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1.
J Clin Rheumatol ; 26(7S Suppl 2): S106-S110, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32045391

RESUMO

BACKGROUND/OBJECTIVE: The epidemiology of vasculitis is variable in different geographic areas, and this issue has not been approached in Brazil yet. The objective of this study was to assess the frequency of vasculitis in specialized centers in Brazil. METHODS: This cross-sectional study was performed in 9 vasculitis outpatient clinics from 6 different states mainly from the Southeast and the Northeast regions of Brazil between 2015 and 2017. Diagnosis and/or classification criteria for Behçet disease (BD), Takayasu arteritis (TA), giant cell arteritis (GCA), polyarteritis nodosa (PAN), granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), and cryoglobulinemic vasculitis (CryoVas) were used to include patients with at least 6 months of follow-up in this hospital-based survey. RESULTS: A total of 1233 patients with systemic vasculitis were included from the Southeast region. Behçet disease was the most frequent vasculitis (35.0%) followed by TA (26.4%), GPA (16.2%), PAN (5.8%), GCA (5.8%), EGPA (4.3%), MPA (3.4%), and CryoVas (3.0%). Up to 7.8% of vasculitis patients had a juvenile onset, and the frequency of vasculitides found in children and adolescents was as follows: TA (52.6%), BD (24.7%), GPA (12.4%), and PAN (10.3%). No cases of EGPA, MPA, and CryoVas were diagnosed before the age of 18 years. As a comparator, 103 vasculitis patients were included in the Northeast of Brazil where TA was found in 36.9% and BD in 31.1% of vasculitis cases. No GCA cases were found in the Northeast part of Brazil. CONCLUSIONS: Similar to the epidemiology of vasculitis in Asia, BD and TA are the most frequent vasculitis in Southeastern Brazilian referral centers.


Assuntos
Síndrome de Churg-Strauss , Granulomatose com Poliangiite , Adolescente , Brasil/epidemiologia , Criança , Estudos Transversais , Hospitais , Humanos
2.
Inflammation ; 46(2): 730-738, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36459355

RESUMO

Inflammatory T lymphocyte cytokines contribute to tissue damage in SLE patients. Vitamin D (Vit D) has a well-established immunomodulatory action, but few studies have addressed the effect of 1,25 dihydroxyvitamin D3 (1,25 (OH)2D3) on peripheral blood mononuclear cells (PBMCs) in SLE patients. The aim of this study was to evaluate the immnunomodulatory effect of 1,25 (OH)2D3 on T lymphocyte-related cytokines. Blood from 27 female SLE patients was collected for PBMC isolation and anti-DNA, complement, and serum 25 (OH)D3 level measurements. PBMCs were stimulated with anti-CD3/anti-CD28 in the presence or absence of dexamethasone or various concentrations of 1,25 (OH)2D3 for 48 h. We assessed IL-17A, IL-22, IL-21, IL-9, IFN-γ, IL-4, IL-10, IL-2, IL-6, and TNF by cytometric bead assay (CBA) and enzyme immune assay (ELISA) on culture supernatant. The mean age of patients was 36.2 (± 10.5 years) and the median Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) was 4 (0-6). The addition of 1,25 (OH)2D3 in PBMC culture reduced IL-17 A, IL-22, IL-9, and IFN-γ levels at 100 nM (p ≤ 0.0001). Furthermore, the addition of 1,25 (OH)2D3 at all concentrations increased IL-4 (p ≤ 0.0006), and 0.1 and 1 nM increased IL-10 (p ≤ 0.0004) and 0.1 nM increased IL-2 levels (p ≤ 0.0001). There was no difference regarding IL-21 and TNF levels. The addition of 1,25 (OH)2D3 in PBMC culture presented an inhibitory effect on proinflammatory cytokines and increased immunoregulatory cytokines in SLE patients, suggesting the beneficial effect of this vitamin.


Assuntos
Citocinas , Lúpus Eritematoso Sistêmico , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Interleucina-10/farmacologia , Leucócitos Mononucleares , Interleucina-2/farmacologia , Interleucina-4/farmacologia , Interleucina-9 , Linfócitos T , Vitamina D/farmacologia , Vitaminas , Lúpus Eritematoso Sistêmico/tratamento farmacológico
3.
Rheumatol Int ; 32(3): 703-9, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21152919

RESUMO

In this retrospective longitudinal cohort study we included 52 patients with Takayasu arteritis (TA) who were on regular follow-up at the Vasculitis Unit of Universidade Federal de São Paulo between 2003 and 2009. The mean age at study was 38 years and the mean age at diagnosis was 29 years. Patients were followed for a mean 74.3 months. A relapse-remitting course was observed in 41 patients (78.8%) whereas 9 (17.3%) had a monophasic course and only 2 (3.8%) patients were chronic-active. Disease remission was achieved in 50 patients (96.2%). Angiographic type V was observed in 42.3% of TA patients at diagnosis and in 61.5% during follow-up. The most affected arteries were the abdominal aorta (63.5%) and left subclavian (60.6%). Prednisone was used by 94% of TA patients and immunosuppressive agents were prescribed for 51 (98%) patients. Methotrexate was used by 82.7%, followed by cyclophosphamide (26.9%), azathioprine (25.0%), anti-TNFα agents (5.8%) and leflunomide (5.8%). Although, forty patients (76.9%) used prednisone and methotrexate as initial treatment, 75% of them developed new vascular lesions along follow-up. Eighteen TA patients (34.6%) needed to change immunosuppressive therapy due to failure or toxicity, among them 83.3% presented new lesions. Surgical treatment was performed in 34.6% of patients and restenosis was observed in 13.5% in a median time of 11 months after surgery. In conclusion besides prednisone and methotrexate is largely used in TA, the majority of patients still develop new arterial lesions along time.


Assuntos
Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Prednisona/uso terapêutico , Arterite de Takayasu/terapia , Adulto , Aorta Abdominal/patologia , Aorta Abdominal/fisiopatologia , Constrição Patológica , Substituição de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Estudos Longitudinais , Masculino , Recidiva , Indução de Remissão , Estudos Retrospectivos , Artéria Subclávia/patologia , Artéria Subclávia/fisiopatologia , Arterite de Takayasu/diagnóstico , Arterite de Takayasu/fisiopatologia , Resultado do Tratamento , Grau de Desobstrução Vascular
4.
Adv Rheumatol ; 62(1): 34, 2022 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-36071498

RESUMO

BACKGROUND: The VI Brazilian Consensus on Autoantibodies against HEp-2 cells for determination of autoantibodies against cellular constituents on HEp-2 cells was held on September, 2019, in Fortaleza (CE, Brazil). The guidelines in this edition were formulated by the group of Brazilian experts discussing the classification of complex patterns, the classification of the nuclear discrete dots (few and multiple), the identification of the discrete fine speckled pattern (AC-4a) and improvements on the ANA report. MAINBODY: Sixteen Brazilian researchers and experts from universities and clinical laboratories representing the various geographical regions of Brazil participated in the meeting. Four main topics were discussed: (1) How to classify patterns with fluorescence in more than one cell compartment considering three relevant categoris: composite patterns, mixed patterns and multiple patterns; (2) The splitting of the discrete nuclear dots pattern into the multiple discrete nuclear dots (AC-6) and few discrete nuclear dots (AC-7) patterns, respectively; (3) Inclusion of a novel nuclear pattern characterized by discrete fine speckled pattern highly associated with antibodies to SS-A/Ro60, classified as AC-4a. In addition, adjustments on the Brazilian Consensus nomenclature were implemented aiming to harmonize the designation of some patterns with the International Consensus on ANA Patterns (ICAP). Furthermore, the designations of the PCNA-like pattern (AC-13), CENP-F-like pattern (AC-14) and Topo I-like pattern (AC-29) were adjusted in accordance to ICAP. Finally, there was a recommendation for adjustment in the test report in order to address the status of nuclear envelope staining. For all topics, the aim was to establish specific guidelines for laboratories and clinicians. All recommendations were based on consensus among participants. All recommendations from the V Consensus were maintained and there was relevant progress in the BCA/HEp-2 guidelines and further harmonization with ICAP. CONCLUSION: The VI BCA/HEp-2 edition was successful in establishing important recommendations regarding the classification of complex patterns, in supporting the identification of a novel pattern within the AC-4 group and in the harmonization process with the ICAP terminology.


Assuntos
Anticorpos Antinucleares , Autoanticorpos , Brasil , Consenso , Humanos
5.
Clin Rheumatol ; 40(5): 1889-1892, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33196983

RESUMO

The Toronto Psoriatic Arthritis Screen II (ToPAS II) was developed as a tool to screen patients with probable psoriatic arthritis. We aimed to evaluate the validation of the ToPAS II questionnaire in a Brazilian population. The Portuguese translation of the ToPAS II was sent to us by the developer authors of the original index, and adapted to Brazilian Portuguese. Subjects were recruited from dermatology, general, and rheumatology outpatient clinics. After patients completed the questionnaire, they were assessed by a rheumatologist, according to standard protocol. Receiver operating characteristics (ROC) was used to obtain the sensitivity and specificity of the Brazilian Portuguese version of the ToPAS II questionnaire. One hundred and eighty-four subjects were recruited in the study. There were 70 subjects from the psoriasis group, 44 subjects from the psoriatic arthritis (PsA) group, 40 subjects from the rheumatology (non-PsA) group, and 45 healthy controls. Twenty-four patients (34.3%) in the psoriasis group had inflammatory pain and met the CASPAR classification criteria. The area under the ROC curve was 0.96, which indicates that an excellent predictor and optimum cutoff threshold to discriminate patients diagnosed with PsA used was eight as originally chosen. The overall sensitivity and specificity based on the cutoff threshold of eight were 91.3 and 90.9%, respectively. The Portuguese Brazilian version of the ToPAS II has good sensitivity and specificity and is a useful tool to screen for PsA. Key Points • Among these psoriasis patients, almost 35% in fact had psoriatic arthritis without correct diagnosis. Keeping alert of the need to disclose screening tool's use. • The TOPAS II can facilitate the screening of patients suggestive of inflammatory joint disease (with high probability of rheumatologic diagnosis) decreasing morbidity of these patients.


Assuntos
Artrite Psoriásica , Psoríase , Artrite Psoriásica/diagnóstico , Brasil , Humanos , Sensibilidade e Especificidade , Inquéritos e Questionários
6.
Lancet Rheumatol ; 3(12): e855-e864, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34778843

RESUMO

BACKGROUND: Patients with primary systemic vasculitis or polymyalgia rheumatica might be at a high risk for poor COVID-19 outcomes due to the treatments used, the potential organ damage cause by primary systemic vasculitis, and the demographic factors associated with these conditions. We therefore aimed to investigate factors associated with COVID-19 outcomes in patients with primary systemic vasculitis or polymyalgia rheumatica. METHODS: In this retrospective cohort study, adult patients (aged ≥18 years) diagnosed with COVID-19 between March 12, 2020, and April 12, 2021, who had a history of primary systemic vasculitis (antineutrophil cytoplasmic antibody [ANCA]-associated vasculitis, giant cell arteritis, Behçet's syndrome, or other vasculitis) or polymyalgia rheumatica, and were reported to the COVID-19 Global Rheumatology Alliance registry were included. To assess COVID-19 outcomes in patients, we used an ordinal COVID-19 severity scale, defined as: (1) no hospitalisation; (2) hospitalisation without supplemental oxygen; (3) hospitalisation with any supplemental oxygen or ventilation; or (4) death. Multivariable ordinal logistic regression analyses were used to estimate odds ratios (ORs), adjusting for age, sex, time period, number of comorbidities, smoking status, obesity, glucocorticoid use, disease activity, region, and medication category. Analyses were also stratified by type of rheumatic disease. FINDINGS: Of 1202 eligible patients identified in the registry, 733 (61·0%) were women and 469 (39·0%) were men, and their mean age was 63·8 years (SD 17·1). A total of 374 (31·1%) patients had polymyalgia rheumatica, 353 (29·4%) had ANCA-associated vasculitis, 183 (15·2%) had giant cell arteritis, 112 (9·3%) had Behçet's syndrome, and 180 (15·0%) had other vasculitis. Of 1020 (84·9%) patients with outcome data, 512 (50·2%) were not hospitalised, 114 (11·2%) were hospitalised and did not receive supplemental oxygen, 239 (23·4%) were hospitalised and received ventilation or supplemental oxygen, and 155 (15·2%) died. A higher odds of poor COVID-19 outcomes were observed in patients who were older (per each additional decade of life OR 1·44 [95% CI 1·31-1·57]), were male compared with female (1·38 [1·05-1·80]), had more comorbidities (per each additional comorbidity 1·39 [1·23-1·58]), were taking 10 mg/day or more of prednisolone compared with none (2·14 [1·50-3·04]), or had moderate, or high or severe disease activity compared with those who had disease remission or low disease activity (2·12 [1·49-3·02]). Risk factors varied among different disease subtypes. INTERPRETATION: Among patients with primary systemic vasculitis and polymyalgia rheumatica, severe COVID-19 outcomes were associated with variable and largely unmodifiable risk factors, such as age, sex, and number of comorbidities, as well as treatments, including high-dose glucocorticoids. Our results could be used to inform mitigation strategies for patients with these diseases. FUNDING: American College of Rheumatology and the European Alliance of Associations for Rheumatology.

7.
Adv Rheumatol ; 62: 34, 2022. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1403088

RESUMO

Abstract Background: The VI Brazilian Consensus on Autoantibodies against HEp-2 cells for determination of autoantibodies against cellular constituents on HEp-2 cells was held on September, 2019, in Fortaleza (CE, Brazil). The guidelines in this edition were formulated by the group of Brazilian experts discussing the classification of complex patterns, the classification of the nuclear discrete dots (few and multiple), the identification of the discrete fine speckled pattern (AC-4a) and improvements on the ANA report. Mainbody: Sixteen Brazilian researchers and experts from universities and clinical laboratories representing the various geographical regions of Brazil participated in the meeting. Four main topics were discussed: (1) How to classify patterns with fluorescence in more than one cell compartment considering three relevant categoris: composite patterns, mixed patterns and multiple patterns; (2) The splitting of the discrete nuclear dots pattern into the multiple discrete nuclear dots (AC-6) and few discrete nuclear dots (AC-7) patterns, respectively; (3) Inclusion of a novel nuclear pattern characterized by discrete fine speckled pattern highly associated with antibodies to SS-A/Ro60, classified as AC-4a. In addition, adjustments on the Brazilian Consensus nomenclature were implemented aiming to harmonize the designation of some patterns with the International Consensus on ANA Patterns (ICAP). Furthermore, the designations of the PCNA-like pattern (AC-13), CENP-F-like pattern (AC-14) and Topo I-like pattern (AC-29) were adjusted in accordance to ICAP. Finally, there was a recommendation for adjustment in the test report in order to address the status of nuclear envelope staining. For all topics, the aim was to establish specific guidelines for laboratories and clinicians. All recommendations were based on consensus among participants. All recommendations from the V Consensus were maintained and there was relevant progress in the BCA/HEp-2 guidelines and further harmonization with ICAP. Conclusion: The VI BCA/HEp-2 edition was successful in establishing important recommendations regarding the classification of complex patterns, in supporting the identification of a novel pattern within the AC-4 group and in the harmonization process with the ICAP terminology.

8.
Clin Rheumatol ; 35(3): 801-5, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26219490

RESUMO

The current treatment for antiphospholipid syndrome (APS) with thrombotic manifestation is long-term anticoagulation. Vitamin K antagonists (VKA) are usually the agents of choice. However, VKA limitations, such as unpredictable anticoagulation effects due to interaction with diet and other drugs, require regular monitoring. This may impact on patients' quality of life. Since the approval of new oral anticoagulants (NOAC) for non-valvular atrial fibrillation and deep vein thrombosis prevention, much has been speculated about its use in APS patients. We report here a series of eight APS patients with failure of thrombotic prevention during rivaroxaban use. All patients had venous thrombosis as the initial manifestation of APS, and two of them also had arterial manifestations. Three patients had triple antibody positivity. Five patients developed arterial events during the treatment with rivaroxaban. Until the results of ongoing trials of rivaroxaban for APS are presented, NOAC should not be recommended to APS patients. Our preliminary experience as well cases previously reported in the literature suggest that there is a high-risk group that is less protected with rivaroxaban, namely those with previous arterial thrombosis or triple positivity. VKA remains to be the mainstay treatment for thrombotic APS.


Assuntos
Síndrome Antifosfolipídica/tratamento farmacológico , Rivaroxabana/efeitos adversos , Trombose/induzido quimicamente , Adolescente , Adulto , Anticoagulantes/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rivaroxabana/uso terapêutico , Trombose/tratamento farmacológico
9.
Rev Bras Reumatol ; 54(6): 452-8, 2014.
Artigo em Português | MEDLINE | ID: mdl-25458027

RESUMO

OBJECTIVE: To evaluate the safety and efficacy of N-acetylcysteine (NAC) orally on digital microcirculation blood flow in patients with Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc). METHODS: This was a randomized, double-blind, placebo-controlled trial in which 42 patients with SSc received oral NAC at a dose of 600mg tid (21 patients, mean age 45.6±9.5 years) or placebo (21 patients, mean age 45.0±12.7 years) for four weeks. The primary endpoint was the change in cutaneous microcirculation blood flow before and after cold stimulation measured by laser Doppler imaging (LDI) at weeks 0 and 4. The frequency and severity of RP and the number of digital ulcers were also measured at weeks 0 and 4. The adverse events were recorded in the fourth week. RESULTS: There was no significant change in digital blood flow assessed by LDI before or after cold stimulus after four weeks of NAC or placebo. Both groups showed significant improvement in the frequency and severity of RP attacks, with no difference between the two groups. At the end of the study, the placebo group had three digital ulcers, while the NAC group showed no ulcers. NAC was well tolerated and no patient discontinued the treatment. CONCLUSIONS: NAC orally at a dose of 1800mg/day showed no vasodilator effect on hands' microcirculation after four weeks of treatment in patients with RP secondary to SSc.


Assuntos
Acetilcisteína/administração & dosagem , Sequestradores de Radicais Livres/administração & dosagem , Doença de Raynaud/tratamento farmacológico , Administração Oral , Método Duplo-Cego , Feminino , Humanos , Masculino , Microcirculação , Pessoa de Meia-Idade , Doença de Raynaud/etiologia , Doença de Raynaud/fisiopatologia , Fluxo Sanguíneo Regional , Escleroderma Sistêmico/complicações
10.
Clinics (Sao Paulo) ; 68(6): 766-71, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23778483

RESUMO

OBJECTIVES: Hydroxychloroquine is an antimalarial agent that has been used in systemic lupus erythematosus and rheumatoid arthritis treatment for many years. Recently, novel mechanisms of action have been proposed, thereby broadening the therapeutic perspective of this medication. The purpose of this study was to evaluate the immunomodulatory activity of hydroxychloroquine in T helper 17 (Th17) cytokines in healthy individuals and patients. METHODS: Eighteen female patients with systemic lupus erythematosus (mean age 39.0±12.9 years) and 13 female patients with rheumatoid arthritis (mean age 51.5±7.7 years) were recruited from Universidade Federal de Pernambuco-Brazil. The patients were included after fulfilling four classification criteria for systemic lupus erythematosus or rheumatoid arthritis from the American College of Rheumatology. After being stimulated with phorbol 12-myristate 13-acetate and ionomycin in the absence or presence of different concentrations of hydroxychloroquine, the interleukin 6, 17 and 22 levels were quantified with an enzyme-linked immunosorbent assay in culture supernatants of peripheral blood mononuclear cells from healthy individuals and patients. RESULTS: We demonstrated that in peripheral blood mononuclear cells from healthy volunteers and in systemic lupus erythematosus and rheumatoid arthritis patients, there was a significant reduction in the IL-6, IL-17 and IL-22 supernatant levels after adding hydroxychloroquine. CONCLUSIONS Our in vitro results demonstrated that hydroxychloroquine inhibits IL-6, IL-17 and IL-22 production and contributes to a better understanding of the mechanism of action of this medication.


Assuntos
Antimaláricos/farmacologia , Artrite Reumatoide/sangue , Hidroxicloroquina/farmacologia , Interleucinas/sangue , Lúpus Eritematoso Sistêmico/sangue , Células Th17/efeitos dos fármacos , Adulto , Idoso , Antimaláricos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Estudos de Casos e Controles , Contagem de Células , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Interleucina-17/sangue , Interleucina-6/sangue , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Células Th17/imunologia , Adulto Jovem , Interleucina 22
11.
J Rheumatol ; 39(7): 1320-5, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22589261

RESUMO

OBJECTIVE: To analyze the role of interleukin 22 (IL-22) in rheumatoid arthritis (RA). METHODS: IL-22 serum levels were measured in 83 patients with established RA under treatment with disease-modifying antirheumatic drugs and in 30 healthy controls matched for age and sex. Patients were assessed for clinical and laboratory variables. Correlations of IL-22 serum levels with disease activity measures [Clinical Disease Activity Index (CDAI) and Disease Activity Score for 28 joints (DAS28)], serological markers, bone erosions, and demographic factors were assessed. Peripheral blood mononuclear cells (PBMC) from 30 patients with RA and 14 controls were purified and stimulated in vitro with phorbol myristate acetate (PMA)/ionomycin. IL-22 production by PBMC and in serum was investigated by ELISA. RESULTS: IL-22 levels were increased in patients with RA compared with controls (mean 432.37 pg/ml and 67.45 pg/ml, respectively; p < 0.001). Levels of IL-22 correlated with DAS28 and CDAI measures. Rheumatoid factor (RF) positivity was correlated with higher levels of IL-22 in patients with RA (mean 575.08 pg/ml; p = 0.001). The presence of bone erosions was associated with high IL-22 levels (p = 0.0001). PBMC stimulated with PMA/ionomycin expressed higher levels of IL-22 in patients with RA than controls but this was not significant (mean 584.75 pg/ml and 295.57 pg/ml; p = 0.553). CONCLUSION: IL-22 is elevated in the serum of patients with established RA. Elevated serum IL-22 allows discrimination between patients with different clinical and laboratory measures and indicates the potential of IL-22 as an additional tool for assessment of activity in RA, particularly in patients with RF antibodies and longterm disease. IL-22 is associated with bone-destructive disease.


Assuntos
Artrite Reumatoide/sangue , Interleucinas/sangue , Adulto , Idoso , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Ionóforos de Cálcio/farmacologia , Carcinógenos/farmacologia , Células Cultivadas , Progressão da Doença , Feminino , Humanos , Ionomicina/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Osteólise/sangue , Osteólise/tratamento farmacológico , Fator Reumatoide/sangue , Índice de Gravidade de Doença , Acetato de Tetradecanoilforbol/farmacologia , Interleucina 22
12.
Rev. bras. reumatol ; 54(6): 452-458, Nov-Dec/2014. tab, graf
Artigo em Português | LILACS | ID: lil-731266

RESUMO

Objetivo Avaliar a segurança e a eficácia da N-acetilcisteína (NAC) por via oral sobre o fluxo sanguíneo da microcirculação digital em pacientes com fenômeno de Raynaud (FRy) secundário à esclerose sistêmica (ES). Métodos Este foi um estudo randomizado, duplo-cego e placebo-controlado, no qual 42 pacientes com ES receberam NAC oral na dose de 600 mg, três vezes ao dia (21 pacientes, idade média 45,6±9,5 anos) ou placebo (21 pacientes, idade média 45,0±12,7 anos) durante quatro semanas. O desfecho primário do estudo foi: melhora no fluxo sanguíneo da microcirculação cutânea antes e após estímulo frio avaliado pelo laser Doppler imaging (LDI) nas semanas 0 e 4. A frequência e a gravidade do FRy e o número de úlceras digitais também foram avaliados nas semanas 0 e 4. Os efeitos adversos foram registrados na quarta semana. Resultados Não houve mudança significativa no fluxo sanguíneo digital avaliado pelo LDI antes ou depois do estímulo frio após quatro semanas de NAC ou placebo. Ambos os grupos apresentaram melhora significativa na frequência e gravidade dos ataques de FRy, sem diferença entre os dois. O grupo placebo apresentou três úlceras digitais enquanto o grupo NAC não apresentou úlceras ao final do estudo. NAC foi bem tolerada e nenhum paciente descontinuou o tratamento. Conclusões NAC por via oral na dose de 1.800mg/dia não demonstrou efeito vasodilatador sobre a microcirculação das mãos após quatro semanas de tratamento em pacientes com FRy secundário à ES. .


Objective To evaluate the safety and efficacy of oral N-acetylcysteine (NAC) on digital microcirculation blood flow in patients with Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc). Methods This was a randomized, double-blind, placebo-controlled trial in which 42 patients with SSc received oral NAC at a dose of 600mg tid (21 patients, mean age 45.6±9.5 years) or placebo (21 patients, mean age 45.0±12.7 years) for four weeks. The primary endpoint was the change in cutaneous microcirculation blood flow before and after cold stimulation measured by laser Doppler imaging (LDI) at weeks 0 and 4. The frequency and severity of RP and the number of digital ulcers were also measured at weeks 0 and 4. The adverse events were recorded in the fourth week. Results There was no significant change in digital blood flow assessed by LDI before or after cold stimulus after four weeks of NAC or placebo. Both groups showed significant improvement in the frequency and severity of RP attacks, with no difference between the two groups. At the end of the study, the placebo group had three digital ulcers, while the NAC group showed no ulcers. NAC was well tolerated and no patient discontinued the treatment. Conclusions NAC orally at a dose of 1800mg/day showed no vasodilator effect on hands’ microcirculation after four weeks of treatment in patients with RP secondary to SSc. .


Assuntos
Humanos , Masculino , Feminino , Acetilcisteína/administração & dosagem , Doença de Raynaud/tratamento farmacológico , Sequestradores de Radicais Livres/administração & dosagem , Doença de Raynaud/etiologia , Doença de Raynaud/fisiopatologia , Fluxo Sanguíneo Regional , Escleroderma Sistêmico/complicações , Método Duplo-Cego , Administração Oral , Microcirculação , Pessoa de Meia-Idade
13.
Clinics ; 68(6): 766-771, jun. 2013. tab, graf
Artigo em Inglês | LILACS | ID: lil-676937

RESUMO

OBJECTIVES: Hydroxychloroquine is an antimalarial agent that has been used in systemic lupus erythematosus and rheumatoid arthritis treatment for many years. Recently, novel mechanisms of action have been proposed, thereby broadening the therapeutic perspective of this medication. The purpose of this study was to evaluate the immunomodulatory activity of hydroxychloroquine in T helper 17 (Th17) cytokines in healthy individuals and patients. METHODS: Eighteen female patients with systemic lupus erythematosus (mean age 39.0±12.9 years) and 13 female patients with rheumatoid arthritis (mean age 51.5±7.7 years) were recruited from Universidade Federal de Pernambuco-Brazil. The patients were included after fulfilling four classification criteria for systemic lupus erythematosus or rheumatoid arthritis from the American College of Rheumatology. After being stimulated with phorbol 12-myristate 13-acetate and ionomycin in the absence or presence of different concentrations of hydroxychloroquine, the interleukin 6, 17 and 22 levels were quantified with an enzyme-linked immunosorbent assay in culture supernatants of peripheral blood mononuclear cells from healthy individuals and patients. RESULTS: We demonstrated that in peripheral blood mononuclear cells from healthy volunteers and in systemic lupus erythematosus and rheumatoid arthritis patients, there was a significant reduction in the IL-6, IL-17 and IL-22 supernatant levels after adding hydroxychloroquine. CONCLUSIONS Our in vitro results demonstrated that hydroxychloroquine inhibits IL-6, IL-17 and IL-22 production and contributes to a better understanding of the mechanism of action of this medication. .


Assuntos
Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Antimaláricos/farmacologia , Artrite Reumatoide/sangue , Hidroxicloroquina/farmacologia , Interleucinas/sangue , Lúpus Eritematoso Sistêmico/sangue , /efeitos dos fármacos , Antimaláricos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Estudos de Casos e Controles , Contagem de Células , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Hidroxicloroquina/uso terapêutico , /sangue , /sangue , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Estatísticas não Paramétricas , /imunologia
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