Sarcoplasmic reticulum (SR) Ca2+ release channel function is modified by ligands (Mg2+, Ca2+, ATP, and H+) that are generated during a bout of exercise. We have examined the effects of changing intracellular metabolites on Ca2+ release, [3H]ryanodine binding, and single-Ca2+ release channel activity of SR isolated from white rabbit skeletal muscle. Increasing Mg2+ (from 0 to 4 mM) and decreasing pH (7.1-6.5) inhibited SR Ca2+ release and [3H]-ryanodine binding. In addition, increasing lactate concentrations from 2 to 20 mM inhibited [3H]ryanodine binding to SR vesicles, inhibited SR Ca2+ release, and decreased the single-channel open probability. These findings suggest that intracellular modifications that disrupt excitation-contraction coupling and decrease Ca2+ transients will promote a decline in tension development and contribute to muscle fatigue. In addition, we show that hydrogen peroxide induces Ca2+ release and increases [3H]ryanodine binding to its receptor, suggesting that reactive oxygen species produced during exercise may compromise muscle function by altering the normal gating of the SR Ca2+ release channel.
#1120 Purpose: Arthralgia is a common clinical phenomenon seen in postmenopausal women receiving aromatase inhibitors (AI). This study aims to evaluate the perceived onset, prevalence, and risk factors for AI-related arthralgia.
 Patients and Methods: We performed a cross-sectional analysis of a cohort of postmenopausal women with stage I-III breast cancer receiving adjuvant AI therapy at an outpatient breast oncology clinic at a large university hospital. Patient-reported symptoms and attribution of AI as a cause of arthralgia were main outcomes. Multivariate logistic regression analyses were performed to assess risk factor(s).
 Results: 300 patients have been enrolled, with a mean age of 61 +/- 10 years, 84% White, and 38(13%) Black. A total of 173 (58%) reported AI-related arhtralgia during the course of AI treatment and 139 (47%) attributed AI as a cause of their current arthralgia. While 103 (34%) reported having “arthritis” prior to AI initiation, 13% reported onset of symptoms within 1 month of medication initiation, 42% between 1-3 months, 27% between 3-6 months, 12% between 6-12 months, and 20% after 12 months. In a multivariate logistic regression model, time since last menstrual period (LMP) was the only significant predictor of reporting AI-related arthralgia; age, race, employment status, chemotherapy, and weight gain since breast cancer were not associated with the clinical syndrome. Controlling for these covariates, those who had LMP within 5 years had the highest probability of reporting AI-related arthralgia (73%), while those with LMP beyond 10 years had the lowest (35%), p=0.017. Prior arthritis was unrelated to AI-related arthralgia either in univariate or multivariate analyses.
 Conclusions: AI-related arthralgia is common and appears to be inversely related to the length of time since cessation of menstrual function. These findings suggest that estrogen withdrawal may compound these symptoms and may play a role in the mechanism of this disorder. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1120.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.