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1.
Sci Rep ; 9(1): 477, 2019 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-30679597

RESUMO

Narcolepsy is a chronic sleep disorder caused by a loss of hypocretin (hcrt) neurons in the hypothalamus. Cerebrospinal fluid (CSF) hcrt-1 measurement has been well established as a gold standard of narcolepsy diagnosis, although some portions of narcoleptic patients show normal hcrt-1 levels. We aimed to examine peptide degradation of hcrt-1 and its abnormality in the CSF of patients by using high performance liquid chromatography (HPLC) followed by radioimmunoassay (RIA). CSF was collected from healthy controls, narcoleptic patients of type 1 with hcrt-1 deficiency, type 1 with normal hcrt-1 level, and type 2 with normal hcrt-1 level. We found that the majority of hcrt-1 immunoreactivity in extracted CSF was derived from unauthentic hcrt-1 peaks, which are predicted to be inactive metabolites, and the intact hcrt-1 peptide was less than 10% of the gross amount, suggesting that the regular RIA for CSF hcrt-1 measures largely reflect the unauthentic hcrt-1-related metabolites rather than the intact one. As expected, all hcrt-1-related peaks were abolished in type 1 with hcrt-1 deficiency. Importantly, we also found that the sum of the authentic hcrt-1 peptide (peaks 3 and 4) significantly decreased in non-deficient type 1 and tended to decrease in type 2 narcoleptic patients although the levels with the regular RIA in non-extracted CSF was equivalent to healthy controls. Immunoreactivity with unauthentic hcrt-1 metabolites may masks the possible decline in authentic hcrt-1 level caused by the partial loss of hcrt neurons. Our findings may provide new insights into the degradation of the hcrt-1 peptide and the pathophysiology of narcolepsy.

2.
PLoS One ; 13(6): e0197521, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29949584

RESUMO

Recently, several new materials for mattresses have been introduced. Although some of these, such as low rebound (pressure-absorbing/memory foam) and high rebound mattresses have fairly different characteristics, effects of these mattresses on sleep have never been scientifically evaluated. In the current study, we have evaluated effects of a high rebound mattress topper [HR] on sleep and its associated physiology, and the effects were compared to those of a low rebound mattress toppers (LR) in healthy young (n = 10) and old (n = 20) adult males with a randomized, single-blind, cross over design. We found that sleeping with HR compared to LR induced a larger decline in core body temperature (CBT) in the initial phase of nocturnal sleep both in young (minimum CBT: 36.05 vs 36.35°C) and old (minimum CBT: 36.47 vs. 36.55°C) subjects, and declines in the CBT were associated with increases in deep sleep/delta power (+27.8% in young and +24.7% in old subjects between 11:00-01:00). We also found significantly smaller muscle activities during roll over motions with HR (-53.0 to -66.1%, depending on the muscle) during a separate daytime testing. These results suggest that sleeping with HR in comparison to with LR, may facilitate restorative sleep at the initial phase of sleep.


Assuntos
Leitos , Sono/fisiologia , Adulto , Idoso , Temperatura Corporal , Humanos , Masculino , Pessoa de Meia-Idade , Pressão , Método Simples-Cego , Adulto Jovem
3.
Expert Opin Investig Drugs ; 27(4): 389-406, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29623725

RESUMO

INTRODUCTION: Narcolepsy with cataplexy is most commonly caused by a loss of hypocretin/orexin peptide-producing neurons in the hypothalamus (i.e., Narcolepsy Type 1). Since hypocretin deficiency is assumed to be the main cause of narcoleptic symptoms, hypocretin replacement will be the most essential treatment for narcolepsy. Unfortunately, this option is still not available clinically. There are many potential approaches to replace hypocretin in the brain for narcolepsy such as intranasal administration of hypocretin peptides, developing small molecule hypocretin receptor agonists, hypocretin neuronal transplantation, transforming hypocretin stem cells into hypothalamic neurons, and hypocretin gene therapy. Together with these options, immunotherapy treatments to prevent hypocretin neuronal death should also be developed. Areas covered: In this review, we overview the pathophysiology of narcolepsy and the current and emerging treatments of narcolepsy especially focusing on hypocretin receptor based treatments. Expert opinion: Among hypocretin replacement strategies, developing non-peptide hypocretin receptor agonists is currently the most encouraging since systemic administration of a newly synthesized, selective hypocretin receptor 2 agonist (YNT-185) has been shown to ameliorate symptoms of narcolepsy in murine models. If this option is effective in humans, hypocretin cell transplants or gene therapy technology may become realistic in the future.


Assuntos
Narcolepsia/terapia , Receptores de Orexina/metabolismo , Orexinas/metabolismo , Animais , Encéfalo/fisiopatologia , Cataplexia/fisiopatologia , Cataplexia/terapia , Modelos Animais de Doenças , Desenho de Drogas , Humanos , Hipotálamo/patologia , Narcolepsia/fisiopatologia , Neurônios/patologia , Receptores de Orexina/agonistas
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