Comparative Proteomic Analysis of Serum from Patients with Systemic Sclerosis and Sclerodermatous GVHD. Evidence of Defective Function of Factor H

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease characterized by immunological and vascular abnormalities. Until now, the cause of SSc remains unclear. Sclerodermatous graft-versus-host disease (ScGVHD) is one of the most severe complications following bone marrow transplantation (BMT) for haematological disorders. Since the first cases, the similarity of ScGVHD to SSc has been reported. However, both diseases could have different etiopathogeneses. The objective of this study was to identify new serum biomarkers involved in SSc and ScGVHD. METHODOLOGY: Serum was obtained from patients with SSc and ScGVHD, patients without ScGVHD who received BMT for haematological disorders and healthy controls. Bi-dimensional electrophoresis (2D) was carried out to generate maps of serum proteins from patients and controls. The 2D maps underwent image analysis and differently expressed proteins were identified. Immuno-blot analysis and ELISA assay were used to validate the proteomic data. Hemolytic assay with sheep erythrocytes was performed to evaluate the capacity of Factor H (FH) to control complement activation on the cellular surface. FH binding to endothelial cells (ECs) was also analysed in order to assess possible dysfunctions of this protein. PRINCIPAL FINDINGS: Fourteen differentially expressed proteins were identified. We detected pneumococcal antibody cross-reacting with double stranded DNA in serum of all bone marrow transplanted patients with ScGVHD. We documented higher levels of FH in serum of SSc and ScGVHD patients compared healthy controls and increased sheep erythrocytes lysis after incubation with serum of diffuse SSc patients. In addition, we observed that FH binding to ECs was reduced when we used serum from these patients. CONCLUSIONS: The comparative proteomic analysis of serum from SSc and ScGVHD patients highlighted proteins involved in either promoting or maintaining an inflammatory state. We also found a defective function of Factor H, possibly associated with ECs damage

Novel analytical study for reaction intermediates in the primary radiation interaction of DNA using a synchrotron radiation induced luminescence spectroscopy

To identify the precise molecular processes to induce DNA lesions, we attempt a novel spectroscopy of luminescence excitation (LEX) induced by soft X-ray synchrotron radiation, which is a non-destructive analysis of the reaction intermediates in the elementary reaction pathway of damage induction and self-organized restoration. Using a liquid micro-jet technique to introduce aqueous samples in a vacuum chamber, we measure UV-visible luminescence from nucleotide solution as a function of the soft X-ray energy from nitrogen to oxygen K-edge region. The LEX intensities for the nucleotide solutions are significantly enhanced in the soft X-ray region (410-530 eV) which is ascribed to the K-shell excitation/ionization of nitrogen atoms in the nucleobases. Furthermore, the LEX spectra do not show any signature of X-ray absorption near-edge structure (XANES) of the nucleobases. This is because the luminescence intensities collected from the integral area of micro-jet only reflect a quantum yield of luminescence of the absorbed X-ray into UV-visible light irrespective of the absorption cross sections, i.e., of XANES. Thus the present result is the first evidence of luminescence as a result of X-ray absorption of aqueous nucleotides

Achados de imagem e alternativas terapêuticas das malformações vasculares periféricas Imaging findings and therapeutic alternatives for peripheral vascular malformations

As malformações vasculares periféricas compreendem um espectro de lesões que se tornam aparentes no decorrer da vida e podem ser encontradas em praticamente todo o corpo. São pouco comuns e frequentemente confundidas com o hemangioma infantil. Estas doenças são completamente distintas tanto em relação à história clínica como ao prognóstico e às formas de tratamento. Nestas lesões, a história evolutiva e as características do exame físico são de extrema importância para o adequado diagnóstico clinicorradiológico, que guiará a melhor alternativa terapêutica. As classificações mais recentes dividem as malformações vasculares periféricas levando em consideração o fluxo sanguíneo (alto e baixo) e os componentes vasculares envolvidos (arteriais, capilares, linfáticos e venosos). As malformações vasculares periféricas representam um desafio diagnóstico e terapêutico, e exames complementares como tomografia computadorizada, ultrassonografia com Doppler e ressonância magnética, em conjunto com a história clínica, podem trazer informações quanto às características de fluxo e à extensão das lesões. Arteriografia e flebografia confirmam o diagnóstico, avaliam a sua extensão e orientam a decisão terapêutica. Malformações de baixo fluxo geralmente são tratadas por abordagem percutânea e injeção de agente esclerosante, enquanto para as malformações de alto fluxo o acesso é endovascular com uso de agentes embolizantes permanentes líquidos ou sólidos.<br>Peripheral vascular malformations represent a spectrum of lesions that appear through the lifetime and can be found in the whole body. Such lesions are uncommon and are frequently confounded with infantile hemangioma, a common benign neoplastic lesion. In the presence of such lesions, the correlation between the clinical and radiological findings is extremely important to achieve a correct diagnosis, which will guide the best therapeutic approach. The most recent classifications for peripheral vascular malformations are based on the blood flow (low or high) and on the main vascular components (arterial, capillary, lymphatic or venous). Peripheral vascular malformations represent a diagnostic and therapeutic challenge, and complementary methods such as computed tomography, Doppler ultrasonography and magnetic resonance imaging, in association with clinical findings can provide information regarding blood flow characteristics and lesions extent. Arteriography and venography confirm the diagnosis, evaluate the lesions extent and guide the therapeutic decision making. Generally, low flow vascular malformations are percutaneously treated with sclerosing agents injection, while in high flow lesions the approach is endovascular, with permanent liquid or solid embolization agents

Dural arteriovenous fistulas with direct cortical venous drainage treated with Onyx®: a case series Fístulas arteriovenosas durais com drenagem cortical direta tratadas com Onyx®: casuística

Dural arteriovenous fistulas (DAVFs) may have aggressive symptoms, especially if there is direct cortical venous drainage. We report our preliminary experience in transarterial embolization of DAVFs with direct cortical venous drainage (CVR) using Onyx®. METHOD: Nine patients with DAVFs with direct cortical venous drainage were treated: eight type IV and one type III (Cognard). Treatment consisted of transarterial embolization using Onyx-18®. Immediate post treatment angiographies, clinical outcome and late follow-up angiographies were studied. RESULTS: Complete occlusion of the fistula was achieved in all patients with only one procedure and injection in only one arterial pedicle. On follow-up, eight patients became free from symptoms, one improved and no one deteriorated. Late angiographies showed no evidence of recurrent DAVF. CONCLUSION: We recommend that transarterial Onyx® embolization of DAVFs with direct cortical venous drainage be considered as a treatment option, while it showed to be feasible, safe and effective.<br>As fistulas arteriovenosas durais (FAVDs) podem se manifestar com sintomas agressivos, especialmente se existe drenagem cortical direta. Relatamos nossa experiência preliminar na embolização transarterial de FAVDs com drenagem cortical direta usando Onyx®. MÉTODO: Nove pacientes com FAVDs com drenagem cortical direta foram tratados: oito do tipo IV e uma do tipo III (Cognard). O tratamento consistiu na embolização transarterial usando Onyx-18®. Angiografias imediatas pós-tratamento, evolução clínica e angiografias de controle tardias foram estudadas. RESULTADOS: A oclusão completa da fístula foi alcançada em todos pacientes através de um só procedimento e injeção em apenas um pedículo arterial. No seguimento, oito pacientes ficaram livres de sintomas, um melhorou e nenhum deteriorou. Angiografias tardias de controle não mostraram evidência de FAVD recorrente. CONCLUSÃO: Nós recomendamos que a embolização transarterial com Onyx® das FAVDs com drenagem cortical direta, seja considerada como uma opção terapêutica, uma vez que mostrou ser factível, segura e efetiva