Desarrollo de una aplicación informática para dispositivos móviles para la mejora del aprendizaje de la nomenclatura de compuestos orgánicos y de fármacos

Depto. de Química en Ciencias FarmacéuticasFac. de FarmaciaFALSEsubmitte

Evaluación de TuFormulas. Diseño y aplicación de indicadores para medir el impacto y la sostenibilidad de este recurso educativo como herramienta de enseñanza y aprendizaje

Depto. de Química en Ciencias FarmacéuticasFac. de FarmaciaFALSEsubmitte

ProspeCtive study to evaluate efficacy, safety and tOlerability of dietary supplemeNT of Curcumin (BCM95) in subjects with Active relapsing MultIple Sclerosis treated with subcutaNeous Interferon beta 1a 44 mcg TIW (CONTAIN): A randomized, controlled trial

Background: multiple sclerosis (MS) is a complex disease sustained by several pathogenic mechanisms. As such, combination therapy strategies, targeting a range of disease mechanisms, might represent the ideal therapeutic approach. Here we investigated the efficacy of curcumin, a naturally occurring poly-phenolic phytochemical with potent anti-inflammatory and antioxidant properties, in subjects under treatment with IFN β-1a, to test the effects of this combination therapy on clinical and MRI parameters of inflammation and neurodegeneration in relapsing MS (RMS). Methods: eighty active RMS were prospectively enrolled, randomized (1:1) to either the IFN-curcumin or the IFN- placebo group and followed up longitudinally with clinical and MRI assessments for 24 months. Primary endpoint was the efficacy of curcumin versus placebo as add-on therapy on new/enlarging T2 lesions in RMS subjects under treatment with subcutaneous IFN β-1a 44 mcg TIW. Efficacy on clinical parameters (relapses and disability progression), other MRI parameters of inflammation (T1 Gd-enhancing lesions, combined unique active-CUA lesions) and neurodegeneration (T1-hypointense lesions, grey matter loss and white matter micro- structural damage) as well as safety and tolerability of curcumin were explored as secondary endpoints. Results: ten subjects dropped out from the study by month 12 (6 in the IFN-curcumin group and 4 in the IFN- placebo group), and 27 by month 24 (11 in the IFN-curcumin group and 16 in the IFN-placebo group). Although no between-group difference was present in terms of proportion of subjects free from new/enlarging T2 lesions, a lower proportion of patients with CUA lesions was noted at month 12 in the IFN-curcumin group in comparison with the IFN-placebo group (7.5% vs 17.5%, χ2 test p= 0.0167). This result was not confirmed at month 24. The statistical analysis failed to reveal any difference between the two treatment groups – IFN- curcumin and IFN-placebo – in terms of relapses, disability progression, other MRI metrics of inflammation and MRI changes suggestive of ongoing neurodegeneration. No difference in the rate and nature of adverse events was observed between the two treatment groups. Conclusion: Although the study drop-out rate was too high to allow definite conclusions, our findings suggest that curcumin might add to IFN β-1a efficacy on radiological signs of inflammation in MS, while it did not seem to exert any neuroprotective effect as assessed by clinical and MRI parameters. (NCT01514370

Coenzyme Q10 supplementation reduces peripheral oxidative stress and inflammation in interferon-β1a-treated multiple sclerosis

Background: Oxidative stress is a driver of multiple sclerosis (MS) pathology. We evaluated the effect of coenzyme Q10 (CoQ10) on laboratory markers of oxidative stress and inflammation, and on MS clinical severity. Methods: We included 60 relapsing–remitting patients with MS treated with interferon beta1a 44μg (IFN-β1a) with CoQ10 for 3 months, and with IFN-β1a 44μg alone for 3 more months (in an open-label crossover design). At baseline and at the 3 and 6-month visits, we measured markers of scavenging activity, oxidative damage and inflammation in the peripheral blood, and collected data on disease severity. Results: After 3 months, CoQ10 supplementation was associated with improved scavenging activity (as mediated by uric acid), reduced intracellular reactive oxygen species production, reduced oxidative DNA damage, and a shift towards a more anti-inflammatory milieu in the peripheral blood [with higher interleukin (IL)-4 and IL-13, and lower eotaxin, granulocyte-macrophage colony-stimulating factor (GM-CSF), hepatocyte growth factor (HGF), interferon (IFN)-γ, IL-1α, IL-2R, IL-9, IL-17F, macrophage inflammatory proteins (MIP)-1α, regulated on activation-normal T cell expressed and secreted (RANTES), tumor necrosis factor (TNF)-α, and vascular endothelial growth factor (VEGF). Also, CoQ10 supplementation was associated with lower Expanded Disability Status Scale, fatigue severity scale, Beck’s depression inventory, and the visual analogue scale for pain. Conclusions: CoQ10 supplementation improved scavenging activity, reduced oxidative damage, and induced a shift towards a more anti-inflammatory milieu, in the peripheral blood of relapsing–remitting MS patients treated with 44μg IFN-β1a 44μg. A possible clinical effect was noted but deserves to be confirmed over longer follow ups