RESUMO
Despite the low prevalence of each rare disease, the total burden is high. Patients with rare diseases encounter numerous barriers, including delayed diagnosis and limited access to high-quality treatments. In order to tackle these challenges, the European Commission launched the European Reference Networks (ERNs), cross-border networks of healthcare providers and patients representatives. In parallel, the aims and structure of these ERNs were translated at the federal and regional levels, resulting in the creation of the Flemish Network of Rare Diseases. In line with the mission of the ERNs and to ensure equal access to care, we describe as first patient pathways for systemic sclerosis (SSc), as a pilot model for other rare connective and musculoskeletal diseases. Consensus was reached on following key messages: 1. Patients with SSc should have multidisciplinary clinical and investigational evaluations in a tertiary reference expert centre at baseline, and subsequently every three to 5 years. Intermediately, a yearly clinical evaluation should be provided in the reference centre, whilst SSc technical evaluations are permissionably executed in a centre that follows SSc-specific clinical practice guidelines. In between, monitoring can take place in secondary care units, under the condition that qualitative examinations and care including interactive multidisciplinary consultations can be provided. 2. Patients with early diffuse cutaneous SSc, (progressive) interstitial lung disease and/or pulmonary arterial hypertension should undergo regular evaluations in specialised tertiary care reference institutions. 3. Monitoring of patients with progressive interstitial lung disease and/or pulmonary (arterial) hypertension will be done in agreement with experts of ERN LUNG.
Assuntos
Doenças do Tecido Conjuntivo , Doenças Pulmonares Intersticiais , Esclerodermia Difusa , Escleroderma Sistêmico , Humanos , Doenças Raras/complicações , Doenças Raras/epidemiologia , Doenças Raras/terapia , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/terapia , Doenças do Tecido Conjuntivo/diagnóstico , Doenças do Tecido Conjuntivo/complicações , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/terapia , Doenças Pulmonares Intersticiais/complicaçõesRESUMO
INTRODUCTION: Osteoarthritis (OA) of the knee joint is caused by genetic and hormonal factors and by inflammation, in combination with biomechanical alterations. It is characterized by loss of articular cartilage, synovial inflammation and subchondral bone sclerosis. Considerable evidence indicates that the menisci, ligaments, periarticular muscles and the joint capsule are also involved in the OA process. This paper will outline the theoretical framework for investigating the infrapatellar fat pad (IPFP) as an additional joint tissue involved in the development and progression of knee-OA. METHODS: A literature search was performed in Pubmed from 1948 until October 2009 with keywords InFrapatellar fat pad, Hoffa fat pad, intraarticular adipose tissue, knee, cartilage, bone, cytokine, adipokine, inflammation, growth factor, arthritis, and OA. RESULTS: The IPFP is situated intracapsularly and extrasynovially in the knee joint. Besides adipocytes, the IPFP from patients with knee-OA contains macrophages, lymphocytes and granulocytes, which are able to contribute to the disease process of knee-OA. Furthermore, the IPFP contains nociceptive nerve fibers that could in part be responsible for anterior pain in knee-OA. These nerve fibers secrete substance P, which is able to induce inflammatory responses and cause vasodilation, which may lead to IPFP edema and extravasation of the immune cells. The IPFP secretes cytokines, interleukins, growth factors and adipokines that influence cartilage by upregulating the production of matrix metalloproteinases (MMPs), stimulating the expression of pro-inflammatory cytokines and inhibiting the production of cartilage matrix proteins. They may also stimulate the production of pro-inflammatory mediators, growth factors and MMPs in synovium. CONCLUSION: These data are consistent with the hypothesis that the IPFP is an osteoarthritic joint tissue capable of modulating inflammatory and destructive responses in knee-OA.
Assuntos
Tecido Adiposo/fisiopatologia , Articulação do Joelho/fisiopatologia , Tecido Adiposo/metabolismo , Cartilagem Articular/metabolismo , Humanos , Articulação do Joelho/metabolismo , Osteoartrite do Joelho/metabolismo , Osteoartrite do Joelho/fisiopatologiaRESUMO
OBJECTIVE: In addition to their cholesterol-lowering action, statins have been suggested to exert anti-inflammatory activities. In this study we evaluate whether simvastatin could influence the production of pro-inflammatory cytokines (interleukin (IL)-6 and IL-8) and nitric oxide (NO) by activated human chondrocytes. METHODS: Human isolated chondrocytes and cartilage explants were pre-incubated with simvastatin (0.5, 5, 10 and 50 micromol/L) for 48 h. Then the cultures were stimulated with a mixture of IL-1Beta and TNF-alpha (10 ng/mL) and co-incubated with simvastatin for an additional 48 h. A flow cytometric microsphere-based immunoassay was performed to detect cytokine secretion in the supernatants. NO production was quantified using the Griess assay. RESULTS: Simvastatin demonstrated significant dose-dependent inhibition of IL-6 and IL-8 production of isolated chondrocytes and cartilage explants up to 99% for IL-6 and up to 88% for IL-8 (p < 0.01). At the higher concentrations simvastatin decreased NO production by both isolated chondrocytes (up to 43%, p < 0.01) and cartilage explants (up to 30%, p < 0.01). CONCLUSION: This study demonstrates anti-inflammatory properties of simvastatin in chondrocytes in vitro, suggesting a potential cartilage-protective role for statins in arthritis.
Assuntos
Condrócitos/efeitos dos fármacos , Interleucina-6/biossíntese , Interleucina-8/biossíntese , Óxido Nítrico/biossíntese , Sinvastatina/farmacologia , Adulto , Idoso , Anti-Inflamatórios/farmacologia , Artrite/metabolismo , Cartilagem/efeitos dos fármacos , Cartilagem/metabolismo , Células Cultivadas , Condrócitos/metabolismo , Humanos , Interleucina-1beta/farmacologia , Pessoa de Meia-Idade , Fragmentos de Peptídeos/farmacologia , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
OBJECTIVE: Bisphosphonates have been reported to possess anti-inflammatory and cartilage protective effects in animal arthritis models but not much is known about their direct effect on chondrocytes. In this study we evaluate the effect of bisphosphonates on nitric oxide (NO) production by activated chondrocytes. METHODS: Isolated bovine chondrocytes and bovine cartilage explants were used. In the second part of the study human cartilage explants (osteoarthritis (OA) and non-OA cartilage) were used. The isolated chondrocytes and cartilage explants were pre-incubated with clodronate, pamidronate or risedronate and stimulated with IL-1 and TNF-alpha (10 ng/mL, 48 h). NO production was quantified using the Griess assay. RESULTS: In bovine cultures, clodronate (10(-4)mol/L) and pamidronate (10(-6)mol/L) showed a small inhibition of NO production (up to 15 % and 25% respectively), whereas risedronate had no effect. In the human cartilage cultures no effect of BPs on the NO production was detected except for the highest concentration of clodronate tested (10(-4)mol/L) which demonstrated a small enhancement (19%) in NO production reaching significance in the non-OA group. CONCLUSION: BPs have a modest effect on NO production by inflammatory activated chondrocytes only in the higher concentrations, indicating that the clinical relevance of these effects is probably negligible.
Assuntos
Conservadores da Densidade Óssea/farmacologia , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Difosfonatos/farmacologia , Óxido Nítrico/biossíntese , Animais , Cartilagem/efeitos dos fármacos , Cartilagem/metabolismo , Bovinos , Células Cultivadas , Ácido Clodrônico/farmacologia , Ácido Etidrônico/análogos & derivados , Ácido Etidrônico/farmacologia , Humanos , Técnicas In Vitro , Inflamação/metabolismo , Interleucina-1/farmacologia , Osteoartrite/metabolismo , Pamidronato , Ácido Risedrônico , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
OBJECTIVE: To investigate whether anti-TNF therapy could have an effect on dendritic cells (DCs) and regulatory T cells in rheumatoid arthritis (RA) patients. METHODS: A four-colour flow cytometric technique was used to measure CD4+CD25+ T cells i.e. CD4+CD25high+ (regulatory T cells) and CD4+CD25low+ (activated T cells)), DCs as well as the in vitro, intracellular, lipopolysaccharide-stimulated cytokine production of DCs. RESULTS: Clinical and laboratory parameters of disease activity decreased after anti-TNF treatment. Before anti-TNF therapy, RA patients demonstrated a decreased count of Th2-promoting lymphoid DCs as compared to controls and after anti-TNF therapy this decrease was sustained. Intracellular cytokine production was only found in the myeloid DCs population and there was a higher production of TNF-alpha and IL1-b as compared to healthy controls. Treatment did not alter this cytokine production. Before anti-TNF therapy, the percentage CD4+CD25+ T cells was significantly elevated in RA patients than in healthy controls. CONCLUSION: These results demonstrate anti-TNF to be a potent anti-inflammatory drug, as mirrored by the decrease in clinical and biological parameters as well as the decrease in activated CD4+ T cells. However, in this study no demonstrable effect on DCs and regulatory T cells was found.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Células Dendríticas/efeitos dos fármacos , Linfócitos T Reguladores/efeitos dos fármacos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab , Adulto , Idoso , Anti-Inflamatórios não Esteroides/uso terapêutico , Anticorpos Monoclonais Humanizados , Artrite Reumatoide/imunologia , Artrite Reumatoide/fisiopatologia , Separação Celular , Citocinas/metabolismo , Células Dendríticas/metabolismo , Quimioterapia Combinada , Feminino , Citometria de Fluxo , Humanos , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Linfócitos T Reguladores/classificação , Linfócitos T Reguladores/imunologia , Resultado do TratamentoRESUMO
Vasculitis leading to intestinal necrosis is a rare complication of rheumatoid arthritis. The introduction of anti-TNF treatment for methotrexate-resistant cases improved disease-control substantially in these often more aggresive forms of rheumatoid arthritis. As far as we know only two cases of severe vasculitis following anti-TNF treatment have been reported. We describe a 45-year old female patient with severe rheumatoid arthritis, who presented with an epileptic insult, renal failure and a quickly deteriorating general condition due to intestinal vasculitis, while she had been receiving anti-TNF treatment for 6 months.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Intestinos/irrigação sanguínea , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Vasculite/etiologia , Artrite Reumatoide/complicações , Feminino , Humanos , Infliximab , Pessoa de Meia-Idade , Necrose , Vasculite/patologiaRESUMO
OBJECTIVES: The aim of this work was to evaluate in a randomised double-blind prospective study the effect of pamidronate on intracellular monocytic cytokine profiles (IL-1, IL-6, TNF-alpha) and bone density in rheumatoid arthritis patients. METHODS: Twenty rheumatoid arthritis patients were treated for one year with methotrexate and a low dose of prednisolone. Double blind randomisation was performed for either i.v. pamidronate (at 3-month intervals) or placebo. The effect of pamidronate was evaluated on intracellular cytokine profiles (IL-1, IL-6, TNF-alpha), disease activity and bone mass measurements. The human monocytic cell line THP-1 was used to evaluate in vitro apoptosis by pamidronate. RESULTS: Spontaneous production of interleukin-1 beta by patient blood monocytes was lower in the pamidronate group and was associated with an increase in bone density of the spine after 12 months of therapy. In vitro a dose-related increase in pamidronate induced apoptosis was found in THP-1 cells. CONCLUSIONS: This prospective double-blind randomised study demonstrated that pamidronate therapy resulted in an increase of bone density despite treatment with steroids. This rise is associated with a suppression of interleukin-1 beta production in monocytes of patients treated with pamidronate. Our in vitro experiments suggest that this anti-inflammatory effect could be due to an increase in the apoptosis of monocytic cells.
Assuntos
Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Apoptose/efeitos dos fármacos , Artrite Reumatoide/tratamento farmacológico , Densidade Óssea/efeitos dos fármacos , Citocinas/efeitos dos fármacos , Imunossupressores/farmacologia , Monócitos/efeitos dos fármacos , Adulto , Idoso , Sedimentação Sanguínea/efeitos dos fármacos , Proteína C-Reativa/efeitos dos fármacos , Difosfonatos/farmacologia , Difosfonatos/uso terapêutico , Método Duplo-Cego , Interações Medicamentosas , Feminino , Humanos , Injeções Intravenosas , Masculino , Metotrexato/farmacologia , Pessoa de Meia-Idade , Pamidronato , Prednisolona/farmacologia , Prednisolona/uso terapêutico , Estudos Prospectivos , Distribuição AleatóriaRESUMO
IgE-containing circulating immune complexes (IgE-CIC) were determined with a 2.5% PEG-precipitation assay in 98 patients with classical or definite rheumatoid arthritis (RA). Of the 45 IgE-CIC positive sera, only 4 had elevated total serum IgE. IgE-CIC positive patients had more active disease than patients without IgE-CIC, as determined by their more swollen joints and higher Ritchie indices (p less than 0.04 and 0.02, respectively). Apart from IgE, other immunoglobulin isotypes, rheumatoid factor (RF) of the IgG-, IgA- and IgM-classes, C3 and antinuclear antibodies could be demonstrated in the IgE-containing PEG-precipitates. IgE-RF could not be demonstrated in serum or in IgE-CIC. Anti-IgE of the IgM-class (IgMaIgE) were frequently found (28/45 patients) in the IgE-positive PEG-precipitates. All 14 patients positive for IgGaIgE in the IgE-CIC were also positive for IgMaIgE in the CIC. As in the serum, there was a good correlation in the CIC between the level of IgGaIgE and the level of IgMaIgE (r = 0.64). The correlation between the respective levels of IgGaIgE and IgMaIgE in serum and in CIC was high (r = 0.93 and 0.79, respectively). On the other hand, only 1 patient was positive for IgAaIgE in the IgE-CIC. We conclude that IgE and aIgE of the IgM- and IgG-classes are frequently present in the immune complex form in RA and that they are correlated with the clinical activity of arthritis.
Assuntos
Anticorpos Anti-Idiotípicos/análise , Formação de Anticorpos , Complexo Antígeno-Anticorpo/análise , Artrite Reumatoide/imunologia , Imunoglobulina E/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antinucleares/análise , Complemento C3/análise , Feminino , Humanos , Imunoglobulina A/análise , Imunoglobulina G/análise , Imunoglobulina M/análise , Masculino , Pessoa de Meia-Idade , Fator Reumatoide/análiseRESUMO
A 72-year-old rheumatoid arthritis patient is described presenting with acute dyspnoea and peripheral oedema. A pericardial effusion with signs of tamponade was diagnosed. Examination of the pericardial fluid revealed the presence of cholesterol crystals and IgE-containing immune complexes. The significance of these findings in the differential diagnosis of pericardial disease is discussed.
Assuntos
Complexo Antígeno-Anticorpo/metabolismo , Artrite Reumatoide/metabolismo , Colesterol/metabolismo , Imunoglobulina G/metabolismo , Pericardite/metabolismo , Idoso , Complexo Antígeno-Anticorpo/análise , Complexo Antígeno-Anticorpo/imunologia , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico , Tamponamento Cardíaco/patologia , Colesterol/análise , Cristalização , Diagnóstico Diferencial , Feminino , Humanos , Imunoglobulina G/análise , Imunoglobulina G/imunologia , Derrame Pericárdico/metabolismo , Derrame Pericárdico/patologia , Pericardite/complicações , Pericardite/diagnósticoRESUMO
Adult-onset Still's disease is an uncommon rheumatological syndrome with a diversity of signs and symptoms. Pulmonary manifestations described are pleuritis and usually transient radiologic infiltrations. The patient presented in this case report had biopsy-proven lung fibrosis when adult-onset Still's disease was diagnosed. Three years after diagnosis, the patient developed clinical signs of the interstitial lung disorder. Radiological and histological progression was observed. Other causes of interstitial lung disorders were excluded. Clinicians should be aware that interstitial lung disease can be a complication of adult-onset Still's disease and can compromise the clinical status of the patient.
Assuntos
Fibrose Pulmonar/etiologia , Doença de Still de Início Tardio/complicações , Adulto , Biópsia , Humanos , Pulmão/patologia , Masculino , Fibrose Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/patologia , Radiografia Torácica , Tomografia Computadorizada por Raios XRESUMO
The clinical manifestations of hypoparathyroidism are mainly characterised by increased neuromuscular irritability as a consequence of hypocalcaemia. Occasionally, elevation of the muscle enzymes may mimic polymyositis. Reduced parathyroid hormone production, but also vitamin D treatment and calcium supplementation, may contribute to the increased bone mass found in patients with postsurgical hypoparathyroidism. We report the case of a 36-year-old woman with untreated idiopathic hypoparathyroidism and a high bone mass despite severe muscle impairment due to hypocalcaemic myopathy.
Assuntos
Densidade Óssea , Osso e Ossos/metabolismo , Hipocalcemia/etiologia , Hipoparatireoidismo/complicações , Doenças Musculares/etiologia , Absorciometria de Fóton , Adulto , Osso e Ossos/diagnóstico por imagem , Cálcio/sangue , Cálcio/uso terapêutico , Cálcio/urina , Colecalciferol/uso terapêutico , Diagnóstico Diferencial , Eletromiografia , Feminino , Humanos , Hipocalcemia/diagnóstico , Hipocalcemia/tratamento farmacológico , Hipocalcemia/metabolismo , Hipoparatireoidismo/metabolismo , Doenças Musculares/diagnóstico , Doenças Musculares/tratamento farmacológico , Doenças Musculares/metabolismoRESUMO
We present a patient who had one episode of prepatellar bursitis and subsequently several episodes of arthritis of his right knee. Cultures of several punctures of his knee remained sterile, but the patient had been taking oral antibiotics on each of these occasions against our medical advice. Ultimately a diagnostic puncture revealed growth of Staphylococcus aureus. An X-ray demonstrated an osteolytic lesion of the patella, but no defect in the articular surface of the patella could be visualised. MRI demonstrated a communication between the osteomyelitic focus through the medial retinaculum to the bursa suprapatellaris and the knee joint. Osteomyelitis of the patella is mainly a disease of childhood. This case is, to our knowledge, the first report on the association between bursitis, osteomyelitis of the patella and recurrent septic arthritis of the knee in an adult. The literature is reviewed and discussed briefly.
Assuntos
Artrite Infecciosa/diagnóstico , Osteomielite/diagnóstico , Infecções Estafilocócicas/diagnóstico , Staphylococcus aureus/isolamento & purificação , Antibacterianos , Artrite Infecciosa/tratamento farmacológico , Diagnóstico Diferencial , Quimioterapia Combinada/administração & dosagem , Seguimentos , Humanos , Articulação do Joelho , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Osteomielite/tratamento farmacológico , Recidiva , Medição de Risco , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Tomografia Computadorizada por Raios XRESUMO
A 39-year-old Ugandan student is described presenting with general malaise, fever and a pulmonary infiltrate. Open lung biopsy showing infarction and positive ANCA lead to a diagnosis of Wegener's granulomatosis and a treatment with immunosuppressive drugs was instituted. Five weeks after admission, however, sputum cultures turned out to be positive for Mycobacterium tuberculosis. The importance of ANCA-interpretation and the possibility of false positive results is discussed.
Assuntos
Autoanticorpos/análise , Citoplasma/imunologia , Neutrófilos/imunologia , Tuberculose Pulmonar/diagnóstico , Adulto , Diagnóstico Diferencial , Erros de Diagnóstico , Granulomatose com Poliangiite/diagnóstico , Humanos , Masculino , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Pulmonar/microbiologiaRESUMO
We present a patient with therapy resistant multicentric reticulohistiocytosis (MRH). MRH is a rare granulomatous, multisystem disease characterised most frequently by disfiguring papulonodular skin lesions and sometimes a destructive polyarthritis, though any organ can be involved. Abnormal histiocytic reactions to an undetermined stimulus (possibly an associated mycobacterial infection, auto immune process or neoplastic process) have been proposed as an underlying mechanism. The diagnosis is confirmed by histopathology of the cutaneous nodules and/or synovial membrane by the presence of CD68-positive histiocytes and multinucleated giant cells with an eosinophilic 'ground-glass' cytoplasm. Recent studies have identified TNFalpha and other inflammatory cytokines to be highly expressed in the synovium and synovial fluid of affected joints in patients with MRH. Based on these findings, we treated our patient with infliximab in combination with methotrexate with marked improvement of morning stiffness, tender and swollen joint count, visual analogue scale and health assessment questionnaire after his third infusion. However, the nodules did not markedly resolve. When treating patients with MRH with TNFa neutralizing drugs, one has to keep the possible association with malignancy in 15-30% of cases in mind and these products should be used with caution.
Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Artrite/tratamento farmacológico , Artrite/epidemiologia , Histiocitose/tratamento farmacológico , Histiocitose/etiologia , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Metotrexato/uso terapêutico , Mãos/diagnóstico por imagem , Histiocitose/patologia , Humanos , Infliximab , Masculino , Pessoa de Meia-Idade , Radiografia , Sinovite/diagnóstico por imagem , Sinovite/tratamento farmacológico , Fator de Necrose Tumoral alfa , UltrassonografiaRESUMO
We present a case of the multicentric plasma cell variant of Castleman's disease (CD) with two rare manifestations. The patient consulted us because of cutaneous vasculitis of the lower limbs, while constitutional symptoms were nearly absent. Imaging studies also revealed pulmonary parenchymal involvement. Furthermore, our patient is the first case in whom association of ankylosing spondylitis with CD is reported. In addition, we present a review of the literature with emphasis on the clinical presentation of CD and its difficult discrimination from autoimmune and infectious disorders. An overview of the therapeutic options is also provided.
Assuntos
Hiperplasia do Linfonodo Gigante/epidemiologia , Hiperplasia do Linfonodo Gigante/patologia , Espondilite Anquilosante/epidemiologia , Vasculite Leucocitoclástica Cutânea/epidemiologia , Idoso , Calcinose/epidemiologia , Hiperplasia do Linfonodo Gigante/diagnóstico , Hiperplasia do Linfonodo Gigante/fisiopatologia , Hiperplasia do Linfonodo Gigante/terapia , Humanos , Masculino , Omento/diagnóstico por imagem , Omento/patologia , Pleura/patologia , Prognóstico , Tomografia Computadorizada por Raios XAssuntos
Artropatias/diagnóstico , Ocronose/diagnóstico , Doenças da Coluna Vertebral/diagnóstico , Espondilite Anquilosante/diagnóstico , Diagnóstico Diferencial , Humanos , Artropatias/complicações , Artropatias/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Ocronose/complicações , Radiografia , Doenças da Coluna Vertebral/complicações , Doenças da Coluna Vertebral/diagnóstico por imagemRESUMO
We describe the case of a 39-year-old Caucasian woman who was admitted to the University Hospital of Antwerp with a clinical picture suggestive of adult Still's disease. Even though a transoesophageal echocardiography showed endocarditis of the aortic valve, blood cultures remained negative. Additional serological testing revealed a positive result for Bartonella henselae. Histology of the supraclavicular lymph node showed a reactive lymph node with a positive polymerase chain reaction (PCR) for Bartonella henselae. Prednisolone treatment was started in a dosage of 10 mg per day and rifampicin 600 mg/d in combination with doxycyclin 200 mg/d was given for 6 months. During therapy the patient gradually improved and signs of endocarditis disappeared on echocardiography.
Assuntos
Infecções por Bartonella/microbiologia , Bartonella henselae/isolamento & purificação , Endocardite Bacteriana/microbiologia , Doença de Still de Início Tardio/diagnóstico , Adulto , Infecções por Bartonella/diagnóstico , Bartonella henselae/genética , Biópsia , DNA Bacteriano/análise , Diagnóstico Diferencial , Ecocardiografia Transesofagiana , Endocardite Bacteriana/diagnóstico , Feminino , Humanos , Reação em Cadeia da PolimeraseRESUMO
The destruction of cartilage is an important characteristic of rheumatoid arthritis (RA). Immune complexes (IC) are usually found in high amounts in RA synovial fluids (SF) and in the superficial layers of RA cartilage. The objective of this study was to investigate if IC have a direct influence on proliferation, survival and production of nitric oxide (NO) of cytokine-activated chondrocytes. Primary bovine chondrocytes were incubated with cytokines (huIL-1alpha, bovIFN-gamma, huTNF-alpha) and IC containing precipitates of peripheral blood (PB) and/or synovial fluid (SF) of 14 RA patients, 5 osteoarthritis (OA) patients and 10 healthy age and sex-matched controls. After 48 h, chondrocyte viability, proliferation, apoptosis, NO production and oxygen radical levels were measured. Staining with May-Grünwald-Giemsa after incubation with IC of RA PB and SF, showed apoptotic chondrocytes with condensation of the nuclei. The proliferation rates of cytokine-activated chondrocytes, incubated with sera and SF IC of RA patients were significantly decreased compared to chondrocytes, incubated with sera and SF IC of OA patients and compared to sera of controls. Quantitative evaluation of apoptotic cells by annexin-V/propidium iodide and TUNEL assays revealed a significant increase after incubation with sera and SF IC of RA patients, compared to control sera and OAs sera and SF. In all TUNEL positive samples, active-caspase-3-positive cells were found. There was a significant increase of chondrocyte NO production, after incubation with SF IC of RA patients, compared to OA SF. These results support the hypothesis that IC, present in serum and SF of RA patients, have a profound influence on chondrocyte growth, NO production and apoptosis, contributing to cartilage destruction in RA.
Assuntos
Complexo Antígeno-Anticorpo/fisiologia , Apoptose/imunologia , Artrite Reumatoide/imunologia , Condrócitos/imunologia , Óxido Nítrico/metabolismo , Líquido Sinovial/imunologia , Animais , Complexo Antígeno-Anticorpo/sangue , Estudos de Casos e Controles , Bovinos , Proliferação de Células , Células Cultivadas , Condrócitos/metabolismo , Feminino , Humanos , Masculino , Osteoartrite do Joelho/imunologiaRESUMO
The objective of this study was to evaluate the effect of bisphosphonates (BPs) and simvastatin on chondrocyte lipid peroxidation. For this purpose, a flow cytometrical method using C11-BODIPY(581/591) was developed to detect hydroperoxide-induced lipid peroxidation in chondrocytes. Tertiary butylhydroperoxide (t-BHP) induced a time and concentration dependent increase in chondrocyte lipid peroxidation. Addition of a Fe2+/EDTA complex to t-BHP or hydrogen peroxide (H2O2) clearly enhanced lipid peroxidation. The lipophilic simvastatin demonstrated a small inhibition in the chondrocyte lipid peroxidation. None of three tested BPs (clodronate, pamidronate, and risedronate) had an effect on chondrocyte lipid peroxidation induced by t-BHP. However, when Fe2+/EDTA complex was added to t-BHP or H2O2, BPs inhibited the lipid peroxidation process varying from 25% to 58%. This study demonstrates that BPs have antioxidant properties as iron chelators, thereby inhibiting the chondrocyte lipid peroxidation. These findings add evidence to the therapeutic potential of bisphosphonates and statins in rheumatoid arthritis.
Assuntos
Antioxidantes/farmacologia , Condrócitos/efeitos dos fármacos , Difosfonatos/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Sinvastatina/farmacologia , Animais , Compostos de Boro , Bovinos , Células Cultivadas , Condrócitos/metabolismo , Ácido Clodrônico/farmacologia , Ácido Edético , Ácido Etidrônico/análogos & derivados , Ácido Etidrônico/farmacologia , Compostos Ferrosos , Citometria de Fluxo , Peróxido de Hidrogênio/farmacologia , Pamidronato , Ácido Risedrônico , terc-Butil Hidroperóxido/farmacologiaRESUMO
The stingray is one of the most dangerous fishes for man. The sting is poisonous and causes a painful wound. Fatalities are reported. Most injuries due to stingrays occur in coast regions of the tropics and subtropics. Therefore, physicians in countries with a moderate climate are less informed about the management about these kinds of injuries. The characteristics, treatment and prevention are discussed in connection with a case that occurred in Belgium in a devotee of aquarium fishes.