The hypothalamus plays an important role in the regulation of sleep/wakefulness states. While the ventrolateral preoptic nucleus (VLPO) plays a critical role in the initiation and maintenance of sleep, the lateral posterior part of the hypothalamus contains neuronal populations implicated in maintenance of arousal, including orexin-producing neurons (orexin neurons) in the lateral hypothalamic area (LHA) and histaminergic neurons in the tuberomammillary nucleus (TMN). During a search for neurons that make direct synaptic contact with histidine decarboxylase-positive (HDCϩ), histaminergic neurons (HDC neurons) in the TMN and orexin neurons in the LHA of male mice, we found that these arousal-related neurons are heavily innervated by GABAergic neurons in the preoptic area including the VLPO. We further characterized GABAergic neurons electrophysiologically in the VLPO (GABA VLPO neurons) that make direct synaptic contact with these hypothalamic arousal-related neurons. These neurons (GABA VLPO¡HDC or GABA VLPO¡orexin neurons) were both potently inhibited by noradrenaline and serotonin, showing typical electrophysiological characteristics of sleep-promoting neurons in the VLPO. This work provides direct evidence of monosynaptic connectivity between GABA VLPO neurons and hypothalamic arousal neurons and identifies the effects of monoamines on these neuronal pathways.
Mechanisms of impaired fatty acid metabolism may not be the same in nondialysis and hemodialysis patients. Correlations between the serum‐free carnitine concentration (FC), acylcarnitine concentration (AC), acyl to free carnitine ratio (AC/FC), and estimated glomerular filtration rate (eGFR) in the nondialysis population and the duration of hemodialysis in hemodialysis patients were investigated. As the eGFR decreased, the FC and AC increased, and as the duration of hemodialysis became longer, the FC and AC decreased. The AC/FC increased consistently as the eGFR decreased and the duration of hemodialysis increased. As an exception, the AC/FC decreased in the patients with a hemodialysis duration less than 90 days, which was not explained by carnitine removal by hemodialysis. In nondialysis patients, a functional, rather than an absolute, carnitine deficiency is a main cause of impaired fatty acid metabolism. Long‐term hemodialysis exacerbates absolute carnitine deficiency, whereas hemodialysis treatment may improve impaired fatty acid metabolism.
Background
Although the angiotensin receptor-neprilysin inhibitor sacubitril-valsartan has demonstrated a valuable effect on cardiac function in patients with heart failure with a reduced ejection fraction, the effect of this agent in hemodialysis patients is not well known.
Case presentation
Sacubitril-valsartan was administered to two anuric hemodialysis patients, an 81-year-old woman and a 79-year-old man, after aortic valve replacement for aortic stenosis. Following sacubitril-valsartan administration, the two patients’ N-terminal pro-brain natriuretic peptide levels decreased from 110,373 to 47,742 and 22,723 to 7692 pg/mL within one month, respectively, and were sustained within the lower levels thereafter. Although the patients’ left ventricular ejection fractions were 40.0% and 28.4%, respectively, these values did not change at seven and four months after sacubitril-valsartan administration (41.0% and 30.0%, respectively) but increased gradually to 56.6% and 54.9% at 11 and 13 months, respectively, and were sustained at the same levels thereafter.
Conclusions
Long-term sacubitril-valsartan administration can improve cardiac function in hemodialysis patients with a reduced ejection fraction.
Introduction: During the application of non-invasive positive pressure ventilation (NPPV) therapy in home mechanical ventilation (HMV), leaks in the NPPV mask may occur owing to the position of the mask due to conditions such as skin disorders. Methods: To investigate whether such a leak affects FiO 2 supplied to the alveoli, we simulated a patient with chronic obstructive pulmonary disorder during NPPV in HMV. In addition, FiO 2 was measured in the portion assumed to be the mouth and lungs while setting the flow of the oxygen concentrator and leak amount based on a previous study. Results: FiO 2 supplied to the lungs increased statistically significantly upon increasing the amount of leak (P < 0.001). Moreover, values measured for the mouth were similar. However, our results were different from those of a previous study. Conclusions: We observed that FiO 2 supplied to alveoli can be reduced by a leak in the NPPV mask. Because our results differ from those previously reported, we believe that further studies should reassess the selection of respirators and oxygen concentrators.
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