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1.
Mod Rheumatol ; : 1-11, 2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31829087

RESUMO

Objectives: The usage of oral therapies, endothelin receptor antagonists (ERAs), phosphodiesterase type-5 (PDE-5) inhibitors and prostaglandin analogs has resulted in improved outcomes in patients with pulmonary arterial hypertension related to systemic sclerosis (SSc-PAH). However, the optimal therapeutics have not been determined.Methods: A systematic searching in the databases of Medline (PubMed), Embase, the Cochrane Library (Central) and unpublished clinical trials (clinicaltrials.gov) was conducted to identify the clinical studies with oral treatment for SSc-PAH patients published before 1 June 2019. The data were extracted and the quality was assessed. The main outcomes are exercise capacity and hemodynamic parameters, which were synthesized and analyzed.Results: In total, 27 clinical trials were enrolled for further analysis. It was demonstrated that bosentan treatment, the widely used drug for PAH, might improve the exercise capacity and pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) in this clinical setting, although without significant difference. Meanwhile, the usage of prostaglandin analogs could improve the parameters mentioned above. Furthermore, combined therapy with ambrisentan and tadalafil significantly increased the treatment efficacy of key parameters in SSc-PAH patients compared with basic treatment.Conclusion: This meta-analysis reveals that combination therapy might provide more benefits to exercise capacity and hemodynamic parameters in SSc-PAH patients. Still more RCTs are needed to provide more solid evidence.

2.
Br J Pharmacol ; 176(16): 2922-2944, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31124139

RESUMO

BACKGROUND AND PURPOSE: Celastrol exhibits anti-arthritic effects in rheumatoid arthritis (RA), but the role of celastrol-mediated Ca2+ mobilization in treatment of RA remains undefined. Here, we describe a regulatory role for celastrol-induced Ca2+ signalling in synovial fibroblasts of RA patients and adjuvant-induced arthritis (AIA) in rats. EXPERIMENTAL APPROACH: We used computational docking, Ca2+ dynamics and functional assays to study the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase pump (SERCA). In rheumatoid arthritis synovial fibroblasts (RASFs)/rheumatoid arthritis fibroblast-like synoviocytes (RAFLS), mechanisms of Ca2+ -mediated autophagy were analysed by histological, immunohistochemical and flow cytometric techniques. Anti-arthritic effects of celastrol, autophagy induction, and growth rate of synovial fibroblasts in AIA rats were monitored by microCT and immunofluorescence staining. mRNA from joint tissues of AIA rats was isolated for transcriptional analysis of inflammatory genes, using siRNA methods to study calmodulin, calpains, and calcineurin. KEY RESULTS: Celastrol inhibited SERCA to induce autophagy-dependent cytotoxicity in RASFs/RAFLS via Ca2+ /calmodulin-dependent kinase kinase-ß-AMP-activated protein kinase-mTOR pathway and repressed arthritis symptoms in AIA rats. BAPTA/AM hampered the in vitro and in vivo effectiveness of celastrol. Inflammatory- and autoimmunity-associated genes down-regulated by celastrol in joint tissues of AIA rat were restored by BAPTA/AM. Knockdown of calmodulin, calpains, and calcineurin in RAFLS confirmed the role of Ca2+ in celastrol-regulated gene expression. CONCLUSION AND IMPLICATIONS: Celastrol triggered Ca2+ signalling to induce autophagic cell death in RASFs/RAFLS and ameliorated arthritis in AIA rats mediated by calcium-dependent/-binding proteins facilitating the exploitation of anti-arthritic drugs based on manipulation of Ca2+ signalling.

3.
Arthritis Res Ther ; 18: 38, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-26832154

RESUMO

BACKGROUND: In this study, the Spondyloarthritis Research Consortium Canada (SPARCC) scoring method was used to compare treatment methods in patients with axial spondyloarthritis (SpA), a form of sacroiliitis. MRI abnormalities in bone marrow edema (BME) were compared before and after treatment in order to compare the efficacy of anti-TNF-α and DMARD, alone or in combination, as treatments for sacroiliitis. METHODS: Fifty-six Chinese patients with axial SpA (mean age 22.6 years) were recruited. Patients were divided into three groups according to different treatments (anti-TNF-α alone vs. DMARDs alone vs. combined anti-TNF-α and DMARDs). MRI examinations were performed before and after treatment. The SPARCC score, clinically relevant AS Disease Activity (ASDAS) indices, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were analyzed. RESULTS: After treatment, ASDAS and SPARCC scores, ESR, and CRP were significantly improved (P < 0.05) in the anti-TNF-α monotherapy and combination groups; however, there were no statistically significant differences (P > 0.05) in clinical disease activity and radiological inflammation of sacroiliac joint (SIJ) in patients in the DMARDs alone group. SPARCC showed a correlation with ASDAS score pre-treatment, but not post-treatment. Furthermore, there were significant changes (P < 0.05) in these patients with axial SpA after only 3 months of treatment. Follow-up studies of patients who continued therapy for 4-6 months and 9-12 months revealed statistically significant differences from baseline (P < 0.05). CONCLUSIONS: SPARCC can be used to assess severity of disease pre-treatment. Anti-TNF-α treatment resulted in effective reduction of disease activity and BME of SIJ after 3 months of therapy.


Assuntos
Sacroileíte/diagnóstico , Sacroileíte/tratamento farmacológico , Índice de Gravidade de Doença , Espondilartrite/diagnóstico , Espondilartrite/tratamento farmacológico , Adolescente , Adulto , Antirreumáticos/farmacologia , Antirreumáticos/uso terapêutico , Canadá , Feminino , Humanos , Masculino , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto Jovem
4.
Zhonghua Yi Xue Za Zhi ; 95(45): 3641-5, 2015 Dec 01.
Artigo em Chinês | MEDLINE | ID: mdl-26849923

RESUMO

OBJECTIVE: To investigate the efficacy and safety of mycophenolate mofetil (MMF) in the treatment of connective tissue disease-related interstitial lung disease (CTD-ILD). METHODS: A total of 60 patients with CTD-ILD, confirmed by high resolution computer tomography (HRCT), were enrolled from five clinical centers from July 2010 to July 2014. In addition to the basic glucocorticoid treatment, patients received intravenous cyclophosphamide (Group A) or oral MMF (Group B) for one year. Pulmonary function was assessed at the 3, 6, 12 months. All adverse events were recorded and efficacy and safety were evaluated at the end of this trial. RESULTS: Total 60 patients were enrolled, each group had 30 patients. 5 patients withdrew voluntarily from each group, 2 and 3 patients died in group A and B, respectively. Total 45 patients completed this trial. Neither lung function, HRCT nor adverse events had differences between the two groups or within group (P>0.05). When the analysis was done among patients with forced vital capacity (FVC) ≤ 75% and forced expiratory volume in one second (FEV1)% ≤ 75%, there were significantly statistical differences in FVC and FEV1 at 6th month compared with prior treatment in group A (both P<0.05). And there were significant increase in FVC and FEV1 at 12 months in group B (both P<0.05). But there was no statistical difference between the two groups. For the patients with diffusion capacity for carbon monoxide (DLco) ≤ 65%, there were significant increase in group A at 3, 6 and 12 months (P<0.01, P<0.05, P<0.05, respectively). but no significant increase was found in patients on MMF. And there was no difference between the two groups. No statistical difference existed in survival rate between these two groups (P>0.05). CONCLUSIONS: MMF has comparative effect as cyclophosphamide in the remission or stability of lung function and HRCT manifestations of CTD-ILD patients. MMF is generally well-tolerated, but its efficacy in maintenance therapy and long-term safety remains to be clarified.


Assuntos
Doenças do Tecido Conjuntivo , Doenças Pulmonares Intersticiais , Ciclofosfamida , Volume Expiratório Forçado , Glucocorticoides , Humanos , Pulmão , Ácido Micofenólico/análogos & derivados , Testes de Função Respiratória , Tomografia Computadorizada por Raios X
5.
Zhonghua Yi Xue Za Zhi ; 90(31): 2205-8, 2010 Aug 17.
Artigo em Chinês | MEDLINE | ID: mdl-21029662

RESUMO

OBJECTIVE: To evaluate the influence of the recombinant human type II tumor necrosis factor receptor-antibody Fc fusion protein (rhTNFR:Fc) on cytokines and bone metabolism in patients with juvenile idiopathic arthritis (JIA). METHODS: This was a prospective, non-randomized, controlled and open-label study. Thirty-one patients with JIA in active state were enrolled at our hospital from December 2006 to June 2009. The mean age was 12.7 ± 2.3 years. Exclusive criteria included infection with tuberculosis and hepatitis B etc., abnormal renal or hepatic function. Study consists of two phases. During the first phase (0-3 months), according to the economic status, all JIA patients were divided into treatment and control groups. The treatment group consisted of 18 patients (enthesitis-related arthritis, n = 15; polyarticular-onset arthritis, n = 2; systemic-onset type, n = 1) on a regimen of rhTNFR:Fc 0.4 mg/kg, subcutaneously injected twice weekly. The control group contained 13 patients (enthesitis-related arthritis, n = 9; polyarticular-onset arthritis, n = 2; systemic-onset type, n = 2) on a regimen of MTX 10 mg × m(-2) × w(-1). Two intolerance patients were given sulfasalazine (SASP) 30-50 mg × kg(-1) × d(-1). During the second phase (3-6 months), the responding patients continued the original therapy. The rhTNFR:Fc group received a reduced dosage of 0.4 mg × kg(-1) × w(-1). All patients of both groups who became complicated with peripheral arthritis or were non-responding had the addition of SASP. Follow-up was conducted at baseline, 1 month, 3 months and 6 months. And TNF-α, MMP-3, IL-1ß, osteocalcin (BGP), ß-collagen fragment (ß-CTx), alkaline phosphatase, erythrocyte sedimentation rate (ESR), c-reactive protein (CRP) and bone mineral density dynamic changes were examined respectively in the treatment process. RESULTS: Alkaline phosphatase and lumbar spine bone mineral density increased while TNF-α, IL-1ß, ESR and CRP decreased significantly in two groups (P < 0.05). ESR were 16 ± 8.0 mm/h vs 60 ± 38 mm/h, CRP 10 ± 7 mg/L vs 47 ± 37 mg/L and ß-CTx 2.1 ± 0.8 vs 1.1 ± 0.9 µg/L at 1 month in two groups respectively with statistic difference (P < 0.05). BGP increased and MMP-3 decreased in both groups with no statistic difference. Femur Ward's triangular area and forearm bone mineral density had no statistic difference between two groups. Interestingly, one case with bone fracture for two years has healed after a 6-month therapy of rhTNFR:Fc as proved by X-ray. CONCLUSION: Both rhTNFR:Fc and traditional DMARDs both can reduce the levels of TNF-α, IL-1ß, ESR and CRP and increase lumbar spine bone mineral density and ALP significantly. RhTNFR: Fc improves the acute phase index and bone metabolism index earlier than the traditional therapy. Thus disease and bone destruction are controlled more earlier.


Assuntos
Artrite Juvenil/metabolismo , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Receptores Tipo II do Fator de Necrose Tumoral/uso terapêutico , Adolescente , Artrite Juvenil/tratamento farmacológico , Densidade Óssea , Criança , Pré-Escolar , Humanos , Interleucina-1/biossíntese , Metaloproteinase 3 da Matriz/biossíntese , Estudos Prospectivos , Proteínas Recombinantes de Fusão/uso terapêutico
6.
Zhonghua Yi Xue Za Zhi ; 89(41): 2934-7, 2009 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-20137654

RESUMO

OBJECTIVE: To understand the prevalence, investigate the correlation of clinical features, explore the early-stage diagnosis and treatment of pulmonary arterial hypertension (PAH) in patients with connective tissue disease (CTD). METHODS: All cases with pulmonary arterial hypertension in 1892 CTD patients were analyzed retrospectively. The risk factor of PAH was evaluated and the prognostic influence of different treatments and primary diseases analyzed. RESULTS: The prevalence of PAH in patients with connective tissue disease was about 4.2%(79/1892). In these patients, systemic sclerosis (SSc) and mixed connective tissue disease (MCTD) had the highest incidence of PAH (18.18% and 12.00%) (P < 0.01). It was obviously higher than polymyositis/dermatomyositis (6.2%), systemic lupus erythematosus (4.4%), Sjogren syndrome (3.8%), rheumatoid arthritis (0.8%) and anti-phospholipid syndrome (0.5%), etc. (P < 0.01). Raynaud's phenomenon was related to a higher pulmonary arterial pressure (P < 0.01). There was a positive correlation (P < 0.01) between the presence of Raynaud's phenomenon and pulmonary arterial pressure. Abnormal lung function was a common finding. There were associations (P < 0.05) between the degree of pulmonary hypertension and IgG, anti-U1RNP antibody positive, antiphospholipid antibody positive, pericardial effusion and interstitial pneumonia. CONCLUSION: PAH is common in connective tissue disease. SSc and MCTD have the highest prevalence of PAH. The presence of Raynaud's phenomenon anti-U1RNP antibody is positively correlated with pulmonary arterial pressure. It can predict the development of PAH. It is useful to perform ultraechocardiogrphy for an early-stage diagnosis and prognostic analysis.


Assuntos
Doenças do Tecido Conjuntivo/complicações , Doenças do Tecido Conjuntivo/diagnóstico , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
7.
Nan Fang Yi Ke Da Xue Xue Bao ; 28(10): 1860-3, 2008 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-18971190

RESUMO

OBJECTIVE: To investigate the clinical manifestations, diagnosis and interventions of pulmonary hypertension (PAH) in patients with systemic lupus erythematosus (SLE). METHODS: From January 2001 to December 2007, 798 SLE patients without prior diagnosis were admitted in our hospital, among whom 39 were identified to have concomitant PAH defined by echocardiography. The clinical data of the 39 cases were analyzed retrospectively. RESULTS: The incidence of PAH was 4.9% in these cohort of SLE patients. The 39 SLE patients with concomitant PAH included 5 men and 34 women with a mean age of 34-/+12 years. Positive correlations were found between the occurrence of PAH and the Raynaud phenomenon, fingertip vasculitis, anti-u1RNP antibody positivity, antiphospholipid antibody positivity, pericardial effusion, and interstitial pneumonia (P < 0.05). Patients with higher scores for SLE Disease Activity Index were liable to PAH. The presence of Raynaud phenomenon, fingertip vasculitis, anti-u1RNP antibody positivity, antiphospholipid antibody positivity, pericardial effusion, and interstitial pneumonia is correlated to greater severity PAH with poor prognosis. CONCLUSION: PAH is not a rare concomitant disease in SLE patients. The presence of Raynaud phenomenon, fingertip vasculitis, anti-u1RNP antibody positivity, antiphospholipid antibody positivity, pericardial effusion, and interstitial pneumonia all suggest the likeliness of PAH in SLE patients, and echocardiographic examination may help derive an early diagnosis.


Assuntos
Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/diagnóstico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Adolescente , Adulto , Idoso , China/epidemiologia , Diagnóstico Precoce , Ecocardiografia , Feminino , Humanos , Hipertensão Pulmonar/epidemiologia , Masculino , Pessoa de Meia-Idade , Doença de Raynaud/complicações , Estudos Retrospectivos
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