Increased antiparkinson efficacy of the combined administration of VEGF- and GDNF-loaded nanospheres in a partial lesion model of Parkinson's disease

Current research efforts are focused on the application of growth factors, such as glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF), as neuroregenerative approaches that will prevent the neurodegenerative process in Parkinson's disease. Continuing a previous work published by our research group, and with the aim to overcome different limitations related to growth factor administration, VEGF and GDNF were encapsulated in poly(lactic-co-glycolic acid) nanospheres (NS). This strategy facilitates the combined administration of the VEGF and GDNF into the brain of 6-hydroxydopamine (6-OHDA) partially lesioned rats, resulting in a continuous and simultaneous drug release. The NS particle size was about 200 nm and the simultaneous addition of VEGF NS and GDNF NS resulted in significant protection of the PC-12 cell line against 6-OHDA in vitro. Once the poly(lactic-co-glycolic acid) NS were implanted into the striatum of 6-OHDA partially lesioned rats, the amphetamine rotation behavior test was carried out over 10 weeks, in order to check for in vivo efficacy. The results showed that VEGF NS and GDNF NS significantly decreased the number of amphetamine-induced rotations at the end of the study. In addition, tyrosine hydroxylase immunohistochemical analysis in the striatum and the external substantia nigra confirmed a significant enhancement of neurons in the VEGF NS and GDNF NS treatment group. The synergistic effect of VEGF NS and GDNF NS allows for a reduction of the dose by half, and may be a valuable neurogenerative/neuroreparative approach for treating Parkinson's disease.

A New Type of Coincidence and Common Fixed Point Theorem with Applications

Coincidence and common fixed point theorems for a class of 'Ciric-Suzuki hybrid contractions involving a multivalued and two single-valued maps in a metric space are obtained. Some applications including the existence of a common solution for certain class of functional equations arising in a dynamic programming are also discussed..

An approach version of fuzzy metric spaces including an ad hoc fixed point theorem

In this paper, inspired by two very different, successful metric theories such us the real view-point of Lowen's approach spaces and the probabilistic field of Kramosil and Michalek's fuzzymetric spaces, we present a family of spaces, called fuzzy approach spaces, that are appropriate to handle, at the same time, both measure conceptions. To do that, we study the underlying metric interrelationships between the above mentioned theories, obtaining six postulates that allow us to consider such kind of spaces in a unique category. As a result, the natural way in which metric spaces can be embedded in both classes leads to a commutative categorical scheme. Each postulate is interpreted in the context of the study of the evolution of fuzzy systems. First properties of fuzzy approach spaces are introduced, including a topology. Finally, we describe a fixed point theorem in the setting of fuzzy approach spaces that can be particularized to the previous existing measure spaces.