Leukocyte-depleted terminal blood cardioplegia provides superior myocardial protective effects in association with myocardium-derived nitric oxide and peroxynitrite production for patients undergoing prolonged aortic crossclamping for more than 120 minutes

AbstractObjectivesThis study was designed to examine the myocardial protective effect of leukocyte-depleted terminal blood cardioplegia in association with nitric oxide and peroxynitrite production, especially for patients undergoing prolonged aortic crossclamping.MethodsFifty-four patients (34 men, 20 women, mean age 56.7 ± 12.7 years) undergoing aortic valve replacement were randomly allocated to one of two groups; group LDTC (n = 27) received 10 minutes of leukocyte-depleted terminal blood cardioplegic solution, and group CONT (n = 27) served as controls. Each group was subdivided into 2 groups: aortic crossclamping for less than 120 minutes in groups LDTC-S (n = 13) and CONT-S (n = 14); aortic crossclamping for 120 minutes or more in groups LDTC-L (n = 14) and CONT-L (n = 13).ResultsAfter aortic unclamping, group LDTC-L showed higher incidence of spontaneous defibrillation (78.6% vs 30.8%, P = .0213), higher plasma nitrate + nitrite in the coronary sinus effluent (32.5 ± 4.1 vs 28.7 ± 3.0 μmol/L, P = .0013), lower differences between coronary sinus effluent and arterial blood in the percentage ratio of nitrotyrosine to tyrosine (myocardium-derived peroxynitrite; 2.987% ± 0.576% vs 3.951% ± 0.952%, P = .0036), and plasma polymorphonuclear-elastase (113.9 ± 21.3 vs 155.5 ± 41.6 μg/L, P = .0029) and malondialdehyde (2.75 ± 0.67 vs 4.02 ± 0.96 μmol/L, P = .0005) than group CONT did. Postoperatively, group LDTC-L showed lower human-heart fatty acid–binding protein (111.4 ± 25.2 vs 156.4 ± 38.6 IU/L, P = .0013), lower creatine kinase–muscle and brain (19.2 ± 4.7 vs 24.8 ± 6.5 IU/L, P = .0120), and smaller requirement of catecholamine (5.44 ± 2.29 vs 8.45 ± 3.42 μg · kg−1 · min−1, P = .0122). There were no significant differences in these parameters between groups LDTC-S and CONT-S.ConclusionsThis study demonstrated that leukocyte-depleted terminal blood cardioplegia provided superior myocardial protective effects and regulated myocardial-derived nitric oxide and peroxynitrite production only for patients undergoing aortic crossclamping for more than 120 minutes. The results suggest that prolonged aortic crossclamping deteriorates the tolerance to leukocyte-mediated myocardial injury accompanied by endothelial dysfunction associated with nitric oxide and peroxynitrite production

Transplantation of a human induced pluripotent stem cell-derived airway epithelial cell sheet into the middle ear of rats

[Introduction] Early postoperative regeneration of the middle ear mucosa is essential for the prevention of postoperative refractory otitis media and recurrent cholesteatoma. As a means for intractable otitis media management, we focused on human induced pluripotent stem cell (hiPSC)-derived airway epithelial cells (AECs), which have been used in upper airway mucosal regeneration and transplantation therapy. In this study, we transplanted hiPSC-derived AECs into the middle ear of immunodeficient rats. [Methods] Following the preparation of AEC sheets from hiPSCs, the bilateral middle ear mucosa of X-linked severe combined immunodeficient rats was scraped, and the AEC sheets were transplanted in the ears unilaterally. [Results] Human nuclear antigen (HNA)-positive ciliated cells were observed on the transplanted side of the middle ear cavity surface in three of six rats in the 1-week postoperative group and in three of eight rats in the 2-week postoperative group. No HNA-positive cells were found on the control side. The percentage of HNA-positive ciliated cells in the transplanted areas increased in the 2-week postoperative group compared with the 1-week group, suggesting survival of hiPSC-derived AECs. Additionally, HNA-positive ciliated cells were mainly located at sites where the original ciliated cells were localized. Immunohistochemical analysis showed that the transplanted AECs contained cytokeratin 5- and mucin 5AC-positive cells, indicating that both basal cells and goblet cells had regenerated within the middle ear cavity. [Conclusions] The results of this study are an important first step in the establishment of a novel transplantation therapy for chronic otitis media

In vivo regeneration of rat laryngeal cartilage with mesenchymal stem cells derived from human induced pluripotent stem cells via neural crest cells

The laryngotracheal cartilage is a cardinal framework for the maintenance of the airway for breathing, which occasionally requires reconstruction. Because hyaline cartilage has a poor intrinsic regenerative ability, various regenerative approaches have been attempted to regenerate laryngotracheal cartilage. The use of autologous mesenchymal stem cells (MSCs) for cartilage regeneration has been widely investigated. However, long-term culture may limit proliferative capacity. Human-induced pluripotent stem cell-derived MSCs (iMSCs) can circumvent this problem due to their unlimited proliferative capacity. This study aimed to investigate the efficacy of iMSCs in the regeneration of thyroid cartilage in immunodeficient rats. Herein, we induced iMSCs through neural crest cell intermediates. For the relevance to prospective future clinical application, induction was conducted under xeno-free/serum-free conditions. Then, clumps fabricated from an iMSC/extracellular matrix complex (C-iMSC) were transplanted into thyroid cartilage defects in immunodeficient rats. Histological examinations revealed cartilage-like regenerated tissue and human nuclear antigen (HNA)-positive surviving transplanted cells in the regenerated lesion. HNA-positive cells co-expressed SOX9, and type II collagen was identified around HNA-positive cells. These results indicated that the transplanted C-iMSCs promoted thyroid cartilage regeneration and some of the iMSCs differentiated into chondrogenic lineage cells. Induced MSCs may be a promising candidate cell therapy for human laryngotracheal reconstruction

Laryngeal Cartilage Regeneration of Nude Rats by Transplantation of Mesenchymal Stem Cells Derived from Human-Induced Pluripotent Stem Cells

Previous studies transplanted human-induced pluripotent stem cells (hiPSCs)-derived mesenchymal stem cells (iMSCs) into thyroid cartilage defect of X-liked severe combined immunodeficiency (X-SCID) rats and confirmed transplanted cell survival and cartilage regeneration. Thus, this study aimed to investigate the contribution of iMSC transplantation to thyroid cartilage regeneration of nude rats. iMSCs were induced from hiPSCs via a neural crest cell lineage. Then, clumps formed from an iMSC/extracellular matrix complex were transplanted into thyroid cartilage defects in nude rats. The larynx was removed and histological and immunohistochemical analyses were performed 4 or 8 weeks after the transplantation. Human nuclear antigen (HNA)-positive cells were observed in 11 of 12 (91.7%) rats, which indicated that transplanted iMSCs survived in thyroid cartilage defects in nude rats. HNA-positive cells co-expressed SOX9, and type II collagen was identified around HNA-positive cells in 8 of 12 rats (66.7%), which indicated cartilage-like regeneration. Cartilage-like regeneration in nude rats in this study was comparable to the previous report on X-SCID rats (HNA-positive cells were observed in all 14 rats and cartilage-like regeneration was observed in 10 of 14 rats). This result suggests that nude rats could be an alternative to X-SCID rats in thyroid cartilage regeneration experiments using iMSCs, and this nude rat cartilage transplantation model may develop cartilage regeneration research concerning fewer problems such as infection due to immunosuppression

Effects of texture modification on the flavor of foods for elderly people with dysmasesis

The aroma and flavor of food before and during eating is a major determinant of the pleasure which drives us to eat. The aim of this study was to investigate how texture modification influences the aroma and flavor of two types of texture-modified teriyaki-based salmon foods (chopped salmon teriyaki and steamed salmon teriyaki-paste) as compared to original salmon teriyaki using gas chromatographyolfactometry and retronasal olfactometry analyses. The results indicated that the odor of soy sauce was weaker in the modified foods as compared to the original, with the past having even less odor than the chopped salmon teriyaki. The sensory evaluation corresponded with the gas chromatography results, and showed that odor was an important factor contributing to preference. Steamed salmon teriyaki-paste is suitable for elderly people with dysmasesis because it is easy to chew and swallow ; thus, optimal cooking conditions to improve its odor should be developed.研究ノー

Associations of Glucose and Blood Pressure Variability with Cardiac Diastolic Function in Patients with Type 2 Diabetes Mellitus and Hypertension: A Retrospective Observational Study

We evaluated the effects of glucose metabolism and blood pressure（BP） variability on cardiac diastolic function in patients with type 2 diabetes mellitus（T2DM） and hypertension. A total of 23 inpatients with T2DM underwent ambulatory BP monitoring（ABPM） and echocardiography. BP variability was assessed by measuring the mean BP and the standard deviation（SD） of systolic and diastolic BP over 24 hours, as well as daytime and nighttime ABPM. Cardiac diastolic function was assessed using the echocardiography E/e′ ratio. Participants had a mean age of 69.0±10.6 years, disease duration of 11.0±10.5 years, glycated hemoglobin（HbA1c） of 8.2％±1.3％, and glycated albumin（GA） of 22.0％±4.2％. Univariate analysis showed that the nighttime systolic BP, nighttime SDs of systolic and diastolic BP, urinary albumin, estimated glomerular filtration rate, and GA/HbA1c ratio were all significantly correlated with the E/e′ ratio. Moreover, stepwise multiple regression analysis identified nighttime SD of diastolic BP, urinary albumin, and GA/HbA1c ratio as independent contributors to the E/e′ ratio. In patients with T2DM and hypertension, cardiac diastolic function was associated with nighttime diastolic BP variability and the GA/HbA1c ratio

Organized and Sustainable Education Program for Drug Abuse Prevention by Yogo-teachers

　学校における喫煙・飲酒・薬物乱用防止教育の充実には，問題行動が顕在化する中学校期だけでなく小学校期 における指導の推進が重要であり，系統的な指導計画を立て，指導者や時間の確保，教材作成などに組織的に取 組み，継続可能なプログラム開発を行う必要がある。そこで，地区内12 校の養護教諭が協働して，発達段階に応 じた系統的・組織的かつ継続可能な地区共通の指導計画を開発し，各校の教育課程・年間計画に位置付けた実践 研究を行った。その結果，指導計画の実施状況は，小学校11 校中，学級活動10 校，ミニ保健指導10 校，長期 休業前指導6 校，広報活動9 校となり，特別支援学校1 校では広報活動のみを行うことができた。小学校におけ る喫煙・飲酒・薬物乱用防止教育の推進には，学校保健活動の中核的役割を担う養護教諭が専門性を活かし協働 して，系統的な指導計画を各校の教育課程に位置付け組織的で継続可能なプログラムとする取組が有効であった