RESUMO
OBJECTIVE: No evidence has shown the efficacy of Sodium Risedronate (Risedronate) for glucocorticoid-induced osteoporosis (GIO) in patients with Rheumatoid arthritis (RA). The aim of this study was to explore the effectiveness and safety of Risedronate for GIO complicated with RA. METHODS: This was a six-month randomized, double-blind, placebo-controlled trial of 95 patients with GIO complicated with RA from 19 centers. The primary endpoint was the change from baseline in lumbar spine bone mineral density (L-BMD). Secondary endpoints included changes in femoral neck and total hip BMD and bone turnover markers, as well as rheumatoid arthritis Disease Activity Score with 28-joint counts. Incident of non-traumatic spine fractures and adverse events were tracked as safety endpoints. RESULTS: Increase in L-BMD was significantly greater in the Risedronate group compared to the Placebo group (Risedronate: 3.49% [95% CI: 1.92-5.05] vs Placebo: 0.12% [95% CI: -2.07 to 2.30], p < .0001). No significant difference was found in the femoral neck and total hip BMD. Although adverse events were observed in 28 patients, none were considered serious. Non-traumatic vertebral fractures were identified in 10 patients. CONCLUSION: Risedronate was effective in increasing L-BMD and was well tolerated in patients with GIO complicated with RA.
Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Osteoporose/tratamento farmacológico , Ácido Risedrônico/uso terapêutico , Idoso , Artrite Reumatoide/tratamento farmacológico , Densidade Óssea , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/efeitos adversos , Método Duplo-Cego , Feminino , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Humanos , Vértebras Lombares/patologia , Masculino , Pessoa de Meia-Idade , Osteoporose/etiologia , Ácido Risedrônico/administração & dosagem , Ácido Risedrônico/efeitos adversosRESUMO
OBJECTIVES: To investigate the role of Foxp3(+) CD25(+) CD4(+) regulatory T cells (Treg) and their transcription factor, Runt-related transcription factor 1 (Runx1), in the pathogenesis and development of systemic sclerosis (SSc). METHODS: We collected 23 blood samples from patients with SSc including 19 females and 4 males, 11 early-stage cases within 3 years from onset and 12 late-stage cases and 22 samples from age-matched healthy subjects (HS). Total CD4(+) T cells were assessed for the expression of Treg-related markers, CD25 and CD127, on their surface and intracellular Foxp3 using flow cytometry. Relative expression of Runx1 mRNA in magnetically purified Treg was analyzed using real-time PCR. RESULTS: Proportion of Foxp3(+) cells in total CD4(+) T cells was decreased in patients with either early- or late-stage SSc compared with that in HS, and Runx1 mRNA expression in purified Treg was lower in patients with SSc than in HS. Runx1 mRNA expression level was related to the frequency of Treg in SSc. CONCLUSIONS: This is the first report on Runx1 expression in Treg of a human autoimmune disease. Low expression of Runx1 along with reduced proportion of Treg in CD4(+) T cells may be associated with development of SSc even in early disease.
Assuntos
Linfócitos T CD4-Positivos/metabolismo , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Escleroderma Sistêmico/metabolismo , Linfócitos T Reguladores/metabolismo , Adolescente , Adulto , Idoso , Linfócitos T CD4-Positivos/imunologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/imunologia , Linfócitos T Reguladores/imunologia , Adulto JovemRESUMO
Obesity is a state in which chronic low-grade inflammation persists in adipose tissues. Pro-inflammatory cytokines, including TNF-α, produced by adipose tissues have been implicated as active participants in the development of obesity-related diseases. Since TNF-α converting enzyme (TACE) is the major factor that induces soluble TNF-α, TACE has been noted as a pivotal regulator in this field. To reveal the role of TACE in adipose tissue inflammation, TACE-transgenic (TACE-Tg) and wild type (WT) mice were fed with high fat diet (HFD) or control diet for 16 weeks. At 13 weeks after the beginning of the diet, serum TNF-α and macrophage-related cytokine/chemokine levels were elevated in TACE-Tg mice fed with HFD (Tg-HFD mice), and the number of the so-called crown-like adipocyte was significantly increased in adipose tissues of Tg-HFD mice at the end of the experiment. Although macrophage infiltration was not detected in the adipose tissues at this time, fibrosis was observed around the crown-like adipocytes. These findings suggested that TACE overexpression induced macrophage infiltration and subsequent fibrosis in adipose tissues under HFD regimen. The collective evidence suggested that TACE could be a therapeutic target of HFD-induced obesity-related adipose tissue inflammation.
Assuntos
Proteínas ADAM/biossíntese , Tecido Adiposo/patologia , Dieta Hiperlipídica/efeitos adversos , Inflamação/metabolismo , Proteína ADAM17 , Animais , Modelos Animais de Doenças , Fibrose/metabolismo , Immunoblotting , Inflamação/patologia , Masculino , Camundongos , Camundongos TransgênicosRESUMO
TNF-α-converting enzyme (TACE) can cleave transmembrane proteins, such as TNF-α, TNF receptors, and epidermal growth factor receptor (EGFR) ligands, to release the extracellular domains from the cell surface. Recent studies have suggested that overexpression of TACE may be associated with the pathogenesis of inflammation and fibrosis. To determine the roles of TACE in inflammation and fibrosis, TACE transgenic (TACE-Tg) mice, which overexpressed TACE systemically, were generated. As the transgene-derived TACE was expressed as an inactive form, no spontaneous phenotype developed in TACE-Tg mice. However, the transgene-derived TACE could be converted to an active form by furin in vitro and by phorbol myristate acetate (PMA) in vivo. Subcutaneous injection of PMA into mice induced inflammatory cell infiltration 1 day later and subsequent dermal fibrosis 7 days later. Interestingly, the degree of dermal fibrosis at day 7 was significantly higher in TACE-Tg mice than in wild-type mice. Correspondingly, PMA increased the expression of type I collagen in the primary culture of dermal fibroblasts derived from TACE-Tg mice. Furthermore, phosphorylated EGFR was increased in the fibroblasts by the PMA treatment. The collective findings suggest that TACE overexpression and activation in fibroblasts could shed off putative EGFR ligands. Subsequently, the soluble EGFR ligands could bind and activate EGFR on fibroblasts, and then increase the type I collagen expression resulting in induction of dermal fibrosis. These results also suggest that TACE and EGFR on fibroblasts may be novel therapeutic targets of dermal fibrosis, which is induced after diverse inflammatory disorders of the skin.
Assuntos
Proteínas ADAM/biossíntese , Fibroblastos/enzimologia , Inflamação/enzimologia , Proteínas ADAM/genética , Proteínas ADAM/metabolismo , Proteína ADAM17 , Animais , Colágeno Tipo I/metabolismo , Receptores ErbB/metabolismo , Feminino , Fibroblastos/imunologia , Fibrose/enzimologia , Fibrose/imunologia , Furina/farmacologia , Histocitoquímica , Fenômenos do Sistema Imunitário/efeitos dos fármacos , Fenômenos do Sistema Imunitário/imunologia , Inflamação/imunologia , Camundongos , Camundongos Transgênicos , Pele/química , Pele/imunologia , Pele/patologia , Acetato de Tetradecanoilforbol/farmacologiaAssuntos
Doenças Autoimunes/diagnóstico por imagem , Glomerulonefrite/diagnóstico por imagem , Necrose do Córtex Renal/diagnóstico por imagem , Nefrite Intersticial/diagnóstico por imagem , Idoso , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Glomerulonefrite/imunologia , Glomerulonefrite/patologia , Humanos , Imunoglobulina G/imunologia , Rim/diagnóstico por imagem , Rim/patologia , Necrose do Córtex Renal/imunologia , Necrose do Córtex Renal/patologia , Masculino , Nefrite Intersticial/imunologia , Nefrite Intersticial/patologia , Peroxidase/imunologia , Tomografia Computadorizada por Raios XRESUMO
To characterize reversible posterior leukoencephalopathy syndrome (RPLS) in systemic lupus erythematosus (SLE) in terms of treatments for resolution and its clinical course, we reviewed 28 cases of RPLS in SLE including our cases in view of the treatment. Of these, 15 cases improved with blood pressure control and 13 required immunosuppressive therapy for activity of SLE presenting neurological manifestations. Patients without immunosuppressants at onset of RPLS more frequently required immunosuppressive therapy to recover it than those precedingly using these agents [31% (4/13) versus 87% (13/15), p = 0.008, chi-square test]. Brain magnetic resonance imaging (MRI) is important for diagnosis of RPLS-SLE in the patient with SLE who develops neurological disturbance and rapidly increasing blood pressure. When 7-day therapy for hypertension and convulsion does not reverse the manifestations, immunosuppressive treatments would be recommended to reverse RPLS.
Assuntos
Imagem de Difusão por Ressonância Magnética , Vasculite Associada ao Lúpus do Sistema Nervoso Central/complicações , Vasculite Associada ao Lúpus do Sistema Nervoso Central/patologia , Síndrome da Leucoencefalopatia Posterior/etiologia , Síndrome da Leucoencefalopatia Posterior/patologia , Adulto , Feminino , Humanos , Imunossupressores/uso terapêutico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/tratamento farmacológico , Masculino , Síndrome da Leucoencefalopatia Posterior/tratamento farmacológicoRESUMO
AIM: To identify the incidence and risk factors for hepatitis B virus (HBV) reactivation in rheumatoid arthritis (RA) patients with resolved HBV receiving biological disease-modifying antirheumatic drugs (bDMARDs). METHOD: Rheumatoid arthritis patients in whom bDMARD therapy was initiated in our departments from April 2009 to July 2016 were reviewed. The patients diagnosed with resolved HBV and whose HBV-DNA levels had been repeatedly measured were enrolled. The endpoint was HBV reactivation (a positive conversion of HBV-DNA or unquantifiable cases with positivity <20 IU/mL). Nucleic acid analogues (NAAs) were administered when the HBV-DNA levels increased beyond 20 IU/mL. The associations between HBV reactivation and the clinical findings were retrospectively analyzed. RESULTS: One hundred and fifty-two RA patients with resolved HBV were enrolled; 133 (88%) patients had antibodies against HBV surface antigen (anti-HBs). The medicines that were administered included: abatacept (n = 29), golimumab (n = 26), etanercept (n = 25), tocilizumab (n = 25), adalimumab (n = 19), infliximab (n = 17) and certolizumab pegol (n = 11). During the observation period (15 [interquartile range 4.0-34] months), 7 (4.6%) patients developed HBV reactivation. In 5 of these patients, the HBV-DNA levels became negative or remained at <20 IU/mL (+) without NAA therapy. HBV-DNA levels of >20 IU/mL were observed in 2 patients but the HBV-DNA levels became negative after NAA treatment. Patients who were negative for anti-HBs showed a significantly higher incidence of HBV reactivation (P = 0.013). CONCLUSION: HBV reactivation occurred in 4.6% of RA patients with resolved HBV during the treatment with bDMARDs and the absence of anti-HBs may be a risk factor for the reactivation of resolved HBV.
Assuntos
Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Vírus da Hepatite B/patogenicidade , Hepatite B/virologia , Hospedeiro Imunocomprometido , Ativação Viral , Idoso , Antivirais/uso terapêutico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/imunologia , DNA Viral/genética , Feminino , Hepatite B/tratamento farmacológico , Hepatite B/epidemiologia , Hepatite B/imunologia , Anticorpos Anti-Hepatite B/sangue , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Interações Hospedeiro-Patógeno , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Ativação Viral/efeitos dos fármacosRESUMO
This study presents a patient who died of acute renal failure (ARF) as a complication of scleroderma. The patient remained normotensive throughout the clinical course. Myeloperoxidase-anti-neutrophil cytoplasmic antibody was negative. Autopsy revealed fibrin thrombi in the glomerular capillaries and afferent arterioles, mesangiolysis, and double contour of the glomerular basement membrane. Contrarily, "onionskin lesions" of renal interlobular arteries, the histological hallmark of scleroderma renal crisis, were not discovered. These findings suggested that thrombotic microangiopathy (TMA) was the cause of ARF. Although the frequency is not high, close monitoring should be given to TMA in scleroderma because of possible mortality.