Advantage of Recording Single-Unit Muscle Sympathetic Nerve Activity in Heart Failure

Elevated sympathetic activation is a characteristic feature of heart failure (HF). Excessive sympathetic activation under resting conditions has been shown to increase from the early stages of the disease, and is related to prognosis. Direct recording of multiunit efferent muscle sympathetic nerve activity (MSNA) by microneurography is the best method for quantifying sympathetic nerve activity in humans. To date, this technique has been used to evaluate the actual central sympathetic outflow to the periphery in HF patients at rest and during exercise; however, because the firing occurrence of sympathetic activation is mainly synchronized by pulse pressure, multiunit MSNA, expressed as burst frequency (bursts/min) and burst incidence (bursts/100 heartbeats), may have limitations for the quantification of sympathetic nerve activity. In HF, multiunit MSNA is near the maximum level, and cannot increase further than the heartbeat. Single-unit MSNA analysis in humans is technically demanding, but provides more detailed information regarding central sympathetic firing. Although a great deal is known about the response of multiunit MSNA to stress, little information is available regarding the responses of single-unit MSNA to physiological stress and disease. The purposes of this review are to describe the differences between multiunit and single-unit MSNA during stress and to discuss the advantages of single-unit MSNA recording in improving our understanding the pathology of increased sympathetic activity in HF

ニホン フクシ ダイガク ニオケル ICT オ カツヨウ シタ ガクシュウ シエン ノ ジッセン

近年， ICT （Information and Communication Technology） を活用した学習支援の報告が各分野よりなされている． 日本福祉大学 （以下本学） でも， ICT を活用した学習方法として早期より e ラーニングに取り組み， 学内 LMS （Learning Management System） である nfu.jp 等を活用しながら様々な学習支援を実践し報告してきた． その後も学内インターネット環境や ICT 機器の充実化を推進し， 2013 年からは教職員と学生間の情報共有や能動的学習 （アクティブラーニング） 促進のために Google 社提供の Google Apps を導入するなど， ICT の活用に対し積極的な取り組みを行ってきた．全学教育センターでは， これらの様々な ICT 環境を活用しながら学習支援を行ってきた． しかし， 「コンピューターが苦手」 「セキュリティが不安」 「効果が解らない」 等の不安， 疑念をすべて払拭するには至っておらず， ICT を活用した学習， 学習支援が学内に十分に浸透したとは言えない． 本稿では ICT 活用事例として， 筆者が取り組んだ 「スポーツ授業における携帯端末を活用した振り返り実践」， 「コミュニケーション力演習における iPad や携帯端末を活用した学習」， 「文章作成力演習における Google Apps を活用した学習」 の事例と， 履修生の動向や実践から得られた知見を提示することで， ICT 活用の普及を助長することを目的とする

Adipose-derived regenerative cells exert beneficial effects on systemic responses following myocardial ischemia/reperfusion

Background: Acute coronary syndrome leads to systemic responses, including activation of the sympathetic nervous system, inflammation of atherosclerotic lesions, changes in metabolism and gene expressions of remote organs such as the spleen, bone marrow, and liver. Clinical trials and experimental studies have demonstrated that therapy with adipose-derived regenerative cells (ADRCs) attenuates myocardial ischemia/reperfusion (I/R) injury. The aim of this study is to investigate the role of ADRCs in regulating systemic reactions following I/R.Methods: Isolated ADRCs were obtained from green fluorescent protein transgenic male mice. Flow cytometry revealed that freshly isolated ADRCs expressed stem cell markers CD90 and Sca-1, and mesenchymal lineage marker. These cells exhibited multilineage differentiation into adipogenic, osteogenic, and chondrogenic lineages. Wild-type mice were subjected to 30 min of left ascending coronary ischemia and 24 h reperfusion. Freshly isolated ADRCs (105 cells) or vehicle (VEH), were administered intravenously through the tail at the time of reperfusion.Results: Compared to VEH, administration of ADRCs significantly reduced circulating troponin levels 24 h after I/R. Using quantitative real-time polymerase chain reaction analysis, the present study confirms that I/R-induced increase of factor X mRNA expression in the liver and was significantly inhibited by ADRCs compared to VEH. Administration of ADRCs significantly reduced the I/R-induced increase in serum levels of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-18 seen in mice receiving VEH.Conclusions: These results suggest that administration of ADRCs could have an important role in reducing myocardial injury and regulating the hepatic gene expression profile following I/R

Separated right and left ventricular excitation during right ventricular septal pacing in a patient with narrow QRS wave: A case report

Introduction. Right ventricular septal pacing is thought to be better than right ventricular apical pacing for shortening the QRS duration and for preserving left ventricular function. However, right ventricular septal pacing may not be effective in all cases. In this case report, we present a rare case in which right ventricular septal pacing induced thoroughly separated right and left ventricular excitation despite the presence of a relatively narrow QRS wave during atrium-only pacing. Case presentation. We report a case of 63-year-old Japanese man with cardiomyopathy with an implantable cardioverter defibrillator placement for ventricular tachycardia. Three years after implantation, he developed second-degree atrio-ventricular block. Therefore, atrio-ventricular sequential pacing was started; then his heart failure was much worsened. His electrocardiogram showed a dissociated biphasic QRS wave during right ventricular high-septal pacing, despite the presence of a non-fragmented QRS morphology during atrium-only pacing. An activation map during right ventricular high-septal pacing showed that right ventricular conduction started at the pacing site and ended at the right ventricular basal inferior site. Subsequently after a 10ms interval, left ventricular conduction started at the left ventricular posteroseptum and ended at the left ventricular lateral wall. These data indicate that during right ventricular high-septal pacing, the first component of the QRS wave supposedly reflects only right ventricular excitation and the second component only left ventricular excitation. Also due to the intracardiac electrograms, it was assumed that this phenomenon was caused by transversely limited severe transseptal conduction disturbance. Conclusion: It should be noted that even ventricular septal pacing could evoke harmful interventricular dyssynchrony due to transversely limited severe septal conduction disturbance, despite the presence of a relatively narrow QRS wave. © 2014 Yaegashi et al.; licensee BioMed Central Ltd

Cable externalization at the proximal portion of the superior vena cava coil in Riata implantable cardioverter defibrillator leads

Many Riata (St. Jude Medical, St. Paul, MN, USA) implantable cardioverter defibrillator (ICD) leads have reportedly developed cable externalization. The most likely cause of cable externalization is insulation abrasion, which often occurs at the can or between the right ventricular coil and superior vena cava (SVC) coil. We report a rare case of an adult male whose ICD lead cable was externalized at the proximal portion of the SVC coil. This lead became fixed to the wall at the subclavian vein and SVC and became bent between these adhesions. Furthermore, the motion of this lead was affected by pulsation of the aortic arch. The ICD lead might develop inside-out abrasion due to mechanical stress evoked by pulsation of the aortic arch at this site.. © 2016 Japanese College of Cardiology.Embargo Period 12 month

Endothelial-mesenchymal transition in human atrial fibrillation

Background: Atrial fibrosis is a hallmark of atrial structural remodeling leading to the persistence of atrial fibrillation. Although fibroblasts play a major role in atrial fibrosis, their source in the adult atrium is unclear. We tested the hypothesis that endothelial cells contribute to fibroblast accumulation through an endothelial-mesenchymal transition in the atrium of patients with atrial fibrillation. Methods and results: The study group consisted of patients with atrial fibrillation and valvular disease or atrial septal defect who underwent left atrial appendectomy during cardiac surgery (n =38). The amount of fibrotic depositions in the left atrium positively correlated with left atrial dimension. Furthermore, snail and S100A4, indicative of endothelial-mesenchymal transition, were quantified in the left atrium using western blot analysis, which showed statistically significant correlations with left atrial dimension. Immunofluorescence assay of the left atrial tissue identified snail and S100A4 being expressed within the endocardium which is composed of CD31+ cells. The snail-positive endocardium also showed the expression of membrane type 1-matrix metalloproteinase. Immunofluorescence multi-labeling experiments identified that heat shock protein 47, prolyl-4-hydroxylase, and procollagen type 1 co-localized with snail and S100A4 within the endothelial cells of the left atrium, indicating the mesenchymal phenotype to produce collagen. Conclusions: In this study, we showed that the endothelial-mesenchymal transition occurs in the atrium of patients with atrial fibrillation. This observation should help in constructing a novel therapeutic approach for preventing atrial structural remodeling. © 2016 Japanese College of Cardiology

G12/13 and Gq mediate S1P2-induced inhibition of Rac and migration in vascular smooth muscle in a manner dependent on Rho but not Rho kinase

金沢大学医薬保健研究域医学系Aims: The lysophospholipid mediator sphingosine-1-phosphate (S1P) activates G protein-coupled receptors (GPCRs) to induce potent inhibition of platelet-derived growth factor (PDGF)-induced Rac activation and, thereby, chemotaxis in rat vascular smooth muscle cells (VSMCs). We explored the heterotrimeric G protein and the downstream mechanism that mediated S1P inhibition of Rac and cell migration in VSMCs. Methods and results: S1P inhibition of PDGF-induced cell migration and Rac activation in VSMCs was abolished by the selective S1P2 receptor antagonist JTE-013. The C-terminal peptides of Gα subunits (Gα-CTs) act as specific inhibitors of respective G protein-GPCR coupling. Adenovirus-mediated expression of Gα12-CT, Gα13-CT, and Gα q-CT, but not that of Gαs-CT or LacZ or pertussis toxin treatment, abrogated S1P inhibition of PDGF-induced Rac activation and migration, indicating that both G12/13 and Gq classes are necessary for the S1P inhibition. The expression of Gαq-CT as well as Gα12-CT and Gα13-CT also abolished S1P-induced Rho stimulation. C3 toxin, but not a Rho kinase inhibitor or a dominant negative form of Rho kinase, abolished S1P inhibition of PDGF-induced Rac activation and cell migration. The angiotensin II receptor AT1, which robustly couples to Gq, did not mediate either Rho activation or inhibition of PDGF-induced Rac activation or migration, suggesting that activation of Gq alone was not sufficient for Rho activation and resultant Rac inhibition. However, the AT1 receptor fused to Gα12 was able to induce not only Rho stimulation but also inhibition of PDGF-induced Rac activation and migration. Phospholipase C inhibition did not affect S1P-induced Rho activation, and protein kinase C activation by a phorbol ester did not mimic S1P action, suggesting that S1P inhibition of migration or Rac was not dependent on the phospholipase C pathway. Conclusion: These observations together suggest that S1P2 mediates inhibition of Rac and migration through the coordinated action of G 12/13 and Gq for Rho activation in VSMCs. © The Author 2008.

DNA Damage Sensor γ

Background. Phosphorylated histone H2AX (γ-H2AX) is a potential regulator of DNA repair and is a useful tool for detecting DNA damage. To evaluate the clinical usefulness of γ-H2AX in hepatocellular carcinoma (HCC), we measured the level of γ-H2AX in HCC, dysplastic nodule, and nontumorous liver diseases. Methods. The level of γ-H2AX was measured by immunohistochemistry in fifty-eight HCC, 18 chronic hepatitis, 22 liver cirrhosis, and 19 dysplastic nodules. Appropriate cases were also examined by fluorescence analysis and western blotting. Results. All cases with chronic liver disease showed increased levels of γ-H2AX expression. In 40 (69.9%) of 58 cases with HCC, the labeling index (LI) of γ-H2AX was above 50% and was inversely correlated with the histological grade. Mean γ-H2AX LI was the highest in dysplastic nodule (74.1±22.1%), which was significantly higher than HCC (P<0.005). Moreover, γ-H2AX was significantly increased in nontumorous tissues of HCC as compared with liver cirrhosis without HCC (62.5±24.7%, from 5.1 to 96.0%, P<0.005). Conclusions. γ-H2AX was increased in the preneoplastic lesions of HCC and might be a useful biomarker for predicting the risk of HCC

Evaluation of Quality of Life in Japanese Normal Pregnant Women

To evaluate QOL changes during pregnancy in developed country, we analyzed 159 pregnant Japanese women (67 nulliparous and 92 multiparous) who had no complications during pregnancy. Subjects were asked to complete the Medical Outcomes Study Short Form (SF-36) every 4 weeks up to 24 weeks of gestation, and every 2 weeks from 24 weeks of gestation until delivery. Subscales that reflect "Physical functioning (p?0.001)", "Role-physical (p?0.001)" and "Bodily pain (p?0.001)" showed significant declines throughout the entire pregnancy. On the other hand, subscales that reflect "Vitality," "General health" and "Mental health" did not change substantially with gestational age. Furthermore, subscales that reflect "Physical functioning," "Role physical," "General health" showed no significant differences between nulliparous and multiparous women. Although subscales that reflect "Bodily pain," "Vitality," "Social functioning," "Role emotional" and "Mental health" showed significant differences between nulliparous and multiparous women, these subscales showed significant interactions. Our results suggest that pregnant women need support, regardless of the number of deliveries. Appropriate supports to pregnant women will be available to improve the birth rate in developed countries