GSK-3 kinase a putative therapeutic target in trypanosomatid parasites.

Trypanosomatids are an important group of parasites that predominate in tropical and subtropical areas of the planet, which cause diseases that are classified as forgotten and neglected by the world health organization. In this group of parasites, we find Trypanosoma cruzi, Trypanosoma brucei, Trypanosoma brucei rhodesiense and Leishmania spp, for which there is no vaccine available, and its control has focused mainly on pharmacological treatment. Due to the poverty situation where these diseases are found and the biological complexity of these parasites, there are multiple variables to control, including the diversity of species, the complexity of their life cycles, drug resistance, cytotoxicity, the limited use in pregnant women, the high costs of treatment and the little-known pharmacological mechanisms of action, among others. It is therefore necessary to find new strategies and approaches for the treatment of these parasitic diseases. Among these new approaches is the rational search for new targets based on the allosteric inhibition of protein kinases, which have been little studied in trypanosomatids. Among these kinases, we find Glycogen Synthase Kinase-3 (GSK-3), a kinase of great pharmacological interest, which is under intense basic and clinical research by pharmaceutical companies for the treatment of cancer. This kinase, highly studied in the PI3K/AKT/mTOR pathway signaling in humans, has an orthologous gene in these parasites (GSK-3 s), which has proven to be essential for them in response to different challenges; Therefore, it is notable to increase research in this kinase in order to achieve a broad structural and functional characterization in the different species of trypanosomatids.

[Sepsis due to multiple-lumen catheters in bone marrow transplantation with total parenteral nutrition. The effect of the type of isolation]. / Sepsis por catéteres multiluz en trasplante de médula ósea con nutrición parenteral total. Influencia del tipo de aislamiento.

The use of catheters for total parenteral nutrition frequently leads to infectious complications which are more common and virulent in patients with marrow aplasia. The main purpose of this paper was to evaluate the influence in the development of catheter-induced sepsis of the place where it was introduced (in the theatre or hospitalization unit), the type of isolation (laminar flux unit or conventional room), and its relation to the period of isolation and of the total parenteral nutrition. Forty-one bone-marrow transplant patients were studied, 18 of them autologous and 23 allogenic, who were administered total parenteral nutrition with a two-way central venous polyurethane catheter. Of the 41 catheters applied, 16 were introduced in the operating theater and 25 in the hospitalization unit: of these, 7 and 11 respectively were infected. Isolation was as follows: 21 in standard rooms and 20 in a laminar flux unit, with 11 and 7 infections respectively. We believe that the lower level of infections in laminar flux isolation was not significant, this being a reduced number of case studies. The duration of the catheter and total parenteral nutrition for the 18 patients with sepsis was 36.5 +/- 15.1 and 23.7 +/- 8.4 days respectively: this was greater--albeit possibly not significantly so because of the special characteristics of these patients--than the 29.1 +/- 12.9 and 19.5 +/- 10.9 days for non-septic cases. This reveals a catheter sepsis rate of 43.9%, in 88% of cases caused by skin flora micro-organisms (66.6% coagulase-negative staphylococcus).(ABSTRACT TRUNCATED AT 250 WORDS)

Alergia a medicamentos. / Drug allergy

En el presente articulo se efectua una exaustiva revision de este importante capitulo de la alergia. Se discuten en esta revision de un modo completo los mecanismos etiopatogenicos de la alergia a medicamentos ubicando los diferentes mecanismos de produccion de la misma dentro del modelo de Gell y Coombs. Se tratan asimismo con gran detalle los elementos del diagnostico de esta entidad remarcando los elementos de diagnostico diferencial con otros cuadros alergicos a traves de diferentes pruebas de reactividad alergica a drogas. Por ultimo, se describen las modalidades terapeuticas dependientes de la intensidad de los sintomas y la naturaleza del alergeno desencadenante, enfatizando los limites y posibilidades de las tecnicas de desensibilizacion