Dehydroepiandrosterone (DHEA): Pharmacological Effects and Potential Therapeutic Application.

Dehydroepiandrosterone (DHEA) is the most abundant steroid hormone in primates, which is predominantly synthesized in the adrenal cortex. A characteristic curve of growth and decline of its synthesis during life was observed, together with the corresponding formation of its sulphate ester (DHEAS). High levels of plasma circulating DHEA are suggested as a marker of human longevity, and various pathophysiological conditions lead to a decreased DHEA level, including adrenal insufficiency, severe systemic diseases, acute stress, and anorexia. More recent studies have established the importance of DHEA in the central nervous system (CNS). A specific intranuclear receptor for DHEA has not yet been identified; however, highly specific membrane receptors have been detected in endothelial cells, the heart, kidney, liver, and the brain. Research shows that DHEA and DHEAS, as well as their metabolites, have a wide range of effects on numerous organs and organ systems, which places them in the group of potential pharmacological agents useful in various clinical entities. Their action as neurosteroids is especially interesting due to potential neuroprotective, pro-cognitive, anxiolytic, and antidepressant effects. Evidence from clinical studies supports the use of DHEA in hypoadrenal individuals and in treating depression and associated cognitive disorders. However, there is also an increasing trend of recreational DHEA misuse in healthy people, as it is classified as a dietary supplement in some countries. This article aims to provide a critical review regarding the biological and pharmacological effects of DHEA, its mechanism of action, and potential therapeutic use, especially in CNS disorders.

Introduction to the EQIPD quality system.

While high risk of failure is an inherent part of developing innovative therapies, it can be reduced by adherence to evidence-based rigorous research practices. Supported through the European Union's Innovative Medicines Initiative, the EQIPD consortium has developed a novel preclinical research quality system that can be applied in both public and private sectors and is free for anyone to use. The EQIPD Quality System was designed to be suited to boost innovation by ensuring the generation of robust and reliable preclinical data while being lean, effective and not becoming a burden that could negatively impact the freedom to explore scientific questions. EQIPD defines research quality as the extent to which research data are fit for their intended use. Fitness, in this context, is defined by the stakeholders, who are the scientists directly involved in the research, but also their funders, sponsors, publishers, research tool manufacturers, and collaboration partners such as peers in a multi-site research project. The essence of the EQIPD Quality System is the set of 18 core requirements that can be addressed flexibly, according to user-specific needs and following a user-defined trajectory. The EQIPD Quality System proposes guidance on expectations for quality-related measures, defines criteria for adequate processes (i.e. performance standards) and provides examples of how such measures can be developed and implemented. However, it does not prescribe any pre-determined solutions. EQIPD has also developed tools (for optional use) to support users in implementing the system and assessment services for those research units that successfully implement the quality system and seek formal accreditation. Building upon the feedback from users and continuous improvement, a sustainable EQIPD Quality System will ultimately serve the entire community of scientists conducting non-regulated preclinical research, by helping them generate reliable data that are fit for their intended use.

Comorbidity of Migraine and Epilepsy in Pediatrics: A Review.

Migraine and epilepsy are classified as chronic paroxysmal neurologic disorders sharing many clinical features, as well as possible treatment options. This review highlights the similarities between migraine and epilepsy in pediatrics, focusing on epidemiologic, pathophysiological, genetic, clinical, and pharmacologic aspects. Despite the fact that several syndromes share symptoms of both migraine and epilepsy, further research is needed to clarify the pathophysiological and genetic basis of their comorbidity. Drugs used for prophylactic therapy of migraine and epilepsy have similar pharmacologic properties. The role of epileptic pharmacotherapy in the prophylaxis of migraine is assessed, including the use of conventional antiepileptic drugs, calcium channel blockers, and nonpharmacologic methods such as dietary therapy, supplements, and vagal nerve stimulation. Further randomized, controlled clinical trials assessing pharmacologic and nonpharmacologic methods for the treatment of both disorders are essential, in order to initiate new therapeutic approaches.