Changes In Muscle Function Research Articles

EFFECT OF DENERVATION ON REDOX‐REGULATION IN SKELETAL MUSCLE

Changes in skeletal muscle mass and function occur during aging and are accompanied by loss of integrity and stability of the neuromuscular junction. Previous studies from our group have shown a significant increase in the mitochondrial generation of hydrogen peroxide (H202) and other peroxides in denervated muscle fibers. The mechanisms of generation of these peroxides and the effect on muscle responses are unknown. Our aim was to determine the effect of denervation on proteins that may contribute to peroxide release and proteins that regulate redox responses.The Anterior Tibialis (AT) and Extensor Digitorum Longus (EDL) muscles of wild type mice were denervated under anaesthesia by surgical removal of a small section of the peroneal nerve. Western blotting and immunohistochemical techniques were used to examine protein contents. AT and EDL muscles of thy‐1YFP mice, in which YFP expression in neuronal cells allow visualisation of the muscle innervation, were also denervated and used for morphological examination and analysis of muscle mitochondrial peroxide release.Previous work from our group has shown that, following denervation, hydrogen peroxide can be generated by several sources within mitochondria (Pollock et al, Free Rad. Biol. Med 2017) and the current data show that the increased peroxide generation was maintained to 21 days and was associated with a significant increase in Monoamine Oxidase A and NADPH Oxidase components. An increased content of proteins involved in the activation of the NADPH oxidase complex such as Peroxiredoxin 6 and Phospholipase A2 was also observed together with a significant increase in the content of several enzymes involved in the protection of cells against oxidative damage. Oxyblot analysis to assess the levels of carbonylation, showed that by 7 days post‐denervation there was a significant increase in protein carbonylation of low molecular weight (25–35 kDa) proteins. Morphological analysis indicated a progressive significant loss of muscle mass in the AT muscle from 7 days up to 21 days following denervation due to fiber atrophy without fiber loss. These results support the possibility that (at least initially) the increase in peroxide production may stimulate adaptations to protect the muscle fibers but, together with data on structural changes indicating significant fiber atrophy from 7 days after denervation, increased peroxide generation over the longer term may activate degenerative processes, such as apoptosis of the denervated muscle fibers.Support or Funding InformationThis project was funded by the US National Institutes of Health (NIA) and the Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Prolonged Dietary Curcumin Supplementation Augments Nrf2 Nuclear Translocation and Attenuates Oxidative Stress in Skeletal Muscle of Aging Rats

The development of sarcopenia, which is the aging‐related loss of muscle mass, function and quality, can be attributed to a myriad of factors. Oxidative stress has received particular attention as a key factor in the development of sarcopenia and can collectively be a result of a decreased antioxidant reserve and increased production of reactive oxygen species (ROS). Interestingly, nuclear factor erythroid‐2‐related factor 2 (Nrf2), a transcription factor responsible for activating the antioxidant response element (ARE), has shown decreased nuclear activation with age. Curcumin, the active ingredient in the spice turmeric, has properties that can both increase antioxidant capacity through the activation of Nrf2 and directly quench ROS. These beneficial traits of curcumin were documented in numerous studies that implemented an oral administration method of supplementation. Hence, it is possible that curcumin supplementation through the diet can favorably alter the redox status of muscle and attenuate sarcopenia. This study examined the effects of 4‐months of dietary curcumin exposure on oxidative stress, Nrf2 activation, and the antioxidant response in a rodent model of aging skeletal muscle. Thirty‐two‐month‐old male F344xBN rats (n=54) were provided a purified AIN‐93M diet with or without 0.2% curcumin per food weight for a period of 4 months. One group received the control diet ad libitum (CON, n=18) and another received the same diet containing 0.2% curcumin (CUR, n=18). A third group received the control purified diet, but in equal amounts to those consumed by the CUR animals (PAIR, n=18) to account for any changes in food consumption due to curcumin palatability. After the 4‐month supplementation period, plantaris muscle was tested in vivo for force measures and hindlimb muscle tissue was harvested for biochemical and functional analyses. Body mass, muscle mass, contractile force, measures of oxidative damage, antioxidant expression/activity, and Nrf2 nuclear activation were analyzed using 1‐way ANOVA. All values are reported as mean ± SEM. CUR animals consumed less food than CON rats, and thus a difference between the CON and PAIR groups was also observed (p < 0.05). The CUR rats displayed a significantly larger plantaris mass compared to the PAIR animals (0.198 ± 0.013g vs. 0.326 ± 0.018g; p < 0.05). Plantaris twitch and tetanic force largely mirrored muscle mass changes, where the CUR rats produced larger force than the PAIR rats (p < 0.05). No significant difference in measures of antioxidant expression were observed between the groups (p > 0.05). However, Nrf2 nuclear levels (p < 0.01), and measures of oxidative damage including 3‐nitrotyrosine (3NT; 1.16 ± 0.226 vs. 0.337 ± 0.108 O.D.; p < 0.05), and protein carbonyls (2.29 ± 0.195 vs. 1.43 ± 0.328 O.D.; p < 0.05) were significantly different between the PAIR and CUR groups, respectively. Thus, this study suggests that curcumin supplementation exerts favorable effects on aging muscle that include changes in oxidative stress and muscle mass and function when animals are subjected to food restriction.Support or Funding InformationSupported by the NIH, National Institute on Aging, Grant #1R36AG050734 ‐ 01 (CNR).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Muscle function deterioration in patients with haemophilia: Prospective experience from Costa Rica.

In haemophilia, recurrent joint bleeds are responsible for the development of chronic joint damage, because blood induces biochemical changes in joint structures. Joint degeneration is a long process, and structural damage is often preceded by joint dysfunction, which is represented by quantitative and qualitative changes in the contraction pattern of muscles around the joints. Muscle function in patients with haemophilia is still poorly investigated. The aim of this 2-year prospective study was to assess the changes in muscle function of lower limbs in a group of patients affected with haemophilia in San José, Costa Rica. Muscle function of lower limbs was assessed by means of surface electromyography (sEMG) accomplished at study enrolment and after 2years of follow-up. Gluteus medius, vastus medialis, biceps femoris, gastrocnemius and tibialis anterior were examined. All patients underwent concurrent clinical examination using Haemophilia Joint Health Score (HJHS). Sixty patients aged 2-43years with severe haemophilia underwent clinical and sEMG evaluation. Thirty-two patients (53%) had target joints. sEMG parameters were altered in all patients and were not correlated to the presence of target joints and/or an abnormal HJHS. Muscle function deterioration was observed after 2years of follow-up despite an unmodified HJHS. Muscle function of lower limbs as detected by means of sEMG was impaired in patients with haemophilia irrespective of the presence of overt joint damage. sEMG is a simple and sensitive assessment tool able to detect muscle dysfunction and so favouring the implementation of early rehabilitation therapy.

Relative changes in handgrip strength and skeletal muscle volume in patients with chronic liver disease over a 2-year observation period.

There are few reports regarding relative changes in muscle function of patients with chronic liver disease (CLD). We examined CLD patients to evaluate relative changes in handgrip strength and muscle volume. We enrolled 413 CLD outpatients who underwent handgrip strength measurements in both 2015 and 2017 (age 67.9 ± 10.0years; male/female = 242/171; hepatitis C virus [HCV]/hepatitis B virus [HBV]/HBV and HCV/alcohol/others = 239/92/4/22/56; Child-Pugh score [CPS] in 2015 [5/6/7/8/9/≥10 = 335/51/12/11/3/1]). Relative change in muscle volume (ΔPI) from 2015 to 2017 was evaluated using computed tomography findings in 230 of the patients, using a previously reported method. Clinical characteristics, as well as relative changes of handgrip strength (ΔHGS) and ΔPI were analyzed. For the patient cohort as a whole, CPS became significantly worse in 2017 (5/6/7/8/9/≥10 = 319/56/13/11/5/9; P = 0.002). In individual patients with CPS decline, serum albumin level was significantly decreased (3.78 ± 0.50 to 3.33 ± 0.61g/dL; P < 0.001), whereas no decrease was seen in those without such a decline (4.16 ± 0.48 to 4.20 ± 0.44g/dL; P = 0.028). Furthermore, ΔHGS (-1.4 ± 4.8 [n = 59] vs. 0.7 ± 4.8kg [n = 354]; P = 0.002) and ΔPI (-0.44 ± 0.88 [n = 38] vs. 0.03 ± 0.64cm2 /m2 [n = 192]; P = 0.003) were worse in patients with, compared to those without, a decline in CPS. Age was not significantly different between patients with and without handgrip strength decline (66.5 ± 10.3 vs. 65.3 ± 9.9years; P = 0.256). There was a significant relationship between ΔHGS, ΔPI and relative change in serum albumin (r = 0.161, P = 0.001 and r = 0.225, P < 0.001, respectively). Decline in CPS, especially decreasing serum albumin level, showed a significant relationship with muscle function reduction and muscle volume loss.

Comparison of muscular activities between subjects with and without scapular downward rotation impairment during diagonal pattern of exercises

BackgroundsOne form of abnormal scapular alignment is scapular downward rotation (SDR). Changes in muscle function in SDR have not been clearly identified, and SDR exercises also require investigation. Although a diagonal pattern of exercise is commonly used as part of the exercise protocol, a direct comparison of shoulder and scapular diagonal exercises has not yet been conducted. The objectives of this study were to determine the altered activation of the scapular musculature in the SDR group and to investigate which diagonal pattern of exercise effectively activates the scapular musculature. MethodsThirty-two participants (18 in the control group and 14 in the SDR group) volunteered to participate in this study. Electromyographic signals were collected from four muscles, the upper trapezius (UT), lower trapezius (LT), serratus anterior (SA), and anterior deltoid (AD), during standing performance of diagonal shoulder and scapular exercises. ResultsThe control group showed significantly lower UT activity, UT/LT ratio, and UT/SA values than the SDR group (p < .05). Activation of the AD was significantly higher in the SDR than in the control group (p < .05). SA and AD activation were significantly higher in shoulder diagonal pattern exercises than in scapular diagonal pattern exercises (p < .05). The scapular posterior elevation pattern exercise showed significantly higher UT and LT activities than anterior elevation and shoulder diagonal pattern exercises (p < .05). ConclusionOur findings suggest that reduced activation of the UT could lead to greater activation in the AD in SDR. Scapular posterior elevation exercise is advantageous as selectively activates the trapezius musculature, and shoulder diagonal pattern exercise is advantageous in activating the SA and AD.

Markers of oxidative stress, skeletal muscle mass and function, and their responses to resistance exercise training in older adults

BackgroundOxidative stress (OS) negatively affects skeletal muscle homeostasis in experimental models of ageing. However, little is known about the associations between circulating OS markers and parameters of muscle mass and function, and their responses to exercise training, in humans. MethodsMaximal voluntary contraction (MVC, primary outcome) and isokinetic torque of the knee extensors at 30° s−1 (MIT), muscle cross-sectional area (MCSA) and quality (MQ, secondary outcomes), and plasma concentrations of malondialdehyde (MDA, pro-OS), homocysteine (HCY, pro-OS), taurine (TAU, anti-OS), and protein sulphydryl groups (PSH, anti-OS) were measured in 27 healthy older males and 23 females at baseline and after an 18-week resistance exercise program, with or without a nutritional intervention (fish oil vs. placebo). ResultsAfter adjusting for age, glomerular filtration rate, and nutritional intervention, there were no significant correlations between baseline OS markers and muscle parameters, barring a positive association between TAU and MIT in females (r = 0.53, P = .035) and between MDA and MCSA in males (r = 0.69, P = .001). Training did not significantly change OS markers, except for a reduction in MDA in females (−0.27 μmol/L, 95% CI −0.51 to −0.02, P = .034). In females, there were significant correlations between baseline MDA and exercise-induced changes in MVC (P = .018), baseline TAU and changes in MCSA (P = .026), and baseline HCY and changes in MCSA (P = .046) and MQ (P = .022). In males, baseline MDA was significantly associated with exercise-induced changes in MVC (P = .040). ConclusionsPlasma MDA, HCY, and TAU were significantly associated with baseline and/or exercise-induced changes in muscle mass and function in healthy older adults, primarily in females. Pending further confirmation in other populations, specific OS markers, particularly MDA, might predict muscle responses to resistance exercise programs in old age.

Muscle function decline and mitochondria changes in middle age precede sarcopenia in mice.

Sarcopenia is the degenerative loss of muscle mass and strength with aging. Although a role of mitochondrial metabolism in muscle function and in the development of many diseases has been described, the role of mitochondrial topology and dynamics in the process of muscle aging is not fully understood. This work shows a time line of changes in both mitochondrial distribution and skeletal muscle function during mice lifespan. We isolated muscle fibers from flexor digitorum brevis of mice of different ages. A fusion-like phenotype of mitochondria, together with a change in orientation perpendicular to the fiber axis was evident in the Adult group compared to Juvenile and Older groups. Moreover, an increase in the contact area between sarcoplasmic reticulum and mitochondria was evident in the same group. Together with the morphological changes, mitochondrial Ca2+ resting levels were reduced at age 10-14 months and significantly increased in the Older group. This was consistent with a reduced number of mitochondria-to-jSR pairs in the Older group compared to the Juvenile. Our results support the idea of several age-dependent changes in mitochondria that are accentuated in midlife prior to a complete sarcopenic phenotype.

The Effect of Increasing Age on the Concentric and Eccentric Contractile Properties of Isolated Mouse Soleus and Extensor Digitorum Longus Muscles.

There is currently a limited amount of literature investigating the age-related changes in eccentric muscle function in vitro. The present study uniquely uses the work loop (WL) technique, to better replicate in vivo muscle function, in the assessment of the age- and muscle-specific changes in acute and sustained concentric and eccentric power and recovery. Whole soleus or extensor digitorum longus (EDL) muscles were isolated from 10-week and 78-week-old mice and acute and sustained concentric and eccentric WL power assessed. Despite an age-related increase in body and muscle mass, peak absolute power for both muscles was unaffected by age. Peak concentric power normalized to muscle mass declined significantly for each muscle, while peak normalized eccentric power declined only for soleus. Fatigue resistance and recovery for the soleus did not differ between age or contraction type. Older EDL was less resistant to concentric fatigue, but was better able to withstand sustained eccentric activity than young EDL. We have shown that age-related changes in muscle quality are more limited for eccentric function than concentric function. A greater bodily inertia is likely to further reduce in vivo locomotor performance in older animals.

Changes in contractile and metabolic parameters of skeletal muscle as rats age from 3 to 12 months.

Laboratory rats are considered mature at 3months despite that musculoskeletal growth is still occurring. Changes in muscle physiological and biochemical characteristics during development from 3 months, however, are not well understood. Whole muscles and single skinned fibres from fast-twitch extensor digitorum longus (EDL) and predominantly slow-twitch soleus (SOL) muscles were examined from male Sprague-Dawley rats (3, 6, 9, 12months). Ca2+ sensitivity of contractile apparatus decreased with age in both fast- (~ 0.04 pCa units) and slow-twitch (~ 0.07 pCa units) muscle fibres, and specific force increased (by ~ 50% and ~ 25%, respectively). Myosin heavy chain composition of EDL and SOL muscles altered to a small extent with age (decrease in MHCIIa proportion after 3 months). Glycogen content increased with age (~ 80% in EDL and 25% in SOL) and GLUT4 protein density decreased (~ 35 and 20%, respectively), whereas the glycogen-related enzymes were little changed. GAPDH protein content was relatively constant in both muscle types, but COXIV protein decreased ~ 40% in SOL muscle. Calsequestrin (CSQ) and SERCA densities remained relatively constant with age, whereas there was a progressive ~ 2-3 fold increase in CSQ-like proteins, though their role and importance remain unclear. There was also ~ 40% decrease in the density of the Na+, K+-ATPase (NKA) α1 subunit in EDL and the α2 subunit in SOL. These findings emphasise there are substantial changes in skeletal muscle function and the density of key proteins during early to mid-adulthood in rats, which need to be considered in the design and interpretation of experiments.

Age-related differences in rate of power development exceed differences in peak power

Peak power (pP) declines during aging, resulting in reduced functional performance. However, the rate of power development (RPD) takes into account the short response times available during many functional tasks and may therefore add valuable information to functional declines. This study examined the age-related effects on pP and RPD of the knee-extensors across different loads and how these are related to functional performance.36 young (♂21, ♀15, age=22±2years) and 56 older adults (♂26, ♀30, age=68±5years) performed four maximal isotonic contractions against three loads (40, 20 and 60% of maximal isometric strength) on a Biodex System 3 dynamometer. pP was calculated as the highest value and RPD as the linear slope of the power-time curve. Functional performance in the older group was tested by 7.5-meter fast walk, timed up-and-go and stair climbing.pP and RPD were higher in young compared to old and this was more pronounced with lower loads. Age-related differences in RPD (range from 37 to 44% across loads) were higher than in pP (24–37%). Both pP and RPD showed a positive correlation with functional performance (r: 0.59–0.64).To conclude, percent differences in RPD exceed differences in pP between young and old. This emphasizes the inability to generate power rapidly at older age and underlines the importance of time-dependent measures to detect age-related changes in muscle function.

PGC-1α affects aging-related changes in muscle and motor function by modulating specific exercise-mediated changes in old mice.

SummaryThe age‐related impairment in muscle function results in a drastic decline in motor coordination and mobility in elderly individuals. Regular physical activity is the only efficient intervention to prevent and treat this age‐associated degeneration. However, the mechanisms that underlie the therapeutic effect of exercise in this context remain unclear. We assessed whether endurance exercise training in old age is sufficient to affect muscle and motor function. Moreover, as muscle peroxisome proliferator‐activated receptor γ coactivator 1α (PGC‐1α) is a key regulatory hub in endurance exercise adaptation with decreased expression in old muscle, we studied the involvement of PGC‐1α in the therapeutic effect of exercise in aging. Intriguingly, PGC‐1α muscle‐specific knockout and overexpression, respectively, precipitated and alleviated specific aspects of aging‐related deterioration of muscle function in old mice, while other muscle dysfunctions remained unchanged upon PGC‐1α modulation. Surprisingly, we discovered that muscle PGC‐1α was not only involved in improving muscle endurance and mitochondrial remodeling, but also phenocopied endurance exercise training in advanced age by contributing to maintaining balance and motor coordination in old animals. Our data therefore suggest that the benefits of exercise, even when performed at old age, extend beyond skeletal muscle and are at least in part mediated by PGC‐1α.

Gut Microbiota Contribute to Age-Related Changes in Skeletal Muscle Size, Composition, and Function: Biological Basis for a Gut-Muscle Axis.

Skeletal muscle is a highly plastic tissue that plays a central role in human health and disease. Aging is associated with a decrease in muscle mass and function (sarcopenia) that is associated with a loss of independence and reduced quality of life. Gut microbiota, the bacteria, archaea, viruses, and eukaryotic microbes residing in the gastrointestinal tract are emerging as a potential contributor to age-associated muscle decline. Specifically, advancing age is characterized by a dysbiosis of gut microbiota that is associated with increased intestinal permeability, facilitating the passage of endotoxin and other microbial products (e.g., indoxyl sulfate) into the circulation. Upon entering the circulation, LPS and other microbial factors promote inflammatory signaling and skeletal muscle changes that are hallmarks of the aging muscle phenotype. This review will summarize existing literature suggesting cross-talk between gut microbiota and skeletal muscle health, with emphasis on the significance of this axis for mediating changes in aging skeletal muscle size, composition, and function.

Intramuscular Electrical Stimulation for Muscle Activation of the Tibialis Anterior After Surgical Repair: A Case Report

Background Loss of voluntary activation of musculature can result in muscle weakness. External neuromuscular stimulation can be utilized to improve voluntary activation but is often poorly tolerated because of pain associated with required stimulus level. Intramuscular electrical stimulation requires much lower voltage and may be better tolerated, and therefore more effective at restoring voluntary muscle activation. Case Description A 71-year-old man sustained a rupture of the distal attachment of the tibialis anterior tendon. Thirty-two weeks after surgical repair, there was no palpable or visible tension development in the muscle belly or tendon. Dorsiflexion was dependent on toe extensors. Electrical stimulation applied via a dry needling placement in the muscle belly was utilized to induce an isometric contraction. Outcomes Five sessions of intramuscular electrical stimulation were delivered. By day 4 (second visit), the patient was able to dorsiflex without prominent use of the extensor hallucis longus. By day 6 (third visit), active-range-of-motion dorsiflexion with toes flexed increased 20° (-10° to 10°). Eighteen days after the initial treatment, the patient walked without his previous high-step gait pattern, and the tibialis anterior muscle test improved to withstanding moderate resistance (manual muscle test score, 4/5). Discussion The rapid change in muscle function observed suggests that intramuscular electrical stimulation may facilitate voluntary muscle activation. Level of Evidence Therapy, level 5. J Orthop Sports Phys Ther 2017;47(12):965-969. Epub 15 Oct 2017. doi:10.2519/jospt.2017.7368.

Increased sensory noise and not muscle weakness explains changes in non-stepping postural responses following stance perturbations in healthy elderly

The response to stance perturbations changes with age. The shift from an ankle to a hip strategy with increasing perturbation magnitude occurs at lower accelerations in older than in young adults. This strategy shift has been related to age-related changes in muscle and sensory function. However, the effect of isolated changes in muscle or sensory function on the responses following stance perturbations cannot be determined experimentally since changes in muscle and sensory function occur simultaneously. Therefore, we used predictive simulations to estimate the effect of isolated changes in (rates of change in) maximal joint torques, functional base of support, and sensory noise on the response to backward platform translations. To evaluate whether these modeled changes in muscle and sensory function could explain the observed changes in strategy; simulated postural responses with a torque-driven double inverted pendulum model controlled using optimal state feedback were compared to measured postural responses in ten healthy young and ten healthy older adults. The experimentally observed peak hip angle during the response was significantly larger (5°) and the functional base of support was smaller (0.04m) in the older than in the young adults but peak joint torques and rates of joint torque were similar during the recovery. The addition of noise to the sensed states in the predictive simulations could explain the observed increase in peak hip angle in the elderly, whereas changes in muscle function could not. Hence, our results suggest that strength training alone might be insufficient to improve postural control in elderly.

Transcriptional profile of breast muscle in heat stressed layers is similar to that of broiler chickens at control temperature

BackgroundIn recent years, the commercial importance of changes in muscle function of broiler chickens and of the corresponding effects on meat quality has increased. Furthermore, broilers are more sensitive to heat stress during transport and at high ambient temperatures than smaller egg-laying chickens. We hypothesised that heat stress would amplify muscle damage and expression of genes that are involved in such changes and, thus, lead to the identification of pathways and networks associated with broiler muscle and meat quality traits. Broiler and layer chickens were exposed to control or high ambient temperatures to characterise differences in gene expression between the two genotypes and the two environments.ResultsWhole-genome expression studies in breast muscles of broiler and layer chickens were conducted before and after heat stress; 2213 differentially-expressed genes were detected based on a significant (P < 0.05) genotype × treatment interaction. This gene set was analysed with the BioLayout Express3D and Ingenuity Pathway Analysis software and relevant biological pathways and networks were identified. Genes involved in functions related to inflammatory reactions, cell death, oxidative stress and tissue damage were upregulated in control broilers compared with control and heat-stressed layers. Expression of these genes was further increased in heat-stressed broilers.ConclusionsDifferences in gene expression between broiler and layer chickens under control and heat stress conditions suggest that damage of breast muscles in broilers at normal ambient temperatures is similar to that in heat-stressed layers and is amplified when broilers are exposed to heat stress. The patterns of gene expression of the two genotypes under heat stress were almost the polar opposite of each other, which is consistent with the conclusion that broiler chickens were not able to cope with heat stress by dissipating their body heat. The differentially expressed gene networks and pathways were consistent with the pathological changes that are observed in the breast muscle of heat-stressed broilers.

РОЛЬ ЭНДОТЕЛИАЛЬНОЙ ДИСФУНКЦИИ В ФОРМИРОВАНИИ ОСЛОЖНЕНИЙ САХАРНОГО ДИАБЕТА И ПЕРСПЕКТИВЫ ЕЕ КОРРЕКЦИИ РЕЦЕПТОРНЫМ АНТАГОНИСТОМ ИНТЕРЛЕЙКИНА-1

Цукровий діабет (ЦД) – неухильно прогресуюче захворювання, що вражає переважно осіб працездатного віку і швидко приводить до розвитку системних ускладнень. ЦД посідає третє місце в статистиці смертності після серцево-судинних і онкологічних захворювань. Основною причиною інвалідизації і летальності при ЦД є мікро- і макросудинних ускладнення, що призводять до розвитку серцево-судинних та цереброваскулярних захворювань. Діабет асоціюється з підвищеним ризиком розвитку інфаркту міокарда та ішемічного інсульту і з їх менш успішним результатом.Мета дослідження – провести загальний огляд і теоретичний аналіз репрезентативних фактів у галузі досліджень різних аспектів формування та прогресування ендотеліальної дисфункції при цукровому діабеті.Матеріали і методи. У статті використано дані з наукових праць, літературних джерел, офіційних документів, архівів, статистичних збірників, що опираються на фактичний матеріал. Застосовано поаспектний метод вирішення завдань оптимізації оцінки взаємозв'язків, взаємозалежності та значимості фактів, аргументованих доказів і теоретичних узагальнень, обґрунтування логічних висновків і практичних рекомендацій.Результати досліджень та їх обговорення. Основним фактором, що ушкоджує, є гіперглікемія, яка через активацію сорбітолового шляху, протеїнкінази С і глікування білків призводить до розвитку оксидативного стресу, зменшення утворення оксиду азоту, активації прозапального шляху NF-kB, що сприяє прискореному прогресуванню макроангіопатій, а також викликає ушкодження мікросудинного русла. Церебральна мікроангіопатія є частиною генералізованих судинних ускладнень, що спостерігаються при діабеті, і більш частий несприятливий результат у цих хворих може бути зумовлений системним характером судинного ураження і негативним впливом гіперглікемії на перебіг ішемічного процесу. Передбачається, що при ЦД раніше спостерігається пошкодження внутрішнього шару судинної стінки – ендотелію. Ендотелій у нормі забезпечує трофічну і захисну функції відносно інших верств судинної стінки. Саме ендотелію належить головна роль у підтримці тонусу судин і гемостазу, в розвитку ремоделювання і місцевого запалення (вироблення про- і протизапальних факторів). Порушення функції ендотелію і формування дисфункції ендотелію у хворих з інсулінорезистентністю призводить до підвищення судинної реактивності. Дисбаланс вазоконстрикторів і вазодилататорів є одним із ланок патогенезу діабетичних ангіопатій, оскільки тригерні фактори включають процеси запалення зі зміною функції гладком’язового шару і надмірним утворенням прозапальних цитокінів.Висновки. Застосування препаратів з ендотеліопротекторними властивостями можна розглядати як першочергову лінію ефективного попередження судинних і неврологічних ускладнень у хворих на ЦД. У статті обґрунтовуються перспективи корекції ендотеліальної дисфункції протизапальним цитокіновим препаратом – рецепторним антагоністом інтерлейкіну-1.

Mechanical isolation, and measurement of force and myoplasmic free [Ca2+] in fully intact single skeletal muscle fibers.

Mechanical dissection of single intact mammalian skeletal muscle fibers permits real-time measurement of intracellular properties and contractile function of living fibers. A major advantage of mechanical over enzymatic fiber dissociation is that single fibers can be isolated with their tendons remaining attached, which allows contractile forces (in the normal expected range of 300-450 kN/m2) to be measured during electrical stimulation. Furthermore, the sarcolemma of single fibers remains fully intact after mechanical dissection, and hence the living fibers can be studied with intact intracellular milieu and normal function and metabolic properties, as well as ionic control. Given that Ca2+ is the principal regulator of the contractile force, measurements of myoplasmic free [Ca2+] ([Ca2+]i) can be used to further delineate the intrinsic mechanisms underlying changes in skeletal muscle function. [Ca2+]i measurements are most commonly performed in intact single fibers using ratiometric fluorescent indicators such as indo-1 or fura-2. These Ca2+ indicators are introduced into the fiber by pressure injection or by using the membrane-permeable indo-1 AM, and [Ca2+]i is measured by calculating a ratio of the fluorescence at specific wavelengths emitted for the Ca2+-free and Ca2+-bound forms of the dye. We describe here the procedures for mechanical dissection, and for force and [Ca2+]i measurement in intact single fibers from mouse flexor digitorum brevis (FDB) muscle, which is the most commonly used muscle in studies using intact single fibers. This technique can also be used to isolate intact single fibers from various muscles and from various species. As an alternative to Ca2+ indicators, single fibers can also be loaded with fluorescent indicators to measure, for instance, reactive oxygen species, pH, and [Mg2+], or they can be injected with proteins to change functional properties. The entire protocol, from dissection to the start of an experiment on a single fiber, takes ∼3 h.

Multiscale and Multiaxial Mechanics of Vascular Smooth Muscle

Mathematical models can facilitate an integrative understanding of the complexity underlying biological structure and function, but they must be informed and validated by empirical data. Uniaxial contraction of an arterial ring is a well-used in vitro approach for studying characteristics of smooth muscle contractility even though this experimental arrangement does not mimic the in vivo vascular geometry or loading. In contrast, biaxial contraction of an inflated and axially extended excised vessel provides broader information, both passive and active, under more realistic conditions. Few investigations have compared these two in vitro approaches directly, namely how their results overlap, how they differ, or if each provides unique complementary information. Toward this end, we present, to our knowledge, a new multiscale mathematical model of arterial contractility accounting for structural and functional constituents at molecular, cellular, and tissue levels. The artery is assumed to be a thick-walled incompressible cylinder described by an anisotropic model of the extracellular matrix and, to our knowledge, novel model of smooth muscle contractility. The latter includes a 3D structural sensitivity to deformation, including microscale muscle filament overlap and filament lattice spacing. The overall model captures uniaxial and biaxial experimental contraction data, which was not possible when accounting for filament overlap alone. The model also enables parameter sensitivity studies, which confirmed that uniaxial contraction tests are not as efficient as biaxial tests for identifying changes in vascular smooth muscle function.

Congenital muscle dystrophy and diet consistency affect mouse skull shape differently.

The bones of the mammalian skull respond plastically to changes in masticatory function. However, the extent to which muscle function affects the growth and development of the skull, whose regions have different maturity patterns, remains unclear. Using muscle dissection and 3D landmark-based geometric morphometrics we investigated the effect of changes in muscle function established either before or after weaning, on skull shape and muscle mass in adult mice. We compared temporalis and masseter mass and skull shape in mice with a congenital muscle dystrophy (mdx) and wild type (wt) mice fed on either a hard or a soft diet. We found that dystrophy and diet have distinct effects on the morphology of the skull and the masticatory muscles. Mdx mice show a flattened neurocranium with a more dorsally displaced foramen magnum and an anteriorly placed mandibular condyle compared with wt mice. Compared with hard diet mice, soft diet mice had lower masseter mass and a face with more gracile features as well as labially inclined incisors, suggesting reduced bite strength. Thus, while the early-maturing neurocranium and the posterior portion of the mandible are affected by the congenital dystrophy, the late-maturing face including the anterior part of the mandible responds to dietary differences irrespective of the mdx mutation. Our study confirms a hierarchical, tripartite organisation of the skull (comprising neurocranium, face and mandible) with a modular division based on development and function. Moreover, we provide further experimental evidence that masticatory loading is one of the main environmental stimuli that generate craniofacial variation.

Changes in lower limb muscle function and muscle mass following exercise-based interventions in patients with chronic obstructive pulmonary disease: A review of the English-language literature.

Chronic obstructive pulmonary disease (COPD) patients often experience lower limb muscle dysfunction and wasting. Exercise-based training has potential to improve muscle function and mass, but literature on this topic is extensive and heterogeneous including numerous interventions and outcome measures. This review uses a detailed systematic approach to investigate the effect of this wide range of exercise-based interventions on muscle function and mass. PUBMED and PEDro databases were searched. In all, 70 studies (n = 2504 COPD patients) that implemented an exercise-based intervention and reported muscle strength, endurance, or mass in clinically stable COPD patients were critically appraised. Aerobic and/or resistance training, high-intensity interval training, electrical or magnetic muscle stimulation, whole-body vibration, and water-based training were investigated. Muscle strength increased in 78%, muscle endurance in 92%, and muscle mass in 88% of the cases where that specific outcome was measured. Despite large heterogeneity in exercise-based interventions and outcome measures used, most exercise-based trials showed improvements in muscle strength, endurance, and mass in COPD patients. Which intervention(s) is (are) best for which subgroup of patients remains currently unknown. Furthermore, this literature review identifies gaps in the current knowledge and generates recommendations for future research to enhance our knowledge on exercise-based interventions in COPD patients.