RESUMO
Juvenile-onset systemic lupus erythematosus (JSLE) presents with an aggressive course and high morbidity associated with disease and treatment. JSLE patients have a poorer health-related quality of life (HRQoL) when compared with age-matched patients with other rheumatologic disorders. We aim to summarize the impact of current pharmacological therapies on the HRQoL of JSLE patients. Search strategies were developed across seven databases. Randomized clinical trials (RCTs) and cohort studies comparing interventions to standard therapy, placebo or pre-post cohort comparisons for more than 4 weeks were included. The outcome included self-reported scales compared at baseline and a therapeutic time point. Risk of bias was evaluated by using the Cochrane risk of bias tool and the Newcastle-Ottawa quality assessment scale. A total of 2812 articles were narrowed down to 309 for full-text screening. Four RCTs and one prospective cohort study, with a total of 634 JSLE patients, met the inclusion criteria. Four of the studies had a controlled intervention plus standard therapy compared with standard therapy alone or placebo. Multiple indices were used to evaluate HRQoL. These included the Pediatric Quality of Life Inventory, Childhood Health Assessment Questionnaire, Simple Measure of Impact of Lupus Erythematosus in Youngsters tool, Kids Fatigue Severity Scale and Child Depression Inventory. A single study reported a significant improvement while remaining studies reported no difference or failed to report the statistical analysis. Although HRQoL is significantly impaired in JSLE, evidence regarding its improvement is limited due to the small number of eligible studies, heterogeneity in scales, and HRQoL domains. A universal HRQoL questionnaire for JSLE needs to be established and used in both the research and clinical setting. All studies should adhere to reporting guidelines.
Assuntos
Antirreumáticos/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Qualidade de Vida , Adolescente , Idade de Início , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de DoençaRESUMO
A large enhancement of the magnetic anisotropy of Ni nanowires (NWs) embedded in anodic aluminium oxide porous membranes is obtained as a result of an induced magnetoelastic (ME) anisotropy contribution. This unusual large anisotropy enhancement depends on the diameter of the NWs and exceeds the magnetostatic (MS) contribution. As a consequence, it leads to effective magnetic anisotropy energies as large as 1.4 × 10(6) erg cm(-3), which are of the same order of magnitude and comparable to the MS energies of harder magnetic materials like Co NWs. Specifically, from ferromagnetic resonance experiments, the magnetic anisotropy of the NWs has been observed to increase as its diameter is decreased, leading to values that are about four times larger than the corresponding value when only the MS anisotropy is present. Our results are consistent with the recently proposed growth mechanism of Ni NWs that proceeds via a poly-crystalline stage at the bottom followed by a single-crystalline stage with texture [110] parallel to the axis of the NWs. A strong correlation between reducing the diameter of the NWs with the decrease of the length of the poly-crystalline segment and the enhancement of the effective magnetic anisotropy has been shown. Magnetization curves obtained from alternating gradient magnetometry experiments show that the average ME anisotropy results from the competition between the magnetic anisotropies of both crystalline segments of the NWs. Understanding the influence of size and confinement effects on the magnetic properties of nanocomposites is of prime interest for the development of novel and agile devices.
RESUMO
OBJECTIVE: To determine the extent of mitochondrial DNA (mtDNA) damage in systemic lupus erythematosus (SLE) patients compared to healthy subjects and to determine the factors associated with mtDNA damage among SLE patients. METHODS: A cross-sectional study was performed in 86 SLE patients (per American College of Rheumatology classification criteria) and 86 healthy individuals matched for age and gender. Peripheral blood mononuclear cells (PBMCs) were collected from subjects to assess the relative amounts of mtDNA damage. Quantitative polymerase chain reaction assay was used to measure the frequency of mtDNA lesions and mtDNA abundance. Socioeconomic-demographic features, clinical manifestations, pharmacologic treatment, disease activity, and damage accrual were determined. Statistical analyses were performed using t test, pairwise correlation, and Pearson's chi-square test (or Fisher's exact test) as appropriate. RESULTS: Among SLE patients, 93.0% were women. The mean (SD) age was 38.0 (10.4) years and the mean (SD) disease duration was 8.7 (7.5) years. SLE patients exhibited increased levels of mtDNA damage as shown by higher levels of mtDNA lesions and decreased mtDNA abundance as compared to healthy individuals. There was a negative correlation between disease damage and mtDNA abundance and a positive correlation between mtDNA lesions and disease duration. No association was found between disease activity and mtDNA damage. CONCLUSION: PBMCs from SLE patients exhibited more mtDNA damage compared to healthy subjects. Higher levels of mtDNA damage were observed among SLE patients with major organ involvement and damage accrual. These results suggest that mtDNA damage have a potential role in the pathogenesis of SLE.
Assuntos
Dano ao DNA , DNA Mitocondrial/metabolismo , Leucócitos Mononucleares/metabolismo , Lúpus Eritematoso Sistêmico/fisiopatologia , Adulto , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Índice de Gravidade de Doença , Fatores de TempoRESUMO
OBJECTIVES: We sought to determine the effect of statin therapy on the levels of proinflammatory/prothrombotic markers and disease activity scores in patients with SLE in a multi-ethnic, multi-centre cohort (LUMINA). METHODS: Plasma/serum samples from SLE patients placed on statins (n=21) therapy taken before and after at least 6 months of treatment were tested. Disease activity was assessed using SLAM-R scores. Interleukin (IL)-1ß, IL-6, IL-8, tumour necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF) and soluble CD40 ligand (sCD40L) levels were determined by a multiplex immunoassay. Soluble intercellular cell adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1 and anticardiolipin (aCL) antibodies were evaluated using ELISA assays while high sensitivity C-reactive protein (hsCRP) was assessed by nephelometry. Plasma/serum samples from frequency- matched healthy donors were used as controls. RESULTS: Levels of IL-6, VEGF, sCD40L and TNF-α were significantly elevated in SLE patients versus controls. Statin therapy resulted in a significant decrease in SLAM-R scores (p=0.0199) but no significant changes in biomarker levels were observed. There was no significant association of biomarkers with SLAM-R scores. CONCLUSIONS: Statin therapy resulted in significant clinical improvement in SLE patients, underscoring the use of statins in the treatment of SLE.
Assuntos
Biomarcadores/sangue , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Lúpus Eritematoso Sistêmico , Adulto , Proteína C-Reativa/análise , Ligante de CD40/sangue , Etnicidade , Feminino , Humanos , Molécula 1 de Adesão Intercelular/sangue , Interleucinas/sangue , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Gravidade do Paciente , Porto Rico/epidemiologia , Projetos de Pesquisa , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangue , Estados Unidos/epidemiologia , Molécula 1 de Adesão de Célula Vascular/sangueRESUMO
Glucocorticoid sensitivity can be measured in vitro using the lymphocyte sensitivity assay (LSA). In this test, dexamethasone is used to inhibit the proliferation of peripheral blood mononuclear cells (PBMC) in response to mitogens. If the proliferation of PBMC is suppressed the subjects are considered to be GC sensitive; if not, they are considered to be resistant. The LSA has been used to test GC sensitivity in some inflammatory diseases but its clinical value in systemic lupus erythematosus (SLE) has not been determined. Herein, we present the results of the LSA from two sisters with SLE who had different disease outcomes. Patient 1 presented with higher disease activity and damage accrual, and poorer response to corticosteroids than patient 2. In the LSA, patient 1 had a lower dexamethasone suppression of mitogen-stimulated PBMC than patient 2 and one control subject. The LSA could be helpful in identifying patients with GC resistance, thus allowing the consideration of alternative immunosuppressive drugs.
Assuntos
Glucocorticoides/farmacologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Ativação Linfocitária/efeitos dos fármacos , Adulto , Resistência a Medicamentos , Feminino , Glucocorticoides/uso terapêutico , Humanos , Adulto JovemRESUMO
There are few cases of Guillain-Barré syndrome (GBS), particularly of atypical variants, occurring in association with systemic lupus erythematous (SLE). Reports addressing a specific therapy thus remain almost anecdotal. It is therefore challenging to determine the treatment that is best suited for this subset of patients, especially if initial conventional therapy for GBS fails. We present two cases of GBS-like acute axonal neuropathies, one with acute motor axonal neuropathy (AMAN), and another with acute motor sensory axonal neuropathy (AMSAN), presenting early in the course of SLE. The first case failed to respond to therapy with intravenous immunoglobulins (IVIG) and plasmapheresis, but achieved a favorable outcome when high-dose glucocorticoids along with low-dose intravenous (IV) cyclophosphamide pulses were given. The second case responded favorably to high-dose glucocorticoids, IVIG, and low-dose IV cyclophosphamide pulses. Both patients have remained in clinical remission and without neurologic sequelae after 10 and three years of follow-up, respectively.
Assuntos
Ciclofosfamida/administração & dosagem , Síndrome de Guillain-Barré/tratamento farmacológico , Imunossupressores/administração & dosagem , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Polineuropatias/tratamento farmacológico , Adulto , Feminino , Síndrome de Guillain-Barré/diagnóstico , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Polineuropatias/diagnóstico , Adulto JovemRESUMO
The coexistence of human immunodeficiency virus (HIV) infection and systemic lupus erythematosus (SLE) is unusual, but the occurrence of SLE after HIV infection is even less common. Both conditions share similar clinical features including constitutional symptoms, facial rash, oral ulcers, alopecia, arthralgias, arthritis, seizures, cytopenias, glomerulonephritis, and antinuclear and antiphospholipid antibodies. This clinical overlap makes the diagnosis of SLE in a patient with pre-existing HIV infection difficult. Furthermore, immune complex glomerulonephritis with features resembling lupus nephritis has been described in HIV-positive patients. We present the case of a 45-year-old Hispanic woman with long-standing HIV infection who developed membranous glomerulonephritis with histological features of lupus nephritis. Five years after onset of renal disease she developed clinically evident SLE.
Assuntos
Glomerulonefrite Membranosa/patologia , Infecções por HIV/complicações , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Feminino , Glomerulonefrite Membranosa/etiologia , Infecções por HIV/tratamento farmacológico , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Pessoa de Meia-IdadeRESUMO
We have previously developed and validated a self-administered questionnaire, modelled after the Systemic Lupus International Collaborating Clinics Damage Index (SDI), the Lupus Damage Index Questionnaire (LDIQ), which may allow the ascertainment of this construct in systemic lupus erythematosus (SLE) patients followed in the community and thus expand observations made about damage. We have now translated, back-translated and adapted the LDIQ to Spanish, Portuguese and French and applied it to patients followed at academic and non-academic centres in North and South America, Portugal and Spain while their physicians scored the SDI. A total of 887 patients (659 Spanish-speaking, 140 Portuguese-speaking and 80 French-speaking patients) and 40 physicians participated. Overall, patients scored all LDIQ versions higher than their physicians (total score and all domains). Infrequent manifestations had less optimal clinimetric properties but overall agreement was more than 95% for the majority of items. Higher correlations were observed among the Spanish-speaking patients than the Portuguese-speaking and French-speaking patients; further adjustments may be needed before the Portuguese and French versions of the LDIQ are applied in community-based studies. The relationship between the LDIQ and other outcome parameters is currently being investigated in a different patient sample.
Assuntos
Idioma , Lúpus Eritematoso Sistêmico , Inquéritos e Questionários , Adulto , Feminino , Inquéritos Epidemiológicos , Humanos , Lúpus Eritematoso Sistêmico/patologia , Lúpus Eritematoso Sistêmico/fisiopatologia , América do Norte , Portugal , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , América do Sul , Espanha , Inquéritos e Questionários/normasRESUMO
INTRODUCTION: Posttransplant lymphoproliferative disorder (PTLD) constitutes a heterogeneous group of diseases. We summarize the experience of our hospital, one of Spain's largest series of renal (294), liver (47) and allogeneic stem cell transplants (67), where four cases of PTLD have developed related to complex viral infections. METHODS: Case 1 was a 24-month-old boy diagnosed with acute lymphoblastic leukemia who underwent allogeneic stem-cell transplantation (SCT). He was seropositive for Epstein-Barr virus (EBV) and developed an aggressive Bcell non-Hodgkin's lymphoma (B-NHL) related to EBV reactivation and human herpesvirus 6 (HHV-6) infection. Cases 2, 3, and 4 developed after kidney transplantation and were all EBV seronegative. Case 2 had associated cytomegalovirus (CMV) and EBV infection. Cases 3 and 4 only revealed EBV viral load. Cases 1, 3, and 4 progressed rapidly, with fatal outcome. Global incidence of PTLD in our series is 1.1%. CONCLUSION: PTLD is a rare but life-threatening condition. Although EBV plays a clear role in its pathogenesis, other associated viral infections could trigger this situation. Current therapies include rituximab, decreasing immunosuppressive drugs. and conventional chemotherapy.
Assuntos
Transtornos Linfoproliferativos/virologia , Complicações Pós-Operatórias/virologia , Infecções Tumorais por Vírus/virologia , Viroses/complicações , Criança , Pré-Escolar , Citomegalovirus , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/epidemiologia , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/epidemiologia , Herpesvirus Humano 4 , Humanos , Lactente , Recém-Nascido , Transplante de Rim/efeitos adversos , Masculino , Transplante de Células-Tronco/efeitos adversos , Infecções Tumorais por Vírus/complicações , Infecções Tumorais por Vírus/epidemiologia , Carga Viral , Viroses/epidemiologiaRESUMO
The aim of this study was to determine the factors associated with metabolic syndrome in patients with systemic lupus erythematosus from Puerto Rico. A total of 204 patients with systemic lupus erythematosus (per the American College of Rheumatology classification criteria) were evaluated. Metabolic syndrome was assessed using the American Heart Association and the National Heart, Lung, and Blood Institute classification. Socioeconomic-demographic parameters, health-related behaviours, clinical manifestations, autoantibodies, pharmacological treatments, disease activity (per the Systemic Lupus Activity Measure--Revised), and damage accrual (per the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) were determined at study visit. Factors associated with metabolic syndrome were examined by univariable analyses and multivariable logistic regression models. A total of 196 (96.2%) were women. The mean age at study visit was 43.6 +/- 13.0 years, and the mean disease duration was 8.7 +/- 7.7 years. Seventy-eight patients (38.2%) had metabolic syndrome. In the multivariable analysis, age (odds ratio [OR] = 1.05; 95% confidence interval [CI] 1.02-1.09), government health insurance (OR = 2.06; 95% CI 1.07-4.22), exercise (OR = 0.33; 95% CI 0.14-0.92), thrombocytopenia (OR = 4.19; 95% CI 1.54-11.37), erythrocyte sedimentation rate (OR = 1.64; 95% CI 1.03-2.63), disease activity (OR = 1.14; 95% CI 1.00-1.30), and prednisone >10 mg/day (OR = 3.69; 95% CI 1.22-11.11) were associated with metabolic syndrome. In conclusion, older age, low socioeconomic status, lack of exercise, thrombocytopenia, increased erythrocyte sedimentation rate , higher disease activity, and prednisone >10 mg/day were independently associated with metabolic syndrome in patients with systemic lupus erythematosus from Puerto Rico.
Assuntos
Lúpus Eritematoso Cutâneo/complicações , Síndrome Metabólica/etiologia , Adulto , Distribuição por Idade , Feminino , Humanos , Incidência , Lúpus Eritematoso Cutâneo/epidemiologia , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Porto Rico/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Distribuição por Sexo , Fatores SocioeconômicosRESUMO
OBJECTIVE: To determine the features associated with acute onset systemic lupus erythaematosus (SLE). METHODS: A total of 631 SLE patients from LUMINA (for "lupus in minority populations: nature vs nurture"), a multiethnic (Hispanics, African-Americans and Caucasians) cohort, were studied. Acute disease onset was defined as the accrual of > or = 4 American College of Rheumatology (ACR) criteria for the classification of SLE in < or = 4 weeks. Socioeconomic demographic features, clinical manifestations, disease activity, damage accrual, mortality, autoantibodies, HLA class II and FCGR alleles, behavioural/psychological variables were compared between patients with acute and insidious disease onset by univariable (chi(2) and Student t test) and multivariable (stepwise logistic regression) analyses. RESULTS: A total of 94 (15%) patients had acute disease onset. In the multivariable analysis, patients with acute onset lupus had more renal involvement (odds ratio (OR) = 1.845, 95% CI 1.076-3.162; p = 0.026) and higher disease activity (OR = 1.057, 95% CI 1.005-1.112; p = 0.030). By contrast, age (OR = 0.976, 95% CI 0.956-0.997; p = 0.025), education (OR = 0.901, 95% CI 0.827-0.983, p = 0.019), health insurance (OR = 0.423, 95% CI 0.249-0.718; p = 0.001) and skin involvement (OR = 0.346, 95% CI 0.142-0.843; p = 0.019) were negatively associated with acute onset lupus. No differences were found regarding the serological, genetic and behavioural/psychological features; this was also the case for damage accrual and mortality. CONCLUSIONS: Patients with acute onset lupus seem to be younger, have a lower socio-economic status and display more severe disease in terms of clinical manifestations and disease activity. However, intermediate (damage) and long-term (mortality) outcomes appear not to be influenced by the type of disease onset in SLE.
Assuntos
Lúpus Eritematoso Sistêmico/diagnóstico , Doença Aguda , Adulto , Fatores Etários , Métodos Epidemiológicos , Feminino , Humanos , Lúpus Eritematoso Sistêmico/etnologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Índice de Gravidade de Doença , Fatores Socioeconômicos , Estados Unidos/epidemiologiaRESUMO
The objective of this study was to determine the factors predictive of time to the occurrence of pulmonary damage in systemic lupus erythematosus (SLE). Six-hundred and twenty-six SLE patients from a multiethnic (Hispanics, African Americans and Caucasians) longitudinal study of outcome were studied. Pulmonary damage was defined as per the Systemic Lupus International Collaborating Clinics Damage Index. Socioeconomic-demographic, clinical, genetic, serological features, pharmacologic treatments, behavioural, psychological and disease activity [as per the Systemic Lupus Activity Measure-Revised (SLAM-R)] were examined. Factors associated with time to the occurrence of pulmonary damage were examined by Cox proportional hazards regressions. A Kaplan-Meier survival curve was also examined. Forty-six (7.3%) patients had pulmonary damage after a mean (SD) total disease duration of 5.3 (3.6) years. Among those patients, 25 had pulmonary fibrosis, 12 pulmonary hypertension, eight pleural fibrosis, four pulmonary infarction and four shrinking lung syndrome. Seven patients had more than one type of lung damage. Cumulative rates of pulmonary damage at five and 10 years were 7.6% and 11.6%, respectively. In the multivariable analyses, age (HR = 1.033, 95% CI 1.006-1.060; P = 0.0170), pneumonitis (HR = 2.307, 95% CI 1.123-4.739; P = 0.0229) and anti-RNP antibodies (HR = 2.344, 95% CI 1.190-4.618; P = 0.0138) were associated with a shorter time to the occurrence of pulmonary damage while photosensitivity (HR = 0.388, 95% CI 0.184-0.818; P = 0.0128) and oral ulcers (HR = 0.466, 95% CI 0.230-0.942; P = 0.0335) with a longer time. Pulmonary damage is relatively common in SLE. Age, pneumonitis and anti-RNP antibodies were associated with a shorter time to the development of permanent lung disease.
Assuntos
Negro ou Afro-Americano , Hispânico ou Latino , Pneumopatias/etiologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/etnologia , População Branca , Adulto , Fatores Etários , Autoanticorpos/sangue , Autoantígenos/imunologia , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pneumonia/complicações , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Análise de Sobrevida , Fatores de Tempo , Estados Unidos , Proteínas Centrais de snRNPRESUMO
OBJECTIVE: To determine the impact of pregnancy on systemic lupus erythematosus (SLE) outcome. METHODS: SLE patients, age >or=16 yrs, disease duration Assuntos
Lúpus Eritematoso Sistêmico
, Complicações na Gravidez
, Transtornos Puerperais/etiologia
, Adulto
, Negro ou Afro-Americano/estatística & dados numéricos
, Métodos Epidemiológicos
, Feminino
, Hispânico ou Latino/estatística & dados numéricos
, Humanos
, Lúpus Eritematoso Sistêmico/etnologia
, Gravidez
, Complicações na Gravidez/etnologia
, Resultado da Gravidez
, Transtornos Puerperais/etnologia
, Porto Rico/epidemiologia
, Índice de Gravidade de Doença
, Fatores Socioeconômicos
, Estados Unidos/epidemiologia
, População Branca/estatística & dados numéricos
RESUMO
The aim of this study was to determine the association between lupus autoantibodies and the clinical manifestations and outcome in a cohort of Puerto Ricans patients with systemic lupus erythematosus (SLE). All patients fulfilled the American College of Rheumatology classification criteria for SLE. Demographic parameters, clinical manifestations over time and damage accrual were obtained at the last study visit. Disease damage was assessed with the Systemic Lupus International Collaborating Clinics Damage Index (SDI). ANA, ANA pattern, and anti-dsDNA, anti-Smith, anti-Ro (SSA), anti-La (SSB) and anti-snRNP antibodies were measured at the time of SLE diagnosis. Chi-square test, Fisher exact test, ANOVA, logistic regression and general lineal model analyses were used to evaluate these associations. Ninety-six percent of patients were females. The cohort had a mean age of 40.2 +/- 12.0 years and mean disease duration of 9.6 +/- 7.0 years. Patients with elevated anti-dsDNA antibodies were more likely to have vasculitis, pericardial effusion, renal involvement, anaemia, leukopenia, lymphopenia and thrombocytopenia. Anti-Smith antibodies were positively associated with skin ulcerations, elevated liver enzymes, renal involvement and thrombocytopenia. Anti-Ro antibodies were related with the presence of discoid lupus, serositis, pneumonitis, elevated liver enzymes, hemolytic anaemia, leukopenia and lymphopenia. No positive associations were found for anti-snRNP or anti-La antibodies. The presence of anti-dsDNA, anti-Smith and anti-Ro antibodies was associated with higher SDI scores. In conclusion, anti-dsDNA, anti-Smith and anti-Ro antibodies are associated with several clinical manifestations and more damage accrual in Puerto Ricans with SLE. These findings provide valuable clinical and prognostic information for this ethnic population.
Assuntos
Autoanticorpos/sangue , Hispânico ou Latino , Lúpus Eritematoso Sistêmico/etnologia , Lúpus Eritematoso Sistêmico/imunologia , Adulto , Autoantígenos/imunologia , Estudos de Coortes , DNA/imunologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Prognóstico , Porto Rico , Ribonucleoproteínas/imunologia , Ribonucleoproteínas Nucleares Pequenas/imunologia , Proteínas Centrais de snRNP , Antígeno SS-BRESUMO
Enzymatic activity was analyzed in the soleus, gastrocnemius (red and white) and plantaris muscles of acutely exercised rats after long-term administration of Panax ginseng extract in order to evaluate the protective role of ginseng against skeletal muscle oxidation. Ginseng extract (3, 10, 100, or 500 mg/kg) was administered orally for three months to male Wistar rats weighing 200 ± 50 g before exercise and to non-exercised rats (N = 8/group). The results showed a membrane stabilizing capacity of the extract since mitochondrial function measured on the basis of citrate synthase and 3-hydroxyacyl-CoA dehydrogenase activities was reduced, on average, by 20 percent (P < 0.05) after exercise but the activities remained unchanged in animals treated with a ginseng dose of 100 mg/kg. Glutathione status did not show significant changes after exercise or treatment. Lipid peroxidation, measured on the basis of malondialdehyde levels, was significantly higher in all muscles after exercise, and again was reduced by about 74 percent (P < 0.05) by the use of ginseng extract. The administration of ginseng extract was able to protect muscle from exercise-induced oxidative stress irrespective of fiber type.
Assuntos
Animais , Masculino , Ratos , Antioxidantes/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Mitocôndrias Musculares/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Condicionamento Físico Animal , Panax/química , /metabolismo , Antioxidantes/administração & dosagem , Citrato (si)-Sintase/metabolismo , Glutationa/efeitos dos fármacos , Glutationa/metabolismo , Malondialdeído/análise , Mitocôndrias Musculares/metabolismo , Músculo Esquelético/metabolismo , Extratos Vegetais/farmacologia , Ratos Wistar , Superóxido Dismutase/metabolismoRESUMO
Enzymatic activity was analyzed in the soleus, gastrocnemius (red and white) and plantaris muscles of acutely exercised rats after long-term administration of Panax ginseng extract in order to evaluate the protective role of ginseng against skeletal muscle oxidation. Ginseng extract (3, 10, 100, or 500 mg/kg) was administered orally for three months to male Wistar rats weighing 200 +/- 50 g before exercise and to non-exercised rats (N = 8/group). The results showed a membrane stabilizing capacity of the extract since mitochondrial function measured on the basis of citrate synthase and 3-hydroxyacyl-CoA dehydrogenase activities was reduced, on average, by 20% (P < 0.05) after exercise but the activities remained unchanged in animals treated with a ginseng dose of 100 mg/kg. Glutathione status did not show significant changes after exercise or treatment. Lipid peroxidation, measured on the basis of malondialdehyde levels, was significantly higher in all muscles after exercise, and again was reduced by about 74% (P < 0.05) by the use of ginseng extract. The administration of ginseng extract was able to protect muscle from exercise-induced oxidative stress irrespective of fiber type.
Assuntos
Antioxidantes/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Mitocôndrias Musculares/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Panax/química , Condicionamento Físico Animal , 3-Hidroxiacil-CoA Desidrogenases/metabolismo , Animais , Antioxidantes/administração & dosagem , Citrato (si)-Sintase/metabolismo , Glutationa/efeitos dos fármacos , Glutationa/metabolismo , Masculino , Malondialdeído/análise , Mitocôndrias Musculares/metabolismo , Músculo Esquelético/metabolismo , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismoRESUMO
OBJECTIVES: To compare the baseline clinical manifestations, immunological features, disease activity and damage accrual in systemic lupus erythematosus (SLE) patients from two US Hispanic subgroups. METHODS: A total of 105 Hispanic SLE patients from Texas (a population of Mexican or Central American ancestry) and 81 from the island of Puerto Rico (all Puerto Ricans) participating in a longitudinal study of outcome were examined. The socio-economic/demographic, clinical and immunological variables were obtained at the time of enrollment (T(0)). Disease activity was determined with the Systemic Lupus Activity Measure (SLAM), and disease damage with the Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (SDI). Disease activity was also determined at the time of diagnosis (T(D)). RESULTS: At T(0) Hispanics from Texas were younger than those from Puerto Rico (33.1 +/- 12.0 vs 37.5 +/- 11.6 yr, P = 0.0125). Both groups were similar with regard to gender distribution (92.4 vs 95.1% females) and disease duration (1.4 +/- 1.4 vs 1.7 +/- 1.3 yr). Hispanics from Texas were more likely to have serositis (60.0 vs 8.6%, P < 0.0001), renal involvement (41.0 vs 13.6%, P < 0.0001), psychosis (5.7 vs 0.0%, P = 0.0365) and thrombocytopenia (21.0 vs 3.7%, P = 0.0006). On the other hand, Hispanics from Puerto Rico were more likely to have photosensitivity (81.5 vs 41.0%, P < 0.0001), malar rash (65.4 vs 45.7%, P = 0.0074) and discoid rash (13.6 vs 2.9%, P = 0.0060). At baseline, the presence of anti-dsDNA antibodies was higher in Hispanics from Texas (69.5% vs 46.9%, P = 0.0018) while anti-Ro antibodies were more frequent in Hispanics from Puerto Rico (24.7 vs 11.4%, P = 0.0175). Mean SLAM scores at T(D) (12.9 +/- 6.4 vs 9.1 +/- 4.6, P < 0.0001) and T(0) (10.9 +/- 6.3 vs 6.6 +/- 3.8, P < 0.0001) were significantly higher in Hispanics from Texas. Similarly, mean SDI scores at T(0) were higher in Hispanics from Texas (0.67 +/- 1.08 vs 0.26 +/- 0.54, P = 0.0026). By stepwise Poisson regression, SDI scores were associated with older age, disease activity and ethnicity (Hispanics from Texas). CONCLUSIONS: Early in SLE, marked differences are observed between Hispanics from Texas and Puerto Rico. Higher disease activity, more major organ involvement, higher frequency of anti-dsDNA antibodies and more damage accrual occur in Hispanic lupus patients from Texas than in those from Puerto Rico.
Assuntos
Autoanticorpos/sangue , Hispânico ou Latino , Lúpus Eritematoso Sistêmico/etnologia , Adulto , Fatores Etários , Anticorpos Antinucleares/sangue , Feminino , Humanos , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/terapia , Masculino , Pessoa de Meia-Idade , Porto Rico , Análise de Regressão , Texas , Resultado do TratamentoRESUMO
Philodryas olfersii is found in South America, from Amazonas to Patagonia. It is important to characterize the venom of P. olfersii, who inhabits the North-East region of Argentina, since snake venoms are known to exhibit considerable variability in composition and biological activities. In this work, mice weighing 18-20 g (n = 4 for each experimental group) were used. For the edematogenic activity mice were injected s.c. in the right foot pad with 50 microl of solutions containing different amounts of venom, whereas the left foot pad was injected with 50 microl of PBS. Two hours after injection mice were killed by cervical dislocation and both feet were cut off and weighed individually. For the myotoxic activity mice were injected i.m. with 100 microl of solutions containing 40 microg of venom. Blood samples were extracted after 1, 3, 6, 8, 10, 12, 14, 16 and 24 h of venom injection to determinate serum CPK activity and mice were sacrificed at the same time intervals to obtain the inoculated gastrocnemius muscle. They were fixed with Bouin solution and stained with Hematoxylin-Eosin. Results showed that P. olfersii venom exhibits a high edematogenic activity (MED = 0.31 microg) and a moderate myotoxic activity. Myonecrosis reached its highest level after 12 h of venom injection as shown by plasmatic CPK levels (5,401 +/- 330 IU/l) and microscopic assay. It demonstrates the potential toxicity of the venom of P. olfersii, who inhabits the North-East region of Argentina. It also reinforces the original warning concerning the potential danger of bites by colubrids.
Assuntos
Colubridae/fisiologia , Edema/induzido quimicamente , Músculo Esquelético/efeitos dos fármacos , Venenos de Serpentes , Argentina , Colubridae/anatomia & histologia , Creatina Quinase/sangue , Edema/fisiopatologia , Glândulas Salivares/metabolismo , Glândulas Salivares , Hemorragia/induzido quimicamente , Hemorragia/fisiopatologia , Camundongos , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Necrose , Tempo de Reação/fisiologiaRESUMO
Philodryas olfersii is found in South America, from Amazonas to Patagonia. It is important to characterize the venom of P. olfersii, who inhabits the North-East region of Argentina, since snake venoms are known to exhibit considerable variability in composition and biological activities. In this work, mice weighing 18-20 g (n = 4 for each experimental group) were used. For the edematogenic activity mice were injected s.c. in the right foot pad with 50 microl of solutions containing different amounts of venom, whereas the left foot pad was injected with 50 microl of PBS. Two hours after injection mice were killed by cervical dislocation and both feet were cut off and weighed individually. For the myotoxic activity mice were injected i.m. with 100 microl of solutions containing 40 microg of venom. Blood samples were extracted after 1, 3, 6, 8, 10, 12, 14, 16 and 24 h of venom injection to determinate serum CPK activity and mice were sacrificed at the same time intervals to obtain the inoculated gastrocnemius muscle. They were fixed with Bouin solution and stained with Hematoxylin-Eosin. Results showed that P. olfersii venom exhibits a high edematogenic activity (MED = 0.31 microg) and a moderate myotoxic activity. Myonecrosis reached its highest level after 12 h of venom injection as shown by plasmatic CPK levels (5,401 +/- 330 IU/l) and microscopic assay. It demonstrates the potential toxicity of the venom of P. olfersii, who inhabits the North-East region of Argentina. It also reinforces the original warning concerning the potential danger of bites by colubrids. (AU)
Assuntos
Colubridae/fisiologia , Edema/induzido quimicamente , Músculo Esquelético/efeitos dos fármacos , Venenos de Serpentes/toxicidade , Argentina , Colubridae/anatomia & histologia , Creatina Quinase/sangue , Edema/fisiopatologia , Hemorragia/induzido quimicamente , Hemorragia/fisiopatologia , Camundongos , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Necrose , Tempo de Reação/fisiologia , Glândulas Salivares/metabolismo , Glândulas Salivares/metabolismoRESUMO
Variations in systemic lupus erythematosus (SLE) clinical manifestations, serologies and outcomes have been related to gender differences. However, these associations have not been evaluated in Puerto Ricans. A cross-sectional study was performed in a cohort of 235 Puerto Rican SLE patients. Clinical variables, autoantibodies, SLICC/ACR damage index and mortality rate were determined. Of the 235 SLE patients, 12 (5%) were males. Male and female patients were similar with respect to age, disease duration and follow up. Men were more likely to have pericardial effusion (41% vs 5%, p<0.01), pleural effusion (58% vs 10%, p<0.01), proteinuria (>0.5 g/24 hr) (58% vs 24%, p=0.02), renal insufficiency (42% vs 11%, p<0.01) and end-stage renal disease (33% vs 6%, p<0.01) than women. Anti-Sm antibodies (60.0% vs 13%, p<0.01) and anti-snRNP antibodies (56% vs 21%, p=0.03) were more prevalent in men. SLICC/ACR mean damage index (2.7 +/- 2.7 vs 1.0 +/- 1.6, p<0.01) and mortality rate (25% vs 4.5%, p=0.02) were higher in men. In conclusion, male SLE patients of this cohort had higher prevalence of serositis and renal involvement than women. They also had a poorer outcome, presenting higher disease damage and mortality.