genus Orthoreovirus). In this study, we evaluated the occurrence of these two pathogens in arthritis or tenosynovitis lesions of broilers and breeder flocks in southern Brazil using molecular detection. Tissue sections from tibiotarsal joints with visible lesions from 719 broilers and 505 breeders were analysed using pathogen-specific polymerase chain reaction (PCR) assays. In breeders, 41.2% (n = 296) of lesions were positive for M. synoviae, 26.4% (n = 190) were positive for ARV, while co-infection was present in 12.2% (n = 88) of the samples. In broilers, 20.8% (n = 105) of lesions were positive for M. synoviae, 11.9% (n = 60) for ARV and 7.7% (n = 39) of these cases were positive for both pathogens. Post-mortem examination revealed lesions with varying degrees of gross pathological severity. Histopathological examination showed intense, diffuse lymphohistiocytic inflammatory infiltrates with heterophil accumulation, primarily in the synovial capsule and digital flexor tendon, in all samples. Improved strategies for early detection and control of these major avian pathogens are highly desirable for preventing the spread of infection and reducing economic losses in the poultry industry.


Assuntos
Artrite/veterinária , Infecções por Mycoplasma/veterinária , Doenças das Aves Domésticas/microbiologia , Infecções por Reoviridae/veterinária , Tenossinovite/veterinária , Animais , Artrite/epidemiologia , Artrite/microbiologia , Artrite/patologia , Autopsia/veterinária , Brasil , Galinhas , Infecções por Mycoplasma/epidemiologia , Infecções por Mycoplasma/patologia , Mycoplasma synoviae/isolamento & purificação , Orthoreovirus Aviário/isolamento & purificação , Reação em Cadeia da Polimerase/veterinária , Doenças das Aves Domésticas/epidemiologia , Doenças das Aves Domésticas/virologia , Infecções por Reoviridae/epidemiologia , Infecções por Reoviridae/patologia , Tenossinovite/epidemiologia , Tenossinovite/microbiologia , Tenossinovite/patologia
4.
Biochemistry (Mosc) ; 84(11): 1375-1389, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31760924

RESUMO

Mesenchymal stromal cell (MSCs) represent a class of biologics with the prospects for employment as immunomodulatory, tissue-protective, and regenerative therapeutics. In parallel with cellular therapy, cell-free therapy based on MSC-secreted bioactive factors is being actively developed. MSCs secrete a variety of protein, peptide, RNA, and lipid mediators which can be concentrated, frozen, or even lyophilized without loss of activity, which gives them a certain advantage over cellular products requiring liquid nitrogen storage and infrastructure to revive frozen cells. This review (i) describes currently conducted clinical trials of cell-free products containing MSC secretome; (ii) summarizes main approaches to the generation and characterization of conditioned media concentrates and extracellular vesicle isolates; (iii) analyzes a variety of preclinical studies where effectiveness of secretome products has been shown; and (iv) summarizes current knowledge about secretome bioactive components obtained by analysis of in vivo models testing the therapeutic potential of the MSC secretome.


Assuntos
Meios de Cultivo Condicionados/química , Células-Tronco Mesenquimais/metabolismo , Lesão Renal Aguda/patologia , Lesão Renal Aguda/prevenção & controle , Animais , Artrite/patologia , Artrite/prevenção & controle , Células da Medula Óssea/citologia , Meios de Cultivo Condicionados/farmacologia , Avaliação Pré-Clínica de Medicamentos , Exossomos/metabolismo , Lesão Pulmonar/patologia , Lesão Pulmonar/prevenção & controle , Células-Tronco Mesenquimais/citologia
5.
Dtsch Med Wochenschr ; 144(22): 1585-1589, 2019 11.
Artigo em Alemão | MEDLINE | ID: mdl-31658483

RESUMO

The work-up of acute monoarthritis is challenging due to the abundance of differential diagnoses. In addition to a bacterial septic arthritis, which can, if not treated promptly, cause rapid irreversible joint damage, many diseases have to be considered: inflammatory rheumatic diseases, activated osteoarthritis, other infectious arthritis, cristal induced arthritis, and rare tumorous diseases. In cases with high urgency, and/or when medical history, physical examination and laboratory parameters remain without a specific etiologic clue, septic arthritis has to be excluded by immediate diagnostic joint aspiration. In many patients the cause of monoarthritis can already be determined by ordering a leucocyte count of the synovial fluid sample, a microscopy for crystals, and gram staining and culture for bacterial pathogens.


Assuntos
Artrite/diagnóstico , Artrite/classificação , Artrite/etiologia , Artrite/patologia , Diagnóstico Diferencial , Humanos , Ultrassonografia
6.
J Appl Oral Sci ; 27: e20180602, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31508794

RESUMO

OBJECTIVE: This study aimed to evaluate the effect of avocado/soybean unsaponifiables (ASU) on periodontal repair in rats with induced periodontitis and arthritis. METHODOLOGY: Forty-five rats were submitted to periodontitis induction by insertion of ligatures into the upper second molars, maintained for 15 days. These animals were randomly allocated to 3 groups according to the presence of induced arthritis (ART) and the application of the ASU: Control (CTR) group-healthy animals, where saline solution was administered; ART-animals with induced arthritis, where saline solution was administered; ART/ASU-animals with induced arthritis, where ASU (0.6 mg/ kg) was administered. The drugs were administered daily by gavage and the animals were euthanized after 7, 15 and 30 days of the ligature removal. Bone resorption, inflammatory infiltrate composition and marker proteins expression of the differentiation and formation of osteoclasts (RANKL and TRAP) were assessed. RESULTS: The ART/ASU group presented higher bone volume than the ART group at 7 and 30 days after the ligature removal. Furthermore, the ART group presented higher quantity of inflammatory cells and expression of TRAP and RANKL than the other groups. CONCLUSION: ASU administration improves the repair of periodontal tissues in an experimental periodontitis model in rats with induced arthritis.


Assuntos
Artrite/tratamento farmacológico , Periodontite/tratamento farmacológico , Persea/química , Extratos Vegetais/farmacologia , Soja/química , Animais , Artrite/patologia , Imuno-Histoquímica , Masculino , Periodontite/patologia , Ligante RANK/análise , Distribuição Aleatória , Ratos , Reprodutibilidade dos Testes , Fosfatase Ácida Resistente a Tartarato/análise , Fatores de Tempo , Resultado do Tratamento , Microtomografia por Raio-X
7.
Korean J Gastroenterol ; 74(3): 175-182, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31554034

RESUMO

Pancreatitis, panniculitis, and polyarthritis (PPP) syndrome is a rare but critical disease with a high mortality rate. The diagnostic dilemma of PPP syndrome is the fact that symptoms occur unexpectedly. A 48-year-old man presented with fever and painful swelling of the left foot that was initially mistaken for cellulitis and gouty arthritis. The diagnosis of PPP syndrome was made based on the abdominal CT findings and elevated pancreatic enzyme levels, lobular panniculitis with ghost cells on a skin biopsy, and polyarthritis on a bone scan. The pancreatitis and panniculitis disappeared spontaneously over time, but the polyarthritis followed its own course despite the use of anti-inflammatory agents. In addition to this case, 30 cases of PPP syndrome in the English literature were reviewed. Most of the patients had initial symptoms other than abdominal pain, leading to misdiagnosis. About one-third of them were finally diagnosed with a pancreatic tumor, of which pancreatic acinar cell carcinoma was the most dominant. They showed a mortality rate of 32.3%, associated mainly with the pancreatic malignancy. Therefore, PPP syndrome should be considered when cutaneous or osteoarticular manifestations occur in patients with pancreatitis. Active investigation and continued observations are needed for patients suspected of PPP syndrome.


Assuntos
Artrite/diagnóstico , Pancreatite/diagnóstico , Paniculite/diagnóstico , Artrite/tratamento farmacológico , Artrite/patologia , Artrite Gotosa/diagnóstico , Osso e Ossos/diagnóstico por imagem , Celulite (Flegmão)/diagnóstico , Diagnóstico Diferencial , Eritema/diagnóstico , Eritema/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Octreotida/uso terapêutico , Pancreatite/tratamento farmacológico , Pancreatite/patologia , Paniculite/tratamento farmacológico , Paniculite/patologia , Tomografia Computadorizada por Raios X
8.
Nature ; 572(7771): 670-675, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31391580

RESUMO

Macrophages are considered to contribute to chronic inflammatory diseases such as rheumatoid arthritis1. However, both the exact origin and the role of macrophages in inflammatory joint disease remain unclear. Here we use fate-mapping approaches in conjunction with three-dimensional light-sheet fluorescence microscopy and single-cell RNA sequencing to perform a comprehensive spatiotemporal analysis of the composition, origin and differentiation of subsets of macrophages within healthy and inflamed joints, and study the roles of these macrophages during arthritis. We find that dynamic membrane-like structures, consisting of a distinct population of CX3CR1+ tissue-resident macrophages, form an internal immunological barrier at the synovial lining and physically seclude the joint. These barrier-forming macrophages display features that are otherwise typical of epithelial cells, and maintain their numbers through a pool of locally proliferating CX3CR1- mononuclear cells that are embedded into the synovial tissue. Unlike recruited monocyte-derived macrophages, which actively contribute to joint inflammation, these epithelial-like CX3CR1+ lining macrophages restrict the inflammatory reaction by providing a tight-junction-mediated shield for intra-articular structures. Our data reveal an unexpected functional diversification among synovial macrophages and have important implications for the general role of macrophages in health and disease.


Assuntos
Articulações/citologia , Macrófagos/citologia , Macrófagos/fisiologia , Membrana Sinovial/citologia , Sinoviócitos/citologia , Sinoviócitos/fisiologia , Junções Íntimas/fisiologia , Animais , Artrite/imunologia , Artrite/patologia , Receptor 1 de Quimiocina CX3C/análise , Receptor 1 de Quimiocina CX3C/metabolismo , Rastreamento de Células , Feminino , Perfilação da Expressão Gênica , Humanos , Inflamação/imunologia , Inflamação/patologia , Articulações/patologia , Macrófagos/classificação , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Análise de Componente Principal , Análise de Célula Única , Sinoviócitos/classificação , Sinoviócitos/metabolismo , Transcriptoma/genética
9.
Artif Cells Nanomed Biotechnol ; 47(1): 3188-3193, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31366242

RESUMO

Objective: To investigate the effects of miR-15a on proliferation and apoptosis of human knee articular chondrocytes and explore its underlying mechanism. Methods: qRT-PCR was used to detect the expression of miR-15a in normal chondrocytes and knee arthritic chondrocytes; miR-con (transfected miR-con), miR-15a (transfected miR-15a mimics), anti-miR-con group (transfected anti-miR-con), anti-miR-15a group (transfected anti-miR-15a mimics), pcDNA group (transfected pcDNA), pcDNA-SMAD2 group (transfected pcDNA-SMAD2), the miR-15a + pcDNA group (co-transfected miR-15a and pcDNA), miR-15a + pcDNA-SMAD2 group (co-transfected miR-15a mimics and pcDNA-SMAD2), were transfected into knee articular chondrocytes by liposome method, respectively. The cell proliferation and apoptosis of each group were detected by MTT assay and flow cytometry. The protein expression of SMAD2 was detected by Western blot. The fluorescence activity of each group was detected by dual luciferase reporter gene assay. Results: The expression of miR-15a in knee arthritis chondrocytes was significantly increased (p < .05) compared with that in normal chondrocytes. Moreover, overexpression of miR-15a and silencing of SMAD2 inhibited proliferation and promoted apoptosis in knee arthritis chondrocyte. MiR-15a targeted SMAD2. Overexpression of SMAD2 reversed the inhibitory effects on proliferation and promotion effects on apoptosis induced by miR-15a in knee arthritis chondrocytes. Conclusion: miR-15a can inhibit the proliferation and promote apoptosis of knee arthritis chondrocytes. The mechanism may be related to SMAD2, which will provide a new target for the treatment of knee arthritis.


Assuntos
Apoptose/genética , Condrócitos/citologia , Articulação do Joelho/citologia , MicroRNAs/genética , Proteína Smad2/genética , Artrite/genética , Artrite/patologia , Sequência de Bases , Proliferação de Células/genética , Condrócitos/patologia , Regulação da Expressão Gênica/genética , Humanos , Articulação do Joelho/patologia
10.
Clin Chim Acta ; 496: 76-83, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31271739

RESUMO

OBJECTIVES: Previous studies found that the interleukin (IL)-17 level was elevated in inflammatory arthritis, but results were inconsistent. This meta-analysis aimed to investigate the association of IL-17 cytokine with osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). METHODS: Relevant studies were searched using databases. Standardized mean difference (SMD) was calculated. Correlation coefficient was utilized to evaluate the relationship between IL-17 and disease activity of AS and RA. Subgroup analysis, sensitivity analysis and meta-regression were applied to explore the sources of heterogeneity. RESULTS: 83 records were enrolled. The IL-17 level was elevated in AS (SMD = 2.348, P < .001), RA (SMD = 1.502, P < .001), PsA (SMD = 1.710, P < .001) and OA (SMD = 1.192, P = .016), and similar results occurred in subgroup analysis. Furthermore, the IL-17 level was positively associated with disease activity of AS and RA. CONCLUSION: Circulating IL-17 level is significantly elevated in inflammatory arthritis and is related to the disease activity of AS and RA, suggesting that it plays an important role in the pathogenesis and progression of inflammatory arthritis (especially in AS and RA).


Assuntos
Artrite/sangue , Interleucina-17/sangue , Artrite/complicações , Artrite/patologia , Humanos , Inflamação/complicações
11.
Int J Mol Sci ; 20(14)2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31340433

RESUMO

Lysyl oxidase like 3 (LOXL3) is a copper-dependent amine oxidase responsible for the crosslinking of collagen and elastin in the extracellular matrix. LOXL3 belongs to a family including other members: LOX, LOXL1, LOXL2, and LOXL4. Autosomal recessive mutations are rare and described in patients with Stickler syndrome, early-onset myopia and non-syndromic cleft palate. Along with an essential function in embryonic development, multiple biological functions have been attributed to LOXL3 in various pathologies related to amino oxidase activity. Additionally, various novel roles have been described for LOXL3, such as the oxidation of fibronectin in myotendinous junction formation, and of deacetylation and deacetylimination activities of STAT3 to control of inflammatory response. In tumors, three distinct roles were described: (1) LOXL3 interacts with SNAIL and contributes to proliferation and metastasis by inducing epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma cells; (2) LOXL3 is localized predominantly in the nucleus associated with invasion and poor gastric cancer prognosis; (3) LOXL3 interacts with proteins involved in DNA stability and mitosis completion, contributing to melanoma progression and sustained proliferation. Here we review the structure, function and activity of LOXL3 in normal and pathological conditions and discuss the potential of LOXL3 as a therapeutic target in various diseases.


Assuntos
Aminoácido Oxirredutases/genética , Artrite/genética , Fissura Palatina/genética , Doenças do Tecido Conjuntivo/genética , Matriz Extracelular/genética , Perda Auditiva Neurossensorial/genética , Miopia/genética , Neoplasias/genética , Descolamento Retiniano/genética , Aminoácido Oxirredutases/química , Aminoácido Oxirredutases/metabolismo , Artrite/enzimologia , Artrite/patologia , Fissura Palatina/enzimologia , Fissura Palatina/patologia , Colágeno/química , Colágeno/genética , Colágeno/metabolismo , Doenças do Tecido Conjuntivo/enzimologia , Doenças do Tecido Conjuntivo/patologia , Elastina/química , Elastina/genética , Elastina/metabolismo , Transição Epitelial-Mesenquimal/genética , Matriz Extracelular/química , Matriz Extracelular/enzimologia , Regulação da Expressão Gênica , Perda Auditiva Neurossensorial/enzimologia , Perda Auditiva Neurossensorial/patologia , Humanos , Isoenzimas/química , Isoenzimas/genética , Isoenzimas/metabolismo , Miopia/enzimologia , Miopia/patologia , Neoplasias/enzimologia , Neoplasias/patologia , Especificidade de Órgãos , Descolamento Retiniano/enzimologia , Descolamento Retiniano/patologia , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Fatores de Transcrição da Família Snail/genética , Fatores de Transcrição da Família Snail/metabolismo
12.
Redox Biol ; 26: 101273, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31325723

RESUMO

Neutrophil infiltration plays a significant pathological role in inflammatory diseases. NADPH oxidase type 2 (NOX2) is a respiratory burst oxidase that generates large amounts of superoxide anion (O2•-) and subsequent other reactive oxygen species (ROS). NOX2 is an emerging therapeutic target for treating neutrophilic inflammatory diseases. Herein, we show that 4-[(4-(dimethylamino)butoxy)imino]-1-methyl-1H-benzo[f]indol-9(4H)-one (CYR5099) acts as a NOX2 inhibitor and exerts a protective effect against complete Freund's adjuvant (CFA)-induced inflammatory arthritis in mice. CYR5099 restricted the production of O2•- and ROS, but not the elastase release, in human neutrophils activated with various stimulators. The upstream signaling pathways of NOX2 were not inhibited by CYR5099. Significantly, CYR5099 inhibited NOX2 activity in activated human neutrophils and in reconstituted subcellular assays. In addition, CYR5099 reduced ROS production, neutrophil infiltration, and edema in CFA-induced arthritis in mice. Our findings suggest that CYR5099 is a NOX2 inhibitor and has therapeutic potential for treating neutrophil-dominant oxidative inflammatory disorders.


Assuntos
Artrite/metabolismo , Inibidores Enzimáticos/farmacologia , NADPH Oxidase 2/antagonistas & inibidores , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Animais , Artrite/tratamento farmacológico , Artrite/etiologia , Artrite/patologia , Biomarcadores , Cálcio/metabolismo , Células Endoteliais , Inibidores Enzimáticos/química , Espaço Extracelular/metabolismo , Adjuvante de Freund , Humanos , Masculino , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NADPH Oxidase 2/química , Ligação Proteica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade
13.
BMC Musculoskelet Disord ; 20(1): 286, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31200688

RESUMO

BACKGROUND: McH-lpr/lpr-RA1 mice are a new strain of mice which spontaneously develop destructive arthritis and enthesitis in the ankle. There is no published data that drug treatment has been trialed on these mice. This study examined the effect of the mouse anti-IL-6 receptor antibody, MR16-1, for the treatment of arthritis and enthesitis in McH-lpr/lpr-RA1 mice. METHODS: Male McH-lpr/lpr-RA1 mice were randomly divided into control and treatment groups. MR16-1 was administered from 10 weeks of age for the treatment group. Saline was applied for the control group. The drug was administered once a week, at an initial dose of 2 mg, then maintained at 0.5 mg once per week thereafter. The effects were evaluated by the histopathological synovitis score, in vivo imaging using indocyanine green liposomes, and analysis of the gene expression of inflammatory cytokines. RESULTS: Tissue analyses were carried out at 14, 17 and 20 weeks of age. The synovitis scores of treated groups were significantly lower compared with those of the control group at 14 and 17 weeks of age. The kappa coefficient was 0.77. However, progression of entheseal ossification persisted in the MR16-1 treated group. In vivo imaging using indocyanine green liposomes showed significant decreases in signal intensities of treated groups at week 14, but no significant differences were observed at week 18. Blood serum amyloid A levels in treated groups were significantly lower at 17 weeks of age. The gene expression levels of Tnf and Il17 were also significantly lower in MR16-1 treated groups. CONCLUSIONS: Administration of the anti-IL-6 receptor antibody is effective for the treatment of synovitis and bone destruction of McH-lpr/lpr-RA1 mice. McH-lpr/lpr-RA1 mice may be a suitable experimental model for the development of new treatments for destructive arthritis and enthesitis. IL-6 signal blockade could contribute to the treatment of destructive arthritis, and further studies should be carried out to confirm its potential in the prevention of enthesopathy developed to ossification.


Assuntos
Anticorpos/administração & dosagem , Artrite/tratamento farmacológico , Entesopatia/tratamento farmacológico , Receptores de Interleucina-6/antagonistas & inibidores , Animais , Artrite/imunologia , Artrite/patologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Entesopatia/imunologia , Entesopatia/patologia , Humanos , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Endogâmicos , Distribuição Aleatória , Receptores de Interleucina-6/imunologia , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/imunologia , Membrana Sinovial/patologia
14.
PLoS Pathog ; 15(6): e1007880, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31211814

RESUMO

The largest ever recorded epidemic of the Chikungunya virus (CHIKV) broke out in 2004 and affected four continents. Acute symptomatic infections are typically associated with the onset of fever and often debilitating polyarthralgia/polyarthritis. In this study, a systems biology approach was adopted to analyze the blood transcriptomes of adults acutely infected with the CHIKV. Gene signatures that were associated with viral RNA levels and the onset of symptoms were identified. Among these genes, the putative role of the Eukaryotic Initiation Factor (eIF) family genes and apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC3A) in the CHIKV replication process were displayed. We further compared these signatures with signatures induced by the Dengue virus infection and rheumatoid arthritis. Finally, we demonstrated that the CHIKV in vitro infection of murine bone marrow-derived macrophages induced IL-1 beta production in a mechanism that is significantly dependent on the inflammasome NLRP3 activation. The observations provided valuable insights into virus-host interactions during the acute phase and can be instrumental in the investigation of new and effective therapeutic interventions.


Assuntos
Artrite/imunologia , Febre de Chikungunya/imunologia , Vírus Chikungunya/fisiologia , Citidina Desaminase/imunologia , Proteínas/imunologia , Replicação Viral/imunologia , Adulto , Animais , Artrite/patologia , Artrite/virologia , Febre de Chikungunya/patologia , Vírus da Dengue/imunologia , Vírus da Dengue/patogenicidade , Feminino , Febre/imunologia , Febre/patologia , Febre/virologia , Seguimentos , Humanos , Interleucina-1beta/imunologia , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia
15.
Zhonghua Nei Ke Za Zhi ; 58(6): 439-443, 2019 Jun 01.
Artigo em Chinês | MEDLINE | ID: mdl-31159523

RESUMO

Objective: To investigate the efficacy of arthroscopic synovectomy on refractory knee arthritis complicated with popliteal cyst. Methods: Patients diagnosed as rheumatoid arthritis (RA) or spondyloarthritis (SpA) with refractory knee arthritis who underwent knee arthroscopic synovectomy in our hospital from 2010 to 2017 were enrolled, including 20 patients (16 RA, 4 SpA) with popliteal cyst. Clinical data, RA disease activity score (DAS28), SpA back pain score, etc, were collected to evaluate the efficacy of knee surgery. Results: Erythrocyte sedimentation rate (ESR) [58(17, 79)mm/1h vs. 19(9, 30)mm/1h, P< 0.001],C reactive protein (CRP) [3.72(0.92,8.14) mg/L vs. 0.85(0.10,3.08) mg/L,P<0.001], rheumatoid factor [64.6(20.2,193.3) vs. 20.5(10.0,58.4),P<0.001], DAS28 score(4.67±1.25 vs. 2.81±1.23,P<0.001), knee joint discomfort score [5(4,6) vs. 2(1,3),P<0.001] and the volume of knee joint effusion by ultrasound (P<0.05) in 95 RA patients were significantly decreased compared to those before operation. ESR [27(12,54)mm/1h vs. 20 (16,28) mm/1 h,P<0.001], CRP [3.27(1.06,6.95) mg/L vs. 1.41(0.34,3.03)mg/L,P<0.001],knee discomfort score [2(0,5) vs. 1(0,3),P<0.05], back pain visual analogue score (VAS) [5(4,5) vs. 2(1,3), P<0.001], and the volume of knee joint effusion by ultrasound (P<0.001) in 58 SpA patients were significantly lower than those before the operation.The rate [16.84%(16/95) vs. 6.32%(6/95),P=0.023] and grading (P=0.007) of popliteal cyst in RA were decreased after the operation. No statistically difference was observed in the rate [6.90% (4/58) vs. 5.17%(3/58), P=0.697] of popliteal cyst in patients with SpA, yet with a trend of decrease in 4 patients. Conclusion: This study provide evidence that knee arthroscopic synovectomy has a good effect for refractory knee arthritis, which can reduce disease activity, improve joint symptoms and decrease the grading of popliteal cyst.


Assuntos
Artrite/cirurgia , Artroscopia/efeitos adversos , Articulação do Joelho/fisiopatologia , Articulação do Joelho/cirurgia , Cisto Popliteal/cirurgia , Sinovectomia/efeitos adversos , Artrite/complicações , Artrite/patologia , Artroscopia/métodos , Humanos , Articulação do Joelho/patologia , Cisto Popliteal/patologia , Sinovectomia/métodos , Resultado do Tratamento
16.
Appl Microbiol Biotechnol ; 103(15): 6287-6296, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31168650

RESUMO

In the present study, the modulatory effects of bifidobacterial spp. (Bifidobacterium breve NCIM 5671, Bifidobacterium longum NCIM 5672 and Bifidobacterium bifidum NCIM 5697) on adjuvant induced arthritis in rats were evaluated. Arthritis was induced in male Wistar rats by injecting 250 µg of Freund's adjuvant directly into the paw. Fifteen days before and 15 days after the induction of arthritis, suspended cultures of bifidobacteria (109 cfu/ml) were administered by oral gavage. Paw volume, bone mineral content, oxidative stress markers, antioxidant enzymes, cytokines, eicosanoids and expression of COX2, as well as bone hydrolytic enzymes, were assessed by RT PCR. Although piroxicam-treated groups (drug control) had better effects than bifidobacteria-treated groups, bifidobacteria probiotics administration exhibited significant (P < 0.05) prophylactic effects in terms of downregulating arthritis markers. Parameters including paw volume, bone mineral content, cytokines, and eicosanoids level were significantly (p < 0.05) modulated in bifidobacteria administered groups compared to arthritic control group. Among the three strains tested, B. breve NCIM 5671 exhibited superior prophylactic effects as assessed in the experimental rat model of arthritis. In conclusion, bifidobacteria probiotics administration can downregulate the markers of arthritis and hence can be a potential therapeutic regimen in the treatment of arthritis.


Assuntos
Anti-Inflamatórios/administração & dosagem , Artrite/prevenção & controle , Bifidobacterium/crescimento & desenvolvimento , Probióticos/administração & dosagem , Administração Oral , Animais , Artrite/patologia , Artrite/terapia , Modelos Animais de Doenças , Masculino , Ratos Wistar , Resultado do Tratamento
17.
PLoS Pathog ; 15(6): e1007877, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31226163

RESUMO

Rapid bone destruction often leads to permanent joint dysfunction in patients with septic arthritis, which is mainly caused by Staphylococcus aureus (S. aureus). Staphylococcal cell wall components are known to induce joint inflammation and bone destruction. Here, we show that a single intra-articular injection of S. aureus lipoproteins (Lpps) into mouse knee joints induced chronic destructive macroscopic arthritis through TLR2. Arthritis was characterized by rapid infiltration of neutrophils and monocytes. The arthritogenic effect was mediated mainly by macrophages/monocytes and partially via TNF-α but not by neutrophils. Surprisingly, a S. aureus mutant lacking Lpp diacylglyceryl transferase (lgt) caused more severe joint inflammation, which coincided with higher bacterial loads of the lgt mutant in local joints than those of its parental strain. Coinjection of pathogenic S. aureus LS-1 with staphylococcal Lpps into mouse knee joints caused improved bacterial elimination and diminished bone erosion. The protective effect of the Lpps was mediated by their lipid moiety and was fully dependent on TLR2 and neutrophils. The blocking of CXCR2 on neutrophils resulted in total abrogation of the protective effect of the Lpps. Our data demonstrate that S. aureus Lpps elicit innate immune responses, resulting in a double-edged effect. On the one hand, staphylococcal Lpps boost septic arthritis. On the other hand, Lpps act as adjuvants and activate innate immunity, which could be useful for combating infections with multiple drug-resistant strains.


Assuntos
Artrite/imunologia , Proteínas de Bactérias/imunologia , Lipoproteínas/imunologia , Neutrófilos/imunologia , Staphylococcus aureus/imunologia , Animais , Artrite/genética , Artrite/microbiologia , Artrite/patologia , Proteínas de Bactérias/genética , Feminino , Lipoproteínas/genética , Camundongos , Neutrófilos/patologia , Receptores de Interleucina-8B/genética , Receptores de Interleucina-8B/imunologia , Infecções Estafilocócicas/genética , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Staphylococcus aureus/genética , Staphylococcus aureus/patogenicidade , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
19.
J Am Anim Hosp Assoc ; 55(4): 210-214, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31099600

RESUMO

Ligament laxity is a known complication of erosive immune-mediated polyarthritis (IMPA) in dogs. The purpose of this study was to describe the occurrence and clinical features of carpal or tarsal ligament laxity in cases of nonerosive IMPA in dogs for the first time. Five client-owned dogs with a diagnosis of nonerosive IMPA and carpal or tarsal ligament laxity in which the influence of corticosteroids was excluded were identified. Medical records were reviewed, and data including signalment, investigative findings, and treatment regimen (e.g., surgical management) was extracted. Primary care practices were contacted to obtain follow-up, and the data was descriptively analyzed. The affected joints were either carpi and tarsi (n = 3) or carpi only (n = 2). In three cases, surgical arthrodesis was performed. Three dogs were euthanized (1 mo, 12 mo, and 5 yr) as a result of the severity of clinical signs and poor control. In the four dogs surviving >6 mo, multiple episodes of relapse were recorded, and multimodal immunosuppression was needed. The prognosis for the dogs described was poor, with none achieving control of the disease without ongoing immunosuppressive therapy. Damage to soft-tissue periarticular structures may be related to prolonged clinical disease or a more severe presentation. Jaccoud's arthropathy in humans with systemic lupus erythematosus may represent a homologous presentation.


Assuntos
Artrite/veterinária , Doenças do Cão/patologia , Instabilidade Articular/veterinária , Ligamentos/patologia , Animais , Artrite/imunologia , Artrite/patologia , Cães , Instabilidade Articular/patologia , Julgamento Moral Retrospectivo
20.
Nat Cell Biol ; 21(6): 731-742, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31086261

RESUMO

Deficiency in the deubiquitinating enzyme A20 causes severe inflammation in mice, and impaired A20 function is associated with human inflammatory diseases. A20 has been implicated in negatively regulating NF-κB signalling, cell death and inflammasome activation; however, the mechanisms by which A20 inhibits inflammation in vivo remain poorly understood. Genetic studies in mice revealed that its deubiquitinase activity is not essential for A20 anti-inflammatory function. Here we show that A20 prevents inflammasome-dependent arthritis by inhibiting macrophage necroptosis and that this function depends on its zinc finger 7 (ZnF7). We provide genetic evidence that RIPK1 kinase-dependent, RIPK3-MLKL-mediated necroptosis drives inflammasome activation in A20-deficient macrophages and causes inflammatory arthritis in mice. Single-cell imaging revealed that RIPK3-dependent death caused inflammasome-dependent IL-1ß release from lipopolysaccharide-stimulated A20-deficient macrophages. Importantly, mutation of the A20 ZnF7 ubiquitin binding domain caused arthritis in mice, arguing that ZnF7-dependent inhibition of necroptosis is critical for A20 anti-inflammatory function in vivo.


Assuntos
Artrite/genética , Inflamação/genética , Fatores de Transcrição Kruppel-Like/genética , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genética , Animais , Artrite/induzido quimicamente , Artrite/patologia , Humanos , Inflamassomos/genética , Inflamassomos/metabolismo , Inflamação/induzido quimicamente , Inflamação/patologia , Interleucina-1beta/genética , Lipopolissacarídeos/toxicidade , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Mutação , NF-kappa B/genética , Necrose/genética , Necrose/patologia , Ligação Proteica , Proteínas Quinases/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Ubiquitina/genética
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