Journal of internal medicine
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Cerebrotendinous xanthomatosis (CTX) is an autosomal recessively inherited inborn error of metabolism. Neurological symptoms are considered to be a clinical hallmark of untreated adult patients. We describe a 'milder CTX phenotype', without neurological involvement. ⋯ This study shows the clinical heterogeneity of CTX, highlighting the existence of a 'milder phenotype', that is without neurological involvement at diagnosis. Adult patients with CTX may present with tendon xanthomas as the sole or predominant feature, mimicking familial hypercholesterolemia. It is important to realize that the absence of neurological symptoms does not rule out the development of future neurological symptoms. As CTX is a treatable disorder, early diagnosis and initiation of treatment when additional clinical signs occur is therefore essential.
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Brain oscillations underlie the function of our brains, dictating how we both think and react to the world around us. The synchronous activity of neurons generates these rhythms, which allow different parts of the brain to communicate and orchestrate responses to internal and external stimuli. Perturbations of cognitive rhythms and the underlying oscillator neurons that synchronize different parts of the brain contribute to the pathophysiology of diseases including Alzheimer's disease, (AD), Parkinson's disease (PD), epilepsy and other diseases of rhythm that have been studied extensively by Gyorgy Buzsaki. ⋯ While multiple modalities of neuromodulation are currently clinically indicated for some disorders, nothing is yet approved for improving memory in AD. Recent investigations into novel methods of neuromodulation show potential for improving cognition in memory disorders. Here, we demonstrate that neuronal stimulation using audiovisual sensory stimulation that generated 40-HZ gamma waves reduced AD-specific pathology and improved performance in behavioural tests in mouse models of AD, making this new mode of neuromodulation a promising new avenue for developing a new therapeutic intervention for the treatment of dementia.
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Preeclampsia (PE) is a complex pregnancy syndrome characterised by maternal hypertension and organ damage after 20 weeks of gestation and is associated with an increased risk of cardiovascular disease later in life. Extracellular haemoglobin (Hb) and its metabolites heme and iron are highly toxic molecules and several defence mechanisms have evolved to protect the tissue. ⋯ In PE, oxidative stress causes syncytiotrophoblast (STB) stress and increased shedding of placental STB-derived extracellular vesicles (STBEV). The level in maternal circulation correlates with the severity of hypertension and supports the involvement of STBEVs in causing maternal symptoms in PE. In PE and FGR, iron homeostasis is changed, and iron levels significantly correlate with the severity of the disease. The normal increase in plasma volume taking place during pregnancy is less for PE and FGR and therefore have a different impact on, for example, iron concentration, compared to normal pregnancy. Excess iron promotes ferroptosis is suggested to play a role in trophoblast stress and lipotoxicity. Non-erythroid α-globin regulates vasodilation through the endothelial nitric oxide synthase pathway, and hypoxia-induced α-globin expression in STBs in PE placentas is suggested to contribute to hypertension in PE. Underlying placental pathology in PE with and without FGR might be amplified by iron and heme overload causing oxidative stress and ferroptosis. As the placenta becomes stressed, the release of STBEVs increases and affects the maternal vasculature.
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The mechanisms underlying rupture of a coronary atherosclerotic plaque and development of myocardial ischemia-reperfusion injury in ST-elevation myocardial infarction (STEMI) remain unresolved. Increased arginase 1 activity leads to reduced nitric oxide (NO) production and increased formation of reactive oxygen species due to uncoupling of the NO-producing enzyme endothelial NO synthase (eNOS). This contributes to endothelial dysfunction, plaque instability and increased susceptibility to ischemia-reperfusion injury in acute myocardial infarction. ⋯ The markedly increased gene and protein expression of arginase 1 already at admission indicates a role of arginase 1 in the development of STEMI.