Development of a transplantable glioma tumour model from genetically engineered mice: MRI/MRS/MRSI characterisation.

The initial aim of this study was to generate a transplantable glial tumour model of low-intermediate grade by disaggregation of a spontaneous tumour mass from genetically engineered models (GEM). This should result in an increased tumour incidence in comparison to GEM animals. An anaplastic oligoastrocytoma (OA) tumour of World Health Organization (WHO) grade III was obtained from a female GEM mouse with the S100ß-v-erbB/inK4a-Arf (+/-) genotype maintained in the C57BL/6 background. The tumour tissue was disaggregated; tumour cells from it were grown in aggregates and stereotactically injected into C57BL/6 mice. Tumour development was followed using Magnetic Resonance Imaging (MRI), while changes in the metabolomics pattern of the masses were evaluated by Magnetic Resonance Spectroscopy/Spectroscopic Imaging (MRS/MRSI). Final tumour grade was evaluated by histopathological analysis. The total number of tumours generated from GEM cells from disaggregated tumour (CDT) was 67 with up to 100 % penetrance, as compared to 16 % in the local GEM model, with an average survival time of 66 ± 55 days, up to 4.3-fold significantly higher than the standard GL261 glioblastoma (GBM) tumour model. Tumours produced by transplantation of cells freshly obtained from disaggregated GEM tumour were diagnosed as WHO grade III anaplastic oligodendroglioma (ODG) and OA, while tumours produced from a previously frozen sample were diagnosed as WHO grade IV GBM. We successfully grew CDT and generated tumours from a grade III GEM glial tumour. Freezing and cell culture protocols produced progression to grade IV GBM, which makes the developed transplantable model qualify as potential secondary GBM model in mice.

A new ex vivo method to evaluate the performance of candidate MRI contrast agents: a proof-of-concept study.

BACKGROUND: Magnetic resonance imaging (MRI) plays an important role in tumor detection/diagnosis. The use of exogenous contrast agents (CAs) helps to improve the discrimination between lesion and neighbouring tissue, but most of the currently available CAs are non-specific. Assessing the performance of new, selective CAs requires exhaustive assays and large amounts of material. Accordingly, in a preliminary screening of new CAs, it is important to choose candidate compounds with good potential for in vivo efficiency. This screening method should reproduce as close as possible the in vivo environment. In this sense, a fast and reliable method to select the best candidate CAs for in vivo studies would minimize time and investment cost, and would benefit the development of better CAs. RESULTS: The post-mortem ex vivo relative contrast enhancement (RCE) was evaluated as a method to screen different types of CAs, including paramagnetic and superparamagnetic agents. In detail, sugar/gadolinium-loaded gold nanoparticles (Gd-GNPs) and iron nanoparticles (SPIONs) were tested. Our results indicate that the post-mortem ex vivo RCE of evaluated CAs, did not correlate well with their respective in vitro relaxivities. The results obtained with different Gd-GNPs suggest that the linker length of the sugar conjugate could modulate the interactions with cellular receptors and therefore the relaxivity value. A paramagnetic CA (GNP (E_2)), which performed best among a series of Gd-GNPs, was evaluated both ex vivo and in vivo. The ex vivo RCE was slightly worst than gadoterate meglumine (201.9 ± 9.3% versus 237 ± 14%, respectively), while the in vivo RCE, measured at the time-to-maximum enhancement for both compounds, pointed to GNP E_2 being a better CA in vivo than gadoterate meglumine. This is suggested to be related to the nanoparticule characteristics of the evaluated GNP. CONCLUSION: We have developed a simple, cost-effective relatively high-throughput method for selecting CAs for in vivo experiments. This method requires approximately 800 times less quantity of material than the amount used for in vivo administrations.

Parámetros biométricos oculares en candidatos a cirugía de catarata / Ocular biometric parameters in cataract surgery candidates

Introducción: Las estructuras ópticas pueden variar en su configuración y medida dependiendo de la edad, el sexo y la raza, por lo que su medición previa a la cirugía es un pilar fundamental para el cálculo correcto del lente intraocular. Caracterizar los rangos normales de estos parámetros en nuestra población suministra información importante que puede mejorar los resultados visuales tras la cirugía de catarata y alertar en aquellos casos que distan de la media de los rangos conocidos. Objetivo: Describir los parámetros biométricos oculares en pacientes candidatos a cirugía de catarata y analizar sus variaciones según la edad y el sexo. Método: Estudio observacional descriptivo, de corte transversal. Análisis retrospectivo de biometrías oculares realizadas con reflectometría óptica de baja coherencia en pacientes candidatos a cirugía de catarata. Resultados: Se evaluaron 820 ojos de 820 pacientes candidatos a cirugía de catarata, con una edad media de 68.1 ± 11.1 años, el 53.7% de sexo femenino. Los parámetros oculares promedios encontrados fueron: longitud axial (AL) 23.39 ± 1.11 mm, profundidad de cámara anterior (ACD) 3.37 ± 0.49 mm, astigmatismo corneal (AST) 1.09 ± 0.85 D, espesor corneal central (CCT) 529.43 ± 35.02 µm, poder queratométrico (K) 43.81 ± 1.64 D, queratometría plana 43.28 ± 1.69 D, queratometría curva 44.37 ± 1.74 D y distancia blanco a blanco 11.82 ± 0.52 mm. El promedio de AL y ACD fue mayor en los hombres que en las mujeres (p < 0.0001), y con el aumento de la edad el AST y el K mostraron una tendencia al incremento. Se encontró un 23.78% de astigmatismo con la regla, un 54.88% de astigmatismo contra la regla y un 21.34% de astigmatismo oblicuo. Conclusiones: El perfil de los datos biométricos evidenció diferencias significativas entre sexos y grupos de edad. Se encontró una buena correlación entre la AL, la ACD y la potencia corneal, y los promedios encontrados se corresponden bien con los de otras poblaciones de similar origen étnico.

Introduction: Optical structures can vary in their configuration and measurement depending on age, sex and race, so their measurement, prior to surgery, is a fundamental pillar for the correct calculation of the intraocular lens. Characterizing the normal ranges of these parameters in our population provides important information that can improve the visual results of cataract surgery and alert in those cases that are far from the mean of the known ranges. Objective: To describe the ocular biometric parameters in cataract surgery candidates. Method: Descriptive, cross-sectional study. Retrospective analysis of biometric parameters measured by optical low-coherence reflectometry in cataract surgery candidates. Results: The study evaluated 820 eyes of 820 cataract patients, the mean age was 68.1 ± 11.1 years, 53.7% female. Mean ocular parameters found were: axial length (AL) 23.39 ± 1.11 mm, anterior chamber depth (ACD) 3.37 ± 0.49 mm, corneal astigmatism (AST) 1.09 ± 0.85 D, central corneal thickness (CCT) 529.43 ± 35.02 µm, keratometry (K) 43.81 ± 1.64 D, flat keratometry (K1) 43.28 ± 1.69 D, steep keratometry (K2) 44.37 ± 1.74 D and white-to-white distance (WTW) 11.82 ± 0.52 mm. Mean AL and ACD were significantly longer in men (p < 0.0001) and with increasing age, AST and K showed an upward trend. 23.78% of astigmatism with the rule, 54.88% of astigmatism against the rule and 21.34% of oblique astigmatism were found. Conclusions: The profile of the biometric data showed significant differences between sex and age groups, a good correlation was found between axial length, chamber depth and keratometry. The averages found correspond well to those of other populations of similar ethnic origin

Efficient γ-amino-proline-derived cell penetrating peptide-superparamagnetic iron oxide nanoparticle conjugates via aniline-catalyzed oxime chemistry as bimodal imaging nanoagents.

Aniline-catalyzed oxime chemistry was employed to conjugate a γ-amino-proline-derived cell penetrating peptide to superparamagnetic iron oxide nanoparticles (SPIONs). Internalization of the novel nanoconjugate into HeLa cells was found to be remarkably higher compared to the analogous TAT-SPION conjugate.