Evaluation of Anti-Neuroinflammatory Activity of Isatin Derivatives in Activated Microglia.

Neuroinflammation plays a crucial role in the progression of Alzheimer's disease and other neurodegenerative disorders. Overactivated microglia cause neurotoxicity and prolong the inflammatory response in many neuropathologies. In this study, we have synthesised a series of isatin derivatives to evaluate their anti-neuroinflammatory potential using lipopolysaccharide activated microglia as a cell model. We explored four different substitutions of the isatin moiety by testing their anti-neuroinflammatory activity on BV2 microglia cells. Based on the low cytotoxicity and the activity in reducing the release of nitric oxide, pro-inflammatory interleukin 6 and tumour necrosis factor α by microglial cells, the N1-alkylated compound 10 and the chlorinated 20 showed the best results at 25 µM. Taken together, the data suggest that 10 and 20 are promising lead compounds for developing new neuroprotective agents.

Papel de la ecocardiografía speckle-tracking (rastreo de marcas) y la resonancia magnética cardíaca-feature tracking en la circulación de Fontan. Diferencias entre los ventrículos derecho e izquierdo / Speckle-tracking echocardiography and MCR-feature tracking in Fontan circulation. Differences between right and left ventricles

Resumen Introducción: En los pacientes con DCPT, la disfunción ventricular es inevitable, y más temprana en VU derechos. La deformación miocárdica por STE y RMC-FT parece promisoria. Objetivo: Analizar la función ventricular mediante STE y RMC-FT en pacientes con DCPT, en comparación con RMC convencional según la morfología del VU y la posible implicación en su diagnóstico temprano. Método: Se recogieron medidas del strain longitudinal y circunferencial por STE y RMC-FT, volúmenes ventriculares y FE por RMC en 64 pacientes con DCPT. Resultados: La morfología ventricular no se relacionó con disfunción por RMC. Los VU derechos tuvieron valores por STE y RMC-FT disminuidos respecto de los VU izquierdos, con FE similares. Existe correlación entre STE y RMC-FT, no equivalentes, con buena factibilidad y reproducibilidad. Conclusiones: La RMC-FT y el STE son técnicas útiles en el diagnóstico temprano y la vigilancia de la función ventricular en VU derechos con FE preservada.

Abstract Introduction: In patients with TCPC, the development of ventricular dysfunction is inevitable and is more precocious in SRVs. Myocardial deformation by STE and CMR-FT is promising. Objective: To analize ventricular function in patients with TCPC using STE and CMR-FT compared with conventional cMRI, depending on SV morphology, to determine their role in early diagnosis of ventricular dysfunction. Method: Sixty-four patients with TCPC were included. Longitudinal and circumferential strain by STE and CMR-FT and ventricular volume and EF were obtained. Results: Dysfunction analyzed by cMRI showed no association with ventricular morphology. SRVs had lower values in STE and CMR-FT compared with SLVs, with similar EF. While not equivalent, correlation was observed between the STE and the CMR-FT values, demonstrating good feasibility and reproducibility. Conclusion: The strain data in CMR-FT and STE could be useful for diagnosis and monitoring of ventricular function and as markers of early SRV dysfunction with preserved EF.

Hip Preservation Surgery in Osteoarthritis Prevention: Potential Benefits of the Radiographic Angular Correction.

Objective: The aim of the study is to describe the morphology associated with the development of osteoarthritis (OA) in three different age groups. These data will contribute to defining the morphology associated with early and late hip OA. Methods: We studied 400 hips in 377 patients who had undergone primary THA due to idiopathic OA. Three groups were compared: group 1 (n = 147), younger patients, aged up to 60 years; group 2 (n = 155), patients aged between 61 and 74 years; and group 3 (n = 98), aged 75 or over. Five independent researchers measured the hip angles and the mean values were used to build a database. Results: No differences between groups in sex distribution and BMI were detected. Less coverage of the head (extrusion index), higher Tönnis angle, lower Wiberg and alpha angles characterized early OA hips. These differences increased with age, being greater between group 2 and group 3 (p < 0.01). However, significant differences were still present in the comparison between group 1 and group 2 (p < 0.01)). No differences were detected between group 2 and group 3. Conclusion: Elevated acetabular angle, head extrusion and decreased Wiberg angle characterize hip osteoarthritis at younger ages and should be the focus of hip preservation surgery in terms of osteoarthritis prevention. Pincer-type FAI (higher Wiberg and lower Tönnis angle) and higher alpha angle (CAM) are correlated with the development of later OA. These results shed doubt on applying the hip preservation surgery concept in terms of osteoarthritis prevention in FAI, especially in Pincer-type FAI patients.

Vaccination with recombinant adenovirus expressing peste des petits ruminants virus-F or -H proteins elicits T cell responses to epitopes that arises during PPRV infection.

Peste des petits ruminants virus (PPRV) causes an economically important disease that limits productivity in small domestic ruminants and often affects the livestock of the poorest populations in developing countries. Animals that survive PPRV develop strong cellular and humoral responses, which are probably necessary for protection. Vaccination should thus aim at mimicking these natural responses. Immunization strategies against this morbillivirus using recombinant adenoviruses expressing PPRV-F or -H proteins can protect PPRV-challenged animals and permit differentiation of infected from vaccinated animals. Little is known of the T cell repertoire these recombinant vaccines induce. In the present work, we identified several CD4+ and CD8+ T cell epitopes in sheep infected with PPRV. We also show that recombinant adenovirus vaccination induced T cell responses to the same epitopes, and led to memory T cell differentiation. T cells primed by these recombinant adenovirus vaccines expanded after PPRV challenge and probably contributed to protection. These data validate the use of recombinant adenovirus expressing PPRV genes as DIVA strategies to control this highly contagious disease.

Protective Efficacy in Sheep of Adenovirus-Vectored Vaccines against Bluetongue Virus Is Associated with Specific T Cell Responses.

Bluetongue virus (BTV) is an economically important Orbivirus of the Reoviridae family that causes a hemorrhagic disease in ruminants. Its control has been achieved by inactivated-vaccines that have proven to protect against homologous BTV challenge although unable to induce long-term immunity. Therefore, a more efficient control strategy needs to be developed. Recombinant adenovirus vectors are lead vaccine candidates for protection of several diseases, mainly because of their potency to induce potent T cell immunity. Here we report the induction of humoral and T-cell mediated responses able to protect animals against BTV challenge by recombinant replication-defective human adenovirus serotype 5 (Ad5) expressing either VP7, VP2 or NS3 BTV proteins. First we used the IFNAR(-/-) mouse model system to establish a proof of principle, and afterwards we assayed the protective efficacy in sheep, the natural host of BTV. Mice were completely protected against BTV challenge, developing humoral and BTV-specific CD8+- and CD4+-T cell responses by vaccination with the different rAd5. Sheep vaccinated with Ad5-BTV-VP2 and Ad5-BTV-VP7 or only with Ad5-BTV-VP7 and challenged with BTV showed mild disease symptoms and reduced viremia. This partial protection was achieved in the absence of neutralizing antibodies but strong BTV-specific CD8+ T cell responses in those sheep vaccinated with Ad5-BTV-VP7. These data indicate that rAd5 is a suitable vaccine vector to induce T cell immunity during BTV vaccination and provide new data regarding the relevance of T cell responses in protection during BTV infection.