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2.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(4): 351-354, 2019 Jul 28.
Artigo em Chinês | MEDLINE | ID: mdl-31701721

RESUMO

OBJECTIVE: To study the preventive and therapeutic effects of safflower water extract on systemic scleroderma (SSc) in mice and its mechanism. METHODS: Sixty BALB/C mice were randomly divided into the control group, model group, prednisone group and safflower low, middle, high dose groups, 10 mice in each group.The control group was injected with normal saline, and the other five groups were subcutaneously injected with bleomycin hydrochloride with 100 µl at the concentration of 200 µg /ml on the back, once a day for 28 days to establish the SSc models.At the same time, the control group and model group were treated with normal saline (10 ml/kg), the prednisone group was treated with prednisone 4.5 mg/kg (10 ml/kg), and the low, middle, and high dose safflower groups were treated with safflower at the doses of 1.5, 3, 6 g/kg (10 ml/kg), and all groups were treated for 28 days.After 28 days, all mice were decapitated. The blood samples and back skin of the BLM injection part were collected.After that, all the tissue slices were taken to measure the dermal thickness, and the content of hydroxyproline (HYP) in the skin tissues was detected by hydrolysis method.The contents of tissue growth factor (CTGF) and transforming growth factor-ß (TGF-ß ) in the skin tissues and the levels of interleukin-6 (IL-6) and interleukin-17 (IL-17) in serum were determined by ELISA. RESULTS: Compared with the control group, the dermal thickness of the model group was increased(P<0.05), the contents of CTGF, TGF-ß and HYP in the skin tissues and the levels of IL-6 and IL-17 in the serum of the model group were increased(P<0.05); compared with the model group, the dermal thickness in the prednisone group and safflower groups was decreased (P<0.05), the levels of CTGF, TGF-ß and HYP in the skin tissues and the serum levels of IL-6 and IL-17 in the prednisone group and safflower groups were decreased (P<0.05). CONCLUSION: Safflower water extract can improve skin condition (or dermal thickness) in SSc mice, and its mechanism may be related to reducing immune inflammatory response.


Assuntos
Carthamus tinctorius/química , Extratos Vegetais/farmacologia , Escleroderma Sistêmico/tratamento farmacológico , Animais , Bleomicina , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Modelos Animais de Doenças , Hidroxiprolina/análise , Interleucina-17/metabolismo , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Aleatória , Pele/patologia , Fator de Crescimento Transformador beta1/metabolismo
3.
Z Rheumatol ; 78(10): 967-978, 2019 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-31712897

RESUMO

Raynaud's phenomenon (RP) is a frequent and painful vasospasm of small arteries localized in acral body regions (most frequently the fingers). The more frequent so-called primary RP is caused merely by a functional dysregulation of the tonus of vascular walls. In contrast, the rarer secondary RP is additionally associated with structural abnormalities of blood vessels. Knowledge of RP is important for rheumatologists because secondary RP can be associated with the presence or development of severe underlying diseases, especially with systemic sclerosis. Thus, the rheumatologist has to be aware of this condition. In this article the diagnostic procedures and the most important treatment approaches are summarized.


Assuntos
Doença de Raynaud , Escleroderma Sistêmico , Humanos , Doença de Raynaud/complicações , Doença de Raynaud/terapia , Reumatologistas , Escleroderma Sistêmico/complicações
4.
Internist (Berl) ; 60(12): 1251-1269, 2019 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-31754753

RESUMO

Systemic sclerosis (SSc) is a rare fibrosing rheumatic multi-systemic disease involving many medical specialties. The mortality of SSc is determined by lung fibrosis, pulmonary arterial hypertension and cardiac involvement. With early and intensive treatment, the disease can be stabilized and symptoms relieved. This review summarizes insights into pathophysiology, disease classification, clinical manifestations and successful therapies, as well as recent studies on new immunosuppressant, biological and vasoactive therapies.


Assuntos
Hipertensão Pulmonar/fisiopatologia , Fibrose Pulmonar/fisiopatologia , Escleroderma Sistêmico/fisiopatologia , Humanos , Hipertensão Pulmonar/etiologia , Imunossupressores/uso terapêutico , Doenças Pulmonares Intersticiais/etiologia , Fibrose Pulmonar/etiologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/terapia
5.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(5): 654-659, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31762233

RESUMO

OBJECTIVE: To investigate the expression of ß-catenin in the skin lesions of patients with systemic scleroderma (SSc) and its effect on epithelial-mesenchymal transition (EMT) of human epidermal keratinocytes. METHODS: The expression of ß-catenin, Snail1 and E-cadherin in the skin lesions sample of 45 SSc patients and normal skin sample from 20 healthy adults was detected with SP immunohistochemistry. HaCaT, the human epidermal keratinocytes, were treated with different concentrations of Wnt10b (0 ng/mL (control), 2 ng/mL and 4 ng/mL) for 48 h. then detected the localization of ß-catenin in HaCaT cells by immunofluorescence assay, determined the mRNA levels of Snail1 and Snail2 in HaCaT cells by real-time fluorescent quantitative PCR, detected the proteins expression of ß-catenin, Vimentin, N-cadherin and E-cadherin in HaCaT cells by Western blot. RESULTS: The positive rates of ß-catenin, Snail1 and E-cadherin in skin lesions of SSc patients were 100%, 88.89% and 2.22% respectively, while in healthy adult skin, the corresponding positive rates were 0%, 10.00%, and 95.00%. The difference between the two groups was significant. Compared with control group, treatment with different concentrations of Wnt10b (2 ng/mL and 4 ng/mL) induced up-regulation of ß-catenin expression and promoted translocation of ß-catenin from cytoplasm to nucleus, increased the mRNA levels of Snail1 and Snail2 (P < 0.05), and up-regulated the proteins expression of Vimentin, N-cadherin, down-regulated the E-cadherin protein expression in HaCaT cells (P < 0.05). CONCLUSIONS: Abnormally activated Wnt/ß-catenin signaling pathway and abnormally expressed EMT-related proteins are observed in SSc lesions. Activation of Wnt/ß-catenin signaling pathway may promote EMT in HaCaT cells.


Assuntos
Transição Epitelial-Mesenquimal , Queratinócitos/metabolismo , Escleroderma Sistêmico/metabolismo , Pele/metabolismo , beta Catenina/metabolismo , Adulto , Antígenos CD/metabolismo , Caderinas/metabolismo , Humanos , Queratinócitos/citologia , Escleroderma Sistêmico/patologia , Pele/patologia , Fatores de Transcrição da Família Snail/metabolismo , Vimentina/metabolismo , Via de Sinalização Wnt
6.
Recurso na Internet em Português | LIS - Localizador de Informação em Saúde, LIS-bvsms | ID: lis-LISBR1.1-46849

RESUMO

Doença do sistema imunológico que provoca o endurecimento da pele, a qual se torna espessa, lisa e sem elasticidade.


Assuntos
Esclerodermia Localizada , Esclerodermia Limitada , Esclerodermia Difusa , Escleroderma Sistêmico , Doenças Reumáticas
7.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(8): 707-713, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31638568

RESUMO

Objective To investigate the relationship between mitochondria and systemic sclerosis (SSc) by analyzing the expression of mitochondrial function-related genes in skin biopsy samples from patients with SSc. Methods Gene chip expression profile of SSc skin biopsy in Gene Expression Omnibus (GEO) database was used, and differently expressed genes (DEGs) related to mitochondrial function were identified by t test and fold change (FC). What's more, functional annotation, functional enrichment and protein interaction network analysis were performed. Results A total of 422 significant DEGs were identified between the SSc group and the normal group. Among them, 23 DEGs were mitochondrial function-related genes. Functional annotation and enrichment analysis of 23 DEGs revealed that abnormally expressed mitochondrial function-related genes mainly affected several biological processes, such as mitochondrial energy supply and cell metabolism. Conclusion The dysregulation of mitochondrial function-related genes in SSc patients affects the function of mitochondria, suggesting that the abnormality of mitochondrial function may be associated with the development of SSc.


Assuntos
Biologia Computacional , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Mitocôndrias , Escleroderma Sistêmico , Perfilação da Expressão Gênica , Humanos , Mitocôndrias/genética , Mitocôndrias/patologia , Escleroderma Sistêmico/genética , Escleroderma Sistêmico/fisiopatologia , Transcriptoma
9.
Presse Med ; 48(10): e284-e291, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31653544

RESUMO

OBJECTIVE: The Prevalence of systemic sclerosis (SSc) and different clinical subsets varies across the world. Few data have been published on SSc patients in North Africa. Our objective was to describe a SSc cohort in south of Tunisia and to compare clinical findings, disease subsets and antibodies with other international SSc populations. METHODS: In this retrospective observational study, Folders of patients with SSc seen in the internal medicine section of the Hedi Chaker Hospital between 2000 and 2013 were retrospectively analyzed. The diagnosis of SSc was retained according to ACR/EULAR 2013 criteria. Patients were classified into diffuse cutaneous SSc and limited cutaneous SSc subsets. Comparison with other cohorts was made based on published information. RESULTS: A higher female: male ratio (8:1) and a higher diffuse subset prevalence (82%) was found in this Tunisian cohort comparing with others. We also found a lower prevalence of calcinosis and anticentromere antibodies. Within each subset, diffuse cutaneous and limited cutaneous scleroderma clinical findings were similar with other systemic sclerosis populations except for a very low prevalence in renal crisis and pulmonary hypertension. Our results indicate overlap syndrome defined as scleroderma associated with others connective tissue disorder's is a relatively common condition. CONCLUSION: With slight variations, perhaps due to genetic, environmental or referral factors, SSc in this cohort appears to be similar to that described in other part of the world.


Assuntos
Esclerodermia Limitada , Escleroderma Sistêmico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Calcinose/epidemiologia , Centrômero/imunologia , Estudos Transversais , DNA Topoisomerases Tipo I/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Esclerodermia Limitada/complicações , Esclerodermia Limitada/diagnóstico , Esclerodermia Limitada/imunologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/imunologia , Tunísia , Adulto Jovem
10.
J Drugs Dermatol ; 18(10): 995-998, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31584777

RESUMO

Background: Autoimmune connective tissue diseases (ACTDs) are a broad range of diseases featured by immune dysregulation, and often have multisystem involvement with prominent skin manifestations. Pruritus is one of the most common symptoms in these diseases, with significant impact on the quality of life of patients. Objective: To characterize the frequency, location, severity, and timing relative to disease onset of pruritus in different ACTDs. Methods: A chart review of all patients seen in the Rheumatology-Dermatology clinic at Massachusetts General Hospital. Results: Itch was a troubling symptom in 83% of dermatomyositis (DM), 61% of systemic lupus erythematosus (SLE), 59% of Sjogren syndrome (SJO), 22% of systemic sclerosis (SSc), and 60% of mixed connective tissue disease. In DM and SLE, itch paralleled the course of inflammatory skin manifestations in 83% and 45%, respectively. Itch in DM is more intense and more treatment resistant in 12% vs 1% in SLE. In contrast, itch in SSc and SJO tended to occur later in the disease course, 86% vs 42%, respectively. Conclusion: Itch is common in all ACTDs and often under-evaluated and under treated. Pruritus is more common and more severe in DM than in SLE. Treatment of pruritus in ACTDs can be challenging, and sometimes multi-modal therapy is warranted. J Drugs Dermatol. 2019;18(10):995-998.


Assuntos
Dermatomiosite/complicações , Lúpus Eritematoso Sistêmico/complicações , Prurido/diagnóstico , Escleroderma Sistêmico/complicações , Síndrome de Sjogren/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada/métodos , Dermatomiosite/imunologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Prurido/imunologia , Prurido/terapia , Qualidade de Vida , Estudos Retrospectivos , Escleroderma Sistêmico/imunologia , Índice de Gravidade de Doença , Síndrome de Sjogren/imunologia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
11.
BMC Neurol ; 19(1): 234, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31607267

RESUMO

BACKGROUND: This article reports a case diagnosis of a 44-year-old female who presented with intractable hiccups and vomit complicated with an acute onset of paraplegia. Transverse myelitis was evident on MRI and serological studies were consistent with Neuromyelitis Optica (NMO) based on NMO-IgG sero-positivity. Further studies revealed positive ANA, anti-RNA polymerase III autoantibodies, and Scl-70, leading to a concurrent diagnosis of systemic sclerosis (SSc). The coexistence of these two disease processes and their underlying clinical manifestations and therapeutic interventions are seldom reported in literature and are worth reporting. CASE PRESENTATION: The patient was treated with high dose steroids, and subsequently developed malignant hypertension and acute renal failure, later identified on biopsy as steroids-induced scleroderma renal crisis. Although Neuromyelitis Optica spectrum disorder (NMOSD) has often been associated with various collagen and autoimmune diseases, the coexistence of NMOSD and SSc presented a challenge where the patient underwent aggressive physical therapy and necessitated an intervention with Rituximab to achieve an appropriate clinical response. We have received a written consent forms from the participant in our study, and we have them on file in case they are requested. We have also received the patient's written consent for the data and images presented in this article. CONCLUSION: This article expands on NMOSD associated autoimmune diseases. Systemic Sclerosis is an insidious disease that is often diagnosed late as not all patients often report skin manifestation. The finding suggests that patients presenting with acute neurological manifestations get tested for NMO-IgG/AQP-4 antibodies and other immunological studies based on clinical findings.


Assuntos
Mielite Transversa/etiologia , Neuromielite Óptica/complicações , Escleroderma Sistêmico/complicações , Adulto , Autoanticorpos/sangue , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Imagem por Ressonância Magnética , Mielite Transversa/tratamento farmacológico , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/tratamento farmacológico , Rituximab/uso terapêutico , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/tratamento farmacológico , Síndrome
14.
Clin Exp Rheumatol ; 37 Suppl 119(4): 76-81, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31587692

RESUMO

OBJECTIVES: Vitamin D status influences the risk to develop autoimmune diseases affecting the percentage and/or functions of regulatory T cells (Tregs). Since low levels of 25 (OH) D have been decreased in patients with systemic sclerosis (SSc), we aimed to study the effect of Vitamin D3 (cholecalciferol) supplementation on Tregs frequencies and functions. METHODS: Peripheral blood and sera samples were obtained from 45 SSc patients and controls (HC). A number of eighteen SSc patients had consumed Cholecalciferol (orally) at the dose of 25.000 UI/month for 6 months at the time of enrollment. 25(OH)D serum levels were measured and VDR polymorphisms, were genotyped by polymerase chain reaction (PCR). Tregs isolated from peripheral blood mononuclear cells were in vitro expanded and a suppression assay was performed. Flow cytometry analysis was then carried out. Finally, IL-10 production was assayed by ELISA. RESULTS: Low serum levels of 25(OH)D were detected in SSc patients. The percentage of Tregs in SSc patients was similar to controls, but, among SSc patients, it was higher in those patients taking cholecalciferol. Tregs capability to suppress T cell proliferation was impaired in SSc patients and not restored after in vitro pre-treatment with the active form of Vitamin D (1,25(OH)2D3); but at the same time the production of IL-10 was increased in treated samples obtained from patients. The lack of response of Tregs from SSc patients to 1,25(OH)2D3 treatment in vitro was not due to altered Vitamin D/VDR signalling. CONCLUSIONS: Altogether, our results indicate that the increased production of IL-10 by 1,25(OH)2D3 -treated Tregs could provide a "suppressive" cytokine milieu able to modulate immune response but it is not sufficient to restore the immune suppressive functions of Tregs.


Assuntos
Interleucina-10/biossíntese , Escleroderma Sistêmico , Linfócitos T Reguladores/efeitos dos fármacos , Vitamina D , Estudos de Casos e Controles , Suplementos Nutricionais , Feminino , Humanos , Leucócitos Mononucleares , Masculino , Pessoa de Meia-Idade , Escleroderma Sistêmico/metabolismo , Vitamina D/farmacologia
16.
Clin Exp Rheumatol ; 37 Suppl 119(4): 82-87, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31587694

RESUMO

OBJECTIVES: To determine whether cumulative endogenous estrogen exposure (CEEE) is associated with severity of microvascular damage or with presence of clinical characteristics in women with systemic sclerosis (SSc). METHODS: The population was composed of female SSc patients from the Leiden CCISS (combined care in SSc) cohort. Reproductive life history was investigated through structured questionnaires and CEEE was calculated with a mathematical equation. Demographic, laboratory and clinical characteristics were available for all patients. The most recent nailfold videocapillaroscopy (NVC) was used to semiquantitatively score microangiopathy parameters. RESULTS: We included 97 patients, with a mean age of 59.6±14 years and a mean CEEE of 9±5.5 years. Ordinal logistic regression using CEEE as independent variable failed to demonstrate an association with loss (OR 1.05, 95% CI 0.97-1.14), dilated capillaries (OR 1.05, 95% CI 0.96-1.14), giants (OR 1.03, 95% CI 0.95-1.12) and ramifications (OR 0.99, 95% CI 0.92-1.07). Binary logistic regression did not show an effect of CEEE on presence of scleroderma pattern vs. non-scleroderma pattern, (OR 0.99, 95% CI 0.89-1.1) or of late scleroderma pattern vs. non-late patterns (OR 0.96, 95% CI 0.88-1.05) at NVC. Furthermore, no association was found between CEEE and presence of interstitial lung involvement (OR 0.98, 95% CI 0.88-1.08) but a trend for occurrence of digital ulcers (OR 1.09, 95% CI 0.99-1.19) was observed. CONCLUSIONS: In SSc patients, CEEE is not associated with the extent of microvascular derangement. No associations between CEEE and organ involvement were found.


Assuntos
Capilares , Estrogênios/farmacologia , Angioscopia Microscópica/métodos , Unhas/irrigação sanguínea , Escleroderma Sistêmico , Idoso , Capilares/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Escleroderma Sistêmico/patologia
17.
Clin Exp Rheumatol ; 37 Suppl 119(4): 102-107, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31587695

RESUMO

OBJECTIVES: To retrospectively study nailfold videocapillaroscopy (NVC) changes in mixed connective tissue disease (MCTD) patients and to compare the capillary morphological abnormalities between patients affected by MCTD and systemic sclerosis (SSc) over time. METHODS: Ten MCTD patients on whom NVC had been performed, with a follow-up of three years, were selected. In addition, ten patients affected by SSc with similar age and disease duration of MCTD patients were enrolled to compare NVC abnormalities at baseline (T0). RESULTS: Seven out of ten patients with MCTD showed a "scleroderma-like pattern" at first NVC. No statistically significant variation of the detected NVC parameters was observed during the 3-year follow-up, and no statistically significant correlation was observed between capillary parameters and MCTD clinical aspects at first visit and during the follow-up. The scores of enlarged capillaries, giant capillaries and microhaemorrhages were significantly lower (p<0.05) in MCTD versus SSc patients at T0, moreover, the absolute number of total capillaries and normal capillaries was found significantly higher (p<0.05) in MCTD versus SSc patients. CONCLUSIONS: This study suggests that nailfold microvascular damage does not seem to be significantly progressive in MCTD patients during a three-year follow-up. MCTD patients show significantly lower number of enlarged/giant capillaries, but higher number of total and normal capillaries than SSc patients at first nailfold capillaroscopy. The identification of a specific NVC pattern in MCTD patients is not yet possible.


Assuntos
Angioscopia Microscópica/métodos , Doença Mista do Tecido Conjuntivo , Unhas , Escleroderma Sistêmico , Capilares , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Doença Mista do Tecido Conjuntivo/diagnóstico por imagem , Unhas/irrigação sanguínea , Unhas/diagnóstico por imagem , Estudos Retrospectivos , Escleroderma Sistêmico/diagnóstico por imagem
18.
Clin Exp Rheumatol ; 37 Suppl 119(4): 108-114, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31587696

RESUMO

OBJECTIVES: The aim of our study was to assess the role of videofluorography (VFG) in the evaluation of swallowing and oesophageal peristalsis in patients with systemic sclerosis (SSc). METHODS: From June 2014 to September 2017, 55 consecutive SSc patients, defined according to the 2013 ACR/EULAR classification criteria, underwent VFG study using a remote-controlled digital device. In order to evaluate possible abnormalities, 18 dynamic parameters were chosen, dividing the act of swallowing into three phases: oral, pharyngeal and oesophageal phases. The following dynamic radiological findings were considered: veil motility in phonation, leakage, drooling, salivation and presence of residues in the oral cavity, pharyngeal residues, penetration, aspiration, altered motility of the upper oesophageal sphincter, efficacy of primary peristaltic contractions, oesophageal clearance capacity, reflux, oesophagitis and motility of the lower oesophageal sphincter. RESULTS: The VFG study was well tolerated in all patients. Dysfunctions of oesophageal motility were common and included abnormal motility of UES (12.7%) and LES (76.4%), inadequate primary peristalsis (52.7%), abnormal secondary peristalsis (29.1%) and non-peristaltic contractions (40%). A defective oesophageal clearance was observed in 69.4% of patients. Moreover, most patients presented signs of oesophageal reflux (63.6%), oesophagitis (81.8%) and hiatal hernia (80%). Pharyngeal abnormalities were less common and involved up to 50% of patients. Oesophageal dysfunction and defective clearance were associated with dcSSc and pulmonary involvement. CONCLUSIONS: The VFG study is a useful technique for the morphological and functional evaluation of swallowing in SSc patients.


Assuntos
Cinerradiografia/métodos , Transtornos de Deglutição , Fluoroscopia/métodos , Escleroderma Sistêmico , Transtornos de Deglutição/diagnóstico por imagem , Transtornos de Deglutição/etiologia , Feminino , Refluxo Gastroesofágico , Humanos , Masculino , Manometria , Pessoa de Meia-Idade , Peristaltismo , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico por imagem
19.
Clin Exp Rheumatol ; 37 Suppl 119(4): 3-14, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31587697

RESUMO

Systemic sclerosis (SSc) is a complex disorder characterised by the involvement of small arteries, microvessels and connective tissue, with deposition of fibrotic tissue and microvascular obliteration in the skin and internal organs. Due to the multifaceted nature of the disease, several articles are published in the medical literature every year, aimed at exploring different aspects of the pathogenesis, internal organ involvement and clinical aspects, and possible therapeutic approaches. In this article we have reviewed the literature on SSc of the past year, with the aim of identifying novel approaches that may help the treating physician in the clinical management of patients.


Assuntos
Microvasos/patologia , Escleroderma Sistêmico , Vasos Sanguíneos/patologia , Fibrose , Humanos , Escleroderma Sistêmico/fisiopatologia , Escleroderma Sistêmico/terapia , Pele
20.
Clin Exp Rheumatol ; 37 Suppl 119(4): 115-124, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31573469

RESUMO

OBJECTIVES: Nintedanib is approved for the treatment of idiopathic pulmonary fibrosis (IPF) and was demonstrated to slow disease progression in patients with IPF by reducing decline in forced vital capacity by 50%. Recently, nintedanib has been reported to exert anti-fibrotic activity on systemic sclerosis (scleroderma, SSc) skin fibroblasts and to diminish skin and lung fibrosis in mouse models. The goal of the present study was to determine the effects of nintedanib on a cellular model of SSc-associated interstitial lung disease (ILD). METHODS: Study was performed using lung fibroblasts (LF) isolated from five patients with SSc-ILD and from three control subjects. RESULTS: Nintedanib inhibited LF proliferation and migration in a concentration- and time-dependent manner. The proliferation rate of LF stimulated with PDGF in the presence of nintedanib was reduced 1.9-fold within 24 h as compared to cells stimulated with PDGF alone. Migration of SSc-ILD LF incubated with 100 nM nintedanib was reduced from 62.8±12.5% to 39.1±9.0% in the presence of PDGF and from 38.2±7.9% to 26.6±7.2% in serum-free medium. Nintedanib attenuated PDGF-induced Ca2+ efflux, reduced α-SMA promoter activity and α-SMA protein expression. Furthermore, nintedanib blocked PDGF-induced differentiation of normal LF to myofibroblasts, reduced production of collagen and fibronectin, and decreased contractility of SSc-ILD LF in both floating and fixed collagen gels. CONCLUSIONS: Our data demonstrate significant antifibrotic efficacy of nintedanib in SSc-ILD LF suggesting that nintedanib has the potential not only to prevent but also to reverse the increased activity of LF consequently attenuating excessive lung fibrosis observed in SSc-ILD.


Assuntos
Fibrose Pulmonar Idiopática , Indóis/uso terapêutico , Doenças Pulmonares Intersticiais , Inibidores de Proteínas Quinases/uso terapêutico , Escleroderma Sistêmico , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/etiologia , Pulmão/citologia , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Escleroderma Sistêmico/complicações
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