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      The Effect of Gender and Menstrual Phase on Serum Creatine Kinase Activity and Muscle Soreness Following Downhill Running

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          Abstract

          Serum creatine kinase (CK) activity reflects muscle membrane disruption. Oestrogen has antioxidant and membrane stabilising properties, yet no study has compared the CK and muscle soreness (DOMS) response to unaccustomed exercise between genders when all menstrual phases are represented in women. Fifteen eumenorrhoeic women (early follicular, EF ( n = 5); late follicular, LF ( n = 5); mid-luteal, ML ( n = 5) phase) and six men performed 20 min of downhill running (−10% gradient) at 9 km/h. Serum CK activity and visual analogue scale rating of perceived muscle soreness were measured before, immediately, 24-h, 48-h and 72-h after exercise. The 24-h peak CK response (relative to pre-exercise) was similar between women and men (mean change (95% confidence interval): 58.5 (25.2 to 91.7) IU/L; 68.8 (31.3 to 106.3) IU/L, respectively). However, serum CK activity was restored to pre-exercise levels quicker in women (regardless of menstrual phase) than men; after 48-h post exercise in women (16.3 (−4.4 to 37.0) IU/L; 56.3 (37.0 to 75.6) IU/L, respectively) but only after 72-h in men (14.9 (−14.8 to 44.6) IU/L). Parallel to the CK response, muscle soreness recovered by 72-h in men. Conversely, the women still reported muscle soreness at 72-h despite CK levels being restored by 48-h; delayed recovery of muscle soreness appeared mainly in EF and LF. The CK and DOMS response to downhill running is gender-specific. The CK response recovers quicker in women than men. The CK and DOMS response occur in concert in men but not in women. The DOMS response in women is prolonged and may be influenced by menstrual phase.

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          Muscle damage and inflammation during recovery from exercise.

          Unaccustomed exercise consisting of eccentric (i.e., lengthening) muscle contractions often results in muscle damage characterized by ultrastructural alterations in muscle tissue, clinical signs, and symptoms (e.g., reduced muscle strength and range of motion, increased muscle soreness and swelling, efflux of myocellular proteins). The time course of recovery following exercise-induced muscle damage depends on the extent of initial muscle damage, which in turn is influenced by the intensity and duration of exercise, joint angle/muscle length, and muscle groups used during exercise. The effects of these factors on muscle strength, soreness, and swelling are well characterized. By contrast, much less is known about how they affect intramuscular inflammation and molecular aspects of muscle adaptation/remodeling. Although inflammation has historically been viewed as detrimental for recovery from exercise, it is now generally accepted that inflammatory responses, if tightly regulated, are integral to muscle repair and regeneration. Animal studies have revealed that various cell types, including neutrophils, macrophages, mast cells, eosinophils, CD8 and T-regulatory lymphocytes, fibro-adipogenic progenitors, and pericytes help to facilitate muscle tissue regeneration. However, more research is required to determine whether these cells respond to exercise-induced muscle damage. A large body of research has investigated the efficacy of physicotherapeutic, pharmacological, and nutritional interventions for reducing the signs and symptoms of exercise-induced muscle damage, with mixed results. More research is needed to examine if/how these treatments influence inflammation and muscle remodeling during recovery from exercise.
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            The influence of estrogen on skeletal muscle: sex matters.

            As women enter menopause, the concentration of estrogen and other female hormones declines. This hormonal decrease has been associated with a number of negative outcomes, including a greater incidence of injury as well as a delay in recovery from these injuries. Over the past two decades, our understanding of the protective effects of estrogen against various types of injury and disease states has grown immensely. In skeletal muscle, studies with animals have demonstrated that sex and estrogen may potentially influence muscle contractile properties and attenuate indices of post-exercise muscle damage, including the release of creatine kinase into the bloodstream and activity of the intramuscular lysosomal acid hydrolase, beta-glucuronidase. Furthermore, numerous studies have revealed an estrogen-mediated attenuation of infiltration of inflammatory cells such as neutrophils and macrophages into the skeletal muscles of rats following exercise or injury. Estrogen has also been shown to play a significant role in stimulating muscle repair and regenerative processes, including the activation and proliferation of satellite cells. Although the mechanisms by which estrogen exerts its influence upon indices of skeletal muscle damage, inflammation and repair have not been fully elucidated, it is thought that estrogen may potentially exert its protective effects by: (i) acting as an antioxidant, thus limiting oxidative damage; (ii) acting as a membrane stabilizer by intercalating within membrane phospholipids; and (iii) binding to estrogen receptors, thus governing the regulation of a number of downstream genes and molecular targets. In contrast to animal studies, studies with humans have not as clearly delineated an effect of estrogen on muscle contractile function or on indices of post-exercise muscle damage and inflammation. These inconsistencies have been attributed to a number of factors, including age and fitness level of subjects, the type and intensity of exercise protocols, and a focus on sex differences that typically involve factors and hormones in addition to estrogen. In recent years, hormone replacement therapy (HRT) or estrogen combined with exercise have been proposed as potentially therapeutic agents for postmenopausal women, as these agents may potentially limit muscle damage and inflammation and stimulate repair in this population. While the benefits and potential health risks of long-term HRT use have been widely debated, controlled studies using short-term HRT or other estrogen agonists may provide future new and valuable insights into understanding the effects of estrogen on skeletal muscle, and greatly benefit the aging female population. Recent studies with older females have begun to demonstrate their benefits.
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              Reference intervals for serum creatine kinase in athletes.

              The serum concentration of creatine kinase (CK) is used widely as an index of skeletal muscle fibre damage in sport and exercise. Since athletes have higher CK values than non-athletes, comparing the values of athletes to the normal values established in non-athletes is pointless. The purpose of this study was to introduce reference intervals for CK in athletes. CK was assayed in serum samples from 483 male athletes and 245 female athletes, aged 7-44. Samples had been obtained throughout the training and competition period. For comparison, CK was also assayed in a smaller number of non-athletes. Reference intervals (2.5th to 97.5th percentile) were calculated by the non-parametric method. The reference intervals were 82-1083 U/L (37 degrees C) in male and 47-513 U/L in female athletes. The upper reference limits were twice the limits reported for moderately active non-athletes in the literature or calculated in the non-athletes in this study. The upper limits were up to six times higher than the limits reported for inactive individuals in the literature. When reference intervals were calculated specifically in male football (soccer) players and swimmers, a threefold difference in the upper reference limit was found (1492 vs 523 U/L, respectively), probably resulting from the different training and competition demands of the two sports. Sport training and competition have profound effects on the reference intervals for serum CK. Introducing sport-specific reference intervals may help to avoid misinterpretation of high values and to optimise training.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Antioxidants (Basel)
                Antioxidants (Basel)
                antioxidants
                Antioxidants
                MDPI
                2076-3921
                23 February 2017
                March 2017
                : 6
                : 1
                : 16
                Affiliations
                [1 ]Exercise Laboratory, School of Physiology, University of the Witwatersrand, Medical School, Johannesburg 2193, South Africa
                [2 ]Division for Exercise Science and Sports Medicine, Department of Human Biology, University of Cape Town, Cape Town 7700, South Africa; andrew.bosch@ 123456uct.ac.za
                Author notes
                [* ]Correspondence: oosthuyse@ 123456polka.co.za ; Tel.: +27-11-717-2363
                Article
                antioxidants-06-00016
                10.3390/antiox6010016
                5384179
                28241459
                a35c4ca7-b88a-496d-a7e4-8d7503b30d87
                © 2017 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 30 December 2016
                : 19 February 2017
                Categories
                Article

                oestrogen,progesterone,eccentric exercise,membrane stability,creatine kinase,delayed onset muscle soreness

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