論文

Because cardiomyocyte generation is limited, the turnover of cardiomyocytes in adult heart tissues is much debated. We report here that cardiac pacemaker cells can generate cardiomyocytes from fibroblasts in vitro. Sinoatrial node cells (SANCs) were isolated from adult guinea pig hearts and were cultured at relatively low cell densities. Within a week, a number of fibroblast-like cells were observed to gather around SANCs, and these formed spontaneously beating clusters with cardiomyocyte structures. The clusters expressed genes and proteins that are characteristic of atrial cardiomyocytes. Pharmacological blocking of pacemaker currents inhibited generation of action potentials, and the spontaneous beating were ceased by physically destroying a few central cells. Inhibition of beating during culture also hampered the cluster formation. Moreover, purified guinea pig cardiac fibroblasts (GCFs) expressed cardiac-specific proteins in co-culture with SANCs or in SANC-preconditioned culture medium under electrical stimulation. These results indicate that SANCs can generate cardiomyocytes from cardiac fibroblasts through the influence of humoral factor(s) and electrophysiological activities followed by intracellular Ca2+ oscillations. This potential of SANCs to generate cardiomyocytes indicates a novel mechanism by which cardiomyocytes turns over in the vicinity of pacemaker cells and could be exploited in the development of strategies for cardiac regenerative therapy in adult hearts.

Background/Aim: The topoisomerase 1 catalytic inhibitor 3EZ, 20Ac-ingenol specifically induces apoptosis through the activation of ATR and the up-regulation of PTEN by enhancing the DNA damage response (DDR) in human B lymphoma (BALL-1) cells. The accumulation of cyclin D1 in cancer is known to be related to chemoresistance to DNA damage agents and nuclei of BALL-1 cells exhibit high levels of cyclin D1. However, 3EZ, 20Ac-ingenol effectively induced apoptosis of BALL-1 cells. Materials and Methods: Cell growth, protein levels, and apoptosis were determined by an MTT assay, immunoblotting and DNA fragmentation assay, respectively. Results: 3EZ, 20Ac-ingenol strongly induced inhibition of cell proliferation and apoptosis in Jeko-1 and Panc-1 cell lines through the activation of tumor suppressor proteins and caspase 3. Conclusion: 3EZ, 20Ac-ingenol-induced apoptosis might occur in cells with cyclin D1 accumulation through enhancing DDR, regardless of the cancer cell type.

平成31年度より導入された改訂薬学教育モデル・コアカリキュラムによる実務実習では、実習生が代表的8疾患に継続して関わることが求められ、また実習は薬局、病院の順で行うことを原則としているが、それらの教育効果が新たに導入された概略評価に与える影響は明らかにされていない。そこで本研究では、慶應義塾大学病院薬剤部で独自に作成した「学生個別記録用紙」を用い、代表的8疾患の継続的関わりと薬局実習経験が病院実習における概略評価到達度に与える影響について検討した。平成30年度I期実習生20名（薬局実習未経験）、II期21名（薬局実習経験済）を対象とし、服薬指導と関連した評価項目「（2）-2 処方せんと疑義照会」、「（2）-4 患者・来局者対応、服薬指導、患者教育」、「（3）-1 患者情報の把握」、「（3）-2 医薬品情報の収集と活用」、「（3）-3 処方設計と提案」、「（3）-4 薬物療法における効果と副作用の評価」の概略評価到達度をアウトカムとした。いずれの項目も代表的8疾患の継続経験疾患数は、実習生の概略評価到達度に影響するとは示されなかった。一方で、薬局実習経験は「（3）-1 患者情報の把握」において、病院実習の概略評価到達度を有意に上昇させた（偏回帰係数1.305, P = 0.044; 95%CI, 0.036–2.575）。代表的8疾患には柔軟に対応し、指導薬剤師と共に患者の問題を解決する実習を行うことが重要である。