Generation of Tetrafluoroethylene–Propylene Elastomer-Based Microfluidic Devices for Drug Toxicity and Metabolism Studies

フッ素系エラストマー素材を用いた肝臓チップの開発と薬物代謝・毒性試験への応用. 京都大学プレスリリース. 2021-09-16.Drug testing on miniatured livers. 京都大学プレスリリース. 2021-09-17.Polydimethylsiloxane (PDMS) is widely used to fabricate microfluidic organs-on-chips. Using these devices (PDMS-based devices), the mechanical microenvironment of living tissues, such as pulmonary respiration and intestinal peristalsis, can be reproduced in vitro. However, the use of PDMS-based devices in drug discovery research is limited because of their extensive absorption of drugs. In this study, we investigated the feasibility of the tetrafluoroethylene–propylene (FEPM) elastomer to fabricate a hepatocyte-on-a-chip (FEPM-based hepatocyte chip) with lower drug absorption. The FEPM-based hepatocyte chip expressed drug-metabolizing enzymes, drug-conjugating enzymes, and drug transporters. Also, it could produce human albumin. Although the metabolites of midazolam and bufuralol were hardly detected in the PDMS-based hepatocyte chip, they were detected abundantly in the FEPM-based hepatocyte chip. Finally, coumarin-induced hepatocyte cytotoxicity was less severe in the PDMS-based hepatocyte chip than in the FEPM-based hepatocyte chip, reflecting the different drug absorptions of the two chips. In conclusion, the FEPM-based hepatocyte chip could be a useful tool in drug discovery research, including drug metabolism and toxicity studies

思春期女性の踵骨骨評価値に対する利き足の影響に関する検討

When I perform bone evaluation by supersonic wave measurement，I only evaluate the right foot without considering the subject’s laterality，or potential differences between right and left foot bone density. Puberty is the period during which bone density rises，and during which the influence of mechanical stress is considered great，and evaluation of the right foot has been considered sufficient to clarify this effect. From the viewpoint of general health and prevention of osteoporosis we must measure one’s bone density in puberty， raise the peak bone mass，and maintain it. The present experiment was performed to clarify what kind of influence laterality of foot and exercise habits had on the bone density of the right calcaneus. Exercise habits did not have much influence on the bone density rise if the right foot was non-dominant. However，a meaningful connection was recognized between exercise habits and bone density rise if the right foot was dominant. From these results，it was thought that the measurement of calcaneus bone density by a supersonic wave method in puberty is more effective if the dominant foot is used

授業「キャンプ実習」に関する研究（4） ― 4 ヶ年の基礎研究と総合評価―

This research of the fourth stage executed mainly the comparison of the basic researches into four years. The chief purpose was clarification of a universal part of four years. The results were summarized as follows: 1．The reason for participation was“Cheap expenditure”and“Course credit”．The expected program was“Observation of constellation”and“Outdoors cooking”．The expectation and the acquisition target were“Enjoyment”，“Safety”and“Peace”． 2．This year’s problem was a discovery of the method of thoroughly improving students’knowledge and technologies. 3．Students’leadership was extent to be able to do“Life guidance”and“Standard program”． 4．The factor analysis has extracted the following six factors.“Mutual guidance and Consideration”， “Impartiality and Democratic”，“Inspiration and Commitment”，“Active collaboration and Device”，“ Pleasant sharing”and“Self management and Health condition”． 5．The attitude to the students’outdoors activities has changed independent and positively.The practice gave the good influence to students’“Standpoint and Attitude”．The practice was effective in“Understanding and Goodwill”to nature. There was a difficulty of controlling the influence by the weather when doing outdoor sports

体組成と脈波伝播速度からみた思春期女性の生活習慣病危険因子の検討

We reviewed what kind of factors became lifestyle-related diseases risk factors in girls at puberty. The purpose of this study was to gather data for the primary prevention of lifestyle-related diseases. Subjects were 57 basically healthy girls at the age of puberty，from seventh grade to twelfth grade. We measured body composition including bone density of the whole body using Dual Energy X-ray Absorptiometry. We used form PWV/ABI（Omron Colin Co.，Ltd.，Japan）for the measurement of Pulse Wave Velocity. It became clear that there was a danger of elevated baPWV values in girls whose percentage of body fat and soft tissue fat rate were low. On the other hand，it became clear that bone mineral density（BMD）was likely high in subjects whose percentage of body fat and soft tissue fat rate were high. It is thought that a higher-than-standard percent of body fat becomes an advantage for elevated bone density. From these results，it was concluded that lifestyle-related disease risk factors for girls at puberty with a high rate of body fat are low

若年女性の生活習慣と脂質代謝の関連に関する検討

The purpose of this study is to review the factors influencing lipid metabolism of young women in terms of both exercise and nutrition. From the side of nutrition，we reviewed how lipid metabolism is influenced by taking a commercial fish oil supplement（LIQUAMEN）. Total cholesterol deteriorated significantly by taking LIQUAMEN. Improvement of lipid metabolism by LIQUAMEN was suggested. The value of HDL-cholesterol，adiponectin，and leptin were significantly lower in the group of living activity strength Ⅱ while the values of TG and TNF-α increased significantly. This result suggested the possibility that lipid metabolism deteriorated in subjects whose activity was below a certain amount. It also suggested the possibility that lipid metabolism improved in those whose activity was above a certain amount. In the body fat-to-weight ratio， the living activity strengthⅢ・ Ⅳ group showed a significantly lower tendency compared to the group of living activity strength Ⅱ and the group of living activity strengthⅢ・ Ⅳ . This finding suggested that if activity was greater than a certain amount，the body fat-to-weight ratio tended to be comparatively low

Association between facility-level adherence to phosphorus management guidelines and mortality in haemodialysis patients: a prospective cohort study

[Objectives] To examine the association between facility-level adherence to phosphorus management guidelines and mortality among patients with haemodialysis, and to explore the facility-related factors associated with facility-level guideline adherence. [Design] Prospective cohort study. [Setting] The Dialysis Outcomes and Practice Pattern Study, which included 57 representative dialysis facilities in Japan between 2012 and 2015. [Participants] A total of 2054 adult patients who received maintenance haemodialysis were included. We defined exposure according to the following four categories, depending on whether facility-level target ranges of serum phosphorus concentration adhered to the Japanese clinical practice guidelines: adherence group (lower limit ≥3.5 mg/dL and upper limit ≤6.0 mg/dL), low-target group (lower limit 6.0) and high-target group (lower limit ≥3.5 and upper limit >6.0). [Primary outcome measure] The primary outcome was the patient all-cause mortality rate. [Results] The mortality rate among the patients was 7.3 per 100 person-years; 27 facilities (47%) set targets according to the guidelines. HRs for mortality with reference to the adherence group were 1.04 (95% CI 0.76 to 1.43) in the low-target group, 1.11 (95% CI 0.68 to 1.81) in the wide-target group and 1.95 (95% CI 1.12 to 3.38) in the high-target group. Involvement of dieticians in dialysis treatment was associated with facility-level guideline adherence (OR 4.51; 95% CI 1.15 to 17.7). [Conclusions] A higher facility-level target range for phosphorus was associated with increased patient mortality. Among facilities that set the target according to the guidelines, dieticians tended to be involved in dialysis care. These findings suggest the importance of reviewing facilities’ treatment policies in relation to updated guidelines and the need to work with relevant professionals

Cesarean section following idiopathic rupture of renal artery aneurysm leading to fetal dysfunction

Abstract Background Renal artery aneurysms (RAAs) in pregnancy are uncommon, with most found after rupturing. The risk of RAA rupture increases during pregnancy and delivery. Case presentation A 29-year-old woman at 36 weeks and 5 days of gestation presented with severe back and abdominal pain. No fetal movements were identified. Cesarean section (C/S) was performed due to severe fetal bradycardia. No signs of placental abruption or abnormalities of the placenta were apparent intraoperatively, but gross hematoma was identified intraoperatively in the left retroperitoneal space. To evaluate persistent hypotension and retroperitoneal hematoma, contrast-enhanced computed tomography was performed and revealed ruptured RAA in the left kidney. Transcatheter arterial embolization (TAE) was performed. Conclusions This case report describes fetal dysfunction caused by RAA rupture and controlled by TAE

Nardilysin prevents amyloid plaque formation by enhancing α-secretase activity in an Alzheimer's disease mouse model.

Amyloid beta (Aβ) peptide, the main component of senile plaques in patients with Alzheimer's disease (AD), is derived from proteolytic cleavage of amyloid precursor protein (APP) by β- and γ-secretases. Alpha-cleavage of APP by α-secretase has a potential to preclude the generation of Aβ because it occurs within the Aβ domain. We previously reported that a metalloendopeptidase, nardilysin (N-arginine dibasic convertase; NRDc) enhances α-cleavage of APP, which results in the decreased generation of Aβ in vitro. To clarify the in vivo role of NRDc in AD, we intercrossed transgenic mice expressing NRDc in the forebrain with an AD mouse model. Here we demonstrate that the neuron-specific overexpression of NRDc prevents Aβ deposition in the AD mouse model. The activity of α-secretase in the mouse brain was enhanced by the overexpression of NRDc, and was reduced by the deletion of NRDc. However, reactive gliosis adjacent to the Aβ plaques, one of the pathological features of AD, was not affected by the overexpression of NRDc. Taken together, our results indicate that NRDc controls Aβ formation through the regulation of α-secretase