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  • 1
    In: Journal of Cellular Physiology, Wiley, Vol. 230, No. 6 ( 2015-06), p. 1352-1364
    Abstract: Phosphorylation of regulatory light chain (MLC) activates myosin II, which enables it to promote contractile and motile activities of cells. We report here a novel signaling mechanism that activates MLC phosphorylation and smooth muscle contraction. Contractile agonists activated Rac1, and Rac1 inhibition diminished agonist‐induced MLC phosphorylation, thus inhibiting smooth muscle contraction. Rac1 inhibits the activity of MLC phosphatase (MLCP) but not that of MLC kinase, through a phosphatase that targets MYPT1 (a regulatory subunit of MLCP) and CPI‐17 (a MLCP specific inhibitor) rather than through the RhoA‐Rho dependent kinase (ROCK) pathway. Rac1 inhibition decreased the activity of protein kinase C (PKC), which also contributes to the change in CPI‐17 phosphorylation. We propose that activation of Rac1 increases the activity of PKC, which increases the phosphorylation of CPI‐17 and MYPT1 by inhibiting the phosphatase that targets these proteins, thereby decreasing the activity of MLCP and increasing phosphorylation of MLC. Our results suggest that Rac1 coordinates with RhoA to increase MLC phosphorylation by inactivation of CPI‐17/MYPT1 phosphatase, which decreases MLCP activity thus promoting MLC phosphorylation and cell contraction. J. Cell. Physiol. 230: 1352–1364, 2015. © 2014 Wiley Periodicals, Inc., A Wiley Company
    Type of Medium: Online Resource
    ISSN: 0021-9541 , 1097-4652
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2015
    detail.hit.zdb_id: 1478143-8
    SSG: 12
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  • 2
    In: ESC Heart Failure, Wiley, Vol. 8, No. 4 ( 2021-08), p. 3354-3359
    Abstract: Optimal pharmacological treatment for chronic heart failure has been established. However, treatments that can improve the prognosis of acute heart failure (AHF) are controversial. Although intravenous diuretics may be one optimal treatment option, little evidence has shown the effect of early administration of diuretics on clinical outcomes in patients with AHF. The aim of this study was to evaluate the association between door‐to‐furosemide (D2F) time, improved oxygenation, and in‐hospital mortality in patients hospitalized for AHF. Methods and results We screened 494 patients hospitalized for AHF in Miyazaki Prefectural Nobeoka Hospital. AHF patients who were treated with intravenous furosemide within 24 h of arrival at the hospital were included in this study. D2F time was defined as the time from patient arrival at the hospital to the first intravenous dose of furosemide. The early administration group was defined as those with D2F time ≤60 min, whereas the non‐early group was defined as those with D2F time 〉 60 min. The primary outcome was the rate of improved oxygenation at Day 1. The secondary outcomes were in‐hospital mortality and cardiac death. There were 219 patients treated with the first intravenous dose of furosemide within 24 h analysed after the exclusion of 275 patients. The median D2F time was 55 min (interquartile range: 30–120 min) in the final cohort. The early administration group included 121 patients (55.3%). The rate of improved oxygenation was higher in the early group than the non‐early group [median 16.7% (interquartile range: 0.0–40.0) vs. 0.0% (0.0–20.6), respectively, P   〈  0.001]. During the study period, there were six patients (5.0%) with in‐hospital mortality in the early group and nine patients (9.2%) in the non‐early group ( P  = 0.218). Cardiac death was observed less frequently in the early group than in the non‐early group, but without statistical significance (3.3% and 9.2%, respectively) ( P  = 0.067). The univariable logistic regression analyses showed that early administration of furosemide was associated with improved oxygenation [odds ratio (OR): 2.26; 95% confidence interval (CI): 1.31–3.91; P  = 0.004], but not with in‐hospital mortality (OR: 0.52; 95% CI: 0.18–1.50; P  = 0.225) or cardiac death (OR: 0.34; 95% CI: 0.10–1.13; P  = 0.079). In multivariable analyses adjusted for risk score or relevant variables, early administration of furosemide was consistently associated with improvement of oxygenation. Conclusions The present study showed that in AHF patients, the early administration of furosemide was associated with improved oxygenation.
    Type of Medium: Online Resource
    ISSN: 2055-5822 , 2055-5822
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2814355-3
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