Development of a Prodrug of Camptothecin for Enhanced Treatment of Glioblastoma Multiforme.

A novel therapeutic approach for glioblastoma multiforme (GBM) therapy has been carried out through in vitro and in vivo testing by using the prodrug camptothecin-20-O-(5-aminolevulinate) (CPT-ALA). The incorporation of ALA to CPT may promote uptake of the cytotoxic molecule by glioblastoma cells where the heme synthesis pathway is active, improving the therapeutic action and reducing the side effects over healthy tissue. The antitumor properties of CPT-ALA have been tested on different GBM cell lines (U87, U251, and C6) as well as in an orthotopic GBM model in rat, where potential toxicity in central nervous system cells was analyzed. In vitro results indicated no significant differences in the cytotoxic effect over the different GBM cell lines for CPT and CPT-ALA, albeit cell mortality induced by CPT over normal cell lines was significantly higher than CPT-ALA. Moreover, intracranial GBM in rat was significantly reduced (30% volume) with 2 weeks of CPT-ALA treatment with no significant side effects or alterations to the well-being of the animals tested. 5-ALA moiety enhances CPT diffusion into tumors due to solubility improvement and its metabolic-based targeting, increasing the CPT cytotoxic effect on malignant cells while reducing CPT diffusion to other proliferative healthy tissue. We demonstrate that CPT-ALA blocks proliferation of GBM cells, reducing the infiltrative capacity of GBM and promoting the success of surgical removal, which improves life expectancy by reducing tumor recurrence.

Individualized exercise prescription in non-alcoholic steatohepatitis: a case report.

The effect of an individualized exercise programme on a non-alcoholic steatohepatitis case is presented. Before entering the programme the patient was treated with conventional recommendations on diet plus aerobic exercise during fourteen years, without major improvements of his analytical parameters.Two years after including him in a tailored exercise programme, aimed to fulfil the recommendations of the American College of Sports Medicine, his blood markers of liver dysfunction and cardiometabolic risk tended to improve. Consequently, our data support the idea that in non-alcoholic steatohepatitis the exercise-based therapeutic interventions should be individualized taking into account the cardio-respiratory and muscular fitness of the patient, rather than using generic behavioural recommendations.

Prescripción individualizada de ejercicio en un caso de esteatohepatitis no alcohólica / Ultrasound-guided percutaneous drainage and sclerotherapy in a patient with isolated autosomal dominant polycystic liver disease

Se presenta un caso de esteatohepatitis no alcohólica de dieciséis años de evolución, tratado durante catorce años con recomendaciones dietéticas y de práctica de actividad física regular y que, en los dos últimos años, fue incluido en un programa de ejercicio controlado, monitorizado y supervisado, acorde a las recomendaciones del American College of Sports Medicine. Tras la inclusión del paciente en este programa se observó un cambio en la tendencia de diferentes parámetros analíticos de función hepática y riesgo cardiometabólico, que pasaron de mostrar una tendencia al alza, a estabilizarse o tender a disminuir. A raíz de estas observaciones se sugiere que la mera recomendación de realización autónoma de ejercicio regularmente, sin evaluación de la condición física del sujeto, así como sin unas adecuadas planificación y periodización del mismo, puede resultar una medida ineficaz en el tratamiento de esta enfermedad

The effect of an individualized exercise programme on a non-alcoholic steatohepatitis case is presented. Before entering the programme the patient was treated with conventional recommendations on diet plus aerobic exercise during fourteen years, without major improvements of his analytical parameters. Two years after including him in a tailored exercise programme, aimed to fulfil the recommendations of the American College of Sports Medicine, his blood markers of liver dysfunction and cardiometabolic risk tended to improve. Consequently, our data support the idea that in non-alcoholic steatohepatitis the exercise-based therapeutic interventions should be individualized taking into account the cardio-respiratory and muscular fitness of the patient, rather than using generic behavioural recommendations