The involvement of endothelial mediators in leprosy

Leprosy is a chronic infectious disease that requires better understanding since it continues to be a significant health problem in many parts of the world. Leprosy reactions are acute inflammatory episodes regarded as the central etiology of nerve damage in the disease. The activation of endothelium is a relevant phenomenon to be investigated in leprosy reactions. The present study evaluated the expression of endothelial factors in skin lesions and serum samples of leprosy patients. Immunohistochemical analysis of skin samples and serum measurements of VCAM-1, VEGF, tissue factor and thrombomodulin were performed in 77 leprosy patients and 12 controls. We observed significant increase of VCAM-1 circulating levels in non-reactional leprosy (p = 0.0009). The immunostaining of VEGF and tissue factor was higher in endothelium of non-reactional leprosy (p = 0.02 for both) than healthy controls. Patients with type 1 reaction presented increased thrombomodulin serum levels, compared with non-reactional leprosy (p = 0.02). In type 2 reaction, no significant modifications were observed for the endothelial factors investigated. The anti-inflammatory and antimicrobial activities of the endotfhelial factors may play key-roles in the pathogenesis of leprosy and should be enrolled in studies focusing on alternative targets to improve the management of leprosy and its reactions.

Marcadores morfológicos de prognóstico no mesotelioma maligno: um estudo de 58 casos / Morphological aspects as prognostic factors in malignant mesothelioma: a study of 58 cases

OBJETIVO: Diversos marcadores têm se mostrados promissórios como preditores do diagnóstico e prognóstico do mesotelioma maligno (MM). MÉTODO: Mediante estudo morfométrico e inmunomarcação de componentes estromais (calretinina, CEA, Leu-M1 e trombomodulina) e nucleares (p53 e Ki-67), avaliamos a sobrevida após o diagnóstico de 58 pacientes com tumores malignos de pleura. RESULTADOS: O padrão histológico típico do mesotelioma maligno foi encontrado em 50 casos e o padrão atípico em 8 casos. Imunohistoquimicamente foram confirmados 40 casos como sendo mesoteliomas, 11 como adenocarcimonas e 7 casos do padrão atípico não puderam ser classificados. A análise multivariavel do Cox demonstrou a coexistência de um maior fator de risco de morte (476.2), nos pacientes com idade avançada, subtipo histológico bifásico e componentes de expressão nuclear. CONCLUSÃO: A calretinina foi o marcador inmunohistoquímico (IHQ) mais útil para o diagnóstico do mesotelioma e o CEA para o de adenocarcinoma. A quantificação por IHQ da trombomodulina foi fundamental na diferenciação do mesotelioma quando este foi positivo tanto para calretinina e como para o CEA. A informação prognostica mais valiosa foi a fornecida pela análise rotineira histopatológica do tipo histológico tumoral. Um ponto importante, divisor natural, foi a idade com uma media de 55 anos e 30.5 por cento de componentes nucleares de marcação IHQ, separando os pacientes em dois grupos: pacientes com uma sobrevivência curta contra pacientes com uma sobrevivência mais longa que a esperada. Assim, a análise histopatológica oferece uma arma poderosa e de elevado potencial para guiar no tratamento adjuvante de quimioterápicos após a retirada cirúrgica do mesotelioma.

OBJECTIVE: Various markers have shown promise as diagnostic markers and prognostic predictors in malignant mesothelioma (MM). METHODS: Through morphometric and immunological studies of markers in stromal components (calretinin, CEA, Leu-M1 and thrombomodulin) and nuclear components (p53 and Ki-67), we evaluated post-diagnosis survival in 58 patients with MM. RESULTS: The histologic pattern of the MM was typical in 50 cases and atypical in 8. Through immunohistochemistry, we confirmed 40 cases of mesothelioma and 11 cases of adenocarcinoma, although we were unable to classify 7 of the 8 cases presenting atypical histologic patterns. Cox multivariate analysis revealed that the risk factor for death was higher (476.2) among patients of advanced age, presenting the biphasic subtype and testing positive for components expressed at the nuclear level. CONCLUSION: The most useful immunohistochemical markers were was calretinin (for mesothelioma) and CEA (for adenocarcinoma). Immunohistochemical quantification of thrombomodulin facilitated the diagnosis of mesothelioma in patients testing positive for both calretinin and CEA. The most useful prognostic information was that provided by the routine histopathological analysis of the tumor type. It is of note that the combination of a mean age of 55 years and 30.5 percent immunohistochemical markers in nuclear components created a natural dividing point between patients in which survival was shorter than expected and those in which it was longer than expected. Therefore, histopathological analysis offers a powerful weapon with great potential to inform decisions regarding the use of adjuvant chemotherapy after surgical excision of a mesothelioma.

Protein C and soluble thrombomodulin in relation to tumor necrosis factor-alpha in critically ill septic patients and their correlation with sofa score

The objective of this study was to investigate the influence of sepsis on protein C [PC] activity and soluble thrombomodulin [s-TM] in relation to tumor necrosis factor-alpha [TNF-alpha]. Also, to orrelate these parameters with the SOFA score and serum lactate concentration as predictors of morbidity and mortality in septic patients. Thirty two adult patients [17 with sepsis and 15 with severe sepsis] in the intensive care unit [ICU], as well as 10 healthy age- and sex- matched controls were accrued to the study. The results showed that the baseline values of PC activity were significantly lower in both groups of septic patients compared to the controls, whereas, the serum levels of s-TM, TNF-alpha and lactate were significantly higher in the former compared to the latter. Moreover, survivors in both patient groups had higher PC activity and lower serum levels of s-TM, TNF-alpha and lactate compared to non survivors, both on day [1] and day [3] of ICU admission with variable statistical significance reflecting the heterogeneity of sepsis and the well-known individual patient variation. In addition, day [3] samples showed significant increase in PC activity and reduction in serum levels of s-TM, TNF-alpha, lactate and SOFA scores in survivors and the reverse in non survivors compared to baseline levels. Also, baseline PC activity was correlated negatively with SOFA score but not with serum TNF-alpha in both groups of septic patients. It was also negatively correlated with serum TM and lactate in sepsis but not in severe sepsis

Avaliacao da lesao e disfuncao endotelial atraves da analise da trombomodulina e fator de von Willebrand, no grupo multibacilar da hanseniase / ?

A hanseniase e uma doenca infecciosa cronica, cujo curso evolutivo, lento e insidioso, pode ser interrompido por episodios agudos ou subagudos, caracterizando os periodos reacionais. O comprometimento vascular e muito frequente, sendo a vasculite cronica um achado comum no doente multibacilar. Durante os surtos de reacao tipo II foram relatados episodios de tromboses venosa e/ ou arterial, muitas vezes constituindo a causa de obito desses doentes. Analisamos as dosagens plasmaticas de trombomodulina e do antigeno do fator de von Willebrand como marcadores de lesao e disfuncao endotelial, respectivamente, em doentes multibacilares, durante episodios de reacao tipo II e fora dos periodos reacionais. Apos consentimento previo informado, foram coletadas 163 amostras de um total de 34 doentes com hanseniase, formas multibacilares de sofrerem reacao tipo II