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Sample records for brain-type creatine kinase

  1. Mice lacking brain-type creatine kinase activity show defective thermoregulation.

    NARCIS (Netherlands)

    Streijger, F.; Pluk, H.; Oerlemans, F.T.J.J.; Beckers, G.; Bianco, A.C.; Ribeiro, M.O.; Wieringa, B.; Zee, C.E.E.M. van der

    2009-01-01

    The cytosolic brain-type creatine kinase and mitochondrial ubiquitous creatine kinase (CK-B and UbCKmit) are expressed during the prepubescent and adult period of mammalian life. These creatine kinase (CK) isoforms are present in neural cell types throughout the central and peripheral nervous system

  2. Complete brain-type creatine kinase deficiency in mice blocks seizure activity and affects intracellular calcium kinetics

    NARCIS (Netherlands)

    Streijger, F.; Scheenen, W.J.J.M.; Luijtelaar, E.L.J.M. van; Oerlemans, F.T.J.J.; Wieringa, B.; Zee, C.E.E.M. van der

    2010-01-01

    Purpose: Brain-type creatine kinase (CK-B) and ubiquitous mitochondrial creatine kinase (UbCKmit) act as components of local phosphocreatine ATP shuttles that help in the compartmentalization and maintenance of pools of high-energy phosphate molecules in both neurons and glial cells. We investigated

  3. Complete brain-type creatine kinase deficiency in mice blocks seizure activity and affects intracellular calcium kinetics.

    NARCIS (Netherlands)

    Streijger, F.; Scheenen, W.J.J.M.; Luijtelaar, G. van; Oerlemans, F.T.J.J.; Wieringa, B.; Zee, C.E.E.M. van der

    2010-01-01

    PURPOSE: Brain-type creatine kinase (CK-B) and ubiquitous mitochondrial creatine kinase (UbCKmit) act as components of local phosphocreatine ATP shuttles that help in the compartmentalization and maintenance of pools of high-energy phosphate molecules in both neurons and glial cells. We investigated

  4. Mice lacking brain-type creatine kinase activity show defective thermoregulation

    Science.gov (United States)

    Streijger, Femke; Pluk, Helma; Oerlemans, Frank; Beckers, Gaby; Bianco, Antonio C.; Ribeiro, Miriam O.; Wieringa, Bé; Van der Zee, Catharina E.E.M.

    2010-01-01

    The cytosolic brain-type creatine kinase and mitochondrial ubiquitous creatine kinase (CK-B and UbCKmit) are expressed during the prepubescent and adult period of mammalian life. These creatine kinase (CK) isoforms are present in neural cell types throughout the central and peripheral nervous system and in smooth muscle containing tissues, where they have an important role in cellular energy homeostasis. Here, we report on the coupling of CK activity to body temperature rhythm and adaptive thermoregulation in mice. With both brain-type CK isoforms being absent, the body temperature reproducibly drops ~1.0°C below normal during every morning (inactive) period in the daily cycle. Facultative non-shivering thermogenesis is also impaired, since CK−−/−− mice develop severe hypothermia during 24 h cold exposure. A relationship with fat metabolism was suggested because comparison of CK−−/−− mice with wildtype controls revealed decreased weight gain associated with less white and brown fat accumulation and smaller brown adipocytes. Also, circulating levels of glucose, triglycerides and leptin are reduced. Extensive physiological testing and uncoupling protein1 analysis showed, however, that the thermogenic problems are not due to abnormal responsiveness of brown adipocytes, since noradrenaline infusion produced a normal increase of body temperature. Moreover, we demonstrate that the cyclic drop in morning temperature is also not related to altered rhythmicity with reduced locomotion, diminished food intake or increased torpor sensitivity. Although several integral functions appear altered when CK is absent in the brain, combined findings point into the direction of inefficient neuronal transmission as the dominant factor in the thermoregulatory defect. PMID:19419668

  5. Local ATP generation by brain-type creatine kinase (CK-B facilitates cell motility.

    Directory of Open Access Journals (Sweden)

    Jan W P Kuiper

    Full Text Available BACKGROUND: Creatine Kinases (CK catalyze the reversible transfer of high-energy phosphate groups between ATP and phosphocreatine, thereby playing a storage and distribution role in cellular energetics. Brain-type CK (CK-B deficiency is coupled to loss of function in neural cell circuits, altered bone-remodeling by osteoclasts and complement-mediated phagocytotic activity of macrophages, processes sharing dependency on actomyosin dynamics. METHODOLOGY/PRINCIPAL FINDINGS: Here, we provide evidence for direct coupling between CK-B and actomyosin activities in cortical microdomains of astrocytes and fibroblasts during spreading and migration. CK-B transiently accumulates in membrane ruffles and ablation of CK-B activity affects spreading and migration performance. Complementation experiments in CK-B-deficient fibroblasts, using new strategies to force protein relocalization from cytosol to cortical sites at membranes, confirmed the contribution of compartmentalized CK-B to cell morphogenetic dynamics. CONCLUSION/SIGNIFICANCE: Our results provide evidence that local cytoskeletal dynamics during cell motility is coupled to on-site availability of ATP generated by CK-B.

  6. Sequential Events in the Irreversible Thermal Denaturation of Human Brain-Type Creatine Kinase by Spectroscopic Methods

    Directory of Open Access Journals (Sweden)

    Yan-Song Gao

    2010-06-01

    Full Text Available The non-cooperative or sequential events which occur during protein thermal denaturation are closely correlated with protein folding, stability, and physiological functions. In this research, the sequential events of human brain-type creatine kinase (hBBCK thermal denaturation were studied by differential scanning calorimetry (DSC, CD, and intrinsic fluorescence spectroscopy. DSC experiments revealed that the thermal denaturation of hBBCK was calorimetrically irreversible. The existence of several endothermic peaks suggested that the denaturation involved stepwise conformational changes, which were further verified by the discrepancy in the transition curves obtained from various spectroscopic probes. During heating, the disruption of the active site structure occurred prior to the secondary and tertiary structural changes. The thermal unfolding and aggregation of hBBCK was found to occur through sequential events. This is quite different from that of muscle-type CK (MMCK. The results herein suggest that BBCK and MMCK undergo quite dissimilar thermal unfolding pathways, although they are highly conserved in the primary and tertiary structures. A minor difference in structure might endow the isoenzymes dissimilar local stabilities in structure, which further contribute to isoenzyme-specific thermal stabilities.

  7. High levels of brain-type creatine kinase activity in human platelets and leukocytes: a genetic anomaly with autosomal dominant inheritance.

    Science.gov (United States)

    Arnold, Heidwolf; Wienker, Thomas F; Hoffmann, Michael M; Scheuerbrandt, Günter; Kemp, Katharina; Bugert, Peter

    2012-01-15

    The ectopic expression in peripheral blood cells of the brain-type creatine kinase (CKB) is an autosomal dominant inherited anomaly named CKBE (MIM ID 123270). Here, we characterized the CK activity in serum, platelets (PLT) and leukocytes (WBC) of 22 probands (from 8 unrelated families) and 10 controls. CK activity was measured by standard UV-photometry. Expression of the CKB gene was analyzed by real-time PCR and Western blotting. DNA sequencing including bisulfite treatment was used for molecular analysis of the CKB gene. Serum CK levels were comparable between probands and controls. CKBE probands revealed significantly higher CK activity in PLT (3.7 ± 2.7 versus 179.2 ± 83.0 U/10(12) PLT; p<0.001) and WBC (0.4 ± 0.3 versus 2.6 ± 2.1 U/10(9) WBC; p=0.004). Inhibitory anti-CKM antibodies did not affect CK activity indicating that the CK activity is generated exclusively by the CK-BB isoenzyme. CKB mRNA and protein levels were significantly higher in PLT and WBC from probands compared to controls. Re-sequencing of the entire CKB gene and methylation analysis of a CpG island revealed no alteration in CKBE probands. The genetic basis of CKBE remains unclear, however, we propose that a de-methylated CKB gene is inherited that leads to high CKB expression levels in myeloic precursor cells in the bone marrow. Copyright © 2011. Published by Elsevier Inc.

  8. 21 CFR 862.1215 - Creatine phosphokinase/creatine kinase or isoenzymes test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 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...

  9. Phenylbutazone radicals inactivate creatine kinase.

    Science.gov (United States)

    Miura, T; Muraoka, S; Fujimoto, Y

    2001-02-01

    Creatine kinase (CK) was used as a marker molecule to examine the side effect of damage to tissues by phenylbutazone (PB), an effective drug to treat rheumatic and arthritic diseases, with horseradish peroxidase and hydrogen peroxide (HRP-H(2)O2). PB inactivated CK during its interaction with HRP-H(2) O(2), and inactivated CK in rat heart homogenate. PB carbon-centered radicals were formed during the interaction of PB with HRP-H(2)O2. The CK efficiently reduced electron spin resonance signals of the PB carbon-centered radicals. The spin trap agent 2-methyl-2-nitrosopropane strongly prevented CK inactivation. These results show that CK was inactivated through interaction with PB carbon-centered radicals. Sulfhydryl groups and tryptophan residues in CK were lost during the interaction of PB with HRP-H(2)O2, suggesting that cysteine and tryptophan residues are oxidized by PB carbon-centered radicals. Other enzymes, including alcohol dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, but not lactate dehydrogenase, were also inactivated. Sulfhydryl enzymes seem to be sensitive to attack by PB carbon-centered radicals. Inhibition of SH enzymes may explain some of the deleterious effects induced by PB.

  10. Creatine kinase activity is associated with blood pressure

    NARCIS (Netherlands)

    Brewster, Lizzy M.; Mairuhu, Gideon; Bindraban, Navin R.; Koopmans, Richard P.; Clark, Joseph F.; van Montfrans, Gert A.

    2006-01-01

    BACKGROUND: We previously hypothesized that high activity of creatine kinase, the central regulatory enzyme of energy metabolism, facilitates the development of high blood pressure. Creatine kinase rapidly provides adenosine triphosphate to highly energy-demanding processes, including cardiovascular

  11. Creatine kinase isozyme expression in embryonic chicken heart

    NARCIS (Netherlands)

    Lamers, W. H.; Geerts, W. J.; Moorman, A. F.; Dottin, R. P.

    1989-01-01

    The distribution pattern of creatine kinase (EC 2.7.3.2) isozymes in developing chicken heart was studied by immunohistochemistry. Creatine kinase M, which is absent from adult heart, is transiently expressed between 4 and 11 days of incubation. During that period, numerous muscular cells in the

  12. Creatine kinase and creatine kinase subunit-B in coronary sinus blood in pacing-induced angina pectoris

    DEFF Research Database (Denmark)

    Bagger, J P; Ingerslev, J; Heinsvig, E M

    1982-01-01

    In nine out of 10 patients with angiographic documented coronary artery disease, pacing-induced angina pectoris provoked myocardial production of lactate, whereas no significant release of either creatine kinase or creatine kinase subunit-B to coronary sinus and peripheral venous blood could...

  13. Creatine-creatine phosphate shuttle modeled as two-compartment system at different levels of creatine kinase activity

    DEFF Research Database (Denmark)

    Fedosov, Sergey

    1994-01-01

    In order to characterize ADP-ATP and creatine-creatine phosphate (Cr-CrP) shuttles a minimal mathematical model with two compartments and cyclic turnover of matter was designed. The 'mitochondrial' compartment contained 'ATP-synthase' and 'mitochondrial ereatine kinase' (mitCK). The 'cytoplasmic......' compartment consisted of 'ATPase', 'cytoplasmic creatine kinase' (cytCK) and an 'ADP-binding structure'. The exchange of metabolites between these compartments was limited. Different levels of cytCK and mitCK expression as welt as different exchange rate constants between the compartments were assigned...

  14. Evaluation of Creatine Kinase Activity and Inorganic Phosphate ...

    African Journals Online (AJOL)

    Abstract. Background: Biochemical parameters vary in subjects with different hemoglobin phenotypes, compared with normal controls. Aim: The aim was to evaluate serum creatine kinase (CK) activity and inorganic phosphate concentrations in Nigerian adults with homozygous and heterozygous hemoglobin phenotypes.

  15. Creatine Kinase Clinical Considerations: Ethnicity, Gender and Genetics

    Science.gov (United States)

    2009-10-01

    phosphorylcreatine shuttle. Science. 211:448-452, 1981. [4] Brancaccio, P., N. Maffulli, R. Buonauro, and F.M. Limongelli. Serum enzyme monitoring in sports ...medicine. Clin Sports Med. 27:1-18, vii, 2008. [5] Brancaccio, P., N. Maffulli, and F.M. Limongelli. Creatine kinase monitoring in sport medicine. Br Med...Study. Obesity (Silver Spring). 14:14-18, 2006. [18] Kumbhare, D., W. Parkinson , and B. Dunlop. Validity of serum creatine kinase as a measure of

  16. Creatine supplementation: effects on blood creatine kinase activity responses to resistance exercise and creatine kinase activity measurement

    Directory of Open Access Journals (Sweden)

    Marco Machado

    2009-12-01

    Full Text Available The purpose of this study was to determine the effects of creatine supplementation and exercise on the integrity of muscle fiber, as well as the effect of the supplementation on the creatine kinase (CK assay measurement. Forty-nine sedentary individuals participated in a double-blind study and were divided into two groups: C (n=26 received 4x5-day packages of 0.6 g.kg-1 of body weight contained 50% of creatine + 50% of dextrose, and P (n=23 received packages containing only dextrose. On the first day the groups performed a 1RM test for bench press, seated row, leg extension, leg curl and leg press. On D7 they received the supplements. On the fourteenth day, they performed a training session of five exercises, each in three sets of ten repetitions at 75% of 1RM. Blood was collected before (D14 and after the exercise session (D15. Differing levels of blood creatine were tested to determine the influence on the assay measurements of CK. ANOVA and Tukey's post-hoc tests were used to compare groups and different times of study protocol (PO objetivo do presente estudo foi determinar o efeito da suplementação de creatina e do exercício na integridade das fibras musculares e, também, o efeito da suplementação na técnica de mensuração da atividade da creatina kinase (CK. Quarenta e nove sedentários participaram de um estudo duplo-cego e foram divididos em dois grupos: C (n=26 que receberam 4x5 dias embalagens com 0,6 g.kg-1 de massa corporal com 50% de creatina + 50% de dextrose, e P (n=23 que receberam embalagens contendo apenas dextrose. No primeiro dia, eles realizaram o teste de 1RM para os exercícios supino reto, remada sentada, cadeira extensora, mesa flexora, e leg press. No D7 receberam os suplementos. No décimo quarto dia eles realizaram uma sessão de treinos com os cinco exercícios, cada um com 3x10 repetições a 75% de 1RM. Sangue foi coletado antes (D14 e depois da sessão de exercícios (D15. Diferentes concentrações de

  17. Creatine kinase monitoring in sport medicine.

    Science.gov (United States)

    Brancaccio, Paola; Maffulli, Nicola; Limongelli, Francesco Mario

    2007-01-01

    AREAS OF GENERAL AGREEMENT: Total creatine kinase (CK) levels depend on age, gender, race, muscle mass, physical activity and climatic condition. High levels of serum CK in apparently healthy subjects may be correlated with physical training status, as they depend on sarcomeric damage: strenuous exercise that damages skeletal muscle cells results in increased total serum CK. The highest post-exercise serum enzyme activities are found after prolonged exercise such as ultradistance marathon running or weight-bearing exercises and downhill running, which include eccentric muscular contractions. Total serum CK activity is markedly elevated for 24 h after the exercise bout and, when patients rest, it gradually returns to basal levels. Persistently increased serum CK levels are occasionally encountered in healthy individuals and are also markedly increased in the pre-clinical stages of muscle diseases. Some authors, studying subjects with high levels of CK at rest, observed that, years later, subjects developed muscle weakness and suggested that early myopathy may be asymptomatic. Others demonstrated that, in most of these patients, hyperCKemia probably does not imply disease. In many instances, the diagnosis is not formulated following routine examination with the patients at rest, as symptoms become manifest only after exercise. Some authors think that strength training seems to be safe for patients with myopathy, even though the evidence for routine exercise prescription is still insufficient. Others believe that, in these conditions, intense prolonged exercise may produce negative effects, as it does not induce the physiological muscle adaptations to physical training given the continuous loss of muscle proteins. High CK serum levels in athletes following absolute rest and without any further predisposing factors should prompt a full diagnostic workup with special regards to signs of muscle weakness or other simple signs that, in both athletes and sedentary subjects

  18. Creatine kinase response to high-intensity aerobic exercise in adult-onset muscular dystrophy

    DEFF Research Database (Denmark)

    Andersen, Søren P; Sveen, Marie-Louise; Hansen, Regitze S

    2013-01-01

    We investigated the effect of high-intensity exercise on plasma creatine kinase (CK) in patients with muscular dystrophies.......We investigated the effect of high-intensity exercise on plasma creatine kinase (CK) in patients with muscular dystrophies....

  19. Differences in muscle pain and plasma creatine kinase activity after ...

    African Journals Online (AJOL)

    Objective. The aim of this study was to compare the acute changes in muscle pain and plasma creatine kinase (CK) activity following the 'up' and 'down' Comrades marathon. Design. This was a quasi-experimental design. Eleven male runners (39.7±9.3 years) completed the 'up' Comrades marathon, and 11 male runners ...

  20. Evaluation of Creatine Kinase Activity and Inorganic Phosphate ...

    African Journals Online (AJOL)

    Background: Biochemical parameters vary in subjects with different hemoglobin phenotypes, compared with normal controls. Aim: The aim was to evaluate serum creatine kinase (CK) activity and inorganic phosphate concentrations in Nigerian adults with homozygous and heterozygous hemoglobin phenotypes. Subjects ...

  1. Cardiac Troponin T and Creatine Kinase MB Fraction Levels Among ...

    African Journals Online (AJOL)

    Background: Stroke has been a global burden, with increasing morbidity and mortality. Serum cardiac troponin t (cTnT) and creatine kinase (CK-MB) fraction are reported to be elevated in patients admitted with acute ischaemic stroke and high level of these biomarkers indicated more severe stroke and neurologic deficit in ...

  2. Assessment of creatine kinase and lactate dehydrogenase activities ...

    African Journals Online (AJOL)

    Ina bid to investigate the influence of menopausal on coronary heart disease, plasma creatine kinase (CK) and lactate dehydrogenase (LDH) enzymes were analysed on a prospective cohort of 100 women attending Irrua Specialist Teaching Hospital (ISTH), Irrua, Edo state-Nigeria. They were divided into two groups; ...

  3. Changes in neutrophil count, creatine kinases and muscle soreness ...

    African Journals Online (AJOL)

    Objective. A primary objective was to examine circulating neutrophil count after repeated bouts of downhill running. An additional aim was to determine creatine kinase (CK) levels during the initial 12 hours, after repeated DHRs. Design. Eleven healthy, untrained Caucasian males performed 2 x 60 min bouts of DHR ...

  4. Creatine kinase is associated with failure of hypertension treatment

    NARCIS (Netherlands)

    Oudman, Inge; Kewalbansingh, Preschana V.; van Valkengoed, Irene; Zwinderman, Aeilko H.; Clark, Joseph F.; van Montfrans, Gert A.; Brewster, Lizzy M.

    2013-01-01

    Failure of hypertension treatment is a major clinical issue because of the high prevalence and the associated mortality risk. We have reported evidence that creatine kinase increases blood pressure through greater sodium retention and cardiovascular contractility, by rapidly providing ATP for these

  5. Serum creatine kinase and lactate dehydrogenase activities in ...

    African Journals Online (AJOL)

    Background and Objectives: There is the recognition of a pattern of elevations of serum enzymes in hyperthyroid and hypothyroid patients. The aims of this study were to determine the activities of serum creatine kinase (CK) and lactate deydrogenase (LDH) in thyroid disorders, and to evaluate the relationship between CK, ...

  6. Proteinase K processing of rabbit muscle creatine kinase

    DEFF Research Database (Denmark)

    Leydier, C; Andersen, Jens S.; Couthon, F

    1997-01-01

    of monomer cleavage. N-terminal sequencing of the K2 fragments from rabbit cytosolic and pig mitochondrial creatine kinase shows that these peptides begin with A328 and A324, respectively. Electrospray ionization mass spectrometry demonstrates that K2 peptide is composed of 53 residues (A328-K380). However...

  7. Periodontal status and serum creatine kinase levels among young ...

    African Journals Online (AJOL)

    Objectives: It is hypothesized that soccer players with periodontal disease exhibit raised serum creatine kinase (CK) levels as compared to those without periodontal disease. We assessed the clinical gingival status and serum CK levels among young soccer players. Materials and Methods: Demographic data were ...

  8. Exclusion of acute myocardial infarction. The value of measuring creatine kinase slope

    NARCIS (Netherlands)

    Bakker, A. J.; Koelemay, M. J.; van Vlies, B.; Gorgels, J. P.; Smits, R.; Tijssen, J. G.; Haagen, F. D.

    1995-01-01

    For the exclusion (and diagnosis) of acute myocardial infarction, we studied timed sequential (slope) measurements of creatine kinase and creatine kinase-MB catalytic activity concentration, creatine kinase-MB mass concentration, troponin T and myoglobin, using data from 242 patients consecutively

  9. Serum creatine kinase isoenzymes in children with osteogenesis imperfecta.

    Science.gov (United States)

    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.

  10. Creatine kinase activity in dogs with experimentally induced acute inflammation

    Directory of Open Access Journals (Sweden)

    Dimitrinka Zapryanova

    2013-01-01

    Full Text Available The main purpose of this study was to investigate the effect of acute inflammation on total creatine kinase (CK activity in dogs. In these animals, CK is an enzyme found predominantly in skeletal muscle and significantly elevated serum activity is largely associated with muscle damage. Plasma increases in dogs are associated with cell membrane leakage and will therefore be seen in any condition associated with muscular inflammation. The study was induced in 15 mongrel male dogs (n=9 in experimental group and n=6 in control group at the age of two years and body weight 12-15 kg. The inflammation was reproduced by inoculation of 2 ml turpentine oil subcutaneously in lumbar region. The plasma activity of creatine kinase was evaluated at 0, 6, 24, 48, 72 hours after inoculation and on days 7, 14 and 21 by a kit from Hospitex Diagnostics. In the experimental group, the plasma concentrations of the CK-activity were increased at the 48th hour (97.48±6.92 U/L and remained significantly higher (p<0.05 at the 72 hour (97.43±2.93 U/L compared to the control group (77.08±5.27 U/L. The results of this study suggest that the evaluation of creatine kinase in dogs with experimentally induced acute inflammation has a limited diagnostic value. It was observed that the creatine kinase activity is slightly affected by the experimentally induced acute inflammation in dogs.

  11. Creatine kinase deficiency in striated mouse muscle : biochemical and physiological studies

    NARCIS (Netherlands)

    Veld, Frank ter

    2003-01-01

    The balance between ATP energy demand and supply is essential in muscle cells. The creatine kinase system fulfils both a transporting and buffering role in muscle cells, whereby fluctuations in ATP free-energy demand can be counterbalanced. Removal of the creatine kinase proteins with the aid of

  12. Creatine kinase and its relationship with match performance in elite Australian Rules football.

    Science.gov (United States)

    Hunkin, Shannon L; Fahrner, Brendan; Gastin, Paul B

    2014-05-01

    The purpose of this study was to examine the relationships of pre-match creatine kinase on match performance measures in elite Australian Rules football. Repeated measures single cohort longitudinal. Twenty-nine elite Australian Rules football players were assessed across a competitive season. Creatine kinase was collected 24-36 h pre-match, and investigated against two measures of match performance; performance ranking scores (based on playing statistics) and coach's performance ratings. Multi-level modelling was applied and player characteristics were considered as moderating variables in the analysis. Average player pre-match creatine kinase was 485% greater than baseline values. Six-minute running performance was negatively related with average player pre-match creatine kinase (r=-0.432, p=0.019). Creatine kinase was negatively associated with performance ranking scores (r=-0.149, p=0.035), although increases in playing experience reversed this relationship (p=0.003). Coach's subjective ratings declined with elevations in pre-match creatine kinase (p=0.002). Increases in creatine kinase from baseline to pre-match indicate residual muscle damage. Small decrements in match performance were explained by increases in pre-match creatine kinase. However, player characteristics related to age and experience appear to be important moderating variables. Elevated pre-match creatine kinase likely represents a state of incomplete recovery from the preceding week, and over time, residual muscle damage. Creatine kinase monitoring may be most appropriately used with young and inexperienced players, and those with lower aerobic running performance to assist in the modulation of training and recovery loads to optimise match preparation and performance. Copyright © 2013 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  13. Creatine

    Science.gov (United States)

    ... taken by mouth to slow the worsening of amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease), osteoarthritis, rheumatoid arthritis, McArdle's ... body strength in both younger and older adults. Amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease). Taking creatine by mouth ...

  14. Creatine kinase-mediated ATP supply fuels actin-based events in phagocytosis.

    Directory of Open Access Journals (Sweden)

    Jan W P Kuiper

    2008-03-01

    Full Text Available Phagocytosis requires locally coordinated cytoskeletal rearrangements driven by actin polymerization and myosin motor activity. How this actomyosin dynamics is dependent upon systems that provide access to ATP at phagosome microdomains has not been determined. We analyzed the role of brain-type creatine kinase (CK-B, an enzyme involved in high-energy phosphoryl transfer. We demonstrate that endogenous CK-B in macrophages is mobilized from the cytosolic pool and coaccumulates with F-actin at nascent phagosomes. Live cell imaging with XFP-tagged CK-B and beta-actin revealed the transient and specific nature of this partitioning process. Overexpression of a catalytic dead CK-B or CK-specific cyclocreatine inhibition caused a significant reduction of actin accumulation in the phagocytic cup area, and reduced complement receptor-mediated, but not Fc-gammaR-mediated, ingestion capacity of macrophages. Finally, we found that inhibition of CK-B affected phagocytosis already at the stage of particle adhesion, most likely via effects on actin polymerization behavior. We propose that CK-B activity in macrophages contributes to complement-induced F-actin assembly events in early phagocytosis by providing local ATP supply.

  15. Exercise responses in patients with chronically high creatine kinase levels.

    Science.gov (United States)

    Cooper, Christopher B; Dolezal, Brett A; Neufeld, Eric V; Shieh, Perry; Jenner, John R; Riley, Marshall

    2017-08-01

    Elevated serum creatine kinase (CK) is often taken to reflect muscle disease, but many individuals have elevated CK without a specific diagnosis. How elevated CK reflects muscle metabolism during exercise is not known. Participants (46 men, 48 women) underwent incremental exercise testing to assess aerobic performance, cardiovascular response, and ventilatory response. Serum lactate, ammonia, and CK were measured at rest, 4 minutes into exercise, and 2 minutes into recovery. High-CK and control subjects demonstrated similar aerobic capacities and cardiovascular responses to incremental exercise. Those with CK ≥ 300 U/L exhibited significantly higher lactate and ammonia levels after maximal exercise, together with increased ventilatory responses, whereas those with CK ≥200 U/L but ≤ 300 U/L did not. We recommend measurement of lactate and ammonia profiles during a maximal incremental exercise protocol to help identify patients who warrant muscle biopsy to rule out myopathy. Muscle Nerve 56: 264-270, 2017. © 2016 Wiley Periodicals, Inc.

  16. Brain-type creatine kinase has a crucial role in osteoclast-mediated bone resorption.

    NARCIS (Netherlands)

    Chang, E.J.; Ha, J.; Oerlemans, F.; Lee, Y.J.; Lee, S.W.; Ryu, J.; Kim, H.J.; Lee, Y.; Kim, H.M.; Choi, J.Y.; Kim, J.Y.; Shin, C.S.; Pak, Y.K.; Tanaka, S.; Wieringa, B.; Lee, Z.H.; Kim, H.H.

    2008-01-01

    Osteoclasts differentiate from precursor cells of the monocyte-macrophage lineage and subsequently become activated to be competent for bone resorption through programs primarily governed by receptor activator of nuclear factor-kappaB ligand in cooperation with macrophage colony-stimulating factor.

  17. Ethnic differences in tissue creatine kinase activity: an observational study.

    Directory of Open Access Journals (Sweden)

    Lizzy M Brewster

    Full Text Available BACKGROUND: Serum creatine kinase (CK levels are reported to be around 70% higher in healthy black people, as compared to white people (median value 88 IU/L in white vs 149 IU/L in black people. As serum CK in healthy people is thought to occur from a proportional leak from normal tissues, we hypothesized that the black population subgroup has a generalized higher CK activity in tissues. METHODOLOGY/PRINCIPAL FINDINGS: We compared CK activity spectrophotometrically in tissues with high and fluctuating energy demands including cerebrum, cerebellum, heart, renal artery, and skeletal muscle, obtained post-mortem in black and white men. Based on serum values, we conservatively estimated to find a 50% greater CK activity in black people compared with white people, and calculated a need for 10 subjects of one gender in each group to detect this difference. We used mixed linear regression models to assess the possible influence of ethnicity on CK activity in different tissues, with ethnicity as a fixed categorical subject factor, and CK of different tissues clustered within one person as the repeated effect response variable. We collected post-mortem tissue samples from 17 white and 10 black males, mean age 62 y (SE 4. Mean tissue CK activity was 76% higher in tissues from black people (estimated marginal means 107.2 [95% CI, 76.7 to 137.7] mU/mg protein in white, versus 188.6 [148.8 to 228.4] in black people, p = 0.002. CONCLUSION: We found evidence that black people have higher CK activity in all tissues with high and fluctuating energy demands studied. This finding may help explain the higher serum CK levels found in this population subgroup. Furthermore, our data imply that there are differences in CK-dependent ATP buffer capacity in tissue between the black and the white population subgroup, which may become apparent with high energy demands.

  18. Creatine inhibits adipogenesis by downregulating insulin-induced activation of the phosphatidylinositol 3-kinase signaling pathway.

    Science.gov (United States)

    Lee, Nayeon; Kim, Inhee; Park, Soojeong; Han, Dasol; Ha, Soobong; Kwon, Mookwang; Kim, Juwan; Byun, Sung-Hyun; Oh, Wonil; Jeon, Hong Bae; Kweon, Dae-Hyuk; Cho, Jae Youl; Yoon, Keejung

    2015-04-15

    Creatine is a nitrogenous organic acid known to function in adenosine triphosphate (ATP) metabolism. Recent evidence indicates that creatine regulates the differentiation of mesenchymal stem cells (MSCs) in processes such as osteogenesis and myogenesis. In this study, we show that creatine also has a negative regulatory effect on fat cell formation. Creatine inhibits the accumulation of cytoplasmic triglycerides in a dose-dependent manner irrespective of the adipogenic cell models used, including a C3H10T1/2 MSC line, 3T3-L1 preadipocytes, and primary human MSCs. Consistently, a dramatic reduction in mRNA expression of adipogenic transcription factors, peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), glucose transporters, 1 and 4 (Glut1, Glut4), and adipocyte markers, aP2 and adipsin, was observed in the presence of creatine. Creatine appears to exert its inhibitory effects on adipogenesis during early differentiation, but not late differentiation, or proliferation stages through inhibition of the PI3K-Akt-PPARγ signaling pathway. In an in vivo model, administration of creatine into mice resulted in body mass increase without fat accumulation. In summary, our results indicate that creatine downregulates adipogenesis through inhibition of phosphatidylinositol 3-kinase (PI3K) activation and imply the potent therapeutic value of creatine in treating obesity and obesity-related metabolic disorders.

  19. Evolution of isozyme loci and their differential tissue expression. Creatine kinase as a model system.

    Science.gov (United States)

    Fisher, S E; Whitt, G S

    1978-10-27

    The phylogeny of the creatine kinase (CK, EC 2.7.3.2) isozyme loci and their differential tissue expressions were determined for representatives of 65 families of vertebrates, with emphasis on the fishes. The transition from the single creatine kinase locus, characteristic of certain echinoderms, to the two creatine kinase loci which are orthologous to those present in all vertebrates, occurred early in the chordate line. The majority of pre-teleostean fishes possesses only these two CK loci (A and C). These loci are relatively generalized in their tissue expressions which are variable among species of primitive fishes. The third and fourth creatine kinase loci (B and D) arose separately in the ancestors of the bony fishes and appear to be the result of regional genome duplications. Concomitant with the increase in the number of isozyme loci has been an increase in the specificity of their tissue expression. In the advanced teleost fishes the four CK loci are differentially expressed in a characteristic manner. The A2 isozyme predominates in skeletal muscle, the B2 isozyme in eye and brain, the C2 isozyme in stomach muscle, and the D2 isozyme is found exclusively in testis. We propose a phylogeny of the creatine kinase genes in the lower chordates based on the time of appearance of new CK loci, the sequence in which the loci achieve a tissue restricted expression, and the immunochemical relatedness of the orthologous and paralogous gene products.

  20. Inhibition of creatine kinase activity from rat cerebral cortex by 3-hydroxykynurenine.

    Science.gov (United States)

    Cornelio, Andrea Renata; Rodrigues-Junior, Valnês da Silva; Rech, Virginia Cielo; de Souza Wyse, Angela Terezinha; Dutra-Filho, Carlos Severo; Wajner, Moacir; Wannmacher, Clovis Milton Duval

    2006-12-08

    3-hydroxykynurenine, a tryptophan metabolite, is known to be potential neurotoxic in some neurodegenerative disorders. However, the molecular mechanisms of toxicity are not well understood. Creatine kinase plays a key role in energy metabolism of tissues with intermittently high and fluctuating energy requirements, such as nervous tissue. This study investigated the in vitro effect of 3-hydroxykynurenine on creatine kinase activity in the brain cortex of rats. The results indicated that low micromolar 3-hydroxykynurenine concentrations inhibit uncompetitively mitochondrial and cytosolic creatine kinase activities in a time and dose-dependent way. Inhibition was prevented, but not reversed by incubation with reduced glutathione, dithiothreitol and ascorbic acid plus trolox, suggesting adduct formation. The assay under nitrogen atmosphere suggested that the inhibition was caused by products of 3-hydroxykynurenine autoxidation. Determination of thiol groups suggested that adducts between the enzyme and autoxidation products of 3-hydroxykynurenine were not formed with sulfhydryl groups. The interaction plot between tryptophan and 3-hydroxykynurenine suggested different sites of action on creatine kinase with cross-inhibition. Considering the importance of creatine kinase for the maintenance of energy homeostasis in the brain, it is conceivable that an alteration of this enzyme activity may be one of the mechanisms by which 3-hydroxykynurenine might be neurotoxic.

  1. Creatine kinase in the serum of patients with acute infections of the central nervous system

    DEFF Research Database (Denmark)

    Peterslund, N A; Heinsvig, E M; Christensen, K D

    1985-01-01

    Serum creatine kinase was assessed in 94 consecutive patients without convulsions admitted to hospital due to suspicion of infection of the central nervous system. No reliable discrimination between patients with aseptic and those with bacterial meningitis was obtained. Patients with bacterial...... of bacterial meningitis. The highest serum CK value found in patients with encephalitis was 725 U/l. Reference values for control patients with meningism were 16-269 U/1. In a subset of 9 patients creatine kinase isoenzyme analysis was performed. In all cases only muscle type (MM) isoenzyme was found...

  2. Boehringer immunoinhibition procedure for creatine kinase-MB evaluated and compared with column ion-exchange chromatography

    NARCIS (Netherlands)

    ter Welle, H. F.; Baartscheer, T.; Fiolet, J. W.

    1983-01-01

    In determination of creatine kinase isoenzyme MB (CK-MB), the Boehringer immunoinhibition method gives a high and variable blank activity as compared with column-chromatography. Thus a correction must be applied. Furthermore, a second correction of 1% of total creatine kinase activity is necessary

  3. Stimulation of the creatine transporter SLC6A8 by the protein kinase mTOR.

    Science.gov (United States)

    Shojaiefard, Manzar; Christie, David L; Lang, Florian

    2006-03-24

    Cellular accumulation of creatine is accomplished by the Na(+), Cl(-), and creatine transporter CreaT (SLC6A8). The mammalian target of rapamycin (mTOR) is a kinase stimulating cellular nutrient uptake. The present experiments explored whether SLC6A8 is regulated by mTOR. In Xenopus oocytes expressing SLC6A8 but not in water injected oocytes, creatine-induced a current which was significantly enhanced by coexpression of mTOR. Kinetic analysis revealed that mTOR enhanced maximal current without significantly altering affinity. Preincubation of the oocytes for 32 h with rapamycin (50 nM) decreased the creatine-induced current and abrogated its stimulation by mTOR. The effect of mTOR on CreaT was blunted by additional coexpression of the inactive mutant of the serum and glucocorticoid-inducible kinase (K119N)SGK1 and mimicked by coexpression of wild type SGK1. In conclusion, mTOR stimulates the creatine transporter SLC6A8 through mechanisms at least partially shared by the serum and glucocorticoid-inducible kinase SGK1.

  4. Regulation of the creatine transporter by AMP-activated protein kinase in kidney epithelial cells

    Science.gov (United States)

    Li, Hui; Thali, Ramon F.; Smolak, Christy; Gong, Fan; Alzamora, Rodrigo; Wallimann, Theo; Scholz, Roland; Pastor-Soler, Núria M.; Neumann, Dietbert

    2010-01-01

    The metabolic sensor AMP-activated protein kinase (AMPK) regulates several transport proteins, potentially coupling transport activity to cellular stress and energy levels. The creatine transporter (CRT; SLC6A8) mediates creatine uptake into several cell types, including kidney epithelial cells, where it has been proposed that CRT is important for reclamation of filtered creatine, a process critical for total body creatine homeostasis. Creatine and phosphocreatine provide an intracellular, high-energy phosphate-buffering system essential for maintaining ATP supply in tissues with high energy demands. To test our hypothesis that CRT is regulated by AMPK in the kidney, we examined CRT and AMPK distribution in the kidney and the regulation of CRT by AMPK in cells. By immunofluorescence staining, we detected CRT at the apical pole in a polarized mouse S3 proximal tubule cell line and in native rat kidney proximal tubules, a distribution overlapping with AMPK. Two-electrode voltage-clamp (TEV) measurements of Na+-dependent creatine uptake into CRT-expressing Xenopus laevis oocytes demonstrated that AMPK inhibited CRT via a reduction in its Michaelis-Menten Vmax parameter. [14C]creatine uptake and apical surface biotinylation measurements in polarized S3 cells demonstrated parallel reductions in creatine influx and CRT apical membrane expression after AMPK activation with the AMP-mimetic compound 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside. In oocyte TEV experiments, rapamycin and the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranosyl 5′-monophosphate (ZMP) inhibited CRT currents, but there was no additive inhibition of CRT by ZMP, suggesting that AMPK may inhibit CRT indirectly via the mammalian target of rapamycin pathway. We conclude that AMPK inhibits apical membrane CRT expression in kidney proximal tubule cells, which could be important in reducing cellular energy expenditure and unnecessary creatine reabsorption under conditions of local

  5. Distribution of creatine kinase in the general population: Implications for statin therapy

    NARCIS (Netherlands)

    Brewster, Lizzy M.; Mairuhu, Gideon; Sturk, August; van Montfrans, Gert A.

    2007-01-01

    Background Eligible subjects with mildly elevated serum creatine kinase (CK) activity are often excluded before randomization in statin trials, but patients may potentially be misclassified as having hyperCKemia when inappropriate reference limits are used. Little information is usually given

  6. Contribution of creatine kinase MB mass concentration at admission to early diagnosis of acute myocardial infarction

    NARCIS (Netherlands)

    Bakker, A. J.; Gorgels, J. P.; van Vlies, B.; Koelemay, M. J.; Smits, R.; Tijssen, J. G.; Haagen, F. D.

    1994-01-01

    OBJECTIVE: To assess the diagnostic value at admission of creatine kinase MB mass concentration, alone or in combination with electrocardiographic changes, in suspected myocardial infarction. DESIGN: Prospective study of all consecutive patients admitted within 12 hours after onset of chest pain to

  7. Resistance artery creatine kinase mRNA and blood pressure in humans

    NARCIS (Netherlands)

    Karamat, Fares A.; Oudman, Inge; Ris-Stalpers, Carrie; Afink, Gijs B.; Keijser, Remco; Clark, Joseph F.; van Montfrans, Gert A.; Brewster, Lizzy M.

    2014-01-01

    Hypertension remains the main risk factor for cardiovascular death. Environmental and biological factors are known to contribute to the condition, and circulating creatine kinase was reported to be the main predictor of blood pressure in the general population. This was proposed to be because of

  8. The dilemma of the creatine kinase cardiospecific iso-enzyme (CK ...

    African Journals Online (AJOL)

    Serum creatine kinase iso-enzyme (CK-MB) levels were measured in 51 marathon runners before and after a 50 km marathon event. Ninety-five per cent of the runners were found to have pathologically elevated values, i.e. CK-MB concentrations were elevated to the range normally considered indicative of myocardial ...

  9. Creatine Kinase Activity Weakly Correlates to Volume Completed Following Upper Body Resistance Exercise

    Science.gov (United States)

    Machado, Marco; Willardson, Jeffrey M.; Silva, Dailson P.; Frigulha, Italo C.; Koch, Alexander J.; Souza, Sergio C.

    2012-01-01

    In the current study, we examined the relationship between serum creatine kinase (CK) activity following upper body resistance exercise with a 1- or 3-min rest between sets. Twenty men performed two sessions, each consisting of four sets with a 10-repetition maximum load. The results demonstrated significantly greater volume for the 3-min…

  10. The Effect of Creatine Kinase Inhibition on Contractile Properties of Human Resistance Arteries

    NARCIS (Netherlands)

    Taherzadeh, Zhila; Karamat, Fares A.; Ankum, Willem M.; Clark, Joseph F.; van Montfrans, Gert A.; van Bavel, Ed; Brewster, Lizzy M.

    2016-01-01

    Creatine kinase (CK) is a main predictor of blood pressure, and this is thought to largely depend on high resistance artery contractility. We previously reported an association between vascular contractility and CK in normotensive pregnancy, but pregnancy is a strong CK inducer, and data on human

  11. Dependence of myosin-ATPase on structure bound creatine kinase in cardiac myfibrils from rainbow trout and freshwater turtle

    DEFF Research Database (Denmark)

    Haagensen, L.; Jensen, D.H.; Gesser, Hans

    2008-01-01

    The influence of myofibrillar creatine kinase on the myosin-ATPase activity was examined in cardiac ventricular myofibrils isolated from rainbow trout (Oncorhynchus mykiss) and freshwater turtle (Trachemys scripta). The ATPase rate was assessed by recording the rephosphorylation of ADP by the pyr......The influence of myofibrillar creatine kinase on the myosin-ATPase activity was examined in cardiac ventricular myofibrils isolated from rainbow trout (Oncorhynchus mykiss) and freshwater turtle (Trachemys scripta). The ATPase rate was assessed by recording the rephosphorylation of ADP...... by the pyruvate kinase reaction alone or together with the amount of creatine formed, when myofibrillar bound creatine kinase was activated with phosphocreatine. The steady-state concentration of ADP in the solution was varied through the activity of pyruvate kinase added to the solution. For rainbow trout...... myofibrils at a high pyruvate kinase activity, creatine kinase competed for ADP but did not influence the total ATPase activity. When the ADP concentration was elevated within the physiological range by lowering the pyruvate kinase activity, creatine kinase competed efficiently and increased the ATPase...

  12. Serum concentrations of myoglobin, creatine kinase, lactate dehydrogenase and cardiac isoenzymes in euthyroid, hypothyroid and hyperthyroid subjects.

    Science.gov (United States)

    Roti, E; Bandini, P; Robuschi, G; Emanuele, R; Bolognesi, R; Ciarlini, E; Buzzonetti, P; Gnudi, A

    1980-01-01

    Serum concentrations of myoglobin, creatine kinase and lactate dehydrogenase were measured in 33 euthyroid, 21 hyperthyroid and 15 hypothyroid subjects. The results showed that myoglobin, creatine kinase and lactate dehydrogenase were increased and decreased in the hypo- and hyperthyroid states, respectively. In addition, the concentrations of myoglobin, creatine kinase and lactate dehydrogenase values were inversely related to both the thyroxine and triiodothyronine concentrations. To study the origin of the increased muscle protein values observed in hypothyroidism, the cardiac isoenzyme fractions were measured; the results obtained support the view that the muscle enzymes are mainly derived from skeletal muscles.

  13. Insights into the Phosphoryl Transfer Mechanism of Human Ubiquitous Mitochondrial Creatine Kinase.

    Science.gov (United States)

    Li, Quanjie; Fan, Shuai; Li, Xiaoyu; Jin, Yuanyuan; He, Weiqing; Zhou, Jinming; Cen, Shan; Yang, ZhaoYong

    2016-12-02

    Human ubiquitous mitochondrial creatine kinase (uMtCK) is responsible for the regulation of cellular energy metabolism. To investigate the phosphoryl-transfer mechanism catalyzed by human uMtCK, in this work, molecular dynamic simulations of uMtCK∙ATP-Mg2+∙creatine complex and quantum mechanism calculations were performed to make clear the puzzle. The theoretical studies hereof revealed that human uMtCK utilizes a two-step dissociative mechanism, in which the E227 residue of uMtCK acts as the catalytic base to accept the creatine guanidinium proton. This catalytic role of E227 was further confirmed by our assay on the phosphatase activity. Moreover, the roles of active site residues in phosphoryl transfer reaction were also identified by site directed mutagenesis. This study reveals the structural basis of biochemical activity of uMtCK and gets insights into its phosphoryl transfer mechanism.

  14. Decreased creatine kinase is linked to diastolic dysfunction in rats with right heart failure induced by pulmonary artery hypertension.

    Science.gov (United States)

    Fowler, Ewan D; Benoist, David; Drinkhill, Mark J; Stones, Rachel; Helmes, Michiel; Wüst, Rob C I; Stienen, Ger J M; Steele, Derek S; White, Ed

    2015-09-01

    Our objective was to investigate the role of creatine kinase in the contractile dysfunction of right ventricular failure caused by pulmonary artery hypertension. Pulmonary artery hypertension and right ventricular failure were induced in rats by monocrotaline and compared to saline-injected control animals. In vivo right ventricular diastolic pressure-volume relationships were measured in anesthetized animals; diastolic force-length relationships in single enzymatically dissociated myocytes and myocardial creatine kinase levels by Western blot. We observed diastolic dysfunction in right ventricular failure indicated by significantly steeper diastolic pressure-volume relationships in vivo and diastolic force-length relationships in single myocytes. There was a significant reduction in creatine kinase protein expression in failing right ventricle. Dysfunction also manifested as a shorter diastolic sarcomere length in failing myocytes. This was associated with a Ca(2+)-independent mechanism that was sensitive to cross-bridge cycling inhibition. In saponin-skinned failing myocytes, addition of exogenous creatine kinase significantly lengthened sarcomeres, while in intact healthy myocytes, inhibition of creatine kinase significantly shortened sarcomeres. Creatine kinase inhibition also changed the relatively flat contraction amplitude-stimulation frequency relationship of healthy myocytes into a steeply negative, failing phenotype. Decreased creatine kinase expression leads to diastolic dysfunction. We propose that this is via local reduction in ATP:ADP ratio and thus to Ca(2+)-independent force production and diastolic sarcomere shortening. Creatine kinase inhibition also mimics a definitive characteristic of heart failure, the inability to respond to increased demand. Novel therapies for pulmonary artery hypertension are needed. Our data suggest that cardiac energetics would be a potential ventricular therapeutic target. Copyright © 2015. Published by Elsevier Ltd.

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

    OpenAIRE

    Kucherenko, Ivan S; Soldatkin, Oleksandr O.; Lagarde, Florence; Jaffrezic-Renault, Nicole; Dzyadevych, S. V.; Soldatkin, A. P.

    2015-01-01

    International audience; 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 dete...

  16. [Study on the effect of mild moxibustion combined with cupping therapy on serum creatine kinase in gym-athletes].

    Science.gov (United States)

    Sun, De-li; Zang, A-bao; Xu, Ming; Li, Zhi-jun; Zhu, Xun-sheng; Zang, Yan; Chen, Da-long; Jiang, He-xin; Song, Yi; Hao, Wang-shen

    2007-01-01

    To probe into eliminating action of mild moxibustion combined with cupping therapy on athletic fatigue. Observe changes of serum creatine kinase activity in gym-athletes with once great intensity training or periodic great intensity training, and the interfering effect of mild moxibustion combined with cupping therapy. The mild moxibustion combined with cupping therapy has a significant promoting action on recovery of the increased serum creatine kinase activity induced by once great intensity training or periodic great intensity training in gym-athletes. The method has a better action of eliminating athletic fatigue.

  17. Is greater tissue activity of creatine kinase the genetic factor increasing hypertension risk in black people of sub-Saharan African descent?

    NARCIS (Netherlands)

    Brewster, L. M.; Clark, J. F.; van Montfrans, G. A.

    2000-01-01

    We postulate that the genetic factor increasing the propensity of black people of sub-Saharan African descent to develop high blood pressure is the relatively high activity of creatine kinase, predominantly in vascular and cardiac muscle tissue. Such greater activity of creatine kinase has been

  18. Stimulation of the creatine transporter SLC6A8 by the protein kinases SGK1 and SGK3.

    Science.gov (United States)

    Shojaiefard, Manzar; Christie, David L; Lang, Florian

    2005-09-02

    Creatine binds phosphate thus serving energy storage. Cellular creatine uptake is accomplished by the Na+,Cl-, creatine transporter CreaT (SLC6A8). The present study explored the regulation of SLC6A8 by the serum and glucocorticoid inducible kinase SGK1, a kinase upregulated during ischemia. In Xenopus oocytes expressing SLC6A8 but not in water injected oocytes creatine induced a current which was significantly enhanced by coexpression of wild type SGK1 and constitutively active (S422D)SGK1, but not inactive (K127N)SGK1. Kinetic analysis revealed that (S422D)SGK1 enhanced maximal current without significantly altering affinity. The effect of SGK1 was mimicked by the constitutively active isoform (S419D)SGK3 but not by inactive (K119N)SGK3, wild type isoform SGK2 or constitutively active related kinase (T308D,S473D)PKB. In conclusion, the kinases SGK1 and SGK3 increase SLC6A8 activity by increasing the maximal transport rate of the carrier. Deranged SGK1 and/or SGK3 dependent regulation of SLC6A8 may affect energy storage particularly in skeletal muscle, heart, and neurons.

  19. PUTATIVE CREATINE KINASE M-ISOFORM IN HUMAN SPERM IS IDENTIFIED AS THE 70-KILODALTON HEAT SHOCK PROTEIN HSPA2

    Science.gov (United States)

    THE PUTATIVE CREATINE KINASE M-ISOFORM IN HUMAN SPERM IS IDENTIFIED AS THE 70 kDa HEAT SHOCK PROTEIN HSPA2* Gabor Huszar1, Kathryn Stone2, David Dix3 and Lynne Vigue11The Sperm Physiology Laboratory, Department of Obstetrics and Gynecology, 2 W.M. Keck Foundatio...

  20. Decreased creatine kinase is linked to diastolic dysfunction in rats with right heart failure induced by pulmonary artery hypertension

    NARCIS (Netherlands)

    Fowler, E.D.; Benoist, D.; Drinkhill, M.J.; Stones, R.; Helmes, M.H.B.; Wüst, R.C.I.; Stienen, G.J.M.; Steele, D.S.; White, E.

    2015-01-01

    Our objective was to investigate the role of creatine kinase in the contractile dysfunction of right ventricular failure caused by pulmonary artery hypertension. Pulmonary artery hypertension and right ventricular failure were induced in rats by monocrotaline and compared to saline-injected control

  1. Diagnostic value of serum creatine kinase-BB for acute meningitis in adults

    Directory of Open Access Journals (Sweden)

    Seyed Mohammad Alavi

    2017-01-01

    Full Text Available Objective: To find out an easy and feasible test instead of cerebrospinal fluid analysis for the diagnosis of acute meningitis. Methods: This cross-sectional study was conducted in 2013 in Ahvaz, a city located in the Southwest Iran including 75 patients with clinical diagnosis of fever, headache, vomiting and neck stiffness suspected to have acute meningitis based on cerebrospinal fluid analysis. In the beginning, the patients were divided into two categories as acute meningitis, and non-acute meningitis. Then, 5 L of blood was taken from each patient to determine serum creatine kinase isoenzyme-BB by using ELISA method. After that, the related data including demographics, clinical and laboratory results were analyzed by SPSS software version 16 using Chi-square test for qualitative variables and student’s t-test for quantitative variables. Results: Among the total 75 patients, 37 (49.3% were males and 38 (50.7% were females including 45 patients (60% with acute meningitis and 30 patients (40% without acute meningitis. On the other hand, CK-BB serum levels in acute meningitis and non-acute meningitis patients were 18.23 ± 7.56 and 2.67 ± 1.62, respectively, so significant difference was found between acute meningitis group and non-acute meningitis group (P < 0.000 1. Conclusions: Serum creatine kinase isoenzyme-BB test is a useful test to differentiate acute meningitis from non-acute meningitis among suspected cases of meningitis disease, so measuring the CK-BB serum level in Iran's health system with an expanded health setting especially in remote areas will be useful and helpful in prompt diagnosis and treatment of the acute meningitis.

  2. The influence of individualizing physical loads on speed, creatine kinase activity and lactate dehydrogenase in football players.

    Directory of Open Access Journals (Sweden)

    2008-06-01

    Full Text Available Introduction: One of the most important training problems in: contemporary football is speed preparation of a player for the season and the ability of keeping it on the same, relatively high level throughout the starting period [1]. The main process used for re-synthesis ATP during single, short-lasting efforts of maximal intensity, is decomposition of phospho-creatine under the influence of creatine kinase enzyme. Physical loads imposed during speed trainings often exceed the possibility of producing energy from phosphogenic reserve through oxygen - lactate free processes, because the supply of phospho-creatine is used very quickly. In such circumstances the lacking energy is refilled through processes called oxygen free glicolise with the help of lactate dehydrogenase enzyme. The aim of the work was to answer the question:

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

    Science.gov (United States)

    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.

  4. Decrements in neuromuscular performance and increases in creatine kinase impact training outputs in elite soccer players.

    Science.gov (United States)

    Malone, Shane; Mendes, Bruno; Hughes, Brian; Roe, Mark; Devenney, Simon; Collins, Kieran; Owen, Adam

    2017-05-23

    The aim of the current investigation was to understand the impact of pre-training neuromuscular performance and creatine kinase status on subsequent training performance in elite soccer players. Thirty soccer players (age: 25.3 ± 3.1 years; height: 183 ± 7 cm; mass: 72 ± 7 kg) were involved in this observational study. Each morning prior to training, players completed assessments for neuromuscular performance (countermovement jump; CMJ) and creatine kinase (CK) levels. Global positioning technology provided external load: total distance, high-speed distance, sprint distance, accelerations, decelerations, average metabolic power, explosive distance, high metabolic power distance (>25.5 W·kg). Mixed-effect linear models revealed significant effects for CK and CMJ Z-score on total high speed distance, very high speed distance, accelerations, decelerations, explosive distance and maximal velocity. Effects are reported with 90% confidence limits. A CK Z-score of +1 corresponded to a -5.5 ± 1.1, -3.9 ± 0.5, -4.3 ± 2.9%, 4.1 ± 2.9%, 3.1 ± 2.9% and -4.6 ± 1.9%, reduction in total high-speed distance, very high-speed distance, accelerations, decelerations, explosive distance and maximal velocity respectively. CMJ Z-score of -1 corresponded to a -3.5 ± 1.1, -2.9 ± 0.5, -2.1 ± 1.4, -5.3 ± 2.9%, 3.8 ± 2.9%, 1.1 ± 2.9% and -5.6 ± 1.2% reduction in these external load measures. Magnitude-based analysis revealed that the practical size of the effect of a pre-training CMJ Z-score of -1 and CK Z-score of +1 would have on total high speed distance, very high speed distance, high metabolic power distance (>25.5 W·kg), accelerations, decelerations, explosive distance and maximal velocity was likely negative. The results of this study suggest that systematic pre-training monitoring of neuromuscular and muscle stress within soccer cohorts can provide coaches with information about the training output that can be expected from individual players during a training

  5. Administration of Harmine and Imipramine Alters Creatine Kinase and Mitochondrial Respiratory Chain Activities in the Rat Brain

    Directory of Open Access Journals (Sweden)

    Gislaine Z. Réus

    2012-01-01

    Full Text Available The present study evaluated mitochondrial respiratory chain and creatine kinase activities after administration of harmine (5, 10, and 15 mg/kg and imipramine (10, 20, and 30 mg/kg in rat brain. After acute treatment occurred an increase of creatine kinase in the prefrontal with imipramine (20 and 30 mg/kg and harmine in all doses, in the striatum with imipramine (20 and 30 mg/kg and harmine (5 and 10 mg/kg; harmine (15 mg/kg decreased creatine kinase. In the chronic treatment occurred an increase of creatine kinase with imipramine (20 mg/kg, harmine (5 mg/kg in the prefrontal with imipramine (20 and 30 mg/kg and harmine (5 and 10 mg/kg in the striatum. In the acute treatment, the complex I increased in the prefrontal with harmine (15 mg/kg and in the striatum with harmine (10 mg/kg; the complex II decreased with imipramine (20 and 30 mg/kg in the striatum; the complex IV increased with imipramine (30 mg/kg in the striatum. In the chronic treatment, the complex I increased with harmine (5 mg/kg in the prefrontal; the complex II increased with imipramine (20 mg/kg in the prefrontal; the complex IV increased with harmine (5 mg/kg in the striatum. Finally, these findings further support the hypothesis that harmine and imipramine could be involved in mitochondrial function.

  6. Effects of yoga exercise on maximum oxygen uptake, cortisol level, and creatine kinase myocardial bond activity in female patients with skeletal muscle pain syndrome

    OpenAIRE

    Ha, Min-Sung; Baek, Yeong-Ho; Kim, Jong-Won; Kim, Do-Yeon

    2015-01-01

    [Purpose] This study analyzed the effects of yoga exercise on maximum oxygen uptake, cortisol level, and creatine kinase myocardial bond activity in female patients with skeletal muscle pain syndrome. [Subjects] The subjects were 24 female patients with skeletal muscle pain syndrome. [Methods] The subjects were divided into 2 groups: a yoga exercise group (n = 12) and a non-exercise control group (n = 12). Body composition, maximum oxygen uptake, cortisol level, and creatine kinase myocardial...

  7. Effects of intermittent exercise on cardiac troponin I and creatine kinase-MB

    Directory of Open Access Journals (Sweden)

    Nader Rahnama

    2011-01-01

    Full Text Available Objectives: The aim of this study was to examine the influence of high-intensity intermittent exercise and carbohydrate supplementation on cardiac troponin I (cTnI and creatine kinase-MB (CK-MB in soc-cer players. Methods: Twelve elite soccer players were selected and divided equally into three groups of carbohydrate (CHO, placebo (P and control (C. Blood samples were taken in six phases and were analyzed with the chemiluminescence method. Results: Results showed that three bouts of 90-min exercise along with carbohydrate supplementation did not have any significant effect on the level of cTnI indices. However, there was a significant differ-ence in CK-MB values after the second and third sessions compared with the first day (P < 0.05. Conclusion: In summary, exercises with less duration and intensity like soccer do not seem to be effective on cTnI and CK-MB. When the overall intensity of exercise was moderate, it appeared that carbohy-drate supplementation had less effect on the alteration of biochemical markers of the myocardial muscle.

  8. Elevated Creatine Kinase due to Potential Drug Interaction With Ticagrelor and Atorvastatin.

    Science.gov (United States)

    Beavers, Janna C

    2017-01-01

    Ticagrelor and atorvastatin are commonly used medications in the management of acute coronary syndrome and percutaneous intervention. This is a report of a patient case of a potential drug interaction leading to the use of alternative therapy. A 58-year-old male presented for cardiac catheterization following an abnormal stress test. He underwent placement of a drug-eluting stent and was started on ticagrelor. Three months later, he was noted to have elevated creatine kinase (CK), thought to be related to a potential drug-drug interaction between ticagrelor and atorvastatin. Ticagrelor was discontinued and he was successfully transitioned to clopidogrel. CK returned to normal within weeks of this change. Pharmacokinetic studies have demonstrated a potential interaction between ticagrelor and atorvastatin but have not been deemed clinically significant. To date, only one other case report has been published discussing this interaction and consideration of alternative therapy. This case report is unique, with ticagrelor being the only new medication added prior to the abnormal CK finding. A probable drug-drug interaction occurred with concomitant ticagrelor and atorvastatin. While this interaction may not always be clinically significant, it is reasonable to consider in patients who present with signs and symptoms of adverse effects.

  9. Individual analysis of creatine kinase concentration in Brazilian elite soccer players

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    Adriano Lima Alves

    2015-04-01

    Full Text Available OBJECTIVE: to determine the individual profile of blood concentration of creatine kinase CK in elite soccer players as well as to analyze the CK concentrations in different periods during the Professional Brazilian Championship. METHODS: resting CK of 17 soccer players was evaluated before the competition pre-season and after the matches 36 and 46 hours after the games CKGame for the individual blood CK. The Chi-square test was used to analyze the individual CK during the season. The competitive season was divided into three periods: initial, intermediate and final. The one-way ANOVA with repeated measurements followed by post hoc Student-Newman-Keuls test was used to compare the individual CK of each soccer player in each competitive period. The significance level was set at p<0.05. RESULTS: the highest frequency of individual CK was found in the second quartile 71 observations and the lowest frequency in the first 26 observations and the fourth quartile 40 observations compared to the expected number of 45.8 x2=22.21. CK concentrations were lower in the intermediate mean=66.99% and final mean=60.21% periods than in the initial period mean=89.33%. CONCLUSION: soccer players did not show elevated muscle damage and probably a muscle adaptation occurred in the competition, due to the reduction of CK concentrations observed.

  10. Creatine-kinase and dialysis patients, a helpful tool for stratifying cardiovascular risk?

    Science.gov (United States)

    Quiroga, Borja; Vega, Almudena; Abad, Soraya; Villaverde, Maite; Reque, Javier; López-Gómez, Juan Manuel

    2016-01-01

    Hemodialysis patients have an enhanced risk for cardiovascular events. Cardiac biomarkers provide useful information for stratifying their risk. However the prognosis value of creatine kinase MB isoenzyme (CKMB) has not yet been validated in this population. The aim of the present study is to determine the predictable value of CK-MB in hemodialysis. A cohort of 211 hemodialysis patients (58.3% male, median age 73 (60-80) years) were followed for 39 (19-56) months. Cardiac biomarkers including CKMB were recorded at baseline. Factors associated to CKMB and prognosis value of this biomarker was studied. The median value of CKMB was 1 (1-2) ng/mL with no patient exceeding normal laboratory values. Previous heart disease, diabetes mellitus, peripheral vascular disease and systolic and diastolic dysfunction were associated with higher levels of CKMB. Ninety-four patients (44.5%) cardiovascular events were recorded. CKMB levels ≥2ng/mL was independently associated to cardiovascular events during the follow up after adjusting. Adding CKMB to a model including several variables for predicting cardiovascular events, resulted in 17% improvement in risk discrimination (IDI) with a relative IDI of 9.9% (p=0.04). CKMB is a good marker for stratifying cardiovascular risk in hemodialysis patients and adds prognosis information to other well known independent predictors for cardiovascular events. Copyright © 2015 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  11. Effects of osmolytes on Pelodiscus sinensis creatine kinase: a study on thermal denaturation and aggregation.

    Science.gov (United States)

    Wang, Wei; Lee, Jinhyuk; Jin, Qin-Xin; Fang, Nai-Yun; Si, Yue-Xiu; Yin, Shang-Jun; Qian, Guo-Ying; Park, Yong-Doo

    2013-09-01

    The protective effect of osmolytes on the thermal denaturation and aggregation of Pelodiscus sinensis muscle creatine kinase (PSCK) was investigated by a combination of spectroscopic methods and thermodynamic analysis. Our results demonstrated that the addition of osmolytes, such as glycine and proline, could prevent thermal denaturation and aggregation of PSCK in a concentration-dependent manner. When the concentration of glycine and proline increased in the denatured system, the relative activation was significantly enhanced; meanwhile, the aggregation of PSCK during thermal denaturation was decreased. Spectrofluorometer results showed that glycine and proline significantly decreased the tertiary structural changes of PSCK and that thermal denaturation directly induced PSCK aggregation. In addition, we also built the 3D structure of PSCK and osmolytes by homology models. The results of computational docking simulations showed that the docking energy was relatively low and that the clustering groups were spread to the surface of PSCK, indicating that osmolytes directly protect the surface of the protein. P. sinensis are poikilothermic and quite sensitive to the change of ambient temperature; however, there were few studies on the thermal denaturation of reptile CK. Our study provides important insight into the protective effects of osmolytes on thermal denaturation and aggregation of PSCK. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. [Compulsory measures and pathological creatine kinase levels in psychiatric in-patients].

    Science.gov (United States)

    Grube, Michael

    2014-04-01

    The aim of this study was to investigate the association of compulsory measures (CM) with pathological Creatine Kinase (CK) levels in 317 patients admitted to a secure psychiatric ward. The assumptions is that CK-activity is increased prior to administration of CM because increases in CK-levels may represent aggressive behaviour as precursors of a higher chance of administrating CM. The CK-levels were assessed immediately following admission. During the course of the patients' stay the frequency of different CM was assessed by the use of the Staff Observation Aggression Scale. In a CHAID analysis pathological CK-levels were associated with subsequent administration of CM. Lifetime aggression and main diagnosis were associated with administration of CM as well. In a ROC analysis concerning pathological CK-activity the AUC for subsequent administration of CM was 70.5 % with a sensitivity of 73.5 % and a specifity of 67.5 %. Despite some methodological shortcomings the study indicates that it could be useful to measure CK-activity at the time of admission because pathological levels may indicate an increased probability of administration of CM subsequent to aggressive behaviour. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Molecular Characterization and Expression Analysis of Creatine Kinase Muscle ( Gene in Horse

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    Kyong-Tak Do

    2015-12-01

    Full Text Available Since ancient days, domestic horses have been closely associated with human civilization. Today, horse racing is an important industry. Various genes involved in energy production and muscle contraction are differentially regulated during a race. Among them, creatine kinase (CK is well known for its regulation of energy preservation in animal cells. CK is an iso-enzyme, encoded by different genes and expressed in skeletal muscle, heart, brain and leucocytes. We confirmed that the expression of CK-M significantly increased in the blood after a 30 minute exercise period, while no considerable change was observed in skeletal muscle. Analysis of various tissues showed an ubiquitous expression of the CK-M gene in the horse; CK-M mRNA expression was predominant in the skeletal muscle and the cardiac muscle compared to other tissues. An evolutionary study by synonymous and non-synonymous single nucleotide polymorphism ratio of CK-M gene revealed a positive selection that was conserved in the horse. More studies are warranted in order to develop the expression of CK-M gene as a biomarker in blood of thoroughbred horses.

  14. Measurement of Creatine kinase and Aspartate aminotransferase in saliva of dogs: a pilot study.

    Science.gov (United States)

    Tvarijonaviciute, Asta; Barranco, Tomas; Rubio, Monica; Carrillo, Jose Maria; Martinez-Subiela, Silvia; Tecles, Fernando; Carrillo, Juana Dolores; Cerón, José J

    2017-06-09

    Muscle enzymes in saliva have been reported to be possible markers of heart and muscle damage in humans. The aim of this study was to assess if Creatine kinase (CK) and Aspartate aminotransferase (AST) activities could be measured in canine saliva, and to evaluate their possible changes in situations of muscle damage. The spectrophotometric assays for CK and AST measurement in saliva of dogs showed intra- and inter-assay imprecision lower than 1 and 16% and coefficients of correlation close to 1 in linearity under dilution tests. Healthy dogs showed activities in saliva of CK between 27 and 121 U/L and AST between 46 and 144 U/L, whereas in saliva of dogs with muscle damage CK ranged between 132 and 3862 U/L and AST between 154 and 4340 U/L. Positive moderate correlations were found between saliva and serum activities of the two enzymes (CK, r = 0.579; P = 0.001; AST, r = 0.674; P = 0.001). CK and AST activities can be measured in canine saliva with commercially available spectrophotometric assays. In addition these enzymes show higher values in saliva of dogs with muscle damage and their values are moderately correlated with those of serum.

  15. Delirium and High Creatine Kinase and Myoglobin Levels Related to Synthetic Cannabinoid Withdrawal

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    Ahmet Bulent Yazici

    2017-01-01

    Full Text Available Synthetic cannabinoids (SCs are included in a group of drugs called new psychoactive substances. Effects of SCs on the central nervous system are similar to other cannabinoids, but 2–100 times more potent than marijuana. Thus, addiction and withdrawal symptoms are more severe than natural cannabinoids. Withdrawal symptoms of SCs were reported in the literature previously. But there is no report about SC withdrawal delirium and its treatment. Several studies reported that agonists of CB1 receptors play a role in GABA and glutamatergic neurotransmission, which is similar to the effects of alcohol on GABA and glutamatergic receptors. Previous studies on alcohol delirium cases suggested that elevated creatine kinase (CK can be a marker of progress. This study reports delirium and high serum CK levels related to SC withdrawal and offers a treatment with benzodiazepine for them. We described two cases treated in our inpatient clinic about SC withdrawal with increase of serum CK level and other laboratory parameters. One of them demonstrated delirium symptoms and the other did not with early rapid treatment.

  16. Creatine kinase in relation to body fat in a Caucasian overweight and obese population.

    Science.gov (United States)

    Bekkelund, Svein I; Jorde, Rolf

    2017-12-19

    We investigated the association between serum creatine kinase (CK) and body fat mass in an overweight and obese population. In this cross-sectional study, 454 Caucasian overweight and obese individuals recruited from a medical outpatient clinic and via newspaper advertising underwent dual-energy X-ray absorptiometry (DEXA). Serum CK was obtained along with supplementary blood samples. This report is based on a secondary analysis from a previous randomized controlled trial treating obesity with vitamin D3. Serum CK correlated negatively with body fat mass in men (r = -.18, p = .025) but not in women (r = -.11, p = .069). An insignificant negative trend for logCK across quartiles of fat mass in men was found (p = .098). CK did not associate significantly with lean mass, but lean mass correlated positively with fat mass in both groups (p fat mass in men. Fat mass decreased with 7.83 kg per unit logCK increase when adjusted for age and lean mass (95% CI -12.3 to -3.3, p = .001). These data support the view that circulating CK interacts with obesity in a favourable way independent of its muscular connection in men. CK was not associated with fat mass in women.

  17. Hydrogen peroxide (H2O2) irreversibly inactivates creatine kinase from Pelodiscus sinensis by targeting the active site cysteine.

    Science.gov (United States)

    Wang, Wei; Lee, Jinhyuk; Hao, Hao; Park, Yong-Doo; Qian, Guo-Ying

    2017-12-01

    Creatine kinase (EC 2.7.3.2, CK) plays an important role in cellular energy metabolism and homeostasis by catalysing the transfer of phosphate between ATP and creatine phosphate. In this study, we investigated the effects of H2O2 on PSCKM (muscle type creatine kinase from Pelodiscus sinensis) by the integrating method between enzyme kinetics and docking simulations. We found that H2O2 strongly inactivated PSCKM (IC50=0.25mM) in a first-order kinetic process, and targeted the active site cysteine directly. A conformational study showed that H2O2 did not induce the tertiary structural changes in PSCKM with no extensive exposure of hydrophobic surfaces. Sequential docking simulations between PSCKM and H2O2 indicated that H2O2 interacts with the ADP binding region of the active site, consistent with experimental results that demonstrated H2O2-induced inactivation. Our study demonstrates the effect of H2O2 on PSCKM enzymatic function and unfolding, and provides important insight into the changes undergone by this central metabolic enzyme in ectothermic animals in response to the environment. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Incomplete filling of lithium heparin tubes affects the activity of creatine kinase and gamma-glutamyltransferase.

    Science.gov (United States)

    Lippi, G; Avanzini, P; Cosmai, M; Aloe, R; Ernst, D

    2012-01-01

    This study aims to assess whether or not incomplete filling of primary lithium heparin tubes may influence the activity of creatine kinase (CK), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT). Blood was drawn from 20 healthy volunteer using an identical sequence of tubes. First, a 6 mL, 13 x 100 mm 14 unit/mL lithium heparin Vacuette was filled and discharged. Then, three identical lithium heparin Vacuette tubes were filled, one to the nominal volume (i.e., full-draw tube), another with half of the nominal volume (half-draw tube) and the last with one-third of the nominal volume (low-draw tube). The plasma was separated and tested for CK (non-activated by N-acetylcysteine), AST and ALT on a Beckman Coulter Unicel DxC 800. Tests for CK were performed with a different reagent on a Beckman Coulter AU5800 (activated by N-acetylcysteine). Although the concentrations of ASL and ALT measured on the Unicel DxC and that of CK measured on the AU5800 did not change significantly across the different specimens, those of CK and GGT measured on the Unicel DxC 800 were significantly increased in the half-draw and low-draw tubes. The percentage bias of CK on the Unicel DxC 800 (using Bland Altman plots) was 3.3% and 7.9% for the half-draw and low-draw tubes, respectively, whereas that of GGT was 10.3% and 16.6% for the half-draw and low-draw tubes, respectively. These results suggest that short-draw lithium heparin tubes might be unsuitable for testing GGT and CK using specific combinations of reagents and instrumentation.

  19. Creatine Kinase and Lactate Dehydrogenase Responses After Different Resistance and Aerobic Exercise Protocols

    Directory of Open Access Journals (Sweden)

    Callegari Gustavo A.

    2017-08-01

    Full Text Available The aim of this study was to investigate the responses of creatine kinase (CK and lactate dehydrogenase (LDH after performing different resistance and aerobic exercise protocols. Twelve recreationally trained men (age, 23.2 ± 5.6 years; body mass, 84.3 ± 9.3 kg; body height, 178.9 ± 4.5 cm; and BMI, 26.3 ± 2.3 kg·m2 volunteered to participate in this study. All subjects were randomly assigned to four experimental protocols (crossover: (a aerobic training at 60% of VO2max, (b aerobic training at 80% of VO2max, (c a resistance exercise (RE session with a bi-set protocol, and (d an RE session with a multiple sets protocol. Blood samples were collected before, immediately after and 24 hours following the experimental protocols. After 24 hours, there was a significant increase in CK for the 80% of VO2max protocol vs. the bi-set RE session (p = 0.016. Immediately after the protocols, we observed a significant increase in LDH among certain groups compared to others, as follows: multiple sets RE session vs. 60% of VO2max, bi-set RE session vs. 60% of VO2max, multiple sets RE session vs. 80% of VO2max, and bi-set RE session vs. 80% of VO2max (p = 0.008, p = 0.013; p = 0.002, p = 0.004, respectively. In conclusion, aerobic exercise performed at 80% of VO2max appears to elevate plasma CK levels more than bi-set RE sessions. However, the bi-set and multiple sets RE sessions appeared to trigger greater levels of blood LDH compared to aerobic protocols performed at 60% and 80% of VO2max.

  20. Ethnicity, aggression and serum creatine kinase in hospitalized male forensic patients.

    Science.gov (United States)

    Spitz, R T; Hillbrand, M; Foster, H G; Svetina, C J

    1997-01-01

    This study examined the relationship of serum creatine kinase (CK) levels with aggressive behavior as a function of psychosis and ethnicity in a sample of violent forensic patients. CK levels were determined on admission in a sample of 195 males consecutively admitted to a forensic hospital. The patients' aggressive behavior during their hospital stay was monitored using the Overt Aggression Scale (OAS). All data for this study was archival and gathered from hospital records. Multivariate analysis of variance was used to examine whether African-American and Caucasian patients differed in serum CK levels and severity, frequency, and type (verbal vs physical) of aggression. T-tests were performed to compare ethnic groups in terms of age, weight, height, systolic and diastolic blood pressure. All patients who had been in restraints, had been administered intramuscular medications, had a history of drug or alcohol abuse, and were classified as schizophrenic were compared using chi-square analysis. For each of these variables further comparisons were made of CK levels between African-American and Caucasian patients. Mean serum CK in African-American patients was 64% higher than in Caucasians. African Americans displayed significantly greater physical aggression than Caucasian patients. In addition, African-American patients with a diagnosis of schizophrenia had significantly higher CK levels than African Americans with other diagnoses, with no significant differences related to schizophrenia noted within the Caucasian group. No significant differences in aggressive behavior related to schizophrenia were found in African-American patients. This study confirms the findings of previous reports which observed higher CK levels in African Americans than in Caucasians. It is also proposed that a confluence of physiologic and psychosocial factors may affect biological marker presentation, particularly as manifest in CK differences between ethnic groups.

  1. How the ankyrin and SOCS box protein, ASB9, binds to creatine kinase.

    Science.gov (United States)

    Balasubramaniam, Deepa; Schiffer, Jamie; Parnell, Jonathan; Mir, Stephan P; Amaro, Rommie E; Komives, Elizabeth A

    2015-03-03

    The ankyrin repeat and SOCS box (ASB) family is composed of 18 proteins and belongs to the suppressor of cytokine signaling (SOCS) box protein superfamily. The ASB proteins function as the substrate-recognition subunits of ECS-type (ElonginBC-Cullin-SOCS-box) Cullin RING E3 ubiquitin ligase (CRL) complexes that specifically transfer ubiquitin to cellular proteins targeting them for degradation by the proteasome. ASB9 binds to creatine kinase (CK) and targets it for degradation; however, the way in which ASB9 interacts with CK is not yet known. We present a complete characterization of the binding of ASB9 to CK. One ASB9 molecule binds to a dimer of CK. The binding affinity of ASB9(1-252) was extremely tight, and no dissociation could be observed. Deletion of the 34 N-terminal amino acids forming ASB9(35-252) resulted in weakening of the binding, so that a binding affinity of 2.6 nM could be measured. Amide hydrogen-deuterium exchange (HDXMS) experiments showed that both ASB9(1-252) and ASB9(35-252) protected the same region of CK, residues 182-203, which forms one side of the active site. The HDXMS experiments indicated that the N-terminal disordered region and first ankyrin repeat of ASB9 are protected from exchange in the complex. Molecular docking yielded a structural model consistent with all of the data that suggested the N-terminal residues of ASB9(1-252) may lie in one CK active site. This model was corroborated by enzymatic activity assays and mutational analysis.

  2. Differentiation and fiber type-specific activity of a muscle creatine kinase intronic enhancer

    Directory of Open Access Journals (Sweden)

    Tai Phillip WL

    2011-07-01

    Full Text Available Abstract Background Hundreds of genes, including muscle creatine kinase (MCK, are differentially expressed in fast- and slow-twitch muscle fibers, but the fiber type-specific regulatory mechanisms are not well understood. Results Modulatory region 1 (MR1 is a 1-kb regulatory region within MCK intron 1 that is highly active in terminally differentiating skeletal myocytes in vitro. A MCK small intronic enhancer (MCK-SIE containing a paired E-box/myocyte enhancer factor 2 (MEF2 regulatory motif resides within MR1. The SIE's transcriptional activity equals that of the extensively characterized 206-bp MCK 5'-enhancer, but the MCK-SIE is flanked by regions that can repress its activity via the individual and combined effects of about 15 different but highly conserved 9- to 24-bp sequences. ChIP and ChIP-Seq analyses indicate that the SIE and the MCK 5'-enhancer are occupied by MyoD, myogenin and MEF2. Many other E-boxes located within or immediately adjacent to intron 1 are not occupied by MyoD or myogenin. Transgenic analysis of a 6.5-kb MCK genomic fragment containing the 5'-enhancer and proximal promoter plus the 3.2-kb intron 1, with and without MR1, indicates that MR1 is critical for MCK expression in slow- and intermediate-twitch muscle fibers (types I and IIa, respectively, but is not required for expression in fast-twitch muscle fibers (types IIb and IId. Conclusions In this study, we discovered that MR1 is critical for MCK expression in slow- and intermediate-twitch muscle fibers and that MR1's positive transcriptional activity depends on a paired E-box MEF2 site motif within a SIE. This is the first study to delineate the DNA controls for MCK expression in different skeletal muscle fiber types.

  3. The evolution from asparagine or threonine to cysteine in position 146 contributes to generation of a more efficient and stable form of muscle creatine kinase in higher vertebrates.

    Science.gov (United States)

    Zhao, Tong-Jin; Liu, Yang; Chen, Zhao; Yan, Yong-Bin; Zhou, Hai-Meng

    2006-01-01

    Creatine kinase, a key enzyme in vertebrate excitable tissues that require large energy fluxes, catalyzes the reversible transfer of phosphate between adenosine triphosphate and creatine. Sequence alignment indicated that the 146th amino acid is cysteine in the muscle creatine kinase of higher vertebrates including Amphibia, Reptilia, Aves and Mammalia. In fishes, it is cysteine in Agnatha and Chondrichthyes, and asparagine or threonine in Osteichthyes, which is the ancestor of Amphibia, Reptilia, Aves and Mammalia. To explore the structural and functional role of this special residue, a series of site-directed mutants of rabbit muscle creatine kinase were constructed, including C146S, C146N, C146T, C146G, C146A, C146D and C146R. A detailed comparison was made between wild-type creatine kinase and the mutants in catalytic activity, physico-chemical properties and structural stability against thermal inactivation and guanidine hydrochloride denaturation. It was found that except for C146S, the mutants had relatively lower catalytic activity and structural stability than Wt-CK. Wt-CK and C146S were the most stable ones, followed by C146N and C146T, and then C146G and C146A, and C146D and C146R were the least stable mutants. These results suggested that the 146th residue plays a crucial role in maintaining the structural stability of creatine kinase, and that the evolution in this amino acid from asparagine or threonine to cysteine contributes to the generation of a more efficient and more stable form of creatine kinase in higher vertebrates.

  4. CERTIFICATION REPORT The certification of the catalytic activity concentration of creatine kinase in ERM®-AD455k/IFCC

    OpenAIRE

    KUHLMANN JULIA; TOUSSAINT Brigitte; Schimmel, Heinz; Emons, Hendrik

    2016-01-01

    This report describes the production of ERM®-AD455k/IFCC, which is a material certified for the catalytic activity concentration of creatine kinase (CK). This material was produced in collaboration with the International Federation for Clinical Chemistry and Laboratory Medicine (IFCC) following ISO Guide 34:2009 and it is certified in accordance with ISO Guide 35:2006. The starting material was a recombinant form of human CK isoenzyme MM (CK-MM) expressed in E. coli. It was produced, purif...

  5. Correlation of Creatine Kinase Levels with Clinical Features and Survival in Amyotrophic Lateral Sclerosis

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    Hongfei Tai

    2017-07-01

    Full Text Available ObjectiveTo evaluate serum creatine kinase (CK levels of amyotrophic lateral sclerosis (ALS patients and to explore the relationship between CK levels and the clinical characteristics and survival prognosis of ALS patients.MethodsWe analyzed the CK levels of 185 ALS patients who underwent long-term follow-up. The relationship between CK levels and clinical features including sex, age, disease duration, site of onset, body mass index (BMI, serum creatinine (Cr, and spontaneous electromyographic activity was analyzed by univariate analysis and multiple linear regression. Kaplan–Meier and Cox proportional hazards models were used to explore whether CK levels were independently correlated with survival prognosis of ALS.ResultsBaseline serum CK was raised in 43% of participants. The median CK level was 160 U/L (range: 20–2,574 U/L, and 99% of patients had a baseline serum CK level less than 1,000 U/L. CK levels were significantly higher in male patients than in female patients [204 (169 versus 117 (111 U/L, p < 0.001] and in patients with limb onset ALS than with bulbar onset ALS (p < 0.001. CK levels were also correlated with serum Cr (p = 0.011 and the spontaneous potential score of electromyography (EMG (p = 0.037 but not correlated with age (p = 0.883, disease duration (p = 0.116, or BMI (p = 0.481. Log CK was independently correlated with survival of ALS patients (HR = 0.457, 95% confidence interval 0.221–0.947, p = 0.035 after adjusting for age, sex, site of onset, serum Cr, and BMI.ConclusionSerum CK levels of ALS patients were correlated with sex, site of onsite, serum Cr, and spontaneous activity in EMG. Serum CK could be an independent prognostic factor for survival of ALS patients.

  6. Temporal changes in serum creatine kinase concentration and degree of muscle rigidity in 24 patients with neuroleptic malignant syndrome

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    Nisijima K

    2013-06-01

    Full Text Available Koichi Nisijima, Katutoshi ShiodaDepartment of Psychiatry, Jichi Medical University, Tochigi, JapanAbstract: Neuroleptic malignant syndrome (NMS is a dangerous adverse response to antipsychotic drugs. It is characterized by the four major clinical symptoms of hyperthermia, severe muscle rigidity, autonomic dysfunction, and altered mental state. Serum creatine kinase (CK elevation occurs in over 90% of NMS cases. In the present study, the detailed temporal changes in serum CK and degree of muscle rigidity, and the relationship between CK concentration and degree of muscle rigidity over the time course from fever onset, were evaluated in 24 affected patients. The results showed that serum CK peaked on day 2 after onset of fever and returned to within normal limits at day 12. Mild muscle rigidity was observed before the onset of fever in 17 of 24 cases (71%. Muscle rigidity was gradually exacerbated and worsened until day 4 after onset of fever. These findings confirm physicians' empirical understanding of serum CK concentrations and muscle rigidity in NMS based on data accumulated from numerous patients with the syndrome, and they indicate that serum CK may contribute to the early detection of NMS.Keywords: neuroleptic malignant syndrome, creatine kinase, muscle rigidity

  7. AMP kinase expression and activity in human skeletal muscle: effects of immobilization, retraining, and creatine supplementation

    DEFF Research Database (Denmark)

    Eijnde, Bert O.; Derave, Wim; Wojtaszewski, Jørgen

    2005-01-01

    the right leg for 2 wk, whereafter the knee-extensor muscles of that leg were retrained for 6 wk. Half of the subjects received creatine monohydrate throughout the study (Cr; from 15 g down to 2.5 g daily), and the others ingested placebo (P; maltodextrin). Before and after immobilization and retraining...

  8. Creatine kinase-mediated ATP supply fuels actin-based events in phagocytosis.

    NARCIS (Netherlands)

    Kuiper, J.W.P.; Pluk, H.; Oerlemans, F.; Leeuwen, F.N. van; Lange, F. de; Fransen, J.; Wieringa, B.

    2008-01-01

    Phagocytosis requires locally coordinated cytoskeletal rearrangements driven by actin polymerization and myosin motor activity. How this actomyosin dynamics is dependent upon systems that provide access to ATP at phagosome microdomains has not been determined. We analyzed the role of brain-type

  9. Regulation of the Na+,Cl- Coupled Creatine Transporter CreaT (SLC6A8) by the Janus Kinase JAK3.

    Science.gov (United States)

    Fezai, Myriam; Warsi, Jamshed; Lang, Florian

    2015-01-01

    The creatine transporter CreaT (SLC6A8), a Na+,Cl- coupled transporter is expressed in diverse tissues including the brain. Genetic defects of SLC6A8 result in mental retardation with seizures. The present study explored the regulation of CreaT by Janus kinase JAK3, which is expressed in a variety of tissues including the brain and participates in the regulation of cell survival and differentiation of neuronal precursor cells. CreaT was expressed in Xenopus laevis oocytes with or without wild-type JAK3, constitutively active A568V JAK3 and inactive K851A JAK3. Creatine transport in those oocytes was quantified utilizing dual electrode voltage clamp. Electrogenic creatine transport was observed in CreaT expressing oocytes but not in water-injected oocytes. In CreaT expressing oocytes co-expression of JAK3 or A568VJAK3, but not co-expression of K851A JAK3 was followed by a significant decrease of creatine induced current. According to kinetic analysis JAK3 significantly decreased the maximal creatine transport rate. In CreaT and JAK3 expressing oocytes the creatine induced current was significantly increased by JAK3 inhibitor WHI-P154 (22 µM). JAK3 is a powerful negative regulator of the creatine transporter CreaT. © 2015 The Author(s) Published by S. Karger AG, Basel.

  10. Regulation of the Na+,Cl- Coupled Creatine Transporter CreaT (SLC6A8 by the Janus Kinase JAK3

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    Myriam Fezai

    2015-12-01

    Full Text Available Background: The creatine transporter CreaT (SLC6A8, a Na+,Cl- coupled transporter is expressed in diverse tissues including the brain. Genetic defects of SLC6A8 result in mental retardation with seizures. The present study explored the regulation of CreaT by Janus kinase JAK3, which is expressed in a variety of tissues including the brain and participates in the regulation of cell survival and differentiation of neuronal precursor cells. Methods: CreaT was expressed in Xenopus laevis oocytes with or without wild-type JAK3, constitutively active A568VJAK3 and inactive K851AJAK3. Creatine transport in those oocytes was quantified utilizing dual electrode voltage clamp. Results: Electrogenic creatine transport was observed in CreaT expressing oocytes but not in water-injected oocytes. In CreaT expressing oocytes co-expression of JAK3 or A568VJAK3, but not co-expression of K851AJAK3 was followed by a significant decrease of creatine induced current. According to kinetic analysis JAK3 significantly decreased the maximal creatine transport rate. In CreaT and JAK3 expressing oocytes the creatine induced current was significantly increased by JAK3 inhibitor WHI-P154 (22 µM. Conclusion: JAK3 is a powerful negative regulator of the creatine transporter CreaT.

  11. Cytoplasmic and mitochondrial creatine kinases from the skeletal muscle of sperm whale (Physeter macrocephalus). Molecular cloning and enzyme characterization.

    Science.gov (United States)

    Iwanami, Kentaro; Uda, Kouji; Tada, Hiroshi; Suzuki, Tomohiko

    2008-01-01

    We have amplified two cDNAs, coding for creatine kinases (CKs), from the skeletal muscle of sperm whale Physeter macrocephalus by PCR, and cloned these cDNAs into pMAL plasmid. These are the first CK cDNA and deduced amino acid sequences from cetaceans to be reported. One of the two amino acid sequences is a cytoplasmic, muscle-type isoform (MCK), while the other was identified as a sarcomeric, mitochondrial isoform (sMiCK) that included a mitochondrial targeting peptide. The amino acid sequences of sperm whale MCK and sMiCK showed 94-96% sequence identity with corresponding isoforms of mammalian CKs, and all of the key residues necessary for CK function were conserved. The phylogenetic analyses of vertebrate CKs with three independent methods (neighbor-joining, maximum-likelihood and Bayes) supported the clustering of sperm whale MCK with Bos and Sus MCKs, in agreement with the contemporary view that these groups are closely related. Sperm whale MCK and sMiCK were expressed in Escherichia coli as a fusion protein with maltose-binding protein, and the kinetic constants (K (m), K (d) and k (cat)) were determined for the forward reaction. Comparison of kinetic constants with those of human and mouse CKs indicated that sperm whale MCK has a comparable affinity for creatine (K (m) (Cr) = 9.38 mM) to that of human MCK, and the sMiCK has two times higher affinity for creatine than the human enzyme. Both the MCK and sMiCK of sperm whale display a synergistic substrate binding (K (d) /K (m) = 3.1-7.8) like those of other mammalian CKs.

  12. Spatial distribution of "tissue-specific" antigens in the developing human heart and skeletal muscle. I. An immunohistochemical analysis of creatine kinase isoenzyme expression patterns

    NARCIS (Netherlands)

    Wessels, A.; Vermeulen, J. L.; Virágh, S.; Kálmán, F.; Morris, G. E.; Man, N. T.; Lamers, W. H.; Moorman, A. F.

    1990-01-01

    Using monoclonal antibodies against the M and B subunit isoforms of creatine kinase (CK) we have investigated their distribution in developing human skeletal and cardiac muscle immunohistochemically. It is demonstrated that in skeletal muscle, a switch from CK-B to CK-M takes place around the week 8

  13. Early detection of response in small cell bronchogenic carcinoma by changes in serum concentrations of creatine kinase, neuron specific enolase, calcitonin, ACTH, serotonin and gastrin releasing peptide

    DEFF Research Database (Denmark)

    Bork, E; Hansen, M; Urdal, P

    1988-01-01

    Creatine kinase (CK-BB), neuron specific enolase (NSE), ACTH, calcitonin, serotonin and gastrin releasing peptide (GRP) were measured in serum or plasma before and immediately after initiation of treatment in patients with small cell lung cancer (SCC). Pretherapeutic elevated concentrations of CK...

  14. In Vitro Inhibition of Human Sperm Creatine Kinase by Nicotine,Cotinine and Cadmium, as a Mechanism in Smoker Men Infertility

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    Mohammad Ali Ghaffari

    2009-01-01

    Full Text Available Background: Nicotine, cotinine and cadmium are harmful components of cigarettes that have aneffect on human reproductive function. Although the effects of cigarette smoke on male reproductivefunction is characterized in several articles its mechanism of action is still unknown.In the present study, we investigate the effect of nicotine, cotinine and cadmium on human spermcreatine kinase activity in vitro.Materials and Methods: Total creatine kinase activity is measured in sperm homogenates afterchromatography on a diethylaminoethyl cellulose (DEAE-32 column.Results: We show that creatine kinase activity is significantly inhibited by nicotine (44%, cotinine(39% and cadmium (65% at a concentration of 60 μg/ml. Kinetic studies reveal that the inhibitoryeffect of nicotine, cotinine and cadmium are competitive in relation to creatine phosphate.Conclusion: Considering the importance of creatine kinase activity for normal sperm energymetabolism, our results suggest that inhibition of this enzyme by nicotine, cotinine and cadmium maybe an important mechanism in infertility amongst male smokers. However, further investigationsare needed to elucidate the exact mechanism of cigarette effect on male reproductive function atthe molecular level.

  15. Mitochondrial affinity for ADP is twofold lower in creatine kinase knock-out muscles - Possible role in rescuing cellular energy homeostasis

    NARCIS (Netherlands)

    ter Veld, F; Jeneson, JAL; Nicolay, K

    Adaptations of the kinetic properties of mitochondria in striated muscle lacking cytosolic (M) and/or mitochondrial (Mi) creatine kinase (CK) isoforms in comparison to wild-type (WT) were investigated in vitro. Intact mitochondria were isolated from heart and gastrocnemius muscle of WT and single-

  16. In Vitro Inhibition of Human Sperm Creatine Kinase by Nicotine,Cotinine and Cadmium, as a Mechanism in Smoker Men Infertility

    OpenAIRE

    Mohammad Ali Ghaffari; Mohammad Abromand; Behrooz Motlagh

    2009-01-01

    Background: Nicotine, cotinine and cadmium are harmful components of cigarettes that have aneffect on human reproductive function. Although the effects of cigarette smoke on male reproductivefunction is characterized in several articles its mechanism of action is still unknown.In the present study, we investigate the effect of nicotine, cotinine and cadmium on human spermcreatine kinase activity in vitro.Materials and Methods: Total creatine kinase activity is measured in sperm homogenates af...

  17. Creatine kinase BB and beta-2-microglobulin as markers of CNS metastases in patients with small-cell lung cancer

    DEFF Research Database (Denmark)

    Pedersen, A G; Bach, F W; Nissen, Mogens Holst

    1985-01-01

    Creatine kinase (CK) and its BB isoenzyme (CK-BB) were measured in CSF in 65 evaluable patients suspected of CNS metastases secondary to small-cell lung cancer (SCLC). In addition, CSF and plasma levels of beta-2-microglobulin (beta-2-m) were measured in a group of 73 evaluable patients. Of the 65...... patients analysed for CK-BB, 17 had meningeal carcinomatosis (MC), 26 had parenchymal metastases only, and 22 had no CNS disease. Patients with MC had a significantly higher CK-BB concentration in CSF than did patients belonging to the other two groups (P less than .01). Taking 0.4 U/L (upper limit...... in patients without CNS disease) as a cut-off point, 15 patients (88%) with MC had elevated CSF concentrations of CK-BB. Patients without CNS metastases had no CSF levels exceeding this value, whereas five patients with multiple CNS metastases did. Receiver operating characteristic (ROC) analysis suggests...

  18. Acute and chronic administration of cannabidiol increases mitochondrial complex and creatine kinase activity in the rat brain

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    Samira S. Valvassori

    2013-12-01

    Full Text Available Objective: To investigate the effects of cannabidiol (CBD on mitochondrial complex and creatine kinase (CK activity in the rat brain using spectrophotometry. Method: Male adult Wistar rats were given intraperitoneal injections of vehicle or CBD (15, 30, or 60 mg/kg in an acute (single dose or chronic (once daily for 14 consecutive days regimen. The activities of mitochondrial complexes and CK were measured in the hippocampus, striatum, and prefrontal cortex. Results: Both acute and chronic injection of CBD increased the activity of the mitochondrial complexes (I, II, II-III, and IV and CK in the rat brain. Conclusions: Considering that metabolism impairment is certainly involved in the pathophysiology of mood disorders, the modulation of energy metabolism (e.g., by increased mitochondrial complex and CK activity by CBD could be an important mechanism implicated in the action of CBD.

  19. Dexamethasone effects on creatine kinase activity and insulin-like growth factor receptors in cultured muscle cells

    Science.gov (United States)

    Whitson, Peggy A.; Stuart, Charles A.; Huls, M. H.; Sams, Clarence F.; Cintron, Nitza M.

    1989-01-01

    The effect of dexamethasone on the activity of creatine kinase (CK) and the insulin-like growth factor I (IGF-I) binding were investigated using skeletal- and cardiac-muscle-derived cultured cell lines (mouse, C2C12; rat, L6 and H9c2). It was found that, in skeletal muscle cells, dexamethasone treatment during differentiation of skeletal-muscle cells caused dose-dependent increases in CK activity and increases in the degree of myotube formation, whereas cardiac cells (H9c2) exhibited very low CK activity during culture or dexamethasone treatment. Results for IGF-I binding were similar in all three cell lines. The IGF-I binding to dexamethasone-treated cells (50 nM for 24 hr on the day prior to confluence) resulted in an increased number of available binding sites, with no effect on the binding affinities.

  20. Selective decrease of components of the creatine kinase system and ATP synthase complex in chronic Chagas disease cardiomyopathy.

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    Priscila Camillo Teixeira

    2011-06-01

    Full Text Available BACKGROUND: Chronic Chagas disease cardiomyopathy (CCC is an inflammatory dilated cardiomyopathy with a worse prognosis than other cardiomyopathies. CCC occurs in 30 % of individuals infected with Trypanosoma cruzi, endemic in Latin America. Heart failure is associated with impaired energy metabolism, which may be correlated to contractile dysfunction. We thus analyzed the myocardial gene and protein expression, as well as activity, of key mitochondrial enzymes related to ATP production, in myocardial samples of end-stage CCC, idiopathic dilated (IDC and ischemic (IC cardiomyopathies. METHODOLOGY/PRINCIPAL FINDINGS: Myocardium homogenates from CCC (N=5, IC (N=5 and IDC (N=5 patients, as well as from heart donors (N=5 were analyzed for protein and mRNA expression of mitochondrial creatine kinase (CKMit and muscular creatine kinase (CKM and ATP synthase subunits aplha and beta by immunoblotting and by real-time RT-PCR. Total myocardial CK activity was also assessed. Protein levels of CKM and CK activity were reduced in all three cardiomyopathy groups. However, total CK activity, as well as ATP synthase alpha chain protein levels, were significantly lower in CCC samples than IC and IDC samples. CCC myocardium displayed selective reduction of protein levels and activity of enzymes crucial for maintaining cytoplasmic ATP levels. CONCLUSIONS/SIGNIFICANCE: The selective impairment of the CK system may be associated to the loss of inotropic reserve observed in CCC. Reduction of ATP synthase alpha levels is consistent with a decrease in myocardial ATP generation through oxidative phosphorylation. Together, these results suggest that the energetic deficit is more intense in the myocardium of CCC patients than in the other tested dilated cardiomyopathies.

  1. Towards Binding Mechanism of Cu2+ on Creatine Kinase from Pelodiscus sinensis: Molecular Dynamics Simulation Integrating Inhibition Kinetics Study.

    Science.gov (United States)

    Cai, Yan; Lee, Jinhyuk; Wang, Wei; Park, Yong-Doo; Qian, Guo-Ying

    2017-01-01

    Cu2+ is well known to play important roles in living organisms having bifacial distinction: essential microelement that is necessary for a wide range of metabolic processes but hyper-accumulation of Cu2+ can be toxic. The physiological function of Cu2+ in ectothermic animals such as Pelodiscus sinensis (Chinese soft-shelled turtle) has not been elucidated. In this study, we elucidated effect of Cu2+ on the energy producing metabolic enzyme creatine kinase (CK), which might directly affect energy metabolism and homeostasis of P. sinensis. We first conducted molecular dynamics (MD) simulations between P-CK and Cu2+ and conducted the inactivation kinetics including spectrofluorimetry study. MD simulation showed that Cu2+ blocked the binding site of the ATP cofactor, indicating that Cu2+ could directly inactivate P-CK. We prepared the muscle type of CK (P-CK) and confirmed that Cu2+ conspicuously inactivated the activity of P-CK (IC50 = 24.3 μM) and exhibited non-competitive inhibition manner with creatine and ATP in a first-order kinetic process. This result was well matched to the MD simulation results that Cu2+-induced non-competitive inactivation of P-CK. The spectrofluorimetry study revealed that Cu2+ induced tertiary structure changes in PCK accompanying with the exposure of hydrophobic surfaces. Interestingly, the addition of osmolytes (glycine, proline, and liquaemin) effectively restored activity of the Cu2+-inactivated P-CK. Our study illustrates the Cu2+-mediated unfolding of P-CK with disruption of the enzymatic function and the protective restoration role of osmolytes on P-CK inactivation. This study provides information of interest on P-CK as a metabolic enzyme of ectothermic animal in response to Cu2+ binding. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Down-Regulation of the Na+,Cl- Coupled Creatine Transporter CreaT (SLC6A8) by Glycogen Synthase Kinase GSK3ß.

    Science.gov (United States)

    Fezai, Myriam; Jemaà, Mohamed; Fakhri, Hajar; Chen, Hong; Elsir, Bhaeldin; Pelzl, Lisann; Lang, Florian

    2016-01-01

    The Na+,Cl- coupled creatine transporter CreaT (SLC6A8) is expressed in a variety of tissues including the brain. Genetic defects of CreaT lead to mental retardation with seizures. The present study explored the regulation of CreaT by the ubiquitously expressed glycogen synthase kinase GSK3ß, which contributes to the regulation of neuroexcitation. GSK3ß is phosphorylated and thus inhibited by PKB/Akt. Moreover, GSK3ß is inhibited by the antidepressant lithium. The present study thus further tested for the effects of PKB/Akt and of lithium. CreaT was expressed in Xenopus laevis oocytes with or without wild-type GSK3ß or inactive K85RGSK3ß. CreaT and GSK3ß were further expressed without and with additional expression of wild type PKB/Akt. Creatine transport in those oocytes was quantified utilizing dual electrode voltage clamp. Electrogenic creatine transport was observed in CreaT expressing oocytes but not in water-injected oocytes. In CreaT expressing oocytes, co-expression of GSK3ß but not of K85RGSK3ß, resulted in a significant decrease of creatine induced current. Kinetic analysis revealed that GSK3ß significantly decreased the maximal creatine transport rate. Exposure of CreaT and GSK3ß expressing oocytes for 24 hours to Lithium was followed by a significant increase of the creatine induced current. The effect of GSK3ß on CreaT was abolished by co-expression of PKB/Akt. GSK3ß down-regulates the creatine transporter CreaT, an effect reversed by treatment with the antidepressant Lithium and by co-expression of PKB/Akt. © 2016 The Author(s) Published by S. Karger AG, Basel.

  3. Down-Regulation of the Na+,Cl- Coupled Creatine Transporter CreaT (SLC6A8 by Glycogen Synthase Kinase GSK3ß

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    Myriam Fezai

    2016-12-01

    Full Text Available Background: The Na+,Cl- coupled creatine transporter CreaT (SLC6A8 is expressed in a variety of tissues including the brain. Genetic defects of CreaT lead to mental retardation with seizures. The present study explored the regulation of CreaT by the ubiquitously expressed glycogen synthase kinase GSK3ß, which contributes to the regulation of neuroexcitation. GSK3ß is phosphorylated and thus inhibited by PKB/Akt. Moreover, GSK3ß is inhibited by the antidepressant lithium. The present study thus further tested for the effects of PKB/Akt and of lithium. Methods: CreaT was expressed in Xenopus laevis oocytes with or without wild-type GSK3ß or inactive K85RGSK3ß. CreaT and GSK3ß were further expressed without and with additional expression of wild type PKB/Akt. Creatine transport in those oocytes was quantified utilizing dual electrode voltage clamp. Results: Electrogenic creatine transport was observed in CreaT expressing oocytes but not in water-injected oocytes. In CreaT expressing oocytes, co-expression of GSK3ß but not of K85RGSK3ß, resulted in a significant decrease of creatine induced current. Kinetic analysis revealed that GSK3ß significantly decreased the maximal creatine transport rate. Exposure of CreaT and GSK3ß expressing oocytes for 24 hours to Lithium was followed by a significant increase of the creatine induced current. The effect of GSK3ß on CreaT was abolished by co-expression of PKB/Akt. Conclusion: GSK3ß down-regulates the creatine transporter CreaT, an effect reversed by treatment with the antidepressant Lithium and by co-expression of PKB/Akt.

  4. Changes in creatine kinase and cortisol in National Collegiate Athletic Association Division I American football players during a season.

    Science.gov (United States)

    Kraemer, William J; Looney, David P; Martin, Gerard J; Ratamess, Nicholas A; Vingren, Jakob L; French, Duncan N; Hatfield, Disa L; Fragala, Maren S; Spiering, Barry A; Howard, Robert L; Cortis, Cristina; Szivak, Tunde K; Comstock, Brett A; Dunn-Lewis, Courtenay; Hooper, David R; Flanagan, Shawn D; Volek, Jeff S; Anderson, Jeffrey M; Maresh, Carl M; Fleck, Steven J

    2013-02-01

    The purpose of this study was to track creatine kinase (CK) and serum cortisol over an American college football season starting with the preseason practice. A secondary purpose was to observe changes in basic clinical chemistries. Twenty-two National Collegiate Athletic Association Division I football players (age: 20.4 ± 1.1 years, height: 188.27 ± 8.3 cm, weight: 115.8 ± 29.7 kg) volunteered to participate in this study. Each of the players had participated in the summer strength and conditioning supervised program. Resting blood samples were obtained just before the start of preseason practice (T-1), 2 weeks later (T-2), and the day after game 2 (T-3), game 4 (T-4), game 6 (T-5), and game 9 (T-6) of a 12-game season. Creatine kinase, a panel of clinical chemistries, cortisol, and testosterone were assayed at each time point. No significant changes in CK concentrations were observed over the season with peak values of each range ≤1,070.0 IU·L(-1), but the largest range was observed at T-6 after game 9 (119-2,834 IU·L(-1). The analysis of covariance analysis demonstrated that the number of plays in the ninth game (T-6) explained the magnitude of the changes in CK. No changes in serum cortisol concentrations were observed yet, again large variations existed with peak values of each range ≤465.0 nmol·L(-1). Clinical chemistries showed various significant changes from T-1, but none were considered clinically relevant changes for any player over the time course of the study. In conclusion, the strength and conditioning program before preseason camp or the structure of summer camp practices and the in-season strength and conditioning appeared to mute muscle damage and the stress response of cortisol. Such data demonstrate that changes in muscle damage and adrenal cortical stress over the season are minimal, yet large individual variations can be observed. Management of these variables appears to be related to optimal strength and conditioning and sports

  5. Resistance imparted by traditional Chinese medicines to the acute change of glutamic pyruvic transaminase, alkaline phosphatase and creatine kinase activities in rat blood caused by noise.

    Science.gov (United States)

    Zhu, Bei-Wei; Sun, Yu-Mei; Yun, Xia; Han, Song; Piao, Mei-Lan; Murata, Yoshiyuki; Tada, Mikiro

    2004-05-01

    The activities of serum glutamic pyruvic transaminase (GPT), alkaline phosphatase (ALP) and creatine kinase (CK) in rats injected or not with the Chinese medicines, Astragali, Rhodiolae and Ligusticum, were determined after noise exposure. Noise at 95 and 105 dB significantly increased the activities of GPT, ALP and CK, and showed a dependence on the exposure time. The injection of each medicine significantly suppressed the increased enzyme activities by 95 and 105 dB noise.

  6. Association of Plasma Heat Shock Protein 70, Interleukin 6, and Creatine Kinase Concentrations in a Healthy, Young Adult Population

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    Carmen Contreras-Sesvold

    2015-01-01

    Full Text Available Variations of baseline plasma concentrations of creatine kinase (CK, heat shock protein 70 (HSP70, and interleukin 6 (IL-6 have been reported. We report categorical associations which may influence these protein levels. Methods. Blood was harvested for DNA and plasma protein analysis from 567 adults. Mean protein levels of CK, HSP70, and IL-6 were compared by sex, ethnicity, genetic variants—CKMM Nco1 (rs1803285, HSPA1B +A1538G (rs1061581, and IL6 G-174C (rs1800795—self-reported history of exercise, oral contraceptive use, and dietary supplement use. Results. SNP major allele frequencies for CKMM, HSPA1B, and IL6 were 70% A, 57% A, and 60%. Mean CK statistically differed by sex, ethnicity, oral contraceptives, and caffeine. Plasma HSP70 differed by caffeine and protein. Mean IL-6 concentration differed by sex, ethnicity, and genotype. Plasma IL-6 was significantly lower (29% in males (1.92 ± 0.08 pg/mL and higher (29% among African Americans (2.85 ± 0.50 pg/mL relative to the others. IL6 G-174C GG genotype (2.23 ± 0.14 pg/mL was 19% greater than CG or CC genotypes. Conclusion. Differences in baseline CK and IL-6 plasma protein concentrations are associated with genetics, sex, ethnicity, and the use of oral contraceptives, caffeine, and protein supplements in this young and athletic population.

  7. The effects of athletic massage on delayed onset muscle soreness, creatine kinase, and neutrophil count: a preliminary report.

    Science.gov (United States)

    Smith, L L; Keating, M N; Holbert, D; Spratt, D J; McCammon, M R; Smith, S S; Israel, R G

    1994-02-01

    It was hypothesized that athletic massage administered 2 hours after eccentric exercise would disrupt an initial crucial event in acute inflammation, the accumulation of neutrophils. This would result in a diminished inflammatory response and a concomitant reduction in delayed onset muscle soreness (DOMS) and serum creatine kinase (CK). Untrained males were randomly assigned to a massage (N = 7) or control (N = 7) group. All performed five sets of isokinetic eccentric exercise of the elbow flexors and extensors. Two hours after exercise, massage subjects received a 30-minute athletic massage; control subjects rested. Delayed onset muscle soreness and CK were assessed before exercise and at 8, 24, 48, 72, 96, and 120 hours after exercise. Circulating neutrophils were assessed before and immediately after exercise, and at 30-minute intervals for 8 hours; cortisol was assessed before and immediately after exercise, and at 30-minute intervals for 8 hours; cortisol was assessed at similar times. A trend analysis revealed a significant (p massage group reporting reduced levels; 2) CK, with the massage group displaying reduced levels; 3) neutrophils, with the massage group displaying a prolonged elevation; and 4) cortisol, with the massage group showing a diminished diurnal reduction. The results of this study suggest that sports massage will reduce DOMS and CK when administered 2 hours after the termination of eccentric exercise. This may be due to a reduced emigration of neutrophils and/or higher levels of serum cortisol.

  8. Bruising in slaughter cattle and its relationship with creatine kinase levels and beef quality as affected by animal related factors.

    Science.gov (United States)

    Mpakama, T; Chulayo, A Y; Muchenje, V

    2014-05-01

    The objective of the study was to determine the effects of animal related factors on bruising in slaughter cattle, creatine kinase (CK) and beef quality. Three hundred and twenty one cattle from three breeds (108 Bonsmara, 130 Beefmaster and 83 Brahman) were used in this study. The animals were grouped as follows: Group 1 (16 months old), Group 2 (18 months old) and Group 3 (24 months old). At exsanguinations, blood samples for CK determination were collected using disposable vacutainer tubes. Muscularis longissimus thoracis et lumborum (LTL) was collected 24 h after slaughter to determine the colour (L*, a*, and b*) and ultimate pH (pHu) of beef. Breed, sex and age had significant effects (panimal factors (sex, breed and animal age at slaughter) contribute to the development of bruises and have an effect on the levels of CK and meat quality. It was also concluded that there is no significant relationship between meat parameters (L,* a*, and b*) and CK levels.

  9. Efflux of Creatine Kinase from Isolated Soleus Muscle Depends on Age, Sex and Type of Exercise in Mice

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    Juozas Baltusnikas, Tomas Venckunas, Audrius Kilikevicius, Andrej Fokin, Aivaras Ratkevicius

    2015-06-01

    Full Text Available Elevated plasma creatine kinase (CK activity is often used as an indicator of exercise-induced muscle damage. Our aim was to study effects of contraction type, sex and age on CK efflux from isolated skeletal muscles of mice. The soleus muscle (SOL of adult (7.5-month old female C57BL/6J mice was subjected to either 100 passive stretches, isometric contractions or eccentric contractions, and muscle CK efflux was assessed after two-hour incubation in vitro. SOL of young (3-month old male and female mice was studied after 100 eccentric contractions. For adult females, muscle CK efflux was larger (p < 0.05 after eccentric contractions than after incubation without exercise (698 ± 344 vs. 268 ± 184 mU·h−1, respectively, but smaller (p < 0.05 than for young females after the same type of exercise (1069 ± 341 mU·h−1. Eccentric exercise-induced CK efflux was larger in muscles of young males compared to young females (2046 ± 317 vs 1069 ± 341 mU · h−1, respectively, p < 0.001. Our results show that eccentric contractions induce a significant increase in muscle CK efflux immediately after exercise. Isolated muscle resistance to exercise-induced CK efflux depends on age and sex of mice.

  10. Detection of myocardial infarct extension by CK-B radioimmunoassay. [/sup 125/I; creatine kinase-B

    Energy Technology Data Exchange (ETDEWEB)

    Rothkopf, M.; Boerner, J.; Stone, M.J.; Smitherman, T.C.; Buja, L.M.; Parkey, R.W.; Willerson, J.T.

    1979-02-01

    Myocardial infarct extension after the acute event was defined as a second rise in the myocardial isoenzyme of serum creatine kinase (CK-B) after the initial return of CK-B to normal values. In 43 patients with acute myocardial infarct, CK-B was measured by radioimmunoassay every 12 hrs for 14 days. Nineteen patients had anterior transmural myocardial infarcts (AMI), 14 had inferior transmural myocardial infarcts (IMI), and 10 had subendocardial myocardial infarcts (SEMI). Infarct extension as detected by a second rise in serum CK-B occurred in six patients (32%) with AMI, two (14%) with IMI, and two (20%) with SEMI. Four patients with AMI also had clinically evident infarct extension. In the other six, the infarct extension was undetected clinically. The measurement of serum CK-B values with a quantitative and sensitive assay suggests that myocardial infarct extension occurs more commonly than clinically recognized, but the frequency of extension may be less than that reported in patients in whom precordial mapping and total serum CK values were measured to identify this phenomenon.

  11. The Response of Creatine Kinase Specific Activity in Rat Pituitary to Estrogenic Compounds and Vitamin D Less-Calcemic Analogs

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    D. Somjen

    2009-01-01

    Full Text Available We examined the response of rat female pituitary at different metabolic stages to treatments with estrogenic compounds and vitamin D analogs. Immature or ovariectomized (Ovx female rats responded by increased creatine kinase specific activity (CK to estradiol-17β (E2, genistein (G, daidzein (D, biochainin A (BA, quecertin (Qu, carboxy- G (cG, carboxy- BA (cBA, and raloxifene (Ral. The response was inhibited when Ral was injected together with the estrogens. CK was increased when hormones were injected daily into Ovx rats for 4 different time periods. Pretreatment with the less-calcemic vitamin D analogs JK 1624 F2-2 (JKF or QW 1624 F2-2 (QW followed by estrogenic injection resulted in increased response and sensitivity to E2 and loss of inhibition of E2 by Ral. CK was also increased by feeding with E2 or licorice or its components dose- and time- dependent in immature or Ovxrats. Diabetic female rats did not respond to increased doses of E2. In conclusion, rat female pituitary is estrogens-responsive organ, suggesting to consider its response for HRT in postmenopausal women for both beneficial and hazardous aspects.

  12. Early detection of skeletal muscle injury by assay of creatine kinase MM isoforms in serum after acute exercise

    DEFF Research Database (Denmark)

    Apple, F. S.; Hellsten, Ylva; Clarkson, P. M.

    1988-01-01

    We could detect skeletal muscle injury early after an acute exercise bout by measuring creatine kinase (CK, EC 2.7.3.2) MM isoforms in serum. Eleven men performed 120 alternating-arm, eccentric (muscle lengthening) biceps contractions with the intensity of each contraction being 110% of maximal...... concentric strength--a form of exercise previously shown to cause significant increases of CK in serum at 24 h and muscle soreness 48 h after exercise. Total CK and CK-MM isoform activities in serum were determined before and at 0.5, 0.75, 1, 1.5, 2, and 6 h after exercise. Using thin-film agarose gels...... and a rapid isoelectric focusing technique, we separated the MM isoforms into MM3 (skeletal muscle form), MM2, and MM1 (in vivo conversion forms). The isoforms reflected the MM form released into the serum from tissue as well as the conversion of one form to another. There were no significant increases...

  13. Kinesiology Tape does not Affect Serum Creatine Kinase Level and Quadriceps Activity during Recovery from Delayed-Onset Muscle Soreness

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    Naoko Aminaka

    2017-01-01

    Full Text Available Background: Delayed-onset muscle soreness (DOMS causes muscle damage and edema that can hinder performance and increase risks for secondary injuries. Kinesiology Tape (KT may be an effective modality for aiding in recovery, however, no study has investigated the effects of KT on the physiological biomarkers such as serum creatine kinase (CK level, concurrently with measures of performance and function, during recovery from DOMS. Objective: Investigate the effects of KT on serum CK level, electromyographic (EMG activity of the quadriceps muscles, and performances of countermovement jump (CMJ and triple single-leg hop for distance (HopD during recovery from DOMS. Method: Fifty-eight healthy college-age participants were randomly assigned to KT (n=15, placebo (n=19, and control (n=24 groups. Serum CK level and quadriceps EMG activity and performance during CMJ and HopD were collected at baseline, immediately after repetitive eccentric quadriceps exercise, 48 hours, and 72 hours post-exercise. The EMG recording of rectus femoris, vastus medialis, and vastus lateralis during the CMJ and HopD were normalized to the baseline maximum voluntary isometric contraction. Results: A significant main effect of time on the serum CK level, EMG activity, and performance (p0.05. Conclusion: Taping interventions did not improve the serum CK level or muscle activity and performance during recovery from DOMS. Kinesiology tape may not be the first choice of method for enhancing recovery from DOMS in otherwise healthy individuals.

  14. Effect of oral administration of dantrolene sodium on serum creatine kinase activity after exercise in horses with recurrent exertional rhabdomyolysis.

    Science.gov (United States)

    McKenzie, Erica C; Valberg, Stephanie J; Godden, Sandra M; Finno, Carrie J; Murphy, Michael J

    2004-01-01

    To determine the effect of oral administration of dantrolene sodium on serum creatine kinase (CK) activity after exercise in horses with recurrent exertional rhabdomyolysis (RER). 2 healthy horses and 5 Thoroughbreds with RER. 3 horses received 2 doses of dantrolene (4, 6, or 8 mg/kg, p.o., with and without withdrawal of food) 2 days apart; 90 minutes after dosing, plasma dantrolene concentration was measured spectrofluorometrically. On the basis of these results, 5 Thoroughbreds with RER from which food was withheld received dantrolene (4 mg/kg) or an inert treatment (water [20 mL]) orally 90 minutes before treadmill exercise (30 minutes, 5 d/wk) during two 3-week periods. Serum CK activity was determined 4 hours after exercise. Plasma dantrolene concentration was measured before and 90 minutes after dosing on the first and last days of dantrolene treatment and before dosing on the first day of the inert treatment period, 90 minutes after dosing, mean +/- SEM plasma dantrolene concentration was 0.62 +/- 0.13 and 0 microg/mL in the dantrolene and inert treatment groups, respectively. Serum CK activity was lower in dantrolene-treated horses (264 +/- 13 U/L), compared with activity in water-treated horses (1,088 +/- 264 U/L). Two horses displayed marked muscle stiffness on the inert treatment. In 5 horses with RER from which food had been withheld, 4 mg of dantrolene/kg administered orally provided measurable, though variable, plasma concentrations and significantly decreased serum CK activity after exercise in 4 of those horses.

  15. The Effect of Gender and Menstrual Phase on Serum Creatine Kinase Activity and Muscle Soreness Following Downhill Running

    Directory of Open Access Journals (Sweden)

    Tanja Oosthuyse

    2017-02-01

    Full Text Available Serum creatine kinase (CK activity reflects muscle membrane disruption. Oestrogen has antioxidant and membrane stabilising properties, yet no study has compared the CK and muscle soreness (DOMS response to unaccustomed exercise between genders when all menstrual phases are represented in women. Fifteen eumenorrhoeic women (early follicular, EF (n = 5; late follicular, LF (n = 5; mid-luteal, ML (n = 5 phase and six men performed 20 min of downhill running (−10% gradient at 9 km/h. Serum CK activity and visual analogue scale rating of perceived muscle soreness were measured before, immediately, 24-h, 48-h and 72-h after exercise. The 24-h peak CK response (relative to pre-exercise was similar between women and men (mean change (95% confidence interval: 58.5 (25.2 to 91.7 IU/L; 68.8 (31.3 to 106.3 IU/L, respectively. However, serum CK activity was restored to pre-exercise levels quicker in women (regardless of menstrual phase than men; after 48-h post exercise in women (16.3 (−4.4 to 37.0 IU/L; 56.3 (37.0 to 75.6 IU/L, respectively but only after 72-h in men (14.9 (−14.8 to 44.6 IU/L. Parallel to the CK response, muscle soreness recovered by 72-h in men. Conversely, the women still reported muscle soreness at 72-h despite CK levels being restored by 48-h; delayed recovery of muscle soreness appeared mainly in EF and LF. The CK and DOMS response to downhill running is gender-specific. The CK response recovers quicker in women than men. The CK and DOMS response occur in concert in men but not in women. The DOMS response in women is prolonged and may be influenced by menstrual phase.

  16. Creatine kinase rate constant in the human heart measured with 3D‐localization at 7 tesla

    Science.gov (United States)

    Robson, Matthew D.; Neubauer, Stefan; Rodgers, Christopher T.

    2016-01-01

    Purpose We present a new Bloch‐Siegert four Angle Saturation Transfer (BOAST) method for measuring the creatine kinase (CK) first‐order effective rate constant kf in human myocardium at 7 tesla (T). BOAST combines a variant of the four‐angle saturation transfer (FAST) method using amplitude‐modulated radiofrequency pulses, phosphorus Bloch‐Siegert B1+‐mapping to determine the per‐voxel flip angles, and nonlinear fitting to Bloch simulations for postprocessing. Methods Optimal flip angles and repetition time parameters were determined from Monte Carlo simulations. BOAST was validated in the calf muscle of two volunteers at 3T and 7T. The myocardial CK forward rate constant was then measured in 10 volunteers at 7T in 82 min (after 1H localization). Results BOAST kfCK values were 0.281 ± 0.002 s−1 in the calf and 0.35 ± 0.05 s−1 in myocardium. These are consistent with literature values from lower fields. Using a literature values for adenosine triphosphate concentration, we computed CK flux values of 4.55 ± 1.52 mmol kg−1 s−1. The sensitive volume for BOAST depends on the B1 inhomogeneity of the transmit coil. Conclusion BOAST enables measurement of the CK rate constant in the human heart at 7T, with spatial localization in three dimensions to 5.6 mL voxels, using a 10‐cm loop coil. Magn Reson Med 78:20–32, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. PMID:27579566

  17. EFFECTS OF AMANTADINE ON BEHAVIOR, RESPIRATORY CHAIN ENZYMES AND CREATINE KINASE IN AN ANIMAL MODEL OF SCHIZOPHRENIA

    Directory of Open Access Journals (Sweden)

    David de Lucena

    2013-03-01

    Full Text Available Introduction: Glutamate dysregulation may be involved in the pathophysiology of schizophrenia, and NMDA antagonists seem to be effective in its treatment. We evaluated the efficacy of amantadine (AMA in preventing ketamine (KET-induced effects in an animal model of schizophrenia. Methods: Adult Wistar rats received 10 mg/kg AMA for 10 days, followed by 7 days of 25 mg/kg KET ip. Thirty minutes after the last injection, rats were placed in an open-field apparatus for 60 minutes and killed by decapitation afterwards. Amygdala, hippocampus, prefrontal cortex and striatum were isolated and analyzed for creatine kinase (CK and respiratory chain enzyme activities. Results: KET increased crossings and reduced grooming, which was not prevented by AMA. KET also increased stereotypic movements, which was partially prevented by AMA. As for CK activity, KET increased it in the prefrontal cortex, striatum and amygdala, and AMA prevented it only in prefrontal cortex and striatum. The activity of complex I was not altered by KET, however, AMA+KET increased it in the striatum and amygdala. KET increased the activity of complex II in the striatum as well, whereas AMA+KET increased it in hippocampus, prefrontal cortex, and striatum. KET did not alter complex I-III activity, whereas AMA+KET increased it in hippocampus and amygdala. AMA+KET also increased complex IV activity in hippocampus and striatum, whereas KET had no effect on this activity. Conclusion: AMA did not prevent most of KET-induced alterations. New animal models should be employed in the study of AMA as a potential novel drug for schizophrenia.

  18. The Effect of One Session Continuous and Intermittent Aerobic Exercise on Blood Responses of HSP72 , Cortisol and Creatine Kinase

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    M. Amani

    2013-10-01

    Full Text Available Introduction & Objective: Heat shock proteins help the cells’ ability to keep their structures against different stresses. The purpose of this study was to investigate the effect of one ses-sion continuous and intermittent aerobic exercise on blood responses of HSP72, cortisol and creatine kinase (CK. Materials & Methods: This study is semi-experimental in which 21 male student athletes were divided in continuous group (n=7, intermittent group (n=7 and control group (n=7. Exer-cise protocol of continuous group included 1 hour running with 80% maximum heart rate in-tensity and that of intermittent group was 3 stages of 20 minute running with the same inten-sity as of continuous group . Blood sampling of basal, pre exercise, immediately after exer-cise and 90 minutes after exercise were gathered and the amounts of HSP72, cortisol and CK, were measured by ELISA, RIA and Enzymatic methods respectively. The data was analyzed with one way ANOVA and repeated measure analysis of variance at P?0.05 significance level. Results: HSP72 levels in the continuous group and intermittent group despite an increase in the average did not show a statistically significant difference. Changes between the groups were significant in immediately after exercise and 90 minutes after exercise (P.values respectively 0.017 and 0.002. CK changes in continuous group were significant but cortisol changes in different stages hadn’t significant difference Conclusion: Exercise with its role associated with cortisol and CK will stimulate HSP72 and continuous exercise will make further increase in HSP72 and CK increasing leads to a greater HSP72 response. (Sci J Hamadan Univ Med Sci 2013; 20 (3:223-231

  19. EFFECTS OF DIFFERENT RESISTANCE EXERCISE PROTOCOLS ON NITRIC OXIDE, LIPID PEROXIDATION AND CREATINE KINASE ACTIVITY IN SEDENTARY MALES

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    Nevin Atalay Güzel

    2007-12-01

    Full Text Available The purpose of this study was to determine the changes of oxidative response and exercise-induced muscle damage after two different resistance exercise protocols. Whether training with low or high intensity resistance programs cause alterations in the activities of lipid peroxidation, nitric oxide (NOx, and creatine kinase (CK activity in human plasma was investigated. Twenty untrained males participated into this study. Ten of the subjects performed high intensity resistance (HR exercise circuit and the rest of them performed low intensity resistance (LR exercise circuit of 4 different exercises as a single bout. Venous blood samples were drawn pre-exercise, immediately after the exercise, and at the 6th, 24th, 48th and the72nd hours of post-exercise. Samples were analyzed for markers of muscle damage (CK, lipid peroxidation (MDA and NOx. NOx production increased in HR group (p < 0.05. The MDA response to the two different resistance exercise protocol in this study caused a significant increase between pre and post-exercise values in both groups (p < 0.05. Also, there was a significant difference in the MDA level between the two groups in post-exercise values (p < 0.05 and higher values were observed in HR group. CK activities showed a significant increase in all post exercise values (p < 0.05 of both groups but there were no difference between HR and LR groups. These findings support that high intensity resistance exercise induces free radical production more than low intensity resistance exercise program

  20. High ubiquitous mitochondrial creatine kinase expression in hepatocellular carcinoma denotes a poor prognosis with highly malignant potential.

    Science.gov (United States)

    Uranbileg, Baasanjav; Enooku, Kenichiro; Soroida, Yoko; Ohkawa, Ryunosuke; Kudo, Yotaro; Nakagawa, Hayato; Tateishi, Ryosuke; Yoshida, Haruhiko; Shinzawa, Seiko; Moriya, Kyoji; Ohtomo, Natsuko; Nishikawa, Takako; Inoue, Yukiko; Tomiya, Tomoaki; Kojima, Soichi; Matsuura, Tomokazu; Koike, Kazuhiko; Yatomi, Yutaka; Ikeda, Hitoshi

    2014-05-01

    We previously reported the increased serum mitochondrial creatine kinase (MtCK) activity in patients with hepatocellular carcinoma (HCC), mostly due to the increase in ubiquitous MtCK (uMtCK), and high uMtCK mRNA expression in HCC cell lines. We explored the mechanism(s) and the relevance of high uMtCK expression in HCC. In hepatitis C virus core gene transgenic mice, known to lose mitochondrial integrity in liver and subsequently develop HCC, uMtCK mRNA and protein levels were increased in HCC tissues but not in non-tumorous liver tissues. Transient overexpression of ankyrin repeat and suppressor of cytokine signaling box protein 9 (ASB9) reduced uMtCK protein levels in HCC cells, suggesting that increased uMtCK levels in HCC cells may be caused by increased gene expression and decreased protein degradation due to reduced ASB9 expression. The reduction of uMtCK expression by siRNA led to increased cell death, and reduced proliferation, migration and invasion in HCC cell lines. Then, consecutive 105 HCC patients, who underwent radiofrequency ablation with curative intent, were enrolled to analyze their prognosis. The patients with serum MtCK activity >19.4 U/L prior to the treatment had significantly shorter survival time than those with serum MtCK activity ≤ 19.4 U/L, where higher serum MtCK activity was retained as an independent risk for HCC-related death on multivariate analysis. In conclusion, high uMtCK expression in HCC may be caused by hepatocarcinogenesis per se but not by loss of mitochondrial integrity, of which ASB9 could be a negative regulator, and associated with highly malignant potential to suggest a poor prognosis. © 2013 UICC.

  1. Regulation of the Na+,Cl- Coupled Creatine Transporter CreaT (SLC6A8) by the Janus Kinase JAK3

    OpenAIRE

    Myriam Fezai; Jamshed Warsi; Florian Lang

    2015-01-01

    Background: The creatine transporter CreaT (SLC6A8), a Na+,Cl- coupled transporter is expressed in diverse tissues including the brain. Genetic defects of SLC6A8 result in mental retardation with seizures. The present study explored the regulation of CreaT by Janus kinase JAK3, which is expressed in a variety of tissues including the brain and participates in the regulation of cell survival and differentiation of neuronal precursor cells. Methods: CreaT was expressed in Xenopus laevis oocytes...

  2. Creatine kinase rate constant in the human heart measured with 3D-localization at 7 tesla.

    Science.gov (United States)

    Clarke, William T; Robson, Matthew D; Neubauer, Stefan; Rodgers, Christopher T

    2017-07-01

    We present a new Bloch-Siegert four Angle Saturation Transfer (BOAST) method for measuring the creatine kinase (CK) first-order effective rate constant kf in human myocardium at 7 tesla (T). BOAST combines a variant of the four-angle saturation transfer (FAST) method using amplitude-modulated radiofrequency pulses, phosphorus Bloch-Siegert B1+-mapping to determine the per-voxel flip angles, and nonlinear fitting to Bloch simulations for postprocessing. Optimal flip angles and repetition time parameters were determined from Monte Carlo simulations. BOAST was validated in the calf muscle of two volunteers at 3T and 7T. The myocardial CK forward rate constant was then measured in 10 volunteers at 7T in 82 min (after 1 H localization). BOAST kfCK values were 0.281 ± 0.002 s-1 in the calf and 0.35 ± 0.05 s-1 in myocardium. These are consistent with literature values from lower fields. Using a literature values for adenosine triphosphate concentration, we computed CK flux values of 4.55 ± 1.52 mmol kg-1 s-1 . The sensitive volume for BOAST depends on the B1 inhomogeneity of the transmit coil. BOAST enables measurement of the CK rate constant in the human heart at 7T, with spatial localization in three dimensions to 5.6 mL voxels, using a 10-cm loop coil. Magn Reson Med 78:20-32, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

  3. CK (Creatine Kinase) Test

    Science.gov (United States)

    ... thyroid disorders , Addison disease or Cushing disease Strenuous exercise Prolonged surgeries Seizures Infections – viral (such as influenza and HIV ), bacterial , fungal , and parasitic (such as malaria ) Connective tissue disorders (e.g. lupus , rheumatoid arthritis ) Celiac disease Renal failure In critically ...

  4. CK (Creatine Kinase) Test

    Science.gov (United States)

    ... gamma-carboxy prothrombin (DCP) DHEAS Diabetes-related Autoantibodies Digoxin Direct Antiglobulin Test Direct LDL Cholesterol Drug Abuse ... Gout Graves Disease Guillain-Barré Syndrome Hashimoto Thyroiditis Heart Attack and Acute Coronary Syndrome Heart Disease Hemochromatosis Hemoglobin ...

  5. Presence of enolase in the M-band of skeletal muscle and possible indirect interaction with the cytosolic muscle isoform of creatine kinase.

    Science.gov (United States)

    Foucault, G; Vacher, M; Merkulova, T; Keller, A; Arrio-Dupont, M

    1999-01-01

    Glycerol-skinned skeletal muscle fibres retain the defined sarcomeric structure of the myofibrils. We show here that a small fraction of two enzymes important for energy metabolism, the cytosolic muscle isoform of creatine kinase (EC 2.7.3.2), MM-creatine kinase (MM-CK), and enolase (EC 4.2.1.11), remains bound to skinned fibres. CK is slowly exchangeable, whereas enolase is firmly bound. Two-dimensional gel electrophoresis followed by Western blot analyses demonstrates that both alpha (ubiquitous) and beta (muscle-specific) subunits of enolase are present in these preparations. Enolase and CK were co-localized at the M-band of the sarcomeres, as observed by indirect immunofluorescence and confocal microscopy. Cross-linking experiments were performed on skinned fibres with three bifunctional succinimidyl esters of different lengths and yielded a protein complex of 150 kDa that reacted with antibodies directed against either M-CK or beta-enolase. The cross-linking efficiency was greatest for the longest reagent and zero for the shortest one. The length of the cross-linker giving a covalent complex between the two enzymes does not support the notion of a direct interaction between M-CK and enolase. This is the first demonstration of the presence of an enzyme of energy metabolism other than CK at the M-band of myofibres. PMID:9931306

  6. Creatine kinase as an indicator for hysterectomy in postpartum endomyometritis due to group A streptococci: a hypothesis illustrated by a case report.

    Science.gov (United States)

    Dehaene, Isabelle; Loccufier, Anne; Temmerman, Marleen; De Keersmaecker, Bart; De Baene, Luc

    2012-01-01

    Puerperal group A streptococcus (GAS) infection, once the leading cause of postpartum sepsis, has been increasing again since the 1980s. Streptococcal toxic shock syndrome (STSS) is a serious complication characterized by rapidly spreading GAS infection, shock, and multiple organ failure. Immediate recognition and implementation of therapy is crucial for survival. Making informed decisions regarding surgical debridement, namely hysterectomy, based on clinical indicators is difficult for practitioners. This article discusses the potential role of creatine kinase in the decision-making process for treatment of STSS, particularly with regard to hysterectomy. A case report is presented. The literature was searched using the key words 'group A streptococcus', 'postpartum hysterectomy', 'creatine kinase', 'endomyometritis', and 'streptococcal toxic shock syndrome' in PubMed and the UptoDate database. Relevant articles published between 1991 and 2011 were evaluated. Decisions regarding hysterectomy in STSS management are difficult. A rise in CK levels in the serum may indicate involvement of the myometrium and may be an important parameter in the difficult decision of hysterectomy when treating STSS. Copyright © 2011 S. Karger AG, Basel.

  7. Effect of sex and time to slaughter (transportation and lairage duration) on the levels of cortisol, creatine kinase and subsequent relationship with pork quality.

    Science.gov (United States)

    Jama, N; Maphosa, V; Hoffman, L C; Muchenje, V

    2016-06-01

    The study determined the effect of sex and time to slaughter on cortisol and creatine kinase levels, and pork quality in commercial crossbred pigs. Saliva samples were before collected transportation, on arrival at the abattoir, and after a 20 hour lairage period. Cortisol levels from saliva (SC), serum (SeC) and urine (UC) were determined. Creatine kinase (CK) levels were determined from serum samples. Fifteen boars vs. 15 gilts were immediately slaughtered on arrival (SOA), and the other 15 boars vs. 15 gilts were rested for 20 h before slaughter. Meat quality parameters were also determined. In both sexes, SC significantly increased in response to time to slaughter. There was a significant interaction of sex and time to slaughter on SeC. Gilts had higher CK levels and lower muscle L* values than boars. There were correlations among baseline SC, SeC, UC and most meat quality parameters. Time to slaughter influenced levels of SC, UC, CK and pork quality between boars and gilts. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. The Effects of Pre-slaughter Stress and Season on the Activity of Plasma Creatine Kinase and Mutton Quality from Different Sheep Breeds Slaughtered at a Smallholder Abattoir

    Directory of Open Access Journals (Sweden)

    A. Y. Chulayo

    2013-12-01

    Full Text Available The objective of the current study was to determine the effect of pre-slaughter stress, season and breed on the activity of plasma creatine kinase (CK and the quality of mutton. One hundred and seventy-three (173 castrated sheep from Dormer (DM, South African Mutton Merino (SAMM, Dorper (DP and Blackhead Persian (BP sheep breeds were used in the study. The animals were grouped according to age-groups as follows: Group 1 (6 to 8 months, Group 2 (9 to 12 months and Group 3 (13 to 16 months. Blood samples were collected during exsanguinations using disposable vacutainer tubes for CK analysis. Representative samples of the Muscularis longissimuss thoracis et. lumborum (LTL were collected from 84 castrated sheep, of different breeds (28 per breed 24 h after slaughter. The following physico-chemical characteristics of mutton were determined; meat pH (pH24, color (L*, a* and b*, thawing and cooking losses and Warner Braztler Shear Force (WBSF. The activity of plasma CK was significantly higher (p0.001 levels (1,358.6±191.08 of CK. South African Mutton Merino had higher values for pH24 (5.9±0.06, L* (34.2±0.97, b* (12.2±0.50 and WBSF (26.8±1.51 and Blackhead Persian had higher values (35.5±2.17 for cooking loss (CL% than the other breeds. Computed Principal Component Analyses (PCA on the activity of plasma CK and physico-chemical characteristics of mutton revealed no correlations between these variables. However, positive correlations were observed between pH24, L*, a*, b*, CL% and WBSF. Relationships between pre-slaughter stress, CK activity and physico-chemical characteristics of mutton were also observed. It was therefore concluded that although mutton quality and creatine kinase were not related, pre-slaughter stress, season and breed affected the activity of creatine kinase and mutton quality.

  9. Growth inhibition in response to estrogen withdrawal and tamoxifen therapy of human breast cancer xenografts evaluated by in vivo 31P magnetic resonance spectroscopy, creatine kinase activity, and apoptotic index

    DEFF Research Database (Denmark)

    Kristensen, C A; Kristjansen, P E; Brünner, N

    1995-01-01

    index, and creatine kinase (CK) activity. Tumors of each line were grown in ovariectomized nude mice during stimulation from a s.c. 17 beta-estradiol pellet. At a tumor size of approximately 350 mm3, the pellet was removed from one-half of the animals. The remaining one-half served as controls...

  10. High creatine kinase levels and white matter changes: clinical and genetic spectrum of congenital muscular dystrophies with laminin alpha-2 deficiency.

    Science.gov (United States)

    Beytía, Maria de los Angeles; Dekomien, Gabriele; Hoffjan, Sabine; Haug, Verena; Anastasopoulos, Constantin; Kirschner, Janbernd

    2014-08-01

    Primary deficiency of laminin alpha-2 due to mutations in the LAMA2 gene accounts for 30% of all patients with congenital muscular dystrophy. Here, we present seven patients with partial or total laminin alpha-2 deficiency (MDC1A) with a wide clinical spectrum, ranging from ambulant patients to patients who were never able to stand or sit. We identified two pathogenic mutations in the LAMA2 gene in all patients except for one patient in whom only one mutation was found. Six of the mutations were previously undescribed. In some of the milder cases, laminin alpha-2 expression in the muscle biopsy was only slightly reduced. These findings emphasize that analysis of the LAMA2 gene might be necessary in patients with muscle weakness, cerebral white matter changes and high creatine kinase levels, even in the presence of laminin alpha-2 in the muscle biopsy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Serum concentrations of creatine kinase and of triglycerides during lactation in gilts bred older and in multiparous sows fed ad libitum

    Directory of Open Access Journals (Sweden)

    Nogueira R.H.G.

    2000-01-01

    Full Text Available The aim of this paper was to assess the possible variation in blood concentrations of creatine kinase (CK and triglycerides in gilts bred older in comparison with multiparous sows. Ten primiparous and ten Camborough multiparous sows from the fourth to seventh parities were used. Breeding age and weight of gilts averaged respectively 231 days and 149.5kg. All females were moved into individual farrowing crates and were managed under the same conditions. Blood samples were collected by puncturing the coccygeal artery on day 7 before expected farrowing, and on days 2, 7, 14, 21 of lactation and 2 days after weaning. No difference in triglycerides and CK serum concentrations between groups were observed. The CK levels were low before farrowing, increased substantially on days 2 and 7 and decreased toward the end of lactation. The concentrations of triglycerides were slightly high before the parturition, diminished on days 2, 7, 14 and 21 and increased after weaning.

  12. Elevation of serum creatine kinase as the only manifestation of an intragenic deletion of the dystrophin gene in three unrelated families.

    Science.gov (United States)

    Melis, M A; Cau, M; Muntoni, F; Mateddu, A; Galanello, R; Boccone, L; Deidda, F; Loi, D; Cao, A

    1998-01-01

    This study reports three children from three unrelated families, aged from 9 to 12 years, who were investigated because of the incidental finding of elevated serum creatine kinase (CK) levels and were found to have a dystrophinopathy. The molecular defect consisted of a deletion of variable extent within the central rod domain of the dystrophin gene, involving either exons 32-44 or 48-51 or 48-53. In each family we found the same deletion in at least one adult male relative aged from 40 to 77 years, who was either completely asymptomatic or had very mild muscle involvement (thin muscles and/or mild scoliosis), with normal or borderline CK levels. This study suggests once again that deletions of the central rod domain of dystrophin may be associated with elevation of serum CK as the only manifestation and that prediction of the clinical severity based solely on the molecular findings should be interpreted with caution.

  13. 31P NMR 2D Mapping of Creatine Kinase Forward Flux Rate in Hearts with Postinfarction Left Ventricular Remodeling in Response to Cell Therapy.

    Directory of Open Access Journals (Sweden)

    Ling Gao

    Full Text Available Utilizing a fast 31P magnetic resonance spectroscopy (MRS 2-dimensional chemical shift imaging (2D-CSI method, this study examined the heterogeneity of creatine kinase (CK forward flux rate of hearts with postinfarction left ventricular (LV remodeling. Immunosuppressed Yorkshire pigs were assigned to 4 groups: 1 A sham-operated normal group (SHAM, n = 6; 2 A 60 minutes distal left anterior descending coronary artery ligation and reperfusion (MI, n = 6; 3 Open patch group; ligation injury plus open fibrin patch over the site of injury (Patch, n = 6; and 4 Cell group, hiPSCs-cardiomyocytes, -endothelial cells, and -smooth muscle cells (2 million, each were injected into the injured myocardium pass through a fibrin patch (Cell+Patch, n = 5. At 4 weeks, the creatine phosphate (PCr/ATP ratio, CK forward flux rate (Flux PCr→ATP, and k constant of CK forward flux rate (kPCr→ATP were severely decreased at border zone myocardium (BZ adjacent to MI. Cell treatment results in significantly increase of PCr/ATP ratio and improve the value of kPCr→ATP and Flux PCr→ATP in BZ myocardium. Moreover, the BZ myocardial CK total activity and protein expression of CK mitochondria isozyme and CK myocardial isozyme were significantly reduced, but recovered in response to cell treatment. Thus, cell therapy results in improvement of BZ bioenergetic abnormality in hearts with postinfarction LV remodeling, which is accompanied by significantly improvements in BZ CK activity and CK isozyme expression. The fast 2D 31P MR CSI mapping can reliably measure the heterogeneity of bioenergetics in hearts with post infarction LV remodeling.

  14. On the theoretical limits of detecting cyclic changes in cardiac high-energy phosphates and creatine kinase reaction kinetics using in vivo ³¹P MRS.

    Science.gov (United States)

    Weiss, Kilian; Bottomley, Paul A; Weiss, Robert G

    2015-06-01

    Adenosine triphosphate (ATP) is absolutely required to fuel normal cyclic contractions of the heart. The creatine kinase (CK) reaction is a major energy reserve reaction that rapidly converts creatine phosphate (PCr) to ATP during the cardiac cycle and at times of stress and ischemia, but is significantly impaired in conditions such as hypertrophy and heart failure. Because the magnitudes of possible in vivo cyclic changes in cardiac high-energy phosphates (HEPs) during the cardiac cycle are not well known from previous work, this study uses mathematical modeling to assess whether, and to what extent, cyclic variations in HEPs and in the rate of ATP synthesis through CK (CK flux) could exist in the human heart, and whether they could be measured with current in vivo (31)P MRS methods. Multi-site exchange models incorporating enzymatic rate equations were used to study the cyclic dynamics of the CK reaction, and Bloch equations were used to simulate (31)P MRS saturation transfer measurements of the CK reaction. The simulations show that short-term buffering of ATP by CK requires temporal variations over the cardiac cycle in the CK reaction velocities modeled by enzymatic rate equations. The maximum variation in HEPs in the normal human heart beating at 60 min(-1) was approximately 0.4 mM and proportional to the velocity of ATP hydrolysis. Such HEP variations are at or below the current limits of detection by in vivo (31)P MRS methods. Bloch equation simulations show that (31)P MRS saturation transfer estimates the time-averaged, pseudo-first-order forward rate constant, k(f,ap)', of the CK reaction, and that periodic short-term fluctuations in kf ' and CK flux are not likely to be detectable in human studies employing current in vivo (31)P MRS methods. Copyright © 2015 John Wiley & Sons, Ltd.

  15. the Effect of six weeks of high intensity interval training and zinc ‎supplement on serum ‎creatine kinase and uric acid levels in ‎futsal players ‎

    Directory of Open Access Journals (Sweden)

    Malihe Saeedy

    2017-01-01

    Full Text Available Background: strenuous training‎-induced reactive oxygen species is associated with several ‎chronic diseases‎ by damaging cell proteins and membrane lipids; it seems uric acid as a major ‎intracellular antioxidant could lower membranous lipid peroxidation and muscle damage. The aim ‎of this study was to examine the effect of six weeks of high-intensity interval training with and ‎‎without zinc ‎on serum Creatine Kinase and uric acid in female futsal players.‎ Methods: Thirty-two female futsal players were randomly divided into four groups: placebo, ‎Zinc, ‎HIT ‎and Zinc+HIT. All subjects had to attend futsal-specific training three sessions per ‎week. Zinc and ‎Placebo groups took ‎30 mg ‎day−1 of zinc gluconate or dextrose, respectively; ‎HIT groups accomplished high-intensity interval training contained 6 to 10 repetitions of a 30-‎second ‎running at 100% of VO2peak with a 4-minutes rest between efforts, during six weeks.‎ Results: After six weeks, Creatine Kinase ‎levels augmented insignificantly from 83.98 to 120.19‎ ‎‎(P=0.101 in ‎placebo, from 99.58 to 150.1(P=0.167 in HIT and from 81.07 to 107.90‎ ‎‎(P=0.152 ‎in HIT+Zinc group; while Creatine Kinase ‎levels increased significantly from 66.86 to ‎‎‎124.81(P=0.004 only in Zinc group. Uric acid levels increased in all groups (Placebo (P=1, Zinc ‎‎(P=‎0.317‎, HIT (P=‎0.157‎, ‎Zinc+HIT (P=1 insignificantly Conclusions: The findings indicated that ‎after six weeks, serum Creatine Kinase and uric acid ‎levels increased insignificantly in all groups; Creatine Kinase ‎levels augmented significantly, only ‎in Zinc group. Zinc as an antioxidant supplement could not decrease the muscle damage, and even ‎increased the serum Creatine Kinase as a marker of muscle damage, significantly

  16. Análise dos níveis séricos de creatina quinase em atletas de futebol universitário após uma sessão intermitente/Analysis of serum creatine kinase in athletes in college football after an intermittent session

    National Research Council Canada - National Science Library

    L L Soares; E M Pimenta; A F S Barros; L B Lessa; G A Pussieldi

    2012-01-01

      Lately football has been the target of numerous studies. The biochemical analysis has helped to better control the coaches training, and minimize the removal of the athletes for muscle stress. Creatine Kinase (CK...

  17. Influence of racing on the serum concentrations of the cardiac biomarkers troponin I and creatine kinase myocardial band (CK-MB) in racing greyhounds.

    Science.gov (United States)

    Tharwat, Mohamed; Al-Sobayil, Fahd; Buczinski, Sébastien

    2013-09-01

    The objective of this study was to investigate the effect of racing on the serum concentrations of cardiac troponin I (cTnI) and creatine kinase myocardial band (CK-MB) in 32 racing greyhounds. Blood samples were collected 24h prior to a 7 km race (T0), within 2h of completion of the race (T1), and 24h post-race (T2). Blood samples were also collected from 20 non-racing greyhounds. The median cTnI concentration in the racing greyhounds was not significantly different from that in the non-racing greyhounds (0.045 ng/mL). Before racing, the median cTnI concentration in the racing greyhounds was 0.050 ng/mL. Following the 7 km race, 31/32 greyhounds showed increases in cTnI concentrations which were significantly higher than the pre-race concentrations (Prace to values not significantly different from the pre-race concentrations. Following the race, 5/32 greyhounds showed mild increases in CK-MB concentrations but these were not significantly different from the pre-race values. These findings could be of importance when evaluating greyhounds with suspected cardiac disease that have recently performed hard exercise. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Early postictal serum lactate concentrations are superior to serum creatine kinase concentrations in distinguishing generalized tonic-clonic seizures from syncopes.

    Science.gov (United States)

    Matz, Oliver; Heckelmann, Jan; Zechbauer, Sebastian; Litmathe, Jens; Brokmann, Jörg C; Willmes, Klaus; Schulz, Jörg B; Dafotakis, Manuel

    2017-09-12

    Concentrations of serum creatine kinase (CK) and serum lactate are frequently measured to help differentiate between generalized tonic-clonic seizures (GTCS) and syncope. The aim of this prospective cohort study was to systematically compare these two markers. The primary outcome is the measurement of serum lactate and CK in blood samples drawn within 2 h of the event in patients admitted with either a GTCS (n = 49) or a syncope (n = 36). Furthermore, the specificity and sensitivity of serum lactate and CK are determined as diagnostic markers in distinguishing between GTCS and syncope. GTCS patients have significantly higher serum lactate levels compared to syncope patients (p seizure, we identify a cut-off for serum lactate of 2.45 mmol/l for diagnosing GTCS as the cause of an impairment of consciousness with a sensitivity of 0.94 and a specificity of 0.93 (AUC: 0.97; 95% CI 0.94-1.0). In the second hour after the event, the ROC analysis yields similar results (AUC: 0.94; 95% CI 0.85-1.0). Serum lactate is a sensitive and specific diagnostic marker to discriminate GTCS from syncope and is superior to CK early after admission to the emergency department.

  19. Assessment of serum creatine kinase among adolescent patients following jimsonweed (Datura stramonium) and moonflower (Datura inoxia) ingestions: a review of 11 cases.

    Science.gov (United States)

    Blackford, Martha G; Fitzgibbon, James J; Reed, Michael D

    2010-06-01

    Datura stramonium (DS) (jimsonweed) is well known for its abuse potential for hallucinogenic effects and Datura inoxia (DI) (moonflower) has been abused for similar effects. To our knowledge, only one case report describes rhabdomyolysis in association with DS or DI ingestion. Patient hospital charts were retrospectively screened from January 1, 2002 to December 31, 2007 to identify patients with qualifying ICD-9 codes for toxic plant ingestions. We report on 11 patient cases of DS/DI ingestions in which serum creatine kinase (CK) concentrations were monitored. These admissions occurred at our hospital over a 6-year period. Serum CK concentrations ranged from 72 to 70,230 U/L. Only three patients had serum CK concentrations greater than 1,000 U/L. One patient with a peak concentration of 70,230 U/L and a positive myoglobinuria was diagnosed with rhabdomyolysis. Based on our review of the literature and these cases, it is possible that serum CK concentrations may be elevated more frequently than previously realized. The clinical significance of this abnormal laboratory value is uncertain with the majority of patients remaining asymptomatic without any clinical evidence of rhabdomyolysis.

  20. The value of serum creatine kinase in predicting the risk of rhabdomyolysis-induced acute kidney injury: a systematic review and meta-analysis.

    Science.gov (United States)

    Safari, Saeed; Yousefifard, Mahmoud; Hashemi, Behrooz; Baratloo, Alireza; Forouzanfar, Mohammad Mehdi; Rahmati, Farhad; Motamedi, Maryam; Najafi, Iraj

    2016-04-01

    Identifying the potential effective factors of rhabdomyolysis-induced acute kidney injury (AKI) is of major importance for both treatment and logistic concerns. The present study aimed to evaluate the value of creatine kinase (CK) in predicting the risk of rhabdomyolysis-induced AKI through meta-analysis. Two reviewers searched the electronic databases of Medline, EMBASE, Cochrane library, Scopus, and Google Scholar. Data regarding study design, patient characteristics, number of cases, mean and screening characteristics of CK, and final patient outcome were extracted from relevant studies. Pooled measures of standardized mean difference, OR, and diagnostic accuracy were calculated using STATA version 11.0. 5997 non-redundant studies were found (143 potentially relevant). 27 articles met the inclusion criteria but 9 were excluded due to lack of data. The correlation between serum CK and AKI occurrence was stronger in traumatic cases (SMD = 1.34, 95 % CI = 1.25-1.42, I(2) = 94 %; p rhabdomyolysis etiology (traumatic/non-traumatic) in predictive performance of CK. There was a significant correlation between mean CK level and risk of crush-induced AKI. The pooled OR of CK was considerable, but its screening performance characteristics were not desirable.

  1. N-Acetylcysteine Supplementation Controls Total Antioxidant Capacity, Creatine Kinase, Lactate, and Tumor Necrotic Factor-Alpha against Oxidative Stress Induced by Graded Exercise in Sedentary Men

    Directory of Open Access Journals (Sweden)

    Donrawee Leelarungrayub

    2011-01-01

    Full Text Available Aim of this study was to evaluate the effects of short-term (7 days N-acetylcysteine (NAC at 1,200 mg daily supplementation on muscle fatigue, maximal oxygen uptake (VO2max, total antioxidant capacity (TAC, lactate, creatine kinase (CK, and tumor necrotic factor-alpha (TNF-α. Twenty-nine sedentary men (13 controls; 16 in the supplement group from a randomized control were included. At before and after supplementation, fatigue index (FI was evaluated in the quadriceps muscle, and performed a graded exercise treadmill test to induce oxidative stress, and as a measure of VO2max. Blood samples were taken before exercise and 20 minutes after it at before and after supplementation, to determine TAC, CK, lactate, and TNF-α levels. Results showed that FI and VO2max increased significantly in the supplement group. After exercise decreased the levels of TAC and increased lactate, CK, and TNF-α of both groups at before supplementation. After supplementation, lactate, CK, and TNF-α levels significantly increased and TAC decreased after exercise in the control group. Whereas the TAC and lactate levels did not change significantly, but CK and TNF-α increased significantly in the supplement group. Therefore, this results showed that NAC improved the muscle fatigue, VO2max, maintained TAC, controlled lactate production, but had no influence on CK and TNF-α.

  2. N-acetylcysteine supplementation controls total antioxidant capacity, creatine kinase, lactate, and tumor necrotic factor-alpha against oxidative stress induced by graded exercise in sedentary men.

    Science.gov (United States)

    Leelarungrayub, Donrawee; Khansuwan, Raphiphat; Pothongsunun, Prapas; Klaphajone, Jakkrit

    2011-01-01

    Aim of this study was to evaluate the effects of short-term (7 days) N-acetylcysteine (NAC) at 1,200 mg daily supplementation on muscle fatigue, maximal oxygen uptake (VO(2max)), total antioxidant capacity (TAC), lactate, creatine kinase (CK), and tumor necrotic factor-alpha (TNF-α). Twenty-nine sedentary men (13 controls; 16 in the supplement group) from a randomized control were included. At before and after supplementation, fatigue index (FI) was evaluated in the quadriceps muscle, and performed a graded exercise treadmill test to induce oxidative stress, and as a measure of VO(2max). Blood samples were taken before exercise and 20 minutes after it at before and after supplementation, to determine TAC, CK, lactate, and TNF-α levels. Results showed that FI and VO(2max) increased significantly in the supplement group. After exercise decreased the levels of TAC and increased lactate, CK, and TNF-α of both groups at before supplementation. After supplementation, lactate, CK, and TNF-α levels significantly increased and TAC decreased after exercise in the control group. Whereas the TAC and lactate levels did not change significantly, but CK and TNF-α increased significantly in the supplement group. Therefore, this results showed that NAC improved the muscle fatigue, VO(2max), maintained TAC, controlled lactate production, but had no influence on CK and TNF-α.

  3. Effects of Sesame (Sesamum indicumL.) Supplementation on Creatine Kinase, Lactate Dehydrogenase, Oxidative Stress Markers, and Aerobic Capacity in Semi-Professional Soccer Players.

    Science.gov (United States)

    Barbosa, Carlos V da Silva; Silva, Alexandre S; de Oliveira, Caio V C; Massa, Nayara M L; de Sousa, Yasmim R F; da Costa, Whyara K A; Silva, Ayice C; Delatorre, Plínio; Carvalho, Rhayane; Braga, Valdir de Andrade; Magnani, Marciane

    2017-01-01

    Nutritional intervention with antioxidants rich foods has been considered a strategy to minimize the effects of overtraining in athletes. This experimental, randomized, and placebo-controlled study evaluated the effects of consumption of sesame ( Sesamum indicum L.) on muscle damage markers, oxidative stress, systemic inflammation, and aerobic performance in male semi-professional soccer players. Twenty athletes were randomly assigned to groups that received 40 g (two tablespoons) per day of sesame or a placebo during 28 days of regular training (exposed to routine training that includes loads of heavy training in the final half of the season). Before and after intervention, creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), C-reactive protein (hs-CRP), and aerobic capacity were evaluated. Before intervention, a physiologic imbalance was noted in both groups related to CK and LDH levels. Sesame intake caused a reduction of CK (19%, p sesame consumption may reduce muscle damage and oxidative stress while improving the aerobic capacity in soccer players.

  4. Expression of the brain creatine kinase gene in rat RT4 peripheral neurotumor cell lines and its modulation by cell confluence.

    Science.gov (United States)

    Wilson, C D; Shen, W; Kuzhikandathil, E V; Molloy, G R

    1997-01-01

    Creatine kinases (CK) catalyze the reversible transfer of a high energy phosphate group between creatine phosphate and ADP to regenerate ATP in cell types where the requirements for ATP are extensive and/or sudden. Previously, we have shown in primary rat brain cell cultures that brain CK (CKB) mRNA levels are highest in astrocytes and oligodendrocytes and much lower in neuronal cells. However, little is known of the factors which regulate CKB expression in the central nervous system and peripheral nervous system. To begin to investigate these factors, we asked in this report (1) if this pattern of CKB expression was also characteristic of some established glial and neuronal cell lines derived from the PNS; (2) whether CKB expression could be rapidly modulated by culture conditions, and (3) if CKB is expressed in cells with characteristics of glial cell progenitors. In subconfluent cells, CKB mRNA and enzyme activity were found to be high in both the rat RT4 peripheral neurotumor stem cell RT4-AC36A and its glial cell derivative RT4-D6. Conversely, CKB mRNA and activity were 5- and 8-fold lower, respectively, in the neuronal derivative RT4-E5 and, more dramatically, CKB was undetectable in neuronal RT4-B8 cells. Maintaining RT4-D6 glial cells at confluence rapidly increased CKB enzyme activity by 7-fold, such that D6 cells contained about 25% of the CKB level in lysates prepared from either whole adult rat brain or primary cultures of rat brain astrocytes. The levels of CKB mRNA and immunoreactive protein were also correspondingly increased in confluent D6 cells. These confluence-mediated increases in CKB appeared to be due to cell-cell contact and not the depletion of serum growth factors or an increase in intracellular cAMP. This study indicates that CKB expression is highest in cells displaying glial properties and can be rapidly modulated by appropriate culture conditions. The results are discussed in relation to the factors which may regulate CKB expression in

  5. Creatine and creatine analogues in hypertension and cardiovascular disease

    NARCIS (Netherlands)

    Horjus, Deborah L.; Oudman, Inge; van Montfrans, Gert A.; Brewster, Lizzy M.

    2011-01-01

    The creatine kinase system, the central regulatory system of cellular energy metabolism, provides ATP in situ at ATP-ases involved in ion transport and muscle contraction. Furthermore, the enzyme system provides relative protection from tissue ischaemia and acidosis. The system could therefore be a

  6. Relationship of creatine kinase, aspartate aminotransferase, lactate dehydrogenase, and proteinuria to cardiomyopathy in the owl monkey (Aotus vociferans)

    Energy Technology Data Exchange (ETDEWEB)

    Gozalo, Alfonso S.; Chavera, Alfonso; Montoya, Enrique J.; Takano, Juan; Weller, Richard E.

    2008-02-01

    The purpose of this study was to determine serum reference values for crea- tine kinase (CK), aspartate aminotransferase (AST), and lactate dehydroge- nase (LDH) in captive-born and wild-caught owl monkeys to assess their usefulness for diagnosing myocardial disease. Urine samples were also collected and semi-quantitative tests performed. There was no statistically significant difference between CK, AST, and LDH when comparing both groups. However, when comparing monkeys with proteinuria to those without proteinuria, a statistically significant difference in CK value was observed (P = 0.021). In addition, the CK/AST ratio revealed that 29% of the animals included in this study had values suggesting cardiac infarction. Grossly, cardiac concentric hypertrophy of the left ventricle and small, pitted kidneys were the most common findings. Microscopically, myocardial fibrosis, contraction band necrosis, hypertrophy and hyperplasia of coronary arteries, medium-sized renal arteries, and afferent glomerular arteriolae were the most significant lesions, along with increased mesangial matrix and hypercellularity of glomeruli, Bowman’s capsule, and peritubular space fibroplasia. These findings suggest that CK, AST, and LDH along with urinalysis provide a reliable method for diagnosing cardiomyopathies in the owl monkey. In addition, CK/AST ratio, proteinuria, and the observed histological and ultrastructural changes suggest that Aotus vociferans suffer from arterial hypertension and chronic myocardial infarction.

  7. The Ca2+/CaMKK2 axis mediates the telbivudine induced upregulation of creatine kinase: Implications for mechanism of antiviral nucleoside analogs' side effect.

    Science.gov (United States)

    Jianfei, Long; Min, Wang; Chunlai, Ma; Bicui, Chen; Jiming, Zhang; Bin, Wang

    2017-12-15

    Telbivudine (LdT), a widely prescribed anti-hepatitis B virus (HBV) drug for the treatment of chronic Hepatitis B (CHB), causes adverse reactions ranging from creatine kinase (CK) elevation to myopathy. The purpose of this study was to explore the mechanism(s) of LdT induced CK elevation. The effects of LdT on mitochondrial morphology and proteins (TK2 and β-actin), oxidative stress, intracellular Ca2+ levels, Ca2+-related signaling pathway (CaMKK2/AMPK), and Ca2+-related biomarkers such as superoxide dismutase (SOD) and malondialdehyde (MDA) were assessed in human skeletal muscle cells (HSKMCs). The results showed that LdT induced a dose-dependent increase in CK activity in HSKMCs, without affecting mitochondrial morphology, and TK2 and β-actin protein levels, following 72 h of treatment. In addition, LdT increased Ca2+ production, ROS generation, MDA and lipid peroxide (LPO) levels, and activated the CaMKK2/AMPK signaling pathway. Moreover, these effects were attenuated by the BAPIA-AM (the calcium chelator). We also confirmed the presence of relevant markers (MDA, LPO, and SOD) in serum from CHB patients after LdT treatment, and found that CK was positively correlated with MDA and LPO, and negatively associated with SOD. These findings indicate that LdT induces CK elevation and oxidative stress associated with imbalance of intracellular Ca2+ in HSKMCs, suggesting that Ca2+/CaMKK2 axis imbalance may underlie human LdT-induced CK elevation. The present findings provide a solid basis for assessing the mechanism of drug-induced CK elevation, which can help develop new tools for the prevention and treatment of diseases associated with drug-induced CK elevation. Copyright © 2017. Published by Elsevier Inc.

  8. Gender-differences in the associations between circulating creatine kinase, blood pressure, body mass and non-alcoholic fatty liver disease in asymptomatic asians.

    Directory of Open Access Journals (Sweden)

    Chih-Hsuan Yen

    Full Text Available Creatine kinase (CK is a pivotal regulatory enzyme in energy metabolism linked to both blood pressure and cardio-metabolic components. However, data is lacking in a large population of asymptomatic Asians.Cardio-metabolic assessment including anthropometric measures and non-alcoholic fatty liver disease (NAFLD were evaluated by abdominal echo in 4,562 consecutive subjects who underwent an annual health survey. Serum CK levels were related to blood pressure components [systolic blood pressure (SBP, diastolic blood pressure (DBP, and pulse pressure (PP], anthropometric measures, and excessive adiposity in liver as indicated by NAFLD. Circulating CK levels ranged from 4 to 1842 IU/L (mean [SE]: 108.7 [1.1] IU/L in the study population which consisted of 2522 males (mean age: 48.7 ± 11.2 and 2040 females (mean age: 49.4±11.5. In general, male subjects presented with higher circulating CK levels than females (mean ± SE: 127.3 ± 1.5 vs. 85.5 ± 1.3 IU/L, respectively, p < .001. Gender-differences in circulating CK levels were also observed with increasing age, which showed a more pronounced positive relationship with age in female subjects (gender interaction: p < .05. Furthermore, an elevated circulating CK level was independently associated with higher blood pressure, waist circumference and fat mass (FM, greater body mass index (BMI, increased lower estimated glomerular filtration rate (eGFR and presence of NAFLD in multivariate analysis (all p < .05, with CK elevation more pronounced with greater BMI and FM in males compared with females (sex interaction: p < .05.In a large asymptomatic Asian population, circulating CK levels were increased with more advanced age, higher blood pressure, and greater body mass with gender differences. Our findings may be useful in interpreting elevated CK from subjects free of ongoing myocardial damage.

  9. Light-emitting diode therapy (LEDT) before matches prevents increase in creatine kinase with a light dose response in volleyball players.

    Science.gov (United States)

    Ferraresi, Cleber; Dos Santos, Ricardo Vinicius; Marques, Guilherme; Zangrande, Marcelo; Leonaldo, Roberley; Hamblin, Michael R; Bagnato, Vanderlei Salvador; Parizotto, Nivaldo Antonio

    2015-05-01

    Low-level laser (light) therapy (LLLT) has been applied over skeletal muscles before intense exercise (muscular pre-conditioning) in order to reduce fatigue and muscle damage (measured by creatine kinase, CK) in clinical trials. However, previous exercise protocols do not exactly simulate the real muscle demand required in sports. For this reason, the aim of this randomized and double-blind placebo-controlled trial was to investigate whether light-emitting diode therapy (LEDT) applied over the quadriceps femoris muscles, hamstrings, and triceps surae of volleyball players before official matches could prevent muscle damage (CK) with a dose response, establishing a therapeutic window. A professional male volleyball team (12 athletes) was enrolled in this study, and LEDT was applied before 4 matches during a national championship. LEDT used an array of 200 light-emitting diodes (LEDs) arranged in 25 clusters of 4 infrared LEDs (850 ± 20 nm; 130 mW) and 25 clusters of 4 red LEDs (630 ± 10 nm; 80 mW). Athletes were randomized to receive one of four different total doses over each muscle group in a double-blind protocol: 105 J (20 s), 210 J (40 s), 315 J (60 s), and placebo (no light for 30 s). CK in blood was assessed 1 h before and 24 h after each match. LEDT at 210 J avoided significant increases in CK (+10 %; P = 0.993) as well as 315 J (+31 %, P = 0.407). Placebo (0 J) allowed a significant increase in CK (+53 %; P = 0.012) as well as LEDT at 105 J (+59 %; P = 0.001). LEDT prevented significant increases of CK in blood in athletes when applied before official matches with a light dose response of 210-315 J, suggesting athletes might consider applying LEDT before competition.

  10. Creatine kinase kinetics in professional soccer players during a competitive season. DOI: 10.5007/1980-0037.2011v13n3p189

    Directory of Open Access Journals (Sweden)

    Daniel Barbosa Coelho

    2011-04-01

    Full Text Available Serum creatine kinase (CK concentration has been widely used as an indicator of skeletal muscle damage in sports. However, there are no longitunal studies on post-game CK kinetics in Soccer during a competitive season. The aim of this study was to evaluate serum CK kinetics in professional Soccer players at different post-game times during a competitive season without training interruption. Seventeen professional soccer players (age: 22.2±3.1 years, height: 179±6.0 cm, body fat percentage: 9.5±1.1, and 67.0±3.5 mL O2/kg/min were evaluated over a period of 3 months of the national championship. Serum CK concentration was measured before the beginning of the season (baseline and at four different times after a soccer game (post-1: 12-20 h, post-2: 36-48 h, post-3: 60-65 h, and post-4: 90-110 h. Plasma CK concentrations were higher at all times when compared to baseline (p<0.05. Post-2 CK concentration was lower than post-1 and higher than post-3 and -4 (p<0.05, with no significant differences between post-3 and post-4. In conclusion, serum CK kinetics was influenced by the training routine of the soccer players, with a peak between 12 and 20 h after the game, returning to normal within 60-65 h. This procedure can be used to monitor the recovery state of athletes and game and training intensities.

  11. Creatine kinase kinetics in professional soccer players during a competitive season. DOI: 10.5007/1980-0037.2011v13n3p189

    Directory of Open Access Journals (Sweden)

    Daniel Barbosa Coelho

    2011-04-01

    Full Text Available Serum creatine kinase (CK concentration has been widely used as an indicator of skeletal muscle damage in sports. However, there are no longitunal studies on post-game CK kinetics in Soccer during a competitive season. The aim of this study was to evaluate serum CK kinetics in professional Soccer players at different post-game times during a competitive season without training interruption. Seventeen professional soccer players (age: 22.2±3.1 years, height: 179±6.0 cm, body fat percentage: 9.5±1.1, and 67.0±3.5 mL O2/kg/min were evaluated over a period of 3 months of the national championship. Serum CK concentration was measured before the beginning of the season (baseline and at four different times after a soccer game (post-1: 12-20 h, post-2: 36-48 h, post-3: 60-65 h, and post-4: 90-110 h. Plasma CK concentrations were higher at all times when compared to baseline (p<0.05. Post-2 CK concentration was lower than post-1 and higher than post-3 and -4 (p<0.05, with no significant differences between post-3 and post-4. In conclusion, serum CK kinetics was influenced by the training routine of the soccer players, with a peak between 12 and 20 h after the game, returning to normal within 60-65 h. This procedure can be used to monitor the recovery state of athletes and game and training intensities.

  12. Effects of Sesame (Sesamum indicum L.) Supplementation on Creatine Kinase, Lactate Dehydrogenase, Oxidative Stress Markers, and Aerobic Capacity in Semi-Professional Soccer Players

    Science.gov (United States)

    Barbosa, Carlos V. da Silva; Silva, Alexandre S.; de Oliveira, Caio V. C.; Massa, Nayara M. L.; de Sousa, Yasmim R. F.; da Costa, Whyara K. A.; Silva, Ayice C.; Delatorre, Plínio; Carvalho, Rhayane; Braga, Valdir de Andrade; Magnani, Marciane

    2017-01-01

    Nutritional intervention with antioxidants rich foods has been considered a strategy to minimize the effects of overtraining in athletes. This experimental, randomized, and placebo-controlled study evaluated the effects of consumption of sesame (Sesamum indicum L.) on muscle damage markers, oxidative stress, systemic inflammation, and aerobic performance in male semi-professional soccer players. Twenty athletes were randomly assigned to groups that received 40 g (two tablespoons) per day of sesame or a placebo during 28 days of regular training (exposed to routine training that includes loads of heavy training in the final half of the season). Before and after intervention, creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), C-reactive protein (hs-CRP), and aerobic capacity were evaluated. Before intervention, a physiologic imbalance was noted in both groups related to CK and LDH levels. Sesame intake caused a reduction of CK (19%, p < 0.05), LDH (37%, p < 0.05), MDA (55%, p < 0.05) and hs-CRP (53%, p < 0.05) and increased SOD (14%, p < 0.05), vitamin A (25%, p < 0.05), and vitamin E (65%, p < 0.05) in the experimental group. These phenomena were accompanied by increased aerobic capacity (17%, p < 0.05). The placebo group showed an increase in CK (5%, p < 0.05) and no significant change in LDH, SOD or vitamin A. MDA levels decreased (21%, p < 0.05) and vitamin E increased (14%, p < 0.05) in the placebo group, but to a much lesser extent than in the experimental group. These results show that sesame consumption may reduce muscle damage and oxidative stress while improving the aerobic capacity in soccer players. PMID:28408889

  13. Effect of racing on the serum concentrations of cardiac troponin I and creatine kinase myocardial band in racing camels (Camelus dromedarius).

    Science.gov (United States)

    Tharwat, Mohamed; Al-Sobayil, Fahd; Buczinski, Sébastien

    2013-06-01

    This study was designed to investigate the effect of racing on the serum concentrations of cardiac troponin I (cTnI) and creatine kinase myocardial (CK-MB) in healthy racing camels (Camelus dromedarius). Twenty-three racing camels scheduled for a 5 km race were investigated in this study. From each camel, 3 blood samples were collected: 24 h before racing (T0), within 2 h after the race (T1) and 24 h post-race (T2). Following the 5 km race, 91.3 % of the racing camels had increases in serum cTnI concentrations, while concentrations remained unchanged in 8.7 %. The cTnI concentration (median 0.06 ng/mL; range, 0.03-0.15 ng/mL) was significantly higher (P race values (median 0.04 ng/mL; range, 0.01-0.07 ng/mL). Twenty-four hours post-race, the cTnI concentrations had returned very nearly to their pre-race values (median 0.04 ng/mL; range, 0.00-0.09 ng/mL) and were not significantly different (P = 0.35) from the pre-race values. Following the 5 km race, increases in CK-MB mass were seen in 17.4 % of the camels, with no changes in 4.3 % and decreases in 78.3 %. The CK-MB mass (median 0.41 ng/mL; range, 0.19-0.60 ng/mL) did not differ significantly (P = 0.84) when compared to the pre-race values (median 0.42 ng/mL; range, 0.32-0.55 ng/mL). Twenty-four hours post-race, the CK-MB mass concentrations (median 0.41 ng/mL; range, 0.15-0.55 ng/mL) did not differ significantly (P > 0.05) compared to pre-race or immediate post-race values. Resting cTnI concentrations in the racing camels were initially low, but increased above the baseline level in most of the camels immediately after racing, and returned to pre-race values within the 24-h post-race period. CK-MB is a less sensitive biomarker for myocardial activity as compared with cTnI. These findings could be of importance when evaluating racing camels with suspected cardiac disease after recent hard exercise.

  14. Ins(1,4,5)P{sub 3} facilitates ATP accumulation via phosphocreatine/creatine kinase in the endoplasmic reticulum extracted from MDCK cells

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Jing [Medical Research Center, School of Medicine, Fukuoka University, Fukuoka 814-0180 (Japan); Department of Dental Implantology, School of Stomatology, Tongji University, Shanghai 200072 (China); Ogata, Shigenori [Joint Laboratory for Frontier Medical Science, School of Medicine, Fukuoka University, Fukuoka 814-0180 (Japan); Segawa, Masaru [Central Laboratory for Pathology and Morphology, School of Medicine, Fukuoka University, Fukuoka 814-0180 (Japan); Usune, Sadaharu [Research Laboratory of Biodynamics, School of Medicine, Fukuoka University, Fukuoka 814-0180 (Japan); Zhao, Yumei [Department of Pediatric Dentistry, School of Dentistry of Shanghai Tongji University, Shanghai 200072 (China); Katsuragi, Takeshi, E-mail: katsurag@fukuoka-u.ac.jp [Medical Research Center, School of Medicine, Fukuoka University, Fukuoka 814-0180 (Japan)

    2010-07-02

    So far, the content and accumulation of ATP in isolated endoplasmic reticulum (ER) are little understood. First, we confirmed using electron microscopic and Western blotting techniques that the samples extracted from MDCK cells are endoplasmic reticulum (ER). The amounts of ATP in the extracted ER were measured from the filtrate after a spinning down of ultrafiltration spin column packed with ER. When the ER sample (5 {mu}g) after 3 days freezing was suspended in intracellular medium (ICM), 0.1% Triton X and ultrapure water (UPW), ATP amounts from the ER with UPW were the highest and over 10 times compared with that from the control with ICM, indicating that UPW is the most effective tool in destroying the ER membrane. After a 10-min-incubation with ICM containing phosphocreatine (PCr)/creatine kinase (CK) of the fresh ER. ATP amounts in the filtrate obtained by spinning down were not changed from that in the control (no PCr/CK). However, ATP amounts in the filtrate from the second spinning down of the ER (treated with PCr/CK) suspended in UPW became over 10-fold compared with the control. When 1 {mu}M inositol(1,4,5)trisphosphate (Ins(1,4,5)P{sub 3}) was added in the incubation medium (ICM with PCr/CK), ATP amounts from the filtrate after the second spinning down were further enhanced around three times. This enhancement was almost canceled by Ca{sup 2+}-removal from ICM and by adding thapsigargin, a Ca{sup 2+}-ATPase inhibitor, but not by 2-APB and heparin, Ins(1,4,5)P{sub 3} receptor antagonists. Administration of 500 {mu}M adenosine to the incubation medium (with PCr/CK) failed to enhance the accumulation of ATP in the ER. These findings suggest that the ER originally contains ATP and ATP accumulation in the ER is promoted by PCr/CK and Ins(1,4,5)P{sub 3}.

  15. Positioning injury, rhabdomyolysis, and serum creatine kinase-concentration course in patients undergoing robot-assisted radical prostatectomy and extended pelvic lymph node dissection.

    Science.gov (United States)

    Mattei, Agostino; Di Pierro, Giovanni Battista; Rafeld, Verena; Konrad, Christoph; Beutler, Jonas; Danuser, Hansjörg

    2013-01-01

    During robot-assisted radical prostatectomy (RARP), patients remain in a steep Trendelenburg position. This can cause positioning injuries as well as rhabdomyolysis. The primary diagnostic indicator of rhabdomyolysis is elevated serum creatine kinase (CK). We investigate whether RARP with extended pelvic lymph node dissection (ePLND) in a prolonged extreme Trendelenburg position can cause positioning injuries and rhabdomyolysis. We performed a prospective study of the first 60 patients undergoing RARP and ePLND for organ-confined prostate cancer at our institute. Positioning injuries were graded according to three degrees of clinical severity. Serum-CK, serum-pH, and base excess (BE) were measured before, during, and for 5 days after surgery. Rhabdomyolysis was defined by serum-CK levels >5000 IU/L. Median operative time was 317 minutes (range 200-475 min); median time in the Trendelenburg position was 282 minutes (range 170-470 min). Serum-CK was significantly elevated 6 hours postoperatively, peaking at 18 hours postoperatively. Serum-CK levels did not correlate with pH, BE, and perioperative creatinine values. Serum-CK course shows weak correlation with body mass index (BMI), operative time, Trendelenburg position time, and medium correlation with positioning injuries of any degree. Twenty-one of the 60 (35%) patients showed positioning-related injuries: 16 (27%) patients degree I, 2 (3%) patients degree II, and 3 (5%) patients degree III. Rhabdomyolysis developed in 10 patients. Postoperative renal failure did not develop in any patient receiving postoperative hypervolemic diuretic therapy nor any patient with injuries degrees I, II, or III. conclusion: Clinically relevant positioning injuries and rhabdomyolysis can occur in patients who are subjected to prolonged extreme Trendelenburg position during RARP and ePLND, especially at the beginning of the learning curve. Serum-CK increases significantly after surgery, peaking 18 hours postoperatively. Serum

  16. Creatine biosynthesis and transport in health and disease.

    Science.gov (United States)

    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

  17. Creatine phosphokinase test

    Science.gov (United States)

    ... 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. ...

  18. The contemporary value of peak creatine kinase-MB after ST-segment elevation myocardial infarction above other clinical and angiographic characteristics in predicting infarct size, left ventricular ejection fraction, and mortality.

    Science.gov (United States)

    Hartman, Minke H T; Eppinga, Ruben N; Vlaar, Pieter J J; Lexis, Chris P H; Lipsic, Erik; Haeck, Joost D E; van Veldhuisen, Dirk J; van der Horst, Iwan C C; van der Harst, Pim

    2017-05-01

    Complex multimarker approaches to predict outcome after ST-elevation myocardial infarction (STEMI) have only considered a single baseline sample, while neglecting easily obtainable peak creatine kinase and creatine kinase-MB (CK-MB) values during hospitalization. We studied 476 patients undergoing primary percutaneous coronary intervention for STEMI and cardiac magnetic resonance imaging (CMRI) at 4-6 months after STEMI. We determined the association with cardiac biomarkers (peak CK-MB, peak troponin T, N-terminal pro-brain natriuretic peptide), clinical and angiographic characteristics with infarct size, and LVEF, followed by association with mortality in 1120 STEMI patients. Peak CK-MB was the strongest predictor for infarct size (P<0.001, R (2) =0.60) and LVEF (P<0.001, R (2) =0.40). The additional value of clinical and angiographic characteristics was limited. The optimal peak CK-MB cutpoints, for differentiation among small (<10% of the left ventricle), moderate (≥10%-<30%), and large infarct size (≥30%), were 210 U/L and 380 U/L, respectively. These cutpoints were associated with 90-day mortality; the hazard ratio for moderate infarct was 2.99 (95% confidence interval [CI]: 1.51-5.93, P=0.002) and for large infarct 6.53 (95% CI: 3.63-11.76, P<0.001). Classical peak CK-MB measured during hospitalization for STEMI was superior to other clinical and angiographic characteristics in predicting CMRI-defined infarct size and LVEF, and should be included and validated in future multimarker studies. Peak CK-MB cutpoints differentiated among infarct size categories and were associated with increased 90-day mortality risk. © 2016 Wiley Periodicals, Inc.

  19. Creatine Use in Sports.

    Science.gov (United States)

    Butts, Jessica; Jacobs, Bret; Silvis, Matthew

    2017-10-01

    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.

  20. Cloning and characterization of the promoter regions from the parent and paralogobs creatine transporter genes

    NARCIS (Netherlands)

    Ndika, J.D.T.; Lusink, V.; Beaubrun, C.; Kanhai, W.; Martinez-Munoz, C.; Jakobs, C.A.J.M.; Salomons, G.S.

    2014-01-01

    Interconversion between phosphocreatine and creatine, catalyzed by creatine kinase is crucial in the supply of ATP to tissues with high energy demand. Creatine's importance has been established by its use as an ergogenic aid in sport, as well as the development of intellectual disability in patients

  1. Investigation of Brain Creatine Levels Under the Mental Stress Conditions

    Directory of Open Access Journals (Sweden)

    George Burjanadze

    2016-12-01

    Full Text Available Alterations in brain creatine levels are considered to be associated with various pathological conditions. However, there is still no exact evidence on character of this changes and clear link between disorders and upstream and downstream direction of creatine changes. Chronic mental stress conditions are thought to be connected with upstream regulation of cellular oxidative pathways, thus oxidizing various structural and active compounds. Oxidative stress also takes part in increase of permeability of blood brain barrier (BBB that, in turn, makes it possible for a number of molecules to cross the BBB in both directions. Observations on long-term social isolation and circadian rhythm violation show a rising trend in brain creatine amount, while there was remarkable down-regulation in creatine synthesizing system, as the key-enzymes’ (AGAT and GAMT activity was decreased. Investigations of BBB permeability for creatine under the stress conditions by mass-spectrometric analyses revealed no changes in creatine transport in the stress group, compared to the control. However, the activity of mitochondrial CK was reduced for about 25% and Vmax had fallen down in the stressed group, the Km was not drastically changed. To sum up, it could be supposed that the reason for the elevations of creatine levels in brain under the mental stress conditions could be stimulated by the activated oxidative stress that induces conformational changes in mitochondrial Creatine Kinase structure and decreasing the ability of enzyme to phosphorylate the creatine and as a result free creatine levels in brain are being arisen.

  2. Creatine and entrepreneurship

    NARCIS (Netherlands)

    C.A. Rietveld (Niels); P. Böckerman (Petri); J. Viinikainen (Jutta); A. Bryson (Alex); O. Raitakari (Olli); J. Pehkonen (Jaakko)

    2016-01-01

    textabstractCreatine is a nitrogenous organic acid which supplies energy to body cells and enhances physical performance. Using the Young Finns Study combined with the Finnish Linked employer-employee data we show that quantities of creatine measured in 1980 prior to labour market entry affect

  3. Preventive effects of physical exercise on the inhibition of creatine kinase in the cerebral cortex of mice exposed to cigarette smoke. DOI: 10.5007/1980-0037.2011v13n2p106

    Directory of Open Access Journals (Sweden)

    Daiane Bittencourt Fraga

    2011-02-01

    Full Text Available Recent studies have shown the health benefits of physical exercise, increasing the oxidative response of muscle. However, the effects of exercise on the brain are poorly understood and contradictory. The inhibition of creatine kinase (CK activity has been associated with the pathogenesis of a large number of diseases, especially in the brain. The objective of this study was to determine the preventive effects of physical exercise in the hippocampus and cerebral cortex of mice after chronic cigarette smoke exposure. Eight to 10-week-old male mice (C57BL-6 were divided into four groups and submitted to an exercise program (swimming, 5 times a week, for 8 weeks. After this period, the animals were passively exposed to cigarette smoke for 60 consecutive days, 3 times a day (4 Marlboro red cigarettes per session, for a total of 12 cigarettes. CK activity was measured in cerebral cortex and hippocampal homogenates. Enzyme activity was inhibited in the cerebral cortex of animals submitted to the inhalation of cigarette smoke. However, exercise prevented this inhibition. In contrast, CK activity remained unchanged in the hippocampus. This inhibition of CK by inhalation of cigarette smoke might be related to the process of cell death. Physical exercise played a preventive role in the inhibition of CK activity caused by exposure to cigarette smoke.

  4. Preventive effects of physical exercise on the inhibition of creatine kinase in the cerebral cortex of mice exposed to cigarette smoke. DOI: 10.5007/1980-0037.2011v13n2p106

    Directory of Open Access Journals (Sweden)

    Daiane Bittencourt Fraga

    2011-03-01

    Full Text Available Recent studies have shown the health benefits of physical exercise, increasing the oxidative response of muscle. However, the effects of exercise on the brain are poorly understood and contradictory. The inhibition of creatine kinase (CK activity has been associated with the pathogenesis of a large number of diseases, especially in the brain. The objective of this study was to determine the preventive effects of physical exercise in the hippocampus and cerebral cortex of mice after chronic cigarette smoke exposure. Eight to 10-week-old male mice (C57BL-6 were divided into four groups and submitted to an exercise program (swimming, 5 times a week, for 8 weeks. After this period, the animals were passively exposed to cigarette smoke for 60 consecutive days, 3 times a day (4 Marlboro red cigarettes per session, for a total of 12 cigarettes. CK activity was measured in cerebral cortex and hippocampal homogenates. Enzyme activity was inhibited in the cerebral cortex of animals submitted to the inhalation of cigarette smoke. However, exercise prevented this inhibition. In contrast, CK activity remained unchanged in the hippocampus. This inhibition of CK by inhalation of cigarette smoke might be related to the process of cell death. Physical exercise played a preventive role in the inhibition of CK activity caused by exposure to cigarette smoke.

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

    Science.gov (United States)

    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

  6. SERUM ACTIVITIES OF ASPARTATE AMINOTRANSFERASE, CREATINE KINASE AND LACTATE DEHYDROGENASE IN HORSES WITH COLIC ATIVIDADE SÉRICA DAS ENZIMAS ASPARTATO AMINOTRANSFERASE, CREATINA QUINASE E LACTATO DESIDROGENASE EM EQÜINOS COM CÓLICA

    Directory of Open Access Journals (Sweden)

    Aureo Evangelista Santana

    2008-12-01

    Full Text Available Seventy equines distributed in two experimental groups were used, G1 (20 healthy equines, and G2 (50 equines with colic. Blood samples were obtained by jugular vein puncture in ten different moments. The variables aspartate aminotransferase (AST, creatine kinase (CK, and lactate dehydrogenase (LDH were determined by spectrophotometric assay using specific reagents. The average values presented by the animals of the G2 for variables CK, AST, and LDH were higher (P<0.05 than the values presented by the animals of the G1 in all the evaluation moments. The results showed for G2 animals suggest the existence of acute muscle injury. The muscle injuries in equines with colic were attributed to the tissue hypoperfusion, and the muscular damage.

    KEY WORDS: Acute abdomen, horses, muscles enzyme. De setenta eqüinos, distribuídos em dois grupos experimentais – G1 (vinte eqüinos hígidos e G2 (cinqüenta eqüinos com cólica –, colheram-se amostras de sangue em dez diferentes momentos, mediante punção da jugular, para a determinação da atividade sérica das enzimas aspartato aminotransferase (AST, creatina quinase (CK e lactato desidrogenase (LDH. Os valores médios apresentados pelos animais do G2, para as variáveis CK, AST e LDH, foram superiores (P<0,05 aos valores médios apresentados pelos animais do G1 em todos os momentos de avaliação. Os resultados apresentados pelos animais com cólica (G2 sugerem a existência de lesão muscular aguda, porém com tendência a cura, e foram atribuídos a hipoperfusão tecidual e a traumas musculares. A análise seriada das enzimas CK, AST e LDH auxilia tanto no diagnóstico de lesões musculares em eqüinos com cólica como no acompanhamento da evolução do processo de cura.

    PALAVRAS-CHAVES: Abdômen agudo, cavalos, enzimas musculares.

  7. Changes in serum creatinine, uric acid, creatine kinase, and glomerular filtration rate in street runners. http://dx.doi.org/10.5007/1980-0037.2013v15n1p71

    Directory of Open Access Journals (Sweden)

    Anderson Pontes Morales

    2013-01-01

    Full Text Available The strategies adopted by street runners during races are influenced by the distance of the race as well as the technical and physical condition levels of the runners. The objective of this study was to examine the biochemical effects of Creatinine (C, Uric Acid (UA, Creatine Kinase (CK, and of the Glomerular Filtration Rate (GFR caused by a 6-kilometer street race. The participants (n=15 were all male athletes (40.53±8.65 years and were divided into 3 groups: Group 1 Best Times (G1MT n=5, Group 2 Intermediate Times (G2TI n=5, Group 3 Worst Times (G3PT n=5. Blood samples were collected 30 minutes before and immediately after the race. The data was analyzed by Two-Way ANOVA, Wilcoxon, and Mann Whitney. Significant levels were considered as (p<0.05. The results showed that there were significant intragroup increases in serum activities of (C in G1MT pre: 1.18±0.04 mg.dL-¹ post: 1.60±0.15 mg.dL-¹; G2TI pre: 1.04±0.15 mg.dL-¹ post: 1.56±0.21 mg.dL-¹; G3PT pre 1.08±0.13 mg.dL-¹ post 1.52±0.32 mg.dL-¹, and in (AU G1MT pre: 3.80±0.75 mg.dL-¹ post 4.56±0.94 mg.dL-¹; G2TI pre 4.36±1.62 mg.dL-¹ post 5.0±1.69 mg.dL-¹; G3PT pre 4.62±1.08 mg.dL-¹ post: 5.42±0.86 mg.dL-¹, while CK and GFR did not show any significant difference.

  8. Creatine for women in pregnancy for neuroprotection of the fetus.

    Science.gov (United States)

    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

  9. Living Without Creatine: Unchanged Exercise Capacity and Response to Chronic Myocardial Infarction in Creatine-Deficient Mice

    Science.gov (United States)

    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

  10. Creatine use among young athletes.

    Science.gov (United States)

    Metzl, J D; Small, E; Levine, S R; Gershel, J C

    2001-08-01

    Creatine is a nutritional supplement that is purported to be a safe ergogenic aid in adults. Although as many as 28% of collegiate athletes admit taking creatine, there is little information about creatine use or potential health risk in children and adolescents. Although the use of creatine is not recommended in people less than 18 years of age, numerous anecdotal reports indicate widespread use in young athletes. The purpose of this study was to determine the frequency, risk factors, and demographics of creatine use among middle and high school student athletes. Before their annual sports preparticipation physical examinations, middle and high school athletes aged 10 to 18 in Westchester County, a suburb north of New York City, were surveyed in a confidential manner. Information was collected regarding school grade, gender, specific sport participation, and creatine use. Overall, 62 of 1103 participants (5.6%) admitted taking creatine. Creatine use was reported in every grade, from 6 to 12. Forty-four percent of grade 12 athletes surveyed reported using creatine. Creatine use was significantly more common (P sport, use was significantly more common among football players, wrestlers, hockey players, gymnasts, and lacrosse players (P performance (74.2% of users) and improved appearance (61.3%), and the most common reason cited for not taking creatine was safety (45.7% of nonusers). Despite current recommendations against use in adolescents less than 18 years old, creatine is being used by middle and high school athletes at all grade levels. The prevalence in grades 11 and 12 approaches levels reported among collegiate athletes. Until the safety of creatine can be established in adolescents, the use of this product should be discouraged.

  11. Effect of acute administration of ketamine and imipramine on creatine kinase activity in the brain of rats Efeito da administração aguda da cetamina e imipramina sobre a atividade da creatina quinase no encéfalo de ratos

    Directory of Open Access Journals (Sweden)

    Lara C. Assis

    2009-09-01

    Full Text Available OBJECTIVE: Clinical findings suggest that ketamine may be used for the treatment of major depression. The present study aimed to compare behavioral effects and brain Creatine kinase activity in specific brain regions after administration of ketamine and imipramine in rats. METHOD: Rats were acutely given ketamine or imipramine and antidepressant-like activity was assessed by the forced swimming test; Creatine kinase activity was measured in different regions of the brain. RESULTS: The results showed that ketamine (10 and 15mg/kg and imipramine (20 and 30mg/kg reduced immobility time when compared to saline group. We also observed that ketamine (10 and 15mg/kg and imipramine (20 and 30mg/kg increased Creatine kinase activity in striatum and cerebral cortex. Ketamine at the highest dose (15mg/kg and imipramine (20 and 30mg/kg increased Creatine kinase activity in cerebellum and prefrontal cortex. On the other hand, hippocampus was not affected. CONCLUSION: Considering that metabolism impairment is probably involved in the pathophysiology of depressive disorders, the modulation of energy metabolism (like increase in Creatine kinase activity by antidepressants could be an important mechanism of action of these drugs.OBJETIVO: Vários achados clínicos sugerem que a cetamina apresenta efeito antidepressivo. O presente estudo tem como objetivo comparar efeitos comportamentais e a atividade da creatina quinase em regiões específicas do encéfalo após a administração de cetamina e imipramina em ratos. MÉTODO: Ratos Wistar receberam uma administração aguda de cetamina ou imipramina e a atividade antidepressiva foi avaliada pelo teste de nado forçado; a atividade da creatina quinase foi medida em diferentes regiões encefálicas. RESULTADOS: Os resultados mostraram que a cetamina (10 e 15mg/kg e a imipramina (20 e 30mg/kg diminuíram o tempo de imobilidade quando comparados ao grupo salina. Também foi observado que a cetamina (10 e 15mg/kg e a

  12. SHORT AND LONGER-TERM EFFECTS OF CREATINE SUPPLEMENTATION ON EXERCISE INDUCED MUSCLE DAMAGE

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    John Rosene

    2009-03-01

    Full Text Available The purpose of this investigation was to determine if creatine supplementation assisted with reducing the amount of exercise induced muscle damage and if creatine supplementation aided in recovery from exercise induced muscle damage. Two groups of subjects (group 1 = creatine; group 2 = placebo participated in an eccentric exercise protocol following 7 and 30 days of creatine or placebo supplementation (20 g.d-1 for 7 d followed by 6g.d-1 for 23 d = 30 d. Prior to the supplementation period, measurements were obtained for maximal dynamic strength, maximal isometric force, knee range of motion, muscle soreness, and serum levels of creatine kinase (CK and lactate dehydrogenase (LDH. Following 7 days of creatine supplementation, on day 8, subjects began consuming 6 g.d-1 of creatine for 23 days. Additionally on days 8 and 31, subjects performed an eccentric exercise protocol using the knee extensors to induce muscle damage. Indirect markers of muscle damage, including maximal isometric force, knee range of motion, muscle soreness, and serum levels of CK and LDH, were collected at 12, 24, and 48 hours following each exercise bout. The results indicated that acute bouts of creatine have no effect on indirect markers of muscle damage for the acute (7 days bout. However, maximal isometric force was greater for the creatine group versus placebo for the chronic (30 days bout. This suggests that the ergogenic effect of creatine following 30 days of supplementation may have a positive impact on exercise induced muscle damage

  13. Negative Regulation of the Creatine Transporter SLC6A8 by SPAK and OSR1

    OpenAIRE

    Myriam Fezai; Bernat Elvira; Jose Borras; Mossadok Ben-Attia; Zohreh Hoseinzadeh; Florian Lang

    2014-01-01

    Background/Aims: Transport regulation involves several kinases including SPAK (SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase 1), which are under control of WNK (with-no-K[Lys]) kinases. The present study explored whether SPAK and/or OSR1 participate in the regulation of the creatine transporter CreaT (SLC6A8), which accomplishes Na+ coupled cellular uptake of creatine in several tissues including kidney, intestine, heart, skeletal muscle and brain. Met...

  14. Changes in creatine transporter function during cardiac maturation in the rat

    Directory of Open Access Journals (Sweden)

    Watkins Hugh

    2010-06-01

    Full Text Available Abstract Background It is well established that the immature myocardium preferentially utilises non-oxidative energy-generating pathways. It exhibits low energy-transfer capacity via the creatine kinase (CK shuttle, reflected in phosphocreatine (PCr, total creatine and CK levels that are much lower than those of adult myocardium. The mechanisms leading to gradually increasing energy transfer capacity during maturation are poorly understood. Creatine is not synthesised in the heart, but taken up exclusively by the action of the creatine transporter protein (CrT. To determine whether this transporter is ontogenically regulated, the present study serially examined CrT gene expression pattern, together with creatine uptake kinetics and resulting myocardial creatine levels, in rats over the first 80 days of age. Results Rats were studied during the late prenatal period (-2 days before birth and 7, 13, 21, 33, 50 and 80 days after birth. Activity of cardiac citrate synthase, creatine kinase and its isoenzymes as well as lactate dehydrogenase (LDH and its isoenzymes demonstrated the well-described shift from anaerobic towards aerobic metabolism. mRNA levels of CrT in the foetal rat hearts, as determined by real-time PCR, were about 30% of the mRNA levels in the adult rat heart and gradually increased during development. Creatine uptake in isolated perfused rat hearts increased significantly from 3.0 nmol/min/gww at 13 days old to 4.9 nmol/min/gww in 80 day old rats. Accordingly, total creatine content in hearts, measured by HPLC, increased steadily during maturation (30 nmol/mg protein (-2 days vs 87 nmol/mg protein (80 days, and correlated closely with CrT gene expression. Conclusions The maturation-dependant alterations of CK and LDH isoenzyme activities and of mitochondrial oxidative capacity were paralleled by a progressive increase of CrT expression, creatine uptake kinetics and creatine content in the heart.

  15. X-linked creatine transporter deficiency: clinical aspects and pathophysiology

    NARCIS (Netherlands)

    van de Kamp, J.M.; Mancini, G.M.; Salomons, G.S.

    2014-01-01

    Creatine transporter deficiency was discovered in 2001 as an X-linked cause of intellectual disability characterized by cerebral creatine deficiency. This review describes the current knowledge regarding creatine metabolism, the creatine transporter and the clinical aspects of creatine transporter

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

    Science.gov (United States)

    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.

  17. Creatine prevents the inhibition of energy metabolism and lipid peroxidation in rats subjected to GAA administration.

    Science.gov (United States)

    Kolling, Janaína; Wyse, Angela T S

    2010-09-01

    Guanidinoacetate methyltransferase (GAMT) deficiency is an inherited neurometabolic disorder, biochemically characterized by the tissue accumulation of guanidinoacetate (GAA). Affected patients present epilepsy and mental retardation whose etiopathogeny is unclear. Previous reports have shown that GAA alters brain energy metabolism and that creatine, which is depleted in patients with GAMT deficiency, can act as a neuroprotector; as such, in the present study we investigated the effect of creatine administration on some of the altered parameters of energy metabolism (complex II, Na(+),K(+)-ATPase and creatine kinase) and lipid peroxidation caused by intrastriatal administration of GAA in adult rats. Animals were pretreated for 7 days with daily intraperitonial administrations of creatine. Subsequently, these animals were divided into two groups: Group 1 (sham group), rats that suffered surgery and received saline; and group 2 (GAA-treated). Thirty min after GAA or saline, the animals were sacrificed and the striatum dissected out. Results showed that the administration of creatine was able to reverse the activities of complex II, Na(+),K(+)-ATPase and creatine kinase, as well as, the levels of thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation. These findings indicate that the energy metabolism deficit caused by GAA may be prevented by creatine, which probably acts as an antioxidant since it was able to prevent lipid peroxidation. These data may contribute, at least in part, to a better understanding of the mechanisms related to the energy deficit and oxidative stress observed in GAMT deficiency.

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

    Science.gov (United States)

    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

  19. Creatine supplementation: can it improve quality of life in the elderly without associated resistance training?

    Science.gov (United States)

    Moon, Anna; Heywood, Lara; Rutherford, Stephen; Cobbold, Christian

    2013-12-01

    Ageing is associated with decreased muscle mass, strength, power and function, and reduction in bone density and mineral content, leading to reduced independence and increased risk of falls. Creatine supplementation is reported to improve muscular strength and performance with training in younger athletes, and therefore could benefit older individuals. This review critically appraises the current literature on whether creatine supplementation enhances muscular performance and function, body composition, bone mineral density and content in older adults without the addition of resistance training, and thus determines whether creatine supplementation can lead to an improved lifestyle for the sedentary elderly population. There is conflicting evidence regarding the usefulness of creatine supplementation in older subjects. Generally, however, creatine supplementation, without associated resistance training, seems to enhance muscular strength, power and endurance, increase lean body mass (LBM) and improve the functional capacity of the elderly. Furthermore, it has been demonstrated that increased muscle mass due to creatine supplementation can result in increased local bone density. It appears that the effect of creatine supplementation is more beneficial in larger muscles and less effective in smaller muscles, however there are exceptions. The mechanism by which creatine supplementation works requires further research, however it is likely that the effects of creatine are related to creatine kinase activity, providing enhanced energy production for greater muscular contraction. These data indicate that creatine supplementation without associated training in the elderly could potentially delay atrophy of muscle mass, improve endurance and strength, and increase bone strength, and thus may be a safe therapeutic strategy to help decrease loss in functional performance of everyday tasks.

  20. A creatine-driven substrate cycle enhances energy expenditure and thermogenesis in beige fat.

    Science.gov (United States)

    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.

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

    OpenAIRE

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

    2017-01-01

    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 B...

  2. Extracellular creatine regulates creatine transport in rat and human muscle cells.

    OpenAIRE

    Loike, J D; Zalutsky, D L; Kaback, E; Miranda, A F; Silverstein, S C

    1988-01-01

    Muscle cells do not synthesize creatine; they take up exogenous creatine by specific Na+-dependent plasma membrane transporters. We found that extracellular creatine regulates the level of expression of these creatine transporters in L6 rat muscle cells. L6 myoblasts maintained for 24 hr in medium containing 1 mM creatine exhibited 1/3rd of the creatine transport activity of cells maintained for 24 hr in medium without creatine. Down-regulation of creatine transport was partially reversed whe...

  3. Prognostic implications of myocardial creatine kinase and cardiac troponin in coronary artery bypass surgery Implicação prognóstica da creatino-quinase miocárdica e troponina na revascularização do miocárdio

    Directory of Open Access Journals (Sweden)

    Fábio P. Taniguchi

    2003-09-01

    Full Text Available OBJECTIVES: To evaluate the prognostic implications of myocardial creatine kinase and troponin I (cTn I in blood samples from the coronary sinus of patients submitted to coronary artery bypass surgery both with and without ischemic preconditioning. METHODS: From October 1998 to May 1999, 35 patients with coronary artery disease who were submitted to coronary artery bypass surgery were studied. Samples containing creatine kinase and cTn I were obtained from the great cardiac vein during surgery at the onset of cardiopulmonary bypass, at the end of the first anastomosis, and at the end of cardiopulmonary bypass. In May 2002, 29 patients were evaluated in regards to the angina functional class, congestive heart failure, number of hospitalizations, myocardial infarction and death. There were 15 patients in the Preconditioned group and 14 in the Control group. Each group was subdivided into patients with and without cardiovascular symptoms. RESULTS: The Control and Preconditioned groups were not significantly different in relation to frequency of cardiovascular symptoms. There were progressive increases of the creatine kinase and cTn I levels at different Interval s of the study. The cTn I in the Preconditioned group was 1.21 ± 0.64 ng/mL and 3.19 ± 3.21 ng/mL in the Control group (pOBJETIVO: Avaliar a implicação prognóstica da dosagem da creatino-quinase miocárdica (CKMB e Troponina I (cTn I em amostras no seio coronariano, na evolução de pacientes submetidos a revascularização do miocárdio (RM, com e sem o pré-condicionamento isquêmico. MÉTODO: Entre outubro de 1998 e maio de 1999, 35 pacientes com insuficiência coronariana foram submetidos a RM foram estudados. No intra-operatório foram coletadas amostras do seio coronariano para dosagem de CKMB e cTn I. Os momentos de coleta foram: momento 1-no início da circulação extracorpórea (CEC, momento 2- após a primeira anastomose e momento 3- no final da CEC. Em maio de 2002, 29

  4. Essentials of creatine in sports and health

    National Research Council Canada - National Science Library

    Stout, Jeffrey R; Kalman, Douglas; Antonio, Jose

    2008-01-01

    ... and NIH databases. With all of the misinformation regarding the effects of creatine supplementation on health and sports performance, Essentials of Creatine in Sports and Health brings together the information on how creatine affecs body composition, exercise performance, and health. Supported by the International Society of Sports Nutrition, this...

  5. Relation of Post-Coronary Artery Bypass Graft Creatine Kinase-MB Elevations and New Q Waves With Long-Term Cardiovascular Death in Patients With Diabetes Mellitus and Multivessel Coronary Artery Disease.

    Science.gov (United States)

    Domanski, Michael; Farkouh, Michael E; Zak, Victor; French, John; Alexander, John H; Bochenek, Andrzej; Hamon, Martial; Mahaffey, Kenneth; Puskas, John; Smith, Peter; Shrader, Peter; Fuster, Valentin

    2016-12-01

    Associations of early creatine phosphokinase-MB (CK-MB) elevation and new Q waves and their association with cardiovascular death (CVD) after coronary artery bypass grafting (CABG) have been reported, but this association has not been studied in a large population of patients with diabetes mellitus. In this study, we examine the association of periprocedural CK-MB elevations and new Q waves with CVD in the Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease trial. Cox proportional hazards regression was used to assess the relation of CK-MB elevations and new Q waves in the first 24 hours after procedure and their relation to CVD; logistic regression was used to assess odds ratios of these variables. Hazard ratios, 95% confidence intervals, and p values associated with Wald chi-square test are reported. CK-MB elevation in first 24 hours after procedure was independently associated with CVD. CVD hazard increased by 6% (p new post-CABG Q waves increased by a factor of 1.08 (p 2. CK-MB URL multiples of 7, 12, and 15 were associated with new Q-wave odds ratios of 9, 16, and 27 times, respectively (p ≤0.001, C-statistic >0.70). New Q waves were independently associated with survival in the multivariate model only when CK-MB was excluded (p = 0.01). In conclusion, independent associations included (1) CVD and early post-CABG CK-MB elevation; (2) new Q waves with early post-CABG CK-MB elevation; (3) CVD with new Q waves only when CK-MB elevation is excluded from analysis. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Both Creatine and Its Product Phosphocreatine Reduce Oxidative Stress and Afford Neuroprotection in an In Vitro Parkinson’s Model

    Directory of Open Access Journals (Sweden)

    Mauricio Peña Cunha

    2014-10-01

    Full Text Available Creatine is the substrate for creatine kinase in the synthesis of phosphocreatine (PCr. This energetic system is endowed of antioxidant and neuroprotective properties and plays a pivotal role in brain energy homeostasis. The purpose of this study was to investigate the neuroprotective effect of creatine and PCr against 6-hydroxydopamine (6-OHDA-induced mitochondrial dysfunction and cell death in rat striatal slices, used as an in vitro Parkinson’s model. The possible involvement of the signaling pathway mediated by phosphatidylinositol-3 kinase (PI3K, protein kinase B (Akt, and glycogen synthase kinase-3β (GSK3β was also evaluated. Exposure of striatal slices to 6-OHDA caused a significant disruption of the cellular homeostasis measured as 3-(4,5 dimethylthiazol-2-yl-2,5-diphenyl-tetrazolium bromide reduction, lactate dehydrogenase release, and tyrosine hydroxylase levels. 6-OHDA exposure increased the levels of reactive oxygen species and thiobarbituric acid reactive substances production and decreased mitochondrial membrane potential in rat striatal slices. Furthermore, 6-OHDA decreased the phosphorylation of Akt (Serine473 and GSK3β (Serine9. Coincubation with 6-OHDA and creatine or PCr reduced the effects of 6-OHDA toxicity. The protective effect afforded by creatine or PCr against 6-OHDA-induced toxicity was reversed by the PI3K inhibitor LY294002. In conclusion, creatine and PCr minimize oxidative stress in striatum to afford neuroprotection of dopaminergic neurons.

  7. Both creatine and its product phosphocreatine reduce oxidative stress and afford neuroprotection in an in vitro Parkinson's model.

    Science.gov (United States)

    Cunha, Mauricio Peña; Martín-de-Saavedra, Maria D; Romero, Alejandro; Egea, Javier; Ludka, Fabiana K; Tasca, Carla I; Farina, Marcelo; Rodrigues, Ana Lúcia S; López, Manuela G

    2014-01-01

    Creatine is the substrate for creatine kinase in the synthesis of phosphocreatine (PCr). This energetic system is endowed of antioxidant and neuroprotective properties and plays a pivotal role in brain energy homeostasis. The purpose of this study was to investigate the neuroprotective effect of creatine and PCr against 6-hydroxydopamine (6-OHDA)-induced mitochondrial dysfunction and cell death in rat striatal slices, used as an in vitro Parkinson's model. The possible involvement of the signaling pathway mediated by phosphatidylinositol-3 kinase (PI3K), protein kinase B (Akt), and glycogen synthase kinase-3β (GSK3β) was also evaluated. Exposure of striatal slices to 6-OHDA caused a significant disruption of the cellular homeostasis measured as 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide reduction, lactate dehydrogenase release, and tyrosine hydroxylase levels. 6-OHDA exposure increased the levels of reactive oxygen species and thiobarbituric acid reactive substances production and decreased mitochondrial membrane potential in rat striatal slices. Furthermore, 6-OHDA decreased the phosphorylation of Akt (Serine(473)) and GSK3β (Serine(9)). Coincubation with 6-OHDA and creatine or PCr reduced the effects of 6-OHDA toxicity. The protective effect afforded by creatine or PCr against 6-OHDA-induced toxicity was reversed by the PI3K inhibitor LY294002. In conclusion, creatine and PCr minimize oxidative stress in striatum to afford neuroprotection of dopaminergic neurons. © The Author(s) 2014.

  8. Both Creatine and Its Product Phosphocreatine Reduce Oxidative Stress and Afford Neuroprotection in an In Vitro Parkinson’s Model

    Science.gov (United States)

    Martín-de-Saavedra, Maria D.; Romero, Alejandro; Egea, Javier; Ludka, Fabiana K.; Tasca, Carla I.; Farina, Marcelo; Rodrigues, Ana Lúcia S.; López, Manuela G.

    2014-01-01

    Creatine is the substrate for creatine kinase in the synthesis of phosphocreatine (PCr). This energetic system is endowed of antioxidant and neuroprotective properties and plays a pivotal role in brain energy homeostasis. The purpose of this study was to investigate the neuroprotective effect of creatine and PCr against 6-hydroxydopamine (6-OHDA)-induced mitochondrial dysfunction and cell death in rat striatal slices, used as an in vitro Parkinson’s model. The possible involvement of the signaling pathway mediated by phosphatidylinositol-3 kinase (PI3K), protein kinase B (Akt), and glycogen synthase kinase-3β (GSK3β) was also evaluated. Exposure of striatal slices to 6-OHDA caused a significant disruption of the cellular homeostasis measured as 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide reduction, lactate dehydrogenase release, and tyrosine hydroxylase levels. 6-OHDA exposure increased the levels of reactive oxygen species and thiobarbituric acid reactive substances production and decreased mitochondrial membrane potential in rat striatal slices. Furthermore, 6-OHDA decreased the phosphorylation of Akt (Serine473) and GSK3β (Serine9). Coincubation with 6-OHDA and creatine or PCr reduced the effects of 6-OHDA toxicity. The protective effect afforded by creatine or PCr against 6-OHDA-induced toxicity was reversed by the PI3K inhibitor LY294002. In conclusion, creatine and PCr minimize oxidative stress in striatum to afford neuroprotection of dopaminergic neurons. PMID:25424428

  9. Determinação das atividades séricas de creatina quinase, lactato desidrogenase e aspartato aminotransferase em eqüinos de diferentes categorias de atividade Determination of serum activities of creatine kinase, lactate dehydrogenase, and aspartate aminotransferase in horses of different activities classes

    Directory of Open Access Journals (Sweden)

    I.A. Câmara e Silva

    2007-02-01

    Full Text Available The creatine kinase (CK, lactate dehydrogenase (LDH, and aspartate aminotransferase (AST seric activities in horses of different activity classes (athlete, traction, and reproduction, were compared. Fifty-eight horses were alloted into three groups - group 1 with 20 athletes, "vaquejada" competitors; group 2 with 20 breeding horses; and group 3 with 18 draft horses, averaging 10 working hours daily. The average values for CK serum activity were 80.2, 83.9, and 94.4 U/l in groups 1, 2, and 3, respectively. Result of group 3 was significantly different from the other groups. The averages values for LDH were 102.5, 98.6, and 112.8 U/l in groups 1, 2, and 3, respectively, with no statistical difference between groups. The AST averages were 56.8, 33.0, and 50.1 U/l in groups 1, 2, and 3, respectively, with group 2 significantly differing from the others. Clinical biochemistry values of muscular function in horses varied according to activity category.

  10. Concentrações de creatino quinase, aspartato aminotransferase e desidrogenase lática em potros do nascimento até os seis meses de idade Concentration of creatine kinase, aspartate aminotransferase and lactate dehydrogenase in foals from birth up to sixth month

    Directory of Open Access Journals (Sweden)

    Elisiane Lourdes Da Cás

    2001-12-01

    Full Text Available Dez potros da raça Puro Sangue de Corrida (PSC, de ambos os sexos, foram avaliados quanto à concentração das enzimas séricas creatino quinase (CK, aspartato aminotransferase (AST e deshidrogenase lática (DHL. Foram colhidas amostras sangüíneas diariamente do 1º ao 7ºdia de vida e depois aos 15, 30, 60, 90, 120, 150 e 180 dias de idade. A concentração da CK mostrou um decréscimo significativo (pTen Thoroughbred foals, male and female, had the seric concentration of creatine kinase (CK, aspartate aminotransferase (AST and lactate dehydrogenase (LDH determined. Blood samples were collected every day from days 1 to 7 and on days 15, 30, 60, 90, 120, 150 and 180 of age. CK activity decreased significantly (p< 0.0003 in the first week and showed significant variation between day 15 and 6 months of age. AST showed a significant (p< 0.0001 increase in its values until 102 days of age, decreasing subsequently until 6 months of age. LDH values decreased significantly (p< 0.0002 between days 15 and 120, increasing subsequently until 6 months of age. At 6 months of age CK, AST and LDH activities were close to those of adult horses.

  11. Oral creatine supplementation: separating fact from hype.

    Science.gov (United States)

    Juhn, M S

    1999-05-01

    Many athletes-especially those participating in sports that emphasize strength-are taking oral creatine. Creatine supplements appear to enhance performance in repeated short bursts of stationary cycling and weight lifting, but the data on running, swimming, and single cycle sprints are not convincing of an ergogenic effect. Commonly reported side effects include muscle cramping, GI disturbances, and renal dysfunction, but creatine's effect on the heart, brain, reproductive organs, and other organs has yet to be determined. Comprehensive studies with larger samples and crossover design are needed. If patients decide to take oral creatine, physicians need to provide guidance for proper dosing as well as education about potential harmful effects.

  12. Dosha brain-types: A neural model of individual differences

    Directory of Open Access Journals (Sweden)

    Frederick T Travis

    2015-01-01

    Full Text Available This paper explores brain patterns associated with the three categories of regulatory principles of the body, mind, and behavior in Ayurveda, called Vata, Pitta, and Kapha dosha. A growing body of research has reported patterns of blood chemistry, genetic expression, physiological states, and chronic diseases associated with each dosha type. Since metabolic and growth factors are controlled by the nervous system, each dosha type should be associated with patterns of functioning of six major areas of the nervous system: The prefrontal cortex, the reticular activating system, the autonomic nervous system, the enteric nervous system, the limbic system, and the hypothalamus. For instance, the prefrontal cortex, which includes the anterior cingulate, ventral medial, and the dorsal lateral cortices, would exhibit a high range of functioning in the Vata brain-type leading to the possibility of being easily overstimulated. The Vata brain-type performs activity quickly. Learns quickly and forgets quickly. Their fast mind gives them an edge in creative problem solving. The Pitta brain-type reacts strongly to all challenges leading to purposeful and resolute actions. They never give up and are very dynamic and goal oriented. The Kapha brain-type is slow and steady leading to methodical thinking and action. They prefer routine and needs stimulation to get going. A model of dosha brain-types could provide a physiological foundation to understand individual differences. This model could help individualize treatment modalities to address different mental and physical dysfunctions. It also could explain differences in behavior seen in clinical as well as in normal populations.

  13. Dosha brain-types: A neural model of individual differences.

    Science.gov (United States)

    Travis, Frederick T; Wallace, Robert Keith

    2015-01-01

    This paper explores brain patterns associated with the three categories of regulatory principles of the body, mind, and behavior in Ayurveda, called Vata, Pitta, and Kapha dosha. A growing body of research has reported patterns of blood chemistry, genetic expression, physiological states, and chronic diseases associated with each dosha type. Since metabolic and growth factors are controlled by the nervous system, each dosha type should be associated with patterns of functioning of six major areas of the nervous system: The prefrontal cortex, the reticular activating system, the autonomic nervous system, the enteric nervous system, the limbic system, and the hypothalamus. For instance, the prefrontal cortex, which includes the anterior cingulate, ventral medial, and the dorsal lateral cortices, would exhibit a high range of functioning in the Vata brain-type leading to the possibility of being easily overstimulated. The Vata brain-type performs activity quickly. Learns quickly and forgets quickly. Their fast mind gives them an edge in creative problem solving. The Pitta brain-type reacts strongly to all challenges leading to purposeful and resolute actions. They never give up and are very dynamic and goal oriented. The Kapha brain-type is slow and steady leading to methodical thinking and action. They prefer routine and needs stimulation to get going. A model of dosha brain-types could provide a physiological foundation to understand individual differences. This model could help individualize treatment modalities to address different mental and physical dysfunctions. It also could explain differences in behavior seen in clinical as well as in normal populations.

  14. Efeito do exercício nas concentrações séricas de creatina cinase em triatletas de ultradistância Exercise effects on serum levels of creatine kinase in ultra-distance triathletes in the course of a competition period

    Directory of Open Access Journals (Sweden)

    Carolina Neis Machado

    2010-10-01

    supertreinamento, melhorando o desempenho, a saúde e a qualidade de vida do atleta.Triathlon is a popular sport with world wide participation. It combines three different endurance modalities - swimming, cycling and running - within a single event. There is a variety of distances on which triathlon events are made, the Ironman race being the longest. Many authors have already reported injury occurrence after intense exertion, either directly, through histological sarcomere alterations, or indirectly, over the quantification of specific muscle proteins concentration (injury biomarkers in the plasma. Among these markers of muscle injury, Myoglobin and Creatine Kinase stand out. In fact, creatine kinase is the most used biochemical indicator of muscle injury occurrence. Within this context, it is justified the purpose of this study, that intends to verify exercise effects on serum levels of creatine kinase in ultra-distance triathletes in the course of a competition period. Serum levels of CK from 10 triathletes who competed in the Ironman Brazil event, 2007 were evaluated. Blood analyses were done at five distinct periods: 19 days before Ironman Brazil competition (CK1, 48 hours before it (CK2, immediately after it (CK3, five days after the competition (CK4 and 12 days after the event (CK5. The results showed significant increase on CK concentrations at periods 3 and 4, when compared to the other evaluated periods. These alterations evidence the influence of the Ironman competition exhaustive exercise over the CK concentrations, revealing the possibility of muscle injuries development during the event. This fact enhances the importance of biomarkers' monitoring, like CK, that allow coaches and athletes to adapt training loads to increase their benefits and to avoid overtraining, improving performance, health and quality of life.

  15. Negative Regulation of the Creatine Transporter SLC6A8 by SPAK and OSR1

    Directory of Open Access Journals (Sweden)

    Myriam Fezai

    2014-12-01

    Full Text Available Background/Aims: Transport regulation involves several kinases including SPAK (SPS1-related proline/alanine-rich kinase and OSR1 (oxidative stress-responsive kinase 1, which are under control of WNK (with-no-K[Lys] kinases. The present study explored whether SPAK and/or OSR1 participate in the regulation of the creatine transporter CreaT (SLC6A8, which accomplishes Na+ coupled cellular uptake of creatine in several tissues including kidney, intestine, heart, skeletal muscle and brain. Methods: cRNA encoding SLC6A8 was injected into Xenopus laevis oocytes with or without additional injection of cRNA encoding wild-type SPAK, constitutively active T233ESPAK, WNK insensitive T233ASPAK, catalytically inactive D212ASPAK, wild-type OSR1, constitutively active T185EOSR1, WNK insensitive T185AOSR1 and catalytically inactive D164AOSR1. Transporter activity was determined from creatine (1 mM induced current utilizing dual electrode voltage clamp. Results: Coexpression of wild-type SPAK and of T233ESPAK, but not of T233ASPAK or of D212ASPAK was followed by a significant decrease of creatine induced current in SLC6A8 expressing oocytes. Coexpression of SPAK significantly decreased maximal transport rate. Coexpression of wild-type OSR1, T185EOSR1 and T185AOSR1 but not of D164AOSR1 significantly negatively regulated SLC6A8 activity. OSR1 again decreased significantly maximal transport rate. Conclusions: Both, SPAK and OSR1, are negative regulators of the creatine transporter SLC6A8.

  16. Negative regulation of the creatine transporter SLC6A8 by SPAK and OSR1.

    Science.gov (United States)

    Fezai, Myriam; Elvira, Bernat; Borras, Jose; Ben-Attia, Mossadok; Hoseinzadeh, Zohreh; Lang, Florian

    2014-01-01

    Transport regulation involves several kinases including SPAK (SPS1-related proline/alanine-rich kinase) and OSR1 (oxidative stress-responsive kinase 1), which are under control of WNK (with-no-K[Lys]) kinases. The present study explored whether SPAK and/or OSR1 participate in the regulation of the creatine transporter CreaT (SLC6A8), which accomplishes Na+ coupled cellular uptake of creatine in several tissues including kidney, intestine, heart, skeletal muscle and brain. cRNA encoding SLC6A8 was injected into Xenopus laevis oocytes with or without additional injection of cRNA encoding wild-type SPAK, constitutively active (T233E)SPAK, WNK insensitive (T233A)SPAK, catalytically inactive (D212A)SPAK, wild-type OSR1, constitutively active (T185E)OSR1, WNK insensitive (T185A)OSR1 and catalytically inactive (D164A)OSR1. Transporter activity was determined from creatine (1 mM) induced current utilizing dual electrode voltage clamp. Coexpression of wild-type SPAK and of (T233E)SPAK, but not of (T233A)SPAK or of (D212A)SPAK was followed by a significant decrease of creatine induced current in SLC6A8 expressing oocytes. Coexpression of SPAK significantly decreased maximal transport rate. Coexpression of wild-type OSR1, (T185E)OSR1 and (T185A)OSR1 but not of (D164A)OSR1 significantly negatively regulated SLC6A8 activity. OSR1 again decreased significantly maximal transport rate. Both, SPAK and OSR1, are negative regulators of the creatine transporter SLC6A8.

  17. Dodecyl creatine ester and lipid nanocapsule: a double strategy for the treatment of creatine transporter deficiency.

    Science.gov (United States)

    Trotier-Faurion, Alexandra; Passirani, Catherine; Béjaud, Jérôme; Dézard, Sophie; Valayannopoulos, Vassili; Taran, Fréderic; de Lonlay, Pascale; Benoit, Jean-Pierre; Mabondzo, Aloïse

    2015-01-01

    Creatine transporter (CT) deficiency is characterized by mutations in the gene encoding CT, leading to impaired transport of creatine at the cell membrane. Patients with this disease would thus benefit from replenishment of creatine inside the brain cells. We report a therapeutic strategy based on the use of dodecyl creatine ester incorporated into lipid nanocapsules (LNCs). The dodecyl creatine ester was incorporated in the shells of LNCs using Transcutol(®) (Gattefossé SAS, Saint-Priest, France). The interactions of dodecyl creatine ester encapsulated in LNCs with an in vitro cell-based blood-brain barrier model was studied. The entry of the dodecyl creatine ester encapsulated in LNCs and the conversion of dodecyl creatine ester to creatine in the cells were also studied in the pathological context of CT deficiency. We showed that these LNCs can cross the blood-brain barrier and enter brain endothelial cells. In human fibroblasts lacking functional CT, all or part of the dodecyl creatine ester was released from the LNCs and biotransformed to creatine, thus indicating the value of this strategy in this therapeutic context.

  18. Is there a rationale for the use of creatine either as nutritional supplementation or drug administration in humans participating in a sport?

    Science.gov (United States)

    Benzi, G

    2000-03-01

    Even though no unambiguous proof for enhanced performance during high-intensity exercise has yet been reported, the creatine administration is charged to improve physical performance and has become a popular practice among subjects participating in different sports. Appropriate creatine dosage may be also used as a medicinal product since, in accordance with the Council Directive 65/65/CEE, any substance which may be administered with a view to restoring, correcting or modifying physiological functions in human beings is considered a medicinal product. Thus, quality, efficacy and safety must characterize the substance. In biochemical terms, creatine administration enhances both creatine and phosphocreatine concentrations, allowing for an increased total creatine pool in skeletal muscle. In thermodynamics terms, creatine interferes with the creatine-creatine kinase-phosphocreatine circuit, which is related to the mitochondrial function as a highly organized system for the energy control of the subcellular adenylate pool. In pharmacokinetics terms, creatine entry into skeletal muscle is initially dependent on the extracellular concentration, but the creatine transport is subsequently down-regulated. In pharmacodynamics terms, the creatine enhances the possibility to maintain power output during brief periods of high-intensity exercises. In spite of uncontrolled daily dosage and long-term administration, no research on creatine safety in humans has been set up by specific standard protocol of clinical pharmacology and toxicology, as currently occurs in phase I for the products for human use. More or less documented side effects induced by creatine are weight gain; influence on insulin production; feedback inhibition of endogenous creatine synthesis; long-term damages on renal function. A major point that related to the quality of creatine products is the amount of creatine ingested in relation to the amount of contaminants present. During the production of creatine

  19. Cloning and characterization of the promoter regions from the parent and paralogous creatine transporter genes.

    Science.gov (United States)

    Ndika, Joseph D T; Lusink, Vera; Beaubrun, Claudine; Kanhai, Warsha; Martinez-Munoz, Cristina; Jakobs, Cornelis; Salomons, Gajja S

    2014-01-10

    Interconversion between phosphocreatine and creatine, catalyzed by creatine kinase is crucial in the supply of ATP to tissues with high energy demand. Creatine's importance has been established by its use as an ergogenic aid in sport, as well as the development of intellectual disability in patients with congenital creatine deficiency. Creatine biosynthesis is complemented by dietary creatine uptake. Intracellular transport of creatine is carried out by a creatine transporter protein (CT1/CRT/CRTR) encoded by the SLC6A8 gene. Most tissues express this gene, with highest levels detected in skeletal muscle and kidney. There are lower levels of the gene detected in colon, brain, heart, testis and prostate. The mechanism(s) by which this regulation occurs is still poorly understood. A duplicated unprocessed pseudogene of SLC6A8-SLC6A10P has been mapped to chromosome 16p11.2 (contains the entire SLC6A8 gene, plus 2293 bp of 5'flanking sequence and its entire 3'UTR). Expression of SLC6A10P has so far only been shown in human testis and brain. It is still unclear as to what is the function of SLC6A10P. In a patient with autism, a chromosomal breakpoint that intersects the 5'flanking region of SLC6A10P was identified; suggesting that SLC6A10P is a non-coding RNA involved in autism. Our aim was to investigate the presence of cis-acting factor(s) that regulate expression of the creatine transporter, as well as to determine if these factors are functionally conserved upstream of the creatine transporter pseudogene. Via gene-specific PCR, cloning and functional luciferase assays we identified a 1104 bp sequence proximal to the mRNA start site of the SLC6A8 gene with promoter activity in five cell types. The corresponding 5'flanking sequence (1050 bp) on the pseudogene also had promoter activity in all 5 cell lines. Surprisingly the pseudogene promoter was stronger than that of its parent gene in 4 of the cell lines tested. To the best of our knowledge, this is the first

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

    Science.gov (United States)

    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.

  1. Cardiac Troponin T and Creatine Kinase MB Fraction Levels Among ...

    African Journals Online (AJOL)

    2018-01-30

    Jan 30, 2018 ... stroke.[17] It has been suggested that the elevated levels of cardiac markers in acute ischemic stroke patients could be related to cardiac myocytolysis that occurred as a result of activation of the sympathetic nervous system.[19] The presumed cause for this elevation in acute neurologic disease is related to ...

  2. Serum creatine kinase and lactate dehydrogenase activities in ...

    African Journals Online (AJOL)

    Departments of Pathology and 1Medicine, Faculty of Medical Sciences, The University of the West Indies, Mona, Kingston,. 2Health Policy ... hypothyroidism and hyperthyroidism are associated with an increase in risk of ..... Sawin CT, Castelli WP, Hershman JM, McNamara P, Bacharach P. The aging thyroid: Thyroid ...

  3. Periodontal status and serum creatine kinase levels among young ...

    African Journals Online (AJOL)

    2015-12-02

    Dec 2, 2015 ... Nigerian Journal of Clinical Practice • Sep-Oct 2016 • Vol 19 • Issue 5 demonstrated that nearly 50% of the athletes interviewed had not undergone a dental examination and/or hygiene care in the 12 months.[11] The result also demonstrated that dental caries, dental erosion, and periodontal inflammatory.

  4. Creatine kinase and blood pressure: Clinical and therapeutic implications

    NARCIS (Netherlands)

    Oudman, I.

    2013-01-01

    Hypertension affects more than one billion people worldwide and is one of the most powerful contributors to cardiovascular morbidity and mortality. Black people of African descent are more often affected by the disease. One of the biological factors contributing to this difference is the enzyme

  5. Changes in neutrophil count, creatine kinase and muscle soreness ...

    African Journals Online (AJOL)

    screening in the Exercise Testing Laboratory (ETL). During the first visit they were required to read and sign an informed consent previously approved by the University Ethics Com- mittee and in accord with guidelines established by the Amer- ican College of Sports Medicine. Height and body mass were assessed.

  6. Hair bundles are specialized for ATP delivery via creatine kinase.

    NARCIS (Netherlands)

    Shin, J.B.; Streijger, F.; Beynon, A.J.; Peters, T.; Gadzala, L.; McMillen, D.; Bystrom, C.; Zee, C.E.E.M. van der; Wallimann, T.; Gillespie, P.G.

    2007-01-01

    When stimulated strongly, a hair cell's mechanically sensitive hair bundle may consume ATP too rapidly for replenishment by diffusion. To provide a broad view of the bundle's protein complement, including those proteins participating in energy metabolism, we used shotgun mass spectrometry methods to

  7. Differences in muscle pain and plasma creatine kinase activity after ...

    African Journals Online (AJOL)

    for a complete 30-second increment prior to fatigue. HRmax was recorded as the highest heart rate during the last 30 seconds of the treadmill test. Muscle pain. Muscle pain was measured daily for 1 day before, and for 7 days after the Comrades marathon. Muscle pain was measured subjec- tively, where subjects rated ...

  8. Creatine and Caffeine: Considerations for Concurrent Supplementation.

    Science.gov (United States)

    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.

  9. Creatine supplementation in young soccer players.

    Science.gov (United States)

    Ostojic, Sergej M

    2004-02-01

    The purpose of this study was to examine the effects of acute creatine-monohydrate supplementation on soccer-specific performance in young soccer players. Twenty young male soccer players (16.6 +/- 1.9 years) participated in the study and were matched and allocated to 2 randomly assigned trials: ingesting creatine-monohydrate supplement (3 x 10-g doses) or placebo for 7 days. Before and after the supplementation protocol, each subject underwent a series of soccer-specific skill tests: dribble test, sprint-power test, endurance test, and vertical jump test. Specific dribble test times improved significantly in the creatine group (13.0 +/- 1.5 vs. 10.2 +/- 1.8 s; p test times were significantly improved after creatine-monohydrate supplementation (2.7 +/- 0.4 vs. 2.2 +/- 0.5 s; p test times, along with vertical jump height, were superior in creatine versus placebo trial (p test results within or between trials (p > .05). There were no between-trial differences in the placebo trial (p > .05). The main finding of the present study indicates that supplementation with creatine in young soccer players improved soccer-specific skill performance compared with ingestion of placebo.

  10. PIKfyve in the SGK1 mediated regulation of the creatine transporter SLC6A8.

    Science.gov (United States)

    Strutz-Seebohm, Nathalie; Shojaiefard, Manzar; Christie, David; Tavare, Jeremy; Seebohm, Guiscard; Lang, Florian

    2007-01-01

    The Na(+),Cl(-),creatine transporter CreaT (SLC6A8) mediates concentrative cellular uptake of creatine into a wide variety of cells. Previous observations disclosed that SLC6A8 transport activity is enhanced by mammalian target of rapamycin (mTOR) at least partially through the serum and glucocorticoid inducible kinase isoforms SGK1 and SGK3. As SLC6A8 does not contain a putative SGK consensus motif, the mechanism linking SGK1 with SLC6A8 activity remained elusive. A candidate kinase is the mammalian phosphatidylinositol-3-phosphate-5-kinase PIKfyve (PIP5K3), which has previously been shown to regulate the glucose transporter GLUT4. The present experiments explored the possibility that SLC6A8 is regulated by PIKfyve. In Xenopus oocytes expressing SLC6A8 but not in water injected oocytes creatine induced a current which was significantly enhanced by coexpression of PIKfyve. The effect of PIKfyve on SLC6A8 was blunted by additional coexpression of the inactive mutant of the serum and glucocorticoid inducible kinase (K127N)SGK1. The stimulating effect of PIKfyve was abrogated by replacement of the serine in the SGK consensus sequence by alanine ((S318A)PIKfyve). Moreover, coexpression of ( S318A)PIKfyve blunted the effect of SGK1 on SLC6A8 activity. The observations suggest that SGK1 regulates the creatine transporter SLC6A8 at least partially through phosphorylation and activation of PIKfyve and subsequent formation of PI(3,5)P(2).

  11. Plasma Creatine Kinetics After Ingestion of Microencapsulated Creatine Monohydrate with Enhanced Stability in Aqueous Solutions.

    Science.gov (United States)

    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 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.

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

    Science.gov (United States)

    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

  13. Creatine metabolism and psychiatric disorders: Does creatine supplementation have therapeutic value?

    Science.gov (United States)

    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

  14. Creatine metabolism and psychiatric disorders: Does creatine supplementation have therapeutic value?

    Science.gov (United States)

    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.

  15. Genetics Home Reference: X-linked creatine deficiency

    Science.gov (United States)

    ... Almeida LS, Wood TC, Jakobs C, Stevenson RE, Schwartz CE, Salomons GS. X-linked creatine transporter (SLC6A8) ... on PubMed Longo N, Ardon O, Vanzo R, Schwartz E, Pasquali M. Disorders of creatine transport and ...

  16. The Regulation and Expression of the Creatine Transporter: A Brief Review of Creatine Supplementation in Humans and Animals

    Directory of Open Access Journals (Sweden)

    Greenwood Mike

    2006-06-01

    Full Text Available Abstract Creatine monohydrate has become one of the most popular ergogenic sport supplements used today. It is a nonessential dietary compound that is both endogenously synthesized and naturally ingested through diet. Creatine ingested through supplementation has been observed to be absorbed into the muscle exclusively by means of a creatine transporter, CreaT1. The major rationale of creatine supplementation is to maximize the increase within the intracellular pool of total creatine (creatine + phosphocreatine. There is much evidence indicating that creatine supplementation can improve athletic performance and cellular bioenergetics, although variability does exist. It is hypothesized that this variability is due to the process that controls both the influx and efflux of creatine across the cell membrane, and is likely due to a decrease in activity of the creatine transporter from various compounding factors. Furthermore, additional data suggests that an individual's initial biological profile may partially determine the efficacy of a creatine supplementation protocol. This brief review will examine both animal and human research in relation to the regulation and expression of the creatine transporter (CreaT. The current literature is very preliminary in regards to examining how creatine supplementation affects CreaT expression while concomitantly following a resistance training regimen. In conclusion, it is prudent that future research begin to examine CreaT expression due to creatine supplementation in humans in much the same way as in animal models.

  17. Creatine Transporter Deficiency in Two Half-Brothers

    NARCIS (Netherlands)

    Ardon, O.; di San Filippo, C.A.; Salomons, G.S.; Longo, N.

    2010-01-01

    X-linked cerebral creatine deficiency is caused by the deficiency of the creatine transporter encoded by the SLC6A8 gene. Here, we report two half-brothers with this condition and characterize creatine transport in human fibroblasts. The propositus presented at 6 months of age with delays in

  18. Creatine loading elevates the intracellular phosphorylation potential and alters adaptive responses of rat fast-twitch muscle to chronic low-frequency stimulation.

    Science.gov (United States)

    Putman, Charles T; Gallo, Maria; Martins, Karen J B; MacLean, Ian M; Jendral, Michelle J; Gordon, Tessa; Syrotuik, Daniel G; Dixon, Walter T

    2015-07-01

    This study tested the hypothesis that elevating the intracellular phosphorylation potential (IPP = [ATP]/[ADP]free) within rat fast-twitch tibialis anterior muscles by creatine (Cr) loading would prevent fast-to-slow fibre transitions induced by chronic low-frequency electrical stimulation (CLFS, 10 Hz, 12 h/day). Creatine-control and creatine-CLFS groups drank a solution of 1% Cr + 5% dextrose, ad libitum, for 10 days before and during 10 days of CLFS; dextrose-control and dextrose-CLFS groups drank 5% dextrose. Cr loading increased total Cr (P creatine-CLFS than in dextrose-CLFS. Higher IPP was confirmed by a 58% reduction in phospho-AMP-activated protein kinase α (Thr172) (P creatine-CLFS, MyHC-I and MyHC-IIa mRNA were unchanged and MyHC-IIb mRNA decreased by 75% (P creatine-CLFS, but reciprocal reductions in glycolytic reference enzymes occurred only in dextrose-CLFS (P creatine-CLFS coincided with prolonged time to peak tension and half-rise time (P < 0.01). These results highlight the IPP as an important physiological regulator of muscle fibre plasticity and demonstrate that training-induced changes typically associated with improvements in muscular endurance or increased power output are not mutually exclusive in Cr-loaded muscles.

  19. Creatine and the Male Adolescent Athlete

    Science.gov (United States)

    Schumaker, Shauna; Eyers, Christina; Cappaert, Thomas

    2012-01-01

    As the level of competition in youth sports increases, so does athletes' vulnerability to experimenting with performance-enhancing aids (PEAs) at alarmingly young ages. One of the more commonly used PEAs is a supplement called creatine, which has the ability to generate muscular energy, allowing athletes to train at higher intensities for longer…

  20. X-Linked Creatine-Transporter Gene (SLC6A8) Defect: A New Creatine-Deficiency Syndrome

    OpenAIRE

    Salomons, Gajja S.; van Dooren, Silvy J. M.; Verhoeven, Nanda M.; Cecil, Kim M.; Ball, William S.; Degrauw, Ton J.; Jakobs, Cornelis

    2001-01-01

    We report the first X-linked creatine-deficiency syndrome caused by a defective creatine transporter. The male index patient presented with developmental delay and hypotonia. Proton magnetic-resonance spectroscopy of his brain revealed absence of the creatine signal. However, creatine in urine and plasma was increased, and guanidinoacetate levels were normal. In three female relatives of the index patient, mild biochemical abnormalities and learning disabilities were present, to various exten...

  1. Rabbit muscle creatine phosphokinase. CDNA cloning, primary structure and detection of human homologues.

    Science.gov (United States)

    Putney, S; Herlihy, W; Royal, N; Pang, H; Aposhian, H V; Pickering, L; Belagaje, R; Biemann, K; Page, D; Kuby, S

    1984-12-10

    A cDNA library was constructed from rabbit muscle poly(A) RNA. Limited amino acid sequence information was obtained on rabbit muscle creatine phosphokinase and this was the basis for design and synthesis of two oligonucleotide probes complementary to a creatine kinase cDNA sequence which encodes a pentapeptide. Colony hybridizations with the probes and subsequent steps led to isolation of two clones, whose cDNA segments partially overlap and which together encode the entire protein. The primary structure was established from the sequence of two cDNA clones and from independently determined sequences of scattered portions of the polypeptide. The reactive cysteine has been located to position 282 within the 380 amino acid polypeptide. The rabbit cDNA hybridizes to digests of human chromosomal DNA. This reveals a restriction fragment length polymorphism associated with the human homologue(s) which hybridizes to the rabbit cDNA.

  2. Does brain creatine content rely on exogenous creatine in healthy youth? A proof-of-principle study.

    Science.gov (United States)

    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.

  3. Correlation of Students' Brain Types to Their Conceptions of Learning Science and Approaches to Learning Science

    Science.gov (United States)

    Park, Jiyeon; Jeon, Dongryul

    2015-01-01

    The systemizing and empathizing brain type represent two contrasted students' characteristics. The present study investigated differences in the conceptions and approaches to learning science between the systemizing and empathizing brain type students. The instruments are questionnaires on the systematizing and empathizing, questionnaires on the…

  4. X-linked creatine deficiency syndrome: a novel mutation in creatine transporter gene SLC6A8.

    Science.gov (United States)

    Bizzi, Alberto; Bugiani, Marianna; Salomons, Gajja S; Hunneman, Donald H; Moroni, Isabella; Estienne, Margherita; Danesi, Ugo; Jakobs, Cornelis; Uziel, Graziella

    2002-08-01

    Among creatine deficiency syndromes, an X-linked condition related to a defective creatine transport into the central nervous system has been described recently. Hallmarks of the disease are the absence of a creatine signal at brain spectroscopy, increased creatine levels in blood and urine, ineffectiveness of oral supplementation, and a mutation in the SLC6A8 (Online Mendelian Inheritance in Man [OMIM] 300036) creatine transporter gene. We report on a patient in whom a novel mutation (1221-1223delTTC) was identified.

  5. [Creatine: the nutritional supplement for exercise - current concepts].

    Science.gov (United States)

    Mendes, Renata Rebello; Tirapegui, Julio

    2002-06-01

    Creatine, a natural nutrient found in animal foods, is alleged to be an effective nutritional ergogenic aid to enhance sport or exercise performance. It may be formed in kidney and liver from arginina and glicina. Creatine may be delivered to the muscle, where it may combine readily with phosphate to form creatine phosphate, a high-energy phosphagen in the ATP-CP system, and is stored. The ATP-CP energy system is important for rapid energy production, such as in speed and power events. Approximately 120 g of creatine is found in a 70 kg male, 95% in the skeletal muscle. Total creatine exists in muscle as both free creatine (40%) and phosphocreatine (60%). It is only recently that a concerted effort has been undertaken to investigate its potential ergogenic effect relative to sport or exercise performance. It does appear that oral creatine monohydrate may increase muscle total creatine, including both free and phosphocreatine. Many, but not all studies suggest that creatine supplementation may enhance performance in high intensity, short-term exercise task that are dependent primarily on the ATP-CP energy system, particularly on laboratory test involving repeated exercise bouts with limited recovery time between repetitions. Short-term creatine supplementation appears to increase body mass, although the initial increase is most likely water associated with the osmotic effect of increased intramuscular total creatine. Chronic creatine supplementation in conjunction with physical training involving resistance exercise may increase muscle mass. However, confirmatory research data are needed. Creatine supplementation up to 8 weeks, with high doses, has not been associated with major health risks; with low doses, it was demonstrated that in 5 years period supplementation, there are no adverse effects. The decision to use creatine as a mean to enhance sport performance is left to the description to the individual athlete.

  6. EFFECTS OF COMBINED CREATINE PLUS FENUGREEK EXTRACT VS. CREATINE PLUS CARBOHYDRATE SUPPLEMENTATION ON RESISTANCE TRAINING ADAPTATIONS

    Directory of Open Access Journals (Sweden)

    Cliffa Foster

    2011-06-01

    Full Text Available 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 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 0.05. 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

  7. 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.

    Science.gov (United States)

    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

  8. Creatine and creatine pyruvate reduce hypoxia-induced effects on phrenic nerve activity in the juvenile mouse respiratory system.

    Science.gov (United States)

    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.

  9. X-Linked Creatine Transporter Deficiency Presenting as a Mitochondrial Disorder

    NARCIS (Netherlands)

    Hathaway, S.C.; Friez, M.; Limbo, K.; Parker, C.; Salomons, G.S.; Vockley, J.; Wood, T.; Abdul-Rahman, O.A.

    2010-01-01

    X-linked creatine transporter defect is caused by mutations in SLC6A8 at Xq28, which encodes the sodium-dependent creatine transporter. Reduction in creatine uptake results in elevated urine creatine and CSF creatine deficiency, which can be detected on magnetic resonance spectroscopy. We report a

  10. Brain Type or Sex Differences? A Structural Equation Model of the Relation between Brain Type, Sex, and Motivation to Learn Science

    Science.gov (United States)

    Zeyer, Albert; Bolsterli, Katrin; Brovelli, Dorothee; Odermatt, Freia

    2012-01-01

    Sex is considered to be one of the most significant factors influencing attitudes towards science. However, the so-called brain type approach from cognitive science suggests that the difference in motivation to learn science does not primarily differentiate the girls from the boys, but rather the so-called systemisers from the empathizers. The…

  11. Exercise training, creatine supplementation, and bone health in ovariectomized rats.

    Science.gov (United States)

    Murai, I H; Roschel, H; Pabis, L V S; Takayama, L; de Oliveira, R B; Dos Santos Pereira, R T; Dantas, W S; Pereira, R M R; Jorgetti, V; Ballester, R Y; Gualano, B

    2015-04-01

    Evidence suggests that creatine may have some beneficial effects on bone. The study aimed to investigate the effects of exercise alone or combined with creatine on bone health in ovariectomized rats. Findings show that exercise, but not creatine, has an important role in improving bone health. The aim of this study was to investigate the effects of exercise training alone or combined with creatine supplementation on bone health parameters in ovariectomized rats. Wistar rats were randomly allocated into one of five groups: (i) sham-operated, (ii) ovariectomized non-trained placebo-supplemented, (iii) ovariectomized non-trained creatine-supplemented, (iv) ovariectomized exercise-trained placebo-supplemented, and (v) ovariectomized exercise-trained creatine-supplemented. Downhill running training and/or creatine supplementation (300 mg/kg body weight) were administered for 12 weeks. Bone mineral content (BMC), bone mineral density (BMD), and biomechanical and histomorphometric parameters were assessed. No interaction effects were observed for BMC and BMD at whole body, femur, and lumbar spine (p > 0.05). Importantly, a main effect of training was detected for whole body BMC and BMD (p = 0.003 and p creatine supplementation. Main effects of training were also observed for maximal load (p  0.05). No main or interaction effects were observed for any of the histomorphometric parameters evaluated (p > 0.05). Exercise training, but not creatine supplementation, attenuated ovariectomy-induced bone loss in this rat model.

  12. Downregulation of the creatine transporter SLC6A8 by JAK2.

    Science.gov (United States)

    Shojaiefard, Manzar; Hosseinzadeh, Zohreh; Bhavsar, Shefalee K; Lang, Florian

    2012-03-01

    Janus-activated kinase-2 (JAK2) participates in the regulation of the Na⁺-coupled glucose transporter SGLT1 and the Na⁺-coupled amino acid transporter SLC6A19. Concentrative cellular creatine uptake is similarly accomplished by Na⁺-coupled transport. The carrier involved is SLC6A8 (CreaT). The present study thus explored whether JAK2 regulates the activity of SLC6A8. To this end, cRNA encoding SLC6A8 was injected into Xenopus oocytes with or without cRNA encoding wild-type JAK2, constitutively active (V617F)JAK2 or inactive (K882E)JAK2. Electrogenic creatine transport was determined in those oocytes by dual-electrode voltage-clamp experiments. In oocytes injected with cRNA encoding SLC6A8 but not in oocytes injected with water or with cRNA encoding JAK2 alone, addition of 1 mM creatine to the extracellular bath generated an inward current (I (crea)). In SLC6A8 expressing oocytes I (crea) was significantly decreased by coexpression of JAK2 or (V617F)JAK2 but not by coexpression of (K882E)JAK2. According to kinetic analysis, coexpression of JAK2 decreased the maximal transport rate without significantly modifying the affinity of the carrier. In oocytes expressing SLC6A8 and (V617F)JAK2 I (crea) was gradually increased by the JAK2 inhibitor AG490 (40 μM). In SLC6A8 and JAK2 coexpressing oocytes the decline of I (crea) following disruption of carrier insertion with brefeldin A (5 μM) was similar in the absence and presence of JAK2. In conclusion, JAK2 is a novel regulator of the creatine transporter SLC6A8, which downregulates the carrier, presumably by interference with carrier protein insertion into the cell membrane.

  13. An aberrant adenylate kinase isoenzyme from the serum of patients with Duchenne muscular dystrophy.

    Science.gov (United States)

    Hamada, M; Okuda, H; Oka, K; Watanabe, T; Ueda, K; Nojima, M; Kuby, S A; Manship, M; Tyler, F H; Ziter, F A

    1981-08-13

    The sera from patients with human Duchenne (X-linked) progressive muscular dystrophy contain elevated adenylate kinase (ATP: AMP phosphotransferase, EC 2.7.4.3) activities, in addition to their characteristically high creatine kinase (ATP; creatine N-phosphotransferase, EC 2.7.3.2) activities. By agarose gel electrophoresis of human Duchenne dystrophic serum, the presence of an apparently normal human serum adenylate kinase together with a variant species of adenylate kinase was detected. The latter enzyme species appeared, in its mobility, to be similar to that of the normal human liver-type adenylate kinase. The presence of this aberrant liver-type adenylate kinase could also be demonstrated by characteristic (for the liver type) inhibition patterns with P1,P5-di-(adenosine-5')pentaphosphate, 5,5'-dithiobis(2-nitrobenzoate) and phosphoenolpyruvate. On the other hand, by inhibition titrations with an anti-muscle-type adenylate kinase, hemolysates from the erythrocytes of several Duchenne and Becker's dystrophics were found to contain approx. 96% muscle-type adenylate kinase and their serum approx. 97% muscle-type adenylate kinase. These same patients contained approx. 89% M-M type creatine kinase in their serum (by inhibition against anti-human muscle-type creatine kinase) indicative of the presence also of M-B plus B-B type active isoenzymes. All of these data can best be explained by the presence of a variant or mutant adenylate kinase isoenzyme in the dystrophic serum. This isoenzyme appears to resemble the liver type in its inhibition patterns with P1,P5-di(adenosine-5')pentaphosphate, 5,5'-dithiobis(2-nitrobenzoate) and phosphoenolpyruvate, and in its heat stability (compare also the agarose gel electrophoresis pattern); but structurally, it is a muscle type, or derived from a muscle type, as shown immunologically by inhibition reactions with anti-muscle-type adenylate kinase. Whether this is a fetal-type isoenzyme of adenylate kinase will require further

  14. Creatine supplementation does not decrease oxidative stress and inflammation in skeletal muscle after eccentric exercise.

    Science.gov (United States)

    Silva, Luciano A; Tromm, Camila B; Da Rosa, Guilherme; Bom, Karoliny; Luciano, Thais F; Tuon, Talita; De Souza, Cláudio T; Pinho, Ricardo A

    2013-01-01

    Thirty-six male rats were used; divided into 6 groups (n = 6): saline; creatine (Cr); eccentric exercise (EE) plus saline 24 h (saline + 24 h); eccentric exercise plus Cr 24 h (Cr + 24 h); eccentric exercise plus saline 48 h (saline + 48 h); and eccentric exercise plus Cr 48 h (Cr + 48 h). Cr supplementation was administered as a solution of 300 mg · kg body weight(-1) · day(-1) in 1 mL water, for two weeks, before the eccentric exercise. The animals were submitted to one downhill run session at 1.0 km · h(-1) until exhaustion. Twenty-four and forty-eight hours after the exercise, the animals were killed, and the quadriceps were removed. Creatine kinase levels, superoxide production, thiobarbituric acid reactive substances (TBARS) level, carbonyl content, total thiol content, superoxide dismutase, catalase, glutathione peroxidase, interleukin-1b (IL-1β), nuclear factor kappa B (NF-kb), and tumour necrosis factor (TNF) were analysed. Cr supplementation neither decreases Cr kinase, superoxide production, lipoperoxidation, carbonylation, total thiol, IL-1β, NF-kb, or TNF nor alters the enzyme activity of superoxide dismutase, catalase, and glutathione peroxides in relation to the saline group, respectively (P exercise. The present study suggests that Cr supplementation does not decrease oxidative stress and inflammation after eccentric contraction.

  15. A randomized sequential trial of creatine in amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Groeneveld, G. J.; Veldink, Jan H.; van der Tweel, Ingeborg; Kalmijn, Sandra; Beijer, Cornelis; de Visser, Marianne; Wokke, John H. J.; Franssen, Hessel; van den Berg, Leonard H.

    2003-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal disease with no cure. In a transgenic mouse model of ALS, creatine monohydrate showed a promising increase in survival. We performed a double-blind, placebo-controlled, sequential clinical trial to assess the effect of creatine monohydrate on survival

  16. The effects of creatine supplementation on sprint running ...

    African Journals Online (AJOL)

    The purpose of this study was to determine the influence of short-term creatine supplementation on sprint running performance (100 and 200 m) and circulating hormone [growth hormone (GH), testosterone and cortisol] concentrations. Twenty amateur male runners were randomly divided into a creatine supplementation ...

  17. Creatine supplementation and swim performance: a brief review.

    Science.gov (United States)

    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

  18. Creatine, energetic function, metabolism and supplementation effects on sports

    Directory of Open Access Journals (Sweden)

    Emerson Gimenes Bernardo da Silva

    2008-06-01

    Full Text Available The purpose of this work is to review the literature regarding creatine ingestion by athletes and physical activity enthusiasts, discussing its necessity and, if possible, predicting some consequences. In order to achieve this purpose it was necessary to study the relationship between the muscles energetic system and their regulation. It was also proved necessary to investigate the creatine cycle, its endogenous origin, its metabolizing and conversion into creatine-phosphate. A bibliography was used to collect information about the subject. The research lead to the following conclusions: diet supplementation with creatine leads to increased phosphocreatine levels in human muscles. However, new in vivo experiments are most desirable, because it is already known that creatine interferes with the regulation of some metabolic pathways.

  19. CREATINE SUPPLEMENTATION AND SWIM PERFORMANCE: A BRIEF REVIEW

    Directory of Open Access Journals (Sweden)

    Melissa J. Hopwood

    2006-03-01

    Full Text Available 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

  20. Creatine pretreatment protects cortical axons from energy depletion in vitro

    Science.gov (United States)

    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

  1. Treatment by oral creatine, L-arginine and L-glycine in six severely affected patients with creatine transporter defect

    NARCIS (Netherlands)

    Valayannopoulos, V.; Boddaert, N.; Chabli, A.; Barbier, V.; Desguerre, I.; Philippe, A.; Afenjar, A.; Mazzuca, M.; Cheillan, D.; Munnich, A.; de Keyzer, Y.; Jakobs, C.A.J.M.; Salomons, G.S.; de Lonlay, P.

    2012-01-01

    Background X-linked cerebral creatine deficiency is caused by the deficiency of the creatine transporter (CTP) encoded by the SLC6A8 gene. Patients and Methods We report here a series of six patients with severe CTP deficiency, four males and two females; clinical presentations include mild to

  2. Total-body creatine pool size and skeletal muscle mass determination by creatine-(methyl-d3) dilution in rats

    National Research Council Canada - National Science Library

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

    2012-01-01

    .... We tested in rats the hypothesis that the enrichment of creatinine-(methyl-d3) (D3-creatinine) in urine after a defined oral tracer dose of D3-creatine can be used to determine creatine pool size and skeletal muscle mass...

  3. X-linked creatine-transporter gene (SLC6A8) defect: a new creatine-deficiency syndrome.

    Science.gov (United States)

    Salomons, G S; van Dooren, S J; Verhoeven, N M; Cecil, K M; Ball, W S; Degrauw, T J; Jakobs, C

    2001-06-01

    We report the first X-linked creatine-deficiency syndrome caused by a defective creatine transporter. The male index patient presented with developmental delay and hypotonia. Proton magnetic-resonance spectroscopy of his brain revealed absence of the creatine signal. However, creatine in urine and plasma was increased, and guanidinoacetate levels were normal. In three female relatives of the index patient, mild biochemical abnormalities and learning disabilities were present, to various extents. Fibroblasts from the index patient contained a hemizygous nonsense mutation in the gene SLC6A8 and were defective in creatine uptake. The three female relatives were heterozygous for this mutation in SLC6A8, which has been mapped to Xq28.

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

    Directory of Open Access Journals (Sweden)

    Purpura Martin

    2008-02-01

    Full Text Available Abstract 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 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.

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

    Science.gov (United States)

    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.

  6. Creatine and maltodextrine dietetic supplementation in eventing horses at training

    Directory of Open Access Journals (Sweden)

    Alexandre Soares Fagundes

    2011-09-01

    Full Text Available This study was carried out to evaluate the creatine and maltodextrine dietetic supplementation of eventing horses. The experimental period consisted of 56 days, with 20 horses, which were randomly divided into four groups with different diets. Diets were: diet without supplement (Control; diet supplemented with creatine, 44.4 mg/kg body weight/day (20 g creatine/horse/day; diet supplemented with creatine, 88.8 mg/kg body weight/day (40 g creatine/horse/day; diet supplemented with maltodextrine, 222.2 mg/kg body weight/day (100 g/horse/day, during three days before each test. Every horse was submitted to three tests. Blood samples and heart rate were collected at rest, immediately after the tests and 10 and 20 minutes after the test. Supplementation with creatine (44.4 mg/kg body weight/day and maltodextrine reduced plasma concentration of lactate in horses during tests. Supplementation of creatine and maltodextrine did not alter serum concentration of aspartate aminotransferase, γ-glutamyltransferase, urea or creatinine, but training affected blood biochemical variables in eventing horses.

  7. Creatine and the Liver: Metabolism and Possible Interactions.

    Science.gov (United States)

    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.

  8. Strategic creatine supplementation and resistance training in healthy older adults.

    Science.gov (United States)

    Candow, Darren G; Vogt, Emelie; Johannsmeyer, Sarah; Forbes, Scott C; Farthing, Jonathan P

    2015-07-01

    Creatine supplementation in close proximity to resistance training may be an important strategy for increasing muscle mass and strength; however, it is unknown whether creatine supplementation before or after resistance training is more effective for aging adults. Using a double-blind, repeated measures design, older adults (50-71 years) were randomized to 1 of 3 groups: creatine before (CR-B: n = 15; creatine (0.1 g/kg) immediately before resistance training and placebo (0.1 g/kg cornstarch maltodextrin) immediately after resistance training), creatine after (CR-A: n = 12; placebo immediately before resistance training and creatine immediately after resistance training), or placebo (PLA: n = 12; placebo immediately before and immediately after resistance training) for 32 weeks. Prior to and following the study, body composition (lean tissue, fat mass; dual-energy X-ray absorptiometry) and muscle strength (1-repetition maximum leg press and chest press) were assessed. There was an increase over time for lean tissue mass and muscle strength and a decrease in fat mass (p Creatine supplementation, independent of the timing of ingestion, increased muscle strength more than placebo (leg press: CR-B, Δ 36.6 ± 26.6 kg; CR-A, Δ 40.8 ± 38.4 kg; PLA, Δ 5.6 ± 35.1 kg; chest press: CR-B, Δ 15.2 ± 13.0 kg; CR-A, Δ 15.7 ± 12.5 kg; PLA, Δ 1.9 ± 14.7 kg; p creatine supplementation improves muscle strength, with greater gains in lean tissue mass resulting from post-exercise creatine supplementation.

  9. THE USE OF VARYING CREATINE REGIMENS ON SPRINT CYCLING

    Directory of Open Access Journals (Sweden)

    Apostolos Theodorou

    2003-09-01

    Full Text Available This study aimed to determine the effects of different acute creatine loadings (ACRL on repeated cycle sprints. Twenty-eight active subjects divided into the control (n=7 and the experimental (n=21 group. The exercise protocol comprised three 30s Anaerobic Wingate Tests (AWT interspersed with six minutes recovery, without any supplements ingested and following placebo and creatine ingestion, according to each ACRL (40g, 100g and 135g throughout a four-day period. Blood and urinary creatine levels were also determined from the experimental group for each ACRL. Protein intake (across all groups was held constant during the study. There were no changes in protein intake or performance of the control group. For the experimental group creatine supplementation produced significant (p<0.01 increases in body mass (82.5 ± 1.4kg pre vs 82.9 ± 1.2kg post, blood (0.21 ± 0.04mmol·l-1 pre vs 2.24 ± 0.98mmol·l-1 post, and urinary creatine (0.23 ± 0.09mmol·l-1 pre vs 4.29 ± 1.98mmol·l-1 post. No significant differences were found between the non-supplement and placebo condition. Creatine supplementation produced an average improvement of 0.7%, 11.8% and 11.1% for the 40g, 100g and 135g ACRL respectively. However, statistics revealed significant (p<0.01 differences only for the 100g and 135g ACRL. Mean ± SD values for the 100g ACRL for mean and minimum power were 612 ± 180W placebo vs 693 ± 221W creatine and 381 ± 35W placebo vs 415 ± 11W creatine accordingly. For the 135g ACRL the respective performance values were 722 ± 215W placebo vs 810 ± 240W creatine and 405 ± 59W placebo vs 436 ± 30W creatine. These data indicate that a 100g compared to 40g ACRL produces a greater potentiation of performance whilst, greater quantities of creatine ingestion (135g ACRL can not provide a greater benefit.

  10. Creatine Enhances Mitochondrial-Mediated Oligodendrocyte Survival After Demyelinating Injury.

    Science.gov (United States)

    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

  11. Normal cardiac function in mice with supraphysiological cardiac creatine levels

    Science.gov (United States)

    Hernandez, Alejandro; Nienaber, Jeffrey; Mishra, Rajashree; Pinilla, Miguel; Burchette, James; Mao, Lan; Rockman, Howard A.; Jacobs, Danny O.

    2013-01-01

    Creatine and phosphocreatine levels are decreased in heart failure, and reductions in myocellular phosphocreatine levels predict the severity of the disease and portend adverse outcomes. Previous studies of transgenic mouse models with increased creatine content higher than two times baseline showed the development of heart failure and shortened lifespan. Given phosphocreatine's role in buffering ATP content, we tested the hypothesis whether elevated cardiac creatine content would alter cardiac function under normal physiological conditions. Here, we report the creation of transgenic mice that overexpress the human creatine transporter (CrT) in cardiac muscle under the control of the α-myosin heavy chain promoter. Cardiac transgene expression was quantified by qRT-PCR, and human CrT protein expression was documented on Western blots and immunohistochemistry using a specific anti-CrT antibody. High-energy phosphate metabolites and cardiac function were measured in transgenic animals and compared with age-matched, wild-type controls. Adult transgenic animals showed increases of 5.7- and 4.7-fold in the content of creatine and free ADP, respectively. Phosphocreatine and ATP levels were two times as high in young transgenic animals but declined to control levels by the time the animals reached 8 wk of age. Transgenic mice appeared to be healthy and had normal life spans. Cardiac morphometry, conscious echocardiography, and pressure-volume loop studies demonstrated mild hypertrophy but normal function. Based on our characterization of the human CrT protein expression, creatine and phosphocreatine content, and cardiac morphometry and function, these transgenic mice provide an in vivo model for examining the therapeutic value of elevated creatine content for cardiac pathologies. PMID:24271489

  12. Dietary guanidinoacetic acid increases brain creatine levels in healthy men.

    Science.gov (United States)

    Ostojic, Sergej M; Ostojic, Jelena; Drid, Patrik; Vranes, Milan; Jovanov, Pavle

    2017-01-01

    Guanidinoacetic acid (GAA) is an experimental dietary additive that might act as a creatine source in tissues with high-energy requirements. In this case study, we evaluated brain levels of creatine in white matter, gray matter, cerebellum, and thalamus during 8 wk oral GAA administration in five healthy men and monitored the prevalence and severity of side effects of the intervention. Volunteers were supplemented daily with 36 mg/kg body weight (BW) of GAA for the first 4 wk of the intervention; afterward GAA dosage was titrated ≤60 mg/kg BW of GAA daily. At baseline, 4, and 8 wk, the participants underwent brain magnetic resonance spectroscopy, clinical chemistry studies, and open-ended questionnaire for side-effect prevalence and severity. Brain creatine levels increased in similar fashion in cerebellum, and white and gray matter after GAA supplementation, with an initial increase of 10.7% reported after 4 wk, and additional upsurge (7.7%) from the weeks 4 to 8 follow-up (P creatine levels decreased after 4 wk for 6.5% (P = 0.02), and increased nonsignificantly after 8 wk for 8% (P = 0.09). GAA induced an increase in N-acetylaspartate levels at 8-wk follow-up in all brain areas evaluated (P creatine pool in the human brain. This might be relevant for restoring cellular bioenergetics in disorders characterized by low brain creatine and functional enzymatic machinery for creatine synthesis, including neurodegenerative diseases, brain tumors, or cerebrovascular disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Is There a Relationship between Brain Type, Sex and Motivation to Learn Science?

    Science.gov (United States)

    Zeyer, Albert; Wolf, Sarah

    2010-11-01

    Whilst sex is considered to be one of the most significant factors influencing attitudes towards science, previous research seems to suggest that, at least in non-science classes, there is no correlation between sex and motivation to learn science. The present study investigates a mixed group of science and non-science students of upper secondary level. The data show that there is in fact no correlation between sex and motivation to learn science in this group, but that there is a highly significant positive correlation between the students' so-called brain type and their motivation to learn science. At the same time, male students show a more systemizing brain type whilst female students have a more empathizing one. Therefore, the brain type seems in fact to be a basic variable of motivation to learn science, as previous research suggests. Our intention was to explore if involving the science motivation questionnaire (SMQ) could be a strategy to confirm and extend this hypothesis, which seems to be the case. We consider this study as a pilot in preparation for a larger and more systematically sampled project.

  14. Can creatine supplementation form carcinogenic heterocyclic amines in humans?

    Science.gov (United States)

    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

  15. Creatine supplementation, sleep deprivation, cortisol, melatonin and behavior.

    Science.gov (United States)

    McMorris, T; Harris, R C; Howard, A N; Langridge, G; Hall, B; Corbett, J; Dicks, M; Hodgson, C

    2007-01-30

    The effect of creatine supplementation and sleep deprivation, with intermittent moderate-intensity exercise, on cognitive and psychomotor performance, mood state, effort and salivary concentrations of cortisol and melatonin were examined. Subjects were divided into a creatine supplementation group and a placebo group. They took 5 g of creatine monohydrate or a placebo, dependent on their group, four times a day for 7 days immediately prior to the experiment. They undertook tests examining central executive functioning, short-term memory, choice reaction time, balance, mood state and effort at baseline and following 18-, 24- and 36-h sleep deprivation, with moderate intermittent exercise. Saliva samples were taken prior to each set of tests. A group x time analysis of covariance, with baseline performance the covariate, showed that the creatine group performed significantly (p Cortisol concentrations on Day 1 were significantly (p < 0.01) higher than on Day 2. Mood significantly (p < 0.001) deteriorated up to 24 h with no change from 24 to 36 h. Effort at baseline was significantly (p < 0.01) lower than in the other conditions. It was concluded that, during sleep deprivation with moderate-intensity exercise, creatine supplementation only affects performance of complex central executive tasks.

  16. Caffeine, creatine, GRIN2A and Parkinson's disease progression.

    Science.gov (United States)

    Simon, David K; Wu, Cai; Tilley, Barbara C; Lohmann, Katja; Klein, Christine; Payami, Haydeh; Wills, Anne-Marie; Aminoff, Michael J; Bainbridge, Jacquelyn; Dewey, Richard; Hauser, Robert A; Schaake, Susen; Schneider, Jay S; Sharma, Saloni; Singer, Carlos; Tanner, Caroline M; Truong, Daniel; Wei, Peng; Wong, Pei Shieen; Yang, Tianzhong

    2017-04-15

    Caffeine is neuroprotective in animal models of Parkinson's disease (PD) and caffeine intake is inversely associated with the risk of PD. This association may be influenced by the genotype of GRIN2A, which encodes an NMDA-glutamate-receptor subunit. In two placebo-controlled studies, we detected no association of caffeine intake with the rate of clinical progression of PD, except among subjects taking creatine, for whom higher caffeine intake was associated with more rapid progression. We now have analyzed data from 420 subjects for whom DNA samples and caffeine intake data were available from a placebo-controlled study of creatine in PD. The GRIN2A genotype was not associated with the rate of clinical progression of PD in the placebo group. However, there was a 4-way interaction between GRIN2A genotype, caffeine, creatine and the time since baseline. Among subjects in the creatine group with high levels of caffeine intake, but not among those with low caffeine intake, the GRIN2A T allele was associated with more rapid progression (p=0.03). These data indicate that the deleterious interaction between caffeine and creatine with respect to rate of progression of PD is influenced by GRIN2A genotype. This example of a genetic factor interacting with environmental factors illustrates the complexity of gene-environment interactions in the progression of PD. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Cardiac Troponin I, Creatine Phosphokinase and Myoglobine Levels in Preeclampsia

    Directory of Open Access Journals (Sweden)

    Ahmet Kale

    2005-01-01

    Full Text Available To evaluate minor myocardial injury in preeclamptic pregnancies by serum markers of cardiac troponin-I, creatine phosphokinase and myoglobine. Group I consisted of 45 preeclamptic pregnancies, Group 2 consisted of uncomplicated pregnancies. The groups were compared for maternal age, parity, mean troponin–I, creatine phosphokinase and myoglobine values. Student-t test were used in statistical analyses. Significance was accepted as p<0.05. Cardiac troponin-I levels were statistically significantly higher in preeclamptic pregnancies (0,97 ± 0,11ng/ml than control groups (0,12 ± 0.09 ng/ml (p<0.001. No statistically significant difference was found with mean levels of creatine phosphokinase and myoglobin levels between two groups. Higher values of troponin-I’in preeclamptic patients is thought to be a result of myocardial injury and associated with pregnancy-induced hypertension.

  18. Creatine supplementation alters homocysteine level in resistance trained men.

    Science.gov (United States)

    Bereket-Yücel, S

    2015-04-01

    This study was conducted to investigate the effects of creatine loading and resistance training on the homocysteine and lipid profiles of young males. Sixty male University students (22.34 ± 2.19 years, 1.79 ± 0.08 m, 77.18 ± 12.57 kg, 15.48 ± 4.57% body fat) were randomly divided in to three groups; control (CG=20), creatine supplement (CEG=20) and placebo (PEG=20). Both CEG and PEG participated in a same resistance-training regimen and either taking a creatine supplement (25 g/d for the first 5 days followed 5 g/d thereafter) or the same amount of placebo for 8 weeks. Participants in CG did not take any creatine supplementation and not engage any exercise program. After the body composition were assessed, the homocysteine (Hcy) concentrations, blood lipids, folic acid and vitamin B12 levels of all the participants were measured at the beginning and end of the eight weeks of resistance training. The analysis of the data indicated that the Hcy levels of the CEG after resistance training and receiving the creatine supplement (9.33 ± 4.60) was significantly lower than that of baseline (12.66 ± 5.89) measurements, F(1,18)=12.28, P=0.00. No significant differences were seen in the Hcy levels of the PEG (15.01 ± 10.87) after 8 weeks of training and receiving a placebo (12.46 ± 12.50), F(1,16)=4.65, P=0.05. Furthermore, there were no significant differences among groups in terms of Hcy levels, F(2,52)=1.72, P=0.19. The present study suggests that as well as strength gain; creatine supplementation with resistance training may afford some protection against emerging cardiovascular risk factors.

  19. The effects of creatine supplementation on selected factors of tennis specific training

    NARCIS (Netherlands)

    Pluim, B.M.; Ferrauti, A.; Broekhof, F.; Deutekom, M.; Gotzmann, A.; Kuipers, H.; Weber, K.

    2006-01-01

    BACKGROUND: Creatine supplementation is popular among tennis players but it is not clear whether it actually enhances tennis performance. OBJECTIVES: To examine the effects of creatine supplementation on tennis specific performance indices. METHODS: In a randomised, double blind design, 36

  20. The Structure of Lombricine Kinase: Implications for Phosphagen Conformational Changes

    Energy Technology Data Exchange (ETDEWEB)

    Bush, D. Jeffrey; Kirillova, Olga; Clark, Shawn A.; Davulcu, Omar; Fabiola, Felcy; Xie, Qing; Somasundaram, Thayumanasamy; Ellington, W. Ross; Chapman, Michael S. (Oregon HSU); (FSU)

    2012-05-29

    Lombricine kinase is a member of the phosphagen kinase family and a homolog of creatine and arginine kinases, enzymes responsible for buffering cellular ATP levels. Structures of lombricine kinase from the marine worm Urechis caupo were determined by x-ray crystallography. One form was crystallized as a nucleotide complex, and the other was substrate-free. The two structures are similar to each other and more similar to the substrate-free forms of homologs than to the substrate-bound forms of the other phosphagen kinases. Active site specificity loop 309-317, which is disordered in substrate-free structures of homologs and is known from the NMR of arginine kinase to be inherently dynamic, is resolved in both lombricine kinase structures, providing an improved basis for understanding the loop dynamics. Phosphagen kinases undergo a segmented closing on substrate binding, but the lombricine kinase ADP complex is in the open form more typical of substrate-free homologs. Through a comparison with prior complexes of intermediate structure, a correlation was revealed between the overall enzyme conformation and the substrate interactions of His{sup 178}. Comparative modeling provides a rationale for the more relaxed specificity of these kinases, of which the natural substrates are among the largest of the phosphagen substrates.

  1. Creatine transporter (SLC6A8) knockout mice display an increased capacity for in vitro creatine biosynthesis in skeletal muscle

    OpenAIRE

    Russell, Aaron P.; Ghobrial, Lobna; Wright, Craig R.; Lamon, Séverine; Brown, Erin L.; Kon, Michihiro; Skelton, Matthew R.; Snow, Rodney J.

    2014-01-01

    The present study aimed to investigate whether skeletal muscle from whole body creatine transporter (CrT; SLC6A8) knockout mice (CrT-/y) actually contained creatine (Cr) and if so, whether this Cr could result from an up regulation of muscle Cr biosynthesis. Gastrocnemius muscle from CrT-/y and wild type (CrT+/y) mice were analyzed for ATP, Cr, Cr phosphate (CrP), and total Cr (TCr) content. Muscle protein and gene expression of the enzymes responsible for Cr biosynthesis L-arginine:glycine a...

  2. The cataract and glucosuria associated monocarboxylate transporter MCT12 is a new creatine transporter

    Science.gov (United States)

    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

  3. A buffered form of creatine does not promote greater changes in muscle creatine content, body composition, or training adaptations than creatine monohydrate

    Directory of Open Access Journals (Sweden)

    Jagim Andrew R

    2012-09-01

    Full Text Available Abstract Background Creatine monohydrate (CrM has been consistently reported to increase muscle creatine content and improve high-intensity exercise capacity. However, a number of different forms of creatine have been purported to be more efficacious than CrM. The purpose of this study was to determine if a buffered creatine monohydrate (KA that has been purported to promote greater creatine retention and training adaptations with fewer side effects at lower doses is more efficacious than CrM supplementation in resistance-trained individuals. Methods In a double-blind manner, 36 resistance-trained participants (20.2 ± 2 years, 181 ± 7 cm, 82.1 ± 12 kg, and 14.7 ± 5% body fat were randomly assigned to supplement their diet with CrM (Creapure® AlzChem AG, Trostberg, Germany at normal loading (4 x 5 g/d for 7-days and maintenance (5 g/d for 21-days doses; KA (Kre-Alkalyn®, All American Pharmaceutical, Billings, MT, USA at manufacturer’s recommended doses (KA-L, 1.5 g/d for 28-days; or, KA with equivalent loading (4 x 5 g/d for 7-days and maintenance (5 g/d doses of CrM (KA-H. Participants were asked to maintain their current training programs and record all workouts. Muscle biopsies from the vastus lateralis, fasting blood samples, body weight, DEXA determined body composition, and Wingate Anaerobic Capacity (WAC tests were performed at 0, 7, and 28-days while 1RM strength tests were performed at 0 and 28-days. Data were analyzed by a repeated measures multivariate analysis of variance (MANOVA and are presented as mean ± SD changes from baseline after 7 and 28-days, respectively. Results Muscle free creatine content obtained in a subgroup of 25 participants increased in all groups over time (1.4 ± 20.7 and 11.9 ± 24.0 mmol/kg DW, p = 0.03 after 7 and 28-days, respectively, with no significant differences among groups (KA-L −7.9 ± 22.3, 4.7 ± 27.0; KA-H 1.0 ± 12.8, 9.1

  4. 21 CFR 862.1210 - Creatine test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Creatine test system. 862.1210 Section 862.1210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... and endocrine disorders including hyperthyroidism. (b) Classification. Class I (general controls). The...

  5. Neuroprotective effect of creatine against propionic acid toxicity in ...

    African Journals Online (AJOL)

    The obtained in vitro data supports and explains the in vivo neurotoxic effect of PA and proves its DNA damaging effect which could clarify its role in the etiology of autism, a phenomenon recently raised by many researchers. It also supported the accumulating literature which describes creatine as a potential bioactive agent ...

  6. Does maternal-fetal transfer of creatine occur in pregnant sheep?

    Science.gov (United States)

    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 creatine content. Maternal arterial (13)C enrichment was increased (P 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.

  7. The effects of creatine ethyl ester supplementation combined with heavy resistance training on body composition, muscle performance, and serum and muscle creatine levels

    Directory of Open Access Journals (Sweden)

    Greenwood Mike

    2009-02-01

    Full Text Available Abstract Numerous creatine formulations have been developed primarily to maximize creatine absorption. Creatine ethyl ester is alleged to increase creatine bio-availability. This study examined how a seven-week supplementation regimen combined with resistance training affected body composition, muscle mass, muscle strength and power, serum and muscle creatine levels, and serum creatinine levels in 30 non-resistance-trained males. In a double-blind manner, participants were randomly assigned to a maltodextrose placebo (PLA, creatine monohydrate (CRT, or creatine ethyl ester (CEE group. The supplements were orally ingested at a dose of 0.30 g/kg fat-free body mass (approximately 20 g/day for five days followed by ingestion at 0.075 g/kg fat free mass (approximately 5 g/day for 42 days. Results showed significantly higher serum creatine concentrations in PLA (p = 0.007 and CRT (p = 0.005 compared to CEE. Serum creatinine was greater in CEE compared to the PLA (p = 0.001 and CRT (p = 0.001 and increased at days 6, 27, and 48. Total muscle creatine content was significantly higher in CRT (p = 0.026 and CEE (p = 0.041 compared to PLA, with no differences between CRT and CEE. Significant changes over time were observed for body composition, body water, muscle strength and power variables, but no significant differences were observed between groups. In conclusion, when compared to creatine monohydrate, creatine ethyl ester was not as effective at increasing serum and muscle creatine levels or in improving body composition, muscle mass, strength, and power. Therefore, the improvements in these variables can most likely be attributed to the training protocol itself, rather than the supplementation regimen.

  8. Creatine supplementation enhances muscle force recovery after eccentrically-induced muscle damage in healthy individuals

    Directory of Open Access Journals (Sweden)

    Cribb Paul J

    2009-06-01

    Full Text Available Abstract Background Eccentric exercise-induced damage leads to reductions in muscle force, increased soreness, and impaired muscle function. Creatine monohydrate's (Cr ergogenic potential is well established; however few studies have directly examined the effects of Cr supplementation on recovery after damage. We examined the effects of Cr supplementation on muscle proteins and force recovery after eccentrically-induced muscle damage in healthy individuals. Methods Fourteen untrained male participants (22.1 ± 2.3 yrs, 173 ± 7.7 cm, 76.2 ± 9.3 kg were randomly separated into 2 supplement groups: i Cr and carbohydrate (Cr-CHO; n = 7; or ii carbohydrate (CHO; n = 7. Participants consumed their supplement for a period of 5 days prior to, and 14 days following a resistance exercise session. Participants performed 4 sets of 10 eccentric-only repetitions at 120% of their maximum concentric 1-RM on the leg press, leg extension and leg flexion exercise machine. Plasma creatine kinase (CK and lactate dehydrogenase (LDH activity were assessed as relevant blood markers of muscle damage. Muscle strength was examined by voluntary isokinetic knee extension using a Cybex dynamometer. Data were analyzed using repeated measures ANOVA with an alpha of 0.05. Results The Cr-supplemented group had significantly greater isokinetic (10% higher and isometric (21% higher knee extension strength during recovery from exercise-induced muscle damage. Furthermore, plasma CK activity was significantly lower (by an average of 84% after 48 hrs (P Conclusion The major finding of this investigation was a significant improvement in the rate of recovery of knee extensor muscle function after Cr supplementation following injury.

  9. Creatine protects against mitochondrial dysfunction associated with HIV-1 Tat-induced neuronal injury

    Science.gov (United States)

    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

  10. International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine

    OpenAIRE

    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, rehabilit...

  11. Assignment of the creatine transporter gene (SLC6A8) to human chromosome Xq28 telomeric to G6PD

    Energy Technology Data Exchange (ETDEWEB)

    Gregor, P. [National Inst. on Drug Abuse, Baltimore, MD (United States); Nash, S.R.; Caron, M.G. [Duke Univ., Durham, NC (United States)] [and others

    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.

  12. Casein kinases

    DEFF Research Database (Denmark)

    Issinger, O G

    1993-01-01

    The present review on casein kinases focuses mainly on the possible metabolic role of CK-2, with special emphasis on its behavior in pathological tissues. From these data at least three ways to regulate CK-2 activity emerge: (i) CK-2 activity changes during embryogenesis, being high at certain...

  13. Tetrapentylammonium block of chloramine-T and veratridine modified rat brain type IIA sodium channels.

    Science.gov (United States)

    Ghatpande, A S; Rao, S; Sikdar, S K

    2001-04-01

    Tetrapentylammonium (TPeA) block of rat brain type IIA sodium channel alpha subunit was studied using whole cell patch clamp. Results indicate that TPeA blocks the inactivating brain sodium channel in a potential and use-dependent manner similar to that of the cardiac sodium channel. Removal of inactivation using chloramine-T (CT) unmasks a time-dependent block by TPeA consistent with slow blocking kinetics. On the other hand, no time dependence is observed when inactivation is abolished by modification with veratridine. TPeA does not bind in a potential-dependent fashion to veratridine-modified channels and does not significantly affect gating of veratridine-modified channels suggesting that high affinity binding of TPeA to the brain sodium channel is lost after veratridine modification.

  14. Diagnostic methods and recommendations for the cerebral creatine deficiency syndromes.

    Science.gov (United States)

    Clark, Joseph F; Cecil, Kim M

    2015-03-01

    Primary care pediatricians and a variety of specialist physicians strive to define an accurate diagnosis for children presenting with impairment of expressive speech and delay in achieving developmental milestones. Within the past two decades, a group of disorders featuring this presentation have been identified as cerebral creatine deficiency syndromes (CCDS). Patients with these disorders were initially discerned using proton magnetic resonance spectroscopy of the brain within a magnetic resonance imaging (MRI) examination. The objective of this review is to provide the clinician with an overview of the current information available on identifying and treating these conditions. We explain the salient features of creatine metabolism, synthesis, and transport required for normal development. We propose diagnostic approaches for confirming a CCDS diagnosis. Finally, we describe treatment approaches for managing patients with these conditions.

  15. Reduced Creatine Kinase B Activity in Multiple Sclerosis Normal Appearing White Matter

    NARCIS (Netherlands)

    Steen, Christel; Wilczak, Nadine; Hoogduin, Johannes M.; Koch, Marcus; De Keyser, Jacques

    2010-01-01

    Background: Two studies using (31)P-magnetic resonance spectroscopy (MRS) reported enhanced phosphocreatine (PCr) levels in normal appearing white matter (NAWM) of subjects with multiple sclerosis (MS), but this finding could not be properly explained. Methodology/Principal Findings: We performed

  16. Monitoring of Creatine Kinase Levels in Specific Military Populations for Early Treatment

    Science.gov (United States)

    2016-02-01

    CrossFit style approach to exercise. CrossFit , as an exercise construct, has numerous cases of rhabdomyolysis associated with it and is a known risk...among the CrossFit community. The increase prevalence of this style of exercise could be contributing to the uptrend within the military as both...functional fitness” and CrossFit often attract the military and law enforcement populations. This statistical data shows that there is a relevant

  17. Serum creatine kinase isoenzymes and macroenzymes in dogs with different neurologic diseases.

    Science.gov (United States)

    Paltrinieri, Saverio; Pintore, Laura; Balducci, Federica; Giordano, Alessia; Costabile, Annaluce; Bernardini, Marco

    2017-03-01

    Increased serum activity of CK isoenzymes and macroenzymes, and in particular of the brain isoenzyme (CK-BB) has been reported in dogs with central nervous system (CNS) disorders. However, no studies on the possible differences in serum activities of CK iso- or macroenzymes (Macro-CK1 and Macro-CK2) in different neurologic diseases are available. The aim of this study was to describe the electrophoretic distribution of CK iso- and macroenzymes in dogs with CNS disorders in order to assess whether this distribution depends on a specific neurologic disease. This study was done on sera from 45 dogs with neurologic diseases (degenerative, n = 7; idiopathic epilepsy [IE], n = 14; inflammatory, n = 16; space occupying lesions [SOL], n = 8) and from 10 clinically healthy dogs. The separation of serum CK isoenzymes and macroenzymes was performed using an automated electrophoretic method already validated in dogs. Compared with healthy dogs, dogs with CNS disorders had significantly higher total CK and CK-BB activities, and a significantly lower Macro-CK2 activity (P dogs revealed significant differences (P dogs with IE and inflammatory disorders for total CK activity, in all the subgroups for CK-BB (P dogs with IE and SOL for Macro-CK2 (P diseases cannot be differentiated based on CK-BB or Macro-CK2 activities, unless further studies allow the definition of diagnostic thresholds. © 2017 American Society for Veterinary Clinical Pathology.

  18. The biological role of the brain specific creatine kinase energy system in mice : a behavioral approach

    NARCIS (Netherlands)

    Streijger, Femke

    2007-01-01

    For any living cell it is essential to keep energy demand and production well balanced, and have energy homeostasis - i.e. ATP level - under tight regulation. Cells maintain their ATP level and viability by either respiration or glycolysis, whereby the energy provided is needed for the synthesis and

  19. Effects of Acrylamide on the Activity and Structure of Human Brain Creatine Kinase

    Science.gov (United States)

    Sheng, Qing; Zou, He-Chang; Lü, Zhi-Rong; Zou, Fei; Park, Yong-Doo; Yan, Yong-Bin; Yao, Shan-Jing

    2009-01-01

    Acrylamide is widely used worldwide in industry and it can also be produced by the cooking and processing of foods. It is harmful to human beings, and human brain CK (HBCK) has been proposed to be one of the important targets of acrylamide. In this research, we studied the effects of acrylamide on HBCK activity, structure and the potential binding sites. Compared to CKs from rabbit, HBCK was fully inactivated at several-fold lower concentrations of acrylamide, and exhibited distinct properties upon acrylamide-induced inactivation and structural changes. The binding sites of acrylamide were located at the cleft between the N- and C-terminal domains of CK, and Glu232 was one of the key binding residues. The effects of acrylamide on CK were proposed to be isoenzyme- and species-specific, and the underlying molecular mechanisms were discussed. PMID:20057941

  20. Creatine-Kinase- and Exercise-Related Muscle Damage Implications for Muscle Performance and Recovery

    Directory of Open Access Journals (Sweden)

    Marianne F. Baird

    2012-01-01

    The purpose of this paper is to examine current evidence and opinion relating to the release of CK from skeletal muscle in response to physical activity and examine if elevated concentrations are a health concern.

  1. creatine kinase (CK-MB) in The dilemma of the cardiospecific iso ...

    African Journals Online (AJOL)

    Muscle disease. Muscular dystrophies"B-lO. Viral myositis/ischaemic rhabdomyolysis",12. Alcoholic cardiomyopathy". Traumatic 'crush' syndrome'3. Brain disease (confused because of an elevation in CK-BB fraction). Malignant hyperpyrexia14. Other. Hypothyroidism,'S hypopara- thyroidism'S. Carcinoma, e.g. prostatic'6.

  2. Dysregulated brain creatine kinase is associated with hearing impairment in mouse models of Huntington disease

    OpenAIRE

    Lin, Yow-Sien; Chen, Chiung-Mei; Soong, Bing-Wen; Wu, Yih-Ru; Chen, Hui-Mei; Yeh, Wen-Ying; Wu, Dai-Rong; Lin, Yi-Jun; Poon, Paul Wai-Fung; Cheng, Mei-Ling; Wang, Chih-Hung; Chern, Yijuang

    2011-01-01

    Huntington disease (HD) is a degenerative disorder caused by expanded CAG repeats in exon 1 of the huntingtin gene (HTT). Patients with late-stage HD are known to have abnormal auditory processing, but the peripheral auditory functions of HD patients have yet to be thoroughly assessed. In this study, 19 HD patients (aged 40–59 years) were assessed for hearing impairment using pure-tone audiometry and assessment of auditory brainstem responses (ABRs). PTA thresholds were markedly elevated in H...

  3. Study of serum creatine kinase isoenzyme CKMB in endurance horses after prolonged physical exercise

    Directory of Open Access Journals (Sweden)

    Lilian Emy dos Santos Michima

    2010-02-01

    Full Text Available Com o objetivo de estudar a influência do exercício físico prolongado na indução de lesão miocárdica e na desqualificação de equinos em provas de enduro, colheram-se 87 amostras de sangue de equinos adultos Árabes e mestiços para determinação da concentração sérica da isoenzima MB (CKMB, da atividade sérica de creatina quinase (CK e do índice CKMB/CK. Dividiram-se as amostras da seguinte forma: C (controle, n = 34: equinos em repouso, no dia anterior à competição; G1 (n = 24: equinos que finalizaram as competições; G2 (n = 14: equinos desqualificados durante as competições por causa metabólica e G3 (n = 15: equinos desqualificados durante as competições por claudicação. Os valores medianos obtidos de CKMB, para os grupos C, G1, G2 e G3, foram respectivamente 2,25; 2,95; 1,95 e 2,40 ng/mL; para a atividade de CK, os resultados foram 164,2; 1228,0; 840,0 e 581,0 U/L a 30°C; e para o índice CKMB/CK, os resultados foram 1,41; 0,21; 0,23 e 0,42%. Houve média correlação positiva entre distância percorrida e CKMB e CK, e negativa entre distância e índice CKMB/CK. O exercício físico de resistência não leva a aumento significante dos valores da isoenzima CKMB, mas sim da atividade sérica da enzima CK, indicando dano à musculatura esquelética. Animais desqualificados por causa metabólica parecem não apresentar envolvimento de lesão miocárdica na causa de desqualificação. Não foi possível verificar a presença de lesão cardíaca induzida pelo exercício em equinos de enduro e sua relação com causas metabólicas de desqualificação a partir da utilização de CKMB como único marcador cardíaco.

  4. Effect of a Marathon Run on Serum Lipoproteins, Creatine Kinase, and Lactate Dehydrogenase in Recreational Runners

    Science.gov (United States)

    Kobayashi, Yoshio; Takeuchi, Toshiko; Hosoi, Teruo; Yoshizaki, Hidekiyo; Loeppky, Jack A.

    2005-01-01

    The objective of this study was to determine the effect of a marathon run on serum lipid and lipoprotein concentrations and serum muscle enzyme activities and follow their recovery after the run. These blood concentrations were measured before, immediately after, and serially after a marathon run in 15 male recreational runners. The triglyceride…

  5. Overexpression of wild-type creatine transporter (SLC6A8) restores creatine uptake in primary SLC6A8-deficient fibroblasts.

    Science.gov (United States)

    Rosenberg, Efraim H; Muñoz, Cristina Martínez; Degrauw, Ton J; Jakobs, Cor nelis; Salomons, Gajja S

    2006-01-01

    In the study reported, we prove that mutations in the SLC6A8 gene are responsible for SLC6A8 deficiency, a cerebral creatine deficiency syndrome (CCDS), since overexpression of the wild-type SLC6A8 open reading frame (ORF) restores the creatine uptake profile in SLC6A8-deficient fibroblasts.

  6. Stable isotope dilution microquantification of creatine metabolites in plasma, whole blood and dried blood spots for pharmacological studies in mouse models of creatine deficiency.

    Science.gov (United States)

    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.

  7. CREATINE SUPPLEMENTATION AND EXERCISE PERFORMANCE: A BRIEF REVIEW

    Directory of Open Access Journals (Sweden)

    Stephen P. Bird

    2003-12-01

    Full Text Available During the past decade, the nutritional supplement creatine monohydrate has been gaining popularity exponentially. Introduced to the general public in the early 1990s, shortly after the Barcelona Olympic Games, creatine (Cr has become one of the most widely used nutritional supplements or ergogenic aids, with loading doses as high as 20-30 g·day-1 for 5-7 days typical among athletes. This paper reviews the available research that has examined the potential ergogenic value of creatine supplementation (CrS on exercise performance and training adaptations. Short-term CrS has been reported to improve maximal power/strength, work performed during sets of maximal effort muscle contractions, single-effort sprint performance, and work performed during repetitive sprint performance. During training CrS has been reported to promote significantly greater gains in strength, fat free mass, and exercise performance primarily of high intensity tasks. However, not all studies demonstrate a beneficial effect on exercise performance, as CrS does not appear to be effective in improving running and swimming performance. CrS appears to pose no serious health risks when taken at doses described in the literature and may enhance exercise performance in individuals that require maximal single effort and/or repetitive sprint bouts

  8. Creatine supplementation with specific view to exercise/sports performance: an update

    Directory of Open Access Journals (Sweden)

    Cooper Robert

    2012-07-01

    Full Text Available Abstract 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.

  9. Creatine supplementation enhances corticomotor excitability and cognitive performance during oxygen deprivation.

    Science.gov (United States)

    Turner, Clare E; Byblow, Winston D; Gant, Nicholas

    2015-01-28

    Impairment or interruption of oxygen supply compromises brain function and plays a role in neurological and neurodegenerative conditions. Creatine is a naturally occurring compound involved in the buffering, transport, and regulation of cellular energy, with the potential to replenish cellular adenosine triphosphate without oxygen. Creatine is also neuroprotective in vitro against anoxic/hypoxic damage. Dietary creatine supplementation has been associated with improved symptoms in neurological disorders defined by impaired neural energy provision. Here we investigate, for the first time in humans, the utility of creatine as a dietary supplement to protect against energetic insult. The aim of this study was to assess the influence of oral creatine supplementation on the neurophysiological and neuropsychological function of healthy young adults during acute oxygen deprivation. Fifteen healthy adults were supplemented with creatine and placebo treatments for 7 d, which increased brain creatine on average by 9.2%. A hypoxic gas mixture (10% oxygen) was administered for 90 min, causing global oxygen deficit and impairing a range of neuropsychological processes. Hypoxia-induced decrements in cognitive performance, specifically attentional capacity, were restored when participants were creatine supplemented, and corticomotor excitability increased. A neuromodulatory effect of creatine via increased energy availability is presumed to be a contributing factor of the restoration, perhaps by supporting the maintenance of appropriate neuronal membrane potentials. Dietary creatine monohydrate supplementation augments neural creatine, increases corticomotor excitability, and prevents the decline in attention that occurs during severe oxygen deficit. This is the first demonstration of creatine's utility as a neuroprotective supplement when cellular energy provision is compromised. Copyright © 2015 the authors 0270-6474/15/351773-08$15.00/0.

  10. Involvement of hippocampal CAMKII/CREB signaling in the spatial memory retention induced by creatine.

    Science.gov (United States)

    Souza, Mauren Assis; Magni, Danieli Valnes; Guerra, Gustavo Petri; Oliveira, Mauro Schneider; Furian, Ana Flávia; Pereira, Letícia; Marquez, Silvia Vacari; Ferreira, Juliano; Fighera, Michele Rechia; Royes, Luiz Fernando Freire

    2012-12-01

    Although Creatine (Cr) and Phosphocreatine (PCr) systems play a key role in cellular energy and energy transport in neuronal cells, its implications for learning and memory are still controversial. Thus, we decided to investigate the involvement of cAMP-dependent protein kinase A (PKA), Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and cAMP responsive element binding protein (CREB) in the spatial consolidation after an intrahippocampal injection of Cr. Statistical analysis revealed that Cr (2.5 nmol/hippocampus) (post-training) decreased the latency for escape and the mean number of errors on Barnes maze test. Post-training co-administration of the PKA inhibitor (H-89 25 ρmol/hippocampus) did not alter the facilitatory effect of Cr in this memory test. On the other hand, Cr-induced spatial retention was reverted by co-administration of the CaMKII inhibitor (STO-609 5 nmol/hippocampus). Neurochemical analysis revealed that intrahippocampal injection of Cr, when analyzed after 30 min rather than after 3 h, increased the levels of pCREB and pCaMKII but not pPKA levels. Statistical analysis also revealed that the post-training co-administration of STO-609 but not H-89 reversed the increase of pCREB levels induced by Cr. The results presented in this report suggest that intracellular CaMKII/CREB pathway plays a key role in the Cr-induced spatial retention. Thus, it is plausible to propose that Cr plays a putative role as a neuromodulator in the brain, and that at least some of its effects may be mediated by intracellular CaMKII/CREB pathway.

  11. Putting to rest the myth of creatine supplementation leading to muscle cramps and dehydration.

    Science.gov (United States)

    Dalbo, V J; Roberts, M D; Stout, J R; Kerksick, C M

    2008-07-01

    Creatine is one of the most popular athletic supplements with sales surpassing 400 million dollars in 2004. Due to the popularity and efficacy of creatine supplementation over 200 studies have examined the effects of creatine on athletic performance. Despite the abundance of research suggesting the effectiveness and safety of creatine, a fallacy appears to exist among the general public, driven by media claims and anecdotal reports, that creatine supplementation can result in muscle cramps and dehydration. Although a number of published studies have refuted these claims, a recent position statement by the American College of Sports Medicine (ACSM) in 2000 advised individuals who are managing their weight and exercising intensely or in hot environments to avoid creatine supplementation. Recent reports now suggest that creatine may enhance performance in hot and/or humid conditions by maintaining haematocrit, aiding thermoregulation and reducing exercising heart rate and sweat rate. Creatine may also positively influence plasma volume during the onset of dehydration. Considering these new published findings, little evidence exists that creatine supplementation in the heat presents additional risk, and this should be taken into consideration as position statements and other related documents are published.

  12. Dissociation of AGAT, GAMT and SLC6A8 in CNS: relevance to creatine deficiency syndromes.

    Science.gov (United States)

    Braissant, Olivier; Béard, Elidie; Torrent, Céline; Henry, Hugues

    2010-02-01

    AGAT and GAMT, the two enzymes of the creatine synthesis pathway, are well expressed within CNS, suggesting autonomous brain creatine synthesis. This contradicts SLC6A8 deficiency, which causes creatine deficiency despite CNS expression of AGAT and GAMT. We hypothesized that AGAT and GAMT were not co-expressed by brain cells, and that guanidinoacetate must be transported between cells to allow creatine synthesis. We finely analyzed the cell-to-cell co-expression of AGAT, GAMT and SLC6A8 in various regions of rat CNS, and showed that in most structures, cells co-expressing AGAT+GAMT (equipped for autonomous creatine synthesis) were in low proportions (<20%). Using reaggregating brain cell cultures, we also showed that brain cells take up guanidinoacetate and convert it to creatine. Guanidinoacetate uptake was competed by creatine. This suggests that in most brain regions, guanidinoacetate is transported from AGAT- to GAMT-expressing cells through SLC6A8 to allow creatine synthesis, thereby explaining creatine deficiency in SLC6A8-deficient CNS.

  13. Dissociation of AGAT, GAMT and SLC6A8 in CNS: relevance to creatine deficiency syndromes.

    OpenAIRE

    Braissant Olivier; Béard Elidie; Torrent Céline; Henry Hugues

    2010-01-01

    AGAT and GAMT, the two enzymes of the creatine synthesis pathway, are well expressed within CNS, suggesting autonomous brain creatine synthesis. This contradicts SLC6A8 deficiency, which causes creatine deficiency despite CNS expression of AGAT and GAMT. We hypothesized that AGAT and GAMT were not co-expressed by brain cells, and that guanidinoacetate must be transported between cells to allow creatine synthesis. We finely analyzed the cell-to-cell co-expression of AGAT, GAMT and SLC6A8 in va...

  14. Fenugreek increases insulin-stimulated creatine content in L6C11 muscle myotubes.

    Science.gov (United States)

    Tomcik, Kristyen A; Smiles, William J; Camera, Donny M; Hügel, Helmut M; Hawley, John A; Watts, Rani

    2017-04-01

    Creatine uptake by muscle cells is increased in the presence of insulin. Accordingly, compounds with insulin-like actions may also augment creatine uptake. The aim of this study was to investigate whether Trigonella foenum-graecum (fenugreek), an insulin mimetic, increases total intracellular creatine levels in vitro. Total cellular creatine content was measured fluorometrically in L6C11 muscle myotubes treated for 1, 4, and 24 h with 0.5 mM creatine (CR), CR and 20 μg/mL fenugreek seed extract (CR + FEN), CR and 100 nM insulin (CR + INS), and CR + INS + FEN (n = 6 per treatment group). Alterations in the expression of the sodium- and chloride-dependent creatine transporter, SLC6A8, and key signaling proteins in the PI3-K/Akt pathway were determined. Compared to control (CON), CR + INS + FEN increased total creatine content after 4 h (P  CON and CR at 1 h (P  CON, CR, and CR + INS at 4 h (P creatine content via a mechanism which is independent of the activity of SLC6A8, suggesting that an alternative mechanism is responsible for the regulation and facilitation of insulin-mediated creatine uptake in skeletal muscle cells.

  15. Creatine Protects against Excitoxicity in an In Vitro Model of Neurodegeneration

    Science.gov (United States)

    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

  16. Considerations on the role of creatine on physical performance

    Directory of Open Access Journals (Sweden)

    Dilina do Nascimento Marreiro

    2008-06-01

    Full Text Available Creatine, a nitrogenous compound found mainly in food of animal origin, has been used as an ergogenic supplement with the aim of improving performance in physical exercise. The objective of this review is to provide up-todate information about aspects related to creatine metabolism and its role in physical performance. Indexed articles from the Pubmed, Scielo and Lilacs database were analyzed, preference being given to randomized placebo-controlled trials. Previous research has suggested that creatine supplementation may increase muscular concentration of this compound either in its free or phosphorylated form, enhancing performance in high-intensity, short-duration activities. The mechanisms involved in the storage of creatine have not been completely elucidated. Several studies have shown promising results regarding creatine supplementation in sports that require a single high intensity and/or short-term effort. In this context, the biochemical interactions related to the action of creatine in performance improvement are not clear. Further studies into the role of this compound in reactions involved in the storage and production of energy may lead to a better understanding of energy metabolism in physical performance. This knowledge could then guide other experimental tests to establish creatine’s ergogenic potential as a strategy for performance improvement. ResumoA creatina é um composto nitrogenado encontrado principalmente em alimentos de origem animal, sendo utilizado como suplemento ergogênico com vista à melhora do desempenho em exercícios físico. O objetivo da presente revisão foi trazer informações atualizadas sobre os aspectos relacionados ao metabolismo da creatina e de sua participação no desempenho físico. Os artigos indexados no banco de dados Pubmed, Scielo e Lilacs foram analisados, dando preferência aos trabalhos randomizados e com controle placebo. As pesquisas já realizadas sugerem que a suplementação com

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

    Science.gov (United States)

    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.

  18. Effects of creatine supplementation on oxidative stress profile of athletes

    Directory of Open Access Journals (Sweden)

    Percário Sandro

    2012-12-01

    Full Text Available Abstract 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

  19. Contribution of creatine to protein homeostasis in athletes after endurance and sprint running.

    Science.gov (United States)

    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.

  20. Effects of Isotretinoin on Serum Creatine Phosphokinase Levels in Patients with Acne Vulgaris

    Directory of Open Access Journals (Sweden)

    Müge Güler Özden

    2008-07-01

    Full Text Available Background and Design: It has been known that isotretinoin may cause rabdomyolysis besides its many side affects. The purpose of our study was to evaluate the effect of isotretinoin therapy with a cumulative dose of 120 mg/kg on serum creatine phosphokinase levels and muscle physiology in patients with acne vulgaris.MATERIAL-METHOD: A total of 66 patients with severe acne vulgaris were enrolled in the study and treated with isotretinoin twice daily at the dose of 0.6-0.8 mg/kg/day and for approximately 6.1±0.54 (3-7 months. Thirty-seven female (71.2% and 15 male (28.8% patients completed the study. The change in serum creatine kinase levels was measured before and monthly during the treatment course. Electromyography was performed in patients with a high serum CPK level and myalgia for the exclusion myopathy. All patients were evaluated with their laboratory findings and they were questioned for exercise habits and intramuscular injections.RESULTS: The mean age and body weight was 24.6±6.1 years and 62.3±11.9 kg respectively. We have detected 7 patients having elevated (13.5% serum CPK levels. Three of them had associating myalgia and muscle tenderness. The evaluation of these patients with EMG revealed no myopathy sign. (CPK values =1000, 880,726 respectively Only one patient with an elevated serum CPK was performing exercise. There was no history of intramuscular injection history in any of these patients. CONCLUSION: The use of standard isotretinoin therapy appears to have a relation with marked hyperCKemia with or without muscle-related complaints. Isotretinoin could have a potentializing effect on other myotoxicity inducers (drugs, infection, fever, muscular exertion. Although this phenomenon in isotretinoin-treated patients with acne appears to be validated as benign in nature, the clinicians must keep this side affect in mind and should monitorize serum CPK levels since there are some patients who had severe or persistent signs.

  1. Guanidinoacetate is more effective than creatine at enhancing tissue creatine stores while consequently limiting methionine availability in Yucatan miniature pigs.

    Directory of Open Access Journals (Sweden)

    Laura E McBreairty

    Full Text Available Creatine (Cr is an important high-energy phosphate buffer in tissues with a high energy demand such as muscle and brain and is consequently a highly consumed nutritional supplement. Creatine is synthesized via the S-adenosylmethionine (SAM dependent methylation of guanidinoacetate (GAA which is not regulated by a feedback mechanism. The first objective of this study was to determine the effectiveness of GAA at increasing tissue Cr stores. Because SAM is required for other methylation reactions, we also wanted to determine whether an increased creatine synthesis would lead to a lower availability of methyl groups for other methylated products. Three month-old pigs (n = 18 were fed control, GAA- or Cr-supplemented diets twice daily. On day 18 or 19, anesthesia was induced 1-3 hours post feeding and a bolus of [methyl-3H]methionine was intravenously infused. After 30 minutes, the liver was analyzed for methyl-3H incorporation into protein, Cr, phosphatidylcholine (PC and DNA. Although both Cr and GAA led to higher hepatic Cr concentration, only supplementation with GAA led to higher levels of muscle Cr (P < 0.05. Only GAA supplementation resulted in lower methyl-3H incorporation into PC and protein as well as lower hepatic SAM concentration compared to the controls, suggesting that Cr synthesis resulted in a limited methyl supply for PC and protein synthesis (P < 0.05. Although GAA is more effective than Cr at supporting muscle Cr accretion, further research should be conducted into the long term consequences of a limited methyl supply and its effects on protein and PC homeostasis.

  2. Creatine supplementation improves sprint performance in male sprinters.

    Science.gov (United States)

    Skare, O C; Skadberg; Wisnes, A R

    2001-04-01

    The object of this study was to evaluate the effect of creatine (Cr) supplementation in well trained male sprinters. The study was performed as a single blind test on 18 sprinters at a local competition level. During the last two years a substantial part of their training had consisted of a series of maximal sprints with short rest periods to improve their fatigue resistance. The participants consumed either 20 g Cr+20 g glucose per day (Cr group, n=9) or 40 g glucose per day (placebo group, n=9), divided into 4 equal dosages. The effect of Cr on sprint performance was evaluated in two tests, 1 x 100 m sprint and an intermittent 6x60 m sprint. Cr supplementation increased the 100 m sprint velocity (11.68+/-0.27 s vs 11.59+/-0.31 s) and reduced the total time of 6 intermittent 60 m sprints (45.63+/-1.11 s vs 45.12+/-1.1 s), whereas no changes were observed in the placebo group. The sprint velocity was significantly increased in 5 out of 6 intermittent 60 m sprints. Venous blood was drawn 5 min after finishing the final intermittent 60 m run. Plasma lactate, Cr and serum creatinine (Crn) were all increased in the Cr group compared to presupplementation values; no changes were observed in the placebo group. The improved sprint performance suggests an increased availability of energy substrate for performing work, possibly as a result of increased skeletal muscle creatine phosphate (PCr).

  3. Clinical features and X-inactivation in females heterozygous for creatine transporter defect

    NARCIS (Netherlands)

    van de Kamp, J. M.; Mancini, G. M. S.; Pouwels, P. J. W.; Betsalel, O. T.; van Dooren, S. J. M.; de Koning, I.; Steenweg, M. E.; Jakobs, C.; van der Knaap, M. S.; Salomons, G. S.

    2011-01-01

    The creatine transporter defect is an X-linked cause of mental retardation. We investigated the clinical features and pattern of X-inactivation in a Dutch cohort of eight female heterozygotes. We show that symptoms of the creatine transporter defect (mental retardation, learning difficulties, and

  4. The effects of creatine supplementation on selected factors of tennis specific training

    NARCIS (Netherlands)

    Pluim, B. M.; Ferrauti, A.; Broekhof, F.; Deutekom, M.; Gotzmann, A.; Kuipers, H.; Weber, K.

    2006-01-01

    Creatine supplementation is popular among tennis players but it is not clear whether it actually enhances tennis performance. To examine the effects of creatine supplementation on tennis specific performance indices. In a randomised, double blind design, 36 competitive male tennis players (24

  5. Phenotypic Variability in a Portuguese Family With X-Linked Creatine Transport Deficiency

    NARCIS (Netherlands)

    Garcia, P.; Rodrigues, F.; Valongo, C.; Salomons, G.S.; Diogo, L.

    2012-01-01

    Cerebral creatine transporter deficiency, attributable to mutations in the SLC6A8 gene, causes X-linked mental retardation, language delay, epilepsy, and autistic features. In contrast with creatine synthesis defects, the vast majority of patients with SLC6A8 deficiency do not respond to treatment.

  6. Treatment of Creatine Transporter (SLC6A8) Deficiency With Oral S-Adenosyl Methionine as Adjunct to L-arginine, Glycine, and Creatine Supplements.

    Science.gov (United States)

    Jaggumantri, Sravan; Dunbar, Mary; Edgar, Vanessa; Mignone, Cristina; Newlove, Theresa; Elango, Rajavel; Collet, Jean Paul; Sargent, Michael; Stockler-Ipsiroglu, Sylvia; van Karnebeek, Clara D M

    2015-10-01

    Creatine transporter (SLC6A8) deficiency is an X-linked inborn error of metabolism characterized by cerebral creatine deficiency, behavioral problems, seizures, hypotonia, and intellectual developmental disability. A third of patients are amenable to treatment with high-dose oral creatine, glycine, and L-arginine supplementation. Given the limited treatment response, we initiated an open-label observational study to evaluate the effect of adjunct S-adenosyl methionine to further enhance intracerebral creatine synthesis. Significant and reproducible issues with sleep and behavior were noted in both male patients on a dose of 50/mg/kg. One of the two patients stopped S-adenosyl methionine and did not come for any follow-up. A safe and tolerable dose (17 mg/kg/day) was identified in the other patient. On magnetic resonance spectroscopy, this 8-year-old male did not show an increase in intracerebral creatine. However, significant improvement in speech/language skills, muscle mass were observed as well as in personal outcomes as defined by the family in activities related to communication and decision making. Further research is needed to assess the potential of S-adenosyl methionine as an adjunctive therapy for creatine transporter deficiency patients and to define the optimal dose. Our study also illustrates the importance of pathophysiology-based treatment, individualized outcome assessment, and patient/family participation in rare diseases research. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. A novel SLC6A8 mutation associated with motor dysfunction in a child exhibiting creatine transporter deficiency

    OpenAIRE

    Cervera-Acedo, Cristina; Lopez, Maria; Aguirre-Lamban, Jana; Santiba?ez, Paula; Garcia-Oguiza, Alberto; Poch-Olive, Maria Luisa; Dominguez-Garrido, Elena

    2015-01-01

    Creatine transporter (CT) deficiency is an X-linked disorder caused by mutations in the SLC6A8 gene. We describe a clinical, biochemical and molecular examination of a child with X-linked cerebral creatine deficiency. Increased urinary creatine/creatinine ratio, abnormal brain proton magnetic resonance spectroscopy and reduced creatine transport confirmed the clinical diagnosis. SLC6A8 analysis revealed a novel mutation that was hemizygous in the child and not detected in his mother. CT defic...

  8. Effect of age, diet, and tissue type on PCr response to creatine supplementation.

    Science.gov (United States)

    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 children and omnivores (P children experienced greater PCr increases than omnivores (P = 0.0022). In relation to diet, vegetarians (P 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.

  9. A review of creatine supplementation in age-related diseases: more than a supplement for athletes

    Science.gov (United States)

    Smith, Rachel N.; Agharkar, Amruta S.; Gonzales, Eric B.

    2014-01-01

    Creatine is an endogenous compound synthesized from arginine, glycine and methionine. This dietary supplement can be acquired from food sources such as meat and fish, along with athlete supplement powders. Since the majority of creatine is stored in skeletal muscle, dietary creatine supplementation has traditionally been important for athletes and bodybuilders to increase the power, strength, and mass of the skeletal muscle. However, new uses for creatine have emerged suggesting that it may be important in preventing or delaying the onset of neurodegenerative diseases associated with aging. On average, 30% of muscle mass is lost by age 80, while muscular weakness remains a vital cause for loss of independence in the elderly population. In light of these new roles of creatine, the dietary supplement’s usage has been studied to determine its efficacy in treating congestive heart failure, gyrate atrophy, insulin insensitivity, cancer, and high cholesterol. In relation to the brain, creatine has been shown to have antioxidant properties, reduce mental fatigue, protect the brain from neurotoxicity, and improve facets/components of neurological disorders like depression and bipolar disorder. The combination of these benefits has made creatine a leading candidate in the fight against age-related diseases, such as Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, long-term memory impairments associated with the progression of Alzheimer’s disease, and stroke. In this review, we explore the normal mechanisms by which creatine is produced and its necessary physiology, while paying special attention to the importance of creatine supplementation in improving diseases and disorders associated with brain aging and outlining the clinical trials involving creatine to treat these diseases. PMID:25664170

  10. RNA Sequencing of Creatine Transporter (SLC6A8) Deficient Fibroblasts Reveals Impairment of the Extracellular Matrix

    NARCIS (Netherlands)

    Nota, B.; Ndika, J.D.T.; van de Kamp, J.M.; Kanhai, W.A.; van Dooren, S.J.M.; van de Wiel, M.A.; Pals, G.; Salomons, G.S.

    2014-01-01

    Creatine transporter (SLC6A8) deficiency is the most common cause of cerebral creatine syndromes, and is characterized by depletion of creatine in the brain. Manifestations of this X-linked disorder include intellectual disability, speech/language impairment, behavior abnormalities, and seizures. At

  11. RNA sequencing of creatine transporter (SLC6A8) deficient fibroblasts reveals impairment of the extracellular matrix

    NARCIS (Netherlands)

    Nota, Benjamin; Ndika, Joseph D. T.; van de Kamp, Jiddeke M.; Kanhai, Warsha A.; van Dooren, Silvy J. M.; van de Wiel, Mark A.; Pals, Gerard; Salomons, Gajja S.

    2014-01-01

    Creatine transporter (SLC6A8) deficiency is the most common cause of cerebral creatine syndromes, and is characterized by depletion of creatine in the brain. Manifestations of this X-linked disorder include intellectual disability, speech/language impairment, behavior abnormalities, and seizures. At

  12. Functional characterization of missense variants in the creatine transporter gene (SLC6A8): improved diagnostic application.

    NARCIS (Netherlands)

    Rosenberg, E.H.; Martinez Munoz, C.; Betsalel, O.T.; Dooren, S. van; Fernandez, M.; Jakobs, C.; Grauw, T.J. de; Kleefstra, T.; Schwartz, C.E.; Salomons, G.S.

    2007-01-01

    Creatine transporter deficiency is an X-linked mental retardation disorder caused by mutations in the creatine transporter gene (SLC6A8). So far, 20 mutations in the SLC6A8 gene have been described. We have developed a diagnostic assay to test creatine uptake in fibroblasts. Additionally, we

  13. Use of creatine in the elderly and evidence for effects on cognitive function in young and old.

    Science.gov (United States)

    Rawson, Eric S; Venezia, Andrew C

    2011-05-01

    The ingestion of the dietary supplement creatine (about 20 g/day for 5 days or about 2 g/day for 30 days) results in increased skeletal muscle creatine and phosphocreatine. Subsequently, the performance of high-intensity exercise tasks, which rely heavily on the creatine-phosphocreatine energy system, is enhanced. The well documented benefits of creatine supplementation in young adults, including increased lean body mass, increased strength, and enhanced fatigue resistance are particularly important to older adults. With aging and reduced physical activity, there are decreases in muscle creatine, muscle mass, bone density, and strength. However, there is evidence that creatine ingestion may reverse these changes, and subsequently improve activities of daily living. Several groups have demonstrated that in older adults, short-term high-dose creatine supplementation, independent of exercise training, increases body mass, enhances fatigue resistance, increases muscle strength, and improves the performance of activities of daily living. Similarly, in older adults, concurrent creatine supplementation and resistance training increase lean body mass, enhance fatigue resistance, increase muscle strength, and improve performance of activities of daily living to a greater extent than resistance training alone. Additionally, creatine supplementation plus resistance training results in a greater increase in bone mineral density than resistance training alone. Higher brain creatine is associated with improved neuropsychological performance, and recently, creatine supplementation has been shown to increase brain creatine and phosphocreatine. Subsequent studies have demonstrated that cognitive processing, that is either experimentally (following sleep deprivation) or naturally (due to aging) impaired, can be improved with creatine supplementation. Creatine is an inexpensive and safe dietary supplement that has both peripheral and central effects. The benefits afforded to

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

    Directory of Open Access Journals (Sweden)

    I. Bezrati-Benayed

    2014-07-01

    Full Text Available 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.

  15. EXERCISE PERFORMANCE AND MUSCLE CONTRACTILE PROPERTIES AFTER CREATINE MONOHYDRATE SUPPLEMENTATION IN AEROBIC-ANAEROBIC TRAINING RATS

    Directory of Open Access Journals (Sweden)

    Nickolay Boyadjiev

    2007-12-01

    Full Text Available The purpose of this study was to investigate the effects of creatine monohydrate supplementation on exercise performance and contractile variables in aerobic-anaerobic training rats. Twenty 90-day-old male Sprague Dawley rats were divided into two groups - creatine (Cr and controls (K. The creatine group received creatine monohydrate as a nutritional supplement, whereas the control group was given placebo. Both groups were trained 5 days a week on a treadmill for 20 days in a mixed (aerobic-anaerobic metabolic working regimen (27 m·min-1, 15% elevation for 40 min. The exercise performance (sprint-test, contractile properties (m. tibialis anterior, oxidative enzyme activity (SDH, LDH, NADH2 in m. soleus and blood hematological and chemical variables were assessed in the groups at the end of the experiment. It was found out that creatine supplementation improved the exercise performance after 20 days of administration in a dose of 60 mg per day on the background of a mixed (aerobic-anaerobic exercise training. At the end of the trial the Cr-group demonstrated better values for the variables which characterize the contractile properties of m. tibialis anterior containing predominantly types IIA and IIB muscle fibers. On the other hand, a higher oxidative capacity was found out in m. soleus (type I muscle fibers as a result of 20-day creatine supplementation. No side effects of creatine monohydrate supplementation were assessed by the hematological and blood biochemical indices measured in this study

  16. Creatine Metabolism and Safety Profiles after Six-Week Oral Guanidinoacetic Acid Administration in Healthy Humans

    Science.gov (United States)

    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 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

  17. Effect of creatine and pioglitazone on Hk-2 cell line cisplatin nephrotoxicity.

    Science.gov (United States)

    Genc, Gurkan; Kilinc, Veli; Bedir, Abdulkerim; Ozkaya, Ozan

    2014-08-01

    Cisplatin is a chemotherapeutic agent, which is used in the treatment of various solid organ cancers, and its main dose limiting side effect of cisplatin is nephrotoxicity. The aim of this study is to investigate the role of pioglitazone and creatine on cisplatin nephrotoxicity in vitro. Real-time cell analyzer system (RTCA) was used for real-time and time-dependent analysis of the cellular response of HK-2 cells following incubation with cisplatin and combination with creatine or pioglitazone hydrochloride. First, half-maximal inhibitory concentrations (IC50) of cisplatin, creatine and pioglitazone were calculated by RTCA system. Afterwards creatine and pioglitazone was administered with serial dilutions under RTCA system. IC50 dose for cisplatin was 7.69 M × 10(-5) at 24th hour and 3.93 M × 10(-6) at 48th hour. IC50 dose for pioglitazone was 1.61 M × 10(-3) at 24th hour and 2.85 M × 10(-4) at 48th hour. Although cells were treated the dose of 40,225 mM creatine, IC50 dose could not been reached. Neither pioglitazone nor creatine had additional protective effect in any dose. Consequently, beneficial effect of creatine and pioglitazone on cisplatin-induced cell death could not be found. Further studies and clinical trials are needed to evaluate the effect of different doses of these drugs in cisplatin-induced nephrotoxicity.

  18. The Effects of Creatine Supplementation on Explosive Performance and Optimal Individual Postactivation Potentiation Time

    Directory of Open Access Journals (Sweden)

    Chia-Chi Wang

    2016-03-01

    Full Text Available 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.

  19. Effect of creatine on aerobic and anaerobic metabolism in skeletal muscle in swimmers.

    Science.gov (United States)

    Thompson, C H; Kemp, G J; Sanderson, A L; Dixon, R M; Styles, P; Taylor, D J; Radda, G K

    1996-09-01

    To examine the effect of a relatively low dose of creatine on skeletal muscle metabolism and oxygen supply in a group of training athletes. 31P magnetic resonance and near-infrared spectroscopy were used to study calf muscle metabolism in a group of 10 female members of a university swimming team. Studies were performed before and after a six week period of training during which they took either 2 g creatine daily or placebo. Calf muscle metabolism and creatine/choline ratios were studied in resting muscle, during plantar flexion exercise (10-15 min), and during recovery from exercise. There was no effect of creatine on metabolite ratios at rest or on metabolism during exercise and recovery from exercise. Muscle oxygen supply and exercise performance were not improved by creatine if compared to placebo treated subjects. Oral creatine supplementation at 2 g daily has no effect on muscle creatine concentration, muscle oxygen supply or muscle aerobic or anaerobic metabolism during endurance exercise.

  20. Phenotype and genotype in 101 males with X-linked creatine transporter deficiency.

    Science.gov (United States)

    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.

  1. Maternal creatine homeostasis is altered during gestation in the spiny mouse: is this a metabolic adaptation to pregnancy?

    Science.gov (United States)

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

    2015-04-14

    Pregnancy induces adaptations in maternal metabolism to meet the increased need for nutrients by the placenta and fetus. Creatine is an important intracellular metabolite obtained from the diet and also synthesised endogenously. Experimental evidence suggests that the fetus relies on a maternal supply of creatine for much of gestation. However, the impact of pregnancy on maternal creatine homeostasis is unclear. We hypothesise that alteration of maternal creatine homeostasis occurs during pregnancy to ensure adequate levels of this essential substrate are available for maternal tissues, the placenta and fetus. This study aimed to describe maternal creatine homeostasis from mid to late gestation in the precocial spiny mouse. Plasma creatine concentration and urinary excretion were measured from mid to late gestation in pregnant (n = 8) and age-matched virgin female spiny mice (n = 6). At term, body composition and organ weights were assessed and tissue total creatine content determined. mRNA expression of the creatine synthesising enzymes arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT), and the creatine transporter (CrT1) were assessed by RT-qPCR. Protein expression of AGAT and GAMT was also assessed by western blot analysis. Plasma creatine and renal creatine excretion decreased significantly from mid to late gestation (P physiology to pregnancy to meet the metabolic demands of maternal tissues, the placenta and developing fetus.

  2. Creatine as a booster for human brain function. How might it work?

    Science.gov (United States)

    Rae, Caroline D; Bröer, Stefan

    2015-10-01

    Creatine, a naturally occurring nitrogenous organic acid found in animal tissues, has been found to play key roles in the brain including buffering energy supply, improving mitochondrial efficiency, directly acting as an anti-oxidant and acting as a neuroprotectant. Much of the evidence for these roles has been established in vitro or in pre-clinical studies. Here, we examine the roles of creatine and explore the current status of translation of this research into use in humans and the clinic. Some further possibilities for use of creatine in humans are also discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Creatine transporter (SLC6A8) knockout mice display an increased capacity for in vitro creatine biosynthesis in skeletal muscle.

    Science.gov (United States)

    Russell, Aaron P; Ghobrial, Lobna; Wright, Craig R; Lamon, Séverine; Brown, Erin L; Kon, Michihiro; Skelton, Matthew R; Snow, Rodney J

    2014-01-01

    The present study aimed to investigate whether skeletal muscle from whole body creatine transporter (CrT; SLC6A8) knockout mice (CrT(-/y)) actually contained creatine (Cr) and if so, whether this Cr could result from an up regulation of muscle Cr biosynthesis. Gastrocnemius muscle from CrT(-/y) and wild type (CrT(+/y)) mice were analyzed for ATP, Cr, Cr phosphate (CrP), and total Cr (TCr) content. Muscle protein and gene expression of the enzymes responsible for Cr biosynthesis L-arginine:glycine amidotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT) were also determined as were the rates of in vitro Cr biosynthesis. CrT(-/y) mice muscle contained measurable (22.3 ± 4.3 mmol.kg(-1) dry mass), but markedly reduced (P < 0.05) TCr levels compared with CrT(+/y) mice (125.0 ± 3.3 mmol.kg(-1) dry mass). AGAT gene and protein expression were higher (~3 fold; P < 0.05) in CrT(-/y) mice muscle, however GAMT gene and protein expression remained unchanged. The in vitro rate of Cr biosynthesis was elevated 1.5 fold (P < 0.05) in CrT(-/y) mice muscle. These data clearly demonstrate that in the absence of CrT protein, skeletal muscle has reduced, but not absent, levels of Cr. This presence of Cr may be at least partly due to an up regulation of muscle Cr biosynthesis as evidenced by an increased AGAT protein expression and in vitro Cr biosynthesis rates in CrT(-/y) mice. Of note, the up regulation of Cr biosynthesis in CrT(-/y) mice muscle was unable to fully restore Cr levels to that found in wild type muscle.

  4. Benefits and drawbacks of guanidinoacetic acid as a possible treatment to replenish cerebral creatine in AGAT deficiency.

    Science.gov (United States)

    Ostojic, Sergej M

    2017-10-03

    Arginine-glycine amidinotransferase (AGAT) deficiency is a rare inherited metabolic disorder that severely affects brain bioenergetics. Characterized by mental retardation, language impairment, and behavioral disorders, AGAT deficiency is a treatable condition, where long-term creatine supplementation usually restores brain creatine levels and improves its clinical features. In some cases of AGAT deficiency, creatine treatment might be somewhat limited due to possible shortcomings in performance and transport of creatine to the brain. Guanidinoacetic acid (GAA), a direct metabolic precursor of creatine, has recently been suggested as a possible alternative to creatine to tackle brain creatine levels in experimental medicine. AGAT patients might benefit from oral GAA due to upgraded bioavailability and convenient utilization of the compound, while possible drawbacks (e.g. brain methylation issues, neurotoxicity, and hyperhomocysteinemia) should be accounted as well.

  5. Estimated carrier frequency of creatine transporter deficiency in females in the general population using functional characterization of novel missense variants in the SLC6A8 gene

    NARCIS (Netherlands)

    Desroches, C.L.; Patel, J.; Wang, P.X.; Minassian, B.; Salomons, G.; Marshall, C.R.; Mercimek-Mahmutoglu, S.

    2015-01-01

    Creatine transporter deficiency (CRTR-D) is an X-linked inherited disorder of creatine transport. All males and about 50% of females have intellectual disability or cognitive dysfunction. Creatine deficiency on brain proton magnetic resonance spectroscopy and elevated urinary creatine to creatinine

  6. Distribution of creatine, guanidinoacetate and the enzymes for their biosynthesis in the animal kingdom. Implications for phylogeny.

    Science.gov (United States)

    Van Pilsum, J F; Stephens, G C; Taylor, D

    1972-01-01

    1. The distribution of creatine and the creatine-synthesizing enzymes in the animal kingdom has been investigated. Creatine was found in tissues of all vertebrates examined, and in various invertebrates from phyla Annelida, Echinodermata, Hemichordata and Chordata, subphylum Cephalochordata. The activities of the creatine-synthesizing enzymes, arginine-glycine transamidinase and guanidinoacetate methylpherase, were not detected in the hagfish or in any of the invertebrates, including those in which creatine was found, with the exception that transamidinase activities were detected in the amphioxus and salt water clam; however, these activities are considered to be artifacts for reasons mentioned in the text. Additional evidence that the hagfish and various creatine-containing invertebrates could not synthesize creatine was the observation that these animals did not convert one or the other of the likely precursors of creatine (arginine and glycine) into creatine, in vivo. Further, the inability of these animals to synthesize creatine is correlated with the observations that all animals tested were able to abstract creatine from their aqueous environment. 2. The activities of the creatine-synthesizing enzymes were detected in the sea lamprey and in all but a few of the other vertebrates examined. Neither activity could be detected in the sharks and rays (cartilaginous fish), buffalo fish (bony fish) or the snapping turtle. Transamidinase or guanidinoacetate methylpherase activity could not be found in the salamander or garter snake, respectively. 3. The results obtained with the lamprey are in direct contrast with those obtained with the hagfish (both subphylum Agnatha, class Cyclostomata). The lamprey had the ability to synthesize creatine and did not abstract creatine from lake water. The hagfish did not have any apparent ability to synthesize creatine and did abstract creatine from sea water. The present report thus supports the theory that the myxinoid (hagfish

  7. Arginine kinase from Myzostoma cirriferum, a basal member of annelids.

    Science.gov (United States)

    Yano, Daichi; Mimura, Sayo; Uda, Kouji; Suzuki, Tomohiko

    2016-08-01

    We assembled a phosphagen kinase gene from the Expressed Sequence Tags database of Myzostoma cirriferum, a basal member of annelids. The assembled gene sequence was synthesized using an overlap extension polymerase chain reaction method and was expressed in Escherichia coli. The recombinant enzyme (355 residues) exhibited monomeric behavior on a gel filtration column and showed strong activity only for l-arginine. Thus, the enzyme was identified as arginine kinase (AK). The two-substrate kinetic parameters were obtained and compared with other AKs. Phylogenetic analysis of amino acid sequences of phosphagen kinases indicated that the Myzostoma AK gene lineage differed from that of the polychaete Sabellastarte spectabilis AK, which is a dimer of creatine kinase (CK) origin. It is likely that the Myzostoma AK gene lineage was lost at an early stage of annelid evolution and that Sabellastarte AK evolved secondarily from the CK gene. This work contributes to our understanding of the evolution of phosphagen kinases of annelids with marked diversity. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. [Cytoplasmic kinase inhibitors].

    Science.gov (United States)

    Mano, Hiroyuki

    2010-10-01

    Protein kinases play essential roles in the regulation of cell proliferation. Point mutations or/and fusions of protein kinases are frequently identified in human cancers, and targeting such activated kinases provides us with a chance to eradicate tumor cells. This was first proved by imatinib mesylate that inhibits ABL tyrosine kinase and, thereby, efficiently kills malignant cells in chronic myeloid leukemia. In addition, other clinical trials are ongoing for kinase inhibitors against EML4--ALK in lung cancer, JAK2 in myeloproliferative disorders and BRAF in malignant melanoma. Early reports indeed reveal that such targeting compounds are promising drugs for human cancers with activated kinases.

  9. High cerebral guanidinoacetate and variable creatine concentrations in argininosuccinate synthetase and lyase deficiency : Implications for treatment?

    NARCIS (Netherlands)

    van Spronsen, F. J.; Reijngoud, D. J.; Verhoeven, N. M.; Soorani-Lunsing, R. J.; Jakobs, C.; Sijens, P. E.

    2006-01-01

    Cerebral creatine and guanidinoacetate and blood and urine metabolites were studied in four patients with argininosuccinate synthetase (ASS) or argininosuccinate lyase (ASL) deficiency receiving large doses of arginine. Urine and blood metabolites varied largely. Cerebral guanidinoacetate was

  10. In vitro and in vivo studies of creatine monohydrate supplementation to Duroc and Landrace pigs

    DEFF Research Database (Denmark)

    Young, J F; Bertram, H C; Theil, P K

    2007-01-01

    Duroc and Landrace pigs as well as primary myotubes from these breeds were used to investigate mechanisms behind differences in their response to creatine monohydrate (CMH). Pigs were supplemented with 0, 12.5, 25 or 50g CMH/d for 5 days (n=10 per treatment and breed). Plasma levels of creatine...... increased dose-dependently in both breeds, while muscle-creatine phosphate content increased only in the Duroc pigs. (1)H NMR metabolic profiling showed a tendency towards clustering according to CMH supplementation only among Duroc pigs, revealing a stronger response compared to Landrace pigs....... The abundance of insulin-like growth factor I and myostatin mRNA was decreased by CMH supplementation while that of type 1 IGF-receptor and creatine transporter was unaffected. Protein synthesis, increased in the myotubes from both breeds, indicating protein accretion, but no effect was observed on the m...

  11. Creatine monohydrate ingestion-related placebo effects on brief anaerobic exercise performance. A laboratory investigation

    National Research Council Canada - National Science Library

    A Szabo; R Szemerszky; Z Dömötör; R de la Vega; F Köteles

    2017-01-01

    .... In the current study the placebo effects of creatine monohydrate on a one-minute anaerobic step-exercise performance were examined in a double blind laboratory inquiry University students (n = 79, 64.5% women...

  12. 1H magnetic resonance spectroscopy of the brain in paediatrics: The diagnosis of creatine deficiencies

    NARCIS (Netherlands)

    Sijens, P.E.; Oudkerk, M.

    2005-01-01

    The diagnosis of creatine deficiencies, a paediatric application of magnetic resonance spectroscopy that has already become a diagnostic tool in clinical practice, is reviewed and illustrated with results from recent examinations

  13. Does creatine supplementation enhance the effects of physical training during pulmonary rehabilitation in COPD?

    Directory of Open Access Journals (Sweden)

    Sarah. J. Deacon

    2006-12-01

    Full Text Available We conducted a randomised, placebo-controlled trial to examine whether creatine supplementation augments the benefits of pulmonary rehabilitation (PR, containing aerobic exercise and resistance training (RT. 80 subjects with COPD (GOLD stages I–IV [mean (SD age 68 (7.8 yrs, FEV1 44.1 (20.3 % predicted] completed 21 sessions of PR, with enhanced RT, following baseline measurements and randomisation to take creatine (Cr or placebo (Pl supplement. A subgroup had muscle biopsies. Groups were well matched at baseline except for gender (M:F Cr 19:19, Pl 31:11, Chi2 p = 0.03. Mean change in functional performance & muscle strength after PR are shown. Health status (CRQ-SR improved significantly after PR but did not differ between groups. Muscle biopsies showed evidence of creatine uptake. This adequately powered study showed significant improvements in all outcomes following PR. Creatine supplementation did not enhance these benefits.

  14. Abnormal N-Glycosylation of a Novel Missense Creatine Transporter Mutant, G561R, Associated with Cerebral Creatine Deficiency Syndromes Alters Transporter Activity and Localization.

    Science.gov (United States)

    Uemura, Tatsuki; Ito, Shingo; Ohta, Yusuke; Tachikawa, Masanori; Wada, Takahito; Terasaki, Tetsuya; Ohtsuki, Sumio

    2017-01-01

    Cerebral creatine deficiency syndromes (CCDSs) are caused by loss-of-function mutations in creatine transporter (CRT, SLC6A8), which transports creatine at the blood-brain barrier and into neurons of the central nervous system (CNS). This results in low cerebral creatine levels, and patients exhibit mental retardation, poor language skills and epilepsy. We identified a novel human CRT gene missense mutation (c.1681 G>C, G561R) in Japanese CCDSs patients. The purpose of the present study was to evaluate the reduction of creatine transport in G561R-mutant CRT-expressing 293 cells, and to clarify the mechanism of its functional attenuation. G561R-mutant CRT exhibited greatly reduced creatine transport activity compared to wild-type CRT (WT-CRT) when expressed in 293 cells. Also, the mutant protein is localized mainly in intracellular membrane fraction, while WT-CRT is localized in plasma membrane. Western blot analysis revealed a 68 kDa band of WT-CRT protein in plasma membrane fraction, while G561R-mutant CRT protein predominantly showed bands at 55, 110 and 165 kDa in crude membrane fraction. The bands of both WT-CRT and G561R-mutant CRT were shifted to 50 kDa by N-glycosidase treatment. Our results suggest that the functional impairment of G561R-mutant CRT was probably caused by incomplete N-linked glycosylation due to misfolding during protein maturation, leading to oligomer formation and changes of cellular localization.

  15. Studies on the importance of creatine during pregnancy for the mother and newborn

    OpenAIRE

    Ellery, Stacey Joan

    2017-01-01

    The primary focus of this thesis was the use of the spiny mouse to model birth asphyxia-induced neonatal Acute Kidney Injury (AKI). Understanding what effect birth asphyxia has on the neonatal kidney at a molecular, structural and functional level, determining if deficits persist into adulthood, and the potential for intervention using maternal creatine supplementation, were important goals. The work in this thesis also characterised maternal creatine homeostasis during late pregnancy, to ass...

  16. Upregulation of the Creatine Transporter Slc6A8 by Klotho

    Directory of Open Access Journals (Sweden)

    Ahmad Almilaji

    2014-11-01

    Full Text Available Background/Aims: The transmembrane Klotho protein contributes to inhibition of 1,25(OH2D3 formation. The extracellular domain of Klotho protein could function as an enzyme with e.g. β-glucuronidase activity, be cleaved off and be released into blood and cerebrospinal fluid. Klotho regulates several cellular transporters. Klotho protein deficiency accelerates the appearance of age related disorders including neurodegeneration and muscle wasting and eventually leads to premature death. The main site of Klotho protein expression is the kidney. Klotho protein is also appreciably expressed in other tissues including chorioid plexus. The present study explored the effect of Klotho protein on the creatine transporter CreaT (Slc6A8, which participates in the maintenance of neuronal function and survival. Methods: To this end cRNA encoding Slc6A8 was injected into Xenopus oocytes with and without additional injection of cRNA encoding Klotho protein. Creatine transporter CreaT (Slc6A8 activity was estimated from creatine induced current determined by two-electrode voltage-clamp. Results: Coexpression of Klotho protein significantly increased creatine-induced current in Slc6A8 expressing Xenopus oocytes. Coexpression of Klotho protein delayed the decline of creatine induced current following inhibition of carrier insertion into the cell membrane by brefeldin A (5 µM. The increase of creatine induced current by coexpression of Klotho protein in Slc6A8 expressing Xenopus oocytes was reversed by β-glucuronidase inhibitor (DSAL. Similarly, treatment of Slc6A8 expressing Xenopus oocytes with recombinant human alpha Klotho protein significantly increased creatine induced current. Conclusion: Klotho protein up-regulates the activity of creatine transporter CreaT (Slc6A8 by stabilizing the carrier protein in the cell membrane, an effect requiring β-glucuronidase activity of Klotho protein.

  17. Upregulation of the creatine transporter Slc6A8 by Klotho.

    Science.gov (United States)

    Almilaji, Ahmad; Sopjani, Mentor; Elvira, Bernat; Borras, José; Dërmaku-Sopjani, Miribane; Munoz, Carlos; Warsi, Jamshed; Lang, Undine E; Lang, Florian

    2014-01-01

    The transmembrane Klotho protein contributes to inhibition of 1,25(OH)2D3 formation. The extracellular domain of Klotho protein could function as an enzyme with e.g. β-glucuronidase activity, be cleaved off and be released into blood and cerebrospinal fluid. Klotho regulates several cellular transporters. Klotho protein deficiency accelerates the appearance of age related disorders including neurodegeneration and muscle wasting and eventually leads to premature death. The main site of Klotho protein expression is the kidney. Klotho protein is also appreciably expressed in other tissues including chorioid plexus. The present study explored the effect of Klotho protein on the creatine transporter CreaT (Slc6A8), which participates in the maintenance of neuronal function and survival. To this end cRNA encoding Slc6A8 was injected into Xenopus oocytes with and without additional injection of cRNA encoding Klotho protein. Creatine transporter CreaT (Slc6A8) activity was estimated from creatine induced current determined by two-electrode voltage-clamp. Coexpression of Klotho protein significantly increased creatine-induced current in Slc6A8 expressing Xenopus oocytes. Coexpression of Klotho protein delayed the decline of creatine induced current following inhibition of carrier insertion into the cell membrane by brefeldin A (5 µM). The increase of creatine induced current by coexpression of Klotho protein in Slc6A8 expressing Xenopus oocytes was reversed by β-glucuronidase inhibitor (DSAL). Similarly, treatment of Slc6A8 expressing Xenopus oocytes with recombinant human alpha Klotho protein significantly increased creatine induced current. Klotho protein up-regulates the activity of creatine transporter CreaT (Slc6A8) by stabilizing the carrier protein in the cell membrane, an effect requiring β-glucuronidase activity of Klotho protein.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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 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.

  20. Interactions of Aging, Overload, and Creatine Supplementation in Rat Plantaris Muscle

    Directory of Open Access Journals (Sweden)

    Mark D. Schuenke

    2011-01-01

    Full Text Available Attenuation of age-related sarcopenia by creatine supplementation has been equivocal. In this study, plantaris muscles of young (Y; 5m and aging (A; 24m Fisher 344 rats underwent four weeks of either control (C, creatine supplementation (Cr, surgical overload (O, or overload plus creatine (OCr. Creatine alone had no effect on muscle fiber cross-sectional area (CSA or heat shock protein (HSP70 and increased myonuclear domain (MND only in young rats. Overload increased CSA and HSP70 content in I and IIA fibers, regardless of age, and MND in IIA fibers of YO rats. CSA and MND increased in all fast fibers of YOCr, and CSA increased in I and IIA fibers of AOCr. OCR did not alter HSP70, regardless of age. MND did not change in aging rats, regardless of treatment. These data indicate creatine alone had no significant effect. Creatine with overload produced no additional hypertrophy relative to overload alone and attenuated overload-induced HSP70 expression.

  1. Caffeine and Creatine Content of Dietary Supplements Consumed by Brazilian Soccer Players.

    Science.gov (United States)

    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 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.

  2. Proton transfer pathways, energy landscape, and kinetics in creatine-water systems.

    Science.gov (United States)

    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.

  3. Caffeine and Progression of Parkinson Disease: A Deleterious Interaction With Creatine.

    Science.gov (United States)

    Simon, David K; Wu, Cai; Tilley, Barbara C; Wills, Anne-Marie; Aminoff, Michael J; Bainbridge, Jacquelyn; Hauser, Robert A; Schneider, Jay S; Sharma, Saloni; Singer, Carlos; Tanner, Caroline M; Truong, Daniel; Wong, Pei Shieen

    2015-01-01

    Increased caffeine intake is associated with a lower risk of Parkinson disease (PD) and is neuroprotective in mouse models of PD. However, in a previous study, an exploratory analysis suggested that, in patients taking creatine, caffeine intake was associated with a faster rate of progression. In the current study, we investigated the association of caffeine with the rate of progression of PD and the interaction of this association with creatine intake. Data were analyzed from a large phase 3 placebo-controlled clinical study of creatine as a potentially disease-modifying agent in PD. Subjects were recruited for this study from 45 movement disorders centers across the United States and Canada. A total of 1741 subjects with PD participated in the primary clinical study, and caffeine intake data were available for 1549 of these subjects. The association of caffeine intake with rate of progression of PD as measured by the change in the total Unified Parkinson Disease Rating Scale score and the interaction of this association with creatine intake were assessed. Caffeine intake was not associated with the rate of progression of PD in the main analysis, but higher caffeine intake was associated with significantly faster progression among subjects taking creatine. This is the largest and longest study conducted to date that addresses the association of caffeine with the rate of progression of PD. These data indicate a potentially deleterious interaction between caffeine and creatine with respect to the rate of progression of PD.

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

    Science.gov (United States)

    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.

  5. X-linked creatine transporter deficiency: clinical description of a patient with a novel SLC6A8 gene mutation.

    Science.gov (United States)

    Schiaffino, Maria C; Bellini, Carlo; Costabello, Laura; Caruso, Ubaldo; Jakobs, Cornelis; Salomons, Gajja S; Bonioli, Eugenio

    2005-09-01

    Creatine transporter deficiency is an X-linked disorder characterized by mental retardation and language delay. The authors report a patient affected by creatine transport deficiency caused by a novel mutation in the SLC6A8 gene. Impairment in social interaction represents a consistent clinical finding in the few cases described to date and may be a diagnostic clue for creatine transporter deficiency in males affected by mental retardation, seizures, and language impairment.

  6. Effects of Coffee and Caffeine Anhydrous Intake During Creatine Loading.

    Science.gov (United States)

    Trexler, Eric T; Smith-Ryan, Abbie E; Roelofs, Erica J; Hirsch, Katie R; Persky, Adam M; Mock, Meredith G

    2016-05-01

    The purpose of this study was to determine the effect of 5 days of creatine (CRE) loading alone or in combination with caffeine anhydrous (CAF) or coffee (COF) on upper-body and lower-body strength and sprint performance. Physically active males (n = 54; mean ± SD; age = 20.1 ± 2.1 years; weight = 78.8 ± 8.8 kg) completed baseline testing, consisting of 1 repetition maximum (1RM) and repetitions to fatigue with 80% 1RM for bench press and leg press, followed by a repeated sprint test of five, 10-second sprints separated by 60-second rest on a cycle ergometer to determine peak power (PP) and total power (TP). At least 72 hours later, subjects were randomly assigned to supplement with CRE (5 g of CRE monohydrate, 4 times per day; n = 14), CRE + CAF (CRE +300 mg·d of CAF; n = 13), CRE + COF (CRE +8.9 g of COF, yielding 303 mg of CAF; n = 13), or placebo (PLA; n = 14) for 5 days. Serum creatinine (CRN) was measured before and after supplementation, and on day 6, participants repeated pretesting procedures. Strength measures were improved in all groups (p ≤ 0.05), with no significant time × treatment interactions. No significant interaction or main effects were observed for PP. For TP, a time × sprint interaction was observed (p ≤ 0.05), with no significant interactions among treatment groups. A time × treatment interaction was observed for serum CRN values (p ≤ 0.05) that showed increases in all groups except PLA. Four subjects reported mild gastrointestinal discomfort with CRE + CAF, with no side effects reported in other groups. These findings suggest that neither CRE alone nor in combination with CAF or COF significantly affected performance compared with PLA.

  7. A novel SLC6A8 mutation associated with motor dysfunction in a child exhibiting creatine transporter deficiency.

    Science.gov (United States)

    Cervera-Acedo, Cristina; Lopez, Maria; Aguirre-Lamban, Jana; Santibañez, Paula; Garcia-Oguiza, Alberto; Poch-Olive, Maria Luisa; Dominguez-Garrido, Elena

    2015-01-01

    Creatine transporter (CT) deficiency is an X-linked disorder caused by mutations in the SLC6A8 gene. We describe a clinical, biochemical and molecular examination of a child with X-linked cerebral creatine deficiency. Increased urinary creatine/creatinine ratio, abnormal brain proton magnetic resonance spectroscopy and reduced creatine transport confirmed the clinical diagnosis. SLC6A8 analysis revealed a novel mutation that was hemizygous in the child and not detected in his mother. CT deficiency should be considered in children, especially males, with mental retardation.

  8. Creatine-induced activation of antioxidative defence in myotube cultures revealed by explorative NMR-based metabonomics and proteomics

    DEFF Research Database (Denmark)

    Young, Jette F; Larsen, Lotte B; Malmendal, Anders

    2010-01-01

    Creatine is a key intermediate in energy metabolism and supplementation of creatine has been used for increasing muscle mass, strength and endurance. Creatine supplementation has also been reported to trigger the skeletal muscle expression of insulin like growth factor I, to increase the fat......-free mass and improve cognition in elderly, and more explorative approaches like transcriptomics has revealed additional information. The aim of the present study was to reveal additional insight into the biochemical effects of creatine supplementation at the protein and metabolite level by integrating...... to an increased exercise performance mediated by increased ability to cope with training-induced increases in oxidative stress....

  9. Influence of creatine supplementation on indicators of glucose metabolism in skeletal muscle of exercised rats

    Directory of Open Access Journals (Sweden)

    Michel Barbosa de Araújo

    2013-12-01

    Full Text Available The purpose of this study was to evaluate the effect of creatine supplementation in the diet on indicators of glucose metabolism in skeletal muscle of exercised rats. Forty Wistar adult rats were distributed into four groups for eight weeks: 1 Control: sedentary rats that received balanced diet; 2 Creatine control: sedentary rats that received supplementation of 2% creatine in the balanced diet; 3 Trained: rats that ran on a treadmill at the Maximal Lactate Steady State and received balanced diet; and 4 Supplemented-trained: rats that ran on a treadmill at the Maximal Lactate Steady State and received creatine supplementation (2% in the balanced diet. The hydric intake increased and the body weight gain decreased in the supplemented-trained group. In the soleus muscle, the glucose oxidation increased in both supplemented groups. The production of lactate and glycemia during glucose tolerance test decreased in the supplemented-trained group. Creatine supplementation in conjunction with exercise training improved muscular glycidic metabolism of rats.

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

    Directory of Open Access Journals (Sweden)

    Neha Qasim

    Full Text Available 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

  11. Dietary creatine supplementation and exercise performance: why inconsistent results?

    Science.gov (United States)

    Lemon, Peter W R

    2002-12-01

    Over the past few years there has been considerable interest in both the use of creatine (Cr) supplementation by athletes and the documentation of its effects by scientists. Some believe that this nitrogen-containing compound found in meat and fish has a performance-enhancing capability as important for brief intense exercise efforts as dietary carbohydrate is for activities where glycogen supplies limit performance. The mechanisms thought to be responsible for any ergogenic effect of acute (few d) Cr supplementation include: increased stores of muscle phosphocreatine (PCr), faster regeneration of PCr during exercise recovery, enhanced adenosine triphosphate (ATP) production from glycolysis secondary to increased hydrogen ion buffering, and/or possible shortened post contraction muscle relaxation time. With chronic (wk mo) supplementation when combined with strength training, Cr may alter muscle protein metabolism directly (via decreasing protein breakdown or increasing synthesis) and/or indirectly as a result of a greater training load made possible by its acute ergogenic effects on strength and power. Cr supplementation is not banned by the International Olympic Committee and, with the exception of a small increase in body mass (approximately 1 kg) over the initial 36 d, does not appear to have any adverse side effects, at least with short-term use. Few scientific data are available for more prolonged use (mo or y) but considering the large numbers of athletes using Cr over the past 6+ y and the absence of reported problems, it may be that the often discussed somewhat nebulous long term adverse effects are presently being overestimated. Intakes of 285-300 mg Cr/kg body mass 1 over 36 d or 3050 mg/kg body mass 1 over approximately 4 wk are sufficient to produce benefits (muscle mass and high intensity power gains); however, not all study results are consistent. The focus of this review is to outline some possible explanations for the inconsistent observations

  12. N-acetyl-aspartate, total creatine, and myo-inositol in the epileptogenic human hippocampus.

    Science.gov (United States)

    Petroff, Ognen A C; Errante, Laura D; Kim, Jung H; Spencer, Dennis D

    2003-05-27

    Mesial temporal lobe epilepsy (mTLE) is characterized by hippocampal atrophy, decreased N-acetyl-aspartate, and a low N-acetyl-aspartate/total creatine ratio, often attributed to neuron loss and gliosis. Qualitative studies reported that N-acetyl-aspartate content was significantly lower in hippocampal sclerosis. It was proposed to measure the effects of neuron loss and gliosis on the hippocampal content of N-acetyl-aspartate, total creatine, and myo-inositol in mTLE. Twenty hippocampal specimens were obtained during temporal lobectomy and frozen quickly. Perchloric acid extracts of the small metabolites were prepared and analyzed by proton MRS at 11.75 T. Adjacent samples were used for cell counts. There were no significant associations between hippocampal neuron loss and the cellular content of N-acetyl-aspartate, total creatine, or myo-inositol, despite more than a threefold difference in neuron loss and a twofold increase in glial density. Metabolite concentrations varied two- to fourfold. Variation in the cellular content of total creatine accounted for more than three-quarters of the rank-order variance of the N-acetyl-aspartate concentrations. There were no associations between myo-inositol and N-acetyl-aspartate or total creatine. Overall, mean N-acetyl-aspartate levels were below those reported by in vivo MRS studies of control subjects. These data suggest that decreased N-acetyl-aspartate in mesial temporal lobe epilepsy reflects altered mitochondrial metabolism, not merely neuron loss or gliosis. It is hypothesized that the altered N-acetyl-aspartate and creatine metabolism could reflect mitochondrial dysfunction or proliferation of immature glial cells that could contribute to the epileptogenic state.

  13. Raman spectroscopic approach to monitor the in vitro cyclization of creatine → creatinine

    Science.gov (United States)

    Gangopadhyay, Debraj; Sharma, Poornima; Singh, Sachin Kumar; Singh, Pushkar; Tarcea, Nicolae; Deckert, Volker; Popp, Jürgen; Singh, Ranjan K.

    2015-01-01

    The creatine → creatinine cyclization, an important metabolic phenomenon has been initiated in vitro at acidic pH and studied through Raman spectroscopic and DFT approach. The equilibrium composition of neutral, zwitterionic and protonated microspecies of creatine has been monitored with time as the reaction proceeds. Time series Raman spectra show clear signature of creatinine formation at pH 3 after ∼240 min at room temperature and reaction is faster at higher temperature. The spectra at pH 1 and pH 5 do not show such signature up to 270 min implying faster reaction rate at pH 3.

  14. Umbrella sampling of proton transfer in a creatine-water system

    Science.gov (United States)

    Ivchenko, Olga; Bachert, Peter; Imhof, Petra

    2014-04-01

    Proton transfer reactions are among the most common processes in chemistry and biology. Proton transfer between creatine and surrounding solvent water is underlying the chemical exchange saturation transfer used as a contrast in magnetic resonance imaging. The free energy barrier, determined by first-principles umbrella sampling simulations (EaDFT 3 kcal/mol) is in the same order of magnitude as the experimentally obtained activation energy. The underlying mechanism is a first proton transfer from the guanidinium group to the water pool, followed by a second transition where a proton is "transferred back" from the nearest water molecule to the deprotonated nitrogen atom of creatine.

  15. Identification, characterization and cloning of SLC6A8C, a novel splice variant of the creatine transporter gene

    NARCIS (Netherlands)

    Martinez-Munoz, C.; Rosenberg, E.H.; Jakobs, C.A.J.M.; Salomons, G.S.

    2008-01-01

    SLC6A8 deficiency is caused by mutations in the X-linked creatine transporter gene (SLC6A8), which leads to cerebral creatine deficiency, mental retardation, speech and language delay, autistic-like behaviour and epilepsy. Insight in the mechanism of how the transporter is regulated is largely

  16. Muscle phosphorylase kinase deficiency

    DEFF Research Database (Denmark)

    Preisler, N; Orngreen, M C; Echaniz-Laguna, A

    2012-01-01

    To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD).......To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD)....

  17. The Effect of Direct Current Transthoracic Countershock on Human Myocardial Cells Evidenced by Creatine Kinase and Lactic Dehydrogenase Isoenzymes.

    Science.gov (United States)

    1986-05-01

    antiarrhythmic drug , in an attempt to prevent further postshock reversion episodes. The above standardized countershock protocol had been established by the...rhythm. These patients received one gram of intravenous procainamide, an antiarrhythmic agent, prior to a third iv countershock 4 hours later. This...DC-countershock. Oral anti- coagulant therapy was initiated on all patients 3 weeks prior to conversion. Quinidine, an antiarrhyth- mic drug , was begun

  18. The association between serum creatine kinase, mood and psychosis in inpatients with schizophrenia, bipolar and schizoaffective disorders.

    Science.gov (United States)

    Hollander, Sarah; Hochman, Eldar; Shoval, Gal; Taler, Michal; Trommer, Sharon; Hermesh, Haggai; Weizman, Abraham; Krivoy, Amir

    2016-04-30

    Previous studies demonstrated levels of serum CK (sCK) in the majority of patients undergoing acute psychosis. Records of 1054 patients hospitalized in Geha Mental Health Center during the study period were analyzed. Of them, 743 have been diagnosed with schizophrenia (Sz), 170 with schizoaffective disorder (SzA), and 158 with bipolar disorder (BP-I). Baseline sCK and PANSS values were obtained from each patient upon admission. Our results show that LnsCK is higher in patients with BP-I in comparison with patients with SZ, but not significantly different compared to patients with SzA. A multivariate analysis using linear regression model in which LnsCK was predicted by factors such as PANSS-total and sub-scores, IM injection, BMI, gender, and age among patients at each admission, revealed that PANSS-depression was inversely associated with LnsCK level in SzA and BP-I and not in SZ. A positive association was found between PANSS-total and sCK in SzA and BP-I; however, PANSS-positive scores correlated with sCK only in SzA. After controlling for confounders, it seems that sCK level is associated with the both affective and psychotic components. Serum CK may serve as a biomarker for affective exacerbation rather than psychosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Acute Changes in Creatine Kinase Serum Levels in Adults Submitted a Static Stretching and Maximal Strength Test

    Directory of Open Access Journals (Sweden)

    M.G. Bara Filho

    2008-01-01

    Full Text Available Strength and flexibility are common components of a training program and their maximal values are obtained through specific tests. However, little information about the damage effect of these training procedures in a skeletal muscle is known. Objective: To verify a serum CK changes 24 h after a sub maximal stretching routine and after the static flexibility and maximal strength tests. Methods: the sample was composed by 14 subjects (man and women, 28 ± 6 yr. physical education students. The volunteers were divided in a control group (CG and experimental group (EG that was submitted in a stretching routine (EG-ST, in a maximal flexibility static test (EG-FLEX and in 1-RM test (EG-1-RM, with one week interval among tests. The anthropometrics characteristics were obtained by digital scale with stadiometer (Filizola, São Paulo, Brasil, 2002. The blood samples were obtained using the IFCC method with reference values 26-155 U/L. The De Lorme and Watkins technique was used to access maximal maximal strength through bench press and leg press. The maximal flexibility test consisted in three 20 seconds sets until the point of maximal discomfort. The stretching was done in normal movement amplitude during 6 secons. Results: The basal and post 24 h CK values in CG and EG (ST; Flex and 1 RM were respectively 195,0 ± 129,5 vs. 202,1 ± 124,2; 213,3 ± 133,2 vs. 174,7 ± 115,8; 213,3 ± 133,2 vs. 226,6 ± 126,7 e 213,3 ± 133,2 vs. 275,9 ± 157,2. It was only observed a significant difference (p = 0,02 in the pre and post values inGE-1RM. Conclusion: only maximal strength dynamic exercise was capable to cause skeletal muscle damage.

  20. A model of mitochondrial creatine kinase binding to membranes: adsorption constants, essential amino acids and the effect of ionic strength

    DEFF Research Database (Denmark)

    Fedosov, Sergey; Belousova, Lubov; Plesner, Igor

    1993-01-01

    is is suggested as the main candidate to form the adsorption site of mitCK. Deprotonated octameric mitCK easily dissociated from the membrane (View the MathML source at ionic strength View the MathML source and 5°C); after protonation its affinity increased many times (View the MathML source). Determination...... on the enzyme adsorption. An analysis of our own data as well as of the data from the literature is consistent with the adsorption site of the octameric mitCK being composed of 4 amino acid residues with pK = 8.8 in the free enzyme. The pK value changes to 9.8 upon binding of the protein to the membrane. Lysine...

  1. Effect of creatine supplementation during the last week of gestation on birth intervals, stillbirth, and preweaning mortality in pigs.

    Science.gov (United States)

    Vallet, J L; Miles, J R; Rempel, L A

    2013-05-01

    We hypothesized that creatine supplementation would reduce birth intervals, stillbirth rate, and preweaning survival in pigs because of its reported improvement of athletic performance in humans. In Exp. 1, gilts (n = 42) and first parity sows (n = 75) were mated at estrus. Beginning on d 110 of gestation, dams received either no treatment or 20 g creatine daily until farrowing. At farrowing in November 2008, pigs were monitored by video camera to determine individual piglet birth intervals. On d 1, piglets were weighed, euthanized, and the cerebellum, brain stem, and spinal cord were collected from the largest and smallest piglets in each litter to measure myelin basic proteins, myelin cholesterol, glucocerebrosides, phosphatidylethanolamine, phosphatidylcholine, and sphingomyelin. Preweaning mortality of the remaining piglets was recorded, including whether a piglet had been overlayed by the dam. A second experiment was performed using gilts (n = 90), farrowing in July 2010, to test differential effects of creatine supplementation during hot, humid weather when dams typically have more difficulty farrowing. Once again, gilts were provided either no supplementation or 20 g creatine daily from d 110 to the day of farrowing. Gilts were video recorded during farrowing, piglets were weighed on d 1, and preweaning mortality (including overlays) was recorded. In Exp. 1, creatine supplementation had no effect on birth intervals or stillbirth rate. Creatine supplementation improved the amount of myelin lipids in brain regions of piglets, particularly the brain stem. Creatine supplementation also reduced overlays of low birth weight piglets from gilts but not second parity sows. Data from Exp. 2 were combined with gilt data from Exp. 1 to examine the effect of creatine, season, and their interaction. There were no effects of treatment or season on birth intervals, stillbirth rates, or overall preweaning mortality. Creatine treatment reduced the incidence of overlays in low

  2. Maternal serum atrial natriuretic peptide (ANP) and brain-type natriuretic peptide (BNP) levels in gestational diabetes mellitus.

    Science.gov (United States)

    Yuksel, Mehmet Aytac; Alici Davutoglu, Ebru; Temel Yuksel, Ilkbal; Kucur, Mine; Ekmekci, Hakan; Balci Ekmekci, Ozlem; Uludag, Sezin; Uludag, Seyfettin; Madazli, Riza

    2016-01-01

    The aim of the study is to evaluate maternal serum atrial natriuretic peptide (ANP) and brain-type natriuretic peptide (BNP) levels in patients with getational diabetes mellitus compared with a control group. We have measured maternal serum ANP and BNP levels in 35 otherwise healthy and 45 gestational diabetic women between gestational week 24 and 28 referred to our unit in a cross-sectional study. Independent samples t-test or the Mann-Whitney U-test was used for comparison of two groups where appropriate. Mean maternal serum homeostasis model assessment of insulin resistance (HOMA-IR), HbA1c, fasting glucose and insulin levels in gestational diabetes mellitus (GDM) group were significantly higher than the control group (p ANP and BNP levels of women with GDM were significantly lower than the control group (12.9 ± 9.9 versus 34.8 ± 16.9 pg/ml, p ANP and BNP levels were negatively correlated with insulin levels, HbA1c and HOMA-IR values (p ANP and BNP levels are significantly lower in patients with GDM. These biomarkers might be valuable in clinical setting for identifying high-risk women for developing diabetes during pregnancy.

  3. Molecular cloning and chromosomal assignment of the human brain-type phosphodiesterase I/nucleotide pyrophosphatase gene (PDNP2)

    Energy Technology Data Exchange (ETDEWEB)

    Kawagoe, Hiroyuki; Soma, Osamu; Goji, Junko [Kobe Univ. School of Medicine (Japan)] [and others

    1995-11-20

    Phosphodiesterase I/nucleotide pyrophosphatase is a widely expressed membrane-bound enzyme that cleaves diester bonds of a variety of substrates. We have cloned brain-type cDNA for this enzyme from rat brain and designated it PD-I{alpha}. In this study we have isolated cDNA and genomic DNA encoding human PD-I{alpha}. Human PD-I{alpha} cDNA, designated PDNP2 in HGMW nomenclature, has a 2589-nucleotide open reading frame encoding a polypeptide of 863 amino acids with a calculated M{sub r} of 99,034. Northern blot analysis revealed that human PD-I{alpha} transcript was present in brain, lung, placenta, and kidney. The database analysis showed that human PD-I{alpha} was identical with human autotaxin (ATX), a novel tumor motility-stimulating factor, except that human PD-I{alpha} lacks 156 nucleotides and 52 amino acids of human ATX. Human PD-I{alpha} and human ATX are likely to be alternative splicing products from the same gene. The 5{prime} region of the human PDNP2 gene contains four putative binding sites of transcription factor Sp1 without typical TATA or CAAT boxes, and there is a potential octamer binding motif in intron 2. From the results of fluorescence in situ hybridization, the human PDNP2 gene is located at chromosome 8q24.1. 17 refs., 3 figs.

  4. Predictors and outcomes of increases in creatine phosphokinase concentrations or rhabdomyolysis risk during statin treatment

    NARCIS (Netherlands)

    van Staa, Tjeerd P; Carr, Daniel F; O'Meara, Helen; McCann, Gerry; Pirmohamed, Munir

    AIM: The aim was to evaluate clinical risk factors associated with myotoxicity in statin users. METHODS: This was a cohort study of patients prescribed a statin in UK primary care practices contributing to the Clinical Practice Research Datalink. Outcomes of interest were creatine phosphokinase

  5. Phenotype and genotype in 101 males with X-linked creatine transporter deficiency

    NARCIS (Netherlands)

    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.

    2013-01-01

    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

  6. Creatine deficiency syndrome. A treatable myopathy due to arginine-glycine amidinotransferase (AGAT) deficiency

    NARCIS (Netherlands)

    Nouioua, S.; Cheillan, D.; Zaouidi, S.; Salomons, G.S.; Amedjout, N.; Kessaci, F.; Boulandour, N.; Hamadouche, T.; Tazir, M.

    2013-01-01

    We report two sisters, aged 11 and 6. years, with AGAT deficiency syndrome (OMIM 612718) which is the least common creatine deficiency syndrome. They were born full-term to consanguineous parents and had moderate developmental delay. Examination showed an important language delay, a progressive

  7. Effect of free creatine therapy on cisplatin-induced renal damage.

    Science.gov (United States)

    Genc, Gurkan; Okuyucu, Ali; Meydan, Bilge Can; Yavuz, Oguzhan; Nisbet, Ozlem; Hokelek, Murat; Bedir, Abdulkerim; Ozkaya, Ozan

    2014-08-01

    Abstract Cisplatin is one of the commonly used anticancer drugs and nephrotoxicity limits its use. The aim of this study is to investigate the possible protective effect of creatine supplementation on cisplatin-induced nephrotoxicity. Sixty male Sprague-Dawley rats were divided into three groups: Group I: Cisplatin (n=20) (7 mg/kg cisplatin intraperitoneal (i.p.) single dose), group II: Cisplatin+creatine monohydrate (n=20) (7 mg/kg cisplatin i.p. single dose and 300 mg/kg creatine p.o. daily for 30 days starting on first day of cisplatin injection), group III: Control group (n=20) (Serum physiologic, 2.5 mL/kg i.p.). Sacrifications were performed at first week and 30th day. Blood urea nitrogen (BUN) and serum creatinine levels, histopathological evaluation, mitochondrial deoxyribonucleic acid (mtDNA) common deletion rates, and body weights of rats were evaluated. A significant decrease in body weight, higher values of kidney function tests, histopathological scores, and mtDNA deletion ratios were observed in group I compared to control group at days 7 and 30 (pcreatine significantly reversed kidney functions and pathological findings, this improvement was not sufficient to reach normal control group's results at days 7 and 30. In conclusion, the present study demonstrates that creatine administration is a promising adjuvant protective drug for reducing nephrotoxic effect of cisplatin.

  8. STUDIES ON SERUM CREATINE PHOSPHOKINASE ISOENZYME SEVEN CASES OF TETRAPLEGIA IN THE DOG

    OpenAIRE

    Yasuda, Jun; TOO, Kimehiko

    1983-01-01

    Canine serum creatine phosphokinase isoenzymes were determined in seven cases of Spondylosis deformans. The BB fraction of CPK isoenzymes in these cases was superior to that of other fractions except in one case which was accompanied by traumatic muscular damages because of decubitus. The isoenzyme distribution patterns changed into MM fraction superiority as in normal dogs as motor dysfunction improved.

  9. Creatine Loading Does Not Preserve Muscle Mass or Strength During Leg Immobilization in Healthy, Young Males

    NARCIS (Netherlands)

    Backx, Evelien M.P.; Hangelbroek, Roland; Snijders, Tim; Verscheijden, Marie Louise; Verdijk, Lex B.; Groot, de Lisette C.P.G.M.; Loon, van Luc J.C.

    2017-01-01

    Background: A short period of leg immobilization leads to rapid loss of muscle mass and strength. Creatine supplementation has been shown to increase lean body mass in active individuals and can be used to augment gains in muscle mass and strength during prolonged resistance-type exercise

  10. Automated urinalysis technique determines concentration of creatine and creatinine by colorimetry

    Science.gov (United States)

    Rho, J. H.

    1967-01-01

    Continuous urinalysis technique is useful in the study of muscle wastage in primates. Creatinine concentration in urine is determined in an aliquot mixture by a color reaction. Creatine is determined in a second aliquot by converting it to creatinine and measuring the difference in color intensity between the two aliquots.

  11. A Pilot Study of Creatine as a Novel Treatment for Depression in Methamphetamine Using Females

    Science.gov (United States)

    Hellem, Tracy L.; Sung, Young-Hoon; Shi, Xian-Feng; Pett, Marjorie A.; Latendresse, Gwen; Morgan, Jubel; Huber, Rebekah S.; Kuykendall, Danielle; Lundberg, Kelly J.; Renshaw, Perry F.

    2015-01-01

    Objective Depression among methamphetamine users is more prevalent in females than males, but gender specific treatment options for this comorbidity have not been described. Reduced brain phosphocreatine levels have been shown to be lower in female methamphetamine users compared to males, and, of relevance, studies have demonstrated an association between treatment resistant depression and reduced brain phosphocreatine concentrations. The nutritional supplement creatine monohydrate has been reported to reduce symptoms of depression in female adolescents and adults taking antidepressants, as well as to increase brain phosphocreatine in healthy volunteers. Therefore, the purpose of this pilot study was to investigate creatine monohydrate as a treatment for depression in female methamphetamine users. Methods Fourteen females with depression and comorbid methamphetamine dependence were enrolled in an 8 week open label trial of 5 grams of daily creatine monohydrate and of these 14, eleven females completed the study. Depression was measured using the Hamilton Depression Rating Scale (HAMD) and brain phosphocreatine levels were measured using phosphorus magnetic resonance spectroscopy pre- and post-creatine treatment. Secondary outcome measures included anxiety symptoms, measured with the Beck Anxiety Inventory (BAI), as well as methamphetamine use, monitored by twice weekly urine drug screens and self-reported use. Results The results of a linear mixed effects repeated measures model showed significantly reduced HAMD and BAI scores as early as week 2 when compared to baseline scores. This improvement was maintained through study completion. Brain phosphocreatine concentrations were higher at the second phosphorus magnetic resonance spectroscopy scan compared to the baseline scan; Mbaseline = 0.223 (SD = 0.013) vs. Mpost-treatment = 0.233 (SD = 0.009), t(9) = 2.905, p methamphetamine positive urine drug screens of greater than 50% was observed by week 6. Finally

  12. Creatine as a Novel Treatment for Depression in Females Using Methamphetamine: A Pilot Study.

    Science.gov (United States)

    Hellem, Tracy L; Sung, Young-Hoon; Shi, Xian-Feng; Pett, Marjorie A; Latendresse, Gwen; Morgan, Jubel; Huber, Rebekah S; Kuykendall, Danielle; Lundberg, Kelly J; Renshaw, Perry F

    2015-01-01

    Depression among methamphetamine users is more prevalent in females than males, but gender-specific treatment options for this comorbidity have not been described. Reduced brain phosphocreatine levels have been shown to be lower in female methamphetamine users compared to males, and, of relevance, studies have demonstrated an association between treatment-resistant depression and reduced brain phosphocreatine concentrations. The nutritional supplement creatine monohydrate has been reported to reduce symptoms of depression in female adolescents and adults taking antidepressants, as well as to increase brain phosphocreatine in healthy volunteers. Therefore, the purpose of this pilot study was to investigate creatine monohydrate as a treatment for depression in female methamphetamine users. Fourteen females with depression and comorbid methamphetamine dependence were enrolled in an 8-week open label trial of 5 g of daily creatine monohydrate and of these 14, 11 females completed the study. Depression was measured using the Hamilton Depression Rating Scale (HAMD) and brain phosphocreatine levels were measured using phosphorus magnetic resonance spectroscopy pre- and post-creatine treatment. Secondary outcome measures included anxiety symptoms, measured with the Beck Anxiety Inventory (BAI), as well as methamphetamine use, monitored by twice weekly urine drug screens and self-reported use. The results of a linear mixed effects repeated measures model showed significantly reduced HAMD and BAI scores as early as week 2 when compared to baseline scores. This improvement was maintained through study completion. Brain phosphocreatine concentrations were higher at the second phosphorus magnetic resonance spectroscopy scan compared to the baseline scan; Mbaseline = 0.223 (SD = 0.013) vs. Mpost-treatment = 0.233 (SD = 0.009), t (9) = 2.905, p methamphetamine positive urine drug screens of greater than 50% was observed by week 6. Finally, creatine was well tolerated and adverse

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

    Science.gov (United States)

    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

  14. Role of Creatine Supplementation on Exercise-Induced Cardiovascular Function and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Michael I. C. Kingsley

    2009-01-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  16. Studying Kinetochore Kinases

    NARCIS (Netherlands)

    Saurin, Adrian T; Kops, Geert J P L

    2016-01-01

    Mitotic kinetochores are signaling network hubs that regulate chromosome movements, attachment error-correction, and the spindle assembly checkpoint. Key switches in these networks are kinases and phosphatases that enable rapid responses to changing conditions. Describing the mechanisms and dynamics

  17. Pyruvate kinase blood test

    Science.gov (United States)

    ... medlineplus.gov/ency/article/003357.htm Pyruvate kinase blood test To use the sharing features on this page, ... energy when oxygen levels are low. How the Test is Performed A blood sample is needed. In the laboratory, white blood ...

  18. Effects of Creatine Monohydrate Augmentation on Brain Metabolic and Network Outcome Measures in Women With Major Depressive Disorder.

    Science.gov (United States)

    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.

  19. International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine.

    Science.gov (United States)

    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).

  20. AGAT, GAMT and SLC6A8 distribution in the central nervous system, in relation to creatine deficiency syndromes: a review.

    Science.gov (United States)

    Braissant, O; Henry, H

    2008-04-01

    Creatine deficiency syndromes, either due to AGAT, GAMT or SLC6A8 deficiencies, lead to a complete absence, or a very strong decrease, of creatine within the brain, as measured by magnetic resonance spectroscopy. While the mammalian central nervous system (CNS) expresses AGAT, GAMT and SLC6A8, the lack of SLC6A8 in astrocytes around the blood-brain barrier limits the brain capacity to import creatine from the periphery, and suggests that the CNS has to rely mainly on endogenous creatine synthesis through AGAT and GAMT expression. This seems contradictory with SLC6A8 deficiency, which, despite AGAT and GAMT expression, also leads to creatine deficiency in the CNS. We present novel data showing that in cortical grey matter, AGAT and GAMT are expressed in a dissociated way: e.g. only a few cells co-express both genes. This suggests that to allow synthesis of creatine within the CNS, at least for a significant part of it, guanidinoacetate must be transported from AGAT- to GAMT-expressing cells, possibly through SLC6A8. This would explain the creatine deficiency observed in SLC6A8-deficient patients. By bringing together creatine deficiency syndromes, AGAT, GAMT and SLC6A8 distribution in CNS, as well as a synthetic view on creatine and guanidinoacetate levels in the brain, this review presents a comprehensive framework, including new hypotheses, on brain creatine metabolism and transport, both in normal conditions and in case of creatine deficiency.

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

    Science.gov (United States)

    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.

  2. A review of the biochemical, biotechnological and other applications ...

    African Journals Online (AJOL)

    ONOS

    2010-01-25

    Jan 25, 2010 ... creatine kinase (CK), an enzyme that occurs in the brain, heart and skeletal muscle. Appearance of the brain type .... inhibitory effect on LDH. Lactate dehydrogenase has isoenzymes. LDH can be ..... wheat α-amylase, is of importance in the brewing industry. The traditional use of yeasts (e.g. Saccharo-.

  3. The Creatine Transporter Gene Paralogous at 16p11.2 Is Expressed in Human Brain

    Directory of Open Access Journals (Sweden)

    Nadia Bayou

    2008-01-01

    We report on the clinical, cytogenetic, and molecular findings in a boy with autism carrying a de novo translocation t(7;16(p22.1;p11.2. The chromosome 16 breakpoint disrupts the paralogous SLC6A8 gene also called SLC6A10 or CT2. Predicted translation of exons and RT-PCR analysis reveal specific expression of the creatine transporter paralogous in testis and brain. Several studies reported on the role of X-linked creatine transporter mutations in individuals with mental retardation, with or without autism. The existence of disruption in SLC6A8 paralogous gene associated with idiopathic autism suggests that this gene may be involved in the autistic phenotype in our patient.

  4. Application of NMR-based metabonomics suggests a relationship between betaine absorption and elevated creatine plasma concentrations in catheterised sows

    DEFF Research Database (Denmark)

    Yde, Christian Clement; Westerhuis, Johan A.; Bertram, Hanne Christine S.

    2012-01-01

    of these metabolites from the small intestine. The LF diet resulted in a higher betaine concentration in the blood than the two high-fibre diets (P¼0·008). This leads to higher plasma concentrations of methionine (P¼0·0028) and creatine (P¼0·020) of endogenous origin. In conclusion, the use of NMR spectroscopy...... for measuring nutrient uptake in the present study elucidated the relationship between betaine uptake and elevated creatine plasma concentrations....

  5. Effects of acute creatine supplementation on iron homeostasis and uric acid-based antioxidant capacity of plasma after wingate test

    Directory of Open Access Journals (Sweden)

    Barros Marcelo P

    2012-06-01

    Full Text Available Abstract Background Dietary creatine has been largely used as an ergogenic aid to improve strength and athletic performance, especially in short-term and high energy-demanding anaerobic exercise. Recent findings have also suggested a possible antioxidant role for creatine in muscle tissues during exercise. Here we evaluate the effects of a 1-week regimen of 20 g/day creatine supplementation on the plasma antioxidant capacity, free and heme iron content, and uric acid and lipid peroxidation levels of young subjects (23.1 ± 5.8 years old immediately before and 5 and 60 min after the exhaustive Wingate test. Results Maximum anaerobic power was improved by acute creatine supplementation (10.5 %, but it was accompanied by a 2.4-fold increase in pro-oxidant free iron ions in the plasma. However, potential iron-driven oxidative insult was adequately counterbalanced by proportional increases in antioxidant ferric-reducing activity in plasma (FRAP, leading to unaltered lipid peroxidation levels. Interestingly, the FRAP index, found to be highly dependent on uric acid levels in the placebo group, also had an additional contribution from other circulating metabolites in creatine-fed subjects. Conclusions Our data suggest that acute creatine supplementation improved the anaerobic performance of athletes and limited short-term oxidative insults, since creatine-induced iron overload was efficiently circumvented by acquired FRAP capacity attributed to: overproduction of uric acid in energy-depleted muscles (as an end-product of purine metabolism and a powerful iron chelating agent and inherent antioxidant activity of creatine.

  6. The effect of combined supplementation of carbohydrates and creatine on anaerobic performance

    Directory of Open Access Journals (Sweden)

    AS Theodorou

    2017-02-01

    Full Text Available The purpose of the study was to examine the effect of creatine (Cr supplementation on anaerobic performance when ingesting creatine and carbohydrates (CHO together. Twenty male physical education students comprised the two experimental (CR and CRCHO and one control (CON groups of the study. All groups performed three 30 s anaerobic Wingate tests (AWTs interspersed with 6 minutes of recovery. The CR group (n = 7 ingested 5 g of Cr 5 times per day for 4 days. Subjects in the CRCHO group (n = 6 ingested the same quantity but additionally after each 5 g dose of Cr consumed 500 ml of a commercially available energy drink containing 100 g of simple sugars. Over all three AWTs average mean power improved significantly compared to baseline for the CR group (5.51% but not for the CRCHO group (3.06%. Mean power for the second AWT was improved following the acute loading for the CR group only (4.54% and for the third AWT for both CR (8.49% and CRCHO (5.75% groups. Over all three AWTs a significant change was recorded in average peak power following the acute loading for the CR group (8.26% but not for the CRCHO group (4.11%. Peak power was significantly improved following the loading only for the CR group during the third AWT (19.79%. No changes in AWT performance were recorded for the CON group after intervention. The findings of the present study suggest that ingesting creatine together with carbohydrates will not further improve performance compared to the ingestion of creatine only.

  7. Variability of Creatine Metabolism Genes in Children with Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Jessie M. Cameron

    2017-07-01

    Full Text Available 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

  8. Creatine prevents the imbalance of redox homeostasis caused by homocysteine in skeletal muscle of rats.

    Science.gov (United States)

    Kolling, Janaína; Scherer, Emilene B S; Siebert, Cassiana; Marques, Eduardo Peil; Dos Santos, Tiago Marcom; Wyse, Angela T S

    2014-07-15

    Homocystinuria is a neurometabolic disease caused by severe deficiency of cystathionine beta-synthase activity, resulting in severe hyperhomocysteinemia. Affected patients present several symptoms including a variable degree of motor dysfunction, being that the pathomechanism is not fully understood. In the present study we investigated the effect of chronic hyperhomocysteinemia on some parameters of oxidative stress, namely 2'7'dichlorofluorescein (DCFH) oxidation, levels of thiobarbituric acid-reactive substances (TBARS), antioxidant enzyme activities (SOD, CAT and GPx), reduced glutathione (GSH), total sulfhydryl and carbonyl content, as well as nitrite levels in soleus skeletal muscle of young rats subjected to model of severe hyperhomocysteinemia. We also evaluated the effect of creatine on biochemical alterations elicited by hyperhomocysteinemia. Wistar rats received daily subcutaneous injection of homocysteine (0.3-0.6 μmol/g body weight), and/or creatine (50mg/kg body weight) from their 6th to the 28th days age. Controls and treated rats were decapitated at 12h after the last injection. Chronic homocysteine administration increased 2'7'dichlorofluorescein (DCFH) oxidation, an index of production of reactive species and TBARS levels, an index of lipoperoxidation. Antioxidant enzyme activities, such as SOD and CAT were also increased, but GPx activity was not altered. The content of GSH, sulfhydril and carbonyl were decreased, as well as levels of nitrite. Creatine concurrent administration prevented some homocysteine effects probably by its antioxidant properties. Our data suggest that the oxidative insult elicited by chronic hyperhomocystenemia may provide insights into the mechanisms by which homocysteine exerts its effects on skeletal muscle function. Creatine prevents some alterations caused by homocysteine. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Effects of exercise intensity and creatine loading on post-resistance exercise hypotension

    Directory of Open Access Journals (Sweden)

    Moreno Rodrigues Moreno

    2009-01-01

    Postexercise hypotension plays an important role in the non-pharmacological treat-ment of hypertension and is characterized by a decrease in blood pressure after a single exercise bout in relation to pre-exercise levels. This study investigated the effects of exercise intensity and creatine monohydrate supplementation on postexercise hypotension, as well as the possible role of blood lactate in this response. Ten normotensive subjects underwent resistance exercise sessions before (BC and after (AC creatine supplementation: 1 muscle endurance (ME consisting of 30 repetitions at 30% of one-repetition maximum; 2 hypertrophy (HP consisting of 8 repetitions at 75% of one-repetition maximum. Blood pressure was measured before and after the exercise bout. Blood lactate was measured after the exercise bout. The HP and ME sessions promoted a decrease in systolic blood pressure (∆ -19 ± 1.0 mmHg; ∆ -15 ± 0.9 mmHg, respectively, P 0.05. In conclusion, resistance exercise intensity did not influence postexercise hypotension. Creatine supplementation attenuated the decrease in blood pressure after resistance exercise. The results suggest the involvement of blood lactate in post-resistance exercise hypotension.

  10. Effects of exercise intensity and creatine loading on post-resistance exercise hypotension

    Directory of Open Access Journals (Sweden)

    Moreno Rodrigues Moreno

    2009-09-01

    Full Text Available Postexercise hypotension plays an important role in the non-pharmacological treat-ment of hypertension and is characterized by a decrease in blood pressure after a single exercise bout in relation to pre-exercise levels. This study investigated the effects of exercise intensity and creatine monohydrate supplementation on postexercise hypotension, as well as the possible role of blood lactate in this response. Ten normotensive subjects underwent resistance exercise sessions before (BC and after (AC creatine supplementation: 1 muscle endurance (ME consisting of 30 repetitions at 30% of one-repetition maximum; 2 hypertrophy (HP consisting of 8 repetitions at 75% of one-repetition maximum. Blood pressure was measured before and after the exercise bout. Blood lactate was measured after the exercise bout. The HP and ME sessions promoted a decrease in systolic blood pressure (∆ -19 ± 1.0 mmHg; ∆ -15 ± 0.9 mmHg, respectively, P 0.05. In conclusion, resistance exercise intensity did not influence postexercise hypotension. Creatine supplementation attenuated the decrease in blood pressure after resistance exercise. The results suggest the involvement of blood lactate in post-resistance exercise hypotension.

  11. Is Long Term Creatine and Glutamine Supplementation Effective in Enhancing Physical Performance of Military Police Officers?

    Directory of Open Access Journals (Sweden)

    Lázaro da Silveira Celismar

    2014-12-01

    Full Text Available The objective of this study was to analyze the effect of supplementation with creatine and glutamine on physical fitness of military police officers. Therefore, an experimental double blind study was developed, with the final sample composed by 32 men randomly distributed into three groups: a group supplemented with creatine (n=10, glutamine (n=10 and a placebo group (n=12 and evaluated in three distinct moments, in an interval of three months (T1, T2 and T3. The physical training had a weekly frequency of 5 sessions x 90 min, including strength exercises, local muscular resistance, flexibility and both aerobic and anaerobic capacity. After analyzing the effect of time, group and interaction (group x time for measures that indicated the physical capabilities of the subjects, a significant effect of time for the entire variable was identified (p0,05. In face of the results it was concluded that supplementation with creatine and glutamine showed no ergogenic effect on physical performance in military police officers.

  12. Effect of water activity and temperature on the stability of creatine during storage.

    Science.gov (United States)

    Uzzan, Michael; Nechrebeki, Jacob; Zhou, Peng; Labuza, Theodore P

    2009-08-01

    Creatine degradation to creatinine, which has no biological activity, in combinations of glycerol and pH 4.0 buffer solutions followed first-order kinetics up to a point where degradation started to level off, generally beyond the first half-life. Practical data are reported for a wide range of water activity (a(w)) values (0.31-0.983) at 4 degrees C, 23 degrees C, and 35 degrees C. Creatine degradation did not exhibit a dilution effect, that is a decrease in rate about an a(w) of 0.7, as is found for both microbiological growth and chemical reactions in semisolid food matrix systems. The temperature dependence obeyed the Arrhenius relationship with an energy of activation of about 20 kcal/mol at a(w) >or= 0.68 increasing to 23 kcal/mole below that a(w). In addition, a semilog plot of half-life as a function of a(w) at each temperature follows a predicted straight line. The pH and assumed liquid viscosity increase through increased glycerol concentration were not able to completely explain the decrease in rate of degradation as a function of a(w). Furthermore, we confirmed that creatine stability in the crystal form is very high as long as it does not reach the deliquescence state.

  13. From Phosphosites to Kinases

    DEFF Research Database (Denmark)

    Munk, Stephanie; Refsgaard, Jan C; Olsen, Jesper V

    2016-01-01

    Kinases play a pivotal role in propagating the phosphorylation-mediated signaling networks in living cells. With the overwhelming quantities of phosphoproteomics data being generated, the number of identified phosphorylation sites (phosphosites) is ever increasing. Often, proteomics investigations...... sequence motifs, mostly based on large scale in vivo and in vitro experiments. The context of the kinase and the phosphorylated proteins in a biological system is equally important for predicting association between the enzymes and substrates, an aspect that is also being tackled with available...

  14. Effect of creatine monohydrate on clinical progression in patients with Parkinson disease: a randomized clinical trial.

    Science.gov (United States)

    Kieburtz, Karl; Tilley, Barbara C; Elm, Jordan J; Babcock, Debra; Hauser, Robert; Ross, G Webster; Augustine, Alicia H; Augustine, Erika U; Aminoff, Michael J; Bodis-Wollner, Ivan G; Boyd, James; Cambi, Franca; Chou, Kelvin; Christine, Chadwick W; Cines, Michelle; Dahodwala, Nabila; Derwent, Lorelei; Dewey, Richard B; Hawthorne, Katherine; Houghton, David J; Kamp, Cornelia; Leehey, Maureen; Lew, Mark F; Liang, Grace S Lin; Luo, Sheng T; Mari, Zoltan; Morgan, John C; Parashos, Sotirios; Pérez, Adriana; Petrovitch, Helen; Rajan, Suja; Reichwein, Sue; Roth, Jessie Tatsuno; Schneider, Jay S; Shannon, Kathleen M; Simon, David K; Simuni, Tanya; Singer, Carlos; Sudarsky, Lewis; Tanner, Caroline M; Umeh, Chizoba C; Williams, Karen; Wills, Anne-Marie

    2015-02-10

    There are no treatments available to slow or prevent the progression of Parkinson disease, despite its global prevalence and significant health care burden. The National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson Disease program was established to promote discovery of potential therapies. To determine whether creatine monohydrate was more effective than placebo in slowing long-term clinical decline in participants with Parkinson disease. The Long-term Study 1, a multicenter, double-blind, parallel-group, placebo-controlled, 1:1 randomized efficacy trial. Participants were recruited from 45 investigative sites in the United States and Canada and included 1741 men and women with early (within 5 years of diagnosis) and treated (receiving dopaminergic therapy) Parkinson disease. Participants were enrolled from March 2007 to May 2010 and followed up until September 2013. Participants were randomized to placebo or creatine (10 g/d) monohydrate for a minimum of 5 years (maximum follow-up, 8 years). The primary outcome measure was a difference in clinical decline from baseline to 5-year follow-up, compared between the 2 treatment groups using a global statistical test. Clinical status was defined by 5 outcome measures: Modified Rankin Scale, Symbol Digit Modalities Test, PDQ-39 Summary Index, Schwab and England Activities of Daily Living scale, and ambulatory capacity. All outcomes were coded such that higher scores indicated worse outcomes and were analyzed by a global statistical test. Higher summed ranks (range, 5-4775) indicate worse outcomes. The trial was terminated early for futility based on results of a planned interim analysis of participants enrolled at least 5 years prior to the date of the analysis (n = 955). The median follow-up time was 4 years. Of the 955 participants, the mean of the summed ranks for placebo was 2360 (95% CI, 2249-2470) and for creatine was 2414 (95% CI, 2304-2524). The global statistical test

  15. Musculus soleus of rats at physical activity and L-carnitine and creatine phosphate effect

    Directory of Open Access Journals (Sweden)

    Irina A. Khutorskaya

    2017-09-01

    Full Text Available Introduction: The study of the effect of metabolic drugs on the histochemical characteristics of soleus muscle is relevant for solving the problem of providing the training process in Russia with non-doping drugs for safe correction of the consequences of intense physical activity in athletes. Materials and Methods: Dynamic physical activity in rats (n = 24 was simulated by swimming “to the limit” with weighting of 10 % of body weight (20 days, 1 time per day. The experimental animals were divided into four groups (6 animals each: № 1 – control, № 2 – swimming + isotonic NaCl solution, № 3 and № 4 – swimming + L-carnitine or creatine phosphate 100.0 mg/kg daily intraperitoneally. The object of the study was musculus soleus. Differentiation of muscle fibers was carried out by the intensity of histochemical activity of succinate dehydrogenase (SDG and alkaline stable adenosine triphosphate (ATP of myosin. The percentage of muscle fibers was evaluated and their diameter was defined by the direct morphometry. The obtained data were treated statistically by Student’s T-test. Results: Swimming of the animals “to the limit” do not affect the ratio of fibers with different phenotypes in the soleus muscle. This indicator is genetically determined and was not modified by L-carnitine and creatine phosphate. Dynamic physical activity promotes the development of hypertrophy of muscle fibers of various types. The investigated medicaments of the metabolic type either do not influence on the formation of exerciseinduced hypertrophy (predominantly creatine phosphate or reduce the intensity of the hypertrophic process (predominantly L-carnitine under dynamic physical activity. Discussion and Conclusions: The obtained data indicate L-carnitine and creatine phosphate do not have an anabolic effect. Taking into account the relevant data on ability of L-carnitine and creatine phosphate to effectively correct a negative effects of intensive

  16. Creatine Supplementation Associated or Not with Strength Training upon Emotional and Cognitive Measures in Older Women: A Randomized Double-Blind Study

    Science.gov (United States)

    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 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

  17. 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

    OpenAIRE

    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...

  18. Creatine supplementation associated or not with strength training upon emotional and cognitive measures in older women: a randomized double-blind study.

    Directory of Open Access Journals (Sweden)

    Christiano Robles Rodrigues Alves

    Full Text Available To assess the effects of creatine supplementation, associated or not with strength training, upon emotional and cognitive measures in older woman.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.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.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

  19. Cognitive deficits and increases in creatine precursors in a brain-specific knockout of the creatine transporter gene Slc6a8.

    Science.gov (United States)

    Udobi, K C; Kokenge, A N; Hautman, E R; Ullio, G; Coene, J; Williams, M T; Vorhees, C V; Mabondzo, A; Skelton, M R

    2018-01-31

    Creatine transporter (CrT; SLC6A8) deficiency (CTD) is an X-linked disorder characterized by severe cognitive deficits, impairments in language and an absence of brain creatine (Cr). In a previous study, we generated floxed Slc6a8 (Slc6a8 flox ) mice to create ubiquitous Slc6a8 knockout (Slc6a8 -/y ) mice. Slc6a8 -/y mice lacked whole body Cr and exhibited cognitive deficits. While Slc6a8 -/y mice have a similar biochemical phenotype to CTD patients, they also showed a reduction in size and reductions in swim speed that may have contributed to the observed deficits. To address this, we created brain-specific Slc6a8 knockout (bKO) mice by crossing Slc6a8 flox mice with Nestin-cre mice. bKO mice had reduced cerebral Cr levels while maintaining normal Cr levels in peripheral tissue. Interestingly, brain concentrations of the Cr synthesis precursor guanidinoacetic acid were increased in bKO mice. bKO mice had longer latencies and path lengths in the Morris water maze, without reductions in swim speed. In accordance with data from Slc6a8 -/y mice, bKO mice showed deficits in novel object recognition as well as contextual and cued fear conditioning. bKO mice were also hyperactive, in contrast with data from the Slc6a8 -/y mice. The results show that the loss of cerebral Cr is responsible for the learning and memory deficits seen in ubiquitous Slc6a8 -/y mice. © 2018 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  20. Creatine transporter (SLC6A8 knock out mice display an increased capacity for in vitro creatine biosynthesis in skeletal muscle

    Directory of Open Access Journals (Sweden)

    Aaron Paul Russell

    2014-08-01

    Full Text Available The present study aimed to investigate whether skeletal muscle from whole body creatine transporter (CrT; SLC6A8 knockout mice (CrT-/y actually contained creatine (Cr and if so, whether this Cr could result from an up regulation of muscle Cr biosynthesis. Gastrocnemius muscle from CrT-/y and wild type (CrT+/y mice were analysed for ATP, Cr, Cr phosphate (CrP and total Cr (TCr content. Muscle protein and gene expression of the enzymes responsible for Cr biosynthesis L-arginine:glycine amidotransferase (AGAT and guanidinoacetate methyltransferase (GAMT were also determined as were the rates of in vitro Cr biosynthesis. CrT-/y mice muscle contained measurable (22.3 ± 4.3 mmol.kg-1 dry mass, but markedly reduced (P<0.05 TCr levels compared with CrT+/y mice (125.0 ± 3.3 mmol.kg-1 dry mass. AGAT gene and protein expression were higher (~3 fold; P<0.05 in CrT-/y mice muscle, however GAMT gene and protein expression remained unchanged. The in vitro rate of Cr biosynthesis was elevated 1.5 fold (P<0.05 in CrT-/y mice muscle. These data clearly demonstrate that in the absence of CrT protein, skeletal muscle has reduced, but not absent, levels of Cr. This presence of Cr was most likely due to an up regulation of muscle Cr biosynthesis as evidenced by an increased AGAT protein expression and in vitro Cr biosynthesis rates in CrT-/y mice. Of note, the up regulation of Cr biosynthesis in CrT-/y mice muscle was unable to fully restore Cr levels to that found in wild type muscle.

  1. 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

    Science.gov (United States)

    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

  2. JAK protein kinase inhibitors.

    Science.gov (United States)

    Thompson, James E

    2005-06-01

    In humans, the Janus protein tyrosine kinase family (JAKs) contains four members: JAK1, JAK2, JAK3 and TYK2. JAKs phosphorylate signal transducers and activators of transcription (STATs) simultaneously with other phosphorylations required for activation, and there are several cellular mechanisms in place to inhibit JAK/STAT signaling. That one might be able to modulate selected JAK/STAT-mediated cellular signals by inhibiting JAK kinase activity to effect a positive therapeutic outcome is a tantalizing prospect, as yet incompletely realized. While current data suggest no therapeutic use for JAK1 and TYK2 inhibition, JAK2 inhibition seems a promising but not definitively tested mechanism for treatment of leukemia. More promising, however, are data indicating a possible therapeutic use of JAK3 inhibition. The restriction of the JAK3-deficient phenotype to the hematopoietic system and the resulting profound immune suppression suggest that JAK3 could be a target for immunosuppressive therapies used to prevent organ transplant rejection.

  3. Tyrosine kinases in rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Kobayashi Akiko

    2011-08-01

    Full Text Available Abstract Rheumatoid arthritis (RA is an inflammatory, polyarticular joint disease. A number of cellular responses are involved in the pathogenesis of rheumatoid arthritis, including activation of inflammatory cells and cytokine expression. The cellular responses involved in each of these processes depends on the specific signaling pathways that are activated; many of which include protein tyrosine kinases. These pathways include the mitogen-activated protein kinase pathway, Janus kinases/signal transducers and activators transcription pathway, spleen tyrosine kinase signaling, and the nuclear factor κ-light-chain-enhancer of activated B cells pathway. Many drugs are in development to target tyrosine kinases for the treatment of RA. Based on the number of recently published studies, this manuscript reviews the role of tyrosine kinases in the pathogenesis of RA and the potential role of kinase inhibitors as new therapeutic strategies of RA.

  4. Effects of creatine supplementation on high-intensity intermittent exercise: discrepancies and methodological appraisals

    Directory of Open Access Journals (Sweden)

    Patrícia Chackur Brum

    2008-04-01

    Full Text Available After a brief review of the literature on the effects of creatine supplementation on high-intensity intermittent exercise performance, the main aim of this study was to discuss methodological differences between studies which could explain the discrepancies observed in the literature. The effects of creatine supplementation on high-intensity intermittent exercise performance have been investigated in depth. Although the results of much research demonstrates the effi cacy of this supplement, there is just as much evidence that does not support this ergogenic effect. The explanation for this divergence appears to be multifactorial, although it is always linked to methodological characteristics. Study design (crossover or parallel groups, individual variability of muscular creatine content, chronic high meat intake, sample size, exercise protocol characteristics (body weight dependence and time between series, and gender and age all differ between studies and are potentially the variables responsible, to differing extents, for the discrepancies observed in the literature. Studies involving young males, with parallel group design, adequate statistical power, control of the incorporation of creatine into muscles, food intake assessment and intermittent exercise protocols in which performance is independent of body weight and with rest-recovery intervals of 1 to 6 minutes, usually produce positive results. The many methodological factors which can contribute to divergence on the ergogenic effects of creatine should be considered in futures studies, as well as when prescribing creatine supplementation. Resumo Após breve revisão da literatura existente acerca dos efeitos da suplementação de creatina no rendimento em atividades intermitentes de alta intensidade, o objetivo principal dessa revisão foi discutir diferenças metodológicas dos estudos que possam explicar a divergência encontrada na literatura. Os efeitos da suplementação de creatina

  5. RNA sequencing of creatine transporter (SLC6A8) deficient fibroblasts reveals impairment of the extracellular matrix.

    Science.gov (United States)

    Nota, Benjamin; Ndika, Joseph D T; van de Kamp, Jiddeke M; Kanhai, Warsha A; van Dooren, Silvy J M; van de Wiel, Mark A; Pals, Gerard; Salomons, Gajja S

    2014-09-01

    Creatine transporter (SLC6A8) deficiency is the most common cause of cerebral creatine syndromes, and is characterized by depletion of creatine in the brain. Manifestations of this X-linked disorder include intellectual disability, speech/language impairment, behavior abnormalities, and seizures. At the moment, no effective treatment is available. In order to investigate the molecular pathophysiology of this disorder, we performed RNA sequencing on fibroblasts derived from patients. The transcriptomes of fibroblast cells from eight unrelated individuals with SLC6A8 deficiency and three wild-type controls were sequenced. SLC6A8 mutations with different effects on the protein product resulted in different gene expression profiles. Differential gene expression analysis followed by gene ontology term enrichment analysis revealed that especially the expression of genes encoding components of the extracellular matrix and cytoskeleton are altered in SLC6A8 deficiency, such as collagens, keratins, integrins, and cadherins. This suggests an important novel role for creatine in the structural development and maintenance of cells. It is likely that the (extracellular) structure of brain cells is also impaired in SLC6A8-deficient patients, and future studies are necessary to confirm this and to reveal the true functions of creatine in the brain. © 2014 WILEY PERIODICALS, INC.

  6. Creatine supplementation augments the increase in satellite cell and myonuclei number in human skeletal muscle induced by strength training

    DEFF Research Database (Denmark)

    Olsen, Steen; Aagaard, Per; Kadi, Fawzi

    2006-01-01

    The present study investigated the influence of creatine and protein supplementation on satellite cell frequency and number of myonuclei in human skeletal muscle during 16 weeks of heavy-resistance training. In a double-blinded design 32 healthy, male subjects (19-26 years) were assigned to stren......The present study investigated the influence of creatine and protein supplementation on satellite cell frequency and number of myonuclei in human skeletal muscle during 16 weeks of heavy-resistance training. In a double-blinded design 32 healthy, male subjects (19-26 years) were assigned...... to strength training (STR) while receiving a timed intake of creatine (STR-CRE) (n=9), protein (STR-PRO) (n=8) or placebo (STR-CON) (n=8), or serving as a non-training control group (CON) (n=7). Supplementation was given daily (STR-CRE: 6-24 g creatine monohydrate, STR-PRO: 20 g protein, STR-CON: placebo...... histochemical analysis. All training regimes were found to increase the proportion of satellite cells, but significantly greater enhancements were observed with creatine supplementation at week 4 (compared to STR-CON) and at week 8 (compared to STR-PRO and STR-CON) (P

  7. Effects of plyometric training and creatine supplementation on maximal-intensity exercise and endurance in female soccer players.

    Science.gov (United States)

    Ramírez-Campillo, Rodrigo; González-Jurado, José Antonio; Martínez, Cristian; Nakamura, Fábio Yuzo; Peñailillo, Luis; Meylan, Cesar M P; Caniuqueo, Alexis; Cañas-Jamet, Rodrigo; Moran, Jason; Alonso-Martínez, Alicia M; Izquierdo, Mikel

    2016-08-01

    To investigate the effects of a six-week plyometric training and creatine supplementation intervention on maximal-intensity and endurance performance in female soccer players during in-season training. Randomized, double-blind, placebo-controlled trial. Young (age 22.9±2.5y) female players with similar training load and competitive background were assigned to a plyometric training group receiving placebo (PLACEBO, n=10), a plyometric training group receiving creatine supplementation (CREATINE, n=10) or a control group receiving placebo without following a plyometric program (CONTROL, n=10). Athletes were evaluated for jumping, maximal and repeated sprinting, endurance and change-of-direction speed performance before and after six weeks of training. After intervention the CONTROL group did not change, whereas both plyometric training groups improved jumps (ES=0.25-0.49), sprint (ES=0.35-0.41), repeated sprinting (ES=0.48-0.55), endurance (ES=0.32-0.34) and change-of-direction speed performance (ES=0.46-0.55). However, the CREATINE group improved more in the jumps and repeated sprinting performance tests than the CONTROL and the PLACEBO groups. Adaptations to plyometric training may be enhanced with creatine supplementation. Copyright © 2015 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  8. Utilization of glutamate/creatine ratios for proton spectroscopic diagnosis of meningiomas

    Energy Technology Data Exchange (ETDEWEB)

    Hazany, Saman [University of California, School of Medicine, San Diego, CA (United States); Hesselink, John R.; Healy, John F.; Imbesi, Steven G. [UCSD Medical Center, Department of Radiology, San Diego, CA (United States)

    2007-02-15

    Our purpose was to determine the potential of metabolites other than alanine to diagnose intracranial meningiomas on proton magnetic resonance spectroscopy (MRS). Using a 1.5-T MR system the lesions were initially identified on FLAIR, and T1- and T2-weighted images. Employing standard point-resolved spectroscopy (PRESS) for single voxel proton MRS (TR 1500 ms, TE 30 ms, 128 acquisitions, voxel size 2 x 2 x 2 cm, acquisition time 3.12 min), MR spectra were obtained from 5 patients with meningiomas, from 20 with other intracranial lesions, and from 4 normal controls. Peak heights of nine resonances, including lipid, lactate, alanine, NAA (N-acetylaspartate), {beta}/{gamma}-Glx (glutamate + glutamine), creatine, choline, myo-inositol, and {alpha}-Glx/glutathione, were measured in all spectra. The relative quantity of each metabolite was measured as the ratio of its peak height to the peak height of creatine. Relative quantities of {alpha}-Glx/glutathione, {beta}/{gamma}-Glx, and total Glx/glutathione were significantly elevated in meningiomas compared to the 20 other intracranial lesions and the normal control brains. Alanine was found in four of five meningiomas, but lactate partially masked the alanine in three meningiomas. None of the other lesions or control brains showed an alanine peak. The one meningioma with no alanine and the three others with lactate had elevated Glx. While alanine is a relatively unique marker for meningioma, our results support the hypothesis that the combination of glutamate/creatine ratios and alanine on proton MRS is more specific and reliable for the diagnosis of meningiomas than alanine alone. (orig.)

  9. A creatina como suplemento ergogênico para atletas Creatine as an ergogenic supplement for athletes

    Directory of Open Access Journals (Sweden)

    José PERALTA

    2002-01-01

    Full Text Available A creatina vem sendo muito pesquisada devido ao seu potencial efeito no rendimento físico de atletas envolvidos em exercícios de alta intensidade e curta duração, intermitentes e com curtos períodos de recuperação. A creatina fosforilada é uma reserva de energia nas células musculares. Durante um exercício intenso, a sua quebra libera energia é usada para regenerar o trifosfato de adenosina. Aproximadamente 95% do pool de creatina encontra-se na musculatura esquelética e sua regeneração após o exercício é um processo dependente de oxigênio. Estudos mostram que a suplementação com este composto pode aumentar o pool orgânico em 10 a 20%, e este percentual é maior em atletas vegetarianos (até 60%. Ainda existe controvérsia com relação aos benefícios e riscos da suplementação com esta substância. Este estudo revisa alguns dos aspectos relacionados com o metabolismo da creatina e seu uso como substância ergogênica na prática desportiva.Several researches on creatine have been done due to its potential effects on the physical performance of athletes involved in high intensity, short duration and intermittent exercises with short periods of recovery. Phosphorylated creatine is an energy reserve in the muscle cells. During an intense exercise, its breakdown liberates energy used to regenerate adenosine triphosphate. Approximately 95% of the creatine pool is found in the skeletal muscle, and the regenerating process after exercise is oxygen dependent. Studies show that supplementation with this compound may procedure an increase of 10% to 20% in the organic pool, and this percentage is higher in vegetarian athletes (up to 60%. There is still controversy regarding the benefits and risks of supplementation with this substance. This paper reviews some aspects related to the creatine metabolism and its use as an ergogenic substance in sports practice.

  10. Treatment of X-linked creatine transporter (SLC6A8) deficiency: systematic review of the literature and three new cases.

    Science.gov (United States)

    Dunbar, Mary; Jaggumantri, Sravan; Sargent, Michael; Stockler-Ipsiroglu, Sylvia; van Karnebeek, Clara D M

    2014-08-01

    Creatine transporter deficiency (CTD) is an X-linked inborn error of creatine metabolism characterized by reduced intra-cerebral creatine, developmental delay/intellectual disability, (ID), behavioral disturbance, seizures, and hypotonia in individuals harboring mutations in the SLC6A8 gene. Treatment for CTD includes supplementation with creatine, either alone or in combination with creatine precursors (arginine or glycine). Unlike other disorders of creatine metabolism, the efficacy of its treatment remains controversial. We present our systematic literature review (2001-2013) comprising 7 publications (case series/reports), collectively describing 25 patients who met the inclusion criteria, and 3 additional cases treated at our institution. Definitions were established and extracted data analyzed for cognitive ability, psychiatric and behavioral disturbances, epilepsy, and cerebral proton magnetic resonance spectroscopy measurements at pre- and post-treatment. Treatment regimens varied among the 28 cases: 2 patients received creatine-monohydrate supplementation; 7 patients received L-arginine; 2 patients received creatine-monohydrate and L-arginine; and 17 patients received a combination of creatine-monohydrate, L-arginine and glycine. Median treatment duration was 34.6 months (range 3 months-5 years). Level of evidence was IV. A total of 10 patients (36%) demonstrated response to treatment, manifested by either an increase in cerebral creatine, or improved clinical parameters. Seven of the 28 patients had quantified pre- and post-treatment creatine, and it was significantly increased post-treatment. All of the patients with increased cerebral creatine also experienced clinical improvement. In addition, the majority of patients with clinical improvement had detectable cerebral creatine prior to treatment. 90% of the patients who improved were initiated on treatment before nine years of age. Acknowledging the limitations of this systematic review, we conclude

  11. Regulation of Autophagy by Kinases

    Energy Technology Data Exchange (ETDEWEB)

    Sridharan, Savitha; Jain, Kirti; Basu, Alakananda, E-mail: alakananda.basu@unthsc.edu [Department of Molecular Biology and Immunology, Institute for Cancer Research, University of North Texas Health Science Center, Fort Worth, TX 76107 (United States)

    2011-06-09

    Autophagy is a process of self-degradation that maintains cellular viability during periods of metabolic stress. Although autophagy is considered a survival mechanism when faced with cellular stress, extensive autophagy can also lead to cell death. Aberrations in autophagy are associated with several diseases, including cancer. Therapeutic exploitation of this process requires a clear understanding of its regulation. Although the core molecular components involved in the execution of autophagy are well studied there is limited information on how cellular signaling pathways, particularly kinases, regulate this complex process. Protein kinases are integral to the autophagy process. Atg1, the first autophagy-related protein identified, is a serine/threonine kinase and it is regulated by another serine/threonine kinase mTOR. Emerging studies suggest the participation of many different kinases in regulating various components/steps of this catabolic process. This review focuses on the regulation of autophagy by several kinases with particular emphasis on serine/threonine protein kinases such as mTOR, AMP-activated protein kinase, Akt, mitogen-activated protein kinase (ERK, p38 and JNK) and protein kinase C that are often deregulated in cancer and are important therapeutic targets.

  12. Effects of creatine supplementation during resistance training on myosin heavy chain (MHC) expression in rat skeletal muscle fibers.

    Science.gov (United States)

    Aguiar, Andreo F; Aguiar, Danilo H; Felisberto, Alan D S; Carani, Fernanda R; Milanezi, Rachel C; Padovani, Carlos R; Dal-Pai-Silva, Maeli

    2010-01-01

    The purpose of this study was to utilize a rodent model to test the hypothesis that creatine (Cr) supplementation during resistance training would influence the pattern of slow-twitch muscle myosin heavy chain (MHC) isoforms expression. Male Wistar rats (2-3 months old, 250-300 g) were divided into 4 groups: Nontrained without creatine supplementation (CO), nontrained with creatine supplementation (CR), trained without creatine supplementation (TR), and trained with creatine supplementation (TRCR). TR and TRCR groups were submitted to a resistance training program for 5 weeks (5 days/week) for morphological and biochemical analysis of the soleus muscle. Weightlifting exercise involved jump sessions into water, carrying progressive overload equivalent to percentage of body weight. CR and TRCR groups were given creatine at 0.5 g/kg(-1)/d(-1). Both Cr supplementation and resistance training alone or associated did not result in significant alterations (p > 0.05) in body weight gain, food intake, and muscle weight in the CR, TR and TRCR groups compared to the CO group. Also compared to the CO group, the CR group showed a significant (p 0.05) changes in MHC content of the TRCR group compared to the CO group. The data show that Cr supplementation provides a potential action to abolish the exercise-induced MHC isoform transitions from slow to fast in slow-twitch muscle. Thus, Cr supplementation might be a suitable strategy to maintaining a slow phenotype in slow muscle during resistance training, which may be favorable to maintenance of muscle oxidative capacity of endurance athletes.

  13. Creatine Usage and Education of Track and Field Throwers at National Collegiate Athletic Association Division I Universities.

    Science.gov (United States)

    Judge, Lawrence W; Petersen, Jeffrey C; Craig, Bruce W; Hoover, Donald L; Holtzclaw, Kara A; Leitzelar, Brianna N; Tyner, Rebecca M R; Blake, Amy S; Hindawi, Omar S; Bellar, David M

    2015-07-01

    The purpose of this study was to analyze the level of creatine use along with the perceived benefits and barriers of creatine use among collegiate athletes who participate in throwing events within the sport of track and field. A total of 258 throwers from National Collegiate Athletic Association Division I institutions completed an online survey regarding creatine. The results provided baseline levels of creatine use and allowed for the analysis of factors related to athletic conference affiliation. Results indicate that creatine use remains to be a common (32.7%) practice among throwers with significantly higher levels of use among Football Bowl Subdivision (FBS) conference athletes (44.6%) than Football Championship Subdivision (FCS) conference athletes (28.8%), χ² = 5.505, p = 0.019. The most common reasons for using creatine included a desire to improve/increase: strength (83.3%), recovery time (69.0%), and performance (60.7%). The most common perceived obstacles included contamination/quality control (39.5%), cost (33.3%), inconvenience (16.7%), and cramping (14.3%). A desire for additional education and training was noted through an expression of interest (55.6%) with significantly higher levels of interest from FBS athletes (65.6%) than FCS athletes (52.2%), χ² = 6.425, p = 0.039. However, the athletic departments provide nutritional supplement counseling at only 26.6% of the schools. Although the access to full-time nutritionist counsel was available at 57.3% of the schools, there was a significant difference (χ² = 9.096, p = 0.003) between FBS schools (73.7%) and FCS schools (51.7%).

  14. Oral creatine supplementation on performance of Quarter Horses used in barrel racing.

    Science.gov (United States)

    Teixeira, F A; Araújo, A L; Ramalho, L O; Adamkosky, M S; Lacerda, T F; Coelho, C S

    2016-06-01

    The aim of this study was to evaluate the effects of oral creatine supplementation on the athletic performance of equines used for barrel racing. Ten healthy Quarter Horses, or Quarter Horse crossbred, weighing 429.7 ± 25.3 kg and with mean age of 3.8 ± 1.2 years, were used. Animals were evaluated in four different moments (M1, M2, M3, M4), and between M3 and M4, they were supplemented with 28 g of creatine/100 kg of body weight, orally, for 45 days. Although significant alterations for LDH activity, plasma glucose and packed cell volume were observed, it was possible to conclude that there was no improvement in the athletic performance for the animals used on the experiment, as there were no changes in time scores, heart rate and plasma lactate, variables considered as performance indicators, before and after supplementation. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

  15. In silico investigation of molecular effects caused by missense mutations in creatine transporter protein

    Science.gov (United States)

    Zhang, Zhe; Schwatz, Charles; Alexov, Emil

    2011-03-01

    Creatine transporter (CT) protein, which is encoded by SLC6A8 gene, is essential for taking up the creatine in the cell, which in turn plays a key role in the spatial and temporal maintenance of energy in skeletal and cardiac muscle cells. It was shown that some missense mutations in CT cause mental retardation, while others are harmless non-synonymous single nucleoside polymorphism (nsSNP). Currently fifteen missense mutations in CT are known, among which twelve are disease-causing. Sequence analysis reveals that there is no clear trend distinguishing disease-causing from harmless missense mutations. Because of that, we built 3D model of the CT using highly homologous template and use the model to investigate the effects of mutations of CT stability and hydrogen bond network. It is demonstrated that disease-causing mutations affect the folding free energy and ionization states of titratable group in much greater extend as compared with harmless mutations. Supported by grants from NLM, NIH, grant numbers 1R03LM009748 and 1R03LM009748-S1.

  16. Effect of creatine monohydrate supplementation on learning, memory and neuromuscular coordination in female albino mice.

    Science.gov (United States)

    Allahyar, Razia; Akbar, Atif; Iqbal, Furhan

    2017-02-01

    Research findings made over the last few years have highlighted the important role of creatine (Cr) in health and disease. However, limited information is available regarding the effect of Cr supplementation on cognation. Present study was designed to determine the effect of variable doses of Cr (1% and 3%) on selected parameters of female albino mice behaviour. Following weaning, on 20th postnatal day, female albino mice were divided into three groups on the basis of dietary supplementation. Control group were was fed with normal rodent diet, whereas treated groups received diet supplemented with 1% and 3% Creatine monohydrate (Ssniff, Germany) for 10 weeks. Morris water maze (MWM), Rota rod and open field (OF) tests were carried out at the end of diet supplementation for neurofunctional assessment in all the groups. Data analysis showed that Cr supplementation did not affect the muscular activity and during rota rod test as well as locomotor and exploratory behaviour during OF test. Results of MWM probe trial indicated that mice supplemented with 3% Cr had significantly more entries in platform area than other two treatments (p=0.03) indicating improved spatial memory. Body weight remained unaffected (p>0.05) when compared between three experimental treatments. Female mice supplemented with 3% Cr showed improved spatial memory than mice fed on 1% Cr-supplemented diet and mice on normal rodent diet.

  17. Bacterial Protein-Tyrosine Kinases

    DEFF Research Database (Denmark)

    Shi, Lei; Kobir, Ahasanul; Jers, Carsten

    2010-01-01

    enzymes that are unique in exploiting the ATP/GTP-binding Walker motif to catalyze phosphorylation of protein tyrosine residues. Characterized for the first time only a decade ago, BY-kinases have now come to the fore. Important regulatory roles have been linked with these enzymes, via their involvement......Bacteria and Eukarya share essentially the same family of protein-serine/threonine kinases, also known as the Hanks-type kinases. However, when it comes to protein-tyrosine phosphorylation, bacteria seem to have gone their own way. Bacterial protein-tyrosine kinases (BY-kinases) are bacterial...... in exopolysaccharide production, virulence, DNA metabolism, stress response and other key functions of the bacterial cell. BY-kinases act through autophosphorylation (mainly in exopolysaccharide production) and phosphorylation of other proteins, which have in most cases been shown to be activated by tyrosine...

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

    Science.gov (United States)

    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.

  19. The cellular and compartmental profile of mouse retinal glycolysis, tricarboxylic acid cycle, oxidative phosphorylation, and ~P transferring kinases.

    Science.gov (United States)

    Rueda, Elda M; Johnson, Jerry E; Giddabasappa, Anand; Swaroop, Anand; Brooks, Matthew J; Sigel, Irena; Chaney, Shawnta Y; Fox, Donald A

    2016-01-01

    The homeostatic regulation of cellular ATP is achieved by the coordinated activity of ATP utilization, synthesis, and buffering. Glucose is the major substrate for ATP synthesis through glycolysis and oxidative phosphorylation (OXPHOS), whereas intermediary metabolism through the tricarboxylic acid (TCA) cycle utilizes non-glucose-derived monocarboxylates, amino acids, and alpha ketoacids to support mitochondrial ATP and GTP synthesis. Cellular ATP is buffered by specialized equilibrium-driven high-energy phosphate (~P) transferring kinases. Our goals were twofold: 1) to characterize the gene expression, protein expression, and activity of key synthesizing and regulating enzymes of energy metabolism in the whole mouse retina, retinal compartments, and/or cells and 2) to provide an integrative analysis of the results related to function. mRNA expression data of energy-related genes were extracted from our whole retinal Affymetrix microarray data. Fixed-frozen retinas from adult C57BL/6N mice were used for immunohistochemistry, laser scanning confocal microscopy, and enzymatic histochemistry. The immunoreactivity levels of well-characterized antibodies, for all major retinal cells and their compartments, were obtained using our established semiquantitative confocal and imaging techniques. Quantitative cytochrome oxidase (COX) and lactate dehydrogenase (LDH) activity was determined histochemically. The Affymetrix data revealed varied gene expression patterns of the ATP synthesizing and regulating enzymes found in the muscle, liver, and brain. Confocal studies showed differential cellular and compartmental distribution of isozymes involved in glucose, glutamate, glutamine, lactate, and creatine metabolism. The pattern and intensity of the antibodies and of the COX and LDH activity showed the high capacity of photoreceptors for aerobic glycolysis and OXPHOS. Competition assays with pyruvate revealed that LDH-5 was localized in the photoreceptor inner segments. The

  20. A review of creatine supplementation in age-related diseases: more than a supplement for athletes [v1; ref status: indexed, http://f1000r.es/4ak

    OpenAIRE

    Rachel N. Smith; Agharkar, Amruta S.; Gonzales, Eric B.

    2014-01-01

    Creatine is an endogenous compound synthesized from arginine, glycine and methionine. This dietary supplement can be acquired from food sources such as meat and fish, along with athlete supplement powders. Since the majority of creatine is stored in skeletal muscle, dietary creatine supplementation has traditionally been important for athletes and bodybuilders to increase the power, strength, and mass of the skeletal muscle. However, new uses for creatine have emerged suggesting that it may b...

  1. Screening for primary creatine deficiencies in French patients with unexplained neurological symptoms

    Science.gov (United States)

    2012-01-01

    A population of patients with unexplained neurological symptoms from six major French university hospitals was screened over a 28-month period for primary creatine disorder (PCD). Urine guanidinoacetate (GAA) and creatine:creatinine ratios were measured in a cohort of 6,353 subjects to identify PCD patients and compile their clinical, 1H-MRS, biochemical and molecular data. Six GAMT [N-guanidinoacetatemethyltransferase (EC 2.1.1.2)] and 10 X-linked creatine transporter (SLC6A8) but no AGAT (GATM) [L-arginine/glycine amidinotransferase (EC 2.1.4.1)] deficient patients were identified in this manner. Three additional affected sibs were further identified after familial inquiry (1 brother with GAMT deficiency and 2 brothers with SLC6A8 deficiency in two different families). The prevalence of PCD in this population was 0.25% (0.09% and 0.16% for GAMT and SLC6A8 deficiencies, respectively). Seven new PCD-causing mutations were discovered (2 nonsense [c.577C > T and c.289C > T] and 1 splicing [c.391 + 15G > T] mutations for the GAMT gene and, 2 missense [c.1208C > A and c.926C > A], 1 frameshift [c.930delG] and 1 splicing [c.1393-1G > A] mutations for the SLC6A8 gene). No hot spot mutations were observed in these genes, as all the mutations were distributed throughout the entire gene sequences and were essentially patient/family specific. Approximately one fifth of the mutations of SLC6A8, but not GAMT, were attributed to neo-mutation, germinal or somatic mosaicism events. The only SLC6A8-deficient female patient in our series presented with the severe phenotype usually characterizing affected male patients, an observation in agreement with recent evidence that is in support of the fact that this X-linked disorder might be more frequent than expected in the female population with intellectual disability. PMID:23234264

  2. Effects of l-arginine and creatine administration on spatial memory in rats subjected to a chronic variable stress model.

    Science.gov (United States)

    dos Santos, Fabio Seidel; da Silva, Luiz Augusto; Pochapski, José Augusto; Raczenski, Alan; da Silva, Weber Claudio; Grassiolli, Sabrina; Malfatti, Carlos Ricardo Maneck

    2014-08-01

    Chronic stress results from repeated exposure to one or more types of stressors over a period, ranging from days to months, and can be associated with physical, behavioral, and neuropsychiatric manifestations. Some physiological alterations resulting from chronic stress can potentially cause deficits on spatial learning and memory. This study investigated the effects of chronic variable stress (CVS) and administration of l-arginine and creatine on spatial memory in rats. Furthermore, body, heart, adrenal weight, and plasma glucose and corticosterone levels were analyzed. Male Wistar rats were subjected to a CVS model for 40 days and evaluated for spatial memory after the stress period. Chronically stressed animals were treated daily by gavage with: 0.5% carboxymethylcellulose (Group Cs), 500 mg/kg l-arginine (Group Cs/La), 300 mg/kg creatine (Group Cs/Cr); and 500 mg/kg l-arginine and 300 mg/kg creatine (Group Cs/La + Cr) during the entire experimental period. Our results showed that animals in the Cs/Cr and Cs/La + Cr groups presented significantly decreased corticosterone levels compared to group Cs (p working memory task, compared to all other groups (p memory retention compared to controls (p working memory efficiency, and, when co-administrated with l-arginine, improves reference memory retention, a phenomenon that is possibly associated with increased creatine/phosphocreatine levels and l-arginine-derived NO synthesis.

  3. Variable White Matter Atrophy and Intellectual Development in a Family With X-linked Creatine Transporter Deficiency Despite Genotypic Homogeneity.

    Science.gov (United States)

    Heussinger, Nicole; Saake, Marc; Mennecke, Angelika; Dörr, Helmuth-Günther; Trollmann, Regina

    2017-02-01

    The X-linked creatine transporter deficiency (CRTD) caused by an SLC6A8 mutation represents the second most common cause of X-linked intellectual disability. The clinical phenotype ranges from mild to severe intellectual disability, epilepsy, short stature, poor language skills, and autism spectrum disorders. The objective of this study was to investigate phenotypic variability in the context of genotype, cerebral creatine concentration, and volumetric analysis in a family with CRTD. The clinical phenotype and manifestations of epilepsy were assessed in a Caucasian family with CRTD. DNA sequencing and creatine metabolism analysis confirmed the diagnosis. Cerebral magnetic resonance imaging (cMRI) with voxel-based morphometry and magnetic resonance spectroscopy was performed in all family members. An SLC6A8 missense mutation (c.1169C>T; p.Pro390Leu, exon 8) was detected in four of five individuals. Both male siblings were hemizygous, the mother and the affected sister heterozygous for the mutation. Structural cMRI was normal, whereas voxel-based morphometry analysis showed reduced white matter volume below the first percentile of the reference population of 290 subjects in the more severely affected boy compared with family members and controls. Normalized creatine concentration differed significantly between the individuals (P < 0.005). There is a broad phenotypic variability in CRTD even in family members with the same mutation. Differences in mental development could be related to atrophy of the subcortical white matter. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Functional characterization of missense variants in the creatine transporter gene (SLC6A8): improved diagnostic application.

    Science.gov (United States)

    Rosenberg, Efraim H; Martínez Muñoz, Cristina; Betsalel, Ofir T; van Dooren, Silvy J M; Fernandez, Matilde; Jakobs, Cornelis; deGrauw, Ton J; Kleefstra, Tjitske; Schwartz, Charles E; Salomons, Gajja S

    2007-09-01

    Creatine transporter deficiency is an X-linked mental retardation disorder caused by mutations in the creatine transporter gene (SLC6A8). So far, 20 mutations in the SLC6A8 gene have been described. We have developed a diagnostic assay to test creatine uptake in fibroblasts. Additionally, we expanded the assay to characterize novel SLC6A8 missense variants. A total of 13 variants were introduced in the SLC6A8 cDNA by site-directed mutagenesis. All variants were transiently transfected in SLC6A8-deficient fibroblasts and tested for restoration of creatine uptake in deficient primary fibroblasts. Thus, we proved that nine variants (p.Gly87Arg, p.Phe107del, p.Tyr317X, p.Asn336del, p.Cys337Trp, p.Ile347del, p.Pro390Leu, p.Arg391Trp, and p.Pro554Leu) are pathogenic mutations and four variants (p.Lys4Arg, p.Gly26Arg, p.Met560Val, and p.Val629Ile) are nonpathogenic. The present study provides an improved diagnostic tool to classify sequence variants of unknown significance. (c) 2007 Wiley-Liss, Inc.

  5. Functional and electrophysiological characterization of four non-truncating mutations responsible for creatine transporter (SLC6A8) deficiency syndrome

    NARCIS (Netherlands)

    Valayannopoulos, V.; Bakouh, N.; Mazzuca, M.; Nonnenmacher, L.; Hubert, L.; Makaci, F.L.; Chabli, A.; Salomons, G.S.; Mellot-Draznieks, C.; Brule, E.; de Lonlay, P.; Toulhoat, H.; Munnich, A.; Planelles, G.; de Keyzer, Y.

    2013-01-01

    Intellectual disability coupled with epilepsy are clinical hallmarks of the creatine (Cr) transporter deficiency syndrome resulting from mutations in the SLC6A8 gene. So far characterization of pathogenic mutations of SLC6A8 has been limited to Cr uptake. The aim of our study was to characterize the

  6. Skill execution and sleep deprivation: effects of acute caffeine or creatine supplementation - a randomized placebo-controlled trial

    Directory of Open Access Journals (Sweden)

    Kilduff Liam P

    2011-02-01

    Full Text Available Abstract Background We investigated the effects of sleep deprivation with or without acute supplementation of caffeine or creatine on the execution of a repeated rugby passing skill. Method Ten elite rugby players completed 10 trials on a simple rugby passing skill test (20 repeats per trial, following a period of familiarisation. The players had between 7-9 h sleep on 5 of these trials and between 3-5 h sleep (deprivation on the other 5. At a time of 1.5 h before each trial, they undertook administration of either: placebo tablets, 50 or 100 mg/kg creatine, 1 or 5 mg/kg caffeine. Saliva was collected before each trial and assayed for salivary free cortisol and testosterone. Results Sleep deprivation with placebo application resulted in a significant fall in skill performance accuracy on both the dominant and non-dominant passing sides (p Conclusion Acute sleep deprivation affects performance of a simple repeat skill in elite athletes and this was ameliorated by a single dose of either caffeine or creatine. Acute creatine use may help to alleviate decrements in skill performance in situations of sleep deprivation, such as transmeridian travel, and caffeine at low doses appears as efficacious as higher doses, at alleviating sleep deprivation deficits in athletes with a history of low caffeine use. Both options are without the side effects of higher dose caffeine use.

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

    Science.gov (United States)

    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.

  8. Creatine transporter deficiency: molecular and functional tools for diagnosis, and prevalence of this X-linked mental retardation syndrome

    NARCIS (Netherlands)

    Rosenberg, E.H.

    2006-01-01

    Van de verstandelijk gehandicapten is tweederde man. Lang niet altijd wordt voor de handicap een oorzaak gevonden. Uit het promotieonderzoek van Efraim Rosenberg blijkt in één procent van de gevallen een fout in het creatine transporter gen (SLC6A8) hiervoor verantwoordelijk. Patiënten met

  9. The biomechanic origin of sprint performance enhancement after one-week creatine supplementation.

    Science.gov (United States)

    Schedel, J M; Terrier, P; Schutz, Y

    2000-04-01

    In order to test whether an improvement of maximal sprinting speed after creatine (Cr) supplementation was due to the increase of stride frequency (SF), stride length (SL) or both, 7 subjects ran 4 consecutive sprints after 1 week of placebo or Cr supplementation. SF and SL were assessed by a triaxial accelerometer. Compared to the placebo, Cr induced an increase of running speed (+1.4% p < 0.05) and SF (+1.5%, p < 0.01), but not of SL. The drop in performance following repeated sprints was partially prevented by Cr. In conclusion, exogenous Cr enhanced sprinting performance by increasing SF. This result may be related to the recent findings of shortening in muscular relaxation time after Cr supplementation.

  10. The relationship between choline plus creatine- to-citrate ratio in magnetic resonance spectroscopy with the invasion of prostate cancer

    Directory of Open Access Journals (Sweden)

    M Ghafoori

    2012-12-01

    Full Text Available Background: Prostate cancer is the most common cancer and the second cause of cancer mortality in men. Although histopathological examination is the gold-standard for its diagnosis, tendency toward less invasive methods is growing. The purpose of this study was to evaluate the relationship between choline plus creatine- to-citrate ratio in magnetic resonance spectroscopy (MRS with the invasion of prostate cancer in a series of patients with prostate cancer.Methods: Totally, 200 patients with pathologically proven prostate cancer were enrolled in this cross-sectional study by a non-probability sampling method in Hazrat Rasul Akram Hospital in Tehran, Iran during 2009-2010. Pathological staging was the gold standard for the diagnosis of prostate cancer while the patients underwent MRS for choline plus creatine- to-citrate ratio determination. MRS and pathological results were compared and analyzed.Results: The mean (±SD values of choline plus creatine- to-citrate ratio in patients with Gleason scores less than 3, 3 to 4 and greater than 4 were 245.8±146.8, 427.1±173.6 and 427.1±173.6, respectively (P<0.001. The mean (±SD values of choline plus creatine- to-citrate ratio in patients with PSA levels less than 4, 4 to 10 and greater than 10 were 180.7±58.3, 247±93.5 and 385.1±106.6, respectively (P<0.001.Conclusion: Choline plus creatine- to-citrate ratio determined by magnetic resonance spectroscopy has a significant relationship with the degree of invasion of prostate cancer and can be used for the staging of the disease.

  11. Comprehensive Profiling of Amino Acid Response Uncovers Unique Methionine-Deprived Response Dependent on Intact Creatine Biosynthesis

    Science.gov (United States)

    Tang, Xiaohu; Keenan, Melissa M.; Wu, Jianli; Lin, Chih-An; Dubois, Laura; Thompson, J. Will; Freedland, Stephen J.; Murphy, Susan K.; Chi, Jen-Tsan

    2015-01-01

    Besides being building blocks for protein synthesis, amino acids serve a wide variety of cellular functions, including acting as metabolic intermediates for ATP generation and for redox homeostasis. Upon amino acid deprivation, free uncharged tRNAs trigger GCN2-ATF4 to mediate the well-characterized transcriptional amino acid response (AAR). However, it is not clear whether the deprivation of different individual amino acids triggers identical or distinct AARs. Here, we characterized the global transcriptional response upon deprivation of one amino acid at a time. With the exception of glycine, which was not required for the proliferation of MCF7 cells, we found that the deprivation of most amino acids triggered a shared transcriptional response that included the activation of ATF4, p53 and TXNIP. However, there was also significant heterogeneity among different individual AARs. The most dramatic transcriptional response was triggered by methionine deprivation, which activated an extensive and unique response in different cell types. We uncovered that the specific methionine-deprived transcriptional response required creatine biosynthesis. This dependency on creatine biosynthesis was caused by the consumption of S-Adenosyl-L-methionine (SAM) during creatine biosynthesis that helps to deplete SAM under methionine deprivation and reduces histone methylations. As such, the simultaneous deprivation of methionine and sources of creatine biosynthesis (either arginine or glycine) abolished the reduction of histone methylation and the methionine-specific transcriptional response. Arginine-derived ornithine was also required for the complete induction of the methionine-deprived specific gene response. Collectively, our data identify a previously unknown set of heterogeneous amino acid responses and reveal a distinct methionine-deprived transcriptional response that results from the crosstalk of arginine, glycine and methionine metabolism via arginine

  12. Skill execution and sleep deprivation: effects of acute caffeine or creatine supplementation - a randomized placebo-controlled trial.

    Science.gov (United States)

    Cook, Christian J; Crewther, Blair T; Kilduff, Liam P; Drawer, Scott; Gaviglio, Chris M

    2011-02-16

    We investigated the effects of sleep deprivation with or without acute supplementation of caffeine or creatine on the execution of a repeated rugby passing skill. Ten elite rugby players completed 10 trials on a simple rugby passing skill test (20 repeats per trial), following a period of familiarisation. The players had between 7-9 h sleep on 5 of these trials and between 3-5 h sleep (deprivation) on the other 5. At a time of 1.5 h before each trial, they undertook administration of either: placebo tablets, 50 or 100 mg/kg creatine, 1 or 5 mg/kg caffeine. Saliva was collected before each trial and assayed for salivary free cortisol and testosterone. Sleep deprivation with placebo application resulted in a significant fall in skill performance accuracy on both the dominant and non-dominant passing sides (p sleep deprivation, but trended higher with the 100 mg/kg creatine dose, compared to the placebo treatment (p = 0.067). Salivary cortisol was elevated (p = 0.001) with the 5 mg/kg dose of caffeine (vs. placebo). Acute sleep deprivation affects performance of a simple repeat skill in elite athletes and this was ameliorated by a single dose of either caffeine or creatine. Acute creatine use may help to alleviate decrements in skill performance in situations of sleep deprivation, such as transmeridian travel, and caffeine at low doses appears as efficacious as higher doses, at alleviating sleep deprivation deficits in athletes with a history of low caffeine use. Both options are without the side effects of higher dose caffeine use.

  13. CREATINE SUPPLEMENTATION INDUCES ALTERATION IN CROSS-SECTIONAL AREA IN SKELETAL MUSCLE FIBERS OF WISTAR RATS UNDER SWIMMING TRAINING

    Directory of Open Access Journals (Sweden)

    Luiz C. Fernandes

    2002-09-01

    Full Text Available 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 -20ºC, 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

  14. Creatine CEST MRI for Differentiating Gliomas with Different Degrees of Aggressiveness.

    Science.gov (United States)

    Cai, Kejia; Tain, Rong-Wen; Zhou, Xiaohong Joe; Damen, Frederick C; Scotti, Alessandro M; Hariharan, Hari; Poptani, Harish; Reddy, Ravinder

    2017-04-01

    Creatine (Cr) is a major metabolite in the bioenergetic system. Measurement of Cr using conventional MR spectroscopy (MRS) suffers from low spatial resolution and relatively long acquisition times. Creatine chemical exchange saturation transfer (CrCEST) magnetic resonance imaging (MRI) is an emerging molecular imaging method for tissue Cr measurements. Our previous study showed that the CrCEST contrast, obtained through multicomponent Z-spectral fitting, was lower in tumors compared to normal brain, which further reduced with tumor progression. The current study was aimed to investigate if CrCEST MRI can also be useful for differentiating gliomas with different degrees of aggressiveness. Intracranial 9L gliosarcoma and F98 glioma bearing rats with matched tumor size were scanned with a 9.4 T MRI scanner at two time points. CEST Z-spectra were collected using a customized sequence with a frequency-selective rectangular saturation pulse (B1 = 50 Hz, duration = 3 s) followed by a single-shot readout. Z spectral data were fitted pixel-wise with five Lorentzian functions, and maps of CrCEST peak amplitude, linewidth, and integral were produced. For comparison, single-voxel proton MR spectroscopy ((1)H-MRS) was performed to quantify and compare the total Cr concentration in the tumor. CrCEST contrasts decreased with tumor progression from weeks 3 to 4 in both 9L and F98 phenotypes. More importantly, F98 tumors had significantly lower CrCEST integral compared to 9L tumors. On the other hand, integrals of other Z-spectral components were unable to differentiate both tumor progression and phenotype with limited sample size. Given that F98 is a more aggressive tumor than 9L, this study suggests that CrCEST MRI may help differentiate gliomas with different aggressiveness.

  15. Genetics Home Reference: phosphoglycerate kinase deficiency

    Science.gov (United States)

    ... Genetic Testing Registry: Phosphoglycerate kinase 1 deficiency Other Diagnosis and Management Resources (1 link) Children Living with Inherited Metabolic Diseases (CLIMB) (UK): Phosphoglycerate Kinase Deficiency (PDF) General Information ...

  16. Effect of creatine supplementation and sleep deprivation, with mild exercise, on cognitive and psychomotor performance, mood state, and plasma concentrations of catecholamines and cortisol.

    Science.gov (United States)

    McMorris, T; Harris, R C; Swain, J; Corbett, J; Collard, K; Dyson, R J; Dye, L; Hodgson, C; Draper, N

    2006-03-01

    Sleep deprivation has a negative effect on cognitive and psychomotor performance and mood state, partially due to decreases in creatine levels in the brain. Therefore, creatine supplementation should lessen the negative effects of sleep deprivation. The objective of this study was to examine the effect of creatine supplementation and sleep deprivation, with mild exercise, on cognitive and psychomotor performance, mood state, and plasma concentrations of catecholamines and cortisol. Subjects were divided into a creatine group (n=10) and a placebo group (n=9). They took 5 g of creatine monohydrate or a placebo, dependent on their group, four times a time a day for 7 days, immediately prior to the experiment. The study was double blind. Subjects undertook tests of random movement generation (RMG), verbal and spatial recall, choice reaction time, static balance and mood state pre-test (0 h), after 6, 12 and 24 h of sleep deprivation, with intermittent exercise. They were tested for plasma concentrations of catecholamines and cortisol at 0 and 24 h. At 24 h, the creatine group demonstrated significantly less change in performance from 0 h (delta) in RMG, choice reaction time, balance and mood state. There were no significant differences between groups in plasma concentrations of catecholamines and cortisol. Norepinephrine and dopamine concentrations were significantly higher at 24 h than 0 h, but cortisol were lower. Following 24-h sleep deprivation, creatine supplementation had a positive effect on mood state and tasks that place a heavy stress on the prefrontal cortex.

  17. Effects of Creatine Supplementation on Muscle Strength and Optimal Individual Post-Activation Potentiation Time of the Upper Body in Canoeists

    Directory of Open Access Journals (Sweden)

    Chia-Chi Wang

    2017-10-01

    Full Text Available 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.

  18. Low-Dose Creatine Supplementation Lowers Plasma Guanidinoacetate, but Not Plasma Homocysteine, in a Double-Blind, Randomized, Placebo-Controlled Trial123

    Science.gov (United States)

    Peters, Brandilyn A; Hall, Megan N; Liu, Xinhua; Parvez, Faruque; Siddique, Abu B; Shahriar, Hasan; Uddin, Mohammad Nasir; Islam, Tariqul; Ilievski, Vesna; Graziano, Joseph H; Gamble, Mary V

    2015-01-01

    Background: Creatine synthesis from guanidinoacetate consumes ∼50% of s-adenosylmethionine (SAM)–derived methyl groups, accounting for an equivalent proportion of s-adenosylhomocysteine (SAH) and total homocysteine (tHcys) synthesis. Dietary creatine inhibits the synthesis of guanidinoacetate, thereby lowering plasma tHcys in rats. Objective: We tested the hypotheses that creatine supplementation lowers plasma guanidinoacetate, increases blood SAM, lowers blood SAH, and lowers plasma tHcys. Methods: Bangladeshi adults were randomly assigned to receive 1 of 4 treatments for 12 wk: placebo (n = 101), 3 g/d creatine (Cr; n = 101), 400 μg/d folic acid (FA; n = 153), or 3 g/d creatine plus 400 μg/d folic acid (Cr+FA; n = 103). The outcomes of plasma guanidinoacetate and tHcys, as well as whole blood SAM and SAH, were analyzed at baseline and week 12 by HPLC. Treatment effects of creatine supplementation were examined with the use of the group comparisons of Cr vs. placebo and Cr+FA vs. FA. Results: Plasma guanidinoacetate declined by 10.6% (95% CI: 4.9, 15.9) in the Cr group while increasing nonsignificantly in the placebo group (3.7%; 95% CI: −0.8, 8.5) (Pgroup difference = 0.0002). Similarly, plasma guanidinoacetate declined by 9.0% (95% CI: 3.4, 14.2) in the Cr+FA group while increasing in the FA group (7.0%; 95% CI: 2.0, 12.2) (Pgroup difference creatine supplementation downregulates endogenous creatine synthesis, this may not on average lower plasma tHcys in humans. However, tHcys did decrease in those participants who experienced a decline in plasma guanidinoacetate while receiving creatine plus folic acid supplementation. This trial was registered at clinicaltrials.gov as NCT01050556. PMID:26311810

  19. Low-Dose Creatine Supplementation Lowers Plasma Guanidinoacetate, but Not Plasma Homocysteine, in a Double-Blind, Randomized, Placebo-Controlled Trial.

    Science.gov (United States)

    Peters, Brandilyn A; Hall, Megan N; Liu, Xinhua; Parvez, Faruque; Siddique, Abu B; Shahriar, Hasan; Uddin, Mohammad Nasir; Islam, Tariqul; Ilievski, Vesna; Graziano, Joseph H; Gamble, Mary V

    2015-10-01

    Creatine synthesis from guanidinoacetate consumes ~50% of s-adenosylmethionine (SAM)-derived methyl groups, accounting for an equivalent proportion of s-adenosylhomocysteine (SAH) and total homocysteine (tHcys) synthesis. Dietary creatine inhibits the synthesis of guanidinoacetate, thereby lowering plasma tHcys in rats. We tested the hypotheses that creatine supplementation lowers plasma guanidinoacetate, increases blood SAM, lowers blood SAH, and lowers plasma tHcys. Bangladeshi adults were randomly assigned to receive 1 of 4 treatments for 12 wk: placebo (n = 101), 3 g/d creatine (Cr; n = 101), 400 μg/d folic acid (FA; n = 153), or 3 g/d creatine plus 400 μg/d folic acid (Cr+FA; n = 103). The outcomes of plasma guanidinoacetate and tHcys, as well as whole blood SAM and SAH, were analyzed at baseline and week 12 by HPLC. Treatment effects of creatine supplementation were examined with the use of the group comparisons of Cr vs. placebo and Cr+FA vs. FA. Plasma guanidinoacetate declined by 10.6% (95% CI: 4.9, 15.9) in the Cr group while increasing nonsignificantly in the placebo group (3.7%; 95% CI: -0.8, 8.5) (Pgroup difference = 0.0002). Similarly, plasma guanidinoacetate declined by 9.0% (95% CI: 3.4, 14.2) in the Cr+FA group while increasing in the FA group (7.0%; 95% CI: 2.0, 12.2) (Pgroup difference creatine supplementation downregulates endogenous creatine synthesis, this may not on average lower plasma tHcys in humans. However, tHcys did decrease in those participants who experienced a decline in plasma guanidinoacetate while receiving creatine plus folic acid supplementation. This trial was registered at clinicaltrials.gov as NCT01050556. © 2015 American Society for Nutrition.

  20. Incubating Isolated Mouse EDL Muscles with Creatine Improves Force Production and Twitch Kinetics in Fatigue Due to Reduction in Ionic Strength

    Science.gov (United States)

    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

  1. Incubating isolated mouse EDL muscles with creatine improves force production and twitch kinetics in fatigue due to reduction in ionic strength.

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    Stewart I Head

    Full Text Available 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 Ca(2+ sensitivity of contractile proteins as a result of ionic strength decreases following creatine incubation.

  2. Creatine-induced activation of antioxidative defence in myotube cultures revealed by explorative NMR-based metabonomics and proteomics

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    Nielsen Niels

    2010-02-01

    Full Text Available Abstract Background Creatine is a key intermediate in energy metabolism and supplementation of creatine has been used for increasing muscle mass, strength and endurance. Creatine supplementation has also been reported to trigger the skeletal muscle expression of insulin like growth factor I, to increase the fat-free mass and improve cognition in elderly, and more explorative approaches like transcriptomics has revealed additional information. The aim of the present study was to reveal additional insight into the biochemical effects of creatine supplementation at the protein and metabolite level by integrating the explorative techniques, proteomics and NMR metabonomics, in a systems biology approach. Methods Differentiated mouse myotube cultures (C2C12 were exposed to 5 mM creatine monohydrate (CMH for 24 hours. For proteomics studies, lysed myotubes were analyzed in single 2-DGE gels where the first dimension of protein separation was pI 5-8 and second dimension was a 12.5% Criterion gel. Differentially expressed protein spots of significance were excised from the gel, desalted and identified by peptide mass fingerprinting using MALDI-TOF MS. For NMR metabonomic studies, chloroform/methanol extractions of the myotubes were subjected to one-dimensional 1H NMR spectroscopy and the intracellular oxidative status of myotubes was assessed by intracellular DCFH2 oxidation after 24 h pre-incubation with CMH. Results The identified differentially expressed proteins included vimentin, malate dehydrogenase, peroxiredoxin, thioredoxin dependent peroxide reductase, and 75 kDa and 78 kDa glucose regulated protein precursors. After CMH exposure, up-regulated proteomic spots correlated positively with the NMR signals from creatine, while down-regulated proteomic spots were negatively correlated with these NMR signals. The identified differentially regulated proteins were related to energy metabolism, glucose regulated stress, cellular structure and the

  3. Hematological and Hemodynamic Responses to Acute and Short-Term Creatine Nitrate Supplementation

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    Ryan L. Dalton

    2017-12-01

    Full Text Available In a double-blind, crossover, randomized and placebo-controlled trial; 28 men and women ingested a placebo (PLA, 3 g of creatine nitrate (CNL, and 6 g of creatine nitrate (CNH for 6 days. Participants repeated the experiment with the alternate supplements after a 7-day washout. Hemodynamic responses to a postural challenge, fasting blood samples, and bench press, leg press, and cycling time trial performance and recovery were assessed. Data were analyzed by univariate, multivariate, and repeated measures general linear models (GLM. No significant differences were found among treatments for hemodynamic responses, clinical blood markers or self-reported side effects. After 5 days of supplementation, one repetition maximum (1RM bench press improved significantly for CNH (mean change, 95% CI; 6.1 [3.5, 8.7] kg but not PLA (0.7 [−1.6, 3.0] kg or CNL (2.0 [−0.9, 4.9] kg, CNH, p = 0.01. CNH participants also tended to experience an attenuated loss in 1RM strength during the recovery performance tests following supplementation on day 5 (PLA: −9.3 [−13.5, −5.0], CNL: −9.3 [−13.5, −5.1], CNH: −3.9 [−6.6, −1.2] kg, p = 0.07. After 5 days, pre-supplementation 1RM leg press values increased significantly, only with CNH (24.7 [8.8, 40.6] kg, but not PLA (13.9 [−15.7, 43.5] or CNL (14.6 [−0.5, 29.7]. Further, post-supplementation 1RM leg press recovery did not decrease significantly for CNH (−13.3 [−31.9, 5.3], but did for PLA (−30.5 [−53.4, −7.7] and CNL (−29.0 [−49.5, −8.4]. CNL treatment promoted an increase in bench press repetitions at 70% of 1RM during recovery on day 5 (PLA: 0.4 [−0.8, 1.6], CNL: 0.9 [0.35, 1.5], CNH: 0.5 [−0.2, 0.3], p = 0.56, greater leg press endurance prior to supplementation on day 5 (PLA: −0.2 [−1.6, 1.2], CNL: 0.9 [0.2, 1.6], CNH: 0.2 [−0.5, 0.9], p = 0.25 and greater leg press endurance during recovery on day 5 (PLA: −0.03 [−1.2, 1.1], CNL: 1.1 [0.3, 1.9], CNH: 0.4 [−0

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

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    Chilosi Annamaria

    2012-06-01

    Full Text Available Abstract 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

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

    Science.gov (United States)

    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

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

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    Fleck Steven J

    2011-10-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusions 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

  7. How the use of creatine supplements can elevate serum creatinine in the absence of underlying kidney pathology

    Science.gov (United States)

    Williamson, Lydia; New, David

    2014-01-01

    Serum creatinine is a widely used marker in the assessment of renal function. Elevated creatinine levels suggest kidney dysfunction, prompting the need for further investigation. This report describes a case in which the consumption of the bodybuilding supplement creatine ethyl ester resulted in raised serum creatinine in the absence of true underlying kidney pathology. The abnormalities reversed after discontinuation of the supplement. A case of pseudo renal failure was recognised and kidney function was concluded to be normal. This report aims to address the mechanisms by which the ingestion of creatine ethyl ester can mimic the blood results expected in advanced renal failure, and confronts the problems faced when relying on serum creatinine as a diagnostic tool. PMID:25239988

  8. Cerebral proton magnetic resonance spectroscopy demonstrates reversibility of N-acetylaspartate/creatine in gray matter after delayed encephalopathy due to carbon monoxide intoxication

    DEFF Research Database (Denmark)

    Hansen, Marco Bo; Kondziella, Daniel; Danielsen, Else Rubæk

    2014-01-01

    with cerebral proton magnetic resonance spectroscopy showed a dramatically decrease in N-acetylaspartate to total creatine ratios and elevated lactate levels in the gray matter. Subsequently, our patient received six additional sessions of hyperbaric oxygen therapy with only minimal recovery. At six...... reversal of N-acetylaspartate to total creatine ratios in gray matter has, to our knowledge, never been described before and shows that severe, initial measurements may not predict poor long-term patient outcome....

  9. Citron kinase - renaissance of a neglected mitotic kinase.

    Science.gov (United States)

    D'Avino, Pier Paolo

    2017-05-15

    Cell division controls the faithful segregation of genomic and cytoplasmic materials between the two nascent daughter cells. Members of the Aurora, Polo and cyclin-dependent (Cdk) kinase families are known to regulate multiple events throughout cell division, whereas another kinase, citron kinase (CIT-K), for a long time has been considered to function solely during cytokinesis, the last phase of cell division. CIT-K was originally proposed to regulate the ingression of the cleavage furrow that forms at the equatorial cortex of the dividing cell after chromosome segregation. However, studies in the last decade have clarified that this kinase is, instead, required for the organization of the midbody in late cytokinesis, and also revealed novel functions of CIT-K earlier in mitosis and in DNA damage control. Moreover, CIT-K mutations have recently been linked to the development of human microcephaly, and CIT-K has been identified as a potential target in cancer therapy. In this Commentary, I describe and re-evaluate the functions and regulation of CIT-K during cell division and its involvement in human disease. Finally, I offer my perspectives on the open questions and future challenges that are necessary to address, in order to fully understand this important and yet unjustly neglected mitotic kinase. © 2017. Published by The Company of Biologists Ltd.

  10. Creatine supplementation and resistance training in vulnerable older women: a randomized double-blind placebo-controlled clinical trial.

    Science.gov (United States)

    Gualano, Bruno; Macedo, André Regis; Alves, Christiano Robles Rodrigues; Roschel, Hamilton; Benatti, Fabiana Braga; Takayama, Liliam; de Sá Pinto, Ana Lucia; Lima, Fernanda Rodrigues; Pereira, Rosa Maria Rodrigues

    2014-05-01

    This study aimed to examine the efficacy of creatine supplementation, associated or not with resistance training, in vulnerable older women. A 24-week, double-blind, randomized, placebo-controlled trial was performed. Sixty subjects were assigned to compose the following groups: placebo (PL), creatine supplementation (CR), placebo with resistance training (PL+RT), and creatine supplementation with resistance training (CR+RT). The subjects were assessed at baseline and after 24weeks. The primary outcome was muscle strength, as assessed by one-repetition maximum (1-RM) tests. Secondary outcomes included appendicular lean mass, bone mass, biochemical bone markers, and physical function tests. The changes in 1-RM leg press were significantly greater in the CR+RT group (+19.9%) than in the PL (+2.4%) and the CR groups (+3.7%), but not than in the PL+RT group (+15%) (p=0.002, p=0.002, and p=0.357, respectively). The CR+RT group showed superior gains in 1-RM bench press (+10%) when compared with all the other groups (p≤0.05). The CR+RT group (+1.31%) showed greater appendicular lean mass accrual than the PL (-1.2%), the CR (+0.3%), and the PL+RT groups (-0.2%) (p≤0.05). The CR and the PL+RT groups experienced comparable gains in appendicular lean mass (p=0.62), but superior to those seen in the PL group. Changes in fat mass, bone mass and serum bone markers did not significantly differ between the groups (p>0.05). In conclusion, creatine supplementation combined with resistance training improved appendicular lean mass and muscle function, but not bone mass, in older vulnerable women. Clinicaltrials.gov: NCT01472393. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. γ-Aminobutyric acid transporter 2 mediates the hepatic uptake of guanidinoacetate, the creatine biosynthetic precursor, in rats.

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    Masanori Tachikawa

    Full Text Available Guanidinoacetic acid (GAA is the biosynthetic precursor of creatine which is involved in storage and transmission of phosphate-bound energy. Hepatocytes readily convert GAA to creatine, raising the possibility that the active uptake of GAA by hepatocytes is a regulatory factor. The purpose of this study is to investigate and identify the transporter responsible for GAA uptake by hepatocytes. The characteristics of [(14C]GAA uptake by hepatocytes were elucidated using the in vivo liver uptake method, freshly isolated rat hepatocytes, an expression system of Xenopus laevis oocytes, gene knockdown, and an immunohistochemical technique. In vivo injection of [(14C]GAA into the rat femoral vein and portal vein results in the rapid uptake of [(14C]GAA by the liver. The uptake was markedly inhibited by γ-aminobutyric acid (GABA and nipecotinic acid, an inhibitor of GABA transporters (GATs. The characteristics of Na(+- and Cl(--dependent [(14C]GAA uptake by freshly isolated rat hepatocytes were consistent with those of GAT2. The Km value of the GAA uptake (134 µM was close to that of GAT2-mediated GAA transport (78.9 µM. GABA caused a marked inhibition with an IC(50 value of 8.81 µM. The [(14C]GAA uptake exhibited a significant reduction corresponding to the reduction in GAT2 protein expression. GAT2 was localized on the sinusoidal membrane of the hepatocytes predominantly in the periportal region. This distribution pattern was consistent with that of the creatine biosynthetic enzyme, S-adenosylmethionine:guanidinoacetate N-methyltransferase. GAT2 makes a major contribution to the sinusoidal GAA uptake by periportal hepatocytes, thus regulating creatine biosynthesis in the liver.

  12. Functional and electrophysiological characterization of four non-truncating mutations responsible for creatine transporter (SLC6A8) deficiency syndrome.

    Science.gov (United States)

    Valayannopoulos, Vassili; Bakouh, Naziha; Mazzuca, Michel; Nonnenmacher, Luc; Hubert, Laurence; Makaci, Fatna-Léa; Chabli, Allel; Salomons, Gajja S; Mellot-Draznieks, Caroline; Brulé, Emilie; de Lonlay, Pascale; Toulhoat, Hervé; Munnich, Arnold; Planelles, Gabrielle; de Keyzer, Yves

    2013-01-01

    Intellectual disability coupled with epilepsy are clinical hallmarks of the creatine (Cr) transporter deficiency syndrome resulting from mutations in the SLC6A8 gene. So far characterization of pathogenic mutations of SLC6A8 has been limited to Cr uptake. The aim of our study was to characterize the electrogenic and pharmacological properties of non truncating SLC6A8 mutations identified in patients presenting variable clinical severity. Electrophysiological and pharmacological properties of four mutants (including two novel ones) were studied in X. laevis oocyte expression system. Creatine uptake was assessed with [(14)C]-Cr in X. laevis and patients' fibroblasts. Subcellular localization was determined by immunofluorescence and western blot. All mutants were properly targeted to the plasma membrane in both systems. Mutations led to the complete loss of both electrogenic and transport activities in X. laevis and Cr uptake in patients' fibroblasts. Among the Cr analogs tested, guanidinopropionate induced an electrogenic activity with the normal SLC6A8 transporter similar to creatine whereas a phosphocreatine derivative, PCr-Mg-CPLX, resulted in partial activity. SLC6A8 mutants displayed no electrogenic activity with all Cr analogs tested in X. laevis oocytes. Although the mutations altered various domains of SLC6A8 Cr uptake and electrogenic properties were completely inhibited and could not be dissociated. Besides the metabolic functions of Cr, the loss of SLC6A8 electrogenic activity, demonstrated here for the first time, may also play a role in the altered brain functions of the patients.

  13. Effects of creatine and vitamin E on muscle energetic metabolism, antioxidant stability and meat quality of pigs

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    Rudolf Lahučký

    2012-01-01

    Full Text Available The effects of supplementing the diet of pigs with creatine monohydrate (CMH and vitamin E on blood plasma creatine concentration, vitamin E level in muscle, muscle energy metabolism, antioxidant capacity and meat (musculus longissimus dorsi quality of pigs (DNA tested and negative on malignant hyperthermia were investigated. Two treatments were used: supplementation with CMH alone (2 g.kg−1 of feed, 10 days before slaughter; and supplementation with both vitamin E (500 mg α-tocopherol.kg−1 of feed for minimum of 30 days and CMH (2 g.kg−1 of feed, 10 days before slaughter. Pigs supplemented with CMH alone showed elevated plasma creatine concentration (P ≤ 0.05. Phosphorus nuclear magnetic resonance (31P NMR measurements on post mortem (15 min. muscle samples showed the highest phosphocreatine levels and ratio PCr/Pi (P ≤ 0.05 in CMH supplemented pigs alone and in combination with vitamin E. Dietary supplementation with vitamin E significantly (P ≤ 0.05 increased the concentration of α-tocopherol in meat. Supplementation with CMH alone or in combination with vitamin E resulted in higher (P = 0.07 a values of loin chops at 5 days of storage. Antioxidative capacity (measured as MDA production after incubation of longissimus muscle homogenates with Fe2+/ascorbate was substantially improved by vitamin E and somewhat by CMH supplementation.

  14. Long-term creatine supplementation is safe in aged patients with Parkinson disease.

    Science.gov (United States)

    Bender, Andreas; Samtleben, Walter; Elstner, Matthias; Klopstock, Thomas

    2008-03-01

    The food supplement creatine (Cr) is widely used by athletes as a natural ergogenic compound. It has also been increasingly tested in neurodegenerative diseases as a potential neuroprotective agent. Weight gain is the most common side effect of Cr, but sporadic reports about the impairment of renal function cause the most concerns with regard to its long-term use. Data from randomized controlled trials on renal function in Cr-supplemented patients are scarce and apply mainly to healthy young athletes. We systematically evaluated potential side effects of Cr with a special focus on renal function in aged patients with Parkinson disease as well as its current use in clinical medical research. Sixty patients with Parkinson disease received either oral Cr (n = 40) or placebo (n = 20) with a dose of 4 g/d for a period of 2 years. Possible side effects as indicated by a broad range of laboratory blood and urine tests were evaluated during 6 follow-up study visits. Overall, Cr was well tolerated. Main side effects were gastrointestinal complaints. Although serum creatinine levels increased in Cr patients because of the degradation of Cr, all other markers of tubular or glomerular renal function, especially cystatin C, remained normal, indicating unaltered kidney function. The data in this trial provide a thorough analysis and give a detailed overview about the safety profile of Cr in older age patients.

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

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    Beis Lukas Y

    2011-12-01

    Full Text Available Abstract 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 P V˙O2 and therefore RE. Both HR and Tcore were attenuated significantly after supplementation (P Conclusions Combining Cr and Gly is effective in reducing thermal and cardiovascular strain during exercise in the heat without negatively impacting on RE.

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

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    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.

  17. Creatine Phosphokinase and Visual Analogue Scale as Indicators for Muscle Injury in Untrained Bodybuilders

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    Suresh Shanmugam

    2015-06-01

    Full Text Available Background: Skeletal muscle is a vital tissue in the human body to enable breathing, walking and performing several sports activities. However, this muscle is persistently injured throughout every sports session. Some exercises demand a muscle injury occurrence in order to build a stronger muscle through an adaptation process namely bodybuilding exercise. Importantly, every muscle injury should occur within a physiological range which can be identified by several biomarkers as well as pain scale. The aim of this study was to identify changes on the level of Creatine phosphokinase (CPK and Visual analogue scale (VAS between pre and post training sessions and the correlation between these two indicators. Methods: This was an observational analytical cross sectional comparison study which was conducted in October 2012 and the subjects were adult untrained bodybuilders at the Jatinangor fitness center. The data was obtained by measuring serum CPK and marked VAS. The data were analyzed by t-test, Wilcoxon’s test and Spearman’s correlation. Results: Both CPK and VAS increased significantly by 296 U/L and 19.9 mm respectively. There was a strong positive significant correlation between VAS and CPK (p=0.01, r = 0.711. Conclusion: The healthy untrained bodybuilders chosen in this study experienced a mild (<2000 U/L muscle injury throughout the training sessions with general increased CPK levels and VAS measurement.

  18. The Effects of Creatine Supplementation and Physical Exercise on Traumatic Brain Injury.

    Science.gov (United States)

    Freire Royes, Luiz Fernando; Cassol, Gustavo

    2016-01-01

    Traumatic brain injury (TBI) is a devastating disease frequently followed by significant behavioral disabilities and long-term medical complications that include a wide range of behavioral and emotional problems. TBI is characterized by a combination of immediate mechanical dysfunction of brain tissue and secondary damage developed over a longer period of time following the injury. The early inflammatory response after tissue injury can be triggered by several factors such as extravasated blood products and reactive oxygen species (ROS). It is important to note that energy generation and mitochondrial function are closely related to and interconnected with delayed secondary manifestations of brain injury, including early neuromotor dysfunction, cognitive impairment and post-traumatic epilepsy (PTE). Given the extent of post-traumatic changes in neuronal function and the possibility of amplifying secondary cascades, different therapies designed to minimize damage and retain/restore cellular function after TBI are currently being studied. In this context, the present review covers the preclinical and clinical literature investigating the role of inflammation and free radicals in secondary damage generated by several models of TBI. Furthermore, the present review aims to discuss the role of creatine, a guanidine compound popularly used as a performance-enhancing supplement for high-intensity athletic performance, in secondary damage induced by TBI. In this narrative review, we also discuss the beneficial effect of exercise performed in animal models of TBI and how the results from animal studies can be applied to clinical settings.

  19. Association of sequence variants in CKM (creatine kinase, muscle) and COX4I2 (cytochrome c oxidase, subunit 4, isoform 2) genes with racing performance in Thoroughbred horses.

    Science.gov (United States)

    Gu, J; MacHugh, D E; McGivney, B A; Park, S D E; Katz, L M; Hill, E W

    2010-11-01

    The wild progenitors of the domestic horse were subject to natural selection for speed and stamina for millennia. Uniquely, this process has been augmented in Thoroughbreds, which have undergone at least 3 centuries of intense artificial selection for athletic phenotypes. While the phenotypic adaptations to exercise are well described, only a small number of the underlying genetic variants contributing to these phenotypes have been reported. A panel of candidate performance-related genes was examined for DNA sequence variation in Thoroughbreds and the association with racecourse performance investigated. Eighteen candidate genes were chosen for their putative roles in exercise. Re-sequencing in Thoroughbred samples was successful for primer sets in 13 of these genes. SNPs identified in this study and from the EquCab2.0 SNP database were genotyped in 2 sets of Thoroughbred samples (n = 150 and 148) and a series of population-based case-control investigations were performed by separating the samples into discrete cohorts on the basis of retrospective racecourse performance. Twenty novel SNPs were detected in 3 genes: ACTN3, CKM and COX4I2. Genotype frequency distributions for 3 SNPs in CKM and COX4I2 were significantly (P race. These associations were not validated when an additional (n = 130) independent set of samples was genotyped, but when analyses included all samples (n = 278) the significance of association at COX4I2 g.22684390C > T was confirmed (P horse industries, it is vital that rigour is applied to studies generating these data and that adequate and appropriate sample sets, particularly for independent replication, are used. © 2010 EVJ Ltd.

  20. Creatine-kinase MB mass: age and sex-associated reference limits in two different platforms that use the same method.

    Science.gov (United States)

    Zaninotto, M; Mion, M M; Novello, E; Delprete, E; Moretti, M; Plebani, M

    2009-03-01

    Recent updated NACB guidelines suggest that troponins are the biomarker of choice for the detection of myocardial necrosis, but the CK-MB mass is still considered an effective and alternative indicator when troponin assays are not available. The aim of the present study was to compare the reliability of two different analytical platforms in establishing the gender-specific 99th percentile for the CK-MB mass. Serum samples collected from healthy subjects were investigated in two different laboratories, LAB 1 (354 subjects: 222 men, 132 women; median age, 40 years, range 19-64 years) and LAB 2 (330 subjects: 224 men, 106 women; median age, 41 years, range 18-71 years), in order to determine the CK-MB mass (microg/L) using the Access((R)) CKMB method (Beckman Coulter), a two-site immunoenzymatic sandwich assay, on UniCel DxI 800 (LAB 1) and Access((R)) 2 (LAB 2) analyzers (Beckman Coulter). The related plasma samples (lithium-heparin) were also evaluated in LAB 2. Total imprecision (CV%), calculated in control materials, ranged from 6.00 to 9.05 (concentration range, 3.82-36.37) in LAB 1 and from 7.05 to 5.02 in LAB 2 (concentration range, 3.63-34.18). A statistically significant gender-related difference (p<0.05) was found in the whole population studied, values in men being higher than those in women: median=1.86 vs 1.22; 99th percentile=7.64 vs 5.19. The median values in subjects aged 18-28 years (group 1) were lower than those in the other 4 groups (2-5): 1.12 vs 1.59, vs 1.78, vs 1.95 and vs 2.03. The same age-related trend was also observed for CK-MB plasma values, which were comparable to those observed in the matched-serum samples: median 1.12 vs 1.10 (group 1), 1.45 vs 1.50, (group 5). The two different analytical platforms provide comparable results. The finding that CK-MB mass values are significantly higher in males than in females represents a relevant information, that will impact on patient classification when a myocardial necrosis has been suspected. Actually, however, numerous assays commercially available, lack of this information.

  1. FTIR Imaging of Brain Tissue Reveals Crystalline Creatine Deposits Are an ex Vivo Marker of Localized Ischemia during Murine Cerebral Malaria: General Implications for Disease Neurochemistry

    Science.gov (United States)

    2012-01-01

    Phosphocreatine is a major cellular source of high energy phosphates, which is crucial to maintain cell viability under conditions of impaired metabolic states, such as decreased oxygen and energy availability (i.e., ischemia). Many methods exist for the bulk analysis of phosphocreatine and its dephosphorylated product creatine; however, no method exists to image the distribution of creatine or phosphocreatine at the cellular level. In this study, Fourier transform infrared (FTIR) spectroscopic imaging has revealed the ex vivo development of creatine microdeposits in situ in the brain region most affected by the disease, the cerebellum of cerebral malaria (CM) diseased mice; however, such deposits were also observed at significantly lower levels in the brains of control mice and mice with severe malaria. In addition, the number of deposits was observed to increase in a time-dependent manner during dehydration post tissue cutting. This challenges the hypotheses in recent reports of FTIR spectroscopic imaging where creatine microdeposits found in situ within thin sections from epileptic, Alzheimer’s (AD), and amlyoid lateral sclerosis (ALS) diseased brains were proposed to be disease specific markers and/or postulated to contribute to the brain pathogenesis. As such, a detailed investigation was undertaken, which has established that the creatine microdeposits exist as the highly soluble HCl salt or zwitterion and are an ex-vivo tissue processing artifact and, hence, have no effect on disease pathogenesis. They occur as a result of creatine crystallization during dehydration (i.e., air-drying) of thin sections of brain tissue. As ischemia and decreased aerobic (oxidative metabolism) are common to many brain disorders, regions of elevated creatine-to-phosphocreatine ratio are likely to promote crystal formation during tissue dehydration (due to the lower water solubility of creatine relative to phosphocreatine). The results of this study have demonstrated that

  2. Creatine fails to augment the benefits from resistance training in patients with HIV infection: a randomized, double-blind, placebo-controlled study.

    Directory of Open Access Journals (Sweden)

    Giorgos K Sakkas

    Full Text Available Progressive resistance exercise training (PRT improves physical functioning in patients with HIV infection. Creatine supplementation can augment the benefits derived from training in athletes and improve muscle function in patients with muscle wasting. The objective of this study was to determine whether creatine supplementation augments the effects of PRT on muscle strength, energetics, and body composition in HIV-infected patients.This is a randomized, double blind, placebo-controlled, clinical research center-based, outpatient study in San Francisco. 40 HIV-positive men (20 creatine, 20 placebo enrolled in a 14-week study. Subjects were randomly assigned to receive creatine monohydrate or placebo for 14 weeks. Treatment began with a loading dose of 20 g/day or an equivalent number of placebo capsules for 5 days, followed by maintenance dosing of 4.8 g/day or placebo. Beginning at week 2 and continuing to week 14, all subjects underwent thrice-weekly supervised resistance exercise while continuing on the assigned study medication (with repeated 6-week cycles of loading and maintenance. The main outcome measurements included muscle strength (one repetition maximum, energetics ((31P magnetic resonance spectroscopy, composition and size (magnetic resonance imaging, as well as total body composition (dual-energy X-ray absorptiometry. Thirty-three subjects completed the study (17 creatine, 16 placebo. Strength increased in all 8 muscle groups studied following PRT, but this increase was not augmented by creatine supplementation (average increase 44 vs. 42%, difference 2%, 95% CI -9.5% to 13.9% in creatine and placebo, respectively. There were no differences between groups in changes in muscle energetics. Thigh muscle cross-sectional area increased following resistance exercise, with no additive effect of creatine. Lean body mass (LBM increased to a significantly greater extent with creatine. CONCLUSIONS / SIGNIFICANCE: Resistance exercise improved

  3. Structure of the pseudokinase–kinase domains from protein kinase TYK2 reveals a mechanism for Janus kinase (JAK) autoinhibition

    Science.gov (United States)

    Lupardus, Patrick J.; Ultsch, Mark; Wallweber, Heidi; Bir Kohli, Pawan; Johnson, Adam R.; Eigenbrot, Charles

    2014-01-01

    Janus kinases (JAKs) are receptor-associated multidomain tyrosine kinases that act downstream of many cytokines and interferons. JAK kinase activity is regulated by the adjacent pseudokinase domain via an unknown mechanism. Here, we report the 2.8-Å structure of the two-domain pseudokinase–kinase module from the JAK family member TYK2 in its autoinhibited form. We find that the pseudokinase and kinase interact near the kinase active site and that most reported mutations in cancer-associated JAK alleles cluster in or near this interface. Mutation of residues near the TYK2 interface that are analogous to those in cancer-associated JAK alleles, including the V617F and “exon 12” JAK2 mutations, results in increased kinase activity in vitro. These data indicate that JAK pseudokinases are autoinhibitory domains that hold the kinase domain inactive until receptor dimerization stimulates transition to an active state. PMID:24843152

  4. Structure of the pseudokinase-kinase domains from protein kinase TYK2 reveals a mechanism for Janus kinase (JAK) autoinhibition.

    Science.gov (United States)

    Lupardus, Patrick J; Ultsch, Mark; Wallweber, Heidi; Bir Kohli, Pawan; Johnson, Adam R; Eigenbrot, Charles

    2014-06-03

    Janus kinases (JAKs) are receptor-associated multidomain tyrosine kinases that act downstream of many cytokines and interferons. JAK kinase activity is regulated by the adjacent pseudokinase domain via an unknown mechanism. Here, we report the 2.8-Å structure of the two-domain pseudokinase-kinase module from the JAK family member TYK2 in its autoinhibited form. We find that the pseudokinase and kinase interact near the kinase active site and that most reported mutations in cancer-associated JAK alleles cluster in or near this interface. Mutation of residues near the TYK2 interface that are analogous to those in cancer-associated JAK alleles, including the V617F and "exon 12" JAK2 mutations, results in increased kinase activity in vitro. These data indicate that JAK pseudokinases are autoinhibitory domains that hold the kinase domain inactive until receptor dimerization stimulates transition to an active state.

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

    Directory of Open Access Journals (Sweden)

    Carneiro-Junior Miguel A

    2011-03-01

    Full Text Available Abstract Background 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. Methods 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. Results 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 Conclusions 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.

  6. Effects of Creatine and Sodium Bicarbonate Coingestion on Multiple Indices of Mechanical Power Output During Repeated Wingate Tests in Trained Men.

    Science.gov (United States)

    Griffen, Corbin; Rogerson, David; Ranchordas, Mayur; Ruddock, Alan

    2015-06-01

    This study investigated the effects of creatine and sodium bicarbonate coingestion on mechanical power during repeated sprints. Nine well-trained men (age = 21.6 ± 0.9 yr, stature = 1.82 ± 0.05 m, body mass = 80.1 ±12.8 kg) participated in a double-blind, placebo-controlled, counterbalanced, crossover study using six 10-s repeated Wingate tests. Participants ingested either a placebo (0.5 g·kg(-1) of maltodextrin), 20 g·d(-1) of creatine monohydrate + placebo, 0.3 g·kg(-1) of sodium bicarbonate + placebo, or coingestion + placebo for 7 days, with a 7-day washout between conditions. Participants were randomized into two groups with a differential counterbalanced order. Creatine conditions were ordered first and last. Indices of mechanical power output (W), total work (J) and fatigue index (W·s(-1)) were measured during each test and analyzed using the magnitude of differences between groups in relation to the smallest worthwhile change in performance. Compared with placebo, both creatine (effect size (ES) = 0.37-0.83) and sodium bicarbonate (ES = 0.22-0.46) reported meaningful improvements on indices of mechanical power output. Coingestion provided small meaningful improvements on indices of mechanical power output (W) compared with sodium bicarbonate (ES = 0.28-0.41), but not when compared with creatine (ES = -0.21-0.14). Coingestion provided a small meaningful improvement in total work (J; ES = 0.24) compared with creatine. Fatigue index (W·s(-1)) was impaired in all conditions compared with placebo. In conclusion, there was no meaningful additive effect of creatine and sodium bicarbonate coingestion on mechanical power during repeated sprints.

  7. Predictors and outcomes of increases in creatine phosphokinase concentrations or rhabdomyolysis risk during statin treatment.

    Science.gov (United States)

    van Staa, Tjeerd P; Carr, Daniel F; O'Meara, Helen; McCann, Gerry; Pirmohamed, Munir

    2014-09-01

    The aim was to evaluate clinical risk factors associated with myotoxicity in statin users. This was a cohort study of patients prescribed a statin in UK primary care practices contributing to the Clinical Practice Research Datalink. Outcomes of interest were creatine phosphokinase (CPK) concentrations and clinical records of rhabdomyolysis. The cohort comprised 641,703 statin users. Simvastatin was most frequently prescribed (66.3%), followed by atorvastatin (24.4%). CPK was measured in 127,209 patients: 81.4% within normal range and 0.7% above times the upper limit of normal (ULN). Rhabdomyolysis was recorded in 59 patients. Patients with concomitant prescribing of CYP3A4-interacting drugs had an increased odds ratio (OR) of rhabdomyolysis compared with controls (OR 3.71, 95% CI 1.18, 11.61) and >four times ULN CPK compared with normal CPK (OR 1.28, 95% CI 1.01, 1.60). Rosuvastatin users had higher risk of >four times ULN CPK (OR 1.62, 95% CI 1.22, 2.15) as did patients with larger daily doses of other statin types. A recent clinical record of myalgia was associated with an increased OR of >four times ULN CPK (OR 1.73, 95% CI 1.37, 2.18). In patients who were rechallenged to statins and had repeat CPK measurements after >four times ULN CPK abnormalities, 54.8% of the repeat CPK values were within normal range, 32.1% between one to three times and 13.0% >four times ULN. The frequencies of substantive CPK increases and rhabdomyolysis during statin treatment were low, with highest risks seen in those on large daily doses or interacting drugs and on rosuvastatin. CPK measurements appeared to have been done in a haphazard manner and better guidance is needed. © 2014 The British Pharmacological Society.

  8. Muscle cramps and elevated serum creatine phosphokinase levels induced by beta-adrenoceptor blockers.

    Science.gov (United States)

    Imai, Y; Watanabe, N; Hashimoto, J; Nishiyama, A; Sakuma, H; Sekino, H; Omata, K; Abe, K

    1995-01-01

    We have assessed the propensity of beta-adrenoceptor blockers to cause muscle cramps and to raise the serum creatine phosphokinase (CPK) level in 78 patients with essential hypertension. After a control period, a beta-adrenoceptor blocker without intrinsic sympathomimetic activity (ISA; propranolol, metoprolol or arotinolol) was administered for three months. Thereafter, the patients were randomised to receive a beta-adrenoceptor blocker with ISA (pindolol or carteolol) for three months or a beta-adrenoceptor blocker without ISA for a further three months. This pattern was continued until all beta-adrenoceptor blockers had been given. At the end of each period, CPK and CPK-MB levels were measured. Of the 78 subjects, muscle cramps occurred in 27 during treatment with pindolol and 32 during treatment with carteolol. No complaints were made by subjects treated with propranolol and arotinolol, but muscle cramps were reported in 2 treated with metoprolol. While muscle cramps were caused both by pindolol and carteolol in 16 subjects, they were caused by either of these drugs in the remainder of the subjects. Muscle cramp occurred mainly in the calves when the patients were in bed at night. Serum CPK and CPK-MB levels increased significantly during treatment with pindolol (control period vs pindolol, CPK = 96 vs 133 IU.ml-1, CPK-MB = 14 vs 18 IU.ml-1) or carteolol (CPK = 117 IU.ml-1, CPK-MB = 18 IU.ml-1) while the levels during treatment with propranolol, arotinolol and metoprolol did not change from those in the control period.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Anticancer Alkaloid Lamellarins Inhibit Protein Kinases

    Directory of Open Access Journals (Sweden)

    Laurent Meijer

    2008-10-01

    Full Text Available Lamellarins, a family of hexacyclic pyrrole alkaloids originally isolated from marine invertebrates, display promising anti-tumor activity. They induce apoptotic cell death through multi-target mechanisms, including inhibition of topoisomerase I, interaction with DNA and direct effects on mitochondria. We here report that lamellarins inhibit several protein kinases relevant to cancer such as cyclin-dependent kinases, dualspecificity tyrosine phosphorylation activated kinase 1A, casein kinase 1, glycogen synthase kinase-3 and PIM-1. A good correlation is observed between the effects of lamellarins on protein kinases and their action on cell death, suggesting that inhibition of specific kinases may contribute to the cytotoxicity of lamellarins. Structure/activity relationship suggests several paths for the optimization of lamellarins as kinase inhibitors.

  10. A multisubstrate deoxyribonucleoside kinase from plants

    DEFF Research Database (Denmark)

    Clausen, Anders R.; Girandon, Lenart; Knecht, Wolfgang

    2008-01-01

    Deoxyribonucleoside kinases catalyze the rate limiting step during the salvage of deoxyribonucleosides and convert them into the corresponding monophosphate compounds. We have identified and characterized a unique multisubstrate deoxyribonucleoside kinase from plants. The phylogenetic relationshi...

  11. A multisubstrate deoxyribonucleoside kinase from plants.

    Science.gov (United States)

    Clausen, Anders Ranegaard; Girandon, Lenart; Knecht, Wolfgang; Survery, Sabeen; Andreasson, Erik; Munch-Petersen, Birgitte; Piskur, Jure

    2008-01-01

    Deoxyribonucleoside kinases catalyze the rate limiting step during the salvage of deoxyribonucleosides and convert them into the corresponding monophosphate compounds. We have identified and characterized a unique multisubstrate deoxyribonucleoside kinase from plants. The phylogenetic relationship and biochemical properties suggest that this deoxyribonucleoside kinase represents a living fossil resembling the progenitor of the modern animal deoxycytidine, deoxyguanosine and thymidine 2 kinases. The broad substrate specificity makes this enzyme an interesting candidate to be evaluated as a suicide gene in anti-cancer therapy.

  12. Role of calcium in the expression of MAP kinase kinases (MKKs ...

    African Journals Online (AJOL)

    The mitogen activated protein kinase (MAPK) cascade is an important intracellular signaling module that functions as a convergent point for crosstalk during stress signaling. In this study, we constructed a phylogenetic tree for MAP kinase kinases (MKKs) and MAP kinases (MPKs) in Arabidopsis and Lycopersicon ...

  13. The alpha-kinase family: an exceptional branch on the protein kinase tree.

    NARCIS (Netherlands)

    Middelbeek, J.A.J.; Clark, K.; Venselaar, H.; Huynen, M.A.; Leeuwen, F.N. van

    2010-01-01

    The alpha-kinase family represents a class of atypical protein kinases that display little sequence similarity to conventional protein kinases. Early studies on myosin heavy chain kinases in Dictyostelium discoideum revealed their unusual propensity to phosphorylate serine and threonine residues in

  14. A Mitogen-activated protein kinase kinase kinase mediates reactive oxygen species homeostasis in Arabidopsis.

    Science.gov (United States)

    Nakagami, Hirofumi; Soukupová, Hanka; Schikora, Adam; Zárský, Viktor; Hirt, Heribert

    2006-12-15

    Mitogen-activated protein kinase kinase kinases (MAPKKKs) play key roles in intra- and extracellular signaling in eukaryotes. Here we report that the MAPKKK MEKK1 regulates redox homeostasis in Arabidopsis. We show that MEKK1-deficient plants are misregulated in the expression of a number of genes involved in cellular redox control and accumulate reactive oxygen species (ROS). Most strikingly, homozygous mekk1 mutant plants exhibit a lethal phenotype when developing true leaves. MEKK1 kinase activity and protein stability was regulated by H(2)O(2) in a proteasome-dependent manner and mekk1 plants were compromised in ROS-induced MAPK MPK4 activation. Whereas mpk3 and mpk6 knock out plants showed no defects in development or changes in redox control genes, mpk4 null mutant shared several phenotypic and transcript profile features with mekk1 plants. In agreement with the concept that ROS negatively regulates auxin responses in plants, mekk1 and mpk4 mutants show reduced expression of several auxin-inducible marker genes. Overall, our data defines MPK4 as downstream target of MEKK1 and show that MEKK1 functions in integrating ROS homeostasis with plant development and hormone signaling.

  15. Effect of Creatine Monohydrate Supplementation on Various Hematological and Serum Biochemical Parameters of Male Albino Mice following Neonatal Hypoxia-Ischemia Encephalopathy

    Science.gov (United States)

    Nazir, Nabia; Gillani, Quratulane; Akbar, Atif

    2013-01-01

    Background. Present study was designed to report the effect of 2% creatine monohydrate supplementation for 8, 12 and 15 weeks on hematology and serum biochemical profile of male albino mouse following hypoxic ischemic insult on postnatal day 10. Methods. 66 Blood samples (2% creatine monohydrate supplemented (N = 34) and unsupplemented (N = 32)) were analyzed for various hematological (blood glucose, packed cell volume, total WBC count, total RBC count) and serum biochemical parameters (cholesterol, AST, ALT, HDL, LDL, total protein, triglycerides). Results. ALT had higher concentrations in mice feeding on normal diet for 8 (P > 0.01) and 12 weeks (P > 0.01) following asphyxia and in 12 weeks treatment without asphyxia (P = 0.006) when compared with the creatine supplemented mice. LDL (P = 0.011) and cholesterol (P > 0.01) had higher concentrations in mice on normal diet for 12 weeks following hypoxia ischemia. Cholesterol (P > 0.01) in 12 and glucose (P = 0.006) in 15 week treatment group had significantly lower concentrations in creatine supplemented male albino mice when compared with untreated group following hxpoic-ischemic insult. Conclusion. We concluded that creatine supplementation following hypoxic ischemic insult helps in maintain the normal blood chemistry. PMID:24170981

  16. Laboratory diagnosis of creatine deficiency syndromes: a technical standard and guideline of the American College of Medical Genetics and Genomics.

    Science.gov (United States)

    Sharer, J Daniel; Bodamer, Olaf; Longo, Nicola; Tortorelli, Silvia; Wamelink, Mirjam M C; Young, Sarah

    2017-02-01

    Disclaimer: These ACMG Standards and Guidelines are intended as an educational resource for clinical laboratory geneticists to help them provide quality clinical laboratory genetic services. Adherence to these standards and guidelines is voluntary and does not necessarily assure a successful medical outcome. These Standards and Guidelines should not be considered inclusive of all proper procedures and tests or exclusive of others that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, clinical laboratory geneticists should apply their professional judgment to the specific circumstances presented by the patient or specimen. Clinical laboratory geneticists are encouraged to document in the patient's record the rationale for the use of a particular procedure or test, whether or not it is in conformance with these Standards and Guidelines. They also are advised to take notice of the date any particular guideline was adopted, and to consider other relevant medical and scientific information that becomes available after that date. It also would be prudent to consider whether intellectual property interests may restrict the performance of certain tests and other procedures.Cerebral creatine deficiency syndromes are neurometabolic conditions characterized by intellectual disability, seizures, speech delay, and behavioral abnormalities. Several laboratory methods are available for preliminary and confirmatory diagnosis of these conditions, including measurement of creatine and related metabolites in biofluids using liquid chromatography-tandem mass spectrometry or gas chromatography-mass spectrometry, enzyme activity assays in cultured cells, and DNA sequence analysis. These guidelines are intended to standardize these procedures to help optimize the diagnosis of creatine deficiency syndromes. While biochemical methods are emphasized, considerations for confirmatory molecular testing are also discussed

  17. The JAK kinases: not just another kinase drug discovery target.

    Science.gov (United States)

    Wilks, Andrew F

    2008-08-01

    There are four members of the JAK family of protein tyrosine kinases (PTKs) in the human genome. Since their discovery in 1989, great strides have been made in the understanding of their role in normal intracellular signalling. Importantly, their roles in pathologies ranging from cancer to immune deficiencies have placed them front and centre as potential drug targets. The recent discovery of the role of activating mutations in the kinase-like domain (KLD) of JAK2 in the development of polycythemia rubra vera, and the elaboration of KLD mutation as a broader mechanism by which cells might become hyperproliferative has sparked enormous interest in the development of JAK selective drug candidates. I review herein the progress that has been made in the discovery of JAK-targeted inhibitors, and discuss the challenges that face the development of these drugs for use in the clinic.

  18. Creatine Transporter (CrT; Slc6a8) Knockout Mice as a Model of Human CrT Deficiency

    OpenAIRE

    Skelton, Matthew R.; Schaefer, Tori L.; Graham, Devon L.; deGrauw, Ton J.; Clark, Joseph F.; Williams, Michael T.; Vorhees, Charles V.

    2011-01-01

    Mutations in the creatine (Cr) transporter (CrT; Slc6a8) gene lead to absence of brain Cr and intellectual disabilities, loss of speech, and behavioral abnormalities. To date, no mouse model of CrT deficiency exists in which to understand and develop treatments for this condition. The purpose of this study was to generate a mouse model of human CrT deficiency. We created mice with exons 2-4 of Slc6a8 flanked by loxP sites and crossed these to Cre:CMV mice to create a line of ubiquitous CrT kn...

  19. Mental retardation and verbal dyspraxia in a new patient with de novo creatine transporter (SLC6A8) mutation.

    Science.gov (United States)

    Battini, Roberta; Chilosi, Anna; Mei, Davide; Casarano, Manuela; Alessandrì, M Grazia; Leuzzi, Vincenzo; Ferretti, Giovanni; Tosetti, Michela; Bianchi, M Cristina; Cioni, Giovanni

    2007-08-01

    We report on a 9.5-year-old Italian boy affected by creatine transporter deficit (CT1), due to a de novo mutation in SLC6A8 gene. The patient was investigated by means of a comprehensive neuropsychological protocol and presented with an unusual alteration of speech and expressive-language function, associated with mental retardation, that differed from CT1 patients described to date. In particular, he exhibited a developmental apraxia of speech (DAS) with motor planning and execution deficit, while receptive language was consistent with his mental age. (c) 2007 Wiley-Liss, Inc.

  20. Skill execution and sleep deprivation: effects of acute caffeine or creatine supplementation - a randomized placebo-controlled trial

    OpenAIRE

    Kilduff Liam P; Crewther Blair T; Cook Christian J; Drawer Scott; Gaviglio Chris M

    2011-01-01

    Abstract Background We investigated the effects of sleep deprivation with or without acute supplementation of caffeine or creatine on the execution of a repeated rugby passing skill. Method Ten elite rugby players completed 10 trials on a simple rugby passing skill test (20 repeats per trial), following a period of familiarisation. The players had between 7-9 h sleep on 5 of these trials and between 3-5 h sleep (deprivation) on the other 5. At a time of 1.5 h before each trial, they undertook...

  1. Inhibitors of unactivated p38 MAP kinase.

    Science.gov (United States)

    Bullington, James; Argentieri, Dennis; Averill, Kristin; Carter, Demetrius; Cavender, Druie; Fahmy, Bohumila; Fan, Xiaodong; Hall, Daniel; Heintzelman, Geoffrey; Jackson, Paul; Leung, Wai-Ping; Li, Xun; Ling, Ping; Olini, Gilbert; Razler, Thomas; Reuman, Michael; Rupert, Kenneth; Russell, Ronald; Siekierka, John; Wadsworth, Scott; Wolff, Russell; Xiang, Bangping; Zhang, Yue-Mei

    2006-12-01

    Inhibition of the p38 map kinase pathway has been shown to be beneficial in the treatment of inflammatory diseases. The first class of potent p38 kinase inhibitors was the pyridinylimidazole compounds from SKB. Since then several pyridinylimidazole-based compounds have been shown to inhibit activated p38 kinase in vitro and in vivo. We have developed a novel series of pyridinylimidazole-based compounds, which potently inhibit the p38 pathway by binding to unactivated p38 kinase and only weakly inhibiting activated p38 kinase activity in vitro.

  2. Molecular cloning and characterization of taurocyamine kinase from Clonorchis sinensis: a candidate chemotherapeutic target.

    Directory of Open Access Journals (Sweden)

    Jing-Ying Xiao

    2013-11-01

    Full Text Available BACKGROUND: Adult Clonorchis sinensis lives in the bile duct and causes endemic clonorchiasis in East Asian countries. Phosphagen kinases (PK constitute a highly conserved family of enzymes, which play a role in ATP buffering in cells, and are potential targets for chemotherapeutic agents, since variants of PK are found only in invertebrate animals, including helminthic parasites. This work is conducted to characterize a PK from C. sinensis and to address further investigation for future drug development. METHODOLOGY/PRINCIPAL FINDINGS: [corrected] A cDNA clone encoding a putative polypeptide of 717 amino acids was retrieved from a C. sinensis transcriptome. This polypeptide was homologous to taurocyamine kinase (TK of the invertebrate animals and consisted of two contiguous domains. C. sinensis TK (CsTK gene was reported and found consist of 13 exons intercalated with 12 introns. This suggested an evolutionary pathway originating from an arginine kinase gene group, and distinguished annelid TK from the general CK phylogenetic group. CsTK was found not to have a homologous counterpart in sequences analysis of its mammalian hosts from public databases. Individual domains of CsTK, as well as the whole two-domain enzyme, showed enzymatic activity and specificity toward taurocyamine substrate. Of the CsTK residues, R58, I60 and Y84 of domain 1, and H60, I63 and Y87 of domain 2 were found to participate in binding taurocyamine. CsTK expression was distributed in locomotive and reproductive organs of adult C. sinensis. Developmentally, CsTK was stably expressed in both the adult and metacercariae stages. Recombinant CsTK protein was found to have low sensitivity and specificity toward C. sinensis and platyhelminth-infected human sera on ELISA. CONCLUSION: CsTK is a promising anti-C. sinensis drug target since the enzyme is found only in the C. sinensis and has a substrate specificity for taurocyamine, which is different from its mammalian counterpart

  3. Thymidine kinase diversity in bacteria

    DEFF Research Database (Denmark)

    Sandrini, Michael; Clausen, A.R.; Munch-Petersen, B.

    2006-01-01

    Thymidine kinases (TKs) appear to be almost ubiquitous and are found in nearly all prokaryotes, eukaryotes, and several viruses. They are the key enzymes in thymidine salvage and activation of several anti-cancer and antiviral drugs. We show that bacterial TKs can be subdivided into 2 groups. The....... The TKs from Gram-positive bacteria are more closely related to the eukaryotic TK1 enzymes than are TKs from Gram-negative bacteria....

  4. Oncoprotein protein kinase antibody kit

    Science.gov (United States)

    Karin, Michael [San Diego, CA; Hibi, Masahiko [San Diego, CA; Lin, Anning [La Jolla, CA

    2008-12-23

    An isolated polypeptide (JNK) characterized by having a molecular weight of 46 kD as determined by reducing SDS-PAGE, having serine and threonine kinase activity, phosphorylating the c-Jun N-terminal activation domain and polynucleotide sequences and method of detection of JNK are provided herein. JNK phosphorylates c-Jun N-terminal activation domain which affects gene expression from AP-1 sites.

  5. DMPD: Bruton's tyrosine kinase (Btk)-the critical tyrosine kinase in LPS signalling? [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15081522 Bruton's tyrosine kinase (Btk)-the critical tyrosine kinase in LPS signall...ruton's tyrosine kinase (Btk)-the critical tyrosine kinase in LPS signalling? PubmedID 15081522 Title Bruton...'s tyrosine kinase (Btk)-the critical tyrosine kinase in LPS signalling? Authors

  6. A proteomic approach for comprehensively screening substrates of protein kinases such as Rho-kinase.

    Directory of Open Access Journals (Sweden)

    Mutsuki Amano

    Full Text Available BACKGROUND: Protein kinases are major components of signal transduction pathways in multiple cellular processes. Kinases directly interact with and phosphorylate downstream substrates, thus modulating their functions. Despite the importance of identifying substrates in order to more fully understand the signaling network of respective kinases, efficient methods to search for substrates remain poorly explored. METHODOLOGY/PRINCIPAL FINDINGS: We combined mass spectrometry and affinity column chromatography of the catalytic domain of protein kinases to screen potential substrates. Using the active catalytic fragment of Rho-kinase/ROCK/ROK as the model bait, we obtained about 300 interacting proteins from the rat brain cytosol fraction, which included the proteins previously reported as Rho-kinase substrates. Several novel interacting proteins, including doublecortin, were phosphorylated by Rho-kinase both in vitro and in vivo. CONCLUSIONS/SIGNIFICANCE: This method would enable identification of novel specific substrates for kinases such as Rho-kinase with high sensitivity.

  7. Estimated carrier frequency of creatine transporter deficiency in females in the general population using functional characterization of novel missense variants in the SLC6A8 gene.

    Science.gov (United States)

    DesRoches, Caro-Lyne; Patel, Jaina; Wang, Peixiang; Minassian, Berge; Salomons, Gajja S; Marshall, Christian R; Mercimek-Mahmutoglu, Saadet

    2015-07-10

    Creatine transporter deficiency (CRTR-D) is an X-linked inherited disorder of creatine transport. All males and about 50% of females have intellectual disability or cognitive dysfunction. Creatine deficiency on brain proton magnetic resonance spectroscopy and elevated urinary creatine to creatinine ratio are important biomarkers. Mutations in the SLC6A8 gene occur de novo in 30% of males. Despite reports of high prevalence of CRTR-D in males with intellectual disability, there are no true prevalence studies in the general population. To determine carrier frequency of CRTR-D in the general population we studied the variants in the SLC6A8 gene reported in the Exome Variant Server database and performed functional characterization of missense variants. We also analyzed synonymous and intronic variants for their predicted pathogenicity using in silico analysis tools. Nine missense variants were functionally analyzed using transient transfection by site-directed mutagenesis with In-Fusion HD Cloning in HeLa cells. Creatine uptake was measured by liquid chromatography tandem mass spectrometry for creatine measurement. The c.1654G>T (p.Val552Leu) variant showed low residual creatine uptake activity of 35% of wild type transfected HeLa cells and was classified as pathogenic. Three variants (c.808G>A; p.Val270Met, c.942C>G; p.Phe314Leu and c.952G>A; p.Ala318Thr) were predicted to be pathogenic based on in silico analysis, but proved to be non-pathogenic by our functional analysis. The estimated carrier frequency of CRTR-D was 0.024% in females in the general population. We recommend functional studies for all novel missense variants by transient transfection followed by creatine uptake measurement by liquid chromatography tandem mass spectrometry as fast and cost effective method for the functional analysis of missense variants in the SLC6A8 gene. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

  8. Early time course of N-acetylaspartate, creatine and phosphocreatine, and compounds containing choline in the brain after acute stroke. A proton magnetic resonance spectroscopy study

    DEFF Research Database (Denmark)

    Gideon, P; Henriksen, O; Sperling, B

    1992-01-01

    BACKGROUND AND PURPOSE: The early time course after acute stroke of cerebral N-acetylaspartate, creatine and phosphocreatine, and compounds containing choline was studied in vivo by means of localized water-suppressed proton magnetic resonance spectroscopy. METHODS: Eight patients with acute stroke......, with the loss appearing to occur between 6 and 24 hours after the stroke incident. The reduction in N-acetylaspartate content was greater in the central part than in the peripheral part of the infarcted area. Creatine and phosphocreatine were also reduced in the infarcted area, whereas no significant change...

  9. A Randomized, Double-Blind Placebo-Controlled Trial of Oral Creatine Monohydrate Augmentation for Enhanced Response to a Selective Serotonin Reuptake Inhibitor in Women With Major Depressive Disorder

    Science.gov (United States)

    Kim, Tae-Suk; Hwang, Jaeuk; Kim, Jieun E.; Won, Wangyoun; Bae, Sujin; Renshaw, Perry F.

    2015-01-01

    Objective Antidepressants targeting monoaminergic neurotransmitter systems, despite their immediate effects at the synaptic level, usually require several weeks of administration to achieve clinical efficacy. The authors propose a strategy of adding creatine monohydrate (creatine) to a selective serotonin reuptake inhibitor (SSRI) in the treatment of patients with major depressive disorder. Such augmentation may lead to a more rapid onset of antidepressant effects and a greater treatment response, potentially by restoring brain bioenergetics at the cellular level. Method Fifty-two women with major depressive disorder were enrolled in an 8-week double-blind placebo-controlled clinical trial and randomly assigned to receive escitalopram in addition to either creatine (5 g/day, N=25) or placebo (N=27). Efficacy was primarily assessed by changes in the Hamilton Depression Rating Scale (HAM-D) score. Results In comparison to the placebo augmentation group, patients receiving creatine augmentation showed significantly greater improvements in HAM-D score, as early as week 2 of treatment. This differential improvement favoring creatine was maintained at weeks 4 and 8. There were no differences between treatment groups in the proportion of patients who discontinued treatment prematurely (creatine: N=8, 32.0%; placebo: N=5, 18.5%) or in the overall frequency of all reported adverse events (creatine: 36 events; placebo: 45 events). Conclusions The current study suggests that creatine augmentation of SSRI treatment may be a promising therapeutic approach that exhibits more rapid and efficacious responses in women with major depressive disorder. PMID:22864465

  10. X-linked mental retardation with seizures and carrier manifestations is caused by a mutation in the creatine-transporter gene (SLC6A8) located in Xq28.

    Science.gov (United States)

    Hahn, Kimberly A; Salomons, Gajja S; Tackels-Horne, Darci; Wood, Tim C; Taylor, Harold A; Schroer, Richard J; Lubs, Herbert A; Jakobs, Cornelis; Olson, Rick L; Holden, Kenton R; Stevenson, Roger E; Schwartz, Charles E

    2002-05-01

    A family with X-linked mental retardation characterized by severe mental retardation, speech and behavioral abnormalities, and seizures in affected male patients has been found to have a G1141C transversion in the creatine-transporter gene SLC6A8. This mutation results in a glycine being replaced by an arginine (G381R) and alternative splicing, since the G-->C transversion occurs at the -1 position of the 5' splice junction of intron 7. Two female relatives who are heterozygous for the SLC6A8 mutation also exhibit mild mental retardation with behavior and learning problems. Male patients with the mutation have highly elevated creatine in their urine and have decreased creatine uptake in fibroblasts, which reflects the deficiency in creatine transport. The ability to measure elevated creatine in urine makes it possible to diagnose SLC6A8 deficiency in male patients with mental retardation of unknown etiology.

  11. Creatine in combination with resistance training and improvement in muscle strength: evaluation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Sjödin, Anders Mikael

    2016-01-01

    on the scientific substantiation of a health claim related to creatine in combination with resistance training and improvement in muscle strength. The Panel considers that the food constituent, creatine, which is the subject of the health claim, is sufficiently characterised. The Panel considers that improvement...... substantiation of the claim. In weighing the evidence the Panel took into account that, overall, the human intervention studies submitted provide evidence for an effect of creatine, consumed at doses of at least 3 g/day in combination with regular resistance training (three times per week for several weeks......) of moderate intensity, on muscle strength in adults over the age of 55, while no such effect was observed when similar doses of creatine on a weekly basis were given on training days only (three times per week). The Panel also took into account the plausible mechanism by which daily consumption of creatine...

  12. 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

    Directory of Open Access Journals (Sweden)

    Carducci Claudia

    2012-04-01

    Full Text Available Abstract 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