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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.

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    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.

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    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. Macro creatine kinase type 1: a cause of spuriously elevated serum creatine kinase associated with leukoencephalopathy in a child.

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    Bodensteiner, John B

    2014-07-01

    Macro creatine kinase type 1 is a complex formed by the creatine kinase isoenzyme BB and monoclonal IgG and occurs in about 1% of patients studied. First identified as a cause of spurious elevation of the total serum creatine kinase in patients suspected of myocardial infarction, the test has been largely replaced by the measurement of troponin levels. We present a child with delayed milestones and persistently elevated total serum creatine kinase measurements (∼ 1000-4000 IU) normal electromyogram and brisk myotatic reflexes. Creatine kinase isoenzymes and brain imaging showed the presence of macro creatine kinase type 1 and extensive signal abnormality of the cerebral white matter. Macro creatine kinase type 1 has been associated with several conditions though it has not been described in association with leukoencephalopathy or in patients this young. Macro creatine kinase type 1 can be a cause of elevated total creatine kinase in patients without primary muscle disease. The significance of the relationship of the macro creatine kinase to the leukoencephalopathy in this patient is unknown.

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

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    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...

  9. Leukemic cell creatine kinase and its isoenzymes.

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    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

  10. 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.

  11. Macro-creatine kinase: a neglected cause of elevated creatine kinase.

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    Aljuani, F; Tournadre, A; Cecchetti, S; Soubrier, M; Dubost, J J

    2015-04-01

    Macro-creatine kinase (macro-CK) is a neglected cause of raised CK. Over a 10-year period, we observed five cases. Three patients had macro-CK type 1. One patient with fibromyalgia underwent several explorations to find a muscular pathology; another, who had elevated CK-MB (muscle-brain fraction) activity, was referred to a cardiologist, and statin therapy was erroneously discontinued in two patients. Two patients had macro-CK type 2: a man with a neuroendocrine carcinoma and a woman with rheumatoid arthritis. Diagnosis of type 1 obviates the need to carry out pointless and expensive investigations seeking a neuromuscular or cardiac pathology, and also, the unwarranted discontinuation of statin therapy. Type 2 must prompt investigations for a neoplasm.

  12. 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

  13. 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

  14. 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....

  15. 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......, the C-terminal end of the K1 fragment is not A327 as expected, but D325. Thus, the amino acids residues T326 and A327 have been eliminated by the protease....

  16. 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.

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

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    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...

  18. 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

  19. 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.

  20. Immunoglobulin-associated creatine kinase masquerading as macro-creatine kinase type 2 in a statin user.

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    Loh, Tze Ping; Ang, Yan Hoon; Neo, Siew Fong; Yin, Cecilia; Wong, Moh Sim; Leong, Sai Mun; Saw, Sharon; Sethi, Sunil K

    2012-01-01

    Macro-creatine kinase (CK) is a cause of falsely elevated CK. Macro-CK type 1 is immunoglobulin-associated CK; type 2 is polymeric mitochondrial-CK. An elderly asymptomatic lady had an elevated CK level after receiving statin therapy. Her CK gel electrophoresis analysis demonstrated coexisting macro-CK type 1 and type 2 patterns. Further analysis by immunofixation and mixing this patient's serum with CK control material revealed an IgG-associated macro-CK that mimicked the electrophoretic pattern of macro-CK type 2. This highly unusual discovery suggests the possibility of the misinterpretation of macro-CK type 1 as macro-CK type 2. Falsely elevated CK is still common despite modern laboratory instrumentation and should be investigated.

  1. 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.

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

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    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.

  3. Creatine kinase in cell cycle regulation and cancer.

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    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

  4. Serum creatine kinase relationship to postural constraints in manual work.

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    Mairiaux, P; Bettonville, M N; Mawet, M; Malchaire, J

    1986-01-01

    Serum creatine kinase (CK) variations during work and subjective assessments of postural discomfort were analysed in 30 workers assigned to three different tasks in a rolling mill. After four days of work, serum CK levels were significantly increased above control levels. No difference was found between the tasks studied. Inter-individual variability in CK response was large: a marked CK increase was only seen in 21 workers, while 5 workers showed a marked CK decrease. The postural discomfort sensations increased with work in each group, with their location in the body being related to the characteristics of each task or workplace. No relationship was found between the postural discomfort scores and CK changes. Results showed that determination of an individual baseline CK level was difficult to achieve in an occupational setting. It is concluded that CK variations cannot reliably be used in the field for detection of individuals exposed to excessive postural constraints. Their use as a screening tool in groups of workers assigned to similar tasks deserves further study.

  5. 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.

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

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    Lizzy M Brewster

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

  7. [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

  8. Presence of (phospho)creatine in developing and adult skeletal muscle of mice without mitochondrial and cytosolic muscle creatine kinase isoforms.

    NARCIS (Netherlands)

    Zandt, H.J.A. in t; Groof, A.J.C. de; Renema, W.K.J.; Oerlemans, F.T.J.J.; Klomp, D.W.J.; Wieringa, B.; Heerschap, A.

    2003-01-01

    We assessed the relationship between phosphocreatine (PCr) and creatine (Cr) content and creatine kinase (CK) activity in skeletal muscle of mice. The PCr and total Cr (tCr) concentrations, as well as CK activity, in hindlimb muscles of mice, with or without the cytosolic and mitochondrial isoforms

  9. Tyrosine inhibits creatine kinase activity in cerebral cortex of young rats.

    Science.gov (United States)

    de Andrade, Rodrigo Binkowski; Gemelli, Tanise; Rojas, Denise Bertin; Funchal, Cláudia; Dutra-Filho, Carlos Severo; Wannmacher, Clovis Milton Duval

    2011-09-01

    Tyrosine accumulates in inborn errors of tyrosine catabolism, especially in tyrosinemia type II, where tyrosine levels are highly elevated in tissues and physiological fluids of affected patients. Tyrosinemia type II is a disorder of autosomal recessive inheritance characterized by neurological symptoms similar to those observed in patients with creatine deficiency syndromes. Considering that the mechanisms of brain damage in these disorders are poorly known, in the present study our main objective was to investigate the in vivo and in vitro effects of different concentrations and preincubation times of tyrosine on cytosolic and mitochondrial creatine kinase activities of the cerebral cortex from 14-day-old Wistar rats. The cytosolic CK was reduced by 15% at 1 mM and 32% at 2 mM tyrosine. Similarly, the mitochondrial CK was inhibited by 15% at 1 mM and 22% at 2 mM tyrosine. We observed that the inhibition caused by tyrosine was concentration-dependent and was prevented by reduced glutathione. Results also indicated that mitochondrial, but not cytosolic creatine kinase activity was inhibited by tyrosine in a time-dependent way. Finally, a single injection of L-Tyrosine methyl ester administered i.p. decreased cytosolic (31%) and mitochondrial (18%) creatine kinase activities of brain cortex from rats. Considering that creatine kinase is an enzyme dependent of thiol residues for its function and tyrosine induces oxidative stress, the results suggest that the inhibition caused by tyrosine might occur by oxidation of essential sulfhydryl groups of the enzyme. In case this also occurs in patients with tyrosinemia, it is possible that creatine kinase inhibition may contribute to the neurological dysfunction characteristic of tyrosinemia.

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

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    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…

  11. 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.

  12. 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.

  13. 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...

  14. 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...... meningitis and brain oedema, as well as patients with encephalitis, had significantly higher values (P less than 0.01) than patients with meningism, aseptic meningitis and bacterial meningitis without cerebral oedema. Very high values, above 2500 U/1, were encountered in only the most severe cases...... of bacterial meningitis. The highest serum CK value found in patients with encephalitis was 725 U/l. Reference values for control patients with meningism were 16-269 U/1. In a subset of 9 patients creatine kinase isoenzyme analysis was performed. In all cases only muscle type (MM) isoenzyme was found...

  15. 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&...

  16. 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...

  17. 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...

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    The influence of myofibrillar creatine kinase on the myosin-ATPase activity was examined in cardiac ventricular myofibrils isolated from rainbow trout (Oncorhynchus mykiss) and freshwater turtle (Trachemys scripta). The ATPase rate was assessed by recording the rephosphorylation of ADP by the pyr......The influence of myofibrillar creatine kinase on the myosin-ATPase activity was examined in cardiac ventricular myofibrils isolated from rainbow trout (Oncorhynchus mykiss) and freshwater turtle (Trachemys scripta). The ATPase rate was assessed by recording the rephosphorylation of ADP...... activity twice or more for both trout and turtle. As examined for trout myofibrils, the ATPase activity was reduced about four times by inhibiting the activity of myofibril-bound creatine kinase with iodoacetamide and this reduction was only partially counteracted, when the creatine kinase activity...

  19. SERUM CREATINE KINASE MB IN ISCHAEMIC STROKE: A CASE CONTROL STUDY

    Directory of Open Access Journals (Sweden)

    Preethi

    2016-06-01

    Full Text Available AIM To estimate CK-MB levels in ischaemic stroke patients and know its correlation in stroke patients. OBJECTIVES Serum creatine kinase-MB, other cardiac enzymes (CK, SGOT, uric acid, lipid profile, fasting blood glucose, and blood pressure was recorded. CT scan and ECG were also considered for the study. The aim of study was to determine serum creatine kinase-MB and the vascular risk factors for ischaemic stroke in a series of patients with an ischaemic stroke and to compare them with a series of controls of same age. METHODS Fifty (50 consecutive patients with ischaemic stroke were compared with thirty (30 healthy controls of same age. Vascular risk factors were recorded and serum creatine kinase-MB was determined in all of them. RESULTS There was modest rise of CK-MB in initial stages of stroke as compared with controls. The increase in CK-MB among cases is highly significant with a P value of <0.001. CONCLUSION The modest rise in serum CK-MB, which have recorded in the initial stages of stroke suggest that acute myocardial involvement is a common complication than is generally recognized. It is more likely that acute myocardial dysfunction is a consequence rather than a cause of acute cerebrovascular lesion.

  20. 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...

  1. 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...

  2. Transient Creatine Kinase Elevation Followed by Hypocomplementemia in a Case of Rotavirus Myositis

    Science.gov (United States)

    Rokugo, Yuka; Onuma, Ryoichi; Noguchi, Rie; Suzuki, Saeko; Kusaka, Natsuko; Watanabe, Yohei; Kitaoka, Setsuko

    2016-01-01

    We report an infant case of rotavirus myositis, a rare complication of rotavirus infection. Complement levels of the patient were normal when serum creatine kinase (CK) level was at its peak and then decreased when the CK level became normalized. In a previous case report of rotavirus myositis, transient decrease of serum albumin, immunoglobulin, and complement levels was reported. The authors speculated that intravascular complement activation was caused by rotavirus and resulted in the pathogenesis of myositis, although complement levels at onset were not measured by the authors. In this report, however, we demonstrate that the complement activation of our patient is a result of, rather than the cause of, skeletal muscle damage. PMID:27034874

  3. Angiographic adverse events during percutaneous coronary intervention fail to predict creatine kinase-MB elevation.

    Science.gov (United States)

    Blankenship, James C; Islam, M Ashequl; Wood, G Craig; Iliadis, Elias A

    2004-09-01

    We attempted to determine if aggressive detection of angiographic adverse events during coronary intervention could predict subsequent creatine kinase (CK)-MB elevations. During coronary intervention, both fluoroscopy and cine angiography were used to detect angiographic adverse events. At least one angiographic adverse event occurred in 133/251 (53%) of procedures. CK-MB elevation occurred in 24% of procedures. Slow flow during the procedure (P=0.002) and chest discomfort at the end of the procedure (P=0.007) were the strongest predictors of CK-MB elevation. Among procedures with no angiographic adverse events, CK-MB elevation occurred in 15/121 (12%), accounting for 25% of CK-MB elevations. We conclude that CK-MB elevation occurs after angiographically uncomplicated coronary interventions even when angiographic adverse events are aggressively detected. Routine monitoring of cardiac enzymes is necessary to detect all patients who will experience myocardial injury after coronary intervention.

  4. 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...

  5. 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)…

  6. 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...

  7. 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...

  8. Creatine kinase activity in patients with diabetes mellitus type I and type II.

    Science.gov (United States)

    Jevrić-Causević, Adlija; Malenica, Maja; Dujić, Tanja

    2006-08-01

    Diabetes mellitus can be looked upon as an array of diseases, all of which exhibit common symptoms. While pathogenesis of IDDM (insulin dependant diabetes mellitus) is well understood, the same is not true for diabetes mellitus type II. In the latter case, relative contribution of the two factors (insulin resistance or decreased insulin secretion) varies individually, being highly increased in peripheral tissues and strictly dependant on insulin for glucose uptake. Moreover, in patients with diabetes mellitus type II, disbalance at the level of regulation of glucose metabolism as well as lipid metabolism has been noted in skeletal muscles. It is normal to assume that in this type of diabetes, these changes are reflected at the level of total activity of enzyme creatine kinase. This experimental work was performed on a group of 80 regular patients of Sarajevo General Hospital. Forty of those patients were classified as patients with diabetes type I and forty as patients with diabetes type II. Each group of patients was carefully chosen and constituted of equal number of males and females. The same was applied for adequate controls. Concentration of glucose was determined for each patient with GOD method, while activity of creatine kinase was determined with CK-NAC activated kit. Statistical analysis of the results was performed with SPSS software for Windows. Obtained results point out highly expressed differences in enzyme activity between two populations examined. Changes in enzyme activity are more expressed in patients with diabetes type II. Positive correlation between concentration of glucose and serum activity of the enzyme is seen in both categories of diabetic patients which is not the case for the patients in control group. At the same time, correlation between age and type of diabetes does exist . This is not followed at the level of enzyme activity or concentration of glucose.

  9. 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

  10. Fatigue resistance of rat extraocular muscles does not depend on creatine kinase activity

    Directory of Open Access Journals (Sweden)

    Hayeß Katrin

    2005-08-01

    Full Text Available Abstract Background Creatine kinase (CK links phosphocreatine, an energy storage system, to cellular ATPases. CK activity serves as a temporal and spatial buffer for ATP content, particularly in fast-twitch skeletal muscles. The extraocular muscles are notoriously fast and active, suggesting the need for efficient ATP buffering. This study tested the hypotheses that (1 CK isoform expression and activity in rat extraocular muscles would be higher, and (2 the resistance of these muscles to fatigue would depend on CK activity. Results We found that mRNA and protein levels for cytosolic and mitochondrial CK isoforms were lower in the extraocular muscles than in extensor digitorum longus (EDL. Total CK activity was correspondingly decreased in the extraocular muscles. Moreover, cytoskeletal components of the sarcomeric M line, where a fraction of CK activity is found, were downregulated in the extraocular muscles as was shown by immunocytochemistry and western blotting. CK inhibition significantly accelerated the development of fatigue in EDL muscle bundles, but had no major effect on the extraocular muscles. Searching for alternative ATP buffers that could compensate for the relative lack of CK in extraocular muscles, we determined that mRNAs for two adenylate kinase (AK isoforms were expressed at higher levels in these muscles. Total AK activity was similar in EDL and extraocular muscles. Conclusion These data indicate that the characteristic fatigue resistance of the extraocular muscles does not depend on CK activity.

  11. 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

  12. Creatine kinase isoenzyme patterns upon chronic exposure to cigarette smoke: protective effect of Bacoside A.

    Science.gov (United States)

    Anbarasi, K; Vani, G; Balakrishna, K; Devi, C S Shyamala

    2005-01-01

    Cigarette smoking is implicated as a major risk factor in the development of cardiovascular and cerebrovascular diseases. Creatine kinase (CK) and its isoforms (CK-MM, MB, BB) have been advocated as sensitive markers in the assessment of cardiac and cerebral damage. Therefore, in the present study, we report the isoenzyme patterns of CK in rats upon exposure to cigarette smoke and the protective effect of Bacoside A against chronic smoking induced toxicity. Adult male albino rats were exposed to cigarette smoke and simultaneously administered with Bacoside A, the active constituent from the plant Bacopa monniera, for a period of 12 weeks. The activity of CK was assayed in serum, heart and brain, and its isoenzymes in serum were separated electrophoretically. Rats exposed to cigarette smoke showed significant increase in serum CK activity with concomitant decrease in heart and brain. Also cigarette smoke exposure resulted in a marked increase in all the three isoforms in serum. Administration of Bacoside A prevented these alterations induced by cigarette smoking. Cigarette smoking is known to cause free radical mediated lipid peroxidation leading to increased membrane permeability and cellular damage in the heart and brain resulting in the release of CK into the circulation. The protective effect of Bacoside A on the structural and functional integrity of the membrane prevented the leakage of CK from the respective tissues, which could be attributed to its free radical scavenging and anti-lipid peroxidative effect.

  13. 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.

  14. 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

  15. 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.

  16. 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

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

    Science.gov (United States)

    Nisijima, Koichi; Shioda, Katutoshi

    2014-01-01

    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°C, severe muscle rigidity, autonomic dysfunction, and altered mental status. Although serum CK levels were measured three times during the course of NMS, the levels were within the normal range. The patient died of respiratory failure 13 days after the onset of NMS symptoms. As patients without elevated serum CK levels are rarely reported, we discuss potential reasons why the serum CK was not elevated in our patient. This case shows clinicians that although serum CK elevation is a useful indicator for the early detection of NMS, the diagnosis of NMS must be determined by clinical symptoms as otherwise, the appropriate treatment procedures for NMS may be delayed.

  18. 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.

  19. 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...

  20. 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...

  1. 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.

  2. 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

  3. Reversible Amisulpride-induced Elevation of Creatine Kinase (CK): A Case Series from the German AMSP Pharmacovigilance Project.

    Science.gov (United States)

    Laoutidis, Z G; Konstantinidis, A; Grohmann, R; Luckhaus, C; Mobascher, J; Cordes, J

    2015-07-01

    The elevation of creatine kinase (CK) levels without neuroleptic malignant syndrome has been reported for several antipsychotics. We present here 4 cases with CK elevation induced by amisulpride, which have been registered for the German pharmacovigilance project, Arzneimittelsicherheit in der Psychiatrie (AMSP). The magnitude of the CK elevation ranged between 1, 498 IU/L and 21,018 IU/L. All 4 patients reported myalgia. In each case CK returned to normal after amisulpride discontinuation. In the fourth case, fluids were administered intravenously in order to prevent acute renal failure. None of the cases showed deterioration of renal function. Finally, we present recommendations for clinical practice.

  4. Brain hypothermia therapy for neonatal hypoxic-ischemic encephalopathy with a severely elevated serum creatine kinase level

    OpenAIRE

    Kinoshita, Hidetoshi; Imamura, Takashi; Maeda, Hajime; Shibukawa, Yasuko; FUKUDA, Yutaka; Kin, Shogo; Ariga, Hiromichi; Nagasawa, Katsutoshi

    2015-01-01

    Several studies have shown that brain hypothermia therapy (BHT) after neonatal hypoxic-ischemic encephalopathy (HIE) can improve neurodevelopmental outcomes. However, there have been no reports of the neurodevelopmental outcomes for the infant with a serum creatine kinase (CK) level above 20,000 IU/L in association with neonatal HIE. We report a female infant with a very high serum CK level (26,428 IU/L) associated with neonatal asphyxia. We diagnosed this infant with moderate HIE, and BHT wa...

  5. 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

  6. 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.

  7. BRAIN HYPOTHERMIA THERAPY FOR NEONATAL HYPOXIC-ISCHEMIC ENCEPHALOPATHY WITH A SEVERELY ELEVATED SERUM CREATINE KINASE LEVEL.

    Science.gov (United States)

    Kinoshita, Hidetoshi; Imamura, Takashi; Maeda, Hajime; Shibukawa, Yasuko; Fukuda, Yutaka; Kin, Shogo; Ariga, Hiromichi; Nagasawa, Katsutoshi

    2015-01-01

    Several studies have shown that brain hypothermia therapy (BHT) after neonatal hypoxic-ischemic encephalopathy (HIE) can improve neurodevelopmental outcomes. However, there have been no reports of the neurodevelopmental outcomes for the infant with a serum creatine kinase (CK) level above 20,000 IU/L in association with neonatal HIE. We report a female infant with a very high serum CK level (26,428 IU/L) associated with neonatal asphyxia. We diagnosed this infant with moderate HIE, and BHT was achieved by head cooling within 6 hours after birth to an esophageal temperature of 34.5°C. There were no significant adverse events during BHT, and the CK level spontaneously decreased. Although we report only the short-term outcomes for this case, she presents neurodevelopmental delays at the age of 18 months. It may be correlated between high serum CK level and long-term neurodevelopmental delays. PMID:25946908

  8. 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.

  9. 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...

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

    NARCIS (Netherlands)

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

    2005-01-01

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

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

    Science.gov (United States)

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

    2013-02-01

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

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

    DEFF Research Database (Denmark)

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

    1988-01-01

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

  13. 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.

  14. 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

  15. A Fluorescence Immunochromatographic Assay Using Europium (III) Chelate Microparticles for Rapid, Quantitative and Sensitive Detection of Creatine Kinase MB.

    Science.gov (United States)

    Lai, Xiao-Hong; Liang, Rong-Liang; Liu, Tian-Cai; Dong, Zhi-Ning; Wu, Ying-Song; Li, Lin-Hai

    2016-05-01

    The isoenzyme creatine kinase MB is very important for diagnosis of acute myocardial infarction (AMI). Some CK-MB immunoassays are sensitive, accurate and available for clinical application, but they are expensive and time-consuming procedures. Furthermore, conventional fluorescence immunochromatographic assays (FL-ICAs) have suffered from background fluorescence interference and low analytical sensitivity. A rapid and simple FL-ICA with Eu (III) chelate polystyrene microparticles was developed to determine CK-MB in 50uL serum samples using a portable test strip reader by measuring the fluorescence peak heights of the test line (HT) and the control line (HC) in 12 min. The assay was reliable with a good correlation coefficient between HT/HC ratio and CK-MB concentration in samples. A linear range was 0.85-100.29 ng/mL for CK-MB, and the LOD was 0.029 ng/mL. The intra- and inter-assay coefficients of variation (CV) were both chelate microparticles-based FL-ICA is simple, fast, highly sensitive, reliable, and reproducible for point-of-care testing of CK-MB concentrations in serum. Graphical Abstract ᅟ.

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

    Directory of Open Access Journals (Sweden)

    D. Somjen

    2009-01-01

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

  17. 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)

  18. Chaperone-like effect of the linker on the isolated C-terminal domain of rabbit muscle creatine kinase.

    Science.gov (United States)

    Chen, Zhe; Chen, Xiang-Jun; Xia, Mengdie; He, Hua-Wei; Wang, Sha; Liu, Huihui; Gong, Haipeng; Yan, Yong-Bin

    2012-08-01

    Intramolecular chaperones (IMCs), which are specific domains/segments encoded in the primary structure of proteins, exhibit chaperone-like activity against the aggregation of the other domains in the same molecule. In this research, we found that the truncation of the linker greatly promoted the thermal aggregation of the isolated C-terminal domain (CTD) of rabbit muscle creatine kinase (RMCK). Either the existence of the linker covalently linked to CTD or the supply of the synthetic linker peptide additionally could successfully protect the CTD of RMCK against aggregation in a concentration-dependent manner. Truncated fragments of the linker also behaved as a chaperone-like effect with lower efficiency, revealing the importance of its C-terminal half in the IMC function of the linker. The aggregation sites in the CTD of RMCK were identified by molecular dynamics simulations. Mutational analysis of the three key hydrophobic residues resulted in opposing effects on the thermal aggregation between the CTD with intact or partial linker, confirming the role of linker as a lid to protect the hydrophobic residues against exposure to solvent. These observations suggested that the linkers in multidomain proteins could act as IMCs to facilitate the correct folding of the aggregation-prone domains. Furthermore, the intactness of the IMC linker after proteolysis modulates the production of off-pathway aggregates, which may be important to the onset of some diseases caused by the toxic effects of aggregated proteolytic fragments.

  19. 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.

  20. 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.

  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

    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...

  2. Carpal spasms-hypocalcemia-elevated serum creatine kinase%双手搐搦-低钙血症-肌酶升高

    Institute of Scientific and Technical Information of China (English)

    王文博; 胡莹莹; 姜艳; 李梅; 夏维波; 邢小平; 王鸥; 孟迅吾

    2015-01-01

    低钙性肌病是甲状旁腺功能减退症(以下简称甲旁减)的罕见并发症之一。本文报道了1例特发性甲旁减导致肌酸激酶(creatine kinase, CK)升高。患者为23岁男性,因间断双手搐搦10年入院,入院前2个月有一次癫痫样发作,实验室检查示血钙和甲状旁腺素水平降低,血清CK水平明显升高,给予钙剂及维生素D补充治疗后,随血钙水平上升, CK逐渐下降。本文同时对甲旁减合并肌酶升高的相关文献进行了复习和总结。%Hypocalcemic myopathy is a rare manifestation of hypoparathyroidism .Here we reported a case of hy-pocalcemia due to idiopathic hypoparathyroidism associated with elevated serum creatine kinase level .A 23-year-old man suffered from intermittent carpal spasms for 10 years and he had seizure 2 months before the hospitalization .Laboratory tests showed decreased serum calcium and parathyroid hormone levels accompanied with increased serum creatine kinase concentration .With the treatment with calcium and vitamin D supplementation , the serum creatine kinase levels decreased gradually accompanied by the improvement of hypocalcemia .The related literature was reviewed .

  3. 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.

  4. Reproducibility of creatine kinase reaction kinetics in human heart: a (31) P time-dependent saturation transfer spectroscopy study.

    Science.gov (United States)

    Bashir, Adil; Gropler, Robert

    2014-06-01

    Creatine kinase (CK) is essential for the buffering and rapid regeneration of adenosine triphosphate (ATP) in heart tissue. Herein, we demonstrate a (31) P MRS protocol to quantify CK reaction kinetics in human myocardium at 3 T. Furthermore, we sought to quantify the test-retest reliability of the measured metabolic parameters. The method localizes the (31) P signal from the heart using modified one-dimensional 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 in total) were tested. The CK reaction rate constant (kf ) was 0.32 ± 0.05 s(-1) and the coefficient of variation (CV) was 15.62%. The intrinsic T1 for phosphocreatine (PCr) was 7.36 ± 1.79 s with CV = 24.32%. These values are consistent with those reported previously. The 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 seven subjects and inferred parameters, such as kf and T1 , exhibited good reliability [intraclass correlation coefficient (ICC) of 0.90 and 0.79 for kf and T1 , respectively). The reproducibility data provided in this study will enable the calculation of the 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 into the relationship between energy deficit and functional deficiency in the heart.

  5. Metabolic rates of ATP transfer through creatine kinase (CK Flux) predict clinical heart failure events and death.

    Science.gov (United States)

    Bottomley, Paul A; Panjrath, Gurusher S; Lai, Shenghan; Hirsch, Glenn A; Wu, Katherine; Najjar, Samer S; Steinberg, Angela; Gerstenblith, Gary; Weiss, Robert G

    2013-12-11

    Morbidity and mortality from heart failure (HF) are high, and current risk stratification approaches for predicting HF progression are imperfect. Adenosine triphosphate (ATP) is required for normal cardiac contraction, and abnormalities in creatine kinase (CK) energy metabolism, the primary myocardial energy reserve reaction, have been observed in experimental and clinical HF. However, the prognostic value of abnormalities in ATP production rates through CK in human HF has not been investigated. Fifty-eight HF patients with nonischemic cardiomyopathy underwent ³¹P magnetic resonance spectroscopy (MRS) to quantify cardiac high-energy phosphates and the rate of ATP synthesis through CK (CK flux) and were prospectively followed for a median of 4.7 years. Multiple-event analysis (MEA) was performed for HF-related events including all-cause and cardiac death, HF hospitalization, cardiac transplantation, and ventricular-assist device placement. Among baseline demographic, clinical, and metabolic parameters, MEA identified four independent predictors of HF events: New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF), African-American race, and CK flux. Reduced myocardial CK flux was a significant predictor of HF outcomes, even after correction for NYHA class, LVEF, and race. For each increase in CK flux of 1 μmol g⁻¹ s⁻¹, risk of HF-related composite outcomes decreased by 32 to 39%. These findings suggest that reduced CK flux may be a potential HF treatment target. Newer imaging strategies, including noninvasive ³¹P MRS that detect altered ATP kinetics, could thus complement risk stratification in HF and add value in conditions involving other tissues with high energy demands, including skeletal muscle and brain.

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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...

  11. 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

  12. 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.

  13. The Effects of Heart and Skeletal Muscle Inflammation and Cardiomyopathy Syndrome on Creatine Kinase and Lactate Dehydrogenase Levels in Atlantic Salmon (Salmo salar L.

    Directory of Open Access Journals (Sweden)

    Muhammad Naveed Yousaf

    2012-01-01

    Full Text Available Heart and skeletal muscle inflammation (HSMI and cardiomyopathy syndrome (CMS are putative viral cardiac diseases of Atlantic salmon. This study examined the levels and correlated the serum enzymes creatine kinase (CK and lactate dehydrogenase (LDH to the histopathology of clinical outbreaks of HSMI and chronic CMS in farmed Atlantic salmon. A total of 75 fish from 3 different HSMI outbreaks, 30 chronic CMS fish, and 68 fish from 3 nondiseased fish groups were used as the study population (N=173. Serum CK and LDH levels correlated significantly with the total inflammation and total necrosis scores for HSMI fish (P=0.001. However, no correlation was identified for enzyme levels and histopathology scores for chronic CMS fish. The significantly increased CK and LDH levels and their positive correlations to histopathology differentiate HSMI from CMS clinically suggesting the potential use of enzymes for screening for HSMI is promising.

  14. 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

  15. Troponin I Assessment of Cardiac Involvement in Patients With Connective Tissue Disease and an Elevated Creatine Kinase MB Isoform Report of Four Cases and Review of the Literature.

    Science.gov (United States)

    Badsha, H; Gunes, B; Grossman, J; Brahn, E

    1997-06-01

    Levels of creatine kinase MB isoform (CKMB) can be elevated in patients with myopathy, neuropathy, skeletal muscle injury, or renal failure in the absence of myocardial injury. These elevated CKMB levels make it difficult to identify cardiac involvement in conditions that can be associated with a variety of cardiac abnormalities or with symptoms that mimic them. Cardiac troponin I (cTnI), a myocardial regulatory protein, has a high specificity for cardiac muscle and can be used to clarify the etiology of CKMB elevations in such patients. In this report, four patients with diverse causes for increased CKMB levels are discussed with respect to cill.The first three patients, with tentative diagnoses of mixed connective tissue disease, amyotrophic lateral sclerosis, and polymyositis presented with increasing shortness of breath, tachycardia, nonspecific electrocardiogram changes, high creative kinase, and CKMB levels. A normal cTnI helped exclude a diagnosis of a cardiac cause of their symptoms. Patient 4 had a scleroderma variant and experienced sudden, fatal, cardiac decompensation caused by a dilated cardiomyopathy, accompanied by an increased cTnl.The cTnI is a reliable, specific, and quick wav of excluding or determining cardiac involvement in patients with connective tissue disease. As this test is inexpensive and becoming increasingly available, it could become the test of choice, especially in scenarios in which urgent management decisions are needed.

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

    Science.gov (United States)

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

    2015-12-01

    Hepatocyte transplantation has been explored as a therapeutic alternative to liver transplantation, but a means to monitor the success of the procedure is lacking. Published findings support the use of in vivo (31)P MRSI of creatine kinase (CK)-expressing hepatocytes to monitor proliferation of implanted hepatocytes. Phosphocreatine tissue level depends upon creatine (Cr) input to the CK enzyme reaction, but Cr measurement by (1)H MRS suffers from low signal-to-noise ratio (SNR). We examine the possibility of using the Cr analog cyclocreatine (CCr, a substrate for CK), which is quickly phosphorylated to phosphocyclocreatine (PCCr), as a higher SNR alternative to Cr. (1)H MRS and (31)P MRSI were employed to measure the effect of incremental supplementation of CCr upon PCCr, γ-ATP, pH and Pi /ATP in the liver of transgenic mice expressing the BB isoform of CK (CKBB) in hepatocytes. Water supplementation with 0.1% CCr led to a peak total PCCr level of 17.15 ± 1.07 mmol/kg wet weight by 6 weeks, while adding 1.0% CCr led to a stable PCCr liver level of 18.12 ± 3.91 mmol/kg by the fourth day of feeding. PCCr was positively correlated with CCr, and ATP concentration and pH declined with increasing PCCr. Feeding with 1% CCr in water induced an apparent saturated level of PCCr, suggesting that CCr quantization may not be necessary for quantifying expression of CK in mice. These findings support the possibility of using (31)P MRS to noninvasively monitor hepatocyte transplant success with CK-expressing hepatocytes. PMID:26451872

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

    Science.gov (United States)

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

    2015-12-01

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

  18. 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.

  19. 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.

  20. 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.

  1. 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...

  2. PREDICTION OF HIE BY NUCLEATED RBC’S IN CORD BLOOD, SERUM CREATINE KINASE AND ASSESSMENT OF OUTCOME BY FOLLOW UP UPTO 6 MONTHS

    Directory of Open Access Journals (Sweden)

    Shivaprakash

    2013-05-01

    Full Text Available ABSTRACT: OBJECTIVES: Birth asphyxia is the most common cause of preventa ble cerebral injury occurring in the neonatal period and contributes si gnificantly to neonatal morbidity and mortality. This study was conducted to predict the occurrence of HIE by nucleated Red blood cells and creatinine kinase in cord blood of asphyxiated babi es and assessment of outcome by follow up upto 6 months. MATERIALS AND METHODS : Study was conducted on 50 neonates comprising the cases and 50 neonates comprising the controls born in Adi chunchanagiri Institute of Medical Sciences and Research Centre, B.G. Nagara from January 2011 to June 2012.. The cord blood samples for CK and nucleated RBCs was drawn at the time of birth a nd sent for analysis. Anthropometry was done at Birth ,1st month,3rd month and 6th month(final v isit , developmental assessment using DASII along with anthropometric measurements was done. RESULTS: The cut-off CK value of 450 U/ L has 91.3% sensitivity with a specificity of 96.3% & has a positive predictive value of 95.49 with a negative predictive value of 92.85 .The cut-off Nuc leated RBCs value of >6 has 93.48% sensitivity with a specificity of 96.3% & has a positive predic tive value of 97.7 % with a negative predictive value of 94.64%. NRBCs have more diagnostic value t han CK with more Area Under ROC value when compared (0.989 vs. 0.986. On follow up, in the final visit, 8 cases had motor delay and 7 cases had mental delay against no developmental del ay in controls. CONCLUSION : Prediction of HIE in the asphyxiated cases can be done using the cord blood NRBCs and Creatine kinase, & suitable interventions and intensive monitoring can be plann ed thereby helping in identifying the high risk cases

  3. 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

  4. Augmentation of Creatine in the Heart.

    Science.gov (United States)

    Zervou, Sevasti; Whittington, Hannah J; Russell, Angela J; Lygate, Craig A

    2016-01-01

    Creatine is a principle component of the creatine kinase (CK) phosphagen system common to all vertebrates. It is found in excitable cells, such as cardiomyocytes, where it plays an important role in the buffering and transport of chemical energy to ensure that supply meets the dynamic demands of the heart. Multiple components of the CK system, including intracellular creatine levels, are reduced in heart failure, while ischaemia and hypoxia represent acute crises of energy provision. Elevation of myocardial creatine levels has therefore been suggested as potentially beneficial, however, achieving this goal is not trivial. This mini-review outlines the evidence in support of creatine elevation and critically examines the pharmacological approaches that are currently available. In particular, dietary creatine-supplementation does not sufficiently elevate creatine levels in the heart due to subsequent down-regulation of the plasma membrane creatine transporter (CrT). Attempts to increase passive diffusion and bypass the CrT, e.g. via creatine esters, have yet to be tested in the heart. However, studies in mice with genetic overexpression of the CrT demonstrate proof-of-principle that elevated creatine protects the heart from ischaemia-reperfusion injury. This suggests activation of the CrT as a major unmet pharmacological target. However, translation of this finding to the clinic will require a greater understanding of CrT regulation in health and disease and the development of small molecule activators.

  5. 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.

  6. 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

  7. 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}.

  8. 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.

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

    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.

  10. 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

    Estrogen withdrawal versus tamoxifen (TAM) treatment was compared in two human breast cancer xenografts, the estrogen-dependent ZR75-1 and its estrogen-independent subline ZR75/LCC-3. The following parameters were determined: tumor growth, NTP:P(i) by 31P magnetic resonance spectroscopy, apoptotic...... 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 parallel experiments, injections of TAM were initiated instead of estrogen withdrawal. Estrogen withdrawal as well as TAM induced growth inhibition of ZR75-1 tumors, whereas ZR75/LCC-3 was resistant to both types of therapy. Growth inhibition of ZR75-1 by estrogen withdrawal, but not by TAM...

  11. 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

  12. 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

  13. PRENTAL DIAGNOSIS OF CREATINE KINASE DETECTION IN PERNICIOUS PLACENTA PREVIA%凶险型前置胎盘孕妇肌酸激酶检测的产前诊断价值

    Institute of Scientific and Technical Information of China (English)

    周晓

    2014-01-01

    目的:通过比较孕晚期凶险型前置胎盘孕妇和正常妊娠孕妇血清中肌酸激酶的差异,探讨其用于凶险型前置胎盘合并胎盘植入产前诊断的价值。方法回顾性分析2012年6月至2013年6月江西省妇幼保健院凶险型前置胎盘单胎孕妇92例,其中合并胎盘植入者38例,归入凶险型前置胎盘合并胎盘植入组,其余54例归入未合并胎盘植入组,再随机抽取同期分娩的既往有剖宫产史,本次为正常妊娠的孕妇50例作为对照组,比较三组孕妇血清肌酸激酶水平的差异。结果凶险型前置胎盘合并胎盘植入组CK数值为(128.6±19.8)U/L,未合并胎盘植入组为(67.7±21.2) U/L,单纯剖宫产史组为(65.1±20.3) U/L。凶险型前置胎盘合并胎盘植入时,孕妇血清肌酸激酶水平明显升高,差异具有统计学意义。而在中央型前置胎盘、部分型前置胎盘和边缘型前置胎盘中,肌酸激酶分别为(80.3±38.2) U/L、(77.1±36.0) U/L、(79.6±29.7) U/L,三者差异无统计学意义。结论孕妇血清肌酸激酶的测定对凶险型前置胎盘合并胎盘植入的产前预测有价值,与前置胎盘的类型无关。%Objective:Through comparing the content difference of serum creatine kinasebetween pregnant women with pernicious placenta priva and the normal ones to investigate its value in prenatal diagnosing pernicious placenta priva with placenta accreta.Methods:A total of 92 patients of pernicious placenta priva were retrospectively analyzed in Maternal and Child Care Service Centre of Jiangxi Province from June 2012 to June 2013, among them, 38 cases of pernicious placenta priva with placenta accrete after operation were classified into the study group with placenta accreta, others into the study group without placenta accrete, then 50 women having caesarean section ever but normal pregnance this time into the control group. The levels of serum creatine kinase among three groups were

  14. 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

  15. 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

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. The Analysis Of The Change Of Serum Creatine Kinase After Resistance Training%抗阻训练引起血清肌酸激酶变化的分析

    Institute of Scientific and Technical Information of China (English)

    潘梅兵; 孙朋

    2012-01-01

    To explore the change of serum creatine kinase after resistance training, elite male kayak athletes in Anhui province are conducted as the subjects, the study is arranged to continue a resistance training for eight weeks. The results showed that the resistance training, when it was started in preparatory stage, ath- letes serum CK activity kept the same in the nomal condition; when in the muscle hypertrophy in ihe stage of training and strength training, serum CK activity ( during the first week and the forth week ) was increased substantially compared with preparatory stage, all have significant difference ( P 〈 0.01 }, which indicates that strength is increasing, considering the training goal. With the subjects adapting themselves to the training intensity, the second and third week and the first week ( P 〈 0.05 }, the fifth week, the sixth week and the fourth week ( P d0.05) compared with CK activity gradually reducing, the results can explain the subjects can produce certain to adapt to the training intensity. In the strength endurance training phase, the seventh and eighth week's testing CK enzyme activity makes no significant difference ( P 〉0.05), which can ex- plain the adaptation.%为探讨抗阻训练后血清肌酸激酶的变化情况,以安徽省优秀男子皮艇运动员为研究对象,进行为期8周的抗阻训练。结果表明,在通过8周抗阻训练后,开始准备阶段,运动员血清CK的活性与正常人无差异;在肌肉肥大训练阶段和肌力训练,血清CK活肚在第1周、第4周都大幅度上升,与准备阶段相比,均有显著性差异(P〈0.01),说明强度为大强度,符合训练目的。随着机体对训练强度的适应,第2、3周和第1周(P〈0.05)、第5周、第6周和第4周(P〈0.05)相比CK活性逐渐降低,说明机体对训练强度产生一定的适应。力量耐力训练阶段,第7、第8周CK酶活性和准备阶段相比,无显著差异(P〉0

  3. Enzymes of creatine biosynthesis, arginine and methionine metabolism in normal and malignant cells.

    Science.gov (United States)

    Bera, Soumen; Wallimann, Theo; Ray, Subhankar; Ray, Manju

    2008-12-01

    The creatine/creatine kinase system decreases drastically in sarcoma. In the present study, an investigation of catalytic activities, western blot and mRNA expression unambiguously demonstrates the prominent expression of the creatine-synthesizing enzymes l-arginine:glycine amidinotransferase and N-guanidinoacetate methyltransferase in sarcoma, Ehrlich ascites carcinoma and Sarcoma 180 cells, whereas both enzymes were virtually undetectable in normal muscle. Compared to that of normal animals, these enzymes remained unaffected in the kidney or liver of sarcoma-bearing mice. High activity and expression of mitochondrial arginase II in sarcoma indicated increased ornithine formation. Slightly or moderately higher levels of ornithine, guanidinoacetate and creatinine were observed in sarcoma compared to muscle. Despite the intrinsically low level of creatine in Ehrlich ascites carcinoma and Sarcoma 180 cells, these cells could significantly take up and release creatine, suggesting a functional creatine transport, as verified by measuring mRNA levels of creatine transporter. Transcript levels of arginase II, ornithine-decarboxylase, S-adenosyl-homocysteine hydrolase and methionine-synthase were significantly upregulated in sarcoma and in Ehrlich ascites carcinoma and Sarcoma 180 cells. Overall, the enzymes related to creatine and arginine/methionine metabolism were found to be significantly upregulated in malignant cells. However, the low levels of creatine kinase in the same malignant cells do not appear to be sufficient for the building up of an effective creatine/phosphocreatine pool. Instead of supporting creatine biosynthesis, l-arginine:glycine amidinotransferase and N-guanidinoacetate methyltransferase appear to be geared to support cancer cell metabolism in the direction of polyamine and methionine synthesis because both these compounds are in high demand in proliferating cancer cells.

  4. 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

  5. Determination of sperm creatine kinase and its isozyme in infertile patients%不育症患者精子肌酸激酶活性及其同工酶测定

    Institute of Scientific and Technical Information of China (English)

    罗比; 陈建; 漆著

    2006-01-01

    BACKGROUND: As a biochemical marker of cytoplasm, the increased activity of creatine kinase (CK) in human spermatozoa is correlated with both the residual cytoplasma and the ratio of sperm with abnormal func tion. It is a marker of mature sperm and associated with the potential of in semination. OBJECTIVE: To investigate the differences of CK activity in sperm and the relative contents of sperm CK-MM and CK-BB isoenzymes between normal fertile males and infertile males, and evaluate its significance in clinical diagnosis of male infertility. DESIGN: Case-control observation. SETTING: Laboratory of Biochemistry, Family Planning Research Insti tute of Sichuan Province. PARTICIPANTS: Ninety-four male infertile patients between January 1999 and October 2000 were selected from the Department of Family Planning Sciences of Sichuan Province, who had no aspermatism with their wives proved to be fertile. The average age of subjects were 31 years. Eighty subjects with the sperm count > 2×1010 L-1 were taken as normal sperm group and 14 subjects with the sperm counts < 2×1010 L-1 were considered as oligospermia group. Semen obtained from 27 healthy males who were normal in routine examinations and with children was taken as the healthy control group.METHODS: Semen sample collected by masturbation after abstinence of 3 to 5 days was incubated at 37 ℃ for liquefication and routinely analyzed.Total activity of CK in sperm was determined by using a kinetic spectrophotometry and the relative contents of CK isozyme was determined by agarose gel electrophoresis followed by density scanning of CK isozyme.MAIN OUTCOME MEASURES: Sperm counts, percentages of viability and motility of sperm, total CK activity and the relative contents of CK-MM and CK-BB isozyme in spermatozoa.RESULTS: A total of 94 enrolled patients and 27 normal controls were involved in the analysis of results. ①Sperm counts, percentage of viability and motility in oligospermia group ( Ⅱ + Ⅲ, WHO method

  6. 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

  7. 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.

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    I.A. Câmara e Silva

    2007-02-01

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

  10. Creatine

    Science.gov (United States)

    ... athletic performance. In the U.S., a majority of sports nutrition supplements, which total $2.7 billion in ... Committee, National Collegiate Athletic Association (NCAA), and professional sports. However, the NCAA no longer allows colleges and ...

  11. 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

    of the system initially acquired by cytCK expression significantly increased after additional mitCK supplement. Nevertheless, even the complete Cr-CrP shuttle failed to maintain a high [ATP]/[ADP] ratio during long term 'muscle performance' due to the rate limiting CK-transphosphorylation in the mitochondria...... in the [ATP] decrease at 'work'. The partial systems without mitCK were not as effective, and this delay was 0-10 s. However, the ADP-ATP shuttle was of more importance at the steady state achieved under ' working' conditions...

  12. 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.

  13. 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

  14. Creatine supplementation and aging musculoskeletal health.

    Science.gov (United States)

    Candow, Darren G; Chilibeck, Philip D; Forbes, Scott C

    2014-04-01

    Sarcopenia refers to the progressive loss of muscle mass and muscle function and is a contributing factor for cachexia, bone loss, and frailty. Resistance training produces several physiological adaptations which improve aging musculoskeletal health, such as increased muscle and bone mass and strength. The combination of creatine supplementation and resistance training may further lead to greater physiological benefits. We performed meta-analyses which indicate creatine supplementation combined with resistance training has a positive effect on aging muscle mass and upper body strength compared to resistance training alone. Creatine also shows promise for improving bone mineral density and indices of bone biology. The combination of creatine supplementation and resistance training could be an effective intervention to improve aging musculoskeletal health. PMID:24190049

  15. 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

  16. 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.

  17. 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。

  18. 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

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

    Directory of Open Access Journals (Sweden)

    Greenwood Mike

    2006-06-01

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

  20. 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…

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

    Directory of Open Access Journals (Sweden)

    Cliffa Foster

    2011-06-01

    Full Text Available The purpose of this study was to evaluate the effects of combined creatine and fenugreek extract supplementation on strength and body composition. Forty- seven resistance trained men were matched according to body weight to ingest either 70 g of a dextrose placebo (PL, 5 g creatine/70 g of dextrose (CRD or 3.5 g creatine/900 mg fenugreek extract (CRF and participate in a 4-d/wk periodized resistance-training program for 8-weeks. At 0, 4, and 8-weeks, subjects were tested on body composition, muscular strength and endurance, and anaerobic capacity. Statistical analyses utilized a separate 3X3 (condition [PL vs. CRD vs. CRF] x time [T1 vs. T2 vs. T3] ANOVAs with repeated measures for all criterion variables (p 0.05 were observed for any measures of body composition. CRF group showed significant increases in lean mass at T2 (p = 0.001 and T3 (p = 0.001. Bench press 1RM increased in PL group (p = 0.050 from T1-T3 and in CRD from T1-T2 (p = 0. 001 while remaining significant at T3 (p 0.05. In conclusion, creatine plus fenugreek extract supplementation had a significant impact on upper body strength and body composition as effectively as the combination of 5g of creatine with 70g of dextrose. Thus, the use of fenugreek with creatine supplementation may be an effective means for enhancing creatine uptake while eliminating the need for excessive amounts of simple carbohydrates

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

    Science.gov (United States)

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

    1984-12-10

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

  3. 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

  4. Elevated plasma creatinine due to creatine ethyl ester use.

    Science.gov (United States)

    Velema, M S; de Ronde, W

    2011-02-01

    Creatine is a nutritional supplement widely used in sport, physical fitness training and bodybuilding. It is claimed to enhance performance. We describe a case in which serum creatinine is elevated due to the use of creatine ethyl esther. One week after withdrawal, the plasma creatinine had normalised. There are two types of creatine products available: creatine ethyl esther (CEE) and creatine monohydrate (CM). Plasma creatinine is not elevated in all creatine-using subjects. CEE , but not CM, is converted into creatinine in the gastrointestinal tract. As a result the use of CEE may be associated with elevated plasma creatinine levels. Since plasma creatinine is a widely used marker for renal function, the use of CEE may lead to a false assumption of renal failure.

  5. Creatine monohydrate as a therapeutic aid in muscular dystrophy.

    Science.gov (United States)

    Pearlman, Jared P; Fielding, Roger A

    2006-02-01

    In recent years, dietary supplementation with creatine has been shown to enhance neuromuscular function in several diseases. Recent studies have suggested that creatine can be beneficial in patients with muscular dystrophy and other mitochondrial cytopathies, and may attenuate sarcopenia and facilitate rehabilitation of disuse atrophy. Though the mechanisms are still unknown, creatine has been shown to decrease cytoplasmic Ca2+ levels and increase intramuscular and cerebral phosphocreatine stores, providing potential musculoskeletal and neuroprotective effects. PMID:16536185

  6. 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...

  7. 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...

  8. 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

  9. Diagnóstico do infarto agudo do miocárdio. Valor da dosagem de mioglobina sérica comparada com a creatinofosfoquinase e sua fração MB Acute myocardial infarction diagnosis. The value of serum myoglobin levels, compared with creatine kinase and MB fraction

    Directory of Open Access Journals (Sweden)

    Alexandre Biasi Cavalcanti

    1998-02-01

    Full Text Available OBJETIVO: Comparar o desempenho, em termos de teste diagnóstico, da dosagem sérica de mioglobina (Mgb com a creatinofosfoquinase (CK e a sua fração MB (CK-MB, para o diagnóstico de infarto agudo do miocárdio (IAM. MÉTODOS: Estudo observacional, contemporâneo e não controlado de 64 pacientes, admitidos entre setembro/94 e fevereiro/95, em uma emergência especializada em cardiologia, com dor torácica não traumática. Excluíram-se pacientes com sintomas há mais de 6h, trauma muscular, ressuscitação cardiopulmonar e insuficiência renal. O diagnóstico de IAM foi estabelecido quando ao menos dois dos seguintes critérios estavam presentes: dor torácica típica há mais de 20min, alterações eletrocardiográficas compatíveis com necrose (ondas Q, ou elevações tardias de CK e CK-MB. RESULTADOS: Na amostra estudada, 18 tiveram diagnóstico de IAM. A sensibilidade (S encontrada para CK, CK-MB e Mgb foi de 33%, 22% e 61% e a especificidade (E de 85%, 96% e 98%, respectivamente. A diferença entre a S de Mgb e a de CK foi de 28%, com um intervalo de confiança de 95% (IC 95% de -4% a 59%, e a diferença entre a S de Mgb e a de CK-MB foi de 39%, IC 95% de 9% a 69%. A diferença entre a E de Mgb e a de CK foi de 13%, IC 95% de 12% a 14%, e a diferença entre a E de Mgb e a de CK-MB foi de 2%, IC 95% de -5% a 9%. CONCLUSÃO: A mioglobina mostrou ser um marcador mais sensível e tão específico quanto a CK-MB, para o diagnóstico de IAM na população estudada. Em relação a CK, a Mgb foi mais específica e com igual sensibilidade.PURPOSE: To compare the diagnostic performance of two traditional plasma markers of myocardial infarction (MI, creatine kinase (CK and its MB fraction (CK-MB, with plasma myoglobin (Mgb levels, for the diagnosis of MI. METHODS: From September of 94 to February of 95, in an observational, prospective, and non-controlled fashion, 64 patients admitted to a cardiology emergency room (ER, with non-traumatic chest

  10. 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.

  11. The effect of the creatine analogue beta-guanidinopropionic acid on energy metabolism: a systematic review.

    Directory of Open Access Journals (Sweden)

    Inge Oudman

    Full Text Available BACKGROUND: Creatine kinase plays a key role in cellular energy transport. The enzyme transfers high-energy phosphoryl groups from mitochondria to subcellular sites of ATP hydrolysis, where it buffers ADP concentration by catalyzing the reversible transfer of the high-energy phosphate moiety (P between creatine and ADP. Cellular creatine uptake is competitively inhibited by beta-guanidinopropionic acid. This substance is marked as safe for human use, but the effects are unclear. Therefore, we systematically reviewed the effect of beta-guanidinopropionic acid on energy metabolism and function of tissues with high energy demands. METHODS: We performed a systematic review and searched the electronic databases Pubmed, EMBASE, the Cochrane Library, and LILACS from their inception through March 2011. Furthermore, we searched the internet and explored references from textbooks and reviews. RESULTS: After applying the inclusion criteria, we retrieved 131 publications, mainly considering the effect of chronic oral administration of beta-guanidinopropionic acid (0.5 to 3.5% on skeletal muscle, the cardiovascular system, and brain tissue in animals. Beta-guanidinopropionic acid decreased intracellular creatine and phosphocreatine in all tissues studied. In skeletal muscle, this effect induced a shift from glycolytic to oxidative metabolism, increased cellular glucose uptake and increased fatigue tolerance. In heart tissue this shift to mitochondrial metabolism was less pronounced. Myocardial contractility was modestly reduced, including a decreased ventricular developed pressure, albeit with unchanged cardiac output. In brain tissue adaptations in energy metabolism resulted in enhanced ATP stability and survival during hypoxia. CONCLUSION: Chronic beta-guanidinopropionic acid increases fatigue tolerance of skeletal muscle and survival during ischaemia in animal studies, with modestly reduced myocardial contractility. Because it is marked as safe for human

  12. 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…

  13. 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.

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

    Science.gov (United States)

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

    2012-06-01

    There is currently no direct, facile method to determine total-body skeletal muscle mass for the diagnosis and treatment of skeletal muscle wasting conditions such as sarcopenia, cachexia, and disuse. We tested in rats the hypothesis that the enrichment of creatinine-(methyl-d(3)) (D(3)-creatinine) in urine after a defined oral tracer dose of D(3)-creatine can be used to determine creatine pool size and skeletal muscle mass. We determined 1) an oral tracer dose of D(3)-creatine that was completely bioavailable with minimal urinary spillage and sufficient enrichment in the body creatine pool for detection of D(3)-creatine in muscle and D(3)-creatinine in urine, and 2) the time to isotopic steady state. We used cross-sectional studies to compare total creatine pool size determined by the D(3)-creatine dilution method to lean body mass determined by independent methods. The tracer dose of D(3)-creatine (99% bioavailable with 0.2-1.2% urinary spillage. Isotopic steady state was achieved within 24-48 h. Creatine pool size calculated from urinary D(3)-creatinine enrichment at 72 h significantly increased with muscle accrual in rat growth, significantly decreased with dexamethasone-induced skeletal muscle atrophy, was correlated with lean body mass (r = 0.9590; P creatine pool size and skeletal muscle mass can thus be accurately and precisely determined by an orally delivered dose of D(3)-creatine followed by the measurement of D(3)-creatinine enrichment in a single urine sample and is promising as a noninvasive tool for the clinical determination of skeletal muscle mass. PMID:22422801

  15. 肌酸激酶及CT血管造影检查评估肠系膜上动脉栓塞的短期预后%Creatine kinase and computed tomography angiography to evaluate short-term prognosis of patients with superior mesenteric artery embolism

    Institute of Scientific and Technical Information of China (English)

    吕和平; 倪海真; 黄景勇; 陈祥建; 虞冠锋

    2016-01-01

    .8例患者肠系膜上动脉主干栓塞呈低密度影,伴远端分支动脉显影,其中肠缺血3例,部分肠坏死4例,长段肠坏死1例.2例患者肠系膜上动脉非主干栓塞呈低密度影,伴远端分支动脉不显影,均为部分肠坏死.3例患者肠系膜上动脉非主干栓塞呈低密度影,伴远端分支动脉显影,其中肠缺血2例,部分肠坏死1例.②间接征象:5例患者肠壁增厚,其中部分肠坏死3例,长段肠坏死2例.17例患者肠道扩张伴积气、积液,局部肠管内可见气液平,其中肠缺血2例,部分肠坏死5例,长段肠坏死10例.2例患者肠壁积气,呈肠壁气泡影,均为长段肠坏死.(4)治疗及预后:6例肠缺血患者,其中1例行肠系膜上动脉取栓术,其余5例行低分子肝素抗凝、前列地尔扩血管等治疗.8例部分肠坏死患者,行坏死肠管切除术.12例长段肠坏死患者中,5例术后短肠综合征行坏死肠管切除术,术后联合静脉营养支持治疗.上述患者均经对症支持和手术治疗好转出院.12例长段肠坏死患者中,7例全小肠坏死及部分结肠坏死仅行剖腹探查,短期内死亡.结论 肌酸激酶明显升高及CT血管造影检查示肠系膜上动脉主干栓塞伴远端分支不显影,预示肠系膜上动脉栓塞患者短期不良预后.%Objective To investigate the value of creatine kinase and computed tomography(CT)angiography to evaluate short-term prognosis of patients with superior mesenteric artery embolism(SMAE).Methods The retrospective cross-sectional study was adopted.The clinical data of 26 patients with SMAE who were admitted to the first Affiliated Hospital of Wenzhou Medical University between January 2008 and October 2015 were collected.The patients received serologic examination and CT angiography firstly,and then medicinal conservative method and surgical method were respectively conducted according to the results of above examinations.Observation indices:(1)clinical features,(2)serum indicators

  16. 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

  17. 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

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

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    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.

  19. 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

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

    Science.gov (United States)

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

    2016-01-01

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

  1. 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

  2. Creatine and pyruvate prevent the alterations caused by tyrosine on parameters of oxidative stress and enzyme activities of phosphoryltransfer network in cerebral cortex of Wistar rats.

    Science.gov (United States)

    de Andrade, Rodrigo Binkowski; Gemelli, Tanise; Rojas, Denise Bertin; Bonorino, Narielle Ferner; Costa, Bruna May Lopes; Funchal, Cláudia; Dutra-Filho, Carlos Severo; Wannmacher, Clovis Milton Duval

    2015-01-01

    Tyrosine accumulates in inborn errors of tyrosine catabolism, especially in tyrosinemia type II. In this disease caused by tyrosine aminotransferase deficiency, eyes, skin, and central nervous system disturbances are found. In the present study, we investigated the chronic effect of tyrosine methyl ester (TME) and/or creatine plus pyruvate on some parameters of oxidative stress and enzyme activities of phosphoryltransfer network in cerebral cortex homogenates of 21-day-old Wistar. Chronic administration of TME induced oxidative stress and altered the activities of adenylate kinase and mitochondrial and cytosolic creatine kinase. Total sulfhydryls content, GSH content, and GPx activity were significantly diminished, while DCFH oxidation, TBARS content, and SOD activity were significantly enhanced by TME. On the other hand, TME administration decreased the activity of CK from cytosolic and mitochondrial fractions but enhanced AK activity. In contrast, TME did not affect the carbonyl content and PK activity in cerebral cortex of rats. Co-administration of creatine plus pyruvate was effective in the prevention of alterations provoked by TME administration on the oxidative stress and the enzymes of phosphoryltransfer network, except in mitochondrial CK, AK, and SOD activities. These results indicate that chronic administration of TME may stimulate oxidative stress and alter the enzymes of phosphoryltransfer network in cerebral cortex of rats. In case this also occurs in the patients affected by these disorders, it may contribute, along with other mechanisms, to the neurological dysfunction of hypertyrosinemias, and creatine and pyruvate supplementation could be beneficial to the patients.

  3. Effects of creatine supplementation in taekwondo practitioners

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    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.

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

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    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.

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

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

    1981-08-13

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

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

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    Ahmet Kale

    2005-01-01

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

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

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    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

  8. 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...

  9. 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…

  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 EFFECT OF CREATINE SUPPLEMENTATION ON ATHLETE ISOKINETIC PERFORMANCE

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    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

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

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    Greenwood Mike

    2009-02-01

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

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

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    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.

  14. 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.

  15. CREATINE SUPPLEMENTATION AND EXERCISE PERFORMANCE: A BRIEF REVIEW

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    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

  16. Brain Type or Sex Differences? A structural equation model of the relation between brain type, sex, and motivation to learn science

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    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.

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

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    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.

  18. Co-administration of creatine plus pyruvate prevents the effects of phenylalanine administration to female rats during pregnancy and lactation on enzymes activity of energy metabolism in cerebral cortex and hippocampus of the offspring.

    Science.gov (United States)

    Bortoluzzi, Vanessa Trindade; de Franceschi, Itiane Diehl; Rieger, Elenara; Wannmacher, Clóvis Milton Duval

    2014-08-01

    Phenylketonuria (PKU) is the most frequent inborn error of metabolism. It is caused by deficiency in the activity of phenylalanine hydroxylase, leading to accumulation of phenylalanine and its metabolites. Untreated maternal PKU or hyperphenylalaninemia may result in nonphenylketonuric offspring with low birth weight and neonatal sequelae, especially microcephaly and intellectual disability. The mechanisms underlying the neuropathology of brain injury in maternal PKU syndrome are poorly understood. In the present study, we evaluated the possible preventive effect of the co-administration of creatine plus pyruvate on the effects elicited by phenylalanine administration to female Wistar rats during pregnancy and lactation on some enzymes involved in the phosphoryltransfer network in the brain cortex and hippocampus of the offspring at 21 days of age. Phenylalanine administration provoked diminution of body, brain cortex an hippocampus weight and decrease of adenylate kinase, mitochondrial and cytosolic creatine kinase activities. Co-administration of creatine plus pyruvate was effective in the prevention of those alterations provoked by phenylalanine, suggesting that altered energy metabolism may be important in the pathophysiology of maternal PKU. If these alterations also occur in maternal PKU, it is possible that pyruvate and creatine supplementation to the phenylalanine-restricted diet might be beneficial to phenylketonuric mothers.

  19. 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...

  20. Influence of physical activity of racehorses on lactate dehydrogenase and creatine kinase activities, and protein synthesis

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    Jović Slavoljub

    2013-01-01

    Full Text Available The aim of the research was to assess the effects of physical activity of various intensity on the degree of damage to certain organs resulting from increased free radical production, as well as the adaptability of the organism to physical exercise. Two groups of healthy 3-5-year-old full-blooded racehorses were assessed. The first one ran a 2400-meter gallop race, which is considered a short-lasting, intense physical activity; lipid status was assessed prior to, and 48 and 72 h after the race. The second group ran a forty-kilometer endurance ride, which is a long-lasting moderate physical activity; the lipid status was assessed immediately before, on finishing and 48, 72, 96, 120 and 144 h after the race. The total activity of LDH changed 72 h and 96 h following the gallop race (p>0.05, whilst the maximum activity was measured immediately after the endurance ride. By means of electrophoresis LDH in all the horses 5 isoforms were detected. The activity of LDH1 72 h after the gallop race significantly rose in comparison to the one before the race (p0.05. Following the endurance ride LDH1 activity rose at all sampling times, reaching the maximum at 96 h and 144 h in comparison to the values both before and on finishing the ride (p<0.01. The increase in the activity of LDH2 was significantly higher 48 h, 72 h, 96 h and 120 h (p<0.05 after the race in comparison to that before the race, and at 48 h, 72 h, 96 h, 120 h and 144 h (p<0.05 in comparison to the values on finishing the race. LDH3 activity significantly decreased and LDH5 rose immediately after the endurance ride (p<0.01, whilst LDH4 significantly rose at all times following the endurance ride (p<0.01. The CK activity pointed to high, medium and low degree of adaptation of horses to physical activity. The concentrations of total proteins, albumins and globulins remained within the physiological range at all sampling times, with the exception of 96 h after the endurance ride, when the fall in albumin concentration was significant (p<0.01. Long-lasting physical activity of low intensity leads to cellular damage in the myocardium, muscles, liver and to hypoalbuminaemia, which is a consequence of free radical production. [Projekat Ministarstva nauke Republike Srbije, br. 173034 i br. 31085

  1. 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...

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

    NARCIS (Netherlands)

    Streijger, Femke

    2007-01-01

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

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

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    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.

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

    Science.gov (United States)

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

    2005-01-01

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

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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.

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

    Science.gov (United States)

    Rawson, Eric S; Venezia, Andrew C

    2011-05-01

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

  16. 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...

  17. 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...

  18. Casein kinases

    DEFF Research Database (Denmark)

    Issinger, O G

    1993-01-01

    , no 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......-specific expression of CK-2 at the mRNA and at the protein level has also been given attention. The fact that the enzyme activity is surprisingly high in brain and low in heart and lung may be indicative of involvement of CK-2 in processes other than proliferation.(ABSTRACT TRUNCATED AT 400 WORDS)...

  19. 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...

  20. 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

  1. 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

  2. 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...

  3. 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.

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

    Science.gov (United States)

    Taner, Basturk; Aysim, Ozagari; Abdulkadir, Unsal

    2011-02-01

    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. Twenty-five days after stopping the creatine supplements, the patient recovered fully. Even recommended doses of creatine monohydrate supplementation may cause kidney damage; therefore, anybody using this supplement should be warned about this possible side effect, and their renal functions should be monitored regularly.

  5. Creatine for neuroprotection in neurodegenerative disease: end of story?

    Science.gov (United States)

    Bender, Andreas; Klopstock, Thomas

    2016-08-01

    Creatine (Cr) is a natural compound that plays an important role in cellular energy homeostasis. In addition, it ameliorates oxidative stress, glutamatergic excitotoxicity, and apoptosis in vitro as well as in vivo. Since these pathomechanisms are implicated to play a role in several neurodegenerative diseases, Cr supplementation as a neuroprotective strategy has received a lot of attention with several positive animal studies in models of Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). This has led to a number of randomized clinical trials (RCT) with oral Cr supplementation, with durations up to 5 years. In this paper, we review the evidence and consequences stemming from these trials. In the case of PD, the initial phase II RCT was promising and led to a large and well-designed phase III trial, which, however, turned out to be negative for all outcome measures. None of the RCTs that have examined effects of Cr in ALS patients showed any clinical benefit. In HD, Cr in high doses (up to 30 g/day) was shown to slow down brain atrophy in premanifest Huntingtin mutation carriers. In spite of this, proof is still lacking that Cr can also have beneficial clinical effects in this group of patients, who will go on to develop HD symptoms. Taken together, the use of Cr supplementation has so far proved disappointing in clinical studies with a number of symptomatic neurodegenerative diseases.

  6. 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.

  7. 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...

  8. 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.

  9. Interactions of aging, overload, and creatine supplementation in rat plantaris muscle.

    Science.gov (United States)

    Schuenke, Mark D; Brooks, Naomi E; Hikida, Robert S

    2011-01-01

    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. PMID:21876808

  10. No effects of lifelong creatine supplementation on sarcopenia in senescence-accelerated mice (SAMP8).

    Science.gov (United States)

    Derave, Wim; Eijnde, Bert O; Ramaekers, Monique; Hespel, Peter

    2005-08-01

    Oral creatine supplementation can acutely ameliorate skeletal muscle function in older humans, but its value in the prevention of sarcopenia remains unknown. We evaluated the effects of lifelong creatine supplementation on muscle mass and morphology, contractility, and metabolic properties in a mouse model of muscle senescence. Male senescence-accelerated mice (SAMP8) were fed control or creatine-supplemented (2% of food intake) diet from the age of 10 to 60 wk. Soleus and extensor digitorum longus muscles were tested for in vitro contractile properties, creatine content, and morphology at weeks 25 and 60. Both muscle types showed reduced phosphocreatine content at week 60 that could not be prevented by creatine. Accordingly, age-associated decline in muscle mass and contractility was not influenced by treatment. Aged soleus muscles had fewer and smaller fast-twitch glycolytic fibers irrespective of treatment received. It is concluded that lifelong creatine supplementation is no effective strategy to prevent sarcopenia in senescence-accelerated mice. PMID:15727953

  11. 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.

  12. Urinary creatine at rest and after repeated sprints in athletes: a pilot study.

    Science.gov (United States)

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

    2014-03-01

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

  13. Attenuation by creatine of myocardial metabolic stress in Brattleboro rats caused by chronic inhibition of nitric oxide synthase.

    Science.gov (United States)

    Constantin-Teodosiu, D; Greenhaff, P L; Gardiner, S M; Randall, M D; March, J E; Bennett, T

    1995-12-01

    1. The present experiment was undertaken to investigate: (a) the effect of nitric oxide synthase (NOS) inhibition, mediated by oral supplementation of the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on measures of myocardial energy metabolism and function: (b) the effect of oral creatine supplementation on these variables, in the absence and presence of L-NAME. 2. In one series of experiments, 4 weeks oral administration of L-NAME (0.05 mg ml-1 day-1 in the drinking water) to Brattleboro rats caused significant reductions in myocardial ATP, creatine, and total creatine concentrations and an accumulation of tissue lactate when compared with control animals. Administration of creatine (0.63 mg ml-1 day-1 in the drinking water) for 4 weeks elevated myocardial creatine and total creatine concentrations and reduced lactate accumulation, but did not significantly affect ATP or phosphocreatine (PCr). Concurrent treatment with creatine and L-NAME prevented the reduction in creatine and total creatine concentrations, and significantly attenuated the accumulation of lactate and the reduction in ATP seen with L-NAME alone. 3. In a second series of experiments, 4 weeks treatment with L-NAME and creatine plus L-NAME increased mean arterial blood pressure in conscious Brattleboro rats. Hearts isolated from these animals showed decreased coronary flow and left ventricular developed pressure (LVDP), and total mechanical performance. Treatment with creatine alone had no measurable effect on either mean arterial blood pressure or coronary flow in isolated hearts. However, there was an increase in LVDP, but not in total mechanical performance, because there was a bradycardia. 4. These results indicate that creatine supplementation can attenuate the metabolic stress associated with L-NAME administration and that this effect occurs as a consequence of the action of creatine on myocardial energy metabolism.

  14. 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

  15. Protein Kinase D family kinases

    OpenAIRE

    Wille, Christoph; Seufferlein, Thomas; Eiseler, Tim

    2014-01-01

    Highly invasive pancreatic tumors are often recognized in late stages due to a lack of clear symptoms and pose major challenges for treatment and disease management. Broad-band Protein Kinase D (PKD) inhibitors have recently been proposed as additional treatment option for this disease. PKDs are implicated in the control of cancer cell motility, angiogenesis, proliferation and metastasis. In particular, PKD2 expression is elevated in pancreatic cancer, whereas PKD1 expression is comparably lo...

  16. 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

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

    Science.gov (United States)

    Lemon, Peter W R

    2002-12-01

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

  18. Acute renal failure in a young weight lifter taking multiple food supplements, including creatine monohydrate.

    Science.gov (United States)

    Thorsteinsdottir, Bjorg; Grande, Joseph P; Garovic, Vesna D

    2006-10-01

    We report a case of a healthy 24-year-old man who presented with acute renal failure and proteinuria while taking creatine and multiple other supplements for bodybuilding purposes. A renal biopsy showed acute interstitial nephritis. The patient recovered completely after he stopped taking the supplements. Creatine is a performance-enhancing substance that has gained widespread popularity among professional as well as amateur athletes. It is legal and considered relatively safe. Recently there have been case reports of renal dysfunction, including acute interstitial nephritis, associated with its use. Further studies are needed to evaluate the safety of creatine supplementation. It may be prudent to include a warning of this possible side effect in the product insert.

  19. 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.

  20. 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

  1. Effect of creatine supplementation during resistance training on muscle accretion in the elderly.

    Science.gov (United States)

    Candow, D G; Chilibeck, P D

    2007-01-01

    Sarcopenia, defined as the age-related loss of muscle mass, is a serious health concern. Contributing factors to sarcopenia include physical inactivity and undernutrition. Resistance training has a positive effect on muscle mass in the elderly. However, muscle loss is still observed in older adults who perform weight bearing exercise; suggesting that nutrition is important. Creatine supplementation has the potential to increase muscle accretion during resistance training, although the mechanism for its ergogenic effect is unclear. Creatine has the potential to increase cellular hydration and myogenic transcription factors and facilitate the up-regulation of muscle specific-genes such as myosin heavy chain possibly leading to muscle hypertrophy. PMID:17435961

  2. 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.

  3. 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.

  4. 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

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

    Science.gov (United States)

    Vallet, J L; Miles, J R; Rempel, L A

    2013-05-01

    We hypothesized that creatine supplementation would reduce birth intervals, stillbirth rate, and preweaning survival in pigs because of its reported improvement of athletic performance in humans. In Exp. 1, gilts (n = 42) and first parity sows (n = 75) were mated at estrus. Beginning on d 110 of gestation, dams received either no treatment or 20 g creatine daily until farrowing. At farrowing in November 2008, pigs were monitored by video camera to determine individual piglet birth intervals. On d 1, piglets were weighed, euthanized, and the cerebellum, brain stem, and spinal cord were collected from the largest and smallest piglets in each litter to measure myelin basic proteins, myelin cholesterol, glucocerebrosides, phosphatidylethanolamine, phosphatidylcholine, and sphingomyelin. Preweaning mortality of the remaining piglets was recorded, including whether a piglet had been overlayed by the dam. A second experiment was performed using gilts (n = 90), farrowing in July 2010, to test differential effects of creatine supplementation during hot, humid weather when dams typically have more difficulty farrowing. Once again, gilts were provided either no supplementation or 20 g creatine daily from d 110 to the day of farrowing. Gilts were video recorded during farrowing, piglets were weighed on d 1, and preweaning mortality (including overlays) was recorded. In Exp. 1, creatine supplementation had no effect on birth intervals or stillbirth rate. Creatine supplementation improved the amount of myelin lipids in brain regions of piglets, particularly the brain stem. Creatine supplementation also reduced overlays of low birth weight piglets from gilts but not second parity sows. Data from Exp. 2 were combined with gilt data from Exp. 1 to examine the effect of creatine, season, and their interaction. There were no effects of treatment or season on birth intervals, stillbirth rates, or overall preweaning mortality. Creatine treatment reduced the incidence of overlays in low

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

    NARCIS (Netherlands)

    Kamp, J.M. van de; Betsalel, O.T.; Mercimek-Mahmutoglu, S.; Abulhoul, L.; Grunewald, S.; Anselm, I.; Azzouz, H.; Bratkovic, D.; Brouwer, A.; Hamel, B.C.J.; Kleefstra, T.; Yntema, H.G.; Campistol, J.; Vilaseca, M.A.; Cheillan, D.; D'Hooghe, M.; Diogo, L.; Garcia, P.; Valongo, C.; Fonseca, M.; Frints, S.; Wilcken, B.; Haar, S. van der; Meijers-Heijboer, H.E.; Hofstede, F.; Johnson, D.; Kant, S.G.; Lion-Francois, L.; Pitelet, G.; Longo, N.; Maat-Kievit, J.A.; Monteiro, J.P.; Munnich, A.; Muntau, A.C.; Nassogne, M.C.; Osaka, H.; Ounap, K.; Pinard, J.M.; Quijano-Roy, S.; Poggenburg, I.; Poplawski, N.; Abdul-Rahman, O.; Ribes, A.; Arias Vasquez, A.; Yaplito-Lee, J.; Schulze, A.; Schwartz, C.E.; Schwenger, S.; Soares, G.; Sznajer, Y.; Valayannopoulos, V.; Esch, H. van; Waltz, S.; Wamelink, M.M.; Pouwels, P.J.; Errami, A.; Knaap, M.S. van der; Jakobs, C.; Mancini, G.M.; Salomons, G.S.

    2013-01-01

    BACKGROUND: Creatine transporter deficiency is a monogenic cause of X-linked intellectual disability. Since its first description in 2001 several case reports have been published but an overview of phenotype, genotype and phenotype-genotype correlation has been lacking. METHODS: We performed a retro

  7. 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.

  8. 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...

  9. 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.…

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

    Science.gov (United States)

    2013-01-01

    Background Chronic supplementation with creatine monohydrate has been shown to promote increases in total intramuscular creatine, phosphocreatine, skeletal muscle mass, lean body mass and muscle fiber size. Furthermore, there is robust evidence that muscular strength and power will also increase after supplementing with creatine. However, it is not known if the timing of creatine supplementation will affect the adaptive response to exercise. Thus, the purpose of this investigation was to determine the difference between pre versus post exercise supplementation of creatine on measures of body composition and strength. Methods Nineteen healthy recreational male bodybuilders (mean ± SD; age: 23.1 ± 2.9; height: 166.0 ± 23.2 cm; weight: 80.18 ± 10.43 kg) participated in this study. Subjects were randomly assigned to one of the following groups: PRE-SUPP or POST-SUPP workout supplementation of creatine (5 grams). The PRE-SUPP group consumed 5 grams of creatine immediately before exercise. On the other hand, the POST-SUPP group consumed 5 grams immediately after exercise. Subjects trained on average five days per week for four weeks. Subjects consumed the supplement on the two non-training days at their convenience. Subjects performed a periodized, split-routine, bodybuilding workout five days per week (Chest-shoulders-triceps; Back-biceps, Legs, etc.). Body composition (Bod Pod®) and 1-RM bench press (BP) were determined. Diet logs were collected and analyzed (one random day per week; four total days analyzed). Results 2x2 ANOVA results - There was a significant time effect for fat-free mass (FFM) (F = 19.9; p = 0.001) and BP (F = 18.9; p supplementation with creatine post workout is possibly more beneficial in comparison to pre workout supplementation with regards to FFM, FM and 1-RM BP. The mean change in the PRE-SUPP and POST-SUPP groups for body weight (BW kg), FFM (kg), FM (kg) and 1-RM bench press (kg) were as follows

  11. Role of Creatine Supplementation on Exercise-Induced Cardiovascular Function and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Michael I. C. Kingsley

    2009-01-01

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

  12. 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

  13. 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

  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

    of mitCK adsorption capacity by another method at pH 7.4, when the enzyme is almost protonated, gave View the MathML source. The effect of ionic strength on mitCK adsorption may be described in terms of Debye-Hückel's theory for activity coefficients assuming the charges of the interacting species......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 enzyme adsorption. An analysis of our own data as well as of the data from the literature is consistent with the adsorption site of the octameric mitCK being composed of 4 amino acid residues with pK = 8.8 in the free enzyme. The pK value changes to 9.8 upon binding of the protein to the membrane. Lysine...

  15. 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.

  16. 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

  17. 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

  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.

  19. 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.

  20. 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...

  1. 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 ...

  2. 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...

  3. Sarcopenia: current theories and the potential beneficial effect of creatine application strategies.

    Science.gov (United States)

    Candow, Darren G

    2011-08-01

    Sarcopenia, defined as the age-related loss of muscle mass, subsequently has a negative effect on strength, metabolic rate and functionality leading to a reduced quality of life. With the projected increase in life expectancy, the incidence of muscle loss may rise and further drain the health care system, with greater need for hospitalization, treatment, and rehabilitation. Without effective strategies to counteract aging muscle loss, a global health care crisis may be inevitable. Resistance training is well established to increase aging muscle mass and strength. However, muscle and strength loss is still evident in older adults who have maintained resistance training for most of their life, suggesting that other factors such as nutrition may affect aging muscle biology. Supplementing with creatine, a high-energy compound found in red meat and seafood, during resistance training has a beneficial effect on aging muscle. Emerging evidence now suggests that the timing and dosage of creatine supplementation may be important factors for aging muscle accretion. Unfortunately, the long-term effects of different creatine application strategies on aging muscle are relatively unknown. PMID:21373890

  4. 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

  5. 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.

  6. 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.

  7. Effects of creatine monohydrate supplementation and exercise on depression-like behaviors and raphe 5-HT neurons in mice

    Science.gov (United States)

    Ahn, Nari; Leem, Yea Hyun; Kato, Morimasa; Chang, Hyukki

    2016-01-01

    [Purpose] The effects of creatine and exercise on chronic stress-induced depression are unclear. In the present study, we identified the effects of 4-week supplementation of creatine monohydrate and/or exercise on antidepressant behavior and raphe 5-HT expression in a chronic mild stress-induced depressed mouse model. [Methods] Seven-week-old male C57BL/6 mice (n=48) were divided randomly into 5 groups: (1) non-stress control (CON, n=10), (2) stress control (ST-CON, n=10), (3) stress and creatine intake (ST-Cr, n=10), (4) stress and exercise (ST-Ex, n=9), and (5) combined stress, exercise, and creatine intake (ST-Cr+Ex, n=9). After five weeks’ treatment, we investigated using both anti-behavior tests (the Tail Suspension Test (TST) and the Forced Swimming Test (FST)), and 5-HT expression in the raphe nuclei (the dorsal raphe (DR) and median raphe (MnR)). [Results] Stress for 4 weeks significantly increased depressive behaviors in the mice. Treatment with creatine supplementation combined with exercise significantly decreased depressive behaviors as compared with the CON-ST group in both the TST and FST tests. With stress, 5-HT expression in the raphe nuclei decreased significantly. With combined creatine and exercise, 5-HT positive cells increased significantly and had a synergic effect on both DR and MnR. [Conclusion] The present study found that even a single treatment of creatine or exercise has partial effects as an antidepressant in mice with chronic mild stress-induced depression. Furthermore, combined creatine and exercise has synergic effects and is a more effective prescription than a single treatment.

  8. Application of NMR-based metabonomics suggests a relationship between betaine absorption and elevated creatine plasma concentrations in catheterised sows

    DEFF Research Database (Denmark)

    Yde, Christian Clement; Westerhuis, Johan A.; Bertram, Hanne Christine S.;

    2012-01-01

    of these metabolites from the small intestine. The LF diet resulted in a higher betaine concentration in the blood than the two high-fibre diets (P¼0·008). This leads to higher plasma concentrations of methionine (P¼0·0028) and creatine (P¼0·020) of endogenous origin. In conclusion, the use of NMR spectroscopy...... for measuring nutrient uptake in the present study elucidated the relationship between betaine uptake and elevated creatine plasma concentrations....

  9. Effects of acute creatine loading with or without carbohydrate on repeated bouts of maximal swimming in high-performance swimmers.

    Science.gov (United States)

    Theodorou, Apostolos S; Havenetidis, Konstantinos; Zanker, Cathy L; O'Hara, John P; King, Roderick F G J; Hood, Colin; Paradisis, Giorgios; Cooke, Carlton B

    2005-05-01

    The addition of carbohydrate (CHO) to an acute creatine (Cr) loading regimen has been shown to increase muscle total creatine content significantly beyond that achieved through creatine loading alone. However, the potential ergogenic effects of combined Cr and CHO loading have not been assessed. The purpose of this study was to compare swimming performance, assessed as mean swimming velocity over repeated maximal intervals, in high-performance swimmers before and after an acute loading regimen of either creatine alone (Cr) or combined creatine and carbohydrate (Cr + CHO). Ten swimmers (mean +/- SD of age and body mass: 17.8 +/- 1.8 years and 72.3 +/- 6.8 kg, respectively) of international caliber were recruited and were randomized to 1 of 2 groups. Each swimmer ingested five 5 g doses of creatine for 4 days, with the Cr + CHO group also ingesting approximately 100 g of simple CHO 30 minutes after each dose of creatine. Performance was measured on 5 separate occasions: twice at "baseline" (prior to intervention, to assess the repeatability of the performance test), within 48 hours after intervention, and then 2 and 4 weeks later. All subjects swam faster after either dietary loading regimen (p < 0.01, both regimens); however, there was no difference in the extent of improvement of performance between groups. In addition, all swimmers continued to produce faster swim times for up to 4 weeks after intervention. Our findings suggest that no performance advantage was gained from the addition of carbohydrate to a creatine-loading regimen in these high-caliber swimmers.

  10. 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.

  11. 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

  12. 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...

  13. Thymidine kinases in archaea

    DEFF Research Database (Denmark)

    Clausen, A.R.; Matakos, A.; Sandrini, Michael;

    2006-01-01

    Twenty-six fully sequenced archaeal genomes were searched for genes coding for putative deoxyribonucleoside kinases (dNKs). We identified only 5 human-like thymidine kinase 1 genes (TK1s) and none for non-TK1 kinases. Four TK1s were identified in the Euryarchaea and one was found in the Crenarchaea...... that a functional deoxyribonucleoside salvage pathway is not crucial for the archaeal cell....

  14. 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

  15. 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

  16. 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...

  17. 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.

  18. Effects of creatine loading on electromyographic fatigue threshold during cycle ergometry in college-aged women

    Directory of Open Access Journals (Sweden)

    Cramer Joel T

    2007-11-01

    Full Text Available Abstract The purpose of this study was to examine the effects of 5 days of Creatine (Cr loading on the electromyographic fatigue threshold (EMGFT in college-aged women. Fifteen healthy college-aged women (mean ± SD = 22.3 ± 1.7 yrs volunteered to participate in this double-blind, placebo-controlled study and were randomly placed into either placebo (PL – 10 g of flavored dextrose powder; n = 8 or creatine (Cr – 5 g di-creatine citrate plus 10 g of flavored dextrose powder; n = 7; Creatine Edge, FSI Nutrition loading groups. Each group ingested one packet 4 times per day (total of 20 g/day for 5 days. Prior to and following supplementation, each subject performed a discontinuous incremental cycle ergometer test to determine their EMGFT value, using bipolar surface electrodes placed on the longitudinal axis of the right vastus lateralis. Subjects completed a total of four, 60 second work bouts (ranging from 100–350 W. The EMG amplitude was averaged over 10 second intervals and plotted over the 60 second work bout. The resulting slopes from each successive work bouts were used to calculate EMGFT. A two-way ANOVA (group [Cr vs. PL] × time [pre vs. post] resulted in a significant (p = 0.031 interaction. Furthermore, a dependent samples t-test showed a 14.5% ± 3.5% increase in EMGFT from pre- to post-supplementation with Cr (p = 0.009, but no change for the PL treatment (-2.2 ± 5.8%; p = 0.732. In addition, a significant increase (1.0 ± 0.34 kg; p = 0.049 in weight (kg was observed in the Cr group but no change for PL (-0.2 kg ± 0.2 kg. These findings suggest that 5 days of Cr loading in women may be an effective strategy for delaying the onset of neuromuscular fatigue during cycle ergometry.

  19. Muscle phosphorylase kinase deficiency

    DEFF Research Database (Denmark)

    Preisler, N; Orngreen, M C; Echaniz-Laguna, A;

    2012-01-01

    To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD).......To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD)....

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. Fetal-onset severe skeletal muscle glycogenosis associated with phosphorylase-b kinase deficiency.

    Science.gov (United States)

    Bührer, C; van Landeghem, F; Brück, W; Felderhoff-Müser, U; Vorgerd, M; Obladen, M

    2000-04-01

    We report on a premature newborn girl delivered after 32 weeks of gestation by cesarean section after sparse limb movements, fetal tachycardia and late heart rate decelerations had suggested fetal distress. Following 1 day of mechanical ventilation, adequate pulmonary gas exchange was achieved by spontaneous breathing. Main symptoms were virtually complete absence of spontaneous movements, increased flexor tonus of the extremities, and hypotonia of the trunk. Inability to suck or swallow required nasogastric gavage feeding. There were no hypoglycemic episodes. Echocardiography revealed normal myocardial function. Creatine kinase was 237 U/I at 2 days of life, declining to normal values thereafter. Muscle biopsy revealed increased glycogen storage with subsarcolemmal glycogen deposits and low phosphorylase-a activity while total phosphorylase was normal after in vitro activation, suggestive of phosphorylase-b kinase deficiency. No mutation was detected in exon 1 of the myophosphorylase gene. No psychomotor development was observed, and the infant died of central apnea at 3 months of age.

  6. Muscle oxidative phosphorylation quantitation using creatine chemical exchange saturation transfer (CrCEST) MRI in mitochondrial disorders

    Science.gov (United States)

    DeBrosse, Catherine; Nanga, Ravi Prakash Reddy; Wilson, Neil; D’Aquilla, Kevin; Elliott, Mark; Yan, Felicia; Wade, Kristin; Nguyen, Sara; Worsley, Diana; Parris-Skeete, Chevonne; McCormick, Elizabeth; Xiao, Rui; Cunningham, Zuela Zolkipli; Fishbein, Lauren; Nathanson, Katherine L.; Lynch, David R.; Stallings, Virginia A.; Yudkoff, Marc; Falk, Marni J.; Reddy, Ravinder; McCormack, Shana E.

    2016-01-01

    Systemic mitochondrial energy deficiency is implicated in the pathophysiology of many age-related human diseases. Currently available tools to estimate mitochondrial oxidative phosphorylation (OXPHOS) capacity in skeletal muscle in vivo lack high anatomic resolution. Muscle groups vary with respect to their contractile and metabolic properties. Therefore, muscle group–specific estimates of OXPHOS would be advantageous. To address this need, a noninvasive creatine chemical exchange saturation transfer (CrCEST) MRI technique has recently been developed, which provides a measure of free creatine. After exercise, skeletal muscle can be imaged with CrCEST in order to make muscle group–specific measurements of OXPHOS capacity, reflected in the recovery rate (τCr) of free Cr. In this study, we found that individuals with genetic mitochondrial diseases had significantly (P = 0.026) prolonged postexercise τCr in the medial gastrocnemius muscle, suggestive of less OXPHOS capacity. Additionally, we observed that lower resting CrCEST was associated with prolonged τPCr, with a Pearson’s correlation coefficient of –0.42 (P = 0.046), consistent with previous hypotheses predicting that resting creatine levels may correlate with 31P magnetic resonance spectroscopy–based estimates of OXPHOS capacity. We conclude that CrCEST can noninvasively detect changes in muscle creatine content and OXPHOS capacity, with high anatomic resolution, in individuals with mitochondrial disorders. PMID:27812541

  7. 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.

  8. 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...

  9. 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...

  10. Creatine supplementation augments the increase in satellite cell and myonuclei number in human skeletal muscle induced by strength training

    DEFF Research Database (Denmark)

    Olsen, Steen; Aagaard, Per; Kadi, Fawzi;

    2006-01-01

    The present study investigated the influence of creatine and protein supplementation on satellite cell frequency and number of myonuclei in human skeletal muscle during 16 weeks of heavy-resistance training. In a double-blinded design 32 healthy, male subjects (19-26 years) were assigned to stren...

  11. [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

  12. The relationship between choline plus creatine- to-citrate ratio in magnetic resonance spectroscopy with the invasion of prostate cancer

    Directory of Open Access Journals (Sweden)

    M Ghafoori

    2012-12-01

    Full Text Available Background: Prostate cancer is the most common cancer and the second cause of cancer mortality in men. Although histopathological examination is the gold-standard for its diagnosis, tendency toward less invasive methods is growing. The purpose of this study was to evaluate the relationship between choline plus creatine- to-citrate ratio in magnetic resonance spectroscopy (MRS with the invasion of prostate cancer in a series of patients with prostate cancer.Methods: Totally, 200 patients with pathologically proven prostate cancer were enrolled in this cross-sectional study by a non-probability sampling method in Hazrat Rasul Akram Hospital in Tehran, Iran during 2009-2010. Pathological staging was the gold standard for the diagnosis of prostate cancer while the patients underwent MRS for choline plus creatine- to-citrate ratio determination. MRS and pathological results were compared and analyzed.Results: The mean (±SD values of choline plus creatine- to-citrate ratio in patients with Gleason scores less than 3, 3 to 4 and greater than 4 were 245.8±146.8, 427.1±173.6 and 427.1±173.6, respectively (P<0.001. The mean (±SD values of choline plus creatine- to-citrate ratio in patients with PSA levels less than 4, 4 to 10 and greater than 10 were 180.7±58.3, 247±93.5 and 385.1±106.6, respectively (P<0.001.Conclusion: Choline plus creatine- to-citrate ratio determined by magnetic resonance spectroscopy has a significant relationship with the degree of invasion of prostate cancer and can be used for the staging of the disease.

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

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    Stewart I Head

    Full Text Available BACKGROUND: Creatine supplementation can improve performance during high intensity exercise in humans and improve muscle strength in certain myopathies. In this present study, we investigated the direct effects of acute creatine incubation on isolated mouse fast-twitch EDL muscles, and examined how these effects change with fatigue. METHODS AND RESULTS: The extensor digitorum longus muscle from mice aged 12-14 weeks was isolated and stimulated with field electrodes to measure force characteristics in 3 different states: (i before fatigue; (ii immediately after a fatigue protocol; and (iii after recovery. These served as the control measurements for the muscle. The muscle was then incubated in a creatine solution and washed. The measurement of force characteristics in the 3 different states was then repeated. In un-fatigued muscle, creatine incubation increased the maximal tetanic force. In fatigued muscle, creatine treatment increased the force produced at all frequencies of stimulation. Incubation also increased the rate of twitch relaxation and twitch contraction in fatigued muscle. During repetitive fatiguing stimulation, creatine-treated muscles took 55.1±9.5% longer than control muscles to lose half of their original force. Measurement of weight changes showed that creatine incubation increased EDL muscle mass by 7%. CONCLUSION: Acute creatine application improves force production in isolated fast-twitch EDL muscle, and these improvements are particularly apparent when the muscle is fatigued. One likely mechanism for this improvement is an increase in Ca(2+ sensitivity of contractile proteins as a result of ionic strength decreases following creatine incubation.

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

    Directory of Open Access Journals (Sweden)

    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

  15. Creatine supplementation augments the increase in satellite cell and myonuclei number in human skeletal muscle induced by strength training

    Science.gov (United States)

    Olsen, Steen; Aagaard, Per; Kadi, Fawzi; Tufekovic, Goran; Verney, Julien; Olesen, Jens L; Suetta, Charlotte; Kjær, Michael

    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). Furthermore, timed protein/placebo intake were administered at all training sessions. Muscle biopsies were obtained at week 0, 4, 8 (week 8 not CON) and 16 of resistance training (3 days per week). Satellite cells were identified by immunohistochemistry. Muscle mean fibre (MFA) area was determined after 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 number was no longer elevated in STR-CRE, while it remained elevated in STR-PRO and STR-CON. Furthermore, creatine supplementation resulted in an increased number of myonuclei per fibre and increases of 14–17% in MFA at week 4, 8 and 16 (P < 0.01). In contrast, STR-PRO showed increase in MFA only in the later (16 week, +8%) and STR-CON only in the early (week 4, +14%) phases of training, respectively (P < 0.05). In STR-CRE a positive relationship was found between the percentage increases in MFA and myonuclei from baseline to week 16, respectively (r = 0.67, P < 0.05). No changes were observed in the control group (CON). In conclusion, the present study demonstrates for the first time that creatine supplementation in combination with strength training amplifies

  16. 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

  17. 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...

  18. 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

  19. 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...... in the control group (CON). In conclusion, the present study demonstrates for the first time that creatine supplementation in combination with strength training amplifies the training-induced increase in satellite cell number and myonuclei concentration in human skeletal muscle fibres, thereby allowing......). Furthermore, timed protein/placebo intake were administered at all training sessions. Muscle biopsies were obtained at week 0, 4, 8 (week 8 not CON) and 16 of resistance training (3 days per week). Satellite cells were identified by immunohistochemistry. Muscle mean fibre (MFA) area was determined after...

  20. 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

  1. 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

    2014-09-19

    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.

  2. 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.

  3. 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.

  4. Comparison of time-dependent effects of (+-methamphetamine or forced swim on monoamines, corticosterone, glucose, creatine, and creatinine in rats

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    Gudelsky Gary A

    2008-05-01

    Full Text Available Abstract Background Methamphetamine (MA use is a worldwide problem. Abusers can have cognitive deficits, monoamine reductions, and altered magnetic resonance spectroscopy findings. Animal models have been used to investigate some of these effects, however many of these experiments have not examined the impact of MA on the stress response. For example, numerous studies have demonstrated (+-MA-induced neurotoxicity and monoamine reductions, however the effects of MA on other markers that may play a role in neurotoxicity or cell energetics such as glucose, corticosterone, and/or creatine have received less attention. In this experiment, the effects of a neurotoxic regimen of (+-MA (4 doses at 2 h intervals on brain monoamines, neostriatal GFAP, plasma corticosterone, creatinine, and glucose, and brain and muscle creatine were evaluated 1, 7, 24, and 72 h after the first dose. In order to compare MA's effects with stress, animals were subjected to a forced swim test in a temporal pattern similar to MA administration [i.e., (30 min/session 4 times at 2 h intervals]. Results MA increased corticosterone from 1–72 h with a peak 1 h after the first treatment, whereas glucose was only increased 1 h post-treatment. Neostriatal and hippocampal monoamines were decreased at 7, 24, and 72 h, with a concurrent increase in GFAP at 72 h. There was no effect of MA on regional brain creatine, however plasma creatinine was increased during the first 24 h and decreased by 72 h. As with MA treatment, forced swim increased corticosterone more than MA initially. Unlike MA, forced swim reduced creatine in the cerebellum with no change in other brain regions while plasma creatinine was decreased at 1 and 7 h. Glucose in plasma was decreased at 7 h. Conclusion Both MA and forced swim increase demand on energy substrates but in different ways, and MA has persistent effects on corticosterone that are not attributable to stress alone.

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  9. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Quantification of adenosine triphosphate, adenosine diphosphate, and creatine phosphate in sterlet spermatozoa during maturation.

    Science.gov (United States)

    Fedorov, P; Dzyuba, B; Fedorova, G; Grabic, R; Cosson, J; Rodina, M

    2015-11-01

    Sturgeon spermatozoa maturation during their passage through the kidney is a prerequisite for initiation of motility. Samples of sterlet () testicular sperm (TS) were matured in vitro by incubation in seminal fluid (SF) or in SF supplemented with carbonyl cyanide -chlorophenyl hydrazone (CCCP; a respiration uncoupling agent). Sperm was diluted in activation medium (AM) containing 10 m Tris-HCl buffer (pH 8.5) and 0.25% Pluronic, and spermatozoon motility was assessed. Samples were taken and fixed in 3 perchloric acid at 3 points in the incubation process. Quantification of ATP, ADP, and creatine phosphate (CrP) was conducted using liquid chromatography/high-resolution mass spectrometry. We observed a significant decrease in CrP during artificial maturation of TS in SF. In contrast, ATP and ADP were not significantly affected. Addition of CCCP to SF halted maturation and led to significantly lower CrP whereas ADP significantly increased and ATP was unaffected. Dilution of matured and immature TS with AM led to a significant decrease of ATP and CrP and an increase of ADP compared with their levels before dilution, although immature TS were not motile. Energy dependency of TS maturation in sturgeon was confirmed, which suggests that mitochondrial oxidative phosphorylation is needed for maturation of sturgeon TS. PMID:26641041

  12. Effect of in-season creatine supplementation on body composition and performance in rugby union football players.

    Science.gov (United States)

    Chilibeck, Philip D; Magnus, Charlene; Anderson, Matthew

    2007-12-01

    Rugby union football requires muscular strength and endurance, as well as aerobic endurance. Creatine supplementation may enhance muscular performance, but it is unclear if it would interfere with aerobic endurance during running because of increased body mass. The purpose of this study was to determine if creatine supplementation during 8 weeks of a season of rugby union football can increase muscular performance, without negatively affecting aerobic endurance. Rugby union football players were randomized to receive 0.1 g.kg(-1).d(-1) creatine monohydrate (n=9) or placebo (n=9) during 8 weeks of the rugby season. Players practiced twice per week for approximately 2 h per session and played one 80 min game per week. Before and after the 8 weeks, players were measured for body composition (air displacement plethysmography), muscular endurance (number of repetitions at 75% of one repetition maximum (1 RM) for bench press and leg press), and aerobic endurance (Leger shuttle-run test with 1 min stages of progressively increasing speed). There were time main effects for body mass (-0.7+/-0.4 kg; p=0.05), fat mass (-1.9+/-0.8 kg; prugby union football season is effective for increasing muscular endurance, but has no effect on body composition or aerobic endurance.

  13. Formation of mutagenic heterocyclic aromatic amines in fried pork from Duroc and Landrace pigs upon feed supplementation with creatine monohydrate.

    Science.gov (United States)

    Pfau, Wolfgang; Rosenvold, Katja; Young, Jette F

    2006-12-01

    Heterocyclic aromatic amines (HAA) have been shown to induce tumours at various organ sites in experimental animal studies and high levels of dietary intake of HAA have been associated with increased cancer risk in humans. These HAA are formed in meat upon heating from precursors such as amino acids, reducing sugars and creatine or creatinine. Groups of ten Duroc and ten Landrace pigs received feed supplemented with creatine monohydrate (CMH) for five days prior to slaughter at dose levels of 12.5, 25 and 50 g per animal per day. Ten control animals of each breed received the non-supplemented feed. Meat from Duroc pigs had been shown to respond to CMH supplementation with regard to waterholding capacity, juiciness, post slaughter pH and colour parameters, meat from Landrace pigs was unaffected. Indeed, while creatine phosphate levels in meat from Duroc pigs increased in a dose-dependent manner with CMH supplementation, no effect was observed in meat from Landrace pigs. Meat slices from longissimus dorsi were fried and considerable mutagenic activity was detected in meat extracts in Salmonella typhimurium YG1019 in the presence of rat-liver homogenate. However, no effect of breed or CMH supplementation was observed in fried pork on the formation of HAA determined as mutagenic activity. It may be concluded that feed supplementation with CMH at levels up to 50 g per day for five days prior to slaughter does not increase the level of heterocyclic aromatic amines detected as mutagenic activity formed upon frying of pork.

  14. 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....

  15. 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.; C. SANDT; 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 ...

  16. 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.

  17. 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.

  18. 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

  19. Blockades of mitogen-activated protein kinase and calcineurin both change fibre-type markers in skeletal muscle culture

    DEFF Research Database (Denmark)

    Higginson, James; Wackerhage, Henning; Woods, Niall;

    2002-01-01

    Activation of either the calcineurin or the extracellular signal-regulated kinase (ERK1/2) pathway increases the percentage of slow fibres in vivo suggesting that both pathways can regulate fibre phenotypes in skeletal muscle. We investigated the effect of calcineurin blockade with cyclosporin...... increases in the activities of both lactate dehydrogenase and creatine kinase above control values were also seen following cyclosporin A treatment. In conclusion, the results suggest that calcineurin upregulates slow-fibre genes and suppresses fast-fibre genes. Similarly, the ERK1/2 pathway upregulates...... slow-fibre MHC and suppresses fast-fibre MHC isoforms. However, the effect on enzyme activities is not fibre-type specific. The effect of U0126 on the percentage of pyruvate dehydrogenase in the active form suggests that the ERK1/2 pathway may also be involved in regulation of the phosphorylation state...

  20. Pyruvate Dehydrogenase Kinase 4

    OpenAIRE

    Cadoudal, Thomas; Distel, Emilie; Durant, Sylvie; Fouque, Françoise; Blouin, Jean-Marc; Collinet, Martine; Bortoli, Sylvie; Forest, Claude; Benelli, Chantal

    2008-01-01

    OBJECTIVE—Pyruvate dehydrogenase complex (PDC) serves as the metabolic switch between glucose and fatty acid utilization. PDC activity is inhibited by PDC kinase (PDK). PDC shares the same substrate, i.e., pyruvate, as glyceroneogenesis, a pathway controlling fatty acid release from white adipose tissue (WAT). Thiazolidinediones activate glyceroneogenesis. We studied the regulation by rosiglitazone of PDK2 and PDK4 isoforms and tested the hypothesis that glyceroneogenesis could be controlled ...

  1. 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.

  2. Cyclin-dependent kinases.

    Science.gov (United States)

    Malumbres, Marcos

    2014-01-01

    Cyclin-dependent kinases (CDKs) are protein kinases characterized by needing a separate subunit - a cyclin - that provides domains essential for enzymatic activity. CDKs play important roles in the control of cell division and modulate transcription in response to several extra- and intracellular cues. The evolutionary expansion of the CDK family in mammals led to the division of CDKs into three cell-cycle-related subfamilies (Cdk1, Cdk4 and Cdk5) and five transcriptional subfamilies (Cdk7, Cdk8, Cdk9, Cdk11 and Cdk20). Unlike the prototypical Cdc28 kinase of budding yeast, most of these CDKs bind one or a few cyclins, consistent with functional specialization during evolution. This review summarizes how, although CDKs are traditionally separated into cell-cycle or transcriptional CDKs, these activities are frequently combined in many family members. Not surprisingly, deregulation of this family of proteins is a hallmark of several diseases, including cancer, and drug-targeted inhibition of specific members has generated very encouraging results in clinical trials. PMID:25180339

  3. 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

  4. Comparison of creatine monohydrate and carbohydrate supplementation on repeated jump height performance.

    Science.gov (United States)

    Koenig, Chad A; Benardot, Dan; Cody, Mildred; Thompson, Walter R

    2008-07-01

    Creatine monohydrate (CrMH) supplementation aids the ability to maintain performance during repeated bouts of high-intensity exercise, including jump performance. However, carbohydrate supplementation may also provide similar benefits and is less expensive. This study compared the effects of an energy-free placebo, 2 different caloric concentrations of carbohydrate drinks, and a CrMH supplement on repeated jump heights. Sixty active males (mean age, 22 +/- 3.2 years) performed 2 sets of countermovement static jump height tests (10 jumps over 60 seconds) separated by 5 days to determine the differential effects of the placebo, carbohydrate, and CrMH on jump height sustainability over 10 jumps. Subjects were randomly assigned to groups (15 subjects per group) to receive daily doses (x5 days) of carbohydrate drinks containing 100 or 250 kilocalories (kcal), a 25-g CrMH supplement, or an energy-free placebo. After 5 days, the CrMH group experienced a significant weight gain (+1.52; +/-0.89 kg, p energy-free placebo over the final 3-4 jumps. The 250-kcal carbohydrate-supplemented group experienced a level of benefit (p < 0.01) that was at least equal to that of the CrMH group (p < 0.05), suggesting that the higher dose of carbohydrate was as effective as CrMH in maintaining repeated bouts of high-intensity activity as measured by repeated static jumps. Given the equivalent performance improvement and the absence of weight gain, the carbohydrate supplementation could be considered the preferred option for weight-conscious power athletes involved in activities that require repeated- motion high-intensity activities.

  5. 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

  6. Regulation of Autophagy by Kinases

    Energy Technology Data Exchange (ETDEWEB)

    Sridharan, Savitha; Jain, Kirti; Basu, Alakananda, E-mail: alakananda.basu@unthsc.edu [Department of Molecular Biology and Immunology, Institute for Cancer Research, University of North Texas Health Science Center, Fort Worth, TX 76107 (United States)

    2011-06-09

    Autophagy is a process of self-degradation that maintains cellular viability during periods of metabolic stress. Although autophagy is considered a survival mechanism when faced with cellular stress, extensive autophagy can also lead to cell death. Aberrations in autophagy are associated with several diseases, including cancer. Therapeutic exploitation of this process requires a clear understanding of its regulation. Although the core molecular components involved in the execution of autophagy are well studied there is limited information on how cellular signaling pathways, particularly kinases, regulate this complex process. Protein kinases are integral to the autophagy process. Atg1, the first autophagy-related protein identified, is a serine/threonine kinase and it is regulated by another serine/threonine kinase mTOR. Emerging studies suggest the participation of many different kinases in regulating various components/steps of this catabolic process. This review focuses on the regulation of autophagy by several kinases with particular emphasis on serine/threonine protein kinases such as mTOR, AMP-activated protein kinase, Akt, mitogen-activated protein kinase (ERK, p38 and JNK) and protein kinase C that are often deregulated in cancer and are important therapeutic targets.

  7. 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.

  8. Bacterial Protein-Tyrosine Kinases

    DEFF Research Database (Denmark)

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

    2010-01-01

    in exopolysaccharide production, virulence, DNA metabolism, stress response and other key functions of the bacterial cell. BY-kinases act through autophosphorylation (mainly in exopolysaccharide production) and phosphorylation of other proteins, which have in most cases been shown to be activated by tyrosine......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...... and highlighted their importance in bacterial physiology. Having no orthologues in Eukarya, BY-kinases are receiving a growing attention from the biomedical field, since they represent a particularly promising target for anti-bacterial drug design....

  9. Map kinases in fungal pathogens.

    Science.gov (United States)

    Xu, J R

    2000-12-01

    MAP kinases in eukaryotic cells are well known for transducing a variety of extracellular signals to regulate cell growth and differentiation. Recently, MAP kinases homologous to the yeast Fus3/Kss1 MAP kinases have been identified in several fungal pathogens and found to be important for appressorium formation, invasive hyphal growth, and fungal pathogenesis. This MAP kinase pathway also controls diverse growth or differentiation processes, including conidiation, conidial germination, and female fertility. MAP kinases homologous to yeast Slt2 and Hog1 have also been characterized in Candida albicans and Magnaporthe grisea. Mutants disrupted of the Slt2 homologues have weak cell walls, altered hyphal growth, and reduced virulence. The Hog1 homologues are dispensable for growth but are essential for regulating responses to hyperosmotic stress in C. albicans and M. grisea. Overall, recent studies have indicated that MAP kinase pathways may play important roles in regulating growth, differentiation, survival, and pathogenesis in fungal pathogens. PMID:11273677

  10. 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...

  11. 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...

  12. 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

  13. 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.

  14. 精神运动性兴奋对血清肌酸激酶活性的影响%Effect of psychomotor excitement on serum creatine kinase

    Institute of Scientific and Technical Information of China (English)

    路伟; 金通观

    2010-01-01

    @@ 肌酸激酶(CK)主要存在于骨骼肌(MM型)、心肌(MB型),少量(BB型)存在于脑、胎盘、甲状腺[1].有研究显示精神分裂症患者处于精神运动性兴奋时,血清CK显著升高[2].本研究探讨精神运动性兴奋和血清CK间关系.

  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. 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

  18. Creatine Deficiency Syndrome could be Missed Easily: A Case Report of Guanidinoacetate Methyltransferase Deficiency Presented with Neurodevelopmental Delay, Seizures, and Behavioral Changes, but Normal Structural MRI.

    Science.gov (United States)

    Pacheva, Iliyana; Ivanov, Ivan; Penkov, Marin; Kancheva, Daliya; Jordanova, Albena; Ivanova, Mariya

    2016-09-01

    A case with GAMT deficiency (homozygous c.64dupG mutation) presented with neurodevelopmental delay, rare seizures, behavioral disturbances, and mild hypotonia, posing diagnostic challenges. Metabolic investigations showed low creatinine in plasma and urine (guanidinoacetate couldn't be investigated) and slightly elevated lactate. MRI was normal. Correct diagnosis was possible only after MR spectroscopy was performed at age 5½ years. A homozygous c.64dupG mutation of the GAMT gene was identified in the proband. In conclusion, every case with neurodevelopmental delay or arrest, especially when accompanied by seizures, behavioral impairment, muscle hypotonia or extrapyramidal symptoms should undergo MRI with MR spectroscopy. Normal structural MRI doesn't exclude a creatine deficiency syndrome. Biochemical investigations of guanidinoacetate, creatine, and creatinine in body fluid should be done to diagnose cerebral creatine deficiency syndromes and to specify the deficient enzyme. Thus, a treatable disease will not be missed. PMID:27650626

  19. 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

  20. 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.

  1. MAP Kinases in Immune Responses

    Institute of Scientific and Technical Information of China (English)

    YongliangZhang; ChenDong

    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. Cellular & Molecular Immunology. 2005;2(1):20-27.

  2. Effect of minimized perfusion circuit on brain injury markers carnosinase and brain-type fatty binding protein in coronary artery bypass grafting patients.

    Science.gov (United States)

    Pahari, Dipak R; Gu, Y John; van Oeveren, Willem; El-Essawi, Aschraf; Harringer, Wolfgang; Brouwer, René M H

    2013-02-01

    A minimized perfusion circuit (MPC) has proven to be superior to the conventional circulatory perfusion bypass (CCPB) as it reduces the blood-material interaction and hemodilution. Until now not much is known about impact these different perfusion systems have on the brain. The objective of this study is to determine carnosinase and brain-type fatty binding protein (BFABP) activity as novel specific biomarkers for ischemic brain tissue damage and how their activity differs during and after MPC and CCPB as well as to compare the inflammatory response of both perfusion systems. In a prospective pilot study, 28 patients undergoing coronary artery bypass grafting were randomly divided into an MPC group (n = 14) and a CCPB group (n = 14). Blood samples were taken before, during, and after operation until the fifth postoperative day. The brain biomarker carnosinase was determined by measuring the rate of histidine production from the substrate homocarnosine, whereas BFABP and interleukin-6 were determined by enzyme-linked immunosorbent assay (ELISA). C-reactive protein (CRP) and endothelin-1 were determined by enzyme immunoassay. The mean serum carnosinase activity was significantly higher in MPC (0.57 ± 0.34 nM histidine/mL/min) as compared with the CCPB group (0.36 ± 0.13 nM histidine/mL/min) at the end of operation (P = 0.02). The BFABP did not show any difference between the two groups in the immediate postoperative period until the second postoperative day. From that time point onward, it showed a steep increase in the CCPB group (581.3 ± 157.11 pg/mL) as compared with the concentrations in the MPC group (384.6 ± 39 pg/mL) (P = 0.04). The inflammation markers interleukin-6 and CRP showed a similar pattern in both groups without significant difference. In contrast, the leukocyte count on operation day and endothelin-1 on the first postoperative day were significantly higher in the CCPB group (P = 0.01, P = 0

  3. Effect of creatine phosphate disodium on postoperative cognitive function under combined intravenous and volatile anesthesia in geriatric patients

    Directory of Open Access Journals (Sweden)

    Bao-sen JIA

    2016-08-01

    Full Text Available Objective  To explore the relationship of perioperative INVOS cerebral oxygen saturation (rSO2 and postoperative cognition function alteration of geriatric patients under combined intravenous and volatile anesthesia with creatine phosphate disodium to provide guidance for clinical anesthesia. Methods  Sixty ASA Ⅰ-Ⅱpatients aged >60 years scheduled for selective abdominal surgeries or surgeries on lower limb were enrolled in the study. The patients were randomly divided into 3 groups of 20 patients: creatine phosphate disodium group 1 (CPD1, creatine phosphate disodium group 2 (CPD2, control group (C. All the patients were not premedicated with atropine 0.5mg until entering the operation room. Anesthesia was induced with intravenous infusion of propofol, fentanyl and cisatracurium slowly, and maintained by inhalational anesthetics sevoflurane 1 MAC plus intravenous infusion of propofol (6-8mg•kg-1•min-1 and remifentanyl (0.2-0.4μg•kg-1•min-1, and intravenous bolus cisatracurium (0.07-0.10mg•kg-1. After tracheal intubation, all the patients were mechanically ventilated with PETCO2 in the normal range. rSO2 was continuously monitored and recorded during the operation. The Mini-Mental State Examination (MMSE, Trail-making Test and Grooved Pegboard Test were used to access cognitive function 24h before surgery and 4, 8, 12, 24h after surgery. Results  (1 There were no significant differences in general status between the three groups (P>0.05. (2 The scores of MMSE, Trail-making Test and Grooved Pegboard Test were not different 24h before the operation between the three groups (P>0.05. (3 The scores of cognitive tests were higher in group CPD2 and group CPD1 than in group C (P0.05. Conclusion  CPD can reduce the occurrence of postoperative cognitive dysfunction in geriatric patients under combined intravenous and inhalational anesthesia. DOI: 10.11855/j.issn.0577-7402.2016.07.11

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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:

  9. 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.

  10. 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.

  11. Alterations in creatine metabolism observed in experimental autoimmune myocarditis using ex vivo proton magic angle spinning MRS.

    Science.gov (United States)

    Muench, Frédéric; Retel, Joren; Jeuthe, Sarah; O h-Ici, Darach; van Rossum, Barth; Wassilew, Katharina; Schmerler, Patrick; Kuehne, Titus; Berger, Felix; Oschkinat, Hartmut; Messroghli, Daniel R

    2015-12-01

    Experimental autoimmune myocarditis (EAM) in rodents is an accepted model of myocarditis and dilated cardiomyopathy (DCM). Altered metabolism is thought to play an important role in the pathogenesis of DCM and heart failure (HF). Study of the metabolism may provide new diagnostic information and insights into the mechanisms of myocarditis and HF. Proton MRS ((1)H-MRS) has not yet been used to study the changes occurring in myocarditis and subsequent HF. We aimed to explore the changes in creatine metabolism using this model and compare them with the findings in healthy animals. Myocardial function of male young Lewis rats with EAM was quantified by performing left ventricular ejection fraction (LVEF) analysis in short-axis cine images throughout the whole heart. Inflammatory cellular infiltrate was assessed by immunohistochemistry. Myocardial tissue was analyzed using ex vivo proton magic angle spinning MRS ((1)H-MAS-MRS). Myocarditis was confirmed histologically by the presence of an inflammatory cellular infiltrate and CD68 positive staining. A significant increase in the metabolic ratio of Tau/tCr (taurine/total creatine) obtained by (1)H-MAS-MRS was observed in myocarditis compared with healthy controls (21 d acute EAM, 4.38 (±0.23); 21 d control, 2.84 (±0.08); 35 d chronic EAM, 4.47 (±0.83); 35 d control, 2.59 (±0.38); P < 0.001). LVEF was reduced in diseased animals (EAM, 55.2% (±11.3%); control, 72.6% (±3.8%); P < 0.01) and correlated with Tau/tCr ratio (R = 0.937, P < 0.001). Metabolic alterations occur acutely with the development of myocarditis. Myocardial Tau/tCr ratio as detected by (1)H-MRS correlates with LVEF and is able to differentiate between healthy myocardium and myocardium from rats with EAM.

  12. 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

  13. 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.

  14. O-Crystallin, arginine kinase and ferritin from the octopus lens.

    Science.gov (United States)

    Zinovieva, R D; Piatigorsky, J; Tomarev, S I

    1999-05-18

    Three proteins have been identified in the eye lens of the octopus, Octopus dofleini. A 22 kDa protein comprising 3-5% of the soluble protein of the lens is 35-43% identical to a family of phosphatidylethanolamine-binding proteins of vertebrates. Other members of this family include the immunodominant antigen of the filarial parasite, Onchocerca volvulus, putative odorant-binding proteins of Drosophila and a protein with unknown function of Caenorhabditis elegans. We have called this protein O-crystallin on the basis of its abundance in the transparent lens. O-Crystallin mRNA was detected only in the lens. Two tryptic peptides of another octopus lens protein, less abundant than O-crystallin, showed 80% identity to arginine kinase of invertebrates, a relative of creatine kinase of vertebrates. Finally, ferritin cDNA was isolated as an abundant cDNA from the octopus lens library. Northern blots showed that ferritin mRNA is not lens-specific. PMID:10350626

  15. Radiation-induced enzyme efflux from rat heart: sedentary animals. [Gamma radiation, lactate dehydrogenase, creative kinase, glutamate oxaloacetate transaminase

    Energy Technology Data Exchange (ETDEWEB)

    MacWilliam, L.D.; Bhakthan, N.M.G.

    1976-01-01

    Serum levels of lactate dehydrogenase, creatine kinase, and glutamate oxaloacetate transaminase show initial elevations within 12 hr of exposure to 2,000 rads of ..gamma..-radiation to the thoracic region of rats. Significant decreases in heart muscle homogenate levels of these enzymes parallel initial elevations in the serum and may suggest that enhanced leakage of enzymes is a consequence of radiation injury to heart muscle. Insignificant alterations in mitochondrial glutamate oxaloacetate transaminase levels after exposure indicate that in vivo injury to the mitochondria from therapeutic levels of ..gamma..-radiation is questionable. The results support the contention that ionizing radiation instigates alterations in the dynamic permeability of membranes, allowing leakage of biologically active material out of the injured cell.

  16. 磷酸肌酸钠复合氨甲环酸对非体外循环冠状动脉旁路移植术患者心肌和血液保护作用的研究%The myocardial and blood protectivie effects of creatine phosphate sodium combined with tranexamic acid in off-pump coronary artery bypass grafting

    Institute of Scientific and Technical Information of China (English)

    李长营; 郭爱华; 张宗旺; 张学俊; 张雷; 敖虎山

    2011-01-01

    Objective To investigate whether the supplement of creatine phosphate sodium and tranexamic acid to cardioplegic solutions can improve myocardial protection and blood conservation in off-pump coronary artery bypass graft(OPCABG).Methods 280 patients undergoing OPCABG were randomly assigned to experimental group (CP with TA group, n=70 ) , creatine phosphate sodium group (CP group, n=70), tranexamic acid group (TA group, n=70) and control group (n=70). Before BACG,creatine phosphate sodium ( 100 mg/kg) combined with tranexamic acid (30 mg/kg), creatine phosphate sodium ( 100 mg/kg),tranexamic acid (30 mg/kg), and equal volume of normal saline were given intravenously in each group respectively. Venous blood samples were taken preoperatively, and at 0, 6, 12, 24, 48, 72 h, 7 d postoperatively to analyze creatine kinase isoenzyme (CK-MB), troponin (cTnI) ; Meanwhile, the amount of cumulative chest fluid drainage and inotropic agent and blood transfused were also recorded. Results The plasma concentrations of CK-MB in experimental group at 6, 12, 24, 48, 72 h postoperatively (15±6), (14±5), (16±10), (15±6) and (13±6) U/ml and the plasma concentrations of cTnI(235±1.53), (2.72±1.46), (2.64±1.32),(1.16±0.76) and (0.48±0.24) mg/L were significantly lower than those in group CP, group TA and control group (P<0.05). The amount of postoperative cumulative chest fluid at 6, 12, 24, 48, 72 h were (246±56), (420±82), (680±114), (725±126) and (730±130) ml drainage and blood transfuison in experimental group (5/70) were also significantly lower than those in other groups (P<0.05). Conclusion For patients undergoing OPCABG, creatine phosphate sodium combined with tranexamic acid plays an important role in myocardial protection and blood conservation without increasing the surgical mortality and the incidence of postoperative complications.%目的 研究在非体外循环下行冠状动脉旁路移植术(off-pump coronary artery bypass grafting,OPCABG)中应用

  17. 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.

  18. EFFECT OF CREATINE SUPPLEMENTATION ON MUSCLE DAMAGE AND REPAIR FOLLOWING ECCENTRICALLY-INDUCED DAMAGE TO THE ELBOW FLEXOR MUSCLES

    Directory of Open Access Journals (Sweden)

    Neal B. McKinnon

    2012-12-01

    Full Text Available We investigated effects of creatine (Cr supplementation (CrS on exercise-induced muscle damage. Untrained males and females (N = 27 ages 18-25, with no CrS history in the past 4 months, were randomly assigned to CrS (creatine and carbohydrate (n = 9, placebo (P (carbohydrate only (n = 9, or control (C (no supplements groups (n = 9. Participants followed a 5-day Cr loading protocol of 40 g·day-1, divided for 5 days prior to exercise, reduced to 10 g g·day-1 for 5 days following exercise. Testing consisted of 5 maximal isometric contractions at 90 arm flexion with the preferred arm on a CYBEX NORM dynamometer, assessed prior to, immediately following, and 24, 48, 72, and 96 hours post muscle-damaging procedures. Damage was induced to the elbow flexor muscles using 6 sets of 10 eccentric contractions at 75 °/sec, 90 °/sec and 120 °/sec. Participants were asked to rate their muscle soreness on a scale of 1-10. Data was analyzed using repeated-measures ANOVA, with an alpha of 0.05. No significant differences were found between muscle force loss and rate of recovery or muscle soreness between groups over the 96 hr recovery period (p > 0.05. Across all 3 experimental groups an initial decrease in force was observed, followed by a gradual recovery. Significant differences were found between baseline and all others times (p = 0.031,0 .022, 0.012, 0.001 respectively, and between the 48 hour and 96 hour time periods (p = 0.034. A weak negative correlation between subjectively rated muscle soreness and mean peak isometric force loss (R2 = 0.0374 at 96 hours, suggested that muscle soreness and muscle force loss may not be directly related. In conclusion, 5 days of Cr loading, followed by a Cr maintenance protocol did not reduce indices of muscle damage or speed recovery of upper body muscles following eccentrically induced muscle damage

  19. 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...... in anti-cancer therapy....

  20. 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]....

  1. 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

  2. Renal targeting of kinase inhibitors

    NARCIS (Netherlands)

    Dolman, M. E. M.; Fretz, M. M.; Segers, Gj. W.; Lacombe, M.; Prakash, J.; Storm, G.; Hennink, W. E.; Kok, R. J.

    2008-01-01

    Activation of proximal tubular cells by fibrotic and inflammatory mediators is an important hallmark of chronic kidney disease. We have developed a novel strategy to intervene in renal fibrosis, by means of locally delivered kinase inhibitors. Such compounds will display enhanced activity within tub

  3. Inhibitors of protein kinase C

    Institute of Scientific and Technical Information of China (English)

    LIU Shiying; JIANG Yuyang; CAO Jian; LIU Feng; MA Li; ZHAO Yufen

    2005-01-01

    Protein kinase catalyzes the transfer of the γ-phosphoryl group from ATP to the hydroxyl groups of protein side chains, which plays critical roles in signal transduction pathways by transmitting extracellular signals across the plasma membrane and nuclear membrane to the destination sites in the cytoplasm and the nucleus. Protein kinase C (PKC) is a superfamily of phospholipid-dependent Ser/Thr kinase. There are at least 12 isozymes in PKC family. They are distributed in different tissues and play different roles in physiological processes. On account of their concern with a variety of pathophysiologic states, such as cancer, inflammatory conditions, autoimmune disorder, and cardiac diseases, the inhibitors, which can inhibit the activity of PKC and the interaction of cytokine with receptor, and interfere signal transduction pathway, may be candidates of therapeutic drugs. Therefore, intense efforts have been made to develop specific protein kinase inhibitors as biological tools and therapeutic agents. This article reviews the recent development of some of PKC inhibitors based on their interaction with different conserved domains and different inhibition mechanisms.

  4. 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.

  5. 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...

  6. 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.

  7. 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...

  8. 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

  9. 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...

  10. 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.

  11. 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 ...

  12. 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.

  13. 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

  14. 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

  15. 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

  16. Endocytosis of Receptor Tyrosine Kinases

    Science.gov (United States)

    Goh, Lai Kuan

    2013-01-01

    Endocytosis is the major regulator of signaling from receptor tyrosine kinases (RTKs). The canonical model of RTK endocytosis involves rapid internalization of an RTK activated by ligand binding at the cell surface and subsequent sorting of internalized ligand-RTK complexes to lysosomes for degradation. Activation of the intrinsic tyrosine kinase activity of RTKs results in autophosphorylation, which is mechanistically coupled to the recruitment of adaptor proteins and conjugation of ubiquitin to RTKs. Ubiquitination serves to mediate interactions of RTKs with sorting machineries both at the cell surface and on endosomes. The pathways and kinetics of RTK endocytic trafficking, molecular mechanisms underlying sorting processes, and examples of deviations from the standard trafficking itinerary in the RTK family are discussed in this work. PMID:23637288

  17. 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.

  18. Thymidine kinase diversity in bacteria

    DEFF Research Database (Denmark)

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

    2006-01-01

    Thymidine kinases (TKs) appear to be almost ubiquitous and are found in nearly all prokaryotes, eukaryotes, and several viruses. They are the key enzymes in thymidine salvage and activation of several anti-cancer and antiviral drugs. We show that bacterial TKs can be subdivided into 2 groups. The....... The TKs from Gram-positive bacteria are more closely related to the eukaryotic TK1 enzymes than are TKs from Gram-negative bacteria....

  19. 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...

  20. 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.

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

    Science.gov (United States)

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

    2002-11-01

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

  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. 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.

  6. Study on intelligence level and intelligence structure in brain type patients with Wilson's disease%脑型Wilson病患者智力水平及智力结构的研究

    Institute of Scientific and Technical Information of China (English)

    李波; 王共强; 韩咏竹; 韩永升; 马心峰

    2014-01-01

    Objective Through conducting neuropsychological test to evaluate crystallized intelligence and fluid intelligence of brain type patients with Wilson's disease ( WD) ,to analyze the characteristics of intelligence structure changing and other related factors .Methods Wechsler intelligence test and Raven's standard progressive matrices ( R'SPM) were conducted among 32 brain type WD patients ,in order to assess crystallized intelligence and fluid intelligence .The diversities of patients crystallized intelligence , fluid intelligence and other related factors were analysed by using SPSS 11.5 software.Results 43.75%brain type WD patients showed a decrease in crystallized intelligence while 78.13%patients showed fluid intelligence drop .Moreover,Raven's standard progressive matrices intelligence quotient (RWIQ) ranking was significantly less than full measuring scale intelligence quotient (FIQ) (P0.05).Conclusion Brain type WD pa-tients'intelligence structure has unbalanced damage ,and fluid intelligence decreases more obviously than crystallized intelligence .The fluid in-telligence and crystallized intelligence cannot replace with each other .%目的:通过神经心理学测验评估脑型Wilson病(Wilson's disease,WD)患者晶体智力和流体智力水平,探讨其智力结构变化的特点及相关因素。方法选取32例脑型WD患者为研究对象,采用韦氏智力量表、瑞文标准推理测验( R′SPM )进行晶体智力和流体智力测评,运用SPSS 11.5软件分析患者的晶体智力、流体智力变化及相关因素。结果43.75%脑型WD患者晶体智力水平下降,78.13%脑型WD患者流体智力水平下降,瑞文标准推理测验智商(RWIQ)得分低于韦氏智力测定全量表智商(FIQ)得分(P<0.05);韦氏智力测定言语量表智商(VIQ)、韦氏智力测定操作量表智商(PIQ)与FIQ呈正相关(P<0.05),瑞文标准推理测验E分测验(RWE)

  7. 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

  8. 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...

  9. 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....

  10. Protein Kinase D family kinases: roads start to segregate.

    Science.gov (United States)

    Wille, Christoph; Seufferlein, Thomas; Eiseler, Tim

    2014-01-01

    Highly invasive pancreatic tumors are often recognized in late stages due to a lack of clear symptoms and pose major challenges for treatment and disease management. Broad-band Protein Kinase D (PKD) inhibitors have recently been proposed as additional treatment option for this disease. PKDs are implicated in the control of cancer cell motility, angiogenesis, proliferation and metastasis. In particular, PKD2 expression is elevated in pancreatic cancer, whereas PKD1 expression is comparably lower. In our recent study we report that both kinases control PDAC cell invasive properties in an isoform-specific, but opposing manner. PKD1 selectively mediates anti-migratory/anti-invasive features by preferential regulation of the actin-regulatory Cofilin-phosphatase Slingshot1L (SSH1L). PKD2, on the other hand enhances invasion and angiogenesis of PDAC cells in 3D-ECM cultures and chorioallantois tumor models by stimulating expression and secretion of matrix-metalloproteinase 7 and 9 (MMP7/9). MMP9 also enhances PKD2-mediated tumor angiogenesis releasing extracellular matrix-bound VEGF-A. We thus suggest high PKD2 expression and loss of PKD1 may be beneficial for tumor cells to enhance their matrix-invading abilities. In our recent study we demonstrate for the first time PKD1 and 2 isoform-selective effects on pancreatic cancer cell invasion, in-vitro and in-vivo, defining isoform-specific regulation of PKDs as a major future issue. PMID:24847910

  11. 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...

  12. 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.

  13. MAP kinases and histone modification

    Institute of Scientific and Technical Information of China (English)

    Tamaki Suganuma; Jerry L. Workman

    2012-01-01

    Signal transduction pathways alter the gene expression program in response to extracellular or intracellular cues.Mitogen-activated protein kinases (MAPKs) govern numerous cellular processes including cell growth,stress response,apoptosis,and differentiation.In the past decade,MAPKs have been shown to regulate the transcription machinery and associate with chromatin-modifying complexes.Moreover,recent studies demonstrate that several MAPKs bind directly to chromatin at target genes.This review highlights the recent discoveries of MAPK signaling in regard to histone modifications and chromatin regulation.Evidence suggesting that further unknown mechanisms integrate signal transduction with chromatin biology is discussed.

  14. 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...

  15. Protein kinase profiling assays: a technology review.

    Science.gov (United States)

    Wang, Yuren; Ma, Haiching

    2015-11-01

    Protein kinases have become one of the most intensively pursued classes of drug targets for many diseases such as cancers and inflammatory diseases. Kinase profiling work seeks to understand general selectivity trends of lead compounds across the kinome, which help with target selection, compound prioritization, and potential implications in toxicity. Under the current drug discovery process, screening of compounds against comprehensive panels of kinases and their mutants has become the standard approach. Many screening assays and technologies which are compatible for high-throughput screening (HTS) against kinases have been extensively pursued and developed.

  16. 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...... as visualized by magnetic resonance imaging. For quantification, the unsaturated water signal was used as the internal standard. Regional cerebral blood flow in the infarcted area was measured relative to a symmetrically located unaffected area by means of single-photon emission computed tomographic scanning...

  17. 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.

  18. 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 ...

  19. 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

  20. 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.

  1. 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 ...

  2. 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....

  3. 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

  4. 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

  5. Novel Library of Selenocompounds as Kinase Modulators

    Directory of Open Access Journals (Sweden)

    Carmen Sanmartín

    2011-07-01

    Full Text Available Although the causes of cancer lie in mutations or epigenic changes at the genetic level, their molecular manifestation is the dysfunction of biochemical pathways at the protein level. The 518 protein kinases encoded by the human genome play a central role in various diseases, a fact that has encouraged extensive investigations on their biological function and three dimensional structures. Selenium (Se is an important nutritional trace element involved in different physiological functions with antioxidative, antitumoral and chemopreventive properties. The mechanisms of action for selenocompounds as anticancer agents are not fully understood, but kinase modulation seems to be a possible pathway. Various organosulfur compounds have shown antitumoral and kinase inhibition effects but, in many cases, the replacement of sulfur by selenium improves the antitumoral effect of compounds. Although Se atom possesses a larger atomic volume and nucleophilic character than sulfur, Se can also formed interactions with aminoacids of the catalytic centers of proteins. So, we propose a novel chemical library that includes organoselenium compounds as kinase modulators. In this study thirteen selenocompounds have been evaluated at a concentration of 3 or 10 µM in a 24 kinase panel using a Caliper LabChip 3000 Drug Discover Platform. Several receptor (EGFR, IGFR1, FGFR1… and non-receptor (Abl kinases have been selected, as well as serine/threonine/lipid kinases (AurA, Akt, CDKs, MAPKs… implicated in main cancer pathways: cell cycle regulation, signal transduction, angiogenesis regulation among them. The obtained results showed that two compounds presented inhibition values higher than 50% in at least four kinases and seven derivatives selectively inhibited one or two kinases. Furthermore, three compounds selectively activated IGF-1R kinase with values ranging from −98% to −211%. In conclusion, we propose that the replacement of sulfur by selenium seems to be

  6. A novel viral thymidylate kinase with dual kinase activity.

    Science.gov (United States)

    Guevara-Hernandez, Eduardo; Arvizu-Flores, Aldo A; Lugo-Sanchez, Maria E; Velazquez-Contreras, Enrique F; Castillo-Yañez, Francisco J; Brieba, Luis G; Sotelo-Mundo, Rogerio R

    2015-10-01

    Nucleotide phosphorylation is a key step in DNA replication and viral infections, since suitable levels of nucleotide triphosphates pool are required for this process. Deoxythymidine monophosphate (dTMP) is produced either by de novo or salvage pathways, which is further phosphorylated to deoxythymidine triphosphate (dTTP). Thymidyne monophosphate kinase (TMK) is the enzyme in the junction of both pathways, which phosphorylates dTMP to yield deoxythymidine diphosphate (dTDP) using adenosine triphosphate (ATP) as a phosphate donor. White spot syndrome virus (WSSV) genome contains an open reading frame (ORF454) that encodes a thymidine kinase and TMK domains in a single polypeptide. We overexpressed the TMK ORF454 domain (TMKwssv) and its specific activity was measured with dTMP and dTDP as phosphate acceptors. We found that TMKwssv can phosphorylate dTMP to yield dTDP and also is able to use dTDP as a substrate to produce dTTP. Kinetic parameters K M and k cat were calculated for dTMP (110 μM, 3.6 s(-1)), dTDP (251 μM, 0.9 s(-1)) and ATP (92 μM, 3.2 s(-1)) substrates, and TMKwssv showed a sequential ordered bi-bi reaction mechanism. The binding constants K d for dTMP (1.9 μM) and dTDP (10 μM) to TMKwssv were determined by Isothermal Titration Calorimetry. The affinity of the nucleotidic analog stavudine monophosphate was in the same order of magnitude (K d 3.6 μM) to the canonical substrate dTMP. These results suggest that nucleotide analogues such as stavudine could be a suitable antiviral strategy for the WSSV-associated disease.

  7. 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) ...

  8. 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.

  9. Aurora kinase inhibitors: current status and outlook

    Directory of Open Access Journals (Sweden)

    Vassilios eBavetsias

    2015-12-01

    Full Text Available The Aurora kinase family comprises of cell cycle-regulated serine/threonine kinases important for mitosis. Their activity and protein expression are cell cycle regulated, peaking during mitosis to orchestrate important mitotic processes including centrosome maturation, chromosome alignment, chromosome segregation and cytokinesis. In humans, the Aurora kinase family consists of three members; Aurora-A, Aurora-B and Aurora-C, that each share a conserved C-terminal catalytic domain but differ in their sub-cellular localization, substrate specificity and function during mitosis. In addition, Aurora-A and Aurora-B have been found to be overexpressed in a wide variety of human tumors. These observations led to a number of programs among academic and pharmaceutical organizations to discovering small molecule Aurora kinase inhibitors as anti-cancer drugs. This review will summarize the known Aurora kinase inhibitors currently in the clinic and the current and future directions.

  10. Selective regulation of MAP kinase signaling by an endomembrane phosphatidylinositol 4-kinase.

    Science.gov (United States)

    Cappell, Steven D; Dohlman, Henrik G

    2011-04-29

    Multiple MAP kinase pathways share components yet initiate distinct biological processes. Signaling fidelity can be maintained by scaffold proteins and restriction of signaling complexes to discreet subcellular locations. For example, the yeast MAP kinase scaffold Ste5 binds to phospholipids produced at the plasma membrane and promotes selective MAP kinase activation. Here we show that Pik1, a phosphatidylinositol 4-kinase that localizes primarily to the Golgi, also regulates MAP kinase specificity but does so independently of Ste5. Pik1 is required for full activation of the MAP kinases Fus3 and Hog1 and represses activation of Kss1. Further, we show by genetic epistasis analysis that Pik1 likely regulates Ste11 and Ste50, components shared by all three MAP kinase pathways, through their interaction with the scaffold protein Opy2. These findings reveal a new regulator of signaling specificity functioning at endomembranes rather than at the plasma membrane. PMID:21388955

  11. 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...

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. Src family protein tyrosine kinases induce autoactivation of Bruton's tyrosine kinase.

    OpenAIRE

    Mahajan, S.; Fargnoli, J.; Burkhardt, A L; Kut, S A; Saouaf, S J; Bolen, J B

    1995-01-01

    Bruton's tyrosine kinase (Btk) is tyrosine phosphorylated and enzymatically activated following ligation of the B-cell antigen receptor. These events are temporally regulated, and Btk activation follows that of various members of the Src family of protein tyrosine kinases, thus raising the possibility that Src kinases participate in the Btk activation process. We have evaluated the mechanism underlying Btk enzyme activation and have explored the potential regulatory relationship between Btk a...

  20. The Crystal Structure of Cancer Osaka Thyroid Kinase Reveals an Unexpected Kinase Domain Fold*

    Science.gov (United States)

    Gutmann, Sascha; Hinniger, Alexandra; Fendrich, Gabriele; Drückes, Peter; Antz, Sylvie; Mattes, Henri; Möbitz, Henrik; Ofner, Silvio; Schmiedeberg, Niko; Stojanovic, Aleksandar; Rieffel, Sebastien; Strauss, André; Troxler, Thomas; Glatthar, Ralf; Sparrer, Helmut

    2015-01-01

    Macrophages are important cellular effectors in innate immune responses and play a major role in autoimmune diseases such as rheumatoid arthritis. Cancer Osaka thyroid (COT) kinase, also known as mitogen-activated protein kinase kinase kinase 8 (MAP3K8) and tumor progression locus 2 (Tpl-2), is a serine-threonine (ST) kinase and is a key regulator in the production of pro-inflammatory cytokines in macrophages. Due to its pivotal role in immune biology, COT kinase has been identified as an attractive target for pharmaceutical research that is directed at the discovery of orally available, selective, and potent inhibitors for the treatment of autoimmune disorders and cancer. The production of monomeric, recombinant COT kinase has proven to be very difficult, and issues with solubility and stability of the enzyme have hampered the discovery and optimization of potent and selective inhibitors. We developed a protocol for the production of recombinant human COT kinase that yields pure and highly active enzyme in sufficient yields for biochemical and structural studies. The quality of the enzyme allowed us to establish a robust in vitro phosphorylation assay for the efficient biochemical characterization of COT kinase inhibitors and to determine the x-ray co-crystal structures of the COT kinase domain in complex with two ATP-binding site inhibitors. The structures presented in this study reveal two distinct ligand binding modes and a unique kinase domain architecture that has not been observed previously. The structurally versatile active site significantly impacts the design of potent, low molecular weight COT kinase inhibitors. PMID:25918157

  1. 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

  2. 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.

  3. 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 ...

  4. 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 ...

  5. 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.

  6. 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....... In the younger age group, the concentration of NAA was significantly higher in the occipital part than in the other three parts of the brain. No significant regional variation was found for any other metabolite concentration. There was a significantly higher concentration of NAA in the occipital part...... of the brain in the younger age group compared to the older one. No significant regional or age dependent variation was found concerning the T1 and T2 relaxation times....

  7. 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

  8. 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.)

  9. 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

  10. A Molecular Brake in the Kinase Hinge Region Regulates the Activity of Receptor Tyrosine Kinases

    Energy Technology Data Exchange (ETDEWEB)

    Chen,H.; Ma, J.; Li, W.; Eliseenkova, A.; Xu, C.; Neubert, T.; Miller, W.; Mohammadi, M.

    2007-01-01

    Activating mutations in the tyrosine kinase domain of receptor tyrosine kinases (RTKs) cause cancer and skeletal disorders. Comparison of the crystal structures of unphosphorylated and phosphorylated wild-type FGFR2 kinase domains with those of seven unphosphorylated pathogenic mutants reveals an autoinhibitory 'molecular brake' mediated by a triad of residues in the kinase hinge region of all FGFRs. Structural analysis shows that many other RTKs, including PDGFRs, VEGFRs, KIT, CSF1R, FLT3, TEK, and TIE, are also subject to regulation by this brake. Pathogenic mutations activate FGFRs and other RTKs by disengaging the brake either directly or indirectly.

  11. 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

  12. 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...

  13. 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...

  14. 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

  15. 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

  16. Tyrosine kinase inhibitors in hematological malignancies

    Directory of Open Access Journals (Sweden)

    Kamila Kosior

    2011-12-01

    Full Text Available Recently novel treatment modalities has focused on targeted therapies. Tyrosine kinases represent a good target for cancer treatment since they are involved in transferring phosphate groups from ATP to tyrosine residues in specific substrate proteins transducing intracellular signals engaged in the many mechanisms, playing an important role in the modulation of growth factors signaling that are strongly related to carcinogenesis. Deregulation of tyrosine kinases activity was also found in hematological malignancies, particularly overexpression of tyrosine kinases was observed in chronic myeloid leukemia or acute lymphoblastic leukemia. Herein we show that tyrosine kinase inhibitors have revolutionized hematology malignancies therapy in a very short period of time and they still remain one of the most interesting anticancer compounds that could give a hope for cure and not only long-lasting complete remission. This manuscript summarizes current view on the first generation tyrosine kinase inhibititor – imatinib, second generation – dasatinib, nilotinib and bosutnib as well as new generation tyrosine kinase inhibititors – ponatinib and danusertib in hematooncology.

  17. Fibronectin phosphorylation by ecto-protein kinase

    Energy Technology Data Exchange (ETDEWEB)

    Imada, Sumi; Sugiyama, Yayoi; Imada, Masaru (Meiji Institute of Health Science, Odawara (Japan))

    1988-12-01

    The presence of membrane-associated, extracellular protein kinase (ecto-protein kinase) and its substrate proteins was examined with serum-free cultures of Swiss 3T3 fibroblast. When cells were incubated with ({gamma}-{sup 32})ATP for 10 min at 37{degree}C, four proteins with apparent molecular weights between 150 and 220 kDa were prominently phosphorylated. These proteins were also radiolabeled by lactoperoxidase catalyzed iodination and were sensitive to mild tryptic digestion, suggesting that they localized on the cell surface or in the extracellular matrix. Phosphorylation of extracellular proteins with ({gamma}-{sup 32}P)ATP in intact cell culture is consistent with the existence of ecto-protein kinase. Anti-fibronectin antibody immunoprecipitated one of the phosphoproteins which comigrated with a monomer and a dimer form of fibronectin under reducing and nonreducing conditions of electrophoresis, respectively. The protein had affinity for gelatin as demonstrated by retention with gelatin-conjugated agarose. This protein substrate of ecto-protein kinase was thus concluded to be fibronectin. The sites of phosphorylation by ecto-protein kinase were compared with those of intracellularly phosphorylated fibronectin by the analysis of radiolabeled amino acids and peptides. Ecto-protein kinase phosphorylated fibronectin at serine and threonine residues which were distinct from the sites of intracellular fibronectin phosphorylation.

  18. Structural basis for substrate specificities of cellular deoxyribonucleoside kinases

    DEFF Research Database (Denmark)

    Johansson, K.; Ramaswamy, S.; Ljungcrantz, C.;

    2001-01-01

    kinase with ATP at the nucleoside substrate binding site. Compared to the human kinase, the Drosophila kinase has a wider substrate cleft, which may be responsible for the broad substrate specificity of this enzyme. The human deoxyguanosine kinase is highly specific for purine substrates......; this is apparently due to the presence of Arg 118, which provides favorable hydrogen bonding interactions with the substrate. The two new structures provide an explanation for the substrate specificity of cellular deoxyribonucleoside kinases....

  19. 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...

  20. 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.

  1. Crystal structure of Cryptosporidium parvum pyruvate kinase.

    Directory of Open Access Journals (Sweden)

    William J Cook

    Full Text Available Pyruvate kinase plays a critical role in cellular metabolism of glucose by serving as a major regulator of glycolysis. This tetrameric enzyme is allosterically regulated by different effector molecules, mainly phosphosugars. In response to binding of effector molecules and substrates, significant structural changes have been identified in various pyruvate kinase structures. Pyruvate kinase of Cryptosporidium parvum is exceptional among known enzymes of protozoan origin in that it exhibits no allosteric property in the presence of commonly known effector molecules. The crystal structure of pyruvate kinase from C. parvum has been solved by molecular replacement techniques and refined to 2.5 Å resolution. In the active site a glycerol molecule is located near the γ-phosphate site of ATP, and the protein structure displays a partially closed active site. However, unlike other structures where the active site is closed, the α6' helix in C. parvum pyruvate kinase unwinds and assumes an extended conformation. In the crystal structure a sulfate ion is found at a site that is occupied by a phosphate of the effector molecule in many pyruvate kinase structures. A new feature of the C. parvum pyruvate kinase structure is the presence of a disulfide bond cross-linking the two monomers in the asymmetric unit. The disulfide bond is formed between cysteine residue 26 in the short N-helix of one monomer with cysteine residue 312 in a long helix (residues 303-320 of the second monomer at the interface of these monomers. Both cysteine residues are unique to C. parvum, and the disulfide bond remained intact in a reduced environment. However, the significance of this bond, if any, remains unknown at this time.

  2. Non-degradative Ubiquitination of Protein Kinases.

    Science.gov (United States)

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

    2016-06-01

    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 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.

  3. Src family protein tyrosine kinases induce autoactivation of Bruton's tyrosine kinase.

    Science.gov (United States)

    Mahajan, S; Fargnoli, J; Burkhardt, A L; Kut, S A; Saouaf, S J; Bolen, J B

    1995-10-01

    Bruton's tyrosine kinase (Btk) is tyrosine phosphorylated and enzymatically activated following ligation of the B-cell antigen receptor. These events are temporally regulated, and Btk activation follows that of various members of the Src family of protein tyrosine kinases, thus raising the possibility that Src kinases participate in the Btk activation process. We have evaluated the mechanism underlying Btk enzyme activation and have explored the potential regulatory relationship between Btk and Src protein kinases. We demonstrate in COS transient-expression assays that Btk can be activated through intramolecular autophosphorylation at tyrosine 551 and that Btk autophosphorylation is required for Btk catalytic functions. Coexpression of Btk with members of the Src family of protein tyrosine kinases, but not Syk, led to Btk tyrosine phosphorylation and activation. Using a series of point mutations in Blk (a representative Src protein kinase) and Btk, we show that Src kinases activate Btk through an indirect mechanism that requires membrane association of the Src enzymes as well as functional Btk SH3 and SH2 domains. Our results are compatible with the idea that Src protein tyrosine kinases contribute to Btk activation by indirectly stimulating Btk intramolecular autophosphorylation. PMID:7565679

  4. 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

  5. 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

    2016-01-01

    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

  6. 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

  7. 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...

  8. Phosphorylation of nm23/nucleoside diphosphate kinase by casein kinase 2 in vitro

    DEFF Research Database (Denmark)

    Engel, M; Issinger, O G; Lascu, I;

    1994-01-01

    We have investigated phosphorylation of human nucleoside diphosphate kinase (NDPK) and of homologous NDPK from different species by human casein kinase 2 (CK-2). The human NDPK isotypes A and B were phosphorylated by CK-2 in vitro both when the purified proteins and total lysate of HL-60 leukemia...

  9. A systematic evaluation of protein kinase A-A-kinase anchoring protein interaction motifs

    NARCIS (Netherlands)

    Burgers, Pepijn P; van der Heyden, MAG; Kok, Bart; Heck, Albert J R; Scholten, Arjen

    2015-01-01

    Protein kinase A (PKA) in vertebrates is localized to specific locations in the cell via A-kinase anchoring proteins (AKAPs). The regulatory subunits of the four PKA isoforms (RIα, RIβ, RIIα, and RIIβ) each form a homodimer, and their dimerization domain interacts with a small helical region present

  10. Regulation of the MAP kinase cascade in PC12 cells: B-Raf activates MEK-1 (MAP kinase or ERK kinase) and is inhibited by cAMP

    DEFF Research Database (Denmark)

    Peraldi, P; Frödin, M; Barnier, J V;

    1995-01-01

    In PC12 cells, cAMP stimulates the MAP kinase pathway by an unknown mechanism. Firstly, we examined the role of calcium ion mobilization and of protein kinase C in cAMP-stimulated MAP kinase activation. We show that cAMP stimulates p44mapk independently of these events. Secondly, we studied the r...

  11. 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...

  12. Significance of Creatine Kinase Brain Isoenzyme Concentration in Cerebrospinal Fluid with bacterial meningitis%小儿神经系统感染中测定激酸磷酸激酶的意义

    Institute of Scientific and Technical Information of China (English)

    熊顺军; 王红玲; 张渝侯

    2001-01-01

    测定了怀疑为中枢神经系统感染的85例患儿脑脊液中CK-BB浓度。其中,经确诊无中枢神经系统感染患儿17例,病毒性脑膜脑炎患儿36例,细菌性脑膜炎患儿32例。以上病例均常规作脑脊液检查,同时留取3毫升脑脊液作CK-BB浓度测定。结果显示,脑脊液中CK-BB可作为鉴别细菌性脑膜炎和病毒性脑膜脑炎的一项可靠指标。%Activity of CK-BB in cerebrospinal was determined in 85 children as soon as CNS infection was suspected. 17 cases was normal 36 cases with viral meningitis was diagnosed 32 cases was diagnosed with bacterial meningitis. Routine analysis of CSF was performed. When 3ml CSF was available for analysis of CK-BB activity. The data suggest the possibility of utilizing CSF CK-BB activity to differentiate between bacterial and viral meningitis in situations where a routine CSF examination is inconclusive.

  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. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. Protein Kinases and Parkinson’s Disease

    Science.gov (United States)

    Mehdi, Syed Jafar; Rosas-Hernandez, Hector; Cuevas, Elvis; Lantz, Susan M.; Barger, Steven W.; Sarkar, Sumit; Paule, Merle G.; Ali, Syed F.; Imam, Syed Z.

    2016-01-01

    Currently, the lack of new drug candidates for the treatment of major neurological disorders such as Parkinson’s disease has intensified the search for drugs that can be repurposed or repositioned for such treatment. Typically, the search focuses on drugs that have been approved and are used clinically for other indications. Kinase inhibitors represent a family of popular molecules for the treatment and prevention of various cancers, and have emerged as strong candidates for such repurposing because numerous serine/threonine and tyrosine kinases have been implicated in the pathobiology of Parkinson’s disease. This review focuses on various kinase-dependent pathways associated with the expression of Parkinson’s disease pathology, and evaluates how inhibitors of these pathways might play a major role as effective therapeutic molecules. PMID:27657053

  20. 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

  1. 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.

  2. Measuring MAP kinase activity in immune complex assays.

    Science.gov (United States)

    Cherkasova, Vera A

    2006-11-01

    I present an overview of published methods for measuring mitogen activated protein (MAP) kinase activity on endogenous associated substrates, exogenously added substrates as well as determination of activation loop phosphorylation as a read-out of kinase activity in vivo. Detailed procedures for these assays are given for two MAP kinases (MAPKs) Fus3 and Kss1 and compared with other published protocols, including the protocols for Hog1 and Mpk1 MAPKs. Measuring kinase activity in immune complex assays can serve as an approach for identification of potential substrates of protein kinases as well as for detecting other kinase-associated proteins. PMID:16890454

  3. 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.

  4. 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

  5. Cloning and expression of the heterodimeric deoxyguanosine kinase/deoxyadenosine kinase of Lactobacillus acidophilus R-26.

    Science.gov (United States)

    Ma, G T; Hong, Y S; Ives, D H

    1995-03-24

    Two uniquely paired deoxynucleoside kinases, deoxycytidine kinase/deoxyadenosine kinase (dCK/dAK) and deoxyguanosine kinase/deoxyadenosine kinase (dGK/dAK) are required, together with thymidine kinase (TK), for deoxynucleotide synthesis in Lactobacillus acidophilus R-26. Using polymerase chain reaction-generated probes based on N-terminal amino acid sequences, we have cloned tandem genes for 25- and 26-kDa polypeptides, whose derived amino acid sequences and size correspond to wild-type Lactobacillus enzyme subunits. Expression in Escherichia coli uses a single endogenous promoter and yields active dGK/dAK (approximately 3% of extracted protein) closely resembling wild-type dGK/dAK in specificity, kinetics, heterotropic activation, and end product inhibition. Alignment of cloned genes reveals 65% identity in their DNA sequences and 61% identity in derived amino acid sequences. Comparison with herpes-viral TKs reveals three conserved regions: glycine- and arginine-rich ATP-binding motifs and a D/E-R-S/H motif at the putative TK deoxynucleoside site. Greater homology, however, is seen upon multiple alignment of dGK with mammalian deoxycytidine kinases, yielding the consensus sequence-D/E-R-S-I/V-Y-x-D-.dGK also shares a sequence (-Y-D-P-T-I/L-E-D-S/Y-Y-) required for GTP hydrolysis by p21ras.

  6. 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.

  7. 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.

  8. Contribution of casein kinase 2 and spleen tyrosine kinase to CFTR trafficking and protein kinase A-induced activity.

    Science.gov (United States)

    Luz, Simão; Kongsuphol, Patthara; Mendes, Ana Isabel; Romeiras, Francisco; Sousa, Marisa; Schreiber, Rainer; Matos, Paulo; Jordan, Peter; Mehta, Anil; Amaral, Margarida D; Kunzelmann, Karl; Farinha, Carlos M

    2011-11-01

    Previously, the pleiotropic "master kinase" casein kinase 2 (CK2) was shown to interact with CFTR, the protein responsible for cystic fibrosis (CF). Moreover, CK2 inhibition abolished CFTR conductance in cell-attached membrane patches, native epithelial ducts, and Xenopus oocytes. CFTR possesses two CK2 phosphorylation sites (S422 and T1471), with unclear impact on its processing and trafficking. Here, we investigated the effects of mutating these CK2 sites on CFTR abundance, maturation, and degradation coupled to effects on ion channel activity and surface expression. We report that CK2 inhibition significantly decreased processing of wild-type (wt) CFTR, with no effect on F508del CFTR. Eliminating phosphorylation at S422 and T1471 revealed antagonistic roles in CFTR trafficking: S422 activation versus T1471 inhibition, as evidenced by a severe trafficking defect for the T1471D mutant. Notably, mutation of Y512, a consensus sequence for the spleen tyrosine kinase (SYK) possibly acting in a CK2 context adjacent to the common CF-causing defect F508del, had a strong effect on both maturation and CFTR currents, allowing the identification of this kinase as a novel regulator of CFTR. These results reinforce the importance of CK2 and the S422 and T1471 residues for regulation of CFTR and uncover a novel regulation of CFTR by SYK, a recognized controller of inflammation.

  9. Structural evolution of the protein kinase-like superfamily.

    Directory of Open Access Journals (Sweden)

    Eric D Scheeff

    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

  10. 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

  11. 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...

  12. 90-kDa ribosomal S6 kinase is phosphorylated and activated by 3-phosphoinositide-dependent protein kinase-1

    DEFF Research Database (Denmark)

    Jensen, Claus Antonio Juel; Buch, M B; Krag, T O;

    1999-01-01

    90-kDa ribosomal S6 kinase-2 (RSK2) belongs to a family of growth factor-activated serine/threonine kinases composed of two kinase domains connected by a regulatory linker region. The N-terminal kinase of RSK2 is involved in substrate phosphorylation. Its activation requires phosphorylation of th...... of Ser(227), Ser(369), and Ser(386). Our study extend recent findings which implicate PDK1 in the activation of protein kinases B and C and p70(S6K), suggesting that PDK1 controls several major growth factor-activated signal transduction pathways.......90-kDa ribosomal S6 kinase-2 (RSK2) belongs to a family of growth factor-activated serine/threonine kinases composed of two kinase domains connected by a regulatory linker region. The N-terminal kinase of RSK2 is involved in substrate phosphorylation. Its activation requires phosphorylation...... of the linker region at Ser(369), catalyzed by extracellular signal-regulated kinase (ERK), and at Ser(386), catalyzed by the C-terminal kinase, after its activation by ERK. In addition, the N-terminal kinase must be phosphorylated at Ser(227) in the activation loop by an as yet unidentified kinase. Here, we...

  13. 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.

  14. 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.

  15. Periodic fever and mevalonate kinase deficiency

    NARCIS (Netherlands)

    Frenkel, Joost

    2002-01-01

    Mevalonate kinase (MK) deficiency is an autosomal recessive disorder, caused by mutations in the MVK-gene on chromosome 12q24. The affected enzyme catalyzes an early step in isoprenoid biosynthesis, the pathway that produces cholesterol and several non-sterol isoprenoids. The clinical spectrum inclu

  16. 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

  17. Kinase detection with gallium nitride based high electron mobility transistors.

    Science.gov (United States)

    Makowski, Matthew S; Bryan, Isaac; Sitar, Zlatko; Arellano, Consuelo; Xie, Jinqiao; Collazo, Ramon; Ivanisevic, Albena

    2013-07-01

    A label-free kinase detection system was fabricated by the adsorption of gold nanoparticles functionalized with kinase inhibitor onto AlGaN/GaN high electron mobility transistors (HEMTs). The HEMTs were operated near threshold voltage due to the greatest sensitivity in this operational region. The Au NP/HEMT biosensor system electrically detected 1 pM SRC kinase in ionic solutions. These results are pertinent to drug development applications associated with kinase sensing.

  18. 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...... 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....

  19. 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...

  20. 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

  1. 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

  2. Effects of dietary supplementation with creatine monohydrate during the finishing period on growth performance, carcass traits, meat quality and muscle glycolytic potential of broilers subjected to transport stress.

    Science.gov (United States)

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

    2014-12-01

    A total of 320 male Arbor Acres broiler chickens (28 days old) were randomly allotted to one of the three experimental diets supplemented with 0 (160 birds), 600 (80 birds) or 1200 mg/kg (80 birds) creatine monohydrate (CMH) for 14 days. On the morning of 42 day, after an 8-h fast, the birds of CMH-free group were divided into two equal groups, and all birds of these four groups were transported according to the follow protocol: 0.75-h transport without CMH supplementation (as a lower stress control group), 3-h transport without CMH supplementation, 3-h transport with 600 or 1200 mg/kg CMH supplementation. Each treatment group was composed of 8 replicates with 10 birds each. The results showed that supplementation of CMH for 14 days before slaughter did not affect the overall growth performance and carcass traits of stressed broilers (P>0.05). A 3-h transport decreased plasma glucose concentration, elevated plasma corticosterone concentration, increased bird live weight loss, breakdown of muscle glycogen, as well as the accumulation of muscle lactate (Pchanges to breast meat quality (lower ultimate pH and higher drip loss, Pmeat quality by reducing the drip loss (Pmeat quality by supplementation of CMH in transported broilers.

  3. Pyrrolopyridine inhibitors of mitogen-activated protein kinase-activated protein kinase 2 (MK-2).

    Science.gov (United States)

    Anderson, David R; Meyers, Marvin J; Vernier, William F; Mahoney, Matthew W; Kurumbail, Ravi G; Caspers, Nicole; Poda, Gennadiy I; Schindler, John F; Reitz, David B; Mourey, Robert J

    2007-05-31

    A new class of potent kinase inhibitors selective for mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP-K2 or MK-2) for the treatment of rheumatoid arthritis has been prepared and evaluated. These inhibitors have IC50 values as low as 10 nM against the target and have good selectivity profiles against a number of kinases including CDK2, ERK, JNK, and p38. These MK-2 inhibitors have been shown to suppress TNFalpha production in U397 cells and to be efficacious in an acute inflammation model. The structure-activity relationships of this series, the selectivity for MK-2 and their activity in both in vitro and in vivo models are discussed. The observed selectivity is discussed with the aid of an MK-2/inhibitor crystal structure.

  4. 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

  5. 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

  6. 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

  7. The Carboxy-Terminal Tail of Pyruvate Dehydrogenase Kinase 2 Is Required for the Kinase Activity†

    OpenAIRE

    Klyuyeva, Alla; Tuganova, Alina; Popov, Kirill M.

    2005-01-01

    Pyruvate dehydrogenase kinase 2 (PDK2) is a prototypical mitochondrial protein kinase that regulates the activity of the pyruvate dehydrogenase complex. Recent structural studies have established that PDK2 consists of a catalytic core built of the B and K domains and the relatively long amino and carboxyl tails of unknown function. Here, we show that the carboxy-terminal truncation variants of PDK2 display a greatly diminished capacity for phosphorylation of holo-PDC. This effect is due large...

  8. 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.

  9. 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"…

  10. 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.

  11. 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…

  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. Asymmetric Tyrosine Kinase Arrangements in Activation or Autophosphorylation of Receptor Tyrosine Kinases

    Energy Technology Data Exchange (ETDEWEB)

    J Bae; J Schlessinger

    2011-12-31

    Receptor tyrosine kinases (RTKs) play important roles in the control of many cellular processes including cell proliferation, cell adhesion, angiogenesis, and apoptosis. Ligand-induced dimerization of RTKs leads to autophosphorylation and activation of RTKs. Structural studies have shown that while isolated ectodomains of several RTKs form symmetric dimers the isolated cytoplasmic kinase domains of epidermal growth factor receptor (EGFR) and fibroblast growth factor receptor (FGFR) form asymmetric dimers during their activation. Binding of one kinase molecule of EGFR to a second kinase molecule asymmetrically leads to stimulation of kinase activity and enhanced autophosphorylation. Furthermore, the structures of the kinase domain of FGFR1 and FGFR2 reveal the formation of asymmetric interfaces in the processes of autophosphorylation at their specific phosphotyrosine (pY) sites. Disruption of asymmetric dimer interface of EGFR leads to reduction in enzymatic activity and drastic reduction of autophosphorylation of FGFRs in ligandstimulated live cells. These studies demonstrate that asymmetric dimer formation is as a common phenomenon critical for activation and autophosphorylation of RTKs.

  14. 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

  15. In silico analysis reveals 75 members of mitogen-activated protein kinase kinase kinase gene family in rice.

    Science.gov (United States)

    Rao, Kudupudi Prabhakara; Richa, Tambi; Kumar, Kundan; Raghuram, Badmi; Sinha, Alok Krishna

    2010-06-01

    Mitogen-Activated Protein Kinase Kinase Kinases (MAPKKKs) are important components of MAPK cascades, which are universal signal transduction modules and play important role in plant growth and development. In the sequenced Arabidopsis genome 80 MAPKKKs were identified and currently being analysed for its role in different stress. In rice, economically important monocot cereal crop only five MAPKKKs were identified so far. In this study using computational analysis of sequenced rice genome we have identified 75 MAPKKKs. EST hits and full-length cDNA sequences (from KOME or Genbank database) of 75 MAPKKKs supported their existence. Phylogenetic analyses of MAPKKKs from rice and Arabidopsis have classified them into three subgroups, which include Raf, ZIK and MEKK. Conserved motifs in the deduced amino acid sequences of rice MAPKKKs strongly supported their identity as members of Raf, ZIK and MEKK subfamilies. Further expression analysis of the MAPKKKs in MPSS database revealed that their transcripts were differentially regulated in various stress and tissue-specific libraries.

  16. Crystal structure of pyridoxal kinase from the Escherichia coli pdxK gene: implications for the classification of pyridoxal kinases.

    Science.gov (United States)

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

    2006-06-01

    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 determined in the unliganded and binary complexes with either MgATP or pyridoxal to 2.1-, 2.6-, and 3.2-A resolutions, respectively. The active site of ePL kinase 1 does not show significant conformational change upon binding of either pyridoxal or MgATP. Like sheep PL kinase, ePL kinase 1 exhibits a sequential random mechanism. Unlike sheep pyridoxal kinase, ePL kinase 1 may not tolerate wide variation in the size and chemical nature of the 4' substituent on the substrate. This is the result of differences in a key residue at position 59 on a loop (loop II) that partially forms the active site. Residue 59, which is His in ePL kinase 1, interacts with the formyl group at C-4' of pyridoxal and may also determine if residues from another loop (loop I) can fill the active site in the absence of the substrate. Both loop I and loop II are suggested to play significant roles in the functions of PL kinases.

  17. Bisarylmaleimides & the Corresponding Indolocarbazoles as Kinase Inhibitors

    Institute of Scientific and Technical Information of China (English)

    Zhu Guoxin; Cathy Ogg; Bharvin Patel; Richard M. Schultz; Charles D. Spencer; Beverly Teicher; Scou A. Watkins; Scott E. Conner; Zhou Xun; Chuan Shih; Li Tiechao; Harold B. Brooks; Eileen Considine; Jack A. Dempsey; Margaret M. Faul

    2004-01-01

    Cyclin dependent kinases (CDKs) have recently raised considerable attention because of their central role in the regulation of cell cycle progression. A high incidence of genetic mutation of CDK substrates and deregulaton of CDK modulators were found in a number of disease states,particularly in cancer. A novel series of unsymmetrical substituted indolocarbazoles were synthesized and their kinase inhibitory capability was evaluated in vitro. 6-Substtuted indolocarbazoles were found to be highly potent and selective D1/CDK4 inhibitors. These indolocarbazoles exhibited ATP competitive D1/CDK4 activity and inhibited tumor cell growth,arrested tumor cell at G1 phase. These molecules demonstrated potent anti-tumor activity and inhibited pRb phosphorylation at S780 in the human lung carcinoma (Calu6) and non-small cell lung carcinoma (NCI-H460) xenograft models. The results indicate that these small molecules have potential as therapeutic agents in cancer chemotherapeutc agents.

  18. 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....

  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. Transcriptional Regulation of Pyruvate Dehydrogenase Kinase

    OpenAIRE

    Ji Yun Jeong; Nam Ho Jeoung; Keun-Gyu Park; In-Kyu Lee

    2012-01-01

    The pyruvate dehydrogenase complex (PDC) activity is crucial to maintains blood glucose and ATP levels, which largely depends on the phosphorylation status by pyruvate dehydrogenase kinase (PDK) isoenzymes. Although it has been reported that PDC is phosphorylated and inactivated by PDK2 and PDK4 in metabolically active tissues including liver, skeletal muscle, heart, and kidney during starvation and diabetes, the precise mechanisms by which expression of PDK2 and PDK4 are transcriptionally re...

  2. 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.

  3. 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.

  4. 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.

  5. EFFECT OF A DETRAINING COURSE ON SOME PHYSICAL FITNESS INDEXES AND LACTATE DEHYDROGENASE (LDH AND CREATINE PHOSPHOKINASE (CPK ENZYMES IN BLOOD SERUM OF ELITE TAEKWONDO PLAYERS

    Directory of Open Access Journals (Sweden)

    Sayed Abdollah Hashemvarzi

    2011-01-01

    Full Text Available The purpose of this study was to investigate the effects of two weeks of detraining on somephysical fitness indexes and lactate dehydrogenase (LDH and creatine phosphokinase (CPKenzymes in blood serum of elite taekwondo players. Sixteen elite male taekwondo players withthe averages of age of 18/43 ± 1/20 years; weight 64/49 ± 3/03 kg and years of experience 6/46± 1/36 years were selected voluntarily based on interviews and questionnaires and all of themwere participated in taekwondo training for four weeks equally. Then the subjects were dividedrandomly into an experimental and control groups. The experimental group had a two-week detraining;while the control group continued its training program. To calculate of anaerobicpower and speed (physical fitness indexes were used consecutive vertical jumps (Ergojumptest for 30 seconds and speed 40 yards test in two phases (Before and after of detraining. Bloodsamples to determine the desired enzymes were taken in before and after of detraining following12 to 14 hours of being empty-stomached. Data was analyzed via dependent and independent ttestin significant level P ≥ 0.05. The results of this study have demonstrated that two weeks ofdetraining caused insignificantly decrease of anaerobic power (P = 0/057 and significantly decreaseof speed (P = 0/001 in taekwondo players. Also it was observed that the levels of CPKand LDH blood have reduced significantly (P = 0/001 after tow weeks of detraining. Based theabove finding; it can be claimed that two weeks of detraining have a negative effect on speedand levels of CPK and LDH blood in taekwondo players.

  6. 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.

  7. 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

  8. Conservation and early expression of zebrafish tyrosine kinases support the utility of zebrafish as a model for tyrosine kinase biology.

    Science.gov (United States)

    Challa, Anil Kumar; Chatti, Kiranam

    2013-09-01

    Tyrosine kinases have significant roles in cell growth, apoptosis, development, and disease. To explore the use of zebrafish as a vertebrate model for tyrosine kinase signaling and to better understand their roles, we have identified all of the tyrosine kinases encoded in the zebrafish genome and quantified RNA expression of selected tyrosine kinases during early development. Using profile hidden Markov model analysis, we identified 122 zebrafish tyrosine kinase genes and proposed unambiguous gene names where needed. We found them to be organized into 39 nonreceptor and 83 receptor type, and 30 families consistent with human tyrosine kinase family assignments. We found five human tyrosine kinase genes (epha1, bmx, fgr, srm, and insrr) with no identifiable zebrafish ortholog, and one zebrafish gene (yrk) with no identifiable human ortholog. We also found that receptor tyrosine kinase genes were duplicated more often than nonreceptor tyrosine kinase genes in zebrafish. We profiled expression levels of 30 tyrosine kinases representing all families using direct digital detection at different stages during the first 24 hours of development. The profiling experiments clearly indicate regulated expression of tyrosine kinases in the zebrafish, suggesting their role during early embryonic development. In summary, our study has resulted in the first comprehensive description of the zebrafish tyrosine kinome.

  9. 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

  10. 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;

    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....... 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.......7.1.21)-like genes (AtTK1a and AtTK1b). Deoxyadenosine, deoxyguanosine and deoxycytidine kinase activities were encoded by a single AtdNK gene. T-DNA insertion lines of AtTK1a and AtTK1b mutant genes had normal growth, although AtTK1a AtTK1b double mutants died at an early stage, which indicates that AtTK1a...

  11. 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;

    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....... 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.......7.1.21)‐like genes (AtTK1a and AtTK1b). Deoxyadenosine, deoxyguanosine and deoxycytidine kinase activities were encoded by a single AtdNK gene. T‐DNA insertion lines of AtTK1a and AtTK1b mutant genes had normal growth, although AtTK1a AtTK1b double mutants died at an early stage, which indicates that AtTK1a...

  12. Tank binding kinase 1 is a centrosome-associated kinase necessary for microtubule dynamics and mitosis.

    Science.gov (United States)

    Pillai, Smitha; Nguyen, Jonathan; Johnson, Joseph; Haura, Eric; Coppola, Domenico; Chellappan, Srikumar

    2015-01-01

    TANK Binding Kinase 1 (TBK1) is a non-canonical IκB kinase that contributes to KRAS-driven lung cancer. Here we report that TBK1 plays essential roles in mammalian cell division. Specifically, levels of active phospho-TBK1 increase during mitosis and localize to centrosomes, mitotic spindles and midbody, and selective inhibition or silencing of TBK1 triggers defects in spindle assembly and prevents mitotic progression. TBK1 binds to the centrosomal protein CEP170 and to the mitotic apparatus protein NuMA, and both CEP170 and NuMA are TBK1 substrates. Further, TBK1 is necessary for CEP170 centrosomal localization and binding to the microtubule depolymerase Kif2b, and for NuMA binding to dynein. Finally, selective disruption of the TBK1-CEP170 complex augments microtubule stability and triggers defects in mitosis, suggesting that TBK1 functions as a mitotic kinase necessary for microtubule dynamics and mitosis.

  13. 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

  14. Protein Kinase Cδ mediates the activation of Protein Kinase D2 in Platelets

    OpenAIRE

    Bhavanasi, Dheeraj; Kim, Soochong; Goldfinger, Lawrence E.; Kunapuli, Satya P.

    2011-01-01

    Protein Kinase D (PKD) is a subfamily of serine/threonine specific family of kinases, comprised of PKD1, PKD2 and PKD3 (PKCμ, PKD2 and PKCν in humans). It is known that PKCs activate PKD, but the relative expression of isoforms of PKD or the specific PKC isoform/s responsible for its activation in platelets is not known. This study is aimed at investigating the pathway involved in activation of PKD in platelets. We show that PKD2 is the major isoform of PKD that is expressed in human as well ...

  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. 42 CFR 493.931 - Routine chemistry.

    Science.gov (United States)

    2010-10-01

    ... testing. (b) Challenges per testing event. The minimum number of challenges per testing event a program... Cholesterol, total Cholesterol, high density lipoprotein Creatine kinase Creatine kinase, isoenzymes... dehydrogenase (LDH) LDH isoenzymes Magnesium Potassium Sodium Total Protein Triglycerides Urea Nitrogen...

  17. Kinase active Misshapen regulates Notch signaling in Drosophila melanogaster.

    Science.gov (United States)

    Mishra, Abhinava K; Sachan, Nalani; Mutsuddi, Mousumi; Mukherjee, Ashim

    2015-11-15

    Notch signaling pathway represents a principal cellular communication system that plays a pivotal role during development of metazoans. Drosophila misshapen (msn) encodes a protein kinase, which is related to the budding yeast Ste20p (sterile 20 protein) kinase. In a genetic screen, using candidate gene approach to identify novel kinases involved in Notch signaling, we identified msn as a novel regulator of Notch signaling. Data presented here suggest that overexpression of kinase active form of Msn exhibits phenotypes similar to Notch loss-of-function condition and msn genetically interacts with components of Notch signaling pathway. Kinase active form of Msn associates with Notch receptor and regulate its signaling activity. We further show that kinase active Misshapen leads to accumulation of membrane-tethered form of Notch. Moreover, activated Msn also depletes Armadillo and DE-Cadherin from adherens junctions. Thus, this study provides a yet unknown mode of regulation of Notch signaling by Misshapen. PMID:26431585

  18. The secret life of kinases: functions beyond catalysis

    Directory of Open Access Journals (Sweden)

    Romano David

    2011-10-01

    Full Text Available 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. 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.

  20. 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