Influence of Ecto-Nucleoside Triphosphate Diphosphohydrolase Activity on Trypanosoma cruzi Infectivity and Virulence

The protozoan Trypanosoma cruzi is the causative agent of Chagas disease, an endemic zoonosis present in some countries of South and Central Americas. The World Health Organization estimates that 100 million people are at risk of acquiring this disease. The infection affects mainly muscle tissues in the heart and digestive tract. There are no vaccines or effective treatment, especially in the chronic phase when most patients are diagnosed, which makes a strong case for the development of new drugs to treat the disease. In this work we evaluate a family of proteins called Ecto-Nucleoside-Triphosphate-Diphosphohydrolase (Ecto-NTPDase) as new chemotherapy target to block T. cruzi infection in mammalian cells and in mice. We have used inhibitors and antibodies against this protein and demonstrated that T. cruzi Ecto-NTPDases act as facilitators of infection in mammalian cells and virulence factors in mice model. Two of the drugs used in this study (Suramin and Gadolinium) are currently used for other diseases in humans, supporting the possibility of their use in the treatment of Chagas disease

The role of P2 receptors in controlling infections by intracellular pathogens

A growing number of studies have demonstrated the importance of ATPe-signalling via P2 receptors as an important component of the inflammatory response to infection. More recent studies have shown that ATPe can also have a direct effect on infection by intracellular pathogens, by modulating membrane trafficking in cells that contain vacuoles that harbour intracellular pathogens, such as mycobacteria and chlamydiae. A conserved mechanism appears to be involved in controlling infection by both of these pathogens, as a role for phospholipase D in inducing fusion between lysosomes and the vacuoles has been demonstrated. Other P2-dependent mechanisms are most likely operative in the cases of pathogens, such as Leishmania, which survive in an acidic phagolysosomal-like compartment. ATPe may function as a ‘danger signal–that alerts the immune system to the presence of intracellular pathogens that damage the host cell, while different intracellular pathogens have evolved enzymes or other mechanisms to inhibit ATPe-mediated signalling, which should, thus, be viewed as virulence factors for these pathogens

Screening for subtelomeric chromosome abnormalities in children with idiopathic mental retardation using multiprobe telomeric FISH and the new MAPH telomeric assay.

Subtelomeric chromosomal abnormalities are emerging as an important cause of human genetic disorders. The scope of this investigation was to screen a selected group of children with idiopathic mental retardation for subtelomeric anomalies using the multiprobe telomeric FISH method and also to develop and test a new assay, the MAPH telomeric assay, in the same group of patients. The new MAPH telomeric assay uses the recently published MAPH methodology that permits the measurement of locus copy number by hybridisation with a specifically designed set of probes located at the end of human chromosomes. Seventy patients with idiopathic mental retardation have been screened using the established multiprobe telomeric FISH assay and the new MAPH telomeric assay, for all telomeres. One patient with de novo 8p subtelomeric deletion was identified. The new MAPH telomeric assay confirmed the same results in both normal and abnormal samples. This is the first description of the use of MAPH methodology to detect chromosomal imbalances near the telomeres in idiopathic mentally retarded patients. The new MAPH telomeric assay offers a new, fast, accurate and cost effective diagnostic tool to detect chromosomal imbalances near telomeres in mentally retarded patients, as well as the characterisation of known chromosomal abnormalities, spontaneous recurrent miscarriages, infertility, hematological malignancies, preimplantation genetic diagnosis, and other fields of clinical and research interests