Increased Serum Creatine Kinase Research Articles

Loss of membrane integrity drives myofiber death in lipin1-deficient skeletal muscle.

Mutations in lipin1 are suggested to be a common cause of massive rhabdomyolysis episodes in children; however, the molecular mechanisms involved in the regulation of myofiber death caused by the absence of lipin1 are not fully understood. Loss of membrane integrity is considered as an effective inducer of cell death in muscular dystrophy. In this study, we utilized a mouse line with selective homozygous lipin1 deficiency in the skeletal muscle (Lipin1Myf5cKO) to determine the role of compromised membrane integrity in the myofiber death in lipin1‐deficient muscles. We found that Lipin1Myf5cKO muscles had significantly elevated proapoptotic factors (Bax, Bak, and cleaved caspase‐9) and necroptotic proteins such as RIPK1, RIPK3, and MLKL compared with WT mice. Moreover, Lipin1Myf5cKO muscle had significantly higher membrane disruptions, as evidenced by increased IgG staining and elevated uptake of Evans Blue Dye (EBD) and increased serum creatine kinase activity in Lipin1Myf5cKO muscle fibers. EBD‐positive fibers were strongly colocalized with apoptotic or necroptotic myofibers, suggesting an association between compromised plasma membrane integrity and cell death pathways. We further show that the absence of lipin1 leads to a significant decrease in the absolute and specific muscle force (normalized to muscle mass). Our work indicates that apoptosis and necroptosis are associated with a loss of membrane integrity in Lipin1Myf5cKO muscle and that myofiber death and dysfunction may cause a decrease in contractile force.

Synergistic effects of Ficus Carica extract and extra virgin olive oil against oxidative injury, cytokine liberation, and inflammation mediated by 5-Fluorouracil in cardiac and renal tissues of male albino rats.

5-Fluorouracil (5-FU), a chemotherapeutic drug, has adverse effects on heart and kidney functions. Ficus Carica (fig) and extra virgin olive oil (EVOO) are natural sources which have antioxidant effects. This study investigated the synergistic effects of fig extract and EVOO against cardiac and renal damage induced by 5-FU. Forty rats were equally divided into five groups and treated with physiological saline (control), five intravenous injections of 5-FU (40 mg/kg b.w) (5-FU), fig (1 g/kg b.w/day, orally) with 5-FU (Fig/5-FU), EVOO (7 g/kg b.w/day, orally) with 5-FU (EVOO/5-FU), combined treatment of fig and EVOO with five 5-FU injections (Fig/EVOO/5-FU). After 30 days, blood and tissue samples (Heart and kidney) were collected to be used in the examinations. 5-FU significantly increased serum creatine kinase activity, renal biomarkers, cholesterol, triglycerides, C-reactive protein, tumor necrosis factor-α, and interleukin-1β as well as cardiac and renal lipid peroxides (malondialdehyde). Meanwhile, serum levels of immunoglobulins, interleukins (IL-10, IL-12), and antioxidants of heart and kidney tissues were significantly decreased in 5-FU group. It also downregulated cardiac and renal Bcl2, and upregulated cardiac troponin and renin gene expressions. As well, histological alterations clarified that 5-FU induced cardiac cell damage, distorted renal corpuscles and tubules, inflammatory cell infiltrations, and severe congestion and hemorrhage in the blood vessels. The treatment with fig and olive oil, especially the combined treatment, modulated the toxic effect of 5-FU on the heart and kidney. Our results revealed that fig extract and EVOO have a powerful antioxidant and many protective effects against cardiac and renal toxicity induced by 5-FU, especially when using fig and EVOO together as a combined treatment.

The Effects Of Foam Rolling On Exercise Induced Muscle Damage

Exercise-induced muscle damage (EIMD) occurs following strenuous and unaccustomed exercise. EIMD is associated with elevated creatine kinase (CK) blood concentrations, limitations in range of motion (ROM), and cellular swelling. EIMD may negatively affect training quality and performance thus methods to mitigate EIMD may be useful to resistance training populations. Self-myofascial release, in particular foam rolling (FR), has been utilized by competitive and recreational athletes to ameliorate the effects of EIMD. However, the effect of FR on EIMD has yet to be established. PURPOSE: The purpose of this study is to investigate the effect of FR on markers of EIMD after an acute bout of high volume resistance exercise. METHODS: Eight participants (five males and three females), between the ages of 18 and 35, completed two acute resistance exercise bouts (10 sets of 10 repetitions barbell back squat at 60% 1RM) separated by a minimum of seven days. Following one exercise bout, subjects performed FR targeting the thigh (i.e hamstrings and quadriceps), the shank (i.e. calf and tibialis anterior), and the gluteus maximus immediately post, 24, and 48 hours post exercise, while no FR was performed following the alternate bout (CON). In both conditions, participants were asked to refrain from additional recovery methods following exercise. Outcome measures included serum CK, hip ROM, knee ROM, and thigh circumference. All measurements were pre-exercise, immediately post, 24, and 48 hours post. RESULTS: There was a significant increase in serum CK from pre to 24 hours post (p = 0.04), as well as 24 and 48 hours post (p = 0.04). Hip ROM (p = 0.02) and knee ROM (p = 0.03) decreased and thigh circumference (p = 0.03) increased 48 hours post exercise. No significant differences between FR and CON were found for any measures. CONCLUSION: FR does not attenuate markers of muscle damage (i.e. serum CK, hip ROM, knee ROM, and thigh circumference) after an acute bout of high volume resistance training. This study suggests that despite its common practice, FR may not be an effective strategy for mitigating EIMD.

Vitamin D supplementation rescues simvastatin induced myopathy in mice via improving mitochondrial cristae shape

Statin induced myopathy (SIM) is a main deleterious effect leading to the poor treatment compliance, while the preventive or therapeutic treatments are absent. Mounting evidences demonstrated that vitamin D plays a vital role in muscle as a direct modulator. The deficiency of vitamin D was considered as a cause of muscle dysfunction, whereas the supplementation resulted in a remission. However, there is no causal proof that vitamin D supplementation rescues SIM. Here, using the mice model of simvastatin-induced myopathy, we investigated the role of vitamin D supplementation and the mechanisms associated with mitochondria. Results indicated that simvastatin administration (80 mg/kg) impaired skeletal muscle with the increased serum creatine kinase (CK) level and the declined grip strength, which were alleviated by vitamin D supplementation. Moreover, vitamin D supplementation rescued the energy metabolism dysfunction in simvastatin-treated mice gastrocnemius by reducing the abnormal aggregation of muscular glycogen and lactic acid. Mitochondrial homeostasis plays a key role in the process of energy metabolism. Thus, the mitochondrial dysfunction is a mortal damage for the highly energy-requiring tissue. In our study, the mitochondrial cristae observed under transmission electron microscope (TEM) were lytic in simvastatin-treated gastrocnemius. Interestingly, vitamin D supplementation improved the mitochondrial cristae shape by regulating the expression of mitofusin-1/2 (MFN1/2), optic atrophy 1 (OPA1) and dynamin-related protein 1 (Drp1). As expected, the mitochondrial dysfunction and oxidative stress was mitigated by vitamin D supplementation. In conclusion, these findings suggested that moderate vitamin D supplementation rescued simvastatin induced myopathy via improving the mitochondrial cristae shape and function.

Alleviation of Simvastatin-Induced Myopathy in Rats by the Standardized Extract of Ginkgo Biloba (EGb761): Insights into the Mechanisms of Action

Statins are the most widely prescribed cholesterol-lowering drugs to reduce the risk of cardiovascular diseases. Statin-induced myopathy is the major side effect of this class of drugs. Here, we studied whether standardized leaf extracts of ginkgo biloba (EGb761) would improve simvastatin (SIM)-induced muscle changes. Sixty Wistar rats were allotted into six groups: control group, vehicle group receiving 0.5% carboxymethyl cellulose (CMC) for 30 days, SIM group receiving 80 mg/kg/day SIM in 0.5% CMC orally for 30 days, SIM withdrawal group treated with SIM for 16 days and sacrificed 14 days later, and EGb761-100 and EGb761-200 groups posttreated with either 100 or 200 mg/kg/day EGb761 orally. Muscle performance on the rotarod, serum creatine kinase (CK), coenzyme Q₁₀ (CoQ₁₀), serum and muscle nitrite, muscle malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) activities were estimated. Additionally, muscle samples were processed for histopathological evaluation. We found that SIM decreased muscle performance on the rotarod, serum CoQ₁₀, as well as muscle SOD and CAT activities while it increased serum CK, serum and muscle nitrite, as well as muscle MDA levels. SIM also induced sarcoplasmic vacuolation, splitting of myofibers, disorganization of sarcomeres, and disintegration of myofilaments. In contrast, posttreatment with EGb761 increased muscle performance, serum CoQ₁₀, as well as muscle SOD and CAT activities while it reduced serum CK as well as serum and muscle nitrite levels in a dose-dependent manner. Additionally, EGb761 reversed SIM-induced histopathological changes with better results obtained by its higher dose. Interestingly, SIM withdrawal increased muscle performance on the rotarod, reduce serum CK and CoQ₁₀, and reduced serum and muscle nitrite while it reversed SIM-induced histopathological changes. However, SIM withdrawal was not effective enough to restore their normal values. Additionally, SIM withdrawal did not improve SIM-induce muscle MDA, SOD, or CAT activities during the period studied. Our results suggest that EGb761 posttreatment reversed SIM-induces muscle changes possibly through its antioxidant effects, elevation of CoQ₁₀ levels, and antagonizing mitochondrial damage.

Toxinological characterization of venom from Leptodeira annulata (Banded cat-eyed snake; Dipsadidae, Imantodini)

We investigated the histology of Duvernoy’s venom gland and the biochemical and biological activities of Leptodeira annulata snake venom. The venom gland had a lobular organization, with secretory tubules formed by serous epithelial cells surrounding each lobular duct. The latter drained into a common lobular duct and subsequently into a central cistern. In contrast, the supralabial gland was mucous in nature. SDS-PAGE revealed a profile of venom components that differed from pitviper (Bothrops spp.) venoms. RP-HPLC also revealed greater complexity of this venom compared to Bothrops venoms. The venom had no esterase, l-amino acid oxidase or thrombin-like activity, but was proteolytic towards elastin-Congo red, fibrin, fibrinogen, gelatin and hide powder azure. The venom showed strong α-fibrinogenase and fibrinolytic activities and reduced the rate and extent of plasma recalcification. The proteolytic activity was inhibited by EDTA and 1,10-phenanthroline (metalloproteinase inhibitors) but not by AEBSF and PMSF (serine proteinase inhibitors). The venom had phospholipase A2 (PLA2) activity that was inhibited by varespladib. The venom cross-reacted with antivenoms to lancehead (Bothrops spp.), coralsnake (Micrurus spp.) and rattlesnake (Crotalus durissus terrificus) venoms. The venom did not aggregate rat platelets or inhibit collagen-induced aggregation, but partially inhibited thrombin-induced aggregation. The venom was hemorrhagic (inhibited by EDTA) and increased the vascular permeability (inhibited by varespladib) in rat dorsal skin. In gastrocnemius muscle, the venom caused myonecrosis and increased serum creatine kinase concentrations. In conclusion, L. annulata venom has various enzymatic and biological activities, with the local effects being mediated primarily by metalloproteinases and PLA2.

Varicella-zoster virus-induced rhabdomyolysis: A case report and literature review

Infection is a possible cause of rhabdomyolysis. We describe the case of a 63-year-old male with malaise and erythematous papules on the right C5–C7 dermatomes, consistent with herpes zoster. Serum antibody and Tzanck tests of the skin lesion were positive. Increased serum creatine kinase (CK) and myoglobin levels and cola-colored urine indicated the development of rhabdomyolysis. Acute kidney injury was also observed. After excluding other possible predisposing factors, the patient was diagnosed with varicella-zoster virus (VZV)-induced rhabdomyolysis. Extracellular volume with alkalized fluids and topical acyclovir was administered. While CK levels declined to normal by day 13, the renal function was not restored. The skin lesion crusted by day 8 and scaled off gradually by day 13. Our case and literature review highlighted the necessity for systemic antiviral treatment and that poor VZV infection control could lead to irreversible kidney injury. In addition, systemic acyclovir should be administered carefully due to its complication of nephrotoxicity.

LongShengZhi capsule inhibits doxorubicin-induced heart failure by anti-oxidative stress

Heart failure is a major cause of morbidity and mortality worldwide. LongShengZhi capsule (LSZ), a traditional Chinese medicine, is used for treatment of patients with vascular diseases. Herein we investigated the effect of LSZ treatment on doxorubicin (DOX)-induced heart failure in mice. C57BL/6 mice randomly in 3 groups received following treatment: Control group, mice were fed normal chow; DOX group, mice were intraperitoneally injected DOX to induce heart failure and fed normal chow; and LSZ group, mice were injected DOX and fed normal chow containing LSZ. DOX induced heart failure as evidenced by increased serum creatine kinase, lactic dehydrogenase and α-hydroxybutyrate dehydrogenase, and cardiac fibrosis. However, LSZ treatment substantially inhibited DOX-induced heart failure parameters. Mechanistically, LSZ reduced collagen content and fibrosis by inhibiting expression of collagen type I α1 (COL1α1), COL1α2, α-smooth muscle actin and transforming growth factor β1. In addition, DOX-induced cell apoptosis was inhibited by LSZ, coupled with reduced caspase 3 activity and mRNA expression. LSZ decreased inflammatory cytokine levels. More importantly, LSZ decreased oxidative stress by inducing expression of anti-oxidative stress enzymes including superoxide dismutase 1 (SOD1), SOD2, catalase and glutathione peroxidase 1 through activation of forkhead box O3A and sirtuin 3. In conclusion, our study demonstrates that LSZ reduces heart failure by reducing production of reactive oxygen species and inhibiting inflammation/apoptosis. Our study also suggests the potential application of LSZ for heart failure treatment.

Total Absence of Dystrophin Expression Exacerbates Ectopic Myofiber Calcification and Fibrosis and Alters Macrophage Infiltration Patterns

Duchenne muscular dystrophy (DMD) causes severe disability and death of young men because of progressive muscle degeneration aggravated by sterile inflammation. DMD is also associated with cognitive and bone-function impairments. This complex phenotype results from the cumulative loss of a spectrum of dystrophin isoforms expressed from the largest human gene. Although there is evidence for the loss of shorter isoforms having impact in the central nervous system, their role in muscle is unclear. We found that at 8 weeks, the active phase of pathology in dystrophic mice, dystrophin-null mice (mdxβgeo) presented with a mildly exacerbated phenotype but without an earlier onset, increased serum creatine kinase levels, or decreased muscle strength. However, at 12 months, mdxβgeo diaphragm strength was lower, whereas fibrosis increased, compared with mdx. The most striking features of the dystrophin-null phenotype were increased ectopic myofiber calcification and altered macrophage infiltration patterns, particularly the close association of macrophages with calcified fibers. Ectopic calcification had the same temporal pattern of presentation and resolution in mdxβgeo and mdx muscles, despite significant intensity differences across muscle groups. Comparison of the rare dystrophin-null patients against those with mutations affecting full-length dystrophins may provide mechanistic insights for developing more effective treatments for DMD.

Vitamin D Supplementation to Treat Statin-Associated Muscle Symptoms: A Review

For the past 15 years, cardiovascular disease (CVD) has been the leading cause of death for both men and women in the United States and worldwide. With an aging population, there has been increasing use of statin therapy to reduce the risk of CVD. However, statin-associated muscle symptoms (SAMS) remain an obstacle to this treatment, leading to discontinuation and nonadherence to statin therapy. Signs and symptoms of SAMS include muscle pain, tenderness, and increased serum creatine kinase. Despite the idiopathic pathophysiology of SAMS, some studies have shown an association between vitamin D deficiency and SAMS; the use of vitamin D supplements can lead to relief of these symptoms. The purpose of this review was to critique evidence for the association between low serum vitamin D and SAMS and the use of vitamin D supplementation for treatment.

Vitamin D Supplementation to Treat Statin-Associated Muscle Symptoms: A Review.

For the past 15 years, cardiovascular disease (CVD) has been the leading cause of death for both men and women in the United States and worldwide. With an aging population, there has been increasing use of statin therapy to reduce the risk of CVD. However, statin-associated muscle symptoms (SAMS) remain an obstacle to this treatment, leading to discontinuation and nonadherence to statin therapy. Signs and symptoms of SAMS include muscle pain, tenderness, and increased serum creatine kinase. Despite the idiopathic pathophysiology of SAMS, some studies have shown an association between vitamin D deficiency and SAMS; the use of vitamin D supplements can lead to relief of these symptoms. The purpose of this review was to critique evidence for the association between low serum vitamin D and SAMS and the use of vitamin D supplementation for treatment.

Effects of Kinesio Taping on the Relief of Delayed Onset Muscle Soreness: A Randomized, Placebo-Controlled Trial.

The purpose of this study was to examine the effects of Kinesio taping (KT) on delayed onset muscle soreness. Randomized controlled study. Clinical laboratory. Fifty-four nonathletic volunteers were assigned randomly to KT (n = 27) and placebo KT (n = 27) groups. The intense exercise protocol consisted of 100 consecutive drop jumps from a 0.60-m-high platform. Kinesio tape was applied with the fan technique on the quadriceps muscles in the KT group. The placebo KT group received the Kinesio tape with no technique and tension. Muscle soreness, maximal isometric quadriceps muscle strength, vertical jump height, and blood analyses (creatine kinase, lactate dehydrogenase, myoglobin, and C-reactive protein) were measured preexercise, immediately postexercise, 48 hours postexercise, and 72 hours postexercise. There was a significant effect of time in all outcome measures (P < .05) except serum C-reactive protein level (P > .05). The intensity of muscle soreness was significantly lower in the KT group relative to the placebo KT group at 72 hours postexercise (P = .01). The serum creatine kinase level was significantly higher in the KT group compared with the placebo KT group at 72 hours postexercise (P = .01). There were no statistically significant differences between groups for the other outcome measures (P > .05). These findings indicate that KT intervention following the intense exercise protocol reduced muscle soreness. However, it had no effect on maximal quadriceps isometric strength and vertical jump height or serum lactate dehydrogenase, myoglobin, and C-reactive protein levels. Furthermore, KT application after intense exercise also increased serum creatine kinase levels.

Housing and road transport modify the brain neurotransmitter systems of pigs: Do pigs raised in different conditions cope differently with unknown environments?

How housing and transport conditions may affect welfare in porcine production is a leading topic in livestock research. This study investigated whether pigs present a different neurological response to management conditions and to ascertain whether pigs living partially outdoors cope differently with road transport-associated stress. Twenty-four female pigs were divided in two groups: one living indoors (ID, n = 12) and the other housed combining indoor conditions with 4 hours per day of outdoor pasture (OD, n = 12). After one month, one set of animals from each housing condition were driven in a truck to the slaughterhouse in low-stress conditions (5 min drive, no mixing groups, soft management, LS group, n = 12) or high-stress conditions (2 hours drive, mixing groups, harsh management, HS group, n = 12). At the slaughterhouse, blood was collected, and the prefrontal cortex (PFC) and the hippocampus (HC) dissected. OD pigs had lower serum haptoglobin and increased dopaminergic pathway (DA-system) in the PFC, suggesting that living outdoors increases their wellbeing. HS conditions increased serum creatine kinase (CK) and affected several brain pathways: activation of the noradrenergic (NA-system) and DA -system in the PFC and the activation of the DA-system and an increase in c-Fos as well as a decrease in brain-derived neurotrophic factor (BDNF) in the HC. The serotonergic system (5-HT-system) was mildly altered in both areas. There was an interaction between housing and transport in serum NA and the DA-system in the HC, indicating that living conditions affected the response to stress. Multivariate analysis was able to discriminate the four animal groups. In conclusion, this work indicates that housing conditions and road transport markedly modifies the neurophysiology of pigs, and suggests that animals raised partially outdoors respond differently to transport-associated stress than animals raised indoors, indicating that they cope differently with unknown environments.

Effect of ingesting carbohydrate only or carbohydrate plus casein protein hydrolysate during a multiday cycling race on left ventricular function, plasma volume expansion and cardiac biomarkers

Multiday racing causes mild left ventricular (LV) dysfunction from day 1 that persists on successive days. We evaluated ingesting casein protein hydrolysate-carbohydrate (PRO) compared with carbohydrate-only (CHO) during a 3-day mountain bike race. Eighteen male cyclists were randomly assigned to ingest 6.7% carbohydrate without (CHO) or with 1.3% casein hydrolysate (PRO) during racing (~ 4-5h/day; 68/71/71km). Conventional LV echocardiography, plasma albumin content, plasma volume (PV) and blood biomarkers were measured before day 1 and post race on day 3. Fourteen cyclists (n = 7 per group) completed the race. PV increased in CHO (mean increase (95% CI), 10.2% (0.1to 20.2)%, p = 0.045) but not in PRO (0.4% (- 6.1 to 6.9)%). Early diastolic transmitral blood flow (E) was unchanged but deceleration time from peak E increased post race (CHO: 46.7 (11.8to 81.6)ms, p = 0.019; PRO: 24.2 (- 0.5 to 48.9)ms, p = 0.054), suggesting impaired LV relaxation. Tissue Doppler mitral annular velocity was unchanged in CHO, but in PRO septal early-to-late diastolic ratio decreased (p = 0.016) and was compensated by increased lateral early (p = 0.034) and late (p = 0.012) velocities. Systolic function was preserved in both groups; with increased systolic lateral wall velocity in PRO (p = 0.002). Effect size increase in serum creatine kinase (CK) activity, CK-MB and C-reactive protein concentrations was less in PRO than CHO (Cohen's d mean ± SD, PRO: 2.91 ± 2.07; CHO: 7.56 ± 4.81, p = 0.046). Ingesting casein hydrolysate with carbohydrate during a 3-day race prevented secondary hypervolemia and failed to curb impaired LV relaxation despite reducing tissue damage and inflammatory biomarkers. Without PV expansion, systolic function was preserved by lateral wall compensating for septal wall dysfunction.

Fast skeletal troponin I, but not the slow isoform, is increased in patients under statin therapy: a pilot study.

IntroductionStatin therapy is often associated with muscle complaints and increased serum creatine kinase (CK). However, although essential in determining muscle damage, this marker is not specific for skeletal muscle. Recent studies on animal models have shown that slow and fast isoforms of skeletal troponin I (ssTnI and fsTnI, respectively) can be useful markers of skeletal muscle injury. The aim of this study was to evaluate the utility of ssTnI and fsTnI as markers to monitor the statin-induced skeletal muscle damage.Materials and methodsA total of 51 patients (14 using and 37 not using statins) admitted to the intensive care unit of the University of Ferrara Academic Hospital were included in this observational study. Serum activities of CK, aldolase, alanine aminotransferase and myoglobin were determined by spectrophotometric assays or routine laboratory analysis. Isoforms ssTnI and fsTnI were determined by commercially available ELISAs. The creatine kinase MB isoform (CK-MB) and cardiac troponin I (cTnI) were evaluated as biomarkers of cardiac muscle damage by automatic analysers.ResultsAmong the non-specific markers, only CK was significantly higher in statin users (P = 0.027). Isoform fsTnI, but not ssTnI, was specifically increased in those patients using statins (P = 0.009) evidencing the major susceptibility of fast-twitch fibres towards statins. Sub-clinical increase in fsTnI, but not CK, was more frequent in statin users (P = 0.007). Cardiac markers were not significantly altered by statins confirming the selectivity of the effect on skeletal muscle.ConclusionsSerum fsTnI could be a good marker for monitoring statin-associated muscular damage outperforming traditional markers.

Elevated Creatine Kinase and Lactic Acid Dehydrogenase and Decreased Osteocalcin and Uncarboxylated Osteocalcin are Associated with Bone Stress Injuries in Young Female Athletes

Stress fractures are a limitation for athletes not only in sports performance but in activities of daily living. Thus, preventing them is crucial. In female athletes, a triad of symptoms including low energy availability, functional hypothalamic amenorrhea and osteoporosis are considered risk factors for stress injuries, but biomarkers predictive of these outcomes are not available. Here, we evaluated 56 female university athletes and found that 13 had a history of stress bone injuries. Logistic regression analysis demonstrated that dysmenorrhea including amenorrhea, but not reduced food intake or body weight loss, was significantly associated with stress injuries. When we subdivided subjects into stress fracture and non-fracture groups, we found that serum levels of creatine kinase (CK) and lactic acid dehydrogenase (LDH) were significantly higher in the fracture group, while osteocalcin and uncarboxylated osteocalcin (ucOC), which are bone forming parameters, significantly decreased. Low vitamin D levels are associated with stress fractures, but serum vitamin D levels were higher in fracture compared to non-fracture subjects. We followed up 32 subjects for one year, and three exhibited new stress injuries during that period. A history of stress fracture history is significantly associated with experiencing a new stress fracture. We also found that subjects with new fracture performed significantly greater exercise activity than did non-fracture subjects. Taken together, our data indicate that increased serum CK and LDH and decreased serum osteocalcin and ucOC are biomarkers of stress injuries, and evaluating these markers along with dysmenorrhea, stress fracture history or high sports activity could predict future stress fractures in female athletes.

First familial limb-girdle muscular dystrophy 2L in China

Limb-girdle muscular dystrophy 2L (LGMD2L) is mainly characterized by late adult onset, atrophy of proximal muscles, chronic progressive and asymmetric weakness, accompanied by increased creatine kinase (CK) levels, dystrophic pathological changes and electromyography showing myogenic damage. To date, familial LGMD2L was reported in European countries and had not been reported in China.A careful investigation of the clinical manifestations, muscle performance imaging, biopsy, and target next-generation sequencing (NGS) technology was utilized to identify pathogenic genetic variants in a 4-generation pedigree that includes 6 affected individuals.The results revealed mild-to-moderate hypertrophy of bilateral gastrocnemii and slight weakness and atrophy in the proximal muscles of the lower limbs, with obviously increased serum creatine kinase levels. The symptoms were more serious in the male proband but were also observed in females. Obvious and symmetric atrophy and fat infiltration of posterior segments of the thigh was evident in muscle magnetic resonance imaging (MRI). The pathological changes included a small amount of atrophic and hypertrophic fibers, scattered necrotizing fibers, a small number of increased nuclei, inward migration, mild proliferation of interstitial connective tissue, and no inflammatory cell infiltration. The pathogenic allele was a c.220C > T mutation in the anoctamin 5 (ANO5) gene.The LGMD2L family was characterized by mild chronic myopathy and bilateral gastrocnemius hypertrophy with obviously increased CK levels. Pathological changes included atrophy of fibers with interstitial connective tissues hyperplasia. The pathogenic allele was a c.220C> T mutation in the ANO5 gene.

THE EFFECTS OF CARVEDILOL AND Q10 ON ISOPRENALINE-INDUCED CARDIOTOXICITY: ELECTROCARDIOGRAPHIC, BIOCHEMICAL AND HISTOPATHOLOGICAL EVALUATION IN RATS.

Objective: To assess the therapeutic effect of combining of Carvedilol and Q10 on electrocardiographic, biochemical and histopathological changes in isoprenaline induced myocardial infarction. Methods: Myocardial infarction was induced in rats by subcutaneous (s.c) injection of isoprenaline (85mg/kg) for two consecutive days at an interval of 24 h. Rats were treated orally (p.o) with Carvedilol at dose (5 mg/kg/day) and Q10 at dose (10 mg/kg/day) for a period of 14 days. At the end of experiment electrocardiographic, biochemical and histopathological changes were monitored from control and experimental groups. Results: ISP intoxicated rats showed a significant tachycardia , elevation ST and prolongation of QTc (i.e. ST, QTc & HR) due to conduction abnormalities, increased serum creatine kinase isoenzyme-MB (CK-MB) Treatment with Carv+Q10 significantly improved the ISP induced alteration in ECG, biochemical and histopathological changes. Conclusions: The present result shows that treatment with Carv+Q10 significantly attenuates myocardial infarction in ISP-intoxicated rats.

A novel canine model for Duchenne muscular dystrophy (DMD): single nucleotide deletion in DMD gene exon 20

BackgroundBoys with Duchenne muscular dystrophy (DMD) have DMD gene mutations, with associated loss of the dystrophin protein and progressive muscle degeneration and weakness. Corticosteroids and palliative support are currently the best treatment options. The long-term benefits of recently approved compounds such as eteplirsen and ataluren remain to be seen. Dogs with naturally occurring dystrophinopathies show progressive disease akin to that of DMD. Accordingly, canine DMD models are useful for studies of pathogenesis and preclinical therapy development. A dystrophin-deficient, male border collie dog was evaluated at the age of 5 months for progressive muscle weakness and dysphagia.Case presentationDramatically increased serum creatine kinase levels (41,520 U/L; normal range 59–895 U/L) were seen on a biochemistry panel. Histopathologic changes characteristic of dystrophinopathy were seen. Dystrophin was absent in the skeletal muscle on immunofluorescence microscopy and western blot. Whole genome sequencing, polymerase chain reaction, and Sanger sequencing revealed a frameshift, single nucleotide deletion in canine DMD exon 20, position 27,626,466 (c.2841delT mRNA), resulting in a stop codon six nucleotides downstream. Semen was archived for future line perpetuation.ConclusionsThis spontaneous canine dystrophinopathy occurred due to a novel mutation in the minor DMD mutation hotspot (between exons 2 through 20). Perpetuating this line could allow for preclinical testing of genetic therapies targeted to this area of the DMD gene.

Biomarkers of muscle damage increased in anterolateral compared to direct lateral approach to the hip in hemiarthroplasty: no correlation with clinical outcome : Short-term analysis of secondary outcomes from a randomized clinical trial in patients with a displaced femoral neck fracture.

To compare increase in serum creatine kinase (CK) and its association with functional outcome between the muscle-sparing anterolateral approach and the direct lateral approach to the hip in patients with displaced femoral neck fracture (FNF). In this randomized trial, we enrolled eligible patients between 70 and 90years of age with FNF. Patients were allocated to an uncemented hemiarthroplasty inserted through a direct lateral or an anterolateral approach. The primary endpoints were pain and patient satisfaction assessed by the Visual Analogue Scale (VAS). Among secondary endpoints was increase in CK at 24 and 48h compared to baseline and its association with surgical parameters, Timed up and Go Test (TUG), Harris Hip Score (HHS), and the presence of a Trendelenburg sign using correlation analysis. This paper reports on increase in serum CK and its association with functional outcome. At 24h, there was a mean increase from baseline in total CK of 228U/L (95% CI 187 to 269; P < 0.001). There was a difference between groups at 24h in CK increase with higher levels in the anterolateral group (mean difference 80U/L; 95% CI - 0.5 to 162; P = 0.05). Likewise, at 48h, there was a mean difference of 117U/L (95% CI 22 to 212; P = 0.01). No correlation was found between CK values and functional assessments. Compared with the direct lateral approach, the anterolateral approach yielded higher levels of postoperative CK. However, there was no correlation between levels of CK and functional outcome. ClinicalTrials.gov Identifier: NCT02028468.