Effects of Co-Ingestion of ß-Hydroxy-ß-Methylbutyrate and L-Arginine α-Ketoglutarate on Jump Performance in Young Track and Field Athletes.

The aim of the study was to determine the effect of simultaneous supplementation of ß-hydroxy-ß-methylbutyrate and L-Arginine α-ketoglutarate on lower limb power and muscle damage in medium distance runners aged 15.3 (±0.9) years old. METHODS: The study group consisted of 40 volunteers aged 14-17 years practicing medium distance running for at least two years. The study lasted 12 days and followed a randomized, double-blind, placebo-controlled, parallel design. All subjects attended a familiarization session on day 0 before the test. The subjects were randomly divided into two groups: supplements and placebo group. The same training cycle protocol was used in both groups during the 12-day training period. Morning warm-up involved 10 min jogging at 60-75% of maximal heart rate and countermovement jump height measurement. Main training units were carried out for both groups with the same volume. Training load assessment (the daily session Rating of Perceived Exertion (s-RPE) method) method takes into consideration the intensity and the duration of the training session to calculate the "training load" (TL). RESULTS: At the end of the training cycle, a significant (p = 0.002) decrease in the countermovement jump (CMJ) height was found in the placebo group when compared to the baseline. In the supplement group, there was no decrease in the countermovement jump height. Creatine kinase and lactate dehydrogenase concentration increased during the training days similarly in both groups and decreased on rest days. There were no differences between groups in enzymes concentration. The research results indicate that the supplement combination used in the supplements group prevented a reduction in the CMJ values. In contrast to the supplements group, in the placebo group, the CMJ changes were statistically significant: a noticeable (p = 0.002) decrease in CMJ was noted between the baseline measurement and the 6th measurement. The well-being of the subjects from both groups changed significantly during the training period, and the intergroup differences in the mood level were similar and not statistically significant. CONCLUSIONS: The results of this study indicate that the daily co-supplementation with calcium salt of ß-hydroxy-ß-methylbutyrate (7.5 g) and L-Arginine α-ketoglutarate (10 g) during training might help to prevent decline in jump performance. No influence on muscle damage markers or mood was shown.

Effects of grape juice consumption on oxidative stress and inflammation in male volleyball players: A randomized, double-blind, placebo-controlled clinical trial.

INTRODUCTION: Some foods are also demonstrated benefits, such as anti-inflammatory, antioxidant, and ergogenic activity, similar to that of sports supplements. Grape juice has been considered an important source of polyphenols and these compounds could promote positive effects to the sports players. In this sense, the objective was to evaluate the effects of purple grape juice consumption on indicators of oxidative stress, inflammation, muscle damage, global histone H4 acetylation levels, and muscle strength and muscle power in volleyball athletes. METHODS: This is a randomized double-blind clinical trial in which 12 male volleyball players (16 ± 0.6 years old) participated in three different moments with match simulation: control (without beverage) (WB), grape juice (GJ) and placebo (PLA) (400 mL/day of grape juice or placebo (maltodextrin) for 14 days in a cross-over model). Before and immediately after each match, blood collection for analysis of indicators of systemic redox status, systemic concentrations of Interferon-γ (IFN- γ) and Interleukin-4 (IL-4), muscle damage, by Creatine Kinase (CK-NAC) and levels of global histone H4 acetylation were performed, as well as handgrip strength (HG) and lower limb power tests. RESULTS: Consumption of grape juice significantly reduced lipid peroxidation (p = 0.04) and Deoxyribonucleic Acid (DNA) damage (p = 0.01) after the match. IFN-γ levels, IL-4, CK-NAC, and histone H4 acetylation post-match did not alter with the grape juice consumption. Lower limb power improved after acute exercise in WB and GJ conditions (p < 0.001). CONCLUSION: In this pilot trial, the intake of grape juice for two weeks seems to reduce the protein oxidation and DNA damage by intermittent physical exercise, without epigenetics influence.

North American ginseng protects against muscle damage and reduces neutrophil infiltration after an acute bout of downhill running in rats.

Eccentric muscle contractions such as those experienced during downhill running are associated with inflammation, delayed-onset of muscle soreness, myofiber damage, and various functional deficits. North American ginseng (Panax quinquefolius L.) has been reported to possess anti-inflammatory properties and thus may offset some of this exercise-induced damage. Hence, we tested the hypothesis that intervention with North American ginseng would reduce eccentric exercise-induced muscle damage and inflammation. Male Wistar rats were fed (300 mg/(kg·day)(-1)) of either an alcohol (AL) or aqueous (AQ) extract of North American ginseng for 14 days before a single bout of downhill running and were compared with matching nonexercised (C) groups. Plasma creatine kinase levels were significantly reduced in both ginseng treated groups compared with the C group that received a water placebo (p < 0.002). Further, the AQ but not AL group also showed attenuated morphological signs of damage (hemotoxylin and eosin) as well as reduced levels of infiltrating neutrophils (HIS48) in the soleus muscle (p < 0.001). In summary, supplementation with an AQ but not AL extract of North American ginseng was able to reduce eccentric exercise-induced muscle damage and inflammation.

Docosahexaenoic acid affects markers of inflammation and muscle damage after eccentric exercise.

The effect of docosahexaenoic acid (DHA) on inflammatory and muscle damage response to acute eccentric exercise and to the subsequent initiation of a resistance training program was studied in 41 untrained men. Subjects consumed either 2 g·d of either DHA or placebo (PL) for 28 days before a 17-day exercise phase (day 1 to day 17) that began with an eccentric exercise bout of the elbow flexors (day 1). For analysis, the exercise period was further divided into an acute response phase (day 1-4). Isometric muscle strength (STR), range of motion (ROM), and delayed onset muscle soreness (DOMS) were measured on days 1, 2, 3, 4, 7, 12, and 17. Fasted blood was measured for interleukin 6 (IL-6), interleukin 1 receptor antagonist, C-reactive protein (CRP), and creatine kinase (CK) on days 1, 2, and 4. Serum CK and CRP were also measured in blood collected on days 7, 12, and 17. In the acute phase, DHA significantly reduced the serum CK (12.5%) and the IL-6 response (32%) but did not affect STR or DOMS. Over the entire 17-day resistance exercise period, DOMS area under the curve was 183.2 ± 96.2 for DHA and 203.2 ± 120.9 for PL (p = 0.054) and the CK response was numerically lower for DHA (p = 0.093). Docosahexaenoic acid supplementation reduced some but not all indicators of muscle damage and inflammation in the 4 days after an acute eccentric exercise bout but did not significantly affect the response to initiation of resistance exercise.

An investigation of the antidepressant action of xiaoyaosan in rats using ultra performance liquid chromatography-mass spectrometry combined with metabonomics.

A rapid, highly sensitive, and selective method was applied in a non-invasive way to investigate the antidepressant action of Xiaoyaosan (XYS) using ultra performance liquid chromatography-mass spectrometry (UPLC-MS) and chemometrics. Many significantly altered metabolites were used to explain the mechanism. Venlafaxine HCl and fluoxetine HCl were used as chemical positive control drugs with a relatively clear mechanism of action to evaluate the efficiency and to predict the mechanism of action of XYS. Urine obtained from rats subjected to chronic unpredictable mild stress (CUMS) was analyzed by UPLC-MS. Distinct changes in the pattern of metabolites in the rat urine after CUMS production and drug intervention were observed using partial least squares-discriminant analysis. The results of behavioral tests and multivariate analysis showed that CUMS was successfully reproduced, and a moderate-dose XYS produced significant therapeutic effects in the rodent model, equivalent to those of the positive control drugs, venlafaxine HCl and fluoxetine HCl. Metabolites with significant changes induced by CUMS were identified, and 17 biomarker candidates for stress and drug intervention were identified. The therapeutic effect of XYS on depression may involve regulation of the dysfunctions of energy metabolism, amino acid metabolism, and gut microflora changes. Metabonomic methods are valuable tools for measuring efficacy and mechanisms of action in the study of traditional Chinese medicines.

Coenzyme Q10 effects on creatine kinase activity and mood in geriatric bipolar depression.

INTRODUCTION: Despite the prevalence, associated comorbidities, and functional consequences of bipolar depression (BPD), underlying disease mechanisms remain unclear. Published studies of individuals with bipolar disorder implicate abnormalities in cellular energy metabolism. This study tests the hypotheses that the forward rate constant (k(for)) of creatine kinase (CK) is altered in older adults with BPD and that CoEnzyme Q10 (CoQ10), known to have properties that enhance mitochondrial function, increases k(for) in elderly individuals with BPD treated with CoQ10 compared with untreated age- and sex-matched controls. METHODS: Ten older adults (ages 55 and above) with Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition [DSM IV]) bipolar disorder, current episode depressed and 8 older controls underwent two 4 Tesla (31)Phosphorus magnetic resonance spectroscopy ((31)PMRS) scans 8 weeks apart using a magnetization transfer (MT) acquisition scheme to calculate k(for). The BPD group was treated with open-label CoEnzyme Q10 400 mg/d titrated up by 400 mg/d every 2 weeks to a maximum of 1200 mg/d. The Montgomery Asberg Depression Rating Scale (MADRS) was used to measure depression symptom severity. Baseline k(for) and changes in k(for) were compared between individuals with BPD and controls, not receiving CoQ. Clinical ratings were compared across time and associated with k(for) changes using repeated measures linear regression. RESULTS: The k(for) of CK was nonsignificantly lower for BPD than healthy controls at baseline (BPD mean (standard deviation [SD]) = 0.19 (0.02), control mean (SD) = 0.20 (0.02), Wilcoxon rank sum exact P = .40). The k(for) for both CoQ10-treated BPD and controls increased after 8 weeks (mean increase (SD) = 0.03 (0.04), Wilcoxon signed rank exact P = .01), with no significant difference in 8-week changes between groups (BPD mean change (SD) = 0.03 (0.03), control mean change (SD) = 0.03 (0.05), Wilcoxon rank sum exact P = .91). In an exploratory analysis, depression severity decreased with CoQ10 treatment in the group with BPD (F (3,7) = 4.87, P = .04) with significant reductions in the MADRS at weeks 2 (t (9) = -2.40, P = .04) and 4 (t (9) = -3.80, P = .004). CONCLUSIONS: This study employing the novel MRS technique of MT did not demonstrate significance between group differences in the k(for) of CK but did observe a trend that would require confirmation in a larger study. An exploratory analysis suggested a reduction in depression symptom severity during treatment with high-dose CoEnzyme Q10 for older adults with BPD. Further studies exploring alterations of high-energy phosphate metabolites in geriatric BPD and efficacy studies of CoQ10 in a randomized controlled trial are both warranted.

Electrocardiographic and biochemical evidence for the cardioprotective effect of antioxidants in acute doxorubicin-induced cardiotoxicity in the beagle dogs.

Doxorubicin (DOX) is a potent antitumor agent, but the cardiotoxicity mediated by the formation of reactive oxygen species limit its clinical use. The present study aims to explore electrocardiographic and biochemical evidence for the cardioprotective effect of two antioxidants, Lycium barbarum polysaccharides (LBP, the main antioxidant in Lycium barbarum) and edaravone (a potent free radical scavenger, EDA) against DOX-induced acute cardiotoxicity in beagle dogs. In this study, male beagle dogs received daily treatment of either LBP (20 mg/kg, per os (p.o.)) or EDA (2 mg/kg, intravenously (i.v.)) for 7 d and then followed by an intravenous injection of DOX (1.5 mg/kg). DOX (15 mg/kg) significantly induced acute cardiotoxicity in dogs characterized by conduction abnormalities (including decreased heart rate, ST segment elevation, QT intervals prolongation, inverted T wave, arrhythmia, and myocardial ischemia) and increased serum creatine kinase (CK) and aspartate aminotransferase (AST). Pretreatment with LBP or EDA effectively alleviated both DOX-associated conduction abnormalities and increased serum CK and AST. Moreover, physiological and serum biochemical evidences demonstrated that EDA is more effective than LBP in alleviating these abnormalities produced by DOX in heart. All these results confirm and extend previous observations in rats concerning the effectiveness of LBP or EDA against DOX-induced cardiomyopathy.

Anti-venom potential of aqueous extract of stem bark of Mangifera indica L. against Daboia russellii (Russell's viper) venom.

Several plant extracts rich in pharmacologically active compounds have shown to antagonize venom of several species. Mangifera indica has been used against snakebite by the traditional healers. However, there is paucity of scientific data in support. In this study, we evaluated the antivenom potential of aqueous extract of stem bark of M. indica against D. russellii venom-induced pharmacological effects such as life myotoxicity, edema, LD50 etc. The extract inhibited the phospholipase, protease, hyaluronidase, 5'nucleotidase, ATPase and alkaline phosphomonoesterase activities with varying IC50 values. It significantly inhibited both metalloproteases and serine proteases activities. Further, the extract significantly reduced the myotoxicity of the venom, as evident by the reduction of serum creatin kinase and lactate dehydrogenase activities. Though the extract completely inhibited in vitro PLA2 activity, it was unable to completely inhibit in situ hemolytic and in vivo edema-inducing activities, usually brought about by PLA2s. In lethality studies, co-injection of the venom preincubated with the extract showed higher protection than the independent injection of venom, followed by the extract in the mice. However, in both the cases the extract -a cocktail of inhibitors significantly increased the survival time, when compared to that of mice injected (i.p) with the venom alone. These results encourage further studies on the potential use of cocktail of inhibitors in improving the treatment of snake envenomation. Further, this study substantiates the use of M. indica as an antidote against snakebite by the traditional healers.

Taurine supplementation decreases oxidative stress in skeletal muscle after eccentric exercise.

Infrequent exercise, typically involving eccentric actions, has been shown to cause oxidative stress and to damage muscle tissue. High taurine levels are present in skeletal muscle and may play a role in cellular defences against free radical-mediated damage. This study investigates the effects of taurine supplementation on oxidative stress biomarkers after eccentric exercise (EE). Twenty-four male rats were divided into the following groups (n = 6): control; EE; EE plus taurine (EE + Taurine); EE plus saline (EE + Saline). Taurine was administered as a 1-ml 300 mg kg(-1) per body weight (BW) day(-1) solution in water by gavage, for 15 consecutive days. Starting on the 14th day of supplementation, the animals were submitted to one 90-min downhill run session and constant velocity of 1·0 km h(-1) . Forty-eight hours after the exercise session, the animals were killed and the quadriceps muscles were surgically removed. Production of superoxide anion, creatine kinase (CK) levels, lipoperoxidation, carbonylation, total thiol content and antioxidant enzyme were analysed. Taurine supplementation was found to decrease superoxide radical production, CK, lipoperoxidation and carbonylation levels and increased total thiol content in skeletal muscle, but it did not affect antioxidant enzyme activity after EE. The present study suggests that taurine affects skeletal muscle contraction by decreasing oxidative stress, in association with decreased superoxide radical production.

Comparison of simvastatin with Eugenia Jambolana fruit pulp in their effects on alanine transferase, aspartate aminotransferase and creatinine phosphokinase levels of hyperlipidaemic rats.

OBJECTIVES: To compare the effects of Eugenia Jambolana fruit extract with simvastatin on liver enzymes, aspartate aminotransferase (AST), alanine transferase (ALT) and muscle enzyme creatinine phosphokinase (CPK) in diet induced hyperlipidaemic rats. METHODS: An experimental randomized control study was conducted on seventy five male albino rats, divided into five groups labelled A, B, C, D and E with fifteen rats in each group. Group A was kept as normal control, groups B, C, D and E were given hyperlipidaemic diet for six weeks. In group B no further intervention was done, group C and group D were given ethanolic extract of Eugenia Jambolana and Simvastatin respectively for eight weeks. Group E was given combination of both for same duration. Serum Total Cholesterol (TC), Low density lipoprotein (LDL), High density lipoprotein (HDL), Triglycerides (TG), ALT. AST and CPK were measured at zero, six and fourteen weeks. RESULTS: At fourteenth week significant reductions in serum ALT , AST and CPK levels were observed in hyperlipidaemic group C as compared to other hyperlipidaemic groups B, D and E (p<0.05). Serum ALT level which is considered to be the most important parameter of hepatotoxicity returned to normal after 8 weeks in group C fed on Eugenia Jambolana fruit pulp only and the values were equal to control group A. There was no significant difference at baseline (zero weeks) serum TC, LDL, HDL, TG, ALT, AST and CPK of groups A, B, C, D and E; p>0.24, p>0.37, p>0.89, respectively. On sixth week, serum ALT, AST and CPK levels of hyperlipidaemic groups B,C,D and E were found to be significantly higher as compared to group A (p<0.05). CONCLUSION: Ethanolic extract of Eugenia Jambolana fruit caused a reduction in serum ALT, AST and CPK level in male albino rats when compared with simvastatin.

Neurochemical evidence that glycine induces bioenergetical dysfunction.

Glycine tissue concentrations are increased particularly in nonketotic and ketotic hyperglycinemia, inherited metabolic disorders characterized by severe neurologic damage and brain abnormalities. The present work investigated the in vitro effects of glycine on important parameters of energy metabolism in the brain of young rats. The parameters analyzed were CO2 generated from glucose, acetate and citrate and the activities of the respiratory chain complexes I-IV, of the citric acid cycle enzymes citrate synthase, aconitase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, fumarase and malate dehydrogenase, of creatine kinase and Na+,K+-ATPase. Our results show that glycine significantly reduced CO2 production from acetate, but not from glucose and citrate, reflecting an impairment of the citric acid cycle function. We also observed that the activity of the mitochondrial enzyme citrate synthase was markedly inhibited by glycine, whereas the other activities of the citric acid cycle were not altered. Furthermore, the activity of the respiratory chain was reduced at complexes I-III, II-III and II, as well as of the mitochondrial isoform of creatine kinase and Na+,K+-ATPase. The data indicate that glycine severely impairs brain bioenergetics at the level of energy formation, transfer and utilization. Considering the importance of energy metabolism for brain development and functioning, it is presumed that glycine-induced impairment of brain energy homeostasis may be involved at least in part in the neurological damage found in patients affected by disorders in which brain glycine concentrations are increased.

Variegate porphyria induces plasma and neutrophil oxidative stress: effects of dietary supplementation with vitamins E and C.

Our aim was to analyse the influence of variegate porphyria (VP) on the antioxidant defenses and markers of oxidative damage and inflammation in plasma and neutrophils and the effects of dietary supplementation with vitamins E and C on these parameters in plasma, neutrophils and erythrocytes. Twelve women affected by VP and twelve pair-matched healthy control women participated in a double-blind crossover study. Each participant took 50 mg/d of vitamin E and 150 mg/d of vitamin C, or a placebo, for 6 months, by consuming an almond-based beverage as the vehicle. Women affected by VP presented higher C-reactive protein and malondialdehyde (MDA) circulating levels. Plasma antioxidant defenses were not different between porphyric and control women. Neutrophils from VP women presented decreased catalase (CAT) and glutathione reductase (GR) activities together with increased protein carbonyl levels. Reactive oxygen species (ROS) production from stimulated neutrophils was also higher in porphyric women than their controls. Dietary supplementation was effective in increasing alpha-tocopherol levels in neutrophils and in reducing MDA levels in plasma. Erythrocyte CAT and GR activities were enhanced by the enriched beverage only in the control subjects. In conclusion, women affected by VP present a situation of inflammation, plasma oxidative damage and neutrophils more primed to the oxidative burst, with decreased antioxidant activities and increased ROS production capabilities and protein oxidative damage. Dietary supplementation with vitamin E (50 mg/d) and vitamin C (150 mg/d) for 6 months decreased plasma oxidative damage and enhanced the erythrocyte activities of CAT and GR.

Transforming growth factor and nuclear factor kappa B mediated prophylactic cardioprotection by total flavonoids of fructus chorspondiatis in myocardial ischemia.

BACKGROUND: Chorspomias axillaries Batt et Hill, a well-known Chinese herb, has been used in clinical treatment of angina pectoris for hundreds of years, but its effective components and intrinsic cardioprotective mechanism are still beyond us. OBJECTIVES AND METHODS: In this study, we extracted Total Flavonoids of Fructus Chorspondiatis (TFFC), a potential effective component from Chorspomias axillaries Batt et Hill to investigate its effect on myocardial ischemia induced by isoproteronol in rat and elucidated its probable mechanism. RESULTS: The results showed that prophylactically ;;intragastrical administration of TFFC at the dose of 200 mg/kg body weight effectively suppressed the variation of J points in electrocardiogram (0.211 +/- 0.059( )mV versus 0.277 +/- 0.046( )mV, p < 0.05) and inhibited the upregulated serum level of creatine kinase (754 +/- 114( )U/l versus 1,112 +/- 239( )U/l, p < 0.05), creatine kinase -MB (700 +/- 95( )U/l versus 1,012 +/- 252( )U/l, p < 0.05) and lactate dehydrogenase (1,174 +/- 200( )U/l versus 2,025 +/- 975( )U/l, p < 0.05) in myocardial ischemia, revealing its cardioprotective effect. It increased a potent tissue protective polypeptide, transforming growth factor beta(1) (TGF-beta(1)) level as well as its receptors TbetaRI and TbetaRII(p < 0.05) and significantly inhibited the expression of a redox-sensitive transcription factor, nuclear factor kappa B (NF-kappaB). CONCLUSIONS: These data demonstrated that TFFC at the dose of 200 mg/kg body weight exerts prophylactically cardioprotective effect during ischemia injury. Part of its cardioprotective mechanism may relate to induction of TGF-beta(1) to competitively inhibit NF-kappaB signaling pathway. Prophylactically exogenous administration with the component may serve as a novel therapeutic strategy for ischemic cardiovascular diseases.

Effect of coenzyme q10 on myopathic symptoms in patients treated with statins.

Treatment of hypercholesterolemia with statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) is effective in the primary and secondary prevention of cardiovascular disease. However, statin use is often associated with a variety of muscle-related symptoms or myopathies. Myopathy may be related in part to statin inhibition of the endogenous synthesis of coenzyme Q10, an essential cofactor for mitochondrial energy production. The aim of this study is to determine whether coenzyme Q10 supplementation would reduce the degree of muscle pain associated with statin treatment. Patients with myopathic symptoms were randomly assigned in a double-blinded protocol to treatment with coenzyme Q10 (100 mg/day, n = 18) or vitamin E (400 IU/day, n = 14) for 30 days. Muscle pain and pain interference with daily activities were assessed before and after treatment. After a 30-day intervention, pain severity decreased by 40% (p <0.001) and pain interference with daily activities decreased by 38% (p <0.02) in the group treated with coenzyme Q10. In contrast, no changes in pain severity (+9%, p = NS) or pain interference with daily activities (-11%, p = NS) was observed in the group treated with vitamin E. In conclusion, results suggest that coenzyme Q10 supplementation may decrease muscle pain associated with statin treatment. Thus, coenzyme Q10 supplementation may offer an alternative to stopping treatment with these vital drugs.

Effects of vitamin E supplementation on oxidative stress at rest and after exercise to exhaustion in athletic students.

AIM: The purpose of this study is to determine the effect following exercise to exhaustion of vitamin E supplementation on oxidative stress in athletic students. METHODS: Twenty male students voluntarily participated in the study and were randomly assigned (double blind) to either a vitamin E (daily dose of 450 mg of a-tocopherol for a period of 8 weeks) or a placebo group (took capsules containing 450 mg of lactose for 8 weeks). Before and after 8 weeks blood samples were collected at rest and after exercise to exhaustion. Oxidative stress markers were malondialdehyde (MDA), carbonylated proteins (CP) and creatine kinase (CK). Also, the effect of vitamin E on ergometer cycling time, as an example of endurance performance, was evaluated. RESULTS: ANOVA and independent t-tests indicated that vitamin E supplementation did not significantly change (P > 0.05) MDA, CP and CK values at rest, after exercise to exhaustion, and cycling time, but plasma volume after exercise to exhaustion significantly decreased (P < 0.05). CONCLUSIONS: Although vitamin E supplementation had no effect on exercise performance or capacity in athletic students, further investigation is required using larger numbers of subjects and measures of vitamin E before unequivocal conclusion can be stated.

Reactivation of creatine kinase by dithiothreitol prior to use in an in vitro translation extract.

BACKGROUND: In vitro protein synthesis on exogenous messenger ribonucleic acids can be performed in various systems including cytoplasmic extract from eukaryotic cells, rabbit reticulocyte lysate and wheat germ extract. For optimal translation, an energy regeneration system based on creatine phosphate and creatine kinase is commonly employed for the regeneration of the endogenous adenosine triphosphate pools. Creatine kinase purchased from various commercial suppliers can be partially oxidised. Oxidised creatine kinase is not biologically active and might not allow the efficient initiation of translation of exogenous mRNAs in eukaryotic cell extracts in vitro. RESULTS: We successfully used dithiothreitol to reduce and therefore reactivate commercially available creatine kinase. When employed in cytoplasmic extracts obtained from eukaryotic cells grown in monolayers, the reactivated creatine kinase restored translation of the exogenous mRNAs. CONCLUSION: Lyophilised creatine kinase obtained from commercial suppliers can be purchased as an oxidised monomer. The reactivation of creatine kinase using a reducing agent such as dithiothreitol restores the biological activity of this enzyme. This procedure might therefore be extended to various other in vitro conditions and biological systems in which the maintenance of an efficient ATP-regenerating system is critical.

Proanthocyanidin exposure to B6C3F1 mice significantly attenuates dimethylnitrosamine-induced liver tumor induction and mortality by differentially modulating programmed and unprogrammed cell deaths.

Proanthocyanidins are of current interest as chemopreventive agents. The potential of the pre-, post- and co-exposure of proanthocyanidin-rich grape seed extract (GSPE) in preventing, reducing and/or delaying dimethylnitrosamine (N-nitrosodimethylamine, DMN)-induced liver tumorigenesis, carcinogenesis and mortality in male B6C3F1 mice was determined. Animals were divided into six groups: I-control, II-GSPE alone, III-DMN alone, IV-GSPE+DMN, V-DMN exposure (3 months) followed by GSPE diet (9 months) and VI-GSPE diet (3 months)+DMN (3 months)+control diet (6 months). DMN exposure (0-8 weeks: 5mg/kg; 8-12 weeks: 10mg/kg, i.p.) was limited to a total period of 3 months. GSPE was incorporated in laboratory chow (ADI: 100mg/kg b.w.). Animals were sacrificed at 3 month intervals, and serum chemistry, liver histopathology, integrity of hepatic genomic DNA, antioxidant status, and rates of apoptotic and necrotic cell deaths were determined. DMN-induced liver tumor formation (85%) and animal lethality (38%) were powerfully antagonized by co-administration of GSPE+DMN (tumor positive: 45%; death: 11%). More than 75% of the DMN-treated animals had numerous tumors (five or more), which were significantly reduced in the GSPE+DMN group (35%). GSPE also negatively influenced other protocols specifically designed to test initiation and progression phases. Thus, GSPE was instrumental in modulating metabolic cascades and regulated orchestration of cell death processes involved during the multistage tumorigenic process. These results unraveled that long-term exposure to proanthocyanidin-rich grape seed extract may serve as a potent barrier to all three stages of DMN-induced liver carcinogenesis and tumorigenesis by selectively altering oxidative stress, genomic integrity and cell death patterns in vivo.

Extract of Rhodiola rosea radix reduces the level of C-reactive protein and creatinine kinase in the blood.

The effects of extracts of Rhodiola rosea radix on blood levels of inflammatory C-reactive protein and creatinine kinase were studied in healthy untrained volunteers before and after exhausting exercise. Rhodiola rosea extract exhibited an antiinflammatory effect and protected muscle tissue during exercise.

The dual effects of nitric oxide synthase inhibitors on ischemia-reperfusion injury in rat hearts.

OBJECTIVE: Nitric oxide (NO) is known to act as a mediator of tissue injury as well as being a potent endogenous vasodilator. The functional and metabolic effects of NO on ischemia-reperfusion injury are still controversial. The aim of this study was to clarify the relationship between the degree of NO synthase (NOS) inhibition and the effects on ischemia-reperfusion injury. METHODS AND RESULTS: Langendorff-perfused rat hearts were subjected to 30 minutes of global ischemia followed by 30 minutes of reperfusion. The recovery of left ventricular developed pressure (LVDP), creatine kinase (CK) release, and myocardial high energy phosphates were measured in hearts perfused with or without NOS inhibitors, L-N(G)-monomethyl arginine (L-NMMA) or N(G)nitro-L-arginine methylester (L-NAME). NOS inhibitors exerted different effects on the recovery of LVDP and CK release depending on the concentration. The low dose of L-NMMA improved the recovery of LVDP, decreased the CK release during reperfusion, and preserved the myocardial adenosine triphosphate content after reperfusion. In contrast, the high dose of L-NMMA had adverse effects. L-NMMA reduced NO release in coronary effluent in a dose-dependent fashion. Both effects of L-NMMA were abolished by excessive co-administration of L-arginine and the same doses of D-N(G)-monomethyl arginine (D-NMMA) showed no effect on ischemia-reperfusion injury. Therefore, both effects were due to NOS inhibition. In addition, L-NMMA suppressed the myocardial malondialdehyde accumulation, an indicator of oxidative stress, which might be attributed to the beneficial effects by partial NOS inhibition. On the other hand, the high dose L-NMMA significantly decreased coronary fl ow during aerobic perfusion and reperfusion. Therefore, it is conceivable that the vasoactive NOS inhibition contributes to the harmful effects, which might exceed the beneficial effects due to a decrease in oxidative stress. CONCLUSION: The present results showed that NO inhibitors had dual effects on mechanical function and energy metabolism depending on the concentration. Non-vasoactive inhibition of NOS had beneficial effects due to the suppression of oxidative injury. However, strong vasoactive inhibition of NOS exacerbated the ischemia-reperfusion injury.

The effects of beta-hydroxy-beta-methylbutyrate (HMB) and HMB/creatine supplementation on indices of health in highly trained athletes.

This study aimed to investigate the effects of 6 wk oral supplementation of beta-hydroxy-beta-methylbutyrate (HMB) and HMB combined with creatine monohydrate (HMBCr) on indices of health in highly trained athletes. Elite, male rugby league players (n=28) were allocated to 1 of 3 groups: a control group (n=6), a HMB group (3 g/d; n=11), or a HMBCr group (3 g/day HMB, 3 g/d Cr; n=11). Testing prior to, and immediately following, supplementation included a full blood count, plasma testosterone and cortisol, blood electrolytes, lipids, urea and glucose, sperm count and motility, and assessment of psychological state. A 3 x 2 factorial ANOVA revealed no effect of HMB or HMBCr on any of the measured parameters except minor changes in blood bicarbonate and blood monocyte and lymphocyte counts. Blood bicarbonate was significantly decreased in the HMB post-supplementation sample compared to the control and HMBCr groups. Blood monocyte and lymphocyte counts showed no within-group changes for HMB or HMBCr supplementation but were significantly different from the control. However, the majority of these readings remained within normal range. HMB and HMBCr were concluded to have no adverse effects on the parameters evaluated in this study when taken orally by highly trained male athletes over a 6-wk period.