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 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanisms underlying skeletal muscle functional impairment and structural changes with advanced age are only partially understood. In the present study, we support and expand our theory about alterations in sarcolemmal excitation-sarcoplasmic reticulum Ca2+ release-contraction uncoupling as a primary skeletal muscle alteration and major determinant of weakness and fatigue in mammalian species including humans. To test the hypothesis that the number of RYR1 (ryanodine receptor) uncoupled to DHPR (dihydropyridine receptor) increases with age, we performed high-affinity ligand binding studies in soleus, extensor digitorum longus (EDL) and in a pool of several skeletal muscles consisting of a mixture of fast- and slow-twitch muscle fibers in middle-aged (14-month) and old (28-months) Fisher 344 Brown Norway F1 hybrids rats. The number of DHPR, RYR1, the coupling between both receptors expressed as the DHPR/RYR1 maximum binding capacity, and their dissociation constant for high-affinity ligands were measured. The DHPR/RYR1 ratio was significantly reduced in the three groups of muscles (pool: 1.03 +/- 0.15 and 0.80 +/- 0.11, soleus: 0.44 +/- 0. 12 and 0.26 +/- 0.10, and EDL: 0.95 +/- 0.14 and 0.68 +/- 0.10, for middle-aged and old muscles, respectively). These data support the concept that DHPR-RYR1 uncoupling results in alterations in the voltage-gated sarcoplasmic reticulum Ca2+ release mechanism, decreases in myoplasmic Ca2+ elevation in response to sarcolemmal depolarization, reduced Ca2+ supply to contractile proteins and reduced contraction force with aging.
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PMID:Dihydropyridine receptor-ryanodine receptor uncoupling in aged skeletal muscle. 917 12

The dihydropyridine receptor (DHPR) and ryanodine receptor (RYR1) are needed for excitation-contraction coupling in skeletal muscle. Previous studies from this laboratory have shown DHPR-RYR1 uncoupling in 33-month-old Fischer 344 x Brown Norway F1 (F344BNF1) rats fed ad libitum. The purpose of the present study is to determine whether caloric restriction prevents age-related impairments in skeletal muscle function and expression of DHPR and RyR1. Bundles of soleus and extensor digitorum longus (EDL) were studied from rats fed ad libitum and on 60 percent caloric restriction. Significant differences were found in peak twitch or tetanic tension between the ad libitum and calorie-restricted groups in soleus and EDL muscles. A significant increase in the expression of DHPR and RyR1 was observed in caloric restricted rats. These results show that calorie restriction preserves the mechanical properties of aging hind-limb skeletal muscle and maintains the level of DHPR and RyR1 in aged F344BNF1 rats fed ad libitum.
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PMID:Effectiveness of caloric restriction in preventing age-related changes in rat skeletal muscle. 979 Sep 13

This narrative symposium illuminates the problem of clinician moral distress. NIB editorial staff and narrative symposium editors, Cynda Rushton, PhD, RN, FAAN and Renee Boss, MD, MHS, developed a call for stories, which was sent to several list serves and posted on Narrative Inquiry in Bioethics' website. The request for personal stories from inter-professional healthcare providers asked them to: identify specific clinical situations that give rise to moral distress; discuss the sources of this distress; reflect on how they experienced moral distress-physically, psychologically, socially, or spiritually; assess how they managed their situations; and offer suggestions for avoiding future problems of a similar nature. Twelve stories are found in the print version of the journal and an additional eight supplemental stories are published online only through Project MUSE. The clinicians describe a wide range of experiences with patients, other clinicians, and their own professional and personal identities. Embedded in each of the narratives are deeply felt emotions that accompany their experiences of moral distress. Katherine Brown-Saltzman (a nurse), Alisa Carse (a philosopher), Zhanna Bagdasarov and Shane Connelly (industrial-organizational psychologists), and Nancy Berlinger (a bioethicist) provided commentaries.
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PMID:The many faces of moral distress among clinicians. 2440 71