Therapeutic armamentarium against systemic fungal infections

ABSTRACTThe incidence of invasive fungal infections (IFIs) has been following an upward trend over time, due to a continuous increase in the number of patients at risk, while the prognosis remains poor. In the last 10 years, the lipidic formulations of amphotericin B, voriconazole and a new family of antifungal drugs, the echinocandins, have been added to the traditional antifungal agents, for decades limited to just a few drugs such as amphotericin B deoxycholate, flucytosine and, later, fluconazole and itraconazole. These additions have improved both the results and the understanding of antifungal therapy, while at the same time making it more complex, with new questions arising that remain to be answered. This article reviews the mechanisms of action, spectrum of activity, pharmacology, administration, adverse effects and indications of each of the antifungal agents currently commercialised for the treatment of IFI

Stem Cells to Regenerate Cardiac Tissue in Heart Failure

Myocardial regeneration is one of the most promising therapeutic strategies for heart failure patients. Many experimental studies have demonstrated that different types of stem cell can differentiate into myocardial cells and tissues necessary for regeneration of the damaged myocardium, while studies in experimental animals suggest that muscle (myoblast), bone marrow (mesenchymal, endothelial or hematopoietic progenitors) and even heart cells can help to improve heart contractility in vivo. These findings have led several groups to undertake studies in patients with myocardial infarction. However, the use of cellular therapy in clinical trials is not without controversy, mainly related with the need for better knowledge before these therapeutic strategies are used in clinical practice. Although significant enhancement of our knowledge of the processes involved is fundamental, we do not consider it unreasonable to initiate clinical trials in which specific questions are posed, whose answers will allow us to make further progress

Utilización de células madre para la regeneración miocárdica en la insuficiencia cardíaca

La terapia celular en la reparación miocárdica se vislumbra como una de las estrategias terapéuticas con mayor futuro en el tratamiento de la insuficiencia cardíaca. Numerosos estudios in vitro recientes apoyan la potencialidad de distintos tipos de células madre de diferenciarse hacia los tejidos necesarios para regenerar el tejido miocárdico dañado, mientras que estudios en animales de experimentación sugieren que células madre de músculo (mioblastos), médula ósea (progenitores mesenquimales, endoteliales o hematopoyéticos) e incluso del propio corazón pueden contribuir in vivo a mejorar la contractilidad cardíaca. Estos trabajos han conducido a que diversos grupos hayan iniciado estudios en pacientes con infarto de miocardio. Sin embargo, la utilización de la terapia celular en ensayos clínicos no está desprovista de controversia, fundamentalmente relacionada con la necesidad de aumentar nuestro conocimiento antes de pasar a la aplicación clínica de estas estrategias terapéuticas. Aunque es fundamental aumentar significativamente el conocimiento de los procesos, no consideramos irrazonable iniciar ensayos clínicos en los que se identifiquen preguntas concretas cuya respuesta nos permita avanzar en esta dirección

Insecurity for compact surfaces of positive genus

A pair of points in a riemannian manifold $M$ is secure if the geodesics between the points can be blocked by a finite number of point obstacles; otherwise the pair of points is insecure. A manifold is secure if all pairs of points in $M$ are secure. A manifold is insecure if there exists an insecure point pair, and totally insecure if all point pairs are insecure. Compact, flat manifolds are secure. A standing conjecture says that these are the only secure, compact riemannian manifolds. We prove this for surfaces of genus greater than zero. We also prove that a closed surface of genus greater than one with any riemannian metric and a closed surface of genus one with generic metric are totally insecure.Comment: 37 pages, 11 figure

Glycogen synthase kinase-3 is an endogenous inhibitor of Snail transcription: implications for the epithelial-mesenchymal transition

We report that the activity of glycogen synthase kinase-3 (GSK-3) is necessary for the maintenance of the epithelial architecture. Pharmacological inhibition of its activity or reducing its expression using small interfering RNAs in normal breast and skin epithelial cells results in a reduction of E-cadherin expression and a more mesenchymal morphology, both of which are features associated with an epithelial-mesenchymal transition (EMT). Importantly, GSK-3 inhibition also stimulates the transcription of Snail, a repressor of E-cadherin and an inducer of the EMT. We identify NFkappaB as a transcription factor inhibited by GSK-3 in epithelial cells that is relevant for Snail expression. These findings indicate that epithelial cells must sustain activation of a specific kinase to impede a mesenchymal transition

Fibroma desmoplásico del hueso: aportación de un nuevo caso

Se presenta un caso de Fibroma Desmoplásico localizado en cuello femoral en un paciente adulto joven de 34 años, al cual se le practicó una resección amplia de la lesión y una reconstrucción por medio de un compuesto de aloinjerto intercalar proximal y prótesis total de cadera (aloprótesis). Un año después de la intervención no hay recidiva local de la lesión y se objetiva una buena incorporación del aloinjerto al huésped; con buena función de la cadera. Se revisa la literatura y se discuten algunas consideraciones diagnósticas y terapéuticas de la lesión.A case of Desmoplastic Fibroma of the Bone, located in the femoral neck, in a 34 year old male patient is reported. The tumor was treated by wide resection, the reconstruction beem performed with an allograft-prostheses composite. One year after surgery, there was no local recurrence and a good is incorporation of the allograft to the host was observed. The patient showed a good hip function. The literature is reviewed and diagnostic and therapeutic considerations are discussed