Moderate elevation of intracellular creatine by targeting the creatine transporter protects mice from acute myocardial infarction

PubMed Central

Lygate, Craig A.; Bohl, Steffen; ten Hove, Michiel; Faller, Kiterie M.E.; Ostrowski, Philip J.; Zervou, Sevasti; Medway, Debra J.; Aksentijevic, Dunja; Sebag-Montefiore, Liam; Wallis, Julie; Clarke, Kieran; Watkins, Hugh; Schneider, Jürgen E.; Neubauer, Stefan

2012-01-01

Aims Increasing energy storage capacity by elevating creatine and phosphocreatine (PCr) levels to increase ATP availability is an attractive concept for protecting against ischaemia and heart failure. However, testing this hypothesis has not been possible since oral creatine supplementation is ineffectual at elevating myocardial creatine levels. We therefore used mice overexpressing creatine transporter in the heart (CrT-OE) to test for the first time whether elevated creatine is beneficial in clinically relevant disease models of heart failure and ischaemia/reperfusion (I/R) injury. Methods and results CrT-OE mice were selected for left ventricular (LV) creatine 20–100% above wild-type values and subjected to acute and chronic coronary artery ligation. Increasing myocardial creatine up to 100% was not detrimental even in ageing CrT-OE. In chronic heart failure, creatine elevation was neither beneficial nor detrimental, with no effect on survival, LV remodelling or dysfunction. However, CrT-OE hearts were protected against I/R injury in vivo in a dose-dependent manner (average 27% less myocardial necrosis) and exhibited greatly improved functional recovery following ex vivo I/R (59% of baseline vs. 29%). Mechanisms contributing to ischaemic protection in CrT-OE hearts include elevated PCr and glycogen levels and improved energy reserve. Furthermore, creatine loading in HL-1 cells did not alter antioxidant defences, but delayed mitochondrial permeability transition pore opening in response to oxidative stress, suggesting an additional mechanism to prevent reperfusion injury. Conclusion Elevation of myocardial creatine by 20–100% reduced myocardial stunning and I/R injury via pleiotropic mechanisms, suggesting CrT activation as a novel, potentially translatable target for cardiac protection from ischaemia. PMID:22915766

Creatine metabolism: detection of creatine and guanidinoacetate in saliva of healthy subjects.

PubMed

Martínez, Lidia D; Bezard, Miriam; Brunotto, Mabel; Dodelson de Kremer, Raquel

2016-04-01

Creatine (Cr) plays an important role in storage and transmission of phosphate-bound energy. Cerebral creatine deficiency syndromes comprise three inherited defects in Cr biosynthesis and transport. The aim of this study was to investigate whether Cr and Guanidinoacetate (GAA) can be detected in saliva of healthy subjects and to establish the relationship between salivary and plasma levels of these molecules. An adapted gas chromatography (GC) method is described for the quantification of Cr and GAA biomarkers in saliva. Reference values were established for GAA and Cr in saliva. These values were age dependent (p= 0.001). No difference between genders was observed. We detected a difference between GAA and Cr concentrations in saliva and in plasma. The GC method for simultaneous determination of GAA and Cr in human saliva is fast, reliable, sensitive, non-invasive and precise to use as a biochemical approach in early detection of cerebral creatine deficiency syndromes. Sociedad Argentina de Investigación Odontológica.

Monitoring creatine and phosphocreatine by (13)C MR spectroscopic imaging during and after (13)C4 creatine loading: a feasibility study.

PubMed

Janssen, Barbara H; Lassche, Saskia; Hopman, Maria T; Wevers, Ron A; van Engelen, Baziel G M; Heerschap, Arend

2016-08-01

Creatine (Cr) supplementation to enhance muscle performance shows variable responses among individuals and different muscles. Direct monitoring of the supplied Cr in muscles would address these differences. In this feasibility study, we introduce in vivo 3D (13)C MR spectroscopic imaging (MRSI) of the leg with oral ingestion of (13)C4-creatine to observe simultaneously Cr and phosphocreatine (PCr) for assessing Cr uptake, turnover, and the ratio PCr over total Cr (TCr) in individual muscles. (13)C MRSI was performed of five muscles in the posterior thigh in seven subjects (two males and two females of ~20 years, one 82-year-old male, and two neuromuscular patients) with a (1)H/(13)C coil in a 3T MR system before, during and after intake of 15 % (13)C4-enriched Cr. Subjects ingested 20 g Cr/day for 4 days in four 5 g doses at equal time intervals. The PCr/TCr did not vary significantly during supplementation and was similar for all subjects and investigated muscles (average 0.71 ± 0.07), except for the adductor magnus (0.64 ± 0.03). The average Cr turnover rate, assessed in male muscles, was 2.1 ± 0.7 %/day. The linear uptake rates of Cr were variable between muscles, although not significantly different. This assessment was possible in all investigated muscles of young male volunteers, but less so in muscles of the other subjects due to lower signal-to-noise ratio. Improvements for future studies are discussed. In vivo (13)C MRSI after (13)C-Cr ingestion is demonstrated for longitudinal studies of Cr uptake, turnover, and PCr/TCr ratios of individual muscles in one exam.

Effect of low dose, short-term creatine supplementation on muscle power output in elite youth soccer players.

PubMed

Yáñez-Silva, Aquiles; Buzzachera, Cosme F; Piçarro, Ivan Da C; Januario, Renata S B; Ferreira, Luis H B; McAnulty, Steven R; Utter, Alan C; Souza-Junior, Tacito P

2017-01-01

To determine the effects of a low dose, short-term Creatine monohydrate (Cr) supplementation (0.03 g.kg.d -1 during 14 d) on muscle power output in elite youth soccer players. Using a two-group matched, double blind, placebo-controlled design, nineteen male soccer players (mean age = 17.0 ± 0.5 years) were randomly assigned to either Cr ( N  = 9) or placebo ( N  = 10) group. Before and after supplementation, participants performed a 30s Wingate Anaerobic Test (WAnT) to assess peak power output (PPO), mean power output (MPO), fatigue index (FI), and total work. There were significant increases in both PPO and MPO after the Cr supplementation period ( P  ≤ 0.05) but not the placebo period. There were also significant increases in total work, but not FI, after the Cr supplementation and placebo periods ( P  ≤ 0.05). Notably, there were differences in total work between the Cr and placebo groups after ( P  ≤ 0.05) but not before the 14 d supplementation period. There is substantial evidence to indicate that a low-dose, short-term oral Cr supplementation beneficially affected muscle power output in elite youth soccer players.

Creatine in the central nervous system: From magnetic resonance spectroscopy to creatine deficiencies.

PubMed

Rackayova, Veronika; Cudalbu, Cristina; Pouwels, Petra J W; Braissant, Olivier

2017-07-15

Creatine (Cr) is an important organic compound acting as intracellular high-energy phosphate shuttle and in energy storage. While located in most cells where it plays its main roles in energy metabolism and cytoprotection, Cr is highly concentrated in muscle and brain tissues, in which Cr also appears to act in osmoregulation and neurotransmission. This review discusses the basis of Cr metabolism, synthesis and transport within brain cells. The importance of Cr in brain function and the consequences of its impaired metabolism in primary and secondary Cr deficiencies are also discussed. Cr and phosphocreatine (PCr) in living systems can be well characterized using in vivo magnetic resonance spectroscopy (MRS). This review describes how 1 H MRS allows the measurement of Cr and PCr, and how 31 P MRS makes it possible to estimate the creatine kinase (CK) rate constant and so detect dynamic changes in the Cr/PCr/CK system. Absolute quantification by MRS using creatine as internal reference is also debated. The use of in vivo MRS to study brain Cr in a non-invasive way is presented, as well as its use in clinical and preclinical studies, including diagnosis and treatment follow-up in patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Disturbed energy metabolism and muscular dystrophy caused by pure creatine deficiency are reversible by creatine intake

PubMed Central

Nabuurs, C I; Choe, C U; Veltien, A; Kan, H E; van Loon, L J C; Rodenburg, R J T; Matschke, J; Wieringa, B; Kemp, G J; Isbrandt, D; Heerschap, A

2013-01-01

Creatine (Cr) plays an important role in muscle energy homeostasis by its participation in the ATP–phosphocreatine phosphoryl exchange reaction mediated by creatine kinase. Given that the consequences of Cr depletion are incompletely understood, we assessed the morphological, metabolic and functional consequences of systemic depletion on skeletal muscle in a mouse model with deficiency of l-arginine:glycine amidinotransferase (AGAT−/−), which catalyses the first step of Cr biosynthesis. In vivo magnetic resonance spectroscopy showed a near-complete absence of Cr and phosphocreatine in resting hindlimb muscle of AGAT−/− mice. Compared with wild-type, the inorganic phosphate/β-ATP ratio was increased fourfold, while ATP levels were reduced by nearly half. Activities of proton-pumping respiratory chain enzymes were reduced, whereas F1F0-ATPase activity and overall mitochondrial content were increased. The Cr-deficient AGAT−/− mice had a reduced grip strength and suffered from severe muscle atrophy. Electron microscopy revealed increased amounts of intramyocellular lipid droplets and crystal formation within mitochondria of AGAT−/− muscle fibres. Ischaemia resulted in exacerbation of the decrease of pH and increased glycolytic ATP synthesis. Oral Cr administration led to rapid accumulation in skeletal muscle (faster than in brain) and reversed all the muscle abnormalities, revealing that the condition of the AGAT−/− mice can be switched between Cr deficient and normal simply by dietary manipulation. Systemic creatine depletion results in mitochondrial dysfunction and intracellular energy deficiency, as well as structural and physiological abnormalities. The consequences of AGAT deficiency are more pronounced than those of muscle-specific creatine kinase deficiency, which suggests a multifaceted involvement of creatine in muscle energy homeostasis in addition to its role in the phosphocreatine–creatine kinase system. PMID:23129796

[Chemical Exchange Saturation Transfer Imaging of Creatine Metabolites: a 3.0 T MRI Pilot].

PubMed

Guo, Ying-kun; Li, Zhen-lin; Rong, Yu; Xia, Chun-chao; Zhang, Li-zhi; Peng, Wan-ling; Liu, Xi; Xu, Hua-yan; Zhang, Ti-jiang; Zuo, Pan-li; Schmitt, Benjamin

2016-03-01

To determine the feasibility of using chemical exchange saturation transfer (CEST) imaging to measure creatine (Cr) metabolites with 3.0 T MR. Phantoms containing different concentrations of Cr under various pH conditions were studied with CEST sequence on 3.0 T MR imaging. CEST effect and Z spectra were analyzed. Cr exhibited significant CEST effect (± 1.8 ppm, F = 99.08, P < 0.001) on 3.0 T MR imaging, and positive correlation was found between the signal intensity and concentration of Cr (r = 0.963, P < 0.001). The CEST effect showed pH dependency of Cr (r = 0.41, P = 0.035). Creatine CEST imaging can be performed on 3.0 T MR imaging. Creatine concentrations and pH influence CEST effect.

Screening for X-linked creatine transporter (SLC6A8) deficiency via simultaneous determination of urinary creatine to creatinine ratio by tandem mass-spectrometry.

PubMed

Mercimek-Mahmutoglu, Saadet; Muehl, Adolf; Salomons, Gajja S; Neophytou, Birgit; Moeslinger, Dorothea; Struys, Eduard; Bodamer, Olaf A; Jakobs, Cornelis; Stockler-Ipsiroglu, Sylvia

2009-04-01

High urinary creatine to creatinine ratio (U-CrCrtR) is a potential diagnostic marker of X-linked creatine transporter (SLC6A8) deficiency. We developed a tandem mass-spectrometry method to simultaneously determine urinary creatine and creatinine in 975 individuals (0-18 years). U-CrCrtR increased up to 8 years and decreased thereafter. U-CrCrtR was 2.29 and 2.12 (99th percentile: 1.87) in two males with subsequently confirmed SLC6A8 mutations. The frequency of SLC6A8 deficiency was 2.3% in 157 males at risk.

Combined creatine and protein supplementation in conjunction with resistance training promotes muscle GLUT-4 content and glucose tolerance in humans.

PubMed

Derave, Wim; Eijnde, Bert O; Verbessem, Patricia; Ramaekers, Monique; Van Leemputte, Mark; Richter, Erik A; Hespel, Peter

2003-05-01

The present study was undertaken to explore the effects of creatine and creatine plus protein supplementation on GLUT-4 and glycogen content of human skeletal muscle. This was investigated in muscles undergoing a decrease (immobilization) and subsequent increase (resistance training) in activity level, compared with muscles with unaltered activity pattern. A double-blind, placebo-controlled trial was performed by 33 young healthy subjects. The subjects' right legs were immobilized with a cast for 2 wk, followed by a 6-wk resistance training program for the right knee extensor muscles. The participants were supplemented throughout the study with either placebo (Pl group) or creatine (Cr group) or with creatine during immobilization and creatine plus protein during retraining (Cr+P group). Needle biopsies were bilaterally taken from the vastus lateralis. GLUT-4 protein expression was reduced by the immobilization in all groups (P < 0.05). During retraining, GLUT-4 content increased (P < 0.05) in both Cr (+24%) and Cr+P (+33%), which resulted in higher posttraining GLUT-4 expression compared with Pl (P < 0.05). Compared with Pl, muscle glycogen content was higher (P < 0.05) in the trained leg in both Cr and Cr+P. Supplements had no effect on GLUT-4 expression or glycogen content in contralateral control legs. Area under the glucose curve during the oral glucose tolerance test was decreased from 232 +/- 23 mmol. l(-1). min(-1) at baseline to 170 +/- 23 mmol. l(-1). min(-1) at the end of the retraining period in Cr+P (P < 0.05), but it did not change in Cr or Pl. We conclude that creatine intake stimulates GLUT-4 and glycogen content in human muscle only when combined with changes in habitual activity level. Furthermore, combined protein and creatine supplementation improved oral glucose tolerance, which is supposedly unrelated to the changes in muscle GLUT-4 expression.

Effects of creatine supplementation along with resistance training on urinary formaldehyde and serum enzymes in wrestlers.

PubMed

Nasseri, Azadeh; Jafari, Afshar

2016-04-01

Formaldehyde is a cytotoxic agent produced from creatine through a metabolic pathway, and in this regard, it has been claimed that creatine supplementation could be cytotoxic. Even though the cytotoxic effects of creatine supplementation have been widely studied, yet little is known about how resistance training can alter these toxic effects. This study aimed to determine the effects of short-term creatine supplementation plus resistance training on the level of urinary formaldehyde and concentrations of serum enzymes in young male wrestlers. In a double-blind design twenty-one subjects were randomized into creatine supplementation (Cr), creatine supplementation plus resistance training (Cr + T) and placebo plus resistance training (Pl + T) groups. Participants ingested creatine (0.3 g/kg/day) or placebo for 7 days. The training protocol consisted of 3 sessions in one week, each session including three sets of 6-9 repetitions at 80-85% of one-repetition maximum for whole-body exercise. Urine and blood samples were collected at baseline and at the end of the supplementation. Creatine supplementation significantly increased the excretion rate of urinary formaldehyde in the Cr and Cr + T groups by 63.4% and 30.4%, respectively (P<0.05), indicating that resistance training could partially lower this rate by 17.7%. No significant differences were detected in the levels of serum enzymes across time and groups (P>0.05). These findings indicate that resistance training may lower the increase of urinary formaldehyde excretion induced by creatine supplementation, suggesting that creatine consumption could be relatively less toxic when combined with resistance training.

In ovo feeding of creatine pyruvate alters energy reserves, satellite cell mitotic activity and myogenic gene expression of breast muscle in embryos and neonatal broilers.

PubMed

Zhao, M M; Gao, T; Zhang, L; Li, J L; Lv, P A; Yu, L L; Gao, F; Zhou, G H

2017-09-01

We investigated the effects of in ovo feeding (IOF) of creatine pyruvate (CrPyr) on energy reserves, satellite cell mitotic activity (SCMA) and myogenic gene expression in breast muscle of embryos and neonatal broilers. A total of 960 eggs were randomly allocated into three treatments: 1) non-injected control group, 2) saline group injected with 0.6 mL of physiological saline (0.75%), and 3) CrPyr group injected with 0.6 mL of physiological saline (0.75%) containing 12 mg CrPyr/egg at 17.5 d of incubation. After hatching, a total of 120 male chicks were randomly assigned to each treatment group, with eight replicate sets per group. Selected chicks had body BW close to the average of their pooled group. Our results showed that the total and relative breast muscle weights of broilers subjected to CrPyr treatment were higher than those in the control and saline groups on 19 d of incubation (19 E), the day of hatch, 3 and 7 d post-hatch (P < 0.05). The myofiber diameter and cross-sectional area of individuals in the CrPyr group were higher than those in other treatments on 3 and 7 d post-hatch (P < 0.05). Moreover, IOF of CrPyr increased (P < 0.05) creatine concentrations on 19 E, the day of hatch and 3 d post-hatch, the same treatment increased phosphocreatine concentrations on 19 E. Broilers in the CrPyr group showed higher expression of myogenic differentiation 1 (MyoD) (P < 0.05), myogenin and paired box 7 (Pax7), as well as higher index of SCMA on 3 d post-hatch. However, myostatin mRNA expression in CrPyr-treated broilers was down-regulated on 3 d post-hatch (P < 0.05). These results indicated that IOF of CrPyr increased energy reserves of embryos and SCMA of broilers on 3 d post-hatch, which led to enhanced muscle growth in the late embryos and neonatal broilers. Additionally, IOF of CrPyr increased the activity of satellite cells possibly through up-regulating MyoD, myogenin, and Pax7 mRNA expression and down-regulating myostatin mRNA expression. © 2017 Poultry Science Association Inc.

A simple screening method using ion chromatography for the diagnosis of cerebral creatine deficiency syndromes.

PubMed

Wada, Takahito; Shimbo, Hiroko; Osaka, Hitoshi

2012-08-01

Cerebral creatine deficiency syndromes (CCDS) are caused by genetic defects in L-arginine:glycine amidinotransferase, guanidinoacetate methyltransferase or creatine transporter 1. CCDS are characterized by abnormal concentrations of urinary creatine (CR), guanidinoacetic acid (GA), or creatinine (CN). In this study, we describe a simple HPLC method to determine the concentrations of CR, GA, and CN using a weak-acid ion chromatography column with a UV detector without any derivatization. CR, GA, and CN were separated clearly with the retention times (mean ± SD, n = 3) of 5.54 ± 0.0035 min for CR, 6.41 ± 0.0079 min for GA, and 13.53 ± 0.046 min for CN. This new method should provide a simple screening test for the diagnosis of CCDS.

Effects of creatine supplementation associated with resistance training on oxidative stress in different tissues of rats

PubMed Central

2014-01-01

Background Creatine supplementation is known to exert an effect by increasing strength in high intensity and short duration exercises. There is a hypothesis which suggests that creatine supplementation may provide antioxidant activity by scavenging Reactive Oxygen Species. However, the antioxidant effect of creatine supplementation associated with resistance training has not yet been described in the literature. Therefore, we investigated the effect of creatine monohydrate supplementation associated with resistance training over maximum strength gain and oxidative stress in rats. Methods Forty male Wistar rats (250-300 g, 90 days old) were randomly allocated into 4 groups: Sedentary (SED, n = 10), Sedentary + Creatine (SED-Cr, n = 10), Resistance Training (RT, n = 10) and Resistance Training + Creatine (RT-Cr, n = 10). Trained animals were submitted to the RT protocol (4 series of 10–12 repetitions, 90 second interval, 4 times per week, 65% to 75% of 1MR, for 8 weeks). Results In this study, greater strength gain was observed in the SED-Cr, RT and RT-Cr groups compared to the SED group (P < 0.001). The RT-Cr group showed a higher maximum strength gain when compared to other groups (P < 0.001). Creatine supplementation associated with resistance training was able to reduce lipoperoxidation in the plasma (P < 0.05), the heart (P < 0.05), the liver (P < 0.05) and the gastrocnemius (P < 0.05) when compared to control groups. However, the supplementation had no influence on catalase activity (CAT) in the analyzed organs. Only in the heart was the CAT activity higher in the RT-Cr group (P < 0.05). The activity of superoxide dismutase (SOD) was lower in all of the analyzed organs in the SED-Cr group (P < 0.05), while SOD activity was lower in the trained group and sedentary supplemented group (P < 0.05). Conclusions Creatine was shown to be an effective non-enzymatic antioxidant with supplementation alone and also when it was associated with resistance training in rats. PMID:24655435

Dorsolateral prefrontal cortex N-acetylaspartate/total creatine (NAA/tCr) loss in male recreational cannabis users.

PubMed

Hermann, Derik; Sartorius, Alexander; Welzel, Helga; Walter, Sigrid; Skopp, Gisela; Ende, Gabriele; Mann, Karl

2007-06-01

Cannabinoids present neurotoxic and neuroprotective properties in in vitro studies, inconsistent alterations in human neuroimaging studies, neuropsychological deficits, and an increased risk for psychotic episodes. Proton magnetic resonance spectroscopy ((1)H-MRS), neuropsychological testing, and hair analysis for cannabinoids was performed in 13 male nontreatment-seeking recreational cannabis users and 13 male control subjects. A significantly diminished N-acetylaspartate/total creatine (NAA/tCr) ratio in the dorsolateral prefrontal cortex (DLPFC) was observed in cannabis users (p = .0003). The NAA/tCr in the putamen/globus pallidum region correlated significantly with cannabidiol (R(2) = .66, p = .004). Results of the Wisconsin Card Sorting test, Trail making Test, and D2 test for attention were influenced by cannabinoids. Chronic recreational cannabis use is associated with an indication of diminished neuronal and axonal integrity in the DLPFC in this study. As chronic cannabis use is a risk factor for psychosis, these results are interesting because diminished NAA/tCr ratios in the DLPFC and neuropsychological deficits were also reported in schizophrenia. The strong positive correlation of NAA/tCr and cannabidiol in the putamen/globus pallidum is in line with neuroprotective properties of cannabidiol, which were also observed in in vitro model studies of Parkinson's disease.

The effects of creatine pyruvate and creatine citrate on performance during high intensity exercise

PubMed Central

Jäger, Ralf; Metzger, Jan; Lautmann, Karin; Shushakov, Vladimir; Purpura, Martin; Geiss, Kurt-Reiner; Maassen, Norbert

2008-01-01

Background A double-blind, placebo-controlled, randomized study was performed to evaluate the effect of oral creatine pyruvate (Cr-Pyr) and creatine citrate (Cr-Cit) supplementation on exercise performance in healthy young athletes. Methods Performance during intermittent handgrip exercise of maximal intensity was evaluated before (pretest) and after (posttest) 28 days of Cr-Pyr (5 g/d, n = 16), Cr-Cit (5 g/d, n = 16) or placebo (pla, 5 g/d, n = 17) intake. Subjects performed ten 15-sec exercise intervals, each followed by 45 sec rest periods. Results Cr-Pyr (p < 0.001) and Cr-Cit (p < 0.01) significantly increased mean power over all intervals. Cr-Cit increased force during the first and second interval (p < 0.01) compared to placebo. The effect of Cr-Cit on force decreased over time and the improvement was not significant at the sixth and ninth interval, whereas Cr-Pyr significantly increased force during all intervals (p < 0.001). Cr-Pyr (p < 0.001) and Cr-Cit (p < 0.01) resulted in an increase in contraction velocity, whereas only Cr-Pyr intake significantly (p < 0.01) increased relaxation velocity. Oxygen consumption measured during rest periods significantly increased with Cr-Pyr (p < 0.05), whereas Cr-Cit and placebo intake did not result in significant improvements. Conclusion It is concluded that four weeks of Cr-Pyr and Cr-Cit intake significantly improves performance during intermittent handgrip exercise of maximal intensity and that Cr-Pyr might benefit endurance, due to enhanced activity of the aerobic metabolism. PMID:18269769

The Effects of Creatine Supplementation on Exercise-Induced Muscle Damage.

ERIC Educational Resources Information Center

Rawson, Eric S.; Gunn, Bridget; Clarkson, Priscilla M.

2001-01-01

Investigated the effects of oral creatine (Cr) supplementation on markers of exercise-induced muscle damage following high-force eccentric exercise in men randomly administered Cr or placebo. Results indicated that 5 days of Cr supplementation did not reduce indirect makers of muscle damage or enhance recovery from high-force eccentric exercise.…

[Simultaneous determination of guanidinoacetate, creatine and creatinine by liquid chromatography-tandem mass spectrometry: a diagnostic tool for creatine deficiency syndromes in body fluids and a perspective use on cultured fibroblasts].

PubMed

Van Noolen, Laetitia; Monneret, Denis; Ducros, Véronique; Corne, Christelle; Lunardi, Joël; Faure, Patrice

2013-01-01

Guanidinoacetate (GAA) and creatine (Cr) are creatine deficiency syndromes (CDS) biochemical markers. We describe a liquid chromatography - tandem mass spectrometry method (LC/MSMS) performing simultaneous analysis of GAA, Cr and creatinine (Crn). Study of Cr uptake by fibroblasts for Cr transporter defect diagnosis is also assessed. The three butylated compounds were separated by liquid chromatography and MSMS quantification was achieved by isotopic dilution with electrospray positive ion mode. Linearity was demonstrated from 0 to 600, 675 and 4500 μmol/L and limit of quantification was 0.1, 0.04 and 0.9 μmol/L for GAA, Cr, and Crn respectively. Intra- and inter-assay precision for each analyte was better than 11%, and standard recoveries ranged from 83 to 109%. Reference values in cerebrospinal fluid samples for subjects ≥14 years were also established for GAA and Cr. Five fibroblast cell lines were used for Cr uptake study. Cr uptake by fibroblasts increased with the Cr media concentrations and was significantly inhibited by 3-guanidinopropionate (500 μmol/L), a Cr transporter inhibitor (96h incubation, [Cr media] = 25 μmol/L, p<0.05). A reliable LC/MSMS method for the diagnosis of CDS was developed in different biological fluids. Finally, results of the Cr uptake study reinforce the interest of this technique to diagnose Cr transporter deficiencies.

Effect of creatine, creatinine, and creatine ethyl ester on TLR expression in macrophages.

PubMed

Leland, Korey M; McDonald, Thomas L; Drescher, Kristen M

2011-09-01

Despite the widespread availability and use of dietary supplements, minimal work has been performed to assess the potential dangers many of these supplements may have on the host's well-being, in particular the host's ability to respond to infection. One supplement extensively used by both adolescents and adults is creatine. Using Real-time PCR, we examined the impact of short-term exposure of a mouse macrophage cell line (RAW 264.7 cells) to two readily available forms of creatine used in supplements--creatine monohydrate (CR) and creatine ethyl ester (CEE) as well as the end product of creatine metabolism, creatinine (CRN), on expression of toll-like receptor-2 (TLR-2), TLR-3, TLR-4, and TLR-7. CR down-regulated TLR-2, TLR-3, TLR-4 and TLR-7 mRNA levels in RAW cells. Similar results were observed following exposure of RAW cells to CRN. Conversely CEE appears to possess immunostimulatory properties and increases expression of TLR-2, TLR-3, TLR-4, and TLR-7 in RAW cells. These data are supported by immunostaining using antibodies specific for the individual TLRs before and after exposure of RAW cells to CR, CRN, or CEE. To extend these findings, we isolated murine splenocytes and exposed the cells to CR, CEE, or CRN for 24 hours and performed immunofluorescent staining for TLR-2, TLR-3, TLR-4 and TLR-7. The results obtained from this study with primary splenocytes were consistent with the studies using RAW cells. Together, these data suggest that creatine and creatine derivatives may impact the ability of immune cells to sense a wide array of viral and bacterial pathogens. Of great interest, CRN--largely considered to be a waste product of the argenine biosynthesis pathway may also have immunosuppressive properties similar to those of CR. Copyright © 2011 Elsevier B.V. All rights reserved.

Effect of creatine, creatinine, and creatine ethyl ester on TLR expression in macrophages

PubMed Central

Leland, Korey M.; McDonald, Thomas L.; Drescher, Kristen M.

2011-01-01

Despite the widespread availability and use of dietary supplements, minimal work has been performed to assess the potential dangers many of these supplements may have on the host’s well-being, in particular the host’s ability to respond to infection. One supplement extensively used by both adolescents and adults is creatine. Using Real-time PCR, we examined the impact of short-term exposure of a mouse macrophage cell line (RAW 264.7 cells) to two readily available forms of creatine used in supplements – creatine monohydrate (CR) and creatine ethyl ester (CEE) as well as the end product of creatine metabolism, creatinine (CRN), on expression of toll-like receptor-2 (TLR-2), TLR-3, TLR-4, and TLR-7. CR down-regulated TLR-2, TLR-3, TLR-4 and TLR-7 mRNA levels in RAW cells. Similar results were observed following exposure of RAW cells to CRN. Conversely CEE appears to possess immunostimulatory properties and increases expression of TLR-2, TLR-3, TLR-4, and TLR-7 in RAW cells. These data are supported by immunostaining using antibodies specific for the individual TLRs before and after exposure of RAW cells to CR, CRN, or CEE. To extend these findings, we isolated murine splenocytes and exposed the cells to CR, CEE, or CRN for 24 hours and performed immunofluorescent staining for TLR-2, TLR-3, TLR-4 and TLR-7. The results obtained from this study with primary splenocytes were consistent with the studies using RAW cells. Together, these data suggest that creatine and creatine derivatives may impact the ability of immune cells to sense a wide array of viral and bacterial pathogens. Of great interest, CRN - largely considered to be a waste product of the argenine biosynthesis pathway may also have immunosuppressive properties similar to those of CR. PMID:21575742

The influence of high fat diets with different ketogenic ratios on the hippocampal accumulation of creatine - FTIR microspectroscopy study

NASA Astrophysics Data System (ADS)

Skoczen, A.; Setkowicz, Z.; Janeczko, K.; Sandt, Ch.; Borondics, F.; Chwiej, J.

2017-09-01

The main purpose of this study was the determination and comparison of anomalies in creatine (Cr) accumulation occurring within CA3 and DG areas of hippocampal formation as a result of two high-fat, carbohydrate-restricted ketogenic diets (KD) with different ketogenic ratio (KR). To reach this goal, Fourier transformed infrared microspectroscopy with synchrotron radiation source (SRFTIR microspectroscopy) was applied for chemical mapping of creatine absorption bands, occurring around 1304, 1398 and 2800 cm- 1. The samples were taken from three groups of experimental animals: control group (N) fed with standard laboratory diet, KD1 and KD2 groups fed with high-fat diets with KR 5:1 and 9:1 respectively. Additionally, the possible influence on the phosphocreatine (PhCr, the high energetic form of creatine) content was evaluated by comparative analysis of chemical maps obtained for creatine and for compounds containing phosphate groups which manifest in the spectra at the wavenumbers of around 1240 and 1080 cm- 1. Our results showed that KD2 strongly modifies the frequency of Cr inclusions in both analyzed hippocampal areas. Statistical analysis, performed with Mann-Whitney U test revealed increased accumulation of Cr within CA3 and DG areas of KD2 fed rats compared to both normal rats and KD1 experimental group. Moreover, KD2 diet may modify the frequency of PhCr deposits as well as the PhCr to Cr ratio.

Early Support of Intracranial Perfusion

DTIC Science & Technology

2010-10-01

indicated a time evolution of TBI. Schuhmann et al showed that total creatine (tCr), N-acetylaspartate (NAA), glutamate (Glu), and choline (Cho...differences were found in glutamine, myo- inositol , and taurine concentrations among the 30 three time points in either the pericontusional voxel

Effects of creatine supplementation on oxidative stress profile of athletes

PubMed Central

2012-01-01

Background Creatine (Cr) supplementation has been widely used among athletes and physically active individuals. Secondary to its performance-enhancing ability, an increase in oxidative stress may occur, thus prompting concern about its use. The purpose of this study is to investigate the effects of Cr monohydrate supplementation and resistance training on muscle strength and oxidative stress profile in healthy athletes. Methods A randomized, double-blind, placebo-controlled method was used to assess twenty-six male elite Brazilian handball players divided into 3 groups: Cr monohydrate supplemented group (GC, N = 9), placebo group (GP, N = 9), no treatment group (COT, N = 8) for 32 days. All subjects underwent a resistance training program. Blood samples were drawn on 0 and 32 days post Cr supplementation to analyze the oxidative stress markers, thiobarbituric acid reactive species (TBARS), total antioxidant status (TAS), and uric acid. Creatine phosphokinase, urea, and creatinine were also analyzed, as well. Fitness tests (1 repetition maximum - 1RM and muscle endurance) were performed on the bench press. Body weight and height, body fat percentage (by measuring skin folds) and upper muscular area were also evaluated. Statistical analysis was performed using ANOVA. Results Only GC group showed increase in 1RM (54 ± 9 vs. 63 ± 10 kg; p = 0.0356) and uric acid (4.6 ± 1.0 vs. 7.4 ± 1.6 mg/dl; p = 0.025), with a decrease in TAS (1.11 ± 0.34 vs. 0.60 ± 0.19 mmol/l; p = 0.001). No differences (pre- vs. post-training) in TBARS, creatine phosphokinase, urea, creatinine, body weight and height, body fat percentage, or upper muscular area were observed in any group. When compared to COT, GC group showed greater decrease in TAS (−0.51 ± 0.36 vs. -0.02 ± 0.50 mmol/l; p = 0.0268), higher increase in 1RM (8.30 ± 2.26 vs. 5.29 ± 2.36 kg; p = 0.0209) and uric acid (2.77 ± 1.70 vs. 1.00 ± 1.03 mg/dl; p = 0.0276). Conclusion We conclude that Cr monohydrate supplementation associated with a specific resistance program promoted a meaningful increase in muscle strength without inducing changes in body composition. The observed significant increase in uric acid and the decrease in TAS suggest that creatine supplementation, despite promoting acute effects on muscle strength improvement, might induce oxidative stress and decreases total antioxidant status of subjects. PMID:23259853

Echo-Planar Imaging-Based, J-Resolved Spectroscopic Imaging for Improved Metabolite Detection in Prostate Cancer

DTIC Science & Technology

2014-10-01

Imaging (EP-JRESI); Citrate, Choline, Creatine , Spermine, 3Tesla MRI scanner, Endo-rectal MR coil, WET Water Suppression, prostate cancer (PCa...spectroscopic imaging are due to the overlap of metabolite resonances, quantifying few metabolites only (citrate (Cit), choline (Ch), creatine (Cr...concentrations of citrate (Cit), creatine (Cr), choline (Ch) and polyamines that are used to detect and diagnose PCa (2). The challenging task in 1D MRS

Myocardial Creatine Levels Do Not Influence Response to Acute Oxidative Stress in Isolated Perfused Heart

PubMed Central

Aksentijević, Dunja; Zervou, Sevasti; Faller, Kiterie M. E.; McAndrew, Debra J.; Schneider, Jurgen E.; Neubauer, Stefan; Lygate, Craig A.

2014-01-01

Background Multiple studies suggest creatine mediates anti-oxidant activity in addition to its established role in cellular energy metabolism. The functional significance for the heart has yet to be established, but antioxidant activity could contribute to the cardioprotective effect of creatine in ischaemia/reperfusion injury. Objectives To determine whether intracellular creatine levels influence responses to acute reactive oxygen species (ROS) exposure in the intact beating heart. We hypothesised that mice with elevated creatine due to over-expression of the creatine transporter (CrT-OE) would be relatively protected, while mice with creatine-deficiency (GAMT KO) would fare worse. Methods and Results CrT-OE mice were pre-selected for creatine levels 20–100% above wild-type using in vivo 1H–MRS. Hearts were perfused in isovolumic Langendorff mode and cardiac function monitored throughout. After 20 min equilibration, hearts were perfused with either H2O2 0.5 µM (30 min), or the anti-neoplastic drug doxorubicin 15 µM (100 min). Protein carbonylation, creatine kinase isoenzyme activities and phospho-PKCδ expression were quantified in perfused hearts as markers of oxidative damage and apoptotic signalling. Wild-type hearts responded to ROS challenge with a profound decline in contractile function that was ameliorated by co-administration of catalase or dexrazoxane as positive controls. In contrast, the functional deterioration in CrT-OE and GAMT KO hearts was indistinguishable from wild-type controls, as was the extent of oxidative damage and apoptosis. Exogenous creatine supplementation also failed to protect hearts from doxorubicin-induced dysfunction. Conclusions Intracellular creatine levels do not influence the response to acute ROS challenge in the intact beating heart, arguing against creatine exerting (patho-)physiologically relevant anti-oxidant activity. PMID:25272153

Recreational alcohol use induces changes in the concentrations of choline-containing compounds and total creatine in the brain: a (1)H MRS study of healthy subjects.

PubMed

Tunc-Skarka, Nuran; Weber-Fahr, Wolfgang; Ende, Gabriele

2015-10-01

It has previously been reported that even social alcohol consumption affects the magnetic resonance spectroscopy (MRS) signals of choline-containing compounds (tCho). The purpose of this study was to investigate whether the consumption of alcohol affects the concentrations of the metabolites tCho, N-acetylaspartate, creatine, or myo-inositol and/or their T 2 relaxation times. (1)H MR spectra were obtained at 3 T from a frontal white matter voxel of 25 healthy subjects with social alcohol consumption (between 0 and 25.9 g/day). Absolute brain metabolite concentrations and T 2 relaxation times of metabolites were examined via MRS measurements at different echo times. Metabolite concentrations and their T 2 relaxation times were correlated with subjects' alcohol consumption, controlling for age. We observed positive correlations of absolute tCho and phosphocreatine and creatine (tCr) concentrations with alcohol consumption but no correlation between any metabolite T 2 relaxation time and alcohol consumption. This study shows that even social alcohol consumption affects the concentrations of tCho and tCr in cerebral white matter. Future studies assessing brain tCho and tCr levels should control for the confounding factor alcohol consumption.

Chronic Dietary Creatine Enhances Hippocampal-Dependent Spatial Memory, Bioenergetics, and Levels of Plasticity-Related Proteins Associated with NF-?B

ERIC Educational Resources Information Center

Snow, Wanda M.; Cadonic, Chris; Cortes-Perez, Claudia; Chowdhury, Subir K. Roy; Djordjevic, Jelena; Thomson, Ella; Bernstein, Michael J.; Suh, Miyoung; Fernyhough, Paul; Albensi, Benedict C.

2018-01-01

The brain has a high demand for energy, of which creatine (Cr) is an important regulator. Studies document neurocognitive benefits of oral Cr in mammals, yet little is known regarding their physiological basis. This study investigated the effects of Cr supplementation (3%, w/w) on hippocampal function in male C57BL/6 mice, including spatial…

Creatine Loading, Resistance Exercise Performance, and Muscle Mechanics.

ERIC Educational Resources Information Center

Stevenson, Scott W.; Dudley, Gary A.

2001-01-01

Examined whether creatine (CR) monohydrate loading would alter resistance exercise performance, isometric strength, or in vivo contractile properties of the quadriceps femoris muscle compared with placebo loading in resistance-trained athletes. Overall, CR loading did not provide an ergogenic benefit for the unilateral dynamic knee extension…

Proteomic and metabolomic changes driven by elevating myocardial creatine suggest novel metabolic feedback mechanisms.

PubMed

Zervou, Sevasti; Yin, Xiaoke; Nabeebaccus, Adam A; O'Brien, Brett A; Cross, Rebecca L; McAndrew, Debra J; Atkinson, R Andrew; Eykyn, Thomas R; Mayr, Manuel; Neubauer, Stefan; Lygate, Craig A

2016-08-01

Mice over-expressing the creatine transporter have elevated myocardial creatine levels [Cr] and are protected against ischaemia/reperfusion injury via improved energy reserve. However, mice with very high [Cr] develop cardiac hypertrophy and dysfunction. To investigate these contrasting effects, we applied a non-biased hypothesis-generating approach to quantify global protein and metabolite changes in the LV of mice stratified for [Cr] levels: wildtype, moderately elevated, and high [Cr] (65-85; 100-135; 160-250 nmol/mg protein, respectively). Male mice received an echocardiogram at 7 weeks of age with tissue harvested at 8 weeks. RV was used for [Cr] quantification by HPLC to select LV tissue for subsequent analysis. Two-dimensional difference in-gel electrophoresis identified differentially expressed proteins, which were manually picked and trypsin digested for nano-LC-MS/MS. Principal component analysis (PCA) showed efficient group separation (ANOVA P ≤ 0.05) and peptide sequences were identified by mouse database (UniProt 201203) using Mascot. A total of 27 unique proteins were found to be differentially expressed between normal and high [Cr], with proteins showing [Cr]-dependent differential expression, chosen for confirmation, e.g. α-crystallin B, a heat shock protein implicated in cardio-protection and myozenin-2, which could contribute to the hypertrophic phenotype. Nuclear magnetic resonance (¹H-NMR at 700 MHz) identified multiple strong correlations between [Cr] and key cardiac metabolites. For example, positive correlations with α-glucose (r² = 0.45; P = 0.002), acetyl-carnitine (r² = 0.50; P = 0.001), glutamine (r² = 0.59; P = 0.0002); and negative correlations with taurine (r² = 0.74; P < 0.0001), fumarate (r² = 0.45; P = 0.003), aspartate (r² = 0.59; P = 0.0002), alanine (r² = 0.66; P < 0.0001) and phosphocholine (r² = 0.60; P = 0.0002). These findings suggest wide-ranging and hitherto unexpected adaptations in substrate utilisation and energy metabolism with a general pattern of impaired energy generating pathways in mice with very high creatine levels.

NMR studies on /sup 15/N-labeled creatine (CR), creatinine (CRN), phosphocreatine (PCR), and phosphocreatinine (PCRN), and on barriers to rotation in creatine kinase-bound creatine in the enzymatic reaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kenyon, G.L.; Reddick, R.E.

1986-05-01

Recently, the authors have synthesized /sup 15/N-2-Cr, /sup 15/N-3-Crn, /sup 15/N-2-Crn, /sup 15/N-3-PCrn, /sup 15/N-3-PCr, and /sup 15/N-2-PCr. /sup 1/H, /sup 15/N, /sup 31/P NMR data show that Crn protonates exclusively at the non-methylated ring nitrogen, confirm that PCrn is phosphorylated at the exocyclic nitrogen, and demonstrate that the /sup 31/P-/sup 15/N one-bond coupling constant in /sup 15/N-3-PCr is 18 Hz, not 3 Hz as previously reported by Brindle, K.M., Porteous, R. and Radda, G.K.. The authors have found that creatine kinase is capable of catalyzing the /sup 14/N//sup 15/N positional isotope exchange of 3-/sup 15/N-PCr in the presence ofmore » MgADP, but not in its absence. Further, the exchange does not take place when labeled PCr is resynthesized exclusively from the ternary complex E X Cr X MgATP as opposed to either E X Cr or free Cr. This suggests that the enzyme both imparts an additional rotational barrier to creatine in the complex and catalyzes the transfer of phosphoryl group with essentially complete regiospecificity.« less

Intradialytic creatine supplementation: A scientific rationale for improving the health and quality of life of dialysis patients.

PubMed

Wallimann, Theo; Riek, Uwe; Möddel, Michael

2017-02-01

The CK/PCr-system, with creatine (Cr) as an energy precursor, plays a crucial role in cellular physiology. In the kidney, as in other organs and cells with high and fluctuating energy requirements, energy-charged phospho-creatine (PCr) acts as an immediate high-energy source and energy buffer, and as an intracellular energy transport vehicle. A maximally filled total Cr (Cr plus PCr) pool is a prerequisite for optimal functioning of the body and its organs, and health. Skeletal- and cardiac muscles of dialysis patients with chronic kidney disease (CKD) are depleted of Cr in parallel with the duration of dialysis. The accompanying accumulation of cellular damage seen in CKD patients lead to a deterioration of musculo-skeletal and neurological functioning and poor quality of life (QOL). Therefore, to counteract Cr depletion, it is proposed to supplement CKD patients with Cr. The anticipated benefits include previously documented improvements in the musculo-skeletal system, brain and peripheral nervous system, as well as improvements in the common comorbidities of CKD patients (see below). Thus, with a relatively simple, safe and inexpensive Cr supplementation marked improvements in quality of life (QOL) and life span are likely reached. To avoid Cr and fluid overload by oral Cr administration, we propose intradialytic Cr supplementation, whereby a relatively small amount of Cr is added to the large volume of dialysis solution to a final concentration of 1-10mM. From there, Cr enters the patient's circulation by back diffusion during dialysis. Because of the high affinity of the Cr transporter (CRT) for Cr affinity for Cr (Vmax of CRT for Cr=20-40μM Cr), Cr is actively transported from the blood stream into the target cells and organs, including skeletal and cardiac muscle, brain, proximal tubules of kidney epithelial cells, neurons, and leukocytes and erythrocytes, which all express CRT and depend on the CK/PCr system. By this intradialytic strategy, only as much Cr is taken up by the body as is needed to fill the tissue Cr pools and no excess Cr has to be excreted, as is the case with oral Cr. Because aqueous solutions of Cr are not very stable, Cr must be added immediately before dialysis either as solid Cr powder or from a frozen Cr stock solution to the dialysate, or alternatively, Cr could become an additional component of a novel dry dialysate mixture in a cartridge device. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Effect of Exercise on the Creatine Resonances in 1H MR Spectra of Human Skeletal Muscle

NASA Astrophysics Data System (ADS)

Kreis, R.; Jung, B.; Slotboom, J.; Felblinger, J.; Boesch, C.

1999-04-01

1H MR spectra of human muscles were recorded before, during, and after fatiguing exercise. In contrast to expectations, it was found that the spectral contributions of creatine/phosphocreatine (Cr/PCr) were subject to change as a function of exercise. In particular, the dipolar-coupled methylene protons of Cr/PCr were found to be reduced in intensity in proportion to the co-registered PCr levels. Recovery after exercise and behavior under ischemic conditions provide further evidence to suggest that the contributions of the CH2protons of Cr/PCr to1H MR spectra of human musclein vivoreflect PCr rather than Cr levels. Variation of experimental parameters showed that this effect is not due to a trivial change in relaxation times. At present it can only be speculated about why the Cr resonances have reduced NMR visibility. If temporary binding to macromolecules should be involved, the free Cr concentration-important for equilibrium calculations of the creatine kinase reaction-might be different from what was previously assumed.

The Effect and Safety of Short-Term Creatine Supplementation on Performance of Push-Ups

DTIC Science & Technology

2007-03-01

MILITARY MEDICI’lE. 172. 3:312. 2007 The Effect and Safety of Short-Term Creatine Supplementation on Performance of Push-Ups Guarantor: LT Matthew...effects of short-term oral creatine (Cr) supplementation on exercise performance and on blood pressure and renal function were assessed. Thirty-five...before to after supplementation (p 0.437; power 0.98). The Cr group demonstrated a sig- nificant increase in serum creatinine levels (p 0.001), com

In vitro study of uptake and synthesis of creatine and its precursors by cerebellar granule cells and astrocytes suggests some hypotheses on the physiopathology of the inherited disorders of creatine metabolism

PubMed Central

2012-01-01

Background The discovery of the inherited disorders of creatine (Cr) synthesis and transport in the last few years disclosed the importance of blood Cr supply for the normal functioning of the brain. These putatively rare diseases share a common pathogenetic mechanism (the depletion of brain Cr) and similar phenotypes characterized by mental retardation, language disturbances, seizures and movement disorders. In the effort to improve our knowledge on the mechanisms regulating Cr pool inside the nervous tissue, Cr transport and synthesis and related gene transcripts were explored in primary cultures of rat cerebellar granule cells and astrocytes. Methods Cr uptake and synthesis were explored in vitro by incubating monotypic primary cultures of rat type I astrocytes and cerebellar granule cells with: a) D3-Creatine (D3Cr) and D3Cr plus β-guanidinopropionate (GPA, an inhibitor of Cr transporter), and b) labelled precursors of Guanidinoacetate (GAA) and Cr (Arginine, Arg; Glycine, Gly). Intracellular D3Cr and labelled GAA and Cr were assessed by ESI-MS/MS. Creatine transporter (CT1), L-arginine:glycine amidinotransferase (AGAT), and S-adenosylmethionine:guanidinoacetate N-methyltransferase (GAMT) gene expression was assessed in the same cells by real time PCR. Results D3Cr signal was extremely high in cells incubated with this isotope (labelled/unlabelled Cr ratio reached about 10 and 122, respectively in cerebellar granule cells and astrocytes) and was reduced by GPA. Labelled Arg and Gly were taken up by the cells and incorporated in GAA, whose concentration paralleled that of these precursors both in the extracellular medium and inside the cells (astrocytes). In contrast, the increase of labelled Cr was relatively much more limited since labelled Cr after precursors' supplementation did not exceed 2,7% (cerebellar granule cells) and 21% (astrocytes) of unlabelled Cr. Finally, AGAT, GAMT and SLC6A8 were expressed in both kind of cells. Conclusions Our results confirm that both neurons and astrocytes have the capability to synthesize and uptake Cr, and suggest that at least in vitro intracellular Cr can increase to a much greater extent through uptake than through de novo synthesis. Our results are compatible with the clinical observations that when the Cr transporter is defective, intracellular Cr is absent despite the brain should be able to synthesize it. Further research is needed to fully understand to what extent our results reflect the in vivo situation. PMID:22536786

In vitro study of uptake and synthesis of creatine and its precursors by cerebellar granule cells and astrocytes suggests some hypotheses on the physiopathology of the inherited disorders of creatine metabolism.

PubMed

Carducci, Claudia; Carducci, Carla; Santagata, Silvia; Adriano, Enrico; Artiola, Cristiana; Thellung, Stefano; Gatta, Elena; Robello, Mauro; Florio, Tullio; Antonozzi, Italo; Leuzzi, Vincenzo; Balestrino, Maurizio

2012-04-26

The discovery of the inherited disorders of creatine (Cr) synthesis and transport in the last few years disclosed the importance of blood Cr supply for the normal functioning of the brain. These putatively rare diseases share a common pathogenetic mechanism (the depletion of brain Cr) and similar phenotypes characterized by mental retardation, language disturbances, seizures and movement disorders. In the effort to improve our knowledge on the mechanisms regulating Cr pool inside the nervous tissue, Cr transport and synthesis and related gene transcripts were explored in primary cultures of rat cerebellar granule cells and astrocytes. Cr uptake and synthesis were explored in vitro by incubating monotypic primary cultures of rat type I astrocytes and cerebellar granule cells with: a) D3-Creatine (D3Cr) and D3Cr plus β-guanidinopropionate (GPA, an inhibitor of Cr transporter), and b) labelled precursors of Guanidinoacetate (GAA) and Cr (Arginine, Arg; Glycine, Gly). Intracellular D3Cr and labelled GAA and Cr were assessed by ESI-MS/MS. Creatine transporter (CT1), L-arginine:glycine amidinotransferase (AGAT), and S-adenosylmethionine:guanidinoacetate N-methyltransferase (GAMT) gene expression was assessed in the same cells by real time PCR. D3Cr signal was extremely high in cells incubated with this isotope (labelled/unlabelled Cr ratio reached about 10 and 122, respectively in cerebellar granule cells and astrocytes) and was reduced by GPA. Labelled Arg and Gly were taken up by the cells and incorporated in GAA, whose concentration paralleled that of these precursors both in the extracellular medium and inside the cells (astrocytes). In contrast, the increase of labelled Cr was relatively much more limited since labelled Cr after precursors' supplementation did not exceed 2,7% (cerebellar granule cells) and 21% (astrocytes) of unlabelled Cr. Finally, AGAT, GAMT and SLC6A8 were expressed in both kind of cells. Our results confirm that both neurons and astrocytes have the capability to synthesize and uptake Cr, and suggest that at least in vitro intracellular Cr can increase to a much greater extent through uptake than through de novo synthesis. Our results are compatible with the clinical observations that when the Cr transporter is defective, intracellular Cr is absent despite the brain should be able to synthesize it. Further research is needed to fully understand to what extent our results reflect the in vivo situation.

Effects of creatine supplementation on renal function: a randomized, double-blind, placebo-controlled clinical trial.

PubMed

Gualano, Bruno; Ugrinowitsch, Carlos; Novaes, Rafael Batista; Artioli, Guilherme Gianini; Shimizu, Maria Heloisa; Seguro, Antonio Carlos; Harris, Roger Charles; Lancha, Antonio Herbert

2008-05-01

Creatine (CR) supplementation is commonly used by athletes. However, its effects on renal function remain controversial. The aim of this study was to evaluate the effects of creatine supplementation on renal function in healthy sedentary males (18-35 years old) submitted to exercise training. A randomized, double-blind, placebo-controlled trial was performed. Subjects (n = 18) were randomly allocated to receive treatment with either creatine (CR) ( approximately 10 g day(-1) over 3 months) or placebo (PL) (dextrose). All subjects undertook moderate intensity aerobic training, in three 40-min sessions per week, during 3 months. Serum creatinine, serum and urinary sodium and potassium were determined at baseline and at the end of the study. Cystatin C was assessed prior to training (PRE), after 4 (POST 4) and 12 weeks (POST 12). Cystatin C levels (mg L(-1)) (PRE CR: 0.82 +/- 0.09; PL: 0.88 +/- 0.07 vs. POST 12 CR: 0.71 +/- 0.06; PL: 0.75 +/- 0.09, P = 0.0001) were decreased over time, suggesting an increase in glomerular filtration rate. Serum creatinine decreased with training in PL but was unchanged with training in CR. No significant differences were observed within or between groups in other parameters investigated. The decrease in cystatin C indicates that high-dose creatine supplementation over 3 months does not provoke any renal dysfunction in healthy males undergoing aerobic training. In addition, the results suggest that moderate aerobic training per se may improve renal function.

Creatine, arginine alpha-ketoglutarate, amino acids, and medium-chain triglycerides and endurance and performance.

PubMed

Little, Jonathan P; Forbes, Scott C; Candow, Darren G; Cornish, Stephen M; Chilibeck, Philip D

2008-10-01

Creatine (Cr) supplementation increases muscle mass, strength, and power. Arginine a-ketoglutarate (A-AKG) is a precursor for nitric oxide production and has the potential to improve blood flow and nutrient delivery (i.e., Cr) to muscles. This study compared a commercial dietary supplement of Cr, A-AKG, glutamine, taurine, branched-chain amino acids, and medium-chain triglycerides with Cr alone or placebo on exercise performance and body composition. Thirty-five men (approximately 23 yr) were randomized to Cr + A-AKG (0.1 g . kg(-1) . d(-1) Cr + 0.075 g . kg(-1) . d(-1)A-AKG, n = 12), Cr (0.1 g . kg(-1) . d(-1), n = 11), or placebo (1 g . kg(-1) . d(-1) sucrose, n = 12) for 10 d. Body composition, muscle endurance (bench press), and peak and average power (Wingate tests) were measured before and after supplementation. Bench-press repetitions over 3 sets increased with Cr + A-AKG (30.9 +/- 6.6 +/- 34.9 +/- 8.7 reps; p < .01) and Cr (27.6 +/- 5.9 +/- 31.0 +/- 7.6 reps; p < .01), with no change for placebo (26.8 +/- 5.0 +/- 27.1 +/- 6.3 reps). Peak power significantly increased in Cr + A-AKG (741 +/- 112 +/- 794 +/- 92 W; p < .01), with no changes in Cr (722 +/- 138 +/- 730 +/- 144 W) and placebo (696 +/- 63 +/- 705 +/- 77 W). There were no differences in average power between groups over time. Only the Cr-only group increased total body mass (79.9 +/- 13.0 +/- 81.1 +/- 13.8 kg; p < .01), with no significant changes in lean-tissue or fat mass. These results suggest that Cr alone and in combination with A-AKG improves upper body muscle endurance, and Cr + A-AKG supplementation improves peak power output on repeated Wingate tests.

Effects of in ovo feeding of creatine pyruvate on the hatchability, growth performance and energy status in embryos and broiler chickens.

PubMed

Zhao, M M; Gao, T; Zhang, L; Li, J L; Lv, P A; Yu, L L; Gao, F; Zhou, G H

2017-10-01

The effects of in ovo feeding (IOF) of creatine pyruvate (CrPyr) on the hatchability, growth performance and energy status of embryos and broilers (Arbor Acres) were investigated. Five treatments were arranged as non-injected treatment (Control), 0.6 ml physiological saline (0.75%) injected treatment (Saline), and IOF treatments injected with 0.6 ml physiological saline (0.75%) containing 3, 6 or 12 mg CrPyr (CrPyr3, CrPyr6 or CrPyr12) into the amnion per fertile egg on day 17.5 of incubation. After hatching, 80 male chicks from each treatment with similar weight close to the average BW of their pooled group were selected and randomly assigned into eight replicates of 10 chicks each. The results showed that the hatchability was not affected among groups, whereas the hatching weight of broilers in CrPyr12 was significantly higher than the control and saline groups (P0.05). Irrespective of dosage, the concentrations of creatine and phosphocreatine, and activities of creatine kinase in embryos were enhanced in CrPyr treatments at 19 E when compared with the control and saline groups (P<0.05). The activities of glucose-6-phosphatase in liver in CrPyr6 and CrPyr12 treatments were higher than the control and saline groups at 19 E (P<0.05). In conclusion, these results indicated that IOF of CrPyr, especially at the level of 12 mg/egg, could improve energy status of embryos and hatchlings, which was useful for enhancing hatching weight, BW and pectoral muscle weight until the end of the experiments at 21 days post-hatch in broilers.

Creatine monohydrate supplementation during eight weeks of progressive resistance training increases strength in as little as two weeks without reducing markers of muscle damage.

PubMed

Kaviani, Mojtaba; Abassi, Aboozar; Chilibeck, Philip D

2018-05-02

Creatine supplementation (Cr) increases strength during resistance training, but the time course of this strength increase is unclear. The aim was to determine the precise time course by which Cr could increase strength and whether Cr prevents muscle damage during eight weeks of resistance training. Young males were randomized (double blind) to Cr (n=9, 0.07g/kg/d) and placebo (n=9) during 8-weeks of resistance training (3d/week). Strength was assessed across six exercises every two weeks. Venous blood samples obtained at baseline, and 24 and 48 hours after the final resistance training session were assessed for creatine kinase [CK] and lactate dehydrogenase [LDH] as measures of muscle damage. Strength was significantly higher in the Cr versus placebo group (p<0.05) after two weeks of training for three of the six exercises (bench press, leg press, shoulder press). By the end of the eight weeks of training, strength was significantly higher in the Cr versus placebo group (p<0.05) for four of the six exercises (bench press, leg press, shoulder press, and triceps extension, but not biceps curl or lat-pulldown). Creatine supplementation did not prevent muscle damage. Indeed, muscle damage markers increased in the Cr compared to placebo group (p<0.05). Cr increased muscular strength in as little as two weeks during a resistance training program; however, this was not accompanied by decreased muscle damage. Greater muscle damage with Cr may be due to a greater training intensity enabled by Cr supplementation. This might lead to greater protein turnover and enhanced muscle adaptation.

Dietary creatine supplementation during pregnancy: a study on the effects of creatine supplementation on creatine homeostasis and renal excretory function in spiny mice.

PubMed

Ellery, Stacey J; LaRosa, Domenic A; Kett, Michelle M; Della Gatta, Paul A; Snow, Rod J; Walker, David W; Dickinson, Hayley

2016-08-01

Recent evidence obtained from a rodent model of birth asphyxia shows that supplementation of the maternal diet with creatine during pregnancy protects the neonate from multi-organ damage. However, the effect of increasing creatine intake on creatine homeostasis and biosynthesis in females, particularly during pregnancy, is unknown. This study assessed the impact of creatine supplementation on creatine homeostasis, body composition, capacity for de novo creatine synthesis and renal excretory function in non-pregnant and pregnant spiny mice. Mid-gestation pregnant and virgin spiny mice were fed normal chow or chow supplemented with 5 % w/w creatine for 18 days. Weight gain, urinary creatine and electrolyte excretion were assessed during supplementation. At post mortem, body composition was assessed by Dual-energy X-ray absorptiometry, or tissues were collected to assess creatine content and mRNA expression of the creatine synthesising enzymes arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT) and the creatine transporter (CrT1). Protein expression of AGAT and GAMT was also assessed by Western blot. Key findings of this study include no changes in body weight or composition with creatine supplementation; increased urinary creatine excretion in supplemented spiny mice, with increased sodium (P < 0.001) and chloride (P < 0.05) excretion in pregnant dams after 3 days of supplementation; lowered renal AGAT mRNA (P < 0.001) and protein (P < 0.001) expressions, and lowered CrT1 mRNA expression in the kidney (P < 0.01) and brain (P < 0.001). Creatine supplementation had minimal impact on creatine homeostasis in either non-pregnant or pregnant spiny mice. Increasing maternal dietary creatine consumption could be a useful treatment for birth asphyxia.

Creatine Transporter Deficiency: Screening of Males with Neurodevelopmental Disorders and Neurocognitive Characterization of a Case.

PubMed

Thurm, Audrey; Himelstein, Daniel; DʼSouza, Precilla; Rennert, Owen; Jiang, Susanqi; Olatunji, Damilola; Longo, Nicola; Pasquali, Marzia; Swedo, Susan; Salomons, Gajja S; Carrillo, Nuria

2016-05-01

Creatine transporter deficiency (CTD) is an X-linked, neurometabolic disorder associated with intellectual disability that is characterized by brain creatine (Cr) deficiency and caused by mutations in SLC6A8, the Cr transporter 1 protein gene. CTD is identified by elevated urine creatine/creatinine (Cr/Crn) ratio or reduced Cr peak on brain magnetic resonance spectroscopy; the diagnosis is confirmed by decreased Cr uptake in cultured fibroblasts, and/or identification of a mutation in the SLC6A8 gene. Prevalence studies suggest this disorder may be underdiagnosed. We sought to identify cases from a well-characterized cohort of children diagnosed with neurodevelopmental disorders. Urine screening for CTD was performed on a cohort of 46 males with autism spectrum disorder (ASD) and 9 males with a history of non-ASD developmental delay (DD) classified with intellectual disability. We identified 1 patient with CTD in the cohort based on abnormal urine Cr/Crn, and confirmed the diagnosis by the identification of a novel frameshift mutation in the SLC6A8 gene. This patient presented without ASD but with intellectual disability, and was characterized by a nonspecific phenotype of early language delay and DD that persisted into moderate-to-severe intellectual disability, consistent with previous descriptions of CTD. Identification of patients with CTD is possible by measuring urine Cr and Crn levels and the current case adds to the growing literature of neurocognitive deficits associated with the disorder that affect cognition, language and behavior in childhood.

Relaxation-compensated CEST-MRI at 7 T for mapping of creatine content and pH--preliminary application in human muscle tissue in vivo.

PubMed

Rerich, Eugenia; Zaiss, Moritz; Korzowski, Andreas; Ladd, Mark E; Bachert, Peter

2015-11-01

The small biomolecule creatine is involved in energy metabolism. Mapping of the total creatine (mostly PCr and Cr) in vivo has been done with chemical shift imaging. Chemical exchange saturation transfer (CEST) allows an alternative detection of creatine via water MRI. Living tissue exhibits CEST effects from different small metabolites, including creatine, with four exchanging protons of its guanidinium group resonating about 2 ppm from the water peak and hence contributing to the amine proton CEST peak. The intermediate exchange rate (≈ 1000 Hz) of the guanidinium protons requires high RF saturation amplitude B1. However, strong B1 fields also label semi-solid magnetization transfer (MT) effects originating from immobile protons with broad linewidths (~kHz) in the tissue. Recently, it was shown that endogenous CEST contrasts are strongly affected by the MT background as well as by T1 relaxation of the water protons. We show that this influence can be corrected in the acquired CEST data by an inverse metric that yields the apparent exchange-dependent relaxation (AREX). AREX has some useful linearity features that enable preparation of both concentration, and--by using the AREX-ratio of two RF irradiation amplitudes B1--purely exchange-rate-weighted CEST contrasts. These two methods could be verified in phantom experiments with different concentration and pH values, but also varying water relaxation properties. Finally, results from a preliminary application to in vivo CEST imaging data of the human calf muscle before and after exercise are presented. The creatine concentration increases during exercise as expected and as confirmed by (31)P NMR spectroscopic imaging. However, the estimated concentrations obtained by our method were higher than the literature values: cCr,rest=24.5±3.74mM to cCr,ex=38.32±13.05mM. The CEST-based pH method shows a pH decrease during exercise, whereas a slight increase was observed by (31)P NMR spectroscopy. Copyright © 2015 John Wiley & Sons, Ltd.

Creatine Supplementation Induces Alteration in Cross-Sectional Area in Skeletal Muscle Fibers of Wistar Rats Under Swimming Training

PubMed Central

Santos, Fernando Farias Dos; Moura, José A. A.; Curi, Rui; Fernandes, Luiz C.

2002-01-01

Creatine has been shown to increase the total muscle mass. In this study, we investigated the effect of oral creatine monohydrate supplementation on cross-sectional area of type I, IIA and IIB fibers of gastrocnemius, extensor digitorum longus - EDL and soleus muscles from male Wistar rats subjected to swimming training for 33 days. Four groups were set up: sedentary with no supplementation (CON), sedentary with creatine supplementation (3.3 mg creatine per g chow) (CR), exercised with no supplementation (EX) and exercised with supplementation (CREX). The rats performed in a special swimming pool and swam five times a week for 1 hour each day, with a extra lead weight corresponding to 15% of their body weight. At the end of 33 days, skeletal muscles of the animals were dissected and the samples got immediately frozen using liquid nitrogen. Muscle samples were allocated to slices of 10 μm by a cryostat at -20°C, which was followed by histochemical analysis in order to identify fiber types of the muscles, and morphometrical analysis to calculate the muscle fiber areas. All groups gained body weight at the end of 33 days but there was no statistical difference among them. The EX and CREX rats had a larger food intake than the sedentary groups (CON and CR), and the CREX group had a larger food intake than CR rats. The cross-sectional area of type I and IIA fibers of the soleus muscle, type IIA and IIB fibers of EDL muscle and type IIA and IIB fibers of the white portion of gastrocnemius muscle were greater in the EX and CREX groups in comparison to sedentary rats. In addition, these fibers were greater in the CREX rats than in the EX group. There was no change in the cross sectional area of type I fibers in EDL muscle among all groups studied. Our results suggest that creatine supplementation enhances the exercise related muscle fiber hypertrophy in rodents. PMID:24701129

Acute and chronic safety and efficacy of dose dependent creatine nitrate supplementation and exercise performance.

PubMed

Galvan, Elfego; Walker, Dillon K; Simbo, Sunday Y; Dalton, Ryan; Levers, Kyle; O'Connor, Abigail; Goodenough, Chelsea; Barringer, Nicholas D; Greenwood, Mike; Rasmussen, Christopher; Smith, Stephen B; Riechman, Steven E; Fluckey, James D; Murano, Peter S; Earnest, Conrad P; Kreider, Richard B

2016-01-01

Creatine monohydrate (CrM) and nitrate are popular supplements for improving exercise performance; yet have not been investigated in combination. We performed two studies to determine the safety and exercise performance-characteristics of creatine nitrate (CrN) supplementation. Study 1 participants (N = 13) ingested 1.5 g CrN (CrN-Low), 3 g CrN (CrN-High), 5 g CrM or a placebo in a randomized, crossover study (7d washout) to determine supplement safety (hepatorenal and muscle enzymes, heart rate, blood pressure and side effects) measured at time-0 (unsupplemented), 30-min, and then hourly for 5-h post-ingestion. Study 2 participants (N = 48) received the same CrN treatments vs. 3 g CrM in a randomized, double-blind, 28d trial inclusive of a 7-d interim testing period and loading sequence (4 servings/d). Day-7 and d-28 measured Tendo™ bench press performance, Wingate testing and a 6x6-s bicycle ergometer sprint. Data were analyzed using a GLM and results are reported as mean ± SD or mean change ± 95 % CI. In both studies we observed several significant, yet stochastic changes in blood markers that were not indicative of potential harm or consistent for any treatment group. Equally, all treatment groups reported a similar number of minimal side effects. In Study 2, there was a significant increase in plasma nitrates for both CrN groups by d-7, subsequently abating by d-28. Muscle creatine increased significantly by d-7 in the CrM and CrN-High groups, but then decreased by d-28 for CrN-High. By d-28, there were significant increases in bench press lifting volume (kg) for all groups (PLA, 126.6, 95 % CI 26.3, 226.8; CrM, 194.1, 95 % CI 89.0, 299.2; CrN-Low, 118.3, 95 % CI 26.1, 210.5; CrN-High, 267.2, 95 % CI 175.0, 359.4, kg). Only the CrN-High group was significantly greater than PLA (p < 0.05). Similar findings were observed for bench press peak power (PLA, 59.0, 95 % CI 4.5, 113.4; CrM, 68.6, 95 % CI 11.4, 125.8; CrN-Low, 40.9, 95 % CI -9.2, 91.0; CrN-High, 60.9, 95 % CI 10.8, 111.1, W) and average power. Creatine nitrate delivered at 3 g was well-tolerated, demonstrated similar performance benefits to 3 g CrM, in addition, within the confines of this study, there were no safety concerns.

Effects of 4 weeks of creatine supplementation in junior swimmers on freestyle sprint and swim bench performance.

PubMed

Dawson, Brian; Vladich, Todd; Blanksby, Brian A

2002-11-01

To determine whether 4 weeks of oral creatine (Cr) supplementation could enhance single freestyle sprint and swim bench performance in experienced competitive junior swimmers, 10 young men and 10 young women (x age = 16.4 +/- 1.8 years) participated in a 27-day supplementation period and pre- and posttesting sessions. In session 1 (presupplementation testing), subjects swam one 50-m freestyle and then (after approximately 5 minutes of active recovery) one 100-m freestyle at maximum speed. Blood lactate was measured before and 1 minute after each swim trial. Forty-eight hours later, height, mass, and the sum of 6 skinfolds were recorded, and a Biokinetic Swim Bench total work output test (2 x 30-second trials, with a 10-minute passive recovery in between) was undertaken. After the pretests were completed, participants were divided into 2 groups (n = 10, Cr; and n = 10, placebo) by means of matched pairs on the basis of gender and 50-m swim times. A Cr loading phase of 20 g x d(-1) for 5 days was then instituted, followed by a maintenance phase of 5 g x d(-1) for 22 days. Postsupplementation testing replicated the presupplementation tests. Four weeks of Cr supplementation did not influence single sprint performance in the pool or body mass and composition. However, 30-second swim bench total work scores for trial 1 and trial 2 increased after Cr (p < 0.05) but not placebo ingestion. Postexercise blood lactate values were not different after supplementation for the 50- and 100-m sprint trials either within or between groups. It was concluded that 4 weeks of Cr supplementation did not significantly improve single sprint performance in competitive junior swimmers, but it did enhance swim bench test performance.

Creatine metabolism in urea cycle defects.

PubMed

Boenzi, Sara; Pastore, Anna; Martinelli, Diego; Goffredo, Bianca Maria; Boiani, Arianna; Rizzo, Cristiano; Dionisi-Vici, Carlo

2012-07-01

Creatine (Cr) and phosphocreatine play an essential role in energy storage and transmission. Maintenance of creatine pool is provided by the diet and by de novo synthesis, which utilizes arginine, glycine and s-adenosylmethionine as substrates. Three primary Cr deficiencies exists: arginine:glycine amidinotransferase deficiency, guanidinoacetate methyltransferase deficiency and the defect of Cr transporter SLC6A8. Secondary Cr deficiency is characteristic of ornithine-aminotransferase deficiency, whereas non-uniform Cr abnormalities have anecdotally been reported in patients with urea cycle defects (UCDs), a disease category related to arginine metabolism in which Cr must be acquired by de novo synthesis because of low dietary intake. To evaluate the relationships between ureagenesis and Cr synthesis, we systematically measured plasma Cr in a large series of UCD patients (i.e., OTC, ASS, ASL deficiencies, HHH syndrome and lysinuric protein intolerance). Plasma Cr concentrations in UCDs followed two different trends: patients with OTC and ASS deficiencies and HHH syndrome presented a significant Cr decrease, whereas in ASL deficiency and lysinuric protein intolerance Cr levels were significantly increased (23.5 vs. 82.6 μmol/L; p < 0.0001). This trend distribution appears to be regulated upon cellular arginine availability, highlighting its crucial role for both ureagenesis and Cr synthesis. Although decreased Cr contributes to the neurological symptoms in primary Cr deficiencies, still remains to be explored if an altered Cr metabolism may participate to CNS dysfunction also in patients with UCDs. Since arginine in most UCDs becomes a semi-essential aminoacid, measuring plasma Cr concentrations might be of help to optimize the dose of arginine substitution.

Neuropsychological profile and clinical effects of arginine treatment in children with creatine transport deficiency

PubMed Central

2012-01-01

Background SLC6A8, an X-linked gene, encodes the creatine transporter (CRTR) and its mutations lead to cerebral creatine (Cr) deficiency which results in mental retardation, speech and language delay, autistic-like behaviour and epilepsy (CRTR-D, OMIM 300352). CRTR-D represents the most frequent Cr metabolism disorder but, differently from Cr synthesis defects, that are partially reversible by oral Cr supplementation, does not respond to Cr treatment even if precociously administrated. The precursors of Cr are the non-essential amino acids Glycine (Gly) and Arginine (Arg), which have their own transporters at the brain–blood barrier level and, therefore, their supplementation appears an attractive and feasible therapeutic option aimed at stimulating Cr endogenous synthesis and, in this way, at overcoming the block of Cr transport within the brain. However, until now the effects of Arg and/or Gly supplementation on Cr brain levels and behaviour have been controversial. Methods In this study five Italian male patients affected by CRTR-D were supplemented with oral L-Arg at a dosage of 300 mg/kg/day divided into 3 doses, for 24–36 months. Biochemical and plasmatic amino acids examinations and thyroid hormone dosages were periodically performed. Moreover, Proton and Phosphorus Magnetic Resonance Spectroscopy (MRS) was monitored during follow-up in concurrence with neuropsychological evaluations. Results During L-Arg treatment a clinical improvement in motor skills and to a lesser extent in communication and attention was observed. In addition, all patients had a reduction in the number and frequency of epileptic seizures. Daily living skills appeared also to be positively influenced by L-Arg treatment. Moreover, Total Cr and especially PhosphoCr, evaluated by proton and phosphorus spectroscopy, showed a mild increase, although well below the normal range. Conclusion This study provides information to support the effectiveness of L-Arg supplement treatment in CTRT-D patients; in fact the syndromic pattern of cognitive and linguistic deficit presented by CRTR-D patients was partially altered by L-Arg supplementation especially at a qualitative clinical level. Oral L-Arg may represent not only a protective factor towards a further cognitive decline, but can lead to the acquisition of new skills. PMID:22713831

Parkinson's disease: in vivo metabolic changes in the frontal and parietal cortices in 6-OHDA treated rats during different periods.

PubMed

Hou, Zhongyu; Zhang, Zhonghe; Meng, Haiwei; Lin, Xiangtao; Sun, Bo; Lei, Hao; Fang, Ke; Fang, Fang; Liu, Maili; Liu, Shuwei

2014-02-01

This study aims to investigate metabolic changes in frontal and parietal cortices in the 6-OHDA induced Parkinson's rats. Ratios of N-acetyl-aspartic acid/creatine (NAA/Cr), choline/creatine (Cho/Cr), and glumatic acid and glutamine glutaminic acid/creatine (Glx/Cr) of regions of interests (ROIs) in the frontal and parietal cortices, and the substantia nigra were analyzed. NAA/Cr, Cho/Cr and Glx/Cr in the frontal and parietal cortices in the lesion side did not show any significant differences two weeks after operation compared with the contralateral side (p > 0.05). NAA/Cr in the frontal cortex in the lesion side was significantly lower in the five weeks after operation; Cho/Cr remained normal; Glx/Cr increased (p < 0.05), and all ratios of parietal cortex were normal. In the eight weeks after operation, NAA/Cr in the frontal cortex in the lesion side was lower than that of the five weeks (p < 0.01), Cho/Cr still remained normal while Glx/Cr was higher than before (p < 0.01). Regarding the parietal cortex, NAA/Cr increased significantly, while Cho/Cr and Glx/Cr remained normal. In the 12 weeks after operation, NAA/Cr, Cho/Cr and Glx/Cr in frontal cortex were consistent with that of the eight weeks, while they remained at the normal level in parietal cortex. The NAA/Cr in the substantia nigra decreased and Cho/Cr increased significantly during 2-8 weeks, and remained at the same level during 8-12 weeks. There are metabolic disturbances in PD rats. The transient hyperfunction in the parietal cortex can be considered as a compensation for the dysfunction of the frontal cortex and substantia nigra.

Resistance Training and Co-supplementation with Creatine and Protein in Older Subjects with Frailty.

PubMed

Collins, J; Longhurst, G; Roschel, H; Gualano, B

2016-01-01

Studies assessing the effects co-supplementation with creatine and protein, along with resistance training, in older individuals with frailty are lacking. This is an exploratory trial from the Pro-Elderly study ("Protein Intake and Resistance Training in Aging") aimed at gathering knowledge on the feasibility, safety, and efficacy of co-supplementation with creatine and protein supplementation, combined with resistance training, in older individuals with frailty. A 14-week, double-blind, randomized, parallel-group, placebo controlled exploratory trial. The subjects were randomly assigned to whey protein and creatine co-supplementation (WHEY+CR) or whey protein supplementation (WHEY) group. All subjects undertook a supervised exercise training program and were assessed at baseline and after 14 weeks. Muscle function, body composition, blood parameters, and self-reported adverse events were assessed. No interaction effects (between-group differences) were observed for any dependent variables (p > 0.05 for all). However, there were main time-effects in handgrip (WHEY+CR = 26.65 ± 31.29; WHEY = 13.84 ± 14.93 Kg; p = 0.0005), timed-up-and-go (WHEY+CR = -11.20 ± 9.37; WHEY = -17.76 ± 21.74 sec; p = 0.006), and timed-stands test (WHEY+CR = 47.50 ± 35.54; WHEY = 46.87 ± 24.23 reps; p = 0.0001), suggesting that WHEY+CR and WHEY were similarly effective in improving muscle function. All of the subjects showed improvements in at least two of the three functional tests, regardless of their treatments. Body composition and blood parameters were not changed (p > 0.05). No severe adverse effects were observed. Co-supplementation with creatine and whey protein was well-tolerable and free of adverse events in older subjects with frailty undertaking resistance training. Creatine supplementation did not augment the adaptive effects of resistance training along with whey protein on body composition or muscle function in this population. Clinicaltrials.gov: NCT01890382.

Protective Effect of Creatine Elevation against Ischaemia Reperfusion Injury Is Retained in the Presence of Co-Morbidities and during Cardioplegia.

PubMed

Whittington, Hannah J; McAndrew, Debra J; Cross, Rebecca L; Neubauer, Stefan; Lygate, Craig A

2016-01-01

Ischaemic heart disease is most prevalent in the ageing population and often exists with other comorbidities; however the majority of laboratory research uses young, healthy animal models. Several recent workshops and focus meetings have highlighted the importance of using clinically relevant models to help aid translation to realistic patient populations. We have previously shown that mice over-expressing the creatine transporter (CrT-OE) have elevated intracellular creatine levels and are protected against ischaemia-reperfusion injury. Here we test whether elevating intracellular creatine levels retains a cardioprotective effect in the presence of common comorbidities and whether it is additive to protection afforded by hypothermic cardioplegia. CrT-OE mice and wild-type controls were subjected to transverse aortic constriction for two weeks to induce compensated left ventricular hypertrophy (LVH). Hearts were retrogradely perfused in Langendorff mode for 15 minutes, followed by 20 minutes ischaemia and 30 minutes reperfusion. CrT-OE hearts exhibited significantly improved functional recovery (Rate pressure product) during reperfusion compared to WT littermates (76% of baseline vs. 59%, respectively, P = 0.02). Aged CrT-OE mouse hearts (78±5 weeks) also had enhanced recovery following 15 minutes ischaemia (104% of baseline vs. 67%, P = 0.0007). The cardioprotective effect of hypothermic high K+ cardioplegic arrest, as used during cardiac surgery and donor heart transplant, was further enhanced in prolonged ischaemia (90 minutes) in CrT-OE Langendorff perfused mouse hearts (76% of baseline vs. 55% of baseline as seen in WT hearts, P = 0.02). These observations in clinically relevant models further support the development of modulators of intracellular creatine content as a translatable strategy for cardiac protection against ischaemia-reperfusion injury.

In vivo (1)H MRS and (31)P MRSI of the response to cyclocreatine in transgenic mouse liver expressing creatine kinase.

PubMed

Cui, Min-Hui; Jayalakshmi, Kamaiah; Liu, Laibin; Guha, Chandan; Branch, Craig A

2015-12-01

Hepatocyte transplantation has been explored as a therapeutic alternative to liver transplantation, but a means to monitor the success of the procedure is lacking. Published findings support the use of in vivo (31)P MRSI of creatine kinase (CK)-expressing hepatocytes to monitor proliferation of implanted hepatocytes. Phosphocreatine tissue level depends upon creatine (Cr) input to the CK enzyme reaction, but Cr measurement by (1)H MRS suffers from low signal-to-noise ratio (SNR). We examine the possibility of using the Cr analog cyclocreatine (CCr, a substrate for CK), which is quickly phosphorylated to phosphocyclocreatine (PCCr), as a higher SNR alternative to Cr. (1)H MRS and (31)P MRSI were employed to measure the effect of incremental supplementation of CCr upon PCCr, γ-ATP, pH and Pi /ATP in the liver of transgenic mice expressing the BB isoform of CK (CKBB) in hepatocytes. Water supplementation with 0.1% CCr led to a peak total PCCr level of 17.15 ± 1.07 mmol/kg wet weight by 6 weeks, while adding 1.0% CCr led to a stable PCCr liver level of 18.12 ± 3.91 mmol/kg by the fourth day of feeding. PCCr was positively correlated with CCr, and ATP concentration and pH declined with increasing PCCr. Feeding with 1% CCr in water induced an apparent saturated level of PCCr, suggesting that CCr quantization may not be necessary for quantifying expression of CK in mice. These findings support the possibility of using (31)P MRS to noninvasively monitor hepatocyte transplant success with CK-expressing hepatocytes. Copyright © 2015 John Wiley & Sons, Ltd.

Creatine deficiency syndromes.

PubMed

Schulze, Andreas

2013-01-01

The lack of creatine in the central nervous system causes a severe but treatable neurological disease. Three inherited defects, AGAT, GAMT, and CrT deficiency, compromising synthesis and transport of creatine have been discovered recently. Together these so-called creatine deficiency syndromes (CDS) might represent the most frequent metabolic disorders with a primarily neurological phenotype. Patients with CDS present with global developmental delays, mental retardation, speech impairment especially affecting active language, seizures, extrapyramidal movement disorder, and autism spectrum disorder. The two defects in the creatine synthesis, AGAT and GAMT, are autosomal recessive disorders. They can be diagnosed by analysis of the creatine, guanidinoacetate, and creatinine in body fluids. Treatment is available and, especially when introduced in infancy, has a good outcome. The defect of creatine transport, CrT, is an X-linked condition and perhaps the most frequent reasons for X-linked mental retardation. Diagnosis is made by an increased ratio of creatine to creatinine in urine, but successful treatment still needs to be explored. CDS are under-diagnosed because easy to miss in standard diagnostic workup. Because CDS represent a frequent cause of cognitive and neurological impairment that is treatable they warrant consideration in the workup for genetic mental retardation syndromes, for intractable seizure disorders, and for neurological diseases with a predominant lack of active speech. Copyright © 2013 Elsevier B.V. All rights reserved.

Relationships between astrogliosis and 1H MR spectroscopic measures of brain choline/creatine and myo-inositol/creatine in a primate model.

PubMed

Kim, John P; Lentz, Margaret R; Westmoreland, Susan V; Greco, Jane B; Ratai, Eva M; Halpern, Elkan; Lackner, Andrew A; Masliah, Eliezer; González, R Gilberto

2005-04-01

In vivo 1H MR spectroscopy demonstrates elevated choline (Cho)/creatine (Cr) and myo-inositol (MI)/Cr in many neurologic diseases that has been ascribed to gliosis. We tested the hypotheses that in vivo Cho/Cr and/or MI/Cr levels are correlated with glial fibrillary acidic protein (GFAP) immunostains and that the changes are water-soluble metabolites. We performed postmortem 1H MR spectroscopy and GFAP immunohistochemistry in brains from seven rhesus macaques acutely infected with simian immunodeficiency virus (SIV) and in four controls and compared the findings with previous in vivo MR spectroscopic results. Changes in neuropathologic and MR spectroscopic markers after infection and relationships among plasma viral load, GFAP immunostaining results, and ex vivo and in vivo MR spectroscopic measures were statistically evaluated. On GFAP immunostaining and in vivo MR spectroscopy, GFAP, Cho/Cr and MI/Cr were highest near the time of peak plasma viral load at 11 days postinfection (dpi). Immunostains returned to baseline by 14 dpi, whereas Cho/Cr and MI/Cr had different time courses, with the former dropping below baseline and the latter remaining elevated. Viral load and immunostains were significantly correlated. No correlation was found between ex vivo Cho/Cr or MI/Cr and viral load or between metabolite ratios from in vivo and ex vivo MR spectroscopy. In acute SIV infection, plasma viral load was significantly correlated with brain GFAP immunostains and in vivo 1H MR spectroscopic Cho/Cr. In vivo changes in Cho/Cr and MI/Cr were principally due to contributions other than those of low-molecular-weight water-soluble metabolites.

Creatine supplementation prevents fatty liver in rats fed choline-deficient diet: a burden of one-carbon and fatty acid metabolism.

PubMed

Deminice, Rafael; de Castro, Gabriela Salim Ferreira; Francisco, Lucas Vieira; da Silva, Lilian Eslaine Costa Mendes; Cardoso, João Felipe Rito; Frajacomo, Fernando Tadeu Trevisan; Teodoro, Bruno Gonzaga; Dos Reis Silveira, Leonardo; Jordao, Alceu Afonso

2015-04-01

To examine the effects of creatine (Cr) supplementation on liver fat accumulation in rats fed a choline-deficient diet. Twenty-four rats were divided into 3 groups of 8 based on 4 weeks of feeding an AIN-93 control diet (C), a choline-deficient diet (CDD) or a CDD supplemented with 2% Cr. The CDD diet was AIN-93 without choline. The CDD significantly increased plasma homocysteine and TNFα concentration, as well as ALT activity. In liver, the CDD enhanced concentrations of total fat (55%), cholesterol (25%), triglycerides (87%), MDA (30%), TNFα (241%) and decreased SAM concentrations (25%) and the SAM/SAH ratio (33%). Cr supplementation prevented all these metabolic changes, except for hepatic SAM and the SAM/SAH ratio. However, no changes in PEMT gene expression or liver phosphatidylcholine levels were observed among the three experimental groups, and there were no changes in hepatic triglyceride transfer protein (MTP) mRNA level. On the contrary, Cr supplementation normalized expression of the transcription factors PPARα and PPARγ that were altered by the CDD. Further, the downstream targets and fatty acids metabolism genes, UCP2, LCAD and CPT1a, were also normalized in the Cr group as compared to CDD-fed rats. Cr supplementation prevented fat liver accumulation and hepatic injures in rats fed with a CDD for 4 weeks. Our results demonstrated that one-carbon metabolism may have a small role in mitigating hepatic fat accumulation by Cr supplementation. The modulation of key genes related to fatty acid oxidation pathway suggests a new mechanism by which Cr prevents liver fat accumulation. Copyright © 2015 Elsevier Inc. All rights reserved.

A mouse model for creatine transporter deficiency reveals early onset cognitive impairment and neuropathology associated with brain aging.

PubMed

Baroncelli, Laura; Molinaro, Angelo; Cacciante, Francesco; Alessandrì, Maria Grazia; Napoli, Debora; Putignano, Elena; Tola, Jonida; Leuzzi, Vincenzo; Cioni, Giovanni; Pizzorusso, Tommaso

2016-10-01

Mutations in the creatine (Cr) transporter (CrT) gene lead to cerebral creatine deficiency syndrome-1 (CCDS1), an X-linked metabolic disorder characterized by cerebral Cr deficiency causing intellectual disability, seizures, movement and autistic-like behavioural disturbances, language and speech impairment. Since no data are available about the neural and molecular underpinnings of this disease, we performed a longitudinal analysis of behavioural and pathological alterations associated with CrT deficiency in a CCDS1 mouse model. We found precocious cognitive and autistic-like defects, mimicking the early key features of human CCDS1. Moreover, mutant mice displayed a progressive impairment of short and long-term declarative memory denoting an early brain aging. Pathological examination showed a prominent loss of GABAergic synapses, marked activation of microglia, reduction of hippocampal neurogenesis and the accumulation of autofluorescent lipofuscin. Our data suggest that brain Cr depletion causes both early intellectual disability and late progressive cognitive decline, and identify novel targets to design intervention strategies aimed at overcoming brain CCDS1 alterations. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Myoprotective Potential of Creatine Is Greater than Whey Protein after Chemically-Induced Damage in Rat Skeletal Muscle

PubMed Central

Cooke, Matthew B.; Stathis, Christos G.; Hayes, Alan

2018-01-01

The myoprotective effects of creatine monohydrate (CR) and whey protein (WP) are equivocal, with the use of proxy measures of muscle damage making interpretation of their effectiveness limited. The purpose of the study was to determine the effects of CR and WP supplementation on muscle damage and recovery following controlled, chemically-induced muscle damage. Degeneration of the extensor digitorum longus (EDL) muscle was induced by bupivacaine in rats supplemented with either CR, WP, or standard rat chow (CON). At day 7 and 14 post-myotoxic injury, injured EDL muscles were surgically removed and tested for isometric contractile properties, followed by the contralateral, non-injured EDL muscle. At the completion of testing, muscles were snap-frozen in liquid nitrogen and stored for later analysis. Data were analyzed using analysis of variance. Creatine-supplemented muscles displayed a greater proportion of non-damaged (intact) fibers (p = 0.002) and larger cross-sectional areas of regenerating and non-damaged fibers (p = 0.024) compared to CON muscles at day 7 post-injury. At day 14 post-injury, CR-supplemented muscles generated higher absolute forces concomitant with greater contractile protein levels compared to CON (p = 0.001, p = 0.008) and WP-supplemented muscles (p = 0.003, p = 0.006). Creatine supplementation appears to offer an element of myoprotection which was not observed following whey protein supplementation. PMID:29710855

Energizing Eukaryotic Cell-Free Protein Synthesis With Glucose Metabolism

PubMed Central

Hodgman, C. Eric; Jewett, Michael C.

2015-01-01

Eukaryotic cell-free protein synthesis (CFPS) is limited by the dependence on costly high-energy phosphate compounds and exogenous enzymes to power protein synthesis (e.g., creatine phosphate and creatine kinase, CrP/CrK). Here, we report the ability to use glucose as a secondary energy substrate to regenerate ATP in a Saccharomyces cerevisiae crude extract CFPS platform. We observed synthesis of 3.64±0.35 μg mL−1 active luciferase in batch reactions with 16mM glucose and 25mM phosphate, resulting in a 16% increase in relative protein yield (μg protein/$ reagents) compared to the CrP/CrK system. Our demonstration provides the foundation for development of cost-effective eukaryotic CFPS platforms. PMID:26054976

Proton Magnetic Resonance Spectroscopy in Social Anxiety Disorder.

PubMed

Tükel, Raşit; Aydın, Kubilay; Yüksel, Çağrı; Ertekin, Erhan; Koyuncu, Ahmet

2016-01-01

In the present study, 24 nonmedicated patients with social anxiety disorder (SAD) were compared with 24 healthy control subjects to assess metabolite levels in the anterior cingulate, insula, caudate, and putamen using proton magnetic resonance spectroscopy. The ratio of N-acetylaspartate (NAA)/creatine (Cr) was significantly higher in patients with SAD than in healthy control subjects in the anterior cingulate and insula. NAA/Cr ratios in the insula correlated positively with the Liebowitz Social Anxiety Scale total scores in patients with SAD. Our results support the significance and biochemical involvement of the anterior cingulate and insula in the pathophysiology of SAD.

The effects of beta alanine plus creatine administration on performance during repeated bouts of supramaximal exercise in sedentary men.

PubMed

Okudan, N; Belviranli, M; Pepe, H; Gökbel, H

2015-11-01

The aim of this study was to investigate the effects of beta alanine and/or creatine supplementation on performance during repeated bouts of supramaximal exercise in sedentary men. Forty-four untrained healthy men (aged 20-22 years, weight: 68-72 kg, height: 174-178 cm) participated in the present study. After performing the Wingate Test (WAnT) for three times in the baseline exercise session, the subjects were assigned to one of four treatment groups randomly: 1) placebo (P; 10 g maltodextrose); 2) creatine (Cr; 5 g creatine plus 5 g maltodextrose); 3) beta-alanine (β-ALA; 1,6 g beta alanine plus 8,4 g maltodextrose); and 4) beta-alanine plus creatine (β-ALA+Cr; 1,6 g beta alanine plus 5 g creatine plus 3,4 g maltodextrose). Participants were given the supplements orally twice a day for 22 consecutive days, then four times a day for the following 6 days. After 28 days, the second exercise session was applied during which peak power (PP) and mean power (MP) were measured and fatigue index (FI) was calculated. PP and MP decreased and FI increased in all groups during exercise before and after the treatment. During the postsupplementation session PP2 and PP3 increased in creatine supplemented group (from 642.7±148.6 to 825.1±205.2 in PP2 and from 522.9±117.5 to 683.0±148.0 in PP3, respectively). However, MP increased in β-ALA+Cr during the postsupplementation compared to presupplementation in all exercise sessions (from 586.2±55.4 to 620.6±49.6 in MP1, from 418.1±37.2 to 478.3±30.3 in MP2 and from 362.0±41.3 to 399.1±3 in MP3, respectively). FI did not change with beta alanine and beta alanine plus creatine supplementation during the postsupplementation exercise session. Beta-alanine and beta alanine plus creatine supplementations have strong performance enhancing effect by increasing mean power and delaying fatigue Index during the repeated WAnT.

Creatine supports propagation and promotes neuronal differentiation of inner ear progenitor cells.

PubMed

Di Santo, Stefano; Mina, Amir; Ducray, Angélique; Widmer, Hans R; Senn, Pascal

2014-05-07

Long-term propagation of inner ear-derived progenitor/stem cells beyond the third generation and differentiation into inner ear cell types has been shown to be feasible, but challenging. We investigated whether the known neuroprotective guanidine compound creatine (Cr) promotes propagation of inner ear progenitor/stem cells as mitogen-expanded neurosphere cultures judged from the formation of spheres over passages. In addition, we studied whether Cr alone or in combination with brain-derived neurotrophic factor (BDNF) promotes neuronal differentiation of inner ear progenitors. For this purpose, early postnatal rat spiral ganglia, utricle, and organ of Corti-derived progenitors were grown as floating spheres in the absence (controls) or presence of Cr (5 mM) from passage 3 onward. Similarly, dissociated sphere-derived cultures were differentiated for 14 days in the presence or absence of Cr (5 mM) and spiral ganglia sphere-derived cultures in a combination of Cr with the neurotrophin BDNF (50 ng/ml). We found that the cumulative total number of spheres over all passages was significantly higher after Cr supplementation as compared with controls in all the three inner ear cultures. In contrast, sphere sizes were not affected by the administration of Cr. Administration of Cr during differentiation of spiral ganglia cells resulted in a significantly higher density of β-III-tubulin-positive cells compared with controls, whereas densities of myosin VIIa-positive cells in cultures of utricle and organ of Corti were not affected by the treatment. Importantly, a combination of Cr with the neurotrophin BDNF resulted in further significantly increased densities of β-III-tubulin-positive cells in cultures of spiral ganglia cells as compared with single treatments. In sum, Cr promoted continuing propagation of rat inner ear-derived progenitor cells and supported specifically in combination with BDNF the differentiation of neuronal cell types from spiral ganglion-derived spheres.

Modelling in vivo creatine/phosphocreatine in vitro reveals divergent adaptations in human muscle mitochondrial respiratory control by ADP after acute and chronic exercise.

PubMed

Ydfors, Mia; Hughes, Meghan C; Laham, Robert; Schlattner, Uwe; Norrbom, Jessica; Perry, Christopher G R

2016-06-01

Mitochondrial respiratory sensitivity to ADP is thought to influence muscle fitness and is partly regulated by cytosolic-mitochondrial diffusion of ADP or phosphate shuttling via creatine/phosphocreatine (Cr/PCr) through mitochondrial creatine kinase (mtCK). Previous measurements of respiration in vitro with Cr (saturate mtCK) or without (ADP/ATP diffusion) show mixed responses of ADP sensitivity following acute exercise vs. less sensitivity after chronic exercise. In human muscle, modelling in vivo 'exercising' [Cr:PCr] during in vitro assessments revealed novel responses to exercise that differ from detections with or without Cr (±Cr). Acute exercise increased ADP sensitivity when measured without Cr but had no effect ±Cr or with +Cr:PCr, whereas chronic exercise increased sensitivity ±Cr but lowered sensitivity with +Cr:PCr despite increased markers of mitochondrial oxidative capacity. Controlling in vivo conditions during in vitro respiratory assessments reveals responses to exercise that differ from typical ±Cr comparisons and challenges our understanding of how exercise improves metabolic control in human muscle. Mitochondrial respiratory control by ADP (Kmapp ) is viewed as a critical regulator of muscle energy homeostasis. However, acute exercise increases, decreases or has no effect on Kmapp in human muscle, whereas chronic exercise surprisingly decreases sensitivity despite greater mitochondrial content. We hypothesized that modelling in vivo mitochondrial creatine kinase (mtCK)-dependent phosphate-shuttling conditions in vitro would reveal increased sensitivity (lower Kmapp ) after acute and chronic exercise. The Kmapp was determined in vitro with 20 mm Cr (+Cr), 0 mm Cr (-Cr) or 'in vivo exercising' 20 mm Cr/2.4 mm PCr (Cr:PCr) on vastus lateralis biopsies sampled from 11 men before, immediately after and 3 h after exercise on the first, fifth and ninth sessions over 3 weeks. Dynamic responses to acute exercise occurred throughout training, whereby the first session did not change Kmapp with in vivo Cr:PCr despite increases in -Cr. The fifth session decreased sensitivity with Cr:PCr or +Cr despite no change in -Cr. Chronic exercise increased sensitivity ±Cr in association with increased electron transport chain content (+33-62% complexes I-V), supporting classic proposals that link increased sensitivity to oxidative capacity. However, in vivo Cr:PCr reveals a perplexing decreased sensitivity, contrasting the increases seen ±Cr. Functional responses occurred without changes in fibre type or proteins regulating mitochondrial-cytosolic energy exchange (mtCK, VDAC and ANT). Despite the dynamic responses seen with ±Cr, modelling in vivo phosphate-shuttling conditions in vitro reveals that ADP sensitivity is unchanged after high-intensity exercise and is decreased after training. These findings challenge our understanding of how exercise regulates skeletal muscle energy homeostasis. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Effect of creatine supplementation and resistance-exercise training on muscle insulin-like growth factor in young adults.

PubMed

Burke, Darren G; Candow, Darren G; Chilibeck, Philip D; MacNeil, Lauren G; Roy, Brian D; Tarnopolsky, Mark A; Ziegenfuss, Tim

2008-08-01

The purpose of this study was to compare changes in muscle insulin-like growth factor-I (IGF-I) content resulting from resistance-exercise training (RET) and creatine supplementation (CR). Male (n=24) and female (n=18) participants with minimal resistance-exercise-training experience (=1 year) who were participating in at least 30 min of structured physical activity (i.e., walking, jogging, cycling) 3-5 x/wk volunteered for the study. Participants were randomly assigned in blocks (gender) to supplement with creatine (CR: 0.25 g/kg lean-tissue mass for 7 days; 0.06 g/kg lean-tissue mass for 49 days; n=22, 12 males, 10 female) or isocaloric placebo (PL: n=20, 12 male, 8 female) and engage in a whole-body RET program for 8 wk. Eighteen participants were classified as vegetarian (lacto-ovo or vegan; CR: 5 male, 5 female; PL: 3 male, 5 female). Muscle biopsies (vastus lateralis) were taken before and after the intervention and analyzed for IGF-I using standard immunohistochemical procedures. Stained muscle cross-sections were examined microscopically and IGF-I content quantified using image-analysis software. Results showed that RET increased intramuscular IGF-I content by 67%, with greater accumulation from CR (+78%) than PL (+54%; p=.06). There were no differences in IGF-I between vegetarians and nonvegetarians. These findings indicate that creatine supplementation during resistance-exercise training increases intramuscular IGF-I concentration in healthy men and women, independent of habitual dietary routine.

Insular cortex metabolite changes in obstructive sleep apnea.

PubMed

Yadav, Santosh K; Kumar, Rajesh; Macey, Paul M; Woo, Mary A; Yan-Go, Frisca L; Harper, Ronald M

2014-05-01

Adults with obstructive sleep apnea (OSA) show significant autonomic and neuropsychologic deficits, which may derive from damage to insular regions that serve those functions. The aim was to assess glial and neuronal status from anterior insular metabolites in OSA versus controls, using proton magnetic resonance spectroscopy (PMRS), and thus to provide insights for neuroprotection against tissue changes, and to reduce injury consequences. Cross-sectional study. University-based medical center. Thirty-six patients with OSA, 53 controls. None. We performed PMRS in bilateral anterior insulae using a 3.0-Tesla magnetic resonance imaging scanner, calculated N-acetylaspartate/creatine (NAA/Cr), choline/creatine (Cho/Cr), myo-inositol/creatine (MI/Cr), and MI/NAA metabolite ratios, and examined daytime sleepiness (Epworth Sleepiness Scale, ESS), sleep quality (Pittsburgh Sleep Quality Index, PSQI), and neuropsychologic status (Beck Depression Inventory II [BDI-II] and Beck Anxiety Inventory [BAI]). Body mass index, BAI, BDI-II, PSQI, and ESS significantly differed between groups. NAA/ Cr ratios were significantly reduced bilaterally, and left-sided MI/Cr and MI/NAA ratios were increased in OSA over controls. Significant positive correlations emerged between left insular MI/Cr ratios and apnea-hypopnea index values, right insular Cho/Cr ratios and BDI-II and BAI scores, and negative correlations appeared between left insular NAA/Cr ratios and PSQI scores and between right-side MI/Cr ratios and baseline and nadir change in O2 saturation. Adults with obstructive sleep apnea showed bilaterally reduced N-acetylaspartate and left-side increased myo-inositol anterior insular metabolites, indicating neuronal damage and increased glial activation, respectively, which may contribute to abnormal autonomic and neuropsychologic functions in the condition. The activated glial status likely indicates increased inflammatory action that may induce more neuronal injury, and suggests separate approaches for glial and neuronal protection.

Guanidinoacetate and creatine plus creatinine assessment in physiologic fluids: an effective diagnostic tool for the biochemical diagnosis of arginine:glycine amidinotransferase and guanidinoacetate methyltransferase deficiencies.

PubMed

Carducci, Claudia; Birarelli, Maurizio; Leuzzi, Vincenzo; Carducci, Carla; Battini, Roberta; Cioni, Giovanni; Antonozzi, Italo

2002-10-01

Disorders of creatine metabolism arise from genetic alterations of arginine:glycine amidinotransferase (AGAT), guanidinoacetate methyltransferase (GAMT), and the creatine transporter. We developed a strategy for the detection of AGAT and GAMT defects by measurement of guanidinoacetate (GAA) and creatine plus creatinine (Cr+Crn) in biological fluids. Three patients with AGAT deficiency from the same pedigree and their eight relatives, as well as a patient affected by a GAMT defect and his parents were analyzed by a new HPLC procedure in comparison with 90 controls. The method, which uses precolumn derivatization with benzoin, separation with a reversed-phase column, and fluorescence detection, has shown good precision and sensitivity and requires minimal sample handling. In the three AGAT patients, plasma GAA was 0.01-0.04 micro mol/L [mean (SD) for neurologically normal controls was 1.16 (0.59) micromol/L], Cr+Crn was 15-29 micro mol/L [reference limit in our laboratory, 79 (38) micromol/L]. Urinary GAA was 2.4-5.8 micro mol/L [reference, 311 (191) micromol/L], and Cr+Crn was 2.1-3.3 mmol/L [reference, 9.9 (4.1) mmol/L]. We found a smaller decrease in GAA and Cr+Crn in some carriers of an AGAT defect. In the patient with GAMT deficiency, plasma and urine GAA was increased (18.6 and 1783 micromol/L, respectively), and Cr+Crn was decreased in plasma (10.7 micromol/L) and urine (2.1 mmol/L). GAA was increased in the parents' plasmas and in the mother's urine. The assessment of GAA is a new tool for the detection of both GAMT and AGAT deficiencies.

Metabolic and Structural Imaging at 7 Tesla After Repetitive Mild Traumatic Brain Injury in Immature Rats.

PubMed

Fidan, Emin; Foley, Lesley M; New, Lee Ann; Alexander, Henry; Kochanek, Patrick M; Hitchens, T Kevin; Bayır, Hülya

2018-01-01

Mild traumatic brain injury (mTBI) in children is a common and serious public health problem. Traditional neuroimaging findings in children who sustain mTBI are often normal, putting them at risk for repeated mTBI (rmTBI). There is a need for more sensitive imaging techniques capable of detecting subtle neurophysiological alterations after injury. We examined neurochemical and white matter changes using diffusion tensor imaging of the whole brain and proton magnetic resonance spectroscopy of the hippocampi at 7 Tesla in 18-day-old male rats at 7 days after mTBI and rmTBI. Traumatic axonal injury was assessed by beta-amyloid precursor protein accumulation using immunohistochemistry. A significant decrease in fractional anisotropy and increase in axial and radial diffusivity were observed in several brain regions, especially in white matter regions, after a single mTBI versus sham and more prominently after rmTBI. In addition, we observed accumulation of beta-amyloid precursor protein in the external capsule after mTBI and rmTBI. mTBI and rmTBI reduced the N-acetylaspartate/creatine ratio (NAA/Cr) and increased the myoinositol/creatine ratio (Ins/Cr) versus sham. rmTBI exacerbated the reduction in NAA/Cr versus mTBI. The choline/creatine (Cho/Cr) and (lipid/Macro Molecule 1)/creatine (Lip/Cr) ratios were also decreased after rmTBI versus sham. Diffusion tensor imaging findings along with the decrease in Cho and Lip after rmTBI may reflect damage to axonal membrane. NAA and Ins are altered at 7 days after mTBI and rmTBI likely reflecting neuro-axonal damage and glial response, respectively. These findings may be relevant to understanding the extent of disability following mTBI and rmTBI in the immature brain and may identify possible therapeutic targets.

Exercise hyperthermia as a factor limiting physical performance - Temperature effect on muscle metabolism

NASA Technical Reports Server (NTRS)

Kozlowski, S.; Brzezinska, Z.; Kruk, B.; Kaciuba-Uscilko, H.; Greenleaf, J. E.

1985-01-01

The effect of trunk cooling on the muscle contents of ATP, ADP, AMP, creatine phosphate (CrP), and creatine, as well as of glycogen, some glycolytic intermediates, pyruvate, and lactate were assessed in 11 fasted dogs exercised at 20 C on treadmill to exhaustion. Without cooling, dogs were able to run 57 min, and their rectal (Tre) and muscle (Tm) temperatures increased to 41.8 and 43.0 C, respectively. Cooling with ice packs prolonged the ability to run by 45 percent, and resulted in lower Tre (by 1.1 C) and Tm (by 1.2 C). Depletion of muscle content of total high-energy phosphates (ATP + CrP) and glycogen, and increases in contents of AMP, pyruvate, and lactate were lower in cooled dogs than in non-cooled dogs. The muscle content of lactiate correlated positively with TM. These results indicate that hypothermia accelerates glycolysis, and shifts the equilibrium between high- and low-energy phosphates in favor of the latter. The adverse effect of hypothermia on muscle metabolism may be relevant to the limitation of endurance.

Creatine transporter deficiency: prevalence among patients with mental retardation and pitfalls in metabolite screening.

PubMed

Arias, Angela; Corbella, Marc; Fons, Carmen; Sempere, Angela; García-Villoria, Judit; Ormazabal, Aida; Poo, Pilar; Pineda, Mercé; Vilaseca, María Antonia; Campistol, Jaume; Briones, Paz; Pàmpols, Teresa; Salomons, Gajja S; Ribes, Antonia; Artuch, Rafael

2007-11-01

To report the prevalence of creatine transporter deficiency in males with mental retardation and to study whether a protein-rich food intake might be a potential diagnostic pitfall. We determined creatine/creatinine ratio in urine samples from 1600 unrelated male patients with mental retardation and/or autism. Urine creatine was analyzed by HPLC-MS/MS. Thirty-three of 1600 cases showed increased urine creatine/creatinine ratio. Four out of these thirty-three cases were definitively diagnosed with creatine transporter deficiency, while the other 29 were false positive results. Significantly higher values were observed for urine Cr/Crn ratio in healthy volunteers after a meal based on beef or oily fish as compared to eggs, pasta or salad (Wilcoxon test: p<0.005). False positive results may be observed in biochemical screening for creatine transporter deficiency, and they may be due to intake of meals rich in creatine prior to urine samples analysis.

Diminution of Oxidative Damage to Human Erythrocytes and Lymphocytes by Creatine: Possible Role of Creatine in Blood.

PubMed

Qasim, Neha; Mahmood, Riaz

2015-01-01

Creatine (Cr) is naturally produced in the body and stored in muscles where it is involved in energy generation. It is widely used, especially by athletes, as a staple supplement for improving physical performance. Recent reports have shown that Cr displays antioxidant activity which could explain its beneficial cellular effects. We have evaluated the ability of Cr to protect human erythrocytes and lymphocytes against oxidative damage. Erythrocytes were challenged with model oxidants, 2, 2'-azobis(2-amidinopropane) dihydrochloride (AAPH) and hydrogen peroxide (H2O2) in the presence and absence of Cr. Incubation of erythrocytes with oxidant alone increased hemolysis, methemoglobin levels, lipid peroxidation and protein carbonyl content. This was accompanied by decrease in glutathione levels. Antioxidant enzymes and antioxidant power of the cell were compromised while the activity of membrane bound enzyme was lowered. This suggests induction of oxidative stress in erythrocytes by AAPH and H2O2. However, Cr protected the erythrocytes by ameliorating the AAPH and H2O2 induced changes in these parameters. This protective effect was confirmed by electron microscopic analysis which showed that oxidant-induced cell damage was attenuated by Cr. No cellular alterations were induced by Cr alone even at 20 mM, the highest concentration used. Creatinine, a by-product of Cr metabolism, was also shown to exert protective effects, although it was slightly less effective than Cr. Human lymphocytes were similarly treated with H2O2 in absence and presence of different concentrations of Cr. Lymphocytes incubated with oxidant alone had alterations in various biochemical and antioxidant parameters including decrease in cell viability and induction of DNA damage. The presence of Cr attenuated all these H2O2-induced changes in lymphocytes. Thus, Cr can function as a blood antioxidant, protecting cells from oxidative damage, genotoxicity and can potentially increase their lifespan.

Diminution of Oxidative Damage to Human Erythrocytes and Lymphocytes by Creatine: Possible Role of Creatine in Blood

PubMed Central

Qasim, Neha; Mahmood, Riaz

2015-01-01

Creatine (Cr) is naturally produced in the body and stored in muscles where it is involved in energy generation. It is widely used, especially by athletes, as a staple supplement for improving physical performance. Recent reports have shown that Cr displays antioxidant activity which could explain its beneficial cellular effects. We have evaluated the ability of Cr to protect human erythrocytes and lymphocytes against oxidative damage. Erythrocytes were challenged with model oxidants, 2, 2'-azobis(2-amidinopropane) dihydrochloride (AAPH) and hydrogen peroxide (H2O2) in the presence and absence of Cr. Incubation of erythrocytes with oxidant alone increased hemolysis, methemoglobin levels, lipid peroxidation and protein carbonyl content. This was accompanied by decrease in glutathione levels. Antioxidant enzymes and antioxidant power of the cell were compromised while the activity of membrane bound enzyme was lowered. This suggests induction of oxidative stress in erythrocytes by AAPH and H2O2. However, Cr protected the erythrocytes by ameliorating the AAPH and H2O2 induced changes in these parameters. This protective effect was confirmed by electron microscopic analysis which showed that oxidant-induced cell damage was attenuated by Cr. No cellular alterations were induced by Cr alone even at 20 mM, the highest concentration used. Creatinine, a by-product of Cr metabolism, was also shown to exert protective effects, although it was slightly less effective than Cr. Human lymphocytes were similarly treated with H2O2 in absence and presence of different concentrations of Cr. Lymphocytes incubated with oxidant alone had alterations in various biochemical and antioxidant parameters including decrease in cell viability and induction of DNA damage. The presence of Cr attenuated all these H2O2-induced changes in lymphocytes. Thus, Cr can function as a blood antioxidant, protecting cells from oxidative damage, genotoxicity and can potentially increase their lifespan. PMID:26555819

Energizing eukaryotic cell-free protein synthesis with glucose metabolism.

PubMed

Anderson, Mark J; Stark, Jessica C; Hodgman, C Eric; Jewett, Michael C

2015-07-08

Eukaryotic cell-free protein synthesis (CFPS) is limited by the dependence on costly high-energy phosphate compounds and exogenous enzymes to power protein synthesis (e.g., creatine phosphate and creatine kinase, CrP/CrK). Here, we report the ability to use glucose as a secondary energy substrate to regenerate ATP in a Saccharomyces cerevisiae crude extract CFPS platform. We observed synthesis of 3.64±0.35 μg mL(-1) active luciferase in batch reactions with 16 mM glucose and 25 mM phosphate, resulting in a 16% increase in relative protein yield (μg protein/$ reagents) compared to the CrP/CrK system. Our demonstration provides the foundation for development of cost-effective eukaryotic CFPS platforms. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Dose-response effects of oral guanidinoacetic acid on serum creatine, homocysteine and B vitamins levels.

PubMed

Ostojic, Sergej M; Stojanovic, Marko; Drid, Patrik; Hoffman, Jay R

2014-12-01

Guanidinoacetic acid (GAA) is an intermediate in the biosynthesis of creatine (Cr), yet its use in human nutrition is limited due to a lack of a clear understanding of its' dose-response effect. Thus, the purpose of this study was to investigate the effect of three different dosages of GAA (1.2, 2.4 and 4.8 g/day) administered for 6 weeks on serum and urinary variables related to GAA metabolism. Forty-eight healthy volunteers participated in the randomized, placebo-controlled, double-blind, repeated-measure study. At baseline, after 1, 2, 4 and 6 weeks, participants provided both fasting blood samples and 24-h urine. GAA intervention significantly increased serum and urinary GAA, Cr and creatinine as compared to placebo (P < 0.05). Differences were found for serum GAA and Cr responses between the three GAA dosages, with high-dose GAA resulting in a greater increase (P < 0.05) in the plasma concentration of both variables as compared to other GAA dosages. In GAA groups, fasting plasma total homocysteine (T-Hcy) increased by 3.5 μmol/L on average at post-administration, yet no dose-response differences were found between trials. Serum B vitamins were not affected by either placebo or GAA intervention (P > 0.05). Results indicate that low-to-high dosages of exogenous GAA can increase serum concentrations of Cr and T-Hcy while not depleting the B vitamins pool available for remethylation of homocysteine. ClinicalTrials.gov, identification number NCT01133899.

In the absence of phosphate shuttling, exercise reveals the in vivo importance of creatine-independent mitochondrial ADP transport.

PubMed

Miotto, Paula M; Holloway, Graham P

2016-09-15

The transport of cytosolic adenosine diphosphate (ADP) into the mitochondria is a major control point in metabolic homeostasis, as ADP concentrations directly affect glycolytic flux and oxidative phosphorylation rates within mitochondria. A large contributor to the efficiency of this process is thought to involve phosphocreatine (PCr)/Creatine (Cr) shuttling through mitochondrial creatine kinase (Mi-CK), whereas the biological importance of alterations in Cr-independent ADP transport during exercise remains unknown. Therefore, we utilized an Mi-CK knockout (KO) model to determine whether in vivo Cr-independent mechanisms are biologically important for sustaining energy homeostasis during exercise. Ablating Mi-CK did not alter exercise tolerance, as the time to volitional fatigue was similar between wild-type (WT) and KO mice at various exercise intensities. In addition, skeletal muscle metabolic profiles after exercise, including glycogen, PCr/Cr ratios, free ADP/adenosine monophosphate (AMP), and lactate, were similar between genotypes. While these data suggest that the absence of PCr/Cr shuttling is not detrimental to maintaining energy homeostasis during exercise, KO mice displayed a dramatic increase in Cr-independent mitochondrial ADP sensitivity after exercise. Specifically, whereas mitochondrial ADP sensitivity decreased with exercise in WT mice, in stark contrast, exercise increased mitochondrial Cr-independent ADP sensitivity in KO mice. As a result, the apparent ADP Km was 50% lower in KO mice after exercise, suggesting that in vivo activation of voltage-dependent anion channel (VDAC)/adenine nucleotide translocase (ANT) can support mitochondrial ADP transport. Altogether, we provide insight that Cr-independent ADP transport mechanisms are biologically important for regulating ADP sensitivity during exercise, while highlighting complex regulation and the plasticity of the VDAC/ANT axis to support adenosine triphosphate demand. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Effects of chromium and chromium + vitamin C combination on metabolic, oxidative, and fear responses of broilers transported under summer conditions

NASA Astrophysics Data System (ADS)

Perai, A. H.; Kermanshahi, H.; Moghaddam, H. Nassiri; Zarban, A.

2015-04-01

A total of 240 female broilers (42 days old) were randomly assigned to four groups with six replicates and fed either a basal diet (two control groups) or a basal diet supplemented with either 1,200 μg Cr+3 from chromium (Cr) methionine/kg (Cr group) or 1,200 μg Cr+3 from Cr methionine plus 800 mg vitamin C (Vit C)/kg of diet (Cr + Vit C group). After 7 days on the dietary treatment, all groups except one of the controls were transported for 3 h under the summer conditions. Performance parameters were not influenced by dietary treatments. The plasma concentrations of insulin, triiodothyronine, triglyceride, and the ratio of triiodothyronine/thyroxin were decreased and the ratio of glucose/insulin was increased due to transport process. Road transportation also increased the plasma concentrations of protein, cholesterol, aspartate aminotransferase, and creatine kinase and decreased the concentration of low-density lipoprotein cholesterol in the Cr + Vit C group. The pretransport concentrations of insulin and triiodothyronine were highest in the Cr + Vit C group. The concentration of phosphorous was lower in the Cr group than that in the other groups after transport. No significant effects of dietary treatments were observed on the other biochemical parameters. Transport increased malondialdehyde concentration in the control group and did not change plasma total antioxidant capacity and erythrocyte glutathione peroxidase activity. Either in combination or alone, Cr increased plasma total antioxidant capacity (before transport P ≤ 0.05, after transport P = 0.07) but did not affect the concentration of malondialdehyde and activity of glutathione peroxidase. The duration of tonic immobility (TI) was similar between nontransported control chicks and transported chicks without any supplements. Pretreatment with Cr + Vit C significantly reduced the duration of TI.

Insular Cortex Metabolite Changes in Obstructive Sleep Apnea

PubMed Central

Yadav, Santosh K.; Kumar, Rajesh; Macey, Paul M.; Woo, Mary A.; Yan-Go, Frisca L.; Harper, Ronald M.

2014-01-01

Study Objective: Adults with obstructive sleep apnea (OSA) show significant autonomic and neuropsychologic deficits, which may derive from damage to insular regions that serve those functions. The aim was to assess glial and neuronal status from anterior insular metabolites in OSA versus controls, using proton magnetic resonance spectroscopy (PMRS), and thus to provide insights for neuroprotection against tissue changes, and to reduce injury consequences. Design: Cross-sectional study. Setting: University-based medical center. Participants: Thirty-six patients with OSA, 53 controls. Interventions: None. Measurements and Results: We performed PMRS in bilateral anterior insulae using a 3.0-Tesla magnetic resonance imaging scanner, calculated N-acetylaspartate/creatine (NAA/Cr), choline/creatine (Cho/Cr), myo-inositol/creatine (MI/Cr), and MI/NAA metabolite ratios, and examined daytime sleepiness (Epworth Sleepiness Scale, ESS), sleep quality (Pittsburgh Sleep Quality Index, PSQI), and neuropsychologic status (Beck Depression Inventory II [BDI-II] and Beck Anxiety Inventory [BAI]). Body mass index, BAI, BDI-II, PSQI, and ESS significantly differed between groups. NAA/ Cr ratios were significantly reduced bilaterally, and left-sided MI/Cr and MI/NAA ratios were increased in OSA over controls. Significant positive correlations emerged between left insular MI/Cr ratios and apnea-hypopnea index values, right insular Cho/Cr ratios and BDI-II and BAI scores, and negative correlations appeared between left insular NAA/Cr ratios and PSQI scores and between right-side MI/Cr ratios and baseline and nadir change in O2 saturation. Conclusions: Adults with obstructive sleep apnea showed bilaterally reduced N-acetylaspartate and left-side increased myo-inositol anterior insular metabolites, indicating neuronal damage and increased glial activation, respectively, which may contribute to abnormal autonomic and neuropsychologic functions in the condition. The activated glial status likely indicates increased inflammatory action that may induce more neuronal injury, and suggests separate approaches for glial and neuronal protection. Citation: Yadav SK, Kumar R, Macey PM, Woo MA, Yan-Go FL, Harper RM. Insular cortex metabolite changes in obstructive sleep apnea. SLEEP 2014;37(5):951-958. PMID:24790274

Development of an HPLC method for determination of metabolic compounds in myocardial tissue.

PubMed

Volonté, M G; Yuln, G; Quiroga, P; Consolini, A E

2004-05-28

The determination of adenine nucleotides and creatine compounds has great importance in the characterization of ischemic myocardial injury and post-ischemic recovery. It was developed by an HPLC method for the quantification of creatine (Cr), creatine phosphate (CrP), hypoxanthine (HX), AMP, adenosine (Ad), ADP and ATP in isolated perfused rat hearts. The chromatographic conditions were: RP 18 column; mobile phase composed by KH(2)PO(4) (215 mM), tetrabutylammonium hydrogen sulfate (2.3mM), acetonitrile (4%) and KOH (1M 0.4%); flow rate 1 ml min(-1); temperature 25 degrees C; injection volume 20 microl; detection at 220 nm and height peak (HP) as the integration parameter. The method was validated by means of linearity and sensitivity evaluations, using calibration curves done with five concentration levels of each compound. The limits of quantification (LOQ) were also determined. The system precision was calculated as the coefficient of variation for five injections for each compound tested. The purity of the peaks was established using enzymatic peak shift analysis with hexokinase and creatine kinase and also comparing HP at various wavelengths. Frozen hearts were homogenized with a mechanical homogenizer for 3 min at 0 degrees C added with 5 ml of 0.4N HCLO(4). After precipitation with 0.8 ml of 2M KOH the extract was shaked for 2 min and later centrifuged at 0 degrees C for 10 min. The supernatant was kept on ice, filtrated and injected into the HPLC system. The results show that the method for the determination of Cr, CrP, HX, AMP, Ad, ADP and ATP by HPLC here described has good linearity, LOQ, precision, specificity and is simple and rapid to perform.

Creatine supplementation prevents acute strength loss induced by concurrent exercise.

PubMed

de Salles Painelli, Vítor; Alves, Victor Tavares; Ugrinowitsch, Carlos; Benatti, Fabiana Braga; Artioli, Guilherme Giannini; Lancha, Antonio Herbert; Gualano, Bruno; Roschel, Hamilton

2014-08-01

To investigate the effect of creatine (CR) supplementation on the acute interference induced by aerobic exercise on subsequent maximum dynamic strength (1RM) and strength endurance (SE, total number of repetitions) performance. Thirty-two recreationally strength-trained men were submitted to a graded exercise test to determine maximal oxygen consumption (VO2max: 41.56 ± 5.24 ml kg(-1) min(-1)), anaerobic threshold velocity (ATv: 8.3 ± 1.18 km h(-1)), and baseline performance (control) on the 1RM and SE (4 × 80 % 1RM to failure) tests. After the control tests, participants were randomly assigned to either a CR (20 g day(-1) for 7 days followed by 5 g day(-1) throughout the study) or a placebo (PL-dextrose) group, and then completed 4 experimental sessions, consisting of a 5-km run on a treadmill either continuously (90 % ATv) or intermittently (1:1 min at vVO2max) followed by either a leg- or bench-press SE/1RM test. CR was able to maintain the leg-press SE performance after the intermittent aerobic exercise when compared with C (p > 0.05). On the other hand, the PL group showed a significant decrease in leg-press SE (p ≤ 0.05). CR supplementation significantly increased bench-press SE after both aerobic exercise modes, while the bench-press SE was not affected by either mode of aerobic exercise in the PL group. Although small increases in 1RM were observed after either continuous (bench press and leg press) or intermittent (bench press) aerobic exercise in the CR group, they were within the range of variability of the measurement. The PL group only maintained their 1RM. In conclusion, the acute interference effect on strength performance observed in concurrent exercise may be counteracted by CR supplementation.

Reduced N-acetylaspartate to creatine ratio in the posterior cingulate correlates with cognition in Alzheimer's disease following four months of rivastigmine treatment.

PubMed

Penner, Jacob; Wells, Jennie L; Borrie, Michael J; Woolmore-Goodwin, Sarah M; Bartha, Robert

2015-01-01

To determine whether 4 months of rivastigmine treatment would result in metabolic changes and whether metabolic changes correlate with changes in cognition in people with Alzheimer's disease (AD). Magnetic resonance spectra were acquired from the posterior cingulate cortex of subjects with AD at 3 T. Magnetic resonance imaging scans and cognitive tests were performed before and 4 months after the beginning of the treatment. Metabolite concentrations were quantified and used to calculate the metabolite ratios. On average, the N-acetylaspartate/creatine (NAA/Cr) ratio decreased by 12.7% following 4 months of rivastigmine treatment, but changes in the NAA/Cr ratio correlated positively with changes in Mini-Mental State Examination scores. This positive correlation between changes in NAA/Cr and changes in cognitive performance suggests that the NAA/Cr ratio could be an objective indicator of a response to rivastigmine treatment. © 2014 S. Karger AG, Basel

Creatine feeding does not enhance intramyocellular glycogen concentration during carbohydrate loading: an in vivo study by 31P- and 13C-MRS.

PubMed

Rico-Sanz, J; Zehnder, M; Buchli, R; Kühne, G; Boutellier, U

2008-09-01

The main aim of this study was to examine the hypothesis that creatine (Cr) feeding enhances myocellular glycogen storage in humans undergoing carbohydrate loading. Twenty trained male subjects were randomly assigned to have their diets supplemented daily with 252 g of glucose polymer (GP) and either 21 g of Cr (CR-GP, n = 10) or placebo (PL-GP, n = 10) for 5 days. Changes in resting myocellular glycogen and phosphocreatine (PCr) were determined with Magnetic Resonance Spectroscopy (13C- and 31P-MRS, respectively). After CR-GP, the levels of intramyocellular glycogen increased from 147 +/- 13 (standard error) mmol x (kg wet weight(-1)) to 172 +/- 13 m mol x (kg wet weight)(-1), while it increased from 134 +/- 17 mmol x (kg wet weight)(-) to 182 +/- 17 mmol x (kg wet weight)(-1) after PL-GP; the increments in intramyocellular glycogen concentrations were not statistically different. The increment in the PCr/ATP ratio after CR-GP (+ 0.20 +/- 0.12) was significantly different compared to PL-GP (- 0.34 +/- 0.16) (p < 0.05). The present results do not support the hypothesis that Cr loading increases muscle glycogen storage.

An MRspec database query and visualization engine with applications as a clinical diagnostic and research tool.

PubMed

Miscevic, Filip; Foong, Justin; Schmitt, Benjamin; Blaser, Susan; Brudno, Michael; Schulze, Andreas

2016-12-01

Proton magnetic resonance spectroscopy (MRspec), one of the very few techniques for in vivo assessment of neuro-metabolic profiles, is often complicated by lack of standard population norms and paucity of computational tools. 7035 scans and clinical information from 4430 pediatric patients were collected from 2008 to 2014. Scans were conducted using a 1.5T (n=3664) or 3T scanner (n=3371), and with either a long (144ms, n=5559) or short echo time (35ms, n=1476). 3055 of these scans were localized in the basal ganglia (BG), 1211 in parieto-occipital white matter (WM). 34 metabolites were quantified using LCModel. A web application using MySQL, Python and Flask was developed to facilitate the exploration of the data set. Already piloting the application revealed numerous insights. (1), N-acetylaspartate (NAA) increased throughout all ages. During early infancy, total choline was highly varied and myo-inositol demonstrated a downward trend. (2), Total creatine (tCr) and creatine increased throughout childhood and adolescence, though phosphocreatine (PCr) remained constant beyond 200days. (3), tCr was higher in BG than WM. (4), No obvious gender-related differences were observed. (5), Field strength affects quantification using LCModel for some metabolites, most prominently for tCr and total NAA. (6), Outlier analysis identified patients treated with vigabatrin through elevated γ-aminobutyrate, and patients with Klippel-Feil syndrome, Leigh disease and L2-hydroxyglutaric aciduria through low choline in BG. We have established the largest MRSpec database and developed a robust and flexible computational tool for facilitating the exploration of vast metabolite datasets that proved its value for discovering neurochemical trends for clinical diagnosis, treatment monitoring, and research. Open access will lead to its widespread use, improving the diagnostic yield and contributing to better understanding of metabolic processes and conditions in the brain. Copyright © 2016 Elsevier Inc. All rights reserved.

No effect of creatine supplementation on oxidative stress and cardiovascular parameters in spontaneously hypertensive rats

PubMed Central

2012-01-01

Background Exacerbated oxidative stress is thought to be a mediator of arterial hypertension. It has been postulated that creatine (Cr) could act as an antioxidant agent preventing increased oxidative stress. The aim of this study was to investigate the effects of nine weeks of Cr or placebo supplementation on oxidative stress and cardiovascular parameters in spontaneously hypertensive rats (SHR). Findings Lipid hydroperoxidation, one important oxidative stress marker, remained unchanged in the coronary artery (Cr: 12.6 ± 1.5 vs. Pl: 12.2 ± 1.7 nmol·mg-1; p = 0.87), heart (Cr: 11.5 ± 1.8 vs. Pl: 14.6 ± 1.1 nmol·mg-1; p = 0.15), plasma (Cr: 67.7 ± 9.1 vs. Pl: 56.0 ± 3.2 nmol·mg-1; p = 0.19), plantaris (Cr: 10.0 ± 0.8 vs. Pl: 9.0 ± 0.8 nmol·mg-1; p = 0.40), and EDL muscle (Cr: 14.9 ± 1.4 vs. Pl: 17.2 ± 1.5 nmol·mg-1; p = 0.30). Additionally, Cr supplementation affected neither arterial blood pressure nor heart structure in SHR (p > 0.05). Conclusions Using a well-known experimental model of systemic arterial hypertension, this study did not confirm the possible therapeutic effects of Cr supplementation on oxidative stress and cardiovascular dysfunction associated with arterial hypertension. PMID:22480293

No effect of creatine supplementation on oxidative stress and cardiovascular parameters in spontaneously hypertensive rats.

PubMed

Alves, Christiano Rr; Murai, Igor H; Ramona, Pamella; Nicastro, Humberto; Bechara, Luiz Rg; Lancha, Antonio H; Brum, Patrícia C; Irigoyen, Maria C; Gualano, Bruno

2012-04-05

Exacerbated oxidative stress is thought to be a mediator of arterial hypertension. It has been postulated that creatine (Cr) could act as an antioxidant agent preventing increased oxidative stress. The aim of this study was to investigate the effects of nine weeks of Cr or placebo supplementation on oxidative stress and cardiovascular parameters in spontaneously hypertensive rats (SHR). Lipid hydroperoxidation, one important oxidative stress marker, remained unchanged in the coronary artery (Cr: 12.6 ± 1.5 vs. Pl: 12.2 ± 1.7 nmol·mg-1; p = 0.87), heart (Cr: 11.5 ± 1.8 vs. Pl: 14.6 ± 1.1 nmol·mg-1; p = 0.15), plasma (Cr: 67.7 ± 9.1 vs. Pl: 56.0 ± 3.2 nmol·mg-1; p = 0.19), plantaris (Cr: 10.0 ± 0.8 vs. Pl: 9.0 ± 0.8 nmol·mg-1; p = 0.40), and EDL muscle (Cr: 14.9 ± 1.4 vs. Pl: 17.2 ± 1.5 nmol·mg-1; p = 0.30). Additionally, Cr supplementation affected neither arterial blood pressure nor heart structure in SHR (p > 0.05). Using a well-known experimental model of systemic arterial hypertension, this study did not confirm the possible therapeutic effects of Cr supplementation on oxidative stress and cardiovascular dysfunction associated with arterial hypertension.

Brain proton magnetic resonance spectroscopy for hepatic encephalopathy

NASA Astrophysics Data System (ADS)

Ong, Chin-Sing; McConnell, James R.; Chu, Wei-Kom

1993-08-01

Liver failure can induce gradations of encephalopathy from mild to stupor to deep coma. The objective of this study is to investigate and quantify the variation of biochemical compounds in the brain in patients with liver failure and encephalopathy, through the use of water- suppressed, localized in-vivo Proton Magnetic Resonance Spectroscopy (HMRS). The spectral parameters of the compounds quantitated are: N-Acetyl Aspartate (NAA) to Creatine (Cr) ratio, Choline (Cho) to Creatine ratio, Inositol (Ins) to Creatine ratio and Glutamine-Glutamate Amino Acid (AA) to Creatine ratio. The study group consisted of twelve patients with proven advanced chronic liver failure and symptoms of encephalopathy. Comparison has been done with results obtained from five normal subjects without any evidence of encephalopathy or liver diseases.

The effects of creatine and glycerol hyperhydration on running economy in well trained endurance runners

PubMed Central

2011-01-01

Background Ingestion of creatine (Cr) and glycerol (Gly) has been reported to be an effective method in expanding water compartments within the human body, attenuating the rise in heart rate (HR) and core temperature (Tcore) during exercise in the heat. Despite these positive effects, a substantial water retention could potentially impair endurance performance through increasing body mass (BM) and consequently impacting negatively on running economy (RE). The objective of the present study was to investigate the effects of a combined Cr and Gly supplementation on thermoregulatory and cardiovascular responses and RE during running for 30 min at speed corresponding to 60% of maximal oxygen uptake (V˙O2max) in hot and cool conditions. Methods Cr·H2O (11.4 g), Gly (1 g·kg-1 BM) and Glucose polymer (75 g) were administered twice daily to 15 male endurance runners during a 7-day period. Exercise trials were conducted pre- and post-supplementation at 10 and 35°C and 70% relative humidity. Results BM and total body water increased by 0.90 ± 0.40 kg (P < 0.01; mean ± SD) and 0.71 ± 0.42 L (P < 0.01), respectively following supplementation. Despite the significant increase in BM, supplementation had no effect on V˙O2 and therefore RE. Both HR and Tcore were attenuated significantly after supplementation (P < 0.05, for both). Nevertheless, thermal comfort and rating of perceived exertion was not significantly different between pre- and post-supplementation. Similarly, no significant differences were found in sweat loss, serum osmolality, blood lactate and in plasma volume changes between pre- and post-supplementation. Conclusions Combining Cr and Gly is effective in reducing thermal and cardiovascular strain during exercise in the heat without negatively impacting on RE. PMID:22176668

Creatine supplementation reduces sleep need and homeostatic sleep pressure in rats.

PubMed

Dworak, Markus; Kim, Tae; Mccarley, Robert W; Basheer, Radhika

2017-06-01

Sleep has been postulated to promote brain energy restoration. It is as yet unknown if increasing the energy availability within the brain reduces sleep need. The guanidine amino acid creatine (Cr) is a well-known energy booster in cellular energy homeostasis. Oral Cr-monohydrate supplementation (CS) increases exercise performance and has been shown to have substantial effects on cognitive performance, neuroprotection and circadian rhythms. The effect of CS on cellular high-energy molecules and sleep-wake behaviour is unclear. Here, we examined the sleep-wake behaviour and brain energy metabolism before and after 4-week-long oral administration of CS in the rat. CS decreased total sleep time and non-rapid eye movement (NREM) sleep significantly during the light (inactive) but not during the dark (active) period. NREM sleep and NREM delta activity were decreased significantly in CS rats after 6 h of sleep deprivation. Biochemical analysis of brain energy metabolites showed a tendency to increase in phosphocreatine after CS, while cellular adenosine triphosphate (ATP) level decreased. Microdialysis analysis showed that the sleep deprivation-induced increase in extracellular adenosine was attenuated after CS. These results suggest that CS reduces sleep need and homeostatic sleep pressure in rats, thereby indicating its potential in the treatment of sleep-related disorders. © 2017 European Sleep Research Society.

Metabolite ratios to assumed stable creatine level may confound the quantification of proton brain MR spectroscopy.

PubMed

Li, Belinda S Y; Wang, Hao; Gonen, Oded

2003-10-01

In localized brain proton MR spectroscopy ((1)H-MRS), metabolites' levels are often expressed as ratios, rather than as absolute concentrations. Frequently, their denominator is the creatine [Cr], which level is explicitly assumed to be stable in normal as well as in many pathologic states. The rationale is that ratios self-correct for imager and localization method differences, gain instabilities, regional susceptibility variations and partial volume effects. The implicit assumption is that these benefits are worth their cost(w)-(w) propagation of the individual variation of each of the ratio's components. To test this hypothesis, absolute levels of N-acetylaspartate [NAA], choline [Cho] and [Cr] were quantified in various regions of the brains of 8 volunteers, using 3-dimensional (3D) (1)H-MRS at 1.5 T. The results show that in over 50% of approximately 2000 voxels examined, [NAA]/[Cr] and [Cho]/[Cr] exhibited higher coefficients of variations (CV) than [NAA] and [Cho] individually. Furthermore, in approximately 33% of these voxels, the ratios' CVs exceeded even the combined constituents' CVs. Consequently, basing metabolite quantification on ratios and assuming stable [Cr] introduces more variability into (1)H-MRS than it prevents. Therefore, its cost exceeds the benefit.

Creatine Monohydrate Supplementation Does Not Augment Fitness, Performance, or Body Composition Adaptations in Response to Four Weeks of High-Intensity Interval Training in Young Females.

PubMed

Forbes, Scott C; Sletten, Nathan; Durrer, Cody; Myette-Côté, Étienne; Candow, D; Little, Jonathan P

2017-06-01

High-intensity interval training (HIIT) has been shown to improve cardiorespiratory fitness, performance, body composition, and insulin sensitivity. Creatine (Cr) supplementation may augment responses to HIIT, leading to even greater physiological adaptations. The purpose of this study was to determine the effects of 4 weeks of HIIT (three sessions/week) combined with Cr supplementation in recreationally active females. Seventeen females (age = 23 ± 4 yrs; BMI = 23.4 ± 2.4) were randomly assigned to either Cr (Cr; 0.3 g・kg -1 ・d -1 for 5 d followed by 0.1 g・kg -1 ・d -1 for 23 days; n = 9) or placebo (PLA; n = 8). Before and after the intervention, VO 2peak , ventilatory threshold (VT), time-trial performance, lean body mass and fat mass, and insulin sensitivity were assessed. HIIT improved VO 2peak (Cr = +10.2%; PLA = +8.8%), VT (Cr = +12.7%; PLA = +9.9%), and time-trial performance (Cr = -11.5%; PLA = -11.6%) with no differences between groups (time main effects, all p < .001). There were no changes over time for fat mass (Cr = -0.3%; PLA = +4.3%), whole-body lean mass (Cr = +0.5%; PLA = -0.9%), or insulin resistance (Cr = +3.9%; PLA = +18.7%). In conclusion, HIIT is an effective way to improve cardiorespiratory fitness, VT, and time-trial performance. The addition of Cr to HIIT did not augment improvements in cardiorespiratory fitness, performance or body composition in recreationally active females.

Effects of creatine and its analog, β-guanidinopropionic acid, on the differentiation of and nucleoli in myoblasts.

PubMed

Ohira, Yoshinobu; Matsuoka, Yoshikazu; Kawano, Fuminori; Ogura, Akihiko; Higo, Yoko; Ohira, Takashi; Terada, Masahiro; Oke, Yoshihiko; Nakai, Naoya

2011-01-01

The effects of supplementation with creatine (Cr) and its analog, β-guanidinopropionic acid (β-GPA), on the differentiation of myoblasts and the numbers of nucleoli were studied in C2C12 cells. The cells were cultured in differentiation medium for 4 d. Then Cr (1 mM) or β-GPA (1 mM) was added to the cells, and the mixture was cultured for an additional 2 d. Although the number of myotubes was not different among the groups, myotube diameters and nuclear numbers in myotubes were increased by Cr and β-GPA treatment respectively. The expression of differentiation marker proteins, myogenin, and the myosine heavy chain, was increased in the β-GPA group. Supplementation with β-GPA also increased the percentage of p21 (inhibitor for cell cycle progression)-positive myoblasts. Supplementation with Cr inhibited the decrease in nucleoli numbers, whereas β-GPA increased nucleolar sizes in the myotubes. These results suggest that β-GPA supplementation stimulated the differentiation of myoblasts into multi-nucleated myotubes through induction of p21 expression.

Evaluating metabolites in patients with major depressive disorder who received mindfulness-based cognitive therapy and healthy controls using short echo MRSI at 7 Tesla.

PubMed

Li, Yan; Jakary, Angela; Gillung, Erin; Eisendrath, Stuart; Nelson, Sarah J; Mukherjee, Pratik; Luks, Tracy

2016-06-01

Our aim was to evaluate differences in metabolite levels between unmedicated patients with major depressive disorder (MDD) and healthy controls, to assess changes in metabolites in patients after they completed an 8-week course of mindfulness-based cognitive therapy (MBCT), and to exam the correlation between metabolites and depression severity. Sixteen patients with MDD and ten age- and gender-matched healthy controls were studied using 3D short echo-time (20 ms) magnetic resonance spectroscopic imaging (MRSI) at 7 Tesla. Relative metabolite ratios were estimated in five regions of interest corresponding to insula, anterior cingulate cortex (ACC), caudate, putamen, and thalamus. In all cases, MBCT reduced severity of depression. The ratio of total choline-containing compounds/total creatine (tCr) in the right caudate was significantly increased compared to that in healthy controls, while ratios of N-acetyl aspartate (NAA)/tCr in the left ACC, myo-inositol/tCr in the right insula, and glutathione/tCr in the left putamen were significantly decreased. At baseline, the severity of depression was negatively correlated with my-inositol/tCr in the left insula and putamen. The improvement in depression severity was significantly associated with changes in NAA/tCr in the left ACC. This study has successfully evaluated regional differences in metabolites for patients with MDD who received MBCT treatment and in controls using 7 Tesla MRSI.

Increased N-Acetylaspartate/creatine ratio in the medial prefrontal cortex among unmedicated obsessive-compulsive disorder patients.

PubMed

Fan, Qing; Tan, Ling; You, Chao; Wang, Jijun; Ross, Colin A; Wang, Xuemei; Zhang, Tianhong; Li, Jianqi; Chen, Kemin; Xiao, Zeping

2010-10-01

Changes in the fronto-striato-thalamo-cortical-circuit loop have been suggested in the pathogenesis of obsessive-compulsive disorder (OCD), and have been studied using (1)H magnetic resonance spectroscopy ((1)H MRS) with interesting findings. However, whether neural metabolites are abnormal in the medial prefrontal cortex in patients with OCD is unknown. The purpose of the present study was to investigate neural metabolites in this brain region in a sample of patients with OCD. Subjects were 21 unmedicated OCD patients, including 10 who were drug-naïve, and 19 healthy controls. Single-voxel (1)H MRS was used to study the medial prefrontal cortex for each subject. Levels of N-acetylaspartate (NAA), choline-containing compounds and myoinositol were measured in terms of their ratios with creatine (Cr). The NAA/Cr ratio was significantly higher among OCD patients than among healthy controls (F = 4.76, P = 0.037). However, it did not correlate with patients' symptoms or with their illness durations. The NAA/Cr ratio also did not differ between drug-naïve and previously medicated patients. No significant group differences were found between OCD patients and normal controls for the choline-containing compounds/Cr or myoinositol/Cr ratios. In addition, a significant correlation between the NAA/Cr ratio and trait anxiety scores on the State-Trait Anxiety Inventory was found among the controls (r = 0.639, P = 0.010). The N-Acetylaspartate level relative to creatine in the medial prefrontal cortex was increased among unmedicated OCD patients. This cannot be attributed to the effect of medications. The possible significance of this finding in the pathophysiology of OCD is discussed. © 2010 Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine. Psychiatry and Clinical Neurosciences © 2010 Japanese Society of Psychiatry and Neurology.

Analysis of creatine, creatinine, creatine-d3 and creatinine-d3 in urine, plasma, and red blood cells by HPLC and GC-MS to follow the fate of ingested creatine-d3.

PubMed

MacNeil, Lauren; Hill, Lisa; MacDonald, Daniel; Keefe, Lori; Cormier, James F; Burke, Darren G; Smith-Palmer, Truis

2005-12-05

Creatine, which is increasingly being used as an oral supplement, is naturally present in the body. Studies on the fate of a particular dose of creatine require that the creatine be labeled, and for studies in humans the use of a stable isotopic label is desirable. The concentrations of total creatine and total creatinine were determined using HPLC. Creatine and creatinine were then separated using cation exchange chromatography and each fraction was derivatized with trifluoroacetic anhydride and the ratio of the deuterated:undeuterated species determined using GC-MS. Ratios of creatine:creatine-d(3), and creatinine:creatinine-d(3), and the concentrations of each of these species, were able to be determined in urine, plasma and red blood cells. Thus, the uptake of labeled creatine into plasma and red blood cells and its excretion in urine could be followed for a subject who ingested creatine-d(3). Creatine-d(3) was found in the plasma and red blood cells 10 min after ingestion, while creatine-d(3) and creatinine-d(3) were found in the urine collected after the first hour.

Total-body creatine pool size and skeletal muscle mass determination by creatine-(methyl-D3) dilution in rats.

PubMed

Stimpson, Stephen A; Turner, Scott M; Clifton, Lisa G; Poole, James C; Mohammed, Hussein A; Shearer, Todd W; Waitt, Greg M; Hagerty, Laura L; Remlinger, Katja S; Hellerstein, Marc K; Evans, William J

2012-06-01

There is currently no direct, facile method to determine total-body skeletal muscle mass for the diagnosis and treatment of skeletal muscle wasting conditions such as sarcopenia, cachexia, and disuse. We tested in rats the hypothesis that the enrichment of creatinine-(methyl-d(3)) (D(3)-creatinine) in urine after a defined oral tracer dose of D(3)-creatine can be used to determine creatine pool size and skeletal muscle mass. We determined 1) an oral tracer dose of D(3)-creatine that was completely bioavailable with minimal urinary spillage and sufficient enrichment in the body creatine pool for detection of D(3)-creatine in muscle and D(3)-creatinine in urine, and 2) the time to isotopic steady state. We used cross-sectional studies to compare total creatine pool size determined by the D(3)-creatine dilution method to lean body mass determined by independent methods. The tracer dose of D(3)-creatine (<1 mg/rat) was >99% bioavailable with 0.2-1.2% urinary spillage. Isotopic steady state was achieved within 24-48 h. Creatine pool size calculated from urinary D(3)-creatinine enrichment at 72 h significantly increased with muscle accrual in rat growth, significantly decreased with dexamethasone-induced skeletal muscle atrophy, was correlated with lean body mass (r = 0.9590; P < 0.0001), and corresponded to predicted total muscle mass. Total-body creatine pool size and skeletal muscle mass can thus be accurately and precisely determined by an orally delivered dose of D(3)-creatine followed by the measurement of D(3)-creatinine enrichment in a single urine sample and is promising as a noninvasive tool for the clinical determination of skeletal muscle mass.

Magnetic resonance spectroscopy in mild cognitive impairment: systematic review and meta-analysis.

PubMed

Tumati, Shankar; Martens, Sander; Aleman, André

2013-12-01

Research using proton magnetic resonance spectroscopy (MRS) can potentially elucidate metabolite changes representing early degeneration in Mild Cognitive Impairment (MCI), an early stage of dementia. We integrated the published literature using meta-analysis to identify patterns of metabolite changes in MCI. 29 MRS studies (with a total of 607 MCI patients and 862 healthy controls) were classified according to brain regions. Hedges' g was used as effect size in a random effects model. N-Acetyl Aspartate (NAA) measures were consistently reduced in posterior cingulate (PC), hippocampus, and the paratrigonal white matter (PWM). Creatine (Cr) concentration was reduced in the hippocampus and PWM. Choline (Cho) concentration was reduced in the hippocampus while Cho/Cr ratio was raised in the PC. Myo-inositol (mI) concentration was raised in the PC and mI/Cr ratio was raised in the hippocampus. NAA/mI ratio was reduced in the PC. NAA may be the most reliable marker of brain dysfunction in MCI though mI, Cho, and Cr may also contribute towards this. Copyright © 2013 Elsevier Ltd. All rights reserved.

ALTERATIONS IN BRAIN CREATINE CONCENTRATIONS UNDER LONG-TERM SOCIAL ISOLATION (EXPERIMENTAL STUDY).

PubMed

Koshoridze, N; Kuchukashvili, Z; Menabde, K; Lekiashvili, Sh; Koshoridze, M

2016-02-01

Stress represents one of the main problems of modern humanity. This study was done for understanding more clearly alterations in creatine content of the brain under psycho-emotional stress induced by long-term social isolation. It was shown that under 30 days social isolation creatine amount in the brain was arisen, while decreasing concentrations of synthesizing enzymes (AGAT, GAMT) and creatine transporter protein (CrT). Another important point was that such changes were accompanied by down-regulation of creatine kinase (CK), therefore the enzyme's concentration was lowered. In addition, it was observed that content of phosphocreatine (PCr) and ATP were also reduced, thus indicating down-regulation of energy metabolism of brain that is really a crucial point for its normal functioning. To sum up the results it can be underlined that long-term social isolation has negative influence on energy metabolism of brain; and as a result reduce ATP content, while increase of free creatine concentration, supposedly maintaining maximal balance for ATP amount, but here must be also noted that up-regulated oxidative pathways might have impact on blood brain barrier, resulting on its permeability.

Supplemented creatine induces changes in human metabolism of thiocompounds and one- and two-carbon units.

PubMed

Navrátil, T; Kohlíková, E; Petr, M; Pelclová, D; Heyrovský, M; Pristoupilová, K

2010-01-01

The administration of creatine (5 g/day for one month) to 11 young active sportsmen affected their urinary excretion of creatine, creatinine, and thiodiglycolic acid (TDGA) as well as blood levels of homocysteine, vitamin B12 and folates. The probands were divided into four groups, according to the amount of creatine found in urine, and of folates and vitamin B12 determined in blood. The changes of folates and vitamin B12 were mutually reciprocal. Each group utilized CR as donor of one- and two-carbon (1C and 2C) units by means of homocysteine (HoCySH), folates, and vitamin B12, in different metabolic pathways. In 10 men the creatine administration was accompanied by an increase of HoCySH level in blood, while in the last man, with accidentally discovered hyperhomocysteinemia, the HoCySH level dropped by 50%. Differences between initial and terminal TDGA levels indicate that creatine affects equilibria of redox processes. Creatinine excretion into urine changed in the dependence on the extent of metabolic disturbances.

Free creatine available to the creatine phosphate energy shuttle in isolated rat atria

DOE Office of Scientific and Technical Information (OSTI.GOV)

Savabi, F.

1988-10-01

To measure the actual percentage of intracellular free creatine participating in the process of energy transport, the incorporation of (1-{sup 14}C)creatine into the free creatine and phosphocreatine (PCr) pools in spontaneously beating isolated rat atria, under various conditions, was examined. The atria were subjected to three consecutive periods, control, anoxia, and postanoxic recover, in medium containing tracers of (1-{sup 14}C)creatine. The tissue content and specific activity of creatine and PCr were determined at the end of each period. The higher specific activity found for tissue PCr (1.87 times) than creatine, independent of the percentage of total intracellular creatine that wasmore » present as free creatine, provides evidence for the existence of two separate pools of free creatine. Analysis of the data shows that in the normal oxygenated state {approx} 9% of the total intracellular creatine is actually free to participate in the process of energy transport (shuttle pool). About 36% of the total creatine is bound to unknown intracellular components and the rest exists as PCr. The creatine that was taken up and the creatine that was released from the breakdown of PCr have much greater access to the site of phosphorylation than the rest of the intracellular creatine. A sharp increase in the specific activity of residual PCr on prolongation of anoxic time was also observed. This provides evidence for a nonhomogeneous pool of PCr, for the most recently formed (radioactive) PCr appeared to be hydrolyzed last.« less

Does long-term creatine supplementation impair kidney function in resistance-trained individuals consuming a high-protein diet?

PubMed Central

2013-01-01

Background The aim of this study was to determine the effects of creatine supplementation on kidney function in resistance-trained individuals ingesting a high-protein diet. Methods A randomized, double-blind, placebo-controlled trial was performed. The participants were randomly allocated to receive either creatine (20 g/d for 5 d followed by 5 g/d throughout the trial) or placebo for 12 weeks. All of the participants were engaged in resistance training and consumed a high-protein diet (i.e., ≥ 1.2 g/Kg/d). Subjects were assessed at baseline (Pre) and after 12 weeks (Post). Glomerular filtration rate was measured by 51Cr-EDTA clearance. Additionally, blood samples and a 24-h urine collection were obtained for other kidney function assessments. Results No significant differences were observed for 51Cr-EDTA clearance throughout the trial (Creatine: Pre 101.42 ± 13.11, Post 108.78 ± 14.41 mL/min/1.73m2; Placebo: Pre 103.29 ± 17.64, Post 106.68 ± 16.05 mL/min/1.73m2; group x time interaction: F = 0.21, p = 0.64). Creatinine clearance, serum and urinary urea, electrolytes, proteinuria, and albuminuria remained virtually unchanged. Conclusions A 12-week creatine supplementation protocol did not affect kidney function in resistance-trained healthy individuals consuming a high-protein diet; thus reinforcing the safety of this dietary supplement. Trial registration ClinicalTrials.gov NCT01817673 PMID:23680457

The effects of a high dosage of creatine and caffeine supplementation on the lean body mass composition of rats submitted to vertical jumping training.

PubMed

Franco, Frederico Sc; Costa, Neuza Mb; Ferreira, Susana A; Carneiro-Junior, Miguel A; Natali, Antônio J

2011-03-01

The influences of creatine and caffeine supplementation associated with power exercise on lean body mass (LBM) composition are not clear. The purpose of this research was to determine whether supplementation with high doses of creatine and caffeine, either solely or combined, affects the LBM composition of rats submitted to vertical jumping training. Male Wistar rats were randomly divided into 8 groups: Sedentary (S) or Exercised (E) [placebo (Pl), creatine (Cr), caffeine (Caf) or creatine plus caffeine (CrCaf)]. The supplemented groups received creatine [load: 0.430 g/kg of body weight (BW) for 7 days; and maintenance: 0.143 g/kg of BW for 35 days], caffeine (15 mg/kg of BW for 42 days) or creatine plus caffeine. The exercised groups underwent a vertical jump training regime (load: 20 - 50% of BW, 4 sets of 10 jumps interspersed with 1 min resting intervals), 5 days/wk, for 6 weeks. LBM composition was evaluated by portions of water, protein and fat in the rat carcass. Data were submitted to ANOVA followed by the Tukey post hoc test and Student's t test. Exercised animals presented a lower carcass weight (10.9%; P = 0.01), as compared to sedentary animals. However, no effect of supplementation was observed on carcass weight (P > 0.05). There were no significant differences among the groups (P > 0.05) for percentage of water in the carcass. The percentage of fat in the group SCr was higher than in the groups SCaf and ECr (P < 0.05). A higher percentage of protein was observed in the groups EPl and ECaf when compared to the groups SPl and SCaf (P < 0.001). The percentage of fat in the carcass decreased (P < 0.001), while those of water and protein increased (P < 0.05) in exercised animals, compared to sedentary animals. Caffeine groups presented reduced percentage of fat when compared to creatine supplemented groups (P < 0.05). High combined doses of creatine and caffeine does not affect the LBM composition of either sedentary or exercised rats, however, caffeine supplementation alone reduces the percentage of fat. Vertical jumping training increases the percentages of water and protein and reduces the fat percentage in rats.

Total body skeletal muscle mass: estimation by creatine (methyl-d3) dilution in humans

PubMed Central

Walker, Ann C.; O'Connor-Semmes, Robin L.; Leonard, Michael S.; Miller, Ram R.; Stimpson, Stephen A.; Turner, Scott M.; Ravussin, Eric; Cefalu, William T.; Hellerstein, Marc K.; Evans, William J.

2014-01-01

Current methods for clinical estimation of total body skeletal muscle mass have significant limitations. We tested the hypothesis that creatine (methyl-d3) dilution (D3-creatine) measured by enrichment of urine D3-creatinine reveals total body creatine pool size, providing an accurate estimate of total body skeletal muscle mass. Healthy subjects with different muscle masses [n = 35: 20 men (19–30 yr, 70–84 yr), 15 postmenopausal women (51–62 yr, 70–84 yr)] were housed for 5 days. Optimal tracer dose was explored with single oral doses of 30, 60, or 100 mg D3-creatine given on day 1. Serial plasma samples were collected for D3-creatine pharmacokinetics. All urine was collected through day 5. Creatine and creatinine (deuterated and unlabeled) were measured by liquid chromatography mass spectrometry. Total body creatine pool size and muscle mass were calculated from D3-creatinine enrichment in urine. Muscle mass was also measured by magnetic resonance imaging (MRI), dual-energy x-ray absorptiometry (DXA), and traditional 24-h urine creatinine. D3-creatine was rapidly absorbed and cleared with variable urinary excretion. Isotopic steady-state of D3-creatinine enrichment in the urine was achieved by 30.7 ± 11.2 h. Mean steady-state enrichment in urine provided muscle mass estimates that correlated well with MRI estimates for all subjects (r = 0.868, P < 0.0001), with less bias compared with lean body mass assessment by DXA, which overestimated muscle mass compared with MRI. The dilution of an oral D3-creatine dose determined by urine D3-creatinine enrichment provides an estimate of total body muscle mass strongly correlated with estimates from serial MRI with less bias than total lean body mass assessment by DXA. PMID:24764133

Total body skeletal muscle mass: estimation by creatine (methyl-d3) dilution in humans.

PubMed

Clark, Richard V; Walker, Ann C; O'Connor-Semmes, Robin L; Leonard, Michael S; Miller, Ram R; Stimpson, Stephen A; Turner, Scott M; Ravussin, Eric; Cefalu, William T; Hellerstein, Marc K; Evans, William J

2014-06-15

Current methods for clinical estimation of total body skeletal muscle mass have significant limitations. We tested the hypothesis that creatine (methyl-d3) dilution (D3-creatine) measured by enrichment of urine D3-creatinine reveals total body creatine pool size, providing an accurate estimate of total body skeletal muscle mass. Healthy subjects with different muscle masses [n = 35: 20 men (19-30 yr, 70-84 yr), 15 postmenopausal women (51-62 yr, 70-84 yr)] were housed for 5 days. Optimal tracer dose was explored with single oral doses of 30, 60, or 100 mg D3-creatine given on day 1. Serial plasma samples were collected for D3-creatine pharmacokinetics. All urine was collected through day 5. Creatine and creatinine (deuterated and unlabeled) were measured by liquid chromatography mass spectrometry. Total body creatine pool size and muscle mass were calculated from D3-creatinine enrichment in urine. Muscle mass was also measured by magnetic resonance imaging (MRI), dual-energy x-ray absorptiometry (DXA), and traditional 24-h urine creatinine. D3-creatine was rapidly absorbed and cleared with variable urinary excretion. Isotopic steady-state of D3-creatinine enrichment in the urine was achieved by 30.7 ± 11.2 h. Mean steady-state enrichment in urine provided muscle mass estimates that correlated well with MRI estimates for all subjects (r = 0.868, P < 0.0001), with less bias compared with lean body mass assessment by DXA, which overestimated muscle mass compared with MRI. The dilution of an oral D3-creatine dose determined by urine D3-creatinine enrichment provides an estimate of total body muscle mass strongly correlated with estimates from serial MRI with less bias than total lean body mass assessment by DXA. Copyright © 2014 the American Physiological Society.

URINARY CREATINE AT REST AND AFTER REPEATED SPRINTS IN ATHLETES: A PILOT STUDY

PubMed Central

Nasrallah, F.; Feki, M.; Chamari, K.; Omar, S.; Alouane-Trabelsi, L.; Ben Mansour, A.; Kaabachi, N.

2014-01-01

Creatine plays a key role in muscle function and its evaluation is important in athletes. In this study, urinary creatine concentration was measured in order to highlight its possible significance in monitoring sprinters. The study included 51 sprinters and 25 age- and sex-matched untrained subjects as a control group. Body composition was measured and dietary intake estimated. Urine samples were collected before and after standardized physical exercise. Creatine was assessed by gas chromatography mass spectrometry. Basal urinary creatine (UC) was significantly lower in sprinters than controls (34±30 vs. 74±3 µmol/mmol creatinine, p < 0.05). UC was inversely correlated with body mass (r = −0.34, p < 0.01) and lean mass (r = −0.30, p < 0.05), and positively correlated with fat mass (r = 0.32, p < 0.05). After acute exercise, urinary creatine significantly decreased in both athletes and controls. UC is low in sprinters at rest and further decreases after exercise, most likely due to a high uptake and use of creatine by muscles, as muscle mass and physical activity are supposed to be greater in athletes than untrained subjects. Further studies are needed to test the value of urinary creatine as a non-invasive marker of physical condition and as a parameter for managing Cr supplementation in athletes. PMID:24917689

Application of a protocol for magnetic resonance spectroscopy of adrenal glands: an experiment with over 100 cases.

PubMed

Melo, Homero José de Farias E; Goldman, Suzan M; Szejnfeld, Jacob; Faria, Juliano F; Huayllas, Martha K P; Andreoni, Cássio; Kater, Cláudio E

2014-01-01

To evaluate a protocol for two-dimensional (2D) hydrogen proton (1H) magnetic resonance spectroscopy (MRS) (Siemens Medical Systems; Erlangen, Germany) in the detection of adrenal nodules and differentiation between benign and malignant masses (adenomas, pheochromocytomas, carcinomas and metastases). A total of 118 patients (36 men; 82 women) (mean age: 57.3 ± 13.3 years) presenting with 138 adrenal nodules/masses were prospectively assessed. A multivoxel system was utilized with a 2D point-resolved spectroscopy/chemical shift imaging sequence. The following ratios were calculated: choline (Cho)/creatine (Cr), 4.0-4.3/Cr, lipid (Lip)/Cr, Cho/Lip and lactate (Lac)/Cr. 2D-1H-MRS was successful in 123 (89.13%) lesions. Sensitivity and specificity values observed for the ratios and cutoff points were the following: Cho/Cr ≥ 1.2, 100% sensitivity, 98.2% specificity (differences between adenomas/pheochromocytomas and carcinomas/ metastases); 4.0-4.3 ppm/Cr ≥ 1.5, 92.3% sensitivity, 96.9% specificity (differences between carcinomas/pheochromocytomas and adenomas/metastases); Lac/Cr ≤ -7.449, 90.9% sensitivity and 77.8% specificity (differences between pheochromocytomas and carcinomas/adenomas). Information provided by 2D-1H-MRS were effective and allowed for the differentiation between adrenal masses and nodules in most cases of lesions with > 1.0 cm in diameter.

Creatine supplementation increases glycogen storage but not GLUT-4 expression in human skeletal muscle.

PubMed

van Loon, Luc J C; Murphy, Robyn; Oosterlaar, Audrey M; Cameron-Smith, David; Hargreaves, Mark; Wagenmakers, Anton J M; Snow, Rodney

2004-01-01

It has been speculated that creatine supplementation affects muscle glucose metabolism in humans by increasing muscle glycogen storage and up-regulating GLUT-4 protein expression. In the present study, we assessed the effects of creatine loading and prolonged supplementation on muscle glycogen storage and GLUT-4 mRNA and protein content in humans. A total of 20 subjects participated in a 6-week supplementation period during which creatine or a placebo was ingested. Muscle biopsies were taken before and after 5 days of creatine loading (20 g.day(-1)) and after 6 weeks of continued supplementation (2 g.day(-1)). Fasting plasma insulin concentrations, muscle creatine, glycogen and GLUT-4 protein content as well as GLUT-4, glycogen synthase-1 (GS-1) and glycogenin-1 (Gln-1) mRNA expression were determined. Creatine loading significantly increased total creatine, free creatine and creatine phosphate content with a concomitant 18 +/- 5% increase in muscle glycogen content (P<0.05). The subsequent use of a 2 g.day(-1) maintenance dose for 37 days did not maintain total creatine, creatine phosphate and glycogen content at the elevated levels. The initial increase in muscle glycogen accumulation could not be explained by an increase in fasting plasma insulin concentration, muscle GLUT-4 mRNA and/or protein content. In addition, neither muscle GS-1 nor Gln-1 mRNA expression was affected. We conclude that creatine ingestion itself stimulates muscle glycogen storage, but does not affect muscle GLUT-4 expression.

Brain Creatine Elevation and NAA Reduction Indicates Neuronal Dysfunction in the Setting of Enhanced Glial Energy Metabolism in a Macaque Model of neuroAIDS

PubMed Central

Ratai, Eva-Maria; Annamalai, Lakshmanan; Burdo, Tricia; Joo, Chan-Gyu; Bombardier, Jeffrey P.; Fell, Robert; Hakimelahi, Reza; He, Julian; Lentz, Margaret R.; Campbell, Jennifer; Curran, Elizabeth; Halpern, Elkan F.; Masliah, Eliezer; Westmoreland, Susan. V.; Williams, Kenneth C.; González, R. Gilberto

2011-01-01

Proton magnetic resonance spectroscopy (1H MRS) has emerged as one of the most informative neuroimaging modalities for studying the effect of HIV infection in the brain, providing surrogate markers by which to assess disease progression and monitor treatment. Reductions in the level of N-Acetylaspartate (NAA) and NAA/creatine (NAA/Cr) are established markers of neuronal injury or loss. However, the biochemical basis of altered creatine levels in neuroAIDS is not well understood. This study used a rapid progression macaque model of neuroAIDS to elucidate the changes in creatine. As the disease progressed 1H MRS revealed a decrease in NAA, indicative of neuronal injury, and an increase in creatine yet to be elucidated. Subsequently, immunohistochemistry and stereology measures of decreased synaptophysin, microtubule-associated protein 2, and neuronal density confirmed neuronal injury. Furthermore, increases in ionized calcium binding adaptor molecule 1 and glial fibrillary acidic protein indicated microglial and astroglial activation, respectively. Given these data, elevated creatine may reflect enhanced high-energy phosphate turnover in highly metabolizing activated astrocytes and microglia. PMID:21381104

INFLUENCE OF TOTAL BODY X-IRRADIATION ON THE LEVELS OF CREATINE PHOSPHATE, INORGANIC PHOSPHORUS AND ATP IN MUSCLE AND ON THE LEVELS OF CREATINE, CREATININE, N'-METHYL-NICOTINAMIDE AND NITROGEN IN URINE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumta, U.S.; Gurnani, S.U.; Sahasrabudhe, M.B.

1957-09-01

The influence of total-body irradiation on the levels of creatine phosphate (CP), adenosine triphosphate (ATP) and inorganic phosphorus (IP) in muscle has been investigated in rats. CP and ATP levels decrease by about 33% while those of 1P increase 4 times in irradiated rats. Studies on the influence of irradiation on the excretion of creatine, creatinine, and N'-methyl- nicotinamide in urine show that the excretion of creatine and N'-methyl- nlcotinamide is increased two-fold while that of creatinine is increased by 160%. It is suggested that the low levels of creatine phosphate are probably due to an impairment in the phosphorylationmore » of creatine or due to an adaptive breakdown of creatine phosphate leading to increased excretion of creatine and creatinine. (auth)« less

Creatine supplementation elicits greater muscle hypertrophy in upper than lower limbs and trunk in resistance-trained men.

PubMed

Nunes, João Pedro; Ribeiro, Alex S; Schoenfeld, Brad J; Tomeleri, Crisieli M; Avelar, Ademar; Trindade, Michele Cc; Nabuco, Hellen Cg; Cavalcante, Edilaine F; Junior, Paulo Sugihara; Fernandes, Rodrigo R; Carvalho, Ferdinando O; Cyrino, Edilson S

2017-12-01

Creatine (Cr) supplementation associated with resistance training produces greater muscular strength improvements in the upper compared with the lower body; however, no study has investigated if such region-specific results are seen with gains in muscle mass. We aimed to evaluate the effect of Cr supplementation in combination with resistance training on lean soft tissue changes in the upper and lower limbs and trunk in resistance-trained young adult men. In a randomized, double-blind and placebo-controlled design, 43 resistance-trained men (22.7 ± 3.0 years, 72.9 ± 8.7 kg, 177.9 ± 5.7 cm, 23.0 ± 2.5 kg/m 2 ) received either creatine (Cr, n = 22) or placebo (PLA, n = 21) over an 8-week study period. The supplementation protocol included a loading phase (7 days, four doses of 0.3 g/kg per day) and a maintenance phase (7 weeks, single dose of 0.03 g/kg per day). During the same period, subjects performed resistance training four times per week using the following two-way split routine: Monday and Thursday = pectoral, shoulders, triceps, and abdomen, Tuesday and Friday = back, biceps, thighs, and calves. Lean soft tissue of the upper limbs (ULLST), lower limbs (LLLST), and trunk (TLST) was assessed by dual-energy X-ray absorptiometry before and after the intervention. Both groups showed significant ( p < 0.001) improvements in ULLST, LLLST, TLST, and the Cr group achieved greater ( p < 0.001) increases in these outcomes compared with PLA. For the Cr group, improvements in ULLST (7.1 ± 2.9%) were higher than those observed in LLLST (3.2 ± 2.1%) and TLST (2.1 ± 2.2%). Otherwise, for PLA group there was no significant difference in the magnitude of segmental muscle hypertrophy (ULLST = 1.6 ± 3.0%; LLLST = 0.7 ± 2.8%; TLST = 0.7 ± 2.8%). Our results suggest that Cr supplementation can positively augment muscle hypertrophy in resistance-trained young adult men, particularly in the upper limbs.

Effect of creatine supplementation and drop-set resistance training in untrained aging adults.

PubMed

Johannsmeyer, Sarah; Candow, Darren G; Brahms, C Markus; Michel, Deborah; Zello, Gordon A

2016-10-01

To investigate the effects of creatine supplementation and drop-set resistance training in untrained aging adults. Participants were randomized to one of two groups: Creatine (CR: n=14, 7 females, 7 males; 58.0±3.0yrs, 0.1g/kg/day of creatine+0.1g/kg/day of maltodextrin) or Placebo (PLA: n=17, 7 females, 10 males; age: 57.6±5.0yrs, 0.2g/kg/day of maltodextrin) during 12weeks of drop-set resistance training (3days/week; 2 sets of leg press, chest press, hack squat and lat pull-down exercises performed to muscle fatigue at 80% baseline 1-repetition maximum [1-RM] immediately followed by repetitions to muscle fatigue at 30% baseline 1-RM). Prior to and following training and supplementation, assessments were made for body composition, muscle strength, muscle endurance, tasks of functionality, muscle protein catabolism and diet. Drop-set resistance training improved muscle mass, muscle strength, muscle endurance and tasks of functionality (p<0.05). The addition of creatine to drop-set resistance training significantly increased body mass (p=0.002) and muscle mass (p=0.007) compared to placebo. Males on creatine increased muscle strength (lat pull-down only) to a greater extent than females on creatine (p=0.005). Creatine enabled males to resistance train at a greater capacity over time compared to males on placebo (p=0.049) and females on creatine (p=0.012). Males on creatine (p=0.019) and females on placebo (p=0.014) decreased 3-MH compared to females on creatine. The addition of creatine to drop-set resistance training augments the gains in muscle mass from resistance training alone. Creatine is more effective in untrained aging males compared to untrained aging females. Copyright © 2016 Elsevier Inc. All rights reserved.

Neurometabolic characteristics in the anterior cingulate gyrus of Alzheimer's disease patients with depression: a (1)H magnetic resonance spectroscopy study.

PubMed

Guo, Zhongwei; Zhang, Jiangtao; Liu, Xiaozheng; Hou, Hongtao; Cao, Yulin; Wei, Fuquan; Li, Japeng; Chen, Xingli; Shen, Yuedi; Chen, Wei

2015-12-02

Depression is a common comorbid psychiatric symptom in patients with Alzheimer's disease (AD), and the prevalence of depression is higher among people with AD compared with healthy older adults. Comorbid depression in AD may increase the risk of cognitive decline, impair patients' function, and reduce their quality of life. However, the mechanisms of depression in AD remain unclear. Here, our aim was to identify neurometabolic characteristics in the brain that are associated with depression in patients with mild AD. Thirty-seven patients were evaluated using the Neuropsychiatric Inventory (NPI) and Hamilton Depression Rating Scale (HAMD-17), and divided into two groups: 17 AD patients with depression (D-AD) and 20 non-depressed AD patients (nD-AD). Using proton magnetic resonance spectroscopy, we characterized neurometabolites in the anterior cingulate gyrus (ACG) of D-AD and nD-AD patients. Compared with nD-AD patients, D-AD patients showed lower N-acetylaspartate/creatine (NAA/Cr) and higher myo-inositol/creatine (mI/Cr) in the left ACG. NPI score correlated with NAA/Cr and mI/Cr in the left ACG, while HAMD correlated with NAA/Cr. Our findings show neurometabolic alterations in D-AD patients. Thus, D-AD pathogenesis may be attributed to abnormal activity of neurons and glial cells in the left ACG.

Short-echo 3D H-1 Magnetic Resonance Spectroscopic Imaging of patients with glioma at 7T for characterization of differences in metabolite levels

PubMed Central

Li, Yan; Larson, Peder; Chen, Albert P.; Lupo, Janine M.; Ozhinsky, Eugene; Kelley, Douglas; Chang, Susan M.; Nelson, Sarah J.

2014-01-01

Purpose The purpose of this study was to evaluate the feasibility of using a short echo time, 3D H-1 magnetic resonance spectroscopic imaging (MRSI) sequence at 7T to assess the metabolic signature of lesions for patients with glioma. Materials and Methods 29 patients with glioma were studied. MRSI data were obtained using CHESS water suppression, spectrally-selective adiabatic inversion-recovery pulses and automatically prescribed outer-volume-suppression for lipid suppression, and spin echo slice selection (TE=30ms). An interleaved flyback echo-planar trajectory was applied to shorten the total acquisition time (~10min). Relative metabolite ratios were estimated in tumor and in normal-appearing white and gray matter (NAWM, GM). Results Levels of glutamine, myo-inositol, glycine and glutathione relative to total creatine (tCr) were significantly increased in the T2 lesions for all tumor grades compared to those in the NAWM (p < 0.05), while N-acetyl aspartate to tCr were significantly decreased (p < 0.05). In grade 2 gliomas, level of total choline-containing-compounds to tCr was significantly increased (p = 0.0137), while glutamate to tCr was significantly reduced (p = 0.0012). Conclusion The improved sensitivity of MRSI and the increased number of metabolites that can be evaluated using 7T MR scanners is of interest for evaluating patients with glioma. This study has successfully demonstrated the application of a short-echo spin-echo MRSI sequence to detect characteristic differences in regions of tumor versus normal appearing brain. PMID:24935758

Evidence for Metabolic Hypothalamo-Amygdala Dysfunction in Narcolepsy

PubMed Central

Poryazova, Rositsa; Schnepf, Betina; Werth, Esther; Khatami, Ramin; Dydak, Ulrike; Meier, Dieter; Boesiger, Peter; Bassetti, Claudio L.

2009-01-01

Study Objectives: Proton resonance spectroscopy (1H-MRS) allows noninvasive chemical tissue analysis in the living brain. As neuronal loss and gliosis have been described in narcolepsy, metabolites of primary interest are N-acetylaspartate (NAA), a marker of neuronal integrity and myo-Inositol (mI), a glial marker and second messenger involved in the regulation of intracellular calcium. One 1H-MRS study in narcolepsy found no metabolic changes in the pontomedullary junction. Another study showed a reduction in NAA/creatine-phosphocreatine (Cr) in the hypothalamus of narcolepsy patients with cataplexy. We aimed to test for metabolic changes in specific brain areas, “regions of interest,” thought to be involved in emotional processing, sleep regulation and pathophysiology of narcolepsy: hypothalamus, pontomesencephalic junction and both amygdalae. Design: We performed 1H-MRS using a 3T Philips Achieva whole body MR scanner. Single-voxel proton MR spectra were acquired and quantified with LCModel to determine metabolite concentration ratios. Setting: The participants in the study were recruited at the outpatient clinic for sleep medicine, Department of Neurology and magnetic resonance spectroscopy was performed at the MRI facility, University Hospital Zurich. Participants: 1H-MRS was performed in fourteen narcolepsy patients with cataplexy, CSF hypocretin deficiency (10/10) and HLA-DQB1*0602 positivity (14/14) and 14 age, gender and body mass index matched controls. Patients were treatment naïve or off therapy for at least 14 days before scanning. Measurements and Results: No differences were observed in the regions of interest for (total NAA)/Cr ratios. Myo-Inositol (mI)/Cr was significantly lower in the right amygdala of the patients, compared to controls (P < 0.042). Significant negative correlations only in the patients group were found between (total NAA)/Cr in hypothalamus and mI/Cr in the right amygdala (r = −0.89, P < 0.001), between mI/Cr in hypothalamus and (total NAA)/Cr in the right amygdala (r = −63, P < 0.05) and between mI/Cr in the left amygdala and total NAA)/Cr in the pontomesencephalic junction (r = −0.69, P < 0.05). Conclusion: Our findings suggest amygdala involvement and possible hypothalamo-amygdala dysfunction in narcolepsy. Citation: Poryazova R; Werth E; Khatami R; Dydak U; Meier D; Boesiger P; Bassetti CL. Evidence for metabolic hypothalamo-amygdala dysfunction in narcolepsy. SLEEP 2009;32(5):607-613. PMID:19480227

GABA and glutamate in schizophrenia: a 7 T ¹H-MRS study.

PubMed

Marsman, Anouk; Mandl, René C W; Klomp, Dennis W J; Bohlken, Marc M; Boer, Vincent O; Andreychenko, Anna; Cahn, Wiepke; Kahn, René S; Luijten, Peter R; Hulshoff Pol, Hilleke E

2014-01-01

Schizophrenia is characterized by loss of brain volume, which may represent an ongoing pathophysiological process. This loss of brain volume may be explained by reduced neuropil rather than neuronal loss, suggesting abnormal synaptic plasticity and cortical microcircuitry. A possible mechanism is hypofunction of the NMDA-type of glutamate receptor, which reduces the excitation of inhibitory GABAergic interneurons, resulting in a disinhibition of glutamatergic pyramidal neurons. Disinhibition of pyramidal cells may result in excessive stimulation by glutamate, which in turn could cause neuronal damage or death through excitotoxicity. In this study, GABA/creatine ratios, and glutamate, NAA, creatine and choline concentrations in the prefrontal and parieto-occipital cortices were measured in 17 patients with schizophrenia and 23 healthy controls using proton magnetic resonance spectroscopy at an ultra-high magnetic field strength of 7 T. Significantly lower GABA/Cr ratios were found in patients with schizophrenia in the prefrontal cortex as compared to healthy controls, with GABA/Cr ratios inversely correlated with cognitive functioning in the patients. No significant change in the GABA/Cr ratio was found between patients and controls in the parieto-occipital cortex, nor were levels of glutamate, NAA, creatine, and choline differed in patients and controls in the prefrontal and parieto-occipital cortices. Our findings support a mechanism involving altered GABA levels distinguished from glutamate levels in the medial prefrontal cortex in schizophrenia, particularly in high functioning patients. A (compensatory) role for GABA through altered inhibitory neurotransmission in the prefrontal cortex may be ongoing in (higher functioning) patients with schizophrenia.

Strength and hypertrophy responses to constant and decreasing rest intervals in trained men using creatine supplementation.

PubMed

Souza-Junior, Tácito P; Willardson, Jeffrey M; Bloomer, Richard; Leite, Richard D; Fleck, Steven J; Oliveira, Paulo R; Simão, Roberto

2011-10-27

The purpose of the current study was to compare strength and hypertrophy responses to resistance training programs that instituted constant rest intervals (CI) and decreasing rest intervals (DI) between sets over the course of eight weeks by trained men who supplemented with creatine monohydrate (CR). Twenty-two recreationally trained men were randomly assigned to a CI group (n = 11; 22.3 ± 1 years; 77.7 ± 5.4 kg; 180 ± 2.2 cm) or a DI group (n = 11; 22 ± 2.5 years; 75.8 ± 4.9 kg; 178.8 ± 3.4 cm). Subjects in both groups supplemented with CR; the only difference between groups was the rest interval instituted between sets; the CI group used 2 minutes rest intervals between sets and exercises for the entire 8-weeks of training, while the DI group started with a 2 minute rest interval the first two weeks; after which the rest interval between sets was decreased 15 seconds per week (i.e. 2 minutes decreasing to 30 seconds between sets). Pre- and post-intervention maximal strength for the free weight back squat and bench press exercises and isokinetic peak torque were assessed for the knee extensors and flexors. Additionally, muscle cross-sectional area (CSA) of the right thigh and upper arm was measured using magnetic resonance imaging. Both groups demonstrated significant increases in back squat and bench press maximal strength, knee extensor and flexor isokinetic peak torque, and upper arm and right thigh CSA from pre- to post-training (p ≤ 0.0001); however, there were no significant differences between groups for any of these variables. The total volume for the bench press and back squat were significantly greater for CI group versus the DI group. We report that the combination of CR supplementation and resistance training can increase muscular strength, isokinetic peak torque, and muscle CSA, irrespective of the rest interval length between sets. Because the volume of training was greater for the CI group versus the DI group, yet strength gains were similar, the creatine supplementation appeared to bolster adaptations for the DI group, even in the presence of significantly less volume. However, further research is needed with the inclusion of a control group not receiving supplementation combined and resistance training with decreasing rest intervals to further elucidate such hypotheses.

Effect of low-dose, short-duration creatine supplementation on anaerobic exercise performance.

PubMed

Hoffman, Jay R; Stout, Jeffrey R; Falvo, Michael J; Kang, Jie; Ratamess, Nicholas A

2005-05-01

To examine the efficacy of a low-dose, short-duration creatine monohydrate supplement, 40 physically active men were randomly assigned to either a placebo or creatine supplementation group (6 g of creatine monohydrate per day). Testing occurred before and at the end of 6 days of supplementation. During each testing session, subjects performed three 15-second Wingate anaerobic power tests. No significant (p > 0.05) group or time differences were observed in body mass, peak power, mean power, or total work. In addition, no significant (p > 0.05) differences were observed in peak power, mean power, or total work. However, the change in the rate of fatigue of total work was significantly (p < 0.05) lower in the creatine supplementation group than in the placebo group, indicating a reduced fatigue rate in subjects supplementing with creatine compared with the placebo. Although the results of this study demonstrated reduced fatigue rates in patients during high-intensity sprint intervals, further research is necessary in examining the efficacy of low-dose, short-term creatine supplementation.

Strong Relation between Muscle Mass Determined by D3-creatine Dilution, Physical Performance and Incidence of Falls and Mobility Limitations in a Prospective Cohort of Older Men.

PubMed

Cawthon, Peggy M; Orwoll, Eric S; Peters, Katherine E; Ensrud, Kristine E; Cauley, Jane A; Kado, Deborah M; Stefanick, Marcia L; Shikany, James M; Strotmeyer, Elsa S; Glynn, Nancy W; Caserotti, Paolo; Shankaran, Mahalakshmi; Hellerstein, Marc; Cummings, Steven R; Evans, William J

2018-06-12

Direct assessment of skeletal muscle mass in older adults is clinically challenging. Relationships between lean mass and late-life outcomes have been inconsistent. The D3-creatine dilution method provides a direct assessment of muscle mass. Muscle mass was assessed by D3-creatine (D3Cr) dilution in 1,382 men (mean age, 84.2 yrs). Participants completed the Short Physical Performance Battery (SPPB); usual walking speed (6 meters); and DXA lean mass. Men self-reported mobility limitations (difficulty walking 2-3 blocks or climbing 10 steps); recurrent falls (2+); and serious injurious falls in the subsequent year. Across quartiles of D3Cr muscle mass/body mass, multivariate linear models calculated means for SPPB and gait speed; multivariate logistic models calculated odds ratios for incident mobility limitations or falls. Compared to men in the highest quartile, those in the lowest quartile of D3Cr muscle mass/body mass had slower gait speed (Q1: 1.04 vs Q4: 1.17 m/s); lower SPPB (Q1: 8.4 vs Q4: 10.4 points); greater likelihood of incident serious injurious falls (OR Q1 vs Q4: 2.49, 95% CI: 1.37, 4.54); prevalent mobility limitation (OR Q1 vs Q4,: 6.1, 95%CI: 3.7, 10.3) and incident mobility limitation (OR Q1 vs Q4: 2.15 95% CI: 1.42, 3.26); p for trend <.001 for all. Results for incident recurrent falls were in the similar direction (p=0.156). DXA lean mass had weaker associations with the outcomes. Unlike DXA lean mass, low D3Cr muscle mass/body mass is strongly related to physical performance, mobility and incident injurious falls in older me.

The concentration of N-acetyl aspartate, creatine + phosphocreatine, and choline in different parts of the brain in adulthood and senium.

PubMed

Christiansen, P; Toft, P; Larsson, H B; Stubgaard, M; Henriksen, O

1993-01-01

The fully relaxed water signal was used as an internal standard in a STEAM experiment to calculate the concentrations of the metabolites: N-acetyl aspartate (NAA), creatine + phosphocreatine (Cr + PCr), and choline (Cho) containing compounds in four different parts of the brain in two age groups of healthy volunteers (20-30 yr, n = 8) and (60-80 yr, n = 8). Furthermore, T1 and T2 relaxation time of the metabolites and signal ratios: NAA/Cho, NAA/Cr + PCr, and Cho/Cr + PCr at TE = 272 msec were calculated. The experiments were carried out using a Siemens Helicon SP 63/84 wholebody MR-scanner at 1.5 T. In the younger age group, the concentration of NAA was significantly higher in the occipital part than in the other three parts of the brain. No significant regional variation was found for any other metabolite concentration. There was a significantly higher concentration of NAA in the occipital part of the brain in the younger age group compared to the older one. No significant regional or age dependent variation was found concerning the T1 and T2 relaxation times.

Proton magnetic resonance spectroscopy in obsessive-compulsive disorder: evidence for reduced neuronal integrity in the anterior cingulate.

PubMed

Tükel, Raşit; Aydın, Kubilay; Ertekin, Erhan; Özyıldırım, Seda Şahin; Taravari, Vedat

2014-12-30

Neuroimaging studies have suggested that dysfunction of the cortico-striatal-thalamo-cortical (CSTC) circuit is a key pathophysiologic feature of obsessive-compulsive disorder (OCD). Several studies using proton magnetic resonance spectroscopy ((1)H MRS) have found abnormal neural metabolite concentrations among OCD patients. The aim of this study was to investigate the metabolic integrity of the anterior cingulate, caudate and putamen in OCD. In the present study, 32 unmedicated patients with OCD, including 23 who were drug-naïve, were compared using MRS with 32 healthy controls. Metabolite levels of N-acetylaspartate (NAA), choline (Cho) and myo-inositol (mI) were measured in terms of their ratios to creatine (Cr). The ratio of NAA/Cr was significantly lower in OCD patients than in healthy controls in the anterior cingulate. There was a tendency for levels of NAA/Cr to be lower in the caudate and the putamen in patients with OCD compared with healthy controls. NAA/Cr ratios were negatively correlated with the total scores on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) in the anterior cingulate in patients with OCD. Our results support the significance and biochemical involvement of the anterior cingulate cortex (ACC) in the pathophysiology of OCD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Reduced γ-Aminobutyric Acid in Occipital and Anterior Cingulate Cortices in Primary Insomnia: a Link to Major Depressive Disorder?

PubMed Central

Plante, David T; Jensen, J Eric; Schoerning, Laura; Winkelman, John W

2012-01-01

Insomnia is closely related to major depressive disorder (MDD) both cross-sectionally and longitudinally, and as such, offers potential opportunities to refine our understanding of the neurobiology of both sleep and mood disorders. Clinical and basic science data suggest a role for reduced γ-aminobutyric acid (GABA) in both MDD and primary insomnia (PI). Here, we have utilized single-voxel proton magnetic spectroscopy (1H-MRS) at 4 Tesla to examine GABA relative to total creatine (GABA/Cr) in the occipital cortex (OC), anterior cingulate cortex (ACC), and thalamus in 20 non-medicated adults with PI (12 women) and 20 age- and sex-matched healthy sleeper comparison subjects. PI subjects had significantly lower GABA/Cr in the OC (p=0.0005) and ACC (p=0.03) compared with healthy sleepers. There was no significant difference in thalamic GABA/Cr between groups. After correction for multiple comparisons, GABA/Cr did not correlate significantly with insomnia severity measures among PI subjects. This study is the first to demonstrate regional reductions of GABA in PI in the OC and ACC. Reductions in GABA in similar brain regions in MDD using 1H-MRS suggest a common reduction in cortical GABA among PI and mood disorders. PMID:22318195

Comparison of LCModel and SAGE in Analysis of Brain Metabolite Concentrations-A study of Patients with Mild Cognitive Impairment.

PubMed

Shih, Chiu-Ming; Lai, Jui-Jen; Chang, Chin-Ching; Chen, Cheng-Sheng; Yeh, Yi-Chun; Jaw, Twei-Shiun; Hsu, Jui-Sheng; Li, Chun-Wei

2017-03-15

The purpose of this study was to compare brain metabolite concentration ratios determined by LCModel and Spectroscopy Analysis by General Electric (SAGE) quantitative methods to elucidate the advantages and disadvantages of each method. A total of 10 healthy volunteers and 10 patients with mild cognitive impairment (MCI) were recruited in this study. A point-resolved spectroscopy (PRESS) sequence was used to obtain the brain magnetic resonance spectroscopy (MRS) spectra of the volunteers and patients, as well as the General Electric (GE) MRS-HD-sphere phantom. The brain metabolite concentration ratios were estimated based on the peak area obtained from both LCModel and SAGE software. Three brain regions were sampled for each volunteer or patient, and 20 replicates were acquired at different times for the phantom analysis. The metabolite ratios of the GE phantom were estimated to be myo-inositol (mI)/creatine (Cr): 0.70 ± 0.01, choline (Cho)/Cr: 0.37 ± 0.00, N-acetylaspartate (NAA)/Cr: 1.26 ± 0.02, and NAA/mI: 1.81 ± 0.04 by LCModel, and mI/Cr: 0.88 ± 0.15, Cho/Cr: 0.35 ± 0.01, NAA/Cr: 1.33 ± 0.03, and NAA/mI: 1.55 ± 0.26 by SAGE. In the healthy volunteers and MCI patients, the ratios of mI/Cr and Cho/Cr estimated by LCModel were higher than those estimated by SAGE. In contrast, the ratio of NAA/Cr estimated by LCModel was lower than that estimated by SAGE. Both methods were acceptable in estimating brain metabolite concentration ratios. However, LCModel was marginally more accurate than SAGE because of its full automation, basis set, and user independency.

Comparison of accelerated 3-D spiral chemical shift imaging and single-voxel spectroscopy at 3T in the pediatric age group.

PubMed

Yazbek, Sandrine; Prabhu, Sanjay P; Connaughton, Pauline; Grant, Patricia E; Gagoski, Borjan

2015-08-01

Single-voxel spectroscopy (SVS) is usually used in the pediatric population when a short acquisition time is crucial. To overcome the long acquisition time of 3-D phase-encoded chemical shift imaging (CSI) and lack of spatial coverage of single-voxel spectroscopy, efficient encoding schemes using spiral k-space trajectories have been successfully deployed, enabling acquisition of volumetric CSI in <5 min. We assessed feasibility of using 3-D spiral CSI sequence routinely in pediatric clinical settings by comparing its reconstructed spectra against SVS spectra. Volumetric spiral CSI obtained spectra from 2-cc isotropic voxels over a 16×16×10-cm region. SVS acquisition encoded a 3.4-cc (1.5-mm) isotropic voxel. Acquisition time was 3 min for every technique. Data were gathered prospectively from 11 random pediatric patients. Spectra from left basal ganglia were obtained using both techniques and were processed with post-processing software. The following metabolite ratios were calculated: N-acetylaspartate/creatine (NAA/Cr), choline/creatine (Cho/Cr), lactate/creatine (Lac/Cr) and N-acetylapartate/choline (NAA/Cho). We collected data on 11 children ages 4 days to 10 years. In 10/11 cases, spectral quality of both methods was acceptable. Considering 10/11 cases, we found a statistically significant difference between SVS and 3-D spiral CSI for all three ratios. However, this difference was fixed and was probably caused by a fixed bias. This means that 3-D spiral CSI can be used instead of SVS by removing the mean difference between the methods for each ratio. Accelerated 3-D CSI is feasible in pediatric patients and can potentially substitute for SVS.

Reproducibility and reliability of short-TE whole-brain MR spectroscopic imaging of human brain at 3T.

PubMed

Ding, Xiao-Qi; Maudsley, Andrew A; Sabati, Mohammad; Sheriff, Sulaiman; Dellani, Paulo R; Lanfermann, Heinrich

2015-03-01

A feasibility study of an echo-planar spectroscopic imaging (EPSI) using a short echo time (TE) that trades off sensitivity, compared with other short-TE methods, to achieve whole brain coverage using inversion recovery and spatial oversampling to control lipid bleeding. Twenty subjects were scanned to examine intersubject variance. One subject was scanned five times to examine intrasubject reproducibility. Data were analyzed to determine coefficients of variance (COV) and intraclass correlation coefficient (ICC) for N-acetylaspartate (NAA), total creatine (tCr), total choline (tCho), glutamine/glutamate (Glx), and myo-inositol (mI). Regional metabolite concentrations were derived by using multi-voxel analysis based on lobar-level anatomic regions. For whole-brain mean values, the intrasubject COVs were 14%, 15%, and 20% for NAA, tCr, and tCho, respectively, and 31% for Glx and mI. The intersubject COVs were up to 6% higher. For regional distributions, the intrasubject COVs were ≤ 5% for NAA, tCr, and tCho; ≤ 9% for Glx; and ≤15% for mI, with about 6% higher intersubject COVs. The ICCs of 5 metabolites were ≥ 0.7, indicating the reliability of the measurements. The present EPSI method enables estimation of the whole-brain metabolite distributions, including Glx and mI with small voxel size, and a reasonable scan time and reproducibility. © 2014 Wiley Periodicals, Inc.

GABA content within the ventromedial prefrontal cortex is related to trait anxiety.

PubMed

Delli Pizzi, Stefano; Padulo, Caterina; Brancucci, Alfredo; Bubbico, Giovanna; Edden, Richard A; Ferretti, Antonio; Franciotti, Raffaella; Manippa, Valerio; Marzoli, Daniele; Onofrj, Marco; Sepede, Gianna; Tartaro, Armando; Tommasi, Luca; Puglisi-Allegra, Stefano; Bonanni, Laura

2016-05-01

The ventromedial prefrontal cortex (vmPFC) plays a key role in emotion processing and regulation. vmPFC dysfunction may lead to disinhibition of amygdala causing high anxiety levels. γ-Aminobutyric acid (GABA) inter-neurons within vmPFC shape the information flow to amygdala. Thus, we hypothesize that GABA content within vmPFC could be relevant to trait anxiety. Forty-three healthy volunteers aged between 20 and 88 years were assessed for trait anxiety with the Subscale-2 of the State-Trait-Anxiety Inventory (STAI-Y2) and were studied with proton magnetic resonance spectroscopy to investigate GABA and Glx (glutamate+glutamine) contents within vmPFC. Total creatine (tCr) was used as internal reference. Partial correlations assessed the association between metabolite levels and STAI-Y2 scores, removing the effect of possible nuisance factors including age, educational level, volumes of gray matter and white matter within magnetic resonance spectroscopy voxel. We observed a positive relationship between GABA/tCr and STAI-Y2 scores. No significant relationships were found between Glx/tCr and STAI-Y2 and between tCr/water and STAI-Y2. No differences were found between males and females as regards to age, STAI-Y2, GABA/tCr, Glx/tCr, tCr/water, gray matter and white matter volumes. We suggest a close relationship between GABA content within vmPFC and trait anxiety providing new insights in the physiology of emotional brain. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Monitoring interferon β treatment response with magnetic resonance spectroscopy in relapsing remitting multiple sclerosis.

PubMed

Yetkin, Mehmet Fatih; Mirza, Meral; Dönmez, Halil

2016-09-01

The aim of this study is to compare the white matter of multiple sclerosis (MS) patients with healthy controls and to monitor the response to the treatment with magnetic resonance spectroscopy (MRS).Fifteen healthy controls and 36 recently diagnosed MS patients never treated with interferon β were included in this study. In the patient group, MRS was performed before treatment, at 6th and 12th month after the initiation of treatment and once in control group. Patient group was divided into 3 interferon groups randomly. Physical examination findings were recorded as Expanded Disability Status Scale scores before treatment, at 6th and 12th month of interferon treatment.At the end of 1 year follow up, 26 of 36 patients completed the study. In patients' white matter lesions, N-acetylaspartate/creatine (NAA/Cr) ratios were lower than control group's white matters. NAA/Cr ratios were higher in control group's white matter than patient's normal appearing white matter but this difference was not statistically significant. There was no difference in choline/creatine (Cho/Cr) ratios between 2 groups. In follow-up period, NAA/Cr and Cho/Cr ratios obtained from patients' white matter lesions and normal appearing white matter did not change statistically.This study showed that in MS patients' white matters, especially in white matter lesions, neuron viability is reduced compared with healthy controls' normal white matter; and in the patients treated with interferon β NAA/Cr ratios remained stable. These stable levels of metabolite ratios in the patients who received interferon β therapy can be explained with either the shortness of the follow-up period post-treatment or may reflect a positive effect of the beta interferon therapy on the progress of MS.

The effects of copper-histidine therapy on brain metabolism in a patient with Menkes disease: a proton magnetic resonance spectroscopic study.

PubMed

Munakata, Mitsutoshi; Sakamoto, Osamu; Kitamura, Taro; Ishitobi, Mamiko; Yokoyama, Hiroyuki; Haginoya, Kazuhiro; Togashi, Noriko; Tamura, Hajime; Higano, Shuichi; Takahashi, Shoki; Ohura, Toshihiro; Kobayashi, Yasuko; Onuma, Akira; Iinuma, Kazuie

2005-06-01

We report on metabolic changes in the brain of a boy with Menkes disease. He was treated with parenteral copper (Cu)-histidine supplementation, from 5 months of age, and assessed with proton magnetic resonance spectroscopy ((1)H-MRS). The single-voxel (1)H-MRS before treatment revealed an accumulation of lactate and a reduced N-acetyl aspartate (NAA)/total creatine (tCr) ratio with a z-score of -3.0. During treatment, the lactate signal faded away, whereas the NAA signal gradually increased to a z-score of -1.5 at 120 days of treatment. The choline/tCr ratio did not deviate much initially (z-score +0.5), but the ratio increased markedly during treatment (z-score +4.8). Consequently, the Cu-histidine therapy initiated after the critical period still improved the neuronal metabolism, suggesting that some Cu was delivered to neurons. Nevertheless, the brain atrophy, impaired myelination, and severe neurological symptoms were not ameliorated.

Multivoxel proton magnetic resonance spectroscopy in facioscapulohumeral muscular dystrophy.

PubMed

Leung, Doris G; Wang, Xin; Barker, Peter B; Carrino, John A; Wagner, Kathryn R

2018-06-01

Facioscapulohumeral muscular dystrophy (FSHD) is a hereditary disorder that causes progressive muscle wasting. This study evaluates the use of proton magnetic resonance spectroscopy ( 1 H MRS) as a biomarker of muscle strength and function in FSHD. Thirty-six individuals with FSHD and 15 healthy controls underwent multivoxel 1 H MRS of a cross-section of the mid-thigh. Concentrations of creatine, intramyocellular and extramyocellular lipids, and trimethylamine (TMA)-containing compounds in skeletal muscle were calculated. Metabolite concentrations for individuals with FSHD were compared with those of controls. The relationship between metabolite concentrations and muscle strength was also examined. The TMA/creatine (Cr) ratio in individuals with FSHD was reduced compared with controls. The TMA/Cr ratio in the hamstrings also showed a moderate linear correlation with muscle strength. 1 H MRS offers a potential method of detecting early muscle pathology in FSHD prior to the development of fat infiltration. Muscle Nerve 57: 958-963, 2018. © 2017 Wiley Periodicals, Inc.

Lower Choline-Containing Metabolites/Creatine (Cr) Rise and Failure to Sustain NAA/Cr Levels in the Dorsolateral Prefrontal Cortex Are Associated with Depressive Episode Recurrence under Maintenance Therapy: A Proton Magnetic Resonance Spectroscopy Retrospective Cohort Study.

PubMed

Henigsberg, Neven; Šarac, Helena; Radoš, Marko; Radoš, Milan; Ozretić, David; Foro, Tamara; Erdeljić Turk, Viktorija; Hrabač, Pero; Bajs Janović, Maja; Rak, Benedict; Kalember, Petra

2017-01-01

The aim of this study was to evaluate the relationship between changes in proton magnetic resonance spectroscopy (1H-MRS) parameters at the start of the index episode recovery phase and at recurrence in patients with recurrent depression who were treated with prolonged maintenance therapy. 1H-MRS parameters were analyzed in 48 patients with recurrent depression who required maintenance therapy with antidepressant medication prescribed by a psychiatrist and who continued with the same antidepressant during the maintenance phase, either to recurrence of depression, completion of the 10-year observation period, or the start of the withdrawal phase (tapering-off antidepressant). N-acetylaspartate (NAA), choline-containing metabolites (Cho), creatine (Cr), and glutamine/glutamate were measured at the start of the recovery phase and 6 months later. Recurrent depressive episodes occurred in 20 patients. These individuals had a smaller increase in Cho/Cr after the beginning of the recovery phase compared to the non-recurrent patient group and also exhibited a decreased NAA/Cr ratio. Sustainable NAA and increased Cho levels at the onset of the recovery phase of the index episode are early markers of antidepressant effectiveness associated with a lower risk of major depressive disorder recurrence. The NAA and Cho changes in the non-recurrent group may be attributable to increased brain resilience, contrary to the transient temporal effect observed in subjects who experienced a depressive episode.

1H-MR spectroscopy metabolite levels correlate with executive function in vascular cognitive impairment

PubMed Central

Gasparovic, Charles; Prestopnik, Jillian; Thompson, Jeffrey; Taheri, Saeid; Huisa, Branko; Schrader, Ronald; Adair, John C; Rosenberg, Gary A

2013-01-01

Background White matter hyperintensities (WMHs) are associated with vascular cognitive impairment (VCI) but fail to correlate with neuropsychological measures. As proton MR spectroscopy (1H-MRS) can identify ischaemic tissue, we hypothesised that MRS detectable brain metabolites would be superior to WMHs in predicting performance on neuropsychological tests. Methods 60 patients with suspected VCI underwent clinical, neuropsychological, MRI and CSF studies. They were diagnosed as having subcortical ischaemic vascular disease (SIVD), multiple infarcts, mixed dementia and leukoaraiosis. We measured brain metabolites in a white matter region above the lateral ventricles with 1H-MRS and WMH volume in this region and throughout the brain. Results We found a significant correlation between both total creatine (Cr) and N-acetylaspartyl compounds (NAA) and standardised neuropsychological test scores. Cr levels in white matter correlated significantly with executive function (p=0.001), attention (p=0.03) and overall T score (p=0.007). When lesion volume was added as a covariate, NAA also showed a significant correlation with executive function (p=0.003) and overall T score (p=0.015). Furthermore, while metabolite levels also correlated with total white matter lesion volume, adjusting the Cr levels for lesion volume did not diminish the strength of the association between Cr levels and neuropsychological scores. The lowest metabolite levels and neuropsychological scores were found in the SIVD group. Finally, lesion volume alone did not correlate significantly with any neuropsychological test score. Conclusion These results suggest that estimates of neurometabolite levels provide additional and useful information concerning cognitive function in VCI not obtainable by measurements of lesion load. PMID:23418212

Creatine ( methyl-d3) dilution in urine for estimation of total body skeletal muscle mass: accuracy and variability vs. MRI and DXA.

PubMed

Clark, Richard V; Walker, Ann C; Miller, Ram R; O'Connor-Semmes, Robin L; Ravussin, Eric; Cefalu, William T

2018-01-01

A noninvasive method to estimate muscle mass based on creatine ( methyl-d 3 ) (D 3 -creatine) dilution using fasting morning urine was evaluated for accuracy and variability over a 3- to 4-mo period. Healthy older (67- to 80-yr-old) subjects ( n = 14) with muscle wasting secondary to aging and four patients with chronic disease (58-76 yr old) fasted overnight and then received an oral 30-mg dose of D 3 -creatine at 8 AM ( day 1). Urine was collected during 4 h of continued fasting and then at consecutive 4- to 8-h intervals through day 5. Assessment was repeated 3-4 mo later in 13 healthy subjects and 1 patient with congestive heart failure. Deuterated and unlabeled creatine and creatinine were measured using liquid chromatography-tandem mass spectrometry. Total body creatine pool size and muscle mass were calculated from D 3 -creatinine enrichment in urine. Muscle mass was also measured by whole body MRI and 24-h urine creatinine, and lean body mass (LBM) was measured by dual-energy X-ray absorptiometry (DXA). D 3 -creatinine urinary enrichment from day 5 provided muscle mass estimates that correlated with MRI for all subjects ( r = 0.88, P < 0.0001), with less bias [difference from MRI = -3.00 ± 2.75 (SD) kg] than total LBM assessment by DXA, which overestimated muscle mass vs. MRI (+22.5 ± 3.7 kg). However, intraindividual variability was high with the D 3 -creatine dilution method, with intrasubject SD for estimated muscle mass of 2.5 kg vs. MRI (0.5 kg) and DXA (0.8 kg). This study supports further clinical validation of the D 3 -creatine method for estimating muscle mass. NEW & NOTEWORTHY Measurement of creatine ( methyl-d 3 ) (D 3 -creatine) and D 3 -creatinine excretion in fasted morning urine samples may be a simple, less costly alternative to MRI or dual-energy X-ray absorptiometry (DXA) to calculate total body muscle mass. The D 3 -creatine enrichment method provides estimates of muscle mass that correlate well with MRI, and with less bias than DXA. However, intraindividual variability is high with the D 3 -creatine method. Studies to refine the spot urine sample method for estimation of muscle mass may be warranted.

Reduced thalamic N-acetylaspartate in idiopathic normal pressure hydrocephalus: a controlled 1H-magnetic resonance spectroscopy study of frontal deep white matter and the thalamus using absolute quantification.

PubMed

Lundin, F; Tisell, A; Dahlqvist Leinhard, O; Tullberg, M; Wikkelsö, C; Lundberg, P; Leijon, G

2011-07-01

Patients with idiopathic normal pressure hydrocephalus (INPH) frequently have a reduction in cerebral blood flow in the subcortical frontal lobe/basal ganglia/thalamic areas. With magnetic resonance spectroscopy, the metabolism in the brain can be examined. The aim of this study was to investigate if there was a compromised metabolism in the thalamus and in the subcortical frontal areas in INPH patients. This was done by measuring total creatine, myo-inositol, total choline, N-acetylaspartate (NAA), total N-acetylaspartate (tNA), glutamate and lactate levels. A comparison was made with healthy individuals (HI). 16 patients (nine males, seven females, mean age 74 years, range 49-83) diagnosed as INPH and 15 HI (nine males, six females, mean age 74 years, range 62-89) were examined. (1)H magnetic resonance spectroscopy (1.5 T, point-resolved spectroscopy, echo time/relaxation time 30/3000 ms, volume of interest 2.5-3 ml) was performed in frontal deep white matter and in the thalamus. Absolute quantification with internal water as a reference was used. INPH patients had lower NAA (p=0.02) and lower tNA (p=0.05) concentrations in the thalamus compared with HI. NAA and tNA in the frontal deep white matter did not differ between patients and HI. The absolute metabolic concentrations of total creatine, myo-inositol total choline, tNA, lactate and Cr ratios in frontal deep white matter and in the thalamus were similar in INPH patients and HI. Reduced thalamic NAA and tNA in INPH patients suggest a compromised metabolic neuronal function in these regions. Thus, the thalamus might have an important role in the pathogenesis of INPH.

Study of renal and hepatic toxicity in rats supplemented with creatine.

PubMed

Baracho, Nilo Cesar do Vale; Castro, Letícia Pereira de; Borges, Niara da Cunha; Laira, Patrícia Benício

2015-05-01

To evaluate the renal and hepatic function, through biochemical analysis after 14 days of creatine supplementation in physically inactive rats. Twenty four male, adult, Wistar rats were used which were kept in individual metabolic cages and were distributed into four groups, and received the following treatments by gavage:1) CONTROL: distilled water; 2)Creatine 0.5g/Kg/day; 3) Creatine 1g/Kg/day; 4) Creatine 2g/Kg/day. Their urinary outputs as well as food and water intake were daily measured. At the end of the experiment, the animals were euthanized and serum samples were stored for biochemical analysis. Creatine supplementation at the doses given produced no significant changes in plasma levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total protein, albumin, total cholesterol, HDL cholesterol, LDL cholesterol, VLDL cholesterol, triglycerides, glucose, creatinine, urea, and creatinine clearance, compared to control group (p> 0.05) Similarly, water and food intake, as well as urinary output, did not show significant changes among the four groups studied. At the doses used, oral creatine supplementation did not result in renal and/or hepatic toxicity.

Activation induced changes in GABA: Functional MRS at 7T with MEGA-sLASER.

PubMed

Chen, Chen; Sigurdsson, Hilmar P; Pépés, Sophia E; Auer, Dorothee P; Morris, Peter G; Morgan, Paul S; Gowland, Penny A; Jackson, Stephen R

2017-08-01

Functional magnetic resonance spectroscopy (fMRS) has been used to assess the dynamic metabolic responses of the brain to a physiological stimulus non-invasively. However, only limited information on the dynamic functional response of γ-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the brain, is available. We aimed to measure the activation-induced changes in GABA unambiguously using a spectral editing method, instead of the conventional direct detection techniques used in previous fMRS studies. The Mescher-Garwood-semi-localised by adiabatic selective refocusing (MEGA-sLASER) sequence was developed at 7T to obtain the time course of GABA concentration without macromolecular contamination. A significant decrease (-12±5%) in the GABA to total creatine ratio (GABA/tCr) was observed in the motor cortex during a period of 10min of hand-clenching, compared to an initial baseline level (GABA/tCr =0.11±0.02) at rest. An increase in the Glx (glutamate and glutamine) to tCr ratio was also found, which is in agreement with previous findings. In contrast, no significant changes in NAA/tCr and tCr were detected. With consistent and highly efficient editing performance for GABA detection and the advantage of visually identifying GABA resonances in the spectra, MEGA-sLASER is demonstrated to be an effective method for studying of dynamic changes in GABA at 7T. Copyright © 2017 Elsevier Inc. All rights reserved.

Increased myo-inositol level in dorsolateral prefrontal cortex in migraine patients with major depression.

PubMed

Lirng, Jiing-Feng; Chen, Hung-Chieh; Fuh, Jong-Ling; Tsai, Chia-Fen; Liang, Jen-Feng; Wang, Shuu-Jiun

2015-07-01

Although the comorbidity between migraine and major depressive disorder (MDD) has been recognized, the pathophysiology remains unclear. The dorsolateral prefrontal cortex (DLPFC) is a well-known neural substrate for MDD. We investigated the relationship between brain metabolites in DLPFC and comorbid MDD in migraine patients. We recruited migraine patients from a tertiary headache clinic. A board-certified psychiatrist conducted a structured interview for MDD diagnosis. The severity of depression was evaluated by the Beck Depression Inventory (BDI). Thirty migraine patients (five men, 25 women; mean age: 40.4 ± 12.4 years) completed the study, and 16 of them were diagnosed with MDD. All patients underwent a magnetic resonance spectroscopy (MRS) examination focusing on bilateral DLPFC. The ratios of N-acetylaspartate (NAA), choline (Cho), and myo-inositol (mI) to total creatine (tCr) were compared between migraine patients with and without MDD, and were correlated with BDI scores. Relative to patients without MDD, migraine patients with MDD had higher mI/tCr ratios in the bilateral DLPFC (p = 0.02, left; p = 0.02, right, Mann-Whitney U test). The mI/tCr ratios in the right DLPFC were positively correlated with BDI scores (r = 0.52, p = 0.003). The NAA/tCr and Cho/tCr ratios did not differ between migraine patients with and without MDD. Increased mI/tCr within the DLPFC might be associated with the presence of MDD in migraine patients. © International Headache Society 2014.

Blood harmane is correlated with cerebellar metabolism in essential tremor: a pilot study.

PubMed

Louis, Elan D; Zheng, Wei; Mao, Xiangling; Shungu, Dikoma C

2007-08-07

On proton magnetic resonance spectroscopic imaging ((1)H MRSI), there is a decrease in cerebellar N-acetylaspartate/total creatine (NAA/tCr) in essential tremor (ET), signifying cerebellar neuronal dysfunction or degeneration. Harmane, which is present in the human diet, is a potent tremor-producing neurotoxin. Blood harmane concentrations seem to be elevated in ET. To assess in patients with ET whether blood harmane concentration is correlated with cerebellar NAA/tCR, a neuroimaging measure of neuronal dysfunction or degeneration. Twelve patients with ET underwent (1)H MRSI. The major neuroanatomic structure of interest was the cerebellar cortex. Secondary regions were the central cerebellar white matter, cerebellar vermis, thalamus, and basal ganglia. Blood concentrations of harmane and another neurotoxin, lead, were also assessed. Mean +/- SD cerebellar NAA/tCR was 1.52 +/- 0.41. In a linear regression model that adjusted for age and gender, log blood harmane concentration was a predictor of cerebellar NAA/tCR (beta = -0.41, p = 0.009); every 1 g(-10)/mL unit increase in log blood harmane concentration was associated with a 0.41 unit decrease in cerebellar NAA/tCR. The association between blood harmane concentration and brain NAA/tCR only occurred in the cerebellar cortex; it was not observed in secondary brain regions of interest. Furthermore, the association was specific to harmane and not another neurotoxin, lead. This study provides additional support for the emerging link between harmane, a neurotoxin, and ET. Further studies are warranted to address whether cerebellar harmane concentrations are associated with cerebellar pathology in postmortem studies of the ET brain.

Decreased choline and creatine concentrations in centrum semiovale in patients with generalized anxiety disorder: relationship to IQ and early trauma.

PubMed

Coplan, Jeremy D; Mathew, Sanjay J; Mao, Xiangling; Smith, Eric L P; Hof, Patrick R; Coplan, Paul M; Rosenblum, Leonard A; Gorman, Jack M; Shungu, Dikoma C

2006-06-30

We have demonstrated, using proton magnetic resonance spectroscopy imaging ((1)H-MRSI), elevations of N-acetyl-aspartate/creatine (NAA/CR) in right dorsolateral prefrontal cortex (DLPFC) in patients with generalized anxiety disorder (GAD) in comparison to healthy volunteers. A recent study indicates that the volume of prefrontal cortical white matter may be disproportionately increased in man in comparison to other primate species, with evolutionary implications. We therefore re-analyzed the identical scans with a specific focus on the centrum semiovale (CSO) as a representative region of interest of cerebral white matter. The central hypothesis was, in accordance with our gray matter findings, that patients with GAD, in comparison to healthy controls, would exhibit either an increase in NAA in CSO, or alternatively demonstrate reductions in concentrations of choline (CHO)-containing compounds and/or creatine+phosphocreatine (CR). MRSI scans that were obtained from an earlier [Mathew, S.J., Mao, X., Coplan, J.D., Smith, E.L., Sackeim, H.A., Gorman, J.M., Shungu, D.C., 2004. Dorsolateral prefrontal cortical pathology in generalized anxiety disorder: a proton magnetic resonance spectroscopic imaging study. American Journal of Psychiatry 161, 1119-1121] sample of 15 patients with GAD [6 with early trauma (ET)] and 15 healthy age- and sex-matched volunteers were analyzed further for CSO metabolite alterations. Self-reported worry was scored using the Penn State Worry Questionnaire (PSWQ) and intelligence was assessed using the Wechsler Abbreviated Scale of Intelligence (WASI). Serial multislice/multivoxel MRSI scans had been performed on a 1.5-T MRI. Using absolute quantification methods for metabolite concentrations, we examined NAA, CHO and CR. GAD patients without ET exhibited bilaterally decreased concentrations of CHO and CR in CSO in comparison to healthy volunteers, whereas GAD patients with ET were indistinguishable from controls. In patients with GAD, high IQ was paired with greater worry, whereas in healthy volunteers, high IQ was associated with less worry. In all subjects, IQ inversely predicted left and right CSO CHO concentrations, independent of age, sex, group assignment and PSWQ scores. The CSO may therefore represent a neural substrate that exhibits reductions in CHO and CR metabolite concentrations that are inversely associated with GAD symptomatology and, in the case of CHO, with intelligence. These conclusions are deemed preliminary due to small sample size, with further study of cerebral WM in anxiety disorders suggested.

Creatine supplementation in high school football players.

PubMed

McGuine, T A; Sullivan, J C; Bernhardt, D T

2001-10-01

To describe creatine supplementation patterns and behaviors associated with creatine supplementation in high school football players. A cross-sectional, multisite, anonymous, descriptive survey was conducted between October 1999 and February 2000. 37 public high schools in Wisconsin. A total of 1,349 high school football players, grades 9-12. Self-reported prevalence of creatine use, as well as perceived benefits and risks. In addition, sources of information and influence regarding creatine supplementation were assessed. 30% of the respondents reported using creatine. Creatine use was lowest in the 9th grade (10.4%) and highest in the 12th grade (50.5%). 41% of the players at small schools stated they used creatine compared with 29% of the players in large schools. Enhanced recovery following a workout was the most likely perceived benefit of creatine supplementation, while dehydration was cited most often as a risk of creatine use. Users were encouraged to take creatine most often by their friends while their parents discouraged creatine use. Creatine use is widespread in high school football players. High school football players who use creatine may not be aware of the risks and benefits associated with creatine supplementation. Sports medicine professionals who work with this population need to educate athletes, coaches, and parents about the use of creatine as a performance-enhancing supplement.

Creatine supplementation and physical training in patients with COPD: A double blind, placebo-controlled study

PubMed Central

Faager, Gun; Söderlund, Karin; Sköld, Carl Magnus; Rundgren, Siw; Tollbäck, Anna; Jakobsson, Per

2006-01-01

Study objectives Patients with chronic obstructive pulmonary disease (COPD) have low exercise capacity and low content of high energetic phosphates in their skeletal muscles. The aim of the present study was to investigate whether creatine supplementation together with exercise training may increase physical performance compared with exercise training in patients with COPD. Design In a randomized, double-blind, placebo-controlled study, 23 patients with COPD (forced expiratory volume in one second [FEV1] < 70% of predicted) were randomized to oral creatine (n = 13) or placebo (n = 10) supplementation during an 8-week rehabilitation programme including exercise training. Physical performance was assessed by Endurance Shuttle Walking Test (ESWT), dyspnea and leg fatigue with Borg CR-10, quality of life with St George’s Respiratory Questionnaire (SGRQ). In addition, lung function test, artery blood gases, grip strength test, muscle strength and fatigue in knee extensors were measured. Results COPD patients receiving creatine supplementation increased their average walking time by 61% (ESWT) (p < 0.05) after the training period compared with 48% (p = 0.07) in the placebo group. Rated dyspnea directly after the ESWT decreased significantly from 7 to 5 (p < 0.05) in the creatine group. However, the difference between the groups was not statistically significant neither in walking time nor in rated dyspnea. Creatine supplementation did not increase the health related quality of life, lung function, artery blood gases, grip strength and knee extensor strength/fatigue. Conclusions Oral creatine supplementation in combination with exercise training showed no significant improvement in physical performance, measured as ESWT, in patients with COPD compared with exercise training alone. PMID:18044100

1H-MR spectroscopy and diffusion tensor imaging of normal-appearing temporal white matter in patients with nasopharyngeal carcinoma after irradiation: initial experience.

PubMed

Xiong, Wei Feng; Qiu, Shi Jun; Wang, Hong Zhuo; Lv, Xiao Fei

2013-01-01

To detect radiation-induced changes of temporal lobe normal-appearing white mater (NAWM) following radiation therapy (RT) for nasopharyngeal carcinoma (NPC). Seventy-five H(1)-MR spectroscopy and diffusion-tensor imaging (DTI) examinations were performed in 55 patients before and after receiving fractionated radiation therapy (total dose; 66-75GY). We divided the dataset into six groups, a pre-RT control group and five other groups based on time after completion of RT. N-acetylaspartic acid (NAA)/choline (Cho), NAA/creatine (Cr), Cho/Cr, mean diffusibility (MD), functional anisotropy (FA), radial diffusibility (λ(⊥)), and axial diffusibility (λ(||)) were calculated. NAA/Cho and NAA/Cr decreased and λ(⊥) increased significantly within 1 year after RT compared with pre-RT. After 1 year, NAA/Cho, NAA/Cr, and λ(⊥) were not significantly different from pre-RT. In all post-RT groups, FA decreased significantly. λ(||) decreased within 9 months after RT compared with pre-RT, but was not significantly different from pre-RT more than 9 months after RT. DTI and H(1)-MR spectroscopy can be used to detect early radiation-induced changes of temporal lobe NAWM following radiation therapy for NPC. Metabolic alterations and water diffusion characteristics of temporal lobe NAWM in patients with NPC after RT were dynamic and transient. Copyright © 2012 Wiley Periodicals, Inc.

Brain metabolic correlates of decision making in amnestic mild cognitive impairment.

PubMed

Griffith, H Randall; Okonkwo, Ozioma C; den Hollander, Jan A; Belue, Katherine; Copeland, Jacqueline; Harrell, Lindy E; Brockington, John C; Clark, David G; Marson, Daniel C

2010-01-01

Persons with amnestic mild cognitive impairment (MCI) have subtle impairments in medical decision-making capacity (MDC). We examined the relationship between proton magnetic resonance spectroscopy (MRS) and MDC in MCI. Twenty-nine MCI patients and 42 controls underwent MRS to obtain ratios of N-acetylaspartate (NAA)/Creatine (Cr), Choline (Cho)/Cr, and myo-Inositol (mI)/Cr of the posterior cingulate. They also completed the Capacity to Consent to Treatment Instrument (CCTI), a vignette-based instrument measuring decisional standards of expressing choice, appreciating consequences of choice, providing rational reasons for choice, and understanding treatment choices. Patients showed abnormal MRS ratios of mI/Cr and Cho/Cr compared to controls, and impairments on the CCTI understanding and reasoning Standards. Performance on the reasoning standard of the CCTI was correlated with NAA/Cr (r = .46, p < .05). The relationship of NAA/Cr with decision-making suggests a role for posterior cortical neuronal functioning in performance of complex IADLs in MCI.

Lack of effect of oral choline supplement on the concentrations of choline metabolites in human brain.

PubMed

Tan, J; Bluml, S; Hoang, T; Dubowitz, D; Mevenkamp, G; Ross, B

1998-06-01

Recent reports suggest that oral choline supplement may alter the cerebral choline/creatine (Cho/Cr) ratio and might be used to treat neurodegenerative disorders of cholinergic transmission. Using both 1H and 31P MRS, we reexamined the Cho/Cr ratio and quantified cerebral choline and its major constituents: phosphoethanolamine (PE), phosphorylcholine (PC), glycerophosphorylethanolamine (GPE), and glycerophosphorylcholine (GPC). In the four brain locations examined, no significant increases in Cho/Cr, [Cho], or in its major constituents were found in response to an oral challenge of 50 mg/kg of choline bitartrate. Oral choline did not significantly affect human cerebral metabolism in the short term.

Rate equation for creatine kinase predicts the in vivo reaction velocity: /sup 31/P NMR surface coil studies in brain, heart, and skeletal muscle of the living rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bittl, J.A.; DeLayre, J.; Ingwall, J.S.

1987-09-22

Brain, heart, and skeletal muscle contain four different creatine kinase isozymes and various concentrations of substrates for the creatine kinase reaction. To identify if the velocity of the creatine kinase reaction under cellular conditions is regulated by enzyme activity and substrate concentrations as predicted by the rate equation, the authors used /sup 31/P NMR and spectrophotometric techniques to measure reaction velocity, enzyme content, isozyme distribution, and concentrations of substrates in brain, heart, and skeletal muscle of living rat under basal or resting conditions. The total tissue activity of creatine kinase in the direction of MgATP synthesis provided an estimate formore » V/sub max/ and exceeded the NMR-determined in vivo reaction velocities by an order of magnitude. The isozyme composition varied among the three tissues: >99% BB for brain; 14% MB, 61% MM, and 25% mitochondrial for heart; and 98% MM and 2% mitochondrial for skeletal muscle. The NMR-determined reaction velocities agreed with predicted values from the creatine kinase rate equation. The concentrations of free creatine and cytosolic MgADP, being less than or equal to the dissociation constants for each isozyme, were dominant terms in the creatine kinase rate equation for predicting the in vivo reaction velocity. Thus, they observed that the velocity of the creatine kinase reaction is regulated by total tissue enzyme activity and by the concentrations of creatine and MgADP in a manner that is independent of isozyme distribution.« less

Role of creatine supplementation on exercise-induced cardiovascular function and oxidative stress

PubMed Central

Cunningham, Daniel; Mason, Laura; Kilduff, Liam P; McEneny, Jane

2009-01-01

Many degenerative diseases are associated with increased oxidative stress. Creatine has the potential to act as an indirect and direct antioxidant; however, limited data exist to evaluate the antioxidant capabilities of creatine supplementation within in vivo human systems. This study aimed to investigate the effects of oral creatine supplementation on markers of oxidative stress and antioxidant defenses following exhaustive cycling exercise. Following preliminary testing and two additional familiarization sessions, 18 active males repeated two exhaustive incremental cycling trials (T1 and T2) separated by exactly 7 days. The subjects were assigned, in a double-blind manner, to receive either 20 g of creatine (Cr) or a placebo (P) for the 5 days preceding T2. Breath-by-breath respiratory data and heart rate were continually recorded throughout the exercise protocol and blood samples were obtained at rest (preexercise), at the end of exercise (postexercise), and the day following exercise (post24 h). Serum hypdroperoxide concentrations were elevated at postexercise by 17 ± 5% above preexercise values (p = 0.030). However, supplementation did not influence lipid peroxidation (serum hypdroperoxide concentrations), resistance of low density lipoprotein to oxidative stress (t1/2max LDL oxidation) and plasma concentrations of non-enzymatic antioxidants (retinol, α-carotene, β-carotene, α-tocopherol, γ-tocopherol, lycopene and vitamin C). Heart rate and oxygen uptake responses to exercise were not affected by supplementation. These findings suggest that short-term creatine supplementation does not enhance non-enzymatic antioxidant defence or protect against lipid peroxidation induced by exhaustive cycling in healthy males. PMID:20716911

Distinction Between Recurrent Glioma and Radiation Injury Using Magnetic Resonance Spectroscopy in Combination With Diffusion-Weighted Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zeng, Q.-S.; Li, C.-F.; Liu Hong

2007-05-01

Purpose: The aim of this study was to explore the diagnostic effectiveness of magnetic resonance (MR) spectroscopy with diffusion-weighted imaging on the evaluation of the recurrent contrast-enhancing areas at the site of treated gliomas. Methods and Materials: In 55 patients who had new contrast-enhancing lesions in the vicinity of the previously resected and irradiated high-grade gliomas, two-dimensional MR spectroscopy and diffusion-weighted imaging were performed. Spectral data for N-acetylaspartate (NAA), choline (Cho), creatine (Cr), lipid (Lip), and lactate (Lac) were analyzed in conjunction with the apparent diffusion coefficient (ADC) in all patients. Diagnosis of these lesions was assigned by means ofmore » follow-up or histopathology. Results: The Cho/NAA and Cho/Cr ratios were significantly higher in recurrent tumor than in regions of radiation injury (p < 0.01). The ADC value and ADC ratios (ADC of contrast-enhancing lesion to matching structure in the contralateral hemisphere) were significantly higher in radiation injury regions than in recurrent tumor (p < 0.01). With MR spectroscopic data, two variables (Cho/NAA and Cho/Cr ratios) were shown to differentiate recurrent glioma from radiation injury, and 85.5% of total subjects were correctly classified into groups. However, with discriminant analysis of MR spectroscopy imaging plus diffusion-weighted imaging, three variables (Cho/NAA, Cho/Cr, and ADC ratio) were identified and 96.4% of total subjects were correctly classified. There was a significant difference between the diagnostic accuracy of the two discriminant analyses (Chi-square = 3.96, p = 0.046). Conclusion: Using discriminant analysis, this study found that MR spectroscopy in combination with ADC ratio, rather than ADC value, can improve the ability to differentiate recurrent glioma and radiation injury.« less

Global brain metabolic quantification with whole-head proton MRS at 3 T.

PubMed

Kirov, Ivan I; Wu, William E; Soher, Brian J; Davitz, Matthew S; Huang, Jeffrey H; Babb, James S; Lazar, Mariana; Fatterpekar, Girish; Gonen, Oded

2017-10-01

Total N-acetyl-aspartate + N-acetyl-aspartate-glutamate (NAA), total creatine (Cr) and total choline (Cho) proton MRS ( 1 H-MRS) signals are often used as surrogate markers in diffuse neurological pathologies, but spatial coverage of this methodology is limited to 1%-65% of the brain. Here we wish to demonstrate that non-localized, whole-head (WH) 1 H-MRS captures just the brain's contribution to the Cho and Cr signals, ignoring all other compartments. Towards this end, 27 young healthy adults (18 men, 9 women), 29.9 ± 8.5 years old, were recruited and underwent T 1 -weighted MRI for tissue segmentation, non-localizing, approximately 3 min WH 1 H-MRS (T E /T R /T I  = 5/10/940 ms) and 30 min 1 H-MR spectroscopic imaging (MRSI) (T E /T R  = 35/2100 ms) in a 360 cm 3 volume of interest (VOI) at the brain's center. The VOI absolute NAA, Cr and Cho concentrations, 7.7 ± 0.5, 5.5 ± 0.4 and 1.3 ± 0.2 mM, were all within 10% of the WH: 8.6 ± 1.1, 6.0 ± 1.0 and 1.3 ± 0.2 mM. The mean NAA/Cr and NAA/Cho ratios in the WH were only slightly higher than the "brain-only" VOI: 1.5 versus 1.4 (7%) and 6.6 versus 5.9 (11%); Cho/Cr were not different. The brain/WH volume ratio was 0.31 ± 0.03 (brain ≈ 30% of WH volume). Air-tissue susceptibility-driven local magnetic field changes going from the brain outwards showed sharp gradients of more than 100 Hz/cm (1 ppm/cm), explaining the skull's Cr and Cho signal losses through resonance shifts, line broadening and destructive interference. The similarity of non-localized WH and localized VOI NAA, Cr and Cho concentrations and their ratios suggests that their signals originate predominantly from the brain. Therefore, the fast, comprehensive WH- 1 H-MRS method may facilitate quantification of these metabolites, which are common surrogate markers in neurological disorders. Copyright © 2017 John Wiley & Sons, Ltd.

Positron emission tomography-guided magnetic resonance spectroscopy in Alzheimer disease.

PubMed

Sheikh-Bahaei, Nasim; Sajjadi, S Ahmad; Manavaki, Roido; McLean, Mary; O'Brien, John T; Gillard, Jonathan H

2018-04-01

To determine whether the level of metabolites in magnetic resonance spectroscopy (MRS) is a representative marker of underlying pathological changes identified in positron emission tomographic (PET) images in Alzheimer disease (AD). We performed PET-guided MRS in cases of probable AD, mild cognitive impairment (MCI), and healthy controls (HC). All participants were imaged by 11 C-Pittsburgh compound B ( 11 C-PiB) and 18 F-fluorodeoxyglucose ( 18 F-FDG) PET followed by 3T MRS. PET images were assessed both visually and using standardized uptake value ratios (SUVRs). MRS voxels were placed in regions with maximum abnormality on amyloid (Aβ+) and FDG (hypometabolic) areas on PET scans. Corresponding normal areas were selected in controls. The ratios of total N-acetyl (tNA) group, myoinositol (mI), choline, and glutamate + glutamine over creatine (Cr) were compared between these regions. Aβ + regions had significantly higher (p = 0.02) mI/Cr and lower tNA/Cr (p = 0.02), whereas in hypometabolic areas only tNA/Cr was reduced (p = 0.003). Multiple regression analysis adjusting for sex, age, and education showed mI/Cr was only associated with 11 C-PiB SUVR (p < 0.0001). tNA/Cr, however, was associated with both PiB (p = 0.0003) and 18 F-FDG SUVR (p = 0.006). The level of mI/Cr was not significantly different between MCI and AD (p = 0.28), but tNA/Cr showed significant decline from HC to MCI to AD (p = 0.001, p = 0.04). mI/Cr has significant temporal and spatial associations with Aβ and could potentially be considered as a disease state biomarker. tNA is an indicator of early neurodegenerative changes and might have a role as disease stage biomarker and also as a valuable surrogate marker for treatment response. Ann Neurol 2018;83:771-778. © 2018 American Neurological Association.

Single voxel magnetic resonance spectroscopy at 3 Tesla in a memory disorders clinic: early right hippocampal NAA/Cr loss in mildly impaired subjects.

PubMed

Caserta, Maria T; Ragin, Ann; Hermida, Adriana P; Ahrens, R John; Wise, Leon

2008-11-30

In this study, we use magnetic resonance spectroscopy (MRS) at 3 Tesla to measure N-acetyl aspartate (NAA), myo-inositol (mI) and choline (Cho) to creatine (Cr) ratios in R (right) and L (left) hippocampi (H) in 8 mildly memory impaired (MMI), 6 probable Alzheimer's Disease (PRAD), and 17 control subjects. NAA/Cr was significantly reduced in the RH in the MMI group and bilaterally in the PRAD group vs. controls. No other metabolite differences were noted between the three groups. Five MMI subjects have converted to PRAD in follow-up. These findings suggest that RH NAA/Cr ratios measured at 3 Tesla may be a sensitive marker of future progression to dementia in a clinically defined population with isolated memory complaints.

Altered chemical metabolites in the amygdala-hippocampus region contribute to autistic symptoms of autism spectrum disorders.

PubMed

Endo, Taro; Shioiri, Toshiki; Kitamura, Hideaki; Kimura, Teruo; Endo, Sumio; Masuzawa, Naio; Someya, Toshiyuki

2007-11-01

Although several previous studies have been conducted, the neural basis of autism spectrum disorder (ASD) is poorly understood. The objective of the present study was to determine whether individuals with ASD have altered brain chemical metabolites and whether such alterations are related to their autistic symptoms. N-acetylaspartate (NAA)/creatine (Cr) and choline/Cr ratios in the right medial temporal lobe (MTL), medial prefrontal cortex, and cerebellar vermis were measured in 38 individuals with ASD (mean age = 12.9 years), including 12 with autism, 15 with Asperger's Disorder, and 11 with pervasive developmental disorder not otherwise specified (PDD-NOS), and 16 matched healthy control subjects (mean age = 11.5 years) with proton magnetic resonance spectroscopy. Autistic symptoms were assessed by the Childhood Autistic Rating Scale-Tokyo Version. There was a significant group difference for NAA/Cr ratio in the right MTL between the autism, Asperger's Disorder, PDD-NOS, and control groups (p < .001), and the autism group had a significantly lower NAA/Cr ratio compared with the PDD-NOS (p < .001) and control (p < .001) groups. In the ASD group, there was a significant negative correlation between NAA/Cr ratio in the right MTL and their Childhood Autistic Rating Scale-Tokyo Version total scores (r = -.44, p = .01) and subscales of emotional response (r = -.38, p = .02) and listening response (r = -.54, p = .001). The results of the present study suggest that subjects with ASD have abnormalities of neural integrity in the amygdala-hippocampus region that are related to their severity and social impairments.

Creatine Use and Exercise Heat Tolerance in Dehydrated Men

PubMed Central

Watson, Greig; Casa, Douglas J; Fiala, Kelly A; Hile, Amy; Roti, Melissa W; Healey, Julie C; Armstrong, Lawrence E; Maresh, Carl M

2006-01-01

Context: Creatine monohydrate (CrM) use is highly prevalent in team sports (eg, football, lacrosse, ice hockey) and by athletes at the high school, college, professional, and recreational levels. Concerns have been raised about whether creatine use is associated with increased cramping, muscle injury, heat intolerance, and risk of dehydration. Objective: To assess whether 1 week of CrM supplementation would compromise hydration status, alter thermoregulation, or increase the incidence of symptoms of heat illness in dehydrated men performing prolonged exercise in the heat. Design: Double-blind, randomized, crossover design. Setting: Human Performance Laboratory. Patients or Other Participants: Twelve active males, age = 22 ± 1 year, height = 180 ± 3 cm, mass = 78.8 ± 1.2 kg, body fat = 9 ± 1%, V̇o2peak = 50.9 ± 1 ml·kg−1·min−1. Intervention(s): Subjects consumed 21.6 g·d−1 of CrM or placebo for 7 days, underwent 48 ± 10 days of washout between treatments, and then crossed over to the alternate treatment in the creatine group. On day 7 of each treatment, subjects lost 2% body mass by exercising in 33.5°C and then completed an 80-minute exercise heat-tolerance test (33.5°C ± 0.5°C, relative humidity = 41 ± 12%). The test consisted of four 20-minute sequences of 4 minutes of rest, alternating a 3-minute walk and 1-minute high-intensity run 3 times, and walking for 4 minutes. Main Outcome Measures: Thermoregulatory, cardiorespiratory, metabolic, urinary, and perceptual responses. Results: On day 7, body mass had increased 0.88 kg. No interaction or treatment differences for placebo versus CrM during the exercise heat-tolerance test were noted in thermoregulatory (rectal temperature, 39.3 ± 0.4°C versus 39.4 ± 0.4°C) cardiorespiratory (V̇o2, 21.4 ± 2.7 versus 20.0 ± 1.8 ml·kg−1·min−1; heart rate, 192 ± 10 versus 192 ± 11 beats·min−1; mean arterial pressure, 90 ± 9 versus 88 ± 5 mm Hg), metabolic (lactate, 6.7 ± 2.7 versus 7.0 ± 3.0 mmol·L−1), perceptual thirst (thirst, 7 ± 1 versus 7 ± 1; thermal sensation, 8 ± 2 versus 8 ± 1; rating of perceived exertion, 17 ± 3 versus 17 ± 2), plasma glucose (0–20 minutes of exercise heat-tolerance, 6.5 ± 1.2 versus 6.8 ± 0.8 mmol·L−1), plasma (297 ± 5 versus 300 ± 4 mOsm·kg−1) and urine (792 ± 117 versus 651 ± 134 mOsm·kg−1), urine specific gravity (1.025 ± 0.003 versus 1.030 ± 0.005) and urine color (7 ± 1 versus 6 ± 1) measures were increased during CrM. Environmental Symptoms Questionnaire scores were similar between treatments. The levels of dehydration incurred during dehydration and the exercise heat-tolerance test were similar and led to similar cumulative body mass losses (−4.09 ± 0.53 versus −4.38 ± 0.58% body mass). Conclusions: Short-term CrM supplementation did not increase the incidence of symptoms or compromise hydration status or thermoregulation in dehydrated, trained men exercising in the heat. PMID:16619091

Baseline Serum Clinical Chemistry Values in African Green Monkeys Before and After Sulfur Mustard

DTIC Science & Technology

2007-05-01

aspartate transaminase (189 %), blood urea nitrogen (75 %), creatine kinase (721 %), and lactate dehydrogenase (114 %) one day after HD exposure...ALT, 93 %), aspartate transaminase (AST, 189 %), blood urea nitrogen (BUN, 75 %), creatine kinase (CK, 721 %), and lactate dehydrogenase (LDH, 114...alkaline phosphate (ALP), alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), calcium (Ca2+), creatine kinase (CK

Beyond muscles: The untapped potential of creatine.

PubMed

Riesberg, Lisa A; Weed, Stephanie A; McDonald, Thomas L; Eckerson, Joan M; Drescher, Kristen M

2016-08-01

Creatine is widely used by both elite and recreational athletes as an ergogenic aid to enhance anaerobic exercise performance. Older individuals also use creatine to prevent sarcopenia and, accordingly, may have therapeutic benefits for muscle wasting diseases. Although the effect of creatine on the musculoskeletal system has been extensively studied, less attention has been paid to its potential effects on other physiological systems. Because there is a significant pool of creatine in the brain, the utility of creatine supplementation has been examined in vitro as well as in vivo in both animal models of neurological disorders and in humans. While the data are preliminary, there is evidence to suggest that individuals with certain neurological conditions may benefit from exogenous creatine supplementation if treatment protocols can be optimized. A small number of studies that have examined the impact of creatine on the immune system have shown an alteration in soluble mediator production and the expression of molecules involved in recognizing infections, specifically toll-like receptors. Future investigations evaluating the total impact of creatine supplementation are required to better understand the benefits and risks of creatine use, particularly since there is increasing evidence that creatine may have a regulatory impact on the immune system. Copyright © 2016 Elsevier B.V. All rights reserved.

Synthesis of Creatine in X-irradiated Rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nerurkar, M. K.; Sahasrabudhe, M. B.

1960-01-01

BS>Synthesis and excretion of creatine and creatinine in total-body x- irradiated (600 n) rats were investigated. Irradiated rats exhibited a marked creatinuria, whereas creatinine excretion was only slightly increased in comparison to that of non-irradiated control animals. The increased creatine excretion after irradiation was ascribed to accelerated synthesis in the liver and greater release from the muscle. In vitro studies on the synthesis of creatine in liver homogenates revealed that the synthetic activity decreased immediately after irradiation but at later intervals showed a marked rise. The immediate fall in the creatine synthesis was not due to decreased availability of ATPmore » or glutathione. Administration of nicotinamide to animals, to inhibit the new creatine synthesis in the liver. indicated that although the creatine formation in the liver of x-irradiated rats was elevated. it could not account for more than a small fraction of the creatinuria observed. Most of the urinary creatine originated from the muscle, probably because of the impaired reconversion of creatine to phosphocreatine. Since the muscle ATP-creatine transphosphorylase activity was not affected by irradiation, it is suggested that the mobilization of muscle creatine to cause creatinuria is probably due to the diminution of glycolysis in the muscle of irradiated animals.« less

Post‐surgical changes in brain metabolism detected by magnetic resonance spectroscopy in normal pressure hydrocephalus: results of a pilot study

PubMed Central

del Mar Matarín, María; Pueyo, Roser; Poca, María Antonia; Falcón, Carles; Mataró, María; Bargalló, Núria; Sahuquillo, Juan; Junqué, Carme

2007-01-01

Background Adult normal pressure hydrocephalus (NPH) is one of the few potentially treatable causes of dementia. Some morphological and functional abnormalities attributed to hydrocephalus improve following treatment. Objectives We focused on analysis of changes in cerebral metabolites using proton magnetic resonance spectroscopy (1H‐MRS) after NPH treatment, and its clinical and cognitive correlation. Methods 1H‐MRS, neuropsychological and clinical status examinations were performed before and 6 months after shunting in 12 adults with idiopathic NPH. We obtained N‐acetyl‐aspartate (NAA), choline (Cho), myoinositol (MI) and creatine (Cr) values. Results After surgery, NAA/Cr was significantly increased. Moreover, NAA/Cr values were related to cognitive deterioration. Conclusion MRS could be a marker of neuronal dysfunction in NPH. PMID:17299021

Measuring the lactate-to-creatine ratio via 1H NMR spectroscopy can be used to noninvasively evaluate apoptosis in glioma cells after X-ray irradiation.

PubMed

Li, Hongxia; Cui, Yi; Li, Fuyan; Shi, Wenqi; Gao, Wenjing; Wang, Xiao; Zeng, Qingshi

2018-01-01

Radiotherapy is among the commonly applied treatment options for glioma, which is one of the most common types of primary brain tumor. To evaluate the effect of radiotherapy noninvasively, it is vital for oncologists to monitor the effects of X-ray irradiation on glioma cells. Preliminary research had showed that PKC-ι expression correlates with tumor cell apoptosis induced by X-ray irradiation. It is also believed that the lactate-to-creatine (Lac/Cr) ratio can be used as a biomarker to evaluate apoptosis in glioma cells after X-ray irradiation. In this study, we evaluated the relationships between the Lac/Cr ratio, apoptotic rate, and protein kinase C iota (PKC-ι) expression in glioma cells. Cells of the glioma cell lines C6 and U251 were randomly divided into 4 groups, with every group exposed to X-ray irradiation at 0, 1, 5, 10 and 15 Gy. Single cell gel electrophoresis (SCGE) was conducted to evaluate the DNA damage. Flow cytometry was performed to measure the cell cycle blockage and apoptotic rates. Western blot analysis was used to detect the phosphorylated PKC-ι (p-PKC-ι) level. 1 H NMR spectroscopy was employed to determine the Lac/Cr ratio. The DNA damage increased in a radiation dose-dependent manner ( p  < 0.05). With the increase in X-ray irradiation, the apoptotic rate also increased (C6, p  < 0.01; U251, p  < 0.05), and the p-PKC-ι level decreased (C6, p  < 0.01; U251, p  < 0.05). The p-PKC-ι level negatively correlated with apoptosis, whereas the Lac/Cr ratio positively correlated with the p-PKC-ι level. The Lac/Cr ratio decreases with an increase in X-ray irradiation and thus can be used as a biomarker to reflect the effects of X-ray irradiation in glioma cells.

Reproducibility over a 1-month period of 1H-MR spectroscopic imaging NAA/Cr ratios in clinically stable multiple sclerosis patients.

PubMed

Mostert, J P; Blaauw, Y; Koch, M W; Kuiper, A J; Hoogduin, J M; De Keyser, J

2008-08-01

N-acetylaspartate/creatine (NAA/Cr) ratios, assessed with proton magnetic resonance spectroscopy, are increasingly used as a surrogate marker for axonal dysfunction and degeneration in multiple sclerosis (MS). The purpose of this study was to test short-time reproducibility of NAA/Cr ratios in patients with clinically stable MS. In 35 MS patients we analysed NAA/Cr ratios obtained with (1)H-MR spectroscopic imaging at the centrum semiovale either with lateral ventricles partially included (group 1; n=15) or more cranially with no ventricles included (group 2; n=20). To test short-term reproducibility of the NAA/Cr measurements, patients were scanned twice 4 weeks apart. We determined mean NAA/Cr and Cho/Cr ratios of 12 grey matter and 24 white matter voxels. Mean NAA/Cr ratios of both the white and grey matter did not change after 4 weeks. Overall 4-week reproducibility of the NAA/Cr ratio, expressed as coefficient of variation, was 4.8% for grey matter and 3.5% for white matter. Reproducibility of cranial scanning of the ventricles was slightly better than with cerebrospinal fluid included. Our study shows good short-term reproducibility of NAA/Cr ratio measurements in the centrum semiovale, which supports the reliability of this technique for longitudinal studies.

Short-term creatine supplementation has no impact on upper-body anaerobic power in trained wrestlers.

PubMed

Aedma, Martin; Timpmann, Saima; Lätt, Evelin; Ööpik, Vahur

2015-01-01

Creatine (CR) is considered an effective nutritional supplement having ergogenic effects, which appears more pronounced in upper-body compared to lower-body exercise. Nevertheless, results regarding the impact of CR loading on repeated high-intensity arm-cranking exercise are scarce and in some cases conflicting. Interestingly, few of the conducted studies have structured their research designs to mimic real world sporting events. Therefore, our purpose was to address the hypothesis that CR ingestion would increase anaerobic power output in consecutive upper-body intermittent sprint performance (UBISP) tests designed to simulate wrestling matches on a competition-day. In a double-blind, placebo-controlled, parallel-group study, 20 trained wrestlers were assigned to either placebo or CR supplemented group (0.3 g ∙ kg(-1) of body mass per day). Four 6-min UBISP tests interspersed with 30-min recovery periods were performed before (trial 1) and after 5 days (trial 2) of supplementation. Each test consisted of six 15-s periods of arm-cranking at maximal executable cadence against resistance of 0.04 kg ∙ kg(-1) body mass interspersed with 40-s unloaded easy cranking periods and 5-s acceleration intervals (T1-T4). Mean power (MP), peak power (PP), fatigue index and heart rate parameters were measured during UBISP tests. Also, body weight and hydration status were assessed. Principle measures were statistical analysed with mixed-model ANOVAs. Mean individual CR consumption in the CR group was 24.8 ± 2.5 g ∙ d(-1). No significant (P > 0.05) differences occurred in body mass or hydration status indices between the groups or across trials. MP, PP and fatigue index responses were unaffected by supplementation; although, a significant reduction in MP and PP did occurred from T1 to T4 in both trial 1 and 2 (P < 0.001). Overall heart rate responses in the tests tended to be higher in the CR than PLC group (P < 0.05); but, trends in responses in trials and tests were comparable (P > 0.05). These results suggest that 5-day CR supplementation has no impact on upper-body muscle anaerobic power output in consecutive UBISP anaerobic tests mimicking wrestling matches on a competition day.

A Proton Magnetic Resonance Spectroscopic Study in Autism Spectrum Disorder Using a 3-Tesla Clinical Magnetic Resonance Imaging (MRI) System: The Anterior Cingulate Cortex and the Left Cerebellum.

PubMed

Ito, Hiromichi; Mori, Kenji; Harada, Masafumi; Hisaoka, Sonoka; Toda, Yoshihiro; Mori, Tatsuo; Goji, Aya; Abe, Yoko; Miyazaki, Masahito; Kagami, Shoji

2017-07-01

The pathophysiology of autism spectrum disorder (ASD) is not fully understood. We used proton magnetic resonance spectroscopy to investigate metabolite concentration ratios in the anterior cingulate cortex and left cerebellum in ASD. In the ACC and left cerebellum studies, the ASD group and intelligence quotient- and age-matched control group consisted of 112 and 114 subjects and 65 and 45 subjects, respectively. In the ASD group, γ-aminobutyric acid (GABA)+/ creatine/phosphocreatine (Cr) was significantly decreased in the anterior cingulate cortex, and glutamate (Glu)/Cr was significantly increased and GABA+/Cr was significantly decreased in the left cerebellum compared to those in the control group. In addition, both groups showed negative correlations between Glu/Cr and GABA+/Cr in the left cerebellum, and positive correlations between GABA+/Cr in the anterior cingulate cortex and left cerebellum. ASD subjects have hypoGABAergic alterations in the anterior cingulate cortex and hyperglutamatergic/hypoGABAergic alterations in the left cerebellum.

Neurocognitive dysfunction in children with β thalassemia major: psychometric, neurophysiologic and radiologic evaluation.

PubMed

Elalfy, M S; Aly, R H; Azzam, H; Aboelftouh, K; Shatla, R H; Tarif, M; Abdatty, M; Elsayed, R M

2017-12-01

To evaluate the impact of iron chelating drugs and serum ferritin on the neurocognitive functions of patients with β thalassemia major (β-TM), using psychometric, neurophysiologic and radiologic tests. Eighty children with β-TM were enrolled into the study and were compared to 40 healthy controls. All participants were evaluated by measuring serum ferritin, neurocognitive assessment by Benton Visual Retention Test, Wechsler Intelligence Scale for Children, Wisconsin Card Sort Test, P300 and magnetic resonance spectroscopy (MRS). WISC in our study showed that 40% of cases were borderline mental function as regards total IQ. Neurophysiologic tests were significantly impaired in patients compared to control group, with significant impairment in those receiving desferrioxamine (DFO). P300 amplitude was significantly lower in cases compared to controls (2.24 and 4.66 uv, respectively), recording the shortest amplitude in patients receiving DFO. Altered metabolic markers in the brain were detected by MRS in the form of reduced N-acetylaspartate to creatine ratio in 78.3% of our cases. There were significant correlations between psychometric tests and both neurophysiologic (P300) and radiologic (MRS) tests. β-TM is associated with neurocognitive impairment that can be assessed by psychometric, neurophysiologic and radiologic tests. The role of hemosiderosis and iron chelation therapy on cognitive functioning still need more research. β-TM: beta thalassemia major; DFO: Dysferal; DFP: Deferiprone; DFX: Deferasirox; WISC: Wechsler Intelligence Scale for Children; VIQ: verbal IQ; PIQ: performance IQ; TIQ: total IQ; BVRT: Benton Visual Retention Test; WCST: Wisconsin Card Sort Test; MRS: Magnetic resonant spectroscopy; NAA/Cr ratio: N-acetylaspartate to creatine ratio.

Effect of two complex training protocols of back squats in blood indicators of muscular damage in military athletes

PubMed Central

Ojeda, Álvaro Huerta; Ríos, Luis Chirosa; Barrilao, Rafael Guisado; Ríos, Ignacio Chirosa; Serrano, Pablo Cáceres

2016-01-01

[Purpose] The aim of this study was to determine the variations in the blood muscular damage indicators post application of two complex training programs for back squats. [Subjects and Methods] Seven military athletes were the subjects of this study. The study had a quasi-experimental cross-over intra-subject design. Two complex training protocols were applied, and the variables to be measured were cortisol, metabolic creatine kinase, and total creatine kinase. For the statistical analysis, Student’s t-test was used. [Results] Twenty-four hours post effort, a significant decrease in cortisol level was shown for both protocols; however, the metabolic creatine kinase and total creatine kinase levels showed a significant increase. [Conclusion] Both protocols lowered the indicator of main muscular damage in the blood supply (cortisol). This proved that the work weight did not generate significant muscular damage in the 24-hour post-exercise period. PMID:27313356

Effect of two complex training protocols of back squats in blood indicators of muscular damage in military athletes.

PubMed

Ojeda, Álvaro Huerta; Ríos, Luis Chirosa; Barrilao, Rafael Guisado; Ríos, Ignacio Chirosa; Serrano, Pablo Cáceres

2016-05-01

[Purpose] The aim of this study was to determine the variations in the blood muscular damage indicators post application of two complex training programs for back squats. [Subjects and Methods] Seven military athletes were the subjects of this study. The study had a quasi-experimental cross-over intra-subject design. Two complex training protocols were applied, and the variables to be measured were cortisol, metabolic creatine kinase, and total creatine kinase. For the statistical analysis, Student's t-test was used. [Results] Twenty-four hours post effort, a significant decrease in cortisol level was shown for both protocols; however, the metabolic creatine kinase and total creatine kinase levels showed a significant increase. [Conclusion] Both protocols lowered the indicator of main muscular damage in the blood supply (cortisol). This proved that the work weight did not generate significant muscular damage in the 24-hour post-exercise period.

Effects of four weeks of high-intensity interval training and creatine supplementation on critical power and anaerobic working capacity in college-aged men.

PubMed

Kendall, Kristina L; Smith, Abbie E; Graef, Jennifer L; Fukuda, David H; Moon, Jordan R; Beck, Travis W; Cramer, Joel T; Stout, Jeffrey R

2009-09-01

The critical power test provides 2 measures, critical power (CP) and anaerobic working capacity (AWC). In theory, the CP measurement represents the maximal power output that can be maintained without fatigue, and AWC is an estimate of work capacity associated with muscle energy reserves. High-intensity interval training (HIIT) has been shown to be an effective training method for improving endurance performance, including VO2PEAK. In addition, creatine (Cr) supplementation has been reported to improve AWC without training; however, it has shown no effect on CP. The purpose of this study was to examine the effects of 4 weeks of HIIT with Cr supplementation on CP and AWC. Forty-two recreationally active men volunteered to participate in this study. Participants were randomly assigned to 1 of 3 groups: Cr (n = 16), 10 g Cr + 10 g dextrose; placebo (PL, n = 16), 20 g dextrose; control (CON, n = 10), no treatment. Before and after supplementation, each participant performed a maximal oxygen consumption test VO2PEAK on a cycle ergometer to establish peak power output (PPO). Participants then completed a CP test involving 3 exercise bouts with the workloads set as a percentage of their PPO to determine CP and AWC. After a 2-week familiarization period of training and supplementing, PPO, CP, and AWC were remeasured before an additional 4 weeks of HIIT and supplementation were completed. Training consisted of 5 sets of 2-minute exercise bouts with 1 minute rest in between performed on the cycle ergometer, with intensities based on PPO. A significant improvement in CP was observed in the Cr group (6.72% +/- 2.54%), whereas PL showed no significant change (3.87% +/- 2.30%), and CON significantly decreased (6.27% +/- 2.38%). Furthermore, no changes in AWC were observed in any of the groups after treatment. The current findings suggest that Cr supplementation may enhance the effects of intense interval endurance training on endurance performance changes.

Lower "N"-Acetyl-Aspartate Levels in Prefrontal Cortices in Pediatric Bipolar Disorder: A (Superscript 1]H Magnetic Resonance Spectroscopy Study

ERIC Educational Resources Information Center

Caetano, Sheila C.; Olvera, Rene L.; Hatch, John P.; Sanches, Marsal; Chen, Hua Hsuan; Nicoletti, Mark; Stanley, Jeffrey A.; Fonseca, Manoela; Hunter, Kristina; Lafer, Beny; Pliszka, Steven R.; Soares, Jair C.

2011-01-01

Objective: The few studies applying single-voxel [superscript 1]H spectroscopy in children and adolescents with bipolar disorder (BD) have reported low "N"-acetyl-aspartate (NAA) levels in the dorsolateral prefrontal cortex (DLPFC), and high myo-inositol/phosphocreatine plus creatine (PCr+Cr) ratios in the anterior cingulate. The aim of this study…

Creatine and the Liver: Metabolism and Possible Interactions.

PubMed

Barcelos, R P; Stefanello, S T; Mauriz, J L; Gonzalez-Gallego, J; Soares, F A A

2016-01-01

The process of creatine synthesis occurs in two steps, catalyzed by L-arginine:glycine amidinotransferase (AGAT) and guanidinoacetate N-methyltransferase (GAMT), which take place mainly in kidney and liver, respectively. This molecule plays an important energy/pH buffer function in tissues, and to guarantee the maintenance of its total body pool, the lost creatine must be replaced from diet or de novo synthesis. Creatine administration is known to decrease the consumption of Sadenosyl methionine and also reduce the homocysteine production in liver, diminishing fat accumulation and resulting in beneficial effects in fatty liver and non-alcoholic liver disease. Different studies have shown that creatine supplementation could supply brain energy, presenting neuroprotective effects against the encephalopathy induced by hyperammonemia in acute liver failure. Creatine is also taken by many athletes for its ergogenic properties. However, little is known about the adverse effects of creatine supplementation, which are barely described in the literature, with reports of mainly hypothetical effects arising from a small number of scientific publications. Antioxidant effects have been found in several studies, although one of the theories regarding the potential for toxicity from creatine supplementation is that it can increase oxidative stress and potentially form carcinogenic compounds.

Changes in cerebral metabolites in type 2 diabetes mellitus: A meta-analysis of proton magnetic resonance spectroscopy.

PubMed

Wu, Guang-Yao; Zhang, Qing; Wu, Jian-Lin; Jing, Li; Tan, Yang; Qiu, Tai-Chun; Zhao, Jiao

2017-11-01

To investigate whether there were differences and consistent patterns that highlight and consolidate the metabolite changes in type 2 diabetes mellitus (T2DM), a meta-analysis of proton magnetic resonance spectroscopy (MRS) was conducted. PubMed, Web of Science, and Embase databases were searched up to August 2016 for collecting the relevant studies. After an inclusion and exclusion criteria, the data was extracted. The data was analyzed using Stata software v.12.0. The weight mean difference (MD) and 95% confidence interval (CI) were used to compare continuous variables. A total of 10 studies (with a total of 244 T2DM patients and 223 healthy controls) were included. N-Acetyl Aspartate (NAA)/creatine (Cr) levels were decreased in the frontal lobe (MD=-0.20, 95%CI=-0.33 to -0.06, P=0.005) and lenticular nucleus (MD=-0.14, 95%CI=-0.22 to -0.06, P=0.001); choline (Cho)/Cr levels were increased in the lenticular nucleus (MD=0.15, 95%CI=0.02-0.28, P=0.025); myo-inositol (MI)/Cr levels were increased in the in the occipital lobe (MD=0.11, 95%CI=0.02-0.19, P=0.017) and parietal lobe (MD=0.16, 95%CI=0.05-0.28, P=0.006); MI levels were increased in the frontal white matter (MD=0.52, 95%CI=0.14-0.90, P=0.008). The results of our meta-analysis indicated that metabolite levels were altered in different regions of brain, which may be shown with MRS and caused clinical symptoms in T2DM further. Copyright © 2017 Elsevier Ltd. All rights reserved.

Brain metabolite differences in one-year-old infants born small at term and association with neurodevelopmental outcome.

PubMed

Simões, Rui V; Cruz-Lemini, Mónica; Bargalló, Núria; Gratacós, Eduard; Sanz-Cortés, Magdalena

2015-08-01

We assessed brain metabolite levels by magnetic resonance spectroscopy (MRS) in 1-year-old infants born small at term, as compared with infants born appropriate for gestational age (AGA), and their association with neurodevelopment at 2 years of age. A total of 40 infants born small (birthweight <10th centile for gestational age) and 30 AGA infants underwent brain MRS at age 1 year on a 3-T scanner. Small-born infants were subclassified as late intrauterine growth restriction or as small for gestational age, based on the presence or absence of prenatal Doppler and birthweight predictors of an adverse perinatal outcome, respectively. Single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) data were acquired from the frontal lobe at short echo time. Neurodevelopment was evaluated at 2 years of age using the Bayley Scales of Infant and Toddler Development, Third Edition, assessing cognitive, language, motor, social-emotional, and adaptive behavior scales. As compared with AGA controls, infants born small showed significantly higher levels of glutamate and total N-acetylaspartate (NAAt) to creatine (Cr) ratio at age 1 year, and lower Bayley Scales of Infant and Toddler Development, Third Edition scores at 2 years. The subgroup with late intrauterine growth restriction further showed lower estimated glutathione levels at age 1 year. Significant correlations were observed for estimated glutathione levels with adaptive scores, and for myo-inositol with language scores. Significant associations were also noticed for NAA/Cr with cognitive scores, and for glutamate/Cr with motor scores. Infants born small show brain metabolite differences at 1 year of age, which are correlated with later neurodevelopment. These results support further research on MRS to develop imaging biomarkers of abnormal neurodevelopment. Copyright © 2015 Elsevier Inc. All rights reserved.

A magnetic resonance spectroscopy study of antisocial behaviour disorder, psychopathy and violent crime among military conscripts.

PubMed

Basoglu, Cengiz; Semiz, Umit; Oner, Ozgur; Gunay, Huseyin; Ebrinc, Servet; Cetin, Mesut; Sildiroglu, Onur; Algul, Ayhan; Ates, Alpay; Sonmez, Guner

2008-04-01

Prefrontal and/or temporo-limbic abnormalities associated with antisocial personality disorder (APD), high psychopathy scores and violent behaviours can readily be evaluated by neuroimaging methods. In this study, we compared the brain metabolites in adult male military conscripts with APD, high psychopathy scores and serious violent crimes (n = 15) with age- and educational-level-matched healthy controls (n = 15) by means of magnetic resonance spectroscopy. All cases were diagnosed by means of the Diagnostic Statistical Manual-IV APD module of the Structured Clinical Interview for DSM III-R Axis II Disorders (SCID-II) semistructured questionnaire in Turkish. The psychopathy scores were evaluated by means of the Hare Psychopathy Checklist-Revised translated into Turkish (PCL-R). PCL-R is a 20-item, reliable and valid instrument for assessment of psychopathy, both in categorical and dimensional natures. All patients had a total score of 29 (of possible 40) or higher from PCL-R, indicating a high degree of psychopathy. Our results showed no significant differences in ratio of N-acetyl aspartate (NAA), creatine (Cr) and choline-related compounds in the right dorsolateral prefrontal cortex, anterior cingulate cortex (ACC) and amygdala-hippocampus regions of cases compared with controls. ACC NAA/Cr was significantly negatively correlated with both the PCL-R total score and the PCL-R factor I score (interpersonal/affective problems) among the cases. As ACC plays an important role in decision-making and emotional information processing, we postulate that the lower NAA/Cr ratio, suggesting impaired neural integrity, may increase the severity of interpersonal/affective problems of the psychopathy factor in male subjects exhibiting APD, high psychopathy overall scores and violent crimes.

Regulation of respiration in brain mitochondria and synaptosomes: restrictions of ADP diffusion in situ, roles of tubulin, and mitochondrial creatine kinase.

PubMed

Monge, Claire; Beraud, Nathalie; Kuznetsov, Andrey V; Rostovtseva, Tatiana; Sackett, Dan; Schlattner, Uwe; Vendelin, Marko; Saks, Valdur A

2008-11-01

The role of ubiquitous mitochondrial creatine kinase (uMtCK) reaction in regulation of mitochondrial respiration was studied in purified preparations of rat brain synaptosomes and mitochondria. In permeabilized synaptosomes, apparent Km for exogenous ADP, Km (ADP), in regulation of respiration in situ was rather high (110 +/- 11 microM) in comparison with isolated brain mitochondria (9 +/- 1 microM). This apparent Km for ADP observed in isolated mitochondria in vitro dramatically increased to 169 +/- 52 microM after their incubation with 1 muM of dimeric tubulin showing that in rat brain, particularly in synaptosomes, mitochondrial outer membrane permeability for ADP, and ATP may be restricted by tubulin binding to voltage dependent anion channel (VDAC). On the other hand, in synaptosomes apparent Km (ADP) decreased to 25 +/- 1 microM in the presence of 20 mM creatine. To fully understand this effect of creatine on kinetics of respiration regulation, complete kinetic analysis of uMtCK reaction in isolated brain mitochondria was carried out. This showed that oxidative phosphorylation specifically altered only the dissociation constants for MgATP, by decreasing that from ternary complex MtCK.Cr.MgATP (K (a)) from 0.13 +/- 0.02 to 0.018 +/- 0.007 mM and that from binary complex MtCK.MgATP (K (ia)) from 1.1 +/- 0.29 mM to 0.17 +/- 0.07 mM. Apparent decrease of dissociation constants for MgATP reflects effective cycling of ATP and ADP between uMtCK and adenine nucleotide translocase (ANT). These results emphasize important role and various pathophysiological implications of the phosphocreatine-creatine kinase system in energy transfer in brain cells, including synaptosomes.

A spectroscopic approach toward depression diagnosis: local metabolism meets functional connectivity.

PubMed

Demenescu, Liliana Ramona; Colic, Lejla; Li, Meng; Safron, Adam; Biswal, B; Metzger, Coraline Danielle; Li, Shijia; Walter, Martin

2017-03-01

Abnormal anterior insula (AI) response and functional connectivity (FC) is associated with depression. In addition to clinical features, such as severity, AI FC and its metabolism further predicted therapeutic response. Abnormal FC between anterior cingulate and AI covaried with reduced glutamate level within cingulate cortex. Recently, deficient glial glutamate conversion was found in AI in major depression disorder (MDD). We therefore postulate a local glutamatergic mechanism in insula cortex of depressive patients, which is correlated with symptoms severity and itself influences AI's network connectivity in MDD. Twenty-five MDD patients and 25 healthy controls (HC) matched on age and sex underwent resting state functional magnetic resonance imaging and magnetic resonance spectroscopy scans. To determine the role of local glutamate-glutamine complex (Glx) ratio on whole brain AI FC, we conducted regression analysis with Glx relative to creatine (Cr) ratio as factor of interest and age, sex, and voxel tissue composition as nuisance factors. We found that in MDD, but not in HC, AI Glx/Cr ratio correlated positively with AI FC to right supramarginal gyrus and negatively with AI FC toward left occipital cortex (p < 0.05 family wise error). AI Glx/Cr level was negatively correlated with HAMD score (p < 0.05) in MDD patients. We showed that the local AI ratio of glutamatergic-creatine metabolism is an underlying candidate subserving functional network disintegration of insula toward low level and supramodal integration areas, in MDD. While causality cannot directly be inferred from such correlation, our finding helps to define a multilevel network of response-predicting regions based on local metabolism and connectivity strength.

The use of creatine supplements in the military.

PubMed

Havenetidis, Konstantinos

2016-08-01

Creatine is considered an effective nutritional ergogenic aid to enhance exercise performance. In spite of the publication of several reviews in the last decade on the topic of exercise performance/sports and creatine there is a need for an update related to the military given the lack of information in this area. The aim of this study was to critically assess original research addressing the use of creatine supplements in the military. A search of the electronic databases PubMed and SPORTDiscus, for the following key words: military personnel, trainees, recruit, soldier, physical fitness, physical conditioning, creatine supplementation, creatine ingestion, nutritional supplements to identify surveys and randomised clinical trials from journal articles and technical reports investigating the effect of creatine supplementation on military populations. Thirty-three out of 90 articles examined the use of creatine as a dietary supplement in military personnel. Twenty-one studies were finally selected on the basis of stated inclusion criteria for military surveys and randomised clinical trials. Most of the surveys (15/17) in the military indicate a high popularity of creatine (average 27%) among supplement users. In contrast, in most of the exercise protocols used (6/9) during randomised clinical trials creatine has produced a non-significant performance-enhancing effect. Creatine is one of the most widely used supplemental compounds in the military. It is not considered a doping infraction or related to any adverse health effects but its long-term usage needs further investigation. Experimental research suggests that creatine supplementation does not enhance physical performance in the military. However, limitations in creatine dosage, military fitness testing and sample group selection might have underestimated the ergogenic properties of creatine. Recent studies also indicate positive effects on various aspects of total force fitness such as cognitive-psychomotor performance, bone health, musculoskeletal damage and neuromuscular function. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Chronic high-dose creatine has opposing effects on depression-related gene expression and behavior in intact and sex hormone-treated gonadectomized male and female rats

PubMed Central

Allen, Patricia J.; DeBold, Joseph F.; Rios, Maribel; Kanarek, Robin B.

2015-01-01

Creatine is an antioxidant, neuromodulator and key regulator of energy metabolism shown to improve depressive symptoms in humans and animals, especially in females. To better understand the pharmacological effects of creatine, we examined its influence on depression-related hippocampal gene expression and behaviors in the presence and absence of sex steroids. Sham-operated and gonadectomized male and female rats were fed chow alone or chow blended with either 2% or 4% w/w creatine monohydrate for five weeks before forced swim, open field, and wire suspension tests, or seven weeks total. Before supplementation, males were chronically implanted with an empty or a testosterone-filled (T) capsule (10-mm surface release), and females were administered progesterone (P, 250 μg), estradiol benzoate (EB, 2.5 μg), EB+P, or sesame oil vehicle weekly. Relative to non-supplemented shams, all hippocampal plasticity-related mRNAs measured, including brain-derived neurotrophic factor (BDNF), tyrosine kinase B, doublecortin, calretinin, and calbindin, were downregulated in sham males given 4% creatine, and BDNF, doublecortin, and calbindin mRNAs were downregulated in sham females given 4% creatine. In contrast, combined 4% creatine + T in castrates prevented downregulation of BDNF, doublecortin, and calretinin mRNAs. Similarly, combined 4% creatine + EB+P in ovariectomized females attenuated downregulation of BDNF and calbindin mRNA levels. Moderate antidepressant and anxiolytic-like behaviors were observed in EB+P-treated ovariectomized females fed creatine, with similar trends in T-treated castrates fed creatine. Altogether, these data show that chronic, high-dose creatine has opposing effects on neuroplasticity-related genes and depressive behavior in intact and gonadectomized male and female rats. The dose and schedule of creatine used negatively impacted hippocampal neuronal integrity in otherwise healthy brains, possibly through negative compensatory changes in energy metabolism, whereas combined creatine and sex steroids acted in a neuroprotective manner in gonadectomized rats, potentially by reducing metabolic complications associated with castration or ovariectomy. PMID:25560941

Meta-Analysis of Creatine for Neuroprotection Against Parkinson's Disease.

PubMed

Attia; Ahmed, Hussien; Gadelkarim, Mohamed; Morsi, Mahmoud; Awad, Kamal; Elnenny, Mohamed; Ghanem, Esraa; El-Jaafary, Shaimaa; Negida, Ahmed

2017-01-01

Creatine is an antioxidant agent that showed neuroprotective effects in animal models of Parkinson's disease (PD). Creatine was selected by the National Institute of Neurological Disorders and Stroke as a possible disease modifying agent for Parkinson's disease. Therefore, many clinical trials evaluated the efficacy of creatine for patients with PD. The aim of this systematic review and meta-analysis is to synthesize evidence from published randomized controlled trials (RCTs) about the efficacy of Creatine for patients with PD. We followed PRISMA statement guidelines during the preparation of this systematic review and meta-analysis. A computer literature search for PubMed, EBSCO, web of science and Ovid Midline was carried out. We included RCTs comparing creatine with placebo in terms of motor functions and quality of life. Outcomes of total Unified Parkinson's Disease Rating Scale (UPDRS), UPDRS I, UPDRS II, and UPDRS III were pooled as mean difference (MD) between two groups from baseline to the endpoint. Statistical heterogeneity was assessed by visual inspection of the forest plot and measured by chi-square and I square tests. Three RCTs (n=1935) were included in this study. The overall effect did not favor either of the two groups in terms of: UPDRS total score (MD 1.07, 95% CI [3.38 to 1.25], UPDRS III (MD 0.62, 95% CI [2.27 to 1.02]), UPDRS II (MD 0.03, 95% CI [0.81 to 0.86], or UPDRS I (MD 0.03, 95% CI [0.33 to 0.28]). Current evidence does not support the use of creatine for neuroprotection against PD. Future well-designed, randomized controlled trials are needed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Impacts of electroacupuncture on left hippocampus NAA/Cr for patients of Uygur and Han nationality with mild cognitive impairment].

PubMed

Liu, Zhi-Yan; Guo, Hui; Zhang, Xiao-Lin; Liu, Juan; Qu, Hong-Yan; Peng, Wei; Bao, Yi-Mei; Yin, Li-Li; Song, Yi-Xing

2011-09-01

To observe the clinical efficacy of electroacupuncture (EA) on mild cognitive impairment (MCI) for patients of Uygur and Han nationality and explore the national diversity among the patients with MCI. Twenty-five cases were divided into Han nationality group (15 cases) and Uygur nationality group (10 cases) according to patient's nationality. In either group, EA was applied to Baihui (GV 20), Fengchi (GB 20), Xuanzhong (GB 39), Fuliu (KI 7), Sanyinjiao (SP 6) and Taixi (KI 3), once per day, 15 treatments made one session and there were 5 days at the interval among the sessions. Totally, 3 sessions of treatment were required. The proton magnetic resonance spectroscopy (1H-MRS) was used to observe the changes in the ratio of N-acetylaspartate and creatine (NAA/Cr) on the left hippocampus for the patients in two groups before and after treatment as well as the changes in the results of the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) separately. NAA/Cr in Uygur nationality group was higher than that in Han nationality group before treatment (1.659 +/- 0.418 vs 1.137 +/- 0.190, P < 0.05). After treatment, MMSE and MoCA scores all increased apparently as compared with those before treatment in two groups (P < 0.05, P < 0.01), and NAA/Cr on the left hippocampus in either group was up-regulated as compared with that before treatment (both P < 0.01). EA can improve the overall cognitive function for the patients with MCI. There is the national diversity in the partial brain metabolite level between Uygur patients and Han patients with MCI.

HR-MAS MR Spectroscopy of Breast Cancer Tissue Obtained with Core Needle Biopsy: Correlation with Prognostic Factors

PubMed Central

Choi, Ji Soo; Baek, Hyeon-Man; Kim, Suhkmann; Kim, Min Jung; Youk, Ji Hyun; Moon, Hee Jung; Kim, Eun-Kyung; Han, Kyung Hwa; Kim, Dong-hyun; Kim, Seung Il; Koo, Ja Seung

2012-01-01

The purpose of this study was to examine the correlation between high-resolution magic angle spinning (HR-MAS) magnetic resonance (MR) spectroscopy using core needle biopsy (CNB) specimens and histologic prognostic factors currently used in breast cancer patients. After institutional review board approval and informed consent were obtained for this study, CNB specimens were collected from 36 malignant lesions in 34 patients. Concentrations and metabolic ratios of various choline metabolites were estimated by HR-MAS MR spectroscopy using CNB specimens. HR-MAS spectroscopic values were compared according to histopathologic variables [tumor size, lymph node metastasis, histologic grade, status of estrogens receptor (ER), progesterone receptor (PR), HER2 (a receptor for human epidermal growth factor), and Ki-67, and triple negativity]. Multivariate analysis was performed with Orthogonal Projections to Latent Structure-Discriminant Analysis (OPLS-DA). HR-MAS MR spectroscopy quantified and discriminated choline metabolites in all CNB specimens of the 36 breast cancers. Several metabolite markers [free choline (Cho), phosphocholine (PC), creatine (Cr), taurine, myo-inositol, scyllo-inositol, total choline (tCho), glycine, Cho/Cr, tCho/Cr, PC/Cr] on HR-MAS MR spectroscopy were found to correlate with histologic prognostic factors [ER, PR, HER2, histologic grade, triple negativity, Ki-67, poor prognosis]. OPLS-DA multivariate models were generally able to discriminate the status of histologic prognostic factors (ER, PR, HER2, Ki-67) and prognosis groups. Our study suggests that HR-MAS MR spectroscopy using CNB specimens can predict tumor aggressiveness prior to surgery in breast cancer patients. In addition, it may be helpful in the detection of reliable markers for breast cancer characterization. PMID:23272149

Brain metabolites in autonomic regulatory insular sites in heart failure.

PubMed

Woo, Mary A; Yadav, Santosh K; Macey, Paul M; Fonarow, Gregg C; Harper, Ronald M; Kumar, Rajesh

2014-11-15

Autonomic, pain, and neuropsychologic comorbidities appear in heart failure (HF), likely resulting from brain changes, indicated as loss of structural integrity and functional deficits. Among affected brain sites, the anterior insulae are prominent in serving major regulatory roles in many of the disrupted functions commonly seen in HF. Metabolite levels, including N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and myo-inositol (MI), could indicate the nature of anterior insula tissue injury in HF. The study aim was to assess anterior insular metabolites to determine processes mediating autonomic, pain, and neuropsychologic disruptions in HF. We performed magnetic resonance spectroscopy in bilateral anterior insulae in 11 HF and 53 controls, using a 3.0-Tesla magnetic resonance imaging scanner. Peaks for NAA at 2.02 ppm, Cr at 3.02 ppm, Cho at 3.2 ppm, and MI at 3.56 ppm were assigned, peak areas were calculated, and metabolites were expressed as ratios, including NAA/Cr, Cho/Cr, and MI/Cr. HF patients showed significantly increased Cho/Cr ratios, indicative of glial proliferation or injury, on the left anterior insula, and reduced NAA/Cr levels, suggesting neuronal loss/dysfunction, on the right anterior insula over controls. No differences in MI/Cr ratios appeared between groups. Right anterior insular neuronal loss and left glial alterations may contribute to distorted autonomic, pain, and neuropsychologic functions found in HF. Copyright © 2014 Elsevier B.V. All rights reserved.

Hippocampal metabolic dysfunction in juvenile myoclonic epilepsy: 3D multivoxel spectroscopy study.

PubMed

Ristić, Aleksandar J; Ostojić, Jelena; Kozić, Duško; Vojvodić, Nikola M; Popović, Ljubica M; Janković, Slavko; Baščarević, Vladimir; Sokić, Dragoslav V

2011-06-15

To investigate the metabolic differences in hippocampi of patients with juvenile myoclonic epilepsy (JME) and healthy controls using magnetic resonance spectroscopy (MRS). A 3D multivoxel SE 135 MRS study on 1.5 T scanner of both hippocampi was performed in 17 patients with JME and normal brain MRI and in 19 age and sex matched controls. Three dominant signals were measured: Choline (Cho), Creatine (tCr) and N-Acetylaspartate (NAA) and expressed as ratios of Cho:tCr, NAA:tCr, NAA:Cho and NAA:(Cho+tCr). Metabolite ratios in head, body and tail of each hippocampus in the JME group of patients were compared with ratios from corresponding structures in the control group. We found a significant difference in metabolite ratios of both hippocampi between the JME and the control groups. We detected significant differences of Cho:tCr in the head, NAA:tCr in the head, body and tail, NAA:Cho and NAA:(Cho+tCr) in the body and tail of the left hippocampus, and NAA:Cho and NAA:(Cho+tCr) in the body and tail of the right hippocampus. Although not previously recognized as a part of the epileptogenic network, our results suggest that the hippocampus, well recognized as a key player in focal epilepsies, may have a certain role in the pathogenesis of JME. Copyright © 2010. Published by Elsevier B.V.

Brain Metabolites in Autonomic Regulatory Insular Sites in Heart Failure

PubMed Central

Woo, Mary A.; Yadav, Santosh K.; Macey, Paul M.; Fonarow, Gregg C.; Harper, Ronald M.; Kumar, Rajesh

2014-01-01

Autonomic, pain, and neuropsychologic comorbidities appear in heart failure (HF), likely resulting from brain changes, indicated as loss of structural integrity and functional deficits. Among affected brain sites, the anterior insulae are prominent in serving major regulatory roles in many of the disrupted functions commonly seen in HF. Metabolite levels, including N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and myo-inositol (MI), could indicate the nature of anterior insula tissue injury in HF. The study aim was to assess anterior insular metabolites to determine processes mediating autonomic, pain, and neuropsychologic disruptions in HF. We performed magnetic resonance spectroscopy in bilateral anterior insulae in 11 HF and 53 controls, using a 3.0-Tesla magnetic resonance imaging scanner. Peaks for NAA at 2.02ppm, Cr at 3.02ppm, Cho at 3.2ppm, and MI at 3.56ppm were assigned, peak areas calculated, and metabolites expressed as ratios, including NAA/Cr, Cho/Cr, and MI/Cr. HF patients showed significantly increased Cho/Cr ratios, indicative of glial proliferation or injury, on the left anterior insula, and reduced NAA/Cr levels, suggesting neuronal loss/dysfunction, on the right anterior insula over controls. No differences in MI/Cr ratios appeared between groups. Right anterior insular neuronal loss and left glial alterations may contribute to distorted autonomic, pain, and neuropsychologic functions found in HF. PMID:25248953

The effect of epileptic seizures on proton MRS visible neurochemical concentrations.

PubMed

Simister, Robert J; McLean, Mary A; Salmenpera, Tuuli M; Barker, Gareth J; Duncan, John S

2008-09-01

To investigate post-ictal changes in cerebral metabolites. We performed a longitudinal quantitative proton magnetic resonance spectroscopy (MRS) study in 10 patients with epilepsy and 10 control subjects. The patients were studied on two occasions: immediately following a seizure, and on a second occasion at least 7h after the most recent seizure. Each study measured N-acetyl aspartate plus N-acetyl aspartyl glutamate (NAAt), Creatine plus phosphocreatine (Cr), Choline containing compounds (Cho) and glutamate plus glutamine (GLX) concentrations using a short-echo time sequence (TE=30ms), and NAAt, Cr and lactate using a second sequence with longer echo time (TE=144ms). The control group was studied on two occasions using the same sequences. No inter-scan differences were observed for the control group. NAAt and NAAt/Cr levels were lower in the patient group at both measured TEs but did not change significantly between studies. The ratio of Cr at TE 144ms to TE 30ms (Cr(144)/Cr(30)) and GLX/Cr were higher and Cho lower in the post-ictal scan compared to the inter-ictal study. Change in Cr(144)/Cr(30) and NAAt(144)/Cr(144) correlated with the post-ictal interval. Lactate measurement at longer TE was not informative. Proton MRS is sensitive to metabolite changes following epileptic seizures within the immediate post-ictal period. The ratio Cr(144)/Cr(30) is the most sensitive measure of metabolic disturbance and is highest in the post-ictal period but appears to normalise within 2h of the most recent seizure.

Serum and urine chromium as indices of chromium status in tannery workers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Randall, J.A.; Gibson, R.S.

Serum and urinary Cr levels of a selected group of men exposed to CrIII in four Southern Ontario tanneries were compared with those of men not exposed to Cr. Fasted blood samples were obtained from 72 tannery workers (TW; mean age +/- SD = 36 +/- 12 years) and from 52 controls (CS; mean age +/- SD = 41 +/- 13 years). Serum Cr levels as determined by graphite furnace atomic absorption spectrophotometry were significantly higher (P = 0.0001) for TW (median 0.49 ng/ml, range 0.37-0.81) than for CS (median 0.15 ng/ml, range 0.12-0.20). Urine samples were collected from 49more » TW and 43 CS on a Friday pm and from 42 TW on a Monday am. Urinary creatine (Cre) was determined by the Jaffe reaction. For Friday samples, the median urinary Cr/Cre ratio was significantly higher (P = 0.0001) for TW (median 0.83 ng/mg, range 0.48-1.82) than for CS (median 0.18 ng/mg, range 0.13-0.26). For TW, Cr/Cre was correlated with serum Cr (r = 0.72, P = 0.0001). Neither urinary Cr/Cre nor serum Cr was correlated with length of employment in the tanning industry. There were significant differences in serum Cr levels and urinary Cr/Cre ratios among TW employed in different areas of the tanneries. For TW, the median urinary Cr/Cre ratio for Monday morning samples was significantly lower than for Friday afternoon samples (P = 0.03). These data indicate that CrIII is absorbed and that serum and urine Cr in tannery workers may be indices of Cr exposure and status.« less

Serum and urine chromium as indices of chromium status in tannery workers.

PubMed

Randall, J A; Gibson, R S

1987-05-01

Serum and urinary Cr levels of a selected group of men exposed to CrIII in four Southern Ontario tanneries were compared with those of men not exposed to Cr. Fasted blood samples were obtained from 72 tannery workers (TW; mean age +/- SD = 36 +/- 12 years) and from 52 controls (CS; mean age +/- SD = 41 +/- 13 years). Serum Cr levels as determined by graphite furnace atomic absorption spectrophotometry were significantly higher (P = 0.0001) for TW (median 0.49 ng/ml, range 0.37-0.81) than for CS (median 0.15 ng/ml, range 0.12-0.20). Urine samples were collected from 49 TW and 43 CS on a Friday pm and from 42 TW on a Monday am. Urinary creatine (Cre) was determined by the Jaffe reaction. For Friday samples, the median urinary Cr/Cre ratio was significantly higher (P = 0.0001) for TW (median 0.83 ng/mg, range 0.48-1.82) than for CS (median 0.18 ng/mg, range 0.13-0.26). For TW, Cr/Cre was correlated with serum Cr (r = 0.72, P = 0.0001). Neither urinary Cr/Cre nor serum Cr was correlated with length of employment in the tanning industry. There were significant differences in serum Cr levels and urinary Cr/Cre ratios among TW employed in different areas of the tanneries. For TW, the median urinary Cr/Cre ratio for Monday morning samples was significantly lower than for Friday afternoon samples (P = 0.03). These data indicate that CrIII is absorbed and that serum and urine Cr in tannery workers may be indices of Cr exposure and status.

MR Spectra of Normal Adult Testes and Variations with Age: Preliminary Observations.

PubMed

Tsili, Athina C; Astrakas, Loukas G; Ntorkou, Alexandra; Giannakis, Dimitrios; Stavrou, Sotirios; Maliakas, Vasilios; Sofikitis, Nikolaos; Argyropoulou, Maria I

2016-07-01

The aim was to determine the proton MR (1H-MR) spectra of normal adult testes and variations with age. Forty-one MR spectra of normal testes, including 16 testes from men aged 20-39 years (group I) and 25 testes from men aged 40-69 years (group II), were analyzed. A single-voxel point-resolved spectroscopy sequence (PRESS), with TR/TE: 2000/25 ms was used. The volume of interest was placed to include the majority of normal testicular parenchyma. Association between normalized metabolite concentrations, defined as ratios of the calculated metabolite concentrations relative to creatine concentration, and age was assessed. Quantified metabolites of the spectra were choline (Cho), creatine (Cr), myo-inositol (mI), scyllo-inositol, taurine, lactate, GLx compound, glucose, lipids, and macromolecules resonating at 0.9 ppm (LM09), around 20 ppm (LM20), and at 13 ppm (LM13). Most prominent peaks were Cho, Cr, mI, and lipids. A weak negative correlation between mI and age (P = 0.015) was observed. Higher normalized concentrations of Cho (P = 0.03), mI (P = 0.08), and LM13 (P = 0.05) were found in group I than in group II. 1H-MR spectra of a normal adult testis showed several metabolite peaks. A decrease of levels of Cho, mI, and LM13 was observed with advancing age. • Single-voxel PRESS MRS of a normal testis is feasible. • 1H-MR spectra of a normal testis showed several metabolite peaks. • Most prominent peaks were Cho, Cr, mI, and lipids. • A decrease of Cho, mI, and LM13 was seen with advancing age.

Studies of the haemodynamic effects of creatine phosphate in man.

PubMed Central

Hurlow, R A; Aukland, A; Hardman, J; Whittington, J R

1982-01-01

1 The haemodynamic effects of intravenous creatine phosphate 1000 mg have been studied. 2 During the first 60 min following drug administration heart rate and blood pressure did not change but cardiac output fell significantly by approximately 18%. Calculated total peripheral resistance showed a corresponding significant rise, the maximum increase being approximately 24%. All these changes were beginning to diminish within 90 min after the injection. 3 Total limb blood flow measured in both arm and leg (using venous occlusion strain-gauge plethysmography) showed no appreciable changes following injection of creatine phosphate. 4 There was a progressive reduction in leg muscle blood flow (Xe133 clearance method) following injection which was statistically significant with respect to the initial level and reached a minimum (46% reduction) 50 min after the injection. 5 Skin blood flow, estimated by infra-red photoplethysmography, showed changes complementary to those seen with muscle flow. There was a progressive and significant rise to a peak (73% increase) 30 min after the injection. 6 No adverse reactions to the injections were noted. 7 Reduced cardiac output in the absence of altered total limb blood flow presumably reflects a reduction in visceral blood flow, which was not measured in this study. Within the limbs, creatine phosphate appears to result in a redistribution of blood flow from muscle to skin. Thus, these preliminary results suggest that intravenous creatine phosphate could be clinically useful in situations where short term improvement in skin blood flow would be advantageous and that further controlled studies would be justified. PMID:7093109

In vivo1H NMR spectroscopy of the human brain at 9.4 T: Initial results

NASA Astrophysics Data System (ADS)

Deelchand, Dinesh Kumar; Moortele, Pierre-François Van de; Adriany, Gregor; Iltis, Isabelle; Andersen, Peter; Strupp, John P.; Thomas Vaughan, J.; Uğurbil, Kâmil; Henry, Pierre-Gilles

2010-09-01

In vivo proton NMR spectroscopy allows non-invasive detection and quantification of a wide range of biochemical compounds in the brain. Higher field strength is generally considered advantageous for spectroscopy due to increased signal-to-noise and increased spectral dispersion. So far 1H NMR spectra have been reported in the human brain up to 7 T. In this study we show that excellent quality short echo time STEAM and LASER 1H NMR spectra can be measured in the human brain at 9.4 T. The information content of the human brain spectra appears very similar to that measured in the past decade in rodent brains at the same field strength, in spite of broader linewidth in human brain. Compared to lower fields, the T1 relaxation times of metabolites were slightly longer while T2 relaxation values of metabolites were shorter (<100 ms) at 9.4 T. The linewidth of the total creatine (tCr) resonance at 3.03 ppm increased linearly with magnetic field (1.35 Hz/T from 1.5 T to 9.4 T), with a minimum achievable tCr linewidth of around 12.5 Hz at 9.4 T. At very high field, B0 microsusceptibility effects are the main contributor to the minimum achievable linewidth.

Whole-brain patterns of (1)H-magnetic resonance spectroscopy imaging in Alzheimer's disease and dementia with Lewy bodies.

PubMed

Su, L; Blamire, A M; Watson, R; He, J; Hayes, L; O'Brien, J T

2016-08-30

Magnetic resonance spectroscopy has demonstrated metabolite changes in neurodegenerative disorders such as Alzheimer's disease (AD) and dementia with Lewy bodies (DLB); however, their pattern and relationship to clinical symptoms is unclear. To determine whether the spatial patterns of brain-metabolite changes in AD and DLB are regional or diffused, and to examine whether the key metabolite levels are associated with cognitive and non-cognitive symptoms, we acquired whole-brain spatially resolved 3T magnetic resonance spectroscopic imaging (MRSI) data from subjects with AD (N=36), DLB (N=35) and similarly aged controls (N=35). Voxel-wise measurement of N-acetylaspartate to creatine (NAA/Cr), choline to Cr (Cho/Cr), myo-inositol to Cr (mI/Cr) as well as glutamate and glutamine to Cr (Glx/Cr) ratios were determined using MRSI. Compared with controls, AD and DLB groups showed a significant decrease in most brain metabolites, with NAA/Cr, Cho/Cr and mI/Cr levels being reduced in posterior cingulate, thalamus, frontotemporal areas and basal ganglia. The Glx/Cr level was more widely decreased in DLB (posterior cingulate, hippocampus, temporal regions and caudate) than in AD (only in posterior cingulate). DLB was also associated with increased levels of Cho/Cr, NAA/Cr and mI/Cr in occipital regions. Changes in metabolism in the brain were correlated with cognitive and non-cognitive symptoms in the DLB but not in the AD group. The different patterns between AD and DLB may have implications for improving diagnosis, better understanding disease-specific neurobiology and targeting therapeutics. In addition, the study raised important questions about the role of occipital neuroinflammation and glial activation as well as the glutamatergic treatment in DLB.

Brain metabolite changes in patients with type 2 diabetes and cerebral infarction using proton magnetic resonance spectroscopy.

PubMed

Zhang, Min; Sun, Xinhai; Zhang, Zhengjun; Meng, Qiang; Wang, Yuzhong; Chen, Jing; Ma, Xueqin; Geng, Houfa; Sun, Lin

2014-01-01

The aim of this study was to investigate the possible brain metabolic alterations in patients with type 2 diabetes mellitus (T2DM) and cerebral infarction (DMCI) using proton magnetic resonance spectroscopy (MRS). Thirty-four patients with T2DM and DMCI were scanned together with 33 patients with nondiabetic cerebral infarction (NDCI) on a 1.5-T MRI/MRS imager. Voxels were placed in the infarcted area and the contralateral normal area in the basal ganglia. N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/Cr, and lactate (Lac)/Cr ratios were calculated. Cerebral NAA/Cr ratios in the infarcted area were lower than those in the contralateral normal area of the NDCI group. There was a significant decrease in NAA/Cr in the infarcted area of the DMCI group as compared with the infarcted area of the NDCI group. NAA/Cr ratios in the contralateral normal area of DMCI group were lower than those of the NDCI group. Lac/Cr ratios were increased in the infarcted area of both the DMCI group and NDCI group, and Lac/Cr ratios tended to be higher in the infarcted area of the DMCI group than those of the NDCI group. Glycosylated hemoglobin (HbA1c) levels were negatively correlated with NAA/Cr ratios. The study suggested that the metabolite changes were different between DMCI patients and NDCI patients, which may provide important information in the treatment of DMCI.

Longitudinal cerebral metabolic changes in pig-tailed macaques infected with the neurovirulent virus SIVsmmFGb

PubMed Central

Li, Chun-Xia; Zhang, Xiaodong; Komery, Amelia; Li, Yingxia; Mao, Hui; Herndon, James G; Novembre, Francis J

2014-01-01

Longitudinal cerebral metabolite changes in pig-tailed macaques inoculated with the simian immunodeficiency virus SIVsmmFGb were evaluated with in vivo proton MRS at 3T. Blood sample collection, and MRS were carried out before and 2, 4, 8, 12, 16, 20 and 24 weeks after SIV inoculation. Significant reduction of N-acetylaspartate (NAA)/creatine (Cr) and Choline (Cho)/Cr ratios in prefrontal grey matter (PGM) and glutamate/glutamine (Glx)/Cr ratios in striatum, and increase of myo-inositol (mI)/Cr in striatum were observed during acute SIV infection. The metabolite alterations during the SIVsmmFGb infection are largely in agreement with previous findings in other non-human primate models and HIV patients. Also, NAA/Cr in PGM and striatum and Glx/Cr in striatum are negatively correlated with the percentage of CD8+ T cells after the SIV infection, suggesting the interaction between brain metabolite and immune dysfunction. The present study complements previous studies by describing the time course of alterations of brain metabolites during SIVsmmFGb infection. The findings further demonstrate the efficacy of the SIVsmmFGb-infected macaque as a model to characterize central nervous system infection using novel neuroimaging approaches and also as a tool for exploration of novel and advanced neuroimaging techniques in HIV/AIDS studies. PMID:25377443

Longitudinal cerebral metabolic changes in pig-tailed macaques infected with the neurovirulent virus SIVsmmFGb.

PubMed

Li, Chun-Xia; Zhang, Xiaodong; Komery, Amelia; Li, Yingxia; Mao, Hui; Herndon, James G; Novembre, Francis J

2014-12-01

Longitudinal cerebral metabolite changes in pig-tailed macaques inoculated with the simian immunodeficiency virus SIVsmmFGb were evaluated with in vivo proton MRS at 3 T. Blood sample collection, and MRS were carried out before and 2, 4, 8, 12, 16, 20, and 24 weeks after SIV inoculation. Significant reduction of N-acetylaspartate (NAA)/creatine (Cr) and choline (Cho)/Cr ratios in prefrontal gray matter (PGM) and glutamate/glutamine(Glx)/Cr ratio in striatum, and increase of myo-inositol (mI)/Cr in striatum were observed during acute SIV infection. The metabolite alterations during the SIVsmmFGb infection are largely in agreement with previous findings in other non-human primate models and HIV patients. Also, NAA/Cr in PGM and striatum and Glx/Cr in striatum are negatively correlated with the percentage of CD8+ T cells after the SIV infection, suggesting the interaction between brain metabolite and immune dysfunction. The present study complements previous studies by describing the time course of alterations of brain metabolites during SIVsmmFGb infection. The findings further demonstrate the efficacy of the SIVsmmFGb-infected macaque as a model to characterize central nervous system infection using novel neuroimaging approaches and also as a tool for exploration of novel and advanced neuroimaging techniques in HIV/AIDS studies.

The CREST-E study of creatine for Huntington disease

PubMed Central

Schifitto, Giovanni; Oakes, David; Bredlau, Amy-Lee; Meyers, Catherine M.; Nahin, Richard; Rosas, Herminia Diana

2017-01-01

Objective: To investigate whether creatine administration could slow progressive functional decline in adults with early symptoms of Huntington disease. Methods: We conducted a multicenter, randomized, double-blind, placebo-controlled study of up to 40 g daily of creatine monohydrate in participants with stage I and II HD treated for up to 48 months. The primary outcome measure was the rate of change in total functional capacity (TFC) between baseline and end of follow-up. Secondary outcome measures included changes in additional clinical scores, tolerability, and quality of life. Safety was assessed by adverse events and laboratory studies. Results: At 46 sites in North America, Australia, and New Zealand, 553 participants were randomized to creatine (275) or placebo (278). The trial was designed to enroll 650 patients, but was halted for futility after the first interim analysis. The estimated rates of decline in the primary outcome measure (TFC) were 0.82 points per year for participants on creatine, 0.70 points per year for participants on placebo, favoring placebo (nominal 95% confidence limits −0.11 to 0.35). Adverse events, mainly gastrointestinal, were significantly more common in participants on creatine. Serious adverse events, including deaths, were more frequent in the placebo group. Subgroup analysis suggested that men and women may respond differently to creatine treatment. Conclusions: Our data do not support the use of creatine treatment for delaying functional decline in early manifest HD. Clinicaltrials.gov identifier: NCT00712426. Classification of evidence: This study provides Class II evidence that for patients with early symptomatic HD, creatine monohydrate is not beneficial for slowing functional decline. PMID:28701493

Chronic high-dose creatine has opposing effects on depression-related gene expression and behavior in intact and sex hormone-treated gonadectomized male and female rats.

PubMed

Allen, Patricia J; DeBold, Joseph F; Rios, Maribel; Kanarek, Robin B

2015-03-01

Creatine is an antioxidant, neuromodulator and key regulator of energy metabolism shown to improve depressive symptoms in humans and animals, especially in females. To better understand the pharmacological effects of creatine, we examined its influence on depression-related hippocampal gene expression and behaviors in the presence and absence of sex steroids. Sham-operated and gonadectomized male and female rats were fed chow alone or chow blended with either 2% or 4% w/w creatine monohydrate for five weeks before forced swim, open field, and wire suspension tests, or seven weeks total. Before supplementation, males were chronically implanted with an empty or a testosterone-filled (T) capsule (10-mm surface release), and females were administered progesterone (P, 250 μg), estradiol benzoate (EB, 2.5 μg), EB+P, or sesame oil vehicle weekly. Relative to non-supplemented shams, all hippocampal plasticity-related mRNAs measured, including brain-derived neurotrophic factor (BDNF), tyrosine kinase B, doublecortin, calretinin, and calbindin, were downregulated in sham males given 4% creatine, and BDNF, doublecortin, and calbindin mRNAs were downregulated in sham females given 4% creatine. In contrast, combined 4% creatine+T in castrates prevented downregulation of BDNF, doublecortin, and calretinin mRNAs. Similarly, combined 4% creatine+EB+P in ovariectomized females attenuated downregulation of BDNF and calbindin mRNA levels. Moderate antidepressant and anxiolytic-like behaviors were observed in EB+P-treated ovariectomized females fed creatine, with similar trends in T-treated castrates fed creatine. Altogether, these data show that chronic, high-dose creatine has opposing effects on neuroplasticity-related genes and depressive behavior in intact and gonadectomized male and female rats. The dose and schedule of creatine used negatively impacted hippocampal neuronal integrity in otherwise healthy brains, possibly through negative compensatory changes in energy metabolism, whereas combined creatine and sex steroids acted in a neuroprotective manner in gonadectomized rats, potentially by reducing metabolic complications associated with castration or ovariectomy. Copyright © 2014 Elsevier Inc. All rights reserved.

GABA and Glutamate in Children with Primary Complex Motor Stereotypies: A 1H MRS Study at 7T

PubMed Central

Harris, A. D.; Singer, H. S.; Horska, A.; Kline, T.; Ryan, M.; Edden, R. A. E.; Mahone, E. Mark

2015-01-01

Background and Purpose Complex motor stereotypies (CMS) are rhythmic, repetitive, fixed, purposeful but purposeless movements that stop with distraction. They can occur in otherwise normal healthy children (primary stereotypies), as well in those with autism spectrum disorders (secondary stereotypies). The underlying neurobiological basis for these movements is unknown, but thought to involve cortical-striatal-thalamo-cortical pathways. In order to further clarify potential neurochemical alterations, GABA, glutamate (Glu), glutamine (Gln), N-acetyl aspartate (NAA) and choline (Cho) levels were measured in four frontostriatal regions, using 1H MRS at 7T. Materials and Methods A total of 18 children with primary CMS and 24 typically developing controls, ages 5-10 years completed MRS at 7T. Single voxel STEAM acquisitions from the anterior cingulate cortex (ACC), premotor cortex (PMC), dorsolateral prefrontal cortex (DLPFC) and striatum were obtained and metabolites were quantified with respect to creatine using LCModel. Results The 7T scan was well tolerated by all participants. Compared to controls, children with CMS had lower levels of GABA ACC (GABA/Cr, p=0.049; GABA/Glu: p=0.051) and striatum (GABA/Cr: p= 0.028; GABA/Glu: p=0.0037), but not the DLPFC or PMC. Glu, Gln, NAA, and Cho levels did not differ between groups in any of the aforementioned regions. Within the CMS group, reduced GABA/Cr in the ACC was significantly associated with greater severity of motor stereotypies (r=-0.59, p= 0.021). Conclusions These results suggest possible GABAergic dysfunction within corticostriatal pathways in children with primary CMS. PMID:26542237

Accelerated proton echo planar spectroscopic imaging (PEPSI) using GRAPPA with a 32-channel phased-array coil.

PubMed

Tsai, Shang-Yueh; Otazo, Ricardo; Posse, Stefan; Lin, Yi-Ru; Chung, Hsiao-Wen; Wald, Lawrence L; Wiggins, Graham C; Lin, Fa-Hsuan

2008-05-01

Parallel imaging has been demonstrated to reduce the encoding time of MR spectroscopic imaging (MRSI). Here we investigate up to 5-fold acceleration of 2D proton echo planar spectroscopic imaging (PEPSI) at 3T using generalized autocalibrating partial parallel acquisition (GRAPPA) with a 32-channel coil array, 1.5 cm(3) voxel size, TR/TE of 15/2000 ms, and 2.1 Hz spectral resolution. Compared to an 8-channel array, the smaller RF coil elements in this 32-channel array provided a 3.1-fold and 2.8-fold increase in signal-to-noise ratio (SNR) in the peripheral region and the central region, respectively, and more spatial modulated information. Comparison of sensitivity-encoding (SENSE) and GRAPPA reconstruction using an 8-channel array showed that both methods yielded similar quantitative metabolite measures (P > 0.1). Concentration values of N-acetyl-aspartate (NAA), total creatine (tCr), choline (Cho), myo-inositol (mI), and the sum of glutamate and glutamine (Glx) for both methods were consistent with previous studies. Using the 32-channel array coil the mean Cramer-Rao lower bounds (CRLB) were less than 8% for NAA, tCr, and Cho and less than 15% for mI and Glx at 2-fold acceleration. At 4-fold acceleration the mean CRLB for NAA, tCr, and Cho was less than 11%. In conclusion, the use of a 32-channel coil array and GRAPPA reconstruction can significantly reduce the measurement time for mapping brain metabolites. (c) 2008 Wiley-Liss, Inc.

Manipulation of Muscle Creatine and Glycogen Changes Dual X-ray Absorptiometry Estimates of Body Composition.

PubMed

Bone, Julia L; Ross, Megan L; Tomcik, Kristyen A; Jeacocke, Nikki A; Hopkins, Will G; Burke, Louise M

2017-05-01

Standardizing a dual x-ray absorptiometry (DXA) protocol is thought to provide a reliable measurement of body composition. We investigated the effects of manipulating muscle glycogen and creatine content independently and additively on DXA estimates of lean mass. Eighteen well-trained male cyclists undertook a parallel group application of creatine loading (n = 9) (20 g·d for 5 d loading; 3 g·d maintenance) or placebo (n = 9) with crossover application of glycogen loading (12 v 6 g·kg BM per day for 48 h) as part of a larger study involving a glycogen-depleting exercise protocol. Body composition, total body water, muscle glycogen and creatine content were assessed via DXA, bioelectrical impedance spectroscopy and standard biopsy techniques. Changes in the mean were assessed using the following effect-size scale: >0.2 small, >0.6, moderate, >1.2 large and compared with the threshold for the smallest worthwhile effect of the treatment. Glycogen loading, both with and without creatine loading, resulted in substantial increases in estimates of lean body mass (mean ± SD; 3.0% ± 0.7% and 2.0% ± 0.9%) and leg lean mass (3.1% ± 1.8% and 2.6% ± 1.0%) respectively. A substantial decrease in leg lean mass was observed after the glycogen depleting condition (-1.4% ± 1.6%). Total body water showed substantial increases after glycogen loading (2.3% ± 2.3%), creatine loading (1.4% ± 1.9%) and the combined treatment (2.3% ± 1.1%). Changes in muscle metabolites and water content alter DXA estimates of lean mass during periods in which minimal change in muscle protein mass is likely. This information needs to be considered in interpreting the results of DXA-derived estimates of body composition in athletes.

Determination of total creatine kinase activity in blood serum using an amperometric biosensor based on glucose oxidase and hexokinase.

PubMed

Kucherenko, I S; Soldatkin, O O; Lagarde, F; Jaffrezic-Renault, N; Dzyadevych, S V; Soldatkin, A P

2015-11-01

Creatine kinase (CK: adenosine-5-triphosphate-creatine phosphotransferase) is an important enzyme of muscle cells; the presence of a large amount of the enzyme in blood serum is a biomarker of muscular injuries, such as acute myocardial infarction. This work describes a bi-enzyme (glucose oxidase and hexokinase based) biosensor for rapid and convenient determination of CK activity by measuring the rate of ATP production by this enzyme. Simultaneously the biosensor determines glucose concentration in the sample. Platinum disk electrodes were used as amperometric transducers. Glucose oxidase and hexokinase were co-immobilized via cross-linking with BSA by glutaraldehyde and served as a biorecognition element of the biosensor. The biosensor work at different concentrations of CK substrates (ADP and creatine phosphate) was investigated; optimal concentration of ADP was 1mM, and creatine phosphate - 10 mM. The reproducibility of the biosensor responses to glucose, ATP and CK during a day was tested (relative standard deviation of 15 responses to glucose was 2%, to ATP - 6%, to CK - 7-18% depending on concentration of the CK). Total time of CK analysis was 10 min. The measurements of creatine kinase in blood serum samples were carried out (at 20-fold sample dilution). Twentyfold dilution of serum samples was chosen as optimal for CK determination. The biosensor could distinguish healthy and ill people and evaluate the level of CK increase. Thus, the biosensor can be used as a test-system for CK analysis in blood serum or serve as a component of multibiosensors for determination of important blood substances. Determination of activity of other kinases by the developed biosensor is also possible for research purposes. Copyright © 2015 Elsevier B.V. All rights reserved.

The CREST-E study of creatine for Huntington disease: A randomized controlled trial.

PubMed

Hersch, Steven M; Schifitto, Giovanni; Oakes, David; Bredlau, Amy-Lee; Meyers, Catherine M; Nahin, Richard; Rosas, Herminia Diana

2017-08-08

To investigate whether creatine administration could slow progressive functional decline in adults with early symptoms of Huntington disease. We conducted a multicenter, randomized, double-blind, placebo-controlled study of up to 40 g daily of creatine monohydrate in participants with stage I and II HD treated for up to 48 months. The primary outcome measure was the rate of change in total functional capacity (TFC) between baseline and end of follow-up. Secondary outcome measures included changes in additional clinical scores, tolerability, and quality of life. Safety was assessed by adverse events and laboratory studies. At 46 sites in North America, Australia, and New Zealand, 553 participants were randomized to creatine (275) or placebo (278). The trial was designed to enroll 650 patients, but was halted for futility after the first interim analysis. The estimated rates of decline in the primary outcome measure (TFC) were 0.82 points per year for participants on creatine, 0.70 points per year for participants on placebo, favoring placebo (nominal 95% confidence limits -0.11 to 0.35). Adverse events, mainly gastrointestinal, were significantly more common in participants on creatine. Serious adverse events, including deaths, were more frequent in the placebo group. Subgroup analysis suggested that men and women may respond differently to creatine treatment. Our data do not support the use of creatine treatment for delaying functional decline in early manifest HD. NCT00712426. This study provides Class II evidence that for patients with early symptomatic HD, creatine monohydrate is not beneficial for slowing functional decline. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

A comparison of mutagen production in fried ground chicken and beef: effect of supplemental creatine.

PubMed

Knize, M G; Shen, N H; Felton, J S

1988-11-01

Ground chicken breast and ground beef with either endogenous or a 10-fold increase in the concentration of creatine were fried at 220 degrees C for 10 min per side. One patty (100 g) of chicken meat yielded 120,000 Salmonella (TA1538) revertants following metabolic activation. The pan residues had 39% of the total activity. Added creatine (10-fold the endogenous level) increased mutagen yields an average of 2-fold. Beef cooked under identical conditions yielded 150,000 revertants/100 g for the meat patties and pan residues combined. Added creatine to beef prior to cooking increased mutagen yields 3-fold. The mutagenic profiles following initial HPLC separation showed that chicken samples with endogenous or added creatine were remarkably similar. Chicken and beef HPLC mutagenicity profiles were also similar to each other, but not identical. This suggests that the general mutagen-forming reactions with the two different types of muscle are qualitatively similar with only minor quantitative differences. The pan residues from both meat types with and without added creatine showed some significant differences in the mutagen peak profile. This work suggests that the types of mutagens formed in chicken are similar to those formed in beef and that creatine appears to be involved in the formation of all the mutagenic compounds produced from fried muscle tissue.

Changing to a vegetarian diet reduces the body creatine pool in omnivorous women, but appears not to affect carnitine and carnosine homeostasis: a randomised trial.

PubMed

Blancquaert, Laura; Baguet, Audrey; Bex, Tine; Volkaert, Anneke; Everaert, Inge; Delanghe, Joris; Petrovic, Mirko; Vervaet, Chris; De Henauw, Stefaan; Constantin-Teodosiu, Dumitru; Greenhaff, Paul; Derave, Wim

2018-04-01

Balanced vegetarian diets are popular, although they are nearly absent in creatine and carnosine and contain considerably less carnitine than non-vegetarian diets. Few longitudinal intervention studies investigating the effect of a vegetarian diet on the availability of these compounds currently exist. We aimed to investigate the effect of transiently switching omnivores onto a vegetarian diet for 6 months on muscle and plasma creatine, carnitine and carnosine homeostasis. In a 6-month intervention, forty omnivorous women were ascribed to three groups: continued omnivorous diet (control, n 10), vegetarian diet without supplementation (Veg+Pla, n 15) and vegetarian diet combined with daily β-alanine (0·8-0·4 g/d) and creatine supplementation (1 g creatine monohydrate/d) (Veg+Suppl, n 15). Before (0 months; 0M), after 3 months (3M) and 6 months (6M), a fasted venous blood sample and 24-h urine was collected, and muscle carnosine content was determined by proton magnetic resonance spectroscopy (1H-MRS). Muscle biopsies were obtained at 0M and 3M. Plasma creatine and muscle total creatine content declined from 0M to 3M in Veg+Pla (P=0·013 and P=0·009, respectively), whereas plasma creatine increased from 0M in Veg+Suppl (P=0·004). None of the carnitine-related compounds in plasma or muscle showed a significant time×group interaction effect. 1H-MRS-determined muscle carnosine content was unchanged over 6M in control and Veg+Pla, but increased in Veg+Suppl in soleus (P<0·001) and gastrocnemius (P=0·001) muscle. To conclude, the body creatine pool declined over a 3-month vegetarian diet in omnivorous women, which was ameliorated when accompanied by low-dose dietary creatine supplementation. Carnitine and carnosine homeostasis was unaffected by a 3- or 6-month vegetarian diet, respectively.

Reduced creatine kinase release with statin use at the time of myocardial infarction.

PubMed

Bybee, Kevin A; Kopecky, Stephen L; Williams, Brent A; Murphy, Joseph G; Scott Wright, R

2004-09-01

Statin pre-treatment has been shown to reduce myocardial infarct size in animal models. We evaluated peak creatine kinase levels in humans based on concomitant or very early statin initiation following myocardial infarction. We identified 66 consecutive patients who received a statin within 24 h of admission to our coronary care unit for myocardial infarction. Each statin patient was matched with three patients who had not received statin therapy (n=198). Statin patients were subgrouped into those receiving statin therapy at the time of infarction (n=44) and those initiated on statin therapy within 24 h of infarction (n=22). Peak total creatine kinase concentrations were compared between groups. A linear regression model was developed to test for differences in peak creatine kinase after adjusting for differences between groups. Patients receiving statin therapy within 24 h of admission had significantly smaller median peak creatine kinase concentrations compared to those not receiving a statin (416 IU/l [258, 992] vs. 699 IU/l [339, 1728]; p=0.020). Subgroup analysis revealed that the lower peak creatine kinase concentrations within the statin group were a result of lower creatine kinase concentrations in those patients on a statin at the time of myocardial infarction (399 IU/l [255, 869] vs. 678 IU/l [276, 1870]; p<0.05). This difference retained statistical significance after adjustment for differences between groups. Statin therapy at the time of myocardial infarction is associated with lower peak creatine kinase concentrations. This suggests that statins may exhibit protective effects in the setting of myocardial ischemia and/or infarction in humans.

Psychostimulant drug effects on glutamate, Glx, and creatine in the anterior cingulate cortex and subjective response in healthy humans.

PubMed

White, Tara L; Monnig, Mollie A; Walsh, Edward G; Nitenson, Adam Z; Harris, Ashley D; Cohen, Ronald A; Porges, Eric C; Woods, Adam J; Lamb, Damon G; Boyd, Chelsea A; Fekir, Sinda

2018-06-01

Prescription psychostimulants produce rapid changes in mood, energy, and attention. These drugs are widely used and abused. However, their effects in human neocortex on glutamate and glutamine (pooled as Glx), and key neurometabolites such as N-acetylaspartate (tNAA), creatine (tCr), choline (Cho), and myo-inositol (Ins) are poorly understood. Changes in these compounds could inform the mechanism of action of psychostimulant drugs and their abuse potential in humans. We investigated the acute impact of two FDA-approved psychostimulant drugs on neurometabolites using magnetic resonance spectroscopy ( 1 H MRS). Single clinically relevant doses of d-amphetamine (AMP, 20 mg oral), methamphetamine (MA, 20 mg oral; Desoxyn®), or placebo were administered to healthy participants (n = 26) on three separate test days in a placebo-controlled, double-blinded, within-subjects crossover design. Each participant experienced all three conditions and thus served as his/her own control. 1 H MRS was conducted in the dorsal anterior cingulate cortex (dACC), an integrative neocortical hub, during the peak period of drug responses (140-150 m post ingestion). D-amphetamine increased the level of Glu (p = .0001), Glx (p = .003), and tCr (p = .0067) in the dACC. Methamphetamine increased Glu in females, producing a significant crossover interaction pattern with gender (p = .02). Drug effects on Glu, tCr, and Glx were positively correlated with subjective drug responses, predicting both the duration of AMP liking (Glu: r = +.49, p = .02; tCr: r = +.41, p = .047) and the magnitude of peak drug high to MA (Glu: r = +.52, p = .016; Glx: r = +.42, p = .049). Neither drug affected the levels of tNAA, Cho, or Ins after correction for multiple comparisons. We conclude that d-amphetamine increased the concentration of glutamate, Glx, and tCr in the dACC in male and female volunteers 2 1 / 2 hours after drug consumption. There was evidence that methamphetamine differentially affects dACC Glu levels in women and men. These findings provide the first experimental evidence that specific psychostimulants increase the level of glutamatergic compounds in the human brain, and that glutamatergic changes predict the extent and magnitude of subjective responses to psychostimulants.

White matter disease and cognitive impairment in FMR1 premutation carriers.

PubMed

Filley, Christopher M; Brown, Mark S; Onderko, Karen; Ray, Megan; Bennett, Rachael E; Berry-Kravis, Elizabeth; Grigsby, Jim

2015-05-26

This cross-sectional, observational study examined the role of white matter involvement in the cognitive impairment of individuals with the fragile X mental retardation 1 (FMR1) premutation. Eight asymptomatic premutation carriers, 5 participants with fragile X tremor/ataxia syndrome (FXTAS), and 7 noncarrier controls were studied. The mean age of the asymptomatic premutation carriers, participants with FXTAS, and noncarrier controls was 60, 71, and 67 years, respectively. Magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) were used to examine the middle cerebellar peduncles (MCP) and the genu and splenium of the corpus callosum in relation to executive function and processing speed. MRS measures were N-acetyl aspartate/creatine (NAA/Cr) and choline/creatine, and fractional anisotropy (FA) was used for DTI. Executive function was assessed with the Behavioral Dyscontrol Scale and the Controlled Oral Word Association Test (COWAT), and processing speed with the Symbol Digit Modalities Test. Among all 13 FMR1 premutation carriers, significant correlations were found between N-acetyl aspartate/creatine and choline/creatine in the MCP and COWAT scores, and between FA in the genu and performance on the Behavioral Dyscontrol Scale, COWAT, and Symbol Digit Modalities Test; a correlation was also found between FA in the splenium and COWAT performance. In all regions studied, participants with FXTAS had the lowest mean FA. Microstructural white matter disease as determined by MRS and DTI correlated with executive dysfunction and slowed processing speed in these FMR1 premutation carriers. Neuroimaging abnormalities in the genu and MCP suggest that disruption of white matter within frontocerebellar networks has an important role in the cognitive impairment associated with the FMR1 premutation. © 2015 American Academy of Neurology.

Rhabdomyolysis and acute kidney injury: creatine kinase as a prognostic marker and validation of the McMahon Score in a 10-year cohort: A retrospective observational evaluation.

PubMed

Simpson, Joanna P; Taylor, Andrew; Sudhan, Nazneen; Menon, David K; Lavinio, Andrea

2016-12-01

High-volume fluid resuscitation and the administration of sodium bicarbonate and diuretics have a theoretical renoprotective role in patients at high risk of acute kidney injury (AKI) following rhabdomyolysis. Abnormally elevated creatine kinase has previously been used as a biological marker for the identification of patients at high risk of AKI following rhabdomyolysis. To assess the sensitivity and specificity of plasma creatine kinase (admission and peak values) for the prediction of AKI requiring renal replacement therapy (RRT) or of death in patients with confirmed rhabdomyolysis. To compare the diagnostic performance of creatine kinase with the McMahon score. Retrospective observational study. Data collection included McMahon and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores; daily creatine kinase; daily creatinine and electrolytes; ICU length of stay and mortality. Neurosciences and Trauma Critical Care Unit (Cambridge, UK). In total, 232 adults with confirmed rhabdomyolysis (creatine kinase > 1000 Ul) admitted to Neurosciences and Trauma Critical Care Unit between 2002 and 2012. AKI, RRT and mortality. Forty-five (19%) patients developed AKI and 29 (12.5%) patients required RRT. Mortality was significantly higher in patients who developed AKI (62 vs. 18%, P < 0.001). Average creatine kinase on admission was 5009 (range 69-157 860) Ul. Creatine kinase peaked between the day of admission and day 3 in 91% of cases. PEAK creatine kinase of at least 5000 Ul is 55% specific and 83% sensitive for the prediction of AKI requiring RRT. A McMahon Score of at least 6 calculated on admission is 68% specific and 86% sensitive for RRT. Creatine kinase is not a specific or early predictor of AKI in patients with rhabdomyolysis. Although a PEAK creatine kinase of at least 5000 Ul has sensitivity acceptable for screening purposes, this is often a delayed finding. A McMahon score of at least 6 calculated on admission allows for a more sensitive, specific and timely identification of patients who may benefit from high-volume fluid resuscitation.

Elevated cerebral glutamate and myo-inositol levels in cognitively normal middle-aged adults with metabolic syndrome.

PubMed

Haley, Andreana P; Gonzales, Mitzi M; Tarumi, Takashi; Miles, Steven C; Goudarzi, Katayoon; Tanaka, Hirofumi

2010-12-01

Metabolic syndrome (MetS) is a cluster of risk factors associated with significant cardiovascular morbidity and mortality and diminished cognitive function. Given that the cerebral mechanisms mediating the relationship between peripheral metabolic dysfunction and cognitive impairment are unknown, we set out to examine the relationship between diagnosis of metabolic syndrome and cerebral metabolism. Thirteen participants with MetS (aged 48 ± 6 years) and 25 healthy adults (aged 51 ± 6 years) underwent neuropsychological assessment, health screen and proton magnetic resonance spectroscopy ((1)H MRS) examining N-acetyl-aspartate (NAA), myo-inositol (mI), creatine (Cr), choline (Cho), and glutamate (Glu) concentrations in occipitoparietal grey matter. Cerebral metabolite ratios (NAA/Cr, Cho/Cr, mI/Cr, and Glu/Cr) of participants with MetS, defined by the International Diabetes Federation criteria, were compared with controls matched for age, education, cognition, and emotional function. There were no significant differences in global cognitive function, memory, language, and psychomotor performance between the groups. Diagnosis of MetS was associated with significantly higher mI/Cr (F(1,36) = 5.02, p = 0.031) and Glu/Cr ratio (F(1,36) = 4.81, p = 0.035). Even in cognitively normal adults, MetS is related to cerebral metabolic disturbances, a possible indication of early brain vulnerability. Longitudinal studies that begin in mid-life can help validate the use of (1)H MRS markers as indicators of long-term cognitive outcomes.

Cerebral diffusion tensor imaging and in vivo proton magnetic resonance spectroscopy in patients with fulminant hepatic failure.

PubMed

Saksena, Sona; Rai, Vijan; Saraswat, Vivek Anand; Rathore, Ramkishore Singh; Purwar, Ankur; Kumar, Manoj; Thomas, M Albert; Gupta, Rakesh Kumar

2008-07-01

Cerebral edema is a major complication in patients with fulminant hepatic failure (FHF). The aim of this study was to evaluate the metabolite alterations and cerebral edema in patients with FHF using in vivo proton magnetic resonance spectroscopy (MRS) and diffusion tensor imaging, and to look for its reversibility in survivors. Ten FHF patients along with 10 controls were studied. Five of the 10 patients who recovered had a repeat imaging after three weeks. N-acetylaspartate, choline (Cho), glutamine (Gln), glutamine/glutamate (Glx), and myoinositol ratios were calculated with respect to creatine (Cr). Mean diffusivity (MD) and fractional anisotropy (FA) were calculated in different brain regions. Patients exhibited significantly increased Gln/Cr and Glx/Cr, and reduced Cho/Cr ratios, compared to controls. In the follow-up study, all metabolite ratios were normalized except Glx/Cr. Significantly decreased Cho/Cr were observed in deceased patients compared to controls. In patients, significantly decreased MD and FA values were observed in most topographical locations of the brain compared to controls. MD and FA values showed insignificant increase in the follow-up study compared to their first study. We conclude that the Cho/Cr ratio appears to be an in vivo marker of prognosis in FHF. Decreased MD values suggest predominant cytotoxic edema may be present. Persistence of imaging and MRS abnormalities at three weeks' clinical recovery suggests that metabolic recovery may take longer than clinical recovery in FHF patients.

Proton magnetic resonance spectroscopy shows lower intramyocellular lipid accumulation in middle-aged subjects predisposed to familial longevity.

PubMed

Wijsman, C A; van Opstal, A M; Kan, H E; Maier, A B; Westendorp, R G J; Slagboom, P E; Webb, A G; Mooijaart, S P; van Heemst, D

2012-02-01

Families predisposed to longevity show enhanced glucose tolerance and skeletal muscle insulin sensitivity compared with controls, independent of body composition and physical activity. Intramyocellular lipid (IMCL) accumulation in skeletal muscle has been associated with insulin resistance. Here, we assessed whether subjects enriched for familial longevity have lower IMCL levels. We determined IMCL levels in 48 subjects from the Leiden Longevity Study, comprising 24 offspring of nonagenarian siblings and 24 partners thereof as control subjects. IMCL levels were assessed noninvasively using short echo time proton magnetic resonance spectroscopy ((1)H-MRS) of the tibialis anterior muscle with a 7 Tesla human MR scanner. IMCL levels were calculated relative to the total creatine (tCr) CH3 signal. Physical activity was assessed using the International Physical Activity Questionnaire (IPAQ). After correction for age, sex, BMI, and physical activity, offspring of long-lived nonagenarian siblings tended to show lower IMCL levels compared with controls (IMCL/tCr: 3.1 ± 0.5 vs. 4.5 ± 0.5, respectively, P = 0.051). In a pairwise comparison, this difference reached statistical significance (P = 0.038). We conclude that offspring of nonagenarian siblings predisposed to longevity show lower IMCL levels compared with environmentally matched control subjects. Future research should focus on assessing what mechanisms may explain the lower IMCL levels in familial longevity.

Integrative Network-based Analysis of Magnetic Resonance Spectroscopy and Genome Wide Expression in Glioblastoma multiforme

PubMed Central

Heiland, Dieter Henrik; Mader, Irina; Schlosser, Pascal; Pfeifer, Dietmar; Carro, Maria Stella; Lange, Thomas; Schwarzwald, Ralf; Vasilikos, Ioannis; Urbach, Horst; Weyerbrock, Astrid

2016-01-01

The goal of this study was to identify correlations between metabolites from proton MR spectroscopy and genetic pathway activity in glioblastoma multiforme (GBM). Twenty patients with primary GBM were analysed by short echo-time chemical shift imaging and genome-wide expression analyses. Weighed Gene Co-Expression Analysis was used for an integrative analysis of imaging and genetic data. N-acetylaspartate, normalised to the contralateral healthy side (nNAA), was significantly correlated to oligodendrocytic and neural development. For normalised creatine (nCr), a group with low nCr was linked to the mesenchymal subtype, while high nCr could be assigned to the proneural subtype. Moreover, clustering of normalised glutamine and glutamate (nGlx) revealed two groups, one with high nGlx being attributed to the neural subtype, and one with low nGlx associated with the classical subtype. Hence, the metabolites nNAA, nCr, and nGlx correlate with a specific gene expression pattern reflecting the previously described subtypes of GBM. Moreover high nNAA was associated with better clinical prognosis, whereas patients with lower nNAA revealed a shorter progression-free survival (PFS). PMID:27350391

Dyslipidemia links obesity to early cerebral neurochemical alterations.

PubMed

Haley, Andreana P; Gonzales, Mitzi M; Tarumi, Takashi; Tanaka, Hirofumi

2013-10-01

To examine the role of hypertension, hyperglycemia, and dyslipidemia in potentially accounting for obesity-related brain vulnerability in the form of altered cerebral neurochemistry. Sixty-four adults, ages 40-60 years, underwent a health screen and proton magnetic resonance spectroscopy ((1) H MRS) of occipitoparietal gray matter to measure N-acetyl aspartate (NAA), choline (Cho), myo-inositol (mI), and glutamate (Glu) relative to creatine (Cr). The causal steps approach and nonparametric bootstrapping were utilized to assess if fasting glucose, mean arterial pressure or peripheral lipid/lipoprotein levels mediate the relationship between body mass index (BMI) and cerebral neurochemistry. Higher BMI was significantly related to higher mI/Cr, independent of age and sex. BMI was also significantly related to two of the proposed mediators, triglyceride, and HDL-cholesterol, which were also independently related to increased mI/Cr. Finally, the relationship between BMI and mI/Cr was significantly attenuated after inclusion of triglyceride and HDL-cholesterol into the model, one at a time, indicating statistical mediation. Higher triglyceride and lower HDL levels statistically account for the association between BMI and myo-inositol, pointing toward a potentially critical role for dyslipidemia in the development of cerebral neurochemical alterations in obesity. Copyright © 2013 The Obesity Society.

Global developmental delay in guanidionacetate methyltransferase deficiency: differences in formal testing and clinical observation.

PubMed

Verbruggen, Krijn T; Knijff, Wilma A; Soorani-Lunsing, Roelineke J; Sijens, Paul E; Verhoeven, Nanda M; Salomons, Gajja S; Goorhuis-Brouwer, Siena M; van Spronsen, Francjan J

2007-09-01

Guanidinoacetate N-methyltransferase (GAMT) deficiency is a defect in the biosynthesis of creatine (Cr). So far, reports have not focused on the description of developmental abilities in this disorder. Here, we present the result of formal testing of developmental abilities in a GAMT-deficient patient. Our patient, a 3-year-old boy with GAMT deficiency, presented clinically with a severe language production delay and nearly normal nonverbal development. Treatment with oral Cr supplementation led to partial restoration of the cerebral Cr concentration and a clinically remarkable acceleration of language production development. In contrast to clinical observation, formal testing showed a rather harmonic developmental delay before therapy and a general improvement, but no specific acceleration of language development after therapy. From our case, we conclude that in GAMT deficiency language delay is not always more prominent than delays in other developmental areas. The discrepancy between the clinical impression and formal testing underscores the importance of applying standardized tests in children with developmental delays. Screening for Cr deficiency by metabolite analysis of body fluids or proton magnetic resonance spectroscopy of the brain deficiency should be considered in any child with global developmental delay/mental retardation lacking clues for an alternative etiology.

1H-MRS in autism spectrum disorders: a systematic meta-analysis.

PubMed

Ipser, Jonathan C; Syal, Supriya; Bentley, Judy; Adnams, Colleen M; Steyn, Bennie; Stein, Dan J

2012-09-01

We conducted a systematic review and meta-analysis of proton magnetic resonance spectroscopy (1H-MRS) studies comparing autism spectrum disorder (ASD) patients with healthy controls, with the aim of profiling ASD-associated changes in the metabolites N-acetyl-aspartate (NAA) and Creatine (Cr). Meta-regression models of NAA and Cr levels were employed, using data from 20 eligible studies (N = 852), to investigate age-dependent differences in both global brain and region-specific metabolite levels, while controlling for measurement method (Cr-ratio versus absolute concentrations). Decreased NAA concentrations that were specific to children were found for whole-brain grey and white matter. In addition, a significant decrease in NAA was evident across age categories in the parietal cortex, the cerebellum, and the anterior cingulate cortex. Higher levels of Cr were observed for ASD adults than children in global grey matter, with specific increases for adults in the temporal lobe and decreased Cr in the occipital lobe in children. No differences were found for either NAA or Cr in the frontal lobes. These data provide some evidence that ASD is characterized by age-dependent fluctuations in metabolite levels across the whole brain and at the level of specific regions thought to underlie ASD-associated behavioural and affective deficits. Differences in Cr as a function of age and brain region suggests caution in the interpretation of Cr-based ratio measures of metabolites. Despite efforts to control for sources of heterogeneity, considerable variability in metabolite levels was observed in frontal and temporal regions, warranting further investigation.

Decreased frontal N-acetylaspartate levels in adolescents concurrently using both methamphetamine and marijuana.

PubMed

Sung, Young-Hoon; Carey, Paul D; Stein, Dan J; Ferrett, Helen L; Spottiswoode, Bruce S; Renshaw, Perry F; Yurgelun-Todd, Deborah A

2013-06-01

The potential neurochemical toxicity associated with methamphetamine (MA) or marijuana (MJ) use on the developing adolescent brain is unclear, particularly with regard to individuals with concomitant use of MA and MJ (MA+MJ). In this study, proton magnetic resonance spectroscopy (MRS) was utilized to measure in vivo brain N-acetylaspartate plus N-acetylaspartyl glutamate (tNAA, an indicator of intact neuronal integrity) levels. Three adolescent groups from Cape Town, South Africa completed MRS scans as well as clinical measures including a drug use history. Subjects included (1) nine MA (age=15.7±1.37), (2) eight MA+MJ (age=16.2±1.16) using adolescents and (3) ten healthy controls (age=16.8±0.62). Single voxel spectra were acquired from midfrontal gray matter using a point-resolved spectroscopy sequence (PRESS). The MRS data were post-processed in the fully automated approach for quantitation of metabolite ratios to phosphocreatine plus creatine (PCr+Cr). A significant reduction in frontal tNAA/PCr+Cr ratios was seen in the MA+MJ group compared to the healthy controls (p=0.01, by 7.2%) and to the MA group (p=0.04, by 6.9%). Significant relationships were also observed between decreased tNAA/PCr+Cr ratios and drug use history of MA or MJ (total cumulative lifetime dose, age of onset, and duration of MA and MJ exposure) only in the MA+MJ group (all p<0.05). These findings suggest that in adolescents, concomitant heavy MA+MJ use may contribute to altered brain metabolites in frontal gray matter. The significant associations between the abnormal tNAA/PCr+Cr ratios and the drug use history suggest that MA+MJ abuse may induce neurotoxicity in a dose-responsive manner in adolescent brain. Copyright © 2013 Elsevier B.V. All rights reserved.

The effects of creatine supplementation on thermoregulation and isokinetic muscular performance following acute (3-day) supplementation.

PubMed

Rosene, J M; Matthews, T D; Mcbride, K J; Galla, A; Haun, M; Mcdonald, K; Gagne, N; Lea, J; Kasen, J; Farias, C

2015-12-01

The purpose of this investigation was to determine the effects of 3 d of creatine supplementation on thermoregulation and isokinetic muscular performance. Fourteen males performed two exercise bouts following 3 d of creatine supplementation and placebo. Subjects exercised for 60 min at 60-65% of VO2max in the heat followed by isokinetic muscular performance at 60, 180, and 300°·s(-1). Dependent variables for pre- and postexercise included nude body weight, urine specific gravity, and serum creatinine levels. Total body water, extracellular water and intracellular water were measured pre-exercise. Core temperature was assessed every 5 min during exercise. Peak torque and Fatigue Index were used to assess isokinetic muscular performance. Core temperature increased during the run for both conditions. Total body water and extracellular water were significantly greater (P<0.05) following creatine supplementation. No significant difference (P>0.05) was found between conditions for intracellular water, nude body weight, urine specific gravity, and serum creatinine. Pre-exercise scores for urine specific gravity and serum creatinine were significantly less (P<0.05) versus post-exercise. No significant differences (P>0.05) were found in peak torque values or Fatigue Index between conditions for each velocity. A significant (P<0.05) overall velocity effect was found for both flexion and extension. As velocity increased, mean peak torque values decreased. Three d of creatine supplementation does not affect thermoregulation during submaximal exercise in the heat and is not enough to elicit an ergogenic effect for isokinetic muscle performance following endurance activity.

Mild and Short-Term Caloric Restriction Prevents Obesity-Induced Cardiomyopathy in Young Zucker Rats without Changing in Metabolites and Fatty Acids Cardiac Profile

PubMed Central

Ruiz-Hurtado, Gema; García-Prieto, Concha F.; Pulido-Olmo, Helena; Velasco-Martín, Juan P.; Villa-Valverde, Palmira; Fernández-Valle, María E.; Boscá, Lisardo; Fernández-Velasco, María; Regadera, Javier; Somoza, Beatriz; Fernández-Alfonso, María S.

2017-01-01

Caloric restriction (CR) ameliorates cardiac dysfunction associated with obesity. However, most of the studies have been performed under severe CR (30–65% caloric intake decrease) for several months or even years in aged animals. Here, we investigated whether mild (20% food intake reduction) and short-term (2-weeks) CR prevented the obese cardiomyopathy phenotype and improved the metabolic profile of young (14 weeks of age) genetically obese Zucker fa/fa rats. Heart weight (HW) and HW/tibia length ratio was significantly lower in fa/fa rats after 2 weeks of CR than in counterparts fed ad libitum. Invasive pressure measurements showed that systolic blood pressure, maximal rate of positive left ventricle (LV) pressure, LV systolic pressure and LV end-diastolic pressure were all significantly higher in obese fa/fa rats than in lean counterparts, which were prevented by CR. Magnetic resonance imaging revealed that the increase in LV end-systolic volume, stroke volume and LV wall thickness observed in fa/fa rats was significantly lower in animals on CR diet. Histological analysis also revealed that CR blocked the significant increase in cardiomyocyte diameter in obese fa/fa rats. High resolution magic angle spinning magnetic resonance spectroscopy analysis of the LV revealed a global decrease in metabolites such as taurine, creatine and phosphocreatine, glutamate, glutamine and glutathione, in obese fa/fa rats, whereas lactate concentration was increased. By contrast, fatty acid concentrations in LV tissue were significantly elevated in obese fa/fa rats. CR failed to restore the LV metabolomic profile of obese fa/fa rats. In conclusion, mild and short-term CR prevented an obesity-induced cardiomyopathy phenotype in young obese fa/fa rats independently of the cardiac metabolic profile. PMID:28203206

Physiological neuronal decline in healthy aging human brain - An in vivo study with MRI and short echo-time whole-brain (1)H MR spectroscopic imaging.

PubMed

Ding, Xiao-Qi; Maudsley, Andrew A; Sabati, Mohammad; Sheriff, Sulaiman; Schmitz, Birte; Schütze, Martin; Bronzlik, Paul; Kahl, Kai G; Lanfermann, Heinrich

2016-08-15

Knowledge of physiological aging in healthy human brain is increasingly important for neuroscientific research and clinical diagnosis. To investigate neuronal decline in normal aging brain eighty-one healthy subjects aged between 20 and 70years were studied with MRI and whole-brain (1)H MR spectroscopic imaging. Concentrations of brain metabolites N-acetyl-aspartate (NAA), choline (Cho), total creatine (tCr), myo-inositol (mI), and glutamine+glutamate (Glx) in ratios to internal water, and the fractional volumes of brain tissue were estimated simultaneously in eight cerebral lobes and in cerebellum. Results demonstrated that an age-related decrease in gray matter volume was the largest contribution to changes in brain volume. Both lobar NAA and the fractional volume of gray matter (FVGM) decreased with age in all cerebral lobes, indicating that the decreased NAA was predominantly associated with decreased gray matter volume and neuronal density or metabolic activity. In cerebral white matter Cho, tCr, and mI increased with age in association with increased fractional volume, showing altered cellular membrane turn-over, energy metabolism, and glial activity in human aging white matter. In cerebellum tCr increased while brain tissue volume decreased with age, showing difference to cerebral aging. The observed age-related metabolic and microstructural variations suggest that physiological neuronal decline in aging human brain is associated with a reduction of gray matter volume and neuronal density, in combination with cellular aging in white matter indicated by microstructural alterations and altered energy metabolism in the cerebellum. Copyright © 2016 Elsevier Inc. All rights reserved.

Localized 1H-NMR spectroscopy in patients with fibromyalgia: a controlled study of changes in cerebral glutamate/glutamine, inositol, choline, and N-acetylaspartate.

PubMed

Fayed, Nicolas; Garcia-Campayo, Javier; Magallón, Rosa; Andrés-Bergareche, Helena; Luciano, Juan V; Andres, Eva; Beltrán, Julián

2010-01-01

The purpose of this study was to investigate whether single-voxel (SV) proton magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI), and diffusion tensor imaging (DTI) detected differences between fibromyalgia (FM) patients and healthy controls. We also searched for correlations between neuroimaging abnormalities and neuropsychological variables. Ten patients with FM and 10 gender- and age-matched control subjects were studied. A neuropsychological examination, DWI, DTI, and proton MRS were performed on the brain areas known to be associated with pain processing. Compared with healthy controls, FM patients had significantly higher levels of glutamate + glutamine (Glx) (mean ± SD, 10.71 ± 0.50 arbitrary institutional units versus 9.89 ± 1.04; P = 0.049) and higher glutamate + glutamine/creatine (Glx/Cr) ratios (1.90 ± 0.12 versus 1.72 ± 0.23; P = 0.034) in the posterior gyrus. Myoinositol (Ins) levels of the right and left hippocampi were significantly lower in FM patients (4.49 ± 0.74 versus 5.17 ± 0.62; P = 0.008 and 4.91 ± 0.85 versus 6.09 ± 0.78; P = 0.004, respectively). In FM patients, decreased myoinositol/creatine (Ins/Cr) ratios were found in the left sensorimotor area (P = 0.05) and the left hippocampus (P = 0.002) and lower levels of choline (P = 0.019) and N-acetyl aspartate + N-acetyl aspartyl glutamate (NAA + NAG) (P = 0.034) in the left hippocampus. Significant correlations between depression, pain, and global function and the posterior gyrus Glx levels and Glx/Cr ratios were observed. Glx within the posterior gyrus could be a pathologic factor in FM. Hippocampal dysfunction may be partially responsible for the depressive symptoms of FM. Additional studies with larger samples are required to confirm these preliminary data.

Localized 1H-NMR spectroscopy in patients with fibromyalgia: a controlled study of changes in cerebral glutamate/glutamine, inositol, choline, and N-acetylaspartate

PubMed Central

2010-01-01

Introduction The purpose of this study was to investigate whether single-voxel (SV) proton magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI), and diffusion tensor imaging (DTI) detected differences between fibromyalgia (FM) patients and healthy controls. We also searched for correlations between neuroimaging abnormalities and neuropsychological variables. Methods Ten patients with FM and 10 gender- and age-matched control subjects were studied. A neuropsychological examination, DWI, DTI, and proton MRS were performed on the brain areas known to be associated with pain processing. Results Compared with healthy controls, FM patients had significantly higher levels of glutamate + glutamine (Glx) (mean ± SD, 10.71 ± 0.50 arbitrary institutional units versus 9.89 ± 1.04; P = 0.049) and higher glutamate + glutamine/creatine (Glx/Cr) ratios (1.90 ± 0.12 versus 1.72 ± 0.23; P = 0.034) in the posterior gyrus. Myoinositol (Ins) levels of the right and left hippocampi were significantly lower in FM patients (4.49 ± 0.74 versus 5.17 ± 0.62; P = 0.008 and 4.91 ± 0.85 versus 6.09 ± 0.78; P = 0.004, respectively). In FM patients, decreased myoinositol/creatine (Ins/Cr) ratios were found in the left sensorimotor area (P = 0.05) and the left hippocampus (P = 0.002) and lower levels of choline (P = 0.019) and N-acetyl aspartate + N-acetyl aspartyl glutamate (NAA + NAG) (P = 0.034) in the left hippocampus. Significant correlations between depression, pain, and global function and the posterior gyrus Glx levels and Glx/Cr ratios were observed. Conclusions Glx within the posterior gyrus could be a pathologic factor in FM. Hippocampal dysfunction may be partially responsible for the depressive symptoms of FM. Additional studies with larger samples are required to confirm these preliminary data. PMID:20609227

Metabolic injury in a variable rat model of post-status epilepticus.

PubMed

Pearce, Patrice S; Wu, Yijen; Rapuano, Amedeo; Kelly, Kevin M; de Lanerolle, Nihal; Pan, Jullie W

2016-12-01

In vivo studies of epilepsy typically use prolonged status epilepticus to generate recurrent seizures. However, reports on variable status duration have found discrete differences in injury after 40-50 min of seizures, suggesting a pathophysiologic sensitivity to seizure duration. In this report we take a multivariate cluster analysis to study a short duration status epilepticus model using in vivo 7T magnetic resonance spectroscopy (MRS) and histologic evaluation. The Hellier Dudek model was applied with 45 min of status epilepticus after which the animals were imaged twice, at 3 days and 3 weeks post-status epilepticus. Single voxel point resolved spectroscopy (PRESS) MRS was used to acquire data from the dentate gyrus and CA3 region of the hippocampus, assessing metabolite ratios to total creatine (tCr). In a subset of animals after the second imaging study, brains were analyzed histologically by Nissl staining. A hierarchical cluster analysis performed on the 3-day data from 21 kainate-treated animals (dentate gyrus voxel) segregated into two clusters, denoted by KM (more injured, n = 6) and KL (less injured, n = 15). Although there was no difference in kainate dosing or seizure count between them, the metabolic pattern of injury was different. The KM group displayed the largest significant changes in neuronal and glial parameters; the KL group displayed milder but significant changes. At 3 weeks, the KL group returned to normal compared to controls, whereas the KM group persisted with depressed N-acetyl aspartate (NAA)/tCr, glutamate/tCr, and increased inositol/tCr and glutamine/tCr. The classification was also consistent with subsequent histologic patterns at 3 weeks. Although a short status period might be expected to generate a continuous distribution of metabolic injury, these data show that the short Hellier Dudek model appears to generate two levels of injury. The changes seen in segregated groups persisted into 3 weeks, and can be interpreted according to neuronal and glial biomarkers consistent with histology results. © 2016 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.

Assessment of Anterior Cingulate Cortex (ACC) and Left Cerebellar Metabolism in Asperger's Syndrome with Proton Magnetic Resonance Spectroscopy (MRS).

PubMed

Goji, Aya; Ito, Hiromichi; Mori, Kenji; Harada, Masafumi; Hisaoka, Sonoka; Toda, Yoshihiro; Mori, Tatsuo; Abe, Yoko; Miyazaki, Masahito; Kagami, Shoji

2017-01-01

Proton magnetic resonance spectroscopy (1H MRS) is a noninvasive neuroimaging method to quantify biochemical metabolites in vivo and it can serve as a powerful tool to monitor neurobiochemical profiles in the brain. Asperger's syndrome (AS) is a type of autism spectrum disorder, which is characterized by impaired social skills and restrictive, repetitive patterns of interest and activities, while intellectual levels and language skills are relatively preserved. Despite clinical aspects have been well-characterized, neurometabolic profiling in the brain of AS remains to be clear. The present study used proton magnetic resonance spectroscopy (1H MRS) to investigate whether pediatric AS is associated with measurable neurometabolic abnormalities that can contribute new information on the neurobiological underpinnings of the disorder. Study participants consisted of 34 children with AS (2-12 years old; mean age 5.2 (±2.0); 28 boys) and 19 typically developed children (2-11 years old; mean age 5.6 (±2.6); 12 boys) who served as the normal control group. The 1H MRS data were obtained from two regions of interest: the anterior cingulate cortex (ACC) and left cerebellum. In the ACC, levels of N-acetylaspartate (NAA), total creatine (tCr), total choline-containing compounds (tCho) and myo-Inositol (mI) were significantly decreased in children with AS compared to controls. On the other hand, no significant group differences in any of the metabolites were found in the left cerebellum. Neither age nor sex accounted for the metabolic findings in the regions. The finding of decreased levels of NAA, tCr, tCho, and mI in the ACC but not in left cerebellar voxels in the AS, suggests a lower ACC neuronal density in the present AS cohort compared to controls.

[Total brain T2-hyperintense lesion-volume and the axonal damage in the normal-appearing white matter of brainstem in early lapsing-remitting multiple sclerosis].

PubMed

Pascual-Lozano, A M; Martínez-Bisbal, M C; Boscá-Blasco, I; Valero-Merino, C; Coret-Ferrer, F; Martí-Bonmatí, L; Martínez-Granados, B; Celda, B; Casanova-Estruch, B

To evaluate the relationship between the total brain T2-hyperintense lesion volume (TBT2LV) and the axonal damage in the normal-appearing white matter of brainstem measured by 1H-MRS in a group of early relapsing-remitting multiple sclerosis patients. 40 relapsing-remitting multiple sclerosis patients and ten sex- and age-matched healthy subjects were prospectively studied for two years. T2-weighted MR and 1H-MRS imaging were acquired at time of recruitment and at year two. The TBT2LV was calculated with a semiautomatic program; N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) resonances areas were integrated with jMRUI program and the ratios were calculated for four volume elements that represented the brainstem. At basal study we obtained an axonal loss (as a decrement of NAA/ Cho ratio) in the group of patients compared with controls (p = 0.017); this axonal loss increased at the second year of the follow-up for patients (NAA/Cho decrease, p = 0.004, and NAA/Cr decrease, p = 0.002) meanwhile control subjects had no significant metabolic changes. Higher lesion load was correlated with a poor clinical outcome, being the correlation between the basal TBT2LV and the Expanded Disability Status Scale at second year (r = 0.299; p = 0.05). Besides, axonal loss was not homogeneous for all multiple sclerosis patients, being stronger in the subgroup of patients with high basal TBT2LV (p = 0.043; ANOVA). Our data suggest that axonal damage is early in multiple sclerosis and higher in patients high basal TBT2LV, suggesting a possible relationship between these two phenomena.

[1-13C]Glucose entry in neuronal and astrocytic intermediary metabolism of aged rats. A study of the effects of nicergoline treatment by 13C NMR spectroscopy.

PubMed

Miccheli, Alfredo; Puccetti, Caterina; Capuani, Giorgio; Di Cocco, Maria Enrica; Giardino, Luciana; Calzà, Laura; Battaglia, Angelo; Battistin, Leontino; Conti, Filippo

2003-03-14

Age-related changes in glucose utilization through the TCA cycle were studied using [1-13C]glucose and 13C, 1H NMR spectroscopy on rat brain extracts. Significant increases in lactate levels, as well as in creatine/phosphocreatine ratios (Cr/PCr), and a decrease in N-acetyl-aspartate (NAA) and aspartate levels were observed in aged rat brains as compared to adult animals following glucose administration. The total amount of 13C from [1-13C]glucose incorporated in glutamate, glutamine, aspartate and GABA was significantly decreased in control aged rat brains as compared to adult brains. The results showed a decrease in oxidative glucose utilization of control aged rat brains. The long-term nicergoline treatment increased NAA and glutamate levels, and decreased the lactate levels as well as the Cr/PCr ratios in aged rat brains as compared to adult rats. The total amount of 13C incorporated in glutamate, glutamine, aspartate, NAA and GABA was increased by nicergoline treatment, showing an improvement in oxidative glucose metabolism in aged brains. A significant increase in pyruvate carboxylase/pyruvate dehydrogenase activity (PC/PDH) in the synthesis of glutamate in nicergoline-treated aged rats is consistent with an increase in the transport of glutamine from glia to neurons for conversion into glutamate. In adult rat brains, no effect of nicergoline on glutamate PC/PDH activity was observed, although an increase in PC/PDH activity in glutamine was, suggesting that nicergoline affects the glutamate/glutamine cycle between neurons and glia in different ways depending on the age of animals. These results provide new insights into the effects of nicergoline on the CNS.

The effects of pre versus post workout supplementation of creatine monohydrate on body composition and strength

PubMed Central

2013-01-01

Background Chronic supplementation with creatine monohydrate has been shown to promote increases in total intramuscular creatine, phosphocreatine, skeletal muscle mass, lean body mass and muscle fiber size. Furthermore, there is robust evidence that muscular strength and power will also increase after supplementing with creatine. However, it is not known if the timing of creatine supplementation will affect the adaptive response to exercise. Thus, the purpose of this investigation was to determine the difference between pre versus post exercise supplementation of creatine on measures of body composition and strength. Methods Nineteen healthy recreational male bodybuilders (mean ± SD; age: 23.1 ± 2.9; height: 166.0 ± 23.2 cm; weight: 80.18 ± 10.43 kg) participated in this study. Subjects were randomly assigned to one of the following groups: PRE-SUPP or POST-SUPP workout supplementation of creatine (5 grams). The PRE-SUPP group consumed 5 grams of creatine immediately before exercise. On the other hand, the POST-SUPP group consumed 5 grams immediately after exercise. Subjects trained on average five days per week for four weeks. Subjects consumed the supplement on the two non-training days at their convenience. Subjects performed a periodized, split-routine, bodybuilding workout five days per week (Chest-shoulders-triceps; Back-biceps, Legs, etc.). Body composition (Bod Pod®) and 1-RM bench press (BP) were determined. Diet logs were collected and analyzed (one random day per week; four total days analyzed). Results 2x2 ANOVA results - There was a significant time effect for fat-free mass (FFM) (F = 19.9; p = 0.001) and BP (F = 18.9; p < 0.001), however, fat mass (FM) and body weight did not reach significance. While there were trends, no significant interactions were found. However, using magnitude-based inference, supplementation with creatine post workout is possibly more beneficial in comparison to pre workout supplementation with regards to FFM, FM and 1-RM BP. The mean change in the PRE-SUPP and POST-SUPP groups for body weight (BW kg), FFM (kg), FM (kg) and 1-RM bench press (kg) were as follows, respectively: Mean ± SD; BW: 0.4 ± 2.2 vs. 0.8 ± 0.9; FFM: 0.9 ± 1.8 vs. 2.0 ± 1.2; FM: -0.1 ± 2.0 vs. −1.2 ± 1.6; Bench Press 1-RM: 6.6 ± 8.2 vs. 7.6 ± 6.1. Qualitative inference represents the likelihood that the true value will have the observed magnitude. Furthermore, there were no differences in caloric or macronutrient intake between the groups. Conclusions Creatine supplementation plus resistance exercise increases fat-free mass and strength. Based on the magnitude inferences it appears that consuming creatine immediately post-workout is superior to pre-workout vis a vis body composition and strength. PMID:23919405

The effects of pre versus post workout supplementation of creatine monohydrate on body composition and strength.

PubMed

Antonio, Jose; Ciccone, Victoria

2013-01-01

Chronic supplementation with creatine monohydrate has been shown to promote increases in total intramuscular creatine, phosphocreatine, skeletal muscle mass, lean body mass and muscle fiber size. Furthermore, there is robust evidence that muscular strength and power will also increase after supplementing with creatine. However, it is not known if the timing of creatine supplementation will affect the adaptive response to exercise. Thus, the purpose of this investigation was to determine the difference between pre versus post exercise supplementation of creatine on measures of body composition and strength. Nineteen healthy recreational male bodybuilders (mean ± SD; age: 23.1 ± 2.9; height: 166.0 ± 23.2 cm; weight: 80.18 ± 10.43 kg) participated in this study. Subjects were randomly assigned to one of the following groups: PRE-SUPP or POST-SUPP workout supplementation of creatine (5 grams). The PRE-SUPP group consumed 5 grams of creatine immediately before exercise. On the other hand, the POST-SUPP group consumed 5 grams immediately after exercise. Subjects trained on average five days per week for four weeks. Subjects consumed the supplement on the two non-training days at their convenience. Subjects performed a periodized, split-routine, bodybuilding workout five days per week (Chest-shoulders-triceps; Back-biceps, Legs, etc.). Body composition (Bod Pod®) and 1-RM bench press (BP) were determined. Diet logs were collected and analyzed (one random day per week; four total days analyzed). 2x2 ANOVA results - There was a significant time effect for fat-free mass (FFM) (F = 19.9; p = 0.001) and BP (F = 18.9; p < 0.001), however, fat mass (FM) and body weight did not reach significance. While there were trends, no significant interactions were found. However, using magnitude-based inference, supplementation with creatine post workout is possibly more beneficial in comparison to pre workout supplementation with regards to FFM, FM and 1-RM BP. The mean change in the PRE-SUPP and POST-SUPP groups for body weight (BW kg), FFM (kg), FM (kg) and 1-RM bench press (kg) were as follows, respectively: Mean ± SD; BW: 0.4 ± 2.2 vs. 0.8 ± 0.9; FFM: 0.9 ± 1.8 vs. 2.0 ± 1.2; FM: -0.1 ± 2.0 vs. -1.2 ± 1.6; Bench Press 1-RM: 6.6 ± 8.2 vs. 7.6 ± 6.1. Qualitative inference represents the likelihood that the true value will have the observed magnitude. Furthermore, there were no differences in caloric or macronutrient intake between the groups. Creatine supplementation plus resistance exercise increases fat-free mass and strength. Based on the magnitude inferences it appears that consuming creatine immediately post-workout is superior to pre-workout vis a vis body composition and strength.

Prefrontal N-acetylaspartate is strongly associated with memory performance in (abstinent) ecstasy users: preliminary report.

PubMed

Reneman, L; Majoie, C B; Schmand, B; van den Brink, W; den Heeten, G J

2001-10-01

3,4-methylenedioxymethamphetamine (MDMA or "Ecstasy") is known to damage brain serotonin neurons in animals and possibly humans. Because serotonergic damage may adversely affect memory, we compared verbal memory function between MDMA users and MDMA-naïve control subjects and evaluated the relationship between verbal memory function and neuronal dysfunction in the MDMA users. An auditory verbal memory task (Rey Auditory Verbal Learning Test) was used to study eight abstinent MDMA users and seven control subjects. In addition 1H-MRS was used in different brain regions of all MDMA users to measure N-acetylaspartate/creatine (NAA/Cr) ratios, a marker for neuronal viability. The MDMA users recalled significantly fewer words than control subjects on delayed (p =.03) but not immediate recall (p =.08). In MDMA users, delayed memory function was strongly associated with NAA/Cr only in the prefrontal cortex (R(2) =.76, p =.01). Greater decrements in memory function predicted lower NAA/Cr levels-and by inference greater neuronal dysfunction-in the prefrontal cortex of MDMA users.

Metabolite alterations in basal ganglia associated with methamphetamine-related psychiatric symptoms. A proton MRS study.

PubMed

Sekine, Yoshimoto; Minabe, Yoshio; Kawai, Masayoshi; Suzuki, Katsuaki; Iyo, Masaomi; Isoda, Haruo; Sakahara, Harumi; Ashby, Charles R; Takei, Nori; Mori, Norio

2002-09-01

Following the chronic use of methamphetamine, some individuals experience psychosis and anxiety. One reason may be the persistence of metabolite abnormalities in the brain of currently abstinent former methamphetamine users. In this study, N-acetylaspartate (NAA), creatine plus phosphocreatine (Cr+PCr), and choline-containing compound (Cho) levels were measured in the left and right basal ganglia using proton magnetic resonance spectroscopy (MRS) in 13 abstinent methamphetamine users and 11 healthy comparison subjects with no history of illicit drug use. The methamphetamine users showed a significantly reduced Cr+PCr/Cho ratio in the bilateral basal ganglia compared with the healthy comparison subjects. Furthermore, the reduction in the Cr+PCr/Cho ratio was significantly correlated with the duration of methamphetamine use and with the severity of residual psychiatric symptoms. NAA/Cho ratios in the bilateral basal ganglia did not significantly differ between methamphetamine users and comparison subjects. These findings suggest that protracted use of methamphetamine may cause metabolite alterations in the basal ganglia. Furthermore, residual psychiatric symptoms may be attributable to the metabolite alterations in the basal ganglia.

[Effect of anshen jielu recipe in intervening cerebral metabolism in rats with generalized anxiety disorder using magnetic resonance spectroscopy].

PubMed

Tang, Qi-sheng; Li, Ning; Luo, Bin

2011-01-01

To study the metabolic change in brain of rats with generalized anxiety disorder (GAD) and the intervention effect with Anshen Jielu Recipe (AJR) on it. Eight rats selected from 32 Wistar rats as normal group, the others were established as GAD model by using uncertainty empty water bottles method. Then the GAD rats were randomly divided into the model group (saline, by gastrogavage), the control group [buspirone hydrochloride, 2.0 mg/(kg x d), by gastrogavage], the treatment group [AJR, 12.5 g/(kg x d), by gastrogavage], 8 in each group, all were treated for 7 days. The concentration of cerebral metabolites, including N-acetyl aspartate (NAA), choline (Cho), creatine (Cr) and glutamate (Glu), in bilateral prefrontal cortex and hippocampus were measured using high-field strong super-conductivity (7.0T) animal MRI; and the ratio of NAA/Cr, Cho/Cr and Glu/Cr were calculated. The effect of AJR intervention was evaluated by changes of MRI before and after rats being treated with AJR for 7 days. Rats with GAD showed lowered ratios of NAA/Cr and Cho/Cr, and elevated Glu/Cr ratio in the right prefrontal cortex than those in normal rats. After AJR intervention, the abnormal changes in the three indices were restored to certain extents. AJR has apparent antianxiety effect in rats with GAD, with the effect initiation faster than that in the control group. Its mechanism is probably correlated with the regulation of abnormal metabolism in the brain.

Magnetic resonance spectroscopy findings in photosensitive idiopathic generalized epilepsy.

PubMed

Aydin-Ozemir, Zeynep; Terzibasioglu, Ege; Altindag, Ebru; Sencer, Serra; Baykan, Betul

2010-01-01

Studies investigating the pathophysiology of epileptic photosensitivity indicate variable involvement of particular brain regions. Our aim was to identify metabolic differences between photosensitive idiopathic generalized epilepsy (IGE) patients and nonphotosensitive IGE patients and normal healthy subjects by using Magnetic Resonance Spectroscopy (MRS). Fourteen patients diagnosed with photosensitive IGE were investigated. The control groups consisted of 14 age- and sex-matched healthy volunteers and 14 IGE patients without photosensitivity. MRS measurements of N-acetylaspartate (NAA), choline-containing compounds (Cho), creatine (Cr) were performed in the frontal and occipital cortex and the thalamus bilaterally using a stimulated echo acquisition mode (STEAM) technique with a voxel size of 20 x 20 x 20 mm. The values of the patients with IGE were compared with those of the normal controls and within subgroups according to the clinical variables by appropriate statistical tests. Photosensitive IGE patients showed significantly decreased concentrations of NAA in the right frontal lobe and left thalamus, decreased NAA/Cr ratio in left thalamus and significantly increased concentrations of Cho/Cr ratio in the right frontal lobe and NAA/Cr in the left occipital lobe when compared to normal controls. Furthermore, left occipital NAA concentration increased and left thalamus NAA/Cr ratios were decreased from the IGE patients without photosensitivity but without reaching statistical significance. Our results support previous MR studies suggesting an asymmetrical neuronal dysfunction in favor of the dominant occipital cortex and thalamus in photosensitive IGE patients.

Neural metabolite changes in corpus striatum after rat multipotent mesenchymal stem cells transplanted in hemiparkinsonian rats by magnetic resonance spectroscopy.

PubMed

Fu, Wenyu; Zheng, Zhijuan; Zhuang, Wenxin; Chen, Dandan; Wang, Xiaocui; Sun, Xihe; Wang, Xin

2013-12-01

To investigate the biochemical changes in striatum after rat bone marrow mesenchymal stem cells (MSCs) were transplanted into hemiparkinsonian rats and to further confirm the therapeutic effects of rat MSCs for Parkinson's disease (PD). 5-bromo-2-deoxyuridine (BrdU)-labeled MSCs were transplanted into the corpus striatum of the 6-hydroxydopamine (6-OHDA)-injected side of six PD model rats. Before and 8 weeks after MSC transplantation, ethological changes in PD rats were assessed. The expression of tyrosine hydroxylase (TH) in substantia nigra (SN) and striatum were measured using immunohistochemical methods. The differentiation of MSCs was detected by double immunofluorescence techniques. The concentrations of neural metabolites of N-acetylaspartate (NAA), choline (Cho) and creatine (Cr) were measured by ¹H-magnetic resonance spectroscopy (MRS). Relative concentrations of NAA/Cr and Cho/Cr were calculated. The behavior of PD rats in rotarod tests improved, and there were statistical differences in TH-positive cells in SN and TH-positive terminals in striatum after the transplantation of BrdU-labeled MSCs. Transplanted MSCs differentiated into MAP-2-positive neurons. Especially compared with pre-MSC transplantation, the neural metabolite NAA/Cr ratio of the 6-OHDA-injected side of the striatum increased (P < 0.05) and the Cho/Cr ratio decreased (P < 0.05). MSCs transplantation apparently improves neuronal function in the striatum of PD rats.

Tumor Volume and Metabolism of Prostate Cancer Determined by Proton Magnetic Resonance Spectroscopic Imaging at 3T Without Endorectal Coil Reveal Potential Clinical Implications in the Context of Radiation Oncology;Prostate cancer; Magnetic resonance spectroscopic imaging; Radiation oncology; Tumor volume; Biomarkers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crehange, Gilles, E-mail: gcrehange@cgfl.fr; Parfait, Sebastien; Liegard, Melanie

2011-07-15

Purpose: To determine whether a relationship exists between the tumor volume (TV) or relative choline content determined using magnetic resonance spectroscopy imaging (MRSI) at 3T and the clinical prognostic parameters for patients with localized prostate cancer (PCa). Methods and Materials: A total of 72 men (mean age, 67.8 {+-} 6.2 years) were stratified as having low-risk (n = 26), intermediate-risk (n = 24), or high-risk (n = 22) PCa. MRSI was performed at 3T using a phased-array coil. Spectra are expressed as the total choline/citrate, total choline plus creatine/citrate, and total choline plus polyamines plus creatine/citrate ratios. The mean ratiomore » of the most pathologic voxels and the MRSI-based TV were also determined. Results: The mean values of the total choline/citrate, total choline plus creatine/citrate, and total choline plus polyamine plus creatine/citrate ratios were greater for Stage T2b or greater tumors vs. Stage T2a or less tumors: 7.53 {+-} 13.60 vs. 2.31 {+-} 5.65 (p = .018), 8.98 {+-} 14.58 vs. 2.56 {+-} 5.70 (p = .016), and 10.32 {+-} 15.47 vs. 3.55 {+-} 6.16 (p = .014), respectively. The mean MRSI-based TV for Stage T2b or greater and Stage T2a or less tumors was significantly different (2.23 {+-} 2.62 cm{sup 3} vs. 1.26 {+-} 2.06 cm{sup 3}, respectively; p = .030). This TV correlated with increased prostate-specific antigen levels (odds ratio, 1.293; p = .012). Patients with high-risk PCa had a larger TV than did the patients with intermediate-risk PCa. A similar result was found for the intermediate-risk group compared with the low-risk group (odds ratio, 1.225; p = .041). Conclusion: Biomarkers expressing the relative choline content and TV were significant parameters for the localization of PCa and could be helpful for determining the prognosis more accurately.« less

Fast quantification of proton magnetic resonance spectroscopic imaging with artificial neural networks

NASA Astrophysics Data System (ADS)

Bhat, Himanshu; Sajja, Balasrinivasa Rao; Narayana, Ponnada A.

2006-11-01

Accurate quantification of the MRSI-observed regional distribution of metabolites involves relatively long processing times. This is particularly true in dealing with large amount of data that is typically acquired in multi-center clinical studies. To significantly shorten the processing time, an artificial neural network (ANN)-based approach was explored for quantifying the phase corrected (as opposed to magnitude) spectra. Specifically, in these studies radial basis function neural network (RBFNN) was used. This method was tested on simulated and normal human brain data acquired at 3T. The N-acetyl aspartate (NAA)/creatine (Cr), choline (Cho)/Cr, glutamate + glutamine (Glx)/Cr, and myo-inositol (mI)/Cr ratios in normal subjects were compared with the line fitting (LF) technique and jMRUI-AMARES analysis, and published values. The average NAA/Cr, Cho/Cr, Glx/Cr and mI/Cr ratios in normal controls were found to be 1.58 ± 0.13, 0.9 ± 0.08, 0.7 ± 0.17 and 0.42 ± 0.07, respectively. The corresponding ratios using the LF and jMRUI-AMARES methods were 1.6 ± 0.11, 0.95 ± 0.08, 0.78 ± 0.18, 0.49 ± 0.1 and 1.61 ± 0.15, 0.78 ± 0.07, 0.61 ± 0.18, 0.42 ± 0.13, respectively. These results agree with those published in literature. Bland-Altman analysis indicated an excellent agreement and minimal bias between the results obtained with RBFNN and other methods. The computational time for the current method was 15 s compared to approximately 10 min for the LF-based analysis.

Role of diffusion tensor imaging or magnetic resonance spectroscopy in the diagnosis and disability assessment of amyotrophic lateral sclerosis.

PubMed

Liu, Chanchan; Jiang, Rifeng; Yi, Xiyan; Zhu, Wenzhen; Bu, Bitao

2015-01-15

To compare the results of magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) in amyotrophic lateral sclerosis (ALS) patients. Nineteen ALS patients and thirteen age-matched healthy controls underwent MRS and DTI between October 2013 and July 2014. Fractional anisotropy (FA), apparent diffusion coefficient (ADC), N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) were collected as the quantitative results of the imaging study. The ALS functional rating scale-revised (ALSFRS-R) and disease progression rate were evaluated to assess patients' disability. The imaging study results were compared between ALS patients and healthy controls. The relationship between disability assessment and imaging study results was analyzed. NAA/Cr in the motor cortex and FA in the corticospinal tract (CST) of both sides were significantly lower in patients than controls. There was no significant difference between the two groups in Cho/Cr, tract length, tract volume, ADC or NAA. No relationship was found between ALSFRS-R and FA (r=0.243, p=0.316) in the right CST; NAA (r=0.095, p=0.699) or NAA/Cr (r=0.172, p=0.481) in the left motor cortex; or NAA (r=0.320, p=0.182) or NAA/Cr (r=0.193, p=0.492) in the right motor cortex. There was no relationship between the disease progression rate and FA, NAA, or NAA/Cr on either side. NAA/Cr and FA can help diagnose ALS. Regional brain NAA/Cr and FA values could not assess the ALSFRS-R or disease progression rate. Copyright © 2014 Elsevier B.V. All rights reserved.

Early Alzheimer's Disease Neuropathology Detected by Proton MR Spectroscopy

PubMed Central

Murray, Melissa E.; Przybelski, Scott A.; Lesnick, Timothy G.; Liesinger, Amanda M.; Spychalla, Anthony; Zhang, Bing; Gunter, Jeffrey L.; Parisi, Joseph E.; Boeve, Bradley F.; Knopman, David S.; Petersen, Ronald C.; Jack, Clifford R.; Dickson, Dennis W.

2014-01-01

Proton magnetic resonance spectroscopy (1H-MRS) is sensitive to early neurodegenerative processes associated with Alzheimer's disease (AD). Although 1H-MRS metabolite ratios of N-acetyl aspartate (NAA)/creatine (Cr), NAA/myoinositol (mI), and mI/Cr measured in the posterior cingulate gyrus reveal evidence of disease progression in AD, pathologic underpinnings of the 1H-MRS metabolite changes in AD are unknown. Pathologically diagnosed human cases ranging from no likelihood to high likelihood AD (n = 41, 16 females and 25 males) who underwent antemortem 1H-MRS of the posterior cingulate gyrus at 3 tesla were included in this study. Immunohistochemical evaluation was performed on the posterior cingulate gyrus using antibodies to synaptic vesicles, hyperphosphorylated tau (pTau), neurofibrillary tangle conformational-epitope (cNFT), amyloid-β, astrocytes, and microglia. The slides were digitally analyzed using Aperio software, which allows neuropathologic quantification in the posterior cingulate gray matter. MRS and pathology associations were adjusted for time from scan to death. Significant associations across AD and control subjects were found between reduced synaptic immunoreactivity and both NAA/Cr and NAA/mI in the posterior cingulate gyrus. Higher pTau burden was associated with lower NAA/Cr and NAA/mI. Higher amyloid-β burden was associated with elevated mI/Cr and lower NAA/mI ratios, but not with NAA/Cr. 1H-MRS metabolite levels reveal early neurodegenerative changes associated with AD pathology. Our findings support the hypothesis that a decrease in NAA/Cr is associated with loss of synapses and early pTau pathology, but not with amyloid-β or later accumulation of cNFT pathology in the posterior cingulate gyrus. In addition, elevation of mI/Cr is associated with the occurrence of amyloid-β plaques in AD. PMID:25471565

Proton magnetic resonance spectroscopic findings of cerebral fat embolism induced by triolein emulsion in cats.

PubMed

Baik, S K; Kim, Y-W; Kim, H J; Lee, J W; Cho, B M; Kim, D-H; Choi, S H; Lee, S H; Chang, K H

2008-12-01

In experimental studies, embolization of the cerebral hemisphere with triolein emulsion has revealed reversible magnetic resonance imaging (MRI) findings in the subacute stage. To investigate the changes in the major metabolites, by proton magnetic resonance spectroscopy (MRS), in a cerebral fat embolism induced by a triolein emulsion. The internal carotid arteries of 19 cats were injected with a triolein emulsion, and multivoxel MRS was performed 30 min, 1 day, and 7 days later. In the control group, six cats were injected with normal saline. The MR spectra were evaluated for N-acetyl aspartate (NAA), creatine (Cr), and choline (Cho), along with the presence of lipid and lactate. Semiquantitative analyses of NAA/Cr, Cho/Cr, NAA/Cho, and lipid/Cr ratios compared the median values of the ipsilateral metabolite ratios with those of the contralateral side and in the control group for each point in time. The NAA/Cr, Cho/Cr, and NAA/Cho ratios in the ipsilateral cerebral hemisphere of the embolized group after 30 min, 1 day, and 7days were not significantly different from the contralateral hemisphere of the embolized and control groups (P>0.05). The lipid/Cr ratio in the ipsilateral cerebral hemisphere of the embolized group was significantly higher when compared with the control group (P=0.012 at 30 min, P=0.001 on day 1, and P=0.018 on day 7). Cerebral fat embolism induced by a triolein emulsion resulted in no significant change in the major metabolites of the brain in the acute stage, except for an elevated lipid/Cr ratio, which suggests the absence of any significant hypoxic-ischemic changes in the lesions embolized using a fat emulsion.

Creatine and creatine forms intended for sports nutrition.

PubMed

Andres, Susanne; Ziegenhagen, Rainer; Trefflich, Iris; Pevny, Sophie; Schultrich, Katharina; Braun, Hans; Schänzer, Wilhelm; Hirsch-Ernst, Karen Ildico; Schäfer, Bernd; Lampen, Alfonso

2017-06-01

Creatine is a popular ergogenic supplement in sports nutrition. Yet, supplementation of creatine occasionally caused adverse effects such as gastrointestinal complaints, muscle cramps and an increase in body weight. Creatine monohydrate has already been evaluated by different competent authorities and several have come to the conclusion that a daily intake of 3 g creatine per person is unlikely to pose safety concerns, focusing on healthy adults with exclusion of pregnant and breastfeeding women. Possible vulnerable subgroups were also discussed in relation to the safety of creatine. The present review provides an up-to-date overview of the relevant information with special focus on human studies regarding the safety of creatine monohydrate and other marketed creatine forms, in particular creatine pyruvate, creatine citrate, creatine malate, creatine taurinate, creatine phosphate, creatine orotate, creatine ethyl ester, creatine pyroglutamate, creatine gluconate, and magnesium creatine chelate. Limited data are available with regard to the safety of the latter creatine forms. Considering an acceptable creatine intake of 3 g per day, most of the evaluated creatine forms are unlikely to pose safety concerns, however some safety concerns regarding a supplementary intake of creatine orotate, creatine phosphate, and magnesium creatine chelate are discussed here. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effects of six weeks of beta-hydroxy-beta-methylbutyrate (HMB) and HMB/creatine supplementation on strength, power, and anthropometry of highly trained athletes.

PubMed

O'Connor, Donna M; Crowe, Melissa J

2007-05-01

This study investigated the effects of 6 weeks of dietary supplementation of beta-hydroxy-beta-methylbutyrate (HMB) and HMB combined with creatine monohydrate (HMBCr) on the muscular strength and endurance, leg power, and anthropometry of elite male rugby league players. The subjects were divided into a control group (n = 8), a HMB group (n = 11; 3 g.d(-1)) or a HMBCr group (n = 11; 12 g.d(-1) with 3 g HMB, 3 g Cr, 6 g carbohydrates). Three repetition maximum lifts on bench press, deadlifts, prone row, and shoulder press, maximum chin-up repetitions, 10-second maximal cycle test, body mass, girths, and sum of skinfolds were assessed pre- and postsupplementation. Statistical analysis revealed no effect of HMB or HMBCr on any parameter compared with presupplementation measures or the control group. HMB and HMBCr were concluded to have no ergogenic effect on muscular strength and endurance, leg power, or anthropometry when taken orally by highly trained male athletes over 6 weeks.

Effects of hyperglycemia and effects of ketosis on cerebral perfusion, cerebral water distribution, and cerebral metabolism.

PubMed

Glaser, Nicole; Ngo, Catherine; Anderson, Steven; Yuen, Natalie; Trifu, Alexandra; O'Donnell, Martha

2012-07-01

Diabetic ketoacidosis (DKA) may cause brain injuries in children. The mechanisms responsible are difficult to elucidate because DKA involves multiple metabolic derangements. We aimed to determine the independent effects of hyperglycemia and ketosis on cerebral metabolism, blood flow, and water distribution. We used magnetic resonance spectroscopy to measure ratios of cerebral metabolites (ATP to inorganic phosphate [Pi], phosphocreatine [PCr] to Pi, N-acetyl aspartate [NAA] to creatine [Cr], and lactate to Cr) and diffusion-weighted imaging and perfusion-weighted imaging to assess cerebral water distribution (apparent diffusion coefficient [ADC] values) and cerebral blood flow (CBF) in three groups of juvenile rats (hyperglycemic, ketotic, and normal control). ATP-to-Pi ratio was reduced in both hyperglycemic and ketotic rats in comparison with controls. PCr-to-Pi ratio was reduced in the ketotic group, and there was a trend toward reduction in the hyperglycemic group. No significant differences were observed in NAA-to-Cr or lactate-to-Cr ratio. Cortical ADC was reduced in both groups (indicating brain cell swelling). Cortical CBF was also reduced in both groups. We conclude that both hyperglycemia and ketosis independently cause reductions in cerebral high-energy phosphates, CBF, and cortical ADC values. These effects may play a role in the pathophysiology of DKA-related brain injury.

Main Effects of Diagnoses, Brain Regions, and their Interaction Effects for Cerebral Metabolites in Bipolar and Unipolar Depressive Disorders

NASA Astrophysics Data System (ADS)

Tan, Hai-Zhu; Li, Hui; Liu, Chen-Feng; Guan, Ji-Tian; Guo, Xiao-Bo; Wen, Can-Hong; Ou, Shao-Min; Zhang, Yin-Nan; Zhang, Jie; Xu, Chong-Tao; Shen, Zhi-Wei; Wu, Ren-Hua; Wang, Xue-Qin

2016-11-01

Previous studies suggested patients with bipolar depressive disorder (BDd) or unipolar depressive disorder (UDd) have cerebral metabolites abnormalities. These abnormalities may stem from multiple sub-regions of gray matter in brain regions. Thirteen BDd patients, 20 UDd patients and 20 healthy controls (HC) were enrolled to investigate these abnormalities. Absolute concentrations of 5 cerebral metabolites (glutamate-glutamine (Glx), N-acetylaspartate (NAA), choline (Cho), myo-inositol (mI), creatine (Cr), parietal cortex (PC)) were measured from 4 subregions (the medial frontal cortex (mPFC), anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and parietal cortex (PC)) of gray matter. Main and interaction effects of cerebral metabolites across subregions of gray matter were evaluated. For example, the Glx was significantly higher in BDd compared with UDd, and so on. As the interaction analyses showed, some interaction effects existed. The concentrations of BDds’ Glx, Cho, Cr in the ACC and HCs’ mI and Cr in the PC were higher than that of other interaction effects. In addition, the concentrations of BDds’ Glx and Cr in the PC and HCs’ mI in the ACC were statistically significant lower than that of other interaction effects. These findings point to region-related abnormalities of cerebral metabolites across subjects with BDd and UDd.

Dyslipidemia links obesity to early cerebral neurochemical alterations

PubMed Central

Haley, Andreana P.; Gonzales, Mitzi M.; Tarumi, Takashi; Tanaka, Hirofumi

2013-01-01

Objective To examine the role of hypertension, hyperglycemia and dyslipidemia in potentially accounting for obesity-related brain vulnerability in the form of altered cerebral neurochemistry. Design and Methods Sixty-four adults, ages 40 to 60 years, underwent a health screen and proton magnetic resonance spectroscopy (1H MRS) of occipitoparietal grey matter to measure N-acetyl aspartate (NAA), choline (Cho), myo-inositol (mI) and glutamate (Glu) relative to creatine (Cr). The causal steps approach and non-parametric bootstrapping were utilized to assess if fasting glucose, mean arterial pressure or peripheral lipid/lipoprotein levels mediate the relationship between body mass index (BMI) and cerebral neurochemistry. Results Higher BMI was significantly related to higher mI/Cr, independent of age and sex. BMI was also significantly related to two of the proposed mediators, triglyceride and HDL-cholesterol, which were also independently related to increased mI/Cr. Finally, the relationship between BMI and mI/Cr, was significantly attenuated after inclusion of triglyceride and HDL-cholesterol into the model, one at a time, indicating statistical mediation. Conclusions Higher triglyceride and lower HDL levels statistically account for the association between BMI and myo-inositol, pointing towards a potentially critical role for dyslipidemia in the development of cerebral neurochemical alterations in obesity. PMID:23512296

Main Effects of Diagnoses, Brain Regions, and their Interaction Effects for Cerebral Metabolites in Bipolar and Unipolar Depressive Disorders.

PubMed

Tan, Hai-Zhu; Li, Hui; Liu, Chen-Feng; Guan, Ji-Tian; Guo, Xiao-Bo; Wen, Can-Hong; Ou, Shao-Min; Zhang, Yin-Nan; Zhang, Jie; Xu, Chong-Tao; Shen, Zhi-Wei; Wu, Ren-Hua; Wang, Xue-Qin

2016-11-21

Previous studies suggested patients with bipolar depressive disorder (BDd) or unipolar depressive disorder (UDd) have cerebral metabolites abnormalities. These abnormalities may stem from multiple sub-regions of gray matter in brain regions. Thirteen BDd patients, 20 UDd patients and 20 healthy controls (HC) were enrolled to investigate these abnormalities. Absolute concentrations of 5 cerebral metabolites (glutamate-glutamine (Glx), N-acetylaspartate (NAA), choline (Cho), myo-inositol (mI), creatine (Cr), parietal cortex (PC)) were measured from 4 subregions (the medial frontal cortex (mPFC), anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and parietal cortex (PC)) of gray matter. Main and interaction effects of cerebral metabolites across subregions of gray matter were evaluated. For example, the Glx was significantly higher in BDd compared with UDd, and so on. As the interaction analyses showed, some interaction effects existed. The concentrations of BDds' Glx, Cho, Cr in the ACC and HCs' mI and Cr in the PC were higher than that of other interaction effects. In addition, the concentrations of BDds' Glx and Cr in the PC and HCs' mI in the ACC were statistically significant lower than that of other interaction effects. These findings point to region-related abnormalities of cerebral metabolites across subjects with BDd and UDd.

Cerebral white matter blood flow and energy metabolism in multiple sclerosis.

PubMed

Steen, Christel; D'haeseleer, Miguel; Hoogduin, Johannes M; Fierens, Yves; Cambron, Melissa; Mostert, Jop P; Heersema, Dorothea J; Koch, Marcus W; De Keyser, Jacques

2013-09-01

Cerebral blood flow (CBF) is reduced in normal-appearing white matter (NAWM) of subjects with multiple sclerosis (MS), but the underlying mechanism is unknown. The objective of this article is to assess the relationship between reduced NAWM CBF and both axonal mitochondrial metabolism and astrocytic phosphocreatine (PCr) metabolism. Ten healthy controls and 25 MS subjects were studied with 3 Tesla magnetic resonance imaging. CBF was measured using pseudo-continuous arterial spin labeling. N-acetylaspartate/creatine (NAA/Cr) ratios (axonal mitochondrial metabolism) were obtained using (1)H-MR spectroscopy and PCr/β-ATP ratios using (31)P-MR spectroscopy. In centrum semiovale NAWM, we assessed correlations between CBF and both NAA/Cr and PCr/β-ATP ratios. Subjects with MS had a widespread reduction in CBF of NAWM (centrum semiovale, periventricular, frontal and occipital), and gray matter (frontoparietal cortex and thalamus). Compared to controls, NAA/Cr in NAWM of the centrum semiovale of MS subjects was decreased, whereas PCr/β-ATP was increased. We found no correlations between CBF and PCr/β-ATP. CBF and NAA/Cr correlated in controls (p = 0.02), but not in MS subjects (p = 0.68). Our results suggest that in MS patients there is no relationship between reduced CBF in NAWM and impaired axonal mitochondrial metabolism or astrocytic PCr metabolism.

Diffusion tensor spectroscopic imaging of the human brain in children and adults.

PubMed

Fotso, Kevin; Dager, Stephen R; Landow, Alec; Ackley, Elena; Myers, Orrin; Dixon, Mindy; Shaw, Dennis; Corrigan, Neva M; Posse, Stefan

2017-10-01

We developed diffusion tensor spectroscopic imaging (DTSI), based on proton-echo-planar-spectroscopic imaging (PEPSI), and evaluated the feasibility of mapping brain metabolite diffusion in adults and children. PRESS prelocalized DTSI at 3 Tesla (T) was performed using navigator-based correction of movement-related phase errors and cardiac gating with compensation for repetition time (TR) related variability in T 1 saturation. Mean diffusivity (MD) and fractional anisotropy (FA) of total N-acetyl-aspartate (tNAA), total creatine (tCr), and total choline (tCho) were measured in eight adults (17-60 years) and 10 children (3-24 months) using b max  = 1734 s/mm 2 , 1 cc and 4.5 cc voxel sizes, with nominal scan times of 17 min and 8:24 min. Residual movement-related phase encoding ghosting (PEG) was used as a regressor across scans to correct overestimation of MD. After correction for PEG, metabolite slice-averaged MD estimated at 20% PEG were lower (P < 0.042) for adults (0.17/0.20/0.18 × 10 -3 mm 2 /s) than for children (0.26/0.27/0.24 × 10 -3 mm 2 /s). Extrapolated to 0% PEG, the MD estimates decreased further (0.09/0.11/0.11 × 10 -3 mm 2 /s versus 0.15/0.16/0.15 × 10 -3 mm 2 /s). Slice-averaged FA of tNAA (P = 0.049), tCr (P = 0.067), and tCho (P = 0.003) were higher in children. This high-speed DTSI approach with PEG regression allows for estimation of metabolite MD and FA with improved tolerance to movement. Our preliminary data suggesting age-related changes support DTSI as a sensitive technique for investigating intracellular markers of biological processes. Magn Reson Med 78:1246-1256, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Creatine supplementation during pulmonary rehabilitation in chronic obstructive pulmonary disease.

PubMed

Fuld, J P; Kilduff, L P; Neder, J A; Pitsiladis, Y; Lean, M E J; Ward, S A; Cotton, M M

2005-07-01

Skeletal muscle wasting and dysfunction are strong independent predictors of mortality in patients with chronic obstructive pulmonary disease (COPD). Creatine nutritional supplementation produces increased muscle mass and exercise performance in health. A controlled study was performed to look for similar effects in 38 patients with COPD. Thirty eight patients with COPD (mean (SD) forced expiratory volume in 1 second (FEV(1)) 46 (15)% predicted) were randomised to receive placebo (glucose polymer 40.7 g) or creatine (creatine monohydrate 5.7 g, glucose 35 g) supplements in a double blind trial. After 2 weeks loading (one dose three times daily), patients participated in an outpatient pulmonary rehabilitation programme combined with maintenance (once daily) supplementation. Pulmonary function, body composition, and exercise performance (peripheral muscle strength and endurance, shuttle walking, cycle ergometry) took place at baseline (n = 38), post loading (n = 36), and post rehabilitation (n = 25). No difference was found in whole body exercise performance between the groups: for example, incremental shuttle walk distance mean -23.1 m (95% CI -71.7 to 25.5) post loading and -21.5 m (95% CI -90.6 to 47.7) post rehabilitation. Creatine increased fat-free mass by 1.09 kg (95% CI 0.43 to 1.74) post loading and 1.62 kg (95% CI 0.47 to 2.77) post rehabilitation. Peripheral muscle performance improved: knee extensor strength 4.2 N.m (95% CI 1.4 to 7.1) and endurance 411.1 J (95% CI 129.9 to 692.4) post loading, knee extensor strength 7.3 N.m (95% CI 0.69 to 13.92) and endurance 854.3 J (95% CI 131.3 to 1577.4) post rehabilitation. Creatine improved health status between baseline and post rehabilitation (St George's Respiratory Questionnaire total score -7.7 (95% CI -14.9 to -0.5)). Creatine supplementation led to increases in fat-free mass, peripheral muscle strength and endurance, health status, but not exercise capacity. Creatine may constitute a new ergogenic treatment in COPD.

Creatine Supplementation and Upper Limb Strength Performance: A Systematic Review and Meta-Analysis.

PubMed

Lanhers, Charlotte; Pereira, Bruno; Naughton, Geraldine; Trousselard, Marion; Lesage, François-Xavier; Dutheil, Frédéric

2017-01-01

Creatine is the most widely used supplementation to increase performance in strength; however, the most recent meta-analysis focused specifically on supplementation responses in muscles of the lower limbs without regard to upper limbs. We aimed to systematically review the effect of creatine supplementation on upper limb strength performance. We conducted a systematic review and meta-analyses of all randomized controlled trials comparing creatine supplementation with a placebo, with strength performance measured in exercises shorter than 3 min in duration. The search strategy used the keywords 'creatine', 'supplementation', and 'performance'. Independent variables were age, sex and level of physical activity at baseline, while dependent variables were creatine loading, total dose, duration, time interval between baseline (T0) and the end of the supplementation (T1), and any training during supplementation. We conducted three meta-analyses: at T0 and T1, and on changes between T0 and T1. Each meta-analysis was stratified within upper limb muscle groups. We included 53 studies (563 individuals in the creatine supplementation group and 575 controls). Results did not differ at T0, while, at T1, the effect size (ES) for bench press and chest press were 0.265 (95 % CI 0.132-0.398; p < 0.001) and 0.677 (95 % CI 0.149-1.206; p = 0.012), respectively. Overall, pectoral ES was 0.289 (95 % CI 0.160-0.419; p = 0.000), and global upper limb ES was 0.317 (95 % CI 0.185-0.449; p < 0.001). Meta-analysis of changes between T0 and T1 gave similar results. The meta-regression showed no link with characteristics of population or supplementation, demonstrating the efficacy of creatine independently of all listed conditions. Creatine supplementation is effective in upper limb strength performance for exercise with a duration of less than 3  min, independent of population characteristics, training protocols, and supplementary doses or duration.

Creatine Supplementation and Lower Limb Strength Performance: A Systematic Review and Meta-Analyses.

PubMed

Lanhers, Charlotte; Pereira, Bruno; Naughton, Geraldine; Trousselard, Marion; Lesage, François-Xavier; Dutheil, Frédéric

2015-09-01

Creatine is the most widely used supplementation to increase strength performance. However, the few meta-analyses are more than 10 years old and suffer from inclusion bias such as the absence of randomization and placebo, the diversity of the inclusion criteria (aerobic/endurance, anaerobic/strength), no evaluation on specific muscles or group of muscles, and the considerable amount of conflicting results within the last decade. The objective of this systematic review was to evaluate meta-analyzed effects of creatine supplementation on lower limb strength performance. We conducted a systematic review and meta-analyses of all randomized controlled trials comparing creatine supplementation with a placebo, with strength performance of the lower limbs measured in exercises lasting less than 3 min. The search strategy used the keywords "creatine supplementation" and "performance". Dependent variables were creatine loading, total dose, duration, the time-intervals between baseline (T0) and the end of the supplementation (T1), as well as any training during supplementation. Independent variables were age, sex, and level of physical activity at baseline. We conducted meta-analyses at T1, and on changes between T0 and T1. Each meta-analysis was stratified within lower limb muscle groups and exercise tests. We included 60 studies (646 individuals in the creatine supplementation group and 651 controls). At T1, the effect size (ES) among stratification for squat and leg press were, respectively, 0.336 (95 % CI 0.047-0.625, p = 0.023) and 0.297 (95 % CI 0.098-0.496, p = 0.003). Overall quadriceps ES was 0.266 (95 % CI 0.150-0.381, p < 0.001). Global lower limb ES was 0.235 (95 % CI 0.125-0.346, p < 0.001). Meta-analysis on changes between T0 and T1 gave similar results. The meta-regression showed no links with characteristics of population or of supplementation, demonstrating the creatine efficacy effects, independent of all listed conditions. Creatine supplementation is effective in lower limb strength performance for exercise with a duration of less than 3 min, independent of population characteristic, training protocols, and supplementary doses and duration.

Creatine salts provide neuroprotection even after partial impairment of the creatine transporter.

PubMed

Adriano, E; Garbati, P; Salis, A; Damonte, G; Millo, E; Balestrino, M

2017-01-06

Creatine, a compound that is critical for energy metabolism of nervous cells, crosses the blood-brain barrier (BBB) and the neuronal plasma membrane with difficulty, and only using its specific transporter. In the hereditary condition where the creatine transporter is defective (creatine transporter deficiency) there is no creatine in the brain, and administration of creatine is useless lacking the transporter. The disease is severe and incurable. Creatine-derived molecules that could cross BBB and plasma membrane independently of the transporter might be useful to cure this condition. Moreover, such molecules could be useful also in stroke and other brain ischemic conditions. In this paper, we investigated three creatine salts, creatine ascorbate, creatine gluconate and creatine glucose. Of these, creatine glucose was ineffective after transporter block with guanidine acetic acid (GPA) administration. Creatine ascorbate was not superior to creatine in increasing tissue creatine and phosphocreatine content after transporter impairment, however even after such impairment it delayed synaptic failure during anoxia. Finally, creatine gluconate was superior to creatine in increasing tissue content of creatine after transporter block and slowed down PS disappearance during anoxia, an effect that creatine did not have. These findings suggest that coupling creatine to molecules having a specific transporter may be a useful strategy in creatine transporter deficiency. In particular, creatine ascorbate has effects comparable to those of creatine in normal conditions, while being superior to it under conditions of missing or impaired creatine transporter. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

The relationship between white matter brain metabolites and cognition in normal aging: the GENIE study.

PubMed

Charlton, R A; McIntyre, D J O; Howe, F A; Morris, R G; Markus, H S

2007-08-20

Magnetic resonance spectroscopy (MRS) has demonstrated age-related changes in brain metabolites that may underlie micro-structural brain changes, but few studies have examined their relationship with cognitive decline. We performed a cross-sectional study of brain metabolism and cognitive function in 82 healthy adults (aged 50-90) participating in the GENIE (St GEorge's Neuropsychology and Imaging in the Elderly) study. Absolute metabolite concentrations were measured by proton chemical shift imaging within voxels placed in the centrum semiovale white matter. Cognitive abilities assessed were executive function, working memory, information processing speed, long-term memory and fluid intelligence. Correlations showed that all cognitive domains declined with age. Total creatine (tCr) concentration increased with age (r=0.495, p<0.001). Regression analyses were performed for each cognitive variable, including estimated intelligence and the metabolites, with age then added as a final step. A significant relationship was observed between tCr and executive function, long-term memory, and fluid intelligence, although these relationships did not remain significant after age was added as a final step in the regression. The regression analysis also demonstrated a significant relationship between N-acetylaspartate (NAA) and executive function. As there was no age-related decline in NAA, this argues against axonal loss with age; however the relationship between NAA and executive function independent of age and estimated intelligence is consistent with white matter axonal integrity having an important role in executive function in normal individuals.

Effects of normal aging and SCN1A risk-gene expression on brain metabolites: evidence for an association between SCN1A and myo-inositol.

PubMed

Tunc-Skarka, Nuran; Meier, Sandra; Demirakca, Traute; Sack, Markus; Weber-Fahr, Wolfgang; Brusniak, Wencke; Wolf, Isabella; Matthäus, Franziska; Schulze, Thomas G; Diener, Carsten; Ende, Gabriele

2014-02-01

Previously reported MRS findings in the aging brain include lower N-acetylaspartate (NAA) and higher myo-inositol (mI), total creatine (Cr) and choline-containing compound (Cho) concentrations. Alterations in the sodium channel voltage gated type I, alpha subunit SCN1A variant rs10930201 have been reported to be associated with several neurological disorders with cognitive deficits. MRS studies in SCN1A-related diseases have reported striking differences in the mI concentrations between patients and controls. In a study on 'healthy aging', we investigated metabolite spectra in a sample of 83 healthy volunteers and determined their age dependence. We also investigated a potential link between SCN1A and mI. We observed a significantly negative association of NAA (p = 0.004) and significantly positive associations of mI (p ≤ 0.001), Cr (p ≤ 0.001) and Cho (p = 0.034) with age in frontal white matter. The linear association of Cho ends at the age of about 50 years and is followed by an inverted 'U'-shaped curve. Further, mI was higher in C allele carriers of the SCN1A variant rs10930201. Our results corroborated the age-related changes in metabolite concentrations, and found evidence for a link between SCN1A and frontal white matter mI in healthy subjects. Copyright © 2013 John Wiley & Sons, Ltd.

Correlation analysis of expressions of PTEN and p53 with the value obtained by magnetic resonance spectroscopy and apparent diffusion coefficient in the tumor and the tumor-adjacent area in magnetic resonance imaging for glioblastoma.

PubMed

Li, Yunyun; Ji, Feng; Jiang, Yuzhi; Zhao, Ting; Xu, Chongfu

2018-01-01

To explore the correlation of the expression levels of phosphate and tension homology deleted on chromosome ten (PTEN) and p53 of glioblastoma multiforme (GBM) with the value obtained by magnetic resonance spectroscopy (MRS) and apparent diffusion coefficient (ADC) in the tumor and the tumor-adjacent area in magnetic resonance imaging (MRI). A total of 38 patients were operated for GBM. All the patients had received diffusion-weighted imaging (DWI) and MRS prior to surgery. ADC of water molecules and values of metabolite indexes of MRS, including n-acetyl aspartate (NAA), choline (Cho) and creatine (Cr), were recorded, and the ratios of Cho/NAA, Cho/Cr and NAA/Cr were calculated. Hematoxylin-eosin (H&E) staining was done to examine the morphology of tumor and of tumor-adjacent tissues; immunohistochemistry (IHC) was performed to examine the expressions of PTEN and p53 in the tumor and the tumor-adjacent area. Finally, the correlations of the expressions of PTEN and p53 with ADC, Cho/NAA, Cho/Cr and NAA/Cr of the tumor and the tumor-adjacent area were analyzed. H&E staining showed that GBM tissues had disordered morphology, different sizes of cells, large cell nuclei and significant cell heterogeneity. IHC indicated that the expression level of p53 protein in the tumor was significantly higher than in the tumor-adjacent tissues (p<0.05). The expression level of PTEN protein was high in the tumor-adjacent tissues, but significantly deficient in the tumor. DWI showed that the signal of DWI in the tumor was significantly increased, but ADC was decreased compared with the tumor-adjacent area. MRS indicated that the wave band of Cho in the tumor was significantly increased, NAA was significantly lowered, and Cr section was decreased compared with the tumor-adjacent area, while NAA/Cr in the tumor was significantly decreased compared with the tumoradjacent area (p<0.05). Correlation analysis indicated that PTEN levels in the tumor and the tumor-adjacent area were positively correlated with ADC in the corresponding area, while p53 in the tumor and the tumor-adjacent area was negatively correlated with ADC in the corresponding area. Cho/NAA and Cho/Cr in the tumor were positively correlated with p53 in the tumor, but negatively correlated with PTEN in the tumor. However, NAA/Cr of the tumor was irrelevant to the levels of PTEN and p53. The test results of DWI and MRS of patients with GBM can accurately reflect the inactivation or mutation of PTEN and p53.

sup 31 P NMR measurements of the ADP concentration in yeast cells genetically modified to express creatine kinase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brindle, K.; Braddock, P.; Fulton, S.

1990-04-03

Rabbit muscle creatine kinase has been introduced into the yeast Saccharomyces cerevisiae by transforming cells with a multicopy plasmid containing the coding sequence for the enzyme under the control of the yeast phosphoglycerate kinase promoter. The transformed cells showed creating kinase activities similar to those found in mammalian heart muscle. {sup 31}P NMR measurements of the near-equilibrium concentrations of phosphocreatine and cellular pH together with measurements of the total extractable concentrations of phosphocreatine and creatine allowed calculation of the free ADP/ATP ratio in the cell. The calculated ratio of approximately 2 was considerably higher than the ratio of between 0.06more » and 0.1 measured directly in cell extracts.« less

Chromium Biosorption from Cr(VI) Aqueous Solutions by Cupressus lusitanica Bark: Kinetics, Equilibrium and Thermodynamic Studies.

PubMed

Netzahuatl-Muñoz, Alma Rosa; Cristiani-Urbina, María del Carmen; Cristiani-Urbina, Eliseo

2015-01-01

The present study investigated the kinetics, equilibrium and thermodynamics of chromium (Cr) ion biosorption from Cr(VI) aqueous solutions by Cupressus lusitanica bark (CLB). CLB total Cr biosorption capacity strongly depended on operating variables such as initial Cr(VI) concentration and contact time: as these variables rose, total Cr biosorption capacity increased significantly. Total Cr biosorption rate also increased with rising solution temperature. The pseudo-second-order model described the total Cr biosorption kinetic data best. Langmuir´s model fitted the experimental equilibrium biosorption data of total Cr best and predicted a maximum total Cr biosorption capacity of 305.4 mg g(-1). Total Cr biosorption by CLB is an endothermic and non-spontaneous process as indicated by the thermodynamic parameters. Results from the present kinetic, equilibrium and thermodynamic studies suggest that CLB biosorbs Cr ions from Cr(VI) aqueous solutions predominantly by a chemical sorption phenomenon. Low cost, availability, renewable nature, and effective total Cr biosorption make CLB a highly attractive and efficient method to remediate Cr(VI)-contaminated water and wastewater.

Chromium Biosorption from Cr(VI) Aqueous Solutions by Cupressus lusitanica Bark: Kinetics, Equilibrium and Thermodynamic Studies

PubMed Central

Netzahuatl-Muñoz, Alma Rosa; Cristiani-Urbina, María del Carmen; Cristiani-Urbina, Eliseo

2015-01-01

The present study investigated the kinetics, equilibrium and thermodynamics of chromium (Cr) ion biosorption from Cr(VI) aqueous solutions by Cupressus lusitanica bark (CLB). CLB total Cr biosorption capacity strongly depended on operating variables such as initial Cr(VI) concentration and contact time: as these variables rose, total Cr biosorption capacity increased significantly. Total Cr biosorption rate also increased with rising solution temperature. The pseudo-second-order model described the total Cr biosorption kinetic data best. Langmuir´s model fitted the experimental equilibrium biosorption data of total Cr best and predicted a maximum total Cr biosorption capacity of 305.4 mg g-1. Total Cr biosorption by CLB is an endothermic and non-spontaneous process as indicated by the thermodynamic parameters. Results from the present kinetic, equilibrium and thermodynamic studies suggest that CLB biosorbs Cr ions from Cr(VI) aqueous solutions predominantly by a chemical sorption phenomenon. Low cost, availability, renewable nature, and effective total Cr biosorption make CLB a highly attractive and efficient method to remediate Cr(VI)-contaminated water and wastewater. PMID:26352933

Accelerated echo planar J-resolved spectroscopic imaging in prostate cancer: a pilot validation of non-linear reconstruction using total variation and maximum entropy.

PubMed

Nagarajan, Rajakumar; Iqbal, Zohaib; Burns, Brian; Wilson, Neil E; Sarma, Manoj K; Margolis, Daniel A; Reiter, Robert E; Raman, Steven S; Thomas, M Albert

2015-11-01

The overlap of metabolites is a major limitation in one-dimensional (1D) spectral-based single-voxel MRS and multivoxel-based MRSI. By combining echo planar spectroscopic imaging (EPSI) with a two-dimensional (2D) J-resolved spectroscopic (JPRESS) sequence, 2D spectra can be recorded in multiple locations in a single slice of prostate using four-dimensional (4D) echo planar J-resolved spectroscopic imaging (EP-JRESI). The goal of the present work was to validate two different non-linear reconstruction methods independently using compressed sensing-based 4D EP-JRESI in prostate cancer (PCa): maximum entropy (MaxEnt) and total variation (TV). Twenty-two patients with PCa with a mean age of 63.8 years (range, 46-79 years) were investigated in this study. A 4D non-uniformly undersampled (NUS) EP-JRESI sequence was implemented on a Siemens 3-T MRI scanner. The NUS data were reconstructed using two non-linear reconstruction methods, namely MaxEnt and TV. Using both TV and MaxEnt reconstruction methods, the following observations were made in cancerous compared with non-cancerous locations: (i) higher mean (choline + creatine)/citrate metabolite ratios; (ii) increased levels of (choline + creatine)/spermine and (choline + creatine)/myo-inositol; and (iii) decreased levels of (choline + creatine)/(glutamine + glutamate). We have shown that it is possible to accelerate the 4D EP-JRESI sequence by four times and that the data can be reliably reconstructed using the TV and MaxEnt methods. The total acquisition duration was less than 13 min and we were able to detect and quantify several metabolites. Copyright © 2015 John Wiley & Sons, Ltd.

MR Spectroscopy to Distinguish between Supratentorial Intraventricular Subependymoma and Central Neurocytoma.

PubMed

Ueda, Fumiaki; Aburano, Hiroyuki; Ryu, Yasuji; Yoshie, Yuichi; Nakada, Mitsutoshi; Hayashi, Yutaka; Matsui, Osamu; Gabata, Toshifumi

2017-07-10

The purpose of this study was to discriminate supratentorial intraventricular subependymoma (SIS) from central neurocytoma (CNC) using magnetic resonance spectroscopy (MRS). Single-voxel proton MRS using a 1.5T or 3T MR scanner from five SISs, five CNCs, and normal controls were evaluated. They were examined using a point-resolved spectroscopy. Automatically calculated ratios comparing choline (Cho), N-acetylaspartate (NAA), myoinositol (MI), and/or glycine (Gly) to creatine (Cr) were determined. Evaluation of Cr to unsuppressed water (USW) was also performed. Mann-Whitney U test was carried out to test the significance of differences in the metabolite ratios. Detectability of lactate (Lac) and alanine (Ala) was evaluated. Although a statistically significant difference (P < 0.0001) was observed in Cho/Cr among SIS, control spectra, and CNC, no statistical difference was noted between SIS and control spectra (P = 0.11). Statistically significant differences were observed in NAA/Cr between SIS and CNC (P = 0.04) or control spectra (P < 0.0001). A statistically significant difference was observed in MI and/or Gly to Cr between SIS and control spectra (P = 0.03), and CNC and control spectra (P < 0.0006). There were no statistical differences between SIS and CNC for MI and/or Gly to Cr (P = 0.32). Significant statistical differences were found between SIS and control spectra (P < 0.0053), control spectra and CNC (P < 0.0016), and SIS and CNC (P < 0.0083) for Cr to USW. Lac inverted doublets were confirmed in two SISs. Triplets of Lac and Ala were detected in four spectra of CNC. The present study showed that MRS can be useful in discriminating SIS from CNC.

Hypothalamic damage in multiple sclerosis correlates with disease activity, disability, depression, and fatigue.

PubMed

Kantorová, E; Poláček, H; Bittšanský, M; Baranovičová, E; Hnilicová, P; Čierny, D; Sivák, Š; Nosáľ, V; Zeleňák, K; Kurča, E

2017-04-01

Disturbances in the hypothalamo-pituitary axis are supposed to modulate activity of multiple sclerosis (MS). We hypothesised that the extent of HYP damage may determine severity of MS and may be associated with the disease evolution. We suggested fatigue and depression may depend on the degree of damage of the area. 33 MS patients with relapsing-remitting and secondary progressive disease, and 24 age and sex-related healthy individuals (CON) underwent 1H-MR spectroscopy (1H-MRS) of the hypothalamus. Concentrations of glutamate + glutamin (Glx), cholin (Cho), myoinositol (mIns), N-acetyl aspartate (NAA) expressed as ratio with creatine (Cr) and NAA were correlated with markers of disease activity (RIO score), Multiple Sclerosis Severity Scale (MSSS), Depressive-Severity Status Scale and Simple Numerical Fatigue Scale. Cho/Cr and NAA/Cr ratios were decreased and Glx/NAA ratio increased in MS patients vs CON. Glx/NAA, Glx/Cr, and mIns/NAA were significantly higher in active (RIO 1-2) vs non-active MS patients (RIO 0). Glx/NAA and Glx/Cr correlated with MSSS and fatigue score, and Glx/Cr with depressive score of MS patients. In CON, relationships between Glx/Cr and age, and Glx/NAA and fatigue score were inverse. Our study provides the first evidence about significant hypothalamic alterations correlating with clinical outcomes of MS, using 1H-MRS. The combination of increased Glu or mIns with reduced NAA in HYP reflects whole-brain activity of MS. In addition, excess of Glu is linked to severe disease course, depressive mood and fatigue in MS patients, suggesting superiority of Glu over other metabolites in determining MS burden.

Antidepressant effect detected on proton magnetic resonance spectroscopy in drug-naïve female patients with first-episode major depression.

PubMed

Kaymak, Semra Ulusoy; Demir, Başaran; Oğuz, Kader Karli; Sentürk, Senem; Uluğ, Berna

2009-06-01

Recent neuroimaging studies support functional and structural alterations in the dorsolateral prefrontal cortex (DLPFC), particularly on the left side in patients with major depressive disorders (MDD). The aim of the present study was to examine the biochemical characteristics of left DLPFC as measured on proton ((1)H) magnetic resonance spectroscopy (MRS) in patients with drug-naïve first-episode MDD and a healthy control group. A second aim was to assess the effect of antidepressant treatment on the metabolites of DLPFC. Short-echo single-voxel (1)H-MRS was done for the left DLPFC in 17 female drug-free MDD patients (mean age +/- SD, 30.9 +/- 6.9 years) and 13 matched control subjects (mean age +/- SD, 29.1 +/- 6.2 years) and was repeated at 8 weeks following antidepressant treatment. Comparison of baseline values indicated that there were no significant differences in any of the metabolite ratios (N-acetyl aspartate/creatine [NAA/Cr], myoinositol [Ino]/Cr, and choline [Cho]/Cr) between patients and controls. Significant differences were detected between pre- and post-treatment Ino/Cr ratios (0.67 +/- 0.13, 0.58 +/- 0.22, P = 0.032, respectively), although there was no difference in NAA/Cr and Cho/Cr ratios. Although no significant metabolic alterations exist in female patients with drug-naïve first-episode MDD as evaluated on (1)H-MRS, an increase in Ino/Cr was observed following 8-week antidepressant treatment. These findings give rise to the possibility that non-neuronal cells, particularly glial cells that are probably damaged, play a role in the action of antidepressant treatment.

Serial 1H-MRS in GM2 gangliosidoses.

PubMed

Assadi, Mitra; Baseman, Susan; Janson, Christopher; Wang, Dah-Jyuu; Bilaniuk, Larissa; Leone, Paola

2008-03-01

GM2 gangliosidoses are a group of neuronal storage disorders caused by deficiency in the lysosomal enzyme hexosaminidase A. Clinically, the disease is marked by a relentless encephalopathy. Proton magnetic resonance spectroscopy (1H-MRS) provides in-vivo measurement of various brain metabolites including N-acetyl aspartate+N-acetyl aspartate glutamate (NAA), myo-inositol (mI), choline (Cho) and creatine (Cr). The NAA represents neuronal integrity while elevation in the mI reflects abnormal inflammation and gliosis in the brain tissue. An elevation in the Cho levels suggest cell membrane breakdown and demyelination. We report the clinical and laboratory data in two patients with GM2 gangliosidoses. Serial 1H-MRS evaluations were performed to drive metabolite ratios of NAA/Cr, mI/Cr and Cho/Cr. We acquired the data from four regions of interest (ROI) according to a standard protocol. The results documented a progressive elevation in mI/Cr in all four ROI in patient one and only one ROI (occipital gray matter) in patient 2. We also documented a decline in the NAA/Cr ratios in both cases in most ROI. These results were compared to six age-matched controls and confirmed statistically significant elevation in the mI in our cases. In conclusion, 1H-MRS alterations were suggestive of neuronal loss and inflammation in these patients. 1H-MRS may be a valuable tool in monitoring the disease progress and response to therapy in GM2 gangliosidoses. Elevation in the mI may prove to be more sensitive than the other metabolite alterations.

Reduced N-acetylaspartate levels in the frontal cortex of 3,4-methylenedioxymethamphetamine (Ecstasy) users: preliminary results.

PubMed

Reneman, Liesbeth; Majoie, Charles B L M; Flick, Herman; den Heeten, Gerard J

2002-02-01

The perceived safety of the recreational drug methylenedioxymethamphetamine (MDMA), or Ecstasy, conflicts with animal evidence indicating that MDMA damages cortical serotonin (5-HT) neurons at doses similar to those used by humans. Few data are available about the effects of MDMA on the human brain. This study was designed to evaluate MDMA-related alterations in metabolite ratios with single-voxel proton ((1)H) MR spectroscopy. Fifteen male MDMA users (mean lifetime exposure, 723 tablets; mean time since last tablet, 12.0 weeks) and 12 age-matched control subjects underwent single-voxel (1)H MR spectroscopy. N-Acetylaspartate (NAA)/creatine (Cr), NAA/Choline (Cho), and myoinositol (MI)/Cr ratios were measured in midfrontal gray matter, midoccipital gray matter, and right parietal white matter. Data were analyzed with linear model-based multivariate analysis of variance. NAA/Cr (P =.04) and NAA/Cho (P =.03) ratios, markers associated with neuronal loss or dysfunction, were reduced in the frontal cortex of MDMA users. Neither NAA/Cr (P =.72) nor NAA/Cho (P =.12) ratios were different between both groups in occipital gray matter and parietal white matter (P =.18). Extent of previous MDMA use and frontal cortical NAA/Cr (rho = -.50, P =.012) or NAA/Cho (rho = -.550, P <.01) ratios were significantly associated. Reduced NAA/Cr and NAA/Cho ratios at (1)H MR spectroscopy provide evidence for neuronal abnormality in the frontal cortex of MDMA users; these are correlated with the degree of MDMA exposure. These data suggest that MDMA may be a neurotoxin in humans, as it is in animals.

Aerobic fitness and the brain: increased N-acetyl-aspartate and choline concentrations in endurance-trained middle-aged adults.

PubMed

Gonzales, Mitzi M; Tarumi, Takashi; Kaur, Sonya; Nualnim, Nantinee; Fallow, Bennett A; Pyron, Martha; Tanaka, Hirofumi; Haley, Andreana P

2013-01-01

Engagement in regular aerobic exercise is associated with cognitive benefits, but information on the mechanisms governing these changes in humans is limited. The goal of the current study was to compare neurometabolite concentrations relating to cellular metabolism, structure, and viability in endurance-trained and sedentary middle-aged adults. Twenty-eight endurance-trained and 27 sedentary adults, aged 40-65 years, underwent general health assessment, cardiorespiratory fitness measurement, neuropsychological testing, and proton magnetic resonance spectroscopy ((1)H MRS). (1)H MRS was used to examine N-acetyl-aspartate (NAA), creatine (Cr), myo-inositol (mI), choline (Cho), and glutamate (Glu) concentrations in frontal and occipitoparietal grey matter. Group differences in concentrations of NAA, Cho, mI, and Glu, calculated as ratios over Cr, were explored using ANOVA. There were no significant differences in global cognitive function, memory, and executive function performance between the groups. In comparison to sedentary adults, the endurance-trained group displayed significantly higher NAA/Cr in the frontal grey matter (F(1, 53) = 5.367, p = 0.024) and higher Cho/Cr in the occipitoparietal grey matter (F(1, 53) = 5.138, p = 0.028). Within our middle-aged sample, endurance-trained adults demonstrated higher levels of NAA/Cr in the frontal grey matter and higher Cho/Cr in the occipitoparietal grey matter. Higher levels of NAA may indicate greater neuronal integrity and higher cerebral metabolic efficiency in association with cardiorespiratory fitness, whereas increased Cho may represent increased phospholipid levels secondary to neural plasticity.

Single voxel proton magnetic resonance spectroscopy in women with and without intimate partner violence-related posttraumatic stress disorder.

PubMed

Seedat, Soraya; Videen, John S; Kennedy, Colleen M; Stein, Murray B

2005-08-30

Preliminary in vivo proton magnetic spectroscopic ((1)H-MRS) studies of N-acetylaspartate (a putative marker of neuronal viability and function) in combat veterans and maltreated children with posttraumatic stress disorder (PTSD) suggest altered neuronal integrity in anterior cingulate and medial temporal lobe structures. In this study, (1)H-MRS was used to measure N-acetylaspartate (NAA), choline (Cho) and myo-inositol (mI) relative to creatine (Cr) in the anterior cingulate of 16 women with histories of intimate partner violence (7 with a DSM-IV diagnosis of PTSD, 9 without PTSD) and 11 healthy, non-abused comparison subjects. The relationship between anterior cingulate chemistry and performance on the Stroop Color-Word task and Part B of the Trail Making Test was also examined. There were no significant differences in anterior cingulate or occipital gray matter metabolite ratios of NAA/Cr and Cho/Cr between intimate partner violence and healthy comparison subjects. Intimate partner violence subjects with PTSD had significantly higher anterior cingulate Cho/Cr than intimate partner violence subjects without PTSD. There was evidence that the subjects with PTSD suffered more severe intimate partner violence as measured by the Conflict Tactics Scale-Revised. Metabolite ratios were not significantly correlated with performance on the Stroop or Trails B. Our findings, in agreement with earlier studies, showed significant alterations in anterior cingulate chemistry in women with PTSD. In contrast to other studies, we found an increase in Cho/Cr rather than a decrease in NAA/Cr, indicating alterations in glia, instead of neuronal dropout.

[Effect of low-intensity 900 MHz frequency electromagnetic radiation on rat liver and blood serum enzyme activities].

PubMed

Nersesova, L S; Petrosian, M S; Gazariants, M G; Mkrtchian, Z S; Meliksetian, G O; Pogosian, L G; Akopian, Zh I

2014-01-01

The comparative analysis of the rat liver and blood serum creatine kinase, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and purine nucleoside phosphorylase post-radiation activity levels after a total two-hour long single and fractional exposure of the animals to low-intensity 900 MHz frequency electromagnetic field showed that the most sensitive enzymes to the both schedules of radiation are the liver creatine kinase, as well as the blood serum creatine kinase and alkaline phosphatase. According to the comparative analysis of the dynamics of changes in the activity level of the liver and blood serum creatine kinase, alanine aminotransferase, aspartate aminotransferase and purine nucleoside phosphorylase, both single and fractional radiation schedules do not affect the permeability of a hepatocyte cell membrane, but rather cause changes in their energetic metabolism. The correlation analysis of the post-radiation activity level changes of the investigated enzymes did not reveal a clear relationship between them. The dynamics of post-radiation changes in the activity of investigated enzyme levels following a single and short-term fractional schedules of radiation did not differ essentially.

Estimation of skeletal muscle mass from body creatine content

NASA Technical Reports Server (NTRS)

Pace, N.; Rahlmann, D. F.

1982-01-01

Procedures have been developed for studying the effect of changes in gravitational loading on skeletal muscle mass through measurements of the body creatine content. These procedures were developed for studies of gravitational scale effects in a four-species model, comprising the hamster, rat, guinea pig, and rabbit, which provides a sufficient range of body size for assessment of allometric parameters. Since intracellular muscle creatine concentration varies among species, and with age within a given species, the concentration values for metabolically mature individuals of these four species were established. The creatine content of the carcass, skin, viscera, smooth muscle, and skeletal muscle was determined for each species. In addition, the skeletal muscle mass of the major body components was determined, as well as the total and fat-free masses of the body and carcass, and the percent skeletal muscle in each. It is concluded that these procedures are particularly useful for studying the effect of gravitational loading on the skeletal muscle content of the animal carcass, which is the principal weight-bearing organ of the body.

Distribution of chromium species in a Cr-polluted soil: presence of Cr(III) in glomalin related protein fraction.

PubMed

Gil-Cardeza, María L; Ferri, Alejandro; Cornejo, Pablo; Gomez, Elena

2014-09-15

The accumulation of Cr in soil could be highly toxic to human health; therefore Cr soil distribution was studied in rhizosphere soils from Ricinus communis and Conium maculatum and bare soil (BS) from an industrial and urban area in Argentina. Total Cr, Cr(VI) and Cr(III) concentrations were determined in 3 soil fractions: total, extractable and associated to total-glomalin-related protein (T-GRSP). BS had the highest total Cr and total Cr(VI) concentrations. Total Cr(VI) concentration from both rhizosphere soils did not differ from the allowed value for residential area in Argentina (8 μg Cr(VI) g(-1) soil), while total Cr(VI) in BS was 1.8 times higher. Total Cr concentration in all the soils was higher than the allowed value (250 μg Cr g(-1) soil). Extractable and associated to T-GRSP Cr(VI) concentrations were below the detection limit. Cr(III) bound to T-GRSP was the highest in the BS. These findings are in agreement with a long term effect of glomalin in sequestrating Cr. In both plant species, total Cr was higher in root than in shoot and both species presented arbuscular mycorrhizal fungi (AMF). As far as we know, this is the first study that reports the presence of Cr in T-GRSP fraction of soil organic matter. These findings suggest that Cr mycorrhizostabilization could be a predominant mechanism used by R. communis and C. maculatum to diminish Cr soil concentration. Nevertheless, further research is needed to clarify the contribution of native AMF isolated from R. communis and C. maculatum rhizosphere to the Cr phytoremediation process. Copyright © 2014 Elsevier B.V. All rights reserved.

An Open-Label Exploratory Study with Memantine: Correlation between Proton Magnetic Resonance Spectroscopy and Cognition in Patients with Mild to Moderate Alzheimer's Disease

PubMed Central

Gordon, Marc L.; Kingsley, Peter B.; Goldberg, Terry E.; Koppel, Jeremy; Christen, Erica; Keehlisen, Lynda; Kohn, Nina; Davies, Peter

2012-01-01

Aim To characterize progression of Alzheimer's disease (AD) using proton magnetic resonance spectroscopy (1H MRS). Methods Eleven subjects with mild to moderate AD underwent neurocognitive testing and single-voxel 1H MRS from the precuneus and posterior cingulate region at baseline, after 24 weeks of monotherapy with a cholinesterase inhibitor, and after another 24 weeks of combination therapy with open-label memantine and a cholinesterase inhibitor. Baseline metabolites [N-acetylaspartate (NAA), myo-inositol (mI), choline (Cho), and creatine (Cr)] and their ratios in AD subjects were compared with those of an age-matched control group of 28 cognitively normal subjects. Results AD subjects had significantly higher mI/Cr and lower NAA, NAA/Cr, NAA/Cho, and NAA/mI. Baseline Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) scores significantly correlated with NAA/Cr, mI/Cr, and NAA/mI. There was an increase in mI and a decrease in NAA/mI, but no significant change in other metabolites or ratios, or neurocognitive measures, when memantine was added to a cholinesterase inhibitor. Conclusion Metabolite ratios significantly differed between AD and control subjects. Baseline metabolite ratios correlated with function (ADCS-ADL). There was an increase in mI and a decrease in NAA/mI, but no changes in other metabolites, ratios, or cognitive measures, when memantine was added to a cholinesterase inhibitor. PMID:22962555

Chronic intermittent but not constant hypoxia decreases NAA/Cr ratios in neonatal mouse hippocampus and thalamus.

PubMed

Douglas, Robert M; Miyasaka, Naoyuki; Takahashi, Kan; Latuszek-Barrantes, Adrianna; Haddad, Gabriel G; Hetherington, Hoby P

2007-03-01

Chronic constant hypoxia (CCH) and chronic intermittent hypoxia (CIH) are known to have deleterious effects on the central nervous system. Because of the difference in the pattern of hypoxic exposure, it is possible that the pathological outcome would vary. The N-acetyl aspartate/creatine (NAA/Cr) ratio is a reliable marker of neuronal integrity, and this can be noninvasively measured by proton nuclear magnetic resonance spectroscopy. P2 CD1 mouse pups with their dams were exposed to either CCH, where the Fi(O(2)) was maintained at 11% continuously or to CIH, where the Fi(O(2)) was varied between 21 and 11% every 4 min. P30 mice exposed to intermittent hypoxia for 4 wk demonstrated a significant decrease in the NAA/Cr ratio in the hippocampus and thalamus, which was reversed by a subsequent exposure to 4 wk of normoxia. Meanwhile, mice exposed to 4 wk of constant hypoxia did not demonstrate any differences in their NAA/Cr ratios from controls in these brain regions. These results indicate that an intermittent pattern of hypoxic exposure may have a more adverse effect on neuronal function and integrity than a continuous one. The reversal of NAA/Cr levels to baseline during the return to normoxia indicates that therapeutic strategies targeted at alleviating the intermittent hypoxic stress in diseases, such as obstructive sleep apnea, have the potential for inducing significant neurocognitive recovery in these patients.

21 CFR 862.1215 - Creatine phosphokinase/creatine kinase or isoenzymes test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Creatine phosphokinase/creatine kinase or... Clinical Chemistry Test Systems § 862.1215 Creatine phosphokinase/creatine kinase or isoenzymes test system. (a) Identification. A creatine phosphokinase/creatine kinase or isoenzymes test system is a device...

Choline-to-N-acetyl aspartate and lipids-lactate-to-creatine ratios together with age assemble a significant Cox's proportional-hazards regression model for prediction of survival in high-grade gliomas.

PubMed

Roldan-Valadez, Ernesto; Rios, Camilo; Motola-Kuba, Daniel; Matus-Santos, Juan; Villa, Antonio R; Moreno-Jimenez, Sergio

2016-11-01

A long-lasting concern has prevailed for the identification of predictive biomarkers for high-grade gliomas (HGGs) using MRI. However, a consensus of which imaging parameters assemble a significant survival model is still missing in the literature; we investigated the significant positive or negative contribution of several MR biomarkers in this tumour prognosis. A retrospective cohort of supratentorial HGGs [11 glioblastoma multiforme (GBM) and 17 anaplastic astrocytomas] included 28 patients (9 females and 19 males, respectively, with a mean age of 50.4 years, standard deviation: 16.28 years; range: 13-85 years). Oedema and viable tumour measurements were acquired using regions of interest in T 1 weighted, T 2 weighted, fluid-attenuated inversion recovery, apparent diffusion coefficient (ADC) and MR spectroscopy (MRS). We calculated Kaplan-Meier curves and obtained Cox's proportional hazards. During the follow-up period (3-98 months), 17 deaths were recorded. The median survival time was 1.73 years (range, 0.287-8.947 years). Only 3 out of 20 covariates (choline-to-N-acetyl aspartate and lipids-lactate-to-creatine ratios and age) showed significance in explaining the variability in the survival hazards model; score test: χ 2 (3) = 9.098, p = 0.028. MRS metabolites overcome volumetric parameters of peritumoral oedema and viable tumour, as well as tumour region ADC measurements. Specific MRS ratios (Cho/Naa, L-L/Cr) might be considered in a regular follow-up for these tumours. Advances in knowledge: Cho/Naa ratio is the strongest survival predictor with a log-hazard function of 2.672 in GBM. Low levels of lipids-lactate/Cr ratio represent up to a 41.6% reduction in the risk of death in GBM.

Neurochemical evaluation of brain function with 1H magnetic resonance spectroscopy in patients with fragile X syndrome.

PubMed

Utine, G E; Akpınar, B; Arslan, U; Kiper, P Ö Ş; Volkan-Salancı, B; Alanay, Y; Aktaş, D; Haliloğlu, G; Oğuz, K K; Boduroğlu, K; Alikaşifoğlu, M

2014-01-01

Fragile X syndrome (FXS) is the most common hereditary disorder of intellectual disability. Cognitive deficits involve executive function, attention, learning and memory. Advanced neuroimaging techniques are available, and (1)H magnetic resonance spectroscopy (MRS) can be used as a complementary method to MR imaging to understand disease processes in brain, by in vivo demonstration of brain metabolites. MRS was performed in 13 male patients with FXS full mutation, and 13 age- and sex-matched healthy controls. FXS diagnosis was based on clinical evaluation, followed by detection of FMR1 full mutation. Axial T2 TSE, sagittal T1 SE and coronal 3D MPRAGE images were obtained for both morphological imaging and voxel localization. Following evaluation of conventional images, multivoxel MRS (CSI) through supraventricular white matter and single voxel MRS (svs) with an intermediate echo time (TE:135 ms) from the cerebellar vermis were performed. Choline/Creatine (Cho/Cr), N-acetyl aspartate/Creatine (NAA/Cr), and Choline/N-acetyl aspartate (Cho/NAA) ratios were examined at right frontal (RF), left frontal (LF), right parietal (RP), left parietal (LP), and cerebellar vermian (C) white matter. Statistical analyses were done using t-test and Mann-Whitney U tests. A statistically significant difference was observed in RP Cho/NAA ratio (cell membrane marker/neuroaxonal marker), FXS patients having lower levels than controls (P = 0.016). The results should be evaluated cautiously in parallel to consequences in brain metabolism leading to alterations in neurotransmitter levels, osmoregulation, energy metabolism and oxidative stress response described in animal models. MRS may serve to define a metabolic signature and biomarkers associated with FXS. © 2013 Wiley Periodicals, Inc.

Creatine and guanidinoacetate content of human milk and infant formulas: implications for creatine deficiency syndromes and amino acid metabolism.

PubMed

Edison, Erica E; Brosnan, Margaret E; Aziz, Khalid; Brosnan, John T

2013-09-28

Creatine is essential for normal neural development; children with inborn errors of creatine synthesis or transport exhibit neurological symptoms such as mental retardation, speech delay and epilepsy. Creatine accretion may occur through dietary intake or de novo creatine synthesis. The objective of the present study was to determine how much creatine an infant must synthesise de novo. We have calculated how much creatine an infant needs to account for urinary creatinine excretion (creatine's breakdown product) and new muscle lay-down. To measure an infant's dietary creatine intake, we measured creatine in mother's milk and in various commercially available infant formulas. Knowing the amount of milk/formula ingested, we calculated the amount of creatine ingested. We have found that a breast-fed infant receives about 9 % of the creatine needed in the diet and that infants fed cows' milk-based formula receive up to 36 % of the creatine needed. However, infants fed a soya-based infant formula receive negligible dietary creatine and must rely solely on de novo creatine synthesis. This is the first time that it has been shown that neonatal creatine accretion is largely due to de novo synthesis and not through dietary intake of creatine. This has important implications both for infants suffering from creatine deficiency syndromes and for neonatal amino acid metabolism.

Heavy resistance training and peri-exercise ingestion of a multi-ingredient ergogenic nutritional supplement in males: effects on body composition, muscle performance and markers of muscle protein synthesis.

PubMed

Spillane, Mike; Schwarz, Neil; Willoughby, Darryn S

2014-12-01

This study determined the effects of heavy resistance training and peri-exercise ergogenic multi-ingredient nutritional supplement ingestion on blood and skeletal markers of muscle protein synthesis (MPS), body composition, and muscle performance. Twenty-four college-age males were randomly assigned to either a multi-ingredient SizeOn Maximum Performance (SIZE) or protein/carbohydrate/creatine (PCC) comparator supplement group in a double-blind fashion. Body composition and muscle performance were assessed, and venous blood samples and muscle biopsies were obtained before and after 6 weeks of resistance training and supplementation. Data were analyzed by 2-way ANOVA (p ≤ 0.05). Total body mass, body water, and fat mass were not differentially affected (p > 0.05). However, fat-free mass was significantly increased in both groups in response to resistance training (p = 0.037). Lower-body muscle strength (p = 0.029) and endurance (p = 0.027) were significantly increased with resistance training, but not supplementation (p > 0.05). Serum insulin, IGF-1, GH, and cortisol were not differentially affected (p > 0.05). Muscle creatine content was significantly increased in both groups from supplementation (p = 0.044). Total muscle protein (p = 0.038), MHC 1 (p = 0.041), MHC 2A, (p = 0.029), total IRS- (p = 0.041), and total Akt (p = 0.011) were increased from resistance training, but not supplementation. In response to heavy resistance training when compared to PCC, the peri-exercise ingestion of SIZE did not preferentially improve body composition, muscle performance, and markers indicative of MPS. Key pointsIn response to 42 days of heavy resistance training and either SizeOn Maximum Performance or protein/carbohydrate/creatine supplementation, similar increases in muscle mass and strength in both groups occurred; however, the increases were not different between supplement groups.The supplementation of SizeOn Maximum Performance had no preferential effect on augmenting serum insulin, IGF-1, and GH, or in decreasing cortisol.While resistance training was effective in increasing total creatine content in skeletal muscle, myofibrillar protein, and the content of total IRS-1 and Akt, it was not preferentially due to SizeOn Maximum Performance supplementation.At the daily dose of 50 g, SizeOn Maximum Performance supplementation for 42 days combined with resistance training does not increases muscle mass and strength due to its ability to elevate serum hormones and growth factors or in its ability to augment skeletal muscle signaling pathway markers indicative of muscle protein synthesis when compared to an equivalent daily dose of protein/carbohydrate/creatine.

Effects of creatine supplementation on cardiac autonomic functions in bodybuilders.

PubMed

Mert, Kadir Uğur; Ilgüy, Serdar; Dural, Muhammet; Mert, Gurbet Özge; Özakin, Engin

2017-06-01

Bodybuilder-type workouts may affect heart rate variability (HRV), which has considerable potential to assess the role of autonomic nervous system (ANS). A scientifically designed approach is necessary for bodybuilders to achieve better results while protecting their health. In this study, we aimed to investigate HRV parameters in bodybuilders compared to healthy control subjects and effects of creatine supplementation. A total of 48 male participants (16 controls, 16 supplement (-), 16 supplement (+)) were evaluated in our study. Bodybuilders who were taking creatine supplementation were enrolled in supplement (+) group. HRV parameters were measured from 24-hour Holter recordings of all participants. When mean heart rates were compared with control group (71.5 ± 12.6 beats/min), statistically significant difference was revealed in supplement (-) group (61.8 ± 6.8 beats/min; P = 0.022) unlike supplement (+) group (69.63 ± 14.1 beats/min; P = 0.650). HRV analyses revealed significant parasympathetic shift in supplement (-) group. No significant difference was demonstrated on HRV parameters, except high frequency (P = 0.029) in supplement (+) group. Conclusively, elevated parasympathetic modulation, which is favorable cardiovascular outcome of exercise, was demonstrated in bodybuilders. However, our study also revealed that creatine supplementation attenuates this favorable effect in ANS by limiting elevation of parasympathetic modulation. Although the sympathetic slight shift is attributed to creatine supplementation, it cannot be discriminated from the effects of over training. © 2017 Wiley Periodicals, Inc.

Individual and combined effects of in-ovo injection of creatine monohydrate and glucose on somatic characteristics, energy status, and posthatch performance of broiler embryos and hatchlings.

PubMed

Zhang, L; Zhu, X D; Wang, X F; Li, J L; Gao, F; Zhou, G H

2016-10-01

Two trials were conducted to investigate the individual and combined effects of in-ovo injection of creatine monohydrate ( CMH: ) and glucose on the somatic characteristics and energy status of broiler embryos and hatchlings and the growth performance of chicks during the first wk posthatch. In trial 1, 550 17.5-day-old living, fertile eggs were randomly assigned to 1 of 5 treatment groups, including 1) a noninjected control, 2) a 0.4 mL diluent-injected control, or 0.4 mL diluents containing 3) 6 mg CMH, 4) 25 mg glucose, or 5) a combination of 6 mg CMH and 25 mg glucose (identified as CMH+G: ). In trial 2, after hatch, 48 hatchlings with individual body weight ( BW: ) close to the average BW of their incubation group were randomly selected and placed in 6 replicates of 8 birds each to evaluate their growth performance during the first wk posthatch. Compared with the noninjected and the 0.4-mL diluent-injected control groups, individual injection of CMH or glucose did not affect the hatching time, hatchability, somatic characteristics, or concentrations of glycogen and glucose in the liver and pectoralis major ( PM: ) muscle, although injection of CMH increased (P < 0.05) concentrations of creatine ( CR: ) and phosphocreatine ( PCR: ) in the PM muscle on d 19 of incubation (E19.5). However, the CMH+G treatment increased (P < 0.05) BW relative to set egg weight ( SEW: ) on E19.5, as well as residual yolk sac weight on the day of hatch. Moreover, the CMH+G treatment also increased (P < 0.05) concentrations of glycogen and glucose in the liver and concentrations of Cr and PCr in the PM muscle on E19.5. Chicks in the CMH+G group also exhibited higher BW gain during the first wk than controls (P < 0.05). These results indicate that combined injection of CMH and glucose during the last stage of incubation have a synergistic effect on improvement of the energy status of embryos and hatchlings, which is useful for enhancing embryo development, and subsequently improving chick growth during the early posthatch stages. © 2016 Poultry Science Association Inc.

Creatine supplementation during pulmonary rehabilitation in chronic obstructive pulmonary disease

PubMed Central

Fuld, J; Kilduff, L; Neder, J; Pitsiladis, Y; Lean, M; Ward, S; Cotton, M

2005-01-01

Background: Skeletal muscle wasting and dysfunction are strong independent predictors of mortality in patients with chronic obstructive pulmonary disease (COPD). Creatine nutritional supplementation produces increased muscle mass and exercise performance in health. A controlled study was performed to look for similar effects in 38 patients with COPD. Methods: Thirty eight patients with COPD (mean (SD) forced expiratory volume in 1 second (FEV1) 46 (15)% predicted) were randomised to receive placebo (glucose polymer 40.7 g) or creatine (creatine monohydrate 5.7 g, glucose 35 g) supplements in a double blind trial. After 2 weeks loading (one dose three times daily), patients participated in an outpatient pulmonary rehabilitation programme combined with maintenance (once daily) supplementation. Pulmonary function, body composition, and exercise performance (peripheral muscle strength and endurance, shuttle walking, cycle ergometry) took place at baseline (n = 38), post loading (n = 36), and post rehabilitation (n = 25). Results: No difference was found in whole body exercise performance between the groups: for example, incremental shuttle walk distance mean –23.1 m (95% CI –71.7 to 25.5) post loading and –21.5 m (95% CI –90.6 to 47.7) post rehabilitation. Creatine increased fat-free mass by 1.09 kg (95% CI 0.43 to 1.74) post loading and 1.62 kg (95% CI 0.47 to 2.77) post rehabilitation. Peripheral muscle performance improved: knee extensor strength 4.2 N.m (95% CI 1.4 to 7.1) and endurance 411.1 J (95% CI 129.9 to 692.4) post loading, knee extensor strength 7.3 N.m (95% CI 0.69 to 13.92) and endurance 854.3 J (95% CI 131.3 to 1577.4) post rehabilitation. Creatine improved health status between baseline and post rehabilitation (St George's Respiratory Questionnaire total score –7.7 (95% CI –14.9 to –0.5)). Conclusions: Creatine supplementation led to increases in fat-free mass, peripheral muscle strength and endurance, health status, but not exercise capacity. Creatine may constitute a new ergogenic treatment in COPD. PMID:15994258

Long and short echo time proton magnetic resonance spectroscopic imaging of the healthy aging brain.

PubMed

McIntyre, Dominick J O; Charlton, Rebecca A; Markus, Hugh S; Howe, Franklyn A

2007-12-01

To investigate the relationship between subject age and white matter brain metabolite concentrations and R(2) relaxation rates in a cross-sectional study of human brain. Long- and short-echo proton spectroscopic imaging were used to investigate concentrations and R2 relaxation rates of N-acetyl aspartate (NAA) + N-acetyl aspartyl glutamate (NAAG), choline (Cho), creatine (Cr), and myoinositol (mI) in the white matter of the centrum semiovale of 106 healthy volunteers aged 50-90 years; usable data were obtained from 79 subjects. A major aim was to identify which parameters were most sensitive to changes with age. Spectra were analyzed using the LCModel method. The apparent R2 of NAA and the LCModel concentration of Cr at short echo time were significantly correlated with age after multiplicity correction. Large lipid resonances were observed in the brain midline of some subjects, the incidence increasing significantly with age. We believe this to result from lipid deposits in the falx cerebri. Since only short-echo spectroscopy showed a robust relationship between Cr and subject age, and detects more metabolites than long echo time, we conclude that short-echo is superior to long-echo for future aging studies. Future studies could usefully determine whether the Cr-age relationship is due to changes in concentration, T1, or both. (c) 2007 Wiley-Liss, Inc.

Myo-inositol metabolism in appropriately grown and growth-restricted fetuses: a proton magnetic resonance spectroscopy study.

PubMed

Story, Lisa; Damodaram, Mellisa S; Supramaniam, Veena; Allsop, Joanna M; Mcguinness, Amy; Patel, Abhilasha; Wylezinska, Marzena; Kumar, Sailesh; Rutherford, Mary A

2013-09-01

Myo-inositol (Myo-ins) is a marker of neuroglial cells, being present in the astrocytes of brain tissue, but also functions as an osmolyte. Numbers of astrocytes are known to increase following injury to the brain. Growth-restricted fetuses are at increased risk of later neurodevelopmental impairments even in the absence of overt lesions and despite preserved/increased cerebral blood flow. This study aims to investigate brain Myo-ins metabolism in fetuses with intrauterine growth restriction (IUGR) and evidence of cerebral redistribution using magnetic resonance spectroscopy (MRS) at a short echo time. Biometry and Doppler assessment of blood flow was assessed using ultrasound in 28 fetuses with IUGR and 47 appropriately grown control subjects. MRI was used to exclude overt brain injury. Proton magnetic resonance spectroscopy of the fetal brain was then performed at an echo time of 42 ms to examine the Myo-ins:Choline (Cho), Myo-ins:Creatine (Cr) and Cho:Cr ratios. No alterations in brain Myo-ins:Cho, Myo-ins:Cr or Cho:Cr ratios were detected between appropriately grown and growth restricted fetuses. IUGR is not associated with a measureable difference in brain myo-inositol ratios. This may be due to the protective effects of preserved cerebral blood flow in growth restriction and comparable astrocyte numbers when compared to controls. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Reduced NAA-levels in the NAWM of patients with MS is a feature of progression. A study with quantitative magnetic resonance spectroscopy at 3 Tesla.

PubMed

Aboul-Enein, Fahmy; Krssák, Martin; Höftberger, Romana; Prayer, Daniela; Kristoferitsch, Wolfgang

2010-07-20

Reduced N-acetyl-aspartate (NAA) levels in magnetic resonance spectroscopy (MRS) may visualize axonal damage even in the normal appearing white matter (NAWM). Demyelination and axonal degeneration are a hallmark in multiple sclerosis (MS). To define the extent of axonal degeneration in the NAWM in the remote from focal lesions in patients with relapsing-remitting (RRMS) and secondary progressive MS (SPMS). 37 patients with clinical definite MS (27 with RRMS, 10 with SPMS) and 8 controls were included. We used 2D (1)H-MR-chemical shift imaging (TR = 1500ms, TE = 135ms, nominal resolution 1ccm) operating at 3Tesla to assess the metabolic pattern in the fronto-parietal NAWM. Ratios of NAA to creatine (Cr) and choline (Cho) and absolute concentrations of the metabolites in the NAWM were measured in each voxel matching exclusively white matter on the anatomical T2 weighted MR images. No significant difference of absolute concentrations for NAA, Cr and Cho or metabolite ratios were found between RRMS and controls. In SPMS, the NAA/Cr ratio and absolute concentrations for NAA and Cr were significantly reduced compared to RRMS and to controls. In our study SPMS patients, but not RRMS patients were characterized by low NAA levels. Reduced NAA-levels in the NAWM of patients with MS is a feature of progression.

Relationship between opioid therapy, tissue-damaging procedures, and brain metabolites as measured by proton MRS in asphyxiated term neonates.

PubMed

Angeles, Danilyn M; Ashwal, Stephen; Wycliffe, Nathaniel D; Ebner, Charlotte; Fayard, Elba; Sowers, Lawrence; Holshouser, Barbara A

2007-05-01

To examine the effects of opioid and tissue-damaging procedures (TDPs) [i.e. procedures performed in the neonatal intensive care unit (NICU) known to result in pain, stress, and tissue damage] on brain metabolites, we reviewed the medical records of 28 asphyxiated term neonates (eight opioid-treated, 20 non-opioid treated) who had undergone magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) within the first month of life as well as eight newborns with no clinical findings of asphyxial injury. We found that lower creatine (Cr), myoinositol (Ins), and N-acetylaspartate (NAA)/choline (Cho) (p < or = 0.03) and higher Cho/Cr and glutamate/glutamine (Glx) Cr (p < or = 0.02) correlated with increased TDP incidence in the first 2 d of life (DOL). We also found that occipital gray matter (OGM) NAA/Cr was decreased (p = 0.03) and lactate (Lac) was present in a significantly higher amount (40%; p = 0.03) in non-opioid-treated neonates compared with opioid-treated neonates. Compared with controls, untreated neonates showed larger changes in more metabolites in basal ganglia (BG), thalami (TH), and OGM with greater significance than treated neonates. Our data suggest that TDPs affect spectral metabolites and that opioids do not cause harm in asphyxiated term neonates exposed to repetitive TDPs in the first 2-4 DOL and may provide a degree of neuroprotection.

Validation of an electrothermal atomization atomic absorption spectrometry method for quantification of total chromium and chromium(VI) in wild mushrooms and underlying soils.

PubMed

Figueiredo, Estela; Soares, M Elisa; Baptista, Paula; Castro, Marisa; Bastos, M Lourdes

2007-08-22

An ETAAS method was validated to quantify total Cr and Cr(VI) in mushrooms and the underlying soils. The method includes a sample pretreatment for total Cr dissolution using a wet acid digestion procedure and a selective alkaline extraction for Cr(VI). The limits of detection were, expressed in microg/L, 0.15 and 0.17 for total Cr and Cr(VI), respectively. The linearity ranges under the optimized conditions were 0.15-25.0 and 0.17-20.0 microg/L for total Cr and Cr(VI), respectively. The limits of quantification were, expressed in microg/g of dry weight, 0.0163 and 0.0085 for total and hexavalent chromium, respectively. The precision of the instrumental method for total Cr and Cr(VI) was lower than 1.6%, and for the analytical method, it was lower than 10%. The accuracy of the method for Cr(VI) quantification was evaluated by the standard additions method, with the recoveries being higher than 90% for all of the added concentrations. For total Cr, certified reference materials (lichen CRM 482 and soil sample NCS ZC73001) were used. An interference study was also carried out in a mushroom simulated matrix, and it was verified that the deviations of the expected values were lower than 4.0% for both total Cr and Cr(VI). The validated method was applied to the evaluation of total Cr and Cr(VI) in 34 wild mushrooms and 34 respective underlying soil samples collected in two different regions of Portugal (Beira Interior and TrAs-os-Montes), with different locations regarded as noncontaminated or contaminated areas. The species were identified by a mycologist and subdivided into 10 genera and 15 species: Amanita (rubescens, muscaria, and ponderosa), Boletus (regius), Lactarius (deliciosus, vellereus, and piperatus), Suillus (granulatus and luteus), Tricholoma (acerbum), Agaricus (sylvicola), Volvariella (gloiocephala), Lecopaxillus (giganteus), Macrolepiota (procera), and Psilocybe (fascicularis). The mean values found for total Cr were 1.14 and 1.11 microg/g of dry weight, and for Cr(VI), the mean values were 0.103 and 0.143 microg/g of dry weight for cap and stalk, respectively. For soils, the mean concentrations found were, for total Cr, 84.0 microg/g and, for Cr(VI), 0.483 microg/g. The bioconcentration factors (BCFs) based on dry weight for cap and stalk were determined, and the values found, for both total Cr and Cr(VI), were always <1, although for hexavalent chromium, the BCFs were 10 times higher than for total chromium.

Creatine co-ingestion with carbohydrate or cinnamon extract provides no added benefit to anaerobic performance.

PubMed

Islam, Hashim; Yorgason, Nick J; Hazell, Tom J

2016-09-01

The insulin response following carbohydrate ingestion enhances creatine transport into muscle. Cinnamon extract is promoted to have insulin-like effects, therefore this study examined if creatine co-ingestion with carbohydrates or cinnamon extract improved anaerobic capacity, muscular strength, and muscular endurance. Active young males (n = 25; 23.7 ± 2.5 y) were stratified into 3 groups: (1) creatine only (CRE); (2) creatine+ 70 g carbohydrate (CHO); or (3) creatine+ 500 mg cinnamon extract (CIN), based on anaerobic capacity (peak power·kg(-1)) and muscular strength at baseline. Three weeks of supplementation consisted of a 5 d loading phase (20 g/d) and a 16 d maintenance phase (5 g/d). Pre- and post-supplementation measures included a 30-s Wingate and a 30-s maximal running test (on a self-propelled treadmill) for anaerobic capacity. Muscular strength was measured as the one-repetition maximum 1-RM for chest, back, quadriceps, hamstrings, and leg press. Additional sets of the number of repetitions performed at 60% 1-RM until fatigue measured muscular endurance. All three groups significantly improved Wingate relative peak power (CRE: 15.4% P = .004; CHO: 14.6% P = .004; CIN: 15.7%, P = .003), and muscular strength for chest (CRE: 6.6% P < .001; CHO: 6.7% P < .001; CIN: 6.4% P < .001), back (CRE: 5.8% P < .001; CHO: 6.4% P < .001; CIN: 8.1% P < .001), and leg press (CRE: 11.7% P = .013; CHO: 10.0% P = .007; CIN: 17.3% P < .001). Only the CRE (10.4%, P = .021) and CIN (15.5%, P < .001) group improved total muscular endurance. No differences existed between groups post-supplementation. These findings demonstrate that three different methods of creatine ingestion lead to similar changes in anaerobic power, strength, and endurance.

The acute effect of beta-guanidinopropionic acid versus creatine or placebo in healthy men (ABC Trial): study protocol for a randomized controlled trial.

PubMed

Karamat, Fares A; Horjus, Deborah L; Haan, Yentl C; van der Woude, Lisa; Oudman, Inge; van Montfrans, Gert A; Clark, Joseph F; Brewster, Lizzy M

2015-02-22

Despite adequate treatment, up to 30% of treated antihypertensive patients with primary, uncomplicated hypertension remain uncontrolled. We proposed that high intracellular activity of the ATP regenerating enzyme creatine kinase (CK) increases pressor responses and hypertension risk. In line with this, we found that plasma CK activity after rest, a surrogate measure of tissue activity, is the main predictor of blood pressure levels and failure of antihypertensive therapy in the general population. In addition, the creatine analog and competitive oral creatine kinase inhibitor beta-guanidinopropionic acid effectively and safely reduced blood pressure in the spontaneously hypertensive rat. However, to our knowledge there are no human data on the safety of oral supplementation with this substance. Therefore, we will assess the tolerability of beta-guanidinopropionic acid in men, compared to creatine and placebo. This is a randomized, active and placebo controlled, triple blind, double dummy, single center clinical intervention trial in 24 healthy male volunteers, 18 to 50 years old, recruited in the Netherlands. The intervention consists of one week of daily oral administration of beta-guanidinopropionic acid 100 mg, creatine 5 gram, or placebo. The primary outcome is the tolerability of beta-guanidinopropionic acid as a descriptive measure, in an intent-to-treat analysis. Other outcomes include the placebo-adjusted differences with baseline in biochemical and hemodynamic parameters, including plasma markers of muscle tissue damage, urine sodium excretion, resting sitting systolic and diastolic brachial blood pressure, supine systolic and diastolic central blood pressure, pulse wave velocity and augmentation index, heart rate, cardiac contractility, cardiac output, and total peripheral resistance. There is an unfulfilled need for new conservative options to treat resistant hypertension. This study will provide first-in-men data on creatine kinase inhibition as a potential new class of antihypertensive drugs. The Netherlands National Trial Register Trialregister.nl (identifier NTR 4444) , registered 9 March 2014.

Creatine biosynthesis and transport in health and disease.

PubMed

Joncquel-Chevalier Curt, Marie; Voicu, Pia-Manuela; Fontaine, Monique; Dessein, Anne-Frédérique; Porchet, Nicole; Mention-Mulliez, Karine; Dobbelaere, Dries; Soto-Ares, Gustavo; Cheillan, David; Vamecq, Joseph

2015-12-01

Creatine is physiologically provided equally by diet and by endogenous synthesis from arginine and glycine with successive involvements of arginine glycine amidinotransferase [AGAT] and guanidinoacetate methyl transferase [GAMT]. A specific plasma membrane transporter, creatine transporter [CRTR] (SLC6A8), further enables cells to incorporate creatine and through uptake of its precursor, guanidinoacetate, also directly contributes to creatine biosynthesis. Breakthrough in the role of creatine has arisen from studies on creatine deficiency disorders. Primary creatine disorders are inherited as autosomal recessive (mutations affecting GATM [for glycine-amidinotransferase, mitochondrial]) and GAMT genes) or X-linked (SLC6A8 gene) traits. They have highlighted the role of creatine in brain functions altered in patients (global developmental delay, intellectual disability, behavioral disorders). Creatine modulates GABAergic and glutamatergic cerebral pathways, presynaptic CRTR (SLC6A8) ensuring re-uptake of synaptic creatine. Secondary creatine disorders, addressing other genes, have stressed the extraordinary imbrication of creatine metabolism with many other cellular pathways. This high dependence on multiple pathways supports creatine as a cellular sensor, to cell methylation and energy status. Creatine biosynthesis consumes 40% of methyl groups produced as S-adenosylmethionine, and creatine uptake is controlled by AMP activated protein kinase, a ubiquitous sensor of energy depletion. Today, creatine is considered as a potential sensor of cell methylation and energy status, a neurotransmitter influencing key (GABAergic and glutamatergic) CNS neurotransmission, therapeutic agent with anaplerotic properties (towards creatine kinases [creatine-creatine phosphate cycle] and creatine neurotransmission), energetic and antioxidant compound (benefits in degenerative diseases through protection against energy depletion and oxidant species) with osmolyte behavior (retention of water by muscle). This review encompasses all these aspects by providing an illustrated metabolic account for brain and body creatine in health and disease, an algorithm to diagnose metabolic and gene bases of primary and secondary creatine deficiencies, and a metabolic exploration by (1)H-MRS assessment of cerebral creatine levels and response to therapeutic measures. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Creatine Supplementation and Anterior Compartment Pressure During Exercise in the Heat in Dehydrated Men

PubMed Central

Hile, Amy M; Anderson, Jeffrey M; Fiala, Kelly A; Stevenson, J. Herb; Casa, Douglas J; Maresh, Carl M

2006-01-01

Context: Theoretically, the risk of compartment syndrome is increased during creatine monohydrate (CrM) supplementation because of intracellular fluid retention in muscle cells and the overall increased size of the muscle tissue. Whether this change in intracellular fluid is associated with an increase in anterior compartment pressure in the lower leg when subjects are under thermal stress is unknown. Objective: To assess the influence of CrM on the resting and postexercise anterior compartment pressure of the lower leg in mildly to moderately dehydrated males exercising in the heat. Design: Double-blind, randomized, crossover design. Setting: Human Performance Laboratory. Patients or Other Participants: Eleven well-trained, non– heat-acclimated, healthy males (age = 22 ± 2 years, height = 181.1 ± 7 cm, mass = 78.4 ± 4.2 kg, V̇o2max = 50.5 ± 3.4 mL·kg−1·min−1). Intervention(s): Subjects were supplemented with 21.6 g/d of CrM or placebo for 7 days. On day 7, they performed 2 hours of submaximal exercise, alternating 30 minutes of walking with 30 minutes of cycling in the heat, resulting in approximately 2% dehydration. This was followed by an 80-minute heat tolerance test (temperature = 33.5 ± 0.5°C, humidity = 41.0 ± 12%), which included 12 repetitions of a 3-minute walk (pace = 4.0 ± 0.1 miles/h, intensity = 37.1 ± 6.1% V̇o2max) alternating with a 1-minute, high-intensity run (pace = 11.8 ± 0.4 miles/h, intensity = 115.0 ± 5.6% V̇o2max), resulting in an additional 2% decrease in body weight. Main Outcome Measures: Before supplementation and on day 7 of supplementation, anterior compartment pressure was measured at rest, after dehydration, and at 1, 3, 5, 10, 15, and 60 minutes after the heat tolerance test. Analysis of variance with repeated measures was calculated to compare differences within the trials and time points and to identify any interaction between trial and time. Results: The CrM intake was associated with an increase in body weight (P < .05). A moderate effect size was noted for compartment pressures between the trials for the differences between predehydration and postdehydration (η2 = 0.414). This effect diminished substantially by 3 minutes after the heat tolerance test. Compared with the placebo trial, the change in anterior compartment pressure from rest to dehydration was greater, as was the change from rest to 1 minute after the heat tolerance test (P < .05) during the CrM trial. Conclusions: A 7-day loading dose of CrM increased anterior compartment pressures after dehydration and immediately after the heat tolerance tests, but the changes did not induce symptoms and the pressure changes were transient. PMID:16619092

Disrupted metabolic and functional connectivity patterns of the posterior cingulate cortex in cirrhotic patients: a study combining magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging.

PubMed

Lu, Li; Wang, Junpeng; Zhang, Longjiang; Zhang, Zhiqiang; Ni, Ling; Qi, Rongfeng; Kong, Xiang; Lu, Mengjie; Sami, Muhammad U; Xu, Kai; Lu, Guangming

2018-06-26

The association between metabolic activity and functional coupling of the posterior cingulate cortex (PCC) in cirrhotic patients remains undefined. Therefore, this study aimed to assess the association of functional coupling with metabolic patterns of PCC in resting cirrhotic patients. Twenty-six cirrhotic patients, including 10 with hepatic encephalopathy (HE) and 16 without HE, were assessed, alongside 21 control participants. Single-voxel proton magnetic resonance spectroscopy (MRS) of the PCC and resting-state functional MRI (rs-fMRI) were performed on a 3.0-T MR scanner. The ratios of all metabolites to creatine (Cr) and rs-fMRI parameters [including amplitude of low-frequency fluctuation (ALFF), node degree (Ki), and betweenness centrality (Bi)] were evaluated by analysis of variance. Associations of metabolite ratios with rs-fMRI parameters and venous ammonia were determined by Pearson's correlation analysis. Lower chlorine (Cho)/Cr (0.6±0.2 vs. 0.9±0.1, P<0.001) and higher ALFF (1.3±0.5 vs. 1.1±0.3, P=0.01) were found in cirrhotic patients in comparison with controls. In cirrhotic patients, the ALFF values correlated negatively with Cho/Cr (r=-0.397, P=0.044). Meanwhile, Bi values showed positive associations with glutamine+glutamate/Cr (r=0.500, P=0.009) and N-acetyl aspartate/Cr (r=0.581, P=0.006). In the HE subgroup, Ki correlated positively with Cho/Cr (r=0.867, P=0.001). In cirrhotic patients without HE, Bi values showed a high positive correlation with glutamate+glutamine/Cr (r=0.690, P=0.013). These findings suggest a close association between metabolic activity and functional coupling of the PCC in cirrhotic patients, especially those with HE, whose node degree of the PCC shows an overt positive correlation with Cho/Cr.

Proton magnetic resonance spectroscopy in ecstasy (MDMA) users.

PubMed

Daumann, Jörg; Fischermann, Thomas; Pilatus, Ulrich; Thron, Armin; Moeller-Hartmann, Walter; Gouzoulis-Mayfrank, Euphrosyne

2004-05-20

The popular recreational drug 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has well-recognized neurotoxic effects upon central serotonergic systems in animal studies. In humans, the use of MDMA has been linked to cognitive problems, particularly to deficits in long-term memory and learning. Recent studies with proton magnetic resonance spectroscopy (1H MRS) have reported relatively low levels of the neuronal marker N-acetylaspartate (NAA) in MDMA users, however, these results have been ambiguous. Moreover, the only available 1H MRS study of the hippocampus reported normal findings in a small sample of five MDMA users. In the present study, we compared 13 polyvalent ecstasy users with 13 matched controls. We found no differences between the NAA/creatine/phosphocreatine (Cr) ratios of users and controls in neocortical regions, and only a tendency towards lower NAA/Cr ratios in the left hippocampus of MDMA users. Thus, compared with cognitive deficits, 1H MRS appears to be a less sensitive marker of potential neurotoxic damage in ecstasy users. Copyright 2004 Elsevier Ireland Ltd.

Impaired cardiac contractile function in arginine:glycine amidinotransferase knockout mice devoid of creatine is rescued by homoarginine but not creatine

PubMed Central

Faller, Kiterie M E; Atzler, Dorothee; McAndrew, Debra J; Zervou, Sevasti; Whittington, Hannah J; Simon, Jillian N; Aksentijevic, Dunja; ten Hove, Michiel; Choe, Chi-un; Isbrandt, Dirk; Casadei, Barbara; Schneider, Jurgen E; Neubauer, Stefan; Lygate, Craig A

2018-01-01

Abstract Aims Creatine buffers cellular adenosine triphosphate (ATP) via the creatine kinase reaction. Creatine levels are reduced in heart failure, but their contribution to pathophysiology is unclear. Arginine:glycine amidinotransferase (AGAT) in the kidney catalyses both the first step in creatine biosynthesis as well as homoarginine (HA) synthesis. AGAT-/- mice fed a creatine-free diet have a whole body creatine-deficiency. We hypothesized that AGAT-/- mice would develop cardiac dysfunction and rescue by dietary creatine would imply causality. Methods and results Withdrawal of dietary creatine in AGAT-/- mice provided an estimate of myocardial creatine efflux of ∼2.7%/day; however, in vivo cardiac function was maintained despite low levels of myocardial creatine. Using AGAT-/- mice naïve to dietary creatine we confirmed absence of phosphocreatine in the heart, but crucially, ATP levels were unchanged. Potential compensatory adaptations were absent, AMPK was not activated and respiration in isolated mitochondria was normal. AGAT-/- mice had rescuable changes in body water and organ weights suggesting a role for creatine as a compatible osmolyte. Creatine-naïve AGAT-/- mice had haemodynamic impairment with low LV systolic pressure and reduced inotropy, lusitropy, and contractile reserve. Creatine supplementation only corrected systolic pressure despite normalization of myocardial creatine. AGAT-/- mice had low plasma HA and supplementation completely rescued all other haemodynamic parameters. Contractile dysfunction in AGAT-/- was confirmed in Langendorff perfused hearts and in creatine-replete isolated cardiomyocytes, indicating that HA is necessary for normal cardiac function. Conclusions Our findings argue against low myocardial creatine per se as a major contributor to cardiac dysfunction. Conversely, we show that HA deficiency can impair cardiac function, which may explain why low HA is an independent risk factor for multiple cardiovascular diseases. PMID:29236952

Amino acid metabolic processes in the temporal lobes assessed by proton magnetic resonance spectroscopy (1H MRS) in children with Down syndrome.

PubMed

Śmigielska-Kuzia, Joanna; Boćkowski, Leszek; Sobaniec, Wojciech; Kułak, Wojciech; Sendrowski, Krzysztof

2010-01-01

Down syndrome (DS), or trisomy 21, is one of the most common autosomal mutations. The overexpression of the β-amyloid precursor protein gene, located on chromosome 21, causes an increased production of the specific amyloid. The current study is a continuation of our earlier investigations relating to the profile of metabolic changes in the frontal lobes of DS patients as assessed by proton magnetic resonance spectroscopy ((1)H MRS). The aims of the study were the morphological assessment of the brain using magnetic resonance imaging (MRI) and the evaluation of metabolic disorders of the temporal lobes using (1)H MRS in DS children. The study group included 20 children with DS aged 3-15 years and treated in the Department of Pediatric Neurology and Rehabilitation, Medical University of Białystok. The control group included healthy children (n = 20). MRI scans of the heads of DS children were performed using a 1.5 T MR scanner under standard conditions. (1)H MRS investigations were also carried out to assess metabolic changes in the temporal lobes. Metabolites, such as N-acetylaspartate (NAA), glutamate-glutamine complex (Glx), choline (Cho), myoinositol (mI) and γ-aminobutyric acid (GABA), were determined in both temporal lobes with reference to the internal marker creatine (Cr). Results were compared with the control group.We found a statistically significant decrease in NAA/Cr, Cho/Cr, mI/Cr and GABA/Cr ratios. The Glx/Cr ratio in both temporal lobes of DS patients did not differ from the control group. Our results indicate metabolic neurotransmitter disorders in the central nervous system in children with DS.

Serum creatinine and cystatin C provide conflicting evidence of acute kidney injury following acute ingestion of potassium permanganate and oxalic acid.

PubMed

Wijerathna, Thilini Madushanka; Gawarammana, Indika Bandara; Dissanayaka, Dhammika Menike; Palanagasinghe, Chathura; Shihana, Fathima; Dassanayaka, Gihani; Shahmy, Seyed; Endre, Zoltan Huba; Mohamed, Fahim; Buckley, Nicholas Alan

2017-11-01

Acute kidney injury (AKI) is common following deliberate self-poisoning with a combination washing powder containing oxalic acid (H 2 C 2 O 4 ) and potassium permanganate (KMnO 4 ). Early and rapid increases in serum creatinine (sCr) follow severe poisoning. We investigated the relationship of these increases with direct nephrotoxicity in an ongoing multicenter prospective cohort study in Sri Lanka exploring AKI following poisoning. Multiple measures of change in kidney function were evaluated in 48 consenting patients who had serial sCr and serum cystatin C (sCysC) data available. Thirty-eight (38/48, 79%) patients developed AKI (AKIN criteria). Twenty-eight (58%) had AKIN stage 2 or 3. Initial increases in urine creatinine (uCr) excretion were followed by a substantial loss of renal function. The AKIN stage 2 and 3 (AKIN2/3) group had very rapid rises in sCr (a median of 118% at 24 h and by 400% at 72 h post ingestion). We excluded the possibility that the rapid rise resulted from the assay used or muscle damage. In contrast, the average sCysC increase was 65% by 72 h. In most AKI, sCysC increases to the same extent but more rapidly than sCr, as sCysC has a shorter half-life. This suggests either a reduction in Cystatin C production or, conversely, that the rapid early rise of sCr results from increased production of creatine and creatinine to meet energy demands following severe oxidative stress mediated by H 2 C 2 O 4 and KMnO 4 . Increased early creatinine excretion supports the latter explanation, since creatinine excretion usually decreases transiently in AKIN2/3 from other causes.

Postictal in situ MRS brain lactate in the rat kindling model.

PubMed

Maton, B M; Najm, I M; Wang, Y; Lüders, H O; Ng, T C

1999-12-10

To determine the temporal and spatial extent of the lactate (Lact) changes as correlated with seizure characteristics and EEG changes in the rat kindling model. Prior studies using MRS have detected cerebral Lact postictally in animal models of seizures and in patients with intractable focal epilepsy. We performed MRS in sham control rats (n = 4) and in rats stimulated in the right hippocampus at two different stages of the kindling and at three time points after the seizures: <2 hours (n = 8 and 5, stage 0 and stage 5), 2 to 3 hours (n = 5 and 6), and >3 hours (n = 4 and 2). Lact/creatine (Cr) and N-acetylaspartate (NAA)/Cr ratios were measured in six contiguous voxels (three left, three right) covering the hippocampi, anterior and posterior regions, and compared with EEG and ictal behavior. Lact/Cr ratios were measured at a very low level in the sham control rats and in the >3-hour group. In the <2-hour group, Lact/Cr increase was higher in stage-5 rats as compared with stage-0 rats (p = 0.001, unpaired t-test) and sham control rats when all the voxels were considered. Lact/Cr ratios were higher in the stimulated area as compared with all other brain areas in stage-0 rats (p = 0.05, paired t-test) but not in the stage-5 rats. Similar results with more inter-animal variability were measured in the 2- to 3-hour group. NAA/Cr ratios increased significantly after stage-0 kindling in the stimulated hippocampus but not after stage-5 kindling. Postictal Lact increase as assayed by MRS correlates with EEG and behavioral seizures and suggests that it would be an additional noninvasive technique for seizure localization during the presurgical evaluation of patients with intractable focal epilepsy.

Effects of fluoxetine on the amygdala and the hippocampus after administration of a single prolonged stress to male Wistar rates: In vivo proton magnetic resonance spectroscopy findings.

PubMed

Han, Fang; Xiao, Bing; Wen, Lili; Shi, Yuxiu

2015-05-30

Posttraumatic stress disorder (PTSD) is an anxiety- and memory-based disorder. The hippocampus and amygdala are key areas in mood regulation. Fluoxetine was found to improve the anxiety-related symptoms of PTSD patients. However, little work has directly examined the effects of fluoxetine on the hippocampus and the amygdala. In the present study, male Wistar rats received fluoxetine or vehicle after exposure to a single prolonged stress (SPS), an animal model of PTSD. In vivo proton magnetic resonance spectroscopy ((1)H-MRS) was performed -1, 1, 4, 7 and 14 days after SPS to examine the effects of fluoxetine on neurometabolite changes in amygdala, hippocampus and thalamus. SPS increased the N-acetylaspartate (NAA)/creatine (Cr) and choline moieties (Cho)/Cr ratios in the bilateral amygdala on day 4, decreased the NAA/Cr ratio in the left hippocampus on day 1, and increased both ratios in the right hippocampus on day 14. But no significant change was found in the thalamus. Fluoxetine treatment corrected the SPS increases in the NAA/Cr and Cho/Cr levels in the amygdala on day 4 and in the hippocampus on day 14, but it failed to normalise SPS-associated decreases in NAA/Cr levels in the left hippocampus on day 1. These results suggested that metabolic abnormalities in the amygdala and the hippocampus were involved in SPS, and different effects of fluoxetine in correcting SPS-induced neurometabolite changes among the three areas. These findings have implications for fluoxetine treatment in PTSD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Whole Body Creatine and Protein Kinetics in Healthy Men and Women: Effects of creatine and amino acid supplementation

PubMed Central

Kalhan, Satish C; Gruca, Lourdes; Marczewski, Susan; Bennett, Carole; Kummitha, China

2015-01-01

Creatine kinetics were measured in young healthy subjects, eight males and seven females, age 20–30 years, after an overnight fast on creatine free diet. Whole body turnover of glycine and its appearance in creatine was quantified using [1-13C] glycine and the rate of protein turnover was quantified using L-ring [2H5] phenylalanine. The creatine pool size was estimated by the dilution of a bolus [C2H3] creatine. Studies were repeated following a five days supplement creatine 21g.day−1 and following supplement amino acids 14.3 g.day−1. Creatine caused a ten folds increase in the plasma concentration of creatine and a 50% decrease in the concentration of guanidinoacetic acid. Plasma amino acids profile showed a significant decrease in glycine, glutamine and taurine and a significant increase in citrulline, valine, lysine and cysteine. There was a significant decrease in the rate of appearance of glycine, suggesting a decrease in de-novo synthesis (p=0.006). The fractional and absolute rate of synthesis of creatine was significantly decreased by supplemental creatine. Amino acid supplement had no impact on any of the parameters. Creatine supplement caused a significant decrease in the rate of synthesis of creatine. This is the first detailed analysis of creatine kinetics and the effects of creatine supplement in healthy young men and women. These methods can be applied for the analysis of creatine kinetics in different physiological states. PMID:26480831

A new method to synthesize creatine derivatives.

PubMed

Garbati, Patrizia; Salis, Annalisa; Adriano, Enrico; Galatini, Andrea; Damonte, Gianluca; Balestrino, Maurizio; Millo, Enrico

2013-10-01

Creatine is an amino acid that has a pivotal role in energy metabolism of cells. Creatine acts as an "ATP shuttle", carrying ATP to the sites where it is utilized, through its reversible phosphorylation by creatine kinase. Moreover, the creatine-phosphocreatine system delays ATP depletion during anoxia or ischemia, thus exerting a neuroprotective role during those pathological conditions. Thus, its administration has been advocated as a treatment or prevention of several conditions involving the central nervous system. However, creatine crosses poorly the blood-brain barrier and the cell plasma membrane, thus its administration has but a limited effect. The use of more lipophilic creatine derivatives has thus been suggested. However, such a synthesis is complicated by the intrinsic characteristics of the creatine molecule that hardly reacts with other molecules and easily cyclizes to creatinine. We obtained amide derivatives from creatine starting from a new protected creatine molecule synthesized by us, the so-called (Boc)2-creatine. We used a temporary protection only on the creatine guanidine group while allowing a good reactivity on the carboxylic group. This temporary protection ensured efficient creatine dissolution in organic solvents and offered simultaneous protection of creatine toward intramolecular cyclization to creatinine. In this manner, it was possible to selectively conjugate molecules on the carboxylic group. The creatine guanidine group was easily released from the protection at the end of the reaction, thus obtaining the desired creatine derivative.

Primary granulomatous angiitis of the central nervous system: findings of magnetic resonance spectroscopy and fractional anisotropy in diffusion tensor imaging prior to surgery. Case report.

PubMed

Beppu, Takaaki; Inoue, Takashi; Nishimoto, Hideaki; Nakamura, Shinichi; Nakazato, Yoichi; Ogasawara, Kuniaki; Ogawa, Akira

2007-10-01

Primary granulomatous angiitis of the central nervous system (CNS) is extremely rare. Its preoperative diagnosis is difficult as the condition displays nonspecific features on routine neuroimaging investigations. In this paper, the authors report findings of magnetic resonance (MR) spectroscopy and fractional anisotropy (FA) with diffusion tensor MR imaging in a case of granulomatous angiitis of the CNS. A 30-year-old man presented with morning headaches and grand mal seizures. An MR image revealed a mass resembling glioblastoma in the right temporal lobe. Magnetic resonance spectroscopy showed a high choline/creatine (Cho/Cr) ratio indicative of a malignant neoplasm, accompanied by a slight elevation of glutamate and glutamine. The FA value was very low, which is inconsistent with malignant glioma. The mass was totally removed surgically. Histologically, the peripheral lesion of the mass consisted of a rough accumulation of fat granule cells, infiltration of inflammatory cells, and distribution of capillary vessels. Some vessels within the lesion were replaced by granulomas. The histological diagnosis was granulomatous angiitis of the CNS. The MIB-1-positive rate of the granuloma was approximately 5%. Both MR spectroscopy and FA were unable to accurately diagnose granulomatous angiitis of the CNS prior to surgery; however, elevated Cho/Cr and glutamate and glutamine shown by MR spectroscopy may indicate the moderate proliferation potential of the granuloma and the inflammatory process, respectively, in this condition. Although the low FA value in the present case enabled the authors to rule out a diagnosis of glioblastoma, FA values in inflammatory lesions require careful interpretation.

A high fat diet alters metabolic and bioenergetic function in the brain: A magnetic resonance spectroscopy study.

PubMed

Raider, Kayla; Ma, Delin; Harris, Janna L; Fuentes, Isabella; Rogers, Robert S; Wheatley, Joshua L; Geiger, Paige C; Yeh, Hung-Wen; Choi, In-Young; Brooks, William M; Stanford, John A

2016-07-01

Diet-induced obesity and associated metabolic effects can lead to neurological dysfunction and increase the risk of developing Alzheimer's disease (AD) and Parkinson's disease (PD). Despite these risks, the effects of a high-fat diet on the central nervous system are not well understood. To better understand the mechanisms underlying the effects of high fat consumption on brain regions affected by AD and PD, we used proton magnetic resonance spectroscopy ((1)H-MRS) to measure neurochemicals in the hippocampus and striatum of rats fed a high fat diet vs. normal low fat chow. We detected lower concentrations of total creatine (tCr) and a lower glutamate-to-glutamine ratio in the hippocampus of high fat rats. Additional effects observed in the hippocampus of high fat rats included higher N-acetylaspartylglutamic acid (NAAG), and lower myo-inositol (mIns) and serine (Ser) concentrations. Post-mortem tissue analyses revealed lower phosphorylated AMP-activated protein kinase (pAMPK) in the striatum but not in the hippocampus of high fat rats. Hippocampal pAMPK levels correlated significantly with tCr, aspartate (Asp), phosphoethanolamine (PE), and taurine (Tau), indicating beneficial effects of AMPK activation on brain metabolic and energetic function, membrane turnover, and edema. A negative correlation between pAMPK and glucose (Glc) indicates a detrimental effect of brain Glc on cellular energy response. Overall, these changes indicate alterations in neurotransmission and in metabolic and bioenergetic function in the hippocampus and in the striatum of rats fed a high fat diet. Copyright © 2016 Elsevier Ltd. All rights reserved.

Maternal dietary creatine supplementation does not alter the capacity for creatine synthesis in the newborn spiny mouse.

PubMed

Dickinson, Hayley; Ireland, Zoe J; Larosa, Domenic A; O'Connell, Bree A; Ellery, Stacey; Snow, Rod; Walker, David W

2013-09-01

We have previously reported that maternal creatine supplementation protects the neonate from hypoxic injury. Here, we investigated whether maternal creatine supplementation altered expression of the creatine synthesis enzymes (arginine:glycine amidinotransferase [AGAT], guanidinoaceteate methyltransferase [GAMT]) and the creatine transporter (solute carrier family 6 [neurotransmitter transporter, creatine] member 8: SLC6A8) in the term offspring. Pregnant spiny mice were fed a 5% creatine monohydrate diet from midgestation (day 20) to term (39 days). Placentas and neonatal kidney, liver, heart, and brain collected at 24 hours of age underwent quantitative polymerase chain reaction and Western blot analysis. Maternal creatine had no effect on the expression of AGAT and GAMT in neonatal kidney and liver, but mRNA expression of AGAT in brain tissues was significantly decreased in both male and female neonates born to mothers who were fed the creatine diet. SLC6A8 expression was not affected by maternal dietary creatine loading in any tissues. Maternal dietary creatine supplementation from midgestation in the spiny mouse did not alter the capacity for creatine synthesis or transport.

Similarities of biochemical abnormalities between major depressive disorder and bipolar depression: a proton magnetic resonance spectroscopy study.

PubMed

Zhong, Shuming; Wang, Ying; Zhao, Guoxiang; Xiang, Qi; Ling, Xueying; Liu, Sirun; Huang, Li; Jia, Yanbin

2014-10-01

Depression in the context of bipolar disorder (BD) is often misdiagnosed as major depressive disorder (MDD), leading to mistreatments and poor clinical outcomes for many bipolar patients. Previous neuroimaging studies found mixed results on brain structure, and biochemical metabolism of the two disorders. To eliminate the compounding effects of medication, and aging, this study sought to investigate the brain biochemical changes of treatment-naïve, non-late-life patients with MDD and BD in white matter in prefrontal (WMP) lobe, anterior cingulate cortex (ACC) and hippocampus by using proton magnetic resonance spectroscopy ((1)H-MRS). Three groups of participants were recruited: 26 MDD patients, 20 depressed BD patients, and 13 healthy controls. The multi-voxel (1)H-MRS [repetition time (TR)=1000ms; echo-time (TE)=144ms] was used for the measurement of N-acetylaspartate(NAA), choline containg compounds (Cho), and creatine (Cr) in three brain locations: white matter in prefrontal (WMP) lobe, anterior cingulate cortex (ACC), and hippocampus. Two ratios of NAA/Cr and Cho/Cr as a measure of brain biochemical changes were compared among three experimental groups. On the comparison of brain biochemical changes, both MDD patients and BD patients showed many similarities compared to the controls. They both had a significantly lower NAA/Cr ratio in the left WMP lobe. There were no significant differences among three experimental groups for Cho/Cr ratio in the WMP lobe, and for the ratios of NAA/Cr and Cho/Cr in the bilateral ACC and hippocampus. The only difference between MDD and BD patients existed for the NAA/Cr ratio in the right WMP lobe. While MDD patients had a significantly lower NAA/Cr ratio than controls, BD patients showed no such differences. On the comparison of correlation of medical variables and brain biochemical changes, all participants demonstrated no significant correlations. Reduced NAA/Cr ratio at the left WMP lobe indicated the dysfunction of neuronal viability in deep white matter, in both MDD and BD patients who shared similarities of brain biochemical abnormalities, which might imply an overlap in neuropathology of depression. Copyright © 2014 Elsevier B.V. All rights reserved.

Indirect effects of elevated body mass index on memory performance through altered cerebral metabolite concentrations.

PubMed

Gonzales, Mitzi M; Tarumi, Takashi; Eagan, Danielle E; Tanaka, Hirofumi; Vaghasia, Miral; Haley, Andreana P

2012-09-01

Elevated body mass index (BMI) at midlife is associated with increased risk of cognitive decline in later life. The goal of the current study was to assess mechanisms of early brain vulnerability by examining if higher BMI at midlife affects current cognitive performance through alterations in cerebral neurochemistry. Fifty-five participants, aged 40 to 60 years, underwent neuropsychological testing, health screen, and proton magnetic resonance spectroscopy examining N-acetylaspartate, creatine (Cr), myo-inositol (mI), choline, and glutamate concentrations in occipitoparietal gray matter. Concentrations of N-acetylaspartate, choline, mI, and glutamate were calculated as a ratio over Cr and examined in relation to BMI using multivariate regression analyses. Structural equation modeling was used to determine if BMI had an indirect effect on cognition through cerebral metabolite levels. Higher BMI was associated with elevations in mI/Cr (F(5,45) = 3.843, p = .006, β = 0.444, p = .002), independent of age, sex, fasting glucose levels, and systolic blood pressure. Moreover, a χ(2) difference test of the direct and indirect structural equation models revealed that BMI had an indirect effect on global cognitive performance (Δχ(2) = 19.939, df = 2, p < .001). Subsequent follow-up analyses revealed that this effect was specific to memory (Δχ(2) = 22.027, df = 2, p < .001). Higher BMI was associated with elevations in mI/Cr concentrations in the occipitoparietal gray matter and indirectly related to poorer memory performance through mI/Cr levels, potentially implicating plasma hypertonicity and neuroinflammation as mechanisms underlying obesity-related brain vulnerability.

Change in brain magnetic resonance spectroscopy after treatment during acute HIV infection.

PubMed

Sailasuta, Napapon; Ross, William; Ananworanich, Jintanat; Chalermchai, Thep; DeGruttola, Victor; Lerdlum, Sukalaya; Pothisri, Mantana; Busovaca, Edgar; Ratto-Kim, Silvia; Jagodzinski, Linda; Spudich, Serena; Michael, Nelson; Kim, Jerome H; Valcour, Victor

2012-01-01

Single voxel proton magnetic resonance spectroscopy (MRS) can be used to monitor changes in brain inflammation and neuronal integrity associated with HIV infection and its treatments. We used MRS to measure brain changes during the first weeks following HIV infection and in response to antiretroviral therapy (ART). Brain metabolite levels of N-acetyl aspartate (NAA), choline (tCHO), creatine (CR), myoinositol (MI), and glutamate and glutamine (GLX) were measured in acute HIV subjects (n = 31) and compared to chronic HIV+individuals (n = 26) and HIV negative control subjects (n = 10) from Bangkok, Thailand. Metabolites were measured in frontal gray matter (FGM), frontal white matter (FWM), occipital gray matter (OGM), and basal ganglia (BG). Repeat measures were obtained in 17 acute subjects 1, 3 and 6 months following initiation of ART. After adjustment for age we identified elevated BG tCHO/CR in acute HIV cases at baseline (median 14 days after HIV infection) compared to control (p = 0.0014), as well as chronic subjects (p = 0.0023). A similar tCHO/CR elevation was noted in OGM; no other metabolite abnormalities were seen between acute and control subjects. Mixed longitudinal models revealed resolution of BG tCHO/CR elevation after ART (p = 0.022) with tCHO/CR similar to control subjects at 6 months. We detected cellular inflammation in the absence of measurable neuronal injury within the first month of HIV infection, and normalization of this inflammation following acutely administered ART. Our findings suggest that early ART may be neuroprotective in HIV infection by mitigating processes leading to CNS injury.

The positive effects of high-frequency right dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation on memory, correlated with increases in brain metabolites detected by proton magnetic resonance spectroscopy in recently detoxified alcohol-dependent patients.

PubMed

Qiao, Jun; Jin, Guixing; Lei, Licun; Wang, Lan; Du, Yaqiang; Wang, Xueyi

2016-01-01

To explore the effect of right dorsolateral prefrontal cortex (DLPFC) repetitive transcranial magnetic stimulation (rTMS) on memory, and its correlation with levels of hippocampal brain metabolites detected by proton magnetic resonance spectroscopy ( 1 H-MRS) in recently detoxified alcohol-dependent patients. In this randomized, double-blind sham-controlled trial, alcohol-dependent patients were enrolled and randomized into two groups: the experimental group (rTMS, 10 Hz, on right DLPFC, 20 sessions) and the control group (sham stimulation). Memory function was assessed using Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R) before and after treatment. 1 H-MRS was used to detect the levels of N -acetyl aspartic acid (NAA), choline (Cho), and creatine (Cr) in bilateral hippocampi before and after treatment. Thirty-eight patients (18 in the experimental group and 20 in the control group) were included in the analyses. The experimental group showed significantly greater changes in HVLT-R, BVMT-R, NAA/Cr, and Cho/Cr after rTMS from baseline than the control group. The percentage change in BVMT-R and HVLT-R correlated with the percentage change in NAA/Cr and Cho/Cr in the right brain. High-frequency right DLPFC rTMS was associated with improvement in memory dysfunction, which is correlated with levels of hippocampal brain metabolites detected by 1 H-MRS in recently detoxified alcohol-dependent patients.

GABA Levels Are Decreased After Stroke and GABA Changes During Rehabilitation Correlate With Motor Improvement

PubMed Central

Blicher, Jakob Udby; Near, Jamie; Næss-Schmidt, Erhard; Stagg, Charlotte J.; Johansen-Berg, Heidi; Nielsen, Jørgen Feldbæk; Østergaard, Leif; Ho, Yi-Ching Lynn

2017-01-01

Background and Objective γ-Aminobutyric acid (GABA) is the dominant inhibitory neurotransmitter in the brain and is important in motor learning. We aimed to measure GABA content in primary motor cortex poststroke (using GABA-edited magnetic resonance spectroscopy [MRS]) and in relation to motor recovery during 2 weeks of constraint-induced movement therapy (CIMT). Methods Twenty-one patients (3-12 months poststroke) and 20 healthy subjects were recruited. Magnetic resonance imaging structural T1 and GABA-edited MRS were performed at baseline and after CIMT, and once in healthy subjects. GABA:creatine (GABA:Cr) ratio was measured by GABA-edited MRS. Motor function was measured using Wolf Motor Function Test (WMFT). Results Baseline comparison between stroke patients (n = 19) and healthy subjects showed a significantly lower GABA:Cr ratio in stroke patients (P < .001) even after correcting for gray matter content in the voxel (P < .01) and when expressing GABA relative to N-acetylaspartic acid (NAA; P = .03). After 2 weeks of CIMT patients improved significantly on WMFT, but no consistent change across the group was observed for the GABA:Cr ratio (n = 17). However, the extent of improvement on WMFT correlated significantly with the magnitude of GABA:Cr changes (P < .01), with decreases in GABA:Cr ratio being associated with better improvements in motor function. Conclusions In patients 3 to 12 months poststroke, GABA levels are lower in the primary motor cortex than in healthy subjects. The observed association between GABA and recovery warrants further studies on the potential use of GABA MRS as a biomarker in poststroke recovery. PMID:25055837

Interference of ascorbic acid with chemical analytes.

PubMed

Meng, Qing H; Irwin, William C; Fesser, Jennifer; Massey, K Lorne

2005-11-01

Ascorbic acid can interfere with methodologies involving redox reactions, while comprehensive studies on main chemistry analysers have not been reported. We therefore attempted to determine the interference of ascorbic acid with analytes on the Beckman Synchron LX20. Various concentrations of ascorbic acid were added to serum, and the serum analytes were measured on the LX20. With a serum ascorbic acid concentration of 12.0 mmol/L, the values for sodium, potassium, calcium and creatinine increased by 43%, 58%, 103% and 26%, respectively (P<0.01). With a serum ascorbic acid concentration of 12.0 mmol/L, the values for chloride, total bilirubin and uric acid decreased by 33%, 62% and 83%, respectively (P<0.01), and were undetectable for total cholesterol, triglyceride, ammonia and lactate. There was no definite influence of ascorbic acid on analytical values for total CO(2), urea, glucose, phosphate, total protein, albumin, amylase, creatine kinase, creatine kinase-MB, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total iron, unbound iron-binding capacity or magnesium. Ascorbic acid causes a false increase in sodium, potassium, calcium and creatinine results and a false decrease in chloride, total bilirubin, uric acid, total cholesterol, triglyceride, ammonia and lactate results.

Creatine Use in Sports.

PubMed

Butts, Jessica; Jacobs, Bret; Silvis, Matthew

The use of creatine as a dietary supplement has become increasingly popular over the past several decades. Despite the popularity of creatine, questions remain with regard to dosing, effects on sports performance, and safety. PubMed was searched for articles published between 1980 and January 2017 using the terms creatine, creatine supplementation, sports performance, and dietary supplements. An additional Google search was performed to capture National Collegiate Athletic Association-specific creatine usage data and US dietary supplement and creatine sales. Clinical review. Level 4. Short-term use of creatine is considered safe and without significant adverse effects, although caution should be advised as the number of long-term studies is limited. Suggested dosing is variable, with many different regimens showing benefits. The safety of creatine supplementation has not been studied in children and adolescents. Currently, the scientific literature best supports creatine supplementation for increased performance in short-duration, maximal-intensity resistance training. While creatine appears to be safe and effective for particular settings, whether creatine supplementation leads to improved performance on the field of play remains unknown.

Creatine protects against mitochondrial dysfunction associated with HIV-1 Tat-induced neuronal injury.

PubMed

Stevens, Patrick R; Gawryluk, Jeremy W; Hui, Liang; Chen, Xuesong; Geiger, Jonathan D

2014-01-01

HIV-1 infected individuals live longer but experience a prevalence rate of over 50% for HIV-1 associated neurocognitive disorders (HAND) for which no effective treatment is available. Viral and cellular factors secreted by HIV-1 infected cells lead to neuronal injury and HIV-1 Tat continues to be implicated in the pathogenesis of HAND. Here we tested the hypothesis that creatine protected against HIV-1 Tat-induced neuronal injury by preventing mitochondrial bioenergetic crisis and/or redox catastrophe. Creatine blocked HIV-1 Tat(1-72)-induced increases in neuron cell death and synaptic area loss. Creatine protected against HIV-1 Tat-induced decreases in ATP. Creatine and creatine plus HIV-1 Tat increased cellular levels of creatine, and creatine plus HIV-1 Tat further decreased ratios of phosphocreatine to creatine observed with creatine or HIV-1 Tat treatments alone. Additionally, creatine protected against HIV-1 Tat-induced mitochondrial hypopolarization and HIV-1 Tat-induced mitochondrial permeability transition pore opening. Thus, creatine may be a useful adjunctive therapy against HAND.

Cognitive effects of creatine monohydrate adjunctive therapy in patients with bipolar depression: Results from a randomized, double-blind, placebo-controlled trial.

PubMed

Toniolo, Ricardo Alexandre; Fernandes, Francy de Brito Ferreira; Silva, Michelle; Dias, Rodrigo da Silva; Lafer, Beny

2017-12-15

Depressive episodes and cognitive impairment are major causes of morbidity and dysfunction in individuals suffering from bipolar disorder (BD). Novel treatment approaches that target clinical and cognitive aspects of bipolar depression are needed, and research on pathophysiology suggests that mitochondrial modulators such as the nutraceutical creatine monohydrate might have a therapeutic role for this condition. Eighteen (N=18) patients with bipolar depression according to DSM-IV criteria who were enrollled in a 6-week, randomized, double-blind, placebo-controlled trial of creatine monohydrate 6g daily as adjunctive therapy were submitted to neuropsychological assessments (Wisconsin Card Sorting Test, Digit Span subtest of the Wechsler Adult Intelligence Scale-Third Edition, Stroop Color-Word Test, Rey-Osterrieth complex figure test, FAS Verbal Fluency Test) at baseline and week 6. There was a statistically significant difference between the treatment groups of the change on the total scores after 6 weeks in the verbal fluency test, with improvement in the group receiving adjunctive treatment with creatine. We did not find significant differences between the groups of the changes on other neuropsychological tests. Small sample and lack of a control group of healthy subjects. Our trial, which was the first to investigate the cognitive effects of creatine monohydrate on bipolar depression, indicates that supplementation with this nutraceutical for 6 weeks is associated with improvement in verbal fluency tests in patients with this condition. Copyright © 2016 Elsevier B.V. All rights reserved.

Creatine for women: a review of the relationship between creatine and the reproductive cycle and female-specific benefits of creatine therapy.

PubMed

Ellery, Stacey J; Walker, David W; Dickinson, Hayley

2016-08-01

The creatine/phosphocreatine/creatine kinase circuit is instrumental in regulating high-energy phosphate metabolism, and the maintenance of cellular energy turnover. The mechanisms by which creatine is able to buffer and regulate cellular energy balance, maintain acid-base balance, and reduce the effects of oxidative stress have led to a large number of studies into the use of creatine supplementation in exercise performance and to treat diseases associated with cellular energy depletion. Some of these studies have identified sex-specific responses to creatine supplementation, as such; there is the perception, that females might be less receptive to the benefits of creatine supplementation and therapy, compared to males. This review will describe the differences in male and female physique and physiology that may account for such differences, and discuss the apparent endocrine modulation of creatine metabolism in females. Hormone-driven changes to endogenous creatine synthesis, creatine transport and creatine kinase expression suggest that significant changes in this cellular energy circuit occur during specific stages of a female's reproductive life, including pregnancy and menopause. Recent studies suggest that creatine supplementation may be highly beneficial for women under certain conditions, such as depression. A greater understanding of these pathways, and the consequences of alterations to creatine bioavailability in females are needed to ensure that creatine is used to full advantage as a dietary supplement to optimize and enhance health outcomes for women.

Whole body creatine and protein kinetics in healthy men and women: effects of creatine and amino acid supplementation.

PubMed

Kalhan, Satish C; Gruca, Lourdes; Marczewski, Susan; Bennett, Carole; Kummitha, China

2016-03-01

Creatine kinetics were measured in young healthy subjects, eight males and seven females, age 20-30 years, after an overnight fast on creatine-free diet. Whole body turnover of glycine and its appearance in creatine was quantified using [1-(13)C] glycine and the rate of protein turnover was quantified using L-ring [(2)H5] phenylalanine. The creatine pool size was estimated by the dilution of a bolus [C(2)H3] creatine. Studies were repeated following a five days supplement creatine 21 g.day(-1) and following supplement amino acids 14.3 g day(-1). Creatine caused a ten-fold increase in the plasma concentration of creatine and a 50 % decrease in the concentration of guanidinoacetic acid. Plasma amino acids profile showed a significant decrease in glycine, glutamine, and taurine and a significant increase in citrulline, valine, lysine, and cysteine. There was a significant decrease in the rate of appearance of glycine, suggesting a decrease in de-novo synthesis (p = 0.006). The fractional and absolute rate of synthesis of creatine was significantly decreased by supplemental creatine. Amino acid supplement had no impact on any of the parameters. This is the first detailed analysis of creatine kinetics and the effects of creatine supplement in healthy young men and women. These methods can be applied for the analysis of creatine kinetics in different physiological states.

Disorders of creatine transport and metabolism.

PubMed

Longo, Nicola; Ardon, Orly; Vanzo, Rena; Schwartz, Elizabeth; Pasquali, Marzia

2011-02-15

Creatine is a nitrogen containing compound that serves as an energy shuttle between the mitochondrial sites of ATP production and the cytosol where ATP is utilized. There are two known disorders of creatine synthesis (both transmitted as autosomal recessive traits: arginine: glycine amidinotransferase (AGAT) deficiency; OMIM 602360; and guanidinoacetate methyltransferase (GAMT) deficiency (OMIM 601240)) and one disorder of creatine transport (X-linked recessive SLC6A8 creatine transporter deficiency (OMIM 300036)). All these disorders are characterized by brain creatine deficiency, detectable by magnetic resonance spectroscopy. Affected patients can have mental retardation, hypotonia, autism or behavioral problems and seizures. The diagnosis of these conditions relies on the measurement of plasma and urine creatine and guanidinoacetate. Creatine levels in plasma are reduced in both creatine synthesis defects and guanidinoacetate is increased in GAMT deficiency. The urine creatine/creatinine ratio is elevated in creatine transporter deficiency with normal plasma levels of creatine and guanidinoacetate. The diagnosis is confirmed in all cases by DNA testing or functional studies. Defects of creatine biosynthesis are treated with creatine supplements and, in GAMT deficiency, with ornithine and dietary restriction of arginine through limitation of protein intake. No causal therapy is yet available for creatine transporter deficiency and supplementation with the guanidinoacetate precursors arginine and glycine is being explored. The excellent response to therapy of early identified patients with GAMT or AGAT deficiency candidates these condition for inclusion in newborn screening programs. Copyright © 2011 Wiley-Liss, Inc.

Does brain creatine content rely on exogenous creatine in healthy youth? A proof-of-principle study.

PubMed

Merege-Filho, Carlos Alberto Abujabra; Otaduy, Maria Concepción Garcia; de Sá-Pinto, Ana Lúcia; de Oliveira, Maira Okada; de Souza Gonçalves, Lívia; Hayashi, Ana Paula Tanaka; Roschel, Hamilton; Pereira, Rosa Maria Rodrigues; Silva, Clovis Artur; Brucki, Sonia Maria Dozzi; da Costa Leite, Claudia; Gualano, Bruno

2017-02-01

It has been hypothesized that dietary creatine could influence cognitive performance by increasing brain creatine in developing individuals. This double-blind, randomized, placebo-controlled, proof-of-principle study aimed to investigate the effects of creatine supplementation on cognitive function and brain creatine content in healthy youth. The sample comprised 67 healthy participants aged 10 to 12 years. The participants were given creatine or placebo supplementation for 7 days. At baseline and after the intervention, participants undertook a battery of cognitive tests. In a random subsample of participants, brain creatine content was also assessed in the regions of left dorsolateral prefrontal cortex, left hippocampus, and occipital lobe by proton magnetic resonance spectroscopy (1H-MRS) technique. The scores obtained from verbal learning and executive functions tests did not significantly differ between groups at baseline or after the intervention (all p > 0.05). Creatine content was not significantly different between groups in left dorsolateral prefrontal cortex, left hippocampus, and occipital lobe (all p > 0.05). In conclusion, a 7-day creatine supplementation protocol did not elicit improvements in brain creatine content or cognitive performance in healthy youth, suggesting that this population mainly relies on brain creatine synthesis rather than exogenous creatine intake to maintain brain creatine homeostasis.

Increased Ventricular Cerebrospinal Fluid Lactate in Depressed Adolescents

PubMed Central

Bradley, Kailyn A. L.; Mao, Xiangling; Case, Julia A. C.; Kang, Guoxin; Shungu, Dikoma C.; Gabbay, Vilma

2016-01-01

Background Mitochondrial dysfunction has been increasingly examined as a potential pathogenic event in psychiatric disorders, although its role early in the course of major depressive disorder (MDD) is unclear. Therefore, the purpose of this study was to investigate mitochondrial dysfunction in medication-free adolescents with MDD through in vivo measurements of neurometabolites using high-spatial resolution multislice/multivoxel proton magnetic resonance spectroscopy. Methods Twenty-three adolescents with MDD and 29 healthy controls, ages 12–20, were scanned at 3T and concentrations of ventricular cerebrospinal fluid lactate, as well as N-acetyl-aspartate (NAA), total creatine (tCr), and total choline (tCho) in the bilateral caudate, putamen, and thalamus were reported. Results Adolescents with MDD exhibited increased ventricular lactate compared to healthy controls [F(1, 41) = 6.98, p = .01]. However, there were no group differences in the other neurometabolites. Dimensional analyses in the depressed group showed no relation between any of the neurometabolites and symptomatology, including anhedonia and fatigue. Conclusions Increased ventricular lactate in depressed adolescents suggests mitochondrial dysfunction may be present early in the course of MDD; however it is still not known whether the presence of mitochondrial dysfunction is a trait vulnerability of individuals predisposed to psychopathology or a state feature of the disorder. Therefore, there is a need for larger multimodal studies to clarify these chemical findings in the context of network function. PMID:26802978

Creatine protects against mitochondrial dysfunction associated with HIV-1 Tat-induced neuronal injury

PubMed Central

Stevens, Patrick R.; Gawryluk, Jeremy W.; Hui, Liang; Chen, Xuesong; Geiger, Jonathan D.

2015-01-01

HIV-1 infected individuals are living longer but experiencing a prevalence rate of over 50% for HIV-1 associated neurocognitive disorders (HAND) for which no effective treatment is available. Viral and cellular factors secreted by HIV-1 infected cells leads to neuronal injury and HIV-1 Tat continues to be implicated in the pathogenesis of HAND. Here we tested the hypothesis that creatine protected against HIV-1 Tat-induced neuronal injury by preventing mitochondrial bioenergetic crisis and/or redox catastrophe. Creatine blocked HIV-1 Tat1-72-induced increases in neuron cell death and synaptic area loss. Creatine protected against HIV-1 Tat-induced decreases in ATP. Creatine and creatine plus HIV-1 Tat increased cellular levels of creatine, and creatine plus HIV-1 Tat further decreased ratios of phosphocreatine to creatine observed with creatine or HIV-1 Tat treatments alone. Additionally, creatine protected against HIV-1 Tat-induced mitochondrial hypopolarization and HIV-1 Tat-induced mitochondrial permeability transition pore opening. Thus, creatine may be a useful adjunctive therapy against HAND. PMID:25613139

Size Distribution and Estimated Respiratory Deposition of Total Chromium, Hexavalent Chromium, Manganese, and Nickel in Gas Metal Arc Welding Fume Aerosols

PubMed Central

Cena, Lorenzo G.; Chisholm, William P.; Keane, Michael J.; Cumpston, Amy; Chen, Bean T.

2016-01-01

A laboratory study was conducted to determine the mass of total Cr, Cr(VI), Mn, and Ni in 15 size fractions for mild and stainless steel gas-metal arc welding (GMAW) fumes. Samples were collected using a nano multi orifice uniform deposition impactor (MOUDI) with polyvinyl chloride filters on each stage. The filters were analyzed by inductively coupled plasma mass spectrometry (ICP-MS) and ion chromatography. Limits of detection (LODs) and quantitation (LOQs) were experimentally calculated and percent recoveries were measured from spiked metals in solution and dry, certified welding-fume reference material. The fraction of Cr(VI) in total Cr was estimated by calculating the ratio of Cr(VI) to total Cr mass for each particle size range. Expected, regional deposition of each metal was estimated according to respiratory-deposition models. The weight percent (standard deviation) of Mn in mild steel fumes was 9.2% (6.8%). For stainless steel fumes, the weight percentages were 8.4% (5.4%) for total Cr, 12.2% (6.5%) for Mn, 2.1% (1.5%) for Ni and 0.5% (0.4%) for Cr(VI). All metals presented a fraction between 0.04 and 0.6 μm. Total Cr and Ni presented an additional fraction <0.03 μm. On average 6% of the Cr was found in the Cr(VI) valence state. There was no statistical difference between the smallest and largest mean Cr(VI) to total Cr mass ratio (p-value D 0.19), hence our analysis does not show that particle size affects the contribution of Cr(VI) to total Cr. The predicted total respiratory deposition for the metal particles was ∼25%. The sites of principal deposition were the head airways (7–10%) and the alveolar region (11–14%). Estimated Cr(VI) deposition was highest in the alveolar region (14%). PMID:26848207

Size Distribution and Estimated Respiratory Deposition of Total Chromium, Hexavalent Chromium, Manganese, and Nickel in Gas Metal Arc Welding Fume Aerosols.

PubMed

Cena, Lorenzo G; Chisholm, William P; Keane, Michael J; Cumpston, Amy; Chen, Bean T

A laboratory study was conducted to determine the mass of total Cr, Cr(VI), Mn, and Ni in 15 size fractions for mild and stainless steel gas-metal arc welding (GMAW) fumes. Samples were collected using a nano multi orifice uniform deposition impactor (MOUDI) with polyvinyl chloride filters on each stage. The filters were analyzed by inductively coupled plasma mass spectrometry (ICP-MS) and ion chromatography. Limits of detection (LODs) and quantitation (LOQs) were experimentally calculated and percent recoveries were measured from spiked metals in solution and dry, certified welding-fume reference material. The fraction of Cr(VI) in total Cr was estimated by calculating the ratio of Cr(VI) to total Cr mass for each particle size range. Expected, regional deposition of each metal was estimated according to respiratory-deposition models. The weight percent (standard deviation) of Mn in mild steel fumes was 9.2% (6.8%). For stainless steel fumes, the weight percentages were 8.4% (5.4%) for total Cr, 12.2% (6.5%) for Mn, 2.1% (1.5%) for Ni and 0.5% (0.4%) for Cr(VI). All metals presented a fraction between 0.04 and 0.6 μ m. Total Cr and Ni presented an additional fraction <0.03 μ m. On average 6% of the Cr was found in the Cr(VI) valence state. There was no statistical difference between the smallest and largest mean Cr(VI) to total Cr mass ratio ( p -value D 0.19), hence our analysis does not show that particle size affects the contribution of Cr(VI) to total Cr. The predicted total respiratory deposition for the metal particles was ∼25%. The sites of principal deposition were the head airways (7-10%) and the alveolar region (11-14%). Estimated Cr(VI) deposition was highest in the alveolar region (14%).

MRI, volumetry, 1H spectroscopy, and cerebropetal blood flowmetry in childhood idiopathic anatomic megalencephaly.

PubMed

Koudijs, Suzanne M; van der Grond, Jeroen; Hoogendoorn, Mechteld L C; Hulshoff Pol, Hilleke E; Schnack, Hugo G; Witkamp, Theo D; Gooskens, Rob H J M; van Nieuwenhuizen, Onno; Braun, Kees P J

2006-08-01

To evaluate cerebral abnormalities in childhood idiopathic anatomic megalencephaly (MC) by means of different magnetic resonance (MR) modalities. MRI, volumetry, spectroscopy, and cerebropetal blood flowmetry were performed in six children with idiopathic anatomic MC, and seven volunteers. MRI revealed an increased ventricular system in five of six patients. A thalamic hamartoma was found in one patient and a Chiari I malformation was found in two. Volumetric analysis showed a disproportional increase of ventricular volume but normal subarachnoid cerebrospinal fluid (CSF) volume. Supratentorial volume was disproportionally increased compared to cerebellar volume. Intracranial volume correlated significantly with skull circumference. MR spectroscopy (MRS) N-acetyl aspartate/choline (NAA/Cho) peak ratios in WM were significantly higher in patients than in controls. Choline/creatine (Cho/Cr) peak ratios in WM were significantly lower in patients. Cortical gray matter (GM) MRS ratios were unaltered. Cerebropetal flow was increased in MC, possibly related to increased brain volume. This study reveals associated developmental anomalies for idiopathic anatomic MC. A relative ventriculomegaly was found, which should not be misinterpreted as true hydrocephalus. In contrast to metabolic MC, MRS showed no severe disturbances. Total intracranial volume is correlated to skull circumference and cerebropetal blood flow.

Does maternal-fetal transfer of creatine occur in pregnant sheep?

PubMed

Baharom, Syed; De Matteo, Robert; Ellery, Stacey; Della Gatta, Paul; Bruce, Clinton R; Kowalski, Greg M; Hale, Nadia; Dickinson, Hayley; Harding, Richard; Walker, David; Snow, Rodney J

2017-07-01

Our aim was to determine the disposition of creatine in ovine pregnancy and whether creatine is transferred across the placenta from mother to fetus. Pregnant ewes received either 1 ) a continuous intravenous infusion of creatine monohydrate or saline from 122 to 131 days gestation, with maternal and fetal arterial blood and amniotic fluid samples collected daily for creatine analysis and fetal tissues collected at necropsy at 133 days for analysis of creatine content, or 2 ) a single systemic bolus injection of [ 13 C]creatine monohydrate at 130 days of gestation, with maternal and fetal arterial blood, uterine vein blood, and amniotic fluid samples collected before and for 4 h after injection and analyzed for creatine, creatine isotopic enrichment, and guanidinoacetic acid (GAA; precursor of creatine) concentrations. Presence of the creatine transporter-1 (SLC6A8) and l-arginine:glycine amidinotransferase (AGAT; the enzyme synthesizing GAA) proteins were determined by Western blots of placental cotyledons. The 10-day creatine infusion increased maternal plasma creatine concentration three- to fourfold ( P < 0.05) without significantly changing fetal arterial, amniotic fluid, fetal tissues, or placental creatine content. Maternal arterial 13 C enrichment was increased ( P < 0.05) after bolus [ 13 C]creatine injection without change of fetal arterial 13 C enrichment. SLC6A8 and AGAT proteins were identified in placental cotyledons, and GAA concentration was significantly higher in uterine vein than maternal artery plasma. Despite the presence of SLC6A8 protein in cotyledons, these results suggest that creatine is not transferred from mother to fetus in near-term sheep and that the ovine utero-placental unit releases GAA into the maternal circulation. Copyright © 2017 the American Physiological Society.

Altered Cortical GABA in Female Veterans with Suicidal Behavior: Sex Differences and Clinical Correlates.

PubMed

Prescot, Andrew; Sheth, Chandni; Legarreta, Margaret; Renshaw, Perry F; McGlade, Erin; Yurgelun-Todd, Deborah

2018-01-01

Suicide is a public health concern in the civilian and veteran populations. Stressful life events are precipitating factors for suicide. The neurochemical underpinnings of the association between stress/trauma and suicide risk are unclear, especially in regards to sex differences. We hypothesized that gamma-amino butyric acid (GABA), the major inhibitory neurotransmitter may be a neurochemical candidate that is critical in the association between stress and suicide risk in veterans. Proton magnetic resonance spectroscopy ( 1 H MRS) at 3.0 Tesla was used to measure in vivo neurochemistry in the anterior cingulate cortex (ACC; predominantly the dorsal ACC) of 81 veterans (16 females), including 57 (11 females) who endorsed past suicidal ideation (SI) and/or suicide attempt (SA) and 24 (5 females) with no history of SI and/or SA. Suicidal behavior (SB) was defined as the presence of SI and/or SA. We observed no significant differences in GABA/ Creatine+phosphocreatine (Cr+PCr) between veterans with SB (SB+) and without SB (SB-). However, the female SB+ group showed significantly reduced GABA/Cr+PCr vs. the female SB- group. We observed a trend-level significant negative correlation between GABA/Cr+PCr and the defensive avoidance (DA) subscale on the Trauma Symptom Inventory (TSI) in the SB+ group. In contrast, the SB- group exhibited a positive relationship between the two variables. Furthermore, we found significant negative correlations between GABA/Cr+PCr and Hamilton Rating Scale for Depression (HAM-D) scores as well as between GABA/Cr+PCr and several subscales of the TSI in female veterans. This study suggests that reduced GABA/Cr+ PCr ratio in the ACC, which may be related to altered inhibitory capacity, may underlie suicide risk in female veterans. Further, the negative association between GABA/Cr+PCr and stress symptomatology and depression scores suggests that MRS studies may shed light on intermediate phenotypes of SB.

Imaging increased glutamate in children with Sturge-Weber syndrome: Association with epilepsy severity.

PubMed

Juhász, Csaba; Hu, Jiani; Xuan, Yang; Chugani, Harry T

2016-05-01

Sturge-Weber syndrome (SWS) is strongly associated with epilepsy. Brain tissue studies have suggested that epileptic activity in SWS is driven by glutamatergic synaptic activity. Here, we used proton magnetic resonance spectroscopic imaging (MRSI) to test if glutamate (GLU) concentrations are increased in the affected hemisphere and if such increases are associated with severity of epilepsy in children with SWS. We also studied the metabolic correlates of MRSI abnormalities, using glucose positron emission tomography (PET) imaging. 3T MRI and glucose PET were performed in 10 children (age: 7-78 months) with unilateral SWS and a history of epilepsy. MRSI data were acquired from the affected (ipsilateral) and non-affected (contralateral) hemispheres. GLU, N-acetyl-aspartate (NAA) and creatine (Cr) were quantified in multiple voxels; GLU/Cr and NAA/Cr ratios were calculated and compared to seizure frequency as well as glucose PET findings. The highest GLU/Cr ratios were found in the affected hemisphere in all children except one with severe atrophy. The maximum ipsilateral/contralateral GLU/Cr ratios ranged between 1.0 and 2.5 (mean: 1.6). Mean ipsilateral/contralateral GLU/Cr ratios were highest in the youngest children and showed a strong positive correlation with clinical seizure frequency scores assessed at the time of the scan (r=0.88, p=0.001) and also at follow-up (up to 1 year, r=0.80, p=0.009). GLU increases in the affected hemisphere coincided with areas showing current or previous increases of glucose metabolism on PET in 5 children. NAA/Cr ratios showed no association with clinical seizure frequency. Increased glutamate concentrations in the affected hemisphere, measured by MRSI, are common in young children with unilateral SWS and are associated with frequent seizures. The findings lend support to the role of excess glutamate in SWS-associated epilepsy. Copyright © 2016 Elsevier B.V. All rights reserved.

Can fast-twitch muscle fibres be selectively recruited during lengthening contractions? Review and applications to sport movements.

PubMed

Chalmers, Gordon R

2008-01-01

Literature examining the recruitment order of motor units during lengthening (eccentric) contractions was reviewed to determine if fast-twitch motor units can be active while lower threshold slow-twitch motor units are not active. Studies utilizing surface electromyogram (EMG) amplitude, single motor unit activity, spike amplitude-frequency analyses, EMG power spectrum, mechanomyographic, and phosphocreatine-to-creatine ratio (PCr/Cr) techniques were reviewed. Only single motor unit and PCr/Cr data were found to be suitable to address the goals of this review. Nine of ten single motor unit studies, examining joint movement velocities up to 225 degrees/s and forces up to 53% of a maximum voluntary contraction, found that the size principle of motor unit recruitment applied during lengthening contractions. Deviation from the size principle was demonstrated by one study examining movements within a small range of low velocities and modest forces, although other studies examining similar low forces and lengthening velocities reported size-ordered recruitment. The PCr/Cr data demonstrated the activation of all fibre types in lengthening maximal contractions. Most evidence indicates that for lengthening contractions of a wide range of efforts and speeds, fast-twitch muscle fibres cannot be selectively recruited without activity of the slow-twitch fibres of the same muscle.

Methods for determining soluble and insoluble Cr III and Cr VI compounds in welding fumes.

PubMed

Matczak, W; Chmielnicka, J

1989-01-01

An analytical procedure for simultaneous determination of soluble and insoluble Cr III and Cr VI compounds in welding fumes has been proposed. In the welding fume samples collected on a membrane filter, total chromium was determined with atomic absorption spectrophotometry (AAS). Glass filters with collected samples were divided into two parts. In one part of the sample, soluble and insoluble chromium was determined by means of AAS. The separation of soluble chromium III and VI was carried out on diphenylcarbazide resin. In the second part of the sample total chromium VI was determined by means of the colorimetric method with s-diphenylcarbazide. The difference in the results of these determinations allowed the calculation of the content of total Cr III, Cr III insolub. and Cr VI insolub. The results of determining chromium compounds in welding fumes samples collected in the welder's breathing zone and in experimental chambers are also presented in this paper. The content of total chromium in the fumes determined by AAS (from a membrane filtr) and that calculated from the sum of soluble and insoluble chromium (from a glass filter) were concordant and within the limits of the admissible error for the method. Total chromium content in welding fume samples collected individually was found to range from 2.4-4.2%. The percentage of particular chromium compounds as compared to total chromium (100%) amounted: total Cr III--34%, total Cr VI--66%, soluble chromium--66% and in this Cr III--20% and Cr VI--43%, insoluble chromium--34% and in this: Cr III--14% and Cr VI--20%.

Effect of occupational manganese exposure on the central nervous system of welders: 1H magnetic resonance spectroscopy and MRI findings.

PubMed

Kim, Eun A; Cheong, Hae-Kwan; Choi, Dae Seob; Sakong, Joon; Ryoo, Jae Wook; Park, Injeong; Kang, Dong Mug

2007-03-01

This study investigated the relationship between long-term occupational manganese (Mn) exposure on the regional Mn concentration in the brain, neuronal loss, and neurobehavioral effects on welders. 1H MRS of the basal ganglia (BG) was performed on 20 male welders and 10 age- and gender-matched, non-office, control workers in a shipyard to assess the metabolic change, and the N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/Cr and NAA/Cho ratios, by the level of Mn exposure. We also assessed the signal intensity of T1-weighted image of magnetic resonance imaging (MRI) on globus pallidus (GP) compared to that of the frontal white matter (pallidal index, PI). The welders had significantly higher signal intensity than the controls. PI showed a significant dose-response relationship with cumulative exposure index (CEI) (r=0.54, p=0.002). CEI and PI showed different relationships with NAA/Cr according to smoking status, and the correlation was evident only in non-smokers (r=-0.73 and -0.57, respectively). There were no significant differences between the welders and the controls in NAA/Cr, Cho/Cr, and NAA/Cho ratios obtained from BG. CEI was positively correlated with simple reaction time. PI was positively correlated with mean sway (MSWAY), sway area (SWAYA), and sway intensity (SWAYI), and negatively correlated with maximum frequency (MAXF). After categorizing the subjects into two groups according to NAA/Cr ratio level, the low NAA/Cr ratio group showed significantly lower score on digit span backward and significantly higher score on MSWAY, SWAYA and SWAYI in regression analysis than the high NAA/Cr ratio group. We speculated that the NAA/Cr ratio of MRS in BG seems to reflect the cumulative effect of Mn exposure on the human brain. Due to uneven distribution of smoking among the welders and the controls, in addition to the small number of subjects in our study, our findings are needed further studies with a larger number of subjects.

Effects of electroacupuncture on metabolic changes in motor cortex and striatum of 6-hydroxydopamine-induced Parkinsonian rats.

PubMed

Li, Min; Wang, Ke; Su, Wen-Ting; Jia, Jun; Wang, Xiao-Min

2017-10-06

To explore the possible underlying mechanism by investigating the effect of electroacupuncture (EA) treatment on the primary motor cortex and striatum in a unilateral 6-hydroxydopamine (6-OHDA) induced rat Parkinson's disease (PD) model. Male Sprague-Dawley rats were randomly divided into sham group (n=16), model group (n=14), and EA group (n=14). EA stimulation at Dazhui (GV 14) and Baihui (GV20) was applied to PD rats in the EA group for 4 weeks. Behavioral tests were conducted to evaluate the effectiveness of EA treatment. Metabolites were detected by 7.0 T proton nuclear magnetic resonance. Following 4 weeks of EA treatment in PD model rats, the abnormal behavioral impairment induced by 6-OHDA was alleviated. In monitoring changes in metabolic activity, ratios of myoinositol/creatine (Cr) and N-acetyl aspartate (NAA)/Cr in the primary motor cortex were significantly lower at the injected side than the non-injected side in PD rats (P=0.024 and 0.020). The ratios of glutamate + glutamine (Glx)/Cr and NAA/Cr in the striatum were higher and lower, respectively, at the injected side than the non-injected side (P=0.046 and 0.008). EA treatment restored the balance of metabolic activity in the primary motor cortex and striatum. In addition, the taurine/Cr ratio and Glx/Cr ratio were elevated in the striatum of PD model rats compared to sham-lesioned rats (P=0.026 and 0.000). EA treatment alleviated the excessive glutamatergic transmission by down-regulating the striatal Glx/Cr ratio (P=0.001). The Glx/Cr ratio was negatively correlated with floor plane spontaneous locomotion in PD rats (P=0.027 and P=0.0007). EA treatment is able to normalize the metabolic balance in the primary motor cortex and striatum of PD rats, which may contribute to its therapeutic effect on motor deficits. The striatal Glx/Cr ratio may serve as a potential indicator of PD and a therapeutic target of EA treatment.

Proton MR spectroscopy in predicting the increase of perfusion MR imaging for WHO grade II gliomas.

PubMed

Guillevin, Remy; Menuel, Carole; Abud, Lucas; Costalat, Robert; Capelle, Laurent; Hoang-Xuan, Khê; Habas, Christophe; Chiras, Jacques; Vallée, Jean-Noel

2012-03-01

To investigate the correlation between the metabolite ratios obtained from proton magnetic resonance (MR) spectroscopy and those obtained from MR perfusion parameters (relative cerebral blood volume [rCBV]) in a cohort of low-grade glioma (LGG). Patients underwent prospectively conventional MR, proton magnetic resonance spectroscopy ((1) HMRS), and perfusion-weighted images (PWI). Statistical analyses were performed to determine the correlative and independent predictive factors of rCBVmax and the metabolite ratio thresholds with optimum sensitivity and specificity. Thirty-one patients were included in this study. Linear correlations were observed between the metabolic ratios (lactate [Lac]/creatine [Cr], choline [Cho]/N-acetyl-aspartate [NAA], free-lipids/Cr) and rCBVmax (P < 0.05). These metabolic ratios were determined to be independent predictive factors of rCBVmax (P = 0.027, 0.011 and 0.032, respectively). According to the receiver operating characteristic curves, the cutoff values of the metabolic ratios to discriminate between the two populations of rCBVmax (<1.7 versus = 1.7) were 1.72, 1.54, and 1.40, respectively, with a sensitivity = 75% and a specificity >95% for Lac/Cr. This study demonstrated consistent correlations between the data from (1) HMRS and PWI. The Lac/Cr ratio predicts regional hemodynamic changes, which are themselves a useful biomarker of clinical prognosis in patients with LGG. As such, this ratio may provide a new parameter for making improved clinical decisions. Copyright © 2011 Wiley-Liss, Inc.

Comparison of T1 and T2 metabolite relaxation times in glioma and normal brain at 3 T

PubMed Central

Li, Yan; Srinivasan, Radhika; Ratiney, Helene; Lu, Ying; Chang, Susan M.; Nelson, Sarah J.

2011-01-01

Purpose To measure T1 and T2 relaxation times of metabolites in glioma patients at 3T and to investigate how these values influence the observed metabolite levels. Materials and Methods Twenty-three patients with gliomas and ten volunteers were studied with single voxel 2D J-resolved PRESS using a 3T MR scanner. Voxels were chosen in normal appearing white matter and in regions of tumor. The T1 and T2 of choline containing compounds (Cho), creatine (Cr) and N-acetyl aspartate (NAA) were estimated. Results Metabolite T1 relaxation values in gliomas were not significantly different from values in normal white matter. The T2 of Cho and Cr were statistically significantly longer for Grade 4 gliomas than for normal white matter but the T2 of NAA was similar. These differences were large enough to impact the corrections of metabolite levels for relaxation times with tumor grade in terms of metabolite ratios (P<0.001). Conclusion The differential increase in T2 for Cho and Cr relative to NAA means that the ratios of Cho/NAA and Cr/NAA are higher in tumor at longer echo times relative to values in normal appearing brain. Having this information may be useful in defining the acquisition parameters for optimizing contrast between tumor and normal tissue in MRSI data, where limited time is available and only one echo time can be used. PMID:18666155

Assignment of the creatine transporter gene (SLC6A8) to human chromosome Xq28 telomeric to G6PD

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gregor, P.; Nash, S.R.; Caron, M.G.

1995-01-01

The creatine-phosphocreatine shuttle has important functions in the temporal and spatial maintenance of the energy supply to skeletal and cardiac muscle. Muscle cells do not synthesize creatine, but take it up via a specific sodium-dependent transporter - the creatine transporter. Thus, the creatine transporter has an important role in muscular physiology. Furthermore, inhibition of creatine transport in experimental animals causes muscle weakness. Recently, creatine transporter cDNAs have been isolated and characterized from rabbit and human. In this communication we report mapping of the creatine transporter gene to human chromosome Xq28. 12 refs., 1 fig.

Scientific basis and practical aspects of creatine supplementation for athletes.

PubMed

Volek, Jeff S; Rawson, Eric S

2004-01-01

A large number of studies have been published on creatine supplementation over the last decade. Many studies show that creatine supplementation in conjunction with resistance training augments gains in muscle strength and size. The underlying physiological mechanism(s) to explain this ergogenic effect remain unclear. Increases in muscle fiber hypertrophy and myosin heavy chain expression have been observed with creatine supplementation. Creatine supplementation increases acute weightlifting performance and training volume, which may allow for greater overload and adaptations to training. Creatine supplementation may also induce a cellular swelling in muscle cells, which in turn may affect carbohydrate and protein metabolism. Several studies point to the conclusion that elevated intramuscular creatine can enhance glycogen levels but an effect on protein synthesis/degradation has not been consistently detected. As expected there is a distribution of responses to creatine supplementation that can be largely explained by the degree of creatine uptake into muscle. Thus, there is wide interest in methods to maximize muscle creatine levels. A carbohydrate or carbohydrate/protein-induced insulin response appears to benefit creatine uptake. In summary, the predominance of research indicates that creatine supplementation represents a safe, effective, and legal method to enhance muscle size and strength responses to resistance training.

Sex-based differences in plasma chemistry and cardiac marker test results in Siamese fighting fowl.

PubMed

Sribhen, Choosri; Choothesa, Apassara; Songserm, Thaveesak; Issariyodom, Supaporn; Sribhen, Kosit

2006-09-01

Variations in the results of plasma chemistry analysis as a function of sex have rarely been demonstrated in avian species. The aim of the present study was to investigate sex-related differences in values for routine biochemical variables, including conventional muscle enzymes, and novel cardiac markers in female and male Siamese fighting fowl. Plasma chemistry analytes and cardiac marker proteins (creatine kinase-MB and cardiac troponin T) were measured in 70 Siamese fighting fowl using automated chemistry and immunoassay analyzers. Data were compared by 2-tailed t tests between sexes, and Spearman rank correlation between conventional and novel cardiac markers. Male fowl had significantly higher uric acid concentration and gamma-glutamyltransferase activity; whereas, female fowl had significantly higher total cholesterol, triglycerides, and calcium concentrations, and alkaline phosphatase activity. As compared with female fowl, the fighting cocks also had significantly higher plasma concentrations of creatine kinase-MB and cardiac troponin T. Significant correlations between cardiac troponin T, but not creatine kinase-MB, and the activities of conventional muscle enzymes (creatine kinase, aspartate aminotransferase and lactate dehydrogenase) were observed in male but not in female fowl. These results indicate that sex-specific differences exist for several biochemical parameters and cardiac marker proteins in fighting fowl, and that such differences should be considered in interpreting laboratory test results.

Changes in selected serum parameters of broiler chicken fed supplemental chromium.

PubMed

Króliczewska, B; Zawadzki, W; Dobrzanski, Z; Kaczmarek-Oliwa, A

2004-12-01

The present study was conducted to evaluate the effect of chromium (Cr) from Cr yeast on the growth performance and total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triglycerides, glucose, total protein and Cr concentration in the serum of broiler chicken. The birds were fed a control diet or a control diet supplemented with Cr at a level of 300, 500 microg/kg Cr. The supplementation of 500 mug/kg Cr increased body weight, weight gain and feed efficiency (p < 0.05). In addition, supplementation with Cr decreased the serum total cholesterol, LDL cholesterol (p < 0.05), triglycerides (p < 0.05) and glucose (p < 0.05) concentrations whereas serum HDL cholesterol increased. Serum total protein and serum Cr concentration slightly but not significantly increased in both Cr groups. The study suggest that Cr supplementation particularly at 500 microg/kg Cr from Cr yeast can influence on carbohydrate and lipid metabolism of broiler chicken and can be used as additives in animal diet but it still needs more investigations.

Synthesis and biological evaluation of new creatine fatty esters revealed dodecyl creatine ester as a promising drug candidate for the treatment of the creatine transporter deficiency.

PubMed

Trotier-Faurion, Alexandra; Dézard, Sophie; Taran, Frédéric; Valayannopoulos, Vassili; de Lonlay, Pascale; Mabondzo, Aloïse

2013-06-27

The creatine transporter deficiency is a neurological disease caused by impairment of the creatine transporter SLC6A8, resulting in mental retardation associated with a complete absence of creatine within the brain and cellular energy perturbation of neuronal cells. One of the therapeutic hypotheses was to administer lipophilic creatine derivatives which are (1) thought to have better permeability through the cell membrane and (2) would not rely on the activity of SLC6A8 to penetrate the brain. Here, we synthesized creatine fatty esters through original organic chemistry process. A screening on an in vitro rat primary cell-based blood-brain barrier model and on a rat primary neuronal cells model demonstrated interesting properties of these prodrugs to incorporate into endothelial, astroglial, and neuronal cells according to a structure-activity relationship. Dodecyl creatine ester showed then a 20-fold increase in creatine content in pathological human fibroblasts compared with the endogenous creatine content, stating that it could be a promising drug candidate.

Creatine Revealed Anticonvulsant Properties on Chemically and Electrically Induced Seizures in Mice.

PubMed

Shafaroodi, Hamed; Shahbek, Farnaz; Faizi, Mehrdad; Ebrahimi, Farzad; Moezi, Leila

2016-01-01

Creatine exerts beneficial effects on a variety of pathologies in which energy metabolism and oxidative stress play an etiological role. Creatine supplements have shown beneficial effects on neurological disorders including Parkinson׳s disease, Huntington›s disease, amyotrophic lateral sclerosis, as well as Alzheimer›s disease and stroke. However, the potential benefits of creatine for patients with convulsive disorders remain poorly defined. While some authors did not suggest any anti- or pro-convulsant roles for creatine treatment, others suggest that creatine may be an anticonvulsant agent. In this study, we investigated the effects of creatine on seizures in mice. Three models were used to explore the role of creatine on seizures in mice including intravenous pentylenetetrazole (PTZ), intraperitoneal PTZ, and electroshock models. Acute creatine treatment (10, 20, 40 and 80 mg/Kg) significantly increased the clonic seizure threshold in the intravenous PTZ model. Sub-chronic administration of creatine (10 and 20 mg/Kg) revealed a significant anticonvulsant effect in intravenous PTZ model. Acute creatine administration (10, 20 and 40 mg/Kg) significantly decreased the frequency of clonic seizures in the intraperitoneal PTZ model. Besides, acute creatine (40 and 80 mg/Kg) decreased the incidence of tonic seizures after electroshock. In conclusion, creatine exerts anticonvulsant effects in three seizure models; therefore, it may act as a potential drug to help patients with convulsions. However, further investigations should be done to clarify these results more.

Creatine Revealed Anticonvulsant Properties on Chemically and Electrically Induced Seizures in Mice

PubMed Central

Shafaroodi, Hamed; Shahbek, Farnaz; Faizi, Mehrdad; Ebrahimi, Farzad; Moezi, Leila

2016-01-01

Creatine exerts beneficial effects on a variety of pathologies in which energy metabolism and oxidative stress play an etiological role. Creatine supplements have shown beneficial effects on neurological disorders including Parkinson׳s disease, Huntington›s disease, amyotrophic lateral sclerosis, as well as Alzheimer›s disease and stroke. However, the potential benefits of creatine for patients with convulsive disorders remain poorly defined. While some authors did not suggest any anti- or pro-convulsant roles for creatine treatment, others suggest that creatine may be an anticonvulsant agent. In this study, we investigated the effects of creatine on seizures in mice. Three models were used to explore the role of creatine on seizures in mice including intravenous pentylenetetrazole (PTZ), intraperitoneal PTZ, and electroshock models. Acute creatine treatment (10, 20, 40 and 80 mg/Kg) significantly increased the clonic seizure threshold in the intravenous PTZ model. Sub-chronic administration of creatine (10 and 20 mg/Kg) revealed a significant anticonvulsant effect in intravenous PTZ model. Acute creatine administration (10, 20 and 40 mg/Kg) significantly decreased the frequency of clonic seizures in the intraperitoneal PTZ model. Besides, acute creatine (40 and 80 mg/Kg) decreased the incidence of tonic seizures after electroshock. In conclusion, creatine exerts anticonvulsant effects in three seizure models; therefore, it may act as a potential drug to help patients with convulsions. However, further investigations should be done to clarify these results more. PMID:28243281

Guanidinoacetic acid versus creatine for improved brain and muscle creatine levels: a superiority pilot trial in healthy men.

PubMed

Ostojic, Sergej M; Ostojic, Jelena; Drid, Patrik; Vranes, Milan

2016-09-01

In this randomized, double-blind, crossover trial, we evaluated whether 4-week supplementation with guanidinoacetic acid (GAA) is superior to creatine in facilitating creatine levels in healthy men (n = 5). GAA (3.0 g/day) resulted in a more powerful rise (up to 16.2%) in tissue creatine levels in vastus medialis muscle, middle-cerebellar peduncle, and paracentral grey matter, as compared with creatine (P < 0.05). These results indicate that GAA as a preferred alternative to creatine for improved bioenergetics in energy-demanding tissues.

Measurement of Soluble and Total Hexavalent Chromium in the Ambient Airborne Particles in New Jersey

PubMed Central

Huang, Lihui; Yu, Chang Ho; Hopke, Philip K.; Lioy, Paul J.; Buckley, Brian T.; Shin, Jin Young; Fan, Zhihua (Tina)

2015-01-01

Hexavalent chromium (Cr(VI)) in ambient airborne particulate matter (PM) is a known pulmonary carcinogen and may have both soluble and insoluble forms. The sum of the two forms is defined as total Cr(VI). Currently, there were no methods suitable for large-scale monitoring of total Cr(VI) in ambient PM. This study developed a method to measure total Cr(VI) in ambient PM. This method includes PM collection using a Teflon filter, microwave extraction with 3% Na2CO3-2% NaOH at 95°C for 60 minutes, and Cr(VI) analysis by 1,5-diphenylcarbazide colorimetry at 540 nm. The recoveries of total Cr(VI) were 119.5 ± 10.4% and 106.3 ± 16.7% for the Cr(VI)-certified reference materials, SQC 012 and SRM 2700, respectively. Total Cr(VI) in the reference urban PM (NIST 1648a) was 26.0 ± 3.1 mg/kg (%CV = 11.9%) determined by this method. The method detection limit was 0.33 ng/m3. This method and the one previously developed to measure ambient Cr(VI), which is soluble in pH ~9.0 aqueous solution, were applied to measure Cr(VI) in ambient PM10 collected from three urban areas and one suburban area in New Jersey. The total Cr(VI) concentrations were 1.05–1.41 ng/m3 in the winter and 0.99–1.56 ng/m3 in the summer. The soluble Cr(VI) concentrations were 0.03–0.19 ng/m3 in the winter and 0.12–0.37 ng/m3 in the summer. The summer mean ratios of soluble to total Cr(VI) were 14.3–43.7%, significantly higher than 4.2–14.4% in the winter. The winter concentrations of soluble and total Cr(VI) in the suburban area were significantly lower than in the three urban areas. The results suggested that formation of Cr(VI) via atmospheric chemistry may contribute to the higher soluble Cr(VI) concentrations in the summer. PMID:26120324

Macro creatine kinase: determination and differentiation of two types by their activation energies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stein, W.; Bohner, J.; Steinhart, R.

1982-01-01

Determination of the MB isoenzyme of creatine kinase in patients with acute myocardial infarction may be disturbed by the presence of macro creatine kinase. The relative molecular mass of this form of creatine kinase in human serum is at least threefold that of the ordinary enzyme, and it is more thermostable. Here we describe our method for determination of macro creatine kinases and an easy-to-perform test for differentiating two forms of macro creatine kinase, based on their distinct activation energies. The activation energies of serum enzymes are mostly in the range of 40-65 kJ/mol of substrate. Unlike normal cytoplasmatic creatinemore » kinases and IgG-linked CK-BB (macro creatine kinase type 1) a second form of macro creatine kinase (macro creatine kinase type 2) shows activation energies greater than 80 kJ/mol of substrate. The exact composition of macro creatine kinase type 2 is still unknown, but there is good reason to believe that it is of mitochondrial origin.« less

Separation methods applicable to urinary creatine and creatinine.

PubMed

Smith-Palmer, Truis

2002-12-05

Urinary creatinine has been analyzed for many years as an indicator of glomerular filtration rate. More recently, interest in studying the uptake of creatine as a result of creatine supplementation, a practice increasingly common among bodybuilders and athletes, has lead to a need to measure urinary creatine concentrations. Creatine levels are of the same order of magnitude as creatinine levels when subjects have recently ingested creatine, while somewhat elevated urinary creatine concentrations in non-supplementing subjects can be an indication of a degenerative disease of the muscle. Urinary creatine and creatinine can be analyzed by HPLC using a variety of columns. Detection methods include absorption, fluorescence after post-column derivatization, and mass spectrometry, and some methods have been automated. Capillary zone electrophoresis and micellar electrokinetic capillary chromatography have also been used to analyze urinary creatine and creatinine. Creatine and creatinine have also been analyzed in serum and tissue using HPLC and CE, and many of these separations could also be applicable to urinary analysis.

Protective effects of some creatine derivatives in brain tissue anoxia.

PubMed

Perasso, Luisa; Lunardi, Gian Luigi; Risso, Federica; Pohvozcheva, Anna V; Leko, Maria V; Gandolfo, Carlo; Florio, Tullio; Cupello, Aroldo; Burov, Sergey V; Balestrino, Maurizio

2008-05-01

Some derivatives more lipophylic than creatine, thus theoretically being capable to better cross the blood-brain barrier, were studied for their protective effect in mouse hippocampal slices. We found that N-amidino-piperidine is harmful to brain tissue, and that phosphocreatine is ineffective. Creatine, creatine-Mg-complex (acetate) and phosphocreatine-Mg-complex (acetate) increased the latency to population spike disappearance during anoxia. Creatine and creatine-Mg-complex (acetate) also increased the latency of anoxic depolarization, while the delay induced by phosphocreatine-Mg-complex (acetate) was of borderline significance (P = 0.056). Phosphocreatine-Mg-complex (acetate) significantly reduced neuronal hyperexcitability during anoxia, an effect that no other compound (including creatine itself) showed. For all parameters except reduced hyperexcitability the effects statistically correlated with tissue levels of creatine or phosphocreatine. Summing up, exogenous phosphocreatine and N-amidino piperidine are not useful for brain protection, while chelates of both creatine and phosphocreatine do replicate some of the known protective effects of creatine. In addition, phosphocreatine-Mg-complex (acetate) also reduced neuronal hyperexcitability during anoxia.

The role of dietary creatine.

PubMed

Brosnan, Margaret E; Brosnan, John T

2016-08-01

The daily requirement of a 70-kg male for creatine is about 2 g; up to half of this may be obtained from a typical omnivorous diet, with the remainder being synthesized in the body Creatine is a carninutrient, which means that it is only available to adults via animal foodstuffs, principally skeletal muscle, or via supplements. Infants receive creatine in mother's milk or in milk-based formulas. Vegans and infants fed on soy-based formulas receive no dietary creatine. Plasma and muscle creatine levels are usually somewhat lower in vegetarians than in omnivores. Human intake of creatine was probably much higher in Paleolithic times than today; some groups with extreme diets, such as Greenland and Alaskan Inuit, ingest much more than is currently typical. Creatine is synthesized from three amino acids: arginine, glycine and methionine (as S-adenosylmethionine). Humans can synthesize sufficient creatine for normal function unless they have an inborn error in a creatine-synthetic enzyme or a problem with the supply of substrate amino acids. Carnivorous animals, such as lions and wolves, ingest much larger amounts of creatine than humans would. The gastrointestinal tract and the liver are exposed to dietary creatine in higher concentrations before it is assimilated by other tissues. In this regard, our observations that creatine supplementation can prevent hepatic steatosis (Deminice et al. J Nutr 141:1799-1804, 2011) in a rodent model may be a function of the route of dietary assimilation. Creatine supplementation has also been reported to improve the intestinal barrier function of the rodent suffering from inflammatory bowel disease.

Capillary and venous samples of total creatine kinase are similar after eccentric exercise.

PubMed

Knoblauch, Mark A; O'Connor, Daniel P; Clarke, Mark S F

2010-12-01

Circulating creatine kinase (CK) levels are often monitored as an indirect biomarker of muscle damage after resistive exercise. The purpose of the present investigation was to evaluate whether capillary whole-blood sampling, a simpler and less invasive method for obtaining a venous blood sample, would allow for a reliable measurement of total CK compared to venipuncture. Fifteen untrained subjects performed 50 maximal eccentric elbow extensions to induce muscle damage of the biceps brachii. Capillary (fingerstick) and venous whole-blood samples were collected contemporaneously at baseline and again at 24, 48, 72, and 96 hours post-exercise. Using a commercial CK analysis kit with a protocol modification to account for a reduced sample size, total CK activity of the capillary and venous samples was analyzed concurrently via spectrophotometry. Results indicated a 0.997 correlation between sampling sites for total CK, with disagreement between the venous and capillary samples estimated at <12% across the range of CK values. These findings indicate capillary sampling for total CK activity provides a valid alternative to venipuncture and should be considered by researchers, clinicians, and strength and conditioning specialists as an alternate sampling technique when indirectly evaluating muscle damage after exercise.

Cerebral Metabolic Alterations in Rats With Diabetic Ketoacidosis

PubMed Central

Glaser, Nicole; Yuen, Natalie; Anderson, Steven E.; Tancredi, Daniel J.; O'Donnell, Martha E.

2010-01-01

OBJECTIVE Cerebral edema is a life-threatening complication of diabetic ketoacidosis (DKA) in children. Recent data suggest that cerebral hypoperfusion and activation of cerebral ion transporters may be involved, but data describing cerebral metabolic alterations during DKA are lacking. RESEARCH DESIGN AND METHODS We evaluated 50 juvenile rats with DKA and 21 normal control rats using proton and phosphorus magnetic resonance spectroscopy (MRS). MRS measured cerebral intracellular pH and ratios of metabolites including ATP/inorganic phosphate (Pi), phosphocreatine (PCr)/Pi, N-acetyl aspartate (NAA)/creatine (Cr), and lactate/Cr before and during DKA treatment. We determined the effects of treatment with insulin and intravenous saline with or without bumetanide, an inhibitor of Na-K-2Cl cotransport, using ANCOVA with a 2 × 2 factorial study design. RESULTS Cerebral intracellular pH was decreased during DKA compared with control (mean ± SE difference −0.13 ± 0.03; P < 0.001), and lactate/Cr was elevated (0.09 ± 0.02; P < 0.001). DKA rats had lower ATP/Pi and NAA/Cr (−0.32 ± 0.10, P = 0.003, and −0.14 ± 0.04, P < 0.001, respectively) compared with controls, but PCr/Pi was not significantly decreased. During 2-h treatment with insulin/saline, ATP/Pi, PCr/Pi, and NAA/Cr declined significantly despite an increase in intracellular pH. Bumetanide treatment increased ATP/Pi and PCr/Pi and ameliorated the declines in these values with insulin/saline treatment. CONCLUSIONS These data demonstrate that cerebral metabolism is significantly compromised during DKA and that further deterioration occurs during early DKA treatment—consistent with possible effects of cerebral hypoperfusion and reperfusion injury. Treatment with bumetanide may help diminish the adverse effects of initial treatment with insulin/saline. PMID:20028943

Indirect Effects of Elevated Body Mass Index on Memory Performance Through Altered Cerebral Metabolite Concentrations

PubMed Central

Gonzales, Mitzi M.; Takashi, Tarumi; Eagan, Danielle E.; Tanaka, Hirofumi; Vaghasia, Miral; Haley, Andreana P.

2012-01-01

Objective Elevated body mass index (BMI) at midlife is associated with increased risk of cognitive decline in later life. The goal of the current study was to assess mechanisms of early brain vulnerability by examining if higher BMI at midlife has an effect on current cognitive performance through alterations in cerebral neurochemistry. Methods Fifty-five participants, aged 40–60 years, underwent neuropsychological testing, health screen, and proton magnetic resonance spectroscopy (1H MRS) examining N-acetyl-aspartate (NAA), creatine (Cr), myo-inositol (mI), choline (Cho), and glutamate (Glu) concentrations in occipitoparietal grey matter. Concentrations of NAA, Cho, mI, and Glu were calculated as a ratio over Cr and examined in relation to BMI using multivariate regression analyses. Structural equation modeling was used to determine if BMI had an indirect effect on cognition through cerebral metabolite levels. Results Higher BMI was associated with elevations in mI/Cr (F(5,45)= 3.843, p=0.006, β=0.444, p=0.002), independent of age, sex, fasting glucose levels, and systolic blood pressure. Moreover, a chi-square difference test of the direct and indirect structural equation models revealed that BMI had an indirect effect on global cognitive performance (ΔX2(df=2) =19.939, p<0.001). Subsequent follow-up analyses revealed that this effect was specific to memory (ΔX2(df=2) = 22.027, p<0.001). Conclusions Higher BMI was associated with elevations in mI/Cr concentrations in the occipitoparietal grey matter and indirectly related to poorer memory performance through mI/Cr, potentially implicating plasma hypertonicity and neuroinflammation as mechanisms underlying obesity-related brain vulnerability. PMID:22822230

Prefrontal Structure Varies as a Function of Pain Symptoms in Chronic Fatigue Syndrome.

PubMed

van der Schaaf, Marieke E; De Lange, Floris P; Schmits, Iris C; Geurts, Dirk E M; Roelofs, Karin; van der Meer, Jos W M; Toni, Ivan; Knoop, Hans

2017-02-15

Chronic fatigue syndrome (CFS) is characterized by severe fatigue persisting for ≥6 months and leading to considerable impairment in daily functioning. Neuroimaging studies of patients with CFS have revealed alterations in prefrontal brain morphology. However, it remains to be determined whether these alterations are specific for fatigue or whether they relate to other common CFS symptoms (e.g., chronic pain, lower psychomotor speed, and reduced physical activity). We used magnetic resonance imaging to quantify gray matter volume (GMV) and the N-acetylaspartate and N-acetylaspartylglutamate/creatine ratio (NAA/Cr) in a group of 89 women with CFS. Building on previous reports, we tested whether GMV and NAA/Cr in the dorsolateral prefrontal cortex are associated with fatigue severity, pain, psychomotor speed, and physical activity, while controlling for depressive symptoms. We also considered GMV and NAA/Cr differences between patients with CFS and 26 sex-, age-, and education-matched healthy controls. The presence of pain symptoms was the main predictor of both GMV and NAA/Cr in the left dorsolateral prefrontal cortex of patients with CFS. More pain was associated with reduced GMVs and NAA/Cr, over and above the effects of fatigue, depressive symptoms, physical activity, and psychomotor speed. In contrast to previous reports and despite a large representative sample, global GMV did not differ between the CFS and healthy control groups. CFS, as diagnosed by Centers for Disease Control and Prevention criteria, is not a clinical entity reliably associated with reduced GMV. Individual variation in the presence of pain, rather than fatigue, is associated with neuronal alterations in the dorsolateral prefrontal cortex of patients with CFS. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Decreases in Short Term Memory, IQ, and Altered Brain Metabolic Ratios in Urban Apolipoprotein ε4 Children Exposed to Air Pollution.

PubMed

Calderón-Garcidueñas, Lilian; Mora-Tiscareño, Antonieta; Franco-Lira, Maricela; Zhu, Hongtu; Lu, Zhaohua; Solorio, Edelmira; Torres-Jardón, Ricardo; D'Angiulli, Amedeo

2015-01-01

Children's urban air pollution exposures result in systemic and brain inflammation and the early hallmarks of Alzheimer's disease (AD). The apolipoprotein E (APOE) ε4 allele is the most prevalent genetic risk for AD. We assessed whether APOE in healthy children modulates cognition, olfaction, and metabolic brain indices. The Wechsler Intelligence Scale for Children (WISC-R) and the University of Pennsylvania Smell Identification Test were administered to 50 Mexico City Metropolitan Area children (13.4 ± 4.8 years, 28 APOE ε3 and 22 APOE ε4). N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/Cr, myo-inositol (mI)/Cr, and NAA/mI were calculated using proton magnetic resonance spectroscopy in the white matter of the frontal and parietal lobes, hippocampus, and pons. APOE ε4 versus ε3 children had a reduced NAA/Cr ratio in the right frontal white matter and decrements on attention, short-term memory, and below-average scores in Verbal and Full Scale IQ (>10 points). APOE modulated the group effects between WISC-R and left frontal and parietal white matter, and hippocampus metabolites. Soap was the predominantly failed odor in urban children and, in APOE ε4 versus ε3 carriers, strongly correlated with left hippocampus mI/Cr ratio. APOE modulates responses to air pollution in the developing brain. APOE ε4 carriers could have a higher risk of developing early AD if they reside in a polluted environment. APOE, cognition, and olfaction testing and targeted magnetic resonance spectroscopy may contribute to the assessment of urban children and their results could provide new paths toward the unprecedented opportunity for early neuroprotection and AD prevention.

Change in Brain Magnetic Resonance Spectroscopy after Treatment during Acute HIV Infection

PubMed Central

Sailasuta, Napapon; Ross, William; Ananworanich, Jintanat; Chalermchai, Thep; DeGruttola, Victor; Lerdlum, Sukalaya; Pothisri, Mantana; Busovaca, Edgar; Ratto-Kim, Silvia; Jagodzinski, Linda; Spudich, Serena; Michael, Nelson; Kim, Jerome H.; Valcour, Victor

2012-01-01

Objective Single voxel proton magnetic resonance spectroscopy (MRS) can be used to monitor changes in brain inflammation and neuronal integrity associated with HIV infection and its treatments. We used MRS to measure brain changes during the first weeks following HIV infection and in response to antiretroviral therapy (ART). Methods Brain metabolite levels of N-acetyl aspartate (NAA), choline (tCHO), creatine (CR), myoinositol (MI), and glutamate and glutamine (GLX) were measured in acute HIV subjects (n = 31) and compared to chronic HIV+individuals (n = 26) and HIV negative control subjects (n = 10) from Bangkok, Thailand. Metabolites were measured in frontal gray matter (FGM), frontal white matter (FWM), occipital gray matter (OGM), and basal ganglia (BG). Repeat measures were obtained in 17 acute subjects 1, 3 and 6 months following initiation of ART. Results After adjustment for age we identified elevated BG tCHO/CR in acute HIV cases at baseline (median 14 days after HIV infection) compared to control (p = 0.0014), as well as chronic subjects (p = 0.0023). A similar tCHO/CR elevation was noted in OGM; no other metabolite abnormalities were seen between acute and control subjects. Mixed longitudinal models revealed resolution of BG tCHO/CR elevation after ART (p = 0.022) with tCHO/CR similar to control subjects at 6 months. Interpretation We detected cellular inflammation in the absence of measurable neuronal injury within the first month of HIV infection, and normalization of this inflammation following acutely administered ART. Our findings suggest that early ART may be neuroprotective in HIV infection by mitigating processes leading to CNS injury. PMID:23229129

A pilot study of cardiac troponin I in patients with acute myocardial infarction and unstable angina.

PubMed

Selim, Najlaa A; Hmouda, Houssem T

2002-05-01

To assess the value of cardiac troponin I in the initial management of acute myocardial infarction and unstable angina, as well as the concordance between creatine phosphokinase-cardiac isoenzyme and cardiac troponin I. We reviewed retrospectively the charts of 32 patients with acute myocardial infarction or unstable angina admitted to the Intensive Care Unit from the Emergency Room of King Khalid Military City Hospital, Hafar-Al-Batin, Kingdom of Saudi Arabia from April 1998 to September 2000. The time of admission to the intensive care unit, which corresponds to the beginning of thrombolytic therapy, the time when cardiac enzymes (creatine phosphokinase-cardiac isoenzyme and cardiac troponin I) are available as well as number of cardiac troponin I determinations before obtaining a significant positive result (>2ng/ml) and the delay between admission and the first significant positive result of cardiac troponin I, were evaluated. Sixteen patients had confirmed acute myocardial infarction based on the association of typical chest pain, electrocardiographic findings with ST segment elevation and significant increase of the ratio creatine phosphokinase-cardiac isoenzyme/creatine phosphokinase > 10%. Sixteen patients had unstable angina and out of the 16 patients (81.25%) with acute myocardial infarction, 13 received thrombolytic therapy which was initiated on the basis of typical clinical history and electrocardiographic features, before the availability of cardiac enzymes. Troponin I was available in only 13 cases. The number of tests performed in these patients was 32. The first positive result of cardiac troponin I was available within a mean time of 16.66 20.8 hours from admission. The number of negative tests performed before obtaining a frank positive result was 9 in 12 patients. The number of positive tests after having obtained the first frank positive cardiac troponin I result was 10 in 12 patients. In all cases of cardiac troponin I, results were concordant with creatine phosphokinase-cardiac isoenzyme. In the 16 patients with unstable angina, only 11 patients had cardiac troponin I serum level. A total of 21 tests were performed. In 9 patients 14 cardiac troponin I tests were < 2 ng/ml. This was correlated with normal creatine phosphokinase-cardiac isoenzyme/creatine phosphokinase ratio. In 2 patients, 7 cardiac troponin I tests were positive. Both of them had significant increase of creatine phosphokinase-cardiac isoenzyme/creatine phosphokinase ratio and electrocardiographic features of myocardial ischemia and were referred for urgent coronary angiography. Cardiac troponin I levels are not helpful in the initial management of patients with acute myocardial infarction. Thrombolytic therapy should be therefore instituted before the availability of cardiac troponin I results. However, cardiac troponin I results are concordant with creatine phosphokinase-cardiac isoenzyme in retrospective confirmation of the diagnosis of acute myocardial infarction a few hours after onset. In patients with unstable angina, cardiac troponin I should be used mainly for risk stratification.

21 CFR 862.1210 - Creatine test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Creatine test system. 862.1210 Section 862.1210....1210 Creatine test system. (a) Identification. A creatine test system is a device intended to measure creatine (a substance synthesized in the liver and pancreas and found in biological fluids) in plasma...

A Creatine-Driven Substrate Cycle Enhances Energy Expenditure and Thermogenesis in Beige Fat

PubMed Central

Kazak, Lawrence; Chouchani, Edward T.; Jedrychowski, Mark P.; Erickson, Brian K.; Shinoda, Kosaku; Cohen, Paul; Vetrivelan, Ramalingam; Lu, Gina Z.; Laznik-Bogoslavski, Dina; Hasenfuss, Sebastian C.; Kajimura, Shingo; Gygi, Steve P.; Spiegelman, Bruce M.

2015-01-01

SUMMARY Thermogenic brown and beige adipose tissues dissipate chemical energy as heat, and their thermogenic activities can combat obesity and diabetes. Herein the functional adaptations to cold of brown and beige adipose depots are examined using quantitative mitochondrial proteomics. We identify arginine/creatine metabolism as a beige adipose signature and demonstrate that creatine enhances respiration in beige fat mitochondria when ADP is limiting. In murine beige fat, cold exposure stimulates mitochondrial Creatine Kinase activity and induces coordinated expression of genes associated with creatine metabolism. Pharmacological reduction of creatine levels decreases whole body energy expenditure after administration of a β3-agonist and reduces the adipose metabolic rate. Genes of creatine metabolism are compensatorily induced when UCP1-dependent thermogenesis is ablated, and creatine reduction in Ucp1-deficient mice reduces core body temperature. These findings link a futile cycle of creatine metabolism to adipose tissue energy expenditure and thermal homeostasis. PMID:26496606

The cataract and glucosuria associated monocarboxylate transporter MCT12 is a new creatine transporter

PubMed Central

Abplanalp, Jeannette; Laczko, Endre; Philp, Nancy J.; Neidhardt, John; Zuercher, Jurian; Braun, Philipp; Schorderet, Daniel F.; Munier, Francis L.; Verrey, François; Berger, Wolfgang; Camargo, Simone M.R.; Kloeckener-Gruissem, Barbara

2013-01-01

Creatine transport has been assigned to creatine transporter 1 (CRT1), encoded by mental retardation associated SLC6A8. Here, we identified a second creatine transporter (CRT2) known as monocarboxylate transporter 12 (MCT12), encoded by the cataract and glucosuria associated gene SLC16A12. A non-synonymous alteration in MCT12 (p.G407S) found in a patient with age-related cataract (ARC) leads to a significant reduction of creatine transport. Furthermore, Slc16a12 knockout (KO) rats have elevated creatine levels in urine. Transport activity and expression characteristics of the two creatine transporters are distinct. CRT2 (MCT12)-mediated uptake of creatine was not sensitive to sodium and chloride ions or creatine biosynthesis precursors, breakdown product creatinine or creatine phosphate. Increasing pH correlated with increased creatine uptake. Michaelis–Menten kinetics yielded a Vmax of 838.8 pmol/h/oocyte and a Km of 567.4 µm. Relative expression in various human tissues supports the distinct mutation-associated phenotypes of the two transporters. SLC6A8 was predominantly found in brain, heart and muscle, while SLC16A12 was more abundant in kidney and retina. In the lens, the two transcripts were found at comparable levels. We discuss the distinct, but possibly synergistic functions of the two creatine transporters. Our findings infer potential preventive power of creatine supplementation against the most prominent age-related vision impaired condition. PMID:23578822

The cataract and glucosuria associated monocarboxylate transporter MCT12 is a new creatine transporter.

PubMed

Abplanalp, Jeannette; Laczko, Endre; Philp, Nancy J; Neidhardt, John; Zuercher, Jurian; Braun, Philipp; Schorderet, Daniel F; Munier, Francis L; Verrey, François; Berger, Wolfgang; Camargo, Simone M R; Kloeckener-Gruissem, Barbara

2013-08-15

Creatine transport has been assigned to creatine transporter 1 (CRT1), encoded by mental retardation associated SLC6A8. Here, we identified a second creatine transporter (CRT2) known as monocarboxylate transporter 12 (MCT12), encoded by the cataract and glucosuria associated gene SLC16A12. A non-synonymous alteration in MCT12 (p.G407S) found in a patient with age-related cataract (ARC) leads to a significant reduction of creatine transport. Furthermore, Slc16a12 knockout (KO) rats have elevated creatine levels in urine. Transport activity and expression characteristics of the two creatine transporters are distinct. CRT2 (MCT12)-mediated uptake of creatine was not sensitive to sodium and chloride ions or creatine biosynthesis precursors, breakdown product creatinine or creatine phosphate. Increasing pH correlated with increased creatine uptake. Michaelis-Menten kinetics yielded a Vmax of 838.8 pmol/h/oocyte and a Km of 567.4 µm. Relative expression in various human tissues supports the distinct mutation-associated phenotypes of the two transporters. SLC6A8 was predominantly found in brain, heart and muscle, while SLC16A12 was more abundant in kidney and retina. In the lens, the two transcripts were found at comparable levels. We discuss the distinct, but possibly synergistic functions of the two creatine transporters. Our findings infer potential preventive power of creatine supplementation against the most prominent age-related vision impaired condition.

The metabolic burden of creatine synthesis.

PubMed

Brosnan, John T; da Silva, Robin P; Brosnan, Margaret E

2011-05-01

Creatine synthesis is required in adult animals to replace creatine that is spontaneously converted to creatinine and excreted in the urine. Additionally, in growing animals it is necessary to provide creatine to the expanding tissue mass. Creatine synthesis requires three amino acids: glycine, methionine and arginine, and three enzymes: L-arginine:glycine amidinotransferase (AGAT), methionine adenosyltransferase (MAT) and guanidinoacetate methyltransferase (GAMT). The entire glycine molecule is consumed in creatine synthesis but only the methyl and amidino groups, respectively, from methionine and arginine. Creatinine loss averages approximately 2 g (14.6 mmol) for 70 kg males in the 20- to 39-year age group. Creatinine loss is lower in females and in older age groups because of lower muscle mass. Approximately half of this creatine lost to creatinine can be replaced, in omnivorous individuals, by dietary creatine. However, since dietary creatine is only provided in animal products, principally in meat and fish, virtually all of the creatine loss in vegetarians must be replaced via endogenous synthesis. Creatine synthesis does not appear to place a major burden on glycine metabolism in adults since this amino acid is readily synthesized. However, creatine synthesis does account for approximately 40% of all of the labile methyl groups provided by S-adenosylmethionine (SAM) and, as such, places an appreciable burden on the provision of such methyl groups, either from the diet or via de novo methylneogenesis. Creatine synthesis consumes some 20-30% of arginine's amidino groups, whether provided in the diet or synthesized within the body. Creatine synthesis is, therefore, a quantitatively major pathway in amino acid metabolism and imposes an appreciable burden on the metabolism of methionine and of arginine.

Qualitative in vitro NMR analysis of creatine ethyl ester pronutrient in human plasma.

PubMed

Giese, M W; Lecher, C S

2009-10-01

There are a number of forms of creatine available that attempt to improve the solubility and permeability, with the anticipation this will result in an improved pharmacokinetic profile and ultimately an enhanced ergogenic response. Previous research has shown that the different salt forms can improve solubility resulting in slightly altered pharmacokinetic profiles, however specific data exploring the conversion of esterified derivatives to creatine is lacking. The purpose of this study was to examine the assertion that creatine ethyl ester undergoes enzymatic conversion to creatine in human tissues. The IN VITRO response of creatine ethyl ester to incubation in human plasma was examined by H-NMR analysis. Lyophilized human plasma was reconstituted in D2O and phosphate-buffered saline and 1.5 mg of the analyte was added. Following incubation at 37 degrees C for 4 h and subsequent protein precipitation, the supernatant was analyzed by NMR, utilizing the diagnostic chemical shift of the methylene signal to determine the species present in solution, I.E. creatine ethyl ester, creatine, or creatinine. Both creatine and creatinine were run in parallel as control experiments and each assay was run in triplicate. As expected both creatine and creatinine remained unchanged. However, conversion of creatine ethyl ester to creatine by the esterases in human plasma was not observed to any detectable extent and the only species detected after the incubation period was creatinine. While not a definitive characterization of the IN VIVO behavior, these results strongly warrant a complete IN VIVO pharmacokinetic analysis of creatine ethyl ester since it appears these "pronutrients" may actually provide large exogenous sources of pharmacologically inactive creatinine rather than ergogenic creatine.

Human, rat and chicken small intestinal Na+-Cl−-creatine transporter: functional, molecular characterization and localization

PubMed Central

Peral, M J; García-Delgado, M; Calonge, M L; Durán, J M; De La Horra, M C; Wallimann, T; Speer, O; Ilundáin, A A

2002-01-01

In spite of all the fascinating properties of oral creatine supplementation, the mechanism(s) mediating its intestinal absorption has(have) not been investigated. The purpose of this study was to characterize intestinal creatine transport. [14C]Creatine uptake was measured in chicken enterocytes and rat ileum, and expression of the creatine transporter CRT was examined in human, rat and chicken small intestine by reverse transcription-polymerase chain reaction, Northern blot, in situ hybridization, immunoblotting and immunohistochemistry. Results show that enterocytes accumulate creatine against its concentration gradient. This accumulation was electrogenic, Na+- and Cl−-dependent, with a probable stoichiometry of 2 Na+: 1 Cl−: 1 creatine, and inhibited by ouabain and iodoacetic acid. The kinetic study revealed a Km for creatine of 29 μm. [14C]Creatine uptake was efficiently antagonized by non-labelled creatine, guanidinopropionic acid and cyclocreatine. More distant structural analogues of creatine, such as GABA, choline, glycine, β-alanine, taurine and betaine, had no effect on intestinal creatine uptake, indicating a high substrate specificity of the creatine transporter. Consistent with these functional data, messenger RNA for CRT was detected only in the cells lining the intestinal villus. The sequences of partial clones, and of the full-length cDNA clone, isolated from human and rat small intestine were identical to previously cloned CRT cDNAs. Immunological analysis revealed that CRT protein was mainly associated with the apical membrane of the enterocytes. This study reports for the first time that mammalian and avian enterocytes express CRT along the villus, where it mediates high-affinity, Na+- and Cl−-dependent, apical creatine uptake. PMID:12433955

Creatine synthesis and exchanges between brain cells: What can be learned from human creatine deficiencies and various experimental models?

PubMed

Hanna-El-Daher, Layane; Braissant, Olivier

2016-08-01

While it has long been thought that most of cerebral creatine is of peripheral origin, the last 20 years has provided evidence that the creatine synthetic pathway (AGAT and GAMT enzymes) is expressed in the brain together with the creatine transporter (SLC6A8). It has also been shown that SLC6A8 is expressed by microcapillary endothelial cells at the blood-brain barrier, but is absent from surrounding astrocytes, raising the concept that the blood-brain barrier has a limited permeability for peripheral creatine. The first creatine deficiency syndrome in humans was also discovered 20 years ago (GAMT deficiency), followed later by AGAT and SLC6A8 deficiencies, all three diseases being characterized by creatine deficiency in the CNS and essentially affecting the brain. By reviewing the numerous and latest experimental studies addressing creatine transport and synthesis in the CNS, as well as the clinical and biochemical characteristics of creatine-deficient patients, our aim was to delineate a clearer view of the roles of the blood-brain and blood-cerebrospinal fluid barriers in the transport of creatine and guanidinoacetate between periphery and CNS, and on the intracerebral synthesis and transport of creatine. This review also addresses the question of guanidinoacetate toxicity for brain cells, as probably found under GAMT deficiency.

Effects of long-term, low-dose sex hormone replacement therapy on hippocampus and cognition of postmenopausal women of different apoE genotypes.

PubMed

Yue, Yun; Hu, Ling; Tian, Qin-jie; Jiang, Jing-mei; Dong, Yi-long; Jin, Zheng-yu; Cheng, Yu-hang; Hong, Xia; Ge, Qin-sheng; Zuo, Ping-ping

2007-08-01

To study the effects of long-term, low-dose sex hormone replacement therapy (HRT) on the volume and biochemical changes of the hippocampus in postmenopausal women carrying apolipoprotein E (apoE) gene epsilon3 or epsilon4. Eighty-three postmenopausal women who had used a low dose of HRT for over 4 years were selected as the HRT group, and 99 postmenopausal women with matched age and education were enrolled as the control group. ApoE alleles were analyzed by PCR. Magnetic resonance imaging was performed to determine the volume of the brain hippocampus. Proton magnetic resonance spectroscopy was used to detect the biochemical changes in the anterior cingulate cortex and hippocampus in apoE epsilon4 and epsilon3 carriers. Six common cognitive tests were used to make an overall evaluation of cognitive function. Analysis with the apoE epsilon4 carriers showed that the volume of the hippocampus of the control group were significantly lower than those of the HRT group. The biochemical analysis showed that there was an increase of N-acetylaspartate (NAA)/total creatine (tCr) and a decrease of myoinositol (mI)/tCr in the hippocampus of apoE epsilon4 carriers in the HRT group, compared with the control group. For the apoE epsilon3 carriers, the least squares means (LSMEAN) of the HRT group was higher than that of the control group. This study showed that long-term, low dose HRT might be beneficial for reducing the risk of AD development in vulnerable postmenopausal women. Meanwhile, HRT could increase the LSMEAN of apoE epsilon3 carriers.

Choline-to-N-acetyl aspartate and lipids-lactate-to-creatine ratios together with age assemble a significant Cox's proportional-hazards regression model for prediction of survival in high-grade gliomas

PubMed Central

Rios, Camilo; Motola-Kuba, Daniel; Matus-Santos, Juan; Villa, Antonio R; Moreno-Jimenez, Sergio

2016-01-01

Objective: A long-lasting concern has prevailed for the identification of predictive biomarkers for high-grade gliomas (HGGs) using MRI. However, a consensus of which imaging parameters assemble a significant survival model is still missing in the literature; we investigated the significant positive or negative contribution of several MR biomarkers in this tumour prognosis. Methods: A retrospective cohort of supratentorial HGGs [11 glioblastoma multiforme (GBM) and 17 anaplastic astrocytomas] included 28 patients (9 females and 19 males, respectively, with a mean age of 50.4 years, standard deviation: 16.28 years; range: 13–85 years). Oedema and viable tumour measurements were acquired using regions of interest in T1 weighted, T2 weighted, fluid-attenuated inversion recovery, apparent diffusion coefficient (ADC) and MR spectroscopy (MRS). We calculated Kaplan–Meier curves and obtained Cox's proportional hazards. Results: During the follow-up period (3–98 months), 17 deaths were recorded. The median survival time was 1.73 years (range, 0.287–8.947 years). Only 3 out of 20 covariates (choline-to-N-acetyl aspartate and lipids-lactate-to-creatine ratios and age) showed significance in explaining the variability in the survival hazards model; score test: χ2 (3) = 9.098, p = 0.028. Conclusion: MRS metabolites overcome volumetric parameters of peritumoral oedema and viable tumour, as well as tumour region ADC measurements. Specific MRS ratios (Cho/Naa, L-L/Cr) might be considered in a regular follow-up for these tumours. Advances in knowledge: Cho/Naa ratio is the strongest survival predictor with a log-hazard function of 2.672 in GBM. Low levels of lipids–lactate/Cr ratio represent up to a 41.6% reduction in the risk of death in GBM. PMID:27626830

Fab fragments of ovine antibody to colchicine enhance its clearance in the rat.

PubMed

Peake, Philip W; Pianta, Timothy J; Succar, Lena; Fernando, Mangalee; Buckley, Nicholas A; Endre, Zoltan H

2015-06-01

Colchicine is an anti-inflammatory alkaloid used for the treatment of acute gout, but has a narrow therapeutic index. Colchicine overdoses are relatively rare, but have high mortality requiring rapid treatment. To evaluate the ability of a newly available ovine fragment antigen-binding (Fab) antibody to colchicine (ColchiFab(™)) to protect rats against renal and other injury 24 h after colchicine ingestion. Rats were gavaged with colchicine (5 mg/kg), then 2 h later injected intraperitoneally with 5 ml of sterile saline, or Fab anti-colchicine, a newly available ovine antibody to colchicine. Samples of blood were taken at 1, 2, 5 and 24 h after gavage, and urine was collected from 5 to 24 h after gavage. Concentrations of colchicine in tissue, blood and urine were measured by liquid chromatography/mass spectrometry, concentrations of Fab anti-colchicine, urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 or KIM-1 by enzyme-linked immunosorbent assay or ELISA, while concentrations of creatine kinase and creatinine (Cr) were measured enzymatically. Colchicine equilibrated rapidly throughout the body and increased serum creatine kinase. Fab anti-colchicine also rapidly redistributed to the blood and remained at high concentrations over 24 h. Fab anti-colchicine caused a rapid 7.1-fold increase in serum colchicine level, followed by excretion of both colchicine and Fab anti-colchicine through the urine. This was associated with the accumulation of colchicine in the kidney, a reversal of colchicine-induced diarrhoea, and increasing urinary NGAL level; from 168 ± 48 to 477 ± 255 ng/mmol Cr [mean ± standard deviation or SD]. Fab anti-colchicine greatly increased the clearance of colchicine, although increasing NGAL level suggested the presence of mild kidney damage. These data suggest clinical utility for Fab anti-colchicine in the treatment of colchicine overdose.

Co-administration of creatine and guanidinoacetic acid for augmented tissue bioenergetics: A novel approach?

PubMed

Ostojic, Sergej M

2017-07-01

A confined absorption of exogenous creatine through creatine transporter (CRT1) seems to hamper its optimal uptake in bioenergetical deficits. Co-administration of guanidinoacetic acid (GAA) along with creatine could target other transport channels besides CRT1, and supremely improve cellular levels of creatine. This innovative approach might tackle tissues difficult to reach with conventional creatine interventions, providing a potentially more effective and safe mixture in clinical pharmacology and therapeutics. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

A simple LC method with UV detection for the analysis of creatine and creatinine and its application to several creatine formulations.

PubMed

Dash, Alekha K; Sawhney, Angeli

2002-07-31

The objective of this study was to develop a simple and sensitive LC method for the determination of creatine and creatinine in various creatine supplement formulations. The chromatographic system comprised of a LC-600 pump, SCL-6B system controller, and SPD-6AV detector (Shimadzu, Japan). The mobile phase consisted of 0.045 M ammonium sulfate in water. The chromatographic separation was achieved at ambient temperature on a Betabasic C-18 column (250 x 4.6 mm, Keystone Sci.). The flow rate was maintained at 0.75 ml/min and effluents are monitored at 205 nm. 4-(2-Aminoethyl)benzene sulfonamide was used as an internal standard (IS). This method required less than 7 min of chromatographic time. The standard curves were linear over the concentration range of 1-100 microg/ml for creatine and 2-100 microg/ml for creatinine, respectively. The relative standard deviations (RSD) for the within-day and day-to-day precision for creatine were within 1.0-4.6 and 2.2-4.7%, respectively. The RSD for the accuracy of creatine assay was in the range of 2.4-4.7%. The RSD values for the within-day precision, day-to-day precision and accuracy for creatinine validation were 1.7-4.4, 2.3-5.4 and 2.4-4.8%, respectively. This method was used to determine: (i) the creatine concentration in various marketed products; (ii) saturated solubility of various creatine salts; and (iii) stability of creatine in aqueous solution. In conclusion, a simple and sensitive LC method with UV detection was developed for the simultaneous determination of creatine and creatinine in formulations. Di-creatine citrate salt showed a higher aqueous solubility (at 25 degrees C) as compared to creatine and creatine monohydrate. Some of the over-the-counter (OTC) products tested contained a very low level of creatine in contrast to their label claim. Substantial conversion of creatine into creatinine was noticed in liquid formulation.

Increased Concentrations of Glutamate and Glutamine in Normal-Appearing White Matter of Patients with Multiple Sclerosis and Normal MR Imaging Brain Scans

PubMed Central

Tisell, Anders; Leinhard, Olof Dahlqvist; Warntjes, Jan Bertus Marcel; Aalto, Anne; Smedby, Örjan; Landtblom, Anne-Marie; Lundberg, Peter

2013-01-01

In Multiple Sclerosis (MS) the relationship between disease process in normal-appearing white matter (NAWM) and the development of white matter lesions is not well understood. In this study we used single voxel proton ‘Quantitative Magnetic Resonance Spectroscopy’ (qMRS) to characterize the NAWM and thalamus both in atypical ‘Clinically Definite MS’ (CDMS) patients, MRIneg (N = 15) with very few lesions (two or fewer lesions), and in typical CDMS patients, MRIpos (N = 20) with lesions, in comparison with healthy control subjects (N = 20). In addition, the metabolite concentrations were also correlated with extent of brain atrophy measured using Brain Parenchymal Fraction (BPF) and severity of the disease measured using ‘Multiple Sclerosis Severity Score’ (MSSS). Elevated concentrations of glutamate and glutamine (Glx) were observed in both MS groups (MRIneg 8.12 mM, p<0.001 and MRIpos 7.96 mM p<0.001) compared to controls, 6.76 mM. Linear regressions of Glx and total creatine (tCr) with MSSS were 0.16±0.06 mM/MSSS (p = 0.02) for Glx and 0.06±0.03 mM/MSSS (p = 0.04) for tCr, respectively. Moreover, linear regressions of tCr and myo-Inositol (mIns) with BPF were −6.22±1.63 mM/BPF (p<0.001) for tCr and −7.71±2.43 mM/BPF (p = 0.003) for mIns. Furthermore, the MRIpos patients had lower N-acetylaspartate and N-acetylaspartate-glutamate (tNA) and elevated mIns concentrations in NAWM compared to both controls (tNA: p = 0.04 mIns p<0.001) and MRIneg (tNA: p = 0.03 , mIns: p = 0.002). The results suggest that Glx may be an important marker for pathology in non-lesional white matter in MS. Moreover, Glx is related to the severity of MS independent of number of lesions in the patient. In contrast, increased glial density indicated by increased mIns and decreased neuronal density indicated by the decreased tNA, were only observed in NAWM of typical CDMS patients with white matter lesions. PMID:23613944

A creatine-driven substrate cycle enhances energy expenditure and thermogenesis in beige fat.

PubMed

Kazak, Lawrence; Chouchani, Edward T; Jedrychowski, Mark P; Erickson, Brian K; Shinoda, Kosaku; Cohen, Paul; Vetrivelan, Ramalingam; Lu, Gina Z; Laznik-Bogoslavski, Dina; Hasenfuss, Sebastian C; Kajimura, Shingo; Gygi, Steve P; Spiegelman, Bruce M

2015-10-22

Thermogenic brown and beige adipose tissues dissipate chemical energy as heat, and their thermogenic activities can combat obesity and diabetes. Herein the functional adaptations to cold of brown and beige adipose depots are examined using quantitative mitochondrial proteomics. We identify arginine/creatine metabolism as a beige adipose signature and demonstrate that creatine enhances respiration in beige-fat mitochondria when ADP is limiting. In murine beige fat, cold exposure stimulates mitochondrial creatine kinase activity and induces coordinated expression of genes associated with creatine metabolism. Pharmacological reduction of creatine levels decreases whole-body energy expenditure after administration of a β3-agonist and reduces beige and brown adipose metabolic rate. Genes of creatine metabolism are compensatorily induced when UCP1-dependent thermogenesis is ablated, and creatine reduction in Ucp1-deficient mice reduces core body temperature. These findings link a futile cycle of creatine metabolism to adipose tissue energy expenditure and thermal homeostasis. PAPERCLIP. Copyright © 2015 Elsevier Inc. All rights reserved.

Arginine-guanidinoacetate-creatine pathway in preterm newborns: creatine biosynthesis in newborns.

PubMed

Lage, Sergio; Andrade, Fernando; Prieto, José Angel; Asla, Izaskun; Rodríguez, Amaya; Ruiz, Nerea; Echeverría, Juncal; Luz Couce, María; Sanjurjo, Pablo; Aldámiz-Echevarría, Luis

2013-01-01

The phosphocreatine/creatine system is fundamental for the proper development of the embryonic brain. Being born prematurely might alter the creatine biosynthesis pathway, in turn affecting creatine supply to the developing brain. We enrolled 53 preterm and very preterm infants and 55 full-term newborns. The levels of urinary guanidinoacetate, creatine, creatinine and amino acids were measured in the preterm and very preterm groups, 48 h and 9 days after birth and at discharge, and 48 h after birth in the full-term group. Guanidinoacetate concentrations of both preterm and very preterm newborns were significantly higher at discharge than the values for the full-term group at 48 h, while very preterm infants showed urinary creatine values significantly lower than those measured in the full-term group. Our results suggest an impairment of the creatine biosynthesis pathway in preterm and very preterm newborns, which could lead to creatine depletion affecting the neurological outcome in prematurely born infants.

CK-MM Polymorphism is Associated With Physical Fitness Test Scores in Military Recruits.

PubMed

Sprouse, Courtney; Tosi, Laura L; Gordish-Dressman, Heather; Abdel-Ghani, Mai S; Panchapakesan, Karuna; Niederberger, Brenda; Devaney, Joseph M; Kelly, Karen R

2015-09-01

Muscle-specific creatine kinase is thought to play an integral role in maintaining energy homeostasis by providing a supply of creatine phosphate. The genetic variant, rs8111989, contributes to individual differences in physical performance, and thus the purpose of this study was to determine if rs8111989 variant is predictive of Physical Fitness Test (PFT) scores in male, military infantry recruits. DNA was extracted from whole blood, and genotyping was performed in 176 Marines. Relationships between PFT measures (run, sit-ups, and pull-ups) and genotype were determined. Participants with 2 copies of the T allele for rs8111989 variant had higher PFT scores for run time, pull-ups, and total PFT score. Specifically, participants with 2 copies of the TT allele (variant) (n = 97) demonstrated an overall higher total PFT score as compared with those with one copy of the C allele (n = 79) (TT: 250 ± 31 vs. 238 ± 31; p = 0.02), run score (TT: 82 ± 10 vs. 78 ± 11; p = 0.04) and pull-up score (TT: 78 ± 11 vs. 65 ± 21; p = 0.04) or those with the CC/CT genotype. These results demonstrate an association between physical performance measures and genetic variation in the muscle-specific creatine kinase gene (rs8111989). Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

21 CFR 862.1215 - Creatine phosphokinase/creatine kinase or isoenzymes test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1215 Creatine phosphokinase/creatine kinase or isoenzymes test system...

21 CFR 862.1215 - Creatine phosphokinase/creatine kinase or isoenzymes test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1215 Creatine phosphokinase/creatine kinase or isoenzymes test system...

21 CFR 862.1215 - Creatine phosphokinase/creatine kinase or isoenzymes test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1215 Creatine phosphokinase/creatine kinase or isoenzymes test system...

21 CFR 862.1215 - Creatine phosphokinase/creatine kinase or isoenzymes test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1215 Creatine phosphokinase/creatine kinase or isoenzymes test system...

Creatine and creatine pyruvate reduce hypoxia-induced effects on phrenic nerve activity in the juvenile mouse respiratory system.

PubMed

Scheer, Monika; Bischoff, Anna M; Kruzliak, Peter; Opatrilova, Radka; Bovell, Douglas; Büsselberg, Dietrich

2016-08-01

Adequate concentrations of ATP are required to preserve physiological cell functions and protect tissue from hypoxic damage. Decreased oxygen concentration results in ATP synthesis relying increasingly on the presence of phosphocreatine. The lack of ATP through hypoxic insult to neurons that generate or regulate respiratory function, would lead to the cessation of breathing (apnea). It is not clear whether creatine plays a role in maintaining respiratory phrenic nerve (PN) activity during hypoxic challenge. The aim of the study was to test the effects of exogenously applied creatine or creatine pyruvate in maintaining PN induced respiratory rhythm against the deleterious effects of severe hypoxic insult using Working Heart-Brainstem (WHB) preparations of juvenile Swiss type mice. WHB's were perfused with control perfusate or perfusate containing either creatine [100μM] or creatine pyruvate [100μM] prior to hypoxic challenge and PN activity recorded throughout. Results showed that severe hypoxic challenge resulted in an initial transient increase in PN activity, followed by a reduction in that activity leading to respiratory apnea. The results demonstrated that perfusing the WHB preparation with creatine or creatine pyruvate, significantly reduced the onset of apnea compared to control conditions, with creatine pyruvate being the more effective substance. Overall, creatine and creatine pyruvate each produced time-dependent degrees of protection against severe hypoxic-induced disturbances of PN activity. The underlying protective mechanisms are unknown and need further investigations. Copyright © 2016 Elsevier Inc. All rights reserved.

Synthesis of guanidinoacetate and creatine from amino acids by rat pancreas.

PubMed

da Silva, Robin P; Clow, Kathy; Brosnan, John T; Brosnan, Margaret E

2014-02-01

Creatine is an important molecule involved in cellular energy metabolism. Creatine is spontaneously converted to creatinine at a rate of 1·7% per d; creatinine is lost in the urine. Creatine can be obtained from the diet or synthesised from endogenous amino acids via the enzymes arginine:glycine amidinotransferase (AGAT) and guanidinoacetate N-methyltransferase (GAMT). The liver has high GAMT activity and the kidney has high AGAT activity. Although the pancreas has both AGAT and GAMT activities, its possible role in creatine synthesis has not been characterised. In the present study, we examined the enzymes involved in creatine synthesis in the pancreas as well as the synthesis of guanidinoacetate (GAA) and creatine by isolated pancreatic acini. We found significant AGAT activity and somewhat lower GAMT activity in the pancreas and that pancreatic acini had measurable activities of both AGAT and GAMT and the capacity to synthesise GAA and creatine from amino acids. Creatine supplementation led to a decrease in AGAT activity in the pancreas, though it did not affect its mRNA or protein abundance. This was in contrast with the reduction of AGAT activity and mRNA and protein abundance in the kidney, suggesting that the regulatory mechanisms that control the expression of this enzyme in the pancreas are different from those in the kidney. Dietary creatine increased the concentrations of GAA, creatine and phosphocreatine in the pancreas. Unexpectedly, creatine supplementation decreased the concentrations of S-adenosylmethionine, while those of S-adenosylhomocysteine were not altered significantly.

Serum creatine kinase isoenzymes in children with osteogenesis imperfecta.

PubMed

D'Eufemia, P; Finocchiaro, R; Zambrano, A; Lodato, V; Celli, L; Finocchiaro, S; Persiani, P; Turchetti, A; Celli, M

2017-01-01

This study evaluates serum creatine kinase isoenzyme activity in children with osteogenesis imperfecta to determine its usefulness as a biochemical marker during treatment with bisphosphonate. The changes of creatine kinase (CK) isoenzyme activity during and after discontinuation therapy were observed. These results could be useful in addressing over-treatment risk prevention. The brain isoenzyme of creatine kinase (CKbb) is highly expressed in mature osteoclasts during osteoclastogenesis, thus plays an important role in bone resorption. We previously identified high serum CKbb levels in 18 children with osteogenesis imperfect (OI) type 1 treated for 1 year with bisphosphonate (neridronate). In the present study, serum CK isoenzymes were evaluated in the same children with continuous versus discontinued neridronate treatment over a further 2-year follow-up period. This study included 18 children with OI type 1, 12 with continued (group A) and 6 with ceased (group B) neridronate treatment. Auxological data, serum biochemical markers of bone metabolism, bone mineral density z-score, and serum total CK and isoenzyme activities were determined in both groups. Serum CKbb was progressively and significantly increased in group A (p < 0.004) but rapidly decreased to undetectable levels in group B. In both groups, the cardiac muscle creatine kinase isoenzyme (CKmb) showed a marked decrease, while serum C-terminal telopeptide (CTx) levels were almost unchanged. This study provides evidence of the cumulative effect of neridronate administration in increasing serum CKbb levels and the reversible effect after its discontinuation. This approach could be employed for verifying the usefulness of serum CKbb as a biochemical marker in patients receiving prolonged bisphosphonate treatment. Moreover, the decreased serum CKmb levels suggest a systemic effect of these drugs.

Assessing multiple-group diagnostic problems with multi-dimensional receiver operating characteristic surfaces: Application to proton MR Spectroscopy (MRS) in HIV-related neurological injury

PubMed Central

Yiannoutsos, Constantin T.; Nakas, Christos T.; Navia, Bradford A.

2013-01-01

We present the multi-dimensional Receiver Operating Characteristic (ROC) surface, a plot of the true classification rates of tests based on levels of biological markers, for multi-group discrimination, as an extension of the ROC curve, commonly used in two-group diagnostic testing. The volume under this surface (VUS) is a global accuracy measure of a test to classify subjects in multiple groups and useful to detect trends in marker measurements. We used three-dimensional ROC surfaces, and associated VUS, to discriminate between HIV-negative (NEG), HIV-positive neurologically asymptomatic (NAS) subjects and patients with AIDS demential complex (ADC), using brain metabolites measured by proton MRS. These were ratios of markers of inflammation, Choline (Cho) and myoinositol (MI), and brain injury, N-acetyl aspartate (NAA), divided by Creatine (Cr), measured in the basal ganglia and the frontal white matter. Statistically significant trends were observed in the three groups with respect to MI/Cr (VUS=0.43; 95% confidence interval (CI) 0.33-0.53), Cho/Cr (0.36; 0.27-0.45) in the basal ganglia and NAA/Cr in the frontal white matter (FWM) (0.29; 0.20-0.38), suggesting a continuum of injury during the neurologically asymptomatic stage of HIV infection, particularly with respect to brain inflammation. Adjusting for age increased the combined classification accuracy of age and NAA/Cr (p=0.053). Pairwise comparisons suggested that neuronal damage associated with NAA/Cr decreases was mainly observed in individuals with ADC, raising issues of synergism between HIV infection and age and possible acceleration of neurological deterioration in an aging HIV-positive population. The three-dimensional ROC surface and its associated VUS are useful for assessing marker accuracy, detecting data trends and offering insight in disease processes affecting multiple groups. PMID:18191586

Regional metabolic changes in the hippocampus and posterior cingulate area detected with 3-Tesla magnetic resonance spectroscopy in patients with mild cognitive impairment and Alzheimer disease.

PubMed

Wang, Zhiqun; Zhao, Cheng; Yu, Lei; Zhou, Weidong; Li, Kuncheng

2009-04-01

Magnetic resonance spectroscopy (MRS) plays an important role in early diagnosis of Alzheimer disease (AD). There are many reports on MRS studies among individuals with AD and mild cognitive impairment (MCI). However, very few studies have compared spectroscopic data of different limbic regions among AD and MCI subjects. To compare metabolite changes of different regions in the brain of AD and MCI patients by using 3.0 T short-echo-time MRS. Metabolite ratios in the hippocampus and posterior cingulate area were compared in a group of patients with AD (n=16), MCI (n=16), and normal subjects as a control group (n=16). Clinical neuropsychological tests were measured in all subjects. In the hippocampus, there were significant differences in N-acetylaspartate (NAA)/creatine (Cr), myo-inositol (mI)/Cr, and mI/NAA ratios among the three groups. However, there were no significant differences in choline (Cho)/Cr ratio among the three groups. In the posterior cingulate area, there were no significant differences in the NAA/Cr, Cho/Cr, and mI/Cr ratios among the three groups. However, there were significant differences in mI/NAA ratio between patients with AD and the control group, and between the AD and MCI groups. In addition, there was significant correlation between mI/NAA ratio and Mini Mental Status Exam (MMSE) score in subjects with AD and MCI. The study reveals that the elevation of mI/NAA ratio in the hippocampus is more significant than that in the posterior cingulate area, which corresponds to the pathologic procession of AD. The ratios of mI/NAA in the hippocampus and in the posterior cingulate area together provide valuable discrimination among the three groups (AD, MCI, and controls). There is a significant correlation between mI/NAA ratio and cognitive decline.

Experience of diffusion tensor imaging and 1H spectroscopy for outcome prediction in severe traumatic brain injury: Preliminary results.

PubMed

Tollard, Eléonore; Galanaud, Damien; Perlbarg, Vincent; Sanchez-Pena, Paola; Le Fur, Yann; Abdennour, Lamine; Cozzone, Patrick; Lehericy, Stéphane; Chiras, Jacques; Puybasset, Louis

2009-04-01

The objective of the study is to test whether multimodal magnetic resonance imaging can provide a reliable outcome prediction of the clinical status, focusing on consciousness at 1 year after severe traumatic brain injury (TBI). Single center prospective cohort with consecutive inclusions. Critical Care Neurosurgical Unit of a university hospital. Forty-three TBI patients not responding to simple orders after sedation cessation and 15 healthy controls. A multimodal magnetic resonance imaging combining morphologic sequences, diffusion tensor imaging (DTI), and H proton magnetic resonance spectroscopy (MRS) was performed 24 +/- 11 days after severe TBI. The ability of DTI and MRS to predict 1-year outcome was assessed by linear discriminant analysis (LDA). Robustness of the classification was tested using a bootstrap procedure. Fractional anisotropy (FA) was computed as the mean of values at discrete brain sites in the infratentorial and supratentorial regions. The N-acetyl aspartate/creatine (NAA/Cr) ratio was measured in the thalamus, lenticular nucleus, insular cortex, occipital periventricular white matter, and pons. After 1 year, 19 (44%) patients had unfavorable outcomes (death, persistent vegetative state, or minimally conscious state) and 24 (56%) favorable outcomes (normal consciousness with or without functional impairments). Analysis of variance was performed to compare FA and NAA/Cr in the two outcome groups and controls. FA and MRS findings showed highly significant differences between the outcome groups, with significant variables by LDA being supratentorial FA, NAA/Cr (pons), NAA/Cr (thalamus), NAA/Cr (insula), and infratentorial FA. LDA of combined FA and MRS data clearly separated the unfavorable outcome, favorable outcome, and control groups, with no overlap. Unfavorable outcome was predicted with up to 86% sensitivity and 97% specificity; these values were better than those obtained with DTI or MRS alone. FA and NAA/Cr hold potential as quantitative outcome-prediction tools at the subacute phase of TBI.

Differences in the direction of change of cerebral function parameters are evident over three years in HIV-infected individuals electively commencing initial cART.

PubMed

Winston, Alan; Puls, Rebekah; Kerr, Stephen J; Duncombe, Chris; Li, Patrick; Gill, John M; Ramautarsing, Reshmie; Taylor-Robinson, Simon D; Emery, Sean; Cooper, David A

2015-01-01

Changes in cerebral metabolite ratios (CMR) measured on 1H-MRS and changes in cognitive function (CF) are described in subjects commencing combination antiretroviral therapy (cART), although the dynamics of such changes are poorly understood. Neuroasymptomatic, HIV-infected subjects electively commencing cART were eligible. CMR were assessed in three anatomical voxels and CF assessed at baseline, week 48 and week 144. Overall differences in absolute change in CMRs and CF parameters between 0-48 and 48-144 weeks were assessed. Twenty-two subjects completed study procedures. Plasma HIV-RNA was <50 copies/mL in all at week 48 and in all, but two subjects at week 144. In general, between weeks 0-48 a rise in N-acetyl-aspartate(NAA)/Creatine(Cr) ratio and a decline in myo-Inositol(mI)/Cr ratio were observed. Between weeks 48-144, small rises in NAA/Cr ratio were observed in two anatomical voxels, whereas a rise in mI/Cr ratio was observed in all anatomical locations (0.31 (0.66) and -0.27 (1.35) between weeks 0-48 and 0.13 (0.91) and 1.13 (1.71) between weeks 48-144 for absolute changes in NAA/Cr and mI/Cr (SD) in frontal-grey voxel, respectively). Global CF score improved between weeks 0-48 and then declined between weeks 48-144 (0.63 (1.16) and -0.63 (0.1.41) for mean absolute change (SD) between weeks 0-48 and weeks 48-144, respectively). The direction of change of cerebral function parameters differs over time in HIV-infected subjects commencing cART, highlighting the need for long-term follow-up in such studies. The changes we have observed between weeks 48-144 may represent the initial development of cerebral toxicities from cART.

Exposure to hexavalent chromium in welders: Results of the WELDOX II field study.

PubMed

Pesch, Beate; Lehnert, Martin; Weiss, Tobias; Kendzia, Benjamin; Menne, Eleonore; Lotz, Anne; Heinze, Evelyn; Behrens, Thomas; Gabriel, Stefan; Schneider, Wolfgang; Brüning, Thomas

2018-03-12

Exposure to hexavalent chromium (Cr(VI)) has been primarily studied in chromate production. Here, we measured personal exposure to respirable Cr(VI) together with airborne and urinary Cr and Ni in welders to explore levels and associations between various measures of exposure. Shift concentrations of Cr(VI), Cr, and Ni were measured in respirable welding fumes in 50 men who used either gas metal arc welding (GMAW) (n = 24) or tungsten inert gas welding (TIG) (n = 19) as their major technique. Cr and Ni were determined in pre- and post-shift urine samples. Concentrations below the limit of quantification (LOQ) were multiply imputed. Spearman correlation coefficients (rs) were calculated with 95% confidence intervals (CIs) to explore associations between the exposure variables, and regression models were applied to estimate the effect of the parent metal on the urinary concentration. Regarding the respirable Cr(VI), 62% of the measurements were below the LOQ, the 75th percentile was 0.50 µg m-3, and 8 out of 50 (16%) welders exceeded 1 µg m-3. The highest shift concentration that occurred as a result of shielded metal arc welding (SMAW) was 180 µg m-3. The Cr(VI) content in total Cr ranged from 4 to 82% (median 20%), although the concentration correlated with total Cr (rs 0.55, 95% CI 0.46; 0.64). The correlation between Cr(VI) and Ni was weaker (rs 0.42, 95% CI 0.34; 0.51) than that between total Cr and Ni in welding fumes (rs 0.83, 95% CI 0.74; 0.92). Both Cr(VI) and total Cr influenced the urinary Cr concentrations in post-shift samples (P = 0.0008 and P ≤ 0.0001, respectively). The airborne shift exposure was a weaker determinant than the Cr content in pre-shift urine samples, which strongly correlated with post-shift urinary Cr (rs 0.78, 95% CI 0.69; 0.87). The Cr(VI) content in total Cr varied considerably in welding fumes. The majority of welders using GMAW or TIG presented with shift concentrations of respirable Cr(VI) below 1 µg m-3. However, very high Cr(VI) concentrations may occur, for example in SMAW. The urinary concentration of total Cr, cannot be used to precisely determine the shift concentration of respirable Cr(VI) in welders.

Plasma Creatine Kinetics After Ingestion of Microencapsulated Creatine Monohydrate with Enhanced Stability in Aqueous Solutions.

PubMed

Hone, Michelle; Kent, Robert M; Scotto di Palumbo, Alessandro; Bleiel, Sinead B; De Vito, Giuseppe; Egan, Brendan

2017-07-04

Creatine monohydrate represents one of the largest sports supplement markets. Enhancing creatine (CRE) stability in aqueous solutions, such as with microencapsulation, represents innovation potential. Ten physically active male volunteers were randomly assigned in a double-blind design to either placebo (PLA) (3-g maltodextrin; n = 5) or microencapsulated CRE (3-g creatine monohydrate; n = 5) conditions. Experimental conditions involved ingestion of the samples in a 70-mL ready-to-drink format. CRE was delivered in a novel microencapsulation matrix material consisting entirely of hydrolyzed milk protein. Three hours after ingestion, plasma creatine concentrations were unchanged during PLA, and averaged ∼45 μM. During CRE, plasma creatine concentration peaked after 30 min at 101.6 ± 14.9 μM (p < 0.05), representing a 2.3-fold increase over PLA. Thereafter, plasma creatine concentration gradually trended downwards but remained significantly elevated (∼50% above resting levels) 3 hr after ingestion. These results demonstrate that the microencapsulated form of creatine monohydrate reported herein remains bioavailable when delivered in aqueous conditions, and has potential utility in ready-to-drink formulations for creatine supplementation.

Protective effect of creatine against inhibition by methylglyoxal of mitochondrial respiration of cardiac cells.

PubMed Central

Roy, Soumya Sinha; Biswas, Swati; Ray, Manju; Ray, Subhankar

2003-01-01

Previous publications from our laboratory have shown that methylglyoxal inhibits mitochondrial respiration of malignant and cardiac cells, but it has no effect on mitochondrial respiration of other normal cells [Biswas, Ray, Misra, Dutta and Ray (1997) Biochem. J. 323, 343-348; Ray, Biswas and Ray (1997) Mol. Cell. Biochem. 171, 95-103]. However, this inhibitory effect of methylglyoxal is not significant in cardiac tissue slices. Moreover, post-mitochondrial supernatant (PMS) of cardiac cells could almost completely protect the mitochondrial respiration against the inhibitory effect of methylglyoxal. A systematic search indicated that creatine present in cardiac cells is responsible for this protective effect. Glutathione has also some protective effect. However, creatine phosphate, creatinine, urea, glutathione disulphide and beta-mercaptoethanol have no protective effect. The inhibitory and protective effects of methylglyoxal and creatine respectively on cardiac mitochondrial respiration were studied with various concentrations of both methylglyoxal and creatine. Interestingly, neither creatine nor glutathione have any protective effect on the inhibition by methylglyoxal on the mitochondrial respiration of Ehrlich ascites carcinoma cells. The creatine and glutathione contents of several PMS, which were tested for the possible protective effect, were measured. The activities of two important enzymes, namely glyoxalase I and creatine kinase, which act upon glutathione plus methylglyoxal and creatine respectively, were also measured in different PMS. Whether mitochondrial creatine kinase had any role in the protective effect of creatine had also been investigated using 1-fluoro-2,4-dinitrobenzene, an inhibitor of creatine kinase. The differential effect of creatine on mitochondria of cardiac and malignant cells has been discussed with reference to the therapeutic potential of methylglyoxal. PMID:12605598

Recruitment of single muscle fibers during submaximal cycling exercise.

PubMed

Altenburg, T M; Degens, H; van Mechelen, W; Sargeant, A J; de Haan, A

2007-11-01

In literature, an inconsistency exists in the submaximal exercise intensity at which type II fibers are activated. In the present study, the recruitment of type I and II fibers was investigated from the very beginning and throughout a 45-min cycle exercise at 75% of the maximal oxygen uptake, which corresponded to 38% of the maximal dynamic muscle force. Biopsies of the vastus lateralis muscle were taken from six subjects at rest and during the exercise, two at each time point. From the first biopsy single fibers were isolated and characterized as type I and II, and phosphocreatine-to-creatine (PCr/Cr) ratios and periodic acid-Schiff (PAS) stain intensities were measured. Cross sections were cut from the second biopsy, individual fibers were characterized as type I and II, and PAS stain intensities were measured. A decline in PCr/Cr ratio and in PAS stain intensity was used as indication of fiber recruitment. Within 1 min of exercise both type I and, although to a lesser extent, type II fibers were recruited. Furthermore, the PCr/Cr ratio revealed that the same proportion of fibers was recruited during the whole 45 min of exercise, indicating a rather constant recruitment. The PAS staining, however, proved inadequate to fully demonstrate fiber recruitment even after 45 min of exercise. We conclude that during cycling exercise a greater proportion of type II fibers is recruited than previously reported for isometric contractions, probably because of the dynamic character of the exercise. Furthermore, the PCr/Cr ratio method is more sensitive in determining fiber activation than the PAS stain intensity method.

Tai Chi Improves Brain Metabolism and Muscle Energetics in Older Adults.

PubMed

Zhou, Min; Liao, Huijun; Sreepada, Lasya P; Ladner, Joshua R; Balschi, James A; Lin, Alexander P

2018-04-17

Tai Chi is a mind-body exercise that has been shown to improve both mental and physical health. As a result, recent literature suggests the use of Tai Chi to treat both physical and psychological disorders. However, the underlying physiological changes have not been characterized. The aim of this pilot study is to assess the changes in brain metabolites and muscle energetics after Tai Chi training in an aging population using a combined brain-muscle magnetic resonance spectroscopy (MRS) examination. Six healthy older adults were prospectively recruited and enrolled into a 12-week Tai Chi program. A brain 1 H MRS and a muscle 31 P MRS were scanned before and after the training, and postprocessed to measure N-acetylaspartate to creatine (NAA/Cr) ratios and phosphocreatine (PCr) recovery time. Wilcoxon-signed rank tests were utilized to assess the differences between pre- and post-Tai Chi training. A significant within-subject increase in both the NAA/Cr ratios (P = .046) and the PCr recovery time (P = .046) was observed between the baseline and the posttraining scans. The median percentage changes were 5.38% and 16.51% for NAA/Cr and PCr recovery time, respectively. Our pilot study demonstrates significant increase of NAA/Cr ratios in posterior cingulate gyrus and significantly improved PCr recovery time in leg muscles in older adults following short-term Tai Chi training, and thus provides insight into the beneficial mechanisms. Copyright © 2018 The Authors. Journal of Neuroimaging published by Wiley Periodicals, Inc. on behalf of American Society of Neuroimaging.

Cerebral creatine deficiency syndromes: clinical aspects, treatment and pathophysiology.

PubMed

Stockler, Sylvia; Schutz, Peter W; Salomons, Gajja S

2007-01-01

Cerebral creatine deficiency syndromes (CCDSs) are a group of inborn errors of creatine metabolism comprising two autosomal recessive disorders that affect the biosynthesis of creatine--i.e. arginine:glycine amidinotransferase deficiency (AGAT; MIM 602360) and guanidinoacetate methyltransferase deficiency (GAMT; MIM 601240)--and an X-linked defect that affects the creatine transporter, SLC6A8 deficiency (SLC6A8; MIM 300036). The biochemical hallmarks of these disorders include cerebral creatine deficiency as detected in vivo by 1H magnetic resonance spectroscopy (MRS) of the brain, and specific disturbances in metabolites of creatine metabolism in body fluids. In urine and plasma, abnormal guanidinoacetic acid (GAA) levels are found in AGAT deficiency (reduced GAA) and in GAMT deficiency (increased GAA). In urine of males with SLC6A8 deficiency, an increased creatine/creatinine ratio is detected. The common clinical presentation in CCDS includes mental retardation, expressive speech and language delay, autistic like behaviour and epilepsy. Treatment of the creatine biosynthesis defects has yielded clinical improvement, while for creatine transporter deficiency, successful treatment strategies still need to be discovered. CCDSs may be responsible for a considerable fraction of children and adults affected with mental retardation of unknown etiology. Thus, screening for this group of disorders should be included in the differential diagnosis of this population. In this review, also the importance of CCDSs for the unravelling of the (patho)physiology of cerebral creatine metabolism is discussed.

Creatine supplementation with specific view to exercise/sports performance: an update

PubMed Central

2012-01-01

Creatine is one of the most popular and widely researched natural supplements. The majority of studies have focused on the effects of creatine monohydrate on performance and health; however, many other forms of creatine exist and are commercially available in the sports nutrition/supplement market. Regardless of the form, supplementation with creatine has regularly shown to increase strength, fat free mass, and muscle morphology with concurrent heavy resistance training more than resistance training alone. Creatine may be of benefit in other modes of exercise such as high-intensity sprints or endurance training. However, it appears that the effects of creatine diminish as the length of time spent exercising increases. Even though not all individuals respond similarly to creatine supplementation, it is generally accepted that its supplementation increases creatine storage and promotes a faster regeneration of adenosine triphosphate between high intensity exercises. These improved outcomes will increase performance and promote greater training adaptations. More recent research suggests that creatine supplementation in amounts of 0.1 g/kg of body weight combined with resistance training improves training adaptations at a cellular and sub-cellular level. Finally, although presently ingesting creatine as an oral supplement is considered safe and ethical, the perception of safety cannot be guaranteed, especially when administered for long period of time to different populations (athletes, sedentary, patient, active, young or elderly). PMID:22817979

Study of the biochemical indicators of chronic irradiation in rats.

PubMed

Szabo, L D; Benko, A B; Gyenge, L; Predmerszky, T

1976-01-01

Daily urinary excretion of pseudouridine, creatinine and creatine of chronically irradiated Wistar rats was estimated. The irradiation conditions were: 60Co gamma source, dose-rate 10 rad/day, total dose 200, 400 and 600 rad. Control groups were kept under similar conditions. Urine samples were taken three times after the end of the irradiation period. It was found that: (1) pseudouridine excretion seems more suitable for indicating radiation injury than the creatine/creatinine ratio in chronic irradiation in rats; (ii) there are significant changes in dose dependence of pseudouridine excretion in the post-irradiation period; (iii) a new method for pseudouridine estimation gives closely similar data to those of earlier investigations.

Method of empirical dependences in estimation and prediction of activity of creatine kinase isoenzymes in cerebral ischemia

NASA Astrophysics Data System (ADS)

Sergeeva, Tatiana F.; Moshkova, Albina N.; Erlykina, Elena I.; Khvatova, Elena M.

2016-04-01

Creatine kinase is a key enzyme of energy metabolism in the brain. There are known cytoplasmic and mitochondrial creatine kinase isoenzymes. Mitochondrial creatine kinase exists as a mixture of two oligomeric forms - dimer and octamer. The aim of investigation was to study catalytic properties of cytoplasmic and mitochondrial creatine kinase and using of the method of empirical dependences for the possible prediction of the activity of these enzymes in cerebral ischemia. Ischemia was revealed to be accompanied with the changes of the activity of creatine kinase isoenzymes and oligomeric state of mitochondrial isoform. There were made the models of multiple regression that permit to study the activity of creatine kinase system in cerebral ischemia using a calculating method. Therefore, the mathematical method of empirical dependences can be applied for estimation and prediction of the functional state of the brain by the activity of creatine kinase isoenzymes in cerebral ischemia.

Studies on the alterations in haematological indices, micronuclei induction and pathological marker enzyme activities in Channa punctatus (spotted snakehead) perciformes, channidae exposed to thermal power plant effluent.

PubMed

Javed, Mehjbeen; Ahmad, Irshad; Ahmad, Ajaz; Usmani, Nazura; Ahmad, Masood

2016-01-01

The present study was conducted to assess the toxicity of thermal power plant effluent containing heavy metals (Fe > Cu > Zn > Mn > Ni > Co > Cr) on haematological indices, micronuclei, lobed nuclei and activity of pathological marker enzymes [alkaline phosphatase (ALP), aspartate transferase (AST), alanine transferase (ALT) and creatine kinase (CK)] in Channa punctatus. Total erythrocyte count (-54.52 %), hemoglobin (-36.98 %), packed cell volume (-36.25 %), mean corpuscular hemoglobin concentration (-1.41 %) and oxygen (O2) carrying capacity (-37.04 %) declined significantly over reference fish, however total leukocyte count (+25.43 %), mean corpuscular hemoglobin (+33.52 %) and mean corpuscular volume (+35.49 %) showed elevation. High frequency of micronuclei (1133.3 %) and lobed nuclei (150 %) were observed in exposed fish which may indicate mutagenesis. Activities of pathological marker enzymes ALP, AST, ALT and CK increased significantly in serum of exposed fish. The ratio of ALT: AST in exposed fish was beyond 1 which indicates manifestation of pathological processes. These biomarkers show that fish have macrocytic hypochromic anemia. Leukocytosis showed general defence response against heavy metal toxicity and marker enzymes showed tissue degeneration. In conclusion, thermal power plant effluent has strong potential to induce micronuclei, tissue pathology, making the fish anemic, weak, stressed and vulnerable to diseases.

Creatine supplementation and swim performance: a brief review.

PubMed

Hopwood, Melissa J; Graham, Kenneth; Rooney, Kieron B

2006-03-01

Nutritional supplements are popular among athletes participating in a wide variety of sports. Creatine is one of the most commonly used dietary supplements, as it has been shown to be beneficial in improving performance during repeated bouts of high-intensity anaerobic activity. This review examines the specific effects of creatine supplementation on swimming performance, and considers the effects of creatine supplementation on various measures of power development in this population. Research performed on the effect of creatine supplementation on swimming performance indicates that whilst creatine supplementation is ineffective in improving performance during a single sprint swim, dietary creatine supplementation may benefit repeated interval swim set performance. Considering the relationship between sprint swimming performance and measurements of power, the effect of creatine supplementation on power development in swimmers has also been examined. When measured on a swim bench ergometer, power development does show some improvement following a creatine supplementation regime. How this improvement in power output transfers to performance in the pool is uncertain. Although some evidence exists to suggest a gender effect on the performance improvements seen in swimmers following creatine supplementation, the majority of research indicates that male and female swimmers respond equally to supplementation. A major limitation to previous research is the lack of consideration given to the possible stroke dependant effect of creatine supplementation on swimming performance. The majority of the research conducted to date has involved examination of the freestyle swimming stroke only. The potential for performance improvements in the breaststroke and butterfly swimming strokes is discussed, with regards to the biomechanical differences and differences in efficiency between these strokes and freestyle. Key PointsCreatine supplementation does not improve single sprint swimming performance.Creatine supplementation does improve repeated interval swim set performance.Creatine supplementation does improve power development in swimmers when measured on a swim bench ergometer.As a result of the high energy demands of the butterfly and breaststroke competitive swimming styles, potentially, the benefits associated with creatine supplementation and swimming performance could be greater when swimming butterfly or breaststroke, compared to the commonly examined freestyle swimming stroke.

Hibernation-Based Therapy to Improve Survival of Severe Blood Loss

DTIC Science & Technology

2012-10-01

total protein) No differences Renal Function (urea nitrogen, creatine kinase, lactate dehygrogenase) No differences Hematology...change in creatinine kinase. There was no laboratory evidence of damage or toxic effect to the function of major organs. Although there were notable

Dietary creatine supplementation lowers hepatic triacylglycerol by increasing lipoprotein secretion in rats fed high-fat diet.

PubMed

da Silva, Robin P; Leonard, Kelly-Ann; Jacobs, René L

2017-12-01

Recent studies have shown that dietary creatine supplementation can prevent lipid accumulation in the liver. Creatine is a small molecule that plays a large role in energy metabolism, but since the enzyme creatine kinase is not present in the liver, the classical role in energy metabolism does not hold in this tissue. Fat accumulation in the liver can lead to the development of nonalcoholic fatty liver disease (NAFLD), a progressive disease that is prevalent in humans. We have previously reported that creatine can directly influence lipid metabolism in cell culture to promote lipid secretion and oxidation. Our goal in the current study was to determine whether similar mechanisms that occur in cell culture were present in vivo. We also sought to determine whether dietary creatine supplementation could be effective in reversing steatosis. Sprague-Dawley rats were fed a high-fat diet or a high-fat diet supplemented with creatine for 5 weeks. We found that rats supplemented with creatine had significantly improved rates of lipoprotein secretion and alterations in mitochondrial function that were consistent with greater oxidative capacity. We also find that introducing creatine into a high-fat diet halted hepatic lipid accumulation in rats with fatty liver. Our results support our previous report that liver cells in culture with creatine secrete and oxidize more oleic acid, demonstrating that dietary creatine can effectively change hepatic lipid metabolism by increasing lipoprotein secretion and oxidation in vivo. Our data suggest that creatine might be an effective therapy for NAFLD. Copyright © 2017 Elsevier Inc. All rights reserved.

Contribution of creatine to protein homeostasis in athletes after endurance and sprint running.

PubMed

Tang, Fu-Chun; Chan, Chun-Chen; Kuo, Po-Ling

2014-02-01

Few studies have focused on the metabolic changes induced by creatine supplementation. This study investigated the effects of creatine supplementation on plasma and urinary metabolite changes of athletes after endurance and sprint running. Twelve male athletes (20.3 ± 1.4 y) performed two identical (65-70 % maximum heart rate reserved) 60 min running exercises (endurance trial) before and after creatine supplementation (12 g creatine monohydrate/day for 15 days), followed by a 5-day washout period. Subsequently, they performed two identical 100 m sprint running exercises (power trial) before and after 15 days of creatine supplementation in accordance with the supplementary protocol of the endurance trial. Body composition measurements were performed during the entire study. Plasma samples were examined for the concentrations of glucose, lactate, branched-chain amino acids (BCAAs), free-tryptophan (f-TRP), glutamine, alanine, hypoxanthine, and uric acid. Urinary samples were examined for the concentrations of hydroxyproline, 3-methylhistidine, urea nitrogen, and creatinine. Creatine supplementation significantly increased body weights of the athletes of endurance trial. Plasma lactate concentration and ratio of f-TRP/BCAAs after recovery from endurance running were significantly decreased with creatine supplementation. Plasma purine metabolites (the sum of hypoxanthine and uric acid), glutamine, urinary 3-methylhistidine, and urea nitrogen concentrations tended to decrease before running in trials with creatine supplements. After running, urinary hydroxyproline concentration significantly increased in the power trial with creatine supplements. The findings suggest that creatine supplementation tended to decrease muscle glycogen and protein degradation, especially after endurance exercise. However, creatine supplementation might induce collagen proteolysis in athletes after sprint running.

Enzymes of creatine biosynthesis, arginine and methionine metabolism in normal and malignant cells.

PubMed

Bera, Soumen; Wallimann, Theo; Ray, Subhankar; Ray, Manju

2008-12-01

The creatine/creatine kinase system decreases drastically in sarcoma. In the present study, an investigation of catalytic activities, western blot and mRNA expression unambiguously demonstrates the prominent expression of the creatine-synthesizing enzymes l-arginine:glycine amidinotransferase and N-guanidinoacetate methyltransferase in sarcoma, Ehrlich ascites carcinoma and Sarcoma 180 cells, whereas both enzymes were virtually undetectable in normal muscle. Compared to that of normal animals, these enzymes remained unaffected in the kidney or liver of sarcoma-bearing mice. High activity and expression of mitochondrial arginase II in sarcoma indicated increased ornithine formation. Slightly or moderately higher levels of ornithine, guanidinoacetate and creatinine were observed in sarcoma compared to muscle. Despite the intrinsically low level of creatine in Ehrlich ascites carcinoma and Sarcoma 180 cells, these cells could significantly take up and release creatine, suggesting a functional creatine transport, as verified by measuring mRNA levels of creatine transporter. Transcript levels of arginase II, ornithine-decarboxylase, S-adenosyl-homocysteine hydrolase and methionine-synthase were significantly upregulated in sarcoma and in Ehrlich ascites carcinoma and Sarcoma 180 cells. Overall, the enzymes related to creatine and arginine/methionine metabolism were found to be significantly upregulated in malignant cells. However, the low levels of creatine kinase in the same malignant cells do not appear to be sufficient for the building up of an effective creatine/phosphocreatine pool. Instead of supporting creatine biosynthesis, l-arginine:glycine amidinotransferase and N-guanidinoacetate methyltransferase appear to be geared to support cancer cell metabolism in the direction of polyamine and methionine synthesis because both these compounds are in high demand in proliferating cancer cells.

Electrolysis stimulates creatine transport and transporter cell surface expression in incubated mouse skeletal muscle: potential role of ROS.

PubMed

Derave, Wim; Straumann, Nadine; Olek, Robert A; Hespel, Peter

2006-12-01

Electrical field stimulation of isolated, incubated rodent skeletal muscles is a frequently used model to study the effects of contractions on muscle metabolism. In this study, this model was used to investigate the effects of electrically stimulated contractions on creatine transport. Soleus and extensor digitorum longus muscles of male NMRI mice (35-50 g) were incubated in an oxygenated Krebs buffer between platinum electrodes. Muscles were exposed to [(14)C]creatine for 30 min after either 12 min of repeated tetanic isometric contractions (contractions) or electrical stimulation of only the buffer before incubation of the muscle (electrolysis). Electrolysis was also investigated in the presence of the reactive oxygen species (ROS) scavenging enzymes superoxide dismutase (SOD) and catalase. Both contractions and (to a lesser degree) electrolysis stimulated creatine transport severalfold over basal. The amount of electrolysis, but not contractile activity, induced (determined) creatine transport stimulation. Incubation with SOD and catalase at 100 and 200 U/ml decreased electrolysis-induced creatine transport by approximately 50 and approximately 100%, respectively. The electrolysis effects on creatine uptake were completely inhibited by beta-guanidino propionic acid, a competitive inhibitor of (creatine for) the creatine transporter (CRT), and were accompanied by increased cell surface expression of CRT. Muscle glucose transport was not affected by electrolysis. The present results indicate that electrical field stimulation of incubated mouse muscles, independently of contractions per se, stimulates creatine transport by a mechanism that depends on electrolysis-induced formation of ROS in the incubation buffer. The increased creatine uptake is paralleled by an increased cell surface expression of the creatine transporter.

Anterior Cingulate Glutamate Levels Related to Clinical Status Following Treatment in First-Episode Schizophrenia

PubMed Central

Egerton, Alice; Brugger, Stefan; Raffin, Marie; Barker, Gareth J; Lythgoe, David J; McGuire, Philip K; Stone, James M

2012-01-01

Many patients with schizophrenia show a limited symptomatic response to treatment with dopaminergic antipsychotics. This may reflect the additional involvement of non-dopaminergic neurochemical dysfunction in the pathophysiology of the disorder. We tested the hypothesis that brain glutamate levels would differ between patients with first-episode psychosis who were symptomatic compared with those with minimal symptoms following antipsychotic treatment. Proton magnetic resonance spectroscopy (1H-MRS) spectra were acquired at 3 Tesla in the anterior cingulate cortex and left thalamus in 15 patients with first-episode psychosis in symptomatic remission, and 17 patients with first-episode psychosis who were still symptomatic following at least one course of antipsychotic treatment. Metabolite levels were estimated in ratio to creatine (Cr) using LCModel. Levels of glutamate/Cr in the anterior cingulate cortex were significantly higher in patients who were still symptomatic than in those in remission (T(30)=3.02; P=0.005). Across the entire sample, higher levels of glutamate/Cr in the anterior cingulate cortex were associated with a greater severity of negative symptoms (r=0.42; P=0.017) and a lower level of global functioning (r=−0.47; P=0.007). These findings suggest that clinical status following antipsychotic treatment in schizophrenia is linked to glutamate dysfunction. Treatment with compounds acting on the glutamatergic system might therefore be beneficial in patients who respond poorly to dopaminergic antipsychotics. PMID:22763619

Reduced N-acetylaspartate content in the frontal part of the brain in patients with probable Alzheimer's disease.

PubMed

Christiansen, P; Schlosser, A; Henriksen, O

1995-01-01

The fully relaxed water signal was used as an internal standard in a STEAM experiment to calculate the concentrations of the metabolites: N-acetylaspartate (NAA), creatine + phosphocreatine [Cr + PCr], and choline-containing metabolites (Cho) in the frontal part of the brain in 12 patients with probable Alzheimer's disease. Eight age-matched healthy volunteers served as controls. Furthermore, T1 and T2 relaxation times of the metabolites and signal ratios: NAA/Cho, NAA/[Cr + PCr], and [Cr + PCr]/Cho at four different echo times (TE) and two different repetition times (TR) were calculated. The experiments were carried out using a Siemens Helicon SP 63/84 wholebody MR-scanner at 1.5 T. The concentration of NAA was significantly lower in the patients with probable Alzheimer's disease than in the healthy volunteers. No significant difference was found for any other metabolite concentration. For the signal ratios the only statistically significant difference was that the NAA/Cho ratio at TE = 92 ms and TR = 1.6 s was lower in the patients with probable Alzheimer's disease compared with the control group. A trend towards a longer T2 relaxation time for NAA in the patients with probable Alzheimer's disease than among the healthy volunteers was found, but no significant difference was found concerning the T1 and T2 relaxation times.

Elevated plasma creatinine due to creatine ethyl ester use.

PubMed

Velema, M S; de Ronde, W

2011-02-01

Creatine is a nutritional supplement widely used in sport, physical fitness training and bodybuilding. It is claimed to enhance performance. We describe a case in which serum creatinine is elevated due to the use of creatine ethyl esther. One week after withdrawal, the plasma creatinine had normalised. There are two types of creatine products available: creatine ethyl esther (CEE) and creatine monohydrate (CM). Plasma creatinine is not elevated in all creatine-using subjects. CEE , but not CM, is converted into creatinine in the gastrointestinal tract. As a result the use of CEE may be associated with elevated plasma creatinine levels. Since plasma creatinine is a widely used marker for renal function, the use of CEE may lead to a false assumption of renal failure.

Creatine metabolism and psychiatric disorders: Does creatine supplementation have therapeutic value?

PubMed Central

Allen, Patricia J.

2012-01-01

Athletes, body builders, and military personnel use dietary creatine as an ergogenic aid to boost physical performance in sports involving short bursts of high-intensity muscle activity. Lesser known is the essential role creatine, a natural regulator of energy homeostasis, plays in brain function and development. Creatine supplementation has shown promise as a safe, effective, and tolerable adjunct to medication for the treatment of brain-related disorders linked with dysfunctional energy metabolism, such as Huntington’s Disease and Parkinson’s Disease. Impairments in creatine metabolism have also been implicated in the pathogenesis of psychiatric disorders, leaving clinicians, researchers and patients alike wondering if dietary creatine has therapeutic value for treating mental illness. The present review summarizes the neurobiology of the creatine-phosphocreatine circuit and its relation to psychological stress, schizophrenia, mood and anxiety disorders. While present knowledge of the role of creatine in cognitive and emotional processing is in its infancy, further research on this endogenous metabolite has the potential to advance our understanding of the biological bases of psychopathology and improve current therapeutic strategies. PMID:22465051

Creatine metabolism and psychiatric disorders: Does creatine supplementation have therapeutic value?

PubMed

Allen, Patricia J

2012-05-01

Athletes, body builders, and military personnel use dietary creatine as an ergogenic aid to boost physical performance in sports involving short bursts of high-intensity muscle activity. Lesser known is the essential role creatine, a natural regulator of energy homeostasis, plays in brain function and development. Creatine supplementation has shown promise as a safe, effective, and tolerable adjunct to medication for the treatment of brain-related disorders linked with dysfunctional energy metabolism, such as Huntington's Disease and Parkinson's Disease. Impairments in creatine metabolism have also been implicated in the pathogenesis of psychiatric disorders, leaving clinicians, researchers and patients alike wondering if dietary creatine has therapeutic value for treating mental illness. The present review summarizes the neurobiology of the creatine-phosphocreatine circuit and its relation to psychological stress, schizophrenia, mood and anxiety disorders. While present knowledge of the role of creatine in cognitive and emotional processing is in its infancy, further research on this endogenous metabolite has the potential to advance our understanding of the biological bases of psychopathology and improve current therapeutic strategies. Copyright © 2012 Elsevier Ltd. All rights reserved.

Differential determination of chromium(VI) and total chromium in natural waters using flow injection on-line separation and preconcentration electrothermal atomic absorption spectrometry.

PubMed

Sperling, M; Yin, X; Welz, B

1992-03-01

A rapid, sensitive and selective method for the differential determination of CrIII and CrVI in natural waters is described. Chromium(vi) can be determined directly by flow injection on-line sorbent extraction preconcentration coupled with electrothermal atomic absorption spectrometry using sodium diethyldithiocarbamate as the complexing agent and C18 bonded silica reversed-phase sorbent as the column material. Total Cr can be determined after oxidation of CrIII to CrVI by potassium peroxydisulfate. Chromium(III) can be calculated by difference. The optimum conditions for sorbent extraction of CrVI and oxidation of CrIII to CrVI are evaluated. A 12-fold enhancement in sensitivity compared with direct introduction of 40 microliters samples was achieved after preconcentration for 60 s, giving detection limits of 16 ng l-1 for CrVI and 18 ng l-1 for total Cr (based on 3 sigma). Results obtained for sea-water and river water reference materials were all within the certified range for total Cr with a precision of better than 10% relative standard deviation in the range 100-200 ng l-1. The selectivity of the determination of CrVI was evaluated by analysing spiked reference materials in the presence of CrIII, resulting in quantitative recovery of CrVI.

Creatine enhances the duration of sperm capacitation: a novel factor for improving in vitro fertilization with small numbers of sperm.

PubMed

Umehara, Takashi; Kawai, Tomoko; Goto, Masaaki; Richards, JoAnne S; Shimada, Masayuki

2018-06-01

Why are many sperm required for successful fertilization of oocytes in vitro, even though fertilization occurs in vivo when only a few sperm reach the oocyte? Creatine produced in the ovary promotes efficient fertilization in vivo; however, in vitro, creatine is not contained in the in vitro fertilization (IVF) medium. The IVF medium enables capacitation of sperm. However, the IVF medium does not fully mimic the in vivo environment during fertilization. Consequently, fertilization in vitro is more inefficient than in the oviduct. Follicular and oviductal fluids were collected and then analyzed for creatine and glucose levels. To determine the physiological functions of creatine, the creatine antagonist 3-guanidinopropionic acid (GPA) was injected into hormonally primed mice. Using conventional IVF protocols, sperm were pre-incubated in IVF medium with creatine and then co-cultured with 10 ovulated cumulus-oocyte complexes (1-1000 per oocyte) in 50 μl medium droplets. Glucose and creatine levels were measured using commercial enzymatic assay kits. The effect of creatine in vivo was assessed by mating experiments using mice treated with or without GPA just before ovulation. To assess the functions of sperm incubated in IVF medium containing creatine, we analyzed (1) the motility of sperm using computer-assisted sperm assay, (2) the capacitation level of sperm by western blot analyses, and (3) the condition of sperm acrosomes by peanut agglutinin lectin-FITC staining. Oviductal creatine levels were significantly increased following ovulation. Injecting mice with GPA just before ovulation significantly reduced the number of fertilized oocytes. The addition of creatine to IVF medium enhanced sperm capacitation by increasing ATP levels. Successful fertilization was achieved with as few as five sperm/oocyte in the creatine group, and the number of fertilized oocytes was significantly higher than in the control without creatine (P < 0.01). In the present study, a pharmacological approach, creatine antagonist (GPA) treatment, but not a knockout mouse model, was used to understand the role of creatine in vivo. The role of creatine in fertilization processes can only be shown in a mouse model. A modified IVF technique using creatine-containing medium was developed and shown to markedly improve fertilization with small numbers of sperm. This approach has the potential to be highly beneficial for human assisted reproductive technologies, especially for patients with a limited number of good quality sperm. This work was supported in part by JSPS KAKENHI Grant numbers JP24688028, JP16H05017 (to M.S.), and JP15J05331 (to T.U.), the Japan Agency for Medical Research and Development (AMED) (16gk0110015h0001 to M.S.), and National Institutes of Health (NIH-HD-076980 to J.S.R). The authors have nothing to disclose.

Detection of human immunodeficiency virus induced inflammation and oxidative stress in lenticular nuclei with magnetic resonance spectroscopy despite antiretroviral therapy.

PubMed

Roc, Anne C; Ances, Beau M; Chawla, Sanjeev; Korczykowski, Marc; Wolf, Ronald L; Kolson, Dennis L; Detre, John A; Poptani, Harish

2007-09-01

Single-voxel magnetic resonance spectroscopy measurements of N-acetyl aspartate, choline, and creatine (Cr) are affected in patients with human immunodeficiency virus (HIV) and neurocognitive impairment. However, these metabolic markers are often normalized in affected central nervous system regions, such as the lenticular nuclei, after initiation of highly active antiretroviral therapy (HAART). To examine whether lactate (Lac), a marker of inflammation and anaerobic glycolysis, and lipid, an indicator of cell membrane turnover resulting from oxidative stress, could serve as surrogate biomarkers within the lenticular nuclei of HIV-positive patients with different degrees of neurocognitive impairment. Three-tesla 2-dimensional-chemical shift imaging magnetic resonance spectroscopy at echo times of 30 milliseconds and 135 milliseconds was performed in voxels overlapping the lenticular nuclei of seronegative controls and a spectrum of HIV-positive patients (neurocognitively normal, mildly impaired, or moderately to severely impaired). University of Pennsylvania, Philadelphia. Ten seronegative controls and 45 HIV-positive patients with different degrees of neurocognitive impairment (15 neurocognitively normal patients, 12 mildly impaired patients, and 18 moderately to severely impaired patients). In vivo 2-dimensional-chemical shift imaging magnetic resonance spectroscopy analysis of N-acetyl aspartate:Cr, choline:Cr, Lac:Cr, and (lipid + Lac):Cr ratios among the various groups. In addition, the effect of the degree of HAART central nervous system penetration (high vs low) on these ratios was studied. No significant lenticular nuclei atrophy was detected with volumes similar across all of the groups. Both N-acetyl aspartate:Cr and choline:Cr ratios were similar across all of the groups at either echo time. In contrast, the Lac:Cr ratio was significantly greater in HIV-positive patients with moderate to severe impairment compared with seronegative controls. The (lipid + Lac):Cr ratio was significantly elevated within each HIV-positive subgroup compared with seronegative controls. Within HIV-positive patients receiving HAART, the degree of central nervous system penetration (high vs low) did not affect metabolic ratios. As seen with 2-dimensional-chemical shift imaging magnetic resonance spectroscopy, HIV induces inflammation and oxidative stress in HIV-positive patients despite HAART. Lipid and Lac are more sensitive inflammatory biomarkers that may be used to differentiate HIV-positive subgroups. However, no significant difference in efficacy, as measured by metabolic ratios, exists for high- vs low-central nervous system-penetrating HAART.

Effects on Energy Metabolism of Two Guanidine Molecules, (Boc)2 -Creatine and Metformin.

PubMed

Garbati, Patrizia; Ravera, Silvia; Scarfì, Sonia; Salis, Annalisa; Rosano, Camillo; Poggi, Alessandro; Damonte, Gianluca; Millo, Enrico; Balestrino, Maurizio

2017-09-01

Several enzymes are involved in the energy production, becoming a possible target for new anti-cancer drugs. In this paper, we used biochemical and in silico studies to evaluate the effects of two guanidine molecules, (Boc) 2 -creatine and metformin, on creatine kinase, an enzyme involved in the regulation of intracellular energy levels. Our results show that both drugs inhibit creatine kinase activity; however, (Boc) 2 -creatine displays a competitive inhibition, while metformin acts with a non-competitive mechanism. Moreover, (Boc) 2 -creatine is able to inhibit the activity of hexokinase with a non-competitive mechanism. Considering that creatine kinase and hexokinase are involved in energy metabolism, we evaluated the effects of (Boc) 2 -creatine and metformin on the ATP/AMP ratio and on cellular proliferation in healthy fibroblasts, human breast cancer cells (MDA-MB-468), a human neuroblastoma cell line (SH-SY5Y), a human Hodgkin lymphoma cell line (KMH2). We found that healthy fibroblasts were only partially affected by (Boc) 2 -creatine, while both ATP/AMP ratio and viability of the three cancer cell lines were significantly decreased. By inhibiting both creatine kinase and hexokinase, (Boc) 2 -creatine appears as a promising new agent in anticancer treatment. Further research is needed to understand what types of cancer cells are most suitable to treatment by this new compound. J. Cell. Biochem. 118: 2700-2711, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Sex-specific antidepressant effects of dietary creatine with and without sub-acute fluoxetine in rats

PubMed Central

Allen, Patricia J.; D'Anci, Kristen E.; Kanarek, Robin B.; Renshaw, Perry F.

2013-01-01

The potential role of metabolic impairments in the pathophysiology of depression is motivating researchers to evaluate the treatment efficacy of creatine, a naturally occurring energetic and neuroprotective compound found in brain and muscle tissues. Growing evidence is demonstrating the benefit of oral creatine supplements for reducing depressive symptoms in humans and animals. A novel question is whether dietary creatine, when combined with antidepressant drug therapy, would be more effective than either compound alone. To answer this question, four studies were conducted to investigate the behavioral effects of combined creatine and low-dose fluoxetine treatment using the forced swim test in male and female rats. Sprague-Dawley rats were fed powdered rodent chow supplemented with 0%, 2% or 4% w/w creatine monohydrate for 5 weeks. Rats were injected with fluoxetine (5.0 or 10.0 mg/kg) or saline according to a sub-acute dosing schedule. Female rats maintained on a 4% creatine diet displayed antidepressant-like effects compared to non-supplemented females prior to fluoxetine treatment. In contrast, creatine did not alter behavior reliably in males. Following drug treatment and a second forced swim trial, the antidepressant-like profile of creatine remained significant only in females co-administered 5.0 mg/kg fluoxetine. Moreover, in females only, supplementation with 4% creatine produced a more robust antidepressant-like behavioral profile compared to either dose of fluoxetine alone. Estrous cycle data indicated that ovarian hormones influenced the antidepressant-like effects of creatine. Addressing the issue of sex differences in response to treatment may affect our understanding of creatine, its relationship with depressive behavior, and may lead to sex-specific therapeutic strategies. PMID:22429992

Creatine biosynthesis and transport by the term human placenta.

PubMed

Ellery, Stacey J; Della Gatta, Paul A; Bruce, Clinton R; Kowalski, Greg M; Davies-Tuck, Miranda; Mockler, Joanne C; Murthi, Padma; Walker, David W; Snow, Rod J; Dickinson, Hayley

2017-04-01

Creatine is an amino acid derivative that is involved in preserving ATP homeostasis. Previous studies suggest an important role for the creatine kinase circuit for placental ATP turnover. Creatine is obtained from both the diet and endogenous synthesis, usually along the renal-hepatic axis. However, some tissues with a high-energy demand have an inherent capacity to synthesise creatine. In this study, we determined if the term human placenta has the enzymatic machinary to synthesise creatine. Eleven placentae were collected following elective term caesarean section. Samples from the 4 quadrants of each placenta were either fixed in formalin or frozen. qPCR was used to determine the mRNA expression of the creatine synthesising enzymes arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT), and the creatine transporter (SLC6A8). Protein expression of AGAT and GAMT was quantified by Western blot, and observations of cell localisation of AGAT, GAMT and SLC6A8 made with immunohistochemistry. Synthesis of guanidinoacetate (GAA; creatine precursor) and creatine in placental homogenates was determined via GC-MS and HPLC, respectively. AGAT, GAMT and SLC6A8 mRNA and protein were detected in the human placenta. AGAT staining was identified in stromal and endothelial cells of the fetal capillaries. GAMT and SLC6A8 staining was localised to the syncytiotrophoblast of the fetal villi. Ex vivo, tissue homogenates produce both GAA (4.6 nmol mg protein -1 h -1 ) and creatine (52.8 nmol mg protein -1 h -1 ). The term human placenta has the capacity to synthesise creatine. These data present a new understanding of placental energy metabolism. Copyright © 2017 Elsevier Ltd. All rights reserved.

Creatine Supplementation Associated or Not with Strength Training upon Emotional and Cognitive Measures in Older Women: A Randomized Double-Blind Study

PubMed Central

Alves, Christiano Robles Rodrigues; Merege Filho, Carlos Alberto Abujabra; Benatti, Fabiana Braga; Brucki, Sonia; Pereira, Rosa Maria R.; de Sá Pinto, Ana Lucia; Lima, Fernanda Rodrigues; Roschel, Hamilton; Gualano, Bruno

2013-01-01

Purpose To assess the effects of creatine supplementation, associated or not with strength training, upon emotional and cognitive measures in older woman. Methods This is a 24-week, parallel-group, double-blind, randomized, placebo-controlled trial. The individuals were randomly allocated into one of the following groups (n=14 each): 1) placebo, 2) creatine supplementation, 3) placebo associated with strength training or 4) creatine supplementation associated with strength training. According to their allocation, the participants were given creatine (4 x 5 g/d for 5 days followed by 5 g/d) or placebo (dextrose at the same dosage) and were strength trained or not. Cognitive function, assessed by a comprehensive battery of tests involving memory, selective attention, and inhibitory control, and emotional measures, assessed by the Geriatric Depression Scale, were evaluated at baseline, after 12 and 24 weeks of the intervention. Muscle strength and food intake were evaluated at baseline and after 24 weeks. Results After the 24-week intervention, both training groups (ingesting creatine supplementation and placebo) had significant reductions on the Geriatric Depression Scale scores when compared with the non-trained placebo group (p = 0.001 and p = 0.01, respectively) and the non-trained creatine group (p < 0.001 for both comparison). However, no significant differences were observed between the non-trained placebo and creatine (p = 0.60) groups, or between the trained placebo and creatine groups (p = 0.83). Both trained groups, irrespective of creatine supplementation, had better muscle strength performance than the non-trained groups. Neither strength training nor creatine supplementation altered any parameter of cognitive performance. Food intake remained unchanged. Conclusion Creatine supplementation did not promote any significant change in cognitive function and emotional parameters in apparently healthy older individuals. In addition, strength training per se improved emotional state and muscle strength, but not cognition, with no additive effects of creatine supplementation. Trial Registration Clinicaltrials.gov NCT01164020 PMID:24098469

Sex- and sex hormone-related variations in energy-metabolic frontal brain asymmetries: A magnetic resonance spectroscopy study.

PubMed

Hjelmervik, Helene; Hausmann, Markus; Craven, Alexander R; Hirnstein, Marco; Hugdahl, Kenneth; Specht, Karsten

2018-05-15

Creatine is a key regulator of brain energy homeostasis, and well-balanced creatine metabolism is central in healthy brain functioning. Still, the variability of brain creatine metabolism is largely unattended in magnetic resonance spectroscopy (MRS) research. In the human brain, marginal sex differences in creatine levels have been found in the prefrontal cortex. It is however not known to what degree these sex differences are stable or change with varying gonadal hormone levels. The current study therefore investigated creatine in the prefrontal cortex across the menstrual cycle. In addition, we explored cerebral asymmetries. Creatine, Choline (Cho), N-acetylaspartate (NAA), Myo inositol (mI), and glutamate + glutamine (Glx) were assessed three times in 15 women and 14 men using MRS. Women were tested in cycle phases of varying hormone levels (menstrual, follicular, and luteal phase). Prefrontal creatine was found to change across the menstrual cycle, in a hemisphere-specific manner. Women in the follicular phase showed increased left prefrontal creatine accompanied with reduced right prefrontal creatine, while this asymmetry was not present in the luteal phase. In men, the creatine levels remained stable across three testing sessions. In general, both men and women were found to have higher creatine levels in the left as compared to the right prefrontal cortex. Exploratory analyses of other metabolites showed similar asymmetries in NAA, Cho, and mI, while Cho also showed a menstrual cycle effect. This is the first time that sex hormone-related changes in creatine metabolism have been demonstrated in the human brain. These findings may have important methodological implications for MRS research, as it supports previous concerns against uncritical usage of creatine as a reference measure for other metabolites, assumed to be invariant across individuals and conditions. Copyright © 2018 University of Bergen. Published by Elsevier Inc. All rights reserved.

White matter NAA/Cho and Cho/Cr ratios at MR spectroscopy are predictive of motor outcome in preterm infants.

PubMed

Kendall, Giles S; Melbourne, Andrew; Johnson, Samantha; Price, David; Bainbridge, Alan; Gunny, Roxanna; Huertas-Ceballos, Angela; Cady, Ernest B; Ourselin, Sebastian; Marlow, Neil; Robertson, Nicola J

2014-04-01

To determine (a) whether diffuse white matter injury of prematurity is associated with an increased choline (Cho)-to-creatine (Cr) ratio and a reduced N-acetylaspartate (NAA)-to-Cho ratio and whether these measures can be used as biomarkers of outcome and (b) if changes in peak area metabolite ratios at magnetic resonance (MR) spectroscopy are associated with changes in T2 and fractional anisotropy (FA) at MR imaging. The local ethics committee approved this study, and informed parental consent was obtained for each infant. At term-equivalent age, 43 infants born at less than 32 weeks gestation underwent conventional and quantitative diffusion-tensor and T2-weighted MR imaging. Single-voxel point-resolved proton (hydrogen 1) MR spectroscopy was performed from a 2-cm(3) voxel centered in the posterior periventricular white matter. Outcome was evaluated by using Bayley scales at a corrected age of 1 year. Associations were investigated with Pearson product moment or Spearman rank order correlation. Differences in ratios in infants with and infants without impairment were tested by using t tests. NAA/Cho and Cho/Cr ratios correlated with the scaled gross motor score and the composite motor score, independent of gestational age (P < .05). FA at diffusion-tensor MR imaging and T2 at MR imaging correlated with the NAA/Cho ratio (P < .05 for both) but not with the Cho/Cr ratio. Infants with motor scores of less than 85 (impaired) had an increased Cho/Cr ratio (P < .03) and a reduced NAA/Cho ratio (P < .01) compared to those without impairment. A combination of increased Cho/Cr ratio and decreased NAA/Cho ratio predicted impaired motor outcome at a corrected age of 1 year with a sensitivity of 0.80 (95% confidence interval [CI]: 0.57, 0.94) and a specificity of 0.80 (95% CI: 0.66, 0.88). The combination of Cho/Cr and NAA/Cho ratios measured in the posterior periventricular white matter at term-equivalent age is predictive of motor outcome at 1 year in infants born at less than 32 weeks gestation. RSNA, 2013

Long-term normal-appearing brain tissue monitoring after irradiation using proton magnetic resonance spectroscopy in vivo: Statistical analysis of a large group of patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matulewicz, Lukasz; Sokol, Maria; Michnik, Anna

2006-11-01

Purpose: The aim of this study was to detect the non-neoplastic white-matter changes vs. time after irradiation using {sup 1}H nuclear magnetic resonance (NMR) spectroscopy in vivo. Methods and Materials: A total of 394 {sup 1}H MR spectra were acquired from 100 patients (age 19-74 years; mean and median age, 43 years) before and during 2 years after radiation therapy (the mean absorbed doses calculated for the averaged spectroscopy voxels are similar and close to 20 Gy). Results: Ocilations were observed in choline-containing compounds (Cho)/creatine and phosphocreatine (Cr), Cho/N-acetylaspartate (NAA), and center of gravity (CG) of the lipid band inmore » the range of 0.7-1.5 ppm changes over time reveal oscillations. The parameters have the same 8-month cycle period; however the CG changes precede the other by 2 months. Conclusions: The results indicate the oscillative nature of the brain response to irradiation, which may be caused by the blood-brain barrier disruption and repair processes. These oscillations may influence the NMR results, depending on the cycle phase in which the NMR measurements are performed in. The earliest manifestation of radiation injury detected by magnetic resonance spectroscopy is the CG shift.« less

Reduction of hexavalent chromium in water samples acidified for preservation

USGS Publications Warehouse

Stollenwerk, K.G.; Grove, D.B.

1985-01-01

Reduction of hexavalent chromium, Cr(VI), in water samples, preserved by standard techniques, was investigated. The standard preservation technique for water samples that are to be analyzed for Cr(VI) consists of filtration through a 0.45-??m membrane, acidification to a pH < 2, and storage in plastic bottles. Batch experiments were conducted to evaluate the effect of H+ concentration, NO2, temperature, and dissolved organic carbon (DOC) on the reduction of Cr(VI) to Cr(III). The rate of reduction of Cr(VI) to Cr(III) increased with increasing NO2, DOC, H+, and temperature. Reduction of Cr(VI) by organic matter occurred in some samples even though the samples were unacidified. Reduction of Cr(VI) is inhibited to an extent by storing the sample at 4??C. Stability of Cr(VI) in water is variable and depends on the other constituents present in the sample. Water samples collected for the determination of Cr(VI) should be filtered (0.45-??m membrane), refrigerated, and analyzed as quickly as possible. Water samples should not be acidified. Measurement of total Cr in addition to Cr(VI) can serve as a check for Cr(VI) reduction. If total Cr is greater than Cr(VI), the possibility that Cr(VI) reduction has occurred needs to be considered.The rate of reduction of Cr(VI) to Cr(III) increased with increasing NO//2, DOC, H** plus , and temperature. Reduction of Cr(VI) by organic matter occurred in some samples even though the samples were unacidified. Reduction of Cr(VI) is inhibited to an extent by storing the sample at 4 degree C. Stability of Cr(VI) in water is variable and depends on the other constituents present in the sample. Water samples collected for the determination of Cr(VI) should be filtered (0. 45- mu m membrane), refrigerated, and analyzed as quickly as possible. Water samples should not be acidified. Measurement of total Cr in addition to Cr(VI) can serve as a check for Cr(VI) reduction. If total Cr is greater than Cr(VI), the possibility that Cr(VI) reduction has occurred needs to be considered.

Effect and removal mechanisms of 6 different washing agents for building wastes containing chromium.

PubMed

Xing-run, Wang; Yan-xia, Zhang; Qi, Wang; Jian-min, Shu

2012-01-01

With the building wastes contaminated by chromium in Haibei Chemical Plan in China as objects, we studied the contents of total Cr and Cr (VI) of different sizes, analyzed the effect of 6 different washing agents, discussed the removal mechanisms of 6 different washing agents for Cr in various forms, and finally selected applicable washing agent. As per the results, particle size had little impact on the contents of total Cr and Cr (VI); after one washing with water, the removal rate of total Cr and Cr (VI) was 75% and 78%, respectively, and after the second washing with 6 agents, the removal rate of citric acid was the highest, above 90% for total Cr and above 99% for hexavalent chromium; the pH of building wastes were reduced by citric acid, and under acid condition, hexavalent chromium was reduced to trivalent chromium spontaneously by organic acid, which led to better removal rate of acid soluble Cr and reducible Cr; due to the complexing action, citric acid had best removal rate for oxidizable trivalent chromium. In conclusion, citric acid is the most applicable second washing agent for building wastes.

Radioimmunoassay measurement of creatine kinase bb in the serum of schizophrenic patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lerner, M.H.; Friedhoff, A.J.

1980-03-03

Brain type creatine kinase (BB) isoenzyme was measured using a highly sensitive and specific radioimmunoassay procedure in two schizophrenic populations. The data would indicate that in the schizophrenic populations examined there is insufficient tissue disruption to cause abnormal build-up of brain creatine kinase levels. However the possibility of a rapid removal of creatine kinase BB from the circulation exists. The elevated creatine kinase reported in acute schizophrenics is most likely not of brain origin.

Age dependence of myosin heavy chain transitions induced by creatine depletion in rat skeletal muscle

NASA Technical Reports Server (NTRS)

Adams, Gregory R.; Baldwin, Kenneth M.

1995-01-01

This study was designed to test the hypothesis that myosin heavy chain (MHC) plasticity resulting from creatine depletion is an age-dependent process. At weaning (age 28 days), rat pups were placed on either standard rat chow (normal diet juvenile group) or the same chow supplemented with 1% wt/wt of the creatine analogue beta-guanidinopropionic acid (creatine depletion juvenile (CDJ) group). Two groups of adult rats (age approximately 8 wk) were placed on the same diet regimens (normal diet adult and creatine depletion adult (CDA) groups). After 40 days (CDJ and normal diet juvenile groups) and 60 days (CDA and normal diet adult groups), animals were killed and several skeletal muscles were removed for analysis of creatine content or MHC ditribution. In the CDJ group, creatine depletion (78%) was accompanied by significant shifts toward expression of slower MHC isoforms in two slow and three fast skeletal muscles. In contrast, creatine depletion in adult animals did not result in similar shifts toward slow MHC isoform expression in either muscle type. The results of this study indicate that there is a differential effect of creatine depletion on MHC tranitions that appears to be age dependent. These results strongly suggest that investigators contemplating experimental designs involving the use of the creatine analogue beta-guanidinopropionic acid should consider the age of the animals to be used.

Maternal creatine supplementation affects the morpho-functional development of hippocampal neurons in rat offspring.

PubMed

Sartini, S; Lattanzi, D; Ambrogini, P; Di Palma, M; Galati, C; Savelli, D; Polidori, E; Calcabrini, C; Rocchi, M B L; Sestili, P; Cuppini, R

2016-01-15

Creatine supplementation has been shown to protect neurons from oxidative damage due to its antioxidant and ergogenic functions. These features have led to the hypothesis of creatine supplementation use during pregnancy as prophylactic treatment to prevent CNS damage, such as hypoxic-ischemic encephalopathy. Unfortunately, very little is known on the effects of creatine supplementation during neuron differentiation, while in vitro studies revealed an influence on neuron excitability, leaving the possibility of creatine supplementation during the CNS development an open question. Using a multiple approach, we studied the hippocampal neuron morphological and functional development in neonatal rats born by dams supplemented with 1% creatine in drinking water during pregnancy. CA1 pyramidal neurons of supplemented newborn rats showed enhanced dendritic tree development, increased LTP maintenance, larger evoked-synaptic responses, and higher intrinsic excitability in comparison to controls. Moreover, a faster repolarizing phase of action potential with the appearance of a hyperpolarization were recorded in neurons of the creatine-treated group. Consistently, CA1 neurons of creatine exposed pups exhibited a higher maximum firing frequency than controls. In summary, we found that creatine supplementation during pregnancy positively affects morphological and electrophysiological development of CA1 neurons in offspring rats, increasing neuronal excitability. Altogether, these findings emphasize the need to evaluate the benefits and the safety of maternal intake of creatine in humans. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

The Effects of Creatine Monohydrate on Permeability of Coronary Artery Endothelium and Level of Blood Lipoprotein in Diabetic Rats.

PubMed

Rahmani, Asghar; Asadollahi, Khairollah; Soleimannejad, Kourosh; Khalighi, Zahra; Mohsenzadeh, Yosouf; Hemati, Ruhollah; Moradkhani, Atefeh; Abangah, Ghobad

2016-09-01

Creatine monohydrate has beneficial effects on serum glucose. This study aimed to investigate the effects of creatine on serum biochemical markers and permeability of coronary arteries among diabetic rats. 32 Wistar rats, which weighed 150-200 grams were randomly divided into 4 groups including: group I, control; group II, creatine monohydrate; group III, diabetic rats; and group IV, diabetic rats + creatine. Creatine monohydrate was applied by 400 mg/kg/daily for 5 months. Animals' weights and blood samples were taken before and after the study. Endothelial permeability rate was measured by Evans Blue method. Data were analysed by SPSS 16. At the end of fifth month, rats' weights in diabetic group under treatment with creatine, compared to those without, increased significantly (p<0.0001). Also, the serum levels of triglyceride (TG), cholesterol, glucose and low density lipoprotein (LDL)- cholesterol decreased significantly among those under treatment with creatine (p<0.05), but high density lipoprotein (HDL)- cholesterol increased significantly (p<0.002). Permeability rate of coronary arteries was reduced significantly in the diabetic group treated by creatine compared to untreated groups, closed to the intact group (p<0.001). Results of this study showed that creatine monohydrate caused an improvement of serum biochemical markers associated with diabetes and reduced the permeability rate of coronary arteries among diabetic rats. © 2016 by the Association of Clinical Scientists, Inc.

Creatine Protects against Excitoxicity in an In Vitro Model of Neurodegeneration

PubMed Central

Genius, Just; Geiger, Johanna; Bender, Andreas; Möller, Hans-Jürgen; Klopstock, Thomas; Rujescu, Dan

2012-01-01

Creatine has been shown to be neuroprotective in aging, neurodegenerative conditions and brain injury. As a common molecular background, oxidative stress and disturbed cellular energy homeostasis are key aspects in these conditions. Moreover, in a recent report we could demonstrate a life-enhancing and health-promoting potential of creatine in rodents, mainly due to its neuroprotective action. In order to investigate the underlying pharmacology mediating these mainly neuroprotective properties of creatine, cultured primary embryonal hippocampal and cortical cells were challenged with glutamate or H2O2. In good agreement with our in vivo data, creatine mediated a direct effect on the bioenergetic balance, leading to an enhanced cellular energy charge, thereby acting as a neuroprotectant. Moreover, creatine effectively antagonized the H2O2-induced ATP depletion and the excitotoxic response towards glutamate, while not directly acting as an antioxidant. Additionally, creatine mediated a direct inhibitory action on the NMDA receptor-mediated calcium response, which initiates the excitotoxic cascade. Even excessive concentrations of creatine had no neurotoxic effects, so that high-dose creatine supplementation as a health-promoting agent in specific pathological situations or as a primary prophylactic compound in risk populations seems feasible. In conclusion, we were able to demonstrate that the protective potential of creatine was primarily mediated by its impact on cellular energy metabolism and NMDA receptor function, along with reduced glutamate spillover, oxidative stress and subsequent excitotoxicity. PMID:22347384

Stable isotope dilution microquantification of creatine metabolites in plasma, whole blood and dried blood spots for pharmacological studies in mouse models of creatine deficiency.

PubMed

Tran, C; Yazdanpanah, M; Kyriakopoulou, L; Levandovskiy, V; Zahid, H; Naufer, A; Isbrandt, D; Schulze, A

2014-09-25

To develop an accurate stable isotope dilution assay for simultaneous quantification of creatine metabolites ornithine, arginine, creatine, creatinine, and guanidinoacetate in very small blood sample volumes to study creatine metabolism in mice. Liquid-chromatography (C18) tandem mass spectrometry with butylation was performed in positive ionization mode. Stable isotope dilution assay with external calibration was applied to three different specimen types, plasma, whole blood and dried blood spot (DBS). Analytical separation, sensitivity, accuracy, and linearity of the assay were adequate. The stable isotope dilution assay in plasma revealed no significant bias to gold standard methods for the respective analytes. Compared to plasma, we observed an overestimate of creatine and creatinine (2- to 5-fold and 1.2- to 2-fold, respectively) in whole-blood and DBS, and an underestimate of arginine (2.5-fold) in DBS. Validation of the assay in mouse models of creatine deficiency revealed plasma creatine metabolite pattern in good accordance with those observed in human GAMT and AGAT deficiency. Single dose intraperitoneal application of ornithine in wild-type mice lead to fast ornithine uptake (Tmax ≤ 10 min) and elimination (T1/2=24 min), and a decline of guanidinoacetate. The assay is fast and reliable to study creatine metabolism and pharmacokinetics in mouse models of creatine deficiency. Copyright © 2014 Elsevier B.V. All rights reserved.

Creatine kinase and mitochondrial respiration in hearts of trout, cod and freshwater turtle.

PubMed

Birkedal, R; Gesser, H

2003-08-01

The importance of the creatine kinase system in the cardiac muscle of ectothermic vertebrates is unclear. Mammalian cardiac muscle seems to be structurally organized in a manner that compartmentalizes the intracellular environment as evidenced by the substantially higher mitochondrial apparent Km for ADP in skinned fibres compared to isolated mitochondria. A mitochondrial fraction of creatine kinase is functionally coupled to the mitochondrial respiration, and the transport of phosphocreatine and creatine as energy equivalents of ATP and ADP, respectively, increases the mitochondrial apparent ADP affinity, i.e. lowers the Km. This function of creatine kinase seems to be absent in hearts of frog species. To find out whether this applies to hearts of ectothermic vertebrate species in general, we investigated the effect of creatine on the mitochondrial respiration of saponin-skinned fibres from the ventricle of rainbow trout, Atlantic cod and freshwater turtle. For all three species, the apparent Km for ADP appeared to be substantially higher than for isolated mitochondria. Creatine lowered this Km in trout and turtle, thus indicating a functional coupling between mitochondrial creatine kinase and respiration. However, creatine had no effect on Km in cod ventricle. In conclusion, the creatine kinase-system in trout and turtle hearts seems to fulfil the same functions as in the mammalian heart, i.e. facilitating energy transport and communication between cellular compartments. In cod heart, however, this does not seem to be the case.

Influence of Asymptomatic Pneumonia on the Response to Hemorrhage and Resuscitation in Swine

DTIC Science & Technology

2010-01-01

and complete blood count (Pentra-120 Hemato- logy Analyzer, ABX Diagnostics, Irvine, CA); 3) total plasma protein, glucose, creatinine , lactate...dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine kinase (CK), amylase and lactate (Vitros Chemistry System...CK. Creatinine increased at 15 min in both groups and remained elevated throughout the study. Mean total protein, amylase and ALT decreased similarly

Medial Frontal Lobe Neurochemistry in Autism Spectrum Disorder Is Marked by Reduced N-Acetylaspartate and Unchanged Gamma-Aminobutyric Acid and Glutamate + Glutamine Levels

ERIC Educational Resources Information Center

Carvalho Pereira, Andreia; Violante, Inês R.; Mouga, Susana; Oliveira, Guiomar; Castelo-Branco, Miguel

2018-01-01

The nature of neurochemical changes in autism spectrum disorder (ASD) remains controversial. We compared medial prefrontal cortex (mPFC) neurochemistry of twenty high-functioning children and adolescents with ASD without associated comorbidities and fourteen controls. We observed reduced total N-acetylaspartate (tNAA) and total creatine, increased…

Creatine pretreatment protects cortical axons from energy depletion in vitro

PubMed Central

Shen, Hua; Goldberg, Mark P.

2012-01-01

Creatine is a natural nitrogenous guanidino compound involved in bioenergy metabolism. Although creatine has been shown to protect neurons of the central nervous system (CNS) from experimental hypoxia/ischemia, it remains unclear if creatine may also protect CNS axons, and if the potential axonal protection depends on glial cells. To evaluate the direct impact of creatine on CNS axons, cortical axons were cultured in a separate compartment from their somas and proximal neurites using a modified two-compartment culture device. Axons in the axon compartment were subjected to acute energy depletion, an in vitro model of white matter ischemia, by exposure to 6 mM sodium azide for 30 min in the absence of glucose and pyruvate. Energy depletion reduced axonal ATP by 65%, depolarized axonal resting potential, and damaged 75% of axons. Application of creatine (10 mM) to both compartments of the culture at 24 h prior to energy depletion significantly reduced axonal damage by 50%. In line with the role of creatine in the bioenergy metabolism, this application also alleviated the axonal ATP loss and depolarization. Inhibition of axonal depolarization by blocking sodium influx with tetrodotoxin also effectively reduced the axonal damage caused by energy depletion. Further study revealed that the creatine effect was independent of glial cells, as axonal protection was sustained even when creatine was applied only to the axon compartment (free from somas and glial cells) for as little as 2 h. In contrast, application of creatine after energy depletion did not protect axons. The data provide the first evidence that creatine pretreatment may directly protect CNS axons from energy deficiency. PMID:22521466

Living Without Creatine: Unchanged Exercise Capacity and Response to Chronic Myocardial Infarction in Creatine-Deficient Mice

PubMed Central

Lygate, Craig A.; Aksentijevic, Dunja; Dawson, Dana; Hove, Michiel ten; Phillips, Darci; de Bono, Joseph P.; Medway, Debra J.; Sebag-Montefiore, Liam; Hunyor, Imre; Channon, Keith M.; Clarke, Kieran; Zervou, Sevasti; Watkins, Hugh; Balaban, Robert S.; Neubauer, Stefan

2014-01-01

Rationale Creatine is thought to be involved in the spatial and temporal buffering of ATP in energetic organs such as heart and skeletal muscle. Creatine depletion affects force generation during maximal stimulation, while reduced levels of myocardial creatine are a hallmark of the failing heart, leading to the widely held view that creatine is important at high workloads and under conditions of pathological stress. Objective We therefore hypothesised that the consequences of creatine-deficiency in mice would be impaired running capacity, and exacerbation of heart failure following myocardial infarction. Methods and Results Surprisingly, mice with whole-body creatine deficiency due to knockout of the biosynthetic enzyme (guanidinoacetate N-methyltransferase – GAMT) voluntarily ran just as fast and as far as controls (>10km/night) and performed the same level of work when tested to exhaustion on a treadmill. Furthermore, survival following myocardial infarction was not altered, nor was subsequent LV remodelling and development of chronic heart failure exacerbated, as measured by 3D-echocardiography and invasive hemodynamics. These findings could not be accounted for by compensatory adaptations, with no differences detected between WT and GAMT−/− proteomes. Alternative phosphotransfer mechanisms were explored; adenylate kinase activity was unaltered, and although GAMT−/− hearts accumulated the creatine pre-cursor guanidinoacetate, this had negligible energy-transfer activity, while mitochondria retained near normal function. Conclusions Creatine-deficient mice show unaltered maximal exercise capacity and response to chronic myocardial infarction, and no obvious metabolic adaptations. Our results question the paradigm that creatine is essential for high workload and chronic stress responses in heart and skeletal muscle. PMID:23325497

The effects of beta-hydroxy-beta-methylbutyrate (HMB) and HMB/creatine supplementation on indices of health in highly trained athletes.

PubMed

Crowe, Melissa J; O'Connor, Donna M; Lukins, Joann E

2003-06-01

This study aimed to investigate the effects of 6 wk oral supplementation of beta-hydroxy-beta-methylbutyrate (HMB) and HMB combined with creatine monohydrate (HMBCr) on indices of health in highly trained athletes. Elite, male rugby league players (n=28) were allocated to 1 of 3 groups: a control group (n=6), a HMB group (3 g/d; n=11), or a HMBCr group (3 g/day HMB, 3 g/d Cr; n=11). Testing prior to, and immediately following, supplementation included a full blood count, plasma testosterone and cortisol, blood electrolytes, lipids, urea and glucose, sperm count and motility, and assessment of psychological state. A 3 x 2 factorial ANOVA revealed no effect of HMB or HMBCr on any of the measured parameters except minor changes in blood bicarbonate and blood monocyte and lymphocyte counts. Blood bicarbonate was significantly decreased in the HMB post-supplementation sample compared to the control and HMBCr groups. Blood monocyte and lymphocyte counts showed no within-group changes for HMB or HMBCr supplementation but were significantly different from the control. However, the majority of these readings remained within normal range. HMB and HMBCr were concluded to have no adverse effects on the parameters evaluated in this study when taken orally by highly trained male athletes over a 6-wk period.

Metabolic control analysis of integrated energy metabolism in permeabilized cardiomyocytes - experimental study.

PubMed

Tepp, Kersti; Timohhina, Natalja; Chekulayev, Vladimir; Shevchuk, Igor; Kaambre, Tuuli; Saks, Valdur

2010-01-01

The main focus of this research was to apply Metabolic Control Analysis to quantitative investigation of the regulation of respiration by components of the Mitochondrial Interactosome (MI, a supercomplex consisting of ATP Synthasome, mitochondrial creatine kinase (MtCK), voltage dependent anion channel (VDAC), and tubulin) in permeabilized cardiomyocytes. Flux control coefficients (FCC) were measured using two protocols: 1) with direct ADP activation, and 2) with MtCK activation by creatine (Cr) in the presence of ATP and pyruvate kinase-phosphoenolpyruvate system. The results show that the metabolic control is much stronger in the latter case: the sum of the measured FCC is 2.7 versus 0.74 (ADP activation). This is consistent with previous data showing recycling of ADP and ATP inside the MI due to the functional coupling between MtCK and ANT and limited permeability of VDAC for these compounds, PCr being the major energy carrier between the mitochondria and ATPases. In physiological conditions, when the MI is activated, the key sites of regulation of respiration in mitochondria are MtCK (FCC = 0.93), adenine nucleotide translocase ANT (FCC = 0.95) and CoQ cytochrome c oxidoreductase (FCC = 0.4). These results show clearly that under the physiological conditions the energy transfer from mitochondria to the cytoplasm is regulated by the MI supercomplex and is very sensitive to metabolic signals.

Design innovations and baseline findings in a long-term Parkinson’s trial: NET-PD LS-1

PubMed Central

2012-01-01

Background Based on the pre-clinical and the results of a phase 2 futility study, creatine was selected for an efficacy trial in Parkinson’s disease (PD). We present the design rationale and a description of the study cohort at baseline. Methods A randomized, multicenter, double-blind, parallel group, placebo controlled Phase 3 study of creatine (10 gm daily) in participants with early, treated PD, the Long-term Study – 1 (LS-1) is being conducted by the NINDS Exploratory Trials in Parkinson’s Disease (NET-PD) network. The study utilizes a global statistical test (GST) encompassing multiple clinical rating scales to provide a multidimensional assessment of disease progression. Results A total of 1,741 PD participants from 45 sites in the U.S. and Canada were randomized 1:1 to either 10-gm creatine/day or matching placebo. Participants are being evaluated for a minimum of 5 years. The LS-1 baseline cohort includes participants treated with dopaminergic therapy and generally mild PD. Conclusions LS-1 represents the largest cohort of patients with early treated PD ever enrolled in a clinical trial. The GST approach should provide high power to test the hypothesis that daily administration of creatine (10gm/day) is more effective than placebo in slowing clinical decline in PD between baseline and the 5 year follow-up visit against the background of dopaminergic therapy and best PD care. PMID:23079770

Microcomputer Assisted Interpretative Reporting of Sequential Creatine Kinase (CK) and Lactate Dehydrogenase (LDH) Isoenzyme Determination

PubMed Central

Talamo, Thomas S.; Losos, Frank J.; Mercer, Donald W.

1984-01-01

We have developed a microcomputer based system for interpretative reporting of creatine kinase (CK) and lactate dehydrogenase (LDH) isoenzyme studies. Patient demographic data and test results (total CK, CK-MB, LD-1, and LD-2) are entered manually through the keyboard. The test results are compared with normal range values and an interpretative report is generated. This report consists of all pertinent demographic information with a graphic display of up to 12 previous CK and LDH isoenzyme determinations. Diagnostic interpretative statements are printed beneath the graphic display following analysis of previously entered test results. The combination of graphic data display and interpretations based on analysis of up to 12 previous specimens provides useful and accurate information to the cardiologist.

Non-enzymatic cyclization of creatine ethyl ester to creatinine.

PubMed

Giese, Matthew W; Lecher, Carl S

2009-10-16

Creatine ethyl ester was incubated at 37 degrees C in both water and phosphate-buffered saline and the diagnostic methylene resonances in the (1)H NMR spectrum were used to identify the resultant products. It was found that mild aqueous conditions result in the cyclization of creatine ethyl ester to provide inactive creatinine as the exclusive product, and this transformation becomes nearly instantaneous as the pH approaches 7.4. This study demonstrates that mild non-enzymatic conditions are sufficient for the cyclization of creatine ethyl ester into creatinine, and together with previous results obtained under enzymatic conditions suggests that there are no physiological conditions that would result in the production of creatine. It is concluded that creatine ethyl ester is a pronutrient for creatinine rather than creatine under all physiological conditions encountered during transit through the various tissues, thus no ergogenic effect is to be expected from supplementation.

Distribution and bioavailability of Cr in central Euboea, Greece

NASA Astrophysics Data System (ADS)

Megremi, Ifigeneia

2010-06-01

Plants and soils from central Euboea, were analyzed for Cr(totai), Cr(VI), Ni, Mn, Fe and Zn. The range of metal concentrations in soils is typical to those developed on Fe-Ni laterites and ultramafic rocks. Their bioavailability was expressed in terms of concentrations extractable with EDTA and 1 M HNO3, with EDTA having a limited effect on metal recovery. Cr(VI) concentrations in soils evaluated by alkaline digestion solution were lower than phytotoxic levels. Chromium and Ni — and occasionally Zn — in the majority of plants were near or above toxicity levels. Cr(VI) concentrations in plants were extremely low compared to total chromium concentrations. Cr(total) in ground waters ranged from <1 μg.L-1 to 130 μg.L-1, with almost all chromium present as Cr(VI). With the exception of Cr(total) and in some cases Zn, all elements were below regulatory limits for drinking water. On the basis of Ca, Mg, Cr(total) and Si ground waters were classified into three groups: Group(I) with Cr concentrations less than 1 μg.L-1 from a karstic aquifer; Group(II) with average concentrations of 24 μg.L-1 of Cr and relatively high Si associated with ophiolites; and Group(III) with Cr concentrations of up to 130 μg.L-1, likely due to anthropogenic activity. Group(III) is comparable to ground waters from Assopos basin, characterized by high Cr(VI) concentrations, probably due to industrial actrivities.

75 FR 17769 - In the Matter of Certain Products Advertised as Containing Creatine Ethyl Ester; Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-07

... Advertised as Containing Creatine Ethyl Ester; Notice of Commission Issuance of a Limited Exclusion Order Against the Products Advertised as Containing Creatine Ethyl Ester of Respondents Found in Default... importation of certain products advertised as containing creatine ethyl ester by reason of false advertising...

Creatine Supplementation and Skeletal Muscle Metabolism for Building Muscle Mass- Review of the Potential Mechanisms of Action.

PubMed

Farshidfar, Farnaz; Pinder, Mark A; Myrie, Semone B

2017-01-01

Creatine, a very popular supplement among athletic populations, is of growing interest for clinical applications. Since over 90% of creatine is stored in skeletal muscle, the effect of creatine supplementation on muscle metabolism is a widely studied area. While numerous studies over the past few decades have shown that creatine supplementation has many favorable effects on skeletal muscle physiology and metabolism, including enhancing muscle mass (growth/hypertrophy); the underlying mechanisms are poorly understood. This report reviews studies addressing the mechanisms of action of creatine supplementation on skeletal muscle growth/hypertrophy. Early research proposed that the osmotic effect of creatine supplementation serves as a cellular stressor (osmosensing) that acts as an anabolic stimulus for protein synthesis signal pathways. Other reports indicated that creatine directly affects muscle protein synthesis via modulations of components in the mammalian target of rapamycin (mTOR) pathway. Creatine may also directly affect the myogenic process (formation of muscle tissue), by altering secretions of myokines, such as myostatin and insulin-like growth factor-1, and expressions of myogenic regulatory factors, resulting in enhanced satellite cells mitotic activities and differentiation into myofiber. Overall, there is still no clear understanding of the mechanisms of action regarding how creatine affects muscle mass/growth, but current evidence suggests it may exert its effects through multiple approaches, with converging impacts on protein synthesis and myogenesis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Assignment of the molecular origins of CEST signals at 2 ppm in rat brain.

PubMed

Zhang, Xiao-Yong; Xie, Jingping; Wang, Feng; Lin, Eugene C; Xu, Junzhong; Gochberg, Daniel F; Gore, John C; Zu, Zhongliang

2017-09-01

Chemical exchange saturation transfer effects at 2 ppm (CEST@2ppm) in brain have previously been interpreted as originating from creatine. However, protein guanidino amine protons may also contribute to CEST@2ppm. This study aims to investigate the molecular origins and specificity of CEST@2ppm in brain. Two experiments were performed: (i) samples containing egg white albumin and creatine were dialyzed using a semipermeable membrane to demonstrate that proteins and creatine can be separated by this method; and (ii) tissue homogenates of rat brain with and without dialysis to remove creatine were studied to measure the relative contributions of proteins and creatine to CEST@2ppm. The experiments indicate that dialysis can successfully remove creatine from proteins. Measurements on tissue homogenates show that, with the removal of creatine via dialysis, CEST@2ppm decreases to approximately 34% of its value before dialysis, which indicates that proteins and creatine have comparable contribution to the CEST@2ppm in brain. However, considering the contribution from peptides and amino acids to CEST@2ppm, creatine may have much less contribution to CEST@2ppm. The contribution of proteins, peptides, and amino acids to CEST@2ppm cannot be neglected. The CEST@2ppm measurements of creatine in rat brain should be interpreted with caution. Magn Reson Med 78:881-887, 2017. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Evaluation of treatment-induced cerebral white matter injury by using diffusion-tensor MR imaging: initial experience.

PubMed

Kitahara, Sawako; Nakasu, Satoshi; Murata, Kiyoshi; Sho, Keizen; Ito, Ryuta

2005-10-01

Treatment with chemotherapy and radiation therapy for brain tumors can cause white matter (WM) injury. Conventional MR imaging, however, cannot always depict treatment-induced transient WM abnormalities. We investigated the ability of diffusion-tensor (DT) MR imaging and proton MR spectroscopy to detect the treatment-induced transient changes within normal-appearing WM. DT MR imaging and proton MR spectroscopy were performed in 8 patients treated with a combination of surgery, chemotherapy, and radiation therapy for brain tumors (17 examinations) and 11 age-matched controls. Apparent diffusion coefficient (ADC) value, fractional anisotropy (FA) value, and N-acetylaspartate (NAA)/creatine (Cr) ratio were obtained from 27 hemispheres with normal-appearing WM in the patients. We divided the datasets of isotropic ADC, FA, and NAA/Cr, on the basis of the time period after completion of radiation therapy, into 4 groups: group 1 (0-2 months; n = 10), group 2 (3-5 months; n = 5), group 3 (6-9 months; n = 7), and group 4 (10-12 months; n = 5). We compared averages of mean isotropic ADC, mean FA, and NAA/Cr of each patient group with those of the control group by using a t test. In the group 2, averages of mean FA and NAA/Cr decreased and average of mean isotopic ADC increased in comparison with those of the control group (P = .004, .04, and .0085, respectively). There were no significant differences in the averages between the control group and patient groups 1, 3, and 4. DT MR imaging and proton MR spectroscopy can provide quantitative indices that may reflect treatment-induced transient derangement of normal-appearing WM.

Frontal Metabolite Concentration Deficits in Opiate Dependence Relate to Substance Use, Cognition, and Self-Regulation

PubMed Central

Murray, Donna E; Durazzo, Timothy C; Schmidt, Thomas P; Abé, Christoph; Guydish, Joseph; Meyerhoff, Dieter J

2016-01-01

Objective Proton magnetic resonance spectroscopy (1H MRS) in opiate dependence showed abnormalities in neuronal viability and glutamate concentration in the anterior cingulate cortex (ACC). Metabolite levels in dorsolateral prefrontal cortex (DLPFC) or orbitofrontal cortex (OFC) and their neuropsychological correlates have not been investigated in opiate dependence. Methods Single-volume proton MRS at 4 Tesla and neuropsychological testing were conducted in 21 opiate-dependent individuals (OD) on buprenorphine maintenance therapy. Results were compared to 28 controls (CON) and 35 alcohol-dependent individuals (ALC), commonly investigated treatment-seekers providing context for OD evaluation. Metabolite concentrations were measured from ACC, DLPFC, OFC and parieto-occipital cortical (POC) regions. Results Compared to CON, OD had lower concentrations of N-acetylaspartate (NAA), glutamate (Glu), creatine +phosphocreatine (Cr) and myo-Inositol (mI) in the DLPFC and lower NAA, Cr, and mI in the ACC. OD, ALC, and CON were equivalent on metabolite levels in the POC and γ-aminobutyric acid (GABA) concentration did not differ between groups in any region. In OD, prefrontal metabolite deficits in ACC Glu as well as DLPFC NAA and choline containing metabolites (Cho) correlated with poorer working memory, executive and visuospatial functioning; metabolite deficits in DLPFC Glu and ACC GABA and Cr correlated with substance use measures. In the OFC of OD, Glu and choline-containing metabolites were elevated and lower Cr concentration related to higher nonplanning impulsivity. Compared to 3 week abstinent ALC, OD had significant DLPFC metabolite deficits. Conclusion The anterior frontal metabolite profile of OD differed significantly from that of CON and ALC. The frontal lobe metabolite abnormalities in OD and their neuropsychological correlates may play a role in treatment outcome and could be explored as specific targets for improved OD treatment. PMID:27695638

Neonatal hydrocortisone treatment related to 1H-MRS of the hippocampus and short-term memory at school age in preterm born children.

PubMed

Rademaker, Karin J; Rijpert, Maarten; Uiterwaal, Cuno S P M; Lieftink, Arno F; van Bel, Frank; Grobbee, Diederick E; de Vries, Linda S; Groenendaal, Floris

2006-02-01

Animal studies have shown that corticosteroids (dexamethasone) cause neuronal loss in the hippocampus and deficits in short term memory. Proton magnetic resonance spectroscopy can measure brain metabolites in vivo and give an indication of neuronal integrity. We investigated whether prolonged administration of hydrocortisone during the neonatal period for bronchopulmonary dysplasia (BPD) in preterm born children changes the metabolism in the hippocampus, measured at school age. Secondly, we investigated whether hippocampal metabolism and short-term memory and neurodevelopmental outcome are related. In this observational study 37 preterm born children (< or = 32 wk (range 25.0-33.0) and/or a birth weight < or = 1500 g) underwent proton spectroscopy of the hippocampus at school age. Eighteen children were treated with hydrocortisone for BPD (starting dose 5 mg/kg/d tapered over a minimum period of 22 d, median duration 28 d) and 19 never received corticosteroids during the perinatal period. N-acetyl aspartate/ Choline + Creatine/phosphocreatine (NAA/(Cho + Cr)) ratios were determined. A 15-word recall memory test and an IQ measurement were obtained on the same day. Hydrocortisone treated children were younger, lighter and sicker than their nonsteroid treated counterparts. Mean NAA/(Cho + Cr) ratios in the hippocampus were not significantly different in the hydrocortisone group compared with the non-steroid group. Performance on the 15-word memory test and IQ were similar in the two groups. There was no relation between NAA/(Cho + Cr) ratios and memory nor between NAA/(Cho + Cr) ratios and IQ. We conclude that hydrocortisone in the mentioned dose, administered in the neonatal period for BPD, does not appear to have any long-term effects on memory and/or hippocampal metabolism.

Altered white matter metabolism in delayed neurologic sequelae after carbon monoxide poisoning: A proton magnetic resonance spectroscopic study.

PubMed

Kuroda, Hiroshi; Fujihara, Kazuo; Mugikura, Shunji; Takahashi, Shoki; Kushimoto, Shigeki; Aoki, Masashi

2016-01-15

Proton magnetic resonance spectroscopy ((1)H-MRS) was recently used to examine altered metabolism in the white matter (WM) of patients experiencing carbon monoxide (CO) poisoning; however, only a small number of patients with delayed neurologic sequelae (DNS) were analyzed. We aimed to detect altered metabolism in the WM of patients with DNS using (1)H-MRS; to explore its clinical relevance in the management of patients experiencing CO poisoning. Patients experiencing acute CO poisoning underwent (1)H-MRS and cerebrospinal fluid (CSF) examination within 1week and at 1month after acute poisoning. Metabolites including choline-containing compounds (Cho), creatine (Cr), N-acetylaspartate (NAA), and lactate were measured from the periventricular WM. Myelin basic protein (MBP) concentrations were measured in CSF. Fifty-two patients experiencing acute CO poisoning (15 with DNS, 37 without DNS; median age, 49years; 65% males) underwent (1)H-MRS. Within 1week, NAA/Cr ratios, reflecting neuroaxonal viability, were lower in patients with DNS than in those without DNS (P<0.05). At 1month, when 9 of 15 patients (60%) developed DNS, Cho/Cr ratios were higher, and NAA/Cr and NAA/Cho ratios lower in patients with DNS (P=0.0001, <0.0001, and <0.0001, respectively), indicating increased membrane metabolism and decreased neuroaxonal viability. (1)H-MRS parameter abnormalities correlated with the elevation of MBP in CSF. The presence of a lactate peak was a predictor for a poor long-term outcome. (1)H-MRS within 1week may be useful for predicting DNS development; (1)H-MRS at 1month may be useful for discriminating patients with DNS and predicting long-term outcomes. Copyright © 2015 Elsevier B.V. All rights reserved.

Brain metabolite abnormalities in ventromedial prefrontal cortex are related to duration of hypercortisolism and anxiety in patients with Cushing's syndrome.

PubMed

Crespo, Iris; Santos, Alicia; Gómez-Ansón, Beatriz; López-Mourelo, Olga; Pires, Patricia; Vives-Gilabert, Yolanda; Webb, Susan M; Resmini, Eugenia

2016-09-01

Chronic exposure to excessive glucocorticoid (GC) concentration in Cushing's syndrome (CS) can affect the brain structurally and functionally; ventromedial prefrontal cortex (vmPFC) is rich in GC receptors and therefore particularly vulnerable to excessive GC concentration. Proton magnetic resonance spectroscopy ((1)H-MRS) is a sensitive, non-invasive imaging technique that provides information on brain metabolites in vivo. Our aim was to investigate metabolite concentrations in vmPFC of CS patients and their relationship with clinical outcome. Twenty-two right-handed CS patients (7 active/15 in remission, 19 females, 41.6 ± 12.3 years) and 22 right-handed healthy controls (14 females, 41.7 ± 11 years) underwent brain MRI and (1)H-MRS exams at 3 Tesla. Concentrations of glutamate (Glu), glutamate + glutamine (Glx), creatine (Cr), N-Acetyl-aspartate (NAA), N-Acetyl-aspartate + N-acetylaspartylglutamate (total NAA), choline-containing compounds (Cho) and myoinositol (MI) were determined. Moreover, anxiety and depressive symptoms were evaluated with the State-Trait Anxiety Inventory (STAI) and the Beck Depression Inventory-II (BDI-II) test, respectively. CS patients had lower concentrations of glutamate and total NAA in the vmPFC than healthy controls (8.6 ± 1.2 vs. 9.3 ± 0.7 mmol/L, and 6.4 ± 0.8 vs. 6.8 ± 0.4 mmol/L, respectively; p < 0.05). Duration of hypercortisolism was negatively correlated with total NAA (r = -0.488, p < 0.05). Moreover, the concentration of total NAA was negatively correlated with anxiety state (r = -0.359, p < 0.05). Brain metabolites are abnormal in the vmPFC of patients with CS. Decreased total NAA and glutamate concentrations indicate neuronal dysfunction that appear to be related with duration of hypercortisolism and anxiety.

Emissions of chromium (VI) from arc welding.

PubMed

Heung, William; Yun, Myoung-Jin; Chang, Daniel P Y; Green, Peter G; Halm, Chris

2007-02-01

The presence of Cr in the +6 oxidation state (Cr[VI]) is still observed in ambient air samples in California despite steps taken to reduce emissions from plating operations. One known source of emission of Cr(VI) is welding, especially with high Cr-content materials, such as stainless steels. An experimental effort was undertaken to expand and update Cr(VI) emission factors by conducting tests on four types of arc-welding operations: gas-metal arc welding (GMAW), shielded metal arc welding (SMAW), fluxcore arc welding, and pulsed GMAW. Standard American Welding Society hood results were compared with a total enclosure method that permitted isokinetic sampling for particle size-cut measurement, as well as total collection of the aerosol. The fraction of Cr(VI) emitted per unit mass of Cr electrode consumed was determined. Consistent with AP-42 data, initial results indicate that a significant fraction of the total Cr in the aerosol is in the +6 oxidation state. The fraction of Cr(VI) and total aerosol mass produced by the different arc welding methods varies with the type of welding process used. Self-shielded electrodes that do not use a shield gas, for example, SMAW, produce greater amounts of Cr(VI) per unit mass of electrode consumed. The formation of Cr(VI) from standard electrode wires used for welding mild steel was below the method detection limit after eliminating an artifact in the analytical method used.

Anisotropic diffusion of metabolites in peripheral nerve using diffusion weighted magnetic resonance spectroscopy at ultra-high field

NASA Astrophysics Data System (ADS)

Ellegood, Jacob; McKay, Ryan T.; Hanstock, Chris C.; Beaulieu, Christian

2007-01-01

Although the diffusivity and anisotropy of water has been investigated thoroughly in ordered axonal systems (i.e., nervous tissue), there have been very few studies on the directional dependence of diffusion of metabolites. In this study, the mean apparent diffusion coefficient (Trace/3 ADC) and fractional anisotropy (FA) values of the intracellular metabolites N-acetyl aspartate (NAA), creatine and phosphocreatine (tCr), choline (Cho), taurine (Tau), and glutamate and glutamine (Glx) were measured parallel and perpendicular to the length of excised frog sciatic nerve using a water suppressed, diffusion-weighted, spin-echo pulse sequence at 18.8 T. The degree of anisotropy (FA) of NAA (0.41 ± 0.09) was determined to be less than tCr (0.59 ± 0.07) and Cho (0.61 ± 0.11), which is consistent with previously reported human studies of white matter. In contrast, Glx diffusion was found to be almost isotropic with an FA value of 0.20 ± 0.06. The differences of FA between the metabolites is most likely due to their differing micro-environments and could be beneficial as an indicator of compartment specific changes with disease, information not readily available with water diffusion.

Altered neurotransmitter metabolism in adolescents with high-functioning autism

PubMed Central

Drenthen, Gerhard S.; Barendse, Evelien M.; Aldenkamp, Albert P.; van Veenendaal, Tamar M.; Puts, Nicolaas A.J.; Edden, Richard A.E.; Zinger, Svitlana; Thoonen, Geert; Hendriks, Marc P.H.; Kessels, Roy P.C.; Jansen, Jacobus F.A.

2017-01-01

Previous studies have suggested that alterations in excitatory/inhibitory neurotransmitters might play a crucial role in autism spectrum disorder (ASD). Proton magnetic resonance spectroscopy (1H-MRS) can provide valuable information about abnormal brain metabolism and neurotransmitter concentrations. However, few 1H-MRS studies have been published on the imbalance of the two most abundant neurotransmitters in ASD: glutamate (Glu) and gamma-aminobutyric acid (GABA). Moreover, to our knowledge none of these published studies is performed with a study population consisting purely of high-functioning autism (HFA) adolescents. Selecting only individuals with HFA eliminates factors possibly related to intellectual impairment instead of ASD. This study aims to assess Glu and GABA neurotransmitter concentrations in HFA. Occipital concentrations of Glu and GABA plus macromolecules (GABA+) were obtained using 1H-MRS relative to creatine (Cr) in adolescents with HFA (n=15 and n=13 respectively) and a healthy control group (n=17). Multiple linear regression revealed significantly higher Glu/Cr and lower GABA+/Glu concentrations in the HFA group compared to the controls. These results imply that imbalanced neurotransmitter levels of excitation and inhibition are associated with HFA in adolescents. PMID:27685800

Adding Sarcosine to Antipsychotic Treatment in Patients with Stable Schizophrenia Changes the Concentrations of Neuronal and Glial Metabolites in the Left Dorsolateral Prefrontal Cortex.

PubMed

Strzelecki, Dominik; Podgórski, Michał; Kałużyńska, Olga; Stefańczyk, Ludomir; Kotlicka-Antczak, Magdalena; Gmitrowicz, Agnieszka; Grzelak, Piotr

2015-10-15

The glutamatergic system is a key point in pathogenesis of schizophrenia. Sarcosine (N-methylglycine) is an exogenous amino acid that acts as a glycine transporter inhibitor. It modulates glutamatergic transmission by increasing glycine concentration around NMDA (N-methyl-d-aspartate) receptors. In patients with schizophrenia, the function of the glutamatergic system in the prefrontal cortex is impaired, which may promote negative and cognitive symptoms. Proton nuclear magnetic resonance (¹H-NMR) spectroscopy is a non-invasive imaging method enabling the evaluation of brain metabolite concentration, which can be applied to assess pharmacologically induced changes. The aim of the study was to evaluate the influence of a six-month course of sarcosine therapy on the concentration of metabolites (NAA, N-acetylaspartate; Glx, complex of glutamate, glutamine and γ-aminobutyric acid (GABA); mI, myo-inositol; Cr, creatine; Cho, choline) in the left dorso-lateral prefrontal cortex (DLPFC) in patients with stable schizophrenia. Fifty patients with schizophrenia, treated with constant antipsychotics doses, in stable clinical condition were randomly assigned to administration of sarcosine (25 patients) or placebo (25 patients) for six months. Metabolite concentrations in DLPFC were assessed with 1.5 Tesla ¹H-NMR spectroscopy. Clinical symptoms were evaluated with the Positive and Negative Syndrome Scale (PANSS). The first spectroscopy revealed no differences in metabolite concentrations between groups. After six months, NAA/Cho, mI/Cr and mI/Cho ratios in the left DLPFC were significantly higher in the sarcosine than the placebo group. In the sarcosine group, NAA/Cr, NAA/Cho, mI/Cr, mI/Cho ratios also significantly increased compared to baseline values. In the placebo group, only the NAA/Cr ratio increased. The addition of sarcosine to antipsychotic therapy for six months increased markers of neurons viability (NAA) and neurogilal activity (mI) with simultaneous improvement of clinical symptoms. Sarcosine, two grams administered daily, seems to be an effective adjuvant in the pharmacotherapy of schizophrenia.

Evaluation of plasma chemistry and haematological studies on chickens infected with Eimeria tenella and E acervulina.

PubMed

Fukata, T; Komba, Y; Sasai, K; Baba, E; Arakawa, A

1997-07-12

Plasma chemistry and haematological studies were conducted on chickens with coccidiosis. Male White Leghorn chickens, of two weeks old, were inoculated with 5 x 10(4) Eimeria tenella sporulated oocysts or with 1 x 10(6) E acervulina sporulated oocysts. Blood samples were taken four, seven and 11 days after inoculation. A wet chemistry system was applied to measure the plasma activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyltransferase, creatine kinase, amylase and lactate dehydrogenase and the concentrations of creatine, total bilirubin, urate, total cholesterol, total protein, albumin, glucose and triglycerides. A dry chemistry system was applied to measure sodium, potassium, chloride and calcium. The number of red blood cells and packed cell volume were determined by a micro cell counter and blood pH was measured with a blood gas analyser. The erythrocyte count, packed cell volume, sodium and chloride levels in the chickens infected with E tenella were significantly (P < 0.05) lower than those of the uninfected controls. The significant decrease in blood pH of the chickens infected with E acervulina suggests malabsorption associated with duodenal lesions induced by the infection.

Kinetics and Products of Chromium(VI) Reduction by Iron(II/III)-Bearing Clay Minerals.

PubMed

Joe-Wong, Claresta; Brown, Gordon E; Maher, Kate

2017-09-05

Hexavalent chromium is a water-soluble pollutant, the mobility of which can be controlled by reduction of Cr(VI) to less soluble, environmentally benign Cr(III). Iron(II/III)-bearing clay minerals are widespread potential reductants of Cr(VI), but the kinetics and pathways of Cr(VI) reduction by such clay minerals are poorly understood. We reacted aqueous Cr(VI) with two abiotically reduced clay minerals: an Fe-poor montmorillonite and an Fe-rich nontronite. The effects of ionic strength, pH, total Fe content, and the fraction of reduced structural Fe(II) [Fe(II)/Fe(total)] were examined. The last variable had the largest effect on Cr(VI) reduction kinetics: for both clay minerals, the rate constant of Cr(VI) reduction varies by more than 3 orders of magnitude with Fe(II)/Fe(total) and is described by a linear free energy relationship. Under all conditions examined, Cr and Fe K-edge X-ray absorption near-edge structure spectra show that the main Cr-bearing product is a Cr(III)-hydroxide and that Fe remains in the clay structure after reacting with Cr(VI). This study helps to quantify our understanding of the kinetics of Cr(VI) reduction by Fe(II/III)-bearing clay minerals and may improve predictions of Cr(VI) behavior in subsurface environments.

Myo-inositol changes precede amyloid pathology and relate to APOE genotype in Alzheimer disease

PubMed Central

Sundgren, Pia C.; Strandberg, Olof; Zetterberg, Henrik; Minthon, Lennart; Blennow, Kaj; Wahlund, Lars-Olof; Westman, Eric

2016-01-01

Objective: We aimed to test whether in vivo levels of magnetic resonance spectroscopy (MRS) metabolites myo-inositol (mI), N-acetylaspartate (NAA), and choline are abnormal already during preclinical Alzheimer disease (AD), relating these changes to amyloid or tau pathology, and functional connectivity. Methods: In this cross-sectional multicenter study (a subset of the prospective Swedish BioFINDER study), we included 4 groups, representing the different stages of predementia AD: (1) cognitively healthy elderly with normal CSF β-amyloid 42 (Aβ42), (2) cognitively healthy elderly with abnormal CSF Aβ42, (3) patients with subjective cognitive decline and abnormal CSF Aβ42, (4) patients with mild cognitive decline and abnormal CSF Aβ42 (Ntotal = 352). Spectroscopic markers measured in the posterior cingulate/precuneus were considered alongside known disease biomarkers: CSF Aβ42, phosphorylated tau, total tau, [18F]-flutemetamol PET, f-MRI, and the genetic risk factor APOE. Results: Amyloid-positive cognitively healthy participants showed a significant increase in mI/creatine and mI/NAA levels compared to amyloid-negative healthy elderly (p < 0.05). In amyloid-positive healthy elderly, mI/creatine and mI/NAA correlated with cortical retention of [18F] flutemetamol tracer ( = 0.44, p = 0.02 and = 0.51, p = 0.01, respectively). Healthy elderly APOE ε4 carriers with normal CSF Aβ42 levels had significantly higher mI/creatine levels (p < 0.001) than ε4 noncarriers. Finally, elevated mI/creatine was associated with decreased functional connectivity within the default mode network (rpearson = −0.16, p = 0.02), independently of amyloid pathology. Conclusions: mI levels are elevated already at asymptomatic stages of AD. Moreover, mI/creatine concentrations were increased in healthy APOE ε4 carriers with normal CSF Aβ42 levels, suggesting that mI levels may reveal regional brain consequences of APOE ε4 before detectable amyloid pathology. PMID:27164711

Myo-inositol changes precede amyloid pathology and relate to APOE genotype in Alzheimer disease.

PubMed

Voevodskaya, Olga; Sundgren, Pia C; Strandberg, Olof; Zetterberg, Henrik; Minthon, Lennart; Blennow, Kaj; Wahlund, Lars-Olof; Westman, Eric; Hansson, Oskar

2016-05-10

We aimed to test whether in vivo levels of magnetic resonance spectroscopy (MRS) metabolites myo-inositol (mI), N-acetylaspartate (NAA), and choline are abnormal already during preclinical Alzheimer disease (AD), relating these changes to amyloid or tau pathology, and functional connectivity. In this cross-sectional multicenter study (a subset of the prospective Swedish BioFINDER study), we included 4 groups, representing the different stages of predementia AD: (1) cognitively healthy elderly with normal CSF β-amyloid 42 (Aβ42), (2) cognitively healthy elderly with abnormal CSF Aβ42, (3) patients with subjective cognitive decline and abnormal CSF Aβ42, (4) patients with mild cognitive decline and abnormal CSF Aβ42 (Ntotal = 352). Spectroscopic markers measured in the posterior cingulate/precuneus were considered alongside known disease biomarkers: CSF Aβ42, phosphorylated tau, total tau, [(18)F]-flutemetamol PET, f-MRI, and the genetic risk factor APOE. Amyloid-positive cognitively healthy participants showed a significant increase in mI/creatine and mI/NAA levels compared to amyloid-negative healthy elderly (p < 0.05). In amyloid-positive healthy elderly, mI/creatine and mI/NAA correlated with cortical retention of [(18)F] flutemetamol tracer ([Formula: see text] = 0.44, p = 0.02 and [Formula: see text] = 0.51, p = 0.01, respectively). Healthy elderly APOE ε4 carriers with normal CSF Aβ42 levels had significantly higher mI/creatine levels (p < 0.001) than ε4 noncarriers. Finally, elevated mI/creatine was associated with decreased functional connectivity within the default mode network (rpearson = -0.16, p = 0.02), independently of amyloid pathology. mI levels are elevated already at asymptomatic stages of AD. Moreover, mI/creatine concentrations were increased in healthy APOE ε4 carriers with normal CSF Aβ42 levels, suggesting that mI levels may reveal regional brain consequences of APOE ε4 before detectable amyloid pathology. © 2016 American Academy of Neurology.

Variability of Creatine Metabolism Genes in Children with Autism Spectrum Disorder.

PubMed

Cameron, Jessie M; Levandovskiy, Valeriy; Roberts, Wendy; Anagnostou, Evdokia; Scherer, Stephen; Loh, Alvin; Schulze, Andreas

2017-07-31

Creatine deficiency syndrome (CDS) comprises three separate enzyme deficiencies with overlapping clinical presentations: arginine:glycine amidinotransferase ( GATM gene, glycine amidinotransferase), guanidinoacetate methyltransferase ( GAMT gene), and creatine transporter deficiency ( SLC6A8 gene, solute carrier family 6 member 8). CDS presents with developmental delays/regression, intellectual disability, speech and language impairment, autistic behaviour, epileptic seizures, treatment-refractory epilepsy, and extrapyramidal movement disorders; symptoms that are also evident in children with autism. The objective of the study was to test the hypothesis that genetic variability in creatine metabolism genes is associated with autism. We sequenced GATM , GAMT and SLC6A8 genes in 166 patients with autism (coding sequence, introns and adjacent untranslated regions). A total of 29, 16 and 25 variants were identified in each gene, respectively. Four variants were novel in GATM , and 5 in SLC6A8 (not present in the 1000 Genomes, Exome Sequencing Project (ESP) or Exome Aggregation Consortium (ExAC) databases). A single variant in each gene was identified as non-synonymous, and computationally predicted to be potentially damaging. Nine variants in GATM were shown to have a lower minor allele frequency (MAF) in the autism population than in the 1000 Genomes database, specifically in the East Asian population (Fisher's exact test). Two variants also had lower MAFs in the European population. In summary, there were no apparent associations of variants in GAMT and SLC6A8 genes with autism. The data implying there could be a lower association of some specific GATM gene variants with autism is an observation that would need to be corroborated in a larger group of autism patients, and with sub-populations of Asian ethnicities. Overall, our findings suggest that the genetic variability of creatine synthesis/transport is unlikely to play a part in the pathogenesis of autism spectrum disorder (ASD) in children.

Creatine supplementation during pregnancy: summary of experimental studies suggesting a treatment to improve fetal and neonatal morbidity and reduce mortality in high-risk human pregnancy

PubMed Central

2014-01-01

While the use of creatine in human pregnancy is yet to be fully evaluated, its long-term use in healthy adults appears to be safe, and its well documented neuroprotective properties have recently been extended by demonstrations that creatine improves cognitive function in normal and elderly people, and motor skills in sleep-deprived subjects. Creatine has many actions likely to benefit the fetus and newborn, because pregnancy is a state of heightened metabolic activity, and the placenta is a key source of free radicals of oxygen and nitrogen. The multiple benefits of supplementary creatine arise from the fact that the creatine-phosphocreatine [PCr] system has physiologically important roles that include maintenance of intracellular ATP and acid–base balance, post-ischaemic recovery of protein synthesis, cerebral vasodilation, antioxidant actions, and stabilisation of lipid membranes. In the brain, creatine not only reduces lipid peroxidation and improves cerebral perfusion, its interaction with the benzodiazepine site of the GABAA receptor is likely to counteract the effects of glutamate excitotoxicity – actions that may protect the preterm and term fetal brain from the effects of birth hypoxia. In this review we discuss the development of creatine synthesis during fetal life, the transfer of creatine from mother to fetus, and propose that creatine supplementation during pregnancy may have benefits for the fetus and neonate whenever oxidative stress or feto-placental hypoxia arise, as in cases of fetal growth restriction, premature birth, or when parturition is delayed or complicated by oxygen deprivation of the newborn. PMID:24766646

Incubating Isolated Mouse EDL Muscles with Creatine Improves Force Production and Twitch Kinetics in Fatigue Due to Reduction in Ionic Strength

PubMed Central

Head, Stewart I.; Greenaway, Bronwen; Chan, Stephen

2011-01-01

Background Creatine supplementation can improve performance during high intensity exercise in humans and improve muscle strength in certain myopathies. In this present study, we investigated the direct effects of acute creatine incubation on isolated mouse fast-twitch EDL muscles, and examined how these effects change with fatigue. Methods and Results The extensor digitorum longus muscle from mice aged 12–14 weeks was isolated and stimulated with field electrodes to measure force characteristics in 3 different states: (i) before fatigue; (ii) immediately after a fatigue protocol; and (iii) after recovery. These served as the control measurements for the muscle. The muscle was then incubated in a creatine solution and washed. The measurement of force characteristics in the 3 different states was then repeated. In un-fatigued muscle, creatine incubation increased the maximal tetanic force. In fatigued muscle, creatine treatment increased the force produced at all frequencies of stimulation. Incubation also increased the rate of twitch relaxation and twitch contraction in fatigued muscle. During repetitive fatiguing stimulation, creatine-treated muscles took 55.1±9.5% longer than control muscles to lose half of their original force. Measurement of weight changes showed that creatine incubation increased EDL muscle mass by 7%. Conclusion Acute creatine application improves force production in isolated fast-twitch EDL muscle, and these improvements are particularly apparent when the muscle is fatigued. One likely mechanism for this improvement is an increase in Ca2+ sensitivity of contractile proteins as a result of ionic strength decreases following creatine incubation. PMID:21850234

International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine.

PubMed

Kreider, Richard B; Kalman, Douglas S; Antonio, Jose; Ziegenfuss, Tim N; Wildman, Robert; Collins, Rick; Candow, Darren G; Kleiner, Susan M; Almada, Anthony L; Lopez, Hector L

2017-01-01

Creatine is one of the most popular nutritional ergogenic aids for athletes. Studies have consistently shown that creatine supplementation increases intramuscular creatine concentrations which may help explain the observed improvements in high intensity exercise performance leading to greater training adaptations. In addition to athletic and exercise improvement, research has shown that creatine supplementation may enhance post-exercise recovery, injury prevention, thermoregulation, rehabilitation, and concussion and/or spinal cord neuroprotection. Additionally, a number of clinical applications of creatine supplementation have been studied involving neurodegenerative diseases (e.g., muscular dystrophy, Parkinson's, Huntington's disease), diabetes, osteoarthritis, fibromyalgia, aging, brain and heart ischemia, adolescent depression, and pregnancy. These studies provide a large body of evidence that creatine can not only improve exercise performance, but can play a role in preventing and/or reducing the severity of injury, enhancing rehabilitation from injuries, and helping athletes tolerate heavy training loads. Additionally, researchers have identified a number of potentially beneficial clinical uses of creatine supplementation. These studies show that short and long-term supplementation (up to 30 g/day for 5 years) is safe and well-tolerated in healthy individuals and in a number of patient populations ranging from infants to the elderly. Moreover, significant health benefits may be provided by ensuring habitual low dietary creatine ingestion (e.g., 3 g/day) throughout the lifespan. The purpose of this review is to provide an update to the current literature regarding the role and safety of creatine supplementation in exercise, sport, and medicine and to update the position stand of International Society of Sports Nutrition (ISSN).

Effects of Creatine Monohydrate Augmentation on Brain Metabolic and Network Outcome Measures in Women With Major Depressive Disorder.

PubMed

Yoon, Sujung; Kim, Jieun E; Hwang, Jaeuk; Kim, Tae-Suk; Kang, Hee Jin; Namgung, Eun; Ban, Soonhyun; Oh, Subin; Yang, Jeongwon; Renshaw, Perry F; Lyoo, In Kyoon

2016-09-15

Creatine monohydrate (creatine) augmentation has the potential to accelerate the clinical responses to and enhance the overall efficacy of selective serotonin reuptake inhibitor treatment in women with major depressive disorder (MDD). Although it has been suggested that creatine augmentation may involve the restoration of brain energy metabolism, the mechanisms underlying its antidepressant efficacy are unknown. In a randomized, double-blind, placebo-controlled trial, 52 women with MDD were assigned to receive either creatine augmentation or placebo augmentation of escitalopram; 34 subjects participated in multimodal neuroimaging assessments at baseline and week 8. Age-matched healthy women (n = 39) were also assessed twice at the same intervals. Metabolic and network outcomes were measured for changes in prefrontal N-acetylaspartate and changes in rich club hub connections of the structural brain network using proton magnetic resonance spectroscopy and diffusion tensor imaging, respectively. We found MDD-related metabolic and network dysfunction at baseline. Improvement in depressive symptoms was greater in patients receiving creatine augmentation relative to placebo augmentation. After 8 weeks of treatment, prefrontal N-acetylaspartate levels increased significantly in the creatine augmentation group compared with the placebo augmentation group. Increment in rich club hub connections was also greater in the creatine augmentation group than in the placebo augmentation group. N-acetylaspartate levels and rich club connections increased after creatine augmentation of selective serotonin reuptake inhibitor treatment. Effects of creatine administration on brain energy metabolism and network organization may partly underlie its efficacy in treating women with MDD. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Simultaneous Assay of Isotopic Enrichment and Concentration of Guanidinoacetate and Creatine by Gas Chromatography-Mass Spectrometry

PubMed Central

Kasumov, Takhar; Gruca, Lourdes L.; Dasarathy, Srinivasan; Kalhan, Satish C.

2012-01-01

A gas chromatographic-mass spectrometric (GC-MS) method for the simultaneous measurement of isotopic enrichment and concentration of guanidinoacetic acid and creatine in plasma sample for kinetic studies is reported. The method, based on preparation of the bis(trifluoromethyl)-pyrimidine methyl ester derivatives of guanidinoacetic acid and creatine, is robust and sensitive. The lowest measurable m1 and m3 enrichment for guanidinoacetic acid and creatine, respectively, was 0.3%. The calibration curves for measurements of concentration were linear over a range of 0.5-250 μM guanidinoacetic acid and 2-500 μM for creatine. The method was reliable for inter-assay and intra-assay precision, accuracy and linearity. The technique was applied in a healthy adult to determine in vivo fractional synthesis rate of creatine using primed- constant rate infusion of [1-13C]glycine. It was found that isotopic enrichment of guanidinoacetic acid reached plateau by 30 min of infusion of [1-13C]glycine, indicating either a small pool size or a rapid turnover rate or both, of guanidinoacetic acid. In contrast, tracer appearance in creatin was slow (slope: 0.00097), suggesting a large pool size and a slow rate of synthesis of creatine. This method can be used to estimate rate of synthesis of creatine in-vivo in human and animal studies. PMID:19646413

Creatine phosphokinase test

MedlinePlus

... this page: //medlineplus.gov/ency/article/003503.htm Creatine phosphokinase test To use the sharing features on this page, please enable JavaScript. Creatine phosphokinase (CPK) is an enzyme in the body. ...

Creatine

MedlinePlus

... inherited disorders that affect the senses and movement, schizophrenia, muscle breakdown in the spine, and recovery from ... the effects of creatine alone are not clear. Schizophrenia. Early research shows that taking creatine by mouth ...

Creatine metabolism and safety profiles after six-week oral guanidinoacetic acid administration in healthy humans.

PubMed

Ostojic, Sergej M; Niess, Barbara; Stojanovic, Marko; Obrenovic, Milos

2013-01-01

Guanidinoacetic acid (GAA) is a natural precursor of creatine, yet the potential use of GAA as a nutritional additive for restoring creatine availability in humans has been limited by unclear efficacy and safety after exogenous GAA administration. The present study evaluated the effects of orally administered GAA on serum and urinary GAA, creatine and creatinine concentration, and on the occurrence of adverse events in healthy humans. Twenty-four healthy volunteers were randomized in a double-blind design to receive either GAA (2.4 grams daily) or placebo (PLA) by oral administration for 6 weeks. www.clinicaltrials.gov, identification number NCT01133899. Serum creatine and creatinine increased significantly from before to after administration in GAA-supplemented participants (P < 0.05). The proportion of participants who reported minor side effects was 58.3% in the GAA group and 45.5% in the placebo group (P = 0.68). A few participants experienced serum creatine levels above 70 µmol/L. Exogenous GAA is metabolized to creatine, resulting in a significant increase of fasting serum creatine after intervention. GAA had an acceptable side-effects profile with a low incidence of biochemical abnormalities.

Creatine Metabolism and Safety Profiles after Six-Week Oral Guanidinoacetic Acid Administration in Healthy Humans

PubMed Central

Ostojic, Sergej M.; Niess, Barbara; Stojanovic, Marko; Obrenovic, Milos

2013-01-01

Objectives; Guanidinoacetic acid (GAA) is a natural precursor of creatine, yet the potential use of GAA as a nutritional additive for restoring creatine availability in humans has been limited by unclear efficacy and safety after exogenous GAA administration. The present study evaluated the effects of orally administered GAA on serum and urinary GAA, creatine and creatinine concentration, and on the occurrence of adverse events in healthy humans. Methods and Results; Twenty-four healthy volunteers were randomized in a double-blind design to receive either GAA (2.4 grams daily) or placebo (PLA) by oral administration for 6 weeks. Clinical trial registration: www.clinicaltrials.gov, identification number NCT01133899. Serum creatine and creatinine increased significantly from before to after administration in GAA-supplemented participants (P < 0.05). The proportion of participants who reported minor side effects was 58.3% in the GAA group and 45.5% in the placebo group (P = 0.68). A few participants experienced serum creatine levels above 70 µmol/L. Conclusion; Exogenous GAA is metabolized to creatine, resulting in a significant increase of fasting serum creatine after intervention. GAA had an acceptable side-effects profile with a low incidence of biochemical abnormalities. PMID:23329885

Magnetic Resonance T2-Relaxometry and 2D L-Correlated Spectroscopy in Patients with Minimal Hepatic Encephalopathy

PubMed Central

Singhal, Aparna; Nagarajan, Rajakumar; Kumar, Rajesh; Huda, Amir; Gupta, Rakesh K.; Thomas, M. Albert

2010-01-01

Purpose To evaluate T2-relaxation changes in patients with minimal hepatic encephalopathy (MHE) using T2-relaxometry and to correlate T2 values with brain metabolites evaluated using two-dimensional (2D) magnetic resonance spectroscopy (MRS). Materials and Methods Eight MHE patients and 13 healthy subjects were evaluated using T2-relaxometry, and 8 patients and 9 healthy subjects underwent 2D MRS in right frontal and left occipital regions. Whole brain T2-relaxation maps were compared between MHE and control subjects using analysis-of-covariance, with age and gender included as covariates. T2 values derived from the right frontal and left occipital lobes were correlated with the metabolite ratios. Results Multiple brain regions including anterior and mid cingulate cortices, right anterior and left posterior insular cortices, right prefrontal, medial frontal, and right superior temporal cortices showed significantly increased T2 values in MHE patients compared to control subjects. MRS showed significantly increased ratios of glutamine/glutamate (Glx) and decreased ratios of myo-inositol, taurine, choline, and myo-inositol/choline (mICh) with respect to creatine (Cr_d) in patients compared to controls. Frontal Glx/Cr_d showed significantly positive correlation with T2 values. Conclusion MHE patients showed significantly increased T2 values in multiple brain regions reflecting increased free water content and T2 values in frontal lobe correlated with the increased Glx/Cr_d ratio. PMID:19856435

Proton transfer pathways, energy landscape, and kinetics in creatine-water systems.

PubMed

Ivchenko, Olga; Whittleston, Chris S; Carr, Joanne M; Imhof, Petra; Goerke, Steffen; Bachert, Peter; Wales, David J

2014-02-27

We study the exchange processes of the metabolite creatine, which is present in both tumorous and normal tissues and has NH2 and NH groups that can transfer protons to water. Creatine produces chemical exchange saturation transfer (CEST) contrast in magnetic resonance imaging (MRI). The proton transfer pathway from zwitterionic creatine to water is examined using a kinetic transition network constructed from the discrete path sampling approach and an approximate quantum-chemical energy function, employing the self-consistent-charge density-functional tight-binding (SCC-DFTB) method. The resulting potential energy surface is visualized by constructing disconnectivity graphs. The energy landscape consists of two distinct regions corresponding to the zwitterionic creatine structures and deprotonated creatine. The activation energy that characterizes the proton transfer from the creatine NH2 group to water was determined from an Arrhenius fit of rate constants as a function of temperature, obtained from harmonic transition state theory. The result is in reasonable agreement with values obtained in water exchange spectroscopy (WEX) experiments.

Chromium(VI) generation in vadose zone soils and alluvial sediments of the southwestern Sacramento Valley, California: a potential source of geogenic Cr(VI) to groundwater

USGS Publications Warehouse

Mills, Christopher T.; Morrison, Jean M.; Goldhaber, Martin B.; Ellefsen, Karl J.

2011-01-01

Concentrations of geogenic Cr(VI) in groundwater that exceed the World Health Organization’s maximum contaminant level for drinking water (50 μg L−1) occur in several locations globally. The major mechanism for mobilization of this Cr(VI) at these sites is the weathering of Cr(III) from ultramafic rocks and its subsequent oxidation on Mn oxides. This process may be occurring in the southern Sacramento Valley of California where Cr(VI) concentrations in groundwater can approach or exceed 50 μg L−1. To characterize Cr geochemistry in the area, samples from several soil auger cores (approximately 4 m deep) and drill cores (approximately 25 m deep) were analyzed for total concentrations of 44 major, minor and trace elements, Cr associated with labile Mn and Fe oxides, and Cr(VI). Total concentrations of Cr in these samples ranged from 140 to 2220 mg per kg soil. Between 9 and 70 mg per kg soil was released by selective extractions that target Fe oxides, but essentially no Cr was associated with the abundant reactive Mn oxides (up to ~1000 mg hydroxylamine-reducible Mn per kg soil was present). Both borehole magnetic susceptibility surveys performed at some of the drill core sites and relative differences between Cr released in a 4-acid digestion versus total Cr (lithium metaborate fusion digestion) suggest that the majority of total Cr in the samples is present in refractory chromite minerals transported from ultramafic exposures in the Coast Range Mountains. Chromium(VI) in the samples studied ranged from 0 to 42 μg kg−1, representing a minute fraction of total Cr. Chromium(VI) content was typically below detection in surface soils (top 10 cm) where soil organic matter was high, and increased with increasing depth in the soil auger cores as organic matter decreased. Maximum concentrations of Cr(VI) were up to 3 times greater in the deeper drill core samples than the shallow auger cores. Although Cr(VI) in these vadose zone soils and sediments was only a very small fraction of the total solid phase Cr, they are a potentially important source for Cr(VI) to groundwater. Enhanced groundwater recharge through the vadose zone due to irrigation could carry Cr(VI) from the vadose zone to the groundwater and may be the mechanism responsible for the correlation observed between elevated Cr(VI) and NO3- source concentrations in previously published data for valley groundwaters. Incubation of a valley subsoil showed a Cr(VI) production rate of 24 μg kg−1 a−1 suggesting that field Cr(VI) concentrations could be regenerated annually. Increased Cr(VI) production rates in H+-amended soil incubations indicate that soil acidification processes such as nitrification of ammonium in fertilizers could potentially increase the occurrence of geogenic Cr(VI) in groundwater. Thus, despite the natural origin of the Cr, Cr(VI) generation in the Sacramento Valley soils and sediments has the potential to be influenced by human activities.

Assessments of chromium (and other metals) in vegetables and potential bio-accumulations in humans living in areas affected by tannery wastes.

PubMed

Chen, Hualin; Arocena, Joselito M; Li, Jianbing; Thring, Ronald W; Zhou, Jiangmin

2014-10-01

Chromium (Cr) commonly enters the food chain through uptake by vegetables. However, accurate prediction of plant uptake of Cr (and other metals) still remains a challenge. In this study, we evaluated 5 indices of availability for Cr (and other metals) to identify reliable predictors of metal transfer from soils to garlic, onion, bokchoy, radish and celery grown in soils impacted by tannery wastes. The potential bio-accumulation of Cr in humans was calculated from the Cr content of vegetable predicted by the best bio-availability index, amounts of vegetable consumed and recommended daily doses for Cr. Our results show that soil total Cr is the best predictor of Cr transfer from soils to onion (Cr in onion=8.51+0.005 Total Cr) while Cr extractable by Synthetic Precipitation Leaching Procedure at pH 5 correlates very well with Cr uptake by bokchoy (Cr bokchoy=5.86+7.32 SPLP-5 Cr) and garlic (Cr garlic=7.63+2.36 SPLP-5 Cr). The uptake of Cr by radish and celery could not be reliably estimated by any of the 5 indices of availability tested in this study. Potential bio-accumulation of Cr in humans (BA-Cr) increases from soils with low Cr (BA-Cr=11.5) to soil with high total Cr (BA-Cr=31.3). Due to numerous soil factors affecting the behavior of Cr in soils and the physiological differences among vegetables, we suggest that the prediction of the transfer of Cr (and other metals) from soils to plants should be specific to site, metal and vegetable. Potential bio-accumulation of Cr in humans can be derived from a transfer function of Cr from soils to plants and the human consumption of vegetables. Copyright © 2014 Elsevier Ltd. All rights reserved.

Creatine Transporter Deficiency in Two Brothers with Autism Spectrum Disorder.

PubMed

Aydin, Halil Ibrahim

2018-01-15

Creatine transporter deficiency (CTD) is a treatable, X-linked, inborn error of metabolism. Two brothers with autism spectrum disorder were diagnosed with CTD at the ages of 17 and 12 years. Both were found to have a previously reported hemizygous p.408delF (c.1216_1218delTTC) deletion mutation. Both patients were given creatine monohydrate, L-arginine, L-glycine and S-adenosylmethionine, which partially improved the behavioral problems. Serum creatinine levels, creatine peak at brain MR spectroscopy or creatine/creatinine ratio in urine should be evaluated to identify CTD in children with autistic behavior and language disorders.

Creatine for women in pregnancy for neuroprotection of the fetus.

PubMed

Dickinson, Hayley; Bain, Emily; Wilkinson, Dominic; Middleton, Philippa; Crowther, Caroline A; Walker, David W

2014-12-19

Creatine is an amino acid derivative and, when phosphorylated (phosphocreatine), is involved in replenishing adenosine triphosphate (ATP) via the creatine kinase reaction. Cells obtain creatine from a diet rich in fish, meat, or dairy and by endogenous synthesis from the amino acids arginine, glycine, and methionine in an approximate 50:50 ratio. Animal studies have shown that creatine may provide fetal neuroprotection when given to the mother through her diet in pregnancy. It is important to assess whether maternally administered creatine in human pregnancy (at times of known, suspected, or potential fetal compromise) may offer neuroprotection to the fetus and may accordingly reduce the risk of adverse neurodevelopmental outcomes, such as cerebral palsy and associated impairments and disabilities arising from fetal brain injury. To assess the effects of creatine when used for neuroprotection of the fetus. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 November 2014). We planned to include all published, unpublished, and ongoing randomised trials and quasi-randomised trials. We planned to include studies reported as abstracts only as well as full-text manuscripts. Trials using a cross-over or cluster-randomised design were not eligible for inclusion.We planned to include trials comparing creatine given to women in pregnancy for fetal neuroprotection (regardless of the route, timing, dose, or duration of administration) with placebo, no treatment, or with an alternative agent aimed at providing fetal neuroprotection. We also planned to include comparisons of different regimens for administration of creatine. We identified no completed or ongoing randomised controlled trials. We found no randomised controlled trials for inclusion in this review. As we did not identify any randomised controlled trials for inclusion in this review, we are unable to comment on implications for practice. Although evidence from animal studies has supported a fetal neuroprotective role for creatine when administered to the mother during pregnancy, no trials assessing creatine in pregnant women for fetal neuroprotection have been published to date. If creatine is established as safe for the mother and her fetus, research efforts should first be directed towards randomised trials comparing creatine with either no intervention (ideally using a placebo), or with alternative agents aimed at providing fetal neuroprotection (including magnesium sulphate for the very preterm infant). If appropriate, these trials should then be followed by studies comparing different creatine regimens (dosage and duration of exposure). Such trials should be high quality and adequately powered to evaluate maternal and infant short and longer-term outcomes (including neurodevelopmental disabilities such as cerebral palsy), and should consider utilisation/costs of health care.

Can creatine supplementation form carcinogenic heterocyclic amines in humans?

PubMed Central

Pereira, Renato Tavares dos Santos; Dörr, Felipe Augusto; Pinto, Ernani; Solis, Marina Yazigi; Artioli, Guilherme Giannini; Fernandes, Alan Lins; Murai, Igor Hisashi; Dantas, Wagner Silva; Seguro, Antônio Carlos; Santinho, Mirela Aparecida Rodrigues; Roschel, Hamilton; Carpentier, Alain; Poortmans, Jacques Remi; Gualano, Bruno

2015-01-01

Abstract Creatine supplementation has been associated with increased cancer risk. In fact, there is evidence indicating that creatine and/or creatinine are important precursors of carcinogenic heterocyclic amines (HCAs). The present study aimed to investigate the acute and chronic effects of low- and high-dose creatine supplementation on the production of HCAs in healthy humans (i.e. 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (8-MeIQx),  2-amino-(1,6-dimethylfuro[3,2-e]imidazo[4,5-b])pyridine (IFP) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx)). This was a non-counterbalanced single-blind crossover study divided into two phases, in which low- and high-dose creatine protocols were tested. After acute (1 day) and chronic supplementation (30 days), the HCAs PhIP, 8-MeIQx, IFP and 4,8-DiMeIQx were assessed through a newly developed HPLC–MS/MS method. Dietary HCA intake and blood and urinary creatinine were also evaluated. Out of 576 assessments performed (from 149 urine samples), only nine (3 from creatine and 6 from placebo) showed quantifiable levels of HCAs (8-MeIQx: n = 3; 4,8-DiMeIQx: n = 2; PhIP: n = 4). Individual analyses revealed that diet rather than creatine supplementation was the main responsible factor for HCA formation in these cases. This study provides compelling evidence that both low and high doses of creatine supplementation, given either acutely or chronically, did not cause increases in the carcinogenic HCAs PhIP, 8-MeIQx, IFP and 4,8-DiMeIQx in healthy subjects. These findings challenge the long-existing notion that creatine supplementation could potentially increase the risk of cancer by stimulating the formation of these mutagens. Key points There is a long-standing concern that creatine supplementation could be associated with cancer, possibly by facilitating the formation of carcinogenic heterocyclic amines (HCAs). This study provides compelling evidence that both low and high doses of creatine supplementation, given either acutely or chronically, does not cause a significant increase in HCA formation. HCAs detection was unrelated to creatine supplementation. Diet was likely to be the main factor responsible for HCAs formation after either placebo (n = 6) or creatine supplementation (n = 3). These results directly challenge the recently suggested biological plausibility for the association between creatine use and risk of testicular germ cell cancer. PMID:26148133

Can creatine supplementation form carcinogenic heterocyclic amines in humans?

PubMed

Pereira, Renato Tavares dos Santos; Dörr, Felipe Augusto; Pinto, Ernani; Solis, Marina Yazigi; Artioli, Guilherme Giannini; Fernandes, Alan Lins; Murai, Igor Hisashi; Dantas, Wagner Silva; Seguro, Antônio Carlos; Santinho, Mirela Aparecida Rodrigues; Roschel, Hamilton; Carpentier, Alain; Poortmans, Jacques Remi; Gualano, Bruno

2015-09-01

There is a long-standing concern that creatine supplementation could be associated with cancer, possibly by facilitating the formation of carcinogenic heterocyclic amines (HCAs). This study provides compelling evidence that both low and high doses of creatine supplementation, given either acutely or chronically, does not cause a significant increase in HCA formation. HCAs detection was unrelated to creatine supplementation. Diet was likely to be the main factor responsible for HCAs formation after either placebo (n = 6) or creatine supplementation (n = 3). These results directly challenge the recently suggested biological plausibility for the association between creatine use and risk of testicular germ cell cancer. Creatine supplementation has been associated with increased cancer risk. In fact, there is evidence indicating that creatine and/or creatinine are important precursors of carcinogenic heterocyclic amines (HCAs). The present study aimed to investigate the acute and chronic effects of low- and high-dose creatine supplementation on the production of HCAs in healthy humans (i.e. 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (8-MeIQx), 2-amino-(1,6-dimethylfuro[3,2-e]imidazo[4,5-b])pyridine (IFP) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx)). This was a non-counterbalanced single-blind crossover study divided into two phases, in which low- and high-dose creatine protocols were tested. After acute (1 day) and chronic supplementation (30 days), the HCAs PhIP, 8-MeIQx, IFP and 4,8-DiMeIQx were assessed through a newly developed HPLC-MS/MS method. Dietary HCA intake and blood and urinary creatinine were also evaluated. Out of 576 assessments performed (from 149 urine samples), only nine (3 from creatine and 6 from placebo) showed quantifiable levels of HCAs (8-MeIQx: n = 3; 4,8-DiMeIQx: n = 2; PhIP: n = 4). Individual analyses revealed that diet rather than creatine supplementation was the main responsible factor for HCA formation in these cases. This study provides compelling evidence that both low and high doses of creatine supplementation, given either acutely or chronically, did not cause increases in the carcinogenic HCAs PhIP, 8-MeIQx, IFP and 4,8-DiMeIQx in healthy subjects. These findings challenge the long-existing notion that creatine supplementation could potentially increase the risk of cancer by stimulating the formation of these mutagens. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Effects of Combined Creatine Plus Fenugreek Extract vs. Creatine Plus Carbohydrate Supplementation on Resistance Training Adaptations

PubMed Central

Taylor, Lem; Poole, Chris; Pena, Earnest; Lewing, Morgan; Kreider, Richard; Foster, Cliffa; Wilborn, Colin

2011-01-01

The purpose of this study was to evaluate the effects of combined creatine and fenugreek extract supplementation on strength and body composition. Forty- seven resistance trained men were matched according to body weight to ingest either 70 g of a dextrose placebo (PL), 5 g creatine/70 g of dextrose (CRD) or 3.5 g creatine/900 mg fenugreek extract (CRF) and participate in a 4-d/wk periodized resistance-training program for 8-weeks. At 0, 4, and 8-weeks, subjects were tested on body composition, muscular strength and endurance, and anaerobic capacity. Statistical analyses utilized a separate 3X3 (condition [PL vs. CRD vs. CRF] x time [T1 vs. T2 vs. T3]) ANOVAs with repeated measures for all criterion variables (p ≤ 0.05). No group x time interaction effects or main effects (p > 0.05) were observed for any measures of body composition. CRF group showed significant increases in lean mass at T2 (p = 0.001) and T3 (p = 0.001). Bench press 1RM increased in PL group (p = 0.050) from T1-T3 and in CRD from T1-T2 (p = 0. 001) while remaining significant at T3 (p < 0.001). CRF group showed a significant increase in bench press 1RM from T1-T2 (p < 0.001), and also increased from T2-T3 (p = 0.032). Leg press 1RM significantly increased at all time points for PL, CRD, and CRF groups (p < 0.05). No additional between or within group changes were observed for any performance variables and serum clinical safety profiles (p > 0.05). In conclusion, creatine plus fenugreek extract supplementation had a significant impact on upper body strength and body composition as effectively as the combination of 5g of creatine with 70g of dextrose. Thus, the use of fenugreek with creatine supplementation may be an effective means for enhancing creatine uptake while eliminating the need for excessive amounts of simple carbohydrates. Key points Fenugreek plus creatine supplementation may be a new means of increasing creatine uptake. Creatine plus fenugreek seems to be just as effective as the classic creatine plus carbohydrate ingestion in terms of stimulating training adaptations. This is the first study to our knowledge that has combined fenugreek with creatine supplementation in conjunction with a resistance training program. PMID:24149869

Effect of age, diet, and tissue type on PCr response to creatine supplementation.

PubMed

Solis, Marina Yazigi; Artioli, Guilherme Giannini; Otaduy, Maria Concepción García; Leite, Claudia da Costa; Arruda, Walquiria; Veiga, Raquel Ramos; Gualano, Bruno

2017-08-01

Creatine/phosphorylcreatine (PCr) responses to creatine supplementation may be modulated by age, diet, and tissue, but studies assessing this possibility are lacking. Therefore we aimed to determine whether PCr responses vary as a function of age, diet, and tissue. Fifteen children, 17 omnivorous and 14 vegetarian adults, and 18 elderly individuals ("elderly") participated in this study. Participants were given placebo and subsequently creatine (0.3 g·kg -1 ·day -1 ) for 7 days in a single-blind fashion. PCr was measured through phosphorus magnetic resonance spectroscopy ( 31 P-MRS) in muscle and brain. Creatine supplementation increased muscle PCr in children ( P < 0.0003) and elderly ( P < 0.001), whereas the increase in omnivores did not reach statistically significant difference ( P = 0.3348). Elderly had greater PCr increases than children and omnivores ( P < 0.0001 for both), whereas children experienced greater PCr increases than omnivores ( P = 0.0022). In relation to diet, vegetarians ( P < 0.0001), but not omnivores, had significant increases in muscle PCr content. Brain PCr content was not affected by creatine supplementation in any group, and delta changes in brain PCr (-0.7 to +3.9%) were inferior to those in muscle PCr content (+10.3 to +27.6%; P < 0.0001 for all comparisons). PCr responses to a standardized creatine protocol (0.3 g·kg -1 ·day -1 for 7 days) may be affected by age, diet, and tissue. Whereas creatine supplementation was able to increase muscle PCr in all groups, although to different extents, brain PCr was shown to be unresponsive overall. These findings demonstrate the need to tailor creatine protocols to optimize creatine/PCr accumulation both in muscle and in brain, enabling a better appreciation of the pleiotropic properties of creatine. NEW & NOTEWORTHY A standardized creatine supplementation protocol (0.3 g·kg -1 ·day -1 for 7 days) effectively increased muscle, but not brain, phosphorylcreatine. Older participants responded better than younger participants whereas vegetarians responded better than omnivores. Responses to supplementation are thus dependent on age, tissue, and diet. This suggests that a single "universal" protocol, originally designed for increasing muscle creatine in young individuals, may lead to heterogeneous muscle responses in different populations or even no responses in tissues other than skeletal muscle. Copyright © 2017 the American Physiological Society.

Development and application of a method for Cr(III) determination in dairy products by HPLC-ICP-MS.

PubMed

Hernandez, Fanny; Jitaru, Petru; Cormant, Florence; Noël, Laurent; Guérin, Thierry

2018-02-01

This study describes the development of an analytical approach for the determination of Cr(III) in dairy products by microwave assisted extraction, complexation in situ by ethylenediaminetetraacetate (EDTA) and high performance liquid chromatography hyphenated to inductively coupled plasma-mass spectrometry (HPLC-ICP-MS). The extraction step was optimised by using an experimental design. A limit of quantification of 38µgkg -1 dry weight (d.w.) was obtained whereas the bias (%) measured ranged from 10 to 18%. The repeatability and intermediate precision varied between 1.2-5.0% and 7.5-13.5%, respectively. The method was applied to the analysis of several dairy samples beforehand characterized in terms of Cr(VI) and total chromium (Cr total ). Cr(III) concentrations ranged from <13 to 255µgkg -1 d.w. The results showed a good agreement between Cr(III) and Cr total concentration levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

Erythrocyte creatine as a marker of intravascular hemolysis due to left ventricular outflow tract obstruction in hypertrophic cardiomyopathy.

PubMed

Kubo, Toru; Okumiya, Toshika; Baba, Yuichi; Hirota, Takayoshi; Tanioka, Katsutoshi; Yamasaki, Naohito; Sugiura, Tetsuro; Doi, Yoshinori L; Kitaoka, Hiroaki

2016-03-01

Erythrocyte creatine, a marker of erythrocyte age that increases with shortening of erythrocyte survival, has been reported to be a quantitative and reliable marker for intravascular hemolysis. We hypothesized that hemolysis could also occur due to intraventricular obstruction in patients with hypertrophic cardiomyopathy (HCM). The purpose of this study was to examine the presence of subclinical hemolysis and the relation between intravascular hemolysis and intraventricular pressure gradient (IVPG). We measured erythrocyte creatine in 92 HCM patients. Twelve patients had left ventricular outflow tract obstruction (LVOTO), 4 had midventricular obstruction (MVO), and the remaining 76 were non-obstructive. Erythrocyte creatine levels ranged from 0.92 to 4.36μmol/g hemoglobin. Higher levels of erythrocyte creatine were associated with higher IVPG (r=0.437, p<0.001). If erythrocyte creatine levels are high (≥1.8μmol/g hemoglobin), subclinical hemolysis is considered to be present. Half of LVOTO patients and no MVO patients showed high erythrocyte creatine levels. Although non-obstructive patients did not show significant intraventricular obstruction at rest, some showed high erythrocyte creatine levels. When LVOT-PG was measured during the strain phase of the Valsalva maneuver in 20 non-obstructive patients, 7 of those 20 patients showed LVOTO. In the 20 patients, there was no relation between erythrocyte creatine levels and LVOT-PG before the Valsalva maneuver (r=0.125, p=0.600), whereas there was a significant correlation between erythrocyte creatine and LVOT-PG provoked by the Valsalva maneuver (r=0.695, p=0.001). There is biochemical evidence of subclinical hemolysis in patients with HCM, and this hemolysis seems to be associated with LVOTO provoked by daily physical activities. Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Creatine Supplementation Does Not Prevent the Development of Alcoholic Steatosis.

PubMed

Ganesan, Murali; Feng, Dan; Barton, Ryan W; Thomes, Paul G; McVicker, Benita L; Tuma, Dean J; Osna, Natalia A; Kharbanda, Kusum K

2016-11-01

Alcohol-induced reduction in the hepatocellular S-adenosylmethionine (SAM):S-adenosylhomocysteine (SAH) ratio impairs the activities of many SAM-dependent methyltransferases. These impairments ultimately lead to the generation of several hallmark features of alcoholic liver injury including steatosis. Guanidinoacetate methyltransferase (GAMT) is an important enzyme that catalyzes the final reaction in the creatine biosynthetic process. The liver is a major site for creatine synthesis which places a substantial methylation burden on this organ as GAMT-mediated reactions consume as much as 40% of all the SAM-derived methyl groups. We hypothesized that dietary creatine supplementation could potentially spare SAM, preserve the hepatocellular SAM:SAH ratio, and thereby prevent the development of alcoholic steatosis and other consequences of impaired methylation reactions. For these studies, male Wistar rats were pair-fed the Lieber-DeCarli control or ethanol (EtOH) diet with or without 1% creatine supplementation. At the end of 4 to 5 weeks of feeding, relevant biochemical and histological analyses were performed. We observed that creatine supplementation neither prevented alcoholic steatosis nor attenuated the alcohol-induced impairments in proteasome activity. The lower hepatocellular SAM:SAH ratio seen in the EtOH-fed rats was also not normalized or SAM levels spared when these rats were fed the creatine-supplemented EtOH diet. However, a >10-fold increased level of creatine was observed in the liver, serum, and hearts of rats fed the creatine-supplemented diets. Overall, dietary creatine supplementation did not prevent alcoholic liver injury despite its known efficacy in preventing high-fat-diet-induced steatosis. Betaine, a promethylating agent that maintains the hepatocellular SAM:SAH, still remains our best option for treating alcoholic steatosis. Copyright © 2016 by the Research Society on Alcoholism.

Interaction of chronic reatine depletion and muscle unloading effects on postural and locomotor muscles

NASA Technical Reports Server (NTRS)

Adams, Gregory R.; Haddad, Fadia; Baldwin, Kenneth M.

1994-01-01

In this study, creatine depletion was induced separately and in combination with non-weight-bearing activity to determine if the response to lowering this metabolite would counter the MHC transitions expected from non-weight-bearing. Creatine depletion was induced by feeding rats a diet supplemented with the creatine analogue beta-guanidinopropionic acid (beta-GPA). Animals were fed a diet containing the creatine analogue for 68 days. Hindlimb non-weight-bearing in BS and NS animals was accomplished by tail suspension for the final 30 days of this period. Beta-GPA feeding lowered the creatine content of muscles sampled by 65%. Creatine depletion resulted in a 16% increase in citrate synthase activity in the soleus (SOL) and a 24% increase in the plantaris (PLN). In two postural muscles, the SOL and vastus intermedius (VI), tail suspension resulted in large decreases in the type I MHC expression and increases in type IIx and IIb MHCs. In two locomotor muscles, the PLN and medial gastrocnemius, type I MHC declined and type IIb increased with suspension. Creatine depletion did not prevent the suspension-induced decline in type I MHC in any of these muscles. The increase in type IIb MHC was either prevented or reduced by creatine depletion before and during suspension in the SOL, VI, and PLN. Creatine depletion alone resulted in small increases in type I and IIa MHCs in the two locomotor muscles, but it had no effect on the MHC profile of the postural muscles studied. These results indicate that the mechanical signal generated by the hindlimb non-weight-bearing state dominated over the metabolic stimulus of creatine depletion with respect to the primary adaptation involving a reduction in type I MHC.

Creatine affords protection against glutamate-induced nitrosative and oxidative stress.

PubMed

Cunha, Mauricio P; Lieberknecht, Vicente; Ramos-Hryb, Ana Belén; Olescowicz, Gislaine; Ludka, Fabiana K; Tasca, Carla I; Gabilan, Nelson H; Rodrigues, Ana Lúcia S

2016-05-01

Creatine has been reported to exert beneficial effects in several neurodegenerative diseases in which glutamatergic excitotoxicity and oxidative stress play an etiological role. The purpose of this study was to investigate the protective effects of creatine, as compared to the N-Methyl-d-Aspartate (NMDA) receptor antagonist dizocilpine (MK-801), against glutamate or hydrogen peroxide (H2O2)-induced injury in human neuroblastoma SH-SY5Y cells. Exposure of cells to glutamate (60-80 mM) or H2O2 (200-300 μM) for 24 h decreased cellular viability and increased dichlorofluorescein (DCF) fluorescence (indicative of increased reactive oxygen species, ROS) and nitric oxide (NO) production (assessed by mono-nitrogen oxides, NOx, levels). Creatine (1-10 mM) or MK-801 (0.1-10 μM) reduced glutamate- and H2O2-induced toxicity. The protective effect of creatine against glutamate-induced toxicity involves its antioxidant effect, since creatine, similar to MK-801, prevented the increase on DCF fluorescence induced by glutamate or H2O2. Furthermore, creatine or MK-801 blocked glutamate- and H2O2-induced increases in NOx levels. In another set of experiments, the repeated, but not acute, administration of creatine (300 mg/kg, po) in mice prevented the decreases on cellular viability and mitochondrial membrane potential (assessed by tetramethylrhodamine ethyl ester, TMRE, probe) of hippocampal slices incubated with glutamate (10 mM). Creatine concentration-dependent decreased the amount of nitrite formed in the reaction of oxygen with NO produced from sodium nitroprusside solution, suggesting that its protective effect against glutamate or H2O2-induced toxicity might be due to its scavenger activity. Overall, the results suggest that creatine may be useful as adjuvant therapy for neurodegenerative disease treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.

Phenotype and genotype in 101 males with X-linked creatine transporter deficiency.

PubMed

van de Kamp, J M; Betsalel, O T; Mercimek-Mahmutoglu, S; Abulhoul, L; Grünewald, S; Anselm, I; Azzouz, H; Bratkovic, D; de Brouwer, A; Hamel, B; Kleefstra, T; Yntema, H; Campistol, J; Vilaseca, M A; Cheillan, D; D'Hooghe, M; Diogo, L; Garcia, P; Valongo, C; Fonseca, M; Frints, S; Wilcken, B; von der Haar, S; Meijers-Heijboer, H E; Hofstede, F; Johnson, D; Kant, S G; Lion-Francois, L; Pitelet, G; Longo, N; Maat-Kievit, J A; Monteiro, J P; Munnich, A; Muntau, A C; Nassogne, M C; Osaka, H; Ounap, K; Pinard, J M; Quijano-Roy, S; Poggenburg, I; Poplawski, N; Abdul-Rahman, O; Ribes, A; Arias, A; Yaplito-Lee, J; Schulze, A; Schwartz, C E; Schwenger, S; Soares, G; Sznajer, Y; Valayannopoulos, V; Van Esch, H; Waltz, S; Wamelink, M M C; Pouwels, P J W; Errami, A; van der Knaap, M S; Jakobs, C; Mancini, G M; Salomons, G S

2013-07-01

Creatine transporter deficiency is a monogenic cause of X-linked intellectual disability. Since its first description in 2001 several case reports have been published but an overview of phenotype, genotype and phenotype--genotype correlation has been lacking. We performed a retrospective study of clinical, biochemical and molecular genetic data of 101 males with X-linked creatine transporter deficiency from 85 families with a pathogenic mutation in the creatine transporter gene (SLC6A8). Most patients developed moderate to severe intellectual disability; mild intellectual disability was rare in adult patients. Speech language development was especially delayed but almost a third of the patients were able to speak in sentences. Besides behavioural problems and seizures, mild to moderate motor dysfunction, including extrapyramidal movement abnormalities, and gastrointestinal problems were frequent clinical features. Urinary creatine to creatinine ratio proved to be a reliable screening method besides MR spectroscopy, molecular genetic testing and creatine uptake studies, allowing definition of diagnostic guidelines. A third of patients had a de novo mutation in the SLC6A8 gene. Mothers with an affected son with a de novo mutation should be counselled about a recurrence risk in further pregnancies due to the possibility of low level somatic or germline mosaicism. Missense mutations with residual activity might be associated with a milder phenotype and large deletions extending beyond the 3' end of the SLC6A8 gene with a more severe phenotype. Evaluation of the biochemical phenotype revealed unexpected high creatine levels in cerebrospinal fluid suggesting that the brain is able to synthesise creatine and that the cerebral creatine deficiency is caused by a defect in the reuptake of creatine within the neurones.

Kinetics of the creatine kinase reaction in neonatal rabbit heart: An empirical analysis of the rate equation

DOE Office of Scientific and Technical Information (OSTI.GOV)

McAuliffe, J.J.; Perry, S.B.; Brooks, E.E.

1991-03-12

Here the authors define the kinetics of the creatine kinase (CK) reaction in an intact mammalian heart containing the full rnage of CK isoenzymes. Previously derived kinetic constants were refit for the reaction occurring at 37C. Steady-state metabolite concentrations from {sup 31}P NMR and standard biochemical techniques were determined. {sup 31}P magnetization transfer data were obtained to determine unidirectional creatine kinase fluxes in hearts with differing total creatine contents and differing mitochondrial CK activities during KCl arrest and isovolumic work for both the forward reaction (MgATP synthesis) and reverse reaction (phosphocreatine synthesis). The NMR kinetic data and substrate concentrations datamore » were used in conjunction with a kinetic model based on MM-CK in solution to determine the applicability of the solution-based kinetic models to the CK kinetics of the intact heart. The results indicated that no single set of rate equation constants could describe both the KCl-arrested and working hearts. Analysis of the results indicated that the CK reaction is rate limited in the direction of ATP synthesis, the size of the guanidino substrate pool drives the measured CK flux in the intact heart, and during isovolumic work, the CK reaction operates under saturating conditions; that is, the substrate concentrations are at least 2-fold greater than the K{sub m} or K{sub im} for each substrate. However, during KCl arrest the reaction does not operate under saturating conditions and the CK reaction velocity is strongly influenced by the guanidino substrate pool size.« less

Design innovations and baseline findings in a long-term Parkinson's trial: the National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson's Disease Long-Term Study-1.

PubMed

Elm, Jordan J

2012-10-01

Based on the preclinical data and the results of a phase II futility study, creatine was selected for an efficacy trial in Parkinson's disease (PD). We present the design rationale and a description of the study cohort at baseline. A randomized, multicenter, double-blind, parallel-group, placebo-controlled phase III study of creatine (10 g daily) in participants with early, treated PD, the Long-term Study-1 (LS-1), is being conducted by the National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson's Disease network. The study utilizes a global statistical test (GST) encompassing five clinical rating scales to provide a multidimensional assessment of disease progression. A total of 1,741 PD participants from 45 sites in the United States and Canada were randomized 1:1 to either 10 g of creatine/day or matching placebo. Participants are being evaluated for a minimum of 5 years. The LS-1 baseline cohort includes participants treated with dopaminergic therapy and generally mild PD. LS-1 represents the largest cohort of patients with early treated PD ever enrolled in a clinical trial. The GST approach should provide high power to test the hypothesis that daily administration of creatine (10 g/day) is more effective than placebo in slowing clinical decline in PD between baseline and the 5-year follow-up visit against the background of dopaminergic therapy and best PD care. Copyright © 2012 Movement Disorder Society.

Genetics Home Reference: guanidinoacetate methyltransferase deficiency

MedlinePlus

... E, Uldry J. Creatine deficiency syndromes and the importance of creatine synthesis in the brain. Amino Acids. ... Synthesis and transport of creatine in the CNS: importance for cerebral functions. J Neurochem. 2010 Oct;115( ...

Creatine Enhances Mitochondrial-Mediated Oligodendrocyte Survival After Demyelinating Injury

PubMed Central

Nanescu, Sonia E.

2017-01-01

Chronic oligodendrocyte loss, which occurs in the demyelinating disorder multiple sclerosis (MS), contributes to axonal dysfunction and neurodegeneration. Current therapies are able to reduce MS severity, but do not prevent transition into the progressive phase of the disease, which is characterized by chronic neurodegeneration. Therefore, pharmacological compounds that promote oligodendrocyte survival could be beneficial for neuroprotection in MS. Here, we investigated the role of creatine, an organic acid involved in adenosine triphosphate (ATP) buffering, in oligodendrocyte function. We found that creatine increased mitochondrial ATP production directly in oligodendrocyte lineage cell cultures and exerted robust protection on oligodendrocytes by preventing cell death in both naive and lipopolysaccharide-treated mixed glia. Moreover, lysolecithin-mediated demyelination in mice deficient in the creatine-synthesizing enzyme guanidinoacetate-methyltransferase (Gamt) did not affect oligodendrocyte precursor cell recruitment, but resulted in exacerbated apoptosis of regenerated oligodendrocytes in central nervous system (CNS) lesions. Remarkably, creatine administration into Gamt-deficient and wild-type mice with demyelinating injury reduced oligodendrocyte apoptosis, thereby increasing oligodendrocyte density and myelin basic protein staining in CNS lesions. We found that creatine did not affect the recruitment of macrophages/microglia into lesions, suggesting that creatine affects oligodendrocyte survival independently of inflammation. Together, our results demonstrate a novel function for creatine in promoting oligodendrocyte viability during CNS remyelination. SIGNIFICANCE STATEMENT We report that creatine enhances oligodendrocyte mitochondrial function and protects against caspase-dependent oligodendrocyte apoptosis during CNS remyelination. This work has important implications for the development of therapeutic targets for diseases characterized by oligodendrocyte death, including multiple sclerosis. PMID:28069926

Creatine supplementation in the aging population: effects on skeletal muscle, bone and brain.

PubMed

Gualano, Bruno; Rawson, Eric S; Candow, Darren G; Chilibeck, Philip D

2016-08-01

This narrative review aims to summarize the recent findings on the adjuvant application of creatine supplementation in the management of age-related deficits in skeletal muscle, bone and brain metabolism in older individuals. Most studies suggest that creatine supplementation can improve lean mass and muscle function in older populations. Importantly, creatine in conjunction with resistance training can result in greater adaptations in skeletal muscle than training alone. The beneficial effect of creatine upon lean mass and muscle function appears to be applicable to older individuals regardless of sex, fitness or health status, although studies with very old (>90 years old) and severely frail individuals remain scarce. Furthermore, there is evidence that creatine may affect the bone remodeling process; however, the effects of creatine on bone accretion are inconsistent. Additional human clinical trials are needed using larger sample sizes, longer durations of resistance training (>52 weeks), and further evaluation of bone mineral, bone geometry and microarchitecture properties. Finally, a number of studies suggest that creatine supplementation improves cognitive processing under resting and various stressed conditions. However, few data are available on older adults, and the findings are discordant. Future studies should focus on older adults and possibly frail elders or those who have already experienced an age-associated cognitive decline.

Identification of a testis-expressed creatine transporter gene at 16p11.2 and confirmation of the X-linked locus to Xq28

DOE Office of Scientific and Technical Information (OSTI.GOV)

Iyer, G.S.; Funanage, V.L.; Proujansky, R.

1996-05-15

Creatine and creatine phosphate act as a buffer system for the regeneration of ATP in tissues with fluctuating energy demands. Following reports of the cloning of a creatine transporter in rat, rabbit, and human, we cloned and sequenced a creatine transporter from a human intestinal cDNA library. PCR amplification of genomic DNAs from somatic cell hybrid panels localized two creatine transporter (CT) genes: CT1 to Xq26-q28 and CT2 to 16p11.2. Refinement of CT1 to Xq28 was confirmed by FISH. Identification of CT2 sequences in YACs and cosmid contigs that had been ordered on human chromosome 16 enabled its assignment tomore » the proximal end of 16p11.2. Sequencing of the CT2 gene identified sequence differences between CT1 and CT2 transcripts that were utilized to determine that CT2 is expressed in testis only. CT2 is the most proximally identified gene on chromosome 16p to date. The existence of an autosomal, testis-specific form of the human creatine transporter gene suggests that creatine transporter activity is critical for normal function of spermatazoa following meiosis. 17 refs., 2 figs., 2 tabs.« less

The Effects of Creatine Supplementation on Explosive Performance and Optimal Individual Postactivation Potentiation Time.

PubMed

Wang, Chia-Chi; Yang, Ming-Ta; Lu, Kang-Hao; Chan, Kuei-Hui

2016-03-04

Creatine plays an important role in muscle energy metabolism. Postactivation potentiation (PAP) is a phenomenon that can acutely increase muscle power, but it is an individualized process that is influenced by muscle fatigue. This study examined the effects of creatine supplementation on explosive performance and the optimal individual PAP time during a set of complex training bouts. Thirty explosive athletes performed tests of back squat for one repetition maximum (1RM) strength and complex training bouts for determining the individual optimal timing of PAP, height and peak power of a counter movement jump before and after the supplementation. Subjects were assigned to a creatine or placebo group and then consumed 20 g of creatine or carboxymethyl cellulose per day for six days. After the supplementation, the 1RM strength in the creatine group significantly increased (p < 0.05). The optimal individual PAP time in the creatine group was also significant earlier than the pre-supplementation and post-supplementation of the placebo group (p < 0.05). There was no significant difference in jump performance between the groups. This study demonstrates that creatine supplementation improves maximal muscle strength and the optimal individual PAP time of complex training but has no effect on explosive performance.

Biochemical, molecular, and clinical diagnoses of patients with cerebral creatine deficiency syndromes.

PubMed

Comeaux, Matthew S; Wang, Jing; Wang, Guoli; Kleppe, Soledad; Zhang, Victor Wei; Schmitt, Eric S; Craigen, William J; Renaud, Deborah; Sun, Qin; Wong, Lee-Jun

2013-07-01

Cerebral creatine deficiency syndromes (CCDS) are a group of inborn errors of creatine metabolism that involve AGAT and GAMT for creatine biosynthesis disorders and SLC6A8 for creatine transporter (CT1) deficiency. Deficiencies in the three enzymes can be distinguished by intermediate metabolite levels, and a definitive diagnosis relies on the presence of deleterious mutations in the causative genes. Mutations and unclassified variants were identified in 41 unrelated patients, and 22 of these mutations were novel. Correlation of sequencing and biochemical data reveals that using plasma guanidinoacetate (GAA) as a biomarker has 100% specificity for both AGAT and GAMT deficiencies, but AGAT deficiency has decreased sensitivity in this assay. Furthermore, the urine creatine:creatinine ratio is an effective screening test with 100% specificity in males suspected of having creatine transporter deficiency. This test has a high false-positive rate due to dietary factors or dilute urine samples and lacks sensitivity in females. We conclude that biochemical screening for plasma GAA and measuring of the urine creatine:creatinine ratio should be performed for suspected CCDS patients prior to sequencing. Also, based on the results of this study, we feel that sequencing should only be considered if a patient has abnormal biochemical results on repeat testing. Copyright © 2013 Elsevier Inc. All rights reserved.

The Effects of Creatine Supplementation on Explosive Performance and Optimal Individual Postactivation Potentiation Time

PubMed Central

Wang, Chia-Chi; Yang, Ming-Ta; Lu, Kang-Hao; Chan, Kuei-Hui

2016-01-01

Creatine plays an important role in muscle energy metabolism. Postactivation potentiation (PAP) is a phenomenon that can acutely increase muscle power, but it is an individualized process that is influenced by muscle fatigue. This study examined the effects of creatine supplementation on explosive performance and the optimal individual PAP time during a set of complex training bouts. Thirty explosive athletes performed tests of back squat for one repetition maximum (1RM) strength and complex training bouts for determining the individual optimal timing of PAP, height and peak power of a counter movement jump before and after the supplementation. Subjects were assigned to a creatine or placebo group and then consumed 20 g of creatine or carboxymethyl cellulose per day for six days. After the supplementation, the 1RM strength in the creatine group significantly increased (p < 0.05). The optimal individual PAP time in the creatine group was also significant earlier than the pre-supplementation and post-supplementation of the placebo group (p < 0.05). There was no significant difference in jump performance between the groups. This study demonstrates that creatine supplementation improves maximal muscle strength and the optimal individual PAP time of complex training but has no effect on explosive performance. PMID:26959056

Separation and flame atomic absorption spectrometric determination of total chromium and chromium (III) in phosphate rock used for production of fertilizer.

PubMed

El-Sheikh, Amjad H; Al-Degs, Yahya S; Sweileh, Jamal A; Said, Adi J

2013-11-15

Due to the commercial value of phosphate rock (PR) as a fertilizer precursor, it is necessary to investigate its heavy metals content. Chromium (Cr) may present as Cr(III) or Cr(VI) in PR; but quantitative differentiation between them is not an easy task. This is due to possible interconversion of Cr species during the digestion/leaching process. In this work, ultrasound digestion (USD) of PR was optimized (300 mg PR, 4.0 mL of 4.0 mol L(-1) nitric acid, 15 min sonication) for the sake of leaching Cr species prior to their determination by flame atomic absorption spectroscopy. Using multi-walled carbon nanotube (MWCNT) as adsorbent, solid phase extraction (SPE) was used to separate Cr(III) from the digestate at pH 9, while total Cr was estimated after reducing Cr(VI) into Cr(III). The optimum USD/SPE method gave LOQ and LOD of Cr(III) of 0.96 mg kg(-1) and 0.288 mg kg(-1), respectively. The method sensitivity was 1.44×10(-3) AU kg mg(-1) within the studied Cr concentration range (5-400 mg kg(-1)). The USD/SPE method was validated by analyzing lake sediments LKSD-4 certified reference material, and by comparison with classical digestion method (CD). Application of USD/SPE on Jordanian PR samples gave total Cr rang 29.1-122.0 mg kg(-1) (±1.4-6.3), while Cr(III) ranged between 23.8 and 101.7 mg kg(-1) (±1.3-5.5). AFPC Rock Check Program samples gave total Cr range 238.9-394.7 mg kg(-1) (±11.5-24.1), while Cr(III) ranged between 202.4 and 335.8 mg kg(-1) (±11.4-18.3). These results were very close to the results obtained by the CD method. Copyright © 2013 Elsevier B.V. All rights reserved.

Transient giant negative T wave in acute anterior myocardial infarction predicts R wave recovery and preservation of left ventricular function.

PubMed Central

Agetsuma, H.; Hirai, M.; Hirayama, H.; Suzuki, A.; Takanaka, C.; Yabe, S.; Inagaki, H.; Takatsu, F.; Hayashi, H.; Saito, H.

1996-01-01

OBJECTIVE: To investigate the value of a giant negative T wave (> or = 1.0 mV) in precordial leads of 12-lead electrocardiograms in the acute phase of Q wave myocardial infarction as a predictor of myocardial salvage. METHODS: Coronary angiographic and electrocardiographic findings, left ventricular ejection fraction in the chronic stage, and levels of cardiac enzymes were compared in patients with myocardial infarction with (group GNT, n = 31) and without (group N, n = 20) a giant negative T wave. GNT patients were divided into two subgroups according to the presence (GNT:R[+], n = 10) or absence (GNT: R[-], n = 21) of R wave recovery with an amplitude > or = 0.1 mV in at least one lead that had shown Q waves. RESULTS: The maximum level of creatine kinase and the total creatine kinase were lower in group GNT compared with group N (P < 0.05). The left ventricular ejection fraction was higher in group GNT than in group N (P < 0.05). The maximum creatine kinase and total creatine kinase were lower in GNT:R(+) than in GNT:R(-) (P < 0.01). The left ventricular ejection fraction was higher in GNT:R(+) than in GNT:R(-) (P < 0.01). The frequency of R wave recovery was significantly higher when giant negative T waves appeared within 100 h of myocardial infarction or when the maximum potential was > or = 1.4 mV. The appearance of a giant negative T wave > or = 1.4 mV had a sensitivity of 90%, a specificity of 71.4%, a diagnostic accuracy of 77.4%, a positive predictive value of 60%, and a negative predictive value of 93.8% for prediction of R wave recovery. CONCLUSIONS: The appearance of a giant negative T wave, especially within 100 h of the onset of myocardial infarction, with a maximum potential of > or = 1.4 mV, may predict a reappearance of the R wave and a better left ventricular function in patients in the chronic stage of anterior myocardial infarction. PMID:8800983

Complete inhibition of creatine kinase in isolated perfused rat hearts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fossel, E.T.; Hoefeler, H.

1987-01-01

Transient exposure of an isolated isovolumic perfused rat heart to low concentrations (0.5 mM) of perfusate-born iodoacetamide resulted in complete inhibition of creatine kinase and partial inhibition of glyceraldehyde-3-phosphate dehydrogenase in the heart. At low levels of developed pressure, hearts maintained mechanical function, ATP, and creatine phosphate levels at control values. However, iodoacetamide-inhibited hearts were unable to maintain control values of end diastolic pressure or peak systolic pressure as work load increased. Global ischemia resulted in loss of all ATP without loss of creatine phosphate, indicating lack of active creatine kinase. These results indicate that isovolumic perfused rat hearts aremore » able to maintain normal function and normal levels of high-energy phosphates without active creatine kinase at low levels of developed pressure. /sup 31/P-NMR of the heart was carried out.« less

Creatine supplementation and glycemic control: a systematic review.

PubMed

Pinto, Camila Lemos; Botelho, Patrícia Borges; Pimentel, Gustavo Duarte; Campos-Ferraz, Patrícia Lopes; Mota, João Felipe

2016-09-01

The focus of this review is the effects of creatine supplementation with or without exercise on glucose metabolism. A comprehensive examination of the past 16 years of study within the field provided a distillation of key data. Both in animal and human studies, creatine supplementation together with exercise training demonstrated greater beneficial effects on glucose metabolism; creatine supplementation itself demonstrated positive results in only a few of the studies. In the animal studies, the effects of creatine supplementation on glucose metabolism were even more distinct, and caution is needed in extrapolating these data to different species, especially to humans. Regarding human studies, considering the samples characteristics, the findings cannot be extrapolated to patients who have poorer glycemic control, are older, are on a different pharmacological treatment (e.g., exogenous insulin therapy) or are physically inactive. Thus, creatine supplementation is a possible nutritional therapy adjuvant with hypoglycemic effects, particularly when used in conjunction with exercise.

Pressure overload stimulated cardiac hypertrophy leads to a rapid decrease in the mRNA for creatine kinase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boheler, K.; Popovich, B.; Dillmann, W.H.

1987-05-01

Cardiac hypertrophy (CH) leads to a decrease in creatine kinase (CK) enzymatic activity. To determine if the mRNA for CK also decreases with CH, they performed the following studies. Cardiac RNA was isolated from rats subjected to either abdominal aortic stenosis (AS) or sham surgery. Through Northern blot analysis, total cardiac RNA was quantitated with a CK specific /sup 32/P-labelled cDNA clone. At 3 and 8 days post-constriction, the mRNA for CK decreases by 54.6 +/- 7% and 65.3 +/- 18% respectively, whereas the heart weight increases by 19% and 37% relative to controls. Further studies indicate that CK mRNAmore » also decreases by 41.8% in hypothyroid rats (Tx) but decreases by a total of 68.1% in Tx rats subjected to 8 days of AS. Pressure overload stimulated CH leads to a rapid decrease in CK mRNA in normal and Tx rats. This CK mRNA decrease may account for the decreased efficiency of contraction seen in CH.« less

Relation between various chromium compounds and some other elements in fumes from manual metal arc stainless steel welding.

PubMed

Matczak, W; Chmielnicka, J

1993-03-01

For the years 1987-1990 160 individual samples of manual metal arc stainless steel (MMA/SS) welding fumes from the breathing zone of welders in four industrial plants were collected. Concentrations of soluble and insoluble chromium (Cr) III and Cr VI compounds as well as of some other welding fume elements (Fe, Mn, Ni, F) were determined. Concentration of welding fumes in the breathing zone ranged from 0.2 to 23.4 mg/m3. Total Cr amounted to 0.005-0.991 mg/m3 (including 0.005-0.842 mg/m3 Cr VI). Total Cr content of fumes varied from 0.1 to 7.4%. The distribution of particular Cr compounds was: 52.6% soluble Cr (including 50.7% Cr VI), 65.5% total Cr VI, and 11.4% insoluble Cr VI. The results obtained indicate that MMA/SS welding is a process that could be highly hazardous to human health. Evaluation of occupational exposure has shown that MMA/SS welders may exceed the admissible concentrations of soluble and insoluble Cr VI forms as well as of Mn and Ni. In the plants investigated the sum of the ratios of concentrations of particular welding fumes in the breathing zone of welders exceeded corresponding maximum allowable concentration values by 24 times (including 17 times for total Cr VI). Due to the variety and changeability of particular parameters occurring in the working environment, the composition of MMA/SS welding fumes (in the welder's breathing zone) is so variable that it is not possible to assess the exposure by means of one universal exposure indicator (maximum additive hygienic limit value). The evaluation should be based on the results of measurements of concentrations of particular elements in welding fumes.

Relation between various chromium compounds and some other elements in fumes from manual metal arc stainless steel welding.

PubMed Central

Matczak, W; Chmielnicka, J

1993-01-01

For the years 1987-1990 160 individual samples of manual metal arc stainless steel (MMA/SS) welding fumes from the breathing zone of welders in four industrial plants were collected. Concentrations of soluble and insoluble chromium (Cr) III and Cr VI compounds as well as of some other welding fume elements (Fe, Mn, Ni, F) were determined. Concentration of welding fumes in the breathing zone ranged from 0.2 to 23.4 mg/m3. Total Cr amounted to 0.005-0.991 mg/m3 (including 0.005-0.842 mg/m3 Cr VI). Total Cr content of fumes varied from 0.1 to 7.4%. The distribution of particular Cr compounds was: 52.6% soluble Cr (including 50.7% Cr VI), 65.5% total Cr VI, and 11.4% insoluble Cr VI. The results obtained indicate that MMA/SS welding is a process that could be highly hazardous to human health. Evaluation of occupational exposure has shown that MMA/SS welders may exceed the admissible concentrations of soluble and insoluble Cr VI forms as well as of Mn and Ni. In the plants investigated the sum of the ratios of concentrations of particular welding fumes in the breathing zone of welders exceeded corresponding maximum allowable concentration values by 24 times (including 17 times for total Cr VI). Due to the variety and changeability of particular parameters occurring in the working environment, the composition of MMA/SS welding fumes (in the welder's breathing zone) is so variable that it is not possible to assess the exposure by means of one universal exposure indicator (maximum additive hygienic limit value). The evaluation should be based on the results of measurements of concentrations of particular elements in welding fumes. PMID:8457491

Purification and characterization of creatine kinase isozymes from the nurse shark Ginglymostoma cirratum.

PubMed

Gray, K A; Grossman, S H; Summers, D D

1986-01-01

Creatine kinase from nurse shark brain and muscle has been purified to apparent homogeneity. In contrast to creatine kinases from most other vertebrate species, the muscle isozyme and the brain isozyme from nurse shark migrate closely in electrophoresis and, unusually, the muscle isozyme is anodal to the brain isozyme. The isoelectric points are 5.3 and 6.2 for the muscle and brain isozymes, respectively. The purified brain preparation also contains a second active protein with pI 6.0. The amino acid content of the muscle isozyme is compared with other isozymes of creatine kinase using the Metzger Difference Index as an estimation of compositional relatedness. All comparisons show a high degree of compositional similarity including arginine kinase from lobster muscle. The muscle isozyme is marginally more resistant to temperature inactivation than the brain isozyme; the muscle protein does not exhibit unusual stability towards high concentrations of urea. Kinetic analysis of the muscle isozyme reveals Michaelis constants of 1.6 mM MgATP, 12 mM creatine, 1.2 mM MgADP and 50 mM creatine phosphate. Dissociation constants for the same substrate from the binary and ternary enzyme-substrate complex do not differ significantly, indicating limited cooperatively in substrate binding. Enzyme activity is inhibited by small planar anions, most severely by nitrate. Shark muscle creatine kinase hybridizes in vitro with rabbit muscle or monkey brain creatine kinase; shark brain isozyme hybridizes with monkey brain or rabbit brain creatine kinase. Shark muscle and shark brain isozymes, under a wide range of conditions, failed to produce a detectable hybrid.

Creatine Enhances Mitochondrial-Mediated Oligodendrocyte Survival After Demyelinating Injury.

PubMed

Chamberlain, Kelly A; Chapey, Kristen S; Nanescu, Sonia E; Huang, Jeffrey K

2017-02-08

Chronic oligodendrocyte loss, which occurs in the demyelinating disorder multiple sclerosis (MS), contributes to axonal dysfunction and neurodegeneration. Current therapies are able to reduce MS severity, but do not prevent transition into the progressive phase of the disease, which is characterized by chronic neurodegeneration. Therefore, pharmacological compounds that promote oligodendrocyte survival could be beneficial for neuroprotection in MS. Here, we investigated the role of creatine, an organic acid involved in adenosine triphosphate (ATP) buffering, in oligodendrocyte function. We found that creatine increased mitochondrial ATP production directly in oligodendrocyte lineage cell cultures and exerted robust protection on oligodendrocytes by preventing cell death in both naive and lipopolysaccharide-treated mixed glia. Moreover, lysolecithin-mediated demyelination in mice deficient in the creatine-synthesizing enzyme guanidinoacetate-methyltransferase ( Gamt ) did not affect oligodendrocyte precursor cell recruitment, but resulted in exacerbated apoptosis of regenerated oligodendrocytes in central nervous system (CNS) lesions. Remarkably, creatine administration into Gamt -deficient and wild-type mice with demyelinating injury reduced oligodendrocyte apoptosis, thereby increasing oligodendrocyte density and myelin basic protein staining in CNS lesions. We found that creatine did not affect the recruitment of macrophages/microglia into lesions, suggesting that creatine affects oligodendrocyte survival independently of inflammation. Together, our results demonstrate a novel function for creatine in promoting oligodendrocyte viability during CNS remyelination. SIGNIFICANCE STATEMENT We report that creatine enhances oligodendrocyte mitochondrial function and protects against caspase-dependent oligodendrocyte apoptosis during CNS remyelination. This work has important implications for the development of therapeutic targets for diseases characterized by oligodendrocyte death, including multiple sclerosis. Copyright © 2017 Chamberlain et al.

Prevalence of Creatine Deficiency Syndromes in Children With Nonsyndromic Autism.

PubMed

Schulze, Andreas; Bauman, Margaret; Tsai, Anne Chun-Hui; Reynolds, Ann; Roberts, Wendy; Anagnostou, Evdokia; Cameron, Jessie; Nozzolillo, Alixandra A; Chen, Shiyi; Kyriakopoulou, Lianna; Scherer, Stephen W; Loh, Alvin

2016-01-01

Creatine deficiency may play a role in the neurobiology of autism and may represent a treatable cause of autism. The goal of the study was to ascertain the prevalence of creatine deficiency syndromes (CDSs) in children with autism spectrum disorder (ASD). In a prospective multicenter study, 443 children were investigated after a confirmed diagnosis of ASD. Random spot urine screening for creatine metabolites (creatine, guanidinoacetate, creatinine, and arginine) with liquid chromatography-tandem mass spectrometry and second-tier testing with high-performance liquid chromatography methodology was followed by recall testing in 24-hour urines and confirmatory testing by Sanger-based DNA sequencing of GAMT, GATM, and SLC6A8 genes. Additional diagnostic tests included plasma creatine metabolites and in vivo brain proton magnetic resonance spectroscopy. The creatine metabolites in spot urine in the autism group were compared with 128 healthy controls controlled for age. In 443 subjects with ASD investigated for CDS, we had 0 events (event: 0, 95% confidence interval 0-0.0068), therefore with 95% confidence the prevalence of CDS is <7 in 1000 children with ASD. The autism and control groups did not vary in terms of creatine metabolites (P > .0125) in urine. Our study revealed a very low prevalence of CDS in children with nonsyndromic ASD and no obvious association between creatine metabolites and autism. Unlike our study population, we expect more frequent CDS among children with severe developmental delay, speech impairment, seizures, and movement disorders in addition to impairments in social communication, restricted interests, and repetitive behaviors. Copyright © 2016 by the American Academy of Pediatrics.

Simultaneous determination of guanidinoacetate, creatine and creatinine in urine and plasma by un-derivatized liquid chromatography-tandem mass spectrometry.

PubMed

Carling, R S; Hogg, S L; Wood, T C; Calvin, J

2008-11-01

Creatine plays an important role in the storage and transmission of phosphate-bound energy. The cerebral creatine deficiency syndromes (CCDS) comprise three inherited defects in creatine biosynthesis and transport. They are characterized by mental retardation, speech and language delay and epilepsy. All three disorders cause low-creatine signal on brain magnetic resonance spectroscopy (MRS); however, MRS may not be readily available and even when it is, biochemical tests are required to determine the underlying disorder. Analysis was performed by liquid chromatography-tandem mass spectrometry in positive ionization mode. Samples were analysed underivatized using a rapid 'dilute and shoot' approach. Chromatographic separation of the three compounds was achieved. Stable isotope internal standards were used for quantification. Creatine, creatinine and guanidinoacetate were measured with a 2.5 minute run time. For guanidinoacetate, the standard curve was linear to at least 5000 mumol/L and for creatine and creatinine it was linear to at least 25 mmol/L. The lower limit of quantitation was 0.4 mumol/L for creatine and guanidinoacetate and 0.8 mumol/L for creatinine. Recoveries ranged from 86% to 106% for the three analytes. Intra- and inter-assay variation for each analyte was <10% in both urine and plasma. A tandem mass spectrometric method has been developed and validated for the underivatized determination of guanidinoacetate, creatine and creatinine in human urine and plasma. Minimal sample preparation coupled with a rapid run time make the method applicable to the routine screening of patients with suspected CCDS.

Treatment outcome of creatine transporter deficiency: international retrospective cohort study.

PubMed

Bruun, Theodora U J; Sidky, Sarah; Bandeira, Anabela O; Debray, Francoise-Guillaume; Ficicioglu, Can; Goldstein, Jennifer; Joost, Kairit; Koeberl, Dwight D; Luísa, Diogo; Nassogne, Marie-Cecile; O'Sullivan, Siobhan; Õunap, Katrin; Schulze, Andreas; van Maldergem, Lionel; Salomons, Gajja S; Mercimek-Andrews, Saadet

2018-06-01

To evaluate the outcome of current treatment for creatine transporter (CRTR) deficiency, we developed a clinical severity score and initiated an international treatment registry. An online questionnaire was completed by physicians following patients with CRTR deficiency on a treatment, including creatine and/or arginine, and/or glycine. Clinical severity score included 1) global developmental delay/intellectual disability; 2) seizures; 3) behavioural disorder. Phenotype scored 1-3 = mild; 4-6 = moderate; and 7-9 = severe. We applied the clinical severity score pre- and on-treatment. Seventeen patients, 14 males and 3 females, from 16 families were included. Four patients had severe, 6 patients had moderate, and 7 patients had a mild phenotype. The phenotype ranged from mild to severe in patients diagnosed at or before 2 years of age or older than 6 years of age. The phenotype ranged from mild to severe in patients with mildly elevated urine creatine to creatinine ratio. Fourteen patients were on the combined creatine, arginine and glycine therapy. On the combined treatment with creatine, arginine and glycine, none of the males showed either deterioration or improvements in their clinical severity score, whereas two females showed improvements in the clinical severity score. Creatine monotherapy resulted in deterioration of the clinical severity score in one male. There seems to be no correlation between phenotype and degree of elevation in urine creatine to creatinine ratio, genotype, or age at diagnosis. Combined creatine, arginine and glycine therapy might have stopped disease progression in males and improved phenotype in females.

Creatine monohydrate supplementation on lower-limb muscle power in Brazilian elite soccer players.

PubMed

Claudino, João G; Mezêncio, Bruno; Amaral, Sérgio; Zanetti, Vinícius; Benatti, Fabiana; Roschel, Hamilton; Gualano, Bruno; Amadio, Alberto C; Serrão, Julio C

2014-01-01

Studies involving chronic creatine supplementation in elite soccer players are scarce. Therefore, the aim of this study was to examine the effects of creatine monohydrate supplementation on lower-limb muscle power in Brazilian elite soccer players (n = 14 males) during pre-season training. This was a randomized, double-blind, placebo-controlled parallel-group study. Brazilian professional elite soccer players participated in this study. During the pre-season (7 weeks), all the subjects underwent a standardized physical and specific soccer training. Prior to and after either creatine monohydrate or placebo supplementation, the lower-limb muscle power was measured by countermovement jump performance. The Jumping performance was compared between groups at baseline (p = 0.99). After the intervention, jumping performance was lower in the placebo group (percent change = - 0.7%; ES = - 0.3) than in the creatine group (percent change = + 2.4%; ES = + 0.1), but it did not reach statistical significance (p = 0.23 for time x group interaction). Fisher's exact test revealed that the proportion of subjects that experienced a reduction in jumping performance was significantly greater in the placebo group than in the creatine group (5 and 1, respectively; p = 0.05) after the training. The magnitude-based inferences demonstrated that placebo resulted in a possible negative effect (50%) in jumping performance, whereas creatine supplementation led to a very likely trivial effect (96%) in jumping performance in the creatine group. Creatine monohydrate supplementation prevented the decrement in lower-limb muscle power in elite soccer players during a pre-season progressive training.

Concentrations in beef and lamb of taurine, carnosine, coenzyme Q(10), and creatine.

PubMed

Purchas, R W; Rutherfurd, S M; Pearce, P D; Vather, R; Wilkinson, B H P

2004-03-01

Levels of taurine, carnosine, coenzyme Q(10), and creatine were measured in beef liver and several muscles of beef and lamb and in cooked and uncooked meat. The amino acid taurine has numerous biological functions, the dipeptide carnosine is a buffer as well as an antioxidant, coenzyme Q(10) is also an antioxidant present within mitochondria, and creatine along with creatine phosphate is involved with energy metabolism in muscle. Large differences were shown for all compounds between beef cheek muscle (predominantly red fibres) and beef semitendinosus muscle (mainly white fibres), with cheek muscle containing 9.9 times as much taurine, and 3.2 times as much coenzyme Q(10), but only 65% as much creatine and 9% as much carnosine. Levels in lamb relative to beef semitendinosus muscles were higher for taurine but slightly lower for carnosine, coenzyme Q(10) and creatine. Values for all the compounds varied significantly between eight lamb muscles, possibly due in part to differences in the proportion of muscle fibre types. Slow cooking (90 min at 70 °C) of lamb longissimus and semimembranosus muscles led to significant reductions in the content of taurine, carnosine, and creatine (P<0.001), but a slight increase in coenzyme Q(10). There was also a four-fold increase in creatinine, presumably due to its formation from creatine. It is concluded that biologically, and possibly nutritionally, significant levels of taurine, carnosine, coenzyme Q(10), and creatine are present in beef and lamb, but that these levels vary between muscles, between animals, and with cooking.

Abnormal relationship between GABA, neurophysiology and impulsive behavior in neurofibromatosis type 1.

PubMed

Ribeiro, Maria J; Violante, Inês R; Bernardino, Inês; Edden, Richard A E; Castelo-Branco, Miguel

2015-03-01

Neurofibromatosis type 1 (NF1) is a neurodevelopmental disorder characterized by a broad spectrum of cognitive deficits. In particular, executive dysfunction is recognized as a core deficit of NF1, including impairments in executive attention and inhibitory control. Yet, the neural mechanisms behind these important deficits are still unknown. Here, we studied inhibitory control in a visual go/no-go task in children and adolescents with NF1 and age- and gender-matched controls (n = 16 per group). We applied a multimodal approach using high-density electroencephalography (EEG), to study the evoked brain responses, and magnetic resonance spectroscopy (MRS) to measure the levels of GABA and glutamate + glutamine in the medial frontal cortex, a brain region that plays a pivotal role in inhibitory control, and also in a control region, the occipital cortex. Finally, we run correlation analyses to identify the relationship between inhibitory control, levels of neurotransmitters, and EEG markers of neural function. Individuals with NF1 showed impaired impulse control and reduced EEG correlates of early visual processing (parieto-occipital P1) and inhibitory control (frontal P3). MRS data revealed a reduction in medial frontal GABA+/tCr (total Creatine) levels in the NF1 group, in parallel with the already reported reduced occipital GABA levels. In contrast, glutamate + glutamine/tCr levels were normal, suggesting the existence of abnormal inhibition/excitation balance in this disorder. Notably, medial frontal but not occipital GABA levels correlated with general intellectual abilities (IQ) in NF1, and inhibitory control in both groups. Surprisingly, the relationship between inhibitory control and medial frontal GABA was reversed in NF1: higher GABA was associated with a faster response style whereas in controls it was related to a cautious strategy. Abnormal GABAergic physiology appears, thus, as an important factor underlying impaired cognition in NF1, in a level and region dependent manner. Copyright © 2014 Elsevier Ltd. All rights reserved.

Caffeine and Creatine Content of Dietary Supplements Consumed by Brazilian Soccer Players.

PubMed

Inácio, Suelen Galante; de Oliveira, Gustavo Vieira; Alvares, Thiago Silveira

2016-08-01

Caffeine and creatine are ingredients in the most popular dietary supplements consumed by soccer players. However, some products may not contain the disclosed amounts of the ingredients listed on the label, compromising the safe usage and the effectiveness of these supplements. Therefore, the aim of this study was to evaluate the content of caffeine and creatine in dietary supplements consumed by Brazilian soccer players. The results obtained were compared with the caffeine content listed on the product label. Two batches of the supplement brands consumed by ≥ 50% of the players were considered for analysis. The quantification of caffeine and creatine in the supplements was determined by a high-performance liquid chromatography system with UV detector. Nine supplements of caffeine and 7 supplements of creatine met the inclusion criteria for analysis. Eight brands of caffeine and five brands of creatine showed significantly different values (p < .05) as compared with the values stated on the label. There were no significant differences between the two batches of supplements analyzed, except for one caffeine supplement. It can be concluded that caffeine and creatine dietary supplements consumed by Brazilian soccer players present inaccurate values listed on the label, although most presented no difference among batches. To ensure consumer safety and product efficacy, accurate information on caffeine and creatine content should be provided on all dietary supplement labels.

Effects of Creatine Supplementation on Muscle Strength and Optimal Individual Post-Activation Potentiation Time of the Upper Body in Canoeists.

PubMed

Wang, Chia-Chi; Lin, Shu-Cheng; Hsu, Shu-Ching; Yang, Ming-Ta; Chan, Kuei-Hui

2017-10-27

Creatine supplementation reduces the impact of muscle fatigue on post-activation potentiation (PAP) of the lower body, but its effects on the upper body remain unknown. This study examined the effects of creatine supplementation on muscle strength, explosive power, and optimal individual PAP time of the upper body during a set of complex training bouts in canoeists. Seventeen male high school canoeists performed a bench row for one repetition at maximum strength and conducted complex training bouts to determine the optimal individual timing of PAP and distance of overhead medicine ball throw before and after the supplementation. Subjects were assigned to a creatine or placebo group, and later consumed 20 g of creatine or carboxymethyl cellulose per day for six days. After supplementation, the maximal strength in the creatine group significantly increased ( p < 0.05). The optimal individual PAP time in the creatine group was significantly earlier than the pre-supplementation times ( p < 0.05). There was no significant change in explosive power for either group. Our findings support the notion that creatine supplementation increases maximal strength and shortens the optimal individual PAP time of the upper body in high school athletes, but has no effect on explosive power. Moreover, it was found that the recovery time between a bench row and an overhead medicine ball throw in a complex training bout is an individual phenomenon.

Cerebral creatine deficiencies: a group of treatable intellectual developmental disorders.

PubMed

Stockler-Ipsiroglu, Sylvia; van Karnebeek, Clara D M

2014-07-01

Currently there are 91 treatable inborn errors of metabolism that cause intellectual developmental disorders. Cerebral creatine deficiencies (CDD) comprise three of these: arginine: glycine amidinotransferase [AGAT], guanidinoacetate methyltransferase [GAMT], and X-linked creatine transporter deficiency [SLC6A8]. Intellectual developmental disorder and cerebral creatine deficiency are the hallmarks of CDD. Additional clinical features include prominent speech delay, autism, epilepsy, extrapyramidal movement disorders, and signal changes in the globus pallidus. Patients with GAMT deficiency exhibit the most severe clinical spectrum. Myopathy is a distinct feature in AGAT deficiency. Guanidinoacetate (GAA) is the immediate product in the creatine biosynthetic pathway. Low GAA concentrations in urine, plasma, and cerebrospinal fluid are characteristic diagnostic markers for AGAT deficiency, while high GAA concentrations are characteristic markers for GAMT deficiency. An elevated ratio of urinary creatine /creatinine excretion serves as a diagnostic marker in males with SLC6A8 deficiency. Treatment strategies include oral supplementation of high-dose creatine-monohydrate for all three CDD. Guanidinoacetate-reducing strategies (high-dose ornithine, arginine-restricted diet) are additionally employed in GAMT deficiency. Supplementation of substrates for intracerebral creatine synthesis (arginine, glycine) has been used additionally to treat SLC6A8 deficiency. Early recognition and treatment improves outcomes. Normal outcomes in neonatally ascertained siblings from index families with AGAT and GAMT deficiency suggest a potential benefit of newborn screening for these disorders. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Effects of Low-Dose Creatine Supplementation Versus Creatine Loading in Collegiate Football Players

PubMed Central

Deivert, Richard G.; Hagerman, Frederick; Gilders, Roger

2001-01-01

Objective: To compare the effects of low doses of creatine and creatine loading on strength, urinary creatinine concentration, and percentage of body fat. Design and Setting: Division IA collegiate football players took creatine monohydrate for 10 weeks during a sport-specific, periodized, off-season strength and conditioning program. One-repetition maximum (1-RM) squat, urinary creatinine concentrations, and percentage of body fat were analyzed. Subjects: Twenty-five highly trained, Division IA collegiate football players with at least 1 year of college playing experience. Measurements: We tested strength with a 1-RM squat exercise before, during, and after creatine supplementation. Percentage of body fat was measured by hydrostatic weighing before and after supplementation. Urinary creatinine concentration was measured via light spectrophotometer at 0, 1, 3, 7, 14, 21, 28, 35, 42, 48, 56, and 63 days. An analysis of variance with repeated measures was computed to compare means for all variables. Results: Creatine supplementation had no significant group, time, or interaction effects on strength, urinary creatinine concentration, or percentage of body fat. However, significant time effects were found for 1-RM squat and fat-free mass in all groups. Conclusions: Our data suggest that creatine monohydrate in any amount does not have any beneficial ergogenic effects in highly trained collegiate football players. However, a proper resistance training stimulus for 10 weeks can increase strength and fat-free mass in highly trained athletes. PMID:12937451

Surfactant-assisted emulsification dispersive liquid-liquid microextraction using 2-thenoyltrifluoroacetone as a chelating agent coupled with electrothermal atomic absorption spectrometry for the speciation of chromium in water and rice samples.

PubMed

Dokpikul, Nattawut; Chaiyasith, Wipharat Chuachuad; Sananmuang, Ratana; Ampiah-Bonney, Richmond J

2018-04-25

A novel method was developed by SAE-DLLME for chromium speciation in water and rice samples using 2-thenoyltrifluoroacetone (TTA) as a chelating reagent by ETAAS. The speciation of Cr(III) and Cr(VI) was achieved by complexation of Cr(III)-TTA and the total Cr was measured after reduction of Cr(VI) to Cr. The calibration graph was linear in the range of 0.02-2.50 µg L -1 , with a detection limit of 0.0052 µg L -1 . The %RSD was in range of 2.90-3.30% at 0.5, 1.5 and 2.5 µg L -1 of Cr(III), n = 5 and the EF was 54.47. The method was applied to chromium speciation and total chromium determination in real samples and gave recoveries in the range of 96.2-103.5% and 97.1-102.7% for Cr(III) and Cr(VI) in water samples and 93.7-103.5% of total Cr in rice samples. The accuracy of the method was evaluated by analysis of SRM 1573a with good agreement compared to the certified value. Copyright © 2017 Elsevier Ltd. All rights reserved.

Creatine and Caffeine: Considerations for Concurrent Supplementation.

PubMed

Trexler, Eric T; Smith-Ryan, Abbie E

2015-12-01

Nutritional supplementation is a common practice among athletes, with creatine and caffeine among the most commonly used ergogenic aids. Hundreds of studies have investigated the ergogenic potential of creatine supplementation, with consistent improvements in strength and power reported for exercise bouts of short duration (≤ 30 s) and high intensity. Caffeine has been shown to improve endurance exercise performance, but results are mixed in the context of strength and sprint performance. Further, there is conflicting evidence from studies comparing the ergogenic effects of coffee and caffeine anhydrous supplementation. Previous research has identified independent mechanisms by which creatine and caffeine may improve strength and sprint performance, leading to the formulation of multi-ingredient supplements containing both ingredients. Although scarce, research has suggested that caffeine ingestion may blunt the ergogenic effect of creatine. While a pharmacokinetic interaction is unlikely, authors have suggested that this effect may be explained by opposing effects on muscle relaxation time or gastrointestinal side effects from simultaneous consumption. The current review aims to evaluate the ergogenic potential of creatine and caffeine in the context of high-intensity exercise. Research directly comparing coffee and caffeine anhydrous is discussed, along with previous studies evaluating the concurrent supplementation of creatine and caffeine.