Liver-kidney axis and plasma Pi rhythm

Circulating inorganic phosphate exhibits a remarkable daily oscillation based on food intake. In humans and rodents, the daily oscillation in response to food intake may be coordinated to control the intestinal absorption, renal excretion, cellular shifts, and extracellular concentration of inorganic phosphate. However, mechanisms regulating the resulting oscillation are unknown. Here we investigated the roles of the sodium phosphate cotransporter SLC34 (Npt2) family and nicotinamide phosphoribosyltransferase (Nampt) in the daily oscillation of plasma inorganic phosphate levels. First, it is roughly linked to urinary inorganic phosphate excretion. Second, expression of renal Npt2a and Npt2c, and intestinal Npt2b proteins also exhibit a dynamic daily oscillation. Analyses of Npt2a, Npt2b, and Npt2c knockout mice revealed the importance of renal inorganic phosphate reabsorption and cellular inorganic phosphate shifts in the daily oscillation. Third, experiments in which nicotinamide and a specific Nampt inhibitor (FK866) were administered in the active and rest phases revealed that the Nampt/NAD+ system is involved in renal inorganic phosphate excretion. Additionally, for cellular shifts, liver-specific Nampt deletion disturbed the daily oscillation of plasma phosphate during the rest but not the active phase. In systemic Nampt+/- mice, NAD levels were significantly reduced in the liver, kidney, and intestine, and the daily oscillation (active and rest phases) of the plasma phosphate concentration was attenuated. Thus, the Nampt/ NAD+ system for Npt2 regulation and cellular shifts to tissues such as the liver play an important role in generating daily oscillation of plasma inorganic phosphate levels

Phosphate Homeostasis and Osteocyte Ablation

In response to kidney damage, osteocytes increase the production of several hormones critically involved in mineral metabolism. Recent studies suggest that osteocyte function is altered very early in the course of chronic kidney disease. In the present study, to clarify the role of osteocytes and the canalicular network in mineral homeostasis, we performed four experiments. In Experiment 1, we investigated renal and intestinal Pi handling in osteocyte-less (OCL) model mice [transgenic mice with the dentin matrix protein-1 promoter-driven diphtheria toxin (DT)-receptor that were injected with DT]. In Experiment 2, we administered granulocyte colony-stimulating factor to mice to disrupt the osteocyte canalicular network. In Experiment 3, we investigated the role of osteocytes in dietary Pi signaling. In Experiment 4, we analyzed gene expression level fluctuations in the intestine and liver by comparing mice fed a high Pi diet and OCL mice. Together, the findings of these experiments indicate that osteocyte ablation caused rapid renal Pi excretion (P < 0.01) before the plasma fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) levels increased. At the same time, we observed a rapid suppression of renal Klotho (P < 0.01), type II sodium phosphate transporters Npt2a (P < 0.01) and Npt2c (P < 0.05), and an increase in intestinal Npt2b (P < 0.01) protein. In OCL mice, Pi excretion in feces was markedly reduced (P < 0.01). Together, these effects of osteocyte ablation are predicted to markedly increase intestinal Pi absorption (P < 0.01), thus suggesting that increased intestinal Pi absorption stimulates renal Pi excretion in OCL mice. In addition, the ablation of osteocytes and feeding of a high Pi diet affected FGF15/bile acid metabolism and controlled Npt2b expression. In conclusion, OCL mice exhibited increased renal Pi excretion due to enhanced intestinal Pi absorption. We discuss the role of FGF23–Klotho on renal and intestinal Pi metabolism in OCL mice

A Role of Intestinal Alkaline Phosphatase 3 (Akp3) in Inorganic Phosphate Homeostasis

Background/Aims: Hyperphosphatemia is a serious complication of late-stage chronic kidney disease (CKD). Intestinal inorganic phosphate (Pi) handling plays an important role in Pi homeostasis in CKD. We investigated whether intestinal alkaline phosphatase 3 (Akp3), the enzyme that hydrolyzes dietary Pi compounds, is a target for the treatment of hyperphosphatemia in CKD. Methods: We investigated Pi homeostasis in Akp3 knockout mice (Akp3-/-). We also studied the progression of renal failure in an Akp3-/- mouse adenine treated renal failure model. Plasma, fecal, and urinary Pi and Ca concentration were measured with commercially available kit, and plasma fibroblast growth factor 23, parathyroid hormone, and 1,25(OH)2D3 concentration were measured with ELISA. Brush border membrane vesicles were prepared from mouse intestine using the Ca2+ precipitation method and used for Pi transport activity and alkaline phosphatase activity. In vivo intestinal Pi absorption was measured with oral 32P administration. Results: Akp3-/- mice exhibited reduced intestinal type II sodium-dependent Pi transporter (Npt2b) protein levels and Na-dependent Pi co-transport activity. In addition, plasma active vitamin D levels were significantly increased in Akp3-/- mice compared with wild-type animals. In the adenine-induced renal failure model, Akp3 gene deletion suppressed hyperphosphatemia. Conclusion: The present findings indicate that intestinal Akp3 deletion affects Na+-dependent Pi transport in the small intestine. In the adenine-induced renal failure model, Akp3 is predicted to be a factor contributing to suppression of the plasma Pi concentration

小腸のリン恒常性における小腸型アルカリホスファターゼ(Akp3)の役割について

Background/Aims: Hyperphosphatemia is a serious complication of late-stage chronic kidney disease (CKD). Intestinal inorganic phosphate (Pi) handling plays an important role in Pi homeostasis in CKD. We investigated whether intestinal alkaline phosphatase 3 (Akp3), the enzyme that hydrolyzes dietary Pi compounds, is a target for the treatment of hyperphosphatemia in CKD. Methods: We investigated Pi homeostasis in Akp3 knockout mice (Akp3-/-). We also studied the progression of renal failure in an Akp3-/- mouse adenine treated renal failure model. Plasma, fecal, and urinary Pi and Ca concentration were measured with commercially available kit, and plasma fibroblast growth factor 23, parathyroid hormone, and 1,25(OH)2D3 concentration were measured with ELISA. Brush border membrane vesicles were prepared from mouse intestine using the Ca2+ precipitation method and used for Pi transport activity and alkaline phosphatase activity. In vivo intestinal Pi absorption was measured with oral 32P administration. Results: Akp3-/- mice exhibited reduced intestinal type II sodium-dependent Pi transporter (Npt2b) protein levels and Na-dependent Pi co-transport activity. In addition, plasma active vitamin D levels were significantly increased in Akp3-/- mice compared with wild-type animals. In the adenine-induced renal failure model, Akp3 gene deletion suppressed hyperphosphatemia. Conclusion: The present findings indicate that intestinal Akp3 deletion affects Na+-dependent Pi transport in the small intestine. In the adenine-induced renal failure model, Akp3 is predicted to be a factor contributing to suppression of the plasma Pi concentration

Conditional deletion of Npt2b in phosphate transport

Background Hyperphosphatemia is common in chronic kidney disease and is associated with morbidity and mortality. The intestinal Na+-dependent phosphate transporter Npt2b is thought to be an important molecular target for the prevention of hyperphosphatemia. The role of Npt2b in the net absorption of inorganic phosphate (Pi), however, is controversial. Methods In the present study, we made tamoxifen-inducible Npt2b conditional knockout (CKO) mice to analyze systemic Pi metabolism, including intestinal Pi absorption. Results Although the Na+-dependent Pi transport in brush-border membrane vesicle uptake levels were significantly decreased in the distal intestine of Npt2b CKO mice compared with control mice, plasma Pi and fecal Pi excretion levels were not significantly different. Data obtained using the intestinal loop technique showed that Pi uptake in Npt2b CKO mice was not affected at a Pi concentration of 4 mM, which is considered the typical luminal Pi concentration after meals in mice. Claudin, which may be involved in paracellular pathways, as well as claudin-2, 12, and 15 protein levels were significantly decreased in the Npt2b CKO mice. Thus, Npt2b deficiency did not affect Pi absorption within the range of Pi concentrations that normally occurs after meals. Conclusion These findings indicate that abnormal Pi metabolism may also be involved in tight junction molecules such as Cldns that are affected by Npt2b deficiency

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

新しい批判的教育学の課題と方法

近年、1960年代後半のドイツにおいて誕生した批判的教育学の捉え直しと再構成が始まっている。その再構成には二つの方向性がみられる。一つは、1970年代のドイツにおいて誕生していた「批判的人間形成論」を取り入れることによって、新たに批判的教育学を構想する。もう一つは、フーコーの理論に影響をうけて、マッシェラインが展開している新しい批判的教育学である。本稿では、マッシェラインによって展開されている新しい批判的教育学を考察の対象とし、その課題と方法を明らかにすることを目的とする。考察によって明らかになったことは、新しい批判的教育学は、実践を導くという従来の理論的位置から倫理的態度の実践へと、批判の位置をずらす方向へと向かっているということである。These days, critical educational theory, which was born in the late 1960\u27s in Germany, has been reconstructed. There are two directions in reconstructing it. The one is to reconstruct the theory by introducing the kritische Bildungstheorie, which was also born in Germany in 1970\u27s. Another direction is the new critical educational theory developed by Masschelein who inspired by Foucault. The purpose of this thesis is to reveal the problems of Masschelein\u27s new critical educational theory and to find the ways to solve them. From the discussion, now it is clear that the new critical educational theory has been changing in its direction of criticism from leading practice to practice of ethical attitude

Effects of an Artificial Intelligence–Assisted Health Program on Workers With Neck/Shoulder Pain/Stiffness and Low Back Pain: Randomized Controlled Trial

BackgroundMusculoskeletal symptoms such as neck and shoulder pain/stiffness and low back pain are common health problems in the working population. They are the leading causes of presenteeism (employees being physically present at work but unable to be fully engaged). Recently, digital interventions have begun to be used to manage health but their effectiveness has not yet been fully verified, and adherence to such programs is always a problem. ObjectiveThis study aimed to evaluate the improvements in musculoskeletal symptoms in workers with neck/shoulder stiffness/pain and low back pain after the use of an exercise-based artificial intelligence (AI)–assisted interactive health promotion system that operates through a mobile messaging app (the AI-assisted health program). We expected that this program would support participants’ adherence to exercises. MethodsWe conducted a two-armed, randomized, controlled, and unblinded trial in workers with either neck/shoulder stiffness/pain or low back pain or both. We recruited participants with these symptoms through email notifications. The intervention group received the AI-assisted health program, in which the chatbot sent messages to users with the exercise instructions at a fixed time every day through the smartphone’s chatting app (LINE) for 12 weeks. The program was fully automated. The control group continued with their usual care routines. We assessed the subjective severity of the neck and shoulder pain/stiffness and low back pain of the participants by using a scoring scale of 1 to 5 for both the intervention group and the control group at baseline and after 12 weeks of intervention by using a web-based form. We used a logistic regression model to calculate the odds ratios (ORs) of the intervention group to achieve to reduce pain scores with those of the control group, and the ORs of the subjective assessment of the improvement of the symptoms compared to the intervention and control groups, which were performed using Stata software (version 16, StataCorp LLC). ResultsWe analyzed 48 participants in the intervention group and 46 participants in the control group. The adherence rate was 92% (44/48) during the intervention. The participants in the intervention group showed significant improvements in the severity of the neck/shoulder pain/stiffness and low back pain compared to those in the control group (OR 6.36, 95% CI 2.57-15.73; P<.001). Based on the subjective assessment of the improvement of the pain/stiffness at 12 weeks, 36 (75%) out of 48 participants in the intervention group and 3 (7%) out of 46 participants in the control group showed improvements (improved, slightly improved) (OR 43.00, 95% CI 11.25-164.28; P<.001). ConclusionsThis study shows that the short exercises provided by the AI-assisted health program improved both neck/shoulder pain/stiffness and low back pain in 12 weeks. Further studies are needed to identify the elements contributing to the successful outcome of the AI-assisted health program. Trial RegistrationUniversity hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) 000033894; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000038307

Effects of Ag Nanoparticle Coated Metal Electrodes on Electrochemical CO2 Reduction in Aqueous KHCO3

Electrochemical CO2 reduction is crucial for developing a sustainable closed-carbon-cycle society; however, the factors determining product selectivity have not been fully established, especially when the reaction is carried out over metal cathodes. The selectivity of the CO2 reduction pathway can be improved by modifying the cathode’s catalyst surface. This can be achieved by using specific surface of single crystal or by alloying through the addition of an impurity. In this study, the products of electrochemical CO2 reduction were evaluated in an aqueous KHCO3 system at various applied currents and with various metal cathodes. The metal cathodes were coated by Ag nanoparticles, as the Ag cathode was determined to yield the best Faradaic efficiency for CO production in an aqueous KHCO3 system. Our results suggest that some Ag coated cathodes enhance CO2 reduction, and thus the reduction products are tunable through surface modification