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Supplemental oxygen (hyperoxia) improves physical performance during hypoxic exercise. Based on the analysis of metabolome and iron homeostasis from human athlete blood samples, we show that hyperoxia during recovery periods interferes with metabolic alterations following hypoxic exercise. This may impair beneficial adaptations to exercise and/or hypoxia and highlights risks of oxygen supplementation in hypoxia.
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The antidepressant effects of ketamine and esketamine are well-documented. Nonetheless, most of the underlying molecular mechanisms have to be uncovered yet. In the last decade, metabolomics has emerged as a useful means to investigate the metabolic phenotype associated with depression as well as changes induced by antidepressant treatments. This mini-review aims at summarizing the main findings from preclinical and clinical studies that used metabolomics to investigate the metabolic effects of subanesthetic, antidepressant doses of ketamine and esketamine and their relationship with clinical response. Both animal and human studies report alterations in several metabolic pathways - including the tricarboxylic acid cycle, glycolysis, the pentose phosphate pathway, lipid metabolism, amino acid metabolism, the kynurenine pathway, and the urea cycle - following the administration of ketamine or its enantiomers. Although more research is needed to clarify commonalities and differences in molecular mechanisms of action between the racemic compound and its enantiomers, these findings comprehensively support an influence of ketamine and esketamine on mitochondrial and cellular energy production, membrane homeostasis, neurotransmission, and signaling. Metabolomics may thus represent a promising strategy to clarify molecular mechanisms underlying treatment-resistant depression and related markers of clinical response to ketamine and esketamine. This body of preclinical and clinical evidence, if further substantiated, has the potential to guide clinicians towards personalized approaches, contributing to new paradigms in the clinical management of depression.
Assuntos
Antidepressivos , Ketamina , Metabolômica , Ketamina/farmacologia , Ketamina/uso terapêutico , Humanos , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Metabolômica/métodos , Animais , Depressão/tratamento farmacológico , Depressão/metabolismoRESUMO
Blood serves as the primary global biological matrix for health surveillance, disease diagnosis, and response to drug treatment, holding significant promise for personalized medicine. The diverse array of lipids and metabolites in the blood provides a snapshot of both physiological and pathological processes, with many routinely monitored during conventional wellness checks. The conventional method involves intravenous blood collection, extracting a few milliliters via venipuncture, a technique limited to clinical settings due to its dependence on trained personnel. Microsampling methods have evolved to be less invasive (collecting ≤150 µL of capillary blood), user-friendly (enabling self-collection), and suitable for remote collection in longitudinal studies. Dried blood spot (DBS), a pioneering microsampling technique, dominates clinical and research domains. Recent advancements in device technology address critical limitations of classical DBS, specifically variations in hematocrit and volume. This review presents a comprehensive overview of state-of-the-art microsampling devices, emphasizing their applications and potential for monitoring metabolites and lipids in blood. The scope extends to diverse areas, encompassing population studies, nutritional investigations, drug discovery, sports medicine, and multi-omics research.