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Copyright © 2010 Marco Brotto et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is... more
Copyright © 2010 Marco Brotto et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Diabetes is characterized by ventilatory depression due to decreased diaphragm (DPH) function. This study investigated the changes in contractile properties of rat DPH muscles over a time interval encompassing from 4 days to 14 weeks after the onset of streptozotocin-induced diabetes, with and without insulin treatment for 2 weeks. Maximum tetanic force in intact DPH muscle strips and recovery from fatiguing stimulation were measured. An early (4-day) depression in contractile function in diabetic DPH was followed by gradual improvement in muscle function and fatigue recovery (8 weeks). DPH contractile function deteriorated again at 14 weeks, a process that was completely reversed by insulin treatment. Maximal contractile force and cal...
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Inhibition of the Na+-K+ active transport system has been postulated to be one mechanism through which myocardial contractility is increased. Rubidium is one substance which has been shown to increase the contractility of guinea-pig atria... more
Inhibition of the Na+-K+ active transport system has been postulated to be one mechanism through which myocardial contractility is increased. Rubidium is one substance which has been shown to increase the contractility of guinea-pig atria and inhibit the activity of the isolated Na+,K+-adenosine triphosphatase of guinea-pig ventricle. A reexamination of these results confirmed the positive inotropic effect of rubidium on guinea-pig atria and demonstrated that this effect on contractility is accompanied by a decrease in both resting potential and action potential duration. However, it was also found that rubidium produced a transient negative inotropic effect in guinea-pig ventricle. The latter response was closely paralleled by a transient shortening of action potential duration. A concentration of rubidium maximally effective in decreasing contractility (2.0 mM) had no effect on the slow response action potential or contraction. RbCl (0.1 mM) had no effect on cyclic adenosine 3'...
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doi: 10.3389/fphys.2014.00037 Novel excitation-contraction coupling related genes reveal aspects of muscle weakness beyond atrophy—new hopes for treatment of musculoskeletal diseases
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Mitsugumin 29 (MG29), a major protein component of the triad junction in skeletal muscle, has been identified to play roles in the formation of precise junctional membrane structures important for efficient signal conversion in... more
Mitsugumin 29 (MG29), a major protein component of the triad junction in skeletal muscle, has been identified to play roles in the formation of precise junctional membrane structures important for efficient signal conversion in excitation-contraction (E-C) coupling. We carried out several experiments to not only study the role of MG29 in normal muscle contraction but also to determine its role in muscle fatigue. We compared the in vitro contractile properties of three muscles types, extensor digitorum longus (EDL) (fast-twitch muscle), soleus (SOL) (slow-twitch muscle), and diaphragm (DPH) (mixed-fiber muscle), isolated from mice lacking the MG29 gene and wild-type mice prior to and after fatigue. Our results indicate that the mutant EDL and SOL muscles, but not DPH, are more susceptible to fatigue than the wild-type muscles. The mutant muscles not only fatigued to a greater extent but also recovered significantly less than the wild-type muscles. Following fatigue, the mutant EDL an...
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Reactive oxygen species such as superoxide (O2-) and H2O2 are produced at low levels in resting muscles and at substantially higher levels in exercising muscles. Increased respiratory activity with exercise leads to O2- production by the... more
Reactive oxygen species such as superoxide (O2-) and H2O2 are produced at low levels in resting muscles and at substantially higher levels in exercising muscles. Increased respiratory activity with exercise leads to O2- production by the NADPH oxidase reaction and the subsequent generation of H2O2 from O2- by spontaneous dismutation or by the superoxide dismutase reaction. The long-lasting (24-h) depression of contractile function after exercise has been linked to damage of one or more proteins important in the excitation-contraction coupling process. We studied mechanically and chemically skinned fibers from the extensor digitorum longus muscle of the rat to evaluate the effects of a 5-min exposure to 1.0 mM H2O2 on muscle function. We found that H2O2 had no effect on the isometric force-producing properties of the contractile apparatus or on Ca2+ uptake by the sarcoplasmic reticulum. It did, however, significantly affect Ca2+ release from the sarcoplasmic reticulum. Maximum depola...
Research Interests: Biophysics, Chemistry, Calcium, Medicine, Biological Sciences, and 15 moreAnimals, Male, Endoplasmic Reticulum, Applied Physiology, NADPH oxidase, Hydrogen Peroxide, Rats, Rat, Muscle contraction, Isometric Exercise, Oxidants, Isometric Contraction, Depolarization, Medical and Health Sciences, and In Vitro Techniques
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We have recently reported that a novel muscle-specific inositide phosphatase (MIP/MTMR14) plays a critical role in [Ca2+]i homeostasis through dephosphorylation of sn-1-stearoyl-2-arachidonoyl phosphatidylinositol (3,5) bisphosphate... more
We have recently reported that a novel muscle-specific inositide phosphatase (MIP/MTMR14) plays a critical role in [Ca2+]i homeostasis through dephosphorylation of sn-1-stearoyl-2-arachidonoyl phosphatidylinositol (3,5) bisphosphate (PI(3,5)P2). Loss of function mutations in MIP have been identified in human centronuclear myopathy. We developed a MIP knockout (MIPKO) animal model and found that MIPKO mice were more susceptible to exercise-induced muscle damage, a trademark of muscle functional changes in older subjects. We used wild-type (Wt) mice and MIPKO mice to elucidate the roles of MIP in muscle function during aging. We found MIP mRNA expression, MIP protein levels, and MIP phosphatase activity significantly decreased in old Wt mice. The mature MIPKO mice displayed phenotypes that closely resembled those seen in old Wt mice: i) decreased walking speed, ii) decreased treadmill activity, iii) decreased contractile force, and iv) decreased power generation, classical features of...
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Diabetes is characterized by ventilatory depression due to decreased diaphragm (DPH) function. This study investigated the changes in contractile properties of rat DPH muscles over a time interval encompassing from 4 days to 14 weeks... more
Diabetes is characterized by ventilatory depression due to decreased diaphragm (DPH) function. This study investigated the changes in contractile properties of rat DPH muscles over a time interval encompassing from 4 days to 14 weeks after the onset of streptozotocin-induced diabetes, with and without insulin treatment for 2 weeks. Maximum tetanic force in intact DPH muscle strips and recovery from fatiguing stimulation were measured. An early (4-day) depression in contractile function in diabetic DPH was followed by gradual improvement in muscle function and fatigue recovery (8 weeks). DPH contractile function deteriorated again at 14 weeks, a process that was completely reversed by insulin treatment. Maximal contractile force and calcium sensitivity assessed in Triton-skinned DPH fibers showed a similar bimodal pattern and the same beneficial effect of insulin treatment. While an extensive analysis of the isoforms of the contractile and regulatory proteins was not conducted, Weste...
Research Interests: Endocrinology, Medicine, Biological Sciences, Internal Medicine, Insulin, and 15 moreDiabetes mellitus, Animals, Male, Research article, Biomed, Rats, Analysis of Variance, Muscle Fatigue, Muscle contraction, Protein isoforms, Biomedicine and Biotechnology, Diabetic Rat, Contractility, Streptozocin, and diaphragm
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<b>Objective:</b> Pilot test GoWoman, a small-group weight management intervention for mobility impaired women that was a disability- and gender-responsive adaptation of the Diabetes Prevention Program delivered in the online... more
<b>Objective:</b> Pilot test GoWoman, a small-group weight management intervention for mobility impaired women that was a disability- and gender-responsive adaptation of the Diabetes Prevention Program delivered in the online virtual world of Second Life<sup>®</sup>. Objectives were to (1) examine pre-/post-intervention differences in weight, waist circumference, diet, physical activity, self-efficacy for diet and physical activity, nutrition knowledge and social support for weight management, (2) determine intervention feasibility (fidelity, attrition, engagement, acceptability). <b>Design:</b> Single-group modified interrupted time series quasi-experimental design whereby participants served as their own controls. <b>Results:</b> Thirteen women attended ≥8 of 16 GoWoman weekly sessions and lost an average of 5.97 pounds (2.71 kg) (3.31%) body weight (Cohen's <i>d</i> = 0.74) and 1.44 inches (3.66 cm) (3.58%) waist circumference (Cohen's <i>d</i> = 0.83). There were significant improvements in physical activity, diet and self-efficacy for diet and physical activity. All benchmarks for feasibility were met. Ratings of intervention content, group interactions and support and virtual world experiences were highly positive. <b>Conclusion:</b> Findings suggest that a disability- and gender-responsive weight management intervention with peer group support delivered in an online virtual world is feasible, meaningful and may assist with weight management for mobility impaired women.Implications for RehabilitationThis study addresses a gap in the general and rehabilitation research literature by addressing the disproportionately high rates of obesity among women with mobility impairments, who are generally excluded from tests of weight management interventions if they have limited ability to engage in vigorous physical activity.The GoWoman program is an adaptation of the Diabetes Prevention Program Lifestyle Change curriculum that is tailored to meet the unique weight management needs of women with mobility impairments, [...]
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The repeated intense stimulation of skeletal muscle rapidly decreases its force- and motion-generating capacity. This type of fatigue can be temporally correlated with the accumulation of metabolic by-products, including phosphate (Pi)... more
The repeated intense stimulation of skeletal muscle rapidly decreases its force- and motion-generating capacity. This type of fatigue can be temporally correlated with the accumulation of metabolic by-products, including phosphate (Pi) and protons (H). Experiments on skinned single muscle fibers demonstrate that elevated concentrations of these ions can reduce maximal isometric force, unloaded shortening velocity, and peak power, providing strong evidence for a causative role in the fatigue process. This seems to be due, in part, to their direct effect on muscle's molecular motor, myosin, because in assays using isolated proteins, these ions directly inhibit myosin's ability to move actin. Indeed, recent work using a single molecule laser trap assay has revealed the specific steps in the crossbridge cycle affected by these ions. In addition to their direct effects, these ions also indirectly affect myosin by decreasing the sensitivity of the myofilaments to calcium, primaril...
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BACKGROUND There are no known interventions addressing self-esteem in women following spinal cord injury (SCI). OBJECTIVES To test the feasibility of an online self-esteem intervention for women with disabilities, as modified for women... more
BACKGROUND There are no known interventions addressing self-esteem in women following spinal cord injury (SCI). OBJECTIVES To test the feasibility of an online self-esteem intervention for women with disabilities, as modified for women with SCI. METHOD We conducted a randomized, controlled feasibility test of a self-esteem intervention (N = 21). Participants were randomly assigned to the intervention or control group that received intervention materials at the end of the study. Intervention participants met as avatars for 7 weekly real-time group sessions in Second Life (SL), a free online virtual world. Feasibility indicators were study engagement, acceptability of SL and the intervention, and improvements on measures of psychological health promoting behaviors, social support, self-efficacy, self-esteem, and depression. RESULTS Intervention participants (n = 10) were highly engaged, and most described the SL program as more enjoyable and more convenient than in-person programs. All rated the intervention as "good" (n = 4) or "very good" (n = 6), and all 10 rated themselves has having made positive life changes as a result of the program. Intervention participants experienced significantly greater change than controls on two measures of health-promoting behavior (Health Promoting Lifestyle Profile-II Spiritual Growth/Self-actualization; Interpersonal Relations). Examining change in the intervention group using regression analyses, we found medium-to-large effects of the intervention on these behaviors and measures of depression (CESD-10, PHQ-9). The intervention had small effects on remaining measures. CONCLUSION We found preliminary support for the feasibility of this modified self-esteem intervention offered in SL. Such programming may help circumvent barriers to community-based psychological services and may improve psychological health.
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Muscle atrophy alone is insufficient to explain the significant decline in contractile force of skeletal muscle during normal aging. One contributing factor to decreased contractile force in aging skeletal muscle could be compromised... more
Muscle atrophy alone is insufficient to explain the significant decline in contractile force of skeletal muscle during normal aging. One contributing factor to decreased contractile force in aging skeletal muscle could be compromised excitation-contraction (E-C) coupling, without sufficient available Ca2+ to allow for repetitive muscle contractility, skeletal muscles naturally become weaker. Using biophysical approaches, we previously showed that store-operated Ca2+ entry (SOCE) is compromised in aged skeletal muscle but not in young ones. While important, a missing component from previous studies is whether or not SOCE function correlates with contractile function during aging. Here we test the contribution of extracellular Ca2+ to contractile function of skeletal muscle during aging. First, we demonstrate graded coupling between SR Ca2+ release channel-mediated Ca2+ release and activation of SOCE. Inhibition of SOCE produced significant reduction of contractile force in young skel...
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Fatigue studies of isolated, intact muscles typically utilize solutions saturated with O2. However, under in vivo fatiguing conditions, less oxygen is delivered to the muscles and they actually experience hypoxia. No studies to date have... more
Fatigue studies of isolated, intact muscles typically utilize solutions saturated with O2. However, under in vivo fatiguing conditions, less oxygen is delivered to the muscles and they actually experience hypoxia. No studies to date have correlated the effects of acute hypoxia on the isometric contractile properties of intact muscles, skinned fibers isolated from the same muscles, and the cellular content of specific muscle proteins. Therefore, we have studied the effects of in vitro acute hypoxia on the fatigability of intact diaphragm muscle strips and on the isometric contractile properties of single Triton-skinned fibers isolated from control and hypoxic diaphragm muscles. We found that hypoxia and fatiguing stimulation per se affect the tetanic force of intact muscle strips without exhibiting any significant deleterious effects on the calcium-activated force of skinned muscle fibers dissected from the intact muscles. In contrast, fatiguing stimulation under hypoxic conditions d...
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We are developing and investigating the feasibility of a self-esteem enhancement intervention in Second Life for women with physical disabilities. We adapted the curriculum of a previously tested workshop intervention to include features... more
We are developing and investigating the feasibility of a self-esteem enhancement intervention in Second Life for women with physical disabilities. We adapted the curriculum of a previously tested workshop intervention to include features unique to this environment. Results of the beta test were very positive. Everyone involved showed considerable enthusiasm for exploring the new world of SL. The group leaders were challenged to resolve technical problems on every occasion, but these diminished and were perceived as manageable as the intervention progressed. Beta testers gave positive ratings to the information presented, organization, and usefulness of the intervention and found it very enjoyable although fatigue and stress limited the participation of some. They appreciated the use of Internet technology as an accommodation to their disability, in place of requiring transportation and additional energy expenditure to attend face-to-face meetings. Research issues related to engageme...
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Aerobic exercise capacity is critical to bodily health. As a model to investigate the mechanisms that determine health and disease, we employed low (LCR) and high (HCR) capacity running rat models selectively bred to concentrate the genes... more
Aerobic exercise capacity is critical to bodily health. As a model to investigate the mechanisms that determine health and disease, we employed low (LCR) and high (HCR) capacity running rat models selectively bred to concentrate the genes responsible for divergent aerobic running capacity. To investigate the skeletal muscle contribution to this innate difference in running capacity we employed an approach combining examination of the myofilament protein composition and contractile properties of the fast fiber extensor digitorum longus (EDL) and slow fiber soleus (SOL) muscles from LCR and HCR rats. Intact muscle force experiments demonstrate that SOL, but not EDL, muscles from LCR rats exhibit a 3 times greater decrease in fatigued force. To investigate the mechanism of this increased fatigability in the LCR SOL muscle, we determined the myofilament protein composition and functional properties. Force-Ca2+ measurements demonstrate decreased Ca2+ sensitivity of single skinned SOL mus...
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Pilot test GoWoman, a small-group weight management intervention for mobility impaired women that was a disability- and gender-responsive adaptation of the Diabetes Prevention Program delivered in the online virtual world of Second Life.... more
Pilot test GoWoman, a small-group weight management intervention for mobility impaired women that was a disability- and gender-responsive adaptation of the Diabetes Prevention Program delivered in the online virtual world of Second Life. Objectives were to (1) examine pre-/post-intervention differences in weight, waist circumference, diet, physical activity, self-efficacy for diet and physical activity, nutrition knowledge and social support for weight management, (2) determine intervention feasibility (fidelity, attrition, engagement, acceptability). Single-group modified interrupted time series quasi-experimental design whereby participants served as their own controls. Thirteen women attended ≥8 of 16 GoWoman weekly sessions and lost an average of 5.97 pounds (2.71 kg) (3.31%) body weight (Cohen's d = 0.74) and 1.44 inches (3.66 cm) (3.58%) waist circumference (Cohen's d = 0.83). There were significant improvements in physical activity, diet and self-efficacy for diet and...
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To examine the feasibility of an online self-esteem enhancement group program for women with disabilities. A sample of 19 racially and ethnically diverse, community-living women with physical disabilities, 22 to 61 years old, participated... more
To examine the feasibility of an online self-esteem enhancement group program for women with disabilities. A sample of 19 racially and ethnically diverse, community-living women with physical disabilities, 22 to 61 years old, participated in a 7-session interactive group intervention (extending Hughes et al., 2004) in the 3-D, immersive, virtual environment of SecondLife.com, using avatars with voice and text communication. Baseline and postintervention questionnaires were administered online. Criteria for determining feasibility were (a) enrollment, (b) engagement, (c) acceptability, and (d) improvement on measures of self-esteem, depression, self-efficacy, and social support. We attained our enrollment goal and engagement exceeded expectations. Acceptability was positive; participants gave &quot;helpful&quot; and &quot;enjoyable&quot; ratings of 3.21 and 3.27, respectively, (mean on a 1 to 4 Likert scale, where 4 = high) to 5 intervention components-session materials, group sharing and discussion, relaxation exercises, action planning, and group excursions. Significant increases from baseline to postintervention were found on the Rosenberg Self-Esteem Scale (p = .02; Cohen&#39;s d = .60) and the Center for Epidemiologic Studies Depression Scale-10 (p = .005; Cohen&#39;s d = .74), with a trend toward significance on the Generalized Self-Efficacy Scale (p = .08; Cohen&#39;s d = .42). The intervention did not significantly affect the measure of social support. An intervention to enhance self-esteem may have a corollary benefit on depressive symptomatology. Offering psycho-educational, small group interventions using online virtual worlds shows promise for circumventing disability-related and environmental barriers to accessing mental health services experienced by women with mobility limitations, and should undergo further development and testing. (PsycINFO Database Record
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Alpha-adrenoceptor stimulation produces a positive inotropic effect in heart muscle via mechanisms that are not well understood. The purpose of our study was to test the hypothesis that the increase in inositol 1,4,5 trisphosphate... more
Alpha-adrenoceptor stimulation produces a positive inotropic effect in heart muscle via mechanisms that are not well understood. The purpose of our study was to test the hypothesis that the increase in inositol 1,4,5 trisphosphate [Ins(1,4,5)P3] concentration that accompanies alpha stimulation contributes to the inotropic effect by increasing the calcium sensitivity of the contractile proteins, an effect which Ins(1,4,5)P3 has been shown to have in skeletal muscle. We determined the calcium sensitivity of the contractile apparatus of small, chemically skinned bundles from papillary muscles of rabbit, rat and dog hearts. These preparations were chosen because they exhibit a range of sensitivity to alpha agonists. In addition, we measured the calcium sensitivity of chemically skinned, single fibers from rabbit psoas muscle. All preparations were skinned with Triton X-100, a non-ionic detergent that disrupts the sarcolemmal, sarcoplasmic reticular, and mitochondrial membranes. In all cardiac preparations, we found that 38 microM Ins(1,4,5)P3 had no effect on either the calcium sensitivity or maximum calcium-activated force. Thus, there was no correlation between inotropic response to alpha stimulation and myocardial response to Ins(1,4,5)P3. On the other hand, the maximum calcium-activated force of skinned skeletal muscle was slightly increased by Ins(1,4,5)P3. Moreover, Ins(1,4,5)P3 significantly increased the sensitivity of these fibers to calcium.
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ABSTRACT The GoWoman project is developing and pilot testing the first small group weight management program designed to meet the unique needs of women with mobility impairments, a significantly underserved health disparity population.... more
ABSTRACT The GoWoman project is developing and pilot testing the first small group weight management program designed to meet the unique needs of women with mobility impairments, a significantly underserved health disparity population. The project is conducted by a consortium of investigators at five universities in partnership with a Community Advisory Board of five women with mobility impairments. In adapting existing curriculum from the Diabetes Prevention Program, we added content related to the association between disability and weight gain, adaptive cooking, accessible kitchen design, an expanded range of physical activities, precautions against excessive activities and exercises, disability-related stress, and examples that reflect the life situation of women with disabilities. Participants track their progress through MyFitnessPal. Offering this intervention in the online virtual world of Second Life allows us to circumvent many of the geographic, transportation, logistic, disability, and personal barriers that women with mobility impairments face when attempting to participate in public weight loss programs. Our simulated accessible kitchen, caf, and physical activity venues also provide congenial and stigma-free environments for offering social interaction opportunities to reinforce the weight loss programming. The intervention consists of facilitated groups of 8-10 women who gather using their avatar and communicate using voice or text. Sessions last two hours and convene once a week for 16 weeks. We will demonstrate this virtual venue and present the results of the beta-test. We will discuss advantages and technical challenges of implementing interventions in virtual environments, and the implications of this study for mainstream weight loss programs.
... A Comprehensive eCurriculum Management System (eCMS) for a New Self-Directed Medical Curriculum. In T. Reeves & S. Yamashita (Eds.), Proceedings of World Conference on E-Learning in Corporate, Government, Healthcare, and Higher... more
... A Comprehensive eCurriculum Management System (eCMS) for a New Self-Directed Medical Curriculum. In T. Reeves & S. Yamashita (Eds.), Proceedings of World Conference on E-Learning in Corporate, Government, Healthcare, and Higher Education 2006 (pp. 2959-2964). ...
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The Internet holds great promise for increasing women with disabilities' access to disability- and gender-specific health promotion information as well as new opportunities to expand their social network. The Center for Research on... more
The Internet holds great promise for increasing women with disabilities' access to disability- and gender-specific health promotion information as well as new opportunities to expand their social network. The Center for Research on Women with Disabilities is currently testing Internet-based interventions to improve health promoting behaviors, health outcomes, and self-esteem among women with disabilities using the principles of serious games. In developing this new area of research, the first step is to understand Internet usage patterns in this underserved population. Method: Women (N=278) aging with physical disabilities recruited through 12 independent living centers across the US completed written surveys. Sample: Ages ranged from 45-87 years (Mean = 58.9, SD = 9.30); 29% had minority backgrounds; 31% lived in rural areas; 67% had postsecondary education yet 81% were unemployed; the median annual household income was $14,520. More than two-thirds had no intimate relationship...
Reactive oxygen species contribute to diaphragm dysfunction in certain pathophysiological conditions (i.e., sepsis and fatigue). However, the precise alterations induced by reactive oxygen species or the specific species that are... more
Reactive oxygen species contribute to diaphragm dysfunction in certain pathophysiological conditions (i.e., sepsis and fatigue). However, the precise alterations induced by reactive oxygen species or the specific species that are responsible for the derangements in skeletal muscle function are incompletely understood. In this study, we evaluated the effect of the superoxide anion radical (O(2)(-).), hydroxyl radical (.OH), and hydrogen peroxide (H(2)O(2)) on maximum calcium-activated force (F(max)) and calcium sensitivity of the contractile apparatus in chemically skinned (Triton X-100) single rat diaphragm fibers. O(2)(-). was generated using the xanthine/xanthine oxidase system;.OH was generated using 1 mM FeCl(2), 1 mM ascorbate, and 1 mM H(2)O(2); and H(2)O(2) was added directly to the bathing medium. Exposure to O(2)(-). or.OH significantly decreased F(max) by 14.5% (P < 0.05) and 43.9% (P < 0. 005), respectively.OH had no effect on Ca(2+) sensitivity. Neither 10 nor 1,00...
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The influence of inducible heat stress proteins on protecting contracting skeletal muscle against fatigue-induced injury was investigated. A line of transgenic mice overexpressing the inducible form of the 72-kDa heat shock protein... more
The influence of inducible heat stress proteins on protecting contracting skeletal muscle against fatigue-induced injury was investigated. A line of transgenic mice overexpressing the inducible form of the 72-kDa heat shock protein (HSP72) in skeletal muscles was used. We examined the relationship between muscle contractility and levels of the constitutive (HSC73) and inducible (HSP72) forms of the 72-kDa heat shock protein in intact, mouse extensor digitorum longus (EDL), soleus (SOL), and the diaphragm (DPH). In all transgenic muscles, HSP72 was expressed at higher levels compared with transgene-negative controls, where HSP72 was below the level of detection. At the same time, HSC73 levels were downregulated in all transgenic muscle types. Shipment-related stress caused an elevation in the levels of HSP72 in all muscles for 1 wk after arrival of the animals. We also found that, although no statistical differences in response to intermittent fatiguing stimulation in the contractile...