Acta physiologica
-
Circadian rhythms of physiology are the keys to health and fitness, as dysregulation, by genetic mutations or environmental factors, increases disease risk and aggravates progression. Molecular and physiological studies have shed important light on an intrinsic clock that drives circadian rhythms and serves essential roles in metabolic homoeostasis, organ physiology and brain functions. One exciting new area in circadian research is pain, including headache and neuropathic pain for which new mechanistic insights have recently emerged. ⋯ We then provide a detailed review of the circadian relevance in pain disease and physiology, including cluster headache, migraine, hypnic headache and neuropathic pain. Finally, we describe potential therapeutic implications, including existing pain medicines and novel clock-modulating compounds. The physiological basis for the circadian rhythms in pain is an exciting new area of research with profound basic and translational impact.
-
Atherosclerosis is a continuous pathological process that starts early in life and progresses frequently to unstable plaques. Plaque rupture leads to deleterious consequences such as acute coronary syndrome, stroke and atherothrombosis. The vulnerable lesion has several structural and functional hallmarks that distinguish it from the stable plaque. ⋯ Haemorrhages deliver erythrocytes to the necrotic core where they degrade promoting inflammation and oxidative stress. Inflammatory cells mostly presented by monocytes/macrophages, neutrophils and mast cells extravagate from bleeding neovessels and infiltrate adventitia where they support chronic inflammation. Plaque destabilization is an evolutionary process that could start at early atherosclerotic stages and whose progression is influenced by many factors including neovascularization, intraplaque haemorrhages, formation of cholesterol crystals, inflammation, oxidative stress and intraplaque protease activity.
-
Renal tissue hypoperfusion and hypoxia are key elements in the pathophysiology of acute kidney injury and its progression to chronic kidney disease. Yet, in vivo assessment of renal haemodynamics and tissue oxygenation remains a challenge. Many of the established approaches are invasive, hence not applicable in humans. ⋯ Multi-modality in vivo approaches suitable for detailing the role of the confounding factors that govern T2∗ are considered. A schematic approach describing the link between renal perfusion, oxygenation, tissue compartments and renal T2∗ is proposed. Future directions of MRI assessment of renal oxygenation and perfusion are explored.
-
Neutrophil gelatinase-associated lipocalin (NGAL), a 25 kDa protein produced by injured nephron epithelia, is one of the most promising new markers of renal epithelial injury. In contrast to serum creatinine and urinary output, which are the measures of kidney function, NGAL is specifically induced in the damaged nephron and then released into blood and urine, where it can be readily measured. Careful proof-of-concept studies using defined animal models have uncovered the sources and trafficking of NGAL in acute kidney injury (AKI) and have addressed the contributions of renal and non-renal sources. ⋯ In addition, clinical studies have shown that NGAL is a powerful predictor of poor clinical outcomes, which can be used to risk stratify patients when combined with serum creatinine. NGAL has important limitations, including its responsiveness in systemic inflammation, which is partially uncoupled from its response to kidney injury and which needs to be considered when interpreting NGAL results clinically. This review covers the biology and pathophysiology of NGAL and summarizes the results of the growing body of clinical studies that have addressed the utility of NGAL in the early diagnosis of AKI, in the distinction of intrinsic AKI and in the prognostic assessment of broad patient populations.