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1.
Clin Rheumatol ; 28(10): 1207-12, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19468787

RESUMO

Systemic sclerosis (SSc) is a disorder characterized by skin thickness and vasculopathy. The objective of the study was to evaluate the therapeutic effect and safety of the association of pentoxyphylline and vitamin E in SSc patients. Twelve SSc patients (American College of Rheumatology criteria) enrolled this 24-week open-label study. Patients received daily 800 mg of pentoxyphylline and 800 UI of vitamin E and were evaluated at 4-week interval. The primary efficacy endpoint was the change in Modified Rodnan Skin Score (MRSS) at week 24. Nine diffuse SSc patients treated 6 months with cyclophosphamide were used as a historical control group. The mean age of the treated group was 43.6 years, and ten of 12 (84%) patients were women. Their mean MRSS reduced from 25.7 to 18.7 (p = 0.03) at 16th week and remained significantly reduced throughout the study. In contrast, only a trend of MRSS reduction was observed in the historical control group (p = 0.06). Two patients started the study with active ischemic ulcers and ended with a complete healing of them. No serious side effects were reported. Pentoxyphylline and vitamin E might be an alternative therapeutic approach in SSc patients.


Assuntos
Antioxidantes/uso terapêutico , Pentoxifilina/uso terapêutico , Escleroderma Sistêmico/tratamento farmacológico , Escleroderma Sistêmico/patologia , Pele/patologia , Vasodilatadores/uso terapêutico , Vitamina E/uso terapêutico , Adulto , Antioxidantes/efeitos adversos , Quimioterapia Combinada , Feminino , Fibrose , Humanos , Masculino , Pessoa de Meia-Idade , Pentoxifilina/efeitos adversos , Resultado do Tratamento , Vasodilatadores/efeitos adversos , Vitamina E/efeitos adversos
2.
Clin Rheumatol ; 28(7): 847-51, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19225705

RESUMO

The aim of the study was to evaluate the expressions of adhesion molecules (AM) on peripheral blood mononuclear cells (PBMNC) from systemic sclerosis (SSc) patients. Thirty-one SSc patients (ACR) and 20 normal subjects were selected for the study. PBMNC were analyzed for LFA-1alpha, LFA-1beta, ICAM-3, ICAM-1, and L: -selectin expressions. ICAM-3 expression was decreased while ICAM-1 was increased on SSc PBMNC, compared to controls (p = 0.04 and 0.003, respectively). A positive association was found between LFA-1alpha (r = 0.37, p = 0.03), LFA-1beta (r = 0.38, p = 0.002), ICAM-3 (r = 0.42, p = 0.01), and L-selectin (r = 0.38, p = 0.03) expressions and greater number of immunosuppressive drugs taken by SSc patients. Also, anti-centromeric positive SSc patients had lower expressions of LFA-1alpha, LFA-1beta, ICAM-3, and L-selectin. Lower expression of ICAM-3 and higher expression of ICAM-1 suggest that AMs may be involved in the pathogenesis of scleroderma.


Assuntos
Moléculas de Adesão Celular/metabolismo , Leucócitos Mononucleares/metabolismo , Escleroderma Sistêmico/sangue , Adulto , Antígenos CD/metabolismo , Feminino , Humanos , Imunossupressores/uso terapêutico , Molécula 1 de Adesão Intercelular/metabolismo , Selectina L/metabolismo , Antígeno-1 Associado à Função Linfocitária/metabolismo , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/tratamento farmacológico
3.
Respiration ; 77(4): 389-97, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-18799868

RESUMO

BACKGROUND: The impressive association of lung involvement and gastroesophageal reflux in scleroderma raises the possibility of a cause-effect relationship. OBJECTIVES: To determine clinical, radiological and histopathological features of systemic sclerosis (SSc) patients according the presence or absence of centrilobular fibrosis (CLF). METHODS: Twenty-eight SSc patients with lung involvement were submitted to open lung biopsy and the specimens classified for the presence of CLF (bronchocentric distribution of the lesions and intraluminal matter according to the classification of idiopathic interstitial pneumonia). HRCT, pulmonary function tests and esophageal analysis were also performed. Subsequently, cyclophosphamide was introduced for the nonspecific interstitial pneumonia subgroup and antireflux treatment was intensified for isolated CLF patients. RESULTS: Isolated CLF was found in 21% of the biopsies and also found associated to nonspecific interstitial pneumonia in 84% of these patients. The other 3 cases had usual interstitial pneumonia, pulmonary hypertension and respiratory bronchiolitis-associated interstitial lung disease. The histopathological analysis revealed that all 6 patients with isolated CLF had the bronchocentric distribution and intraluminal basophilic content, with foreign bodies detected in one third of them. The central distribution of lung involvement on HRCT was found in 67% of these patients with a consistent patchy distribution (100%). Ground glass (67%) and consolidation (33%) were the predominant patterns found. The constant clinical finding in all isolated CLF cases was dyspnea, esophageal abnormalities and a moderate lung impairment (FVC: 63.83 +/- 16.31%; DLCO: 61.66 +/- 18.84%). Lung function parameters in isolated CLF patients remained stable after 1 year of exclusively intensive antireflux treatment (FVC, p = 0.23; DLCO, p = 0.59). CONCLUSIONS: The novel description of CLF pattern in SSc lung disease with peculiar histological, tomographic and clinical features will certainly contribute to a more appropriate therapeutic approach.


Assuntos
Doenças Pulmonares Intersticiais/etiologia , Escleroderma Sistêmico/complicações , Adulto , Antirreumáticos/uso terapêutico , Ciclofosfamida/uso terapêutico , Esôfago/diagnóstico por imagem , Esôfago/patologia , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores da Bomba de Prótons/uso terapêutico , Testes de Função Respiratória , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/tratamento farmacológico , Tomografia Computadorizada por Raios X
4.
Clin Respir J ; 3(3): 135-42, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20298396

RESUMO

BACKGROUND: Systemic sclerosis (SSc) is a multisystem disorder characterized by inflammation, fibrosis and vascular damage. The aim of this study was to evaluate the interactions between basement membrane disruption, endothelial injury and collagen V deposition on the vascular wall, as well as their association with pulmonary function tests in patients with SSc. METHOD: The endothelial apoptosis was assessed by TUNEL and electron microscopy, and quantified through the point-counting technique. To evaluate basement membrane integrity, laminin immunostaining and electron microscopy were used. Immunofluorescence and morphometric analysis were used to determine the amount of collagen V in the vascular walls in 23 open lung biopsies of patients with SSc without pulmonary hypertension. Normal lung tissue was obtained from five individuals who had died of traumatic injuries. RESULTS: The apoptosis index in SSc was higher in the endothelial cells (13.83 +/- 6.83) when compared with the control (2.51 +/- 2.06) group (P < 0.001) and confirmed by electron microscopy. We observed an important disruption of the basement membrane on the vascular wall shown by discontinuous laminin immunostaining and electron microscopy. An increase in collagen V on the vascular wall of the SSc group was observed (45.28 +/- 13.21), when compared with control group (22.90 +/- 4.13, P < 0.001), and this difference was statistically significant. An inverse correlation was found between vital capacity, forced vital capacity, forced expiratory volume in 1 s, vascular collagen V and endothelial apoptosis (P < 0.05). CONCLUSIONS: We conclude that the endothelial apoptosis and vascular collagen V interaction reinforce the vascular pathway in the SSc pathogenesis. Further studies are needed to determine whether this relationship is causal or consequential.


Assuntos
Colágeno/metabolismo , Células Endoteliais/metabolismo , Pulmão/patologia , Escleroderma Sistêmico/patologia , Adulto , Análise de Variância , Apoptose , Membrana Basal/patologia , Colágeno/ultraestrutura , Células Endoteliais/patologia , Feminino , Imunofluorescência , Humanos , Técnicas Imunoenzimáticas , Marcação In Situ das Extremidades Cortadas , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Escleroderma Sistêmico/fisiopatologia
5.
Respiration ; 76(2): 146-53, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18073456

RESUMO

BACKGROUND: Interstitial lung disease is a well-recognized prognostic factor in systemic sclerosis (SSc). As the prognosis in nonspecific interstitial pneumonia (NSIP) has been described to be better in collagen vascular disorders compared to the idiopathic forms, we hypothesize that the mechanisms of repair and remodeling are different between these 2 forms of the disease. OBJECTIVES: To compare the mechanisms of repair and remodeling between SSc-associated NSIP and the idiopathic form, its impact on pulmonary function tests and survival rates. METHODS: We analyzed 18 biopsies from patients with NSIP associated with SSc and 22 with idiopathic NSIP and compared the epithelial and vascular densities as well as vascular activity. RESULTS: Epithelial cell density was lower in SSc-NSIP when compared with idiopathic NSIP (p < 0.0001). Type II pneumocytes and Clara cells were reduced in idiopathic NSIP (p = 0.02). A decrease in microvessel density was found in SSc-NSIP compared to idiopathic NSIP (p < 0.0001). The vascular activity measured by VCAM expression was higher in NSIP-SSc when compared to the idiopathic group (p < 0.0001). The DLCO/VA in SSc-NSIP was more compromised. A direct association between vascular density and DLCO/VA was found (p = 0.02). There was no difference in the survival rate between the 2 groups after a follow-up of 36 months. CONCLUSIONS: Alterations in the epithelium and vasculature seem to differ in the pathogenesis of SSc-NSIP when compared to the idiopathic form of the disease. Further studies may be required to assess the significance of these findings and explore if they can provide prognostic and/or treatment information.


Assuntos
Doenças Pulmonares Intersticiais/etiologia , Pulmão/fisiopatologia , Escleroderma Sistêmico/complicações , Adulto , Epitélio/patologia , Epitélio/fisiopatologia , Feminino , Humanos , Pulmão/irrigação sanguínea , Pulmão/patologia , Doenças Pulmonares Intersticiais/patologia , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/patologia , Escleroderma Sistêmico/fisiopatologia
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