Phosphocreatine Concentrations Research Articles

Beneficial Effects of RNS60 in Cardiac Ischemic Injury.

RNS60 is a physically modified saline solution hypothesized to contain oxygen nanobubbles. It has been reported to reduce ischemia/reperfusion injury in a pig model of acute myocardial infarction. We investigated the effects of RNS60 during cardiac hypoxia in mice and as an additive to cardioplegic solution in rat hearts. ApoE−/−LDLr−/− mice were treated by intravenous injection of RNS60 or saline as a control while monitoring the ECG and post-hypoxic serum release of troponin T and creatine kinase activity. Hearts infused with Custodiol containing 10% RNS60 or saline as the control were subjected to 4 h of 4 °C preservation, followed by an assessment of myocardial metabolites, purine release, and mechanical function. RNS60 attenuated changes in the ECG STU area during hypoxia, while the troponin T concentration and creatine kinase activity were significantly higher in the serum of the controls. During reperfusion after 4 h of cold ischemia, the Custodiol/RNS60-treated hearts had about 30% lower LVEDP and better dp/dtmax and dp/dtmin together with a decreased release of purine catabolites vs. the controls. The myocardial ATP, total adenine nucleotides, and phosphocreatine concentrations were higher in the RNS60-treated hearts. This study indicates that RNS60 enhances cardioprotection in experimental myocardial hypoxia and under conditions of cardioplegic arrest. Improved cardiac energetics are involved in the protective effect, but complete elucidation of the mechanism requires further study.

Contributions of energy pathways to ATP production and pH variations in postmortem muscles

The roles of energy pathways in postmortem muscles are still debated. In this study, the contributions of different pathways to ATP production and pH variations were analyzed by using a kinetic model based on data from beef longissimus lumborum. Phosphocreatine represents over 92% of the initial ATP production but, after 24 h, glycolysis, phosphocreatine, myokinase reaction, and aerobic respiration contribute, respectively, 89.44%, 5.26%, 4.44%, and 0.86% of the cumulative amount of ATP produced. ATP hydrolysis and glycolysis result in 0.52 and 0.6 units of pH decline, respectively, at 24 h with ATP hydrolysis accounting for most of the early decline. Phosphocreatine, myokinase reaction, and aerobic respiration lead to, respectively, 0.08, 0.07, and 0.004 units of pH increase after 24 h though phosphocreatine is depleted within the first 30 min. Furthermore, electrical stimulation affects pH primarily through ATP hydrolysis and glycolysis. The initial muscle oxygen saturation level and phosphocreatine content affect pH but the influences are small.

Chimeric Agonist of Galanin Receptor GALR2 Reduces Heart Damage in Rats with Streptozotocin-Induced Diabetes.

Neuropeptide galanin and its N-terminal fragments reduce the generation of reactive oxygen species and normalize metabolic and antioxidant states of myocardium in experimental cardiomyopathy and ischemia/reperfusion injury. The aim of this study was to elucidate the effect of WTLNSAGYLLGPβAH-OH (peptide G), a pharmacological agonist of the galanin receptor GalR2, on the cardiac injury induced by administration of streptozotocin (STZ) in rats. Peptide G was prepared by solid phase peptide synthesis using the Fmoc strategy and purified by preparative HPLC; its structure was confirmed by 1H-NMR spectroscopy and MALDI-TOF mass spectrometry. Experimental animals were randomly distributed into five groups: C, control; S, STZ-treated; SG10, STZ + peptide G (10 nmol/kg/day); SG50, STZ + peptide G (50 nmol/kg/day); G, peptide G (50 nmol/kg/day). Administration of peptide G prevented hyperglycemia in SG50 rats. By the end of the experiment, the ATP content, total pool of adenine nucleotides, phosphocreatine (PCr) content, and PCr/ATP ratio in the myocardium of animals of the SG50 group were significantly higher than in rats of the S group. In the SG50 and SG10 groups, the content of lactate and lactate/pyruvate ratio in the myocardium were reduced, while the glucose content was increased vs. the S group. Both doses of peptide G reduced the activation of creatine kinase-MB and lactate dehydrogenase, as well as the concentration of thiobarbituric acid reactive products in the blood plasma of STZ-treated rats to the control values. Taken together, these results suggest that peptide G has cardioprotective properties in type 1 diabetes mellitus. Possible mechanisms of peptide G action in the STZ-induced diabetes are discussed.

Trichloroethylene modifies energy metabolites in the amniotic fluid of Wistar rats

Exposure to trichloroethylene (TCE), an industrial solvent, is associated with several adverse pregnancy outcomes in humans and decreased fetal weight in rats. However, effects of TCE on energy metabolites in amniotic fluid, which have associations with pregnancy outcomes, has not been published previously. In the current exploratory study, timed-pregnant Wistar rats were exposed to 480 mg TCE/kg/day via vanilla wafer or to vehicle (wafer) alone from gestational day (GD) 6–16. Amniotic fluid collected on GD 16 was analyzed for metabolites important in energy metabolism using short chain fatty acid and tricarboxylic acid plus platforms (N = 4 samples/sex/treatment). TCE decreased concentrations of the following metabolites in amniotic fluid for both fetal sexes: 6-phosphogluconate, guanosine diphosphate, adenosine diphosphate, adenosine triphosphate, and flavin adenine dinucleotide. TCE decreased fructose 1,6-bisphosphate and guanosine triphosphate concentrations in amniotic fluid of male but not female fetuses. Moreover, TCE decreased uridine diphosphate-D-glucuronate concentrations, and increased arginine and phosphocreatine concentrations, in amniotic fluid of female fetuses only. No metabolites were increased in amniotic fluid of male fetuses. Pathway analysis suggested that TCE altered folate biosynthesis and pentose phosphate pathway in both sexes. Using metabolite ratios to investigate changes within specific pathways, some ratio alterations, including those in arginine metabolism and phenylalanine metabolism, were detected in females only. Ratio analysis also suggested enzymes, including gluconokinase, as potential TCE targets. Together, results from this exploratory study suggest that TCE differentially modified energy metabolites in amniotic fluid based on sex. These findings may inform future studies of TCE reproductive toxicity.

Differentiation between sepsis survivors and sepsis non-survivors through blood serum metabolomics: A proton nuclear magnetic resonance spectroscopy (NMR) study

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is a subset of sepsis with underlying circulatory cellular and metabolic abnormalities associated with higher mortality rates. However, a detailed understanding of sepsis is still limited. The present study reports the differences in the metabolic profile of serum samples of patients with sepsis compared to healthy controls using Nuclear Magnetic Resonance (NMR) spectroscopy. The study also compares the NMR metabolomics on day zero of admission among sepsis survivors (those who survived till day seven) and sepsis non-survivors (those who succumbed on day zero). Furthermore, the different metabolites in serum were analysed by univariate and multivariate analysis, ROC analysis, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA) methods. Metabolites with VIP score (>1·0) were considered as potential biomarker/s to discriminate sepsis survivors from non- survivors at day zero. Data showed that phenylalanine was significantly higher in sepsis patients compared to healthy controls, whereas isoleucine, valine and histidine were significantly lower in sepsis patients compared to healthy controls. Also, non-survivors had higher serum levels of creatine, phosphocreatine, choline, betaine, tyrosine, histidine and phenylalanine concentrations than survivors. These findings suggest that the metabolic alterations at day zero may predict the survival of patients with sepsis. The significant differences seen in metabolites concentration of amino acids, phospholipids and creatine may be used as early prognostic markers to discriminate non-survivors from survivors of sepsis patients at day zero. Our findings indicate that the metabolite alterations are associated with the progression of the disease.

Nutritional approaches to counter performance constraints in high-level sports competition.

New Findings What is the topic of this review? The nutritional strategies that athletes use during competition events to optimize performance and the reasons they use them. What advances does it highlight? A range of nutritional strategies can be used by competitive athletes, alone or in combination, to address various event‐specific factors that constrain event performance. Evidence for such practices is constantly evolving but must be combined with understanding of the complexities of real‐life sport for optimal implementation. High‐performance athletes share a common goal despite the unique nature of their sport: to pace or manage their performance to achieve the highest sustainable outputs over the duration of the event. Periodic or sustained decline in the optimal performance of event tasks, involves an interplay between central and peripheral phenomena that can often be reduced or delayed in onset by nutritional strategies. Contemporary nutrition practices undertaken before, during or between events include strategies to ensure the availability of limited muscle fuel stores. This includes creatine supplementation to increase muscle phosphocreatine content and consideration of the type, amount and timing of dietary carbohydrate intake to optimize muscle and liver glycogen stores or to provide additional exogenous substrate. Although there is interest in ketogenic low‐carbohydrate high‐fat diets and exogenous ketone supplements to provide alternative fuels to spare muscle carbohydrate use, present evidence suggests a limited utility of these strategies. Mouth sensing of a range of food tastants (e.g., carbohydrate, quinine, menthol, caffeine, fluid, acetic acid) may provide a central nervous system derived boost to sports performance. Finally, despite decades of research on hypohydration and exercise capacity, there is still contention around their effect on sports performance and the best guidance around hydration for sporting events. A unifying model proposes that some scenarios require personalized fluid plans while others might be managed by an ad hoc approach (ad libitum or thirst‐driven drinking) to fluid intake.

Novel Small-Molecule Troponin Activator Increases Cardiac Contractile Function Without Negative Impact on Energetics.

Current heart failure therapies unload the failing heart without targeting the underlying problem of reduced cardiac contractility. Traditional inotropes (ie, calcitropes) stimulate contractility via energetically costly augmentation of calcium cycling and worsen patient survival. A new class of agents-myotropes-activates the sarcomere directly, independent of calcium. We hypothesize that a novel myotrope TA1 increases contractility without the deleterious myocardial energetic impact of a calcitrope dobutamine. We determined the effect of TA1 in bovine cardiac myofibrils and human cardiac microtissues, ex vivo in mouse cardiac fibers and in vivo in anesthetized normal rats. Effects of increasing concentrations of TA1 or dobutamine on contractile function, phosphocreatine and ATP concentrations, and ATP production were assessed by 31P nuclear magnetic resonance spectroscopy on isolated perfused rat hearts. TA1 increased the rate of myosin ATPase activity in isolated bovine myofibrils and calcium sensitivity in intact mouse papillary fibers. Contractility increased dose dependently in human cardiac microtissues and in vivo in rats as assessed by echocardiography. In isolated rat hearts, TA1 and dobutamine similarly increased the rate-pressure product. Dobutamine increased both developed pressure and heart rate accompanied by decreased phosphocreatine-to-ATP ratio and decreased free energy of ATP hydrolysis (ΔG~ATP) and elevated left ventricular end diastolic pressure. In contrast, the TA1 increased developed pressure without any effect on heart rate, left ventricular end diastolic pressure, phosphocreatine/ATP ratio, or ΔG~ATP. Novel myotrope TA1 increased myocardial contractility by sensitizing the sarcomere to calcium without impairing diastolic function or depleting the cardiac energy reserve. Since energetic depletion negatively correlates with long-term survival, myotropes may represent a superior alternative to traditional inotropes in heart failure management.

510 Late-Breaking: Dietary Glycine Supplementation During Growing and Finishing Phases Increases Tissue Concentrations of Total Creatine and Gene Expression of Creatine-synthetic Enzymes in Low-birthweight Pigs

Abstract Dietary glycine is required for maximum growth and development in animals by stimulating muscle protein synthesis and as a component of creatine. Creatine is synthesized from glycine, arginine, and S-adenosylmethionine by arginine:glycine amidinotransferase (AGAT) and guanidinoacetate N-methyltransferase (GAMT). Sufficient creatine synthesis for growth requires adequate substrate supply. However, swine diets are deficient in glycine. Additionally, intrauterine growth restricted (IUGR) pigs have reduced glycine synthesis. This results in decreased creatine synthesis and lower total creatine content in tissues, leading to reduced cellular energy metabolism and diminished muscle protein accretion. This study was designed to test the hypothesis that dietary glycine supplementation in corn-and-soybean-meal-based diets would improve overall growth and skeletal muscle accretion in post-weaning IUGR pigs by increasing the expression of creatine-synthetic enzymes and tissue concentrations of total creatine. Fourteen IUGR pigs (birthweight = 0.98±0.03 kg, mean±SEM) and 20 normal birthweight pigs (birthweight = 1.44±0.02 kg, mean±SEM) were obtained at weaning for this study. Pigs from each birthweight group were randomly assigned to 1% glycine + 0.19% corn starch treatment group or 1.19% alanine group (isonitrogenous control) for the study (21 d to 188 d of age); tissues were collected at d 188. Data were analyzed by using 2-way ANOVA and the Duncan multiple comparison test. Glycine-supplemented IUGR pigs had greater tissue concentrations of creatine, creatinine, and creatine phosphate than control IUGR in all tissues measured (P< 0.05). Control IUGR pigs showed diminished activity and mRNA expression of creatine-synthetic enzymes (P < 0.05); this was mitigated by glycine supplementation as glycine supplemented IUGR pigs showed normal levels of enzyme activity and mRNA expression. Overall, results of this study indicate dietary glycine supplementation to IUGR pigs between weaning and market weight effectively restores creatine-synthetic enzyme activities and increase tissue concentrations of total creatine, leading to increased lean tissue growth. (Supported by USDA-NIFA)

Methodological considerations in measuring specific force in human single skinned muscle fibres.

Chemically skinned fibres allow the study of human muscle contractile function in vitro. A particularly important parameter is specific force (SF), that is, maximal isometric force divided by cross-sectional area, representing contractile quality. Although SF varies substantially between studies, the magnitude and cause of this variability remains puzzling. Here, we aimed to summarize and explore the cause of variability in SF between studies. A systematic search was conducted in Medline, Embase and Web of Science databases in June 2020, yielding 137 data sets from 61 publications which studied healthy, young adults. Five-fold differences in mean SF data were observed. Adjustments to the reported data for key methodological differences allowed between-study comparisons to be made. However, adjustment for fibre shape, swelling and sarcomere length failed to significantly reduce SF variance (I2 = 96%). Interestingly, grouping papers based on shared authorship did reveal consistency within research groups. In addition, lower SF was found to be associated with higher phosphocreatine concentrations in the fibre activating solution and with Triton X-100 being used as a skinning agent. Although the analysis showed variance across the literature, the ratio of SF in single fibres containing myosin heavy chain isoforms IIA or I was found to be consistent across research groups. In conclusion, whilst the skinned fibre technique is reliable for studying in vitro force generation of single fibres, the composition of the solution used to activate fibres, which differs between research groups, is likely to heavily influence SF values.

Assessment of Creatine in Sports Products

The Norwegian Scientific Committee for Food Safety (Vitenskapskomiteen for mattrygghet, VKM) has at the request of the Norwegian Food Safety Authority (Mattilsynet) conducted an assessment of creatine in sports products (e.g. supplements). The evaluation has been performed by an ad hoc group, and assessed by the VKM Panel on nutrition, dietetic products, novel food and allergy.
 
 The evaluation of safety and possible risks of creatine supplementation in this opinion is based on previous reports, 23 original papers and 14 reviews from literature searches.
 
 Marketing and sales of sport products are increasing in the Nordic countries, with creatine supplements being one of four most common categories. In addition to be used by athletes, the use of creatine supplements seems to increase among general exercisers and young people. Creatine supplements are mainly used for their supposed effects on muscles mass and high intensity and short duration sport performances. Supplementation has been shown to result in higher concentration of creatine phosphate in the muscles, which is the limited substrate.
 
 For athletes, it is recommended a loading dose of 10-20 g/day for 4-7 days and a maintenance dose of 2-5 g/day for weeks or months. Some athletes continue the maintenance dose for several years. It is well documented that creatine supplementation has positive effects on muscle mass combined with strength training and performance during maximal exercise. There are however large individual variation in the response, and there are responders and non-responders.
 
 The new scientific literature, including long term studies, is in line with the EFSA (European Food Safety Authority) opinion from 2004.
 
 VKM Panel on nutrition, dietetic products, novel food and allergy supports the EFSA conclusion that supplementation of creatine in doses below 3 g/day is unlikely to pose any risks if the purity of the creatine compound is adequate. 
 
 Scientific long-term studies with doses up to 5-10 g/day in adult athletes have shown no harmful effects, but there are no dose-response studies indicating a safe upper limit for creatine. 
 
 The potential negative effects (impaired kidney function, weight gain and gastrointestinal disturbances) which have been published in non scientific journals and anecdotal reports have not found support in controlled systematic studies on healthy subjects. It has been indicated that individuals with impaired kidney functions should refrain from creatine supplements.
 
 Creatine-monohydrate is the most studied form of creatine supplements, and only creatine monohydrate has been included in the scientific investigations on adverse effects.

Acetylation of muscle creatine kinase negatively impacts high-energy phosphotransfer in heart failure.

A hallmark of impaired myocardial energetics in failing hearts is the downregulation of the creatine kinase (CK) system. In heart failure patients and animal models, myocardial phosphocreatine content and the flux of the CK reaction are negatively correlated with the outcome of heart failure. While decreased CK activity is highly reproducible in failing hearts, the underlying mechanisms remains elusive. Here, we report an inverse relationship between the activity and acetylation of CK muscle form (CKM) in human and mouse failing hearts. Hyperacetylation of recombinant CKM disrupted MM homodimer formation and reduced enzymatic activity, which could be reversed by sirtuin 2 treatment. Mass spectrometry analysis identified multiple lysine residues on the MM dimer interface, which were hyperacetylated in the failing hearts. Molecular modeling of CK MM homodimer suggested that hyperacetylation prevented dimer formation through interfering salt bridges within and between the 2 monomers. Deacetylation by sirtuin 2 reduced acetylation of the critical lysine residues, improved dimer formation, and restored CKM activity from failing heart tissue. These findings reveal a potentially novel mechanism in the regulation of CK activity and provide a potential target for improving high-energy phosphoryl transfer in heart failure.

In Vivo Measurement of Neurochemical Abnormalities in the Hippocampus in a Rat Model of Cuprizone-Induced Demyelination.

This study quantitatively measured the changes in metabolites in the hippocampal lesions of a rat model of cuprizone-induced demyelination as detected using in vivo 7 T proton magnetic resonance spectroscopy. Nineteen Sprague Dawley rats were randomly divided into two groups and fed a normal chow diet or cuprizone (0.2%, w/w) for 7 weeks. Demyelinated hippocampal lesions were quantitatively measured using a 7 T magnetic resonance imaging scanner. All proton spectra were quantified for metabolite concentrations and relative ratios. Compared to those in the controls, the cuprizone-induced rats had significantly higher concentrations of glutamate (p = 0.001), gamma-aminobutyric acid (p = 0.019), and glutamate + glutamine (p = 0.001); however, creatine + phosphocreatine (p = 0.006) and myo-inositol (p = 0.001) concentrations were lower. In addition, we found that the glutamine and glutamate complex/total creatine (p < 0.001), glutamate/total creatine (p < 0.001), and GABA/total creatine (p = 0.002) ratios were significantly higher in cuprizone-treated rats than in control rats. Our results showed that cuprizone-induced neuronal demyelination may influence the severe abnormal metabolism in hippocampal lesions, and these responses could be caused by microglial activation, mitochondrial dysfunction, and astrocytic necrosis.

Muscle and liver metabolomic signatures associated with residual feed intake in Nellore cattle

Identification of those cattle genetics with superior feed efficiency is necessary to increase the productivity of the entire beef industry. The aim of this study was to investigate metabolites profiling in the liver and muscle to identify physiological changes in animals in the livestock system with low or high residual feed intake. Liver and muscle were collected after slaughter from Nellore males, with high and low residual feed intake (H-RFI, n = 10 and L-RFI, n = 10, respectively). Metabolites were extracted with cold methanol/water solution (4:3 v/v). Metabolomics analyses were performed by 1D 1H nuclear magnetic resonance. Metabolites were identified using Chenomx and analysed using MetaboAnalyst 4.0. The residual feed intake classification did not change most of animal performance traits; however, animals with lower residual feed intake presented greater carcass dressing, lower carcass fat deposition. Sixty-three compounds were identified in the liver and 31 in muscle. Coexpression network analysis was carried out and identified four metabolite network modules correlated with the phenotypic traits, indicating common metabolites with a variate important projection score that influences residual feed intake. Metabolites in liver samples was correlated with energy and protein metabolism and on muscle with fat metabolism. Differences on energetic metabolism, including of carbohydrate- and fat-correlated compounds, according to residual feed intake can be assessed by importance of concentration of citrate, isocitrate, glucose-6-phosphate, nicotinamide adenine dinucleotide + hydrogen and creatine phosphate (in liver) and choline, glycine, glycerol, malonate, glucose-6-phosphate and 3-hydroxybutyrate (in muscle). Moreover, differences on protein metabolism, can be assessed by importance of creatinine, glutamine, urea and creatine phosphate concentration in liver and creatinine, creatine, anserine and carnosine in muscle. Animals with low residual feed intake presented changes in energy production, represented by carbohydrate and fatty acid metabolites, and decreased carcass fat deposition and protein turnover.

Oxidative phosphorylation in creatine transporter deficiency.

X-linked creatine transporter deficiency (CTD) is one of the three types of cerebral creatine deficiency disorders. CTD arises from pathogenic variants in the X-linked gene SLC6A8. We report the first phosphorus (31 P) MRS study of patients with CTD, where both phosphocreatine and total creatine concentrations were found to be markedly reduced. Despite the diminished role of creatine and phosphocreatine in oxidative phosphorylation in CTD, we found no elevation of lactate or lowered pH, indicating that the brain energy supply still largely relied on oxidative metabolism. Our results suggest that mitochondrial function is a potential therapeutic target for CTD.

Rescue of myocardial energetic dysfunction in diabetes through the correction of mitochondrial hyperacetylation by honokiol.

Cardiac energetic dysfunction has been reported in patients with type 2 diabetes (T2D) and is an independent predictor of mortality. Identification of the mechanisms driving mitochondrial dysfunction, and therapeutic strategies to rescue these modifications, will improve myocardial energetics in T2D. We demonstrate using 31P-magnetic resonance spectroscopy (31P-MRS) that decreased cardiac ATP and phosphocreatine (PCr) concentrations occurred before contractile dysfunction or a reduction in PCr/ATP ratio in T2D. Real-time mitochondrial ATP synthesis rates and state 3 respiration rates were similarly depressed in T2D, implicating dysfunctional mitochondrial energy production. Driving this energetic dysfunction in T2D was an increase in mitochondrial protein acetylation, and increased ex vivo acetylation was shown to proportionally decrease mitochondrial respiration rates. Treating T2D rats in vivo with the mitochondrial deacetylase SIRT3 activator honokiol reversed the hyperacetylation of mitochondrial proteins and restored mitochondrial respiration rates to control levels. Using 13C-hyperpolarized MRS, respiration with different substrates, and enzyme assays, we localized this improvement to increased glutamate dehydrogenase activity. Finally, honokiol treatment increased ATP and PCr concentrations and increased total ATP synthesis flux in the T2D heart. In conclusion, hyperacetylation drives energetic dysfunction in T2D, and reversing acetylation with the SIRT3 activator honokiol rescued myocardial and mitochondrial energetics in T2D.

Metabolomics of Milk Reflects a Negative Energy Balance in Cows.

Dairy cows can experience a negative energy balance (NEB) in early lactation when feed intake is too low to meet the energy requirements for body maintenance and milk production. Metabolic changes occur in mammary gland cells of animals experiencing a negative energy balance. We studied these metabolic changes in milk samples from dairy cows in relation to energy balance status using liquid chromatography–mass spectrometry (QQQ-LC–MS) and nuclear magnetic resonance (1H NMR). NMR and LC–MS techniques are complementary techniques that enabled a comprehensive overview of milk metabolites in our study. Energy balance and milk samples were obtained from 87 dairy cows. A total of 55 milk metabolites were reliably detected, of which 15 metabolites were positively correlated to energy balance and 20 were negatively correlated to energy balance. Cows in NEB produced more milk with increased milk fat yield and higher concentrations of citrate, cis-aconitate, creatinine, glycine, phosphocreatine, galactose-1-phosphate, glucose-1-phosphate, UDP-N-acetyl-galactosamine, UDP-N-acetyl-glucosamine, and phosphocholine but lower concentrations of choline, ethanolamine, fucose, N-acetyl-neuraminic acid, N-acetyl-glucosamine, and N-acetyl-galactosamine. During NEB, we observed an increased leakage of cellular content, increased synthesis of nucleic acids and cell membrane phospholipids, an increase in one-carbon metabolic processes, and an increase in lipid-triglyceride anabolism. Overall, both apoptosis combined with cellular renewal is paramount in the mammary gland in cows in NEB.

Energy Expenditure of Dynamic Submaximal Human Plantarflexion Movements: Model Prediction and Validation by in-vivo Magnetic Resonance Spectroscopy

To understand the organization and efficiency of biological movement, it is important to evaluate the energy requirements on the level of individual muscles. To this end, predicting energy expenditure with musculoskeletal models in forward-dynamic computer simulations is currently the most promising approach. However, it is challenging to validate muscle models in-vivo in humans, because access to the energy expenditure of single muscles is difficult. Previous approaches focused on whole body energy expenditure, e.g., oxygen consumption (VO2), or on thermal measurements of individual muscles by tracking blood flow and heat release (through measurements of the skin temperature). This study proposes to validate models of muscular energy expenditure by using functional phosphorus magnetic resonance spectroscopy (31P-MRS). 31P-MRS allows to measure phosphocreatine (PCr) concentration which changes in relation to energy expenditure. In the first 25 s of an exercise, PCr breakdown rate reflects ATP hydrolysis, and is therefore a direct measure of muscular enthalpy rate. This method was applied to the gastrocnemius medialis muscle of one healthy subject during repetitive dynamic plantarflexion movements at submaximal contraction, i.e., 20% of the maximum plantarflexion force using a MR compatible ergometer. Furthermore, muscle activity was measured by surface electromyography (EMG). A model (provided as open source) that combines previous models for muscle contraction dynamics and energy expenditure was used to reproduce the experiment in simulation. All parameters (e.g., muscle length and volume, pennation angle) in the model were determined from magnetic resonance imaging or literature (e.g., fiber composition), leaving no free parameters to fit the experimental data. Model prediction and experimental data on the energy supply rates are in good agreement with the validation phase (<25 s) of the dynamic movements. After 25 s, the experimental data differs from the model prediction as the change in PCr does not reflect all metabolic contributions to the energy expenditure anymore and therefore underestimates the energy consumption. This shows that this new approach allows to validate models of muscular energy expenditure in dynamic movements in vivo.

Benefits of Creatine Supplementation for Vegetarians Compared to Omnivorous Athletes: A Systematic Review.

Background: Creatine monohydrate is a nutritional supplement often consumed by athletes in anaerobic sports. Creatine is naturally found in most meat products; therefore, vegetarians have reduced creatine stores and may benefit from supplementation. Objective: to determine the effects of creatine supplementation on vegetarians. Data sources: PubMed and SPORTDiscus. Eligibility criteria: Randomized controlled trials (parallel group, cross-over studies) or prospective studies. Participants: Vegetarians. Intervention: Creatine supplementation. Study appraisal and synthesis: A total of 64 records were identified, and eleven full-text articles (covering nine studies) were included in this systematic review. Results: Creatine supplementation in vegetarians increased total creatine, creatine, and phosphocreatine concentrations in vastus lateralis and gastrocnemius muscle, plasma, and red blood cells, often to levels greater than omnivores. Creatine supplementation had no effect on brain levels of phosphocreatine. Creatine supplementation increased lean tissue mass, type II fiber area, insulin-like growth factor-1, muscular strength, muscular endurance, Wingate mean power output, and brain function (memory and intelligence) in vegetarian participants. Studies were mixed on whether creatine supplementation improved exercise performance in vegetarians to a greater extent compared to omnivores. Limitations: Studies that were reviewed had moderate–high risk of bias. Conclusions: Overall, it appears vegetarian athletes are likely to benefit from creatine supplementation.

The Effect of Creatine Monohydrate Supplementation on Tissue Creatine Concentrations in Male and Female Rats

BackgroundCreatine is an essential compound that can store chemical energy and act as an energy buffer during times of metabolic stress in mammals. Creatine can be synthesized endogenously, however dietary supplementation with creatine monohydrate (CM) is a common medical intervention and is used as a common ergogenic aid in athletes. The aim of this study was to investigate the effect of increasing doses of dietary creatine on creatine uptake in brain, heart, skeletal muscle, and liver tissues in male and female rats in preparation for future dietary interventions.Methods16 male (536g—670g) and 16 female (339g—487g) 12 week old Sprague‐Dawley rats were given access to drinking water with 0 g/L, 2.5 g/L, 5 g/L, or 10 g/L CM and 1% sucrose for 8 weeks. Free creatine and phosphocreatine tissue concentrations were measured using fluorometric assays and combined to report total creatine compound (TCr) concentrations in brain (BR), heart (HRT), liver (LIV), and skeletal muscle [soleus (SOL), extensor digitorum longus (EDL), and gastrocnemius (GAS)] tissues after the 8‐week dietary intervention.ResultsMales were significantly heavier than females (p&lt;0.001) but there were no differences in body weight between groups of either sex. TCr concentrations in BR were higher with 2.5 g/L (p&lt;0.01), 5 g/L (p&lt;0.05), and 10 g/L (p&lt;0.001) CM compared to control, with only the 2.5 g/L CM dose resulting in a higher TCr concentration in females (p&lt;0.05) compared to males. TCr concentrations in SOL were higher with 5 g/L (p&lt; 0.01) and 10 g/L (p&lt;0.001) CM compared to controls. In EDL and GAS TCr concentrations were higher compared to controls with 2.5 g/L (p&lt;0.01, p&lt;0.05), 5 g/L (p&lt;0.001, p&lt;0.05), and 10 g/L (p&lt;0.001, p&lt;0.01) CM. TCr in GAS showed a trend with females (p&lt;0.10) being higher than males. TCr concentrations in HRT of females were higher with 10 g/L (p&lt;0.01) CM compared to controls and trending towards significance with 5 g/L (p&lt;0.10) CM as compared to controls. TCr concentrations in HRT with 10 g/L CM were significantly higher in females (p&lt;0.001) compared to males. No differences in TCr were observed between groups in LIV.ConclusionsCM supplementation provided in water with 1% sucrose for 8 weeks leads to an increase in TCr in brain, heart, and skeletal muscle, but not in liver. Females appeared to be more responsive to CM supplementation in HRT, especially at the highest dose suggesting that dietary interventions involving CM may affect males and females differently.Support or Funding InformationSupported by NSERC, Canada.

Differences in the serum metabolome and lipidome identify potential biomarkers for seronegative rheumatoid arthritis versus psoriatic arthritis

ObjectivesThe differential diagnosis of seronegative rheumatoid arthritis (negRA) and psoriasis arthritis (PsA) is often difficult due to the similarity of symptoms and the unavailability of reliable clinical markers. Since chronic...