Decreased Creatine Kinase Research Articles

Effects of pre-irradiation of low-level laser therapy with different doses and wavelengths in skeletal muscle performance, fatigue, and skeletal muscle damage induced by tetanic contractions in rats

This study aimed to evaluate the effects of low-level laser therapy (LLLT) immediately before tetanic contractions in skeletal muscle fatigue development and possible tissue damage. Male Wistar rats were divided into two control groups and nine active LLLT groups receiving one of three different laser doses (1, 3, and 10 J) with three different wavelengths (660, 830, and 905 nm) before six tetanic contractions induced by electrical stimulation. Skeletal muscle fatigue development was defined by the percentage (%) of the initial force of each contraction and time until 50 % decay of initial force, while total work was calculated for all six contractions combined. Blood and muscle samples were taken immediately after the sixth contraction. Several LLLT doses showed some positive effects on peak force and time to decay for one or more contractions, but in terms of total work, only 3 J/660 nm and 1 J/905 nm wavelengths prevented significantly (p < 0.05) the development of skeletal muscle fatigue. All doses with wavelengths of 905 nm but only the dose of 1 J with 660 nm wavelength decreased creatine kinase (CK) activity (p < 0.05). Qualitative assessment of morphology revealed lesser tissue damage in most LLLT-treated groups, with doses of 1-3 J/660 nm and 1, 3, and 10 J/905 nm providing the best results. Optimal doses of LLLT significantly delayed the development skeletal muscle performance and protected skeletal muscle tissue against damage. Our findings also demonstrate that optimal doses are partly wavelength specific and, consequently, must be differentiated to obtain optimal effects on development of skeletal muscle fatigue and tissue preservation. Our findings also lead us to think that the combined use of wavelengths at the same time can represent a therapeutic advantage in clinical settings.

Successful Detection and Removal of a Functional Parathyroid Adenoma in a Pony Using Technetium Tc 99m Sestamibi Scintigraphy

Successful Detection and Removal of a Functional Parathyroid Adenoma in a Pony Using Technetium Tc 99m Sestamibi Scintigraphy

Antioxidative and Cardioprotective Effects of Total Flavonoids Extracted from Dracocephalum moldavica L. Against Acute Ischemia/Reperfusion-Induced Myocardial Injury in Isolated Rat Heart

This study evaluates antioxidative and cardioprotective effects of total flavonoids extracted from Dracocephalum moldavica L. (DML). The total flavonoids showed remarkable scavenging effects against 1,1-diphenyl-2-picrylhydrazyl, hydroxyl and superoxide anion radicals in vitro. Compared with the ischemia/reperfusion (I/R) group as demonstrated bythe use of improved Langendorff retrograde perfusion technology, the total flavonoids (5μg/mL) pretreatment improved the heart rate and coronary flow, rised left ventricular developed pressure and decreased creatine kinase, lactate dehydrogenase levels in coronary flow. The infarct size/ischemic area at risk of DML-treated hearts was smaller than that of I/R group; the superoxide dismutase activity and glutathione/glutathione disulfide ratio increased and malondialdehyde content reduced obviously (P<0.01) in total flavonoids treatment groups. In conclusion, the total flavonoids possess obvious protective effects on myocardial I/R injury, which may be related to the improvement of myocardial oxidative stress states.

Multiple reaction monitoring for the detection of disease-related synaptic proteins.

Multiple reaction monitoring for the detection of disease-related synaptic proteins.

The Relative Efficacy of Three Recovery Modalities After Professional Rugby League Matches

This study investigated the relative efficacy of postgame recovery modalities on jump height performance and subjective ratings of muscle soreness and muscle damage at 1, 18, and 42 hours after professional rugby league competition games. Twenty-one professional rugby league players performed 3 different postmatch recovery modalities: cold water immersion (CWI), contrast water therapy (CWT), and active recovery (ACT). The effects of the recovery treatments were analyzed with mixed modeling including a covariate (fatigue score) to adjust for changes in the intensity of each match on the postmatch values of the dependent variables of interest. Standardization of effects was used to make magnitude-based inferences, presented as mean with ±90% confidence limits. Cold water immersion and CWT clearly recovered jump height performance (CWI 2.3 ± 3.7%; CWT 3.5 ± 4.1%), reduced muscle soreness (CWI -0.95 ± 0.37; CWT -0.55 ± 0.37), and decreased creatine kinase (CWI -11.0 ± 15.1%; CWT 18.2 ± 20.1%) by 42 hours postgame compared with ACT. Contrast water therapy was however clearly more effective compared with CWI on the recovery of muscle soreness and creatine kinase by 42 hours postgame. Based on these findings, CWT recovery is recommended postmatch for team rugby sports.

Anakinra treatment in patients with refractory inflammatory myopathies and possible predictive response biomarkers: a mechanistic study with 12 months follow-up

ObjectiveTo perform a mechanistic study on the effect of interleukin (IL)-1 blockade by anakinra in patients with refractory myositis and to explore possible predictive biomarkers.MethodsFifteen patients with refractory myositis were...

Acute renal failure potentiates brain energy dysfunction elicited by methylmalonic acid

The influence of acute renal failure induced by gentamicin administration on the effects of MMA on mitochondrial respiratory chain complexes, citrate synthase, succinate dehydrogenase and creatine kinase activities in cerebral cortex and kidney of young rats were investigated. Animals received one intraperitoneal injection of saline or gentamicin (70mg/kg). One hour after, the animals received three consecutive subcutaneous injections of MMA (1.67μmol/g) or saline (11h interval between injections) and 60min after the last injection the animals were killed. Acute MMA administration decreased creatine kinase activity in both tissues and increased complexes I–III activity in cerebral cortex. Creatine kinase activity was also inhibited by gentamicin administration. Simultaneous administration of MMA and gentamicin increased the activities of citrate synthase in cerebral cortex and kidney and complexes II–III in cerebral cortex. The other enzyme activities in cerebral cortex and kidney of animals receiving MMA plus gentamicin did not significantly differ from those observed in animals receiving only MMA. Our present data is line with the hypothesis that MMA acts as a toxin in brain and kidney of rats and suggest that renal injury potentiates the toxicity of MMA on the Krebs cycle and respiratory chain in brain and peripheral tissues.

Effects of fish oil containing eicosapentaenoic acid and docosahexaenoic acid on dystrophic mdx mice

In Duchenne muscular dystrophy (DMD) and in the mdx mouse model of DMD, the lack of dystrophin leads to muscle degeneration and inflammation contributes to progression of the disease. In this study, we evaluated the effects of commercially available fish oil containing EPA and docosahexaenoic acid (DHA) on mdx. Mdx mice (14 days old) were treated with fish oil (FDC Vitamins; 0.002 g EPA and 0.001 g DHA) for 16 days by gavage. Control mdx mice received mineral oil (Nujol). Grip strength measurement was used for functional evaluation. The sternomastoid, diaphragm and biceps brachii muscles were removed and processed for histopathology and Western blot analysis. Fish oil decreased creatine kinase and myonecrosis. In all muscles studied, the inflammatory area was significantly reduced after treatment (18.0 ± 3.0% inflammatory area in untreated mdx mice versus 4.0 ± 1% in treated mdx mice). Fish oil protected against the loss of muscle strength. Fish oil significantly reduced the levels of TNF-α and the levels of 4-HNE-protein adducts (30-34% reduction for both) in all muscles studied. Commercially available fish oil may be potentially useful to ameliorate dystrophic progression of skeletal muscles, deserving further clinical trials in DMD patients.

Drynariae Rhizoma Increases Immune Response in Mice

Drynariae Rhizoma (DR), a traditional Korean herbal medicine, has long been used for vital energy and to strengthen health in Korea. However, it is still unclear how DR has the effects in experimental models. We examined the immune-enhancing effect of DR in mice using the forced swimming test (FST) and in vitro tests with peritoneal macrophages. After daily oral administration of DR, blood biochemical parameters related to fatigue were measured after the FST. The immobility time in the FST was significantly decreased in the DR-treated group (100 mg/kg) on the 3th days. DR (10 and 100 mg/kg) treatment significantly decreased creatine kinase and lactic dehydrogenase levels, which are accurate indicators of muscle damage. Further, we examined how DR regulates nitric oxide (NO) production and tumor necrosis factor alpha (TNF-alpha) production and in mouse peritoneal macrophages. When DR was used in combination with recombinant interferon-gamma (rIFN-gamma), there were noticeable cooperative productions of NO and TNF-alpha. These results suggest that DR improves immune function through the changes in indicators related to fatigue and the regulatory effects on immunological parameters, such as NO and TNF-alpha productions.

Effects of β-Hydroxy-β-Methylbutyrate and γ-Oryzanol on Blood Biochemical Markers in Exercising Thoroughbred Race Horses

In both the horse and the man, nutritional ergogenic aids have been used to improve physical ability in conjunction with an appropriate training regimen. Although training increases physical condition, the ease of taking a nutritional additive to improve training results explains the demand for supplementation, which may increase mechanical energy of work, delay onset of fatigue, or improve neuromuscular coordination. The purpose of this study was to determine the effects of oral supplementation of β-hydroxy-β-methylbutyrate (HMB) and γ-oryzanol (GO) on indices of exercise-induced muscle damage in Thoroughbred race horses. In this 32-week study, the horses were assigned to either a placebo, GO (3.0 g/d), HMB (15 g/d), or GO and HMB treatment groups. The supplements were administered for the first 16 weeks of the study during the training period before the racing season began. Blood samples were taken at baseline, and then during training, before exercise, immediately after exercise, and 30 minutes after exercise. Heart rate and speed were monitored in each exercise session. Hematocrit, glucose, lactate (LA), creatine phosphokinase, and aspartate aminotransferase were measured before and after each exercise session. Analysis of variance showed a significantly greater increase in postexercise creatine kinase activity in placebo-supplemented group than in the other treatment groups, both in the training period and during the racing seasons (P < .05). Blood LA was higher immediately after exercise in the placebo group compared with the supplemented groups. In conclusion, supplementation with HMB and GO resulted in decreased creatine kinase and LA after exercise. These findings support the hypothesis that HMB and GO supplementation helps to prevent exercise-induced muscle damage.

Ascorbic acid protects the diaphragm muscle against myonecrosis in mdx mice

ObjectiveOxidative stress contributes to myonecrosis in the dystrophin-deficient fibers of mdx mice and in Duchenne’s muscular dystrophy. We examined the effects of ascorbic acid (AA), an antioxidant and free radical scavenger, on the dystrophic diaphragm muscle. MethodsMdx mice (14 d old) received AA for 14 d. Control mdx mice received saline. The muscle damage was visualized by the penetration of Evans blue dye into myofibers and the extent of inflammation was assessed by histologic analysis. Creatine kinase levels were measured for the biochemical evaluation of muscle fiber degeneration. The levels of tumor necrosis factor-α (a proinflammatory cytokine) and 4-hydroxynonenal (a marker of lipid peroxidation) were analyzed by immunoblotting. ResultsAscorbic acid decreased creatine kinase levels, myonecrosis, inflammation, and the levels of tumor necrosis factor-α and 4-hydroxynonenal. ConclusionThe present results suggest that AA plays a protective role in dystrophic muscle degeneration, possibly by decreasing reactive oxygen species, and support further investigations of AA as a potential therapy for dystrophinopathies.

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

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

Evaluation of brain and kidney energy metabolism in an animal model of contrast-induced nephropathy

Contrast-induced nephropathy is a common cause of acute renal failure in hospitalized patients, occurring from 24 to 48 h and up to 5 days after the administration of iodinated contrast media. Encephalopathy may accompany acute renal failure and presents with a complex of symptoms progressing from mild sensorial clouding to delirium and coma. The mechanisms responsible for neurological complications in patients with acute renal failure are still poorly known, but several studies suggest that mitochondrial dysfunction plays a crucial role in the pathogenesis of uremic encephalopathy. Thus, we measured mitochondrial respiratory chain complexes and creatine kinase activities in rat brain and kidney after administration of contrast media. Wistar rats were submitted to 6.0 ml/kg meglumine/sodium diatrizoate administration via the tail vein (acute renal failure induced by contrast media) and saline in an equal volume with the radiocontrast material (control group); 6 days after, the animals were killed and kidney and brain were obtained. The results showed that contrast media administration decreased complexes I and IV activities in cerebral cortex; in prefrontal cortex, complex I activity was inhibited. On the other hand, contrast media administration increased complexes I and II-III activities in hippocampus and striatum and complex IV activity in hippocampus. Moreover, that administration of contrast media also decreased creatine kinase activity in the cerebral cortex. The present findings suggest that the inhibition of mitochondrial respiratory chain complexes and creatine kinase caused by the acute renal failure induced by contrast media administration may be involved in the neurological complications reported in patients and might play a role in the pathogenesis of the encephalopathy caused by acute renal failure.

Increased Cardiac Alpha-Myosin Heavy Chain in Left Atria and Decreased Myocardial Insulin-Like Growth Factor (IGF-I) Expression Accompany Low Heart Rate in Hibernating Grizzly Bears

Grizzly bears (Ursus arctos horribilis) tolerate extended periods of extremely low heart rate during hibernation without developing congestive heart failure or cardiac chamber dilation. Left ventricular atrophy and decreased left ventricular compliance have been reported in this species during hibernation. We evaluated the myocardial response to significantly reduced heart rate during hibernation by measuring relative myosin heavy-chain (MyHC) isoform expression and expression of a set of genes important to muscle plasticity and mass regulation in the left atria and left ventricles of active and hibernating bears. We supplemented these data with measurements of systolic and diastolic function via echocardiography in unanesthetized grizzly bears. Atrial strain imaging revealed decreased atrial contractility, decreased expansion/reservoir function (increased atrial stiffness), and decreased passive-filling function (increased ventricular stiffness) in hibernating bears. Relative MyHC-α protein expression increased significantly in the atrium during hibernation. The left ventricle expressed 100% MyHC-β protein in both groups. Insulin-like growth factor (IGF-I) mRNA expression was reduced by ∼50% in both chambers during hibernation, consistent with the ventricular atrophy observed in these bears. Interestingly, mRNA expression of the atrophy-related ubiquitin ligases Muscle Atrophy F-box (MAFBx) and Muscle Ring Finger 1 did not increase, nor did expression of myostatin or hypoxia-inducible factor 1α (HIF-1α). We report atrium-specific decreases of 40% and 50%, respectively, in MAFBx and creatine kinase mRNA expression during hibernation. Decreased creatine kinase expression is consistent with lowered energy requirements and could relate to reduced atrial emptying function during hibernation. Taken together with our hemodynamic assessment, these data suggest a potential downregulation of atrial chamber function during hibernation to prevent fatigue and dilation due to excessive work against an optimally filled ventricle, a response unpredicted by the Frank-Starling mechanism.

Eicosapentaenoic acid decreases TNF-α and protects dystrophic muscles of mdx mice from degeneration

In dystrophin-deficient fibers of mdx mice and in Duchenne muscular dystrophy, inflammation and increased production of tumor necrosis factor alpha (TNF-α) contribute to myonecrosis. We examined the effects of eicosapentaenoic acid (EPA) on dystrophic muscle degeneration. Mdx mice (14days old) received EPA for 16days. The sternomastoid, diaphragm and biceps brachii muscles were removed. Control mdx mice received vehicle. EPA decreased creatine kinase and myonecrosis and reduced the levels of TNF-α. These results suggest that EPA plays a protective role in dystrophic muscle degeneration, possibly by reducing TNF-α, and support further investigations of EPA as a potential therapy for dystrophinopathies.

Prevention of muscle fibrosis and myonecrosis in mdx mice by suramin, a TGF‐β1 blocker

Fibrosis is a pathological feature observed in patients with Duchenne muscular dystrophy (DMD) and in mdx mice, the experimental model of DMD. We evaluated the effect of suramin, a transforming growth factor-beta 1 (TGF-β1) blocker, on fibrosis in mdx mice. mdx mice (6 months old) received suramin for 7 weeks. Suramin- and saline-treated (control) mdx mice performed exercise on a treadmill to worsen disease progression. Immunoblotting showed an increase of TGF-β1 in mdx diaphragm, limb, and cardiac muscles. Suramin decreased creatine kinase in mdx mice and attenuated fibrosis in all muscles studied, except for cardiac muscle. Suramin protected limb muscles against damage and reduced the exercise-induced loss of strength over time. These findings support a role for TGF-β1 in fibrinogenesis and myonecrosis during the later stages of disease in mdx mice. Suramin might be a useful therapeutic alternative for the treatment of dystrophinopathies.

Brain energy metabolism parameters in an animal model of diabetes

A growing body of evidence has indicated that altered mitochondrial function may be involved in mechanism for the development of diabetic complications. Thus, we investigated whether animal model of diabetes induced by alloxan alters energy metabolism parameters. Wistar rats received one single injection of alloxan (250mg/kg) and after 15days we evaluated mitochondrial respiratory chain complexes I, II, II-III and IV, creatine kinase and citrate synthase activities in prefrontal cortex, hippocampus and striatum. We observed that animal model of diabetes induced by alloxan increased complexes I and IV activities in hippocampus, complexes II and II-III activities in prefrontal cortex and striatum and complex IV in prefrontal cortex; however decreased complex IV activity in striatum. Moreover, diabetes rats decreased creatine kinase activity in striatum and increased citrate synthase activity in hippocampus. In conclusion, this study indicates that the alteration in mitochondrial function is probably involved in the pathophysiology of diabetes.

E0016 Tongxinluo reduces myocardial ischaemia-reperfusion injury and no-reflow by stimulating the expression and phosphorylation of eNOS via PKA pathway

ObjectiveTo investigate whether oral administration of Tongxinluo (TXL), a traditional Chinese medicine, at a single low loading dose 1 h before myocardial ischaemia can attenuate ischaemia-reperfusion injury by regulating endothelial...

Tongxinluo reduces myocardial no-reflow and ischemia-reperfusion injury by stimulating the phosphorylation of eNOS via the PKA pathway

The objective of the present study was to investigate whether pretreatment with single low loading dose of tongxinluo (TXL), a traditional Chinese medicine, 1 h before myocardial ischemia could attenuate no-reflow and ischemia-reperfusion injury by regulating endothelial nitric oxide synthase (eNOS) via the PKA pathway. In a 90-min ischemia and 3-h reperfusion model, minipigs were randomly assigned to the following groups: sham, control, TXL (0.05 g/kg, gavaged 1 h before ischemia), TXL + H-89 (a PKA inhibitor, intravenously infused at a dose of 1.0 μg·kg(-1)·min(-1) 30 min before ischemia), and TXL + N(ω)-nitro-L-arginine (L-NNA; an eNOS inhibitor, intravenously administered at a dose of 10 mg/kg 30 min before ischemia). TXL decreased creatine kinase (CK) activity (P < 0.05) and reduced the no-reflow area from 48.6% to 9.5% and infarct size from 78.5% to 59.2% (P < 0.05), whereas these effects of TXL were partially abolished by H-89 and completely reversed by L-NNA. TXL elevated PKA activity and the expression of PKA, Thr(198) phosphorylated PKA, Ser(1179) phosphorylated eNOS, and Ser(635) phosphorylated eNOS in the ischemic myocardium. H-89 repressed the TXL-induced enhancement of PKA activity and phosphorylation of eNOS at Ser(635), and L-NNA counteracted the phosphorylation of eNOS at Ser(1179) and Ser(635) without an apparent influence on PKA activity. In conclusion, pretreatment with a single low loading dose of TXL 1 h before ischemia reduces myocardial no-reflow and ischemia-reperfusion injury by upregulating the phosphorylation of eNOS at Ser(1179) and Ser(635), and this effect is partially mediated by the PKA pathway.

Understanding the muscular dystrophy caused by deletion of choline kinase beta in mice

Choline kinase in mice is encoded by two genes, Chka and Chkb. Disruption of murine Chka leads to embryonic lethality, whereas a spontaneously occurring genomic deletion in murine Chkb results in neonatal bone deformity and hindlimb muscular dystrophy. We have investigated the mechanism by which a lack of choline kinase β, encoded by Chkb, causes hindlimb muscular dystrophy. The biosynthesis of phosphatidylcholine (PC) is impaired in the hindlimbs of Chkb −/− mice, with an accumulation of choline and decreased amount of phosphocholine. The activity of CTP:phosphocholine cytidylyltransferase is also decreased in the hindlimb muscle of mutant mice. Concomitantly, the activities of PC phospholipase C and phospholipase A 2 are increased. The mitochondria in Chkb −/− mice are abnormally large and exhibit decreased inner membrane potential. Despite the muscular dystrophy in Chkb −/− mice, we observed increased expression of insulin like growth factor 1 and proliferating cell nuclear antigen. However, regeneration of hindlimb muscles of Chkb −/− mice was impaired when challenged with cardiotoxin. Injection of CDP-choline increased PC content of hindlimb muscle and decreased creatine kinase activity in plasma of Chkb −/− mice. We conclude that the hindlimb muscular dystrophy in Chkb −/− mice is due to attenuated PC biosynthesis and enhanced catabolism of PC.