Functional intestinal monolayers from organoids derived from human iPS cells for drug discovery research

Inui T., Uraya Y., Yokota J., et al. Functional intestinal monolayers from organoids derived from human iPS cells for drug discovery research. Stem Cell Research and Therapy 15, 57 (2024); https://doi.org/10.1186/s13287-024-03685-5.Background: Human induced pluripotent stem (iPS) cell-derived enterocyte-like cells (ELCs) are expected to be useful for evaluating the intestinal absorption and metabolism of orally administered drugs. However, it is difficult to generate large amounts of ELCs with high quality because they cannot proliferate and be passaged. Methods: To solve the issue above, we have established intestinal organoids from ELCs generated using our protocol. Furthermore, monolayers were produced from the organoids. We evaluated the usefulness of the monolayers by comparing their functions with those of the original ELCs and the organoids. Results: We established organoids from ELCs (ELC-org) that could be passaged and maintained for more than a year. When ELC-org were dissociated into single cells and seeded on cell culture inserts (ELC-org-mono), they formed a tight monolayer in 3 days. Both ELC-org and ELC-org-mono were composed exclusively of epithelial cells. Gene expressions of many drug-metabolizing enzymes and drug transporters in ELC-org-mono were enhanced, as compared with those in ELC-org, to a level comparable to those in adult human small intestine. The CYP3A4 activity level in ELC-org-mono was comparable or higher than that in primary cryopreserved human small intestinal cells. ELC-org-mono had the efflux activities of P-gp and BCRP. Importantly, ELC-org-mono maintained high intestinal functions without any negative effects even after long-term culture (for more than a year) or cryopreservation. RNA-seq analysis showed that ELC-org-mono were more mature as intestinal epithelial cells than ELCs or ELC-org. Conclusions: We have successfully improved the function and convenience of ELCs by utilizing organoid technology

Safety of venipuncture sites at the cubital fossa as informed by ultrasonography

金沢大学医薬保健研究域保健学系Objective The aim of the present observational study was to identify safe and suitable venipuncture sites for nursing in the clinical setting using ultrasonography to measure the depth and cross-sectional area of each superficial vein before and after tourniquet application as well as the distance between each superficial vein and the median nerve or brachial artery.\nMethods and Results Twenty healthy volunteers (21.8 [0.6] y) were recruited. The visible rate of each superficial vein before and after tourniquet application was 65% for the basilic vein, 90% to 95% for the median cubital vein, and 65% to 80% for the cephalic vein. The cross-sectional area of the median cubital vein after tourniquet application was significantly larger than that of the basilic vein and cephalic vein. The distance between the basilic vein or median cubital vein and median nerve was significantly smaller than that between the cephalic vein and median nerve. The distance between the basilic vein or median cubital vein and brachial artery was significantly smaller than that between the cephalic vein and brachial artery.\nConclusions These results demonstrated that the cephalic vein at the cubital fossa is a relatively safe venipuncture site because of its distance from the median nerve and brachial artery. When puncturing the cephalic vein is difficult because it is not visible, the median cubital vein at the cubital fossa may be selected for venipuncture due to its cross-sectional area and visibility; however, care is needed to avoid penetrating the vein because the median nerve and brachial artery are located underneath

医療的ケアを必要とする在宅療養児のきょうだいへの支援

本研究は、医療的ケアを必要とする在宅療養児のきょうだいが抱えた思いや悩み、在宅療養児の疾患認識、きょうだい支援の現状やニーズを明らかにし、それらの結果から今後の支援のあり方を考察することを目的とした。対象は医療的ケアが必要な在宅療養児をきょうだいにもつ青年２名であり、インタビューガイドに基づいて半構成的面接法を実施した。その結果、８つのカテゴリーが抽出され、きょうだいが在宅療養児を通して良い影響を大きく受けていた一方で、課題として在宅療養児の疾患の共有時期・理解度、必然的に医療的ケアに関わらざるを得ない環境、ライフ・イベント時に直面する問題、将来きょうだいが在宅療養児を支える際の問題などが挙がった。きょうだいへの支援においては親の受容状況なども大切な視点であり、保健福祉医療の各側面からのきょうだい支援が必要であることが示唆された

Synthetic Studies on Presporolide, a Putative Enediyne Precursor of Sporolides

A synthesis of the core framework of presporolide, which possesses both a strained bicyclo[7.3.0]­dodecadiyne moiety and a distinctive macrolactone structure, is reported. This synthesis features: (i) a Cu-mediated <i>O</i>-arylation of a hindered tertiary alcohol using triarylbismuth reagent; (ii) stereoselective construction of the strained nine-membered diyne ring; and (iii) atroposelective formation of the macrolactone