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1.
Sympathetic Neural Overdrive in the Obese and Overweight State.
Grassi, G, Biffi, A, Seravalle, G, Trevano, FQ, Dell'Oro, R, Corrao, G, Mancia, G
Hypertension (Dallas, Tex. : 1979). 2019;(2):349-358
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Abstract
Nerve traffic recordings (muscle sympathetic nerve traffic [MSNA]) have shown that sympathetic activation may occur in obesity. However, the small sample size of the available studies, presence of comorbidities, heterogeneity of the subjects examined represented major weaknesses not allowing to draw definite conclusions. This is the case for the overweight state. The present meta-analysis evaluated 1438 obese or overweight subjects recruited in 45 microneurographic studies. The analysis was primarily based on MSNA quantification in obesity and overweight, excluding as concomitant conditions hypertension, metabolic syndrome, and other comorbidities. Assessment was extended to the relationships of MSNA with other neuroadrenergic markers, such as plasma norepinephrine and heart rate, anthropometric variables, as body mass index, waist-to-hip ratio, presence/absence of obstructive sleep apnea, and metabolic profile. Compared with normoweights MSNA was significantly greater in overweight and more in obese individuals (37.0±4.1 versus 43.2±3.5 and 50.4±5.0 burts/100 heartbeats, P<0.01). This was the case even in the absence of obstructive sleep apnea. MSNA was significantly directly related to body mass index and waist-to-hip ratio ( r=0.41 and r=0.64, P<0.04 and <0.01, respectively), clinic blood pressure ( r=0.68, P<0.01), total cholesterol, LDL (low-density lipoprotein) cholesterol, and triglycerides ( r=0.91, r=0.94, and r=0.80, respectively, P<0.01) but unrelated to plasma insulin, glucose, and homeostatic model assessment for insulin resistance. No significant correlation was found between MSNA, heart rate, and norepinephrine. Thus, obesity and overweight are characterized by sympathetic overactivity which mirrors the severity of the clinical condition and reflects metabolic alterations, with the exclusion of glucose/insulin profile. Neither heart rate nor norepinephrine appear to represent faithful markers of the muscle sympathetic overdrive.
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2.
Exercise and immune system as modulators of intestinal microbiome: implications for the gut-muscle axis hypothesis.
Ticinesi, A, Lauretani, F, Tana, C, Nouvenne, A, Ridolo, E, Meschi, T
Exercise immunology review. 2019;:84-95
Abstract
Exercise is a possible modulator of intestinal microbiome composition, since some investigations have shown that it is associated with increased biodiversity and representation of taxa with beneficial metabolic functions. Conversely, training to exhaustion can be associated with dysbiosis of the intestinal microbiome, promoting inflammation and negative metabolic consequences. Gut microbiota can, in turn, influence the pathophysiology of several distant organs, including the skeletal muscle. A gut-muscle axis may in fact regulate muscle protein deposition and muscle function. In older individuals, this axis may be involved in the pathogenesis of muscle wasting disorders through multiple mechanisms, involving transduction of pro-anabolic stimuli from dietary nutrients, modulation of inflammation and insulin sensitivity. The immune system plays a fundamental role in these processes, being influenced by microbiome composition and at the same time contributing to shape microbial communities. In this review, we summarize the most recent literature acquisitions in this field, disentangling the complex relationships between exercise, microbiome, immune system and skeletal muscle function and proposing an interpretative framework that will need verification in future studies.
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3.
The Physiological Roles of Carnosine and β-Alanine in Exercising Human Skeletal Muscle.
Matthews, JJ, Artioli, GG, Turner, MD, Sale, C
Medicine and science in sports and exercise. 2019;(10):2098-2108
Abstract
Carnosine (β-alanyl-L-histidine) plays an important role in exercise performance and skeletal muscle homeostasis. Dietary supplementation with the rate-limiting precursor β-alanine leads to an increase in skeletal muscle carnosine content, which further potentiates its effects. There is significant interest in carnosine and β-alanine across athletic and clinical populations. Traditionally, attention has been given to performance outcomes with less focus on the underlying mechanism(s). Putative physiological roles in human skeletal muscle include acting as an intracellular pH buffer, modulating energy metabolism, regulating Ca handling and myofilament sensitivity, and scavenging of reactive species. Emerging evidence shows that carnosine could also act as a cytoplasmic Ca-H exchanger and form stable conjugates with exercise-induced reactive aldehydes. The enigmatic nature of carnosine means there is still much to learn regarding its actions and applications in exercise, health, and disease. In this review, we examine the research relating to each physiological role attributed to carnosine, and its precursor β-alanine, in exercising human skeletal muscle.
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Effects of dietary sports supplements on metabolite accumulation, vasodilation and cellular swelling in relation to muscle hypertrophy: A focus on "secondary" physiological determinants.
Cholewa, J, Trexler, E, Lima-Soares, F, de Araújo Pessôa, K, Sousa-Silva, R, Santos, AM, Zhi, X, Nicastro, H, Cabido, CET, de Freitas, MC, et al
Nutrition (Burbank, Los Angeles County, Calif.). 2019;:241-251
Abstract
Increased blood flow via vasodilation, metabolite production, and venous pooling contribute to the hyperemia and cellular swelling experienced during resistance training. It has been suggested that these effects play a role in hypertrophic adaptations. Over the past 2 decades, sport supplement products have been marketed to promote exercise hyperemia and intracellular fluid storage, thereby enhancing hypertrophy via acute swelling of myocytes. The three main classes of supplements hypothesized to promote exercise-induced hyperemia include vasodilators, such as nitric oxide precursor supplements; anaerobic energy system ergogenic aids that increase metabolite production, such as β-alanine and creatine; and organic osmolytes, such as creatine and betaine. Previous studies indicated that these dietary supplements are able to improve muscle performance and thus enhance muscle hypertrophy; however, recent evidences also point to these three classes of supplements affecting "secondary" physiological determinants of muscle mass accretion such as vasodilation, metabolite accumulation, and muscle cellular swelling. Although we recognize that the literature is relatively scarce regarding these topics, a better comprehension and discussion of these determinants can lead to increased knowledge and might guide further research regarding the proposed mechanisms of action of the identified compounds. In this case, increased knowledge may contribute to the development of improved efficacy, new products, or direct new research to specifically investigate those secondary effects. The aim of this review was to bring into focus new perspectives associated with secondary physiological effects induced by supplementation and to determine their relevance.
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5.
The clinical impact and biological mechanisms of skeletal muscle aging.
Aversa, Z, Zhang, X, Fielding, RA, Lanza, I, LeBrasseur, NK
Bone. 2019;:26-36
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Abstract
Skeletal muscle is a highly plastic tissue that remarkably adapts to diverse stimuli including exercise, injury, disuse, and, as discussed here, aging. Humans achieve peak skeletal muscle mass and strength in mid-life and then experience a progressive decline of up to 50% by the ninth decade. The loss of muscle mass and function with aging is a phenomenon termed sarcopenia. It is evidenced by the loss and atrophy of muscle fibers and the concomitant accretion of fat and fibrous tissue. Sarcopenia has been recognized as a key driver of limitations in physical function and mobility, but is perhaps less appreciated for its role in age-related metabolic dysfunction and loss of organismal resilience. Similar to other tissues, muscle is prone to multiple forms of age-related molecular and cellular damage, including disrupted protein turnover, impaired regenerative capacity, cellular senescence, and mitochondrial dysfunction. The objective of this review is to highlight the clinical consequences of skeletal muscle aging, and provide insights into potential biological mechanisms. In light of population aging, strategies to improve muscle health in older adults promise to have a profound public health impact.
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6.
Muscle endocrinology and its relation with nutrition.
Romagnoli, C, Pampaloni, B, Brandi, ML
Aging clinical and experimental research. 2019;(6):783-792
Abstract
Recent years have demonstrated clear evidence that skeletal muscle is an active endocrine organ. During contraction of muscle fibers, the skeletal muscle produces and releases, into the blood stream, cytokines and other peptides, called myokines, thanks to which it can both communicate with cells locally within the muscle, in an autocrine and paracrine fashion, or with other distant tissues, exerting its endocrine effects. With the progress of sophisticated technologies, the interest towards the skeletal muscle secretome is rapidly grown and the discovery of new myokines represents a prolific field for the identification of new pharmacological approaches for the management and treatment of many clinical diseases. Considering the importance of the muscle proteome and the cross-talk with other organs, the preservation of a skeletal muscle in good health represents a fundamental aspect in life, especially in ageing. Sarcopenia is the age-dependent loss of skeletal muscle mass and strength, bringing to increases of the risk of adverse outcomes, such as physical disability and poor quality of life, as well as alteration of several hormonal networks. For that reasons, the scientific community has risen its interest to find new interventions to prevent and manage the sarcopenia. Adequate nutrition during ages plays a fundamental role in the health and function of the skeletal muscle and it can represents, alone or in combination with physical exercise, a possible preventive measure against sarcopenia. This review will overview the endocrinology of the skeletal muscle, making a focus on food intake as a strategy for preventing skeletal muscle decay.
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7.
Spontaneous Activity in Urethral Smooth Muscle.
Sergeant, GP, Hollywood, MA, Thornbury, KD
Advances in experimental medicine and biology. 2019;:149-167
Abstract
The urethra is a muscular tube that extends from the bladder neck and is composed of an inner layer of smooth muscle referred to as the internal urethral sphincter and an outer layer of striated muscle which forms the external urethral sphincter. The smooth muscle layer can be separated into an inner layer of longitudinally orientated smooth muscle and an outer, relatively thinner, layer of circular muscle. Tonic contraction of both the smooth and striated muscle components of the urethra generates a urethral closure pressure which exceeds intravesical pressure in the bladder to maintain urinary continence. It is likely that contraction of urethral smooth muscle is involved in the long-term maintenance of tone, since it can achieve this at relatively low energy cost, whereas the striated muscle contributes more to the rise in urethral tone that accompanies increases in bladder pressure secondary to coughing or other sudden increases in intra-abdominal pressure. The level of urethral smooth muscle tone is regulated by several autonomic neurotransmitters, including noradrenaline, acetylcholine, ATP and nitric oxide. However, it is also clear that urethral smooth muscle is capable of generating significant tone in the absence of neural input. In this chapter we will discuss the mechanisms responsible for contraction of urethral smooth muscle, with specific focus on the role of ion channels and Ca2+ handling proteins to this process. The mechanisms underlying spontaneous activity in urethral interstitial cells (UICs), putative pacemaker cells of the urethra, will also be examined along with the modulation of these mechanisms by key excitatory and inhibitory neurotransmitters.
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8.
Severe hyperammonemia from intense skeletal muscle activity: A rare case report and literature review.
Taneja, V, Jasuja, H
Medicine. 2019;(47):e17981
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Abstract
RATIONALE Adult hyperammonemia is most often the result of hepatic dysfunction. Hyperammonemia in the setting of normal hepatic function is a much less common phenomenon and has usually been associated with medications and certain disease states. Here, we present an unusual case of severe hyperammonemia caused physiologically by intense muscle activity in a patient lacking any evidence of liver disease. PATIENT CONCERNS A 36-year-old woman was brought to the emergency department for a suicide attempt after being found covered in Lysol and Clorox germicidal bleach. She was noted to be in a state of violent psychosis with extreme agitation and had to be sedated and intubated for airway protection. DIAGNOSIS AND INTERVENTIONS Initial labs revealed hyperammonemia, lactic acidosis, and anion gap metabolic acidosis. Aminotransferases, bilirubin, and creatine kinase (CK) were normal. Renal function, prothrombin time, activated partial thromboplastin time, and international normalized ratio were also unremarkable and remained so at 24 hours. Ethyl alcohol, acetaminophen, salicylate, and valproic acid were all undetectable in blood. She received 2 doses of lactulose overnight, with a subsequent bowel movement. Next day, her mentation, serum ammonia level, and lactic acid level were back to normal, and she was extubated. Aminotransferases and CK levels were elevated but improved with supportive care. A detailed history and relevant biochemical investigations were unremarkable for any other etiology of hyperammonemia including the common inborn errors of metabolism (IEM). The combination of clinical findings of extreme skeletal muscle activity along with hyperammonemia and lactic acidosis, and subsequently rhabdomyolysis in the setting of unremarkable history and otherwise normal hepatic function strongly suggest the myokinetic origin of hyperammonemia in the patient. OUTCOME The patient recovered well with supportive care and was discharged on day 5. LESSONS This unique case illustrates the important role of skeletal muscle in the human metabolism of ammonia. In our discussion, we also elucidate the underlying pathophysiology, with the objective of improving clinician understanding of various differential diagnoses.
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Metabolic implications of low muscle mass in the pediatric population: a critical review.
Orsso, CE, Tibaes, JRB, Rubin, DA, Field, CJ, Heymsfield, SB, Prado, CM, Haqq, AM
Metabolism: clinical and experimental. 2019;:102-112
Abstract
Skeletal muscle is recognized as a tissue with high metabolic capacity given its key roles in glucose and lipid metabolism. Although low muscle mass has been associated with metabolic disorders in adults, it is not clear if this body composition phenotype is related to metabolic health status earlier in life. In this review, we aim to clarify whether having low muscle mass is associated with increased risk of metabolic dysregulation in the pediatric population. Fifteen original articles investigating the relationship between body composition measures of muscle mass and single or clustered metabolic risk factors in children and adolescents were critically evaluated. Despite a growing body of evidence supporting low muscle mass as a risk factor for metabolic health in children and adolescents, conflicting associations were reported. Differences in body composition techniques, muscle mass indices, and clinical methods used to assess metabolic biomarkers may have contributed to a lack of a consistent conclusion. Moreover, most studies did not control for potential biological and lifestyle confounders. Future studies using precise, reproducible techniques to evaluate body composition and metabolic biomarkers are required to determine the implications of low muscle mass on metabolic health during childhood and adolescence.
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Supplements with purported effects on muscle mass and strength.
Valenzuela, PL, Morales, JS, Emanuele, E, Pareja-Galeano, H, Lucia, A
European journal of nutrition. 2019;(8):2983-3008
Abstract
PURPOSE Several supplements are purported to promote muscle hypertrophy and strength gains in healthy subjects, or to prevent muscle wasting in atrophying situations (e.g., ageing or disuse periods). However, their effectiveness remains unclear. METHODS This review summarizes the available evidence on the beneficial impacts of several popular supplements on muscle mass or strength. RESULTS Among the supplements tested, nitrate and caffeine returned sufficient evidence supporting their acute beneficial effects on muscle strength, whereas the long-term consumption of creatine, protein and polyunsaturated fatty acids seems to consistently increase or preserve muscle mass and strength (evidence level A). On the other hand, mixed or unclear evidence was found for several popular supplements including branched-chain amino acids, adenosine triphosphate, citrulline, β-Hydroxy-β-methylbutyrate, minerals, most vitamins, phosphatidic acid or arginine (evidence level B), weak or scarce evidence was found for conjugated linoleic acid, glutamine, resveratrol, tribulus terrestris or ursolic acid (evidence level C), and no evidence was found for other supplements such as ornithine or α-ketoglutarate (evidence D). Of note, although most supplements appear to be safe when consumed at typical doses, some adverse events have been reported for some of them (e.g., caffeine, vitamins, α-ketoglutarate, tribulus terrestris, arginine) after large intakes, and there is insufficient evidence to determine the safety of many frequently used supplements (e.g., ornithine, conjugated linoleic acid, ursolic acid). CONCLUSION In summary, despite their popularity, there is little evidence supporting the use of most supplements, and some of them have been even proven ineffective or potentially associated with adverse effects.