Shin-Ya Saito

Background: Hemodialysis is a medical technology implemented for various renal diseases and has a significant budget impact in Japan. Hemodialysis also affects health-related quality of life, as it interferes with daily life, but the effect of diagnosis and duration of hemodialysis is not clear. The purpose of this study was to examine the impact of hemodialysis on health-related quality of life, with a focus on diagnosis and duration of hemodialysis. Methods: We conducted EQ-5D-5L surveys among hemodialysis patients at a single hemodialysis hospital between November 2015 and September 2017 and used a scoring algorithm that was developed in Japan to calculate the scores. Results: A total of 274 subjects without missing data were included in the data analysis. The mean score of the entire group was 0.772 ± 0.215. Compared with other domains, pain/discomfort had the highest percentage of problems (59.1%). There were no differences in the distributions with respect to diagnostic names in any domain. Multiple regression analysis showed that hemodialysis duration was the only explanatory variable that had a mild significant effect on EQ-5D-5L scores, but it was not large. Conclusions: QOL measured using the EQ-5D-5L survey score was not affected by age, gender, or diagnosis but was affected by hemodialysis duration. Future studies are needed to investigate the impact of prolonged hemodialysis on health-related quality of life.

The diameter of sinusoid has been shown to be changed by perfusion of adrenaline and acetylcholine. Thus, the liver blood flow is suggested to be regulated by the autonomic nervous systems in the sinusoid. However, it remains to be elucidated which cells in the sinusoid are involved in the response. The present study focused on hepatic stellate cells (HSCs) encircling the sinusoid and aimed to determine 1) whether HSCs constrict in response to noradrenaline (NAd) and 2) whether HSCs regulate liver blood flow. To measure HSC constriction quantitatively, we developed a novel method using fluorescent beads. We observed that HSCs constricted in response to NAd, which was suppressed by the α1-adrenoceptor inhibitor bunazosin and the non-muscle myosin II inhibitor blebbistatin (Bleb;1 µM). In contrast, Bleb (1 µM) had no effect on the contraction of isolated portal veins. The NAd-induced constriction of HSCs was also suppressed by xestospongin C, YM-58483, W-7, ML-9, and H-1152. In addition, Bleb (1 µM) decreased the perfusion pressure of the liver increased by NAd. This response appears to be due to HSC relaxation, since Bleb had the inhibitory effect on HSCs but not on portal veins. These results suggest that NAd induces constriction of HSCs via increasing Ca2+ influx and Ca2+ sensitization, thereby regulating liver blood flow.

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Nicotine in tobacco, tetrahydrocannabinol (delta 9-THC) in marijuana and morphine in opium are well known as drugs associated with dependence or addiction. Endogenous active substances that mimic the effects of the natural drugs and their respective receptors have been found in the mammalian central nervous system (CNS). Such active substances and receptors include acetylcholine (ACh) and the nicotinic ACh receptor (nAChR) for nicotine, anandamide and CB1 for delta 9-THC, and endomorphins (1 and 2) and the mu (OP3) opioid receptor for morphine, respectively. Considerable progress has been made in studies on neurotoxicity, in terms of the habituation, dependence and withdrawal phenomena associated with these drugs and with respect to correlations with endogenous active substances and their receptors. In this article we shall review recent findings related to the neurotoxicity of tobacco, marijuana and opium, and their toxic ingredients, nicotine, delta 9-THC and morphine in relation to their respective endogenous agents and receptors in the CNS.