Epigenetic changes in headache.

INTRODUCTION: Multiple factors, including both genetic and environmental mechanisms, appear to play a role in the aetiology of headache. An interesting area of study is the possible involvement of epigenetic mechanisms in headache development and the transformation to chronic headache, and the potential role of these factors as a therapeutic target. METHODS: We performed a literature review of the involvement of different epigenetic mechanisms in headache, mainly using the Medline/PubMed database. To this end, we used the following English search terms: headache, migraine, epigenetics, DNA methylation, histones, non-coding RNA, and miRNA. RESULTS: A total of 15 English-language publications related to the above terms were obtained. CONCLUSION: There is limited but consistent evidence of the relationship between epigenetics and headache; it is therefore essential to continue research of epigenetic changes in headache. This may help to understand the pathophysiology of headache and even to identify candidate biomarkers and new, more effective, therapeutic targets.

Modificaciones epigenéticas en las cefaleas / Epigenetic changes in headache

Introducción: En las cefaleas parece existir una influencia multifactorial, tanto de mecanismos genéticos como ambientales, siendo interesante el estudio de la posible participación de mecanismos epigenéticos en su desarrollo, cronificación y potencial papel como diana terapéutica.MétodosHemos llevado a cabo una revisión bibliográfica, principalmente a través de la base de datos Medline/PubMed, de la implicación de los distintos mecanismos epigenéticos en las cefaleas. Para ello hemos utilizado los términos de búsqueda en inglés: headache, migraine, epigenetics, DNA methylation, histones, non-coding RNA y miRNA.ResultadosSe obtuvieron un total de 15 publicaciones en idioma inglés relacionadas con los términos anteriores.ConclusionesExisten indicios de la relación entre la epigenética y las cefaleas, siendo imprescindible, debido al reducido número de estudios, continuar con la investigación de las modificaciones epigenéticas en las cefaleas. Esto podría ayudar a comprender la fisiopatología de las cefaleas e incluso identificar biomarcadores y nuevas dianas terapéuticas más eficaces. (AU)

Introduction: Multiple factors, including both genetic and environmental mechanisms, appear to play a role in the aetiology of headache. An interesting area of study is the possible involvement of epigenetic mechanisms in headache development and the transformation to chronic headache, and the potential role of these factors as a therapeutic target.MethodsWe performed a literature review of the involvement of different epigenetic mechanisms in headache, mainly using the Medline/PubMed database. To this end, we used the following English search terms: headache, migraine, epigenetics, DNA methylation, histones, non-coding RNA, and miRNA.ResultsA total of 15 English-language publications related to the above terms were obtained.ConclusionThere is limited but consistent evidence of the relationship between epigenetics and headache; it is therefore essential to continue research of epigenetic changes in headache. This may help to understand the pathophysiology of headache and even to identify candidate biomarkers and new, more effective, therapeutic targets. (AU)

A review of bioanalytical methods for the therapeutic drug monitoring of ß-lactam antibiotics in critically ill patients: Evaluation of the approaches used to develop and validate quality attributes.

Due to their broad spectrum of activity and wide therapeutic index, ß-lactam antibiotics (ß-LA) are commonly used to treat severe sepsis in critically ill patients in intensive care units. This group of patients experiences important physiological changes that alter their pharmacokinetics, and thus, therapeutic drug monitoring (TDM) of ß-LA is increasingly used to improve personalized medicine by optimizing doses and minimizing the emergence of drug-resistant bacterial strains. Reliable and high-quality bioanalytical methods are needed in clinical practice. This review principally focuses on evaluating the development and validation of state-of-the-art analytical methods for the determination of ß-LA in biological samples from critically ill patients. When mentioned, method optimization was performed using a univariate strategy, the currently used analytical quality by design (AQbD) tools were not used for method optimization in any study. Liquid chromatography methods coupled with UV or MS detectors were the main techniques used, and the pretreatment procedures were still considerably complex for a hospital laboratory setting. Given the poly-medication status of many patients, the selectivity of the procedure must be specifically analyzed to avoid possible interference from other drugs. However, this aspect has been assessed in very few studies. We also identified inconsistencies in analytical ranges selected in many published methods, since they are not centered in the therapeutic concentrations of the antibiotics. The precision, accuracy and linearity were mainly evaluated using diverse bioanalytical validation guidelines; however, more detailed information could have been provided about the calibration strategy used for routine laboratory assessments.

Determination of dexamethasone and two excipients (creatinine and propylparaben) in injections by using UV-spectroscopy and multivariate calibrations.

The use of multivariate spectrophotometric calibration for the simultaneous determination of dexamethasone and two typical excipients (creatinine and propylparaben) in injections is presented. The resolution of the three-component mixture in a matrix of excipients has been accomplished by using partial least-squares (PLS-1). Notwithstanding the elevated degree of spectral overlap, they have been rapidly and simultaneously determined with high accuracy and precision (comparable to the HPLC pharmacopeial method), with no interference, and without resorting to extraction procedures using non-aqueous solvents. A simple and fast method for wavelength selection in the calibration step is used, based on the minimisation of the predicted error sum of squares (PRESS) calculated as a function of a moving spectral window.