Estresse oxidativo no lúpus eritematoso sistêmico / Oxidative stress in systemic lupus erythematosus

O lúpus eritematoso sistêmico (LES) é uma doença inflamatória crônica caracterizada pela elevada presença de autoanticorpos e por comprometer diversos órgãos e sistemas. O estresse oxidativo celular está envolvido no desenvolvimento das várias características clínicas observadas nesta doença, além de apresentar importante relação com a sua gênese e patogênese. Neste contexto, esse trabalho tem como objetivo fazer umlevantamento bibliográfico das principais moléculas envolvidas no estresse oxidativo no LES e correlacionar seus efeitos no acompanhamento da evolução e patogênese dessa doença, como ferramentas de diagnóstico e prognóstico. Os marcadores de estresse oxidativo mais comuns encontrados foram o malondialdeído, o 4-hidroxi-nonenal, a 8-hidroxideoxiguanosina, o radical hidroxila, o óxido nítrico, além da substância glutationa e enzimas antioxidantes, glutationa peroxidase, catalase e superóxido dismutase. Sendo assim, embora apareçam algumas divergências entre a correlação de alguns marcadoresde estresse oxidativo com a atividade da doença, a maioria dos estudos mostrou importante relação desses marcadores com o desenvolvimento e agravamento do LES. Apesar danecessidade de estudos longitudinais, podemos sugerir grande potencial das moléculas de estresse oxidativo como ferramenta no diagnóstico e prognóstico no LES.

Severity of chronic experimental Chagas' heart disease parallels tumour necrosis factor and nitric oxide levels in the serum: models of mild and severe disease

Heart tissue inflammation, progressive fibrosis and electrocardiographic alterations occur in approximately 30% of patients infected by Trypanosoma cruzi, 10-30 years after infection. Further, plasma levels of tumour necrosis factor (TNF) and nitric oxide (NO) are associated with the degree of heart dysfunction in chronic chagasic cardiomyopathy (CCC). Thus, our aim was to establish experimental models that mimic a range of parasitological, pathological and cardiac alterations described in patients with chronic Chagas’ heart disease and evaluate whether heart disease severity was associated with increased TNF and NO levels in the serum. Our results show that C3H/He mice chronically infected with the Colombian T. cruzi strain have more severe cardiac parasitism and inflammation than C57BL/6 mice. In addition, connexin 43 disorganisation and fibronectin deposition in the heart tissue, increased levels of creatine kinase cardiac MB isoenzyme activity in the serum and more severe electrical abnormalities were observed in T. cruzi-infected C3H/He mice compared to C57BL/6 mice. Therefore, T. cruzi-infected C3H/He and C57BL/6 mice represent severe and mild models of CCC, respectively. Moreover, the CCC severity paralleled the TNF and NO levels in the serum. Therefore, these models are appropriate for studying the pathophysiology and biomarkers of CCC progression, as well as for testing therapeutic agents for patients with Chagas’ heart disease.

Achados bucais e laboratoriais em pacientes com lúpus eritematoso sistêmico / Oral and laboratorial findings in patients with systemic lupus erythematosus

INTRODUÇÃO: O lúpus eritematoso sistêmico (LES) é uma doença inflamatória crônica caracterizada por manifestações clínicas variadas. Os poucos trabalhos existentes na literatura relatam uma prevalência entre 6,5 por cento e 21 por cento de acometimento bucal. OBJETIVO: Investigar os achados bucais e laboratoriais em pacientes com LES. MATERIAL E MÉTODO: Foram analisados 155 pacientes com diagnóstico de LES, segundo critérios do American College of Rheumatology (ACR). O índice de dentes cariados, perdidos e obturados (CPO-D) foi registrado e avaliou-se a necessidade de tratamento periodontal por meio do índice periodontal comunitário (IPC). Foram realizados esfregaços e biópsias das lesões e bordas laterais de língua para exames citopatológicos. Exames laboratoriais foram correlacionados com os achados bucais destes pacientes. RESULTADOS: Dos 155 pacientes, 94,1 por cento eram mulheres. Altos níveis de anticorpos circulantes (FAN-Hep2) foram observados em todos os pacientes, sendo 41,9 por cento positivos para a pesquisa de anticorpos anti-DNA de fita dupla. O índice CPO-D médio correspondeu a 18,5 e de acordo com o IPC, 18 por cento apresentaram bolsas periodontais de 4-5 mm e 5,9 por cento de 6 mm ou mais. Foram biopsiadas oito lesões bucais, mas somente três casos foram considerados compatíveis com a indicação clínica de LES. Os principais sítios acometidos foram dorso de língua, mucosa jugal e lábios. A prevalência de candidíase correspondeu a 20,1 por cento e a de leucoplasia pilosa oral a 3,7 por cento. CONCLUSÃO: Pacientes com LES apresentam condição periodontal precária e baixa prevalência de lesões bucais e, além disso, a citopatologia mostrou-se importante no diagnóstico de infecções relacionadas com imunossupressão, como candidíase e leucoplasia pilosa oral.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a chronic inflammatory disease, which is characterized by several clinical manifestations. A few studies in the literature state estimated prevalence of 6.5 percent to 21 percent in oral manifestations. OBJECTIVE: To investigate the oral and laboratorial findings in patients with SLE. MATERIAL AND METHOD: One hundred fifty-five patients diagnosed with SLE were analyzed in accordance with the American College of Rheumatology (ACR) criteria. The index of decayed, missed and filled teeth (DMFT) was registered and the necessity of periodontal treatment was evaluated by the Community Periodontal Index (CPI). Furthermore, biopsies and smears of the lateral borders of the tongue were performed for cytopathological exams. Laboratory exams were correlated with patients' oral findings. RESULTS: Ninety-four comma one percent of 155 patients were women. High levels of circulating autoantibodies (ANA-Hep2) were observed in all patients and 41.9 percent of them were positive for anti-double stranded DNA. Mean DMFT index was 18.5. According to CPI, 18 percent showed periodontal pockets of 4-5 mm and 5.9 percent pockets of 6mm or more. Eight oral lesions were biopsied, but only three cases were considered compatible with clinical indication of SLE. The main affected sites were dorsum of the tongue, buccal mucosa and lips. The prevalence of candidiasis and oral hairy leucoplakia corresponded to 20.1 percent and 3.7 percent, respectively. CONCLUSION: These data suggest that patients with SLE present low prevalence of oral lesions and poor periodontal conditions. Moreover, the cytopathology showed infections associated with immunosuppression such as candidiasis and oral hairy leucoplakia.

Chronic Trypanosoma cruzi-elicited cardiomyopathy: from the discovery to the proposal of rational therapeutic interventions targeting cell adhesion molecules and chemokine receptors: how to make a dream come true

One hundred years ago, Carlos Chagas discovered a new disease, the American trypanosomiasis. Chagas and co-workers later characterised the disease's common manifestation, chronic cardiomyopathy, and suggested that parasitic persistence coupled with inflammation was the key underlying pathogenic mechanism. Better comprehension of the molecular mechanisms leading to clinical heart afflictions is a prerequisite to developing new therapies that ameliorate inflammation and improve heart function without hampering parasite control. Here, we review recent data showing that distinct cell adhesion molecules, chemokines and chemokine receptors participate in anti-parasite immunity and/or detrimental leukocyte trafficking to the heart. Moreover, we offer evidence that CC-chemokine receptors may be attractive therapeutic targets aiming to regain homeostatic balance in parasite/host interaction thereby improving prognosis, supporting that it is becoming a non-phantasious proposal.

TNF/TNFR1 signaling up-regulates CCR5 expression by CD8+ T lymphocytes and promotes heart tissue damage during Trypanosoma cruzi infection: beneficial effects of TNF-á blockade

In Chagas disease, understanding how the immune response controls parasite growth but also leads to heart damage may provide insight into the design of new therapeutic strategies. Tumor necrosis factor-alpha (TNF-á) is important for resistance to acute Trypanosoma cruzi infection; however, in patients suffering from chronic T. cruzi infection, plasma TNF-á levels correlate with cardiomyopathy. Recent data suggest that CD8-enriched chagasic myocarditis formation involves CCR1/CCR5-mediated cell migration. Herein, the contribution of TNF-á, especially signaling through the receptor TNFR1/p55, to the pathophysiology of T. cruzi infection was evaluated with a focus on the development of myocarditis and heart dysfunction. Colombian strain-infected C57BL/6 mice had increased frequencies of TNFR1/p55+ and TNF-á+ splenocytes. Although TNFR1-/- mice exhibited reduced myocarditis in the absence of parasite burden, they succumbed to acute infection. Similar to C57BL/6 mice, Benznidazole-treated TNFR1-/- mice survived acute infection. In TNFR1-/- mice, reduced CD8-enriched myocarditis was associated with defective activation of CD44+CD62Llow/- and CCR5+ CD8+ lymphocytes. Also, anti-TNF-á treatment reduced the frequency of CD8+CCR5+ circulating cells and myocarditis, though parasite load was unaltered in infected C3H/HeJ mice. TNFR1-/- and anti-TNF-á-treated infected mice showed regular expression of connexin-43 and reduced fibronectin deposition, respectively. Furthermore, anti-TNF-á treatment resulted in lower levels of CK-MB, a cardiomyocyte lesion marker. Our results suggest that TNF/TNFR1 signaling promotes CD8-enriched myocarditis formation and heart tissue damage, implicating the TNF/TNFR1 signaling pathway as a potential therapeutic target for control of T. cruzi-elicited cardiomyopathy.