Muscle Tissue Damage Research Articles

АТPазна активність актоміозину скелетних м’язів та маркери ушкодження тканин у крові щурів в умовах тривалої хронічної алкоголізації

The activity of creatine kinase and indices of lipid metabolism in the blood and also actomyosin ATPase activity of skeletal muscles of rats under chronic 8-month alcohol abuse were investigated. It is shown that actomyosin K+-ATPase activity of skeletal muscles increases from two months of ethanol use, but actomyosin Mg2+-ATPase activity decreases during 6-8 months of alcoholization. From two months of ethanol use the creatine kinase activity, as an enzyme marker of muscle tissue damage, statistically significantly increases during all the period of the animals alcoholization. The level of total lipid increases after two months of alcohol consumption (in blood plasma by 30% and in erythrocyte mass by 65%). For longer periods of alcoholization (4-8 months) the level of lipids remains almost the same, whereas in erythrocyte mass it does not differ from control values. The level of diene conjugates in the blood plasma reduces and the amount of ketone derivatives of fatty acid residues increases that points to the inhibition of some components of the antioxidant system that control detoxification of hydroperoxides of fatty acids and also to activation of free radical damage of tissues. There were no significant changes of lipid peroxidation level in erythrocyte mass at any stage of alcoholization.

TRATAMENTO DA DOENÇA DE POMPE - DEFICIÊNCIA DA ALFA-GLICOSIDASE ÁCIDA

Este trabalho tem como objetivos descrever a patogênese e o tratamento da doença de Pompe. Foi realizado um estudo de revisão bibliográfica mediante busca de artigos científicos publicados entre 2004 e 2014. Portadores de deficiência na enzima alfa acido glicosidase, desenvolvem a doença de Pompe, que resulta em um acumulo de glicogênio dentro do lisossomo, originando danos e disfunções orgânicas no tecido muscular, ocasionando dificuldades na respiração, locomoção, fala e audição. A terapia de reposição enzimática é a alternativa de tratamento específica para Pompe, melhorando significativamente a função cardíaca e reduzindo a mortalidade. Contudo, a necessidade de injeção de altas doses da enzima, a perda de 80% da enzima por conta do metabolismo hepático e o alto custo do tratamento dificultam o seu uso. A dose que mostrou melhores resultados foi de 20 mg/kg da enzima a cada duas semanas. Todavia, apesar do alto custo do tratamento, os benefícios de diminuição de sintomas dos pacientes são importantes, como melhora na realização de atividades da vida diária, aumento da força muscular, redução da fadiga e incrementos na função pulmonar. Existem ainda, tratamentos alternativos, mas que ainda estão em fase de estudos. Dentre os tratamentos, aquele que possui um melhor prognóstico é a reposição com a enzima humana recombinante. A terapia de reposição enzimática trouxe sobrevida a diversos pacientes devido à diminuição da hipertrofia cardíaca e melhora nos sintomas motores.

G.O.11: Longitudinal quantitative muscle MRI in 5 Duchenne boys treated with exon 51 skipping – A pilot study

Exon skipping in Duchenne muscular dystrophy (DMD) aims to restore dystrophin expression and maintain muscle function. The largest RCT so far targeting exon 51 failed to reach its primary endpoint despite promising results from preceding studies. It underscores the need for biomarkers. Quantitative MRI (qMRI) is promising as it is a non-invasive method which can be repeated easily. qMRI was used in 5 boys from the 48week RCT (DMD114044) and open label extension (OLE) study (DMD114349) assessing exon 51 skipping with weekly subcutaneous dosing at 6mg/kg drisapersen. T1w, 3-point Dixon and quantitative fat suppressed T2 scans were acquired from the left lower leg at 3T at 3 occasions: n =5), around the start of the OLE phase ( n =5) and n =4). Two boys were on placebo during RCT. Outcome measures were % fatty infiltration, contractile cross-sectional area (cCSA), and mean and standard deviation (SD) of T2 relaxation times in five lower leg muscles. Results were compared to three DMD controls from our natural history study. Interval between scans on treatment varied between 322 and 825days. cCSA and fat% did not show a clear pattern. However, in treated boys, a reduction in mean value and SD of the T2 relaxation time was visible especially in the tibialis anterior muscle. In contrast, T2 values of controls increased. The oldest boy with the highest initial fat% showed a large reduction in fat% and increase in cCSA for all lower leg muscles during 10.5months on treatment. Nonetheless he lost ambulation during the extension phase. The observed shift in T2 values opposite to that of controls may point towards less damaged muscle tissue. Subclinical improvement in muscle structure can provide a base for developing more potent drugs or studying prolonged treatment in younger patients as disease progression may lead to a point of no return regarding ambulation. qMRI should be considered as a biomarker in DMD trials.

Roles of adherent myogenic cells and dynamic culture in engineered muscle function and maintenance of satellite cells

Highly functional engineered skeletal muscle constructs could serve as physiological models of muscle function and regeneration and have utility in therapeutic replacement of damaged or diseased muscle tissue. In this study, we examined the roles of different myogenic cell fractions and culturing conditions in the generation of highly functional engineered muscle. Fibrin-based muscle bundles were fabricated using either freshly-isolated myogenic cells or their adherent fraction pre-cultured for 36 h. Muscle bundles made of these cells were cultured in both static and dynamic conditions and systematically characterized with respect to early myogenic events and contractile function. Following 2 weeks of culture, we observed both individual and synergistic benefits of using the adherent cell fraction and dynamic culture on muscle formation and function. In particular, optimal culture conditions resulted in significant increase in the total cross-sectional muscle area (∼3-fold), myofiber size (∼1.6-fold), myonuclei density (∼1.2-fold), and force generation (∼9-fold) compared to traditional use of freshly-isolated cells and static culture. Curiously, we observed that only a simultaneous use of the adherent cell fraction and dynamic culture resulted in accelerated formation of differentiated myofibers which were critical for providing a niche-like environment for maintenance of a satellite cell pool early during culture. Our study identifies key parameters for engineering large-size, highly functional skeletal muscle tissues with improved ability for retention of functional satellite cells.

Molecularly Imprinted Supermacroporous Cryogels for Myoglobin Recognition

Myoglobin is a primary iron, and oxygen-binding protein of muscle tissues and levels can be an important diagnostic biomarker for acute myocardial infarction, myocardial necrosis, or other cardiac diseases. The establishment of myoglobin recognition systems is important because of its protein's structural and functional values in physiology, biochemistry, and diagnostic value in some damaged muscle tissue and cardiac diseases. For this purpose, we used molecular imprinting technique for myoglobin recognition from aqueous solutions and human plasma. In the first step, myoglobin-imprinted poly(hydroxyethyl methacrylate) (PHEMA) cryogels (MGb-MIP) were prepared, and optimum myoglobin adsorption conditions were determined. Selectivity experiments have been done with the competitive proteins, and myoglobin adsorption from IgG and albumin-free human plasma was studied. The purity of the desorbed samples was determined with SDS-PAGE. The desorption efficiency and reusability of the MGb-MIP cryogels were tested, and it was shown that without any significant loss in the adsorption capacity, MGb-MIP cryogels can be used a number of times for myoglobin recognition and separation.

The Effects of High Intensity Short Rest Resistance Exercise on Muscle Damage Markers in Men and Women

Within and between sexes, universal load prescription (as assigned in extreme conditioning programs) creates extreme ranges in individual training intensities. Exercise intensity has been proposed to be the main factor determining the degree of muscle damage. Thus, the purpose of this study was to examine markers of muscle damage in resistance-trained men (n = 9) and women (n = 9) from a high intensity (HI) short rest (SR) (HI/SR) resistance exercise protocol. The HI/SR consisted of a descending pyramid scheme starting at 10 repetitions, decreasing 1 repetition per set for the back squat, bench press, and deadlift, as fast as possible. Blood was drawn pre-exercise (pre), immediately postexercise (IP), 15 minutes postexercise (+15), 60 minutes postexercise (+60), and 24 hours postexercise (+24). Women demonstrated significant increases in interleukin 6 (IL-6; IP), creatine kinase (CK; +24), myoglobin (IP, +15, +60), and a greater relative increase when compared with men (+15, +60). Men demonstrated significant increases in myoglobin (IP, +15, +60, +24), IL-6 (IP, +15), CK (IP, +60, +24), and testosterone (IP, +15). There were significant sex interactions observed in CK (IP, +60, +24) and testosterone (IP, +15, +60, +24). Women completed the protocol faster (women: 34:04 ± 9:40 minutes, men: 39:22 ± 14:43 minutes), and at a slightly higher intensity (women: 70.1 ± 3.5%, men 68.8 ± 3.1%); however, men performed significantly more work (men: 14384.6 ± 1854.5 kg, women: 8774.7 ± 1612.7 kg). Overall, women demonstrated a faster inflammatory response with increased acute damage, whereas men demonstrated a greater prolonged damage response. Therefore, strength and conditioning professionals need to be aware of the level of stress imposed on individuals when creating such volitional high intensity metabolic type workouts and allow for adequate progression and recovery from such workouts.

FOXO3 Promotes Quiescence in Adult Muscle Stem Cells during the Process of Self-Renewal

SummarySkeletal muscle stem cells, or “satellite cells” (SCs), are required for the regeneration of damaged muscle tissue. Although SCs self-renew during regeneration, the mechanisms that govern SC re-entry into quiescence remain elusive. We show that FOXO3, a member of the forkhead family of transcription factors, is expressed in quiescent SCs (QSCs). Conditional deletion of Foxo3 in QSCs impairs self-renewal and increases the propensity of SCs to adopt a differentiated fate. Transcriptional analysis of SCs lacking FOXO3 revealed a downregulation of Notch signaling, a key regulator of SC quiescence. Conversely, overexpression of Notch intracellular domain (NICD) rescued the self-renewal deficit of FOXO3-deficient SCs. We show that FOXO3 regulates NOTCH1 and NOTCH3 receptor expression and that decreasing expression of NOTCH1 and NOTCH3 receptors phenocopies the effect of FOXO3 deficiency in SCs. We demonstrate that FOXO3, perhaps by activating Notch signaling, promotes the quiescent state during SC self-renewal in adult muscle regeneration.

Effects of β-hydroxy-β-methylbutyrate free acid and cold water immersion on expression of CR3 and MIP-1β following resistance exercise

The inflammatory response to muscle-damaging exercise requires monocyte mobilization and adhesion. Complement receptor type 3 (CR3) and macrophage inflammatory protein (MIP)-1β enables monocyte recruitment, adhesion, and subsequent infiltration into damaged muscle tissue. The purpose of this study was to examine the effects of cold water immersion (CWI) and/or β-hydroxy-β-methylbutyrate free acid (HMB-FA) on CR3 expression and MIP-1β concentration after four sets of up to 10 repetitions of squat, dead lift, and split squat exercises at 70-80% 1-repetition maximum. Thirty-nine resistance-trained men (22.2 ± 2.5 yr) were randomly divided into four groups: 1) placebo (PL), 2) HMB-FA, 3) HMB-FA-CWI, and 4) PL-CWI. The HMB-FA groups ingested 3 g/day, and CWI groups were submersed into 10-12°C water for 10 min after exercise. Blood was sampled at baseline (PRE), immediately post- (IP), 30 min post- (30P), 24 h post- (24P), and 48 h post (48P)-exercise. Circulating MIP-1β was assayed and CR3 expression on CD14+ monocytes was measured by flow cytometry. Without treatment, CR3 expression significantly elevated at 30P compared with other time points (P = 0.030-0.047). HMB-FA significantly elevated the percentage of monocytes expressing CR3 between IP and 24P (P = 0.046) and between IP and 48P (P = 0.046). No time effect was observed for MIP-1β concentration. The recovery modalities showed to attenuate the rise in CR3 following exercise. Additionally, supplementation with HMB-FA significantly elevated the percentage of monocytes expressing CR3 during recovery. Although the time course that inflammatory responses are most beneficial remains to be determined, recovery modalities may alter immune cell mobilization and adhesion mechanisms during tissue recovery.

Sleep deprivation impairs functional muscle recovery following injury

Introduction Skeletal muscles possess the ability to completely regenerate following muscular injury. Sleep is believed to play an important role in this regenerative process; however, the nature of this role has not been previously tested. Our aim was to investigate the effects of sleep deprivation on molecular, histological and functional indices of muscle repair following myotoxic injury. Materials and methods Male rats were injected with 1.5% bupivacaine into the masseter muscle to induce myotoxic damage. Subjects were either sleep deprived for 8 h during the light period using a forced locomotion activity wheel, or served as activity controls. They were subsequently sacrificed at 2, 7 or 14 days post-injection. Western Blot analysis was used to assay for protein expression of positive (MyoD, myogenin) and negative (myostatin) molecular repair markers. Evans Blue Dye staining for damaged muscle fibres was used to examine histopathology. Functional muscle repair was evaluated after 2 weeks using in situ contractility testing to measure the force–frequency relationship during isometric contractions. Results Sleep deprivation suppressed MyoD protein levels in the masseter at 2 and 7 days, and myogenin at 2 days post-injection, compared to activity controls. Myostatin levels were unaffected. Histopathology revealed no effect of sleep deprivation on the extent of muscle fibre degeneration following injury. The force-frequency curve tended to shift downward and to the right in response to sleep loss, indicating compromised contractile force at moderate to high stimulation frequencies. Conclusion We demonstrate that sleep loss impairs functional recovery of the masseter muscle following myotoxic injury. Specifically, 8 h of sleep deprivation acutely downregulated molecular markers of muscle repair and resulted in contractile function deficits during recovery. Together, these findings suggest that sleep normally plays a permissive role in the regeneration of damaged muscle tissue. Acknowledgements PS thanks the National Sciences and Engineering Research Council of Canada (NSERC) for his Ph.D. funding. This research is supported by funds from Canadian Institutes of Health Research (CIHR) and NSERC .

Multiplexing-based polarization sensitiveen-faceoptical coherence tomography

We present a time-domain polarization-sensitive (PS) optical coherence tomography configuration operating at 830 nm, equipped with multichannel acousto-optic deflectors and single photodetectors. The system is used to simultaneously acquire interference information from multiple PS channels and to enable measurement and imaging of backscattered intensity to create both PS and polarization insensitive images. Our approach enables multiple channel imaging without need to divide the object signal. Here, we employ our system in order to demonstrate PS imaging of a thermally damaged muscle tissue.

Vascular damage in obese female rats with hypoestrogenism

Increase in body weight and adiposity has deleterious consequences on health. The aim of this study was to compare morphological and metabolic changes in the arterial vessels of Wistar rats with conditions of obesity, hypoestrogenism, and hypoestrogenism plus obesity. Ovariectomized rats (hypoestrogenic condition) received 30 % sugar in drinking water plus standard diet during 10 weeks. The hypoestrogenic-obese (HE-OB) group presented increase in weight, blood pressure, hypertriglyceridemia, and hyperglycemia compared with other groups. The morphological study in aortic vessels from HE showed damage in endothelial smooth muscle tissue compared with the other groups. Adipose cells volume in HE-OB (59.33 ± 2.38 μ(3) × 10(5)) and obese (OB) (54.95 ± 1.36 μ(3) × 10(5)) groups were significantly larger than control group (36.38 ± 0.98 μ(3) × 10(5)). In the HE group adipocyte hyperplasia was observed, while in OB group adipocyte hypertrophy and hyperplasia was shown. The vascular reactivity in HE-OB and OB groups presented decrease in the relaxation to acetylcholine compared with control conditions (p < 0.05), whereas the addition of N(G)-nitro-L-arginine methyl ester resulted in a greater inhibition of relaxation in HE-OB and OB groups compared with control conditions (p < 0.05). These findings suggest that the dysfunction in blood vessels observed in estrogen deficiency and obesity conditions contributes to early cardiovascular alterations.

Macrofinancing Efficient Remodeling of Damaged Muscle Tissue

In this issue of Cell Metabolism, Mounier et al. (2013) show that AMPKα1 is a crucial contributor to the regeneration of damaged muscle tissues, acting in macrophages at the nexus between proinflammatory debris removal and resolution of muscle tissue inflammation.

Augmenter of liver regeneration, a protective factor against ROS-induced oxidative damage in muscle tissue of mitochondrial myopathy affected patients

Mitochondria-related myopathies (MM) are a group of different diseases defined by a varying degree of dysfunctions of the mitochondrial respiratory chain which leads to reactive oxygen species (ROS) generation followed by oxidative stress and cellular damage. In mitochondrial myopathy muscle tissue an overexpression of antioxidant enzymes has been documented probably as an attempt to counteract the free radical generation.We previously documented, in human non-pathological muscle fibres, the expression of the augmenter of liver regeneration (ALR), a sulfhydryl oxidase enzyme, whose presence is related to the mitochondria; indeed it has been demonstrated that ALR mainly localizes in the mitochondrial inter-membrane space. Furthermore we reported, in different experimental models, in vivo and in vitro, the anti-apoptotic and anti-oxidative capacities of ALR, achieved by up-regulating Bcl-2 anti-apoptotic family factors and the anti-apoptotic/anti-oxidative secretory isoform of clusterin (sClu).With the present study we aimed to determine ALR, Bcl-2 protein, clusterin and ROS expression in muscle tissue biopsies from MM-affected patients. Non-pathological muscle tissue was used as control. Enzymatic, histochemical, immunohistochemical and immune electron microscopy techniques were performed.The data obtained revealed in MM-derived muscle tissue, compared to non-pathological tissue, the over-expression of ROS, ALR and Bcl-2 and the induction of the nuclear, pro-apoptotic, isoform of clusterin (nCLU).

Tissue damage in organic rainbow trout muscle investigated by proteomics and bioinformatics

The response to tissue damage is a complex process, which involves the coordinated regulation of multiple proteins to ensure tissue repair. In order to investigate the effect of tissue damage in a lower vertebrate, samples were taken from rainbow trout (Oncorhynchus mykiss) at day 7 after damage and proteins were separated using 2DE. The experimental design included two groups of rainbow trout, which were fed organic feed either with or without astaxanthin. In total, 96 proteins were found to be affected by tissue damage, clearly demonstrating in this lower vertebrate the complexity and magnitude of the cellular response, in the context of a regenerative process. Using a bioinformatics approach, the main biological function of these proteins were assigned, showing the regulation of proteins involved in processes such as apoptosis, iron homeostasis, and regulation of muscular structure. Interestingly, it was established that exclusively within the astaxanthin feed group, three members of the annexin protein family (annexin IV, V, and VI) were regulated in response to tissue damage.

Identification and description of a novel murine model for polytrauma and shock.

To develop a novel polytrauma model that better recapitulates the immunologic response of the severely injured patient by combining long-bone fracture, muscle tissue damage, and cecectomy with hemorrhagic shock, resulting in an equivalent Injury Severity Score of greater than 15. We compared this new polytrauma/shock model to historically used murine trauma-hemorrhage models. Pre-clinical controlled in vivo laboratory study. Laboratory of Inflammation Biology and Surgical Science. Six- to 10-week-old C57BL/6 (B6) mice. Mice underwent 90 minutes of shock (mean arterial pressure 30 mm Hg) and resuscitation via femoral artery cannulation followed by laparotomy (trauma-hemorrhage), hemorrhage with laparotomy and femur fracture, or laparotomy with cecetomy and femur fracture with muscle tissue damage (polytrauma). Mice were euthanized at 2 hours, 1 day, and 3 days postinjury. The spleen, bone marrow, blood, and serum were collected from mice for analysis at the above time points. None of the models were lethal. Mice undergoing polytrauma exhibited a more robust inflammatory response with significant elevations in cytokine/chemokine concentrations when compared with traditional models. Polytrauma was the only model to induce neutrophilia (Ly6G (+)CD11b(+) cells) on days 1 and 3 (p<0.05). Polytrauma, as compared to trauma-hemorrhage and hemorrhage with laparotomy and femur fracture, induced a loss of circulating CD4(+) T cell with simultaneous increased cell activation (CD69(+) and CD25(+)), similar to human trauma. There was a prolonged loss of major histocompatibility complex class II expression on monocytes in the polytrauma model (p<0.05). Results were confirmed by genome-wide expression analysis that revealed a greater magnitude and duration of blood leukocyte gene expression changes in the polytrauma model than the trauma-hemorrhage and sham models. This novel polytrauma model better replicates the human leukocyte, cytokine, and overall inflammatory response following injury and hemorrhagic shock.

Interleukin 6 alters myogenic regulatory factors expression in cultured mammalian satellite cells

Quiescent muscle satellite cells (SCs) express paired box transcription factor 7 (Pax 7) and Sprouty1 (Spry1), expression of these transcription factors decreases upon activation. In contrast, activated SCs increase expression of myogenic regulatory factors (MRFs) such as; myogenin and myogenic differentiation factor (MyoD) as they differentiate and mature. Hence, myogenic activation of SCs and thus myogenesis can be characterized by quantifying mRNA expression of these marker genes using quantitative RT‐PCR. Further, inflammation at the site of myotrauma is known to induce hypertrophic and hyperplastic muscle growth. We hypothesize that following myotrauma in mammals, cytokines such as interleukin 6 (IL6), promote myogenesis through SC activation. We observed decreases in both Pax 7 (p=0.09) and Spry1 (p=0.08) expression, an increase in myogenin (p=0.0014) expression and altered MyoD (p=0.04) expression when cultured SCs were treated with IL6 in vitro. These results support the hypothesis that cytokines mediate the recruitment of quiescent SCs and thereby facilitate the repair of damaged muscle tissue and have a direct promyogenic effect. The role of cytokines in myogenesis may yield feasible means of enhancing muscle growth and repair in response to trauma, pathology or sarcopenia. We acknowledge the UI SRGP FY2012, USDA Hatch Grant NC1184 and IBC Grant FY2013 for funding.

A new standardization in ultrasonography: soft tissue health analysis and resistance flexibility training of Bob Cooley

Purpose: In ultrasonography, while standardizations exist for the evaluation of joint injuries, organ damage, and blood clots in veins and arteries, there is no standardization for the evaluation of soft tissues. Soft tissues visible by ultrasonography include fat, muscle, and fascia. Here, we introduce the use of ultrasound for the detection and analysis of: 1) soft tissue health, disease, and degeneration, 2) dense fascia fibers and scar tissue associated with injury, chronic pain, and poor muscle function, and 3) the effects of Resistance FlexibilityTM (RF), a non-invasive, novel therapeutic modality that uses high levels of eccentric force to remove dense fascia and scar tissue. Standard eccentric training has been shown to prevent injury, reduce pain, and effectively treat tendinopathy. RF differs from other forms of eccentric training, because it includes an advanced biomechanical analysis, uses much greater force, is pain-free, produces rapid biomechanical changes, and requires a high degree of skill by practitioner(s). We introduce the hypotheses that: 1) chronic pain and lack of flexibility, such as that observed in arthritis, is associated with the accumulation of dense fascia fibers, either over time or as a result of trauma, and 2) RF changes the health and structure of fascia, causing an improvement in muscle health and function. Methods: Ultrasound Soft tissue analysis: With high-resolution ultrasound, we captured images of injured and non-injured soft tissue before and after 10 minutes of a) strength training, b) traditional stretching, and c) RF. Video: We collected video of a) strength training, b) traditional stretching, and c) RF in motion. Endoscopy: With high-resolution endoscopy, we filmed a) strength training, b) traditional stretching, and c) RF to analyze the effects of each technique on the fascia of a participant's right lateral hamstring. Results: Ultrasound Soft tissue analysis: Areas of very high echogenicity, likely indicating abnormally dense fascia fibers, were observed in tissues diagnosed as injured. Non-injured tissues did not contain areas of high echogenicity. A decrease in echogenicity was observed in response to RF in both damaged and normal tissues. Traditional stretching and strength training did not cause a decrease in echogenicity. Video: Significant tension and lengthening of fascia fibers and structural changes were seen in response to RF, but not in response to traditional stretching or strength training. Endoscopy: RF training produced fibrillar movement, verticalization of fibers, and changes in the alignment of fascia that traditional stretching and strength training did not produce. Conclusions: These data represent the foundation for a new standardization in the field of ultrasonography to detect diseased and damaged muscle and fascial tissues. Further ultrasound studies are required to investigate how RF may restore fascia to healthier state and to quantify the physical state, hydration, and amount of fascia present in normal and abnormal tissues. The rapid flexibility increases and fascia changes caused by RF are not explainable by current models of muscular change and function. This study represents the first time that a non-invasive modality has been shown to cause a change in fascia in real time by endoscopy.View Large Image Figure ViewerDownload Hi-res image Download (PPT)View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Nutrient timing revisited: is there a post-exercise anabolic window?

Nutrient timing is a popular nutritional strategy that involves the consumption of combinations of nutrients--primarily protein and carbohydrate--in and around an exercise session. Some have claimed that this approach can produce dramatic improvements in body composition. It has even been postulated that the timing of nutritional consumption may be more important than the absolute daily intake of nutrients. The post-exercise period is widely considered the most critical part of nutrient timing. Theoretically, consuming the proper ratio of nutrients during this time not only initiates the rebuilding of damaged muscle tissue and restoration of energy reserves, but it does so in a supercompensated fashion that enhances both body composition and exercise performance. Several researchers have made reference to an anabolic “window of opportunity” whereby a limited time exists after training to optimize training-related muscular adaptations. However, the importance - and even the existence - of a post-exercise ‘window’ can vary according to a number of factors. Not only is nutrient timing research open to question in terms of applicability, but recent evidence has directly challenged the classical view of the relevance of post-exercise nutritional intake with respect to anabolism. Therefore, the purpose of this paper will be twofold: 1) to review the existing literature on the effects of nutrient timing with respect to post-exercise muscular adaptations, and; 2) to draw relevant conclusions that allow practical, evidence-based nutritional recommendations to be made for maximizing the anabolic response to exercise.

Exercise-Induced Inflammatory Response: To Use or Not use Anti-Inflammatory Medication

Intense exercise is a physiological stress capable of inducing damage in the exercised muscle group. As a consequence of this exercise-induced micro lesion, there is an increase in the interaction of leukocytes (neutrophils and monocytes/macrophages) with muscle endothelial cells and their transmigration into skeletal muscle tissue. Mechanisms driving this physiological response are not known, but exercise-induced muscle damage may be associated with a local inflammation involving leukocyte accumulation in damaged muscle tissue. Important recent findings show that this infiltration of leukocytes plays an important role in the skeletal muscle remodeling process by activating angiogenesis and hypertrophic pathways inside the skeletal muscle tissue. There are some speculations suggesting that this inflammatory process should be controlled by anti-inflammation drugs in athletes to accelerate the recovery time. Investigations of the literature in this field up to this point do not offer a sufficient body of evidence confirming the need for an anti-inflammatory drug administration to control the exercise-induced inflammation. On the other hand, anti-inflammatory drug administration as a supplemental diet could inhibit important pathways of tissue adaptative responses and block the benefits of exercise to the skeletal muscle tissue.

Macrophage Plasticity and the Role of Inflammation in Skeletal Muscle Repair

Effective repair of damaged tissues and organs requires the coordinated action of several cell types, including infiltrating inflammatory cells and resident cells. Recent findings have uncovered a central role for macrophages in the repair of skeletal muscle after acute damage. If damage persists, as in skeletal muscle pathologies such as Duchenne muscular dystrophy (DMD), macrophage infiltration perpetuates and leads to progressive fibrosis, thus exacerbating disease severity. Here we discuss how dynamic changes in macrophage populations and activation states in the damaged muscle tissue contribute to its efficient regeneration. We describe how ordered changes in macrophage polarization, from M1 to M2 subtypes, can differently affect muscle stem cell (satellite cell) functions. Finally, we also highlight some of the new mechanisms underlying macrophage plasticity and briefly discuss the emerging implications of lymphocytes and other inflammatory cell types in normal versus pathological muscle repair.