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Sample records for brain-type creatine kinase

  1. 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.

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

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    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.

  3. CK (Creatine Kinase) Test

    Science.gov (United States)

    ... be limited. Home Visit Global Sites Search Help? Creatine Kinase Share this page: Was this page helpful? Also known as: CK; Total CK; Creatine Phosphokinase; CPK Formal name: Creatine Kinase Related tests: ...

  4. 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...

  5. Creatine kinase in ischemic and inflammatory disorders.

    Science.gov (United States)

    Kitzenberg, David; Colgan, Sean P; Glover, Louise E

    2016-12-01

    The creatine/phosphocreatine pathway plays a conserved and central role in energy metabolism. Compartmentalization of specific creatine kinase enzymes permits buffering of local high energy phosphates in a thermodynamically favorable manner, enabling both rapid energy storage and energy transfer within the cell. Augmentation of this metabolic pathway by nutritional creatine supplementation has been shown to elicit beneficial effects in a number of diverse pathologies, particularly those that incur tissue ischemia, hypoxia or oxidative stress. In these settings, creatine and phosphocreatine prevent depletion of intracellular ATP and internal acidification, enhance post-ischemic recovery of protein synthesis and promote free radical scavenging and stabilization of cellular membranes. The creatine kinase energy system is itself further regulated by hypoxic signaling, highlighting the existence of endogenous mechanisms in mammals that can enhance creatine metabolism during oxygen deprivation to promote tissue resolution and homeostasis. Here, we review recent insights into the creatine kinase pathway, and provide rationale for dietary creatine supplementation in human ischemic and inflammatory pathologies. PMID:27527620

  6. Creatine kinase activity is associated with blood pressure

    NARCIS (Netherlands)

    L.M. Brewster; G. Mairuhu; N.R. Bindraban; R.P. Koopmans; J.F. Clark; G.A. van Montfrans

    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 cardiovascula

  7. Serum creatine kinase after intramuscular injections.

    OpenAIRE

    Konikoff, F; Halevy, J.; Theodor, E

    1985-01-01

    Serum creatine kinase (CK) activity was measured after intramuscular injections in 44 patients hospitalized for non-cardiac reasons. The drugs injected were: diazepam, dipyrone, metoclopramide, meperidine, pentazocine and procaine penicillin. Only 3 out of 44 patients (7%) demonstrated significant elevation of CK levels following the intramuscular injections. In these 3 patients the elevation was mainly due to a rise of the MM-isoenzyme fraction with MB levels increased in one patient. These ...

  8. The Creatine Kinase/Creatine Connection to Alzheimer's Disease: CK-Inactivation, APP-CK Complexes and Focal Creatine Deposits

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available Cytosolic brain-type creatine kinase (BB-CK, which is coexpressed with ubiquitous mitochondrial uMtCK, is significantly inactivated by oxidation, in Alzheimer's disease (AD patients. Since CK has been shown to play a fundamental role in cellular energetics of the brain, any disturbance of this enzyme may exasperate the AD disease process. Mutations in amyloid precursor protein (APP are associated with early onset AD and result in abnormal processing of APP, and accumulation of A β peptide, the main constituent of amyloid plaques in AD brain. Recent data on a direct interaction between APP and the precursor of uMtCK support an emerging relationship between AD, cellular energy levels and mitochondrial function. In addition, recently discovered creatine (Cr deposits in the brain of transgenic AD mice, as well as in the hippocampus from AD patients, indicate a direct link between perturbed energy state, Cr metabolism and AD. Here, we review the roles of Cr and Cr-related enzymes and consider the potential value of supplementation with Cr, a potent neuroprotective substance. As a hypothesis, we consider whether Cr, if given at an early time point of the disease, may prevent or delay the course of AD-related neurodegeneration.

  9. 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 to...

  10. 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 be...

  11. Leukemic cell creatine kinase and its isoenzymes.

    Science.gov (United States)

    Fang, S R; Yao, E G; Wei, S Z; Fan, H; Dong, Z R

    1989-06-01

    Using malachite green single agent coloration and acetate membrane electrophoresis, we studied the cellular creatine kinase (CK) activity and its isoenzymes in 7 normal controls and 26 leukemia patients. The leukemic cellular CK activity was 12.62 +/- 4.86 u/mg protein, 2.2 times higher than the normal value (5.73 +/- 2.66 u/mg protein, p less than 0.05). Only 2 of 5 normal leukocyte samples showed '+' CK isoenzyme MM. 22 leukemia patients had CK isoenzyme. CK-BB appeared mainly in acute granulocytic leukemic, and CK-MM mainly in other types. CK-MB was also found in 6 patients. The recurrence of CK-BB may indicate atavism, and the enhanced anaerobic glycolysis and the accelerated energetic turnover may be on of the metabolic characteristics of leukemic cell. PMID:2512061

  12. Creatine supplementation: exploring the role of the creatine kinase/phosphocreatine system in human muscle.

    Science.gov (United States)

    Hespel, P; Eijnde, B O; Derave, W; Richter, E A

    2001-01-01

    The effect of oral creatine supplementation on high-intensity exercise performance has been extensively studied over the past ten years and its ergogenic potential in young healthy subjects is now well documented. Recently, research has shifted from performance evaluation towards elucidating the mechanisms underlying enhanced muscle functional capacity after creatine supplementation. In this review, we attempt to summarise recent advances in the understanding of potential mechanisms of action of creatine supplementation at the level of skeletal muscle cells. By increasing intracellular creatine content, oral creatine ingestion conceivably stimulates operation of the creatine kinase (CK)/phosphocreatine (PCr) system, which in turn facilitates muscle relaxation. Furthermore, evidence is accumulating to suggest that creatine supplementation can beneficially impact on muscle protein and glycogen synthesis. Thus, muscle hypertrophy and glycogen supercompensation are candidate factors to explain the ergogenic potential of creatine ingestion. Additional issues discussed in this review are the fibre-type specificity of muscle creatine metabolism, the identification of responders versus non-responders to creatine intake, and the scientific background concerning potential side effects of creatine supplementation. PMID:11897886

  13. Computational Simulations to Predict Creatine Kinase-Associated Factors: Protein-Protein Interaction Studies of Brain and Muscle Types of Creatine Kinases

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    Wei-Jiang Hu

    2011-01-01

    Full Text Available Creatine kinase (CK; EC 2.7.3.2 is related to several skin diseases such as psoriasis and dermatomyositis. CK is important in skin energy homeostasis because it catalyzes the reversible transfer of a phosphoryl group from MgATP to creatine. In this study, we predicted CK binding proteins via the use of bioinformatic tools such as protein-protein interaction (PPI mappings and suggest the putative hub proteins for CK interactions. We obtained 123 proteins for brain type CK and 85 proteins for muscle type CK in the interaction networks. Among them, several hub proteins such as NFKB1, FHL2, MYOC, and ASB9 were predicted. Determination of the binding factors of CK can further promote our understanding of the roles of CK in physiological conditions.

  14. EVALUATION OF SERUM CREATINE KINASE LEVELS IN PATIENTS WITH HYPOTHYROIDISM

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    Rekha Nanjundasetty

    2016-05-01

    Full Text Available BACKGROUND Thyroid disorders are common endocrine disorders. Thyroid function tests which are usually done are measurement of blood levels of hormones Triiodothyronine (T3, Thyroxine (T4 and Thyroid Stimulating Hormone (TSH, which are affected by various nonspecific conditions. Therefore, the present study is done to evaluate the role of additional biochemical parameter Creatine Kinase (CK in diagnosing hypothyroidism. Thyroid function and Creatine Kinase activity was measured in 70 patients with clinically suspected cases of hypothyroidism. Patients with hypothyroidism will have decreased T3, T4 levels and increased levels of TSH. However, whether there is any correlation of Creatine Kinase with hypothyroidism is not well established. In our study, we found that in hypothyroid patients there is significant increase in CK levels. Measurement of CK levels is an additional biochemical parameter to diagnose hypothyroidism

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

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    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

  16. Proteinase K processing of rabbit muscle creatine kinase

    DEFF Research Database (Denmark)

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

    1997-01-01

    Proteinase K cleaves selectively both cytosolic and mitochondrial isoforms of creatine kinase leading to the appearance of two fragments, a large N-terminal one (K1) and a small C-terminal peptide (K2) which remain associated together. The loss of enzymatic activity correlates with the extent 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...

  17. 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....

  18. Capture of monomeric refolding intermediate of human muscle creatine kinase

    OpenAIRE

    Li, Sen; Bai, Ji-Hong; Park, Yong-Doo; Zhou, Hai-Meng

    2006-01-01

    Human muscle creatine kinase (CK) is an enzyme that plays an important physiological role in the energy metabolism of humans. It also serves as a typical model for studying refolding of proteins. A study of the refolding and reactivation process of guanidine chloride–denatured human muscle CK is described in the present article. The results show that the refolding process can be divided into fast and slow folding phases and that an aggregation process competes with the proper refolding proces...

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

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    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.

  20. Training volume, androgen use and serum creatine kinase activity.

    OpenAIRE

    Häkkinen, K; Alén, M

    1989-01-01

    Serum creatine kinase (CK) activities were investigated in elite male strength athletes (n = 20) during normal weight training and bodybuilding training (one training session per day), during high volume strength training (two sessions per day) and during strength training (one session per day) with the use of high dose synthetic androgens (five athletes in each subgroup). The findings demonstrated that the increase in serum CK was highest in the subgroup using androgens. These results sugges...

  1. Creatine

    Science.gov (United States)

    ... that taking creating daily does not improve lung function. However, other research suggests that taking creatine may improve lung function ... creatine does not improve wrist muscle or hand function. Osteoarthritis. Early research suggests that taking creating by mouth daily in ...

  2. Enzymatic cycling method using creatine kinase to measure creatine by real-time detection.

    Science.gov (United States)

    Ueda, Shigeru; Sakasegawa, Shin-Ichi

    2016-08-01

    We have developed a novel enzymatic cycling method that uses creatine kinase (CK) to measure creatine. The method takes advantage of the reversibility of the CK reaction in which the forward (creatine phosphate forming) and reverse reactions are catalyzed in the presence of an excess amount of ATP and IDP, respectively. Real-time detection was accomplished using ADP-dependent glucokinase (ADP-GK) together with glucose-6-phosphate dehydrogenase. ADP, one of the cycling reaction products, was distinguished from IDP by using the nucleotide selectivity of the ADP-GK. The increasing level of ADP was measured from the level of reduced NADP at 340 nm. The method is appropriate for an assay that requires high sensitivity because the rate of increase in absorbance at 340 nm is proportional to the amount of CK present in the reaction mix. We reasoned that the method with CK in combination with creatinine amidohydrolase could be used to assay creatinine, an important marker of kidney function. Our results confirmed the quantitative capability of the assay. PMID:27173608

  3. Radioimmunoassay of serum creatine kinase-BB as a tumour marker in breast cancer

    International Nuclear Information System (INIS)

    Brain type creatine kinase-BB (CPK-BB) was measured by radioimmunoassay in the serum of 113 women with breast cancer and 354 female controls. 80% of women with metastatic breast cancer had levels above 3 ng/ml (control range 0.5-3.7 ng/ml); the highest level was 23 ng/ml. 60% of women with local disease but no evidence of distant metastases showed levels above 3 ng/ml, the highest being 9.0 ng/ml. Of women who had presented with stage I, II, or III disease and postoperatively had no evidence of persistent disease 30% had levels above 3 ng/ml. Serial measurements in 31 patients indicated that the serum CPK-BB correlated with clinical response to treatment. (author)

  4. Creatine

    Science.gov (United States)

    ... infants does not improve breathing problems while sleeping. Brain injury. Early research shows that taking creatine by mouth daily for 7 days increases the ability to exercise by increasing lung function in people with a spinal cord injury. However, ...

  5. 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 gen

  6. Characterization of the Partially Folded Monomeric Intermediate of Creatine Kinase

    Institute of Scientific and Technical Information of China (English)

    朴龙斗; 周海梦

    2002-01-01

    The importance of understanding the protein folding pathway and intermediates is well recognized on the basis of extensive studies of protein folding in vitro and in vivo. Creatine kinase (CK) is a typical model for studying unfolding and refolding of proteins due to several interesting properties. Recent studies on the folding of CK show that its partially folded monomeric intermediate is present kinetically and is stable at equilibrium. The present paper contains 33 References as a mini review to characterize the properties of CK from studies on the CK folding pathway. Characterization of these intermediates is an essential step toward understanding the mechanism of protein folding. Some well-determined schemes are suggested as protein folding models.

  7. Effects of Glycerol in the Refolding and Unfolding of Creatine Kinase

    Institute of Scientific and Technical Information of China (English)

    欧文斌; 朴龙斗; 孟凡国; 周海梦

    2002-01-01

    The effects of glycerol in the refolding, reactivation, unfolding, and inactivation of guanidine- denatured creatine kinase were studied by observing the fluorescence emission spectra and the circular dichroism spectra, and by recovery and inactivation of enzymatic activity and aggregation. The results show that low concentrations of glycerol (<25%) improve the refolding yields of creatine kinase, but high glycerol concentrations decrease its recovery. Glycerol favors the secondary structural formation and inhibits aggregation of creatine kinase as proline does. These systematic observations further support the suggestion that low concentrations of glycerol possibly play a chaperone role in the refolding of creatine kinase. In addition, glycerol reduces the inactivation and unfolding rate of creatine kinase, increases the change in transition free energy of unfolding (ΔΔGu) and stabilizes its active conformation relative to the partially unfolded state with no glycerol. In the presence of glycerol, the inactivation and unfolding dynamics of creatine kinase are related to glycerol concentrations. Glycerol blocks the exposure of hydrophobic areas and the dissociation of dimers, and protects creatine kinase against guanidine denaturation in a concentration-dependent manner. This study suggests that glycerol as an energy substrate for metabolism and organic components in vivo, assists correct protein folding, maintains adequate rates of enzymatic catalysis and stabilizes the protein secondary and tertiary conformations.

  8. Method of empirical dependences in estimation and prediction of activity of creatine kinase isoenzymes in cerebral ischemia

    Science.gov (United States)

    Sergeeva, Tatiana F.; Moshkova, Albina N.; Erlykina, Elena I.; Khvatova, Elena M.

    2016-04-01

    Creatine kinase is a key enzyme of energy metabolism in the brain. There are known cytoplasmic and mitochondrial creatine kinase isoenzymes. Mitochondrial creatine kinase exists as a mixture of two oligomeric forms - dimer and octamer. The aim of investigation was to study catalytic properties of cytoplasmic and mitochondrial creatine kinase and using of the method of empirical dependences for the possible prediction of the activity of these enzymes in cerebral ischemia. Ischemia was revealed to be accompanied with the changes of the activity of creatine kinase isoenzymes and oligomeric state of mitochondrial isoform. There were made the models of multiple regression that permit to study the activity of creatine kinase system in cerebral ischemia using a calculating method. Therefore, the mathematical method of empirical dependences can be applied for estimation and prediction of the functional state of the brain by the activity of creatine kinase isoenzymes in cerebral ischemia.

  9. Macromolecular Crowding Enhances Thermal Stability of Rabbit Muscle Creatine Kinase

    Institute of Scientific and Technical Information of China (English)

    ZHU Jiang; HE Huawei; LI Sen

    2008-01-01

    The effect of dextran on the conformation (or secondary structure) and thermal stability of creatine kinase (CK) was studied using the far-ultraviolet (UV) circular dichroism (CD) spectra.The results showed that lower concentrations of dextran (less than 60 g/L) induced formation of the secondary CK structures.However,the secondary structure content of CK decreased when the dextran concentrations exceeded 60 g/L.Thermally induced transition curves were measured for CK in the presence of different concentrations of dextran by far-UV CD.The thermal transition curves were fitted to a two-state model by a nonlinear,least-squares method to obtain the transition temperature of the unfolding transition.An increase in the tran- sition temperature was observed with the increase of the dextran concentration.These observations qualita-tively accord with predictions of a previously proposed model for the effect of intermolecular excluded volume (macromolecular crowding) on protein stability and conformation.These findings imply that the effects of macromolecular crowding can have an important influence on our understanding of how protein folding oc-curs in vivo.

  10. Creatine kinase in cell cycle regulation and cancer.

    Science.gov (United States)

    Yan, Yong-Bin

    2016-08-01

    The phosphocreatine-creatine kinase (CK) shuttle system is increasingly recognized as a fundamental mechanism for ATP homeostasis in both excitable and non-excitable cells. Many intracellular processes are ATP dependent. Cell division is a process requiring a rapid rate of energy turnover. Cell cycle regulation is also a key point to understanding the mechanisms underlying cancer progression. It has been known for about 40 years that aberrant CK levels are associated with various cancers and for over 30 years that CK is involved in mitosis regulation. However, the underlying molecular mechanisms have not been investigated sufficiently until recently. By maintaining ATP at sites of high-energy demand, CK can regulate cell cycle progression by affecting the intracellular energy status as well as by influencing signaling pathways that are essential to activate cell division and cytoskeleton reorganization. Aberrant CK levels may impair cell viability under normal or stressed conditions and induce cell death. The involvement of CK in cell cycle regulation and cellular energy metabolism makes it a potential diagnostic biomarker and therapeutic target in cancer. To understand the multiple physiological/pathological functions of CK, it is necessary to identify CK-binding partners and regulators including proteins, non-coding RNAs and participating endogenous small molecular weight chemical compounds. This review will focus on molecular mechanisms of CK in cell cycle regulation and cancer progression. It will also discuss the implications of recent mechanistic studies, the emerging problems and future challenges of the multifunctional enzyme CK. PMID:27020776

  11. [Effect of macro-creatine kinase in serum on dry chemistry methods results for total creatine kinase activity].

    Science.gov (United States)

    Tozawa, T; Hashimoto, M

    1999-02-01

    Most enzymes in serum that are measured in clinical laboratories can occur in macro-molecular forms in a significantly number of patients. Within dry chemistry (DC) multilayer film, physical barriers may prevent contact macro-molecular enzyme forms with the active reagent ingredients. Here, serum samples with macro-creatine kinase (macro-CK) type 1: CK-immunoglobulin complex or type 2: oligomer mitochondrial CK (CKm) were analyzed for total CK activity on three different DC analyzers: VITROS 700XR, FUJIDRYCHEM 5000, SPOTCHEM SP4410 and a classic wet chemistry (WC) analyzer: HITACHI 7350. Macro-CKs were detected and identified by electrophoresis on cellulose acetate. Serum with high amounts of oligomer CKm gave CK values by all of DC methods significantly lower than that by the WC method (p < 0.05). Oligomer CKm gradually converts into monomer forms in serum after storage. With increase in day after storage at 4 degrees C, there was a gradual shift in which percent of total CK activity for oligomer CKm decreased while the ratio of total CK activity, DC method/WC method increased. The principle of analytical method for CK activity determination is commonly to all of the DC methods, the WC method and the electrophoretic analysis. These suggest that oligomer CKm is sieved by DC multilayer film elements. In contrast, each of DC method produced highly corrected CK activities for sample containing CK-immunoglobulin complex. This difference in the effects of macro-CKs may depend upon physicochemical characteristics of analytical DC elements. PMID:10097631

  12. 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...... 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...

  13. 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...... 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...

  14. 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…

  15. Oligosaccharide and Creatine Supplementation on Glucose and Urea Nitrogen in Blood and Serum Creatine Kinase in Basketball Athletes

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    The effects of oligosaccharide and creatine (Cr) supplementation on glucose, lactic acid and urea nitrogen levels in blood and activity of serum creatine kinase (CK) were explored. Twenty CUBA male athletes were divided into 4 groups: group A (supplementation of Cr alone), group B (supplementation of oligosaccharide), group C (supplementation of oligosaccharide and Cr) and group D (placebo control group). By using orthogonal L4 table (23), the experiment was performed. There were factors including oligosaccharide (carbohydrate, CHO), Cr and their correlation. Each factor had two levels: supplementation and no-supplementation. The results showed that the supplementation of CHO or Cr alone, combined supplementation of CHO and Cr could significantly reduce the glucose, urea nitrogen levels in blood and serum CK activity after competition in the athletes. Moreover, the effects of combined supplementation of CHO and Cr were more satisfactory. It was concluded that supplementation of CHO and Cr could promote the recovery of physical performance and athletic abilities after athletics in basketball athletes.

  16. Phosphocreatine kinetics at the onset of contractions in skeletal muscle of MM creatine kinase knockout mice

    Science.gov (United States)

    Roman, Brian B.; Meyer, Ronald A.; Wiseman, Robert W.

    2002-01-01

    Phosphocreatine (PCr) depletion during isometric twitch stimulation at 5 Hz was measured by (31)P-NMR spectroscopy in gastrocnemius muscles of pentobarbital-anesthetized MM creatine kinase knockout (MMKO) vs. wild-type C57B (WT) mice. PCr depletion after 2 s of stimulation, estimated from the difference between spectra gated to times 200 ms and 140 s after 2-s bursts of contractions, was 2.2 +/- 0.6% of initial PCr in MMKO muscle vs. 9.7 +/- 1.6% in WT muscles (mean +/- SE, n = 7, P creatine kinase, and adenylate kinase fluxes during stimulation was consistent with the observed PCr depletion in MMKO muscle after 2 s only if ADP-stimulated oxidative phosphorylation was included in the model. Taken together, the results suggest that cytoplasmic ADP more rapidly increases and oxidative phosphorylation is more rapidly activated at the onset of contractions in MMKO compared with WT muscles.

  17. 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 effects of leg immobilization and retraining in combination with oral creatine intake on muscle AMP-activated protein kinase (AMPK) protein expression and phosphorylation status were investigated. A double-blind trial was performed in young healthy volunteers (n = 22). A cast immobilized 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...... immobilization-induced muscle inactivity for 2 wk does not alter AMPK a1-, a2-, and ß2-subunit expression or a-AMPK phosphorylation status. Furthermore, the present observations indicate that AMPK probably is not implicated in the previously reported beneficial effects of oral creatine supplementation on muscle...

  18. A rare case of neuroleptic malignant syndrome without elevated serum creatine kinase

    OpenAIRE

    Nisijima K; Shioda K

    2014-01-01

    Koichi Nisijima, Katutoshi Shioda Department of Psychiatry, Jichi Medical University, Tochigi, Japan Abstract: Neuroleptic malignant syndrome (NMS) is a life-threatening adverse reaction to antipsychotic drugs. Although there is no specific examination able to diagnose NMS, serum creatine kinase (CK) elevation has been reported in over 90% of NMS patients. In this report, we describe a patient who developed NMS but had normal CK levels. The patient presented with hyperthermia of over 38&...

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

    OpenAIRE

    Nader Rahnama; Mohammad Faramarzi; Abass Ali Gaeini

    2011-01-01

    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...

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

    OpenAIRE

    Baird, Marianne F.; Graham, Scott M.; Baker, Julien S.; Bickerstaff, Gordon F.

    2012-01-01

    The appearance of creatine kinase (CK) in blood has been generally considered to be an indirect marker of muscle damage, particularly for diagnosis of medical conditions such as myocardial infarction, muscular dystrophy, and cerebral diseases. However, there is controversy in the literature concerning its validity in reflecting muscle damage as a consequence of level and intensity of physical exercise. Nonmodifiable factors, for example, ethnicity, age, and gender, can also affect enzyme tiss...

  1. High Creatine Kinase (CK)-MB and Lactate Dehydrogenase in the Absence of Myocardial Injury or Infarction: A Case Report

    OpenAIRE

    Nasrollah Maghamipour; Naser Safaie

    2014-01-01

    Acute myocardial infarction (AMI) is a life threatening condition that needs emergency diagnosis and early treatment in the emergency room. Rapid laboratory testing for creatine kinase (CK)-MB greatly revolutionized the diagnosis and management of acute myocardial infarction. We report a case with chest pain that referred to the emergency department (ED). Laboratory data showed high serum levels of creatine kinase and lactate dehydrogenase. With diagnosis of acute myocardial infarction, he wa...

  2. VDAC electronics: 3. VDAC-Creatine kinase-dependent generation of the outer membrane potential in respiring mitochondria.

    Science.gov (United States)

    Lemeshko, Victor V

    2016-07-01

    Mitochondrial energy in cardiac cells has been reported to be channeled into the cytosol through the intermembrane contact sites formed by the adenine nucleotide translocator, creatine kinase and VDAC. Computational analysis performed in this study showed a high probability of the outer membrane potential (OMP) generation coupled to such a mechanism of energy channeling in respiring mitochondria. OMPs, positive inside, calculated at elevated concentrations of creatine are high enough to restrict ATP release from mitochondria, to significantly decrease the apparent Km,ADP for state 3 respiration and to maintain low concentrations of Ca(2+) in the mitochondrial intermembrane space. An inhibition by creatine of Ca(2+)-induced swelling of isolated mitochondria and other protective effects of creatine reported in the literature might be explained by generated positive OMP. We suggest that VDAC-creatine kinase-dependent generation of OMP represents a novel physiological factor controlling metabolic state of mitochondria, cell energy channeling and resistance to death. PMID:27085978

  3. 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 de...

  4. Roles of the creatine kinase system and myoglobin in maintaining energetic state in the working heart

    Directory of Open Access Journals (Sweden)

    Beard Daniel A

    2009-02-01

    Full Text Available Abstract Background The heart is capable of maintaining contractile function despite a transient decrease in blood flow and increase in cardiac ATP demand during systole. This study analyzes a previously developed model of cardiac energetics and oxygen transport to understand the roles of the creatine kinase system and myoglobin in maintaining the ATP hydrolysis potential during beat-to-beat transient changes in blood flow and ATP hydrolysis rate. Results The theoretical investigation demonstrates that elimination of myoglobin only slightly increases the predicted range of oscillation of cardiac oxygenation level during beat-to-beat transients in blood flow and ATP utilization. In silico elimination of myoglobin has almost no impact on the cytoplasmic ATP hydrolysis potential (ΔGATPase. In contrast, disabling the creatine kinase system results in considerable oscillations of cytoplasmic ADP and ATP levels and seriously deteriorates the stability of ΔGATPase in the beating heart. Conclusion The CK system stabilizes ΔGATPase by both buffering ATP and ADP concentrations and enhancing the feedback signal of inorganic phosphate in regulating mitochondrial oxidative phosphorylation.

  5. 31P NMR saturation transfer study of the creatine kinase reaction in human skeletal muscle at rest and during exercise.

    OpenAIRE

    Goudemant, Jean-François; Francaux, Marc; Mottet, I.; Demeure, R.; Sibomana, M.; Sturbois, Xavier

    1997-01-01

    The creatine kinase reaction has been studied by 31P NMR in exercising human calf muscle. Quantitative analysis of high energy phosphates and saturation transfer study of the creatine kinase flux in the direction of ATP synthesis (Vfor) were performed at rest and during exercise. As expected, exercise induced a [PCr] decrease (from 28.5 +/- 0.9 to 21.9 +/- 1.5 mM, P < 0.01) matched by a Pi increase (from 4.5 +/- 0.2 to 8.9 +/- 1.8 mM, P = 0.06). pHi and [ATP] remained unchanged. Vfor did not ...

  6. 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...

  7. 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...

  8. The Influence of Whole-Body Vibration on Creatine Kinase Activity and Jumping Performance in Young Basketball Players

    Science.gov (United States)

    Fachina, Rafael; da Silva, Antônio; Falcão, William; Montagner, Paulo; Borin, João; Minozzo, Fábio; Falcão, Diego; Vancini, Rodrigo; Poston, Brach; de Lira, Claudio

    2013-01-01

    Purpose: To quantify creatine kinase (CK) activity changes across time following an acute bout of whole-body vibration (WBV) and determine the association between changes in CK activity and jumping performance. Method: Twenty-six elite young basketball players were assigned to 3 groups: 36-Hz and 46-Hz vibration groups (G36 and G46, respectively)…

  9. Increased dietary protein attenuates C-reactive protein and creatine kinase responses to exercise-induced energy deficit

    Science.gov (United States)

    We determined if dietary protein (P) modulates responses of C-reactive protein (CRP) and creatine kinase (CK), biomarkers of inflammation and muscle damage, during exercise-induced energy deficit (DEF). Thirteen healthy men (22 +/- 1 y, VO2peak 60 +/- 2 ml.kg-1.min-1) balanced energy expenditure (EE...

  10. 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...

  11. Effects of acrylamide and acrylic acid on creatine kinase activity in the rat brain

    International Nuclear Information System (INIS)

    In vitro, both acrylamide and acrylic acid inhibited creatine kinase (CK) activity in rat brain homogenates, and acrylic acid was more potent than acrylamide. In vivo, however, when given i.p. 50 mg/kg per day for 8 days to rats, only acrylamide inhibited CK activity in the brain and caused apparent neurological signs. 14C in the brain 24 h after the injection of 14C-labelled chemicals was more than 7 times greater with acrylamide than with acrylic acid. The inhibition of CK activity by acrylamide varied in eight regions of the brain; from 54% in hypothalamus to 27% in cerebellar vermis. The regional difference of CK inhibition, however, did not agree well with either 14C distribution or with the distribution in regions which appear clinically or pathologically vulnerable to acrylamide. (orig.)

  12. 31P NMR measurements of the ADP concentration in yeast cells genetically modified to express creatine kinase

    International Nuclear Information System (INIS)

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

  13. 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. PMID:26452867

  14. Bruising in Slaughter Cattle and Its Relationship with Creatine Kinase Levels and Beef Quality as Affected by Animal Related Factors

    OpenAIRE

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

    2014-01-01

    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...

  15. Reducing Creatine Kinase-MB Levels Following Oxytocin Administration During Ischemia-Reperfusion Periods in Isolated Rat Heart

    OpenAIRE

    Moghimian M; Aali Anvari M; Faghihi M; Imani A; Khansari M; Sadeghipour Roodsari HR

    2012-01-01

    Background: Creatine kinase is a cardiac biomarker that is used for the assessment of ischemic injuries and myocardial infarction. The present study was designed to evaluate effects of oxytocin administration during ischemia and reperfusion periods on CK-MB levels in the coronary effluent of isolated rat heart and the possible role of oxytocin receptor, nitric oxide (NO), prostacyclin and mitochondrial ATP-dependent potassium channels in this regard. Methods: Male wistar rats (n=8) were anest...

  16. Expression of muscle-gene-specific isozymes of phosphorylase and creatine kinase in innervated cultured human muscle

    OpenAIRE

    1986-01-01

    Isozymes of creatine kinase and glycogen phosphorylase are excellent markers of skeletal muscle maturation. In adult innervated muscle only the muscle-gene-specific isozymes are present, whereas aneurally cultured human muscle has predominantly the fetal pattern of isozymes. We have studied the isozyme pattern of human muscle cultured in monolayer and innervated by rat embryo spinal cord explants for 20-42 d. In this culture system, large groups of innervated muscle fibers close to the ventra...

  17. Temporal changes in circulating P-selectin, plasminogen activator inhibitor-1, magnesium, and creatine kinase after percutaneous coronary intervention*

    OpenAIRE

    Ying, Shu-qin; Xiang, Mei-xiang; Fang, Lu; Wang, Jian-an

    2010-01-01

    Objective: This study aims to determine the mechanisms underlying restenosis and ischemia-reperfusion injury of the myocardium after percutaneous coronary intervention (PCI). Methods: The present study examined serial changes (5 min, 30 min, 2 h, 6 h, and 24 h after PCI) in circulating P-selectin, plasminogen activator inhibitor-1 (PAI-1), magnesium (Mg), and creatine kinase-myocardial band fraction (CK-MB) levels, which may be associated with restenosis and myocardial injury in patients unde...

  18. Effects of Different Resistance Exercise Protocols on Nitric Oxide, Lipid Peroxidation and Creatine Kinase Activity in Sedentary Males

    OpenAIRE

    Nevin Atalay Güzel; Serkan Hazar; Deniz Erbas

    2007-01-01

    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 ...

  19. American ginseng supplementation attenuates creatine kinase level induced by submaximal exercise in human beings

    Institute of Scientific and Technical Information of China (English)

    Cheng-Chen Hsu; Min-Chen Ho; Li-Chin Lin; Borcherng Su; Mei-Chich Hsu

    2005-01-01

    AIM: To investigate whether American ginseng (AG, Panax quinquefolium) supplementation was able to improve endurance exercise performance.METHODS: Thirteen physically active male college students were divided into two groups (AG or placebo)and received supplementation for 4 wk, before the exhaustive running exercise. Treadmill speed was increased to a pace equivalent to 80% VO2max of the subject. A 4-wk washout period followed before the subjects crossed over and received the alternate supplement for the next 4 wk.They then completed a second exhaustive running exercise. The physiological variables that were examined included time to exhaustion and oxygen pulse. Moreover,the plasma creatine kinase (CK) and lactate were measured prior to the exercise, at 15 and 30 min during exercise,immediately after exercise, and 20, 40, 60, and 120 min after exercise.RESULTS: The major finding of this investigation was that the production plasma CK during the exercise significantly decreased for group AG than for group P. Secondary physiological finding was that 80% VO2max running was not improved over a 4-wk AG supplementation regimen.CONCLUSION: Supplementation with AG for 4 wk prior to an exhaustive aerobic treadmill running reduced the leakage of CK during exercise, but did not enhance aerobic work capacity. The reduction of plasma CK may be due to the fact that AG is effective for the decrease of skeletal muscle cell membrane damage, induced by exercise during the high-intensity treadmill run.

  20. Comparison of serum cardiac troponin-I and creatine kinase MB isoenzyme concentrations in asphyxiated neonates

    Institute of Scientific and Technical Information of China (English)

    Nouran F.Hussien; Eman A.Abdel Ghany; Amany E.Elwan; Yasser H.Kamel; Dina K.Ali

    2009-01-01

    Objective:To assess the correlation of signs of myocardial damage to serum cardiac tmponin I(cTnI)and creatine kinase MB isoenzyme(CK-MB)concentrations.Methods:Blood samples were collected from 25 term asphyxiated neonates and 25 controls at 12 h of age by immunoassay.The asphyxiated neonates were followed up until discharge or death.Results:Asphyxiated neonates had significanfly higher concentrations of cTnI and CK-MB than controls(P<0.001).Serum cTnI concentrations were significantly higher in asphyxiated neonates who developed hypotension,heart failure or those had low ejection fraction(P<0.01).Serum cTnI concentrations were significantly higher in asphyxiated who died than those who survived(P<0.01).There was no significant difference in selMnl CK-MB mass concentrations between asphyxiated neonates with and without these complications.Conclusion:Unlike CK-MB,serum cTnI concentrations are significantly higher in asphyxiated neonates who died or developed cardiac dysfunction.

  1. 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.

  2. Effects of Intermittent Exercise on Cardiac Troponin I and Creatine Kinase-MB

    Science.gov (United States)

    Rahnama, Nader; Faramarzi, Mohammad; Gaeini, Abass Ali

    2011-01-01

    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 soccer 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 difference 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 carbohydrate supplementation had less effect on the alteration of biochemical markers of the myocardial muscle. PMID:21448400

  3. Effect of statins on creatine kinase levels before and after a marathon run.

    Science.gov (United States)

    Parker, Beth A; Augeri, Amanda L; Capizzi, Jeffrey A; Ballard, Kevin D; Troyanos, Christopher; Baggish, Aaron L; D'Hemecourt, Pierre A; Thompson, Paul D

    2012-01-15

    We measured the serum levels of myoglobin, total creatine kinase (CK), and the CK myocardial (CK-MB), muscle (CK-MM), and brain (CK-BB) isoenzymes in 37 subjects treated with statins and 43 nonstatin-treated controls running the 2011 Boston Marathon. Venous blood samples were obtained the day before (PRE) and within 1 hour (FINISH) and 24 hours after (POST) the race. The hematocrit and hemoglobin values were used to adjust for changes in the plasma volume. The CK distribution was normalized using log transformation before analysis. The exercise-related increase in CK 24 hours after exercise, adjusted for changes in plasma volume, was greater in the statin users (PRE to POST 133 ± 15 to 1,104 ± 150 U/L) than in the controls (PRE to POST 125 ± 12 to 813 ± 137 U/L; p = 0.03 for comparison). The increase in CK-MB 24 hours after exercise was also greater in the statin users (PRE to POST 1.1 ± 3.9 to 8.9 ± 7.0 U/L) than in the controls (PRE to POST 0.0 ± 0.0 to 4.2 ± 5.0 U/L; p 0.42), suggesting that susceptibility to exercise-induced muscle injury with statins increases with age. In conclusion, our results show that statins increase exercise-related muscle injury. PMID:22036108

  4. RXPERIMENTAL AND CLINICAL STUDY OF CREATINE KINASE BB ACTIVITY FOR TH E DIAGNOSIS ON BRAIN DAMAGE

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To study the differential diagnosis o n cerebral concussion and mild cerebral contusion value of the brain type creati n e kinase isoenzyme(CK-BB),and evaluate the seriousness of brain damage and prog nosis of the patients with acute head injury.Methods Chromatographic separating and fluorometric quant ifying technique was used to detect the CK-BB activity in the cerebrospinal flu id(CSF) of 117 patients with acute head injury and 12 patients with increased in tracranial pressure and 20 normal people.Results The CSF-CK-BB activity of the patients with acu te head injury was remarkably higher than that of the normal people and the CSF -CK-BB activity increased with the seriousness of brain damage.There was a clo se relationship between CSF-CK-BB activity and prognosis,and higher activity o f CSF-CK-BB indicated poor prognosis.Conclusion CSF-CK -BB activity could be used as a new index to diagnose brain damage and evaluate the seriousness of brain damage and prognosis.

  5. Admission creatine kinase as a prognostic marker in acute myocardial infarction

    International Nuclear Information System (INIS)

    To investigate the prognostic significance of creatine kinase (CK) in Pakistani patients suffering from acute myocardial infarction (AMI) and to find out if CK combined with troponin T (TnT) could be a better predictor for long-term adverse cardiac event. One hundred and eighty six consecutive patients with AMI who were eligible for streptokinase (SK) treatment were included in this prospective cohort study. The relationship between their serum plasma CK and TnT levels at the time of admission and clinical outcome was investigated over a mean follow up of 24.12 +- 3.75 months. Admission CK was found to be associated with subsequent cardiac event and mortality (P< 0.01 and P< 0.04 respectively). Admission CK was also mildly associated with time interval between onsets of symptoms to SK treatment (correlation coefficient 'r' = 0.23). Odds of encountering a cardiac event in AMI patients with above-normal CK levels (adjusted for gender) were 3.46 times higher than the odds in patients with normal CK levels. Similarly, odds of mortality in patients with positive TnT were 4.6 times the odds in patients with negative TnT. The two biochemical markers, CK and TnT, together did not provide any further information about prognosis of the disease. Admission CK is a better prognostic marker for a subsequent cardiac event, while TnT is a better predictor of mortality over a mean follow up of nearly 2 years. Together, they do not improve predictability of an adverse cardiac event (JPMA 59:819; 2009). (author)

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

    International Nuclear Information System (INIS)

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

  7. Creatine kinase-MB elevation after percutaneous coronary intervention predicts adverse outcomes in patients with acute coronary syndromes.

    OpenAIRE

    Roe, Matthew; Mahaffey, Kenneth; Kilaru, Rakhi; Akkerhuis, Martijn; Simoons, Maarten; Harrington, Robert Alex; Tardiff, Barbara; Granger, Christopher; Ohman, Magnus; Moliterno, David; Lincoff, Michael; Califf, Robert; Topol, Eric; Werf, Frans; Alexander, John

    2004-01-01

    textabstractAIM: To study the relationship between outcomes and peak creatine kinase (CK)-MB levels after percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS). METHODS AND RESULTS: Peak CK-MB ratios (peak CK-MB level/upper limit of normal [ULN]) after PCI were analysed in 6164 patients with NSTE ACS from four randomized trials who underwent in-hospital PCI. We excluded 696 patients with elevated CK or CK-MB levels

  8. Chronic Hypoxia Enhances Expression and Activity of Mitochondrial Creatine Kinase and Hexokinase in the Rat Ventricular Myocardium

    Czech Academy of Sciences Publication Activity Database

    Wasková-Arnoštová, P.; Kašparová, D.; Elsnicová, B.; Novotný, J.; Neckář, Jan; Kolář, František; Žurmanová, J.

    2014-01-01

    Roč. 33, č. 2 (2014), s. 310-320. ISSN 1015-8987 R&D Projects: GA AV ČR(CZ) IAAX01110901; GA ČR(CZ) GAP303/12/1162 Grant ostatní: Univerzita Karlova(CZ) 349211; GA AV ČR(CZ) IAA601110908 Institutional support: RVO:67985823 Keywords : creatine kinase * hexokinase * normobaric hypoxia * left ventricle * right ventricle * mitochondria co-localization Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 2.875, year: 2014

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

    Directory of Open Access Journals (Sweden)

    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

  10. [Dependence of creatine kinase and glycogen synthetase activities of skeletal muscles on state of adenine nucleotide phosphorylation and cAMP metabolism].

    Science.gov (United States)

    Iakovlev, N N; Chagovets, N R; Maksimova, L V

    1980-01-01

    Changes in the contents of adenine nucleotides, creatine phosphate, inorganic phosphate, creatine, glucose-6-phosphate and glycogen and the activity of adenylate cyclase, creatine kinase, glycogen phosphorylase 31:51-AMP-phosphodiesterase and glycogen synthetase in muscles and of blood catecholamines were studied in adult rats before loading, immediately after the cessation of the muscular activity, and at rest. Adenine nucleotides are established to play a regulatory role in catabolic and anabolic processes nucleotides are established to play a regulatory role in catabolic and anabolic processes related to the muscular activity. It is established that compensation and supercompensation of the working losses of muscular creatine phosphate and glycogen are due to activation of anabolic processes under conditions of higher phosphorylation of the adenylic system. PMID:6247797

  11. The Effect of Cigarette Smoking on Human Sperm Creatine Kinase Activity: As An ATP Buffering System in Sperm

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Ghaffari

    2013-01-01

    Full Text Available Background: Spermatozoa are a group of cells that consume adenosine triphosphate (ATP rapidly.Creatine kinase (CK, produced by creatine phosphate, is an energy reservoir for the rapid bufferingand regeneration of ATP and can play an important role in sperm motility. Therefore, this studyinvestigates the effects of cigarette smoking on human sperm CK activity in males who smoke.Materials and Methods: In this case - control study, we obtained semen samples from male smokers(n=64 and nonsmokers (n=83. Smokers were categorized as light, moderate, or heavy smokersaccording to the daily number of cigarettes smoked and the number of years they have smoked. Datawere analyzed by the independent t test and Pearson’s analysis.Results: This investigation showed significantly lower sperm CK activity and movement in malesmokers compared to nonsmokers. In addition, it was demonstrated that cigarette smoking had adose-dependent effect on these parameters. There was a positive relation, although not significant,between sperm CK activity and its motility in male smokers.Conclusion: Smoking, by diminishing sperm CK activity, may potentially impair sperm energyhomeostasis and have an association with damage to sperm motility. This effect can be an importantmechanism that may cause infertility in male smokers. However, further research is necessary toelucidate the underlying mechanism of sperm motility damage caused by cigarette smoking.

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

    Directory of Open Access Journals (Sweden)

    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.

  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. Normal results of post-race thallium-201 myocardial perfusion imaging in marathon runners with elevated serum MB creatine kinase levels

    International Nuclear Information System (INIS)

    Elevated cardiac enzyme values in asymptomatic marathon runners after competition can arise from skeletal muscle through exertional rhabdomyolysis, silent injury to the myocardium, or a combined tissue source. Peak post-race levels of the MB isoenzyme of creatine kinase are similar to values in patients with acute myocardial infarction. Previously reported normal results of infarct-avid myocardial scintigraphy with technetium 99m pyrophosphate in runners after competition suggest a non-cardiac source but cannot exclude silent injury to the myocardium. Therefore, thallium 201 myocardial perfusion imaging was performed in runners immediately after competition together with determination of sequential cardiac enzyme levels. Among 15 runners tested, the average peak in serum MB creatine kinase 24 hours after the race was 128 IU/liter with a cumulative MB creatine kinase release of 117 IU/liter; these values are comparable to those in patients with acute transmural myocardial infarction. Thallium 201 myocardial scintigraphic results were normal in five runners randomly selected from those who volunteered for determination of sequential blood levels. It is concluded that elevations of serum MB creatine kinase in marathon runners arise from a skeletal muscle source and that thallium 201 myocardial scintigraphy is useful to assess runners for myocardial injury when clinical questions arise

  15. 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.

  16. Changes of Serum Creatine Kinase in Recruits during Physical Training%新兵体能训练对血清肌酸激酶的影响

    Institute of Scientific and Technical Information of China (English)

    罗显荣; 罗春生; 蒋崇福; 杨俊; 徐越; 李莎恩; 成艳君

    2013-01-01

    Objective To investigate the changes of serum creatine kinase (CK) in the recruits during physical training and supply reference for reasonable physical training. Methods A total of 114 recruits were randomly selected, and the changes of serum CK and creatine kinase isoenzyme-MB (CK-MB) were determined 1, 4, 12 and 20 weeks after training. Results The average values of CK and CK-MB 4 and 12 weeks after training were significantly higher than those 1 week after training (P<0. 05). Twenty weeks after training, the average values of CK and CK-MB returned to the normal level. Conclusion The physical training can greatly affect the serum CK and CK-MB levels of the recruits.%目的 探讨新兵体能训练期间血清肌酸激酶(creatine kinase,CK)的变化,为科学实施体能训练提供依据.方法 随机选择114名新兵,于训练1、4、12和20周时检测空腹血清肌酸激酶和同功酶(creatine kinase isoenzyme-MB,CK-MB)水平.结果 训练4周和12周时血清CK及CK-MB均明显高于训练1周时(P<0.05),训练20周时血清CK及CK-MB恢复正常水平.结论 新兵体能训练可明显影响血清CK和CK-MB水平.

  17. Creatine kinase binds more firmly to the M-band of rabbit skeletal muscle myofibrils in the presence of its substrates

    Czech Academy of Sciences Publication Activity Database

    Žurmanová, Jitka; Difato, F.; Maláčová, Daniela; Mejsnar, J.; Štefl, B.; Zahradník, I.

    2007-01-01

    Roč. 305, 1-2 (2007), s. 55-61. ISSN 0300-8177 R&D Projects: GA ČR(CZ) GA304/05/0327 Grant ostatní: MYORES(XE) LSHG-CT-2004-511978 Institutional research plan: CEZ:AV0Z50110509 Source of funding: R - rámcový projekt EK Keywords : muscle * creatine kinase * myofibrillar-sarcoplasmic exchange Subject RIV: ED - Physiology Impact factor: 1.707, year: 2007

  18. Conformational state of creatine kinase molecule is not modified by pH changes within the physiological pH range

    Czech Academy of Sciences Publication Activity Database

    Žurmanová, Jitka; Fišer, Radovan; Horníková, D.

    Geneva : Swiss Society for Neuroscience, 2008. s. 156.8-156.8. ISBN 92-990014-3-X. [FENS. Forum of European Neuroscience /6./. 12.07.2008-16.07.2008, Geneva] Grant ostatní: Myores(XE) 511978 Institutional research plan: CEZ:AV0Z50110509 Source of funding: R - rámcový projekt EK Keywords : spo2 * creatine kinase * pH changes Subject RIV: ED - Physiology

  19. Insensibilization of California Breed Rabbits and its Effect on Sanguineous pH, Temperature, Glucose Levels, Creatine Kinase and Slaughter Performance

    OpenAIRE

    Ramirez, R.; J. Toca; M.M. Zamora-Fonseca; M. Alonso-Spilsbury; A. Cardona-Leija; M. Becerril-Herrera; S.C. Flores-Peinado; M.Y. Guerrero; J.A. Toca; D. Mota-Rojas

    2007-01-01

    The aim of this research was to study the effect of cervical dislocation and electric stunning of the California breed rabbit with a rest period before sacrifice (at 70 days of age) as well as the effect of same on sanguineous pH, temperature, glucose levels, creatine kinase, and slaughter performance. Forty male and female rabbits of the California breed were used. The sacrificed animals had either cervical dislocation or electrical stunning performed on them, then sacrificed according to no...

  20. Diagnostic and prognostic value of serum creatine-kinase activity in ill cats: a retrospective study of 601 cases.

    Science.gov (United States)

    Aroch, Itamar; Keidar, Ido; Himelstein, Anat; Schechter, Miri; Shamir, Merav Hagar; Segev, Gilad

    2010-06-01

    In veterinary medicine, serum creatine-kinase (CK) activity is mostly used to assess skeletal muscle damage. This retrospective study aimed to evaluate the prevalence of increased CK activity in a large, ill-cat population and to characterise associated diseases, clinical and laboratory findings and its prognostic value. Cats with a complete serum biochemistry analysis were consecutively enrolled, divided into two CK activity-based groups (within and above reference interval) and compared. The study included 601 cats. Median serum CK was 402 U/l (range 16-506870). Increased CK (>250 U/l) was observed in 364 (60%) cats, and>30-fold its upper reference limit in 43 (7%). Cats with increased CK had greater (P anorexia than cats with normal CK. Cardiac diseases, trauma, bite wounds, systemic bacterial infections, prior anaesthesia and intramuscular injections were more common (P < or = 0.05) in cats with increased compared to normal CK activity. The hospitalisation period was longer (P=0.007) and treatment cost and mortality were higher (P<0.005) in cats with increased CK activity. However, CK activity was an inaccurate outcome predictor (area under the receiver operator characteristics curve 0.58). Increased CK activity is very common in ill cats. PMID:20236849

  1. Effect on hemo-dialysis on concentration of lactate dehyrogenase, creatine kinase and a-amylase in renal failure

    International Nuclear Information System (INIS)

    This study was conducted to compare the concentration of plasma enzymes in chronic renal failure pre dialysis (group A) and post dialysis (group B), and evaluate the concentration of these enzymes between pre and post dialysis. The study was performed in 25 samples of Sudanese patients (chronic renal failure) and compared with 15 samples as the control groups. plasma samples were analyzed using spectrophotometric methods, plasma concentration of these enzymes showed increase in chronic renal failure pre and post dialysis. The mean values of lactate dehydrogenase pre dialysis was 259IU/L, post dialysis was 276IU/L, the mean of creatine kinase pre dialysis was 252IU/L, and post dialysis was 241 IU/L but the mean of amylase pre and post dialysis was the same 144 IU/L. This study showed that there was no difference of concentration of amylase enzyme, but the different in concentration of CK and LDH between pre and post dialysis during chronic renal failure depend on normal range of this enzyme in control groups.(Author)

  2. 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 (pquality. Bonsmara breed had the highest (80%) bruising score percentage, CK (705.3±80.57 U/L) and pHu (6.3±0.05) values while the Bonsmara had the highest L* (24.8±0.78) a* (17.5±0.53) and b* (12.8±0.53) values. Higher CK levels were also observed in winter compared to summer, spring and autumn respectively. Therefore, animal 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. PMID:25050007

  3. Evaluation of total creatine kinase levels in a spectrum of neuro-psychiatric disorders in a tertiary neurosciences centre

    Directory of Open Access Journals (Sweden)

    Anshu Gupta

    2015-01-01

    Full Text Available Introduction: To study usefulness of total creatine kinase (CK as a screening tool in various neurological and psychiatric disorders in emergency setting of a tertiary care hospital. Materials and Methods: A 1-year retrospective study was conducted on 102 patients with complaints pertaining to neurological and psychiatric disorders in a tertiary neurosciences centre in a metropolitan city. Blood samples in plain vial were received in Emergency Laboratory and total CK levels were measured by automated analyzer and its correlation with various diseases was analyzed. Results: It was observed that CK activity was raised in various psychiatric conditions-acute transient psychotic disorder, alcohol dependence syndrome, delirium, psychosis, mental retardation, catatonia, bipolar affective disorder (BAD, depression and mania and also in neurological disorders-seizures, meningitis, myasthenia gravis (multiple sclerosis, Guillain-Barre syndrome, extra pyramidal syndrome, neuroleptic malignant syndrome and infarct. Conclusion: This study demonstrated that CK is a sensitive and an important screening parameter in diagnosis and monitoring of various neurological and psychiatric disorders in emergency setting. It is also helpful in identifying people at high risk for various neuro-psychiatric diseases.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. LPIN1 deficiency with severe recurrent rhabdomyolysis and persistent elevation of creatine kinase levels due to chromosome 2 maternal isodisomy

    Directory of Open Access Journals (Sweden)

    I.A. Meijer

    2015-12-01

    Full Text Available Fatty acid oxidation disorders and lipin-1 deficiency are the commonest genetic causes of rhabdomyolysis in children. We describe a lipin-1-deficient boy with recurrent, severe rhabdomyolytic episodes from the age of 4 years. Analysis of the LPIN1 gene that encodes lipin-1 revealed a novel homozygous frameshift mutation in exon 9, c.1381delC (p.Leu461SerfsX47, and complete uniparental isodisomy of maternal chromosome 2. This mutation is predicted to cause complete lipin-1 deficiency. The patient had six rhabdomyolytic crises, with creatine kinase (CK levels up to 300,000 U/L (normal, 30 to 200. Plasma CK remained elevated between crises. A treatment protocol was instituted, with early aggressive monitoring, hydration, electrolyte replacement and high caloric, high carbohydrate intake. The patient received dexamethasone during two crises, which was well-tolerated and in these episodes, peak CK values were lower than in preceding episodes. Studies of anti-inflammatory therapy may be indicated in lipin-1 deficiency.

  6. Pressure overload stimulated cardiac hypertrophy leads to a rapid decrease in the mRNA for creatine kinase

    International Nuclear Information System (INIS)

    Cardiac hypertrophy (CH) leads to a decrease in creatine kinase (CK) enzymatic activity. To determine if the mRNA for CK also decreases with CH, they performed the following studies. Cardiac RNA was isolated from rats subjected to either abdominal aortic stenosis (AS) or sham surgery. Through Northern blot analysis, total cardiac RNA was quantitated with a CK specific 32P-labelled cDNA clone. At 3 and 8 days post-constriction, the mRNA for CK decreases by 54.6 +/- 7% and 65.3 +/- 18% respectively, whereas the heart weight increases by 19% and 37% relative to controls. Further studies indicate that CK mRNA also decreases by 41.8% in hypothyroid rats (Tx) but decreases by a total of 68.1% in Tx rats subjected to 8 days of AS. Pressure overload stimulated CH leads to a rapid decrease in CK mRNA in normal and Tx rats. This CK mRNA decrease may account for the decreased efficiency of contraction seen in CH

  7. Enalapril in Combination with Benznidazole Reduces Cardiac Inflammation and Creatine Kinases in Mice Chronically Infected with Trypanosoma cruzi.

    Science.gov (United States)

    Penitente, Arlete Rita; Leite, Ana Luísa Junqueira; de Paula Costa, Guilherme; Shrestha, Deena; Horta, Aline Luciano; Natali, Antônio J; Neves, Clóvis A; Talvani, Andre

    2015-11-01

    The protozoan Trypanosoma cruzi triggers an inflammatory process in mammalian heart causing events such as fibrosis, changes in the architecture and functionality in this organ. Enalapril, an angiotensin II-converting enzyme inhibitor, is a drug prescribed to ameliorate this heart dysfunction, and appears to exert a potential role in immune system regulation. Our aim was to evaluate the chronic cardiac inflammatory parameters after therapeutic treatment with enalapril and benznidazole in C57BL/6 mice infected with the VL-10 strain of T. cruzi. After infection, animals were treated with oral doses of enalapril (25 mg/kg), benznidazole (100 mg/kg), or both during 30 days. Morphometric parameters and levels of chemokines (CCL2, CCL5), IL-10, creatine kinases (CKs), and C-reactive protein were evaluated in the heart and serum at the 120th day of infection. Enalapril alone or in combination with benznidazole did not change the number of circulating parasites, but reduced cardiac leukocyte recruitment and total collagen in the cardiac tissue. Interestingly, the combination therapy (enalapril/benznidazole) also reduced the levels of chemokines, CK and CK-MB, and C-reactive proteins in chronic phase. In conclusion, during the chronic experimental T. cruzi infection, the combination therapy using enalapril plus benznidazole potentiated their immunomodulatory effects, resulting in a low production of biomarkers of cardiac lesions. PMID:26350447

  8. Creatine kinase levels in patients with bipolar disorder: depressive, manic, and euthymic phases Comparação das fases de depressão, mania e eutimia sobre os níveis de creatina quinase em pacientes bipolares

    OpenAIRE

    Gustavo Feier; Samira S. Valvassori; Gislaine T. Rezin; Márcio Búrigo; Streck, Emilio L.; Flávio Kapczinski; João Quevedo

    2011-01-01

    OBJECTIVE: Bipolar disorder is a severe, recurrent, and often chronic psychiatric illness associated with significant functional impairment, morbidity, and mortality. Creatine kinase is an important enzyme, particularly for cells with high and fluctuating energy requirements, such as neurons, and is a potential marker of brain injury. The aim of the present study was to compare serum creatine kinase levels between bipolar disorder patients, in the various phases (depressive, manic, and euthym...

  9. Relationship Between Serum Creatine Kinase Isoenzyme MM Subbands and the Gradation of Coronary Stenosis in Patients with Unstable Angina Pectoris

    Institute of Scientific and Technical Information of China (English)

    Wu Ziqiang; Zhu shanju; Meng Suron; Sun Yueh

    2000-01-01

    Objective To observe the relationship between serum creatine kinase isoenzyme MM sub-bands (CKMM3/MM1 ratio) and the gradation of coronary stenosis and provide a simple, reliable, and economical method for identifying high-risk unstable angina pectoris (UAP). Mehtods Blood samples were drawn at different time after onset of chest pain in 21 patients with UAP and only once in 20 each volunteers for control. CKMM3/MM1 ratio was detected by nonserial buffer agarose gel electrophoresis. CKMB and CK were observed by velocity method. An emergent coronary arteriography was performed as soon as patients were admitted into hospital. Results Patients with UAP were divided into two subgroups:patients with elevated serum enzyme [P( + )] and patients with normal serum enzyme [P( - ) ] according to CKMM3/MM1 ratio < 0.5. Patients with UAP(+)had higher serum CKMM3/MM1 ratios from 0.5 to 12hrs and serum CKMB from 2 to 12 hrs than those with UAP( - ) and control ( P < 0.05) . Serum enzyme concentrations of patients with UAP whose coronary lumen had 90% or more than 90% stenosis were significantly higher than those whose coronary lumen had less than 90% stenosis (P<0.01) . AnyCKMM3/MM1 ratio was less than 1.0 and CK within the normal range in patients with UAP( + ) group. Conclusions CKMM3/MM1 ratios in patients with UAP can reflect severity of myocardial ischemia. Serum CKMM3/MM1 ratio provides a simple, reliable, and economical method for identifying high-risk UAP.

  10. 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.

  11. Causes of creatine kinase levels greater than 1000 IU/L in patients referred to rheumatology.

    Science.gov (United States)

    Leverenz, David; Zaha, Oana; Crofford, Leslie J; Chung, Cecilia P

    2016-06-01

    Patients with severely elevated creatine kinase (CK) concentrations are commonly referred to rheumatologists to evaluate for the presence of an idiopathic inflammatory myopathy (IIM). However, no studies have evaluated the frequency with which IIMs are encountered in this clinical scenario. The Vanderbilt Synthetic Derivative, a de-identified copy of over 2 million patient records, was searched to identify adult patients with a CK greater than 1000 IU/L who had been evaluated by a rheumatologist. Each patient was assigned a diagnosis using a pre-determined algorithm. The records were then reviewed for pertinent demographic data and clinical characteristics. A total of 192 patients were included for analysis. Of these patients, 105 (55 %) were diagnosed with an IIM. The non-IIM causes were drug/toxin exposure (n = 16, 8 %), infection (n = 12, 6 %), trauma (n = 10, 5 %), myocardial injury (n = 5, 3 %), hypothyroidism (n = 4, 2 %), muscular dystrophy (n = 4, 2 %), neuropsychiatric disorder (n = 3, 2 %), metabolic myopathy (n = 2, 1 %), idiopathic CK elevation (n = 11, 6 %), and other diagnoses (n = 20, 10 %). Several characteristics were found to be significantly different between IIM and non-IIM cases. In particular, patients with an IIM were more likely to be female, have a positive ANA, have interstitial lung disease, and have proximal, symmetric weakness. This study found that approximately half of patients referred to our division of rheumatology with a CK greater than 1000 IU/L were diagnosed with an IIM. Given the importance of prompt diagnosis and treatment of these disorders, rapid assessment by the consulting rheumatologist for these patients is recommended. PMID:27041384

  12. Clinical usefulness of creatine Kinase BB determination by a Ria method in serum of patients with cerebrovascular accidents

    International Nuclear Information System (INIS)

    The measurement of creatine kinase BB isoenzyme (CK-BB) using RIA methods could have diagnostic utility as a biological marker of cerebral damage. The aim of the present study is to evaluate whether frequent sampling (4 samples/day for 3 days) permits a better correlation between serum CKBB values and the clinical outcomes of patients with cerebrovascular accidents. 16 in-patients (12 men and 4 women) with stroke (15 of an ischemic nature and 1 hemorrhagic) have benn studied. The presence of stroke was confirmed by clinical symptoms and by CAT results. Blood samples were drawn at 6 and 12 a.m. and at 6 and 12 p.m. over 3 consecutive days after hospitalization. Values of serum CK-BB above the normal range (>7 ng/ml) were found in the 5 of the 16 (31.3%) patients studied. The mean CK-BB value observed in the patients' group was significantly higher than that found in a group of 112 control subjects (controls, mean+-SD=2.1+-1.7 ng/ml vs patients 3.3+-3.4 ng/ml, unpaired t-test p<0.025). We observed a very wide range of serum CKBB levels in most of the patients studied. Some prominent peaks of CK-BB concetrations were found in patients' outcame (Spearman correlation coefficient r-s=0.618, p<0,01). Although our results indicate that the measurement of CK-BB concentrations cannot be considered a sensitive marker of stroke, the significant correlation between serum CK-BB values and outcome suggests that high CK-BB levels could be a sign of worse prognosis in patients with cerebrovascular accidents

  13. Reproducibility of Creatine Kinase Reaction Kinetics in Human Heart: A 31P Time Dependent Saturation Transfer Spectroscopy

    Science.gov (United States)

    Bashir, Adil; Gropler, Robert

    2014-01-01

    Creatine Kinase (CK) is essential for buffering and rapid regeneration of adenosine triphosphate (ATP) in heart tissue. Herein we demonstrate a 31P magnetic resonance spectroscopy (MRS) protocol to quantify CK reaction kinetics in human myocardium at 3T. Furthermore we sought to quantify the test–retest reliability of the measured metabolic parameters. The method localizes 31P signal from heart using modified 1D image selected in vivo spectroscopy (ISIS) and a time dependent saturation transfer (TDST) approach was used to measure CK reaction parameters. Fifteen healthy volunteers (22 measurements total) were tested. The CK reaction rate constant (kf) was 0.32 ± 0.05 sec−1 and coefficient of variation (CV) = 15.62%. Intrinsic T1 for phosphocreatine (PCr) was 7.36 ± 1.79 sec with CV = 24.32%. These values are consistent those previously reported. PCr/ATP ratio was equal to 1.94 ± 0.15 with CV = 7.73%, which is within the range of healthy subjects. The reproducibility of the technique was tested in 7 subjects and inferred parameters such as kf and T1 exhibited good reliability (intraclass correlation coefficient (ICC) = 0.90 and 0.79 for kf and T1 respectively). The reproducibility data provided in this study will enable calculation of power and sample sizes required for clinical and research studies. The technique will allow for the examination of cardiac energy metabolism in clinical and research studies providing insight in the relationship between energy deficit and functional deficiency in heart. PMID:24706347

  14. Reducing Creatine Kinase-MB Levels Following Oxytocin Administration During Ischemia-Reperfusion Periods in Isolated Rat Heart

    Directory of Open Access Journals (Sweden)

    Moghimian M

    2012-02-01

    Full Text Available Background: Creatine kinase is a cardiac biomarker that is used for the assessment of ischemic injuries and myocardial infarction. The present study was designed to evaluate effects of oxytocin administration during ischemia and reperfusion periods on CK-MB levels in the coronary effluent of isolated rat heart and the possible role of oxytocin receptor, nitric oxide (NO, prostacyclin and mitochondrial ATP-dependent potassium channels in this regard. Methods: Male wistar rats (n=8 were anesthetized with sodium thiopental and their hearts were transferred to a Langendorff perfusion apparatus. All animals were randomly divided into nine groups as follow; in the ischemia-reperfusion group, hearts underwent 30 min of regional ischemia followed by 120 min of reperfusion. In oxytocin group, hearts were perfused with oxytocin 5 min after ischemia induction for 25 min. In other groups, 35 min prior to oxytocin perfusion, atosiban (a non-specific oxytocin receptor blocker, L-NAME (an NO synthase inhibitor, indomethacin (a non-specific cyclooxygenase blocker and 5-HD (a specific mKATP channel blocker were perfused for 10 min. In all groups, we measured CK-MB levels in the coronary effluent at the end of reperfusion. Moreover, coronary flow (mL/min was measured at baseline, during ischemia period and 60 and 120 min after reperfusion.MB level in oxytocin group as compared to ischemia-reperfusion group. Administration of atosiban, L-NAME, indomethacin and 5-HD prior to oxytocin perfusion abolished the effects of oxytocin on CK-MB levels.Conclusion: Administration of oxytocin during ischemia and reperfusion periods deceased CK-MB levels but infusion of atosiban, L-NAME, 5-HD and indomethacin inhibited oxytocin from exerting its effects.

  15. Relationships between match activities and peak power output and Creatine Kinase responses to professional reserve team soccer match-play.

    Science.gov (United States)

    Russell, M; Sparkes, W; Northeast, J; Cook, C J; Bracken, R M; Kilduff, L P

    2016-02-01

    The specific movement demands of soccer that are linked to post-match recovery and readiness to train are unclear. Therefore, we examined the relationship between Global Positioning System (GPS) variables and the change (Δ; from baseline) in Creatine Kinase (CK) concentrations and peak power output (PPO; during the countermovement jump) at 24h and 48h post-match. Fifteen English Premier League reserve team players were examined over 1-4 matches. Measurements of CK and PPO were taken before (24h prior to match-play) and after (+24h and +48h) each game during which movement demands were quantified using 10Hz GPS data. High intensity distance covered (r=0.386, p=0.029; r=-0.349; p=0.050), high intensity distance covered⋅min(-1) (r=0.365, p=0.040; r=-0.364, p=0.040), high speed running distance (r=0.363, p=0.041; r=-0.360, p=0.043) and the number of sprints⋅min(-1) (r=0.410, p=0.020; r=-0.368, p=0.038) were significantly related to ΔCK and ΔPPO at +24h post-match, respectively. No relationships were observed between any match variables and ΔCK and ΔPPO after +48h of recovery. These findings highlight that high intensity match activities are related to ΔCK and ΔPPO in the 24h, but not 48h, following soccer match-play. Such information is likely of interest to those responsible for the design of soccer player's training schedules in the days following a match. PMID:26615476

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

    Directory of Open Access Journals (Sweden)

    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

  17. POSTNATAL EFFECTS OF HEXACHLOROBENZENE (HCB) ON CARDIAC LACTIC DEHYDROGENASE (LDH) AND CREATINE KINASE (CK) ISOZYMES IN CD-1 MICE

    Science.gov (United States)

    Pregnant CD-1 mice were treated with hexachlorobenzene (HCB) by gavage at doses of 0, 1, 10 and 50 mg HCB/kg body weight on days 6-17 of gestation and studied on day 1 or 21 postpartum (pp). Hearts of the dams and pups were assayed for lactic dehydrogenase (LDH) and creatine kina...

  18. 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. PMID:26855163

  19. 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. In...

  20. 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...... extensive and local disease patients. Serotonin was generally overall elevated in 10% and GRP in 7% but elevations were seen only in patients with extensive disease. Out of the four most frequently elevated substances at least one marker was elevated in 80% of all the patients, including 91% in extensive...... determined within 4-8 weeks. The results indicate that serum CK-BB and NSE are potential markers for SCC at the time of diagnosis and that changes in the concentrations during the first course of cytostatic therapy are promising as biochemical tests for early detection of response to chemotherapy....

  1. 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.

  2. Neuroleptic malignant-like syndrome with a slight elevation of creatine-kinase levels and respiratory failure in a patient with Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Wei L

    2014-02-01

    Full Text Available Li Wei,1,2 Yinghui Chen1,2 1Department of Neurology, Jinshan Hospital, 2Department of Neurology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China Abstract: Neuroleptic malignant-like syndrome (NMLS is a rare but catastrophic complication of drug treatment for Parkinson's disease (PD. Sudden withdrawal and abrupt reduction of antiparkinsonian drugs are major risk factors. Just as its name suggests, the clinical features of NMLS are similar to neuroleptic malignant syndrome, which is a dangerous adverse response to antipsychotic drugs. Both of these conditions can present with hyperthermia, marked muscle rigidity, altered consciousness, autonomic dysfunction, and elevated serum creatine-kinase (CK levels. However, we describe a special NMLS case with a slight elevation of CK levels and respiratory failure in the full course of her treatment. The patient, a 68-year-old woman with a 4-years history of Parkinson's disease, presented with hyperthermia and severe muscular rigidity. During the course of her treatment, her maximum temperature was extremely high (above 41°C. At the beginning, the diagnosis of NMLS secondary to dopamine decrease was difficult to make, because her initial blood examination revealed that her serum CK levels were mildly elevated and decreased to normal range rapidly. Although antiparkinsonian drugs and supportive treatment were applied, the patient developed an acute respiratory failure in the early course of treatment. This case report highlights that when confronted with Parkinson's patients with high body temperature and muscle rigidity, NMLS should be taken into consideration even if there is no CK elevation. Likewise, the need for supportive care is essential, because its complications are severe, even such as respiratory failure. Keywords: antiparkinsonian drugs, creatine kinase, parkinsonism–hyperpyrexia syndrome, respiratory failure

  3. 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

  4. Analysis of the Causes of Mental Illness of Creatine Kinase in Patients with Increased%精神病患者血清肌酸激酶增高探讨

    Institute of Scientific and Technical Information of China (English)

    张文亮

    2015-01-01

    目的探讨住院精神疾病患者出现的血清高水平肌酸激酶(CK)活性的机制。方法对2013年1~10月住院精神疾病患者血清肌酸激酶检测值大于800 U/L病例资料进行统计分析。结果出现肌酸激酶检测值大于800 U/L病例375例,平均值为1384 U/L,诊断以精神分裂症和双相障碍为主。结论精神疾病患者血清肌酸激酶活性存在不同程度的增高,可能与精神疾病的某些症状有关联。%Objective To investigate the hospital patients with mental disease high levels of serum creatine kinase (CK) activity mechanism. Methods 2013.1~ 2013.10 month of hospitalization in patients with mental disorders in detection of serum creatine kinase values greater than 800 U/L were col ected and statistical analysis. Results The emergence of creatine kinase detection value is greater than 800 U/L in 375 cases, the average value is 1384 U/L, diagnosed with schizophrenia and bipolar disorder based. Conclusion The patients with mental disorders of serum creatine kinase activity has increased in dif erent degrees, may be associated with some symptoms of mental il ness.

  5. 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

    OpenAIRE

    Aureo Evangelista Santana; Paula Alessandra Di Filippo

    2008-01-01

    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...

  6. 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.

  7. A novel electrophoretic technique designed to modify the ratio of magnesium isotopes inside the creatine kinase active sites. A preliminary report.

    Science.gov (United States)

    Kouznetsov, Dmitri A; Arkhangelsky, Stanislav E; Berdieva, Alana G; Khasigov, Peter Z; Orlova, Marina A

    2004-09-01

    A simple and efficient preparative electrophoretic technique has been proposed to obtain a modified creatine kinase (CK, E.C.2.7.3.2) molecule with an increased content of 25Mg in the active site. A key point of the method is the special design of a 0.9 x 12.0 cm column for ascendent electrophoresis, packed consecutively, from the bottom to the top, with layers of 30 % PAAG (polyacrylamide grade), 25Mg2+ -containing 7.5 % PAAG, enzyme-binding ADP Sepharose and 2.2 % agarose gels, based on different tris-glycine and tris-HCl separation buffer systems. The isotope substitution process was a result of simultaneous desorption of enzyme from ADP Sepharose and electrically directed extensive flow of 25Mg2+ cations through the porous gel matrix. Greater than 8-fold 25Mg enrichment, i.e. a 10.2-86.3 % increase of 25Mg contribution to total enzyme magnesium, has been reached. The modified 25Mg-rich CK samples manifest higher (2.4-fold increase) values of specific catalytic activity when compared with intact (control) ones. PMID:15370286

  8. Severe falciparum malaria with dengue coinfection complicated by rhabdomyolysis and acute kidney injury: an unusual case with myoglobinemia, myoglobinuria but normal serum creatine kinase

    Directory of Open Access Journals (Sweden)

    Yong Kok Pin

    2012-12-01

    Full Text Available Abstract Background Acute kidney injury (AKI is a complication of severe malaria, and rhabdomyolysis with myoglobinuria is an uncommon cause. We report an unusual case of severe falciparum malaria with dengue coinfection complicated by AKI due to myoglobinemia and myoglobinuria while maintaining a normal creatine kinase (CK. Case presentation A 49-year old Indonesian man presented with fever, chills, and rigors with generalized myalgia and was diagnosed with falciparum malaria based on a positive blood smear. This was complicated by rhabdomyolysis with raised serum and urine myoglobin but normal CK. Despite rapid clearance of the parasitemia with intravenous artesunate and aggressive hydration maintaining good urine output, his myoglobinuria and acidosis worsened, progressing to uremia requiring renal replacement therapy. High-flux hemodiafiltration effectively cleared his serum and urine myoglobin with recovery of renal function. Further evaluation revealed evidence of dengue coinfection and past infection with murine typhus. Conclusion In patients with severe falciparum malaria, the absence of raised CK alone does not exclude a diagnosis of rhabdomyolysis. Raised serum and urine myoglobin levels could lead to AKI and should be monitored. In the event of myoglobin-induced AKI requiring dialysis, clinicians may consider using high-flux hemodiafiltration instead of conventional hemodialysis for more effective myoglobin removal. In Southeast Asia, potential endemic coinfections that can also cause or worsen rhabdomyolysis, such as dengue, rickettsiosis and leptospirosis, should be considered.

  9. Creatine for women: a review of the relationship between creatine and the reproductive cycle and female-specific benefits of creatine therapy.

    Science.gov (United States)

    Ellery, Stacey J; Walker, David W; Dickinson, Hayley

    2016-08-01

    The creatine/phosphocreatine/creatine kinase circuit is instrumental in regulating high-energy phosphate metabolism, and the maintenance of cellular energy turnover. The mechanisms by which creatine is able to buffer and regulate cellular energy balance, maintain acid-base balance, and reduce the effects of oxidative stress have led to a large number of studies into the use of creatine supplementation in exercise performance and to treat diseases associated with cellular energy depletion. Some of these studies have identified sex-specific responses to creatine supplementation, as such; there is the perception, that females might be less receptive to the benefits of creatine supplementation and therapy, compared to males. This review will describe the differences in male and female physique and physiology that may account for such differences, and discuss the apparent endocrine modulation of creatine metabolism in females. Hormone-driven changes to endogenous creatine synthesis, creatine transport and creatine kinase expression suggest that significant changes in this cellular energy circuit occur during specific stages of a female's reproductive life, including pregnancy and menopause. Recent studies suggest that creatine supplementation may be highly beneficial for women under certain conditions, such as depression. A greater understanding of these pathways, and the consequences of alterations to creatine bioavailability in females are needed to ensure that creatine is used to full advantage as a dietary supplement to optimize and enhance health outcomes for women. PMID:26898548

  10. 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.

  11. Ins(1,4,5)P3 facilitates ATP accumulation via phosphocreatine/creatine kinase in the endoplasmic reticulum extracted from MDCK cells

    International Nuclear Information System (INIS)

    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 μg) 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 μM inositol(1,4,5)trisphosphate (Ins(1,4,5)P3) 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 Ca2+-removal from ICM and by adding thapsigargin, a Ca2+-ATPase inhibitor, but not by 2-APB and heparin, Ins(1,4,5)P3 receptor antagonists. Administration of 500 μM 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)P3.

  12. Sildenafil citrate increases myocardial cGMP content in rat heart, decreases its hypertrophic response to isoproterenol and decreases myocardial leak of creatine kinase and troponin T

    Directory of Open Access Journals (Sweden)

    Ketat Amal F

    2005-04-01

    Full Text Available Abstract Background Cardiac hypertrophy is a major risk factor for morbidity and mortality in a number of cardiovascular diseases. Consequently, the signaling pathways that inhibit cardiac hypertrophy are currently receiving much interest. Among them, nitric oxide (NO, signaling via cGMP and cGMP-dependent protein kinase I, has been recognized as a negative regulator of cardiac hypertrophy. The present study investigated the in-vivo effect of sildenafil as a phosphodiestrase-5A (PDE-5A inhibitor on the hypertrophic response of rat heart to isoproterenol and the relation of this effect to the level of myocardial cGMP and integrity of the constitutive nitric oxide synthase (cNOS activity. Results The results showed that daily intraperitoneal administration of sildenafil per se for 10 days was without noticeable adverse effects on survival or myocardium. Conversely, daily subcutaneous administration of isoproterenol for 10 days caused significant myocardial hypertrophy, cell injury and decline in survival. When sildenafil was injected daily, one hour before isoproterenol, survival was significantly improved and the myocardium didn't show significant hypertrophy or cell injury. Interestingly, sildenafil was accompanied by significant rise in myocardial cGMP level, a parameter which was found in the present study to possess a significant negative correlation with cardiac hypertrophy and leak of cardiac troponin T into serum. At the same time, cGMP was found to possess a positive correlation with myocardial creatine kinase activity that reflects the efficiency of the energy utilization processes in the myocardium. However, in rats given Nω-nitro-L-arginine (L-NNA as a competitive inhibitor of cNOS, sildenafil failed to show any favorable effect on survival or the myocardial injury parameters used to assess isoproterenol-induced injury. Conclusion The present study suggests that increased cardiac cGMP level by sildenafil have a cardioprotective effect

  13. Role of creatine in sensitivity and function of the auditory and vestibular system

    Directory of Open Access Journals (Sweden)

    Vahid Moradi

    2015-02-01

    Full Text Available Background and Aim: Creatine plays an important role in the regulation of cellular energy in high energy demand organs such as the inner ear. It is also believed to play a protective role. This article reviewed the mechanisms and effects of creatine on the auditory and vestibular systems.Recent Findings: Creatine transporters and creatine kinase enzymes are involved in converting creatine to creatine phosphate. Phosphate is a fuel cell available in the cochlear and vestibular hair cells and the protective cells, striavascularis, peripheral and central neural pathways to the auditory cortex. It provides essential ATP for auditory and vestibular system performance. Creatine kinase prevents cochlear damage by regulating the metabolism of energy in marginal layers of the striavascularis and preventing free radical production in stressful situations. It also plays an important role in vestibular compensation. Creatine kinase dysfunction leads to an increase in the threshold of auditory brainstem potentials and a reduction in vestibular performance. The use of creatine improves vestibular evoked myogenic potentials and neurologic symptoms.Conclusion: Creatine and creatine kinase protein is essential for normal hearing and balance function and sensitivity. Creatine kinase deficiency impairs the functioning of these two systems; however, creatine consumption may boost the sensitivity of the vestibular system and neurological performance. Effects of the creatine consumption on the auditory system have not yet been examined.

  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. Comparison of serum creatine kinase estimation with short tandem repeats based linkage analysis in carriers and affected children of duchenne muscular dystrophy

    International Nuclear Information System (INIS)

    Background: Duchenne Muscular Dystrophy (DMD) is an X-linked recessive lethal, genetic disorder characterised by progressive weakness of skeletal muscles which is untreatable and transmitted to males by carrier females. Advances in laboratory techniques now focus direct mutational analysis as the most reliable and indirect analysis based on Short Tandem Repeats (STR) based linkage analysis as feasible, inexpensive, and efficient method for carrier detection and prenatal diagnosis. The objective of this study was to compare the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic efficiency of Serum Creatine Kinase (SCK) with Short Tandem Repeats (STR based linkage analysis in carriers and affected children of Duchenne Muscular Dystrophy. Methods: The study was carried out from Dec 2006 to Dec 2007 in families having index clinical cases of DMD who were referred from different hospitals for evaluation/workup of DMD. SCK was done as a preliminary investigation in all index cases. The PCR assay with STR based linkage analysis with Intron 44, 45, 49 and 50 of DMD gene were performed in all families. Six families were informative with Intron 44 of DMD gene and one family was non-informative with all four intronic markers of DMD. SCK analyses were done in all the family members and compared with PCR analysis in informative families. SCK was not performed on Chorionic villous sample (CVS) done for prenatal diagnosis of DMD, and CVS and non-informative family members were excluded from the study. Results: In carriers of DMD, the sensitivity and negative predictive value of SCK were 33.3%, and specificity and positive predictive were 100% with diagnostic efficiency of 50%. In affected cases of DMD the sensitivity and negative predictive value of SCK were 100%, and specificity and positive predictive were 91% and 88.8% respectively and diagnostic efficiency of 94.1%. Conclusion: The SCK is an excellent screening test for

  16. Serum Creatine Kinase and Sports Training Control%血清肌酸激酶与运动训练控制

    Institute of Scientific and Technical Information of China (English)

    陈瑶; 郭子渊

    2014-01-01

    control of glycolysis and mitochondrial. Therefore, in the numerous training monitoring indexes,serum CK has become one of the most important testing indexes which coaches and researchers pay most attention to. The research shows,sports and serum creatine kinase(CK)are closely related,is one of the sensitive indicators for monitoring and evaluation of training load and functional recovery,high strength,high-tempo exercise training or competitions can lead to increase serum CK significantly;With the increase of strength,if not adapting,the special ability movements will decline,if adapting,special abilities will have a breakthrough increase,low CK players,their specific performance is difficult to improve;Serum CK gives a warning effect on the damage of muscle fiber;The use of altitude training,nutrition drugs have influences on CK. In the training of winter sports,track and field,swimming,cycling and other project training,serum CK will be increased at the primary stage,heavy load training stage was positively correlated with serum CK and training load,and the stimulation of exercise intensity is particularly sensitive. In the process of training,coaches and scientific researchers should be timely to monitor the athletes' serum CK,can prevent too large exercise intensity, result injuries,improve the training effect.

  17. Flunarizine and lamotngine propnyiaxis effects on neuron-specific enolase,S-100,and brain-specific creatine kinase in a fetal rat model of hypoxic-ischemic brain damage

    Institute of Scientific and Technical Information of China (English)

    Li He; Jingyi Deng; Wendan He

    2008-01-01

    BACKGROUND:Calcium antagonists may act as neuroprotectants,diminishing the influx of calcium ions through voltage-sensitive calcium channels. When administered prophylactically,they display neuroprotective effects against hypoxic-ischemic brain damage in newborn rats.OBJECTIVE:To investigate the neuroprotective effects of flunarizine(FNZ),lamotrigine (LTG)and the combination of both drugs,on hypoxic-ischemic brain damage in fetal rats.DESIGN AND SETTING:This randomized,complete block design was performed at the Department of Pediatrics.Shenzhen Fourth People's Hospital,Guangdong Medical College.MATERIALS:Forty pregnant Wistar rats,at gestational day 20,were selected for the experiment and were randomly divided into FNZ,LTG,FNZ+LTG,and model groups,with 10 rats in each group.METHODS:Rats in the FNZ.LTG,and FNZ+LTG groups received intragastric injections of FNZ (0.5 mg/kg/d),LTG(10 mg/kg/d),and FNZ(0.5 mg/kg/d)+LTG(10 mg/kg/d),respectively.Drugs were administered once a day for 3 days prior to induction of hypoxia-ischemia.Rats in the modeJ group were not administered any drugs.Three hours after the final administration,eight pregnant rats from each group underwent model establishment hypoxia-ischemia brain damage to the fetal rats.Cesareans were performed at 6,12,24,and 48 hours later;and 5 fetal rats were removed from each mother and kept warm.Twe fetuses without model establishment were removed by planned cesarean at the same time and served as controls.A total of 0.3 mL serum was collected from fetal rats at 6,12,24,and 48 hours,respectively,following birth.MAIN OUTCOME MEASURES:Serum protein concentrations of neuron-specific enolase and S-100 were measured by ELISA.Serum concentrations of brain-specific creatine kinase were measured using an electrogenerated chemiluminescence method.RESULTS:Serum concentrations of neuron-specific enolase,S-100,and brain-specific creatine kinase were significantly higher in the hypoxic-ischemic fetal rats.compared with the non

  18. 运动营养补剂对机体乳酸脱氢酶和肌酸激酶的影响观察%Effect of sports nutrition supplements on lactate dehydrogenase and creatine kinase of aerobics athletes

    Institute of Scientific and Technical Information of China (English)

    王建永

    2015-01-01

    目的:分析健美操运动员在服用运动营养补剂后,机体中乳酸脱氢酶与肌酸激酶的变化情况。方法:以郑州师范学院、郑州大学、郑州大学体育学院的160例健美操运动员作为研究对象,依据随机数字表法分为观察和对照两组。观察组80例,采用服用运动营养补剂后进行训练,对照组80例,进行常规的体能训练。对两组的乳酸脱氢酶和肌酸激酶的影响进行分析比较。结果:对照组优秀12例,良好29例,一般39例,优良率为51.3%,明显低于观察组的优为97.5%;差异具有显著性(P<0.05);在乳酸脱氢酶和肌酸激酶浓度比较中,观察组明显优于对照组,具有差异性(P<0.05)。补给后观察组血清HL水平相比C组均有明显升高(P<0.05),HE组与H组相比明显降低(P<0.05);观察组LPL、ApoCⅡ相比于对照组明显降低(P<0.05),说明运动补给可以使血清LPL、ApoCⅡ显著增高,HL明显下降,从而达到调价脂代谢的目的。结论健美操运动员在运用运动营养补剂后,能够通过对乳酸脱氢酶和肌酸激酶浓度降低,从而调节运动员的精神状态,增加爆发力与柔韧度,使体能得以快速恢复。%Objective:To analyze the changes of lactate dehydrogenase and creatine kinase in aerobics athletes after taking sports nutrition supplements.Methods:160 cases of aerobics athletes from Zhengzhou Normal University, Zhengzhou University and Zhengzhou Sport University were selected as research object and randomly divided into Observation Group (n=80)and Control Group (n=80).The Observation Group had physical training after taking the nutrition supplements while the Control Group carried out training without supplement.An analysis and comparison was made on the effects of the supplement on the lactate dehydrogenase and creatine kinase.Results:in the Control Group,the level was excellent in 12

  19. Value Analysis of Serum Troponin I and Creatine Kinase II Determinated in Patients with Renal Failure%肾衰患者中测定血清肌钙蛋白I和肌酸激酶同工酶II的价值分析

    Institute of Scientific and Technical Information of China (English)

    秦辉

    2014-01-01

    Objective:To investigate the renal failure patients serum troponin I and creatine kinase isoenzymeⅡexpression and clinical diagnosis value.Methods:The ELISA method and enzyme dynamics method were determined in our hospital from 2009 April to 2010 April included 68 cases of renal failure patients between ( observation group) and 68 healthy subjects ( control group) of serum cardiac troponin I and creatine kinase isoenzymeⅡexpression.Results:In the observation group, the patients of cardiac troponin I and creatine kinase isoenzymeⅡwere significantly higher than those in the control group of cardiac troponin I and creatine kinase isoenzymeⅡcontent, the difference was significant (P<0.05);and the severity of renal failure in serum cardiac troponin I and creatine kinase isoenzymeⅡwere significantly higher than that of severity in the light of serum cardiac troponin I and creatine kinase isoenzymeⅡcontent, two groups of data comparison, the difference was significant (P<0.05), statistically meaningful.Conclusion:Renal failure patients serum cardiac troponin I and creatine kinase isoenzymeⅡhave abnormal expression, but as the disease severity in the serum content is also rising, can be used as an important index in diagnosis of renal failure patients.%目的:探讨肾衰患者血清中肌钙蛋白I与肌酸激酶同工酶Ⅱ的表达情况以及临床诊断价值。方法:采取ELISA法和酶动力法分别进行测定我院2009年4月到2010年4月之间收录的68例肾衰患者(观察组)与同期68名健康的对象(对照组)的血清中心肌肌钙蛋白I与肌酸激酶同工酶Ⅱ的表达情况。结果:观察组的患者肌钙蛋白Ⅰ与肌酸激酶同工酶Ⅱ的含量均明显的高于对照组的肌钙蛋白Ⅰ与肌酸激酶同工酶Ⅱ的含量,差异具有显著性(P<0.05);而且肾衰病情严重的血清中的肌钙蛋白Ⅰ与肌酸激酶同工酶Ⅱ的含量明显的高于病情程度轻血清中的肌钙蛋白Ⅰ与肌酸激

  20. Creatine kinase levels in patients with bipolar disorder: depressive, manic, and euthymic phases Comparação das fases de depressão, mania e eutimia sobre os níveis de creatina quinase em pacientes bipolares

    Directory of Open Access Journals (Sweden)

    Gustavo Feier

    2011-01-01

    Full Text Available OBJECTIVE: Bipolar disorder is a severe, recurrent, and often chronic psychiatric illness associated with significant functional impairment, morbidity, and mortality. Creatine kinase is an important enzyme, particularly for cells with high and fluctuating energy requirements, such as neurons, and is a potential marker of brain injury. The aim of the present study was to compare serum creatine kinase levels between bipolar disorder patients, in the various phases (depressive, manic, and euthymic, and healthy volunteers. METHOD: Forty-eight bipolar patients were recruited: 18 in the euthymic phase; 17 in the manic phase; and 13 in the depressive phase. The control group comprised 41 healthy volunteers. The phases of bipolar disorder were defined as follows: euthymic-not meeting the DSM-IV criteria for a mood episode and scoring 7 on the YMRS; depressive-scoring > 7 on the HDRS and OBJETIVO: O transtorno do humor bipolar é uma doença psiquiátrica grave, recorrente e crônica associada a significativo prejuízo funcional, morbidade e mortalidade. A creatina quinase tem sido proposta como um marcador de dano cerebral. A creatina quinase é uma enzima importante principalmente para células que necessitam de uma grande quantidade de energia, como os neurônios. O objetivo do presente estudo foi comparar os níveis de creatina quinase entre as fases depressiva, maníaca e eutímica de pacientes com transtorno do humor bipolar. MÉTODO: Para avaliação dos níveis de creatina quinase no soro, 48 pacientes bipolares foram recrutados; 18 estavam eutímicos, 17 estavam em mania e 13 em episódio depressivo. Foi feita também uma comparação com um grupo controle que incluiu 41 voluntários saudáveis. Grupo eutimia: foram incluídos os pacientes que não cumpriam os critérios do DSM-IV para episódios de humor e deveriam ter a pontuação inferior a oito nas escalas de avaliação de mania (YMRS e depressão (HDRS; grupo mania: foram incluídos os

  1. Creatine kinase levels in patients with bipolar disorder: depressive, manic, and euthymic phases Comparação das fases de depressão, mania e eutimia sobre os níveis de creatina quinase em pacientes bipolares

    Directory of Open Access Journals (Sweden)

    Gustavo Feier

    2011-06-01

    Full Text Available OBJECTIVE: Bipolar disorder is a severe, recurrent, and often chronic psychiatric illness associated with significant functional impairment, morbidity, and mortality. Creatine kinase is an important enzyme, particularly for cells with high and fluctuating energy requirements, such as neurons, and is a potential marker of brain injury. The aim of the present study was to compare serum creatine kinase levels between bipolar disorder patients, in the various phases (depressive, manic, and euthymic, and healthy volunteers. METHOD: Forty-eight bipolar patients were recruited: 18 in the euthymic phase; 17 in the manic phase; and 13 in the depressive phase. The control group comprised 41 healthy volunteers. The phases of bipolar disorder were defined as follows: euthymic-not meeting the DSM-IV criteria for a mood episode and scoring 7 on the YMRS; depressive-scoring > 7 on the HDRS and OBJETIVO: O transtorno do humor bipolar é uma doença psiquiátrica grave, recorrente e crônica associada a significativo prejuízo funcional, morbidade e mortalidade. A creatina quinase tem sido proposta como um marcador de dano cerebral. A creatina quinase é uma enzima importante principalmente para células que necessitam de uma grande quantidade de energia, como os neurônios. O objetivo do presente estudo foi comparar os níveis de creatina quinase entre as fases depressiva, maníaca e eutímica de pacientes com transtorno do humor bipolar. MÉTODO: Para avaliação dos níveis de creatina quinase no soro, 48 pacientes bipolares foram recrutados; 18 estavam eutímicos, 17 estavam em mania e 13 em episódio depressivo. Foi feita também uma comparação com um grupo controle que incluiu 41 voluntários saudáveis. Grupo eutimia: foram incluídos os pacientes que não cumpriam os critérios do DSM-IV para episódios de humor e deveriam ter a pontuação inferior a oito nas escalas de avaliação de mania (YMRS e depressão (HDRS; grupo mania: foram incluídos os

  2. The role of dietary creatine.

    Science.gov (United States)

    Brosnan, Margaret E; Brosnan, John T

    2016-08-01

    The daily requirement of a 70-kg male for creatine is about 2 g; up to half of this may be obtained from a typical omnivorous diet, with the remainder being synthesized in the body Creatine is a carninutrient, which means that it is only available to adults via animal foodstuffs, principally skeletal muscle, or via supplements. Infants receive creatine in mother's milk or in milk-based formulas. Vegans and infants fed on soy-based formulas receive no dietary creatine. Plasma and muscle creatine levels are usually somewhat lower in vegetarians than in omnivores. Human intake of creatine was probably much higher in Paleolithic times than today; some groups with extreme diets, such as Greenland and Alaskan Inuit, ingest much more than is currently typical. Creatine is synthesized from three amino acids: arginine, glycine and methionine (as S-adenosylmethionine). Humans can synthesize sufficient creatine for normal function unless they have an inborn error in a creatine-synthetic enzyme or a problem with the supply of substrate amino acids. Carnivorous animals, such as lions and wolves, ingest much larger amounts of creatine than humans would. The gastrointestinal tract and the liver are exposed to dietary creatine in higher concentrations before it is assimilated by other tissues. In this regard, our observations that creatine supplementation can prevent hepatic steatosis (Deminice et al. J Nutr 141:1799-1804, 2011) in a rodent model may be a function of the route of dietary assimilation. Creatine supplementation has also been reported to improve the intestinal barrier function of the rodent suffering from inflammatory bowel disease. PMID:26874700

  3. The clinical significance of serum creatine kinase isoenzyme MB and troponin I for judging the myocardial injury of hand foot mouth disease (HFMD)children%CK-MB 及 cTnI 检测对手足口病患儿心肌损害的临床意义

    Institute of Scientific and Technical Information of China (English)

    汤淑斌; 庞伟斌

    2015-01-01

    目的:探讨血清肌酸激酶同工酶(CK-MB)及肌钙蛋白 I(cTnI)检测对手足口病(HFMD)患儿心肌损害的临床意义。方法选择2012年7月至2013年6月期间在我院住院的80例手足口病患儿为 HFMD 组;50例健康体检儿童为对照组,比较分析两组 CK-MB 及 cTnI 水平。结果手足口病患儿 CK-MB 水平为38.10±19.50 U/L,cT-nI 水平为0.2±0.07μg/L,均高于对照组(14.80±10.30 U/L,0.07±0.02μg/L),差异有统计学意义(P <0.05)。HFMD 组 CK-MB 检测阳性率56.3%(45/80),明显高于 cTnI 的33.8%(27/80),差异有统计学意义(P <0.05)。经积极治疗后 CK-MB 及 cTnI 水平均明显下降,较入院时比较,差异有统计学意义(P <0.05)。结论联合检测血清CK-MB 及 cTnI 对手足口病合并心肌损害的早期诊断具有重要临床意义。%Objective To explore the clinical significance of serum creatine kinase isoenzyme MB and troponin I for judging the myocardial injury of hand foot mouth disease (HFMD)children.Methods Choose 80 HFMD patients who were hospitalized with in our college from July 2012 to June 2014 as the observation group,and selected 50 healthy check-up children as the control group.We detected and comparatively analyzed the children of the two groups in crea-tine kinase isoenzyme and troponin I difference.Results HFMD group of creatine kinase isoenzyme and troponin I tese results are greatly higher than control group,and in HFMD group the creatine kinase isoenzyme and troponin I test re-sults had significantly reduced after taking effective treatment,and in HFMD group the positive rate of creatine kinase isoenzyme was great higher than the positive rate of troponin I,all the differences were statistically significant(P <0.05).Conclusion Combined detection of serum creatine kinase isoenzyme and troponin I have the important clinical meaning for the early clinical

  4. 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.

  5. Changes of plasma glutathione S-transferase, D-lactate and creatine kinase levels in Wistar rats with acute intestinal ischemia%Wistar大鼠急性小肠缺血时血浆谷胱甘肽S转移酶、D-乳酸盐及肌酸激酶水平变化

    Institute of Scientific and Technical Information of China (English)

    王志伟; 王小艳; 厉建田; 袁琛; 李伟华

    2011-01-01

    Objective To investigate the value of plasma glutathione S-transferase, D-lactate and creatine kinase levels to the diagnosis of acute intestinal ischemia in Wistar rats. Methods Seventy Wistar rats were randomly divided into seven groups: the sham operation group and six mesentery ischemia groups in 15 minutes, 30 minutes, 1 hour, 1. 5 hours, 2 hours and 3 hours, 10 rats each. The levels of plasma glutathione S-transf erase, D-lactate and creatine kinase were determined in each group in 15 minutes, 30 minutes, 1 hour, 1. 5 hours, 2 hours and 3 hours after isolating superior mesenteric artery and blocking blood flow, and were analyzed their relationship with intestinal injury scores. Results The intestinal injury scores increased with the prolong of ischemia time(P<0. 01). Plasma glutathione S-transferase level was higher in 15 minutes than that in the sham operation group (P<0. 05) and was the highest in 1. 5 hours. Plasma D-lactate level was higher in 1 hour than that in the sham operation group(P<0. 05). Plasma creatine kinase level was higher in 1. 5 hours than that in sham operation group, showed a dramatically increase in 2 hours and kept this tendency from then on. The levels of plasma glutathione S-transferase, D-lactate and creatine kinase were positively correlated with the intestinal injury scores(P<0. 05). Conclusion Plasma glutathione S-transferase and D-lactate may be useful markers of early diagnosis of intestinal ischemia. Increased plasma creatine kinase level indicates an unfavorable prognosis.%目的:探讨血浆谷胱甘肽S转移酶(glutathione S-transferase,GST)、D-乳酸盐(D-lactate,DLA)、肌酸激酶(creatine kinase,CK)在急性小肠缺血性疾病中的诊断价值。方法:70只Wistar大鼠随机分为假手术组以及肠系膜缺血15 min,30 min,1 h,1.5 h,2 h和3 h组,每组10只。分别于游离肠系膜上动脉后即刻以及阻断血流15 min,30 min,1 h,1.5 h,2 h和3 h检测血浆中GST,DLA及CK水

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

    Directory of Open Access Journals (Sweden)

    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

  7. Approach to the patient with primary hypothyroidism accompanied by pituitary hyperplasia and increased serum creatine kinase level%伴肌酸激酶升高、垂体增大的原发性甲状腺功能减退症的临诊应对

    Institute of Scientific and Technical Information of China (English)

    郭菲; 戴晨琳; 朱铁虹; 邱明才

    2012-01-01

    原发性甲状腺功能减退症(甲减)患者血中甲状腺激素水平降低,由于负反馈作用减弱使垂体增大,单纯影像学检查易与垂体瘤混淆;同时甲减合并肌酸激酶显著升高的病例也不少见,可能会被误诊为肌炎.本文介绍1例原发性甲减合并明显垂体增生、肌酸激酶升高患者的诊治过程,以引起对甲减非特异临床表现的重视,进行正确的治疗.%Pituitary hyperplasia may be found in patients with primary hypothyroidism as the decreased thyroid hormone level attenuates negative feedback effect.Sometimes the enlarged pituitary may be misdiagnosed as a pituitary tumor.Patients with long term untreated hypothyroidism often have extremely high level of serum creatine kinase and thus may be misdiagnosed as suffering from myositis.In order to increase the awareness of the nonspecific symptoms of primary hypothyroidism,this article introduces the diagnosis and treatment of a patient with primary hypothyroidism with raised serum creatine kinase level and pituitary hyperplasia.

  8. 大强度离心运动大鼠不同时相骨骼肌结构及血白细胞介素6、肌酸激酶、肌酸激酶同工酶的变化%Skeletal muscle structure at different phases after eccentric exercise and changes of blood interleukin-6, creatine kinase and creatine kinase isoenzyme in rats

    Institute of Scientific and Technical Information of China (English)

    华冰; 董柔; 苏全生

    2009-01-01

    -induced muscle damage, thereby to avoid delayed onset muscle soreness. At present, experimental research is scarce that apply intedeukin-6 (IL-6), creatine kinase (CK) and creatine kinase isoenzyme (CK-MM) to evaluate skeletal muscle damage.OBJECTIVE: To observe the effects of exercise precondiUoning on muscle damage at different phases after eccentric exercise and changes of blood IL-6, CK and CK-MM.DESIGN, TIME AND SETTING: The randomized control animal expedmant was carded out in the Animal Laboratory of Chengdu Sports University between 2006 and 2007. MATERIALS: Eighty female adult SD rats, weighing (231.3+12.44) g, were adopted. Eighty rats were randomly divided into without exercise preconditioning group (n=40) and exercise preconditioning group (n=40). Each group was assigned into 5 subsets, termed before exercise, immediately after exercise, 24, 48, 72 hours after exercise, with 8 rats in each subset. METHODS: Except before exercise subset, other rats in the without exercise preconditioning group were forced to do treadmill exercise (19-21 m/min, -16° incline, 90 minutes). All rats of exercise preconditioning group were forced to do eccentric treadmill exercise for two weeks. After two weeks, treadmill test was made for rats except before exercise subset. MAIN OUTCOME MEASURES: Soleus muscle structure, blood IL-6, CK and CK-MM immediately, 24, 48, 72 hours after eccentric exercise.RESULTS: The soleus muscle was damaged after exercise, especially in without exercise preconditioning group at 24-48 hours after exercise. Blood IL-6 of without exercise preconditioning group increased significantly immediately after exercise and then gradually decreased, but again raised at 72 hours after exercise. In the exercise preconditioning group, blood IL-6 slightly reduced immediately after exercise and then gradually increased. Peak value appeared at 48 hours. After exercise, IL-6 of exercise preconditioning group was obviously lower than that of without exercise preconditioning

  9. IFCC primary reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C. International Federation of Clinical Chemistry and Laboratory Medicine. Part 7. Certification of four reference materials for the determination of enzymatic activity of gamma-glutamyltransferase, lactate dehydrogenase, alanine aminotransferase and creatine kinase accord.

    Science.gov (United States)

    Siekmann, Lothar; Bonora, Roberto; Burtis, Carl A; Ceriotti, Ferruccio; Clerc-Renaud, Pascale; Férard, Georges; Ferrero, Carlo A; Forest, Jean-Claude; Franck, Paul F H; Gella, F-Javier; Hoelzel, Wieland; Jørgensen, Poul Jørgen; Kanno, Takashi; Kessner, Art; Klauke, Rainer; Kristiansen, Nina; Lessinger, Jean-Marc; Linsinger, Thomas P J; Misaki, Hideo; Mueller, Mathias M; Panteghini, Mauro; Pauwels, Jean; Schiele, Françoise; Schimmel, Heinz G; Vialle, Arlette; Weidemann, Gerhard; Schumann, Gerhard

    2002-07-01

    This paper is the seventh in a series dealing with reference procedures for the measurement of catalytic activity concentrations of enzymes at 37 degrees C and the certification of reference preparations. Other parts deal with: Part 1. The Concept of Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes; Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase; Part 3. Reference Procedure for the Measurement of Catalytic Concentration of Lactate Dehydrogenase; Part 4. Reference Procedure for the Measurement of Catalytic Concentration of Alanine Aminotransferase; Part 5. Reference Procedure for the Measurement of Catalytic Concentration of Aspartate Aminotransferase; Part 6. Reference Procedure for the Measurement of Catalytic Concentration of Gamma-Glutamyltransferase. A document describing the determination of preliminary reference values is also in preparation. The certification of the catalytic activity concentrations as determined by the recently elaborated IFCC primary reference methods at 37 degrees C of four enzyme preparations, namely IRMM/IFCC 452 (gamma-glutamyltransferase), IRMM/IFCC 453 (lactate dehydrogenase 1), IRMM/IFCC 454 (alanine aminotransferase) and IRMM/IFCC 455 (creatine kinase) is described. Homogeneity data were derived from previous results. Stability was assessed using recently obtained data as well as data from previous stability studies. The collaborative study for value assignment was performed under a strict quality control scheme to ensure traceability to the primary reference method. Uncertainty of the materials was assessed in compliance with the Guide to the Expression of Uncertainty in Measurement. The certified values obtained at 37 degrees C are 1.90 microkat/l +/- 0.04 microkat/l (114.1 U/l +/- 2.4 U/l), for gamma-glutamyltransferase, 8.37 microkat/l +/- 0.12 microkat/l (502 U/l +/- 7 U/l), for lactate dehydrogenase 1, 3.09 microkat/l +/- 0.07 microkat

  10. Beyond muscles: The untapped potential of creatine.

    Science.gov (United States)

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

    2016-08-01

    Creatine is widely used by both elite and recreational athletes as an ergogenic aid to enhance anaerobic exercise performance. Older individuals also use creatine to prevent sarcopenia and, accordingly, may have therapeutic benefits for muscle wasting diseases. Although the effect of creatine on the musculoskeletal system has been extensively studied, less attention has been paid to its potential effects on other physiological systems. Because there is a significant pool of creatine in the brain, the utility of creatine supplementation has been examined in vitro as well as in vivo in both animal models of neurological disorders and in humans. While the data are preliminary, there is evidence to suggest that individuals with certain neurological conditions may benefit from exogenous creatine supplementation if treatment protocols can be optimized. A small number of studies that have examined the impact of creatine on the immune system have shown an alteration in soluble mediator production and the expression of molecules involved in recognizing infections, specifically toll-like receptors. Future investigations evaluating the total impact of creatine supplementation are required to better understand the benefits and risks of creatine use, particularly since there is increasing evidence that creatine may have a regulatory impact on the immune system. PMID:26778152

  11. Neuroprotective effects of some creatine derivative compounds

    Directory of Open Access Journals (Sweden)

    L. Perasso

    2010-01-01

    Full Text Available Some derivatives more lipophylic than creatine, thus theoretically being capable to better cross the blood-brain barrier, were studied for their neuroprotective effect in mouse hippocampal slices. In mouse hippocampal slices we found that EM2 I is ineffective, EM"" weakly increased the latency to population spike disapperance during anoxia. Creatine, Creatine-MG-complex (acetate and Phosphocreatine-Mg-complex (acetate increased more effectively the latency to population spike disappearance during anoxia. Moreover, Phosphocreatine-Mg-complex (acetate significantly reduced neuronal hyperexcitability during anoxia, an effect that no other compound (including creatine itself showed. Summing up, EM2 I is not useful for brain protection, while EM22 and cgelates of both creatine and phosphocreatine di replicate some of the knownn protective effects of creatine. In addition, Phosphocreatine-Mg-complex (acetate also reduced neuronal hyperexcitability during anoxia.

  12. 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.

  13. Biological effects from a static magnetic field generated by a 0.5 T Magnetic Resonance system on the enzyme activity of catalase and creatin kinase in rodents; Effetti biologici del campo magnetico statico di un tomografo a Risonanza Magnetica da 0,5 T sull'attivita' enzimatica della catalasi e della creatinchinasi nel ratto

    Energy Technology Data Exchange (ETDEWEB)

    Salerno, S. [Ist. di Radiologia P. Cignolini, Palermo (Italy); Ciaccio, M.; Bono, A. [Palermo Univ. (Italy). Ist. di Chimica Biologica; Lo Casto, A. [Consiglio Nazionale delle Ricerche, Palermo (Italy). Ist. per lo Studio di Metodologie Diagnostiche Avanzate; De Maria, M.; Lagalla, R.; Cardinale, A.E.

    1999-03-01

    The authors investigated possible alterations in the enzyme activity of catalase and isozyme MB-creatin kinase induced by prolonged exposure of laboratory rodents to a static magnetic field generated by a 0.5 T Magnetic Resonance unit. The results seems to exclude any alterations in the activity of catalase and MB-CK after exposure. However some homeostatic mechanism peculiar to multi cellular organisms might act 'in vivo' to adapt to the effects of the static magnetic field during exposure. [Italian] Scopo del presente lavoro e' indagere l'eventuale verificarsi di alterazioni dell'attivita' enzimatica della catalasi e dell'isoenzima MB della creatinchinasi, indotte dalla prolungata esposizione di animali da laboratorio al campo magnetico statico generato da un Tomografo a Risonanza Magnetica (RM) da 0,5 T. I risultati del lavoro porterebbero a escludere alterazioni dell'attivita' della catalasi e della MB-creatinchinasi conseguenti all'esposizione. Occorre tuttavia rilevare che 'in vivo' possono agire alcuni meccanismo omeospatici, peculiari degli organismi pluricellulari, di adattamento agli effetti dei campi magnetici, che potrebbero essere intervenuti durante l'esposizione.

  14. 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.

  15. 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.

  16. 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

  17. The creatine transporter mediates the uptake of creatine by brain tissue, but not the uptake of two creatine-derived compounds.

    Science.gov (United States)

    Lunardi, G; Parodi, A; Perasso, L; Pohvozcheva, A V; Scarrone, S; Adriano, E; Florio, T; Gandolfo, C; Cupello, A; Burov, S V; Balestrino, M

    2006-11-01

    Hereditary creatine transporter deficiency causes brain damage, despite the brain having the enzymes to synthesize creatine. Such damage occurring despite an endogenous synthesis is not easily explained. This condition is incurable, because creatine may not be delivered to the brain without its transporter. Creatine-derived compounds that crossed the blood-brain barrier in a transporter-independent fashion would be useful in the therapy of hereditary creatine transporter deficiency, and possibly also in neuroprotection against brain anoxia or ischemia. We tested the double hypothesis that: (1) the creatine carrier is needed to make creatine cross the plasma membrane of brain cells and (2) creatine-derived molecules may cross this plasma membrane independently of the creatine carrier. In in vitro mouse hippocampal slices, incubation with creatine increased creatine and phosphocreatine content of the tissue. Inhibition of the creatine transporter with 3-guanidinopropionic acid (GPA) dose-dependently prevented this increase. Incubation with creatine benzyl ester (CrOBzl) or phosphocreatine-Mg-complex acetate (PCr-Mg-CPLX) increased tissue creatine content, not phosphocreatine. This increase was not prevented by GPA. Thus, the creatine transporter is required for creatine uptake through the plasma membrane. Since there is a strong indication that creatine in the brain is mainly synthesized by glial cells and transferred to neurons, this might explain why hereditary transporter deficiency is attended by severe brain damage despite the possibility of an endogenous synthesis. CrOBzl and PCr-Mg-CPLX cross the plasma membrane in a transporter-independent way, and might be useful in the therapy of hereditary creatine transporter deficiency. They may also prove useful in the therapy of brain anoxia or ischemia. PMID:16949212

  18. 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. PMID:26219105

  19. The Uses of Isoforms of Creatine Kinase CK-MM in the Early Diagnosis of the Patient with Duchenne Muscular Dystrophy%肌型肌酸激酶同工酶亚型在早期诊断假肥大型肌营养不良中的价值

    Institute of Scientific and Technical Information of China (English)

    赵昕; 韩靖云; 李红; 叶贤坤; 赵振军

    2001-01-01

    Objective To study the changes of isoforms of creatine kinaseCK-MM in patients with Duchenne muscular dystrophy for the purpose of early diagnosis as well as evaluation of seriousness of the disease. Methods A dis-continuous buffer system was used. CK-MM isoform was separated by electrophoresis under the condition of constant current and low voltage, then fluorescence scanning. Results The nature of DMD patient was gradually getting worse along with the age increase. There was a statistically significant change of the isoform ratio MM2/MM1 in each stage of DMD compared with the normal control ( P< 0.05 ); there was also significant change of the isoform ratio MM2/MM1 between each stage of the subject ( P < 0.05 ). Conclusions The change of CK-MM isoforms is a specific indicator in early diagnosis of DMD. It is a important indicator for evaluation of seriousness of the disease. It is also useful in the evaluation of the real effect of some treatment methods.%目的 研究假肥大型肌营养不良(DMD)患者肌型肌酸激酶(CK-MM)亚型的变化,为早期诊断和正确评价病情提供依据。方法 采用不连续缓冲体系,在稳流低压条件下电泳分离CK-MM亚型,荧光扫描。结果 随着DMD患者病情的加重,其不同阶段的MM2/MM1均与对照组差异显著(P<0.05);DMD患者不同阶段的MM2/MM1值差异也显著(P<0.05)。结论 CK-MM亚型的改变是DMD的早期诊断指标,是判断病情及科学评价治疗效果的依据。

  20. 强迫体位与谐振对兔血清SOD活性、MDA含量和肌肉组织中CK活性的影响*%Influence of the forced posture at resonance on activity of superoxide dismutase (SOD),level of the malondialdehyde (MDA) in the serum,and activity of creatine kinase (CK) in musclar tissue

    Institute of Scientific and Technical Information of China (English)

    左新成; 张广超; 黄昌林

    2015-01-01

    Objective To investigate the influence of activity of superoxide dismutase (SOD),level of malondialdehyde(MDA) in the serum,and activity of creatine kinase(CK) in musclar tissue in the forced posture rabbits at resonance. Methods Animals (75 New Zealand rabbits) were randomly divided into normal control group,modeling control group,4 Hz vibration group,the 5 Hz vibration group and 6 Hz vibration group,n=15 for each. Peripheral blood was taken from 5 rabbits at each group at the end of the 2 ,4 and 6 weeks separately. After the animals were killed,the psoas about 0.2 g were taken. Then the activity of the superoxide dismutase (SOD),the content of the malondialdehyde (MDA) in the serum,and the activity of creatine kinase in the homogenate were detected. Results The activity of SOD of different vibration group was less than normal control group at different time (P<0.05),and with the development of the time the activity of SOD of different group was less and less(P<0.05);the content of the MDA of different vibration group was more than normal control group at different time(P<0.05),and with the development of the time the content of the MDA of different group was more and more (P<0.05);the activity of the CK of different vibration group was more than normal control group at different time (P<0.05),and with the development of the time the activity of the CK of different group was more and more(P<0.05). Conclusion Forced posture and the resonance can cause the change of the activity of SOD, the content of the MDA in the serum and the activity of the CK in muscles of low back ,and related to time. The influence on the serum markers of muscles of resonance at the frequency of 4Hz,acceleration of 1.0g is most obvious. A negative correlation is found between the content of MDA and the activity of SOD. The extent of damage of the muscles is correlated positively with the content of the MDA.%目的:探讨强迫体位下谐振对兔血清超氧化物歧化酶(SOD)活性

  1. 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…

  2. Association of Macroamylasemia and Type I Macro-Creatine Kinasemia. A Case Report

    Directory of Open Access Journals (Sweden)

    Fernando Gallucci

    2007-09-01

    Full Text Available Context Macroenzymes are serum enzymes presenting a higher molecular mass than the corresponding enzymes normally found in physiologic conditions or specific diseases, causing falsely increased total serum enzyme levels. The occurrence of macroenzymes represents a rare event in clinical practice, leading to unnecessary and often invasive additional diagnostic procedures. Macroamylase and macro-creatine kinase belong to this category and may generate diagnostic confusion in the differential diagnosis between acute pancreatitis and acute myocardial infarction. Until now, the association of macroamylase and macrocreatine kinase in the same patient has never been described. Case report A 68-year-old female patient presenting with increased serum levels of creatinine kinase and amylase at admission. Conclusions This article reports the association of macroamylase and macrocreatine kinase in the same patient for the first time.

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

    OpenAIRE

    Alexandre Soares Fagundes; Fernando Queiroz de Almeida; Fernanda Nascimento de Godoi; Eduardo Xavier Ferreira Migon; Tiago Marques dos Santos; Paula Vieira Evans Hossell Laranjeira

    2011-01-01

    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 maltodext...

  4. Acute Changes in Creatine Kinase Serum Levels in Adults Submitted a Static Flexibilizing and Maximal Strength Test Modificaciones agudas de los niveles séricos de creatina quinasa en adultos jóvenes sometidos al trabajo de flexibilidad estática y de fuerza máxima

    Directory of Open Access Journals (Sweden)

    L. Conte

    2010-09-01

    Full Text Available

     

    ABSTRACT

    Strength and flexibility, important components of a training and their maximal values are obtained through specific tests. However, little information about the damage effect in a skeletal muscle is known. The aim was to verify a serum CK changes 24 h after a lengthening and static flexibilizing routine and a maximal dynamic strength tests. The sample, was by 14 subjects (man and women, 28 ± 6 yr., control group (CG N = 7 and experimental group (EG N = 4 that was submitted a lengthening routine (EG-LG, a static flexibilizing routine (EG-FLEX and a 1-RM test (EG-1-RM. The anthropometrics were obtained by digital scale with stadiometer. 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 dynamic strength through bench press and leg press. The static flexibilizing routine consisted in three 20 seconds sets until the point of maximal discomfort. The lengthening was done in normal movement amplitude during 6 seconds. In analysis inter groups was a significant difference (p < .05 in the values of GE-1RM (D = 118,7 U/L, p= .02 when compared to the GC. We concluded that only maximal strength dynamic test was capable to raise the CK serum levels 24 h after exercise
    Key Words:
    Lengthening, Static Flexibilizing, 1-RM, Creatine Kinase

     

    RESUMEN

    La fuerza y flexibilidad, muy importantes en entrenamiento, obtienen sus valores máximos a través de test específicos. Se sabe poco sobre sus efectos perjudiciales en el aparato músculo tendinoso. El objetivo fue verificar las modificaciones séricas de CK 24h después de estiramientos, flexibilidad estática y

  5. The effect of creatine supplementation upon inflammatory and muscle soreness markers after a 30km race.

    Science.gov (United States)

    Santos, R V T; Bassit, R A; Caperuto, E C; Costa Rosa, L F B P

    2004-09-01

    We have evaluated the effect of a creatine supplementation protocol upon inflammatory and muscle soreness markers: creatine kinase (CK), lactate dehydrogenase (LDH), prostaglandin E2) (PGE2) and tumor necrosis factor-alpha (TNF-alpha) after running 30km. Runners with previously experience in running marathons, with their personal best between 2.5-3h were supplemented for 5 days prior to the 30km race with 4 doses of 5g of creatine and 15g of maltodextrine per day while the control group received the same amount of maltodextrine. Pre-race blood samples were collected immediately before running the 30km, and 24h after the end of the test (the post-race samples). After the test, athletes from the control group presented an increase in plasma CK (4.4-fold), LDH (43%), PGE2 6.6-fold) and TNF-alpha (2.34-fold) concentrations, indicating a high level of cell injury and inflammation. Creatine supplementation attenuated the changes observed for CK (by 19%), PGE2 and TNF-alpha (by 60.9% and 33.7%, respectively, p<0.05) and abolished the increase in LDH plasma concentration observed after running 30km, The athletes did not present any side effects such as cramping, dehydration or diarrhea, neither during the period of supplementation, nor during the 30km race. All the athletes finished the race in a time equivalent to their personal best +/- 5.8%. These results indicate that creatine supplementation reduced cell damage and inflammation after an exhaustive intense race. PMID:15306159

  6. [Amides of creatine: perspectives of neuroprotection].

    Science.gov (United States)

    Vlasov, T D; Chefu, S G; Baĭsa, A E; Leko, M V; Burov, S V; Veselkina, O S

    2011-07-01

    We evaluated the efficacy of derivatives of creatine and amino acids (CrAA) for decreasing cerebral injury in rats with transient middle cerebral artery occlusion (MCAO). Neuroprotective effects of amides of creatine and glycine (CrGlyOEt), phenylalanine (CrPheNH2), thyrosine (CrTyrNH2), and GABA (CrGABAOEt) were investigated. Brain injury was evaluated on day 2 after transient MCAO using a TTC staining of brain slices. Compared with the MCAO control group, all the CrAms showed decreased cerebral injury (p < 0.05). However CrPheNH2, CrTyrNH2, and CrGABAOEt were toxic after intravenous administration and investigated only after intraperitoneal injection. CrGlyOEt did not show any toxicity at dose of 1 mmol/kg. These data evidenced that creatinyl amides can represent promising candidates for the development of new drugs useful in brain ischemia treatment. PMID:21961295

  7. Supplementation of Creatine in Sportsman with Hyperhomocysteinemia

    Czech Academy of Sciences Publication Activity Database

    Kohlíková, E.; Petr, M.; Navrátil, Tomáš; Přistoupilová, K.; Přistoupil, T. I.; Pelclová, D.; Žák, J.; Heyrovský, Michael

    Praha: IV. interní klinika 1. LF UK Praha, 2009 - (Tvrznická, E.), s. 23-26 ISBN 978-80-254-5389-6. [Atherosklerosa 2009. Praha (CZ), 09.09.2009-11.09.2009] R&D Projects: GA ČR GA203/07/1195; GA AV ČR IAA400400806 Institutional research plan: CEZ:AV0Z40400503 Keywords : creatine (CR) * creatinine * folates * homocysteine Subject RIV: CF - Physical ; Theoretical Chemistry

  8. 2,5-己二酮染毒大鼠血清肌酸激酶、乳酸脱氢酶活性及髓鞘碱性蛋白含量的变化%Changes of the activities of creatine kinase, lactate dehydrogenates and the levels of myelin protein in HD-treated rats

    Institute of Scientific and Technical Information of China (English)

    董华; 朱明星; 谢克勤; 宋福永

    2011-01-01

    目的 研究2,5-己二酮染毒大鼠血清中肌酸激酶(creatine kinase,CK)、乳酸脱氢酶(lactate dehydrogenates,LDH)活性及髓鞘碱性蛋白含量(myelin basic protein,MBP)的变化,探讨它们作为正己烷中毒性周围神经病生物标志物的可能性.方法 Wistar雄性大鼠48只,随机分为对照组、低剂量染毒组和高剂量染毒组,每组16只.对照组给予生理盐水腹腔注射,低剂量和高剂量染毒组分别给予200和400 mg/kg 2,5-己二酮(2,5-hexanedione,HD)腹腔注射,连续6周.观察动物体重、神经行为学指标变化,实验结束后取腓肠肌做病理检查,取坐骨神经做电镜观察,测定血清CK、LDH活性和MBP含量.结果 HD染毒6周后,染毒大鼠出现步态异常,腓肠肌病理提示神经源性肌肉萎缩,坐骨神经电镜结果显示轴突变性.与对照组相比,200和400 mg/kg染毒组大鼠血清CK活性分别下降19.72%和54.37%,差异有统计学意义(P<0.05);与对照组相比,400 mg/kg染毒组大鼠血清MBP含量增加34.82%,差异有统计学意义(P<0.05);而LDH活性变化无统计学意义(P>0.05).结论 2,5-HD中毒性周围神经病大鼠血清CK活性降低、MBP含量升高,它们有可能成为正已烷中毒性周围神经损害的早期生物标志物.%Objective To investigate changes of the activities of crestine kinase(CK) ,lactate dehydrogenates(LDH) and the level of myelin protein (MBP)in HD-treated rats for seeking potential biomarkers of peripheral nerve injury. Methods Totally 48 healthWistarrats were randomly divided into control group, low and high doses of 2, S-hexanedione (HD) groups. The control group was injected physiological saline; 2,5-HD groups were potentially injected 2,5-HD with the dose of 200 mg/kg,400 mg/kg for one time per day,5 days per week, respectively. All three groups had been treated five times per week for six weeks. Body weight and gait score were measured per week. After the experiment gastrocnemius muscles and

  9. Creatine Supplementation and Swim Performance: A Brief Review

    OpenAIRE

    Hopwood, Melissa J.; Kenneth Graham; Rooney, Kieron B.

    2006-01-01

    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. Researc...

  10. Creatine supplementation and oxidative stress in rat liver

    OpenAIRE

    Araújo, Michel B; Moura, Leandro P; Junior, Roberto C Vieira; Junior, Marcelo C; Dalia, Rodrigo A; Sponton, Amanda C; Ribeiro, Carla; Mello, Maria Alice R

    2013-01-01

    Background The objective of this study was to determine the effects of creatine supplementation on liver biomarkers of oxidative stress in exercise-trained rats. Methods Forty 90-day-old adult male Wistar rats were assigned to four groups for the eight-week experiment. Control group (C) rats received a balanced control diet; creatine control group (CCr) rats received a balanced diet supplemented with 2% creatine; trained group (T) rats received a balanced diet and intense exercise training eq...

  11. Protective effects of some creatine derivatives in brain tissue anoxia.

    Science.gov (United States)

    Perasso, Luisa; Lunardi, Gian Luigi; Risso, Federica; Pohvozcheva, Anna V; Leko, Maria V; Gandolfo, Carlo; Florio, Tullio; Cupello, Aroldo; Burov, Sergey V; Balestrino, Maurizio

    2008-05-01

    Some derivatives more lipophylic than creatine, thus theoretically being capable to better cross the blood-brain barrier, were studied for their protective effect in mouse hippocampal slices. We found that N-amidino-piperidine is harmful to brain tissue, and that phosphocreatine is ineffective. Creatine, creatine-Mg-complex (acetate) and phosphocreatine-Mg-complex (acetate) increased the latency to population spike disappearance during anoxia. Creatine and creatine-Mg-complex (acetate) also increased the latency of anoxic depolarization, while the delay induced by phosphocreatine-Mg-complex (acetate) was of borderline significance (P = 0.056). Phosphocreatine-Mg-complex (acetate) significantly reduced neuronal hyperexcitability during anoxia, an effect that no other compound (including creatine itself) showed. For all parameters except reduced hyperexcitability the effects statistically correlated with tissue levels of creatine or phosphocreatine. Summing up, exogenous phosphocreatine and N-amidino piperidine are not useful for brain protection, while chelates of both creatine and phosphocreatine do replicate some of the known protective effects of creatine. In addition, phosphocreatine-Mg-complex (acetate) also reduced neuronal hyperexcitability during anoxia. PMID:17940889

  12. On the Importance of Exchangeable NH Protons in Creatine for the Magnetic Coupling of Creatine Methyl Protons in Skeletal Muscle

    Science.gov (United States)

    Kruiskamp, M. J.; Nicolay, K.

    2001-03-01

    The methyl protons of creatine in skeletal muscle exhibit a strong off-resonance magnetization transfer effect. The mechanism of this process is unknown. We previously hypothesized that the exchangeable amide/amino protons of creatine might be involved. To test this the characteristics of the creatine magnetization transfer effect were investigated in excised rat hindleg skeletal muscle that was equilibrated in either H2O or D2O solutions containing creatine. The efficiency of off-resonance magnetization transfer to the protons of mobile creatine in excised muscle was similar to that previously reported in intact muscle in vivo. Equilibrating the isolated muscle in D2O solution had no effect on the magnetic coupling to the immobile protons. It is concluded that exchangeable protons play a negligible role in the magnetic coupling of creatine methyl protons in muscle.

  13. Changes of BB Isoenzyme of Creatine Kinase, CaATPase and Calpain in Experimental Autoimmune Encephalomyelitis Mouse Brain and Spinal Cord%实验性自身免疫性脑脊髓炎小鼠脑组织和脊髓中脑型肌酸激酶、钙泵和钙中性蛋白酶的变化

    Institute of Scientific and Technical Information of China (English)

    王沛; 郑荣远; 林福虹; 王赵伟; 厉芳; 张正学

    2011-01-01

    Aim: To investigate the changes ofBB isoenzyme of creatine kinase(CK-BB), CaATPase and calpain in experimental autoimmune encephalomyelitis(EAE) mouse brain and spinal cord. Methods: C57BL/6 mice were induced into the models of EAE with multiple sclerosis by myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) peptides. Behavioral changes of the EAE mice were observed and recorded. With HE staining, LFB myelin staining, the changes of the central nervous tissues, CK-BB, CaATPase and calpain activity were assayed in the peak incidence by using microplate reader and spectrophotometer (19 days after immunization). Results: Compared with the control group, the results of the EAE group were as follows :① Mean daily clinical scores and cumulative scores were mcreased(P<0.01).② HE staining: Central inflammatory cell infiltration became obvious(P<0.05).③ LFB Clinical Analysis of 15 Cases with Spontaneous Intracranial Hypotension HeadacheKEY WORDS spontaneous intracranial hypotension; headache; secondary headacheABSTRACT Aim: To explore the clinical features of spontaneous intracranial hypotension(SIH) headache.Methods: Clinical data of 15 cases of SIH headache were retrospectively analyzed. Results: 12 0f 15 caseswere acute onset, 9 were female. The ages of onset were from 28 t0 56 years. 93.33% cases had posturalheadache, with the common concomitant symptoms of nausea and vomit. The average cerebrospinal fluidpressure was (41.2 + 30.85)mmH20, which was higher in male than in female (P<0.05). Radionuclidecisternography and imaging were normal. All cases were cured after conservative treatment. Conclusion:Typical postural headache and cerebrospinal fluid pressure less than 60 mmH.O were the main features in SIHheadache, which were with favorable prognosis.%目的:观察实验性自身免疫性脑脊髓炎(EAE)小鼠模型脑组织和脊髓中脑型肌酸激酶(CK-BB)、钙泵(CaATPase) 和钙中性蛋白酶(calpain)的变化.方法:C57BL/6

  14. Creatine Use and Exercise Heat Tolerance in Dehydrated Men

    OpenAIRE

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

    2006-01-01

    Context: Creatine monohydrate (CrM) use is highly prevalent in team sports (eg, football, lacrosse, ice hockey) and by athletes at the high school, college, professional, and recreational levels. Concerns have been raised about whether creatine use is associated with increased cramping, muscle injury, heat intolerance, and risk of dehydration.

  15. Creatine Synthesis: An Undergraduate Organic Chemistry Laboratory Experiment

    Science.gov (United States)

    Smith, Andri L.; Tan, Paula

    2006-01-01

    Students in introductory chemistry classes typically appreciate seeing the connection between course content and the "real world". For this reason, we have developed a synthesis of creatine monohydrate--a popular supplement used in sports requiring short bursts of energy--for introductory organic chemistry laboratory courses. Creatine monohydrate…

  16. 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.

  17. Creatine supplementation and glycemic control: a systematic review.

    Science.gov (United States)

    Pinto, Camila Lemos; Botelho, Patrícia Borges; Pimentel, Gustavo Duarte; Campos-Ferraz, Patrícia Lopes; Mota, João Felipe

    2016-09-01

    The focus of this review is the effects of creatine supplementation with or without exercise on glucose metabolism. A comprehensive examination of the past 16 years of study within the field provided a distillation of key data. Both in animal and human studies, creatine supplementation together with exercise training demonstrated greater beneficial effects on glucose metabolism; creatine supplementation itself demonstrated positive results in only a few of the studies. In the animal studies, the effects of creatine supplementation on glucose metabolism were even more distinct, and caution is needed in extrapolating these data to different species, especially to humans. Regarding human studies, considering the samples characteristics, the findings cannot be extrapolated to patients who have poorer glycemic control, are older, are on a different pharmacological treatment (e.g., exogenous insulin therapy) or are physically inactive. Thus, creatine supplementation is a possible nutritional therapy adjuvant with hypoglycemic effects, particularly when used in conjunction with exercise. PMID:27306768

  18. 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

  19. 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.

  20. 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. PMID:23560674

  1. 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…

  2. 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.

  3. Creatine transporter deficiency: Novel mutations and functional studies.

    Science.gov (United States)

    Ardon, O; Procter, M; Mao, R; Longo, N; Landau, Y E; Shilon-Hadass, A; Gabis, L V; Hoffmann, C; Tzadok, M; Heimer, G; Sada, S; Ben-Zeev, B; Anikster, Y

    2016-09-01

    X-linked cerebral creatine deficiency (MIM 300036) is caused by deficiency of the creatine transporter encoded by the SLC6A8 gene. Here we report three patients with this condition from Israel. These unrelated patients were evaluated for global developmental delays and language apraxia. Borderline microcephaly was noted in one of them. Diagnosis was prompted by brain magnetic resonance imaging and spectroscopy which revealed normal white matter distribution, but absence of the creatine peak in all three patients. Biochemical testing indicated normal plasma levels of creatine and guanidinoacetate, but an increased urine creatine/creatinine ratio. The diagnosis was confirmed by demonstrating absent ([14])C-creatine transport in fibroblasts. Molecular studies indicated that the first patient is hemizygous for a single nucleotide change substituting a single amino acid (c.619 C > T, p.R207W). Expression studies in HeLa cells confirmed the causative role of the R207W substitution. The second patient had a three base pair deletion in the SLC6A8 gene (c.1222_1224delTTC, p.F408del) as well as a single base change (c.1254 + 1G > A) at a splicing site in the intron-exon junction of exon 8, the latter occurring de novo. The third patient, had a three base pair deletion (c.1006_1008delAAC, p.N336del) previously reported in other patients with creatine transporter deficiency. These three patients are the first reported cases of creatine transporter deficiency in Israel. PMID:27408820

  4. Effects of creatine supplementation in taekwondo practitioners

    Directory of Open Access Journals (Sweden)

    Rafael Manjarrez-Montes de Oca

    2013-04-01

    Full Text Available Introduction: Taekwondo (TKD is a combat sport, which has also been proposed as a fitness program, with a strong anaerobic component. Creatine (Cr supplementation is used to improve both anaerobic exercise performance and body composition. Therefore, Cr supplementation could be beneficial in TKD. Aims: To determine the effect of Cr supplementation (50 mg/kg body wt on body composition, anaerobic power and blood chemistry in young male TKD practitioners. Methods: Ten male TKD practitioners (age [20 ± 2 yr], height [1.69 ± 0.06 m], and mass [67 ± 9.8 kg] participated in a placebo-controlled, double blind, crossover study. Body composition (DEXA, anaerobic power (Wingate Test, blood lactate and blood chemistry were measured before and after supplementation. Differences between data before and after supplementation were calculated for each treatment (Cr and Placebo and were compared using the Wilcoxon signed-rank test. Results: Fat mass (kg decreased after placebo (Mdn [IqR] = -0.75 [-1.44 to 0.03] and increased following Cr intake (0.17 [-0.77 to 1.13] kg (Z = 2.191, p < 0.028, r = 0.49. Serum triglyceride concentration (mg/mL increased after Cr (45.00 [-7.50 to 75.00] and decrease with placebo (-7.00 [-10.75 to 12.00] (Z = 2.090, p < 0.037, r = 0.47. No changes were found in others parameters. Conclusion: Cr supplementation may increase fat mass and serum triglycerides concentration in young male TKD practitioners without improvement in anaerobic power. Cr supplementation appears to be safe, but athletes should be careful when they want to loss fat.

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

    Science.gov (United States)

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

    1999-04-01

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

  6. Chitosan-g-polyaniline: a creatine amidinohydrolase immobilization matrix for creatine biosensor

    Directory of Open Access Journals (Sweden)

    2009-09-01

    Full Text Available A novel matrix composed of chitosan-graft-polyaniline (CHIT-g-PANI was electrochemically prepared to investigate the immobilization of creatine amidinohydrolase (CAH. CAH enzyme was covalently immobilized with the CHIT-g-PANI matrix using glutaraldehyde as a linker. The resulting CAH/CHIT-g-PANI biomatrix was characterized with Fourier transform infrared spectroscopy (FTIR, atomic force microscopy (AFM, contact angle measurement and cyclic voltammetry (CV taking CHIT-g-PANI as a reference. The influence of various parameters on CAH enzyme activity within the matrix was investigated including pH, temperature, and time. The Michaelis-Menten constant and apparent activities for the CAH enzyme were calculated to be 0.51 mM and 83.59 mg/cm2, respectively; indicating CHIT-g-PANI matrix has a high affinity to immobilize CAH enzyme.

  7. Variable intron/exon structure in the oligochaete lombricine kinase gene.

    Science.gov (United States)

    Doumen, Chris

    2012-09-01

    Lombricine kinase is an annelid enzyme that belongs to the phosphagen kinase family of which creatine kinase and arginine kinase are the typical representatives. The enzymes play important roles in the cellular energy metabolism of animals. Biochemical, physiological and molecular information with respect to lombricine kinase is limited compared to other phosphagen kinases. This study presents data on the cDNA sequences of lombricine kinase from two smaller oligochaetes, Enchytraeus sp. and Stylaria sp. The deduced amino acid sequences are analyzed and compared with other selected phosphagen kinases. The intron/exon structure of the lombricine kinase gene was determined for these two species as well as two additional oligochaetes, Lumbriculus variegatus and Tubifex tubifex, and compared with available data for annelid phosphagen kinases. The data indicate the existence of a variable organization of the proposed 8-intron/9-exon gene structure. The results provide further insights in the evolution and position of these enzymes within the phosphagen kinase family. PMID:22705027

  8. 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

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

    OpenAIRE

    Antonio, Jose; Ciccone, Victoria

    2013-01-01

    Background Chronic supplementation with creatine monohydrate has been shown to promote increases in total intramuscular creatine, phosphocreatine, skeletal muscle mass, lean body mass and muscle fiber size. Furthermore, there is robust evidence that muscular strength and power will also increase after supplementing with creatine. However, it is not known if the timing of creatine supplementation will affect the adaptive response to exercise. Thus, the purpose of this investigation was to dete...

  10. 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) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  11. The Role of Supplemented Creatine in Human Metabolism

    Czech Academy of Sciences Publication Activity Database

    Petr, M.; Navrátil, Tomáš; Heyrovský, Michael; Kohlíková, E.

    2011-01-01

    Roč. 15, č. 17 (2011), s. 3029-3042. ISSN 1385-2728 R&D Projects: GA AV ČR IAA400400806 Institutional research plan: CEZ:AV0Z40400503 Keywords : creatine * creatinine * folates Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.064, year: 2011

  12. Creatine Loading, Resistance Exercise Performance, and Muscle Mechanics.

    Science.gov (United States)

    Stevenson, Scott W.; Dudley, Gary A.

    2001-01-01

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

  13. Changes of lipidemia after one month of creatine supplementation

    Czech Academy of Sciences Publication Activity Database

    Navrátil, Tomáš; Petr, M.; Kohlíková, E.

    2015-01-01

    Roč. 146, č. 5 (2015), s. 771-780. ISSN 0026-9247 R&D Projects: GA ČR(CZ) GAP208/12/1645 Institutional support: RVO:61388955 Keywords : creatine * vitamin B12 * folates Subject RIV: CG - Electrochemistry Impact factor: 1.222, year: 2014

  14. THE EFFECT OF CREATINE SUPPLEMENTATION ON ATHLETE ISOKINETIC PERFORMANCE

    Directory of Open Access Journals (Sweden)

    Erkan Faruk ŞİRİN

    2009-12-01

    Full Text Available The purpose of this study is to find the effects of Creatin Monohydrate (CrH2O on athlete performance (isokinetic power measured as a total workout used as an ergojenic aid in long-term (6 weeks supplementation. There are 38 participants willing to join to the study. Their ages are between 20 and 27. All of them are choosed from active athletes. From the findings of this study; all the participants’ in the creatin group have increased the total workout production in all cycles of isokinetic exercise. The difference between the values in the first and fifth cycles, (both before and after loading are statistically significant. In the creatin group the difference between before loading and 15th day values are statistically significant. But the difference between before loading and 50th day values does not have statistical difference. In placebo group, before and after values in all 5 cycles, there is no statistical difference between the total workout production values. There is also no statistical difference between the before loading and 15th day values. As the same there is no statistical difference between the before loading and the 50th day values. The most important finding in this study is that, there is no affect of long term creatin loading (50 days on maximal voluntary knee extansion, as a total muscle workout values. But the change in values before loading day and 15th day are significantly improved. And so we understand that, for getting better results in total workout production, we better use two weeks period loading instead of long term loading. Key Words: Ergogenic aid, creatine supplementation, isokinetic performance

  15. cDNA identification, comparison and phylogenetic aspects of lombricine kinase from two oligochaete species.

    Science.gov (United States)

    Doumen, Chris

    2010-06-01

    Creatine kinase and arginine kinase are the typical representatives of an eight-member phosphagen kinase family, which play important roles in the cellular energy metabolism of animals. The phylum Annelida underwent a series of evolutionary processes that resulted in rapid divergence and radiation of these enzymes, producing the greatest diversity of the phosphagen kinases within this phylum. Lombricine kinase (EC 2.7.3.5) is one of such enzymes and sequence information is rather limited compared to other phosphagen kinases. This study presents data on the cDNA sequences of lombricine kinase from two oligochaete species, the California blackworm (Lumbriculus variegatus) and the sludge worm (Tubifex tubifex). The deduced amino acid sequences are analyzed and compared with other selected phosphagen kinases, including two additional lombricine kinase sequences extracted from DNA databases and provide further insights in the evolution and position of these enzymes within the phosphagen kinase family. The data confirms the presence of a deleted region within the flexible loop (the GS region) of all six examined lombricine kinases. A phylogenetic analysis of these six lombricine kinases clearly positions the enzymes together in a small subcluster within the larger creatine kinase (EC 2.7.3.2) clade. PMID:20230902

  16. 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.

  17. Effect of creatine applied as food supplement on human metabolism

    Czech Academy of Sciences Publication Activity Database

    Navrátil, Tomáš; Kohlíková, E.; Petr, M.; Přistoupilová, K.

    New York : Nova Sicence Publ., Inc, 2010 - (Haugen, S.; Meijer, S.), s. 317-338 ISBN 978-1-60741-916-7. - (Nutritrition and Diet Research Progress Series) R&D Projects: GA ČR GA203/07/1195; GA AV ČR IAA400400806 Institutional research plan: CEZ:AV0Z40400503 Keywords : creatine * creatinine * folates Subject RIV: CF - Physical ; Theoretical Chemistry

  18. 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; Bölsterli, Katrin; Brovelli, Dorothee; Odermatt, Freia

    2012-03-01

    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 present study investigates this hypothesis by using structural equation modelling on a sex-stratified sample of 500 male and female students of secondary II level. The results show, that the motivation to learn science is directly influenced by the systemizing quotient SQ, but not by sex. The impact of sex on the motivation to learn science, measured by five key concepts, only works indirectly, namely through the influence of sex on the SQ. The empathizing quotient (EQ) has no impact on the motivation to learn science. The SQ explains between 13 and 23 percent of the variation of the five key constructs. In female students, the impact of the SQ is very similar for all key concepts. In male students, it is highest for self-efficacy and lowest for assessment anxiety. The motivation to learn science is significantly larger for male students in all involved SMQ key concepts, but the difference is small. The interpretation of these findings and conclusions for science teaching and further research are discussed.

  19. 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

  20. Estimation of skeletal muscle mass from body creatine content

    Science.gov (United States)

    Pace, N.; Rahlmann, D. F.

    1982-01-01

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

  1. 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.

  2. Effect of oral creatine supplementation on human muscle GLUT4 protein content after immobilization.

    Science.gov (United States)

    Op 't Eijnde, B; Ursø, B; Richter, E A; Greenhaff, P L; Hespel, P

    2001-01-01

    The purpose of this study was to investigate the effect of oral creatine supplementation on muscle GLUT4 protein content and total creatine and glycogen content during muscle disuse and subsequent training. A double-blind placebo-controlled trial was performed with 22 young healthy volunteers. The right leg of each subject was immobilized using a cast for 2 weeks, after which subjects participated in a 10-week heavy resistance training program involving the knee-extensor muscles (three sessions per week). Half of the subjects received creatine monohydrate supplements (20 g daily during the immobilization period and 15 and 5 g daily during the first 3 and the last 7 weeks of rehabilitation training, respectively), whereas the other 11 subjects ingested placebo (maltodextrine). Muscle GLUT4 protein content and glycogen and total creatine concentrations were assayed in needle biopsy samples from the vastus lateralis muscle before and after immobilization and after 3 and 10 weeks of training. Immobilization decreased GLUT4 in the placebo group (-20%, P < 0.05), but not in the creatine group (+9% NS). Glycogen and total creatine were unchanged in both groups during the immobilization period. In the placebo group, during training, GLUT4 was normalized, and glycogen and total creatine were stable. Conversely, in the creatine group, GLUT4 increased by approximately 40% (P < 0.05) during rehabilitation. Muscle glycogen and total creatine levels were higher in the creatine group after 3 weeks of rehabilitation (P < 0.05), but not after 10 weeks of rehabilitation. We concluded that 1) oral creatine supplementation offsets the decline in muscle GLUT4 protein content that occurs during immobilization, and 2) oral creatine supplementation increases GLUT4 protein content during subsequent rehabilitation training in healthy subjects. PMID:11147785

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

    OpenAIRE

    Michel Barbosa de Araújo; Roberto Carlos Vieira Junior; Leandro Pereira de Moura; Marcelo Costa Junior; Rodrigo Augusto Dalia; Amanda Christine da Silva Sponton; Carla Ribeiro; Maria Alice Rostom de Mello

    2013-01-01

    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 balanc...

  4. 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. PMID:18184753

  5. Age dependence of myosin heavy chain transitions induced by creatine depletion in rat skeletal muscle

    Science.gov (United States)

    Adams, Gregory R.; Baldwin, Kenneth M.

    1995-01-01

    This study was designed to test the hypothesis that myosin heavy chain (MHC) plasticity resulting from creatine depletion is an age-dependent process. At weaning (age 28 days), rat pups were placed on either standard rat chow (normal diet juvenile group) or the same chow supplemented with 1% wt/wt of the creatine analogue beta-guanidinopropionic acid (creatine depletion juvenile (CDJ) group). Two groups of adult rats (age approximately 8 wk) were placed on the same diet regimens (normal diet adult and creatine depletion adult (CDA) groups). After 40 days (CDJ and normal diet juvenile groups) and 60 days (CDA and normal diet adult groups), animals were killed and several skeletal muscles were removed for analysis of creatine content or MHC ditribution. In the CDJ group, creatine depletion (78%) was accompanied by significant shifts toward expression of slower MHC isoforms in two slow and three fast skeletal muscles. In contrast, creatine depletion in adult animals did not result in similar shifts toward slow MHC isoform expression in either muscle type. The results of this study indicate that there is a differential effect of creatine depletion on MHC tranitions that appears to be age dependent. These results strongly suggest that investigators contemplating experimental designs involving the use of the creatine analogue beta-guanidinopropionic acid should consider the age of the animals to be used.

  6. 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

  7. Influence of local vibration on plasma creatine phosphokinase (CPK) activity.

    OpenAIRE

    Okada, A; Okuda, H.; Inaba, R; Ariizumi, M

    1985-01-01

    This study was designed to obtain basic information about the mechanism of the occurrence of muscular disorders after exposure to vibration. The hind legs of rats were exposed to acute and chronic local vibration at frequencies of 30, 60, 120, 240, 480, and 960 Hz with a constant acceleration of 50 m/sec2. The exposure time was four hours for acute, and four hours a day for two weeks continuously for chronic exposure. Blood was collected after exposure to measure plasma creatine phosphokinase...

  8. An adenylate kinase is involved in KATP channel regulation of mouse pancreatic beta cells.

    NARCIS (Netherlands)

    Schulze, D.U.; Dufer, M.; Wieringa, B.; Krippeit-Drews, P.; Drews, G.

    2007-01-01

    AIMS/HYPOTHESIS: In a previous study, we demonstrated that a creatine kinase (CK) modulates K(ATP) channel activity in pancreatic beta cells. To explore phosphotransfer signalling pathways in more detail, we examined whether K(ATP) channel regulation in beta cells is determined by a metabolic intera

  9. A Rodent Model of Schizophrenia Reveals Increase in Creatine Kinase Activity with Associated Behavior Changes

    OpenAIRE

    Leila Canever; Larissa de Oliveira; Renata D'Altoé de Luca; Correa, Paulo T. F.; Fraga, Daiane de B.; Maria Paula Matos; Giselli Scaini; João Quevedo; Streck, Emílio L.; Zugno, Alexandra I

    2010-01-01

    Schizophrenia is a debilitating mental disorder characterized by positive (delusions, hallucinations, disorganized speech) and negative (affective flattering, avolition and social withdrawal) symptoms as well as cognitive deficits. The frequency, severity and topography characterize the disorder as heterogeneous, the pathophysiology of schizophrenia is poorly understood. Sub-anesthetic doses of ketamine produce hyperactivity, stereotypy and abnormal social interaction and it is used as a mode...

  10. Asymptomatic hyper-creatine-kinase-emia as sole manifestation of inclusion body myositis

    Directory of Open Access Journals (Sweden)

    Josef Finsterer

    2013-06-01

    Full Text Available Sporadic inclusion body myositis (sIBM usually manifests with painless weakness of the hand, finger and hip flexors. Absence of symptoms or signs, but mild hyper-CK-emia as the sole manifestation of IBM, has not been reported. We report the case of a 73-year-old male who presented with asymptomatic recurrent hyper-CK-emia ranging from 200 to 1324 U/L (n<171 U/L, since 10 years. Clinical neurologic investigation, nerve conduction studies and EMG were non-informative. Muscle biopsy surprisingly revealed sIBM. sIBM may be asymptomatic and may manifest with hyper-CK-emia exclusively. So, it has to be included in the differential diagnoses of asymptomatic hyper-CK-emia.

  11. 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.

  12. 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…

  13. 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.

  14. Kinetics of creatine in blood and brain after intraperitoneal injection in the rat.

    Science.gov (United States)

    Perasso, Luisa; Cupello, Aroldo; Lunardi, Gian Luigi; Principato, Cristina; Gandolfo, Carlo; Balestrino, Maurizio

    2003-06-01

    Creatine has in recent years raised the interest of the neurologist, because it has been used in children with hereditary disorders of creatine metabolism and because experimental data suggest that it may exert a protective effect against various neurological diseases including stroke. Moreover, it is widely used as a nutritional supplement. It is well known that creatine crosses the blood-brain barrier with difficulty, however its accumulation into the brain after systemic administration is still not completely known. In the present experiments we studied its accumulation into rat brain tissue after intraperitoneal (i.p.) single or repeated injections. After a single injection of 160 mg/kg, radioactively labelled creatine (14C-creatine) entered the brain to a limited extent. It reached a plateau value of around 70 microM above baseline, that remained stable for at least 9 h. This amount of exogenous creatine obviously added to the endogenous creatine store. This increase is a minor one, since endogenous creatine has a brain concentration of about 10 mM. In accordance with this conclusion, when single or repeated injections of unlabelled ('cold') creatine were administered to rats, no sizable increase could be measured with high-performance liquid chromatography in the brain levels of either this compound or its phosphorylated derivative, phosphocreatine. Although our data clearly show some passage of serum creatine into the brain, other strategies are needed to improve passage of creatine across the blood-brain barrier in a way that it may be suitable to treat acute conditions like stroke. PMID:12742622

  15. 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.

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

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    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.

  17. Exploring the Potential of Creatine Ingestion to Maintain Muscle Function during Immobilization

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    Jeremy C. Fransen

    2015-08-01

    Full Text Available Limb immobilization (casting results in a loss of muscle mass along with decrements in muscle strength and endurance. In addition, immobilization has been shown to impair high energy phosphate catabolism in skeletal muscle. Creatine ingestion in conjunction with resistance training can significantly increase muscle force production, augment muscle size increases, and improve energy-rich phosphate catabolism in skeletal muscle. Surprisingly, there are few research studies investigating the potential of oral creatine supplementation to mitigate the muscle changes during immobilization. Early investigations found that creatine supplementation can maintain muscle size, strength, and endurance during short-term (1-2 wk immobilization. Future research should focus on whether creatine supplementation can also prevent muscle metabolic consequences during immobilization. Creatine ingestion during short-term immobilization may help to identify the underlying mechanisms that contribute to the reported ergogenic effects.

  18. Plasma guanidino compounds are altered by oral creatine supplementation in healthy humans.

    Science.gov (United States)

    Derave, Wim; Marescau, Bart; Vanden Eede, Els; Eijnde, Bert O; De Deyn, Peter P; Hespel, Peter

    2004-09-01

    Although creatine is one of the most widely used nutritional supplements for athletes as well as for patients with neuromuscular disorders, the effects of oral creatine supplementation on endogenous creatine synthesis in humans remains largely unexplored. The aim of the present study was to investigate the metabolic consequences of a frequently used, long-term creatine ingestion protocol on the circulating creatine synthesis precursor molecules, guanidinoacetate and arginine, and their related guanidino compounds. For this purpose, 16 healthy young volunteers were randomly divided to ingest in a double-blind fashion either creatine monohydrate or placebo (maltodextrine) at a dosage of 20 g/day for the first week (loading phase) and 5 g/day for 19 subsequent wk (maintenance phase). Fasting plasma samples were taken at baseline and at 1, 10, and 20 wk of supplementation, and guanidino compounds were determined. Plasma guanidinoacetate levels were reduced by 50% after creatine loading and remained approximately 30% reduced throughout the maintenance phase. Several circulating guanidino compound levels were significantly altered after creatine loading but not during the maintenance phase: homoarginine (+35%), alpha-keto-delta-guanidinovaleric acid (+45%), and argininic acid (+75%) were increased, whereas guanidinosuccinate was reduced (-25%). The decrease in circulating guanidinoacetate levels suggests that exogenous supply of creatine chronically inhibits endogenous synthesis at the transamidinase step in humans, supporting earlier animal studies showing a powerful repressive effect of creatine on l-arginine:glycine amidinotransferase. Furthermore, these data suggest that this leads to enhanced utilization of arginine as a substrate for secondary pathways. PMID:15107411

  19. Clinical use of creatine in neuromuscular and neurometabolic disorders.

    Science.gov (United States)

    Tarnopolsky, Mark A

    2007-01-01

    Many of the neuromuscular (e.g., muscular dystrophy) and neurometabolic (e.g., mitochondrial cytopathies) disorders share similar final common pathways of cellular dysfunction that may be favorably influenced by creatine monohydrate (CrM) supplementation. Studies using the mdx model of Duchenne muscular dystrophy have found evidence of enhanced mitochondrial function, reduced intra-cellular calcium and improved performance with CrM supplementation. Clinical trials in patients with Duchenne and Becker's muscular dystrophy have shown improved function, fat-free mass, and some evidence of improved bone health with CrM supplementation. In contrast, the improvements in function in myotonic dystrophy and inherited neuropathies (e.g., Charcot-Marie-Tooth) have not been significant. Some studies in patients with mitochondrial cytopathies have shown improved muscle endurance and body composition, yet other studies did not find significant improvements in patients with mitochondrial cytopathy. Lower-dose CrM supplementation in patients with McArdle's disease (myophosphorylase deficiency) improved exercise capacity, yet higher doses actually showed some indication of worsened function. Based upon known cellular pathologies, there are potential benefits from CrM supplementation in patients with steroid myopathy, inflammatory myopathy, myoadenylate deaminase deficiency, and fatty acid oxidation defects. Larger randomized control trials (RCT) using homogeneous patient groups and objective and clinically relevant outcome variables are needed to determine whether creatine supplementation will be of therapeutic benefit to patients with neuromuscular or neurometabolic disorders. Given the relatively low prevalence of some of the neuromuscular and neurometabolic disorders, it will be necessary to use surrogate markers of potential clinical efficacy including markers of oxidative stress, cellular energy charge, and gene expression patterns. PMID:18652078

  20. 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.

  1. Creatine supplementation does not enhance submaximal aerobic training adaptations in healthy young men and women.

    Science.gov (United States)

    Reardon, T F; Ruell, P A; Fiatarone Singh, M A; Thompson, C H; Rooney, K B

    2006-10-01

    The benefits of dietary creatine supplementation on muscle performance are generally related to an increase in muscle phosphocreatine content. However, creatine supplementation may benefit endurance sports through increased glycogen re-synthesis following exercise. This study investigated the effect of creatine supplementation on muscle glycogen content, submaximal exercise fuel utilisation and endurance performance following 4 weeks of endurance training. Thirteen healthy, physically active, non-vegetarian subjects volunteered to take part and completed the study. Subjects were supplemented with either creatine monohydrate (CREAT, n = 7) or placebo-maltodextrin (CON, n = 6). Submaximal fuel utilisation and endurance performance were assessed before and after a 4 week endurance training program. Muscle biopsies were also collected before and following training for assessment of muscle creatine and glycogen content. Training increased quadriceps glycogen content to the same degree (approximately 20%) in both groups (P = 0.04). There was a significant training effect on submaximal fuel utilisation and improved endurance performance. However, there was no significant treatment effect of creatine supplementation. Creatine supplementation does not effect metabolic adaptations to endurance training. PMID:16896727

  2. Creatine supplementation in the aging population: effects on skeletal muscle, bone and brain.

    Science.gov (United States)

    Gualano, Bruno; Rawson, Eric S; Candow, Darren G; Chilibeck, Philip D

    2016-08-01

    This narrative review aims to summarize the recent findings on the adjuvant application of creatine supplementation in the management of age-related deficits in skeletal muscle, bone and brain metabolism in older individuals. Most studies suggest that creatine supplementation can improve lean mass and muscle function in older populations. Importantly, creatine in conjunction with resistance training can result in greater adaptations in skeletal muscle than training alone. The beneficial effect of creatine upon lean mass and muscle function appears to be applicable to older individuals regardless of sex, fitness or health status, although studies with very old (>90 years old) and severely frail individuals remain scarce. Furthermore, there is evidence that creatine may affect the bone remodeling process; however, the effects of creatine on bone accretion are inconsistent. Additional human clinical trials are needed using larger sample sizes, longer durations of resistance training (>52 weeks), and further evaluation of bone mineral, bone geometry and microarchitecture properties. Finally, a number of studies suggest that creatine supplementation improves cognitive processing under resting and various stressed conditions. However, few data are available on older adults, and the findings are discordant. Future studies should focus on older adults and possibly frail elders or those who have already experienced an age-associated cognitive decline. PMID:27108136

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

    OpenAIRE

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

    1996-01-01

    OBJECTIVE: To examine the effect of a relatively low dose of creatine on skeletal muscle metabolism and oxygen supply in a group of training athletes. METHODS: 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 rat...

  4. Screening for primary creatine deficiencies in French patients with unexplained neurological symptoms.

    OpenAIRE

    Cheillan David; Curt Marie Joncquel-Chevalier; Briand Gilbert; Salomons Gajja S; Mention-Mulliez Karine; Dobbelaere Dries; Cuisset Jean-Marie; Lion-François Laurence; Portes Vincent Des; Chabli Allel; Valayannopoulos Vassili; Benoist Jean-François; Pinard Jean-Marc; Simard Gilles; Douay Olivier

    2012-01-01

    Abstract 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 n...

  5. 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

    Trexler, ET, Smith-Ryan, AE, Roelofs, EJ, Hirsch, KR, Persky, AM, and Mock, MG. Effects of coffee and caffeine anhydrous intake during creatine loading. J Strength Cond Res 30(5): 1438-1446, 2016-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. PMID:26439785

  6. Brain-type and liver-type fatty acid-binding proteins: new tumor markers for renal cancer?

    OpenAIRE

    Moch Holger; Miller Kurt; Johannsen Manfred; Lein Michael; Jung Monika; Tölle Angelika; Jung Klaus; Kristiansen Glen

    2009-01-01

    Abstract Background Renal cell carcinoma (RCC) is the most common renal neoplasm. Cancer tissue is often characterized by altered energy regulation. Fatty acid-binding proteins (FABP) are involved in the intracellular transport of fatty acids (FA). We examined the level of brain-type (B) and liver-type (L) FABP mRNA and the protein expression profiles of both FABPs in renal cell carcinoma. Methods Paired tissue samples of cancerous and noncancerous kidney parts were investigated. Quantitative...

  7. Casein kinases

    DEFF Research Database (Denmark)

    Issinger, O G

    1993-01-01

    subunits are highly conserved during evolution. The relationship between CK-2 alpha from humans and plants is still 73%. Similar relationships are reported for the beta-subunit. Chromosomal assignment of CK-2 alpha shows two gene loci, one of which is a pseudogene. They are located on different chromosomes...... genetic changes are necessarily involved; the observed changes may be entirely due to a signal transduction pathway where CK-2 could be phosphorylated by another kinase(s). CK-2 cDNAs from various organisms have been isolated and characterized. From the deduced amino acid sequence it turns out that CK-2...

  8. 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 increa

  9. 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

  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. 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.

  12. 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.

  13. Does creatine supplementation improve the plasma lipid profile in healthy male subjects undergoing aerobic training?

    OpenAIRE

    Scagliusi Fernanda B; Benatti Fabiana B; Artioli Guilherme G; Ugrinowitsch Carlos; Gualano Bruno; Harris Roger C; Lancha Antonio H

    2008-01-01

    Abstract We aimed to investigate the effects of creatine (Cr) supplementation on the plasma lipid profile in sedentary male subjects undergoing aerobic training. Methods Subjects (n = 22) were randomly divided into two groups and were allocated to receive treatment with either creatine monohydrate (CR) (~20 g·day-1 for one week followed by ~10 g·day-1 for a further eleven weeks) or placebo (PL) (dextrose) in a double blind fashion. All subjects undertook moderate intensity aerobic training d...

  14. The effects of the recommended dose of creatine monohydrate on kidney function

    OpenAIRE

    Taner, Basturk; Aysim, Ozagari; Abdulkadir, Unsal

    2010-01-01

    We report a case of a heretofore healthy 18-year-old man who presented with a 2-day history of nausea, vomiting and stomach ache while taking creatine monohydrate for bodybuilding purposes. The patient had acute renal failure, and a renal biopsy was performed to determine the cause of increased creatinine and proteinuria. The biopsy showed acute tubular necrosis. In the literature, creatine monohydrate supplementation and acute tubular necrosis coexistence had not been reported previously. Tw...

  15. In vivo neuroprotection by a creatine-derived compound: phosphocreatine-Mg-complex acetate.

    Science.gov (United States)

    Perasso, L; Adriano, E; Ruggeri, P; Burov, S V; Gandolfo, C; Balestrino, M

    2009-08-18

    Phosphocreatine-Mg-complex acetate (PCr-Mg-CPLX) is a creatine-derived compound that in previous in vitro research was able to increase neuronal creatine independently of the creatine transporter, thus providing hope to cure the hereditary syndrome of creatine transporter deficiency. In previous research we showed that it reproduces in vitro the known neuroprotective effect of creatine against anoxic damage. In the present paper we investigated if PCr-Mg-CPLX reproduces this neuroprotective effect in vivo, too. We used a mouse model of transient middle cerebral artery occlusion. Mice received PCr-Mg-CPLX or a mixture of the two separate compounds phosphocreatine (PCr) and MgSO(4), or vehicle. The injections were done 60 min and 30 min before ischemia. Forty-eight hours after ischemia neurological damage was evaluated with Clark's behavioural tests, then the infarct volume was measured. PCr-Mg-CPLX reduced the infarct volume by 48%, an effect that was not duplicated by the separate administration of PCr and MgSO(4) and the neurological damage was decreased in a statistically significant way. We conclude that PCr-Mg-CPLX affords in vivo neuroprotection when administered before ischemia. These results are comparable to previous research on creatine administration in experimental stroke. PCr-Mg-CPLX maintains creatine-like neuroprotective effects in vivo as well as in vitro. Our study suggests that PCr-Mg-CPLX might have a therapeutic role in the treatment of hereditary creatine transporter deficiency and of conditions where there is a high risk of impending stroke or cerebral ischemic damage, like high-risk transient ischemic attacks, open heart surgery, and carotid surgery. PMID:19523930

  16. The genomic organization of a human creatine transporter (CRTR) gene located in Xq28

    Energy Technology Data Exchange (ETDEWEB)

    Sandoval, N.; Bauer, D.; Brenner, V. [Institute fuer Molekulare Biotechnologie, Jena (Germany)] [and others

    1996-07-15

    During the course of a large-scale sequencing project in Xq28, a human creatine transporter (CRTR) gene was discovered. The gene is located approximately 36 kb centromeric to ALD. The gene contains 13 exons and spans about 8.5 kb of genomic DNA. Since the creatine transporter has a prominent function in muscular physiology, it is a candidate gene for Barth syndrome and infantile cardiomyopathy mapped to Xq28. 19 refs., 1 fig., 1 tab.

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

    OpenAIRE

    Chilosi Annamaria; Casarano Manuela; Comparini Alessandro; Battaglia Francesca; Mancardi Margherita; Schiaffino Cristina; Tosetti Michela; Leuzzi Vincenzo; Battini Roberta; Cioni Giovanni

    2012-01-01

    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 administrate...

  18. 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.

  19. Creatine supplementation with methylglyoxal: a potent therapy for cancer in experimental models.

    Science.gov (United States)

    Pal, Aparajita; Roy, Anirban; Ray, Manju

    2016-08-01

    The anti-cancer effect of methylglyoxal (MG) is now well established in the literature. The main aim of this study was to investigate the effect of creatine as a supplement in combination with MG both in vitro and in vivo. In case of the in vitro studies, two different cell lines, namely MCF-7 (human breast cancer cell line) and C2C12 (mouse myoblast cell line) were chosen. MG in combination with creatine showed enhanced apoptosis as well as higher cytotoxicity in the breast cancer MCF-7 cell line, compared to MG alone. Pre-treatment of well-differentiated C2C12 myotubes with cancerogenic 3-methylcholanthrene (3MC) induced a dedifferentiation of these myotubes towards cancerous cells (that mimic the effect of 3MC observed in solid fibro-sarcoma animal models) and subsequent exposure of these induced cancer cells with MG proved to be cytotoxic. Thus, creatine plus ascorbic acid enhanced the anti-cancer effects of MG. In contrast, when normal C2C12 muscle cells or myotubes (mouse normal myoblast cell line) were treated with MG or MG plus creatine and ascorbic acid, no detrimental effects were seen. This indicated that cytotoxic effects of MG are specifically limited towards cancer cells and are further enhanced when MG is used in combination with creatine and ascorbic acid. For the in vivo studies, tumors were induced by injecting Sarcoma-180 cells (2 × 10(6) cells/mouse) in the left hind leg. After 7 days of tumor inoculation, treatments were started with MG (20 mg/kg body wt/day, via the intravenous route), with or without creatine (150 mg/kg body wt/day, fed orally) and ascorbic acid (50 mg/kg body wt/day, fed orally) and continued for 10 consecutive days. Significant regression of tumor size was observed when Sarcoma-180 tumor-bearing mice were treated with MG and even more so with the aforesaid combination. The creatine-supplemented group demonstrated better overall survival in comparison with tumor-bearing mice without creatine. In conclusion, it may be

  20. 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

  1. Effects of oral creatine supplementation on high intensity, intermittent exercise performance in competitive squash players.

    Science.gov (United States)

    Romer, L M; Barrington, J P; Jeukendrup, A E

    2001-11-01

    The purpose of this study was to determine the effects of oral creatine supplementation on high intensity, intermittent exercise performance in competitive squash players. Nine squash players (mean +/- SEM VO2max = 61.9 +/- 2.1 ml x kg(-1) x min(-1); body mass = 73 +/- 3 kg) performed an on-court "ghosting" routine that involved 10 sets of 2 repetitions of simulated positional play, each set interspersed with 30 s passive recovery. A double blind, crossover design was utilised whereby experimental and control groups supplemented 4 times daily for 5 d with 0.075 g x kg(-1) body mass of creatine monohydrate and maltodextrine, respectively, and a 4 wk washout period separated the crossover of treatments. The experimental group improved mean set sprint time by 3.2 +/- 0.8% over and above the changes noted for the control group (P = 0.004 and 95% Cl = 1.4 to 5.1%). Sets 2 to 10 were completed in a significantly shorter time following creatine supplementation compared to the placebo condition (P < 0.05). In conclusion, these data support existing evidence that creatine supplementation improves high intensity, intermittent exercise performance. In addition, the present study provides new evidence that oral creatine supplementation improves exercise performance in competitive squash players. PMID:11719888

  2. Effects of whole-body x irradiation on the biogenesis of creatine in the rat

    International Nuclear Information System (INIS)

    Influences of whole-body x irradiation on various aspects of creatine metabolism have been studied. Exposures to sublethal or lethal doses of x radiation results in excessive urinary excretion as well as higher accumulation of creatine in the skeletal muscle of x-irradiated rats. A sudden fall in CPK activity in muscle with a concomitant rise in serum suggests that changes in serum and tissue CPK activity are of an adaptive nature in rats exposed to sublethal doses of x radiation. In vitro studies on creatine synthesis shows that transaminidase and methyl transferase activities in kidneys and liver, respectively, are decreased on the 5th day in the x-irradiated, are decreased on the 5th day in the x-irradiated rat. However, on the 8th day, the enzyme activities are restored to normal

  3. Effect of 28 days of creatine ingestion on muscle metabolism and performance of a simulated cycling road race

    Directory of Open Access Journals (Sweden)

    Hatley Holly

    2010-07-01

    Full Text Available Abstract Purpose The effects of creatine supplementation on muscle metabolism and exercise performance during a simulated endurance road race was investigated. Methods Twelve adult male (27.3 ± 1.0 yr, 178.6 ± 1.4 cm, 78.0 ± 2.5 kg, 8.9 ± 1.1 %fat endurance-trained (53.3 ± 2.0 ml* kg-1* min-1, cycling ~160 km/wk cyclists completed a simulated road race on a cycle ergometer (Lode, consisting of a two-hour cycling bout at 60% of peak aerobic capacity (VO2peak with three 10-second sprints performed at 110% VO2 peak every 15 minutes. Cyclists completed the 2-hr cycling bout before and after dietary creatine monohydrate or placebo supplementation (3 g/day for 28 days. Muscle biopsies were taken at rest and five minutes before the end of the two-hour ride. Results There was a 24.5 ± 10.0% increase in resting muscle total creatine and 38.4 ± 23.9% increase in muscle creatine phosphate in the creatine group (P 2 peak, were not affected by creatine supplementation. Submaximal oxygen consumption near the end of the two-hour ride was decreased by approximately 10% by creatine supplementation (P +14.0 ± 6.3% than the placebo group (-10.4 ± 4.4%; P Conclusions It can be concluded that although creatine supplementation may increase resting muscle total creatine, muscle creatine phosphate, and plasma volume, and may lead to a reduction in oxygen consumption during submaximal exercise, creatine supplementation does not improve sprint performance at the end of endurance cycling exercise.

  4. 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 creatine ingestion lead to similar changes in anaerobic power, strength, and endurance. PMID:26313717

  5. 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.

  6. 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.

  7. 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 creatin

  8. Supplemented Creatine Induces Changes in Human Metabolism of Thiocompounds and One- and Two-Carbon Units

    Czech Academy of Sciences Publication Activity Database

    Navrátil, Tomáš; Kohlíková, E.; Petr, M.; Pelclová, D.; Heyrovský, Michael; Přistoupilová, K.

    2010-01-01

    Roč. 59, č. 3 (2010), s. 431-442. ISSN 0862-8408 R&D Projects: GA AV ČR IAA400400806 Institutional research plan: CEZ:AV0Z40400503 Keywords : creatine * creatinine * folates * homocysteine Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.646, year: 2010

  9. 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.

  10. ISOZYME PROFILES OF LACTIC DEHYDROGENASE AND CREATINE PHOSPHOKINASE IN NEONATAL MOUSE HEARTS

    Science.gov (United States)

    Isozyme profiles of lactic dehydrogenase (LDH) and creatine phosphokinase (CPK) were determined in cardiac tissue of mice during postnatal development. LDH isozymes 1 and 5 showed a definite developmental change, achieving the adult values by 20 days of age, while the other three...

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

    Science.gov (United States)

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

    2001-01-01

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

  12. Repeated Supramaximal Exercise-Induced Oxidative Stress: Effect of β-Alanine Plus Creatine Supplementation

    Science.gov (United States)

    Belviranli, Muaz; Okudan, Nilsel; Revan, Serkan; Balci, Serdar; Gokbel, Hakki

    2016-01-01

    Background: Carnosine is a dipeptide formed from the β-alanine and histidine amino acids and found in mainly in the brain and muscle, especially fast twitch muscle. Carnosine and creatine has an antioxidant effect and carnosine accounts for about 10% of the muscle's ability to buffer the H+ ions produced by exercise. Objectives: The aim of the study was to investigate the effects of beta alanine and/or creatine supplementation on oxidant and antioxidant status during repeated Wingate tests (WTs). Patients and Methods: Forty four sedentary males participated in the study. Participants performed three 30s WTs with 2 minutes rest between exercise bouts. After the first exercise session, the subjects were assigned to one of four groups: Placebo, Creatine, Beta-alanine and Beta-alanine plus creatine. Participants ingested twice per day for 22 consecutive days, then four times per day for the following 6 days. After the supplementation period the second exercise session was applied. Blood samples were taken before and immediately after the each exercise session for the analysis of oxidative stress and antioxidant markers. Results: Malondialdehyde levels and superoxide dismutase activities were affected by neither supplementation nor exercise. During the pre-supplementation session, protein carbonyl reduced and oxidized glutathione (GSH and GSSG) levels increased immediately after the exercise. However, during the post-supplementation session GSH and GSSG levels increased in beta-alanine and beta-alanine plus creatine groups immediately after the exercise compared to pre-exercise. In addition, during the post-supplementation session total antioxidant capacity increased in beta-alanine group immediately after the exercise. Conclusions: Beta-alanine supplementation has limited antioxidant effect during the repeated WTs.

  13. The early evolution of the phosphagen kinases--insights from choanoflagellate and poriferan arginine kinases.

    Science.gov (United States)

    Conejo, Maria; Bertin, Matt; Pomponi, Shirley A; Ellington, W Ross

    2008-01-01

    Arginine kinase (AK) is a member of a large family of phosphoryl transfer enzymes called phosphagen (guanidino) kinases. AKs are present in certain protozoans, sponges, cnidarians, and both lophotrochozoan and ecdysozoan protostomes. Another phosphagen kinase, creatine kinase (CK), is found in sponges, cnidarians, and both deuterostome and protostome groups but does not appear to be present in protozoans. To probe the early evolution of phosphagen kinases, we have amplified the cDNAs for AKs from three choanoflagellates and from the hexactinellid sponge Aphrocallistes beatrix and the demosponges Suberites fuscus and Microciona prolifera. Phylogenetic analysis using maximum likelihood of these choanoflagellate and sponge AKs with other AK sequences revealed that the AK from the choanoflagellate Monosiga brevicollis clusters with the AK from the glass sponge Aphrocallistes and is part of a larger cluster containing AKs from the demosponges Suberites and Microciona as well as basal and protostome invertebrates. In contrast, AKs from Codonosiga gracilis and Monosiga ovata form a distinct cluster apart from all other AK sequences. tBLASTn searches of the recently released M. brevicollis genome database showed that this species has three unique AK genes-one virtually identical to the M. brevicollis cDNA and the other two showing great similarity to C. gracilis and M. ovata AKs. Three distinct AK genes are likely present in choanoflagellates. Two of these AKs display extensive similarity to both CKs and an AK from sponges. Previous work has shown CK evolved from an AK-like ancestor prior to the divergence of sponges. The present results provide evidence suggesting that the initial gene duplication event(s) leading to the CK lineage may have occurred before the divergence of the choanoflagellate and animal lineages. PMID:18064398

  14. 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

    The quantitative aspects of mitochondrial creatinekinase (mitCK) binding to mitochondrial membranes were investigated. A simple adsorption and binding model was used for data fitting, taking into account the influence of protein concentration, pH, ionic strength and substrate concentration on the...

  15. 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. PMID:27086253

  16. Sequence verification of human creatine kinase (43 kDa) isozymes by high-resolution tandem mass spectrometry.

    OpenAIRE

    Wood, T D; Chen, L.H.; White, C de B; Babbitt, P C; Kenyon, G L; McLafferty, F W

    1995-01-01

    Amino acid sequencing by recombinant DNA technology, although dramatically useful, is subject to base reading errors, is indirect, and is insensitive to posttranslational processing. Mass spectrometry techniques can provide molecular weight data from even relatively large proteins for such cDNA sequences and can serve as a check of an enzyme's purity and sequence integrity. Multiply-charged ions from electrospray ionization can be dissociated to yield structural information by tandem mass spe...

  17. 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.

  18. Creatine target engagement with brain bioenergetics: a dose-ranging phosphorus-31 magnetic resonance spectroscopy study of adolescent females with SSRI-resistant depression.

    Science.gov (United States)

    Kondo, Douglas G; Forrest, Lauren N; Shi, Xianfeng; Sung, Young-Hoon; Hellem, Tracy L; Huber, Rebekah S; Renshaw, Perry F

    2016-08-01

    Major depressive disorder (MDD) often begins during adolescence and is projected to become the leading cause of global disease burden by the year 2030. Yet, approximately 40 % of depressed adolescents fail to respond to standard antidepressant treatment with a selective serotonin reuptake inhibitor (SSRI). Converging evidence suggests that depression is related to brain mitochondrial dysfunction. Our previous studies of MDD in adult and adolescent females suggest that augmentation of SSRI pharmacotherapy with creatine monohydrate (CM) may improve MDD outcomes. Neuroimaging with phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) can measure the high-energy phosphorus metabolites in vivo that reflect mitochondrial function. These include phosphocreatine (PCr), a substrate for the creatine kinase reaction that produces adenosine triphosphate. As part of the National Institute of Mental Health's experimental medicine initiative, we conducted a placebo-controlled dose-ranging study of adjunctive CM for adolescent females with SSRI-resistant MDD. Participants were randomized to receive placebo or CM 2, 4 or 10 g daily for 8 weeks. Pre- and post-treatment (31)P-MRS scans were used to measure frontal lobe PCr, to assess CM's target engagement with cerebral energy metabolism. Mean frontal lobe PCr increased by 4.6, 4.1 and 9.1 % in the 2, 4 and 10 g groups, respectively; in the placebo group, PCr fell by 0.7 %. There was no group difference in adverse events, weight gain or serum creatinine. Regression analysis of PCr and depression scores across the entire sample showed that frontal lobe PCr was inversely correlated with depression scores (p = 0.02). These results suggest that CM achieves target engagement with brain bioenergetics and that the target is correlated with a clinical signal. Further study of CM as a treatment for adolescent females with SSRI-resistant MDD is warranted. PMID:26907087

  19. Creatine target engagement with brain bioenergetics: a dose-ranging phosphorus-31 magnetic resonance spectroscopy study of adolescent females with SSRI-resistant depression

    Science.gov (United States)

    Kondo, Douglas G.; Forrest, Lauren N.; Shi, Xianfeng; Sung, Young-Hoon; Hellem, Tracy L.; Huber, Rebekah S.; Renshaw, Perry F.

    2016-01-01

    Major depressive disorder (MDD) often begins during adolescence and is projected to become the leading cause of global disease burden by the year 2030. Yet, approximately 40 % of depressed adolescents fail to respond to standard antidepressant treatment with a selective serotonin reuptake inhibitor (SSRI). Converging evidence suggests that depression is related to brain mitochondrial dysfunction. Our previous studies of MDD in adult and adolescent females suggest that augmentation of SSRI pharmacotherapy with creatine monohydrate (CM) may improve MDD outcomes. Neuroimaging with phosphorus-31 magnetic resonance spectroscopy (31P-MRS) can measure the high-energy phosphorus metabolites in vivo that reflect mitochondrial function. These include phosphocreatine (PCr), a substrate for the creatine kinase reaction that produces adenosine triphosphate. As part of the National Institute of Mental Health’s experimental medicine initiative, we conducted a placebo-controlled doseranging study of adjunctive CM for adolescent females with SSRI-resistant MDD. Participants were randomized to receive placebo or CM 2, 4 or 10 g daily for 8 weeks. Pre- and post-treatment 31P-MRS scans were used to measure frontal lobe PCr, to assess CM’s target engagement with cerebral energy metabolism. Mean frontal lobe PCr increased by 4.6, 4.1 and 9.1 % in the 2, 4 and 10 g groups, respectively; in the placebo group, PCr fell by 0.7 %. There was no group difference in adverse events, weight gain or serum creatinine. Regression analysis of PCr and depression scores across the entire sample showed that frontal lobe PCr was inversely correlated with depression scores (p = 0.02). These results suggest that CM achieves target engagement with brain bioenergetics and that the target is correlated with a clinical signal. Further study of CM as a treatment for adolescent females with SSRI-resistant MDD is warranted. PMID:26907087

  20. Evolution of phosphagen kinase V. cDNA-derived amino acid sequences of two molluscan arginine kinases from the chiton Liolophura japonica and the turbanshell Battilus cornutus.

    Science.gov (United States)

    Suzuki, T; Ban, T; Furukohri, T

    1997-06-20

    The cDNAs of arginine kinases from the chiton Liolophura japonica (Polyplacophora) and the turbanshell Battilus cornutus (Gastropoda) were amplified by polymerase chain reaction (PCR), and the complete nucleotide sequences of 1669 and 1624 bp, respectively, were determined. The open reading frame for Liolophura arginine kinase is 1050 nucleotides in length and encodes a protein with 349 amino acid residues, and that for Battilus is 1077 nucleotides and 358 residues. The validity of the cDNA-derived amino acid sequence was supported by chemical sequencing of internal tryptic peptides. The molecular masses were calculated to be 39,057 and 39,795 Da, respectively. The amino acid sequence of Liolophura arginine kinase showed 65-68% identity with those of Battilus and Nordotis (abalone) arginine kinases, and the homology between Battilus and Nordotis was 79%. Molluscan arginine kinases also show lower, but significant homology (38-43%) with rabbit creatine kinase. The sequences of arginine kinases could be used as a molecular clock to elucidate the phylogeny of Mollusca, one of the most diverse animal phyla. PMID:9217008

  1. 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.

  2. Role of submaximal exercise in promoting creatine and glycogen accumulation in human skeletal muscle.

    Science.gov (United States)

    Robinson, T M; Sewell, D A; Hultman, E; Greenhaff, P L

    1999-08-01

    We examined the effect of glycogen-depleting exercise on subsequent muscle total creatine (TCr) accumulation and glycogen resynthesis during postexercise periods when the diet was supplemented with carbohydrate (CHO) or creatine (Cr) + CHO. Fourteen subjects performed one-legged cycling exercise to exhaustion. Muscle biopsies were taken from the exhausted (Ex) and nonexhausted (Nex) limbs after exercise and after 6 h and 5 days of recovery, during which CHO (CHO group, n = 7) or Cr + CHO (Cr+CHO group, n = 7) supplements were ingested. Muscle TCr concentration ([TCr]) was unchanged in both groups 6 h after supplementation commenced but had increased in the Ex (P supercompensation in the exercised muscle. PMID:10444618

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

    OpenAIRE

    Beis Lukas Y; Polyviou Thelma; Malkova Dalia; Pitsiladis Yannis P

    2011-01-01

    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...

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

    OpenAIRE

    Cribb Paul J; Williams Andrew D; Rybalka Emma; Cooke Matthew B; Hayes Alan

    2009-01-01

    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 pa...

  5. Effect of tablet geometrical structure on the dehydration of creatine monohydrate tablets, and their pharmaceutical properties

    OpenAIRE

    Sakata, Yukoh; Shiraishi, Sumihiro; Otsuka, Makoto

    2005-01-01

    The effects of compression and pulverization on the dehydration kinetics and hardness of creatine monohydrate tablets were studied using a variety of kinetic equations and physical models. The dehydration behavior of unpulverized and pulverized tablets was investigated by using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). The hardness of both unpulverized and pulverized monohydrate tablets was significantly decreased after dehydration. The relationship between ...

  6. Creatine supplementation spares muscle glycogen during high intensity intermittent exercise in rats

    OpenAIRE

    Costa André; Marquezi Marcelo; Gualano Bruno; Roschel Hamilton; Lancha Antonio H

    2010-01-01

    Abstract Background The effects of creatine (CR) supplementation on glycogen content are still debatable. Thus, due to the current lack of clarity, we investigated the effects of CR supplementation on muscle glycogen content after high intensity intermittent exercise in rats. Methods First, the animals were submitted to a high intensity intermittent maximal swimming exercise protocol to ensure that CR-supplementation was able to delay fatigue (experiment 1). Then, the CR-mediated glycogen spa...

  7. The effect of supraphysiological doses of creatine on homocysteine metabolism in sportsmen

    Czech Academy of Sciences Publication Activity Database

    Kohlíková, E.; Petr, M.; Přistoupilová, K.; Šenholdová, Z.; Přistoupil, T. I.; Pelclová, D.; Žák, J.; Heyrovský, Michael; Navrátil, Tomáš

    Praha: IV. interní klinika 1. LF UK Praha, 2007, s. 45-48. ISBN 978-80-254-0238-2. [Atherosklerosa 2007. Praha (CZ), 12.09.2007-14.09.2007] R&D Projects: GA ČR GA203/07/1195 Institutional research plan: CEZ:AV0Z40400503 Keywords : Atherosclerosis * homocysteine * creatine * thiodiglyotic acid Subject RIV: CF - Physical ; Theoretical Chemistry

  8. Interaction of creatine metabolism with three possible enzymatic pathways using homocysteine

    Czech Academy of Sciences Publication Activity Database

    Přistoupilová, K.; Navrátil, Tomáš; Petr, M.; Šenholdová, Z.; Přistoupil, T. I.; Pelclová, D.; Žák, J.; Kohlíková, E.; Heyrovský, Michael

    Praha: IV. interní klinika 1. LF UK Praha, 2007, s. 73-76. ISBN 978-80-254-0238-2. [Atherosklerosa 2007. Praha (CZ), 12.09.2007-14.09.2007] R&D Projects: GA ČR GA203/07/1195 Institutional research plan: CEZ:AV0Z40400503 Keywords : Atherosclerosis * homocysteine * creatine * thiodiglyotic acid Subject RIV: CF - Physical ; Theoretical Chemistry

  9. Contribution to explanation of the effect of supplemented creatine in human metabolism

    Czech Academy of Sciences Publication Activity Database

    Navrátil, Tomáš; Kohlíková, E.; Petr, M.; Heyrovský, Michael; Pelclová, D.; Přistoupilová, K.; Přistoupil, T. I.; Šenholdová, Z.

    2009-01-01

    Roč. 112, č. 2 (2009), s. 500-506. ISSN 0308-8146 R&D Projects: GA ČR GA203/07/1195; GA AV ČR IAA400400806 Grant ostatní: Ga MZd(CZ) 8107-3/2004 Institutional research plan: CEZ:AV0Z40400503 Keywords : voltammetry * creatine * creatinine * folates Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.146, year: 2009

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

    OpenAIRE

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

    2006-01-01

    Study objectives Patients with chronic obstructive pulmonary disease (COPD) have low exercise capacity and low content of high energetic phosphates in their skeletal muscles. The aim of the present study was to investigate whether creatine supplementation together with exercise training may increase physical performance compared with exercise training in patients with COPD. Design In a randomized, double-blind, placebo-controlled study, 23 patients with COPD (forced expiratory volume in one s...

  11. Creatine supplementation improves the anaerobic performance of elite junior fin swimmers.

    Science.gov (United States)

    Juhász, Imre; Györe, I; Csende, Zs; Rácz, L; Tihanyi, J

    2009-09-01

    The objective of this study was to determine whether creatine supplementation (CrS) could improve mechanical power output, and swimming performance in highly trained junior competitive fin swimmers. Sixteen male fin swimmers (age:15.9+/-1.6 years) were randomly and evenly assigned to either a creatine (CR, 4x5 g/day creatine monohydrate for 5 days) or placebo group (P, same dose of a dextrose-ascorbic acid placebo) in a double-blind research. Before and after CrS the average power output was determined by a Bosco-test and the swimming time was measured in two maximal 100 m fin swims. After five days of CrS the average power of one minute continuous rebound jumps increased by 20.2%. The lactate concentration was significantly less after 5 minutes restitution at the second measurement in both groups. The swimming time was significantly reduced in both first (pre: 50.69+/-1.41 s; post: 48.86+/-1.34 s) and second (pre: 50.39+/-1.38 s; post: 48.53+/-1.35 s) sessions of swimming in CR group, but remained almost unchanged in the P group.The results of this study indicate that five day Cr supplementation enhances the dynamic strength and may increase anaerobic metabolism in the lower extremity muscles, and improves performance in consecutive maximal swims in highly trained adolescent fin swimmers. PMID:19706374

  12. Impact of creatine supplementation in combination with resistance training on lean mass in the elderly

    Science.gov (United States)

    Pinto, Camila Lemos; Botelho, Patrícia Borges; Carneiro, Juliana Alves

    2016-01-01

    Abstract Background Human ageing is a process characterized by loss of muscle mass, strength, and bone mass. We aimed to examine the efficacy of low‐dose creatine supplementation associated with resistance training on lean mass, strength, and bone mass in the elderly. Methods This was a 12‐week, parallel‐group, double‐blind, randomized, placebo‐controlled trial. The individuals were randomly allocated into one of the following groups: placebo plus resistance training (PL + RT) and creatine supplementation plus resistance training (CR + RT) . The participants were assessed at baseline and after 12 weeks. The primary outcomes were lean mass and strength, assessed by dual energy X‐ray absorptiometry (DXA) and ten‐repetition maximal tests (10 RM), respectively. Secondary outcomes included the lumbar spine, right and left femoral neck, both femur and whole body bone mineral density (BMD), and whole body bone mineral content (BMC), assessed by DXA. Results The CR + RT group had superior gains in lean mass when compared with the PL + RT group (P = 0.02). Changes in the 10 RM tests in bench press and leg press exercises, body composition, BMD, and BMC of all assessed sites did not significantly differ between the groups (P > 0.05). Conclusions Twelve weeks of low‐dose creatine supplementation associated with resistance training resulted in increases in lean mass in the elderly. PMID:27239423

  13. 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.

  14. Is long term creatine and glutamine supplementation effective in enhancing physical performance of military police officers?

    Science.gov (United States)

    da Silveira, Celismar Lázaro; de Souza, Thiago Siqueira Paiva; Batista, Gilmário Ricarte; de Araújo, Adenilson Targino; da Silva, Júlio César Gomes; de Sousa, Maria do Socorro Cirilo; Marta, Carlos; Garrido, Nuno Domingo

    2014-09-29

    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 × 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 × 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. PMID:25713653

  15. 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

    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....

  16. 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.

  17. Creatine transporter (SLC6A8 knock out mice display an increased capacity for in vitro creatine biosynthesis in skeletal muscle

    Directory of Open Access Journals (Sweden)

    AaronPaulRussell

    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.

  18. Myocardial protection of creatine phosphate sodium in patients with acute ST segment elevation myocardial infarction after percutaneous coronary intervention%磷酸肌酸钠对急性ST段抬高型心肌梗死PCI术后的心肌保护作用

    Institute of Scientific and Technical Information of China (English)

    覃秀川; 王春梅; 索旻; 穆希娟; 文勃

    2013-01-01

    Objective To observe the myocardial protective effects of creatine phosphate sodium in patients with acute myocardial infarction after percutaneous coronary intervention. Methods A total of 200 patients with acute ST segment elevation myocardial infarction successfully treated with coronary stent implantation were randomly assigned into two groups; the treatment group(100 cases) comprised 67 men and 33 women with average age of(61.7 ± 10.4)years,the control group(100 cases) comprised 64 men and 36 women with average age of(59.3 ± 11. 2) years. The control group was only treated with routine drug therapy after PCI. The treatment group was treated with routine drug therapy combined with 7 days of intravenous creatine phosphate sodium treatment after PCI. Before and after PCI creatine kinase( CK) , creatine kinase isoenzyme( CK-MB) ,troporin I( cTnl) , hypersensitive C-reaction proteion( hs-CRP) and left ventricular ejection fraction(LVEF)were monitored. Results The content of serum CK,CK-MB,cTnl and hs-CRP in the treatment group was lower than that in the control group. Left ventricular ejection fraction(LVEF) in the treatment group was higher than that in the control group. The differences were statistically significant All P < 0. 05) . Conclusion The application of creatine phosphate sodium in patients with acute myocardial infarction after PCI has a protective effect on myocardium.%目的 观察磷酸肌酸钠对急性心肌梗死PCI术后的心肌保护作用.方法 200例急性ST段抬高型心肌梗死均于急诊行冠脉内支架植入术后收入EICU,随机分为治疗组 100 例[男67例、女33 例,平均年龄(61.7±10.4)岁]和对照组 100 例[男 69 例、女31 例,平均年龄(59.3±11.2)岁].于 PCI术后,对照组给予常规药物治疗,治疗组在常规药物治疗基础上给予静点磷酸肌酸钠治疗 7 d.检测两组患者术前及术后血清中磷酸肌酸激酶(creatine kinase,CK)、磷酸肌酸激酶同工酶(creatine kinase isoenzyme

  19. Brain-type and liver-type fatty acid-binding proteins: new tumor markers for renal cancer?

    Directory of Open Access Journals (Sweden)

    Moch Holger

    2009-07-01

    Full Text Available Abstract Background Renal cell carcinoma (RCC is the most common renal neoplasm. Cancer tissue is often characterized by altered energy regulation. Fatty acid-binding proteins (FABP are involved in the intracellular transport of fatty acids (FA. We examined the level of brain-type (B and liver-type (L FABP mRNA and the protein expression profiles of both FABPs in renal cell carcinoma. Methods Paired tissue samples of cancerous and noncancerous kidney parts were investigated. Quantitative RT-PCR, immunohistochemistry and western blotting were used to determine B- and L-FABP in tumor and normal tissues. The tissue microarray (TMA contained 272 clinico-pathologically characterized renal cell carcinomas of the clear cell, papillary and chromophobe subtype. SPSS 17.0 was used to apply crosstables (χ2-test, correlations and survival analyses. Results B-FABP mRNA was significantly up-regulated in renal cell carcinoma. In normal tissue B-FABP mRNA was very low or often not detectable. RCC with a high tumor grading (G3 + G4 showed significantly lower B-FABP mRNA compared with those with a low grading (G1 + G2. Western blotting analysis detected B-FABP in 78% of the cases with a very strong band but in the corresponding normal tissue it was weak or not detectable. L-FABP showed an inverse relationship for mRNA quantification and western blotting. A strong B-FABP staining was present in 52% of the tumor tissues contained in the TMA. In normal renal tissue, L-FABP showed a moderate to strong immunoreactivity in proximal tubuli. L-FABP was expressed at lower rates compared with the normal tissues in 30.5% of all tumors. There was no correlation between patient survival times and the staining intensity of both FABPs. Conclusion While B-FABP is over expressed in renal cell carcinoma in comparison to normal renal tissues L-FABP appears to be reduced in tumor tissue. Although the expression behavior was not related to the survival outcome of the RCC patients

  20. Brain-type and liver-type fatty acid-binding proteins: new tumor markers for renal cancer?

    International Nuclear Information System (INIS)

    Renal cell carcinoma (RCC) is the most common renal neoplasm. Cancer tissue is often characterized by altered energy regulation. Fatty acid-binding proteins (FABP) are involved in the intracellular transport of fatty acids (FA). We examined the level of brain-type (B) and liver-type (L) FABP mRNA and the protein expression profiles of both FABPs in renal cell carcinoma. Paired tissue samples of cancerous and noncancerous kidney parts were investigated. Quantitative RT-PCR, immunohistochemistry and western blotting were used to determine B- and L-FABP in tumor and normal tissues. The tissue microarray (TMA) contained 272 clinico-pathologically characterized renal cell carcinomas of the clear cell, papillary and chromophobe subtype. SPSS 17.0 was used to apply crosstables (χ2-test), correlations and survival analyses. B-FABP mRNA was significantly up-regulated in renal cell carcinoma. In normal tissue B-FABP mRNA was very low or often not detectable. RCC with a high tumor grading (G3 + G4) showed significantly lower B-FABP mRNA compared with those with a low grading (G1 + G2). Western blotting analysis detected B-FABP in 78% of the cases with a very strong band but in the corresponding normal tissue it was weak or not detectable. L-FABP showed an inverse relationship for mRNA quantification and western blotting. A strong B-FABP staining was present in 52% of the tumor tissues contained in the TMA. In normal renal tissue, L-FABP showed a moderate to strong immunoreactivity in proximal tubuli. L-FABP was expressed at lower rates compared with the normal tissues in 30.5% of all tumors. There was no correlation between patient survival times and the staining intensity of both FABPs. While B-FABP is over expressed in renal cell carcinoma in comparison to normal renal tissues L-FABP appears to be reduced in tumor tissue. Although the expression behavior was not related to the survival outcome of the RCC patients, it can be assumed that these changes indicate fundamental

  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

    OpenAIRE

    Dickinson, Hayley; Ellery, Stacey; Ireland, Zoe; LaRosa, Domenic; Snow, Rodney; Walker, David W.

    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 ...

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

    OpenAIRE

    Carneiro-Junior Miguel A; Ferreira Susana A; Costa Neuza MB; Franco Frederico SC; Natali Antônio J

    2011-01-01

    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), c...

  3. The Relationship Between Creatine and Whey Protein Supplements Consumption and Anesthesia in Rats

    Science.gov (United States)

    Saberi, Kianoush; Gorji Mahlabani, Mohammad Amin; Tashayoie, Mohammad; Nasiri Nejad, Farinaz

    2016-01-01

    Background: Because the trend of pharmacotherapy is toward controlling diet rather than administration of drugs, in our study we examined the probable relationship between Creatine (Cr) or Whey (Wh) consumption and anesthesia (analgesia effect of ketamine). Creatine and Wh are among the most favorable supplements in the market. Whey is a protein, which is extracted from milk and is a rich source of amino acids. Creatine is an amino acid derivative that can change to ATP in the body. Both of these supplements result in Nitric Oxide (NO) retention, which is believed to be effective in N-Methyl-D-aspartate (NMDA) receptor analgesia. Objectives: The main question of this study was whether Wh and Cr are effective on analgesic and anesthetic characteristics of ketamine and whether this is related to NO retention or amino acids’ features Materials and Methods: We divided 30 male Wistar rats to three (n = 10) groups; including Cr, Wh and sham (water only) groups. Each group was administered (by gavage) the supplements for an intermediate dosage during 25 days. After this period, they became anesthetized using a Ketamine-Xylazine (KX) and their time to anesthesia and analgesia, and total sleep time were recorded. Results: Data were analyzed twice using the SPSS 18 software with Analysis of Variance (ANOVA) and post hoc test; first time we expunged the rats that didn’t become anesthetized and the second time we included all of the samples. There was a significant P-value (P < 0.05) for total anesthesia time in the second analysis. Bonferroni multiple comparison indicated that the difference was between Cr and Sham groups (P < 0.021). Conclusions: The data only indicated that there might be a significant relationship between Cr consumption and total sleep time. Further studies, with rats of different gender and different dosage of supplement and anesthetics are suggested.

  4. Creatine and glycerol hyperhydration in trained subjects prior to exercise in the heat.

    OpenAIRE

    Easton, Chris; Turner, Stephen; Pitsiladis, Yannis P

    2007-01-01

    The authors examined the effects of combined creatine (Cr) and glycerol (Gly) supplementation on responses to exercise in the heat. Subjects (N = 24) were matched for body mass and assigned to either a Cr or placebo (Pl) group. Twice daily during two 7-d supplementation regimens, the Cr group received 11.4 g of Cr·H2O and the Pl group received 11.4 g of glucose. Subjects in both groups also ingested 1 g of Gly/kg body mass (twice daily) in either the first or the second supplementation regime...

  5. Effects of oral creatine supplementation on high intensity, intermittent exercise performance in competitive squash players

    OpenAIRE

    Romer, LM; Barrington, JP; Jeukendrup, AE

    2001-01-01

    The purpose of this study was to determine the effects of oral creatine supplementation on high intensity, intermittent exercise performance in competitive squash players. Nine squash players (mean ± SEM V˙O2max = 61.9 ± 2.1ml · kg-1 · min-1; body mass = 73 ± 3 kg) performed an on-court “ghosting” routine that involved 10 sets of 2 repetitions of simulated positional play, each set interspersed with 30 s passive recovery. A double blind, crossover design was utilised whereby experimental and ...

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

    OpenAIRE

    Müge Güler Özden; Geysu Karlıkaya; Yüksel Bek; Nilgün Mutlu

    2008-01-01

    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 app...

  7. 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.

  8. Creatine synthesis and transport during rat embryogenesis: Spatiotemporal expression of AGAT, GAMT and CT1

    Directory of Open Access Journals (Sweden)

    Speer Oliver

    2005-05-01

    Full Text Available Abstract Background Creatine (Cr is synthesized by a two-step mechanism involving arginine:glycine amidinotransferase (AGAT and guanidinoacetate methyltransferase (GAMT, and is taken up by cells through a specific Cr transporter, CT1. Recently, genetic defects of this pathway have been described, that lead to Cr deficiency, neurological symptoms in early infancy and severe neurodevelopmental delay. To investigate the involvement of Cr synthesis and uptake pathways during embryonic development, we determined the spatiotemporal expression of AGAT, GAMT and CT1 during the rat embryogenesis, at the mRNA and protein level. Results We show that AGAT and GAMT are expressed in hepatic primordium as soon as 12.5 days, then progressively acquire their adult pattern of expression, with high levels of AGAT in kidney and pancreas, and high levels of GAMT in liver and pancreas. AGAT and CT1 are prominent in CNS, skeletal muscles and intestine, where they appear earlier than GAMT. High levels of CT1 are found in epithelia. Conclusion Our results suggest that de novo synthesis of Cr by AGAT and GAMT, as well as cellular Cr uptake by CT1, are essential during embryonic development. This work provides new clues on how creatine can be provided to developing tissues, and suggests that Cr deficiencies might induce irreversible damages already in utero, particularly on the nervous system.

  9. Does creatine supplementation improve the plasma lipid profile in healthy male subjects undergoing aerobic training?

    Directory of Open Access Journals (Sweden)

    Scagliusi Fernanda B

    2008-10-01

    Full Text Available Abstract We aimed to investigate the effects of creatine (Cr supplementation on the plasma lipid profile in sedentary male subjects undergoing aerobic training. Methods Subjects (n = 22 were randomly divided into two groups and were allocated to receive treatment with either creatine monohydrate (CR (~20 g·day-1 for one week followed by ~10 g·day-1 for a further eleven weeks or placebo (PL (dextrose in a double blind fashion. All subjects undertook moderate intensity aerobic training during three 40-minute sessions per week, over 3 months. High-density lipoprotein cholesterol (HDL, low-density lipoprotein cholesterol (LDL, very low-density lipoprotein cholesterol (VLDL, total cholesterol (TC, triglyceride (TAG, fasting insulin and fasting glycemia were analyzed in plasma. Thereafter, the homeostasis model assessment (HOMA was calculated. Tests were performed at baseline (Pre and after four (Post 4, eight (Post 8 and twelve (Post 12 weeks. Results We observed main time effects in both groups for HDL (Post 4 versus Post 8; P = 0.01, TAG and VLDL (Pre versus Post 4 and Post 8; P = 0.02 and P = 0.01, respectively. However, no between group differences were noted in HDL, LDL, CT, VLDL and TAG. Additionally, fasting insulin, fasting glycemia and HOMA did not change significantly. Conclusion These findings suggest that Cr supplementation does not exert any additional effect on the improvement in the plasma lipid profile than aerobic training alone.

  10. 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.

  11. 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%). PMID:25559910

  12. Muscle phosphorylase kinase deficiency

    DEFF Research Database (Denmark)

    Preisler, N; Orngreen, M C; Echaniz-Laguna, A; Laforet, P; Lonsdorfer-Wolf, E; Doutreleau, S; Geny, B; Akman, H O; Dimauro, S; Vissing, J

    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)....

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

    Science.gov (United States)

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

    2016-08-01

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

  14. Screening for primary creatine deficiencies in French patients with unexplained neurological symptoms

    Directory of Open Access Journals (Sweden)

    Cheillan David

    2012-12-01

    Full Text Available Abstract 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.

  15. 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.

  16. 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...... 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<0.01-0.05). At week 16, satellite cell...

  17. 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 Schytte

    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...... 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 < 0.01–0.05). At week 16, satellite cell...

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

    DEFF Research Database (Denmark)

    Young, Jette Feveile; Larsen, Lotte Bach; Malmendal, Anders;

    2010-01-01

    -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...

  19. Effect of creatine supplementation during the last week of gestation on birth intervals, stillbirth, and preweaning mortality in pigs

    Science.gov (United States)

    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 ges...

  20. [Effectiveness of protecting the myocardium against ischemia with a normothermic cardioplegic solution and creatine phosphate].

    Science.gov (United States)

    Popov, Iu V; Saprygin, D B; Egorova, I F; Kashtélian, L S; Bakuleva, N P

    1985-01-01

    The protective effects of cardioplegic solutions (CS) containing creatine phosphate (CP) were studied in a rat heart model of cardiopulmonary bypass and ischemic cardiac arrest. Isolated rat hearts were subjected to a 3-minute coronary infusion with CS containing CP in normothermic (37 degrees C) and hypothermic (4-6 degrees C) regimes. In the normothermia group, the postischemic functional recovery was 70-75% of the preischemic control value, while the cellular ATP and CP content was reduced but insignificantly. By contrast, in the hypothermia group, the postischemic functional recovery was markedly depressed, with the tissue high-energy phosphate content being appreciably lowered. The data obtained confirm high efficacy of CP-containing cardioplegic solutions administered under normothermia conditions. PMID:3967061

  1. Pyruvate kinase blood test

    Science.gov (United States)

    ... break down faster than normal, a condition called hemolytic anemia . This test helps diagnose pyruvate kinase deficiency (PKD) . ... Pa: Elsevier Saunders; 2011:chap 32. Gallagher PG. Hemolytic anemias: red cell membrane and metabolic defects In: Goldman ...

  2. Identification of a testis-expressed creatine transporter gene at 16p11.2 and confirmation of the X-linked locus to Xq28

    Energy Technology Data Exchange (ETDEWEB)

    Iyer, G.S.; Funanage, V.L.; Proujansky, R. [Alfred I. duPont Institute, Wilmington, DE (United States)] [and others

    1996-05-15

    Creatine and creatine phosphate act as a buffer system for the regeneration of ATP in tissues with fluctuating energy demands. Following reports of the cloning of a creatine transporter in rat, rabbit, and human, we cloned and sequenced a creatine transporter from a human intestinal cDNA library. PCR amplification of genomic DNAs from somatic cell hybrid panels localized two creatine transporter (CT) genes: CT1 to Xq26-q28 and CT2 to 16p11.2. Refinement of CT1 to Xq28 was confirmed by FISH. Identification of CT2 sequences in YACs and cosmid contigs that had been ordered on human chromosome 16 enabled its assignment to the proximal end of 16p11.2. Sequencing of the CT2 gene identified sequence differences between CT1 and CT2 transcripts that were utilized to determine that CT2 is expressed in testis only. CT2 is the most proximally identified gene on chromosome 16p to date. The existence of an autosomal, testis-specific form of the human creatine transporter gene suggests that creatine transporter activity is critical for normal function of spermatazoa following meiosis. 17 refs., 2 figs., 2 tabs.

  3. Incubating isolated mouse EDL muscles with creatine improves force production and twitch kinetics in fatigue due to reduction in ionic strength.

    Directory of Open Access Journals (Sweden)

    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.

  4. EFFECTS OF HIGH-DOSE CREATINE SUPPLEMENTATION ON KIDNEY AND LIVER RESPONSES IN SEDENTARY AND EXERCISED RATS

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    Wellington Ribeiro

    2009-12-01

    Full Text Available This study evaluated the effects of high-dose of short-term creatine supplementation (5g.kg-1.day-1 to 1 week and long-term creatine supplementation (1g.kg-1. day-1 to 4-8 weeks on kidney and liver structure and function of sedentary and exercised Wistar rats (Exercise sessions consisted of swimming at 80% of maximal work load supported during 5 days per week with daily sessions of 60 minutes throughout the duration of the supplementation. Seventy- two animals (245 ± 5g were divided into four groups (n = 18: control diet Sedentary (SED, Creatine diet Sedentary (CRE, control diet Exercised (EXE, and Creatine diet Exercised (EXECRE. Histological and blood biochemical studies were performed after one, four, and eight weeks of creatine supplementation and exercise (n = 6. No differences were found when comparing SED, EXE and EXECRE groups for kidney and liver structure and function at one, four and eight weeks. However, the CRE group showed higher levels of creatinine (1.1 ± 0.2 vs. 0.4 ± 0.1 mg.dl-1; p < 0.05, and urea (37 ± 3 vs. 19 ± 1 mg.dl-1; p < 0.05 when compared with all others groups at four and eight weeks. At eight weeks, the CRE group presented increased levels of ALT (41 ± 7 vs. 23 ± 7 U.L-1; p < 0.05, AST (89 ± 6 vs. 62 ± 5 U.L-1; p < 0.05, GGT (8.0 ± 0.9 vs. 3.9 ± 1.0 U.L-1; p < 0.05, and AP (125 ± 10 vs. 69 ± 9 U.L-1; p < 0.05 also when compared with all others groups. Moreover, the CRE group demonstrated some structural alterations indicating renal and hepatic damage at four and eight weeks, respectively. These results suggest that long-term creatine supplementation (up to 4-8 weeks may adversely affect kidney and liver structure and function of sedentary but not of exercised rats

  5. 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

  6. 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

  7. 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...

  8. 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

  9. Phosphatidylinositol kinase from rabbit reticulocytes

    International Nuclear Information System (INIS)

    Phosphatidylinositol (PI) kinase was isolated from the postribosomal supernatant of rabbit reticulocytes. This activity was identified by the formation of a product that comigrated with phosphatidylinositol-4-phosphate (PIP) when purified PI was phosphorylated in the presence of [32P]ATP and Mg2+. Three major peaks of PI kinase activity were resolved by chromatography on DEAE-cellulose. The first peak eluted at 50-100 mM NaCl together with several serine protein kinases, casein kinase (CK) I and protease activated kinase (PAK) I and II. The PI kinase was subsequently separated from the protein kinases by chromatography on phosphocellulose. The second peak eluted at 125-160 mM NaCl and contained another lipid kinase activity that produced a product which comigrated with phosphatidic acid on thin layer chromatography. The third peak, which eluted at 165-200 mM NaCl, partly comigrated with casein kinase (CK) II and an active protein kinase(s) which phosphorylated mixed histone and histone I. CK II and the histone kinase activities were also separated by chromatography on phosphocelluslose. The different forms of PI kinase were characterized and compared with respect to substrate and salt requirements

  10. The effects of Isotretinoin on serum levels of creatine phosphokinase and musculoskeletal symptoms in patients with acne vulgaris

    OpenAIRE

    Azizzadeh M; Yahyaee M; Ghorbani R

    2011-01-01

    "nBackground: Acne vulgaris is a common dermatologic disease. Isotretinoin is one of the medications prescribed in severe cases of acne. Despite its high efficacy, isotretinoin use for acne is associated with some side effects. This study was done to evaluate the effects of isotretinoin on serum levels of creatine phosphokinase (CPK) and musculoskeletal symptoms in patients with acne vulgaris."n "nMethods: This study was done on forty 15- to 30-year-old patients with moderate t...

  11. Spectroscopic and quantum chemical study of the structure of a new paramagnetic dimeric palladium(II,III) complex with creatine

    Science.gov (United States)

    Mitewa, Mariana; Enchev, Venelin; Bakalova, Tatyana

    2002-05-01

    The structure and coordination mode of the newly synthesized dimeric paramagnetic Pd(II,III) complex are studied using magneto-chemical, EPR and IR spectroscopic methods. In order to perform reliable assignment of the IR bands, the structure and IR spectrum of the free creatine were calculated using ab initio method. For calculation of the configuration of its deprotonated and doubly deprotonated forms the semiempirical AM1 method was used.

  12. Reciprocal changes of folates and vitamin B12 balance the individual reactions of organisms to creatine supplementation

    Czech Academy of Sciences Publication Activity Database

    Heyrovský, Michael; Přistoupilová, K.; Petr, M.; Šenholdová, Z.; Přistoupil, T. I.; Pelclová, D.; Žák, J.; Kohlíková, E.; Navrátil, Tomáš

    Pardubice: Univerzita Pardubice, 2007 - (Blattná, J.; Horna, A.; Macka, M.; Zima, T.). s. 89-90 ISBN 978-80-7194-937-4. [Vitamins 2007. 19.09.2007-21.09.2007, Praha] R&D Projects: GA MPO 1H-PK/42; GA ČR GA203/07/1195 Institutional research plan: CEZ:AV0Z40400503 Keywords : folates * creatine * vitamin B12 Subject RIV: CF - Physical ; Theoretical Chemistry

  13. Effects of Glycerol and Creatine Hyperhydration on Doping-Relevant Blood Parameters

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    Karsten Koehler

    2012-08-01

    Full Text Available Glycerol is prohibited as an ergogenic aid by the World Anti-Doping Agency (WADA due to the potential for its plasma expansion properties to have masking effects. However, the scientific basis of the inclusion of Gly as a “masking agent” remains inconclusive. The purpose of this study was to determine the effects of a hyperhydrating supplement containing Gly on doping-relevant blood parameters. Nine trained males ingested a hyperhydrating mixture twice per day for 7 days containing 1.0 g•kg−1 body mass (BM of Gly, 10.0 g of creatine and 75.0 g of glucose. Blood samples were collected and total hemoglobin (Hb mass determined using the optimized carbon monoxide (CO rebreathing method pre- and post-supplementation. BM and total body water (TBW increased significantly following supplementation by 1.1 ± 1.2 and 1.0 ± 1.2 L (BM, P < 0.01; TBW, P < 0.01, respectively. This hyperhydration did not significantly alter plasma volume or any of the doping-relevant blood parameters (e.g., hematocrit, Hb, reticulocytes and total Hb-mass even when Gly was clearly detectable in urine samples. In conclusion, this study shows that supplementation with hyperhydrating solution containing Gly for 7 days does not significantly alter doping-relevant blood parameters.

  14. 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.

  15. Effects of glycerol and creatine hyperhydration on doping-relevant blood parameters.

    Science.gov (United States)

    Polyviou, Thelma P; Easton, Chris; Beis, Lukas; Malkova, Dalia; Takas, Pantazis; Hambly, Catherine; Speakman, John R; Koehler, Karsten; Pitsiladis, Yannis P

    2012-09-01

    Glycerol is prohibited as an ergogenic aid by the World Anti-Doping Agency (WADA) due to the potential for its plasma expansion properties to have masking effects. However, the scientific basis of the inclusion of Gly as a "masking agent" remains inconclusive. The purpose of this study was to determine the effects of a hyperhydrating supplement containing Gly on doping-relevant blood parameters. Nine trained males ingested a hyperhydrating mixture twice per day for 7 days containing 1.0 g·kg(-1) body mass (BM) of Gly, 10.0 g of creatine and 75.0 g of glucose. Blood samples were collected and total hemoglobin (Hb) mass determined using the optimized carbon monoxide (CO) rebreathing method pre- and post-supplementation. BM and total body water (TBW) increased significantly following supplementation by 1.1 ± 1.2 and 1.0 ± 1.2 L (BM, P hyperhydration did not significantly alter plasma volume or any of the doping-relevant blood parameters (e.g., hematocrit, Hb, reticulocytes and total Hb-mass) even when Gly was clearly detectable in urine samples. In conclusion, this study shows that supplementation with hyperhydrating solution containing Gly for 7 days does not significantly alter doping-relevant blood parameters. PMID:23112907

  16. Creatine transporter deficiency leads to increased whole body and cellular metabolism.

    Science.gov (United States)

    Perna, Marla K; Kokenge, Amanda N; Miles, Keila N; Udobi, Kenea C; Clark, Joseph F; Pyne-Geithman, Gail J; Khuchua, Zaza; Skelton, Matthew R

    2016-08-01

    Creatine (Cr) is a guanidino compound required for rapid replenishment of ATP in cells with a high-energy demand. In humans, mutations in the Cr transporter (CRT;SLC6A8) prevent Cr entry into tissue and result in a significant intellectual impairment, epilepsy, and aphasia. The lack of Cr on both the whole body and cellular metabolism was evaluated in Crt knockout (Crt (-/y) ) mice, a high-fidelity model of human CRT deficiency. Crt (-/y) mice have reduced body mass and, however, show a twofold increase in body fat. There was increased energy expenditure in a home cage environment and during treadmill running in Crt (-/y) mice. Consistent with the increases in the whole-body metabolic function, Crt (-/y) mice show increased cellular metabolism as well. Mitochondrial respiration increased in skeletal muscle fibers and hippocampal lysates from Crt (-/y) mice. In addition, Crt (-/y) mice had increased citrate synthase activity, suggesting a higher number of mitochondria instead of an increase in mitochondrial activity. To determine if the increase in respiration was due to increased mitochondrial numbers, we measured oxygen consumption in an equal number of mitochondria from Crt (+/y) and Crt (-/y) mice. There were no changes in mitochondrial respiration when normalized to mitochondrial number, suggesting that the increase in respiration observed could be to higher mitochondrial content in Crt (-/y) mice. PMID:27401086

  17. Creatine supplementation spares muscle glycogen during high intensity intermittent exercise in rats

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    Costa André

    2010-01-01

    Full Text Available Abstract Background The effects of creatine (CR supplementation on glycogen content are still debatable. Thus, due to the current lack of clarity, we investigated the effects of CR supplementation on muscle glycogen content after high intensity intermittent exercise in rats. Methods First, the animals were submitted to a high intensity intermittent maximal swimming exercise protocol to ensure that CR-supplementation was able to delay fatigue (experiment 1. Then, the CR-mediated glycogen sparing effect was examined using a high intensity intermittent sub-maximal exercise test (fixed number of bouts; six bouts of 30-second duration interspersed by two-minute rest interval (experiment 2. For both experiments, male Wistar rats were given either CR supplementation or placebo (Pl for 5 days. Results As expected, CR-supplemented animals were able to exercise for a significant higher number of bouts than Pl. Experiment 2 revealed a higher gastrocnemius glycogen content for the CR vs. the Pl group (33.59%. Additionally, CR animals presented lower blood lactate concentrations throughout the intermittent exercise bouts compared to Pl. No difference was found between groups in soleus glycogen content. Conclusion The major finding of this study is that CR supplementation was able to spare muscle glycogen during a high intensity intermittent exercise in rats.

  18. Structural Basis for a Reciprocating Mechanism of Negative Cooperativity in Dimeric Phosphagen Kinase Activity

    Energy Technology Data Exchange (ETDEWEB)

    Wu, X.; Ye, S; Guo, S; Yan, W; Bartlam, M; Rao, Z

    2010-01-01

    Phosphagen kinase (PK) family members catalyze the reversible phosphoryl transfer between phosphagen and ADP to reserve or release energy in cell energy metabolism. The structures of classic quaternary complexes of dimeric creatine kinase (CK) revealed asymmetric ligand binding states of two protomers, but the significance and mechanism remain unclear. To understand this negative cooperativity further, we determined the first structure of dimeric arginine kinase (dAK), another PK family member, at 1.75 {angstrom}, as well as the structure of its ternary complex with AMPPNP and arginine. Further structural analysis shows that the ligand-free protomer in a ligand-bound dimer opens more widely than the protomers in a ligand-free dimer, which leads to three different states of a dAK protomer. The unexpected allostery of the ligand-free protomer in a ligand-bound dimer should be relayed from the ligand-binding-induced allostery of its adjacent protomer. Mutations that weaken the interprotomer connections dramatically reduced the catalytic activities of dAK, indicating the importance of the allosteric propagation mediated by the homodimer interface. These results suggest a reciprocating mechanism of dimeric PK, which is shared by other ATP related oligomeric enzymes, e.g., ATP synthase. - Wu, X., Ye, S., Guo, S., Yan, W., Bartlam, M., Rao, Z. Structural basis for a reciprocating mechanism of negative cooperativity in dimeric phosphagen kinase activity.

  19. Effects of Complementary Creatine Monohydrate and Physical Training on Inflammatory and Endothelial Dysfunction Markers Among Heart Failure Patients

    Science.gov (United States)

    Hemati, Farajollah; Rahmani, Asghar; Asadollahi, Khairollah; Soleimannejad, Koroush; Khalighi, Zahra

    2016-01-01

    Background: Previous studies have reported endothelial dysfunction and inflammatory cytokine in heart failure patients (HF). Objectives: The purpose of this study was to determine the effects of creatine monohydrate and exercise on inflammatory and endothelial dysfunction markers among HF patients. Patients and Methods: One hundred patients were prospectively randomized into two groups: Intervention group which received 5 grams/day creatine monohydrate and exercised for 8 weeks; and control group which did not receive any interventions. Interleukine-6 (IL-6), high sensitivity C reactive protein (hs-CRP), P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) were measured at the start and end of the study for both groups. Results: In total, 100 patients including 50 controls and 50 intervention group (54% male, mean EF of 34.2 ± 10.5% and 52% male, mean EF of 35.6 ± 12.7%, respectively) were analyzed. The serum levels of hs-CRP and IL-6 increased at the end of the study in the control group compared to the baseline, (7.5 ± 1.5 mg/L vs. 6.9 ± 1.3 mg/L, P 0.05). Conclusions: Combination of creatine monohydrate and exercise attenuated inflammation and endothelial dysfunction markers among heart failure patients.

  20. 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....

  1. Synchrotron radiation Fourier-transform infrared and Raman microspectroscopy study showing an increased frequency of creatine inclusions in the rat hippocampal formation following pilocarpine-induced seizures

    OpenAIRE

    Dulinska, J.; Setkowicz, Z.; Janeczko, K.; Sandt, C.; Dumas, P.; Uram, L.; Gzielo-Jurek, K.; Chwiej, J.

    2011-01-01

    In the present work, synchrotron radiation Fourier-transform infrared (SRFTIR) and Raman microspectroscopies were used to evaluate a possible role of creatine in the pathogenesis and progress of pilocarpine-evoked seizures and seizure-induced neurodegenerative changes in the rat hippocampal tissue. The main goal of this study was to identify creatine deposits within the examined brain area, to analyze their frequency in epileptic animals and naive controls and to examine correlations between ...

  2. The effects of four weeks of creatine supplementation and high-intensity interval training on cardiorespiratory fitness: a randomized controlled trial

    OpenAIRE

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

    2009-01-01

    Abstract Background High-intensity interval training has been shown to be a time-efficient way to induce physiological adaptations similar to those of traditional endurance training. Creatine supplementation may enhance high-intensity interval training, leading to even greater physiological adaptations. The purpose of this study was to determine the effects of high-intensity interval training (HIIT) and creatine supplementation on cardiorespiratory fitness and endurance performance (maximal o...

  3. Protective effect of creatine elevation against ischaemia reperfusion injury is retained in the presence of co-morbidities and during cardioplegia.

    OpenAIRE

    Whittington, HJ; McAndrew, DJ; Cross, RL; Neubauer, SK; Lygate, CA

    2016-01-01

    Aims Ischaemic heart disease is most prevalent in the ageing population and often exists with other comorbidities; however the majority of laboratory research uses young, healthy animal models. Several recent workshops and focus meetings have highlighted the importance of using clinically relevant models to help aid translation to realistic patient populations. We have previously shown that mice over-expressing the creatine transporter (CrT-OE) have elevated intracellular creatine levels a...

  4. Kinase Inhibitors from Marine Sponges

    Directory of Open Access Journals (Sweden)

    Ana Zivanovic

    2011-10-01

    Full Text Available Protein kinases play a critical role in cell regulation and their deregulation is a contributing factor in an increasing list of diseases including cancer. Marine sponges have yielded over 70 novel compounds to date that exhibit significant inhibitory activity towards a range of protein kinases. These compounds, which belong to diverse structural classes, are reviewed herein, and ordered based upon the kinase that they inhibit. Relevant synthetic studies on the marine natural product kinase inhibitors have also been included.

  5. Quantitative 3.0T MR spectroscopy reveals decreased creatine concentration in the dorsolateral prefrontal cortex of patients with social anxiety disorder.

    Directory of Open Access Journals (Sweden)

    Qiang Yue

    Full Text Available BACKGROUND: The brain biochemical changes of social anxiety have not been clarified although there have been a limited number of MR spectroscopic studies which utilized metabolite/creatine ratios. Present study aimed to explore the alteration of absolute metabolite concentration in social anxiety disorder using quantitative MR spectroscopy. MATERIALS AND METHODS: With a 3.0T MR scanner, single voxel MR spectroscopy (stimulated echo acquisition mode, TR/TE/TM = 2000/20/16 ms was performed in the left dorsolateral prefrontal cortex and related regions of nine medication-free patients with social anxiety disorder and nine controls. Absolute metabolite concentration was calculated using tissue water as the internal reference and corrected for the partial volume of cerebrospinal fluid. RESULTS: In the left dorsolateral prefrontal cortex, the N-acetyl aspartate/creatine ratio of patients was significantly higher than that of controls, and this was due to the decrease of creatine concentration instead of the increase of N-acetyl aspartate concentration. Furthermore, the creatine concentration of the left dorsolateral prefrontal cortex was negatively correlated with the scores of Liebowitz social anxiety scale. CONCLUSIONS: The alteration of creatine level in the left dorsolateral prefrontal cortex suggests abnormal energy metabolism and correlates with symptom severity in social anxiety disorder. And metabolite concentration is preferable to metabolite/creatine ratio for the investigation of individual, absolute metabolite changes in this region of social anxiety disorder.

  6. 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 BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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

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

    Directory of Open Access Journals (Sweden)

    Alves Christiano RR

    2012-04-01

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

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

    Science.gov (United States)

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

    2008-10-01

    Creatine (Cr) supplementation increases muscle mass, strength, and power. Arginine a-ketoglutarate (A-AKG) is a precursor for nitric oxide production and has the potential to improve blood flow and nutrient delivery (i.e., Cr) to muscles. This study compared a commercial dietary supplement of Cr, A-AKG, glutamine, taurine, branched-chain amino acids, and medium-chain triglycerides with Cr alone or placebo on exercise performance and body composition. Thirty-five men (approximately 23 yr) were randomized to Cr + A-AKG (0.1 g . kg(-1) . d(-1) Cr + 0.075 g . kg(-1) . d(-1)A-AKG, n = 12), Cr (0.1 g . kg(-1) . d(-1), n = 11), or placebo (1 g . kg(-1) . d(-1) sucrose, n = 12) for 10 d. Body composition, muscle endurance (bench press), and peak and average power (Wingate tests) were measured before and after supplementation. Bench-press repetitions over 3 sets increased with Cr + A-AKG (30.9 +/- 6.6 +/- 34.9 +/- 8.7 reps; p < .01) and Cr (27.6 +/- 5.9 +/- 31.0 +/- 7.6 reps; p < .01), with no change for placebo (26.8 +/- 5.0 +/- 27.1 +/- 6.3 reps). Peak power significantly increased in Cr + A-AKG (741 +/- 112 +/- 794 +/- 92 W; p < .01), with no changes in Cr (722 +/- 138 +/- 730 +/- 144 W) and placebo (696 +/- 63 +/- 705 +/- 77 W). There were no differences in average power between groups over time. Only the Cr-only group increased total body mass (79.9 +/- 13.0 +/- 81.1 +/- 13.8 kg; p < .01), with no significant changes in lean-tissue or fat mass. These results suggest that Cr alone and in combination with A-AKG improves upper body muscle endurance, and Cr + A-AKG supplementation improves peak power output on repeated Wingate tests. PMID:19033611

  9. 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.

  10. Structural basis for the mechanism and substrate specificity of glycocyamine kinase, a phosphagen kinase family member

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Kap; Pullalarevu, Sadhana; Surabian, Karen Talin; Howard, Andrew; Suzuki, Tomohiko; Moult, John; Herzberg, Osnat (Kochi); (IIT); (UMBI)

    2010-03-12

    Glycocyamine kinase (GK), a member of the phosphagen kinase family, catalyzes the Mg{sup 2+}-dependent reversible phosphoryl group transfer of the N-phosphoryl group of phosphoglycocyamine to ADP to yield glycocyamine and ATP. This reaction helps to maintain the energy homeostasis of the cell in some multicelullar organisms that encounter high and variable energy turnover. GK from the marine worm Namalycastis sp. is heterodimeric, with two homologous polypeptide chains, {alpha} and {beta}, derived from a common pre-mRNA by mutually exclusive N-terminal alternative exons. The N-terminal exon of GK{beta} encodes a peptide that is different in sequence and is 16 amino acids longer than that encoded by the N-terminal exon of GK{alpha}. The crystal structures of recombinant GK{alpha}{beta} and GK{beta}{beta} from Namalycastis sp. were determined at 2.6 and 2.4 {angstrom} resolution, respectively. In addition, the structure of the GK{beta}{beta} was determined at 2.3 {angstrom} resolution in complex with a transition state analogue, Mg{sup 2+}-ADP-NO{sub 3}{sup -}-glycocyamine. Consistent with the sequence homology, the GK subunits adopt the same overall fold as that of other phosphagen kinases of known structure (the homodimeric creatine kinase (CK) and the monomeric arginine kinase (AK)). As with CK, the GK N-termini mediate the dimer interface. In both heterodimeric and homodimeric GK forms, the conformations of the two N-termini are asymmetric, and the asymmetry is different than that reported previously for the homodimeric CKs from several organisms. The entire polypeptide chains of GK{alpha}{beta} are structurally defined, and the longer N-terminus of the {beta} subunit is anchored at the dimer interface. In GK{beta}{beta} the 24 N-terminal residues of one subunit and 11 N-terminal residues of the second subunit are disordered. This observation is consistent with a proposal that the GK{alpha}{beta} amino acids involved in the interface formation were optimized once

  11. Oncoprotein protein kinase

    Energy Technology Data Exchange (ETDEWEB)

    Karin, Michael (San Diego, CA); Hibi, Masahiko (San Diego, CA); Lin, Anning (La Jolla, CA); Davis, Roger (Princeton, MA); Derijard, Benoit (Shrewsbury, MA)

    2003-02-04

    An isolated polypeptide (JNK) characterized by having a molecular weight of 46kD 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.

  12. Kinase-Catalyzed Biotinylation

    OpenAIRE

    Senevirathne, Chamara; Green, Keith D.; Pflum, Mary Kay H.

    2012-01-01

    Kinase-catalyzed protein phosphorylation plays an essential role in a variety of biological processes. Methods to detect phosphoproteins and phosphopeptides in cellular mixtures will aid in cell biological and signaling research. Our laboratory recently discovered the utility of γ-modified ATP analogues as tools for studying phosphorylation. Specifically, ATP-biotin can be used for labeling and visualizing phosphoproteins from cell lysates. Because the biotin tag is suitable for protein detec...

  13. 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.

  14. Regulation of Autophagy by Kinases

    International Nuclear Information System (INIS)

    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

  15. THE INFLUENCE OF CREATINE SUPPLEMENTATION ON THE GROWTH OF MUSCLE STRENGTH IN MEN PRACTISING BODY-BUILDING

    OpenAIRE

    Jagiello, Wladyslaw; Banach, Jakub

    2009-01-01

    The research group comprised 14 men training recreational body-building in the "TKKF Raj Lodz" Club in Lódź. The subjects were divided into two groups. The experimental group used supplementation with creatine monohydrate (twice daily with 5 g) without the saturation phase. The control group comprised athletes not subject to the supplementation. Both groups trained in consistence with the "P-RR-S" scheme ("Power, Rep-Range, Shock"). The subjects from both groups ate according to a menu contai...

  16. 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. PMID:17603797

  17. Bacterial Protein-Tyrosine Kinases

    DEFF Research Database (Denmark)

    Shi, Lei; Kobir, Ahasanul; Jers, Carsten;

    2010-01-01

    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...... 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...... 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...

  18. The effects of creatine supplementation on thermoregulation and physical (cognitive) performance: a review and future prospects.

    Science.gov (United States)

    Twycross-Lewis, R; Kilduff, L P; Wang, G; Pitsiladis, Y P

    2016-08-01

    Creatine (Cr) is produced endogenously in the liver or obtained exogenously from foods, such as meat and fish. In the human body, 95 % of Cr is located in the cytoplasm of skeletal muscle either in a phosphorylated (PCr) or free form (Cr). PCr is essential for the immediate rephosphorylation of adenosine diphosphate to adenosine triphosphate. PCr is rapidly degraded at the onset of maximal exercise at a rate that results in muscle PCr reservoirs being substantially depleted. A well-established strategy followed to increase muscle total Cr content is to increase exogenous intake by supplementation with chemically pure synthetic Cr. Most Cr supplementation regimens typically follow a well-established loading protocol of 20 g day(-1) of Cr for approximately 5-7 days, followed by a maintenance dose at between 2 and 5 g day(-1) for the duration of interest, although more recent studies tend to utilize a 0.3-g kg(-1) day(-1) supplementation regimen. Some studies have also investigated long-term supplementation of up to 1 year. Uptake of Cr is enhanced when taken together with carbohydrate and protein and/or while undertaking exercise. Cr supplementation has been shown to augment muscle total Cr content and enhance anaerobic performance; however, there is also some evidence of indirect benefits to aerobic endurance exercise through enhanced thermoregulation. While there is an abundance of data supporting the ergogenic effects of Cr supplementation in a variety of different applications, some individuals do not respond, the efficacy of which is dependent on a number of factors, such as dose, age, muscle fiber type, and diet, although further work in this field is warranted. Cr is increasingly being used in the management of some clinical conditions to enhance muscle mass and strength. The application of Cr in studies of health and disease has widened recently with encouraging results in studies involving sleep deprivation and cognitive performance. PMID:27085634

  19. The Effect of Creatin and Carnitine Supplementation on 5 kmClassic and 10 km Free Styles Race Performance of Cross Country Skiers

    Directory of Open Access Journals (Sweden)

    Ebru ÇETİN

    2004-12-01

    Full Text Available This İnvestigation examined the effect of creatin and carnitine supplementation on 5 km classic and 10 km free styles race performance of competitive cross country skiers.Eighteen highly trained (12 male and 6 female cross country skiers aged 13-16 years seperated into 3 equal groups. All groups participated in the 5 km classic and 10 km free races styles in Erciyes at 2200m altitude ski center before the carnitine and creatine loading. After the race subjects were seperated into carnitine, creatine and control groups. Creatine supplementation was given with the dosege of 20gr divided 4 times per day and carnite wasgicen with the dossage of 2gr divided 3 times per day, for seven days.After the last race all results were analysed by repeated measure analysis of variance and SPSS statistical program.According to the study there were no significant effects of carnitin and creatin supplement on 5 km classic and 10 km free styles race performans as in groups. The increased performances which were reperted can be explained by 9 days aerobic, on competition course.

  20. Synchrotron radiation Fourier-transform infrared and Raman microspectroscopy study showing an increased frequency of creatine inclusions in the rat hippocampal formation following pilocarpine-induced seizures.

    Science.gov (United States)

    Dulinska, J; Setkowicz, Z; Janeczko, K; Sandt, C; Dumas, P; Uram, L; Gzielo-Jurek, K; Chwiej, J

    2012-03-01

    In the present work, synchrotron radiation Fourier-transform infrared (SRFTIR) and Raman microspectroscopies were used to evaluate a possible role of creatine in the pathogenesis and progress of pilocarpine-evoked seizures and seizure-induced neurodegenerative changes in the rat hippocampal tissue. The main goal of this study was to identify creatine deposits within the examined brain area, to analyze their frequency in epileptic animals and naive controls and to examine correlations between the number of inclusions in the hippocampal formation of epileptic rats and the quantitative parameters describing animal behavior during 6-h observation period after pilocarpine injection. The presence of creatine in the brain tissue was confirmed based on the vibrational bands specific for this compound in the infrared and Raman spectra. These were the bands occurring at the wavenumbers around 2800, 1621, 1398, and 1304 cm(-1) in IR spectra and around 1056, 908 and 834 cm(-1) in the Raman spectra. Creatine was detected in eight of ten analyzed epileptic samples and in only one of six controls under the study. The number of deposits in epileptic animals varied from 1 to 100 and a relative majority of inclusions were detected in the area of the Dentate Gyrus and in the multiform hippocampal layer. Moreover, the number of creatine inclusions was positively correlated with the total time of seizure activity. PMID:22038587

  1. Study on serum creatine kinase activity in patients with psychopathy%精神疾病患者血清肌酸激酶活性研究

    Institute of Scientific and Technical Information of China (English)

    李筠; 王艳娉; 罗敏; 赵鹏; 王维洁

    2010-01-01

    目的 探讨精神疾病患者血清肌酸激酶活性及临床意义.方法 选择入院时血清肌酸激酶异常增高精神病患者450例做为研究组,同期入院时血清肌酸激酶值在正常范围内的精神病患者400例为对照组,于治疗前、治疗2周末和4周末分别进行血清肌酸激酶、肌酸激酶同工酶,心电图检测,同时以阳性症状与阴性症状量表评定病情.结果 研究组在发病期的血清肌酸激酶值与阳性症状与阴性症状量表有关兴奋行为条目评分及病情严重程度呈正相关,且随着治疗后病情得到控制,阳性症状与阳性症状量表评分阳性症状减少,血清肌酸激酶值及心率亦逐渐下降,4周末已降至正常范围.结论 精神病患者在发病期的阳性症状及病情程度与血清肌酸激酶活性关系密切且相平行,血清肌酸激酶活性有可能成为其生物学标志之一.

  2. Therapeutic targeting of Janus kinases

    OpenAIRE

    Pesu, Marko; Laurence, Arian; Kishore, Nandini; Zwillich, Sam; Chan, Gary; O’Shea, John J.

    2008-01-01

    Cytokines play pivotal roles in immunity and inflammation, and targeting cytokines and their receptors is an effective means of treating such disorders. Type I and II cytokine receptors associate with Janus family kinases (JAKs) to effect intracellular signaling. These structurally unique protein kinases play essential and specific roles in immune cell development and function. One JAK, JAK3, has particularly selective functions. Mutations of this kinase underlie severe combined immunodeficie...

  3. Visualizing autophosphorylation in histidine kinases

    OpenAIRE

    Casino, Patricia; Miguel-Romero, Laura; Marina, Alberto

    2014-01-01

    Reversible protein phosphorylation is the most widespread regulatory mechanism in signal transduction. Autophosphorylation in a dimeric sensor histidine kinase is the first step in two-component signalling, the predominant signal-transduction device in bacteria. Despite being the most abundant sensor kinases in nature, the molecular bases of the histidine kinase autophosphorylation mechanism are still unknown. Furthermore, it has been demonstrated that autophosphorylation can occur in two dir...

  4. Tau-tubulin kinase

    Directory of Open Access Journals (Sweden)

    Seiko Ikezu

    2014-04-01

    Full Text Available Tau-tubulin kinase (TTBK belongs to casein kinase superfamily and can phosphorylate microtubule-associated protein tau and tubulin. TTBK has two isoforms, TTBK1 and TTBK2, which contain highly homologous catalytic domains but their non-catalytic domains are distinctly different. TTBK1 is expressed specifically in the central nervous system and is involved in phosphorylation and aggregation of tau. TTBK2 is ubiquitously expressed in multiple tissues and genetically linked to spinocerebellar ataxia type 11. TTBK1 directly phosphorylates tau protein, especially at Ser422, and also activates cycline-dependent kinase 5 in a unique mechanism. TTBK1 protein expression is significantly elevated in Alzheimer’s disease brains, and genetic variations of the TTBK1 gene are associated with late-onset Alzheimer’s disease in two cohorts of Chinese and Spanish populations. TTBK1 transgenic mice harboring the entire 55-kilobase genomic sequence of human TTBK1 show progression of tau accumulation, neuroinflammation, and neurodegeneration when crossed with tau mutant mice. Our recent study shows that there is a striking switch in mononuclear phagocyte and activation phenotypes in the anterior horn of the spinal cord from alternatively activated (M2-skewed microglia to pro-inflammatory (M1-skewed infiltrating peripheral monocytes in P301L tau mutant mice by crossing with TTBK1 transgenic mice. TTBK1 is responsible for mediating M1-activated microglia-induced neurotoxicity, and its overexpression induces axonal degeneration in vitro. These studies suggest that TTBK1 is an important molecule for the inflammatory axonal degeneration, which may be relevant to the pathobiology of tauopathy including Alzheimer’s disease.

  5. Phosphatidylinositol 3-kinase in myogenesis.

    Science.gov (United States)

    Kaliman, P; Zorzano, A

    1997-08-01

    Phosphatidylinositol 3-kinase (PI 3-kinase) has been cloned and characterized in a wide range of organisms. PI 3-kinases are activated by a diversity of extracellular stimuli and are involved in multiple cell processes such as cell proliferation, protein trafficking, cell motility, differentiation, regulation of cytoskeletal structure, and apoptosis. It has recently been shown that PI 3-kinase is a crucial second messenger in the signaling of myogenesis. Two structurally unrelated highly specific inhibitors of PI 3-kinase-wortmannin and LY294002-block the morphological and biochemical differentiation program of different skeletal-muscle cell models. Moreover, L6E9 myoblasts overexpressing a dominant-negative mutant of PI 3-kinase p85 regulatory subunit (Δp85) are unable to differentiate. Furthermore, PI 3-kinase is specifically involved in the insulinlike growth factor (IGF)-dependent myogenic pathway. Indeed, the ability of IGF-I, des-1,3-IGF-I, and IGF-II to promote cell fusion and muscle-specific protein expression is impaired after treatment with PI 3-kinase inhibitors or in cells overexpressing Δp85. The identification of additional key downstream elements of the IGF/PI 3-kinase myogenic cascade is crucial to a detailed understanding of the process of muscle differentiation and may generate new tools for skeletal and cardiac muscle regeneration therapies. (Trends Cardiovasc Med 1997;7:198-202). © 1997, Elsevier Science Inc. PMID:21235885

  6. The influence of dietary protein on market barrows and gilts supplemented creatine monohydrate in conjunction with a high glycemic carbohydrate.

    Science.gov (United States)

    Berg, E P; Stahl, C A; Shannon, M S; McNamara-Perry, D L; Schmidt, T B; Wiegand, B R

    2011-07-01

    The objective of the study was to determine if additional dietary protein improves the lean tissue deposition and carcass merit of pigs supplemented creatine monohydrate in combination with a high glycemic carbohydrate (dextrose). Forty-eight crossbred barrows and gilts (91±0.18 kg) were blocked by sex assigned to 1 of 12 pens (4 pigs/pen, 16 pigs/treatment). Treatments included: control (CON; basal diet consisting of a ground corn-soybean base), combination diet (COMBO; basal diet supplemented with 0.92% creatine monohydrate and 2.75% dextrose), and a combination high protein diet (COMBOHP; COMBO formulated to contain a minimum of 16% crude protein). Barrows on the COMBOHP gained the least 10th rib fat and expressed the highest percentage fat-free carcass lean (P<0.01) after 28 days on test. No significant treatment differences were noted in the fat and lean tissue accretion of gilts. Treatments had no affect the meat quality parameters of barrow and gilt carcasses. PMID:21333458

  7. 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...

  8. Thermoregulatory and cardiovascular responses to creatine, glycerol and alpha lipoic acid in trained cyclists

    Directory of Open Access Journals (Sweden)

    Polyviou Thelma P

    2012-06-01

    Full Text Available Abstract Background It has been shown that supplementation with creatine (Cr and glycerol (Gly, when combined with glucose (Glu necessary for the enhancement of Cr uptake by skeletal muscle, induces significant improvements in thermoregulatory and cardiovascular responses during exercise in the heat. Purpose To determine whether Cr/Gly-induced thermoregulatory and cardiovascular responses are maintained when the majority (~75% of the Glu in the Cr/Gly supplement is replaced with the insulintropic agent alpha lipoic acid (Ala. Methods 22 healthy endurance trained cyclists were randomly assigned to receive either 20 g/day (4 × 5 g/day of Cr, 2 g .kg-1 BM per day (4 × 0.5 g .kg-1 BM per day of Gly and 150 g/day (4 × 37.5 g/day of Glu or 20 g/day (4 × 5 g/day of Cr monohydrate, 2 g .kg-1 BM per day (4 × 0.5 g .kg-1 BM per day of Gly (100 g/day (4 × 25 g/day of Glu and 1000 mg/day (4 × 250 mg/day of Ala for 7 days for 7 days. Exercise trials were conducted pre- and post-supplementation and involved 40 min of constant-load cycling exercise at 70% O2 max by a self-paced 16.1 km time trial at 30°C and 70% relative humidity. Results Median and range values of TBW increased significantly by 2.1 (1.3-3.3 L and 1.8 (0.2-4.6 L in Cr/Gly/Glu and Cr/Gly/Glu/Ala groups respectively (P = 0.03 and of BM not significantly by 1.8 (0.2-3.0 kg and 1.2 (0.5-2.1 kg in Cr/Gly/Glu and in Cr/Gly/Glu/Ala, respectively (P = 0.75. During constant load exercise, heart rate (HR and core temperature (Tcore were significantly lower post-supplementation: HR was reduced on average by 3.3 ± 2.1 beats/min and by 4.8 ± 3.3 beats/min (mean ± SD and Tcore by 0.2 ± 0.1 (mean ± SD in the Cr/Gly/Glu and Cr/Gly/Glu/Ala, respectively The reduction in HR and Tcore was not significantly different between the supplementation groups. Conclusions In comparison to the established hyper hydrating Cr

  9. 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 precursors both in the extracellular medium and inside the cells (astrocytes. In contrast, the increase of labelled Cr was relatively much more limited since labelled Cr after precursors' supplementation did not exceed 2,7% (cerebellar granule cells and 21% (astrocytes of unlabelled Cr. Finally, AGAT, GAMT and SLC6A8 were expressed in both kind of cells. Conclusions Our

  10. MET Receptor Tyrosine Kinase

    Science.gov (United States)

    Faoro, Leonardo; Cervantes, Gustavo M.; El-Hashani, Essam; Salgia, Ravi

    2010-01-01

    MET receptor tyrosine kinase (RTK) and its ligand hepatocyte growth factor (HGF) have become important therapeutic target in oncology, especially lung cancer. MET RTK is involved in cancer cell growth/survival, motility/migration, invasion/metastasis, and in angiogenesis. MET can be overexpressed in lung cancer, sometimes mutated, and sometimes amplified. Not only can MET be overexpressed, there are subsets of lung cancer tumors that have HGF overexpression. The mutations of MET can occur in the semaphorin and/or juxtamembrane domain in a majority of times. Amplification of MET can occur de novo in primary/metastatic tumors, as well arise in the context of therapeutic inhibition. There are a number of clinical inhibitors that have been developed against MET/HGF. Small molecule inhibitors such as XL184 and PF02341066 have come to clinical fruition, as well as antibodies against MET (such as MetMAb). These inhibitors will be discussed. PMID:19861919

  11. A review of creatine supplementation in age-related diseases: more than a supplement for athletes [v1; ref status: indexed, http://f1000r.es/4ak

    Directory of Open Access Journals (Sweden)

    Rachel N. Smith

    2014-09-01

    Full Text Available 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.

  12. MAP Kinases in Immune Responses

    Institute of Scientific and Technical Information of China (English)

    Yongliang Zhang; Chen Dong

    2005-01-01

    MAP kinases are evolutionarily conserved signaling regulators from budding yeast to mammals and play essential roles in both innate and adaptive immune responses. There are three main families of MAPKs in mammals. Each of them has its own activators, inactivators, substrates and scaffolds, which altogether form a fine signaling network in response to different extracellular or intracellular stimulation. In this review, we summarize recent advances in understanding of the regulation of MAP kinases and the roles of MAP kinases in innate and adaptive immune responses.

  13. In vivo relaxation of N-acetyl-aspartate, creatine plus phosphocreatine, and choline containing compounds during the course of brain infarction: a proton MRS study

    DEFF Research Database (Denmark)

    Gideon, P; Henriksen, O

    1992-01-01

    course of infarction can be explained by changes in T1 and T2 relaxation times, eight patients with acute stroke were studied. STEAM sequences with varying echo delay times and repetition times were used to measure T1 and T2 of N-acetyl-aspartate (NAA), creatine plus phosphocreatine (Cr+PCr) and choline...

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

    DEFF Research Database (Denmark)

    Christiansen, P; Toft, P; Larsson, H B;

    1993-01-01

    The fully relaxed water signal was used as an internal standard in a STEAM experiment to calculate the concentrations of the metabolites: N-acetyl aspartate (NAA), creatine + phosphocreatine (Cr + PCr), and choline (Cho) containing compounds in four different parts of the brain in two age groups of...

  15. Creatine is a scavenger for methylglyoxal under physiological conditions via formation of N-(4-methyl-5-oxo-1-imidazolin-2-yl)sarcosine (MG-HCr).

    Science.gov (United States)

    Löbner, Jürgen; Degen, Julia; Henle, Thomas

    2015-03-01

    Following incubation of methylglyoxal and creatine under physiological conditions, N-(4-methyl-5-oxo-1-imidazolin-2-yl)sarcosine (MG-HCr) was isolated and identified by NMR and mass spectrometry. Due to its rapid formation, MG-HCr represents a specific product following "scavenging" of methylglyoxal by creatine. Using hydrophilic interaction chromatography coupled to mass spectrometry, MG-HCr was analyzed in urine samples of healthy volunteers. Daily MG-HCr excretion of nonvegetarians ranged from 0.35 to 3.84 μmol/24 h urine (median: 0.90 μmol/24 h urine) and of vegetarians from 0.11 to 0.31 μmol/24 h urine (median: 0.19 μmol/24 h urine), indicating that formation of MG-HCr in vivo is influenced by the dietary intake of creatine. The trapping of methylglyoxal by creatine may delay the formation of advanced glycation compounds in vivo and, therefore, could be of special importance in situations in which the body has to deal with pathophysiologically increased amounts of dicarbonyl compounds ("carbonyl stress"), for instance in diabetic patients. PMID:25655840

  16. Mitochondrial myopathy in rats fed with a diet containing beta-guanidine propionic acid, an inhibitor of creatine entry in muscle cells.

    OpenAIRE

    Gori, Z.; De Tata, V.; Pollera, M.; Bergamini, E

    1988-01-01

    In rats with phosphoryl-creatine depletion (fed a standard Randoin-Causeret diet containing 1% beta-guanidine propionic acid) abnormal mitochondria were observed in slow skeletal muscles, often containing paracrystalline inclusions very like those induced by ischaemia or mitochondrial poisons and in human mitochondrial myopathy.

  17. EFFECTS OF CREATINE, GINSENG, AND ASTRAGALUS SUPPLEMENTATION ON STRENGTH, BODY COMPOSITION, MOOD, AND BLOOD LIPIDS DURING STRENGTH-TRAINING IN OLDER ADULTS

    Directory of Open Access Journals (Sweden)

    Michael E. Rogers

    2006-03-01

    Full Text Available The effects of supplemental dietary creatine and a botanical extract consisting of ginseng and astragalus were evaluated in 44 adults aged 55-84 years participating in a 12-week strength-training program. Participants consumed creatine only (Cr, creatine plus botanical extract (CrBE, or placebo (PL, and performed bench press, lat pull down, biceps curl, leg press, knee extension, and knee flexion for 3 sets of 8-12 reps on 3 days per week for 12 weeks. The 1-repetition maximum for each exercise, body composition (full-body DEXA, blood lipids, and mood states were evaluated before and after the intervention. Training improved (p < 0.05 strength and lean mass for all groups, however greater gains were observed with Cr and CrBE compared with placebo (but no difference was found between Cr and CrBE. Only CrBE improved blood lipids and self-reported vigor, and the CrBE group lost significantly more body fat and gained more bench press strength than Cr. These results indicate that strength and lean mass gains achieved by older adults participating in a strength training program can be enhanced with creatine supplementation, and that ginseng and astragalus may provide additional health and psychological benefits. However, these herbs do not appear to have an additive effect on strength and lean mass gains during training

  18. Study on Assay of Creatine Phosphate%磷酸肌酸含量测定方法的研究

    Institute of Scientific and Technical Information of China (English)

    郝苏丽; 刘金秀

    2003-01-01

    @@ 磷酸肌酸(creatine phosphate,CP)是一种心肌保护剂,临床用于心麻痹症的心脏保护及心肌代谢窘迫的其他状况,如心肌缺血、肥厚、心梗及心衰的治疗.国外进口药CP含量测定采用特异性联合酶测定法,但终点不明显,结果误差较大.因此本文对其方法进行修改,找出终点判断最佳点,修改后的方法易于操作,实验误差小.现介绍如下:

  19. 肌酸缺乏综合征诊断与治疗%Diagnosis and treatment of creatine deficiency syndrome

    Institute of Scientific and Technical Information of China (English)

    方方; 杨蕾

    2014-01-01

    肌酸缺乏综合征(creatine deficiency syndromes,CDS)是一组影响肌酸合成及转运的先天性遗传代谢性疾病,临床表现为智力缺损、语言发育迟缓、孤独症、癫痫发作、肌张力减退、以锥体外系损害为主的运动障碍和行为问题等.早期诊断并给予肌酸治疗,可改善预后.了解CDS的临床特点,有利于提高临床认识.

  20. Creatine, L-Carnitine, and ω3 Polyunsaturated Fatty Acid Supplementation from Healthy to Diseased Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Giuseppe D’Antona

    2014-01-01

    Full Text Available Myopathies are chronic degenerative pathologies that induce the deterioration of the structure and function of skeletal muscle. So far a definitive therapy has not yet been developed and the main aim of myopathy treatment is to slow the progression of the disease. Current nonpharmacological therapies include rehabilitation, ventilator assistance, and nutritional supplements, all of which aim to delay the onset of the disease and relieve its symptoms. Besides an adequate diet, nutritional supplements could play an important role in the treatment of myopathic patients. Here we review the most recent in vitro and in vivo studies investigating the role supplementation with creatine, L-carnitine, and ω3 PUFAs plays in myopathy treatment. Our results suggest that these dietary supplements could have beneficial effects; nevertheless continued studies are required before they could be recommended as a routine treatment in muscle diseases.

  1. Comparison of the eight weeks of supplementation Creatine and Glutamine consumption along with resistance exercise on the level of ALP in female mice

    Directory of Open Access Journals (Sweden)

    A eskandari

    2015-11-01

    Full Text Available Background and purpose: in recent years, in order to improve power, speed, the increase in the volume of the musculature, preventing sports injuries and maintain the muscle performance athletes use from different resistance exercises and food supplements. In this regard, present study has been conducted with the aim of comparison the influence of an 8 week period consumption of creatine (2 gr.kg-1.day-1 in 1st week and 0.48 gr.kg-1.day-1during 2nd to 8th weeks and glutamine (1 gr.kg-1.day-1 from first to eighth weeks along with resistance exercise on level of ALP of female mice. Materials and methods: This experimental study was done on 80 Small adult female mice of Surrey species (28 ± 5 gram. The animals were randomly divided into 8 groups of: resistance exercise, resistance exercise + creatine, resistance exercise + glutamine, resistance exercise + glutamine + creatine, creatine, glutamine, creatine + glutamine and control groups (N= 10. Resistance exercise (5 days a week was including: climbing (4 sets, 5 times repetition with two minutes rest between the sets from a ladder (with the height of one meter and including 26 steps and bearing 30 percent of the weight of the Mouse body (hanging from tail in the first week and the increasing it up to 200 percent of body weight till the last week of the experiment. During 48 hours after the last practice session of resistance exercise, the blood sample was taken and the the level of ALP has been measured. Findings:The results showed that the level of ALP enzyme in creatine + glutamine + resistance exercise groug had been increased in comparison with the control group (144.3 ± 15.86 in comparison with 234.7 ± 25.69 U.L-1 P < 0.05. Conclusion: The results of this research indicate Creatine and Glutamine supplementation consumption along with resistance exercise increases in the level of ALP enzyme in the liver of mice.

  2. Effect of dietary creatine monohydrate supplementation on muscle lipid peroxidation and antioxidant capacity of transported broilers in summer.

    Science.gov (United States)

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

    2015-11-01

    This experiment was to evaluate the effect of dietary supplementation with creatine monohydrate (CMH) during the finishing period on the muscle lipid peroxidation and antioxidant capacity of broilers that experienced transport stress in summer. A total of 320 male Arbor Acres broilers (28 d in age) were randomly allotted to 3 dietary treatments including a basal control diet without additional CMH (160 birds), or with 600 (80 birds) or 1,200 mg/kg (80 birds) CMH for 14 d. On the morning of d 42, after an 8-h fast, the birds fed the basal diets were divided into 2 equal groups, and all birds in the 4 groups of 80 birds were transported according to the following protocols: 1) a 0.75-h transport of birds on basal diets (as a lower-stress control group), 2) a 3-h transport of birds on basal diets, 3) a 3-h transport of birds on 600 or 4) 1,200 mg/kg CMH supplementation diets. The results showed that the 3-h transport decreased the concentration of creatine (Cr) in both the pectoralis major (PM) and the tibialis anterior (TA) muscles, increased the concentration of phosphocreatine (PCr) and PCr/Cr ratio in PM muscle, and elevated the concentrations of thiobarbituric acid-reactive substances and the activities of total superoxide dismutase and glutathione peroxidase in both the PM and TA muscles of birds (P protein and heat shock protein 70 in both the PM and TA muscles, as well as avian peroxisome proliferator-activated receptor γ coactivator-1α in the TA muscle (P 0.05). These results indicate that dietary CMH supplementation does not provide any significant protection via directly scavenging free radicals or increased antioxidant capacity of transported broilers. PMID:26371332

  3. Isolation of chloroplastic phosphoglycerate kinase

    Energy Technology Data Exchange (ETDEWEB)

    Macioszek, J.; Anderson, L.E. (Univ. of Illinois, Chicago (USA)); Anderson, J.B. (Pennsylvania State Univ., University Park (USA))

    1990-09-01

    We report here a method for the isolation of high specific activity phosphoglycerate kinase (EC 2.7.2.3) from chloroplasts. The enzyme has been purified over 200-fold from pea (Pisum sativum L.) stromal extracts to apparent homogeneity with 23% recovery. Negative cooperativity is observed with the two enzyme phosphoglycerate kinase/glyceraldehyde-3-P dehydrogenase (EC 1.2.1.13) couple restored from the purified enzymes when NADPH is the reducing pyridine nucleotide, consistent with earlier results obtained with crude chloroplastic extracts. Michaelis Menten kinetics are observed when 3-phosphoglycerate is held constant and phosphoglycerate kinase is varied, which suggests that phosphoglycerate kinase-bound 1,3-bisphosphoglycerate may be the preferred substrate for glyceraldehyde-3-P dehydrogenase in the chloroplast.

  4. Protein Crystals of Raf Kinase

    Science.gov (United States)

    1995-01-01

    This image shows crystals of the protein raf kinase grown on Earth (photo a) and on USML-2 (photo b). The space-grown crystals are an order of magnitude larger. Principal Investigator: Dan Carter of New Century Pharmaceuticals

  5. Research and application of creatine as sports nutrition product%肌酸作为运动营养品使用的研究和应用

    Institute of Scientific and Technical Information of China (English)

    杨则宜; 弭苗苗

    2013-01-01

    肌酸或称甲胍乙酸是天然存在于我们机体中的营养素.从上世纪90年代开始,就被运动员使用,现已成为使用最广泛的运动营养品.肌酸的主要作用是增加肌肉中肌酸和磷酸肌酸的含量,增加糖元合成并快速提供能量.在阻力运动的同时使用肌酸,有助于肌肉和力量增长.多年来,国外大量的临床研究证明了这些作用及长期补充肌酸的安全性,并得到了法规的保障.本文旨在通过综述国外的研究成果,帮助我国食品、卫生和体育界对肌酸形成共识.%Creatine or methyl guanidine acetic acid is the nutrient found naturally in our body.From the beginning of the last century 90' s,it was used by athletes.Now it has become a kind of sports nutrition product most widely used in the sports field.The main effect of creatine administration are to increase the retention of creatine and glycogen synthesis in muscle,subsequently resulting in quick provision of energy.Creatine supplementation plus resistance training contributes to muscle and strength increase.Over the years,the beneficial effect and the security of long-term creatine supplementation has been proven by a large number of clinical study as well as the laws and regulations safeguard were obtained in foreign countries.This article aimed to form consensus on creatine in the fields of food,health and sports in our country,through the studies abroad.

  6. Creatina: auxílio ergogênico com potencial antioxidante? Creatine: ergogenic aid with antioxidant potential?

    Directory of Open Access Journals (Sweden)

    Tácito Pessoa de Souza Junior

    2008-06-01

    Full Text Available A creatina é largamente utilizada como auxilio ergogênico, com algumas evidências quanto ao seu efeito positivo na massa magra, força/potência e resistência muscular. Entretanto, esses estudos não conseguiram identificar potenciais mecanismos bioquímicos que pudessem explicar seu efeito na fadiga ou turnover de proteína muscular, existindo a possibilidade de que alguns indivíduos não sejam responsivos a esse suplemento. Outro possível efeito da creatina, que vem sendo recentemente investigado, é a sua ação antioxidante. Mesmo com poucos trabalhos disponíveis, duas possibilidades existem para explicar esse efeito: 1 Ação indireta como tampão energético, devido ao aumento na concentração tecidual de fosfocreatina, que favoreceria a menor produção de metabólitos do ciclo de degradação de purinas (ciclo de Lowenstein, resultando em queda na formação de hipoxantina, xantina e ácido úrico, assim como em espécies reativas de oxigênio (superóxido, peróxido de hidrogênio e radical hidroxil; 2 Por ação direta, apesar de essa propriedade ser inferior à dos antioxidantes já bem conhecidos, como a glutationa reduzida. Mesmo assim, poderia atuar conjuntamente com estes. O objetivo desta comunicação é relatar dados disponíveis sobre esses dois itens.Creatine is largely used as an ergogenic aid with some evidence regarding its positive effect on lean body mass, strength/power and muscle endurance. However, most studies were not capable of identifying biochemical mechanisms that could explain its effect on fatigue or muscle protein turnover. There is also the possibility that some individuals are non-responsive to this supplement. Another possible effect of creatine that has been recently investigated is its antioxidant action, but few studies explored this subject. Nonetheless, it can be emphasized that the antioxidant effect of creatine works in the organism in the following way: 1 Indirect action as an energy buffer

  7. Two novel mutations in SLC6A8 cause creatine transporter defect and distinctive X-linked mental retardation in two unrelated Dutch families.

    Science.gov (United States)

    Mancini, G M S; Catsman-Berrevoets, C E; de Coo, I F M; Aarsen, F K; Kamphoven, J H J; Huijmans, J G; Duran, M; van der Knaap, M S; Jakobs, C; Salomons, G S

    2005-01-30

    Four Dutch male patients, two brothers from unrelated families were referred for investigation of psychomotor and severe language/speech delay. All four patients showed growth deficiency over the years. Facial features and poor body habitus were quite similar in the patients and in their mothers. Brain MRI showed nonspecific periventricular white matter lesions. In all the patients neuropsychological tests revealed moderate mental retardation, attention deficit and hyperactivity with impulsivity, a semantic-pragmatic language disorder, and oral dyspraxia. This specific cognitive profile is different from other children with mental retardation syndromes and seems to be unique. Excretion of creatine to creatinine ratio in urine of the four boys was increased compared to controls and their creatine uptake in fibroblasts was deficient. In the two brothers from the first pedigree, DNA sequence analysis revealed a novel mutation in the splice donor site in intron 10 (IVS10 + 5G>C, c.1495 + 5G>C) of the SLC6A8 gene leading to skipping of exon 10. In the other sib pair a novel missense mutation (c. 1361C>T; p.Pro544Leu) was found. These are the first families reported, in which the clinical suspicion of a creatine transporter disorder was raised on clinical grounds, before a brain 1H-MRS suggested the diagnosis. Screening of apparently X-linked mental retarded patients with this somatic and behavioral phenotype by the biochemical assay of creatine to creatinine ratio in the urine or DNA sequence analysis of SLC6A8 is worthwhile even when 1H-MRS is not available. PMID:15690373

  8. Reduction in temporal N-acetylaspartate and creatine (or choline) ratio in temporal lobe epilepsy: does this 1H-magnetic resonance spectroscopy finding mean poor seizure control?

    OpenAIRE

    Mendes-Ribeiro, J.; Soares, R.,; Simoes-Ribeiro, F.; Guimaraes, M

    1998-01-01

    BACKGROUND—Proton magnetic resonance spectroscopy (1H-MRS) is a potentially useful tool in the in vivo investigation of brain metabolites in intractable temporal lobe epilepsy (TLE). Focal N-acetylaspartatate (NAA) reductions have been correlated with mesial temporal sclerosis (MTS) in surgically resected epileptogenic foci.
OBJECTIVE—To evaluate the abnormalities in the metabolites NAA, creatine+ phosphocreatine (Cr), and choline containing compounds (Cho) in the tempora...

  9. Quantitative 3.0T MR Spectroscopy Reveals Decreased Creatine Concentration in the Dorsolateral Prefrontal Cortex of Patients with Social Anxiety Disorder

    OpenAIRE

    Qiang Yue; Mengqi Liu; Xiaojing Nie; Qizhu Wu; Jun Li; Wei Zhang; Xiaoqi Huang; Qiyong Gong

    2012-01-01

    BACKGROUND: The brain biochemical changes of social anxiety have not been clarified although there have been a limited number of MR spectroscopic studies which utilized metabolite/creatine ratios. Present study aimed to explore the alteration of absolute metabolite concentration in social anxiety disorder using quantitative MR spectroscopy. MATERIALS AND METHODS: With a 3.0T MR scanner, single voxel MR spectroscopy (stimulated echo acquisition mode, TR/TE/TM = 2000/20/16 ms) was performed in ...

  10. Pigmented Creatine Deposits in Amyotrophic Lateral Sclerosis Central Nervous System Tissues Identified by Synchrotron Fourier Transform Infrared Microspectroscopy and X-ray Fluorescence Spectromicroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Kastyak, M.; Szczerbowska-Boruchowska, M; Adamek, D; Tomik, B; Lankosz, M; Gough, K

    2010-01-01

    Amyotrophic Lateral Sclerosis (ALS) is an untreatable, neurodegenerative disease of motor neurons characterized by progressive muscle atrophy, limb paralysis, dysarthria, dysphagia, dyspnae and finally death. Large motor neurons in ventral horns of spinal cord and motor nuclei in brainstem, large pyramidal neurons of motor cortex and/or large myelinated axons of corticospinal tracts are affected. In recent synchrotron Fourier Transform Infrared microspectroscopy (sFTIR) studies of ALS CNS autopsy tissue, we discovered a small deposit of crystalline creatine, which has a crucial role in energy metabolism. We have now examined unfixed, snap frozen, post-autopsy tissue sections of motor cortex, brain stem, spinal cord, hippocampus and substantia nigra from six ALS and three non-degenerated cases with FTIR and micro-X-ray fluorescence (XRF). Heterogeneous pigmented deposits were discovered in spinal cord, brain stem and motor neuron cortex of two ALS cases. The FTIR signature of creatine has been identified in these deposits and in numerous large, non-pigmented deposits in four of the ALS cases. Comparable pigmentation and creatine deposits were not found in controls or in ALS hippocampus and substantia nigra. Ca, K, Fe, Cu and Zn, as determined by XRF, were not correlated with the pigmented deposits; however, there was a higher incidence of hot spots (Ca, Zn, Fe and Cu) in the ALS cases. The identity of the pigmented deposits remains unknown, although the absence of Fe argues against both erythrocytes and neuromelanin. We conclude that elevated creatine deposits may be indicators of dysfunctional oxidative processes in some ALS cases.

  11. The effects of four weeks of creatine supplementation and high-intensity interval training on cardiorespiratory fitness: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Cramer Joel T

    2009-11-01

    Full Text Available Abstract Background High-intensity interval training has been shown to be a time-efficient way to induce physiological adaptations similar to those of traditional endurance training. Creatine supplementation may enhance high-intensity interval training, leading to even greater physiological adaptations. The purpose of this study was to determine the effects of high-intensity interval training (HIIT and creatine supplementation on cardiorespiratory fitness and endurance performance (maximal oxygen consumption (VO2PEAK, time-to-exhaustion (VO2PEAKTTE, ventilatory threshold (VT, and total work done (TWD in college-aged men. Methods Forty-three recreationally active men completed a graded exercise test to determine VO2PEAK, VO2PEAKTTE, and VT. In addition, participants completed a time to exhaustion (TTE ride at 110% of the maximum workload reached during the graded exercise test to determine TWD (TTE (sec × W = J. Following testing, participants were randomly assigned to one of three groups: creatine (creatine citrate (Cr; n = 16, placebo (PL; n = 17, or control (n = 10 groups. The Cr and PL groups completed four weeks of HIIT prior to post-testing. Results Significant improvements in VO2PEAK and VO2PEAKTTE occurred in both training groups. Only the Cr group significantly improved VT (16% vs. 10% improvement in PL. No changes occurred in TWD in any group. Conclusion In conclusion, HIIT is an effective and time-efficient way to improve maximal endurance performance. The addition of Cr improved VT, but did not increase TWD. Therefore, 10 g of Cr per day for five days per week for four weeks does not seem to further augment maximal oxygen consumption, greater than HIIT alone; however, Cr supplementation may improve submaximal exercise performance.

  12. Treatment of glycogenosys type V (McArdle disease) with creatine and ketogenic diet with clinical scores and with 31P-MRS on working leg muscle

    OpenAIRE

    Vorgerd, M; Zange, J

    2007-01-01

    McArdle’s disease is caused by genetic defects of the musclespecific isozyme of glycogen phosphorylase, which block ATP formation from glycogen in skeletal muscle. Creatine supplementation and ketogenic diet have been tested as potential supplements for muscle energy metabolism which may improve muscle symptomatic. Outcome measures were clinical scores describing muscle symptomatic and parameters derived from 31P-MRS examinations on working muscle. In two placebo controlled cross-over studies...

  13. 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

  14. Decrease in N-acetylaspartate/creatine ratio in the motor area and the frontal lobe in amyotrophic lateral sclerosis

    International Nuclear Information System (INIS)

    We studied whether N-acetylaspartate (NAA), a neuronal marker, is reduced in the brain of 14 patients with clinically definite amyotrophic lateral sclerosis (ALS) and whether NAA levels in the motor area and frontal lobe correlate with the clinical features, including frontal lobe function. We also studied 14 normal controls were evaluated. We obtained peak integrals in 1H magnetic resonance spectroscopy (MRS) for NAA, creatine (Cr), and choline-containing compounds (Cho). Severity of the disease was determined using the manual muscle strength test, and the Norris limb and bulbar scales. In the patients, the NAA/Cr ratio was reduced in the motor area and frontal lobe, while the Cho/Cr ratio was normal throughout the brain. There were significant correlations between the NAA/Cr ratio in the motor area and the Norris limb scale (r = 0.50; P < 0.01) and between the NAA/Cr ratio in the frontal lobe and the number of categories achieved in the Wisconsin Card Sorting test (r = 0.71; P < 0.05), implying frontal lobe dysfunction. These correlations suggest that a reduced NAA/Cr ratio is a marker of cortical neuronal loss and dysfunction in ALS. (orig.)

  15. Creatine transporter (CrT; Slc6a8 knockout mice as a model of human CrT deficiency.

    Directory of Open Access Journals (Sweden)

    Matthew R Skelton

    Full Text Available 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 knockout expressing mice. Mice were tested for learning and memory deficits and assayed for Cr and neurotransmitter levels. Male CrT(⁻/y (affected mice lack Cr in the brain and muscle with significant reductions of Cr in other tissues including heart and testes. CrT(⁻/y mice showed increased path length during acquisition and reversal learning in the Morris water maze. During probe trials, CrT(⁻/y mice showed increased average distance from the platform site. CrT(⁻/y mice showed reduced novel object recognition and conditioned fear memory compared to CrT(+/y. CrT(⁻/y mice had increased serotonin and 5-hydroxyindole acetic acid in the hippocampus and prefrontal cortex. Ubiquitous CrT knockout mice have learning and memory deficits resembling human CrT deficiency and this model should be useful in understanding this disorder.

  16. Protein kinase CK2 in human diseases

    DEFF Research Database (Denmark)

    Guerra, Barbara; Issinger, Olaf-Georg

    2008-01-01

    Protein kinase CK2 (formerly referred to as casein kinase II) is an evolutionary conserved, ubiquitous protein kinase. There are two paralog catalytic subunits, i.e. alpha (A1) and alpha' (A2). The alpha and alpha' subunits are linked to two beta subunits to produce a heterotetrameric structure....... The catalytic alpha subunits are distantly related to the CMGC subfamily of kinases, such as the Cdk kinases. There are some peculiarities associated with protein kinase CK2, which are not found with most other protein kinases: (i) the enzyme is constitutively active, (ii) it can use ATP and GTP and...... specifically target this protein kinase [10]. Since not all the aspects of what has been published on CK2 can be covered in this review, we would like to recommend the following reviews; (i) for general information on CK2 [11-18] and (ii) with a focus on aberrant CK2 [19-22]....

  17. Degradation of Activated Protein Kinases by Ubiquitination

    OpenAIRE

    Lu, Zhimin; Hunter, Tony

    2009-01-01

    Protein kinases are important regulators of intracellular signal transduction pathways and play critical roles in diverse cellular functions. Once a protein kinase is activated, its activity is subsequently downregulated through a variety of mechanisms. Accumulating evidence indicates that the activation of protein kinases commonly initiates their downregulation via the ubiquitin/proteasome pathway. Failure to regulate protein kinase activity or expression levels can cause human diseases.

  18. Determinants of homodimerization specificity in histidine kinases

    OpenAIRE

    Ashenberg, Orr; Rozen-Gagnon, Kathryn; Laub, Michael T; Keating, Amy E.

    2011-01-01

    Two-component signal transduction pathways consisting of a histidine kinase and a response regulator are used by prokaryotes to respond to diverse environmental and intracellular stimuli. Most species encode numerous paralogous histidine kinases that exhibit significant structural similarity. Yet in almost all known examples, histidine kinases are thought to function as homodimers. We investigated the molecular basis of dimerization specificity, focusing on the model histidine kinase EnvZ and...

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

    Science.gov (United States)

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

    2015-11-01

    The small biomolecule creatine is involved in energy metabolism. Mapping of the total creatine (mostly PCr and Cr) in vivo has been done with chemical shift imaging. Chemical exchange saturation transfer (CEST) allows an alternative detection of creatine via water MRI. Living tissue exhibits CEST effects from different small metabolites, including creatine, with four exchanging protons of its guanidinium group resonating about 2 ppm from the water peak and hence contributing to the amine proton CEST peak. The intermediate exchange rate (≈ 1000 Hz) of the guanidinium protons requires high RF saturation amplitude B1. However, strong B1 fields also label semi-solid magnetization transfer (MT) effects originating from immobile protons with broad linewidths (~kHz) in the tissue. Recently, it was shown that endogenous CEST contrasts are strongly affected by the MT background as well as by T1 relaxation of the water protons. We show that this influence can be corrected in the acquired CEST data by an inverse metric that yields the apparent exchange-dependent relaxation (AREX). AREX has some useful linearity features that enable preparation of both concentration, and--by using the AREX-ratio of two RF irradiation amplitudes B1--purely exchange-rate-weighted CEST contrasts. These two methods could be verified in phantom experiments with different concentration and pH values, but also varying water relaxation properties. Finally, results from a preliminary application to in vivo CEST imaging data of the human calf muscle before and after exercise are presented. The creatine concentration increases during exercise as expected and as confirmed by (31)P NMR spectroscopic imaging. However, the estimated concentrations obtained by our method were higher than the literature values: cCr,rest=24.5±3.74mM to cCr,ex=38.32±13.05mM. The CEST-based pH method shows a pH decrease during exercise, whereas a slight increase was observed by (31)P NMR spectroscopy. PMID:26374674

  20. Effect of creatine phosphate on perioperative myocardial injury caused by living donor fiver transplantation in adult patients%磷酸肌酸钠对活体肝移植术患者围术期心肌损伤的影响

    Institute of Scientific and Technical Information of China (English)

    喻文立; 杜洪印; 翁亦齐

    2010-01-01

    Objective To investigate the effect of creatine phosphate on perioperative myocardial injury caused by living donor liver transplantation(LDLT)in adult patients.Methods Forty ASA Ⅱ -Ⅳ patients(liver function Child-Pugh grade B or C)aged 45-62 yr weighing 47-91 kg undergoing LDLT were randomly divided into 2 groups(n = 20 each): control group(group C)and creatine phosphate group(group CP).In group CP,creatine phosphate 30 mg/kg was injected intravenously at skin incision followed by creatine phosphate infusion at 4 mg· kg- 1 · h- 1 until the end of surgery.In group C,equal volume of normal saline was infused instead of creatine phosphate.HR,MAP,CVP,PCWP,CO and SvO2 were recorded immediately before skin incision,at 5 and 30 min of anhepatic phase,at 5 and 30 min of neohepatic phase and at the end of operation.Blood samples were taken from central vein immediately before skin incision(baseline,T0),at 30 min of anhepatic phase(T1),at 30min of neohepatic phase(T2),at the end of operation(T3)and at 4 and 24 h after operation(T4,5)for determination of serum cardiac troponin I(cTnI)and creatine kinase MB(CK-MB)concentrations and lactate dehydrogenase(LDH)activity.Postoperative adverse events were recorded.Results The serum cTnI and CK-MB concentrations and LDH activity were significantly increased at T2-5 as compared with the baseline value at T0 in both groups(P <0.05 or 0.01).MAP and CO were significantly higher from 5 min of neohepatic phase to the end of operation,the serum cTnI and CK-MB concentrations and LDH activity were significantly lower at T2-5,and the incidence of ventricular arrhythmia was significantly lower in group CP than in group C(P < 0.05 or 0.01).Conclusion Creatine phosphate can attenuate perioperative myocardial injury caused by LDLT in adult patients.%目的 评价磷酸肌酸钠对活体肝移植术患者围术期心肌损伤的影响.方法 活体肝移植术患者40例,ASA分级Ⅱ~Ⅳ级,肝功能Child-Pugh分级B或C级,年龄45

  1. 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

  2. New insights into the trophic and cytoprotective effects of creatine in in vitro and in vivo models of cell maturation.

    Science.gov (United States)

    Sestili, Piero; Ambrogini, Patrizia; Barbieri, Elena; Sartini, Stefano; Fimognari, Carmela; Calcabrini, Cinzia; Diaz, Anna Rita; Guescini, Michele; Polidori, Emanuela; Luchetti, Francesca; Canonico, Barbara; Lattanzi, Davide; Cuppini, Riccardo; Papa, Stefano; Stocchi, Vilberto

    2016-08-01

    A growing body of scientific reports indicates that the role of creatine (Cr) in cellular biochemistry and physiology goes beyond its contribution to cell energy. Indeed Cr has been shown to exert multiple effects promoting a wide range of physiological responses in vitro as well as in vivo. Included in these, Cr promotes in vitro neuron and muscle cell differentiation, viability and survival under normal or adverse conditions; anabolic, protective and pro-differentiative effects have also been observed in vivo. For example Cr has been shown to accelerate in vitro differentiation of cultured C2C12 myoblasts into myotubes, where it also induces a slight but significant hypertrophic effect as compared to unsupplemented cultures; Cr also prevents the anti-differentiation effects caused by oxidative stress in the same cells. In trained adults, Cr increases the mRNA expression of relevant myogemic factors, protein synthesis, muscle strength and size, in cooperation with physical exercise. As to neurons and central nervous system, Cr favors the electrophysiological maturation of chick neuroblasts in vitro and protects them from oxidative stress-caused killing; similarly, Cr promotes the survival and differentiation of GABA-ergic neurons in fetal spinal cord cultures in vitro; in vivo, maternal Cr supplementation promotes the morpho-functional development of hippocampal neurons in rat offsprings. This article, which presents also some new experimental data, focuses on the trophic, pro-survival and pro-differentiation effects of Cr and examines the ensuing preventive and therapeutic potential in pathological muscle and brain conditions. PMID:26724921

  3. The Effects of Hyperhydrating Supplements Containing Creatine and Glucose on Plasma Lipids and Insulin Sensitivity in Endurance-Trained Athletes

    Directory of Open Access Journals (Sweden)

    Thelma P. Polyviou

    2015-01-01

    Full Text Available The addition of carbohydrate (CHO in the form of simple sugars to creatine (Cr supplements is central. The study aimed to determine whether ingestion of glucose (Glu simultaneously with Cr and glycerol (Cr/Gly supplement is detrimental to plasma lipids of endurance-trained individuals and find out whether modification arising can be attenuated by replacing part of the Glu with alpha lipoic acid (Ala. Twenty-two endurance-trained cyclists were randomized to receive Cr/Gly/Glu (11.4 g Cr-H2O, 1 g Gly/kg BM, and 150 g Glu or Cr/Gly/Glu/Ala (11.4 g Cr-H2O, 1 g Gly/kg BM, 100 g Glu, and 1 g Ala for 7 days. Fasting concentration of TAG increased significantly (P < 0.01 after supplementation with Cr/Gly/Glu (before: 0.9 ± 0.2 mmol/L; after: 1.3 ± 0.4 mmol/L and Cr/Gly/Glu/Ala (before: 0.8 ± 0.2 mmol/L; after: 1.2 ± 0.5 mmol/L but changes were not different between the groups. Supplementation significantly (P < 0.05 increased the TAG to HDL-cholesterol ratio but had no effect on fasting concentration of total, HDL-, and LDL-cholesterol and insulin resistance. Thus, addition of Glu to Cr containing supplements enhances plasma TAG concentration and the TAG to HDL-cholesterol ratio and this enhancement cannot be attenuated by partial replacement of Glu with Ala.

  4. The Effects of Hyperhydrating Supplements Containing Creatine and Glucose on Plasma Lipids and Insulin Sensitivity in Endurance-Trained Athletes

    Science.gov (United States)

    Polyviou, Thelma P.; Pitsiladis, Yannis P.; Celis-Morales, Carlos; Brown, Benjamin; Speakman, John R.; Malkova, Dalia

    2015-01-01

    The addition of carbohydrate (CHO) in the form of simple sugars to creatine (Cr) supplements is central. The study aimed to determine whether ingestion of glucose (Glu) simultaneously with Cr and glycerol (Cr/Gly) supplement is detrimental to plasma lipids of endurance-trained individuals and find out whether modification arising can be attenuated by replacing part of the Glu with alpha lipoic acid (Ala). Twenty-two endurance-trained cyclists were randomized to receive Cr/Gly/Glu (11.4 g Cr-H2O, 1 g Gly/kg BM, and 150 g Glu) or Cr/Gly/Glu/Ala (11.4 g Cr-H2O, 1 g Gly/kg BM, 100 g Glu, and 1 g Ala) for 7 days. Fasting concentration of TAG increased significantly (P < 0.01) after supplementation with Cr/Gly/Glu (before: 0.9 ± 0.2 mmol/L; after: 1.3 ± 0.4 mmol/L) and Cr/Gly/Glu/Ala (before: 0.8 ± 0.2 mmol/L; after: 1.2 ± 0.5 mmol/L) but changes were not different between the groups. Supplementation significantly (P < 0.05) increased the TAG to HDL-cholesterol ratio but had no effect on fasting concentration of total, HDL-, and LDL-cholesterol and insulin resistance. Thus, addition of Glu to Cr containing supplements enhances plasma TAG concentration and the TAG to HDL-cholesterol ratio and this enhancement cannot be attenuated by partial replacement of Glu with Ala. PMID:26167296

  5. The effects of Isotretinoin on serum levels of creatine phosphokinase and musculoskeletal symptoms in patients with acne vulgaris

    Directory of Open Access Journals (Sweden)

    Azizzadeh M

    2011-08-01

    Full Text Available "nBackground: Acne vulgaris is a common dermatologic disease. Isotretinoin is one of the medications prescribed in severe cases of acne. Despite its high efficacy, isotretinoin use for acne is associated with some side effects. This study was done to evaluate the effects of isotretinoin on serum levels of creatine phosphokinase (CPK and musculoskeletal symptoms in patients with acne vulgaris."n "nMethods: This study was done on forty 15- to 30-year-old patients with moderate to severe acne vulgaris recruited from Semnan dermatology clinics in 2010. The participants were all candidates for isotretinoin therapy. Serum CPK levels and musculoskeletal physical exam were checked before the treatment and every 2 months for 6 months. Isotretinoin was prescribed 0.5-1 mg/kg/body weight and continued throughout the study period with the same dosage."n "nResults: Thirty-three (82.5% patients were female. The mean (±Standard Deviation age of the participants was 22.3±3.4 years. The mean serum CPK levels increased significantly, (P< 0.05, 2, 4 and 6 months after the treatment, but they remained below the upper limit of normal range (45-160 IU/L, except in an 18-year old patient, which it was 162 IU/L. Moreover, they did not exhibit noticeable musculoskeletal symptoms. Musculoskeletal symptoms, such as mild myalgia, were reported in 10% of the patients but they were relieved gradually."n "nConclusion: It seems that the increase in serum levels of CPK, with or without musculoskeletal symptoms, in patients who are on isotretinoin, is a benign phenomenon. Therefore, we do not recommend measurement of CPK levels in patients with mild myalgia.

  6. RIP Kinases Initiate Programmed Necrosis

    Institute of Scientific and Technical Information of China (English)

    Lorenzo Galluzzi; Oliver Kepp; Guido Kroemer

    2009-01-01

    Some lethal stimuli can induce either apoptosis or necrosis, depending on the cell type and/or experimental setting. Until recently,the molecular bases of this phenomenon were largely unknown. Now, two members of the receptor-interacting serine-threonine kinase (RIP) family, RIP1 and RIP3, have been demonstrated to control the switch between apoptotic and necrotic cell death.Some mechanistic details, however, remain controversial.

  7. 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...... TKs from Gram-positive bacteria are more closely related to the eukaryotic TK1 enzymes than are TKs from Gram-negative bacteria....

  8. Pantothenate Kinase-Associated Neurodegeneration

    OpenAIRE

    Meitinger, Thomas; Prokisch, Holger; Hartig, Monika B.; Klopstock, Thomas

    2012-01-01

    Pantothenate kinase-associated neurodegeneration (PKAN) is a hereditary progressive disorder and the most frequent form of neurodegeneration with brain iron accumulation (NBIA). PKAN patients present with a progressive movement disorder, dysarthria, cognitive impairment and retinitis pigmentosa. In magnetic resonance imaging, PKAN patients exhibit the pathognonomic "eye of the tiger" sign in the globus pallidus which corresponds to iron accumulation and gliosis as shown in neuropathological e...

  9. Oncoprotein protein kinase antibody kit

    Science.gov (United States)

    Karin, Michael; Hibi, Masahiko; Lin, Anning

    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.

  10. Thymidine kinase diversity in bacteria

    DEFF Research Database (Denmark)

    Sandrini, Michael; Clausen, A.R.; Munch-Petersen, B.; Piskur, Jure

    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...... TKs from Gram-positive bacteria are more closely related to the eukaryotic TK1 enzymes than are TKs from Gram-negative bacteria....

  11. Regulation and function of TPL-2,an IκB kinase-regulated MAP kinase kinase kinase

    Institute of Scientific and Technical Information of China (English)

    Thorsten Gantke; Srividya Sriskantharajah; Steven C Ley

    2011-01-01

    The IκB kinase(IKK)complex plays a well-documented role in innate and adaptive immunity.This function has been widely attributed to its role as the central activator of the NF-κB family of transcription factors.However,another important consequence of IKK activation is the regulation of TPL-2,a MEK kinase that is required for activation of ERK-1/2 MAP kinases in myeioid cells following Toll-like receptor and TNF receptor stimulation.In unstimulated cells,TPL-2 is stoichiometrically complexed with the NF-κB inhibitory protein NF-κB1 p105,which blocks TPL-2 access to its substrate MEK,and the ubiquitin-binding protein ABIN-2(A20-binding inhibitor of NF-κB 2),both of which are required to maintain TPL-2 protein stability.Following agonist stimulation,the IKK complex phosphorylates p105,triggering its K48-1inked ubiquitination and degradation by the proteasome.This releases TPL-2 from p105-mediated inhibition,facilitating activation of MEK,in addition to modulating NF-κB activation by liberating associated Rel subunits for translocation into the nucleus.IKK-induced proteolysis of 0105,therefore,can directly regulate both NF-κB and ERK MAP kinase activation via NF-κB1 p105.TPL-2 is critical for production of the proinflammatory cytokine TNF during inflammatory responses.Consequently,there has been considerable interest in the pharmaceutical industry to develop selective TPL-2 inhibitors as drugs for the treatment of TNF-dependent inflammatory,diseases,such as rheumatoid arthritis and inflammatory bowel disease.This review summarizes our current understanding of the regulation of TPL-2 signaling function,and also the complex positive and negative roles of TPL-2 in immune and inflammatory responses.

  12. 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.

  13. Immunochemical characterization of rat brain protein kinase

    International Nuclear Information System (INIS)

    Polyclonal antibodies against rat brain protein kinase C (the Ca2+/phospholipid-dependent enzyme) were raised in goat. These antibodies can neutralize completely the kinase activity in purified enzyme preparation as well as that in the crude homogenate. Immunoblot analysis of the purified and the crude protein kinase C preparations revealed a major immunoreactive band of 80 kDa. The antibodies also recognize the same enzyme from other rat tissues. Neuronal tissues (cerebral cortex, cerebellum, hypothalamus, and retina) and lymphoid organs (thymus and spleen) were found to be enriched in protein kinase C, whereas lung, kidney, liver, heart, and skeletal muscle contained relatively low amounts of this kinase. Limited proteolysis of the purified rat brain protein kinase C with trypsin results in an initial degradation of the kinase into two major fragments of 48 and 38 kDa. Both fragments are recognized by the antibodies. However, further digestion of the 48-kDa fragment to 45 kDa and the 38-kDa fragment to 33 kDa causes a loss of the immunoreactivity. Upon incubation of the cerebellar extract with Ca2+, the 48-kDa fragment was also identified as a major proteolytic product of protein kinase C. Proteolytic degradation of protein kinase C converts the Ca2+/phospholipid-dependent kinase to an independent form without causing a large impairment of the binding of [3H]phorbol 12,13-dibutyrate. The two major proteolytic fragments were separated by ion exchange chromatography and one of them (45-48 kDa) was identified as a protein kinase and the other (33-38 kDa) as a phorbol ester-binding protein. These results demonstrate that rat brain protein kinase C is composed of two functionally distinct units, namely, a protein kinase and a Ca2+-independent/phospholipid-dependent phorbol ester-binding protein

  14. EFSA Panel on Dietetic Products, Nutrition and Allergies; Scientific Opinion on the substantiation of health claims related to creatine and increased attention (ID 1524) and improvement of memory (ID 1528) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    claims in relation to creatine and increased attention and improvement of memory. The scientific substantiation is based on the information provided by the Member States in the consolidated list of Article 13 health claims and references that EFSA has received from Member States or directly from...... stakeholders. The food constituent that is the subject of the health claims is creatine. The Panel considers that creatine is sufficiently characterised....

  15. Determinaciones de niveles de creatina y lípidos mediante espectroscopia por resonancia magnética en miocardio de pacientes con insuficiencia cardiaca no isquémica Myocardial lipids and creatine measured by magnetic resonance spectroscopy among patients with heart failure

    OpenAIRE

    JOSÉ LUIS WINTER; PABLO CASTRO; LUIS MENESES; MÓNICA CHALHUB; HUGO VERDEJO; DOUGLAS GREIG; LUIGI GABRIELLI; MARIO CHIONG; ROBERTO CONCEPCIÓN; ROSEMERIE MELLADO; CLAUDIA HERNÁNDEZ; SERGIO URIBE; SERGIO LAVANDERO

    2010-01-01

    Background: Heart failure (HF) is characterized, among other features, by the development of alterations in myocardial energy metabolism, involving a decrease in glucose utilization and increased free fatty acid uptake by cardiomyocytes, associated with decreased deposits of high-energy phosphates (creatine phosphate/ creatine transporter). Magnetic resonance (MR) imaging allows a direct and noninvasive assessment of myocardial metabolites. Aim: To measure myocardial creatine and lipids by MR...

  16. A suplementação de creatina prejudica a função renal? Does creatine supplementation harm renal function?

    Directory of Open Access Journals (Sweden)

    Bruno Gualano

    2008-02-01

    Full Text Available Enquanto o consumo de creatina por atletas e praticantes de atividade física tem crescido vertiginosamente, os efeitos adversos desse suplemento continuam sendo alvos de calorosos debates científicos, sobretudo no que se refere à função renal. O objetivo dessa revisão é descrever as falhas metodológicas e lacunas na literatura, que contribuem para a divergência do tema. Relatos de caso sugerem que a creatina é um potencial agente nefrotóxico. Em contrapartida, estudos longitudinais, embora possuam diversas limitações, indicam o oposto. Pesquisas com humanos não demonstram efeitos deletérios da suplementação de creatina à função renal, porém a falta de controle experimental e o caráter retrospectivo da maioria delas comprometem as conclusões dos autores. Já os estudos experimentais com ratos empregam bons marcadores de função renal e possuem controle de variáveis satisfatório. Contudo, os resultados destes são contraditórios. Estudos futuros devem investigar os efeitos da suplementação de creatina em diversas patologias renais, assim como em idosos, diabéticos do tipo 2 e hipertensos, cuja propensão a nefropatia é bem descrita. Não há evidências de que a suplementação de creatina prejudique a função renal em sujeitos saudáveis, quando consumida na dosagem preconizada. Diante disso, questiona-se a legitimidade científica da proibição do comércio de creatina no Brasil.While creatine consumption has been greatly increasing among athletes and physical activity practitioners, the adverse effects of this supplement remain scientifically controversial, especially concerning renal function. The aim of this review is to describe the methodological limitations and gaps in the literature which contribute to the topic’s divergence. Case reports suggest that creatine is a nephrotoxic agent. On the other hand, despite having several limitations, longitudinal studies have indicated the opposite. Research with

  17. Effect of creatine phosphate sodium combined with spleen amino peptide on hand-foot-mouth disease in children with myocardial damage

    Institute of Scientific and Technical Information of China (English)

    Yong-Zhi Ye; Ai-Fen Ma; Xiao-Hong Xu

    2016-01-01

    Objective:To explore the clinical effect of creatine phosphate sodium combined with spleen aminopeptide on treatment of hand-foot-mouth disease in children with myocardial damage. Methods:A total of 86 cases with hand-foot-mouth disease combined with cardiac damage in our hospital from January 2012 to July 2014 were randomly divided into the observation group and the control group with 43 cases in each group. Patients in the control group received conventional treatment while observation group patients were treated with creatine phosphate sodium combined with spleen amino peptide treatment. Hs-CRP, myocardial enzymes indexes, serum cytokines, NT-proBNP, PCT, endotoxin, D-lactate and immune related indicators were compared between two groups of children after treatment.Results:In observation group patients' serum IL-4, IL-6 and IL-17 levels were lower than those of of the control group after treatment (P < 0.05) while IFN-γ and IL-10 levels were higher than those of the control group (P < 0.05). In observation group patients' NT-proBNP, PCT, endotoxin and D-lactate levels were lower than those of the control group after treatment (P < 0.05). In observation group patients’ CD3+, CD4+ T lymphocytes, IgA, IgM and IgG levels were higher than those of the control group after treatment while CD8+ T lymphocyte level was lower than that of the control group (P < 0.05).Conclusions:Creatine phosphate sodium combined with spleen amino peptide treatment can effectively protect myocardial and regulate immune as well as optimize systemic inflammatory state.

  18. Regulation of the interaction between protein kinase C-related protein kinase 2 (PRK2) and its upstream kinase, 3-phosphoinositide-dependent protein kinase 1 (PDK1)

    DEFF Research Database (Denmark)

    Dettori, Rosalia; Sonzogni, Silvina; Meyer, Lucas;

    2009-01-01

    The members of the AGC kinase family frequently exhibit three conserved phosphorylation sites: the activation loop, the hydrophobic motif (HM), and the zipper (Z)/turn-motif (TM) phosphorylation site. 3-Phosphoinositide-dependent protein kinase 1 (PDK1) phosphorylates the activation loop of...... numerous AGC kinases, including the protein kinase C-related protein kinases (PRKs). Here we studied the docking interaction between PDK1 and PRK2 and analyzed the mechanisms that regulate this interaction. In vivo labeling of recombinant PRK2 by (32)P(i) revealed phosphorylation at two sites, the...... the mechanism that negatively regulates the docking interaction of PRK2 to the upstream kinase PDK1 is directly linked to the activation mechanism of PRK2 itself. Finally, our results indicate that the mechanisms underlying the regulation of the interaction between PRK2 and PDK1 are specific for PRK2...

  19. Backbone and sidechain 1H, 13C and 15N resonance assignments of the human brain-type fatty acid binding protein (FABP7) in its apo form and the holo forms binding to DHA, oleic acid, linoleic acid and elaidic acid

    DEFF Research Database (Denmark)

    Oeemig, Jesper S; Jørgensen, Mathilde L; Hansen, Mikka S;

    2009-01-01

    In this manuscript, we present the backbone and side chain assignments of human brain-type fatty acid binding protein, also known as FABP7, in its apo form and in four different holo forms, bound to DHA, oleic acid, linoleic acid and elaidic acid.......In this manuscript, we present the backbone and side chain assignments of human brain-type fatty acid binding protein, also known as FABP7, in its apo form and in four different holo forms, bound to DHA, oleic acid, linoleic acid and elaidic acid....

  20. Technical note: Evaluation of the uncertainties in (choline+creatine)/citrate ratios measured by proton MR spectroscopic imaging in patients suspicious for prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zbyn, S.; Krssak, M.; Memarsadeghi, M.; Gholami, B.; Haitel, A.; Weber, M.; Helbich, T.H.; Trattnig, S.; Moser, E.; Gruber, S.

    2014-07-15

    The presented evaluation of the relative uncertainty (δ'CCC) of the (choline + creatine)/citrate (CC/C) ratios can provide objective information about the quality and diagnostic value of prostate MR spectroscopic imaging data. This information can be combined with the numeric values of CC/C ratios and provides metabolic-quality maps enabling accurate cancer detection and user-independent data evaluation. In addition, the prostate areas suffering most from the low precision of CC/C ratios (e. g., prostate base) were identified.

  1. Effects of creatine monohydrate supplementation on exercise-induced apoptosis in athletes: A randomized, double-blind, and placebo-controlled study

    OpenAIRE

    Rahman Rahimi; Bahman Mirzaei; Farhad Rahmani-Nia; Zivar Salehi

    2015-01-01

    Background: Creatine monohydrate (CrM) has been shown to be beneficial to health due to its antioxidant potential. Strenuous exercise is associated with oxidative stress, which could lead to apoptosis. We investigated the ability of CrM in amelioration of apoptosis induced by incremental aerobic exercise (AE) to exhaustion in young athletes. Materials and Methods: In a placebo-controlled, double-blind, randomized, parallel study, 31 young athletes (age 19.52 ± 2.75 years, body mass 79.24 ± 16...

  2. Comparison of the eight weeks of supplementation Creatine and Glutamine consumption along with resistance exercise on the level of ALP in female mice

    OpenAIRE

    Eskandari, A.; Gh Sharifi; M Modaresi

    2015-01-01

    Background and purpose: in recent years, in order to improve power, speed, the increase in the volume of the musculature, preventing sports injuries and maintain the muscle performance athletes use from different resistance exercises and food supplements. In this regard, present study has been conducted with the aim of comparison the influence of an 8 week period consumption of creatine (2 gr.kg-1.day-1 in 1st week and 0.48 gr.kg-1.day-1during 2nd to 8th weeks) and glutamine (1 gr.kg-1.day-1 ...

  3. The potential benefits of creatine and conjugated linoleic acid as adjuncts to resistance training in older adults.

    Science.gov (United States)

    Tarnopolsky, Mark A; Safdar, Adeel

    2008-02-01

    Human aging is associated with a significant reduction in muscle mass (sarcopenia) resulting in muscle weakness and functional limitations in the elderly. Sarcopenia has been associated with mitochondrial dysfunction and the accumulation of mtDNA deletions. Resistance training increases muscle strength and size and can increase mitochondrial capacity and decrease oxidative stress in older adults. Creatine monohydrate (CrM) and conjugated linoleic acid (CLA) have biological effects that could enhance some of the beneficial effects of resistance training in older adults (i.e., up arrow fat-free mass, down arrow total body fat). We have completed two resistance-training studies with CrM alone and CrM+CLA supplementation in older adults to evaluate the independent effects of exercise and dietary supplements, as well as their interactive effects. Our studies, and several others, have found that CrM enhanced the resistance exercise mediated gains in fat-free mass and strength. More recently, we found that the addition of CLA also lead to a significant reduction of body fat after six months of resistance training in older adults. Older adults have fewer wild-type mtDNA copies and higher amounts of mtDNA deletions as compared with younger adults in mature skeletal muscle; however, these deletions are not seen in the satellite cell-derived myoblast cultures. These findings, and the fact that mtDNA deletions are lower and wild-type mtDNA copy number is higher after resistance training in older adults, suggests that activation of satellite cells secondary to resistance exercise-induced muscle damage can dilute or "shift" the proportion of mtDNA genotype towards that of a younger adult. Recent evidence suggests that CrM supplementation in combination with strength training can enhance satellite cell activation and total myonuclei number per muscle fiber in young men. Future studies are required to determine whether the mitochondrial adaptations to resistance exercise in older

  4. Brain serotonin and dopamine modulators, perceptual responses and endurance performance during exercise in the heat following creatine supplementation

    Directory of Open Access Journals (Sweden)

    Kilduff Liam P

    2008-09-01

    Full Text Available Abstract Background The present experiment examined the responses of peripheral modulators and indices of brain serotonin (5-HT and dopamine (DA function and their association with perception of effort during prolonged exercise in the heat after creatine (Cr supplementation. Methods Twenty one endurance-trained males performed, in a double-blind fashion, two constant-load exercise tests to exhaustion at 63 ± 5% V˙ MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi=xH8viVGI8Gi=hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY=rqGqVepae9pg0db9vqaiVgFr0xfr=xfr=xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGafeOvayLbaiaaaaa@2D11@O2 max in the heat (ambient temperature: 30.3 ± 0.5 °C, relative humidity: 70 ± 2% before and after 7 days of Cr (20 g·d-1 Cr + 140 g·d-1 glucose polymer or placebo (Plc (160 g·d-1 glucose polymer supplementation. Results 3-way interaction has shown that Cr supplementation reduced rectal temperature, heart rate, ratings of perceived leg fatigue (P P P P > 0.05; Cr group, n = 11: 47.0 ± 4.7 min vs. 49.7 ± 7.5 min, P > 0.05. However, after dividing the participants into "responders" and "non-responders" to Cr, based on their intramuscular Cr uptake, performance was higher in the "responders" relative to "non-responders" group (51.7 ± 7.4 min vs.47.3 ± 4.9 min, p Conclusion although Cr influenced key modulators of brain 5-HT and DA function and reduced various thermophysiological parameters which all may have contributed to the reduced effort perception during exercise in the heat, performance was improved only in the "responders" to Cr supplementation. The present results may also suggest the demanding of the pre-experimental identification of the participants into "responders" and "non-responders" to Cr supplementation before performing the main experimentation. Otherwise, the possibility of the type II error may be enhanced.

  5. Creatine phosphokinase test

    Science.gov (United States)

    CPK test ... vein. The procedure is called a venipuncture . This test may be repeated over 2 or 3 days ... helps determine which tissue has been damaged. This test may be used to: Diagnose heart attack Evaluate ...

  6. Diacylglycerol Kinase Inhibition and Vascular Function

    OpenAIRE

    Choi, Hyehun; Allahdadi, Kyan J.; Tostes, Rita C A; Webb, R. Clinton

    2009-01-01

    Diacylglycerol kinases (DGKs), a family of lipid kinases, convert diacylglycerol (DG) to phosphatidic acid (PA). Acting as a second messenger, DG activates protein kinase C (PKC). PA, a signaling lipid, regulates diverse functions involved in physiological responses. Since DGK modulates two lipid second messengers, DG and PA, regulation of DGK could induce related cellular responses. Currently, there are 10 mammalian isoforms of DGK that are categorized into five groups based on their structu...

  7. Allosteric small-molecule kinase inhibitors

    DEFF Research Database (Denmark)

    Wu, Peng; Clausen, Mads Hartvig; Nielsen, Thomas E.

    2015-01-01

    Small-molecule kinase inhibitors are invaluable targeted therapeutics for the treatment of various human diseases, especially cancers. While the majority of approved and developed preclinical small-molecule inhibitors are characterized as type I or type II inhibitors that target the ATP......-binding pocket of kinases, the remarkable sequential and structural similarity among ATP pockets renders the selective inhibition of kinases a daunting challenge. Therefore, targeting allosteric pockets of kinases outside the highly conversed ATP pocket has been proposed as a promising alternative to overcome...

  8. MST kinases in development and disease

    OpenAIRE

    Thompson, Barry J.; Sahai, Erik

    2015-01-01

    The mammalian MST kinase family, which is related to the Hippo kinase in Drosophila melanogaster, includes five related proteins: MST1 (also called STK4), MST2 (also called STK3), MST3 (also called STK24), MST4, and YSK1 (also called STK25 or SOK1). MST kinases are emerging as key signaling molecules that influence cell proliferation, organ size, cell migration, and cell polarity. Here we review the regulation and function of these kinases in normal physiology and pathologies, including cance...

  9. Seeding Collaborations to Advance Kinase Science with the GSK Published Kinase Inhibitor Set (PKIS)

    OpenAIRE

    Drewry, David H.; Willson, Timothy M.; Zuercher, William J

    2014-01-01

    To catalyze research on historically untargeted protein kinases, we created the PKIS, an annotated set of 367 small molecule kinase inhibitors. The set has been widely distributed to academic collaborators as an open access tool. It has been used to identify chemical starting points for development of chemical probes for orphan kinases and to investigate kinase signaling in high content phenotypic assays. Access to the set comes with few restrictions other than the requirement that assay resu...

  10. Sensitive kinase assay linked with phosphoproteomics for identifying direct kinase substrates.

    Science.gov (United States)

    Xue, Liang; Wang, Wen-Horng; Iliuk, Anton; Hu, Lianghai; Galan, Jacob A; Yu, Shuai; Hans, Michael; Geahlen, Robert L; Tao, W Andy

    2012-04-10

    Our understanding of the molecular control of many disease pathologies requires the identification of direct substrates targeted by specific protein kinases. Here we describe an integrated proteomic strategy, termed kinase assay linked with phosphoproteomics, which combines a sensitive kinase reaction with endogenous kinase-dependent phosphoproteomics to identify direct substrates of protein kinases. The unique in vitro kinase reaction is carried out in a highly efficient manner using a pool of peptides derived directly from cellular kinase substrates and then dephosphorylated as substrate candidates. The resulting newly phosphorylated peptides are then isolated and identified by mass spectrometry. A further comparison of these in vitro phosphorylated peptides with phosphopeptides derived from endogenous proteins isolated from cells in which the kinase is either active or inhibited reveals new candidate protein substrates. The kinase assay linked with phosphoproteomics strategy was applied to identify unique substrates of spleen tyrosine kinase (Syk), a protein-tyrosine kinase with duel properties of an oncogene and a tumor suppressor in distinctive cell types. We identified 64 and 23 direct substrates of Syk specific to B cells and breast cancer cells, respectively. Both known and unique substrates, including multiple centrosomal substrates for Syk, were identified, supporting a unique mechanism that Syk negatively affects cell division through its centrosomal kinase activity. PMID:22451900

  11. Comparison of Peptide Array Substrate Phosphorylation of c-Raf and Mitogen Activated Protein Kinase Kinase Kinase 8

    NARCIS (Netherlands)

    Parikh, Kaushal; Diks, Sander H.; Tuynman, Jurriaan H. B.; Verhaar, Auke; Lowenberg, Mark; Hommes, Daan W.; Joore, Jos; Pandey, Akhilesh; Peppelenbosch, Maikel P.

    2009-01-01

    Kinases are pivotal regulators of cellular physiology. The human genome contains more than 500 putative kinases, which exert their action via the phosphorylation of specific substrates. The determinants of this specificity are still only partly understood and as a consequence it is difficult to pred

  12. A novel mouse model of creatine transporter deficiency [v2; ref status: indexed, http://f1000r.es/4zb

    Directory of Open Access Journals (Sweden)

    Laura Baroncelli

    2015-01-01

    Full Text Available Mutations in the creatine (Cr transporter (CrT gene lead to cerebral creatine deficiency syndrome-1 (CCDS1, an X-linked metabolic disorder characterized by cerebral Cr deficiency causing intellectual disability, seizures, movement  and behavioral disturbances, language and speech impairment ( OMIM #300352. CCDS1 is still an untreatable pathology that can be very invalidating for patients and caregivers. Only two murine models of CCDS1, one of which is an ubiquitous knockout mouse, are currently available to study the possible mechanisms underlying the pathologic phenotype of CCDS1 and to develop therapeutic strategies. Given the importance of validating phenotypes and efficacy of promising treatments in more than one mouse model we have generated a new murine model of CCDS1 obtained by ubiquitous deletion of 5-7 exons in the Slc6a8 gene. We showed a remarkable Cr depletion in the murine brain tissues and cognitive defects, thus resembling the key features of human CCDS1. These results confirm that CCDS1 can be well modeled in mice. This CrT−/y murine model will provide a new tool for increasing the relevance of preclinical studies to the human disease.

  13. Genetics Home Reference: pyruvate kinase deficiency

    Science.gov (United States)

    ... National (UK) Information Centre for Metabolic Diseases National Organization for Rare Disorders (NORD): Pyruvate Kinase Deficiency Genetic Testing Registry (1 link) Pyruvate kinase deficiency of red cells Scientific articles on PubMed (1 link) PubMed OMIM (1 link) ...

  14. 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 relationship...... suicide gene in anti-cancer therapy....

  15. Protein kinases associated with the yeast phosphoproteome

    Directory of Open Access Journals (Sweden)

    Munn Alan L

    2006-01-01

    Full Text Available Abstract Background Protein phosphorylation is an extremely important mechanism of cellular regulation. A large-scale study of phosphoproteins in a whole-cell lysate of Saccharomyces cerevisiae has previously identified 383 phosphorylation sites in 216 peptide sequences. However, the protein kinases responsible for the phosphorylation of the identified proteins have not previously been assigned. Results We used Predikin in combination with other bioinformatic tools, to predict which of 116 unique protein kinases in yeast phosphorylates each experimentally determined site in the phosphoproteome. The prediction was based on the match between the phosphorylated 7-residue sequence and the predicted substrate specificity of each kinase, with the highest weight applied to the residues or positions that contribute most to the substrate specificity. We estimated the reliability of the predictions by performing a parallel prediction on phosphopeptides for which the kinase has been experimentally determined. Conclusion The results reveal that the functions of the protein kinases and their predicted phosphoprotein substrates are often correlated, for example in endocytosis, cytokinesis, transcription, replication, carbohydrate metabolism and stress response. The predictions link phosphoproteins of unknown function with protein kinases with known functions and vice versa, suggesting functions for the uncharacterized proteins. The study indicates that the phosphoproteins and the associated protein kinases represented in our dataset have housekeeping cellular roles; certain kinases are not represented because they may only be activated during specific cellular responses. Our results demonstrate the utility of our previously reported protein kinase substrate prediction approach (Predikin as a tool for establishing links between kinases and phosphoproteins that can subsequently be tested experimentally.

  16. Differential phosphorylation of ribosomal acidic proteins from yeast cell by two endogenous protein kinases: casein kinase-2 and 60S kinase

    International Nuclear Information System (INIS)

    The native 80S ribosomes isolated from ''Saccharomyces cerevisiae'' (strain W303) cells was phosphorylated by two endogenous protein kinases: multifunctional casein kinase-2 (CK-2) and specific 60S kinase. Three acidic proteins within the 60S ribosomal subunit: YP1β, YP1β' and YP2α are phosphorylated by both kinases. The other two proteins: YP1α and YP2β are predominantly phosphorylated by CK-2 but not by 60S kinase. This was confirmed in the experiment with the recombinant protein, YP2β, as a substrate, which is practically not phosphorylated by specific 60S kinase. These results together with the previous data based on the target amino-acid sequences suggest that, in addition to the multifunctional casein kinase-2 and specific 60S kinase, there exist probably other protein kinase(s) which phosphorylate the ribosomal acidic proteins in the cell. (author). 23 refs, 3 figs, 1 tab

  17. Crystal Structure of Pyridoxal Kinase from the Escherichia coli pdxK Gene: Implications for the Classification of Pyridoxal Kinases

    OpenAIRE

    Safo, Martin K.; Musayev, Faik N.; di Salvo, Martino L.; Hunt, Sharyn; Claude, Jean-Baptiste; Schirch, Verne

    2006-01-01

    The pdxK and pdxY genes have been found to code for pyridoxal kinases, enzymes involved in the pyridoxal phosphate salvage pathway. Two pyridoxal kinase structures have recently been published, including Escherichia coli pyridoxal kinase 2 (ePL kinase 2) and sheep pyridoxal kinase, products of the pdxY and pdxK genes, respectively. We now report the crystal structure of E. coli pyridoxal kinase 1 (ePL kinase 1), encoded by a pdxK gene, and an isoform of ePL kinase 2. The structures were deter...

  18. Efficacy of creatine phosphate sodium on myocardial ischemia in neonatal asphyxia%磷酸肌酸钠治疗新生儿窒息心肌缺血

    Institute of Scientific and Technical Information of China (English)

    张佳磊

    2015-01-01

    目的:探讨磷酸肌酸钠治疗新生儿窒息心肌缺血的疗效。方法选择2013年1月至2014年11月新生儿窒息致心肌缺血的早产儿53例,随机分为实验组27例和对照组26例。对照组给予维生素 C 和三磷酸腺苷的常规治疗,实验组在此基础上加用磷酸肌酸钠。比较两组疗效。结果实验组总有效率为81.5%,对照组为53.8%,实验组总有效率高于对照组,差异有统计学意义(P <0.05)。结论磷酸肌酸钠治疗新生儿窒息心肌缺血有效,值得临床应用。%Objective To investigate the efficacy of creatine phosphate sodiym on myocardial ischemia in neonatal asphyxia. Methods From Janyary 2013 to November 2014,53 patients with myocardial ischemia in neonatal asphyxia were selected,and they were randomly divided into control groyp with 26 cases and experimental groyp with 27 caces. The control groyp was given the conventional treatment of vitamin C and adenosine triphosphate,the experimental groyp based on the yse of creatine phos-phate sodiym. The effects of the two groyps were observed. Results The total effective rate of experimental groyp was 81. 5% , while that of control groyp was 53. 8% ,the difference was significant(P < 0. 05). Conclusion Creatine phosphate sodiym has positive effect on neonatal asphyxia with myocardial damage,so it is worthy of application.

  19. Impact of Precursors Creatine, Creatinine, and Glucose on the Formation of Heterocyclic Aromatic Amines in Grilled Patties of Various Animal Species.

    Science.gov (United States)

    Gibis, Monika; Weiss, Jochen

    2015-11-01

    The impact of precursors such as creatine, creatinine, and glucose on the formation of mutagenic/carcinogenic heterocyclic amines (HAs) were studied in patties of 9 different animal species equally heat treated with a double-plate contact grill. All grilled patties of the various species (veal, beef, pork, lamb, horse, venison, turkey, chicken, ostrich) contained several HAs such as MeIQx (2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline; 0.5-1.4 ng/g), 4,8-DiMeIQx (2-amino-3,4,8-trimethylimidazo[4,5-f] quinoxaline, 0 to 1.3 ng/g), PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine, 1.2 to 10.5 ng/g), harman (1-methyl-9H-pyrido[3,4-b] indole; 0.5 to 3.2 ng/g), and/or norharman (9H-pyrido[3,4-b]indole 0.5 to 1.9 ng/g). Residual glycogen (glucose) content varied greatly from 0.07 to 1.46 wt% on a dry matter (DM) basis. Total creatin(in)e content in raw meat (1.36 to 2.0 wt% DM) hardly differed between species, except in turkey and ostrich (1.1 wt% DM). Chicken contained, compared to all other species, very low concentrations of glucose (0.07 wt% DM) and the highest levels of nonprotein nitrogen compounds. The free amino acids lysine (r = 0.77, P < 0.001), tyrosine, phenylalanine, proline, isoleucine, and aspartic acid (r = 0.47-0.56, P < 0.05) showed significant correlation to PhIP in chicken. Also a linear correlation was found to exist between PhIP (r = 0.87, P < 0.001) and MeIQx (r = 0.35, P < 0.01), and the molar ratio of creatin(in)e to glucose, respectively. Harman as co-mutagens was linearly correlated to the concentration of glucose (r = 0.65, P < 0.001). By contrast, norharman was not significant correlated to glucose levels. PMID:26445401

  20. Physiological roles of mitogen-activated-protein-kinase-activated p38-regulated/activated protein kinase

    Institute of Scientific and Technical Information of China (English)

    Sergiy; Kostenko; Gianina; Dumitriu; Kari; Jenssen; Lgreid; Ugo; Moens

    2011-01-01

    Mitogen-activated protein kinases(MAPKs)are a family of proteins that constitute signaling pathways involved in processes that control gene expression,cell division, cell survival,apoptosis,metabolism,differentiation and motility.The MAPK pathways can be divided into conventional and atypical MAPK pathways.The first group converts a signal into a cellular response through a relay of three consecutive phosphorylation events exerted by MAPK kinase kinases,MAPK kinase,and MAPK.Atypical MAPK pathways are not organized into this three-tiered cascade.MAPK that belongs to both conventional and atypical MAPK pathways can phosphorylate both non-protein kinase substrates and other protein kinases.The latter are referred to as MAPK-activated protein kinases.This review focuses on one such MAPK-activated protein kinase,MAPK-activated protein kinase 5(MK5)or p38-regulated/activated protein kinase(PRAK).This protein is highly conserved throughout the animal kingdom and seems to be the target of both conventional and atypical MAPK pathways.Recent findings on the regulation of the activity and subcellular localization,bona fide interaction partners and physiological roles of MK5/PRAK are discussed.

  1. Mitogen-activated protein kinases in atherosclerosis

    Directory of Open Access Journals (Sweden)

    Dorota Bryk

    2014-01-01

    Full Text Available Intracellular signalling cascades, in which MAPK (mitogen-activated protein kinases intermediate, are responsible for a biological response of a cell to an external stimulus. MAP kinases, which include ERK1/2 (extracellular signalling-regulated kinase, JNK (c-Jun N-terminal kinase and p 38 MAPK, regulate the activity of many proteins, enzymes and transcription factors and thus have a wide spectrum of biological effects. Many basic scientific studies have defined numerous details of their pathway organization and activation. There are also more and more studies suggesting that individual MAP kinases probably play an important role in the pathogenesis of atherosclerosis. They may mediate inflammatory processes, endothelial cell activation, monocyte/macrophage recruitment and activation, smooth muscle cell proliferation and T-lymphocyte differentiation, all of which represent crucial mechanisms involved in pathogenesis of atherosclerosis. The specific inhibition of an activity of the respective MAP kinases may prove a new therapeutic approach to attenuate atherosclerotic plaque formation in the future. In this paper, we review the current state of knowledge concerning MAP kinase-dependent cellular and molecular mechanisms underlying atherosclerosis.

  2. [Mitogen-activated protein kinases in atherosclerosis].

    Science.gov (United States)

    Bryk, Dorota; Olejarz, Wioletta; Zapolska-Downar, Danuta

    2014-01-01

    Intracellular signalling cascades, in which MAPK (mitogen-activated protein kinases) intermediate, are responsible for a biological response of a cell to an external stimulus. MAP kinases, which include ERK1/2 (extracellular signalling-regulated kinase), JNK (c-Jun N-terminal kinase) and p 38 MAPK, regulate the activity of many proteins, enzymes and transcription factors and thus have a wide spectrum of biological effects. Many basic scientific studies have defined numerous details of their pathway organization and activation. There are also more and more studies suggesting that individual MAP kinases probably play an important role in the pathogenesis of atherosclerosis. They may mediate inflammatory processes, endothelial cell activation, monocyte/macrophage recruitment and activation, smooth muscle cell proliferation and T-lymphocyte differentiation, all of which represent crucial mechanisms involved in pathogenesis of atherosclerosis. The specific inhibition of an activity of the respective MAP kinases may prove a new therapeutic approach to attenuate atherosclerotic plaque formation in the future. In this paper, we review the current state of knowledge concerning MAP kinase-dependent cellular and molecular mechanisms underlying atherosclerosis. PMID:24491891

  3. Mitotic regulation by NIMA-related kinases

    Directory of Open Access Journals (Sweden)

    Blot Joelle

    2007-08-01

    Full Text Available Abstract The NIMA-related kinases represent a family of serine/threonine kinases implicated in cell cycle control. The founding member of this family, the NIMA kinase of Aspergillus nidulans, as well as the fission yeast homologue Fin1, contribute to multiple aspects of mitotic progression including the timing of mitotic entry, chromatin condensation, spindle organization and cytokinesis. Mammals contain a large family of eleven NIMA-related kinases, named Nek1 to Nek11. Of these, there is now substantial evidence that Nek2, Nek6, Nek7 and Nek9 also regulate mitotic events. At least three of these kinases, as well as NIMA and Fin1, have been localized to the microtubule organizing centre of their respective species, namely the centrosome or spindle pole body. Here, they have important functions in microtubule organization and mitotic spindle assembly. Other Nek kinases have been proposed to play microtubule-dependent roles in non-dividing cells, most notably in regulating the axonemal microtubules of cilia and flagella. In this review, we discuss the evidence that NIMA-related kinases make a significant contribution to the orchestration of mitotic progression and thereby protect cells from chromosome instability. Furthermore, we highlight their potential as novel chemotherapeutic targets.

  4. The mechanism of protein kinase C regulation

    Institute of Scientific and Technical Information of China (English)

    Julhash U. KAZI

    2011-01-01

    Protein kinase C (PKC) is a family ofserine/threonine protein kinases that plays a central role in transducing extracellular signals into a variety of intracellular responses ranging from cell proliferation to apoptosis.Nine PKC genes have been identified in the human genome,which encode 10 proteins.Each member of this protein kinase family displays distinct biochemical characteristics and is enriched in different cellular and subcellular locations.Activation of PKC has been implicated in the regulation of cell growth and differentiation.This review summarizes works of the past years in the field of PKC biochemistry that covers regulation and activation mechanism of different PKC isoforms.

  5. Differential AMP-activated Protein Kinase (AMPK) Recognition Mechanism of Ca2+/Calmodulin-dependent Protein Kinase Kinase Isoforms.

    Science.gov (United States)

    Fujiwara, Yuya; Kawaguchi, Yoshinori; Fujimoto, Tomohito; Kanayama, Naoki; Magari, Masaki; Tokumitsu, Hiroshi

    2016-06-24

    Ca(2+)/calmodulin-dependent protein kinase kinase β (CaMKKβ) is a known activating kinase for AMP-activated protein kinase (AMPK). In vitro, CaMKKβ phosphorylates Thr(172) in the AMPKα subunit more efficiently than CaMKKα, with a lower Km (∼2 μm) for AMPK, whereas the CaMKIα phosphorylation efficiencies by both CaMKKs are indistinguishable. Here we found that subdomain VIII of CaMKK is involved in the discrimination of AMPK as a native substrate by measuring the activities of various CaMKKα/CaMKKβ chimera mutants. Site-directed mutagenesis analysis revealed that Leu(358) in CaMKKβ/Ile(322) in CaMKKα confer, at least in part, a distinct recognition of AMPK but not of CaMKIα. PMID:27151216

  6. 磷酸肌酸钠在治疗急性心梗的作用%The Role of Creatine Phosphate Sodium in the Treatment of Acute Myocar-dial Infarction (ami)

    Institute of Scientific and Technical Information of China (English)

    王庆奎; 李永东

    2015-01-01

    磷酸肌酸为人体内的一类能量供应商,可以为各个组织提供能量支持。磷酸肌酸钠为一种商业化磷酸肌酸药物,近年来在急性心肌梗死中的应用越来越广泛,并取得良好的效果。该文将综述磷酸肌酸的作用、磷酸肌酸钠的作用机制及其应用进展,为磷酸肌酸钠的进一步临床应用提供参考。%the creatine phosphate is the body of energy suppliers, can provide energy support to various organizations. Creatine phosphate sodium for a commercial, creatine phosphate drugs application in acute myocardial infarction in recent years, more and more widely, and achieved good effect. This article will review the effect of creatine phosphate, sodium phosphocreatine, action mechanism and application of progress for sodium phosphocreatine can provide reference for clinical application.

  7. 1H chemical shift imaging of the brain in guanidino methyltransferase deficiency, a creatine deficiency syndrome; guanidinoacetate accumulation in the gray matter

    International Nuclear Information System (INIS)

    MR spectroscopy results in a mild case of guanidinoacetate methyltransferase (GAMT) deficiency are presented. The approach differs from previous MRS studies in the acquisition of a chemical shift imaging spectral map showing gray and white matter with the corresponding spectra in one overview. MR spectroscopy revealed guanidinoacetate (GAA) in the absence of creatine. New is that GAA signals are more prominent in gray matter than in white. In the prevailing view, that enzyme deficiency is localized in liver and pancreas and that all GAA is transported into the brain from the blood and the cerebrospinal fluid, this would be compatible with a more limited uptake and/or better clearance of GAA from the white matter compared to the grey matter. (orig.)

  8. The effect of production system and age on levels of iron, taurine, carnosine, coenzyme Q(10), and creatine in beef muscles and liver.

    Science.gov (United States)

    Purchas, R W; Busboom, J R

    2005-08-01

    Samples of longissimus (LL) and triceps brachii (TB) muscles from Angus-cross heifers finished either on a high-concentrate ration in Washington, USA, (US cattle, n=15) or on pasture in New Zealand (NZ cattle, n=16) were assessed for composition characteristics. Half of the NZ cattle were of a similar age to the US cattle (NZAge) and half were of a similar weight (NZWt). Iron concentration was higher in TB (20.9 vs. 17.5μgg(-1); Pcarnosine, creatine and creatinine, as expected for a muscle with a more aerobic metabolism. These differences were magnified for the even more aerobic cheek muscle. Differences between the two NZ groups were small, but muscles from the US cattle contained less taurine, carnosine, coenzyme Q(10), and creatinine. Reasons for these differences in various meat components for similar cattle from different production systems are not clear. PMID:22063884

  9. Rac-1 and Raf-1 kinases, components of distinct signaling pathways, activate myotonic dystrophy protein kinase

    Science.gov (United States)

    Shimizu, M.; Wang, W.; Walch, E. T.; Dunne, P. W.; Epstein, H. F.

    2000-01-01

    Myotonic dystrophy protein kinase (DMPK) is a serine-threonine protein kinase encoded by the myotonic dystrophy (DM) locus on human chromosome 19q13.3. It is a close relative of other kinases that interact with members of the Rho family of small GTPases. We show here that the actin cytoskeleton-linked GTPase Rac-1 binds to DMPK, and coexpression of Rac-1 and DMPK activates its transphosphorylation activity in a GTP-sensitive manner. DMPK can also bind Raf-1 kinase, the Ras-activated molecule of the MAP kinase pathway. Purified Raf-1 kinase phosphorylates and activates DMPK. The interaction of DMPK with these distinct signals suggests that it may play a role as a nexus for cross-talk between their respective pathways and may partially explain the remarkable pleiotropy of DM.

  10. Efeitos da suplementação de creatina sobre força e hipertrofia muscular: atualizações Effects of creatine supplementation on strength and muscle hypertrophy: current concepts

    Directory of Open Access Journals (Sweden)

    Bruno Gualano

    2010-06-01

    Full Text Available A suplementação de creatina vem sendo utilizada amplamente na tentativa de aumentar força e massa magra em sujeitos saudáveis e atletas. Além disso, diversos estudos têm sido conduzidos no intuito de desvendar os mecanismos responsáveis pelas eventuais adaptações a esse suplemento. Diante disso, essa revisão teve como objetivos: 1 discutir os principais estudos que investigaram os efeitos da suplementação de creatina na força e hipertrofia; e 2 reunir as evidências acerca dos possíveis mecanismos responsáveis pelo aumento de força e massa magra como consequência desse suplemento, enfatizando os mais recentes achados e as perspectivas sobre o tema. De fato, existem fortes evidências demonstrando que a suplementação de creatina é capaz de promover aumentos de força e hipertrofia. Os efeitos desse suplemento sobre a retenção hídrica, o balanço proteico, a expressão de genes/proteínas associados à hipertrofia e ativação de células satélites, podem explicar as adaptações musculoesqueléticas observadas. Diante desses achados, os potenciais efeitos terapêuticos desse suplemento emergem como um futuro e promissor campo de estudo.Creatine supplementation has been widely used to increase both muscle strength and lean mass in healthy individuals and athletes. Furthermore, several studies have investigated the mechanisms responsible for such adaptations. Thus, this review aimed at 1 examining the major studies investigating the effects of creatine supplementation on strength and hypertrophy, and 2 exploring the mechanisms underlying these responses, stressing the most recent findings and perspectives regarding creatine supplementation. There is strong evidence demonstrating that creatine supplementation is able to enhance strength and hypertrophy. The effects of creatine on water retention, protein balance, genes/proteins related to hypertrophy, and satellite cells activation may explain the creatine-mediated muscle

  11. Creatine ingestion augments dietary carbohydrate mediated muscle glycogen supercompensation during the initial 24 h of recovery following prolonged exhaustive exercise in humans.

    Science.gov (United States)

    Roberts, Paul A; Fox, John; Peirce, Nicholas; Jones, Simon W; Casey, Anna; Greenhaff, Paul L

    2016-08-01

    Muscle glycogen availability can limit endurance exercise performance. We previously demonstrated 5 days of creatine (Cr) and carbohydrate (CHO) ingestion augmented post-exercise muscle glycogen storage compared to CHO feeding alone in healthy volunteers. Here, we aimed to characterise the time-course of this Cr-induced response under more stringent and controlled experimental conditions and identify potential mechanisms underpinning this phenomenon. Fourteen healthy, male volunteers cycled to exhaustion at 70 % VO2peak. Muscle biopsies were obtained at rest immediately post-exercise and after 1, 3 and 6 days of recovery, during which Cr or placebo supplements (20 g day(-1)) were ingested along with a prescribed high CHO diet (37.5 kcal kg body mass(-1) day(-1), >80 % calories CHO). Oral-glucose tolerance tests (oral-GTT) were performed pre-exercise and after 1, 3 and 6 days of Cr and placebo supplementation. Exercise depleted muscle glycogen content to the same extent in both treatment groups. Creatine supplementation increased muscle total-Cr, free-Cr and phosphocreatine (PCr) content above placebo following 1, 3 and 6 days of supplementation (all P supplementation also increased muscle glycogen content noticeably above placebo after 1 day of supplementation (P < 0.05), which was sustained thereafter. This study confirmed dietary Cr augments post-exercise muscle glycogen super-compensation, and demonstrates this occurred during the initial 24 h of post-exercise recovery (when muscle total-Cr had increased by <10 %). This marked response ensued without apparent treatment differences in muscle insulin sensitivity (oral-GTT, muscle GLUT4 mRNA), osmotic stress (muscle c-fos and HSP72 mRNA) or muscle cell volume (muscle water content) responses, such that another mechanism must be causative. PMID:27193231

  12. Pantothenate kinase-associated neurodegeneration.

    Science.gov (United States)

    Hartig, Monika B; Prokisch, Holger; Meitinger, Thomas; Klopstock, Thomas

    2012-08-01

    Pantothenate kinase-associated neurodegeneration (PKAN) is a hereditary progressive disorder and the most frequent form of neurodegeneration with brain iron accumulation (NBIA). PKAN patients present with a progressive movement disorder, dysarthria, cognitive impairment and retinitis pigmentosa. In magnetic resonance imaging, PKAN patients exhibit the pathognonomic "eye of the tiger" sign in the globus pallidus which corresponds to iron accumulation and gliosis as shown in neuropathological examinations. The discovery of the disease causing mutations in PANK2 has linked the disorder to coenzyme A (CoA) metabolism. PANK2 is the only one out of four PANK genes encoding an isoform which localizes to mitochondria. At least two other NBIA genes (PLA2G6, C19orf12) encode proteins that share with PANK2 a mitochondrial localization and all are suggested to play a role in lipid homeostasis. With no causal therapy available for PKAN until now, only symptomatic treatment is possible. A multi-centre retrospective study with bilateral pallidal deep brain stimulation in patients with NBIA revealed a significant improvement of dystonia. Recently, studies in the PANK Drosophila model "fumble" revealed improvement by the compound pantethine which is hypothesized to feed an alternate CoA biosynthesis pathway. In addition, pilot studies with the iron chelator deferiprone that crosses the blood brain barrier showed a good safety profile and some indication of efficacy. An adequately powered randomized clinical trial will start in 2012. This review summarizes clinical presentation, neuropathology and pathogenesis of PKAN. PMID:22515741

  13. Protein Kinase A in Cancer

    Directory of Open Access Journals (Sweden)

    Antonio Caretta

    2011-02-01

    Full Text Available In the past, many chromosomal and genetic alterations have been examined as possible causes of cancer. However, some tumors do not display a clear molecular and/or genetic signature. Therefore, other cellular processes may be involved in carcinogenesis. Genetic alterations of proteins involved in signal transduction have been extensively studied, for example oncogenes, while modifications in intracellular compartmentalization of these molecules, or changes in the expression of unmodified genes have received less attention. Yet, epigenetic modulation of second messenger systems can deeply modify cellular functioning and in the end may cause instability of many processes, including cell mitosis. It is important to understand the functional meaning of modifications in second messenger intracellular pathways and unravel the role of downstream proteins in the initiation and growth of tumors. Within this framework, the cAMP system has been examined. cAMP is a second messenger involved in regulation of a variety of cellular functions. It acts mainly through its binding to cAMP-activated protein kinases (PKA, that were suggested to participate in the onset and progression of various tumors. PKA may represent a biomarker for tumor detection, identification and staging, and may be a potential target for pharmacological treatment of tumors.

  14. Protein Kinase A in Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Caretta, Antonio; Mucignat-Caretta, Carla, E-mail: carla.mucignat@unipd.it [Department of Human Anatomy and Physiology, University of Padova, Via Marzolo 3, 35131 Padova (Italy)

    2011-02-28

    In the past, many chromosomal and genetic alterations have been examined as possible causes of cancer. However, some tumors do not display a clear molecular and/or genetic signature. Therefore, other cellular processes may be involved in carcinogenesis. Genetic alterations of proteins involved in signal transduction have been extensively studied, for example oncogenes, while modifications in intracellular compartmentalization of these molecules, or changes in the expression of unmodified genes have received less attention. Yet, epigenetic modulation of second messenger systems can deeply modify cellular functioning and in the end may cause instability of many processes, including cell mitosis. It is important to understand the functional meaning of modifications in second messenger intracellular pathways and unravel the role of downstream proteins in the initiation and growth of tumors. Within this framework, the cAMP system has been examined. cAMP is a second messenger involved in regulation of a variety of cellular functions. It acts mainly through its binding to cAMP-activated protein kinases (PKA), that were suggested to participate in the onset and progression of various tumors. PKA may represent a biomarker for tumor detection, identification and staging, and may be a potential target for pharmacological treatment of tumors.

  15. Genetics Home Reference: phosphoglycerate kinase deficiency

    Science.gov (United States)

    ... Children Living with Inherited Metabolic Diseases (CLIMB) (UK) Muscular Dystrophy Association National Organization for Rare Disorders (NORD) Resource list from the University of Kansas Medical Center: Metabolic Conditions Genetic Testing Registry (2 links) Deficiency of phosphoglycerate kinase ...

  16. Genetics Home Reference: mevalonate kinase deficiency

    Science.gov (United States)

    ... net Patient Support and Advocacy Resources (2 links) Autoinflammatory Alliance National Organization for Rare Disorders (NORD): Hyper ... Haas D, Hoffmann GF. Mevalonate kinase deficiency and autoinflammatory disorders. N Engl J Med. 2007 Jun 28; ...

  17. Genetics Home Reference: deoxyguanosine kinase deficiency

    Science.gov (United States)

    ... or mtDNA, which is essential for the normal function of these structures. Deoxyguanosine kinase is involved in producing and maintaining the ... DNA (known as mitochondrial DNA depletion) impairs mitochondrial function ... deficiency . Learn more about the gene associated ...

  18. Kinase inhibitors for advanced medullary thyroid carcinoma

    Directory of Open Access Journals (Sweden)

    Martin Schlumberger

    2012-01-01

    Full Text Available The recent availability of molecular targeted therapies leads to a reconsideration of the treatment strategy for patients with distant metastases from medullary thyroid carcinoma. In patients with progressive disease, treatment with kinase inhibitors should be offered.

  19. Kinome profiling of Arabidopsis using arrays of kinase consensus substrates

    NARCIS (Netherlands)

    Ritsema, T.; Joore, J.; Workum, W. van; Pieterse, C.M.J.

    2007-01-01

    Background: Kinome profiling aims at the parallel analysis of kinase activities in a cell. Novel developed arrays containing consensus substrates for kinases are used to assess those kinase activities. The arrays described in this paper were already used to determine kinase activities in mammalian s

  20. The Ca2+/Calmodulin-Dependent Protein Kinase Kinase, CaMKK2, Inhibits Preadipocyte Differentiation

    OpenAIRE

    Lin, Fumin; Ribar, Thomas J.; Means, Anthony R.

    2011-01-01

    When fed a standard chow diet, CaMKK2 null mice have increased adiposity and larger adipocytes than do wild-type mice, whereas energy balance is unchanged. Here, we show that Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is expressed in preadipocytes, where it functions as an AMP-activated protein kinase (AMPK)α kinase. Acute inhibition or deletion of CaMKK2 in preadipocytes enhances their differentiation into mature adipocytes, which can be reversed by 5-aminoimidazole-4-carboxa...

  1. Protein kinase domain of twitchin has protein kinase activity and an autoinhibitory region.

    Science.gov (United States)

    Lei, J; Tang, X; Chambers, T C; Pohl, J; Benian, G M

    1994-08-19

    Twitchin is a 753-kDa polypeptide located in the muscle A-bands of the nematode, Caenorhabditis elegans. It consists of multiple copies of both fibronectin III and immunoglobulin C2 domains and, near the C terminus, a protein kinase domain with greatest homology to the catalytic domains of myosin light chain kinases. We have expressed and purified from Escherichia coli twitchin's protein kinase catalytic core and flanking sequences that do not include fibronectin III and immunoglobulin C2 domains. The protein was shown to phosphorylate a model substrate and to undergo autophosphorylation. The autophosphorylation occurs at a slow rate, attaining a maximum at 3 h with a stoichiometry of about 1.0 mol of phosphate/mol of protein, probably through an intramolecular mechanism. Sequence analysis of proteolytically derived phosphopeptides revealed that autophosphorylation occurred N-terminal to the catalytic core, predominantly at Thr-5910, with possible minor sites at Ser5912 and/or Ser-5913. This portion of twitchin (residues 5890-6268) was also phosphorylated in vitro by protein kinase C in the absence of calcium and phosphotidylserine, but not by cAMP-dependent protein kinase. By comparing the activities of three twitchin segments, the enzyme appears to be inhibited by the 60-amino acid residues lying just C-terminal to the kinase catalytic core. Thus, like a number of other protein kinases including myosin light chain kinases, the twitchin kinase appears to be autoregulated. PMID:8063727

  2. Seeding collaborations to advance kinase science with the GSK Published Kinase Inhibitor Set (PKIS).

    Science.gov (United States)

    Drewry, David H; Willson, Timothy M; Zuercher, William J

    2014-01-01

    To catalyze research on historically untargeted protein kinases, we created the PKIS, an annotated set of 367 small molecule kinase inhibitors. The set has been widely distributed to academic collaborators as an open access tool. It has been used to identify chemical starting points for development of chemical probes for orphan kinases and to investigate kinase signaling in high content phenotypic assays. Access to the set comes with few restrictions other than the requirement that assay results be released into the public domain for the benefit of the entire research community. Examples from the efforts of several collaborators are summarized. PMID:24283969

  3. Janus kinases in immune cell signaling

    OpenAIRE

    Ghoreschi, Kamran; Laurence, Arian; O’Shea, John J.

    2009-01-01

    The Janus family kinases (Jaks), Jak1, Jak2, Jak3, and Tyk2, form one subgroup of the non-receptor protein tyrosine kinases. They are involved in cell growth, survival, development, and differentiation of a variety of cells but are critically important for immune cells and hematopoietic cells. Data from experimental mice and clinical observations have unraveled multiple signaling events mediated by Jak in innate and adaptive immunity. Deficiency of Jak3 or Tyk2 results in defined clinical dis...

  4. Non-degradative Ubiquitination of Protein Kinases.

    OpenAIRE

    K Aurelia Ball; Johnson, Jeffrey R.; Lewinski, Mary K; John Guatelli; Erik Verschueren; Krogan, Nevan J.; Matthew P Jacobson

    2016-01-01

    Growing evidence supports other regulatory roles for protein ubiquitination in addition to serving as a tag for proteasomal degradation. In contrast to other common post-translational modifications, such as phosphorylation, little is known about how non-degradative ubiquitination modulates protein structure, dynamics, and function. Due to the wealth of knowledge concerning protein kinase structure and regulation, we examined kinase ubiquitination using ubiquitin remnant immunoaffinity enrichm...

  5. Evolutionary Reconstruction and Population Genetics Analysis of Aurora Kinases

    OpenAIRE

    Balu Kamaraj; Ambuj Kumar; Rituraj Purohit

    2013-01-01

    BACKGROUND: Aurora kinases belong to the highly conserved kinase family and play a vital role in cell cycle regulation. The structure and function of these kinases are inter-related and sometimes they also act as substitutes in case of knockdown of other aurora kinases. METHOD: In this work we carried out the evolutionary reconstruction and population genetic studies of aurora kinase proteins. Substitution saturation test, CAI (Codon adaptation index), gene expression and RSCU (Relative synon...

  6. Non-degradative Ubiquitination of Protein Kinases.

    Directory of Open Access Journals (Sweden)

    K Aurelia Ball

    2016-06-01

    Full Text Available Growing evidence supports other regulatory roles for protein ubiquitination in addition to serving as a tag for proteasomal degradation. In contrast to other common post-translational modifications, such as phosphorylation, little is known about how non-degradative ubiquitination modulates protein structure, dynamics, and function. Due to the wealth of knowledge concerning protein kinase structure and regulation, we examined kinase ubiquitination using ubiquitin remnant immunoaffinity enrichment and quantitative mass spectrometry to identify ubiquitinated kinases and the sites of ubiquitination in Jurkat and HEK293 cells. We find that, unlike phosphorylation, ubiquitination most commonly occurs in structured domains, and on the kinase domain, ubiquitination is concentrated in regions known to be important for regulating activity. We hypothesized that ubiquitination, like other post-translational modifications, may alter the conformational equilibrium of the modified protein. We chose one human kinase, ZAP-70, to simulate using molecular dynamics with and without a monoubiquitin modification. In Jurkat cells, ZAP-70 is ubiquitinated at several sites that are not sensitive to proteasome inhibition and thus may have other regulatory roles. Our simulations show that ubiquitination influences the conformational ensemble of ZAP-70 in a site-dependent manner. When monoubiquitinated at K377, near the C-helix, the active conformation of the ZAP-70 C-helix is disrupted. In contrast, when monoubiquitinated at K476, near the kinase hinge region, an active-like ZAP-70 C-helix conformation is stabilized. These results lead to testable hypotheses that ubiquitination directly modulates kinase activity, and that ubiquitination is likely to alter structure, dynamics, and function in other protein classes as well.

  7. Phospho-kinase profile of colorectal tumors guides in the selection of multi-kinase inhibitors.

    Science.gov (United States)

    Serrano-Heras, Gemma; Cuenca-López, María Dolores; Montero, Juan Carlos; Corrales-Sanchez, Verónica; Morales, Jorge Carlos; Núñez, Luz-Elena; Morís, Francisco; Pandiella, Atanasio; Ocaña, Alberto

    2015-10-13

    Protein kinases play a central role in the oncogenesis of colorectal tumors and are attractive druggable targets. Detection of activated kinases within a tumor could open avenues for drug selection and optimization of new kinase inhibitors. By using a phosphokinase arrays with human colorectal tumors we identified activated kinases, including the Epidermal Growth Factor Receptor (EGFR), components of the PI3K/mTOR pathway (AKT and S6), and STAT, among others. A pharmacological screening with kinase inhibitors against these proteins helped us to identify a new kinase inhibitor, termed EC-70124 that showed the highest anti-proliferative activity in cell lines. EC-70124 also inhibited cell migration and biochemical experiments demonstrated its effect targeting the PI3K/mTOR pathway. This drug also arrested cells at G2/M and induced apoptosis. Experiments in combination with standard chemotherapy used in the clinical setting indicated a synergistic effect. EC-70124 also reduced tumor growth in vivo and inhibited pS6 in the implanted tumors. In conclusion, by studying the kinase profile of colorectal tumors, we identified relevant activated pathways, and a new multi-kinase compound with significant antitumor properties. PMID:26418718

  8. CDPKs are dual-specificity protein kinases and tyrosine autophosphorylation attenuates kinase activity

    Science.gov (United States)

    Calcium-dependent protein kinases (CDPKs or CPKs) are classified as serine/threonine protein kinases but we made the surprising observation that soybean CDPK' and several Arabidopsis isoforms (AtCPK4 and AtCPK34) could also autophosphorylate on tyrosine residues. In studies with His6-GmCDPK', we ide...

  9. KinasePA: Phosphoproteomics data annotation using hypothesis driven kinase perturbation analysis.

    Science.gov (United States)

    Yang, Pengyi; Patrick, Ellis; Humphrey, Sean J; Ghazanfar, Shila; James, David E; Jothi, Raja; Yang, Jean Yee Hwa

    2016-07-01

    Mass spectrometry (MS)-based quantitative phosphoproteomics has become a key approach for proteome-wide profiling of phosphorylation in tissues and cells. Traditional experimental design often compares a single treatment with a control, whereas increasingly more experiments are designed to compare multiple treatments with respect to a control. To this end, the development of bioinformatic tools that can integrate multiple treatments and visualise kinases and substrates under combinatorial perturbations is vital for dissecting concordant and/or independent effects of each treatment. Here, we propose a hypothesis driven kinase perturbation analysis (KinasePA) to annotate and visualise kinases and their substrates that are perturbed by various combinatorial effects of treatments in phosphoproteomics experiments. We demonstrate the utility of KinasePA through its application to two large-scale phosphoproteomics datasets and show its effectiveness in dissecting kinases and substrates within signalling pathways driven by unique combinations of cellular stimuli and inhibitors. We implemented and incorporated KinasePA as part of the "directPA" R package available from the comprehensive R archive network (CRAN). Furthermore, KinasePA also has an interactive web interface that can be readily applied to annotate user provided phosphoproteomics data (http://kinasepa.pengyiyang.org). PMID:27145998

  10. Effect of hyaluronidase on mortality and morbidity in patients with early peaking of plasma creatine kinase MB and non-transmural ischaemia. Multicentre investigation for the limitation of infarct size (MILIS).

    OpenAIRE

    Roberts, R; Braunwald, E.; Muller, J. E.; Croft, C; Gold, H K; Hartwell, T D; Jaffe, A S; Mullin, S M; Parker, C.; Passamani, E R

    1988-01-01

    A multicentred, randomised, blind study was started in 1978 to compare propranolol or hyaluronidase with placebo in patients with acute myocardial infarction admitted within 18 hours of onset of symptoms. Patients were randomised to group A and received hyaluronidase, propranolol, or placebo, or, if propranolol was contraindicated, to group B and received hyaluronidase or placebo. Hyaluronidase (500 U/kg given every six hours for 48 hours) had no effect on mortality or infarct size in the ove...

  11. 无症状/轻症状高肌酸激酶血症20例临床研究%Clinical Studies of Twenty Patients with Asymptomatic/Pauci-symptomatic Hyper Creatine Kinase Emia

    Institute of Scientific and Technical Information of China (English)

    蔡爽; 罗苏珊; 赵重波; 朱雯华; 奚剑英; 岳冬曰; 宋捷; 孙翀; 敬思思

    2016-01-01

    目的 明确无症状/轻症状高肌酸激酶血症的病因及肌肉病理的诊断价值.方法 对20例无症状/轻症状高肌酸激酶血症患者行肌肉病理检测,部分病例进一步行酶学和基因检测.结果 纳入的20例患者中,病理异常17例(85.0%),提示诊断11例(55.0%):dysferlin相关肌病6例,dystrophin相关肌病4例,Pompe病1例;另3例分别确诊为calpain相关肌病、炎性肌病及药物相关肌病.共14例(70.0%)获得确诊.肌酸激酶<2 000 U·L-1、2 000~10 000 U·L-1和>10 000 U·L-1患者中分别确诊2/4例(50.0%)、9/13例(69.2%)和3/3例(100.0%).结论 肌肉活检对无症状/轻症状高肌酸激酶血症患者的诊断有重要价值;肌酸激酶水平与确诊率有一定关联.

  12. Retrospective study of juvenile patients with chronic raised serum creatine kinase levels%25例慢性肌酸磷酸肌酶升高患儿的临床分析

    Institute of Scientific and Technical Information of China (English)

    仇佳晶; 邱正庆; 魏珉; 赵时敏; 陈琳; 黄尚志

    2007-01-01

    目的 明确慢性血清肌酸磷酸肌酶(CK)升高的儿童患者的病因诊断.方法 对2005-01-2007-03,北京协和医院遗传门诊入院的CK持续升高超过3个月患儿的临床资料进行回顾性分析.结果 16例获得诊断,确诊率64%,诊断分别为:7例dystrophin相关肌营养不良症,1例携带者;2例Pompe病,1例糖原累积症;1例线粒体肌肉病,1例戊二酸尿症,2例炎症性肌肉病,1例脊肌萎缩症.其余9例未能明确诊断.结论 血清肌酶持续增高在儿童病人多提示神经肌肉疾病或累及肌肉的代谢性疾病,病因复杂,除常规生化检查外,肌电图、肌活检、酶生化测定、基因检测等多种检查的综合应用有助于提高诊断率.

  13. Influence of Sport Nutrition Supplement on Lactate Dehydrogenase and Creatine Kinase%运动营养补剂对机体乳酸脱氢酶和肌酸激酶的影响研究

    Institute of Scientific and Technical Information of China (English)

    万利; 毕曼; 杨林

    2009-01-01

    通过查阅大量文献资料,阐述了运动营养补荆的研究情况,综述了运动营养补剂对机体乳酸脱氢酶和肌酸激酶的影响,以期为运动营养补剂的运用及新的研究方向提供理论参考依据.

  14. 参加肌酸激酶参考方法国际室间比对计划结果分析%Analysis of the results of creatine kinase reference method in ring trial program

    Institute of Scientific and Technical Information of China (English)

    迟珊; 沈默; 张曼

    2010-01-01

    ObjectiveTo provide a reference for the establishment and appliance of enzyme reference measurement of CK in China by comparing and analyzing the RELA results of CK in IFCC from 2006-2008. Methods The RELA samples of CK were measured according to the reference procedure for the measurement of catalytic activity concentration of CK (37 ℃) ,which had been published by IFCC. The EP5A2 protocol was used for evaluation of the imprecision and ERM was used for verification of the trueness. Results In RELA 2006, the result of sample A was (9. 896 ±0. 112) μkat/L, and the result of sample B was (4.953 ±0. 120) μkat/L. In RELA 2007, the result of sample A was (2.684 ±0.054)μkat/L, and the result of sample B was (8.798 μ0. 101) μkat/L. In RELA 2008, the result of sample A was (10. 523 ±0. 149) μkat/L,and the result of sample B was (10. 551 ±0. 141) μkat/L. The precision of the CK reference method in the year 2006 to 2008 was 0. 92%, 0. 86% and 0. 88% respectively, each of them is less than 1% and the results of ERMs were consistent with the certified value(1. 68 ± 0. 07)μkat/L,which verify the imprecision and accuracy of the reference method. Conclusions All of the results in the continuous three years were in the range of equivalence limits suggested by IFCC. The CK reference method suggested by IFCC has been established and it is getting better.%目的 对2006-2008年3年来参加IFCC组织的参考实验室RELA的CK的测定结果 进行比较和分析,为我国CK参考方法 的建立和应用提供借鉴.方法 按照IFCC公布的酶学活性测定(37℃)参考方法 的标准操作程序(SOP)测定CK国际样本,不精密度评价按美国CLSI的EP5-A2进行,准确度评价采用国际有证参考物质(ERM).结果 2006年测定结果 ,样本A CK值为(9.896±0.112)μkat/L,样本B为(4.953±0.120)μkat/L;2007年测定结果 ,样本A为(2.684 ±0.054)μkat/L,样本B为(8.798 ±0.101)μkat/L;2008年测定结果 ,样本A为(10.523±0.149)μkat/L,样本B为(10.551±0.141)μkat/L.2006-2008年CK参考方法 的不精密度分别为0.92%、0.86%、0.88%,均<1%,ERM测定均值在"靶值±不确定度[(1.68±0.07)μkat/L]"范围内,初步验证了参考方法 的不精密度和准确度.结论 连续3年的CK国际样本测定结果 均在IFCC公布的置信区间(limit of equivalence)±5%范围内,CK的IFCC参考方法 已经建立并且日趋成熟.

  15. Janus kinase inhibitors: jackpot or potluck?

    Directory of Open Access Journals (Sweden)

    Pavithran Keechilat

    2012-06-01

    Full Text Available The reports of a unique mutation in the Janus kinase-2 gene (JAK2 in polycythemia vera by several independent groups in 2005 quickly spurred the development of the Janus kinase inhibitors. In one of the great victories of translational research in recent times, the first smallmolecule Janus kinase inhibitor ruxolitinib entered a phase I trial in 2007. With the approval of ruxolitinib by the US Federal Drug Administration in November 2011 for high-risk and intermediate-2 risk myelofibrosis, a change in paradigm has occurred in the management of a subset of myeloproliferative neoplasms (MPN: primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. Whereas the current evidence for ruxolitinib only covers high-risk and intermediate-2 risk myelofibrosis, inhibitors with greater potency are likely to offer better disease control and survival advantage in patients belonging to these categories, and possibly to the low-risk and intermediate-1 risk categories of MPN as well. But use of the Janus kinase inhibitors also probably has certain disadvantages, such as toxicity, resistance, withdrawal phenomenon, non-reversal of histology, and an implausible goal of disease clone eradication, some of which could offset the gains. In spite of this, Janus kinase inhibitors are here to stay, and for use in more than just myeloproliferative neoplasms.

  16. Mechanism of polyphosphate kinase from Propionibacterium shermanii

    International Nuclear Information System (INIS)

    Polyphosphate kinase, which catalyzes the reaction shown below, is one of two enzymes which have been reported to catalyze the synthesis of polyphosphate. Purification performed by ammonium sulfate precipitation (0-40% fraction) was followed by chromatography. The enzyme represents 70% of the protein in the hydroxylapatite pool and is stable at this level of purity. The subunit molecular weight was determined by SDS polyacrylamide gel analysis, (83,000 +/- 3000), nondenaturing polyacrylamide gel electrophoresis, (80,000 and 86,000 daltons), gel filtration (Biogel A 0.5m column was 85,000 +/- 4000.) Polyphosphate kinase appears to be a monomeric enzyme of ∼83,000 daltons. Four assays were developed for polyphosphate kinase. Basic proteins such as polylysine stimulate the synthesis of polyphosphate, these proteins cause precipitation of polyphosphate kinase from relatively impure enzyme extracts: Synthesized polyphosphate interacts noncovalently with the basic protein-enzyme precipitate. Efficient synthesis of polyphosphate requires the addition of either phosphate or short chain polyphosphate. Synthesis did occur at 1/10 the rate when neither of these two compounds were included. Initiation, elongation, and termination events of polyphosphate synthesis were examined. Short chain polyphosphate acts as a primer, with [32P] short-chain polyphosphate incorporation into long chain polyphosphate by the kinase

  17. Effects of the creatine oral supplement in handball players to improve jump EFECTO DEL SUPLEMENTO ORAL DE CREATINA A JUGADORES DE BALONMANO PARA LA MEJORA DEL SALTO

    Directory of Open Access Journals (Sweden)

    P. Padial

    2010-09-01

    Full Text Available

    The knowledge of the efficiency creatine supplements for the improvement of the performanceis the main motive that it has carried us to accomplish this study. There is a huge controversy in this regard. To prove its efficiency have been used N = 10 (20 ± 2y (82Kg.± 5Kg. trained subjects, Team Handbal players (1st National Division. The protocol has been the following: They have been divided the subjects in two groups G1 = 5 and G2= 5 in a random way. To the G1 have been administered 4 x 5 g per day of creatine monohydratate (CRH2O during five days. To the G2 (control group has been administered glucose. A pretest and a posttest were done after ending the feed. In the tests were controlled the following parameters: SJ and CMJ in a platform of pressure and the corporal weight in kgs. Al the subjects accomplished the same training (6 days of training: 3 of them destined to improve strength. Once completed t Student for independent samples, the results did not show meaningful improvements in the variables analyzed. These results demonstrate that an increase in the capacity of the fosfogenolitic route by exogenous way it is not possible in explosive movements in Team handbal players.
    KEY WORDS: Handbal, Supplements Creatine, Training, Explosive Power.

     

    El conocimiento de la efectividad de los suplementos de creatina para la mejora del rendimiento es el principal motivo que nos ha llevado a realizar este estudio. La controversia existente al respecto es grande. Para comprobar su eficacia se han utilizado N = 10 (20 ± 2 a. (82 Kg. ± 5 kgr. sujetos entrenados, jugadores de balonmano (1ª División Nacional. El protocolo seg uido ha sido el siguiente: Se han dividido los sujetos en dos grupos G1 = 5 y G2= 5 de forma aleatoria. Al G1 se le han administrado 4 x 5 g./día de creatina monohidratada (CRH20 durante cinco d

  18. Phosphatidylinositol 3-Kinase (PI3K) and phosphatidylinositol 3-kinase-related kinase (PIKK) inhibitors: importance of the morpholine ring

    Czech Academy of Sciences Publication Activity Database

    Andrs, M.; Kobarecny, J.; Jun, D.; Hodný, Zdeněk; Bartek, Jiří; Kuca, K.

    2015-01-01

    Roč. 58, č. 1 (2015), s. 41-71. ISSN 0022-2623 R&D Projects: GA MŠk(CZ) CZ.1.07/2.3.00/30.0044 Grant ostatní: University Hospital Hradec Kralove(CZ) 00179906; Faculty of Military Health Sciences, University of Defence(CZ) SV/FVZ201402 Institutional support: RVO:68378050 Keywords : DEPENDENT PROTEIN-KINASE * STRAND BREAK REPAIR * SELECTIVE PI3K-BETA INHIBITORS * TELANGIECTASIA MUTATED KINASE Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.447, year: 2014

  19. The Role of PAS Kinase in PASsing the Glucose Signal

    Directory of Open Access Journals (Sweden)

    Julianne H. Grose

    2010-06-01

    Full Text Available PAS kinase is an evolutionarily conserved nutrient responsive protein kinase that regulates glucose homeostasis. Mammalian PAS kinase is activated by glucose in pancreatic beta cells, and knockout mice are protected from obesity, liver triglyceride accumulation, and insulin resistance when fed a high-fat diet. Yeast PAS kinase is regulated by both carbon source and cell integrity stress and stimulates the partitioning of glucose toward structural carbohydrate biosynthesis. In our current model for PAS kinase regulation, a small molecule metabolite binds the sensory PAS domain and activates the enzyme. Although bona fide PAS kinase substrates are scarce, in vitro substrate searches provide putative targets for exploration.

  20. Interleukin 3-dependent survival by the Akt protein kinase

    OpenAIRE

    Songyang, Zhou; Baltimore, David; Cantley, Lewis C.; Kaplan, David R; Franke, Thomas F.

    1997-01-01

    Interleukin 3 (IL-3)-dependent survival of hematopoietic cells is known to rely on the activity of multiple signaling pathways, including a pathway leading to activation of phosphoinositide 3-kinase (PI 3-kinase), and protein kinase Akt is a direct target of PI 3-kinase. We find that Akt kinase activity is rapidly induced by the cytokine IL-3, suggesting a role for Akt in PI 3-kinase-dependent signaling in hematopoetic cells. Dominant-negative mutants of Akt specifically block Akt activation ...

  1. Kinase signaling in the spindle checkpoint.

    Science.gov (United States)

    Kang, Jungseog; Yu, Hongtao

    2009-06-01

    The spindle checkpoint is a cell cycle surveillance system that ensures the fidelity of chromosome segregation. In mitosis, it elicits the "wait anaphase" signal to inhibit the anaphase-promoting complex or cyclosome until all chromosomes achieve bipolar microtubule attachment and align at the metaphase plate. Because a single kinetochore unattached to microtubules activates the checkpoint, the wait anaphase signal is thought to be generated by this kinetochore and is then amplified and distributed throughout the cell to inhibit the anaphase-promoting complex/cyclosome. Several spindle checkpoint kinases participate in the generation and amplification of this signal. Recent studies have begun to reveal the activation mechanisms of these checkpoint kinases. Increasing evidence also indicates that the checkpoint kinases not only help to generate the wait anaphase signal but also actively correct kinetochore-microtubule attachment defects. PMID:19228686

  2. X-Ray Crystal Structure of Bone Marrow Kinase in the X Chromosome: A Tec Family Kinase

    Energy Technology Data Exchange (ETDEWEB)

    Muckelbauer, Jodi; Sack, John S.; Ahmed, Nazia; Burke, James; Chang, ChiehYing Y.; Gao, Mian; Tino, Joseph; Xie, Dianlin; Tebben, Andrew J. (BMS)

    2012-06-27

    Bone marrow kinase in the X chromosome, a member of the Tec family of tyrosine kinases, plays a role in both monocyte/macrophage trafficking as well as cytokine secretion. Although the structures of Tec family kinases Bruton's tyrosine kinase and IL-2-inducible T-cell kinase are known, the crystal structures of other Tec family kinases have remained elusive. We report the X-ray crystal structures of bone marrow kinase in the X chromosome in complex with dasatinib at 2.4 {angstrom} resolution and PP2 at 1.9 {angstrom} resolution. The bone marrow kinase in the X chromosome structures reveal a typical kinase protein fold; with well-ordered protein conformation that includes an open/extended activation loop and a stabilized DFG-motif rendering the kinase in an inactive conformation. Dasatinib and PP2 bind to bone marrow kinase in the X chromosome in the ATP binding pocket and display similar binding modes to that observed in other Tec and Src protein kinases. The bone marrow kinase in the X chromosome structures identify conformational elements of the DFG-motif that could potentially be utilized to design potent and/or selective bone marrow kinase in the X chromosome inhibitors.

  3. Phosphorylation of varicella-zoster virus glycoprotein gpI by mammalian casein kinase II and casein kinase I

    International Nuclear Information System (INIS)

    Varicella-zoster virus (VZV) glycoprotein gpI is the predominant viral glycoprotein within the plasma membranes of infected cells. This viral glycoprotein is phosphorylated on its polypeptide backbone during biosynthesis. In this report, the authors investigated the protein kinases which participate in the phosphorylation events. Under in vivo conditions, VZV gpI was phosphorylated on its serine and threonine residues by protein kinases present within lysates of either VZV-infected or uninfected cells. Because this activity was diminished by heparin, a known inhibitor of casein kinase II, isolated gpI was incubated with purified casein kinase II and shown to be phosphorylated in an in vitro assay containing [γ-32P]ATP. The same glycoprotein was phosphorylated when [32P]GTP was substituted for [32P]ATP in the protein kinase assay. They also tested whether VZV gpI was phosphorylated by two other ubiquitous mammalian protein kinases--casein kinase I and cyclic AMP-dependent kinase--and found that only casein kinase I modified gpI. When the predicted 623-amino-acid sequence of gpI was examined, two phosphorylation sites known to be optimal for casein kinase II were observed. In summary, this study showed that VZV gpI was phosphorylated by each of two mammalian protein kinases (casein kinase I and casein kinase II) and that potential serine-threonine phosphorylation sites for each of these two kinases were present in the viral glycoprotein

  4. Rational design of protein kinase inhibitors

    Directory of Open Access Journals (Sweden)

    Yarmoluk S. M.

    2013-07-01

    Full Text Available Modern methodological approaches to rational design of low molecular weight compounds with specific activity in relation to predetermined biomolecular targets are considered by example of development of high effective protein kinase inhibitors. The application of new computational methods that allow to significantly improve the quality of computational experiments (in, particular, accuracy of low molecular weight compounds activity prediction without increase of computational and time costs are highlighted. The effectiveness of strategy of rational design is demonstrated by examples of several own investigations devoted to development of new inhibitors that are high effective and selective towards protein kinases CK2, FGFR1 and ASK1.

  5. Purification and characterization of a casein kinase 2-type protein kinase from pea nuclei

    Science.gov (United States)

    Li, H.; Roux, S. J.

    1992-01-01

    Almost all the polyamine-stimulated protein kinase activity associated with the chromatin fraction of nuclei purified from etiolated pea (Pisum sativum L.) plumules is present in a single enzyme that can be extracted from chromatin by 0.35 molar NaCl. This protein kinase can be further purified over 2000-fold by salt fractionation and anion-exchange and casein-agarose column chromatography, after which it is more than 90% pure. The purified kinase has a specific activity of about 650 nanomoles per minute per milligram protein in the absence of polyamines, with either ATP or GTP as phosphoryl donor. Spermidine can stimulate its activity fourfold, with half-maximal activation at about 2 millimolar. Spermine and putrescine also stimulate activity, although somewhat less effectively. This kinase has a tetrameric alpha 2 beta 2 structure with a native molecular weight of 130,000, and subunit molecular weights of 36,000 for the catalytic subunit (alpha) and 29,000 for the regulatory subunit (beta). In western blot analyses, only the alpha subunit reacts strongly with polyclonal antibodies to a Drosophila casein kinase II. The pea kinase can use casein and phosvitin as artificial substrates, phosphorylating both the serine and threonine residues of casein. It has a pH optimum near 8.0, a Vmax of 1.5 micromoles per minute per milligram protein, and a Km for ATP of approximately 75 micromolar. Its activity can be almost completely inhibited by heparin at 5 micrograms per milliliter, but is relatively insensitive to concentrations of staurosporine, K252a, and chlorpromazine that strongly antagonize Ca(2+) -regulated protein kinases. These results are discussed in relation to recent findings that casein kinase 2-type kinases may phosphorylate trans-acting factors that bind to light-regulated promoters in plants.

  6. Structural Evolution of the Protein Kinase-Like Superfamily.

    Directory of Open Access Journals (Sweden)

    2005-10-01

    Full Text Available The protein kinase family is large and important, but it is only one family in a larger superfamily of homologous kinases that phosphorylate a variety of substrates and play important roles in all three superkingdoms of life. We used a carefully constructed structural alignment of selected kinases as the basis for a study of the structural evolution of the protein kinase-like superfamily. The comparison of structures revealed a "universal core" domain consisting only of regions required for ATP binding and the phosphotransfer reaction. Remarkably, even within the universal core some kinase structures display notable changes, while still retaining essential activity. Hence, the protein kinase-like superfamily has undergone substantial structural and sequence revision over long evolutionary timescales. We constructed a phylogenetic tree for the superfamily using a novel approach that allowed for the combination of sequence and structure information into a unified quantitative analysis. When considered against the backdrop of species distribution and other metrics, our tree provides a compelling scenario for the development of the various kinase families from a shared common ancestor. We propose that most of the so-called "atypical kinases" are not intermittently derived from protein kinases, but rather diverged early in evolution to form a distinct phyletic group. Within the atypical kinases, the aminoglycoside and choline kinase families appear to share the closest relationship. These two families in turn appear to be the most closely related to the protein kinase family. In addition, our analysis suggests that the actin-fragmin kinase, an atypical protein kinase, is more closely related to the phosphoinositide-3 kinase family than to the protein kinase family. The two most divergent families, alpha-kinases and phosphatidylinositol phosphate kinases (PIPKs, appear to have distinct evolutionary histories. While the PIPKs probably have an

  7. Protein kinase CK2 in health and disease: Protein kinase CK2: from structures to insights

    DEFF Research Database (Denmark)

    Niefind, K; Raaf, J; Issinger, Olaf-Georg

    2009-01-01

    Within the last decade, 40 crystal structures corresponding to protein kinase CK2 (former name 'casein kinase 2'), to its catalytic subunit CK2alpha and to its regulatory subunit CK2beta were published. Together they provide a valuable, yet by far not complete basis to rationalize the biochemical...... critical region of CK2alpha recruitment is pre-formed in the unbound state. In CK2alpha the activation segment - a key element of protein kinase regulation - adapts invariably the typical conformation of the active enzymes. Recent structures of human CK2alpha revealed a surprising plasticity in the ATP...

  8. LC-QTOF-MS-based targeted metabolomics of arginine-creatine metabolic pathway-related compounds in plasma: application to identify potential biomarkers in pediatric chronic kidney disease.

    Science.gov (United States)

    Benito, Sandra; Sánchez, Alicia; Unceta, Nora; Andrade, Fernando; Aldámiz-Echevarria, Luis; Goicolea, M Aránzazu; Barrio, Ramón J

    2016-01-01

    Chronic kidney disease (CKD) is a major epidemiologic problem which causes several disturbances in adults and in pediatrics. Despite being a worldwide public health problem, information available for CKD in the pediatric population is scarce. For that reason, an ion-pair reversed-phase liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) method has been developed and validated in order to analyze 16 amino acids, amino acid derivatives, and analogous compounds related to the arginine-creatine metabolic pathway that are suspicious of being increased or decreased in plasma from patients with CKD. The analytical method involved the addition of dithiothreitol, a reducing agent which reduces disulfide and thus giving total aminothiol concentration, as well as a simple precipitation of plasma proteins. Moreover, despite amino acids being usually derivatized to improve their retention time and to enhance their signal, for this method, an ion-pairing reagent was used, thus avoiding the need for derivatization. Subsequently, analysis of plasma from pediatric patients suffering from CKD and control pediatrics was carried out. As a result, glycine, citrulline, creatinine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) were significantly increased in patients with CKD, regardless of their creatinine level, whereas in addition to these compounds dimethylglycine was also increased when CKD patients had plasma creatinine concentrations above 12 μg mL(-1), thus all are suggested as potential biomarkers for renal impairment. PMID:26537926

  9. Creatine Prevents the Structural and Functional Damage to Mitochondria in Myogenic, Oxidatively Stressed C2C12 Cells and Restores Their Differentiation Capacity.

    Science.gov (United States)

    Barbieri, Elena; Guescini, Michele; Calcabrini, Cinzia; Vallorani, Luciana; Diaz, Anna Rita; Fimognari, Carmela; Canonico, Barbara; Luchetti, Francesca; Papa, Stefano; Battistelli, Michela; Falcieri, Elisabetta; Romanello, Vanina; Sandri, Marco; Stocchi, Vilberto; Ciacci, Caterina; Sestili, Piero

    2016-01-01

    Creatine (Cr) is a nutritional supplement promoting a number of health benefits. Indeed Cr has been shown to be beneficial in disease-induced muscle atrophy, improve rehabilitation, and afford mild antioxidant activity. The beneficial effects are likely to derive from pleiotropic interactions. In accord with this notion, we previously demonstrated that multiple pleiotropic effects, including preservation of mitochondrial damage, account for the capacity of Cr to prevent the differentiation arrest caused by oxidative stress in C2C12 myoblasts. Given the importance of mitochondria in supporting the myogenic process, here we further explored the protective effects of Cr on the structure, function, and networking of these organelles in C2C12 cells differentiating under oxidative stressing conditions; the effects on the energy sensor AMPK, on PGC-1α, which is involved in mitochondrial biogenesis and its downstream effector Tfam were also investigated. Our results indicate that damage to mitochondria is crucial in the differentiation imbalance caused by oxidative stress and that the Cr-prevention of these injuries is invariably associated with the recovery of the normal myogenic capacity. We also found that Cr activates AMPK and induces an upregulation of PGC-1α expression, two events which are likely to contribute to the protection of mitochondrial quality and function. PMID:27610211

  10. Effects of dietary creatine supplementation for 8 weeks on neuromuscular coordination and learning in male albino mouse following neonatal hypoxic ischemic insult.

    Science.gov (United States)

    Iqbal, Shahid; Ali, Muhammad; Akbar, Atif; Iqbal, Furhan

    2015-05-01

    Creatine monohydrate (Cr) is a dietary supplement known to improve cognitive functions and has positive therapeutic results under various clinical conditions. The aim of this study was to determine the effect of 2 % Cr supplementation on learning, memory formation, neuromuscular coordination, exploratory and locomotory in male albino mice following hypoxic ischemic insult. At postnatal day, 10 male albino mice pups were subjected to right common carotid artery ligation followed by 8 % hypoxia for 25 min. On postnatal day 20, male mice were separated from the litter and divided into two groups on the basis of special diet supplementation. One group was supplemented with 2 % Cr in diet while the other group was raised on ordinary rodent chow for 8 weeks. Behavioral observations were made during rota rod, open field and Morris water maze test for both treatments. It was observed that supplementation with 2 % Cr for 8 weeks following neonatal brain damage resulted in enhanced muscular strength, neuromuscular coordination and improved body weight. In Morris water maze test, it was observed that Cr supplementation significantly improved mean swimming speed and mice on 2 % Cr diet covered more distance but the spatial memory was not improved significantly following hypoxia ischemia encephalopathy (HIE). Open field parameters and percentage of infarct volume remained unaffected following Cr supplementation. We concluded that 2 % dietary Cr supplementation has a potential to improve the muscle strength and body weight in male albino mice following (HIE) and should be considered for the treatment of neurological ailments. PMID:25511980

  11. Effect of Creatine Phosphate Sodium in the Treatment of Pediatric Myocarditis%小儿心肌炎采用磷酸肌酸钠治疗的临床疗效观察

    Institute of Scientific and Technical Information of China (English)

    孙锐

    2016-01-01

    目的:探讨磷酸肌酸钠治疗小儿心肌炎的疗效。方法随机将90例心肌炎患儿平均分为两组,对照组行果糖二磷酸钠治疗,观察组行磷酸肌酸钠治疗,比较两组临床疗效。结果观察组总有效率、心肌酶降低程度等指标均优于对照组(P <0.05)。结论磷酸肌酸钠治疗小儿心肌炎疗效理想,可有效保护心肌细胞。%Objective To investigate the effect of creatine phosphate sodium in the treatment of pediatric myocarditis. Methods We divided 90 patients into two groups,control group used fructose diphosphate sodium treatment,and observation group used creatine phosphate sodium,comparing efficacy of two groups. Results The total efficiency,reduction in myocardial enzyme of observation group were significantly better than control group(P < 0.05). Conclusion The effect of creatine phosphate sodium in the treatment of pediatric myocarditis is ideal,and can effectively protect the myocardial cel s.

  12. 肉鸡饲粮中添加-水肌酸对骨骼肌肌酸吸收和代谢的影响%Effects of Diets Supplemented with Creatine Monohydrate on Creatine Uptake and Metabolism in Skeletal Muscle of Broilers

    Institute of Scientific and Technical Information of China (English)

    夏伟光; 左建军; 冯定远

    2013-01-01

    地增强肌酸代谢池的能量缓冲作用,并以添加低水平(250 mg/kg) CMH的效果更为显著.%This study was conducted to evaluate the effects of creatine monhydrate (CMH) on creatine uptake and its biochemical metabolism in skeletal muscle of broilers. A total of nine hundred 42-day-old healthy Ling-nan yellow-feathered broilers [ initial body weight = (0. 73 ± 0. 01) kg; male ] were randomly allotted to four groups with five replicates per group. The control group were fed a basal diet without CMH, and the experimental groups were fed the basal diets supplemented with 250, 500 and 1 000 mg/kg CMH, respectively. The experiment lasted for 21 days. The results showed as follows; 1) the supplementation of 500 and 1 000 mg/kg CMH significantly up-regulated creatine transporter (CrT) mRNA expression in breast muscle compared with the control group (P 0. 05). Different CMH supplemental levels did not affect CrT mRNA expression in thigh muscle (P >0. 05). 2) Compared with the control group, feeding the diet with250 mg/kg CMH significantly decreased serum creatine content (P 0. 05) , but significantly increased creatine content in breast muscle (P 0.05). 4) Compared with the control group, the supplementation of CMH did not affect ATP, ADP, AMP and total adenine nucleotides (TAN) contents, energy charge (EC), and ATP/ADP in breast muscle (P >0.05). and the same results showed in these indexes of ADP content, EC, ATP/ADP and AMP/ATP in thigh muscle, too (P > 0. 05). However, 250, 500, and 1 000 mg/kg CMH supplemented in diets significantly decreased the AMP/ATP in breast muscle (P < 0.05 or P <0. 01), and 250 mg/kg CMH supplemental improved ATP, AMP and TAN content in thigh muscle (P < 0. 05). The results suggest that the supplementation of 250, 500 and 1 000 mg/kg CMH are be-nificial to improve creatine uptake in skeletal muscle, as well as the storage of creatine and phosphocreatine in breast muscle. Those indicate that some CHM added in diets for broilers can

  13. Casein kinase-2 structure-function relationship

    DEFF Research Database (Denmark)

    Boldyreff, B; Meggio, F; Pinna, L A;

    1992-01-01

    Nine mutants of human casein kinase-2 beta subunit have been created and assayed for their ability to assemble with the catalytic alpha subunit to give, at a 1:1 molar ratio, a fully competent CK-2 holoenzyme as judged by the following criteria: 1) the generation of an active heterotetrameric for...

  14. Discovery of inhibitors of bacterial histidine kinases

    NARCIS (Netherlands)

    Velikova, N.R.

    2014-01-01

    Discovery of Inhibitors of Bacterial Histidine Kinases

    Summary

    The thesis is on novel antibacterial drug discovery (http://youtu.be/NRMWOGgeysM). Using structure-based and fragment-based dru

  15. Pink1, the first ubiquitin kinase

    OpenAIRE

    Zheng, Xinde; Hunter, Tony

    2014-01-01

    Pink1 and Parkin, identified through studies of hereditary early onset Parkinson's disease, are involved in mitochondria quality control. Parkin E3 ubiquitin ligase activity is activated by Pink1 kinase activity, although the mechanism is still elusive. Three recent reports uncover a surprising mechanism in which Pink1 directly phosphorylates ubiquitin to boost Parkin activity.

  16. The IKK Kinases: Operators of Antiviral Signaling

    Directory of Open Access Journals (Sweden)

    Alissa M. Pham

    2010-01-01

    Full Text Available The ability of a cell to combat an intracellular pathogen requires a mechanism to recognize the threat and elicit a transcriptional response against it. In the context of virus infection, the cell must take measures to inhibit viral replication, meanwhile, convey warning signals to neighboring cells of the imminent threat. This immune response is predominantly mediated by the production of cytokines, notably, interferon beta (IFNβ. IFNβ signaling results in the transcriptional induction of over one hundred antiviral gene products whose timely expression renders infected cells more capable of inhibiting virus replication, while providing the uninfected cells with the reinforcements to generate a less permissive cellular environment. Induction of IFNβ and many aspects of the antiviral response pivot on the function of the IKK and IKK-related kinases. Despite sharing high levels of homology and some degree of functional redundancy, the classic IKK kinases: IKKα and IKKβ, and the IKK-related kinases: TBK1 and IKKε, perform distinct roles in regulating the host antiviral defense. These kinases serve as molecular operators in their cooperative ability to integrate incoming cellular cues and act on a range of essential antiviral transcription factors to reshape the cellular transcriptome during infection.

  17. CK2: a protein kinase in need of control

    DEFF Research Database (Denmark)

    Guerra, B; Boldyreff, B; Sarno, S;

    1999-01-01

    Protein kinase CK2 is a heterotetrameric alpha2beta2 Ser/Thr protein kinase with some features unusual among the eukaryotic protein kinases: (1) CK2 recognizes phosphoacceptor sites specified by several acidic determinants; (2) CK2 can use both ATP and GTP as phosphoryl donors; and (3) the...... response to nucleotide analogs. The increasing knowledge of CK2 structure-function relationships will allow the design of highly selective inhibitors of this pleiotropic kinase with oncogenic potential....

  18. New Class of Competitive Inhibitor of Bacterial Histidine Kinases

    OpenAIRE

    Gilmour, Raymond; Foster, J. Estelle; Sheng, Qin; McClain, Jonathan R.; Riley, Anna; Sun, Pei-Ming; Ng, Wai-Leung; Yan, Dalai; Nicas, Thalia I.; Henry, Kenneth; Winkler, Malcolm E.

    2005-01-01

    Bacterial histidine kinases have been proposed as targets for the discovery of new antibiotics, yet few specific inhibitors of bacterial histidine kinases have been reported. We report here a novel thienopyridine (TEP) compound that inhibits bacterial histidine kinases competitively with respect to ATP but does not comparably inhibit mammalian serine/threonine kinases. Although it partitions into membranes and does not inhibit the growth of bacterial or mammalian cells, TEP could serve as a s...

  19. Two thymidine kinases and one multisubstrate deoxyribonucleoside kinase salvage DNA precursors in Arabidopsis thaliana

    DEFF Research Database (Denmark)

    Anders Ranegaard Clausen, Anders Ranegaard; Girandon, Lenart; Ali, Ashfaq; Knecht, Wolfgang; Rozpedowska, Elzbieta; Sandrini, Michael Paolo; Andreasson, Erik; Munch-Petersen, Birgitte; Piskur, Jure

    2012-01-01

    Deoxyribonucleotides are the building blocks of DNA and can be synthesized via de novo and salvage pathways. Deoxyribonucleoside kinases (EC 2.7.1.145) salvage deoxyribonucleosides by transfer of a phosphate group to the 5' of a deoxyribonucleoside. This salvage pathway is well characterized in...... mammals, but in contrast, little is known about how plants salvage deoxyribonucleosides. We show that during salvage, deoxyribonucleosides can be phosphorylated by extracts of Arabidopsis thaliana into corresponding monophosphate compounds with an unexpected preference for purines over pyrimidines....... Deoxyribonucleoside kinase activities were present in all tissues during all growth stages. In the A. thaliana genome, we identified two types of genes that could encode enzymes which are involved in the salvage of deoxyribonucleosides. Thymidine kinase activity was encoded by two thymidine kinase 1 (EC 2...

  20. Two thymidine kinases and one multisubstrate deoxyribonucleoside kinase salvage DNA precursors in Arabidopsis thaliana

    DEFF Research Database (Denmark)

    Clausen, Anders R.; Girandon, Lenart; Ali, Ashfaq; Knecht, Wolfgang; Rozpedowska, Elzbieta; Sandrini, Michael; Andreasson, Erik; Munch‐Petersen, Birgitte; Piskur, Jure

    2012-01-01

    Deoxyribonucleotides are the building blocks of DNA and can be synthesized via de novo and salvage pathways. Deoxyribonucleoside kinases (EC 2.7.1.145) salvage deoxyribonucleosides by transfer of a phosphate group to the 5′ of a deoxyribonucleoside. This salvage pathway is well characterized in...... mammals, but in contrast, little is known about how plants salvage deoxyribonucleosides. We show that during salvage, deoxyribonucleosides can be phosphorylated by extracts of Arabidopsis thaliana into corresponding monophosphate compounds with an unexpected preference for purines over pyrimidines....... Deoxyribonucleoside kinase activities were present in all tissues during all growth stages. In the A. thaliana genome, we identified two types of genes that could encode enzymes which are involved in the salvage of deoxyribonucleosides. Thymidine kinase activity was encoded by two thymidine kinase 1 (EC 2...

  1. Unraveling Kinase Activation Dynamics Using Kinase-Substrate Relationships from Temporal Large-Scale Phosphoproteomics Studies.

    Science.gov (United States)

    Domanova, Westa; Krycer, James; Chaudhuri, Rima; Yang, Pengyi; Vafaee, Fatemeh; Fazakerley, Daniel; Humphrey, Sean; James, David; Kuncic, Zdenka

    2016-01-01

    In response to stimuli, biological processes are tightly controlled by dynamic cellular signaling mechanisms. Reversible protein phosphorylation occurs on rapid time-scales (milliseconds to seconds), making it an ideal carrier of these signals. Advances in mass spectrometry-based proteomics have led to the identification of many tens of thousands of phosphorylation sites, yet for the majority of these the kinase is unknown and the underlying network topology of signaling networks therefore remains obscured. Identifying kinase substrate relationships (KSRs) is therefore an important goal in cell signaling research. Existing consensus sequence motif based prediction algorithms do not consider the biological context of KSRs, and are therefore insensitive to many other mechanisms guiding kinase-substrate recognition in cellular contexts. Here, we use temporal information to identify biologically relevant KSRs from Large-scale In Vivo Experiments (KSR-LIVE) in a data-dependent and automated fashion. First, we used available phosphorylation databases to construct a repository of existing experimentally-predicted KSRs. For each kinase in this database, we used time-resolved phosphoproteomics data to examine how its substrates changed in phosphorylation over time. Although substrates for a particular kinase clustered together, they often exhibited a different temporal pattern to the phosphorylation of the kinase. Therefore, although phosphorylation regulates kinase activity, our findings imply that substrate phosphorylation likely serve as a better proxy for kinase activity than kinase phosphorylation. KSR-LIVE can thereby infer which kinases are regulated within a biological context. Moreover, KSR-LIVE can also be used to automatically generate positive training sets for the subsequent prediction of novel KSRs using machine learning approaches. We demonstrate that this approach can distinguish between Akt and Rps6kb1, two kinases that share the same linear consensus motif

  2. Unraveling Kinase Activation Dynamics Using Kinase-Substrate Relationships from Temporal Large-Scale Phosphoproteomics Studies

    Science.gov (United States)

    Chaudhuri, Rima; Yang, Pengyi; Vafaee, Fatemeh; Fazakerley, Daniel; Humphrey, Sean; James, David; Kuncic, Zdenka

    2016-01-01

    In response to stimuli, biological processes are tightly controlled by dynamic cellular signaling mechanisms. Reversible protein phosphorylation occurs on rapid time-scales (milliseconds to seconds), making it an ideal carrier of these signals. Advances in mass spectrometry-based proteomics have led to the identification of many tens of thousands of phosphorylation sites, yet for the majority of these the kinase is unknown and the underlying network topology of signaling networks therefore remains obscured. Identifying kinase substrate relationships (KSRs) is therefore an important goal in cell signaling research. Existing consensus sequence motif based prediction algorithms do not consider the biological context of KSRs, and are therefore insensitive to many other mechanisms guiding kinase-substrate recognition in cellular contexts. Here, we use temporal information to identify biologically relevant KSRs from Large-scale In Vivo Experiments (KSR-LIVE) in a data-dependent and automated fashion. First, we used available phosphorylation databases to construct a repository of existing experimentally-predicted KSRs. For each kinase in this database, we used time-resolved phosphoproteomics data to examine how its substrates changed in phosphorylation over time. Although substrates for a particular kinase clustered together, they often exhibited a different temporal pattern to the phosphorylation of the kinase. Therefore, although phosphorylation regulates kinase activity, our findings imply that substrate phosphorylation likely serve as a better proxy for kinase activity than kinase phosphorylation. KSR-LIVE can thereby infer which kinases are regulated within a biological context. Moreover, KSR-LIVE can also be used to automatically generate positive training sets for the subsequent prediction of novel KSRs using machine learning approaches. We demonstrate that this approach can distinguish between Akt and Rps6kb1, two kinases that share the same linear consensus motif

  3. Unraveling Kinase Activation Dynamics Using Kinase-Substrate Relationships from Temporal Large-Scale Phosphoproteomics Studies.

    Directory of Open Access Journals (Sweden)

    Westa Domanova

    Full Text Available In response to stimuli, biological processes are tightly controlled by dynamic cellular signaling mechanisms. Reversible protein phosphorylation occurs on rapid time-scales (milliseconds to seconds, making it an ideal carrier of these signals. Advances in mass spectrometry-based proteomics have led to the identification of many tens of thousands of phosphorylation sites, yet for the majority of these the kinase is unknown and the underlying network topology of signaling networks therefore remains obscured. Identifying kinase substrate relationships (KSRs is therefore an important goal in cell signaling research. Existing consensus sequence motif based prediction algorithms do not consider the biological context of KSRs, and are therefore insensitive to many other mechanisms guiding kinase-substrate recognition in cellular contexts. Here, we use temporal information to identify biologically relevant KSRs from Large-scale In Vivo Experiments (KSR-LIVE in a data-dependent and automated fashion. First, we used available phosphorylation databases to construct a repository of existing experimentally-predicted KSRs. For each kinase in this database, we used time-resolved phosphoproteomics data to examine how its substrates changed in phosphorylation over time. Although substrates for a particular kinase clustered together, they often exhibited a different temporal pattern to the phosphorylation of the kinase. Therefore, although phosphorylation regulates kinase activity, our findings imply that substrate phosphorylation likely serve as a better proxy for kinase activity than kinase phosphorylation. KSR-LIVE can thereby infer which kinases are regulated within a biological context. Moreover, KSR-LIVE can also be used to automatically generate positive training sets for the subsequent prediction of novel KSRs using machine learning approaches. We demonstrate that this approach can distinguish between Akt and Rps6kb1, two kinases that share the same

  4. Problem-Solving Test: "In Vitro" Protein Kinase A Reaction

    Science.gov (United States)

    Szeberenyi, Jozsef

    2009-01-01

    Phosphorylation of proteins by protein kinases is an important mechanism in the regulation of protein activity. Among hundreds of protein kinases present in human cells, PKA, the first kinase discovered, belongs to the most important and best characterized group of these enzymes. The author presents an experiment that analyzes the "in vitro"…

  5. Mnk kinase pathway: Cellular functions and biological outcomes

    Institute of Scientific and Technical Information of China (English)

    Sonali; Joshi; Leonidas; C; Platanias

    2014-01-01

    The mitogen-activated protein kinase(MAPK) interacting protein kinases 1 and 2(Mnk1 and Mnk2) play important roles in controlling signals involved in mRNA translation. In addition to the MAPKs(p38 or Erk), multiple studies suggest that the Mnk kinases can be regulated by other known kinases such as Pak2 and/or other unidentified kinases by phosphorylation of residues distinct from the sites phosphorylated by the MAPKs. Several studies have established multiple Mnk protein targets, including PSF, heterogenous nuclear ribonucleoprotein A1, Sprouty 2 and have lead to the identification of distinct biological functions and substrate specificity for the Mnk kinases. In this review we discuss the pathways regulating the Mnk kinases, their known substrates as well as the functional consequences of engagement of pathways controlled by Mnk kinases. These kinases play an important role in mRNA translation via their regulation of eukaryotic initiation factor 4E(eIF4E) and their functions have important implications in tumor biology as well as the regulation of drug resistance to anti-oncogenic therapies. Other studies have identified a role for the Mnk kinases in cap-independent mRNA translation, suggesting that the Mnk kinases can exert important functional effects independently of the phosphorylation of eIF4 E. The role of Mnk kinases in inflammation and inflammationinduced malignancies is also discussed.

  6. The Roles of Protein Kinases in Learning and Memory

    Science.gov (United States)

    Giese, Karl Peter; Mizuno, Keiko

    2013-01-01

    In the adult mammalian brain, more than 250 protein kinases are expressed, but only a few of these kinases are currently known to enable learning and memory. Based on this information it appears that learning and memory-related kinases either impact on synaptic transmission by altering ion channel properties or ion channel density, or regulate…

  7. Oral protein kinase c β inhibition using ruboxistaurin

    DEFF Research Database (Denmark)

    Aiello, Lloyd Paul; Vignati, Louis; Sheetz, Matthew J;

    2011-01-01

    To evaluate efficacy, safety, and causes of vision loss among 813 patients (1,392 eyes) with moderately severe to very severe nonproliferative diabetic retinopathy from the Protein Kinase C β Inhibitor-Diabetic Retinopathy Study and Protein Kinase C β Inhibitor-Diabetic Retinopathy Study 2...... ruboxistaurin (RBX) protein kinase C β inhibitor trials....

  8. TPX2 Protein of Arabidopsis Activates Aurora Kinase 1, But Not Aurora Kinase 3 In Vitro

    Czech Academy of Sciences Publication Activity Database

    Tomaštíková, Eva; Demidov, D.; Jeřábková, Hana; Binarová, Pavla; Houben, A.; Doležel, Jaroslav; Petrovská, Beáta

    2015-01-01

    Roč. 33, č. 6 (2015), s. 1988-1995. ISSN 0735-9640 R&D Projects: GA ČR(CZ) GA14-28443S; GA MŠk(CZ) LO1204; GA ČR GAP501/12/2333 Institutional support: RVO:61389030 ; RVO:61388971 Keywords : Aurora kinase * Targeting protein for Xklp2 * In vitro kinase assay Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.656, year: 2014

  9. Inactivation of a MAPK-like protein kinase and activation of a MBP kinase in germinating barley embryos

    NARCIS (Netherlands)

    Testerink, C.; Vennik, M.; Kijne, J.W.; Wang, M.; Heimovaara-Dijkstra, S.

    2000-01-01

    We provide evidence for involvement of two different 45 kDa protein kinases in rehydration and germination of barley embryos. In dry embryos, a myelin basic protein (MBP) phosphorylating kinase was detected, which could be immunoprecipitated with an anti-MAPK (mitogen-activated protein kinase) antib

  10. Alternative splicing produces transcripts coding for alpha and beta chains of a hetero-dimeric phosphagen kinase.

    Science.gov (United States)

    Ellington, W Ross; Yamashita, Daisuke; Suzuki, Tomohiko

    2004-06-01

    Glycocyamine kinase (GK) catalyzes the reversible phosphorylation of glycocyamine (guanidinoacetate), a reaction central to cellular energy homeostasis in certain animals. GK is a member of the phosphagen kinase enzyme family and appears to have evolved from creatine kinase (CK) early in the evolution of multi-cellular animals. Prior work has shown that GK from the polychaete Neanthes (Nereis) diversicolor exits as a hetero-dimer in vivo and that the two polypeptide chains (termed alpha and beta) are coded for by unique transcripts. In the present study, we demonstrate that the GK from a congener Nereis virens is also hetero-dimeric and is coded for by alpha and beta transcripts, which are virtually identical to the corresponding forms in N. diversicolor. The GK gene from N. diversicolor was amplified by PCR. Sequencing of the PCR products showed that the alpha and beta chains are the result of alternative splicing of the GK primary mRNA transcript. These results also strongly suggest that this gene underwent an early tandem exon duplication event. Full-length cDNAs for N. virens GKalpha and GKbeta were individually ligated into expression vectors and the resulting constructs used to transform Escherichia coli expression hosts. Regardless of expression conditions, minimal GK activity was observed in both GKalpha and GKbeta constructs. Inclusion bodies for both were harvested, unfolded in urea and alpha chains, beta chains and mixtures of alpha and beta chains were refolded by sequential dialysis. Only modest amounts of GK activity were observed when alpha and beta were refolded individually. In contrast, when refolded the alpha and beta mixture yielded highly active hetero-dimers, as validated by size exclusion chromatography, electrophoresis and mass spectrometry, with a specific activity comparable to that of natural GK. The above evidence suggests that there is a preference for hetero-dimer formation in the GKs from these two polychaetes. The evolution of the

  11. Evaluation of Kinase Activity Profiling Using Chemical Proteomics.

    Science.gov (United States)

    Ruprecht, Benjamin; Zecha, Jana; Heinzlmeir, Stephanie; Médard, Guillaume; Lemeer, Simone; Kuster, Bernhard

    2015-12-18

    Protein kinases are important mediators of intracellular signaling and are reversibly activated by phosphorylation. Immobilized kinase inhibitors can be used to enrich these often low-abundance proteins, to identify targets of kinase inhibitors, or to probe their selectivity. It has been suggested that the binding of kinases to affinity beads reflects a kinase's activation status, a concept that is under considerable debate. To assess the merits of the idea, we performed a series of experiments including quantitative phosphoproteomics and purification of kinases by single or mixed affinity matrices from signaling activated or resting cancer cells. The data show that mixed affinity beads largely bind kinases independent of their activation status, and experiments using individual immobilized kinase inhibitors show mixed results in terms of preference for binding the active or inactive conformation. Taken together, activity- or conformation-dependent binding to such affinity resins depends (i) on the kinase, (ii) on the affinity probe, and (iii) on the activation status of the lysate or cell. As a result, great caution should be exercised when inferring kinase activity from such binding data. The results also suggest that assaying kinase activity using binding data is restricted to a limited number of well-chosen cases. PMID:26378887

  12. Effects of creatine monohydrate supplementation on exercise-induced apoptosis in athletes: A randomized, double-blind, and placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Rahman Rahimi

    2015-01-01

    Full Text Available Background: Creatine monohydrate (CrM has been shown to be beneficial to health due to its antioxidant potential. Strenuous exercise is associated with oxidative stress, which could lead to apoptosis. We investigated the ability of CrM in amelioration of apoptosis induced by incremental aerobic exercise (AE to exhaustion in young athletes. Materials and Methods: In a placebo-controlled, double-blind, randomized, parallel study, 31 young athletes (age 19.52 ± 2.75 years, body mass 79.24 ± 16.13 kg, height 1.73 ± 6.49 m, body fat 16.37% ± 5.92% were randomly assigned to CrM (4 × 5 g/day, n = 15 or placebo (PL: 4 × 5 g/day of maltodextrine powder; n = 16 to investigate the effect of 7 days CrM on serum p53 and insulin-like growth factor-1 (IGF-1 concentration after acute incremental AE test to exhaustion. Subjects performed AE before (test 1 and after 7 days of supplementation (test 2. Results: Before supplementation, AE to exhaustion induced a significant increase in serum p53 and IGF-1 concentrations at both CrM and PL groups (P 0.05. Conclusion: Our results suggest that supplementation with CrM prevents apoptosis, as measured by decreases in p53 concentration, induced by AE to exhaustion in young athletes. However, CrM had no effect on IGF-1 concentration after AE to exhaustion in young athletes.

  13. Metabolic Agents that Enhance ATP can Improve Cognitive Functioning: A Review of the Evidence for Glucose, Oxygen, Pyruvate, Creatine, and l-Carnitine

    Directory of Open Access Journals (Sweden)

    Lauren Owen

    2011-08-01

    Full Text Available Over the past four or five decades, there has been increasing interest in the neurochemical regulation of cognition. This field received considerable attention in the 1980s, with the identification of possible cognition enhancing agents or “smart drugs”. Even though many of the optimistic claims for some agents have proven premature, evidence suggests that several metabolic agents may prove to be effective in improving and preserving cognitive performance and may lead to better cognitive aging through the lifespan. Aging is characterized by a progressive deterioration in physiological functions and metabolic processes. There are a number of agents with the potential to improve metabolic activity. Research is now beginning to identify these various agents and delineate their potential usefulness for improving cognition in health and disease. This review provides a brief overview of the metabolic agents glucose, oxygen, pyruvate, creatine, and l-carnitine and their beneficial effects on cognitive function. These agents are directly responsible for generating ATP (adenosine triphosphate the main cellular currency of energy. The brain is the most metabolically active organ in the body and as such is particularly vulnerable to disruption of energy resources. Therefore interventions that sustain adenosine triphosphate (ATP levels may have importance for improving neuronal dysfunction and loss. Moreover, recently, it has been observed that environmental conditions and diet can affect transgenerational gene expression via epigenetic mechanisms. Metabolic agents might play a role in regulation of nutritional epigenetic effects. In summary, the reviewed metabolic agents represent a promising strategy for improving cognitive function and possibly slowing or preventing cognitive decline.

  14. The age dependence of T2 relaxation times of N-acetyl aspartate, creatine and choline in the human brain at 3 and 4T.

    Science.gov (United States)

    Jiru, F; Skoch, A; Wagnerova, D; Dezortova, M; Viskova, J; Profant, O; Syka, J; Hajek, M

    2016-03-01

    Knowledge of the T2 age dependence is of importance for MRS clinical studies involving subject groups with a wide age range. A number of studies have focused on the age dependence of T2 values in the human brain, with rather conflicting results. The aim of this study was to analyze the age dependence of T2 values of N-acetyl aspartate (NAA), creatine (Cr) and choline (Cho) in the human brain using data acquired at 3T and 4T and to assess the influence of the macromolecule (MM) baseline handling on the obtained results. Two distinct groups of young and elderly controls have been measured at 3T (TE = 30-540 ms, 9 young and 11 elderly subjects) and 4T (TE = 10-180 ms, 18 young and 14 elderly subjects) using single-voxel spectroscopy. In addition, MM spectra were measured from two subjects using the inversion-recovery technique at 4T. All spectra were processed with LCModel using basis sets with different MM signals (measured or simulated) and also with MM signals included for a different TE range. Individual estimated T2 values were statistically analyzed using the R programming language for the age dependence of T2 values as well as the influence of the MM baseline handling. A significant decrease of T2 values of NAA and Cr in elderly subjects compared with young subjects was confirmed. The same trend was observed for Cho. Significantly higher T2 values calculated using the measured MM baseline for all studied metabolites at 4T were observed for both young and elderly subjects. To conclude, while the handling of MM and lipid signals may have a significant effect on estimated T2 values, we confirmed the age dependence of T2 values of NAA and Cr and the same trend for Cho in the human brain. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26752593

  15. Protein phosphatases active on acetyl-CoA carboxylase phosphorylated by casein kinase I, casein kinase II and the cAMP-dependent protein kinase

    International Nuclear Information System (INIS)

    The protein phosphatases in rat liver cytosol, active on rat liver acetyl-CoA carboxylase (ACC) phosphorylated by casein kinase I, casein kinase II and the cAMP-dependent protein kinase, have been partially purified by anion-exchange and gel filtration chromatography. The major phosphatase activities against all three substrates copurify through fractionation and appear to be identical to protein phosphatases 2A1 and 2A2. No unique protein phosphatase active on 32P-ACC phosphorylated by the casein kinases was identified

  16. Contractions activate hormone-sensitive lipase in rat muscle by protein kinase C and mitogen-activated protein kinase

    DEFF Research Database (Denmark)

    Donsmark, Morten; Langfort, Jozef; Holm, Cecilia;

    2003-01-01

    contractions. Adrenaline acts via cAMP-dependent protein kinase (PKA). The signalling mediating the effect of contractions is unknown and was explored in this study. Incubated soleus muscles from 70 g male rats were electrically stimulated to perform repeated tetanic contractions for 5 min. The contraction......-induced activation of HSL was abolished by the protein kinase C (PKC) inhibitors bisindolylmaleimide I and calphostin C and reduced 50% by the mitogen-activated protein kinase kinase (MEK) inhibitor U0126, which also completely blocked extracellular signal-regulated kinase (ERK) 1 and 2 phosphorylation. None of the...

  17. Statistical analysis of protein kinase specificity determinants

    DEFF Research Database (Denmark)

    Kreegipuu, Andres; Blom, Nikolaj; Brunak, Søren;

    1998-01-01

    The site and sequence specificity of protein kinase, as well as the role of the secondary structure and surface accessibility of the phosphorylation sites on substrate proteins, was statistically analyzed. The experimental data were collected from the literature and are available on the World Wide...... Web at http://www.cbs.dtu.dk/databases/PhosphoBase/. The set of data involved 1008 phosphorylatable sites in 406 proteins, which were phosphorylated by 58 protein kinases. It was found that there exists almost absolute SER/Thr or Tyr specificity, with rare exceptions. The sequence specificity...... determinants were less strict and were located between positions -4 and +4 relative to the phosphorylation site. Secondary structure and surface accessibility predictions revealed that most of the phosphorylation sites were located on the surface of the target proteins....

  18. Tyrosine kinase signalling in breast cancer

    International Nuclear Information System (INIS)

    Cells are continuously exposed to diverse stimuli ranging from soluble endocrine and paracrine factors to signalling molecules on neighbouring cells. Receptors of the tyrosine kinase family play an important role in the integration and interpretation of these external stimuli, allowing a cell to respond appropriately to its environment. The activation of receptor tyrosine kinases (RTKs) is tightly controlled, allowing a normal cell to correctly integrate its external environment with internal signal transduction pathways. In contrast, due to numerous molecular alterations arising during the course of malignancy, a tumour is characterized by an abnormal response to its environment, which allows cancer cells to evade the normal mechanisms controlling cellular proliferation. Alterations in the expression of various RTKs, in their activation, and in the signalling molecules lying downstream of the receptors play important roles in the development of cancer. This topic is the major focus of the thematic review section of this issue of Breast Cancer Research

  19. Phosphatidylinositol 4-kinases: Function, structure, and inhibition

    International Nuclear Information System (INIS)

    The phosphatidylinositol 4-kinases (PI4Ks) synthesize phosphatidylinositol 4-phosphate (PI4P), a key member of the phosphoinositide family. PI4P defines the membranes of Golgi and trans-Golgi network (TGN) and regulates trafficking to and from the Golgi. Humans have two type II PI4Ks (α and β) and two type III enzymes (α and β). Recently, the crystal structures were solved for both type II and type III kinase revealing atomic details of their function. Importantly, the type III PI4Ks are hijacked by +RNA viruses to create so-called membranous web, an extensively phosphorylated and modified membrane system dedicated to their replication. Therefore, selective and potent inhibitors of PI4Ks have been developed as potential antiviral agents. Here we focus on the structure and function of PI4Ks and their potential in human medicine

  20. Phosphatidylinositol 4-kinases: Function, structure, and inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Boura, Evzen, E-mail: boura@uochb.cas.cz; Nencka, Radim, E-mail: nencka@uochb.cas.cz

    2015-10-01

    The phosphatidylinositol 4-kinases (PI4Ks) synthesize phosphatidylinositol 4-phosphate (PI4P), a key member of the phosphoinositide family. PI4P defines the membranes of Golgi and trans-Golgi network (TGN) and regulates trafficking to and from the Golgi. Humans have two type II PI4Ks (α and β) and two type III enzymes (α and β). Recently, the crystal structures were solved for both type II and type III kinase revealing atomic details of their function. Importantly, the type III PI4Ks are hijacked by +RNA viruses to create so-called membranous web, an extensively phosphorylated and modified membrane system dedicated to their replication. Therefore, selective and potent inhibitors of PI4Ks have been developed as potential antiviral agents. Here we focus on the structure and function of PI4Ks and their potential in human medicine.

  1. Phosphatidylinositol 4-kinases: Function, structure, and inhibition

    Czech Academy of Sciences Publication Activity Database

    Bouřa, Evžen; Nencka, Radim

    2015-01-01

    Roč. 337, č. 2 (2015), s. 136-145. ISSN 0014-4827 R&D Projects: GA ČR GJ15-21030Y; GA MŠk LO1302; GA ČR GA15-09310S EU Projects: European Commission(XE) 333916 - STARPI4K Institutional support: RVO:61388963 Keywords : phosphatidylinositol 4-kinase * inhibitor * crystal structure * virus Subject RIV: CC - Organic Chemistry Impact factor: 3.246, year: 2014

  2. Association of Common Genetic Variants in Mitogen-activated Protein Kinase Kinase Kinase Kinase 4 with Type 2 Diabetes Mellitus in a Chinese Han Population

    Institute of Scientific and Technical Information of China (English)

    Ting-Ting Li; Hong Qiao; Hui-Xin Tong; Tian-Wei Zhuang; Tong-Tong Wang

    2016-01-01

    Background:A study has identified several novel susceptibility variants of the mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) gene for type 2 diabetes mellitus (T2DM) within the German population.Among the variants,five single nucleotide polymorphisms (SNPs) of MAP4K4 (rs1003376,rs11674694,rs2236935,rs2236936,and rs6543087) showed significant association with T2DM or diabetes-related quantitative traits.We aimed to evaluate whether common SNPs in the MAP4K4 gene were associated with T2DM in the Chinese population.Methods:Five candidate SNPs were genotyped in 996 patients newly diagnosed with T2DM and in 976 control subjects,using the SNPscanTM method.All subjects were recruited from the Second Affiliated Hospital,Harbin Medical University from October 2010 to September 2013.We evaluated the T2DM risk conferred by individual SNPs and haplotypes using logistic analysis,and the association between the five SNPs and metabolic traits in the subgroups.Results:Of the five variants,SNP rs2236935T/C was significantly associated with T2DM in this study population (odds ratio =1.293;95% confidence interval:1.034-1.619,P =0.025).In addition,among the controls,rs 1003376 was significantly associated with an increased body mass index (P =0.045) and homeostatic model assessment-insulin resistance (P =0.037).Conclusions:MAP4K4 gene is associated with T2DM in a Chinese Han population,and MAP4K4 gene variants may contribute to the risk toward the development of T2DM.

  3. Molecular Imaging of the ATM Kinase Activity

    International Nuclear Information System (INIS)

    Purpose: Ataxia telangiectasia mutated (ATM) is a serine/threonine kinase critical to the cellular DNA-damage response, including from DNA double-strand breaks. ATM activation results in the initiation of a complex cascade of events including DNA damage repair, cell cycle checkpoint control, and survival. We sought to create a bioluminescent reporter that dynamically and noninvasively measures ATM kinase activity in living cells and subjects. Methods and Materials: Using the split luciferase technology, we constructed a hybrid cDNA, ATM-reporter (ATMR), coding for a protein that quantitatively reports on changes in ATM kinase activity through changes in bioluminescence. Results: Treatment of ATMR-expressing cells with ATM inhibitors resulted in a dose-dependent increase in bioluminescence activity. In contrast, induction of ATM kinase activity upon irradiation resulted in a decrease in reporter activity that correlated with ATM and Chk2 activation by immunoblotting in a time-dependent fashion. Nuclear targeting improved ATMR sensitivity to both ATM inhibitors and radiation, whereas a mutant ATMR (lacking the target phosphorylation site) displayed a muted response. Treatment with ATM inhibitors and small interfering (si)RNA-targeted knockdown of ATM confirm the specificity of the reporter. Using reporter expressing xenografted tumors demonstrated the ability of ATMR to report in ATM activity in mouse models that correlated in a time-dependent fashion with changes in Chk2 activity. Conclusions: We describe the development and validation of a novel, specific, noninvasive bioluminescent reporter that enables monitoring of ATM activity in real time, in vitro and in vivo. Potential applications of this reporter include the identification and development of novel ATM inhibitors or ATM-interacting partners through high-throughput screens and in vivo pharmacokinetic/pharmacodynamic studies of ATM inhibitors in preclinical models

  4. Complexity of Receptor Tyrosine Kinase Signal Processing

    OpenAIRE

    Volinsky, Natalia; Kholodenko, Boris N.

    2013-01-01

    Our knowledge of molecular mechanisms of receptor tyrosine kinase (RTK) signaling advances with ever-increasing pace. Yet our understanding of how the spatiotemporal dynamics of RTK signaling control specific cellular outcomes has lagged behind. Systems-centered experimental and computational approaches can help reveal how overlapping networks of signal transducers downstream of RTKs orchestrate specific cell-fate decisions. We discuss how RTK network regulatory structures, which involve the ...

  5. Aurora kinase inhibitors: Progress towards the clinic

    Czech Academy of Sciences Publication Activity Database

    Kollareddy, M.; Zheleva, D.; Dzubak, P.; Brahmkshatriya, Pathik; Lepšík, Martin; Hajduch, M.

    2012-01-01

    Roč. 30, č. 6 (2012), s. 2411-2432. ISSN 0167-6997 Grant ostatní: GA ČR(CZ) GA301/08/1649; GA ČR(CZ) GD303/09/H048 Institutional research plan: CEZ:AV0Z40550506 Keywords : Aurora kinases * cancer * inhibitors Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.498, year: 2012

  6. Molecular Imaging of the ATM Kinase Activity

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Terence M. [Department of Radiation Oncology, Ohio State University, Columbus, Ohio (United States); Nyati, Shyam [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Center for Molecular Imaging, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Ross, Brian D. [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Rehemtulla, Alnawaz, E-mail: alnawaz@umich.edu [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Center for Molecular Imaging, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan (United States)

    2013-08-01

    Purpose: Ataxia telangiectasia mutated (ATM) is a serine/threonine kinase critical to the cellular DNA-damage response, including from DNA double-strand breaks. ATM activation results in the initiation of a complex cascade of events including DNA damage repair, cell cycle checkpoint control, and survival. We sought to create a bioluminescent reporter that dynamically and noninvasively measures ATM kinase activity in living cells and subjects. Methods and Materials: Using the split luciferase technology, we constructed a hybrid cDNA, ATM-reporter (ATMR), coding for a protein that quantitatively reports on changes in ATM kinase activity through changes in bioluminescence. Results: Treatment of ATMR-expressing cells with ATM inhibitors resulted in a dose-dependent increase in bioluminescence activity. In contrast, induction of ATM kinase activity upon irradiation resulted in a decrease in reporter activity that correlated with ATM and Chk2 activation by immunoblotting in a time-dependent fashion. Nuclear targeting improved ATMR sensitivity to both ATM inhibitors and radiation, whereas a mutant ATMR (lacking the target phosphorylation site) displayed a muted response. Treatment with ATM inhibitors and small interfering (si)RNA-targeted knockdown of ATM confirm the specificity of the reporter. Using reporter expressing xenografted tumors demonstrated the ability of ATMR to report in ATM activity in mouse models that correlated in a time-dependent fashion with changes in Chk2 activity. Conclusions: We describe the development and validation of a novel, specific, noninvasive bioluminescent reporter that enables monitoring of ATM activity in real time, in vitro and in vivo. Potential applications of this reporter include the identification and development of novel ATM inhibitors or ATM-interacting partners through high-throughput screens and in vivo pharmacokinetic/pharmacodynamic studies of ATM inhibitors in preclinical models.

  7. Janus Activated Kinase inhibition in Myelofibrosis

    Directory of Open Access Journals (Sweden)

    H Malhotra

    2012-01-01

    Full Text Available Janus Activated Kinase (JAK 2 plays an important role in the pathogenesis of myelofibrosis (MF. Ruxolitinib (INCB018424, Jakafi is a potent dual JAK1 and JAK2 inhibitor. In November 2011, it became approved by the US FDA for the treatment of intermediate or high-risk MF. This review shall outline the role of Ruxolitinib in the current management of MF and its potential future.

  8. Diacylglycerol Kinase Inhibition and Vascular Function.

    Science.gov (United States)

    Choi, Hyehun; Allahdadi, Kyan J; Tostes, Rita C A; Webb, R Clinton

    2009-01-01

    Diacylglycerol kinases (DGKs), a family of lipid kinases, convert diacylglycerol (DG) to phosphatidic acid (PA). Acting as a second messenger, DG activates protein kinase C (PKC). PA, a signaling lipid, regulates diverse functions involved in physiological responses. Since DGK modulates two lipid second messengers, DG and PA, regulation of DGK could induce related cellular responses. Currently, there are 10 mammalian isoforms of DGK that are categorized into five groups based on their structural features. These diverse isoforms of DGK are considered to activate distinct cellular functions according to extracellular stimuli. Each DGK isoform is thought to play various roles inside the cell, depending on its subcellular localization (nuclear, ER, Golgi complex or cytoplasm). In vascular smooth muscle, vasoconstrictors such as angiotensin II, endothelin-1 and norepinephrine stimulate contraction by increasing inositol trisphosphate (IP(3)), calcium, DG and PKC activity. Inhibition of DGK could increase DG availability and decrease PA levels, as well as alter intracellular responses, including calcium-mediated and PKC-mediated vascular contraction. The purpose of this review is to demonstrate a role of DGK in vascular function. Selective inhibition of DGK isoforms may represent a novel therapeutic approach in vascular dysfunction. PMID:21547002

  9. Statistical analysis of protein kinase specificity determinants

    DEFF Research Database (Denmark)

    Kreegipuu, Andres; Blom, Nikolaj; Brunak, Søren; Jarv, Jaak

    1998-01-01

    The site and sequence specificity of protein kinase, as well as the role of the secondary structure and surface accessibility of the phosphorylation sites on substrate proteins, was statistically analyzed. The experimental data were collected from the literature and are available on the World Wid...... determinants were less strict and were located between positions -4 and +4 relative to the phosphorylation site. Secondary structure and surface accessibility predictions revealed that most of the phosphorylation sites were located on the surface of the target proteins.......The site and sequence specificity of protein kinase, as well as the role of the secondary structure and surface accessibility of the phosphorylation sites on substrate proteins, was statistically analyzed. The experimental data were collected from the literature and are available on the World Wide...... Web at http://www.cbs.dtu.dk/databases/PhosphoBase/. The set of data involved 1008 phosphorylatable sites in 406 proteins, which were phosphorylated by 58 protein kinases. It was found that there exists almost absolute SER/Thr or Tyr specificity, with rare exceptions. The sequence specificity...

  10. Cellular trafficking of the IL-1RI-associated kinase-1 requires intact kinase activity

    International Nuclear Information System (INIS)

    Upon stimulation of cells with interleukin-1 (IL-1) the IL-1 receptor type I (IL-1RI) associated kinase-1 (IRAK-1) transiently associates to and dissociates from the IL-1RI and thereafter translocates into the nucleus. Here we show that nuclear translocation of IRAK-1 depends on its kinase activity since translocation was not observed in EL-4 cells overexpressing a kinase negative IRAK-1 mutant (EL-4IRAK-1-K239S). IRAK-1 itself, an endogenous substrate with an apparent molecular weight of 24 kDa (p24), and exogenous substrates like histone and myelin basic protein are phosphorylated by nuclear located IRAK-1. Phosphorylation of p24 cannot be detected in EL-4IRAK-1-K239S cells. IL-1-dependent recruitment of IRAK-1 to the IL-1RI and subsequent phosphorylation of IRAK-1 is a prerequisite for nuclear translocation of IRAK-1. It is therefore concluded that intracellular localization of IRAK-1 depends on its kinase activity and that IRAK-1 may also function as a kinase in the nucleus as shown by a new putative endogenous substrate

  11. Protein kinase A signalling in Schistosoma mansoni cercariae and schistosomules.

    Science.gov (United States)

    Hirst, Natasha L; Lawton, Scott P; Walker, Anthony J

    2016-06-01

    Cyclic AMP (cAMP)-dependent protein kinase/protein kinase A regulates multiple processes in eukaryotes by phosphorylating diverse cellular substrates, including metabolic and signalling enzymes, ion channels and transcription factors. Here we provide insight into protein kinase A signalling in cercariae and 24h in vitro cultured somules of the blood parasite, Schistosoma mansoni, which causes human intestinal schistosomiasis. Functional mapping of activated protein kinase A using anti-phospho protein kinase A antibodies and confocal laser scanning microscopy revealed activated protein kinase A in the central and peripheral nervous system, oral-tip sensory papillae, oesophagus and excretory system of intact cercariae. Cultured 24h somules, which biologically represent the skin-resident stage of the parasite, exhibited similar activation patterns in oesophageal and nerve tissues but also displayed striking activation at the tegument and activation in a region resembling the germinal 'stem' cell cluster. The adenylyl cyclase activator, forskolin, stimulated somule protein kinase A activation and produced a hyperkinesia phenotype. The biogenic amines, serotonin and dopamine known to be present in skin also induced protein kinase A activation in somules, whereas neuropeptide Y or [Leu(31),Pro(34)]-neuropeptide Y attenuated protein kinase A activation. However, neuropeptide Y did not block the forskolin-induced somule hyperkinesia. Bioinformatic investigation of potential protein associations revealed 193 medium confidence and 59 high confidence protein kinase A interacting partners in S. mansoni, many of which possess putative protein kinase A phosphorylation sites. These data provide valuable insight into the intricacies of protein kinase A signalling in S. mansoni and a framework for further physiological investigations into the roles of protein kinase A in schistosomes, particularly in the context of interactions between the parasite and the host. PMID:26777870

  12. A-Raf kinase is a new interacting partner of protein kinase CK2 beta subunit

    DEFF Research Database (Denmark)

    Boldyreff, B; Issinger, O G

    1997-01-01

    In a search for protein kinase CK2 beta subunit binding proteins using the two-hybrid system, more than 1000 positive clones were isolated. Beside clones for the alpha' and beta subunit of CK2, there were clones coding for a so far unknown protein, whose partial cDNA sequence was already deposited...... in the EMBL database under the accession numbers R08806 and Z17360, for the ribosomal protein L5 and for A-Raf kinase. All isolated clones except the one for CK2 beta showed no interaction with the catalytic alpha subunit of CK2. A-Raf kinase is a new interesting partner of CK2 beta. The isolated A...

  13. Clinical effects of creatine phosphate on multifactor heart failure in aged patients%磷酸肌酸钠治疗老年多病因心力衰竭的临床疗效

    Institute of Scientific and Technical Information of China (English)

    陈力量; 殷兰芳; 章纪平

    2011-01-01

    Objective: To observe effects of creatine phosphate on cardiac function and plasma brain natriuretic pep-tide (BNP) in aged patients with heart failure. Methods: A total of 68 aged patients with multifactor heart failure were randomly divided into routine treatment group (received routine drug treatment) and creatine phosphate group (received creatine phosphate lg/d intravenous drip, once a day for 14d based on routine treatment). Clinical effects of the two groups were observed before and two weeks after treatment; changes of plasma concentrations of BNP and adverse drug reaction were observed. Results: After treatment, clinical symptoms of both groups improved, and total effective rate (94. 1% vs. 64. 7%) and marked effective rate (29. 4% vs. 14. 7%) of creatine phosphate group were significantly higher than those of routine treatment group creatine phosphate group significantly decreased compared with routine treatment group [ (262±168) pg/ml vs. (538±264) pg/ml, P<0. 01]. Conclusion: Creatine phosphate can significantly improve clinical symptoms and decrease plasma brain natriuretic peptide level in aged patients with multifactor heart failure and it's safe and reliable.%目的:观察磷酸肌酸钠对老年多病因心力衰竭患者的心功能及血浆脑钠肽(BNP)的影响.方法:68例老年多病因心力衰竭患者被随机分为:常规治疗组,予常规药物治疗;磷酸肌酸钠组,在常规治疗基础上加用磷酸肌酸钠静脉滴注1g/d,1次/d,疗程14d.观察两组治疗前及治疗后2周临床疗效,检测血浆BNP浓度的变化,并观察药物不良反应.结果:两组治疗后临床症状均有好转,但磷酸肌酸钠组的总有效率(94.1%比64.7%)及显效率(29.4%比14.7%)均明显高于常规治疗组(P均<0.01);磷酸肌酸钠组血浆BNP浓度较常规治疗组显著降低[ (262±168) pg/ml比(538±264) pg/ml,P<0.01].结论:磷酸肌酸钠能明显改善老年多病因心力

  14. 毛细管胶束电动色谱法检测尿液肌酸和肌酐含量%Determination of creatin and creatinine in urine by capillary micelle electro-kinetic chromatography

    Institute of Scientific and Technical Information of China (English)

    吉艳; 吴惠毅; 朱海宁; 赵绍林; 杨晋

    2011-01-01

    Objective To establish a method for determination of the concentration of creatin and creatinine in urine by high performance capillary electrophoresis (HPCE). Methods The determination was established by capillary micelle electro-kinetic chromatography (MEKC). The electrophoresis buffer was the solution containing 20 mmol/L Na2HPO4-H3PO4 supplemented with 100 mmol/L SDS with pH 5.50. An uncoated fused silica capillary with length of 53 cm and diameter of 75 m was used to separate the urine specimen which was 20-fold dilution and imported with pressure of 1 psi for 4 seconds, then circulated for 15 minutes under voltage of 15 kV. The data were detected by diode-array detector (DAD) ( λ = 200 nm). Results The linear range of creatin was 4.9-2500 mol/L (r = 0.9998) and creatinine was 4.9-2500 mol/L (r = 1. 0000). The recovery rate of creatin was 97.8% -100.8% ( mean of 99.2% ), and that of creatin was 99.5% -104% ( mean of 101.8% ). The coefficients of variation of inter-and intra-assay for creatin and creatinine were 3.2% and 8.0%, and 2.3% and 6.8%, respectively. The detection limit of creatin was 1.4 mol/L and creatinine was 3.31 mol/L. Conclusion The established method in this study is less amount for applied sample, high precision and accuracy, wide range for linearity and low cost, and is suitable for routine clinical application.%目的 建立高效毛细管电泳技术(HPCE)测定尿液中肌酸(Car)和肌酐(Cr)的方法.方法 运用毛细管胶束电动色谱技术(MEKC),以pH 5.5、20mmol/L的Na2HPO4-H3PO4(含100 mmol/L SDS)作为电泳缓冲液,非涂层石英毛细管进行分离,样品经过20倍稀释后以1 psi压力进样4 s,15 kV电压下分离尿液中的Cri和Cr,二极管阵列检测器(DAD)( λ=200 nm)检测.结果 Cri和Cr的线性范围为4.9~2500μmol、L和4.9~2 500μmol/L(r值分别为0.9998和1);Cri回收率为97.8%~100.8%、平均99.2%,Cr回收率为99.5%~104%、平均101.8%;Cri迁移时间批内和

  15. Distribution of protein kinase Mzeta and the complete protein kinase C isoform family in rat brain

    DEFF Research Database (Denmark)

    Naik, M U; Benedikz, Eirikur; Hernandez, I;

    2000-01-01

    Protein kinase C (PKC) is a multigene family of at least ten isoforms, nine of which are expressed in brain (alpha, betaI, betaII, gamma, delta, straightepsilon, eta, zeta, iota/lambda). Our previous studies have shown that many of these PKCs participate in synaptic plasticity in the CA1 region of......, protein kinase Mzeta (PKMzeta). In this study, we used immunoblot and immunocytochemical techniques with isoform-specific antisera to examine the distribution of the complete family of PKC isozymes and PKMzeta in rat brain. Each form of PKC showed a widespread distribution in the brain with a distinct...

  16. High quality, small molecule-activity datasets for kinase research.

    Science.gov (United States)

    Sharma, Rajan; Schürer, Stephan C; Muskal, Steven M

    2016-01-01

    Kinases regulate cell growth, movement, and death. Deregulated kinase activity is a frequent cause of disease. The therapeutic potential of kinase inhibitors has led to large amounts of published structure activity relationship (SAR) data. Bioactivity databases such as the Kinase Knowledgebase (KKB), WOMBAT, GOSTAR, and ChEMBL provide researchers with quantitative data characterizing the activity of compounds across many biological assays. The KKB, for example, contains over 1.8M kinase structure-activity data points reported in peer-reviewed journals and patents. In the spirit of fostering methods development and validation worldwide, we have extracted and have made available from the KKB 258K structure activity data points and 76K associated unique chemical structures across eight kinase targets. These data are freely available for download within this data note. PMID:27429748

  17. Protein kinase C involvement in focal adhesion formation

    DEFF Research Database (Denmark)

    Woods, A; Couchman, J R

    1992-01-01

    still to be elucidated. We show here that the kinase inhibitors H7 and HA1004 reduce focal adhesion and stress fiber formation in response to fibronectin in a dose-dependent manner, and that activators of protein kinase C can promote their formation under conditions where they do not normally form...... then treated with kinase inhibitors H7 and HA1004 for 2h, IRM indicated a reduction in focal adhesion formation at concentrations where protein kinase C (PKC) should be inhibited. In contrast, focal adhesions formed normally at concentrations of these inhibitors where cyclic AMP- or cyclic GMP......-dependent kinases should be inactivated. Inhibition of PKC, but not that of cyclic AMP- or cyclic GMP-dependent kinases, also prevented the formation of stress fibers and induced a dispersal of talin and vinculin, but not integrin beta 1 subunits, from small condensations present at 1h. Consistent with the...

  18. The secret life of kinases: functions beyond catalysis.

    LENUS (Irish Health Repository)

    Rauch, Jens

    2011-10-28

    Abstract Protein phosphorylation participates in the regulation of all fundamental biological processes, and protein kinases have been intensively studied. However, while the focus was on catalytic activities, accumulating evidence suggests that non-catalytic properties of protein kinases are essential, and in some cases even sufficient for their functions. These non-catalytic functions include the scaffolding of protein complexes, the competition for protein interactions, allosteric effects on other enzymes, subcellular targeting, and DNA binding. This rich repertoire often is used to coordinate phosphorylation events and enhance the specificity of substrate phosphorylation, but also can adopt functions that do not rely on kinase activity. Here, we discuss such kinase independent functions of protein and lipid kinases focussing on kinases that play a role in the regulation of cell proliferation, differentiation, apoptosis, and motility.

  19. Effects of creatine phosphate disodium on the uncoupling protein 2 in myocardial mitochondria and the energy metabolism in rats after exhaustive exercise

    Directory of Open Access Journals (Sweden)

    Xiao-yan LI

    2015-11-01

    Full Text Available Objective To explore the effect of creatine phosphate disodium (CPDS on the energy metabolism of myocardial mitochondria in rats after single exhaustive exercise, and the underline mechanism of protection effects of CPDS on myocardium under stress situation. Methods Thirty six male Wistar rats were randomly divided into control group, once exhaustive exercise group, and CPDS group (12 for each. The concentrations of myocardial ATP, plasma epinephrine (E, norepinephrine (NE and free fatty acid (FFA were determined. RT-PCR and Western blotting were performed to detect the expressions of uncoupling protein 2 (UCP2 in myocardial mitochondria. Results The concentrations of plasma FFA, E and NE increased and the contents of myocardial ATP declined significantly in single exhaustive exercise group and CPDS group as compared with that in control group (P<0.05. RT-PCR revealed that the expressions of UCP2 mRNA were up-regulated by 64% and 24%, respectively, in single exhaustive exercise group and CPDS group when compared with that in control group. Western blotting showed that the expressions of UCP2 were increased by 65% and 26%, respectively, in single exhaustive exercise group and CPDS group when compared with that in control group. Correlation analysis showed a significant positive correlation of the expression of myocardial UCP2 to the concentration of plasma FFA (r=0.98, P<0.01, also of the concentration of plasma FFA to the levels of plasma E and NE (r=0.93, r=0.88, P<0.01. Conclusions After exhaustive exercise, the expression of myocardial UCP2 is significantly up-regulated, the synthesis of ATP reduced, and the energy metabolism disturbed, which may be one of the mechanisms leading to sudden cardiac death in sports training. Meanwhile, supplement of external CPDS may antagonize the increased expression of UCP2 induced by exercise stress, increase ATP reserves and improve the energy metabolism, and it may have a positive effect on

  20. Clinical characteristics of megaconial congenital muscular dystrophy due to choline kinase beta gene defects in a series of 15 patients.

    Science.gov (United States)

    Haliloglu, Goknur; Talim, Beril; Sel, Cigdem Genc; Topaloglu, Haluk

    2015-11-01

    A new form of congenital muscular dystrophy (CMD) with multisystem involvement and characteristic mitochondrial structural changes, due to choline kinase beta (CHKB) gene defects has been characterized by intellectual disability, autistic features, ichthyosis-like skin changes, and dilated cardiomyopathy. We define the clinical characteristics in 15 patients, from 14 unrelated families with so-called 'megaconial CMD', all having mutations in CHKB. Core clinical phenotype included global developmental delay prominent in gross-motor and language domains, severe intellectual disability (ID), and/or muscle weakness in all cases. Muscle biopsies were equivocally 'megaconial' in all. Other peculiarities were: ichthyosis-like skin changes (n = 11), increased serum CK levels (n = 12), microcephaly (n = 6), dysmorphic facial features (n = 7), neonatal hypotonia (n = 3), seizures (n = 3), epileptiform activity without clinically overt seizures (n = 2), dilated cardiomyopathy (n = 2), decreased left ventricular systolic function (n = 2), congenital heart defects (n = 3), sensorineural (n = 1), and conductive hearing loss (n = 1). Ten patients had cranial neuroimaging (MRI-MRS) study, which was notably normal in all, other than one patient having a decreased choline: creatine peak. Intra-familial variability in clinical expression of the disease is noted in four families. Two siblings from the same family, one presenting with global developmental delay and dilated cardiomyopathy, and the other with ichthyosis, ID and proximal weakness without cardiomyopathy died at the ages of 2 years 1 month, and 7 years 4 months respectively. Evolution was progressive (n = 13) and static (n = 2). PMID:26067811