Nocturnal hypoxic stress activates invasive ability of monocytes in patients with obstructive sleep apnea syndrome

Backgrounds: Obstructive sleep apnea syndrome (OSAS) is known to be a risk factor of cardiovascular events. However, the precise mechanism has not been fully elucidated. OSAS-induced hypoxic stress may promote the production of inflammatory cytokines and chemokines by monocytes, which has a crucial role in the development of atherosclerosis. In addition, adhesion to the vascular endothelium and transendothelial migration of monocytes are considered to induce atherosclerosis. The aim of this study was to investigate the effects of hypoxic stress on the invasive ability of monocytes in OSAS. Methods; Twenty-one male OSAS patients and 17 male healthy control subjects, age- and body mass index-matched, were enrolled. Venous blood samples were collected not only before and after sleep but also after CPAP titration for the purpose of monocyte isolation. The invasive ability of monocytes was evaluated by counting the number of invasive cells using a BD BioCoat Matrigel Invasion Chamber. Results; The number of cells which represents invasive ability was significantly higher in OSAS patients as compared to control subjects in the early morning (p<0.001). Invasive ability in the early morning was significantly elevated as compared to that before sleep in OSAS patients (p<0.001), and it was positively correlated with oxygen desaturation index (p<0.05). CPAP titration led to alleviation of the invasive ability (p<0.001). Conclusions; The results indicate that OSAS-induced hypoxic stress activates the invasive ability of monocytes, and that this phenomenon observed during sleep may contribute to the development of atherosclerosis in OSAS.The definitive version is available at " http://dx.doi.org/10.1111/j.1440-1843.2009.01540.x "アジア太平洋呼吸器学会（APSR：Asia Pacific Society of Respirology）第1回最優秀論文賞「Fukuchi Award」受賞論

CPAPアドヒランスの予測因子としてのCPAP装着下覚醒時の呼吸不規則性

BACKGROUND AND OBJECTIVE: The standard therapy for obstructive sleep apnoea (OSA) is continuous positive airway pressure (CPAP) therapy. However, long-term adherence remains at ~50% despite improvements in behavioural and educational interventions. Based on prior work, we explored whether regularity of breathing during wakefulness might be a physiologic predictor of CPAP adherence. METHODS: Of the 117 consecutive patients who were diagnosed with OSA and prescribed CPAP, 79 CPAP naïve patients were enrolled in this prospective study. During CPAP initiation, respiratory signals were collected using respiratory inductance plethysmography while wearing CPAP during wakefulness in a seated position. Breathing regularity was assessed by the coefficient of variation (CV) for breath-by-breath estimated tidal volume (VT ) and total duration of respiratory cycle (Ttot). In a derivation group (n = 36), we determined the cut-off CV value which predicted poor CPAP adherence at the first month of therapy, and verified the validity of this predetermined cut-off value in the remaining participants (validation group; n = 43). RESULTS: In the derivation group, the CV for estimated VT was significantly higher in patients with poor adherence than with good adherence (median (interquartile range): 44.2 (33.4-57.4) vs 26.0 (20.4-33.2), P 34.0 confirmed to be predicting poor CPAP adherence (sensitivity, 0.78; specificity, 0.83). CONCLUSION: At the initiation of therapy, breathing regularity during wakefulness while wearing CPAP is an objective predictor of short-term CPAP adherence.博士（医学）・乙第1391号・平成29年3月15日© 2016 Asian Pacific Society of RespirologyThis is the peer reviewed version of the following article: Respirology Vol.22 No.2 p.386-393 (2017 Feb), which has been published in final form at http://dx.doi.org/10.1111/resp.12900. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving

慢性閉塞性肺疾患患者における骨塩量の分布と体重および運動能との関連

Background: Although low bone mineral density is highly prevalent in patients with chronic obstructive pulmonary disease (COPD), the distribution of the reduced bone mass has not been fully elucidated. Objectives: To determine regional bone mass loss in patients with COPD and investigate whether the change in distribution may be associated with body weight loss and functional capacity. Methods: Body mass index (BMI) was assessed, and height squared indices were derived for the bone mineral content index (BMCI) of the arms, legs and trunk by dual-energy X-ray absorptiometry in 45 male patients with COPD and 12 age- and sex-matched control subjects. Pulmonary function tests were performed, and maximal oxygen uptake (V·O2max) was measured. Results: The BMCI was lower in the total bone, legs and trunk of patients with COPD than in control subjects, although the BMCI in the arms was similar between the groups. BMI correlated significantly with the BMCI in all 3 segments. Bone mineral content (BMC) in the trunk, expressed as a percentage of total BMC (BMC trunk/total BMC), correlated significantly with BMI. The BMCI in the trunk was closely related with V·O2max but not with airflow limitation. Conclusions: There was a regional difference in BMC reduction, but a predominant reduction of bone mass in the trunk was not associated with the severity of airflow limitation but rather with body weight loss and exercise intolerance. These data suggest that body weight loss and exercise intolerance are important risk factors for vertebral fracture in patients with COPD.博士（医学）・乙第1341号・平成26年7月22日The definitive version is available at " http://dx.doi.org/10.1159/000355095

A new crystal phase of N,N,N′,N′-tetra­phenyl-1,1′-biphenyl-4,4′-diamine

The complete molecule of the title compound, C36H28N2, is generated by a crystallographic centre of inversion. The biphenyl unit is forced by symmetry to be essentially flat (r.m.s. deviation = 0.008 Å); the dihedral angles between it and the two terminal phenyl rings are 69.39 (5) and 59.53 (5)°

Fibrocytes are involved in the pathogenesis of human chronic kidney disease

金沢大学医薬保健研究域医学系The presence of chronic kidney disease in humans is associated with a risk of kidney function loss as well as the development of cardiovascular disease. Fibrocytes have been shown to contribute to organ fibrosis. In this study, the presence of fibrocytes was investigated immunohistochemically in kidney biopsy specimens from 100 patients with chronic kidney disease. In addition, 6 patients with thin basement membrane disease were studied as a disease control. In patients with chronic kidney disease, the infiltration of fibrocytes was observed mainly in the interstitium. The number of interstitial fibrocytes in patients with chronic kidney disease was higher than that in patients with thin basement membrane disease. The number of infiltrated fibrocytes in the interstitium correlated well with the severity of tubulointerstitial lesions, such as interstitial fibrosis, in patients with chronic kidney disease. In addition, there were significant correlations between the number of interstitial fibrocytes and the number of CD68-positive macrophages in the interstitium as well as urinary monocyte chemoattractant protein-1/CCL2 levels. In particular, there was an inverse correlation between the number of interstitial fibrocytes and kidney function at the time of biopsy. Finally, the numbers of interstitial fibrocytes and macrophages as well as urinary CCL2 levels were significantly decreased during convalescence induced by glucocorticoid therapy. These results suggest that fibrocytes may be involved in the pathogenesis of chronic kidney disease through the interaction with macrophages as well as CCL2. © 2010 Elsevier Inc. All rights reserved

Obstructive sleep apnea and its malajemente in patients with atrial fibrillation: An International Collaboration of Sleep Apnea Cardiovascular Trialists (INCOSACT) global survey of practicing cardiologists

Background: Among international cardiologists it is unclear whether equipoise exists regarding the benefit of diagnosing and managing obstructive sleep apnea (OSA) to improve atrial fibrillation (AF) outcomes and whether clinical practice and equipoise are linked. Methods: Between January 2019 and June 2020 we distributed a web-based 12-question survey regarding OSA and AF management to practicing cardiologists in 16 countries. Results: The United States, Japan, Sweden, and Turkey accounted for two-thirds of responses. 863 cardiologists responded; half were general cardiologists, a quarter electrophysiologists. Responses regarding treating OSA with CPAP to improve AF endpoints were mixed. 33% of respondents referred AF patients for OSA screening. OSA was diagnosed in 48% of referred patients and continuous positive airway pressure (CPAP) was prescribed for 59% of them. Nearly 70% of respondents believed randomized controlled trials (RCTs) of OSA treatment in AF patients were necessary and indicated willingness to contribute to such trials. Conclusions: There was no clinical equipoise among surveyed cardiologists; a majority expressed certainty that combined OSA and AF treatment is superior to AF treatment alone for improving AF outcomes. However, a minority of surveyed cardiologists referred AF patients for OSA testing, and while half of screened AF patients had OSA, CPAP was prescribed in little more than half of them, reflecting the view that better clinical trial evidence is needed to support this practice. Our results underscore the need for larger, multi-national prospective studies of OSA treatment and AF outcomes to inform more uniform society guideline recommendations

Effects of buspirone on posthypoxic ventilatory behavior in the C57BL/6J and A/J mouse strains

Buspirone, a partial agonist of the serotonergic 5-HT1A receptor, improves breathing irregularities in humans with Rett syndrome or brain stem injury. The purpose of this study was to examine whether buspirone alters posthypoxic ventilatory behavior in C57BL/6J (B6) and A/J mouse strains. Measurements of ventilatory behavior were collected from unanesthetized adult male mice (n = 6 for each strain) using the plethysmographic method. Mice were given intraperitoneal injections of vehicle or several doses of buspirone and exposed to 2 min of hypoxia (10% O2) followed by rapid reoxygenation (100% O2). Twenty minutes later, mice were tested for hypercapnic response (8% CO2-92% O2). On a separate day, mice were injected with the 5-HT1A receptor antagonist 4-iodo-N-{2-[4-(methoxyphenyl)-1-piperazinyl] ethyl}-N-2-pyridinylbenzamide (p-MPPI) before the injection of buspirone, and measurements were repeated. In separate studies, arterial blood-gas analysis was performed for each strain (n = 12 in B6 and 10 in A/J) with buspirone or vehicle. In both strains, buspirone stimulated ventilation at rest. In the B6 mice, the hypoxic response was unchanged, but the response to hypercapnia was reduced with buspirone (5 mg/kg; P < 0.05). With reoxygenation, vehicle-treated B6 exhibited periodic breathing and greater variation in ventilation compared with A/J (P < 0.01). In B6 animals, ≥3 mg/kg of buspirone reduced variation and prevented the occurrence of posthypoxic periodic breathing. Both effects were reversed by p-MPPI. Treatment effect of buspirone was not explained by a difference in resting arterial blood gases. We conclude that buspirone improves posthypoxic ventilatory irregularities in the B6 mouse through its agonist effects on the 5-HT1A receptor