Developing effective drug therapies for arrhythmic diseases is hampered by the fact that the same drug can work well in some individuals but not in others. Human induced pluripotent stem (iPS) cells have been vetted as useful tools for drug screening. However, cardioactive drugs have not been shown to have the same effects on iPS cell-derived human cardiomyocytes as on embryonic stem (ES) cell-derived cardiomyocytes or human cardiomyocytes in a clinical setting. Here we show that current cardioactive drugs affect the beating frequency and contractility of iPS cell-derived cardiomyocytes in much the same way as they do ES cell-derived cardiomyocytes, and the results were compatible with empirical results in the clinic. Thus, human iPS cells could become an attractive tool to investigate the effects of cardioactive drugs at the individual level and to screen for individually tailored drugs against cardiac arrhythmic diseases.
Mouse iPS cells differentiate into cardiomyocytes in a cell line-dependent manner. TSA induces myocardial differentiation in mouse iPS cells and might be useful to overcome cell line variation in the differentiation efficiency.
Background: Intravenous immunoglobulin (IVIG) is the mainstay of initial treatment for Kawasaki disease (KD). Previously, 5 immunoglobulin was used for the treatment of patients with KD; however, a 10 immunoglobulin preparation has recently become available. Purpose: To analyze the safety and e ectiveness of treatment with 10 immunoglobulin in patients with KD. Additionally, we sought to determine whether it was possible to shorten the interval between the initial IVIG dose and the second IVIG dose, among the patients who did not respond to the initial IVIG dose (non-responders) in the 10 IVIG group. Methods: We retrospectively compared the clinical ndings of 103 patients who were administered 5 IVIG, and 60 patients who were administered 10 IVIG between January 2015 and May 2019. Results: e clinical pro les were not signi cantly di erent between the 5 and 10 groups. A total of 31 (30) patients in the 5 group, and 20 (33) patients in the 10 group, were nonresponsive to the initial IVIG dose, although these di erences were not signi cant (p 0.727). e interval between the initial IVIG dose and the second IVIG dose among the non-responders was signi cantly shorter in the 10 IVIG group than the 5 IVIG group (48.8 vs 45.4 hours, p 0.004). Only one patient in the 5 group developed coronary artery lesions, and no serious adverse events were observed. Conclusion: Results showed that 10 immunoglobulin is as safe and e ective as 5 immunoglobulin for the treatment of patients with KD, and can provide additional early treatment for non-responders to the initial IVIG dose.
Background
Because disease progression is so fast in sudden death of acute fulminant myocarditis, damage of myocardial cells is not evident in routine hematoxylin and eosin staining. To understand damage to myocardial cells and the mechanism of sudden death, immunohistochemical staining was performed for two forensic autopsy cases.
Case presentation
The patients were a healthy 5-year-old girl and 8-year-old boy. They suddenly died within 2 days of appearance of flu-like symptoms. An autopsy showed accumulation of yellowish-clear pericardial fluid containing fibrin deposits, fluid blood in the heart, and congestion of visceral organs. Histologically, minor necrosis or degeneration of myocardial cells with mainly lymphocytic infiltration was observed sometimes in tissue sections. Immunohistochemically, positive complement C9 staining and negative sirtuin 1 staining were found. These findings suggested wide damage of myocardial cells, even in regions with no marked changes in myocardial cells with hematoxylin and eosin staining. These areas corresponded to those with strong accumulation of lymphocytes.
Conclusions
Immunohistochemistry for complement C9 and sirtuin 1 might become a new tool for evaluating damage of myocardial cells of fulminant acute myocarditis.
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