Nanodelivery of Cerebrolysin and Rearing in Enriched Environment Induce Neuroprotective Effects in a Preclinical Rat Model of Parkinson's Disease.

Rearing in enriched environment (EE) improves the recuperation in animal models of Parkinson's disease (PD). Administration of TiO2-nanowired cerebrolysin (CBL) could represent an additional strategy to protect or repair the nigrostriatal system. This study aims to explore morphofunctional and biochemical changes in a preclinical stage of PD testing the synergistic efficiency of combining both strategies, housing in EE, and nanodelivery of CBL. Sprague-Dawley male rats receiving intrastriatally 6-hydroxydopamine after a short evolution time were segregated into CBL group (rats receiving nanowired CBL), EE group (rats housed in EE), CBL + EE group (rats housed in EE and receiving nanowired CBL), and control group (rats without additional treatment). Prodromic stage and treatment effects were characterized by the presence of motor symptoms (amphetamine-induced rotational behavior test). Tyrosine hydroxylase (TH) immunohistochemistry and Western blot (p-Akt/Akt and p-ERK/ERK 1/2 as survival markers and caspase-3 as apoptotic marker) were performed in striatum and SN. A decrease in motor symptoms was shown by rats receiving CBL. EE monitoring cages revealed that rats from CBL + EE group showed more significant number of laps in the wheel than EE group. In SN, CBL + EE group also presented the highest neuronal density. Moreover, p-Akt/Akt and p-ERK/ERK 1/2 ratio was significant higher and caspase-3 expression was lower in CBL + EE group. In conclusion, the combination of CBL and EE provided evidence of neuoprotective-neurorestorative mechanisms by which this combined strategy promoted morphofunctional improvement by activation of survival pathways after dopamine depletion in a preclinical model of PD.

[DNA ploidy determination with flow cytometry, Ki-67 index and overexpression of p53 protein in 121 T1 superficial bladder carcinomas. Retrospective studies. Part II: Prognostic value and usefulness in the indication for prophylactic treatment with BCG]. / Determinación de ploidía de ADN mediante citometría de flujo, indice Ki-67 y sobre-expresión de proteína p53 en 121 carcinomas superficiales de vejiga T1. Estudio retrospectivo. 2a Parte: Valor pronóstico y utilidad en la indicación de tratamiento profiláctico con BCG.

OBJECTIVE: Evaluate the utility of Ki-67 label index, p53 expression and flow cytometry-DNA ploidy in the selection of groups to be treated with prophylactic BCG and the prognostic value compared with the classic variables (grade, lymphatic permeation, multiplicity, volume, primary). MATERIAL & METHOD: 121 superficial bladder tumors T1. 10% Cut-off level for Ki-67 and p53. Aneuplody is defined as a tumor with DNA index different of 1 or more than 20% in G2-M phase. 71 (58.7%) received BCG. RESULTS: In uni and multivariate analysis positivity to Ki-67 is correlated with recurrence. Progression is correlated with lymphatic permeation (p .0003), volume (p .016), ploidy (p .022) and positivity to p53 (p .007). In multivariate analysis, volume and positivity to p53 are independent variables. None were of utility to prevent recurrence, but Ki-67 positive or aneuploid treated tumors had less progression (p .025 and p .009 respectively). The p53 negative treated tumors had less progression too. CONCLUSIONS: Only Ki-67 is correlated with tumoral recurrence. P53 and tumor volume are correlated with stage progression. If the results are confirmed with bigger series, the Ki-67 positive and/or aneuploid tumors would obtain benefits of prophylactic treatment with BCG.