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2.
Osteoarthritis Cartilage ; 27(3): 493-503, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30502449

RESUMO

OBJECTIVE: Transforming growth factor-ß (TGFß) is a major regulator of cartilage homeostasis and its deregulation has been associated with osteoarthritis (OA). Deregulation of the TGFß pathway in mesenchymal stem cells (MSCs) has been proposed to be at the onset of OA. Using a secretome analysis, we identified a member of the TGFß family, TGFß-induced protein (TGFßi or ßIGH3), expressed in MSCs and we investigated its function and regulation during OA. DESIGN: Cartilage, bone, synovium, infrapatellar fat pad and bone marrow-MSCs were isolated from patients with OA or healthy subjects. Chondrogenesis of BM-MSCs was induced by TGFß3 in micropellet culture. Expression of TGFßi was quantified by RT-qPCR, ELISA or immunohistochemistry. Role of TGFßi was investigated in gain and loss of function experiments in BM-MSCs and chondrocytes. RESULTS: TGFßi was up-regulated in early stages of chondrogenesis and its knock-down in BM-MSCs resulted in the down-regulation of mature and hypertrophic chondrocyte markers. It likely occurred through the modulation of adhesion molecules including integrin (ITG)ß1, ITGß5 and N-cadherin. We also showed that TGFßi was upregulated in vitro in a model of OA chondrocytes, and its silencing enhanced the hypertrophic marker type X collagen. In addition, TGFßi was up-regulated in bone and cartilage from OA patients while its expression was reduced in BM-MSCs. Similar findings were observed in a murine model of OA. CONCLUSIONS: Our results revealed a dual role of TGFßi during chondrogenesis and pointed its deregulation in OA joint tissues. Modulating TGFßi in BM-MSCs might be of interest in cartilage regenerative medicine.


Assuntos
Condrogênese , Células-Tronco Mesenquimais/metabolismo , Osteoartrite/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Condrócitos/metabolismo , Humanos , Camundongos , Pessoa de Meia-Idade
3.
Clin Pharmacol Ther ; 101(2): 281-289, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27648725

RESUMO

European medical students should have acquired adequate prescribing competencies before graduation, but it is not known whether this is the case. In this international multicenter study, we evaluated the essential knowledge, skills, and attitudes in clinical pharmacology and therapeutics (CPT) of final-year medical students across Europe. In a cross-sectional design, 26 medical schools from 17 European countries were asked to administer a standardized assessment and questionnaire to 50 final-year students. Although there were differences between schools, our results show an overall lack of essential prescribing competencies among final-year students in Europe. Students had a poor knowledge of drug interactions and contraindications, and chose inappropriate therapies for common diseases or made prescribing errors. Our results suggest that undergraduate teaching in CPT is inadequate in many European schools, leading to incompetent prescribers and potentially unsafe patient care. A European core curriculum with clear learning outcomes and assessments should be urgently developed.


Assuntos
Competência Clínica/normas , Prescrições de Medicamentos/estatística & dados numéricos , Prescrições de Medicamentos/normas , Conhecimentos, Atitudes e Prática em Saúde , Estudantes de Medicina/estatística & dados numéricos , Atitude do Pessoal de Saúde , Estudos Transversais , Interações Medicamentosas , Europa (Continente) , Humanos , Farmacologia Clínica/normas , Farmacologia Clínica/estatística & dados numéricos
5.
Lupus ; 25(13): 1440-1447, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27013663

RESUMO

Objective The objective of this study was to assess the safety and efficacy of abatacept in patients with SLE refractory to conventional treatment in routine clinical practice. Methods This retrospective study included 11 SLE patients treated with abatacept for an active and refractory disease. The primary endpoint was the change in SLE Disease Activity Index (SLEDAI) score at six months. Response was defined as a decrease of SLEDAI ≥4 in a patient continuing abatacept. Results Indications of abatacept treatment were articular ( n=8), renal ( n=1) and cutaneous ( n=1) involvement and autoimmune thrombocytopenia ( n=1). Abatacept was discontinued before six months in two patients, because of adverse event ( n=1) and/or lupus flare ( n=2). The median SLEDAI decreased from 6 (2-20) to 4 (0-20) ( p=0.031). Decrease of SLEDAI ≥4 was observed in 6/11 patients (55%) and response to treatment according to the physician's judgement in 8/11 (73%) patients. Improvement of articular involvement was observed in 7/8 (87.5%) patients. Four adverse events were observed in three patients, but no severe infection occurred. Conclusion This study suggests some efficacy of abatacept in patients with refractory disease in routine clinical practice, particularly in the case of articular manifestations, with an acceptable safety profile. These data support conducting new controlled trials of abatacept in SLE patients.


Assuntos
Abatacepte/administração & dosagem , Imunossupressores/administração & dosagem , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Abatacepte/uso terapêutico , Adulto , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
6.
Osteoarthritis Cartilage ; 23(11): 2027-35, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26521749

RESUMO

Osteoarthritis (OA) is the most common form of degenerative arthritis, mainly characterized by the degradation of articular cartilage and associated with subchondral bone lesions. Novel therapeutic approaches for OA include cell-based therapies that have become thriving areas of research and development. In this context, mesenchymal stem or stromal cells (MSCs) have gained much interest based on their trophic and immunomodulatory properties that can help tissue repair/regeneration. The present review article discusses the interest of using MSCs in cell-therapy approaches with a focus on the mechanisms by which MSCs might exhibit a therapeutic potential in OA. Special attention is given to the anti-inflammatory function of MSCs and on miRNA modulation in OA for possible future innovative strategies. The paper also presents the current data on the undergoing MSCs-based clinical trials in OA.


Assuntos
Inflamação/cirurgia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Osteoartrite/cirurgia , Engenharia Tecidual/métodos , Humanos , Inflamação/patologia , Osteoartrite/patologia
9.
Arthritis Rheumatol ; 66(2): 273-83, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24504799

RESUMO

OBJECTIVE: The rationale for blocking interleukin-6 (IL-6) in rheumatoid arthritis (RA) lies chiefly in the proinflammatory effect of this cytokine. Few studies have evaluated the consequences of anti-IL-6 receptor (IL-6R) antibody treatment on Treg cells. This study was undertaken to elucidate the mechanism of action of anti-IL-6R antibody treatment by studying the effects on Treg cells in an experimental arthritis model and in patients with RA. METHODS: Mice with collagen-induced arthritis (CIA) were treated with a mouse anti-IL-6R antibody (MR16-1), and changes in Treg, Th1, and Th17 cells were assessed at key time points during the course of the disease. Peripheral blood from 15 RA patients was collected on day 0 and after 3 months of tocilizumab treatment for flow cytometry analysis of Th17 and Treg cells. RESULTS: In MR16-1-treated mice, Th17 cell frequencies were unchanged, whereas Treg cell frequencies were increased. The Treg cell phenotype showed marked changes, with an increase in the frequency of CD39+ Treg cells in the lymph nodes and spleen. Interestingly, similar CD39+ Treg cell expansion was observed in RA patients who were tocilizumab responders at 3 months, with no change in Th17 cell frequency. Moreover, fluorescence-activated cell-sorted CD39+ Treg cells from responder RA patients were functionally able to suppress the proliferation of conventional T cells. CONCLUSION: In both CIA and RA, the frequency of functionally suppressive CD39+ Treg cells is increased as a result of anti-IL-6R treatment, whereas Th17 cells are unaffected. The modification of Treg cell frequency and phenotype may be one of the mechanisms involved in the therapeutic effect of IL-6 blockade in RA.


Assuntos
Antígenos CD/metabolismo , Apirase/metabolismo , Artrite Experimental/patologia , Artrite Reumatoide/patologia , Receptores de Interleucina-6/antagonistas & inibidores , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/patologia , Animais , Anticorpos Anti-Idiotípicos/farmacologia , Anticorpos Anti-Idiotípicos/uso terapêutico , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos DBA , Pessoa de Meia-Idade , Fenótipo , Receptores de Interleucina-6/efeitos dos fármacos , Linfócitos T Reguladores/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Células Th17/patologia
10.
Ann Phys Rehabil Med ; 53(1): 3-14, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20022577

RESUMO

AIM: To evaluate fear, beliefs, catastrophizing and kinesiophobia in chronic low back pain patients about to begin a training programme in a rehabilitation centre. PATIENTS AND METHODS: Fifty chronic low back pain patients (including both males and females) were assessed in our physical medicine department. We used validated French-language scales to score the patients' pain-related disability, quality of life and psychosocial factors. RESULTS: Seventy percent of the patients had a major functional disability (i.e., a Roland-Morris Scale score over 12) and nearly 73% reported an altered quality of life (the daily living score in the Dallas Pain Questionnaire). Pain correlated with functional impairment and depression but not with catastrophizing or kinesiophobia. Disability was correlated with catastrophizing and kinesiophobia. CONCLUSION: Psychosocial factors are strongly associated with disability and altered quality of life in chronic low back pain patients. Future rehabilitation programs could optimizing patient management by taking these factors into account.


Assuntos
Dor Lombar/psicologia , Dor Lombar/reabilitação , Adulto , Idoso , Atitude Frente a Saúde , Avaliação da Deficiência , Medo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida
11.
Acta Neurol Belg ; 109(4): 330-2, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20120217

RESUMO

We described an overlap syndrome associating Miller Fisher syndrome (MFS) and acute inflammatory demyelinating polyradiculoneuropathy (AIDP). Furthermore, the patient presented unusual neurological manifestations including headache, T10 sensory level, urinary urgency, and gadolinium enhancement of the spinal roots. One year follow-up was characterized by clinical recovery and persistent high rates of anti-GQ1b, -GD1b and -GT1b antibodies. Our case suggests broad phenotype of persistent antigangliosides antibodies.


Assuntos
Gangliosídeos/imunologia , Síndrome de Guillain-Barré/imunologia , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/terapia , Humanos , Imunoglobulinas/uso terapêutico , Resultado do Tratamento
12.
Rev Med Interne ; 30(3): 250-4, 2009 Mar.
Artigo em Francês | MEDLINE | ID: mdl-19026472

RESUMO

INTRODUCTION: Antiphospholipid antibodies (aPL) can be associated with numerous infectious and particularly Q fever. Data on the pathogenicity of aPL in the course of acute Q fever are scarce. CASE REPORT: We report the case an acute Coxiella burnetii infection associated with clinical and biological manifestations of the aPL syndrome, including a renal infarction. Along with antibiotic treatment, anticoagulation and intravenous immunoglobulins, the clinical outcome was favourable. Antiphospholipid antibodies and Q fever antibody titers had a closely related evolution. CONCLUSION: Arterial thrombosis associated with Q fever and aPL is exceptional. The nosology and potential mechanisms are discussed.


Assuntos
Síndrome Antifosfolipídica/complicações , Febre Q/complicações , Obstrução da Artéria Renal/complicações , Trombose/complicações , Doença Aguda , Adulto , Anticorpos Anticardiolipina , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Seguimentos , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Febre Q/diagnóstico , Febre Q/tratamento farmacológico , Obstrução da Artéria Renal/diagnóstico por imagem , Obstrução da Artéria Renal/tratamento farmacológico , Trombose/diagnóstico por imagem , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
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