Striatal Neuronal Ensembles Reveal Differential Actions of Amantadine and Clozapine to Ameliorate Mice L-DOPA-Induced Dyskinesia.

Amantadine and clozapine have proved to reduce abnormal involuntary movements (AIMs) in preclinical and clinical studies of L-DOPA-Induced Dyskinesias (LID). Even though both drugs decrease AIMs, they may have different action mechanisms by using different receptors and signaling profiles. Here we asked whether there are differences in how they modulate neuronal activity of multiple striatal neurons within the striatal microcircuit at histological level during the dose-peak of L-DOPA in ex-vivo brain slices obtained from dyskinetic mice. To answer this question, we used calcium imaging to record the activity of dozens of neurons of the dorsolateral striatum before and after drugs administration in vitro. We also developed an analysis framework to extract encoding insights from calcium imaging data by quantifying neuronal activity, identifying neuronal ensembles by linking neurons that coactivate using hierarchical cluster analysis and extracting network parameters using Graph Theory. The results show that while both drugs reduce LIDs scores behaviorally in a similar way, they have several different and specific actions on modulating the dyskinetic striatal microcircuit. The extracted features were highly accurate in separating amantadine and clozapine effects by means of principal components analysis (PCA) and support vector machine (SVM) algorithms. These results predict possible synergistic actions of amantadine and clozapine on the dyskinetic striatal microcircuit establishing a framework for a bioassay to test novel antidyskinetic drugs or treatments in vitro.

Metástasis en glándula parótida por tumoraciones cutáneas melanoma y no melanoma de cabeza y cuello. Pronóstico y tratamiento / Parotid metastatic from cutaneous melanoma y no melanoma of head and neck. Prognostic and treatment

Introducción y objetivo: El melanoma y las tumoraciones cutáneas no melanomas (TCNM) situadas en cabeza y cuello pueden extenderse a la glándula parótida (GP), bien por continuidad o por diseminación a través del sistema linfático. Cuando esto ocurre, el tratamiento a seguir es preferentemente quirúrgico, siempre y cuando la evolución tumoral, el estado general del paciente y la no diseminación del tumor a otras zonas del organismo lo permitan. Nuestro objetivo es analizar el tratamiento seguido, el número de recidivas y la mortalidad en nuestra serie de las citadas tumoraciones, con invasión de la GP. Material y método: Presentamos una serie de 26 pacientes (24 varones y 2 mujeres) con afectación tumoral parotídea consecuencia de metástasis de melanoma o de TCNM. A todos se les realizó tratamiento quirúrgico, parotidectomía del lóbulo superficial en 5 casos y parotidectomía total en 21. La disección cervical radical modificada tipo III se efectuó en 19 pacientes. Posteriormente siguieron tratamiento radio y/o quimio o inmunoterápico. Resultados: Desarrollamos el estudio desde 2012 a 2018, con un seguimiento de los pacientes de 0 a 114 meses, encontrando un grado de recidiva del 15.38% y una mortalidad del 34.6%. La complicación más frecuente como consecuencia de la cirugía ablativa realizada fue la parálisis facial en los 3 casos en que no se preservó el nervio facial y la neuropraxia del nervio facial, principalmente de sus ramas bucal y marginal, que cedió con el tiempo. Conclusiones: El tratamiento de las tumoraciones metastásicas de la GP consecuencia de este tipo de tumoraciones cutáneas, es preferentemente quirúrgico con exéresis de la glándula y respetando el nervio facial siempre que la invasión tumoral no lo afecte. La radioterapia postoperatoria será también útil como complemento del tratamiento. Los resultados con el tratamiento combinado son actualmente poco esperanzadores, pero se espera una mejoría de las expectativas principalmente por los tratamientos inmunoterápicos en el caso de los melanomas y radioterápicos en las invasiones por carcinomas espinocelulares. Seguramente todo ello permitirá que el tratamiento quirúrgico sea menos radical y con secuelas escasas

Background and objective: When developed on head and neck, both melanoma and non-melanoma skin cancer (NMSC) can be spread to the parotid gland (PG) because of its permanence or due to the lymphatic spreading. In this case, the most appropriate option is the surgical procedure, provided that the progression of the tumor, the general condition of the patient and the non-dissemination of the tumor allow it. Our aim is to analyze the treatment followed and the number of recurrences, as well as mortality of our series in which the tumors cited invades the GP. Methods: The study includes a selection of 26 patients (22 male and 2 female) with a parotid gland tumor diagnosis as a consequence of a melanoma/ NMSC metastasis. All of them had undergone surgical procedure, 5 with a superficial lobe parotidectomy, and the remaining 19 with a total parotidectomy. Modified radical neck dissection Type III was applied to 19 patients. After that, they continued receiving radiotherapy and/or chemo o inmunotherapy. Results: This study was conducted between 2012 and 2018, with a patient’s follow-up from 0 to 114 months. Patients had a recurrence rate of 15.38% a mortality of 34.6%. The most frequent complications as a result of the surgical ablation were the facial paralysis in all 3 cases where the facial nerve was not preserved, and the neurapraxia in the facial nerve, specifically the marginal mandibular branches and the buccal branches, which decreased over time. Conclusions: The preferred treatment of metastasis of PG tumors as a consequence of this kind of skin cancer is the surgical procedure with gland exeresis and keeping the facial nerve, as long as the tumor invasion does not affect it. Postoperative radiotherapy will also be an essentially useful resource as a treatment complement. For the moment, the results of the combinated therapy are not encouraging. However, thanks to the immunotherapies applied in melanoma cases and to the radiotherapy applied in squamous cell carcinoma invasions, best prospects are expected. Probably, this will result in less radical surgical procedures with few sequelae

Measurement of cell traction forces with ImageJ.

The quantification of cell traction forces requires three key steps: cell plating on a deformable substrate, measurement of substrate deformation, and the numerical estimation of the corresponding cell traction forces. The computing steps to measure gel deformation and estimate the force field have somehow limited the adoption of this method in cell biology labs. Here we propose a set of ImageJ plug-ins so that every lab equipped with a fluorescent microscope can measure cell traction forces.