Carbohydrate-naphthalene diimide conjugates as potential antiparasitic drugs: Synthesis, evaluation and structure-activity studies.

The neglected tropical diseases Human African Trypanosomiasis and leishmaniasis are caused by infection with trypanosomatid parasites Trypanosoma brucei and Leishmania spp, respectively. The genomes of these organisms contain multiple putative G-quadruplex (G4) forming sequences which have recently been proposed to mediate processes relevant for parasite survival. Therefore, G4 could be considered as potential targets for a novel approach towards the development of antiparasitic drugs. Recently, we have demonstrated that G4 ligands such as carbohydrate naphthalene diimide conjugates (carb-NDIs) possess notable antiparasitic activity. Herein, we have synthesized a new family of carb-NDIs, characterized by significant structural variability, and evaluated their anti-parasitic activity, with special focus on T. brucei. The interaction with relevant G4 sequences was evaluated in vitro through independent biophysical methods (FRET melting assays under competing conditions with double stranded DNA, circular dichroism and fluorescence titrations). Finally, flow cytometry and confocal microscopy experiments demonstrated that the conjugates exhibit excellent uptake into T. brucei parasites, localizing in the nuclei and kinetoplasts. Promising antiparasitic activity and selectivity against control mammalian cells, together with their peculiar mechanism of action, render the carb-NDI conjugates as suitable candidates for the development of an innovative treatment of trypanosomiasis.

A red-NIR fluorescent dye detecting nuclear DNA G-quadruplexes: in vitro analysis and cell imaging.

Aggregation, red-NIR emission and light-up upon nucleic acid G-quadruplex binding have been investigated for a prototype core-extended naphthalene diimide, which is capable of fast cellular entry and nucleolar localization. Both high-level colocalization with an anti-G-quadruplex antibody and nucleolin displacement reveal that the compound targets and thus makes visible nuclear DNA G-quadruplexes.

Estimation of the tissue composition of the tumour mass in neuroblastoma using segmented CT images.

Neuroblastoma is the most common extra-cranial, solid, malignant tumour in children. Advances in radiology have made possible the detection and staging of the disease. Nevertheless, there is no method available at present that can go beyond detection and qualitative analysis, towards quantitative assessment of the tissue composition of the primary tumour mass in neuroblastoma. Such quantitative analysis could provide important information and serve as a decision-support tool to the radiologist and the oncologist, result in better treatment and follow-up and even lead to the avoidance of delayed surgery. The problem investigated was the improvement of the analysis of the primary tumour mass, in patients with neuroblastoma, using X-ray computed tomography (CT) images. A methodology was proposed for the estimation of the tissue content of the mass: it comprised a Gaussian mixture model for estimation, from segmented CT images, of the tissue composition of the primary tumour. To demonstrate the potential of the method, the results are presented of its application to ten CT examinations of four patients. The method provides quantitative information, and it was observed that the tumour in one of the patients reduced from 523 cm3 to 81 cm3 in volume, with an increase in calcification from about 20% to about 88% of the tumour volume, in response to chemotherapy over a period of five months. Results indicate that the proposed technique may be of considerable value in assessing the response to therapy of patients with neuroblastoma.

A virtual reality simulator for bone marrow harvest for pediatric transplant.

Bone marrow transplant is a relatively new procedure to treat recently considered incurable diseases. One important part of the procedure is the process of harvesting the donor bone marrow. We are developing a virtual reality simulator for bone marrow harvest that integrates interactive stereo visualization and force feedback techniques. The main objective is to offer a low cost virtual reality system to boost current adopted training methodologies for bone marrow harvesting.

Interactive stereoscopic full-color direct volume visualization for virtual reality applications in medicine.

Only recently, advanced direct volume visualization techniques have been widely used due to the availability of low cost hardware accelerators; such techniques have a great potential of use for many applications of the virtual reality in medicine. We proposed and implemented a low cost system for interactive and stereoscopic 3D visualization of the full color visible human dataset. Potential use of the proposed system includes anatomical atlases and surgical simulators. A prototype of the proposed system is rendering full color volumes with 256 x 152 x 470 in real time (15-20 Hz) with stereoscopy.

Development of a telemedicine model for emerging countries: a case study on pediatric oncology in Brazil.

This article discusses a telemedicine model for emerging countries, through the description of ONCONET, a telemedicine initiative applied to pediatric oncology in Brazil. The ONCONET core technology is a Web-based system that offers health information and other services specialized in childhood cancer such as electronic medical records and cooperative protocols for complex treatments. All Web-based services are supported by the use of high performance computing infrastructure based on clusters of commodity computers. The system was fully implemented on an open-source and free-software approach. Aspects of modeling, implementation and integration are covered. A model, both technologically and economically viable, was created through the research and development of in-house solutions adapted to the emerging countries reality and with focus on scalability both in the total number of patients and in the national infrastructure.