Changes in Chemokines and Chemokine Receptors Expression in a Mouse Model of Alzheimer's Disease.

The amyloid precursor protein plus presenilin-1 (APP/PS1) mice are a frequently-used model for Alzheimer's disease studies (AD). However, the data relevant to which proteins are involved in inflammatory mechanism are not sufficiently well-studied using the AD mouse model. Using behavioral studies, quantitative RT-PCR and Western-blot techniques, significant findings were determined by the expression of proteins involved in inflammation comparing APP/PS1 and Wild type mice. Increased GFAP expression could be associated with the elevation in number of reactive astrocytes. IL-3 is involved in inflammation and ABDF1 intervenes normally in the transport across cell membranes and both were found up-regulated in APP/PS1 mice compared to Wild type mice. Furthermore, CCR5 expression was decreased and both CCL3 and CCL4 chemokines were highly expressed indicating a possible gliosis and probably an increase in chemotaxis from lymphocytes and T cell generation. We also noted for the first time, a CCR8 increase expression with diminution of its CCL1 chemokine, both normally involved in protection from bacterial infection and demyelination. Control of inflammatory proteins will be the next step in understanding the progression of AD and also in determining the mechanisms that can develop in this disease.

[Therapeutic plasma exchange: applications in neurology]. / Recambio plasmático terapéutico: aplicaciones en neurología.

INTRODUCTION: Plasma exchange is a technique used in the treatment of some neurological autoimmune disorders since the 80s, especially in acute conditions. In recent years new data about it use has been published in many diseases with autoimmune basis, expanding the range of use of this technique. AIM: To update the current indications of this technique in the treatment of neurological diseases. DEVELOPMENT: We conducted a thorough review of all articles about the efficacy of plasma exchange in the treatment of different neurological diseases published since the 80s. We have also carried out a detailed analysis of recommendations and evidence of the use of this procedure by analyzing the guidelines of different scientific societies. CONCLUSIONS: Plasma exchange has proven to be an effective alternative treatment with high grade scientific evidence in diseases such as Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy and myasthenia gravis. It has been effective in treating acute demyelinating episodes unresponsive to other therapies, neuromyelitis optica relapses and other central nervous system diseases induced by antibodies. In comparative studies with intravenous immunoglobulin efficacy of both therapies is similar. Comparative studies should continue to be conducted in order to better understand the mechanisms of action, prioritize indications and compare the cost-effectiveness ratio of both procedures.

TITLE: Recambio plasmatico terapeutico: aplicaciones en neurologia.Introduccion. El recambio plasmatico es una tecnica utilizada en el tratamiento de algunas enfermedades neurologicas de base autoinmune desde los años ochenta, especialmente en situaciones agudas. En los ultimos años se han publicado nuevos datos sobre su empleo en numerosas entidades con base autoinmune, ampliando, con ello, el espectro de utilizacion. Objetivo. Actualizar las indicaciones de esta tecnica en el tratamiento de las enfermedades neurologicas. Desarrollo. Se ha realizado una revision exhaustiva de todos los articulos publicados desde los años ochenta sobre la eficacia del recambio plasmatico en el tratamiento de las diferentes enfermedades neurologicas. Tambien se ha efectuado un analisis detallado de las recomendaciones y evidencias de la utilizacion de este procedimiento por parte de las diferentes sociedades cientificas. Conclusiones. El recambio plasmatico ha demostrado ser una alternativa eficaz con evidencia cientifica de primer nivel en enfermedades como el sindrome de Guillain-Barre, la polineuropatia desmielinizante inflamatoria cronica o la miastenia grave. Ha mostrado ser eficaz en el tratamiento de episodios desmielinizantes agudos sin respuesta a otras terapias, en los brotes de neuromielitis optica y en otras enfermedades del sistema nervioso central producidas por anticuerpos. En los estudios comparativos con inmunoglobulinas intravenosas, la eficacia de ambas terapias es similar. Es preciso seguir realizando estudios comparativos para conocer mejor los mecanismos y establecer indicaciones prioritarias y comparar la relacion coste-eficacia de ambos procedimientos.

Topiramate in the prophylactic treatment of cluster headache.

OBJECTIVE: The role of topiramate in the prophylactic treatment of cluster headache is still unclear. The aim of this study was to evaluate the effectiveness of topiramate in a group of patients with refractory episodic or chronic cluster headache. BACKGROUND: Proof of efficacy of preventive treatment of cluster headache is limited, especially for the chronic form of the disorder. There are very few randomized clinical trials on this condition with topiramate or other new anticonvulsant agents. Recent case reports and series involving topiramate have shown good results. The mechanism of action of topiramate is unknown, but is presumably mediated by gamma-aminobutyric acid. METHODS: Twenty-six patients with episodic (n = 12) or chronic (n = 14) cluster headache were studied prospectively. All patients had been treated with some preventive treatment, with poor or no response. Treatment with topiramate was initiated with 25 mg once a day, and the dose was titrated every 3 to 7 days to a maximum of 200 mg, according to clinical response and tolerability. RESULTS: Topiramate rapidly induced cluster remission in 15 patients, reduced the number of attacks more than 50% in 6 patients, and reduced the cluster period duration in 12. The mean time to remission was 14 days (range, 1 to 27), but in 7 patients remission was obtained within the first days of treatment with very low doses (25 to 75 mg a day). Tolerability was good within the lower range of doses used. Six patients discontinued treatment due to side effects (all with daily doses over 100 mg) or lack of efficacy. CONCLUSIONS: Our results confirm that topiramate can be an effective option for the preventive treatment of episodic and chronic cluster headache.