Plasma CK Levels Research Articles

The Preventive Efficacy of Selenium Supplements on Muscle Soreness Post Heavy Eccentric Exercise

Delayed Onset Muscle Soreness (DOMS) is the muscle pain and stiffness following unaccustomed or strenuous physical activity that initially appears 8 – 20 h after exercise, peaks at 24 – 48 h after exercise and persists for several days and affect performance. The aim of the present study was to examine the physiological effects of selenium supplementation on delayed-onset muscle soreness and muscle damage. Thirty-two recreational male students of Sports Science Department, Universitas Negeri Surabaya were randomly and double-blindly assigned to either a selenium supplementation group (n=16) or a Placebo group (n=16) and were directed to take either a selenium capsule or a placebo for a period of 3-weeks. Following the 3-weeks supplementation period, both groups underwent a 10-set x 10-rep countermovement jump (1-min recovery between sets) as an eccentric exercise protocol. Pain of DOMS and CK level were measured prior to the eccentric exercise 1-hr before, 24-hr and 48-hr after eccentric exercise. the result of this study showed that both groups experienced Delayed Onset Muscle Soreness (DOMS) and increased total CK serum within 24 to 48 hours post heavy eccentric exercise. The results indicated that the selenium-supplemented group had a significantly greater reduction in plasma DOMS and total CK serum compared to the Placebo group (p<0.05). In summary, selenium supplementation might lower the risk of muscle injury after heavy eccentric exercise, as it effectively reduces plasma DOMS and CK levels in the bloodstream

Integrating serum pharmacochemistry and network pharmacology to explore the molecular mechanisms of Acanthopanax senticosus (Rupr. & Maxim.) Harms on attenuating doxorubicin-induced myocardial injury

Ethnopharmacological relevanceAcanthopanax senticosus (Rupr. & Maxim.) Harms (AS), also known as Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. or Siberian ginseng, has a rich history of use as an adaptogen, a substance believed to increase the body's resistance to stress, fatigue, and infectious diseases. As a traditional Chinese medicine, AS is popular for its cardioprotective effects which can protect the cardiovascular system from hazardous conditions. Doxorubicin (DOX), on the other hand, is a first-line chemotherapeutic agent against a variety of cancers, including breast cancer, lung cancer, gastric cancer, and leukemia, etc. Despite its effectiveness, the clinical use of DOX is limited by its side effects, the most serious of which is cardiotoxicity. Considering AS could be applied as an adjuvant to anticancer agents, the combination of AS and DOX might exert synergistic effects on certain malignancies with mitigated cardiotoxicity. Given this, it is necessary and meaningful to confirm whether AS would neutralize the DOX-induced cardiotoxicity and its underlying molecular mechanisms. Aim of the studyThis paper aims to validate the cardioprotective effects of AS against DOX-induced myocardial injury (MI) while deciphering the molecular mechanisms underlying such effects. Materials and methodsFirstly, the cardioprotective effects of AS against DOX-induced MI were confirmed both in vitro and in vivo. Secondly, serum pharmacochemistry and network pharmacology were orchestrated to explore the in vivo active compounds of AS and predict their ways of functioning in the treatment of DOX-induced MI. Finally, the predicted mechanisms were validated by Western blot analysis during in vivo experiments. ResultsThe results demonstrated that AS possessed excellent antioxidative ability, and could alleviate the apoptosis of H9C2 cells and the damage to mitochondria induced by DOX. In vivo experiments indicated that AS could restore the conduction abnormalities and ameliorate histopathological changes according to the electrocardiogram and cardiac morphology. Meanwhile, it markedly downregulated the inflammatory factors (TNF-α, IL-6, and IL-1β), decreased plasma ALT, AST, LDH, CK, CK-MB, and MDA levels, as well as increased SOD and GSH levels compared to the model group, which collectively substantiate the effectiveness of AS. Afterward, 14 compounds were identified from different batches of AS-dosed serum and selected for mechanism prediction through HPLC-HRMS analysis and network pharmacology. Consequently, the MAPKs and caspase cascade were confirmed as primary targets among which the interplay between the JNK/Caspase 3 feedback loop and the phosphorylation of ERK1/2 were highlighted. ConclusionsIn conclusion, the integrated approach employed in this paper illuminated the molecular mechanism of AS against DOX-induced MI, whilst providing a valuable strategy to elucidate the therapeutic effects of complicated TCM systems more reliably and efficiently.

​​Effect of Environmental Heavy Metal Pollution on Metabolic Profile of Buffaloes in Ludhiana

Background: The industrial hub of Punjab, Ludhiana is polluted with heavy metals. The dairy animals experience stress due to pollution of heavy metals as well as the hot summer season. The stressors lead to disturbance in metabolic profile and affect milk production. The present study aimed at evaluation of detrimental effect of environmental heavy metal pollution on the metabolic profile of buffaloes during summer and winter seasons in Ludhiana district of Punjab, India. A total of 100 buffaloes were randomly selected from heavy metal exposed (n=60) and control area (n=40) during summer and winter seasons. Methods: The location of the experimental area surveyed on the basis of levels of heavy metals. The dairy farms are located in and around Ludhiana, Punjab were identified with levels of heavy metal above the permissible limits (FSSAI, 2010) viz. Chromium-0.05 µg /ml; Nickel-0.02 µg /ml; Arsenic-0.05 µg /ml and Lead -0.05µg /ml. The plasma samples were analyzed for metabolic profile. The water levels of heavy metals were below the permissible limits; therefore, it was taken as uncontaminated or control area. Result: Buffaloes of heavy metal exposed areas exhibited significantly (P less than 0.05) higher levels of glucose, total cholesterol, triglycerides, BUN, creatinine, AST, ALT, GGT, ALP and CK levels as compared to control area. A significant (P less than 0.05) decrease was observed in plasma total protein, albumin, A:G ratio, BUN: creatinine ratio in the buffaloes of exposed area as compared to the control area. However, significantly (P less than 0.05) higher levels of plasma glucose, BUN, creatinine, AST, ALT, GGT, ALP and CK levels were observed during summer as compared to winter season in both exposed and control areas. Significantly (P less than 0.05) decreased levels of plasma total cholesterol, triglycerides, total protein, albumin and BUN: Creatinine ratio were observed in the buffaloes during summer as compared to winter in both exposed and control areas. The Cr, Ni, As and Pb levels showed highly significant (P less than 0.01) positive correlation with plasma levels of glucose, total cholesterol, creatinine, ALT, AST, CK and GGT. Highly significant positive relationship (P less than 0.01) was observed among plasma levels of glucose, total cholesterol, creatinine, BUN, ALT, AST, ALP, CK and GGT whereas, plasma BUN had highly significant (P less than 0.01) negative correlation with plasma total protein and A:G ratio considering both the areas together. Plasma levels of total protein showed significant (P less than 0.01) negative correlation with all other metabolic profile constituents of both control and heavy metal exposed areas. Thus it may be concluded that the metabolic disturbance in heavy metal exposed buffaloes may have been mediated by heavy metal pollution.

Hypophosphatemia compared to classical biomarkers of tonic clonic seizures

BackgroundHypophosphatemia was recently reported as a potential marker of tonic-clonic (TC) seizures among patients with transitory loss of consciousness (TLOC). Its value compared to classical markers (creatine kinase [CK] and lactate) is however unknown. AimCompare the diagnostic performance of hypophosphatemia, plasma CK, and lactate levels for distinguishing TC seizures from other TLOCs, alone or in combination. Methods128 patients aged 18−90, consecutively admitted to our hospital emergency department for TLOC were included. Diagnostic accuracy of plasma phosphate, CK, and lactate levels were compared with ROC curves. ResultsWe found significantly higher CK (median 154 U/l, range 38–5608; vs 115.5, 37–2340 U/l; p = 0.037) and lower phosphatemia (median 0.79 mmol/l, 0.34–1.37; vs 0.93, 0.52–1.89 mmol/l, p = 0.007) in TC seizures compared to other TLOCs; lactatemia was not different, although using a smaller sample (n = 72). Hypophosphatemia was the only independent predictor of TC seizures, even in later samples (>2 h). Comparing ROC curves, Combining hypophosphatemia and hyperCKemia had higher diagnostic accuracy for TC seizures than hyper-CKemia alone (AUC 0.68, 95 % CI 0.571−0.783 vs. 0.59, 95 % CI 0.475−0.706; p = 0.018), but the combination was only marginally better than hypophosphatemia alone (AUC 0.67, 95 % CI 0.559−0.778). ConclusionHypophosphatemia seems to be more useful than CK levels for diagnosing TC seizures in patients assessed in an emergency setting for TLOC. Combining both parameters together does not significantly increase the diagnostic yield. No conclusion could be drawn regarding the comparison with lactate. A prospective study is needed.

Outbreak of monensin poisoning in cattle due to supplementation error

ABSTRACT: Iatrogenic intoxications occur in domestic animals. Mortality was observed in a group of calves, reaching 20 deaths until the day of the technical visit, with or without sudden clinical signs, on a farm in the city of Pires do Rio, State of Goiás, Brazil. Deaths after the visit were not accounted systematically. Clinical signs included muscle weakness, ataxia, recumbency, bilateral jugular distention, and death. Suspected diagnosis of poisoning by ionophore antibiotics was made based on clinical and laboratory findings from nine animals, which included high plasma CK and LDH levels, as well as on anatomopathological findings of a recently dead calf, which showed myocardial and skeletal muscle degeneration and necrosis. Monensin overdose (25.5 µg/kg in skeletal muscle and 209.4 µg/kg in the liver) was detected by liquid-chromatography and mass-spectrophotometry analysis, contributing to the confirmation of ionophore poisoning diagnosis.

2519. The Prognostic Significance of Neutrophil-to-Lymphocyte Ratio in Patients With Crimean-Congo Haemorrhagic Fever

BackgroundThe neutrophil-to-lymphocyte ratio (NLR) has been shown to be associated with poor prognosis in both malign and benign disorders. However, the studies regarding NLR as a prognostic marker in Crimean-Congo hemorrhagic fever (CCHF) are limited. This study aimed to investigate the relationship between NLR and survival outcome in patients with CCHF.MethodsThe demographic and laboratory characteristics of 723 adult patients having a positive IgM and/or a positive PCR result for CCHF in the blood sample between 2007 and 2017 were reviewed. The patients were divided into two groups according to survival and fatal outcome. The area under an ROC curve was calculated to evaluate the relationship between NLR and survival outcome. The statistical significance was set at P < 0.05.ResultsPlasma NLR, creatinine, AST, ALT, LDH and CK levels in fatal cases were significantly higher than those in survival ones (P < 0.001 for all parameters), while platelet count was significantly lower (P < 0.001). All population were re-evaluated according to NLR. Plasma ALT, AST, LDH, CK, and creatinine levels when NLR was ≤ 2 were significantly lower than those when NLR was > 2 (P = 0.006, P = 0.017, P < 0.001, P < 0.001, and P < 0.001, respectively) (Table 1). The area under an ROC curve for NLR was 72% (P < 0.001).Table 1:Demographic and Laboratory Characteristics in the Patients With Crimean-Congo Hemorrhagic FeverCharacteristicsSurvival Patients (n = 693)Fatal Patients (n = 30) P-ValueNLR ≤ 2 (n = 384)NLR > 2 (n = 339)P-ValueAge (%)49.1 (17.5)64.6 (14.3)0.00148.6 (17.0)51 (18.3)0.080Gender (% Female)46.6400.47751.340.70.004Platelet count, (×103 platelets/mm3)49.8 (35.4)17.8 (7.5)0.00149.9 (33.7)46.7 (36.9)0.032ALT (U/L)230.2 (429.4)1386 (1295.6)0.001225.3(320.5)338.1(715.5)0.006AST (U/L)387.7 (529.1)3327.1(3478.8)0.001406.7(801.2)626.4(1262.3)0.017LDH (U/L)857.3(1049.9)5385.1(5404.3)0.001813.4(972.3)1307.6(2303.4)0.001CK (U/L)850.0(1173.3)3171.5(5353.2)0.001743.5(1023.3)1176.2(2109.3)0.001Creatinine (mg/dl)0.9 (0.5)2.7 (2.5)0.0010.9 (0.6)1,1 (0.9)0.001NLR2.9 (3.5)4.5 (3.3)0.001Dead (%)1.67.10.001ConclusionNLR for clinicians may be an additional test as useful as platelet count and plasma creatinine, AST, ALT, LDH, and CK levels. Our study shows that NLR might be used as a prognostic marker to predict the severity of the disease in CCHF.Disclosures All authors: No reported disclosures.

Light emitting diode (LED) therapy reduces local pathological changes induced by Bothrops asper snake venom

The therapeutic effect of the Light Emitting Diode (LED) treatment in two wavelengths (635 or 945 nm) was evaluated in the local pathological alterations induced by Bothrops asper snake venom. Mice received irradiation of infrared LED (120 mW, 945 nm) or red LED (110 mW, 635 nm) applied immediately, 1 and 2 h after venom injection. LED treatment reduced edema formation in the plantar region and gastrocnemius muscle and significantly reduced neutrophil migration and hyperalgesia after the venom injection. Also, both infrared LED and red LED treatment significantly reduced myonecrosis, as revealed by muscle CK and plasma CK levels. Histological analysis corroborated the reduction in the extent of venom-induced myonecrosis. In conclusion, our data demonstrates that PBM with LED light in both red and infrared wavelengths, when applied after envenomation in mice, reduces the extent of myotoxicity, edema, inflammatory infiltrate and hyperalgesia, suggesting that photobiomodulation is a potential therapeutic approach that should be further investigated for the treatment of local effects of Bothrops snakebite.

High-intensity interval training in facioscapulohumeral muscular dystrophy type 1: a randomized clinical trial.

Increasing evidence suggests that high-intensity training (HIT) is a time-efficient exercise strategy to improve fitness. HIT has never been explored in neuromuscular diseases, likely because it may seem counterintuitive. A single session of high-intensity exercise has been studied without signs of muscle damage in facioscapulohumeral muscular dystrophy type 1 (FSHD1). We aimed to determine whether HIT is safe and effective in FSHD1 in a randomized, controlled parallel study. Untrained adults with genetically verified FSHD1 (n=13) able to perform cycle-ergometer exercise were randomized to 8weeks of supervised HIT (n=6) (3×10-min cycle-ergometer-HIT/week) or 8weeks of usual care (n=7). Following this, all participants performed 8weeks of unsupervised HIT (3×10-min cycle-ergometer-HIT/week). Primary outcome was fitness, maximal oxygen uptake/min/kg body weight. Furthermore, workload, 6-min walk distance, 5-time sit-to-stand time, muscle strength, and daily activity levels were measured. Pain, fatigue, and plasma-CK were monitored. Twelve patients completed the randomized part of the study. Plasma-CK levels and pain scores were unaffected by HIT. Supervised HIT improved fitness (3.3mlO2/min/kg, CI 1.2-5.5, P<0.01, n=6, NNT=1.4). Unsupervised HIT also improved fitness (2.0mlO2/min/kg, CI 0.1-3.9, P=0.04, n=4). There was no training effect on other outcomes. Patients preferred HIT over strength and moderate-intensity aerobic training. It may seem counterintuitive to perform HIT in muscular dystrophies, but this RCT shows that regular HIT is safe, efficacious, and well liked by moderately affected patients with FSHD1, which suggests that HIT is a feasible method for rehabilitating patients with FSHD1.

RBaltMIP, a recombinant alpha-type myotoxin inhibitor from Bothrops alternatus (Rhinocerophis alternatus) snake, as a potential candidate to complement the antivenom therapy

Phospholipase A2 inhibitors (PLIs) are important targets in the search and development of new drugs. This study aimed at evaluating the potential of an alpha-type phospholipase A2 inhibitor from Bothrops alternatus (Rhinocerophis alternatus) snake in its recombinant form (rBaltMIP) to complement the conventional antivenom therapy. Biochemical experiments showed that rBaltMIP presented pI 5.8 and molecular masses of ∼21 kDa by SDS-PAGE and 19.57 kDa by MALDI/TOF MS. After tryptic peptides sequencing, the results were compared with other PLIs available in databases, showing 100% identity between rBaltMIP and its native inhibitor BaltMIP and from 92% to 96% identity with other inhibitors. Myotoxic activities of BthTX-I and BthTX-II toxins were measured via plasma CK levels, showing myotoxic effective concentrations (EC50) of 0.1256 μg/μL and 0.6183 μg/μL, respectively. rBaltMIP neutralized the myotoxicity caused by these two toxins up to 65%, without promoting primary antibody response against itself. Nevertheless, this recombinant PLI was immunogenic when standard immunization protocol with Freud's adjuvant was used. In paw edema assays, EC50 of 0.02581 μg/μL and 0.02810 μg/μL, respectively, were observed with edema reductions of up to 40% by rBaltMIP, suggesting its use as an additional antivenom. In addition, myotoxicity neutralization experiments with the myotoxin BthTX-I showed that rBaltMIP was more effective in inhibiting muscle damage than the conventional antivenom. Thus, considering the severity of envenomations due to Bothrops alternatus (Rhinocerophis alternatus) and the low neutralization of their local effects (such as myotoxicity) by the current antivenoms, rBaltMIP is a promising molecule for the development of novel therapeutic strategies for clinical applications.

P.1.7 Contiguous gene syndrome causing ColVI myopathy, dysmorphism, frontal atrophy and diaphragmatic hernia

Collagen VI (Col6) deficiency results in a broad spectrum of clinical manifestations ranging from Ullrich Congenital Muscular Dystrophy (UCMD) to Bethlem Myopathy with intermediate phenotypes. The COL6A3 gene encodes the α3(VI) subunit and maps to chromosome 2 in one of the most commonly deleted subtelomeric region, del2q37. UCMD is not classically associated with central nervous system involvement. However, some cases with intellectual disability have been reported, without any molecular explanation. We report the case of a 4-year-old boy born to unrelated French parents presenting with hypotonia, torticollis and club foot at birth. He had a motor delay (walked unaided at 3 years). Diaphragmatic hernia was discovered fortuitously and surgically corrected at 2y10m. At 3 years, he presented facial (mostly oral) and proximal weakness, distal hyperlaxity, no retractions and pectus excavatum. Moreover, we noted a mild facial dysmorphism with prominent forehead, down-slanted eyes, thin upper lip and low-set big ears. Scars from the diaphragmatic and muscle biopsy surgeries were slightly hypertrophic. The evolution was marked by seizures and two episodes of spontaneous fractures. Plasma CK levels were normal and the muscle biopsy findings were not specific. Cerebral MRI showed atrophy of the frontal lobe. Given the muscular phenotype, collagen VI immunolabeling was studied in cultured fibroblasts and demonstrated reduced Col secretion associated with intracytoplasmic retention. Currently aged 4y3m, the patient presents a positive evolution regarding motor and intellectual development. Interestingly, CGH array revealed a de novo translocation (2;4) with 2qter deletion (2q37.2–q37.3) and genomic gain at 4qter (4q35.1–q35.2), resulting in deletion of one COL6A3 allele. This is to our knowledge the 1st case report of a patient with Col6 myopathy phenotype associated with central nervous system involvement ascribed to a contiguous gene syndrome involving the COL6A3 locus.

Resistance training in patients with limb‐girdle and becker muscular dystrophies

In this study we investigated the effect of strength training in patients with limb-girdle muscular dystrophy (LGMD) and Becker muscular dystrophy (BMD). In 2 studies we compared the effect of low-intensity training (LOIT; n = 8) and high-intensity training (HIT; n = 4) in muscles of the upper and lower extremities. Patients were tested for maximal strength and endurance before and after the training program. LOIT training over 6 months resulted in increased biceps strength and endurance. HIT training increased endurance and strength in wrist flexion and extension and in elbow flexion. One patient discontinued HIT training due to muscle soreness and mildly increased plasma CK levels without strength deterioration. Both LOIT and HIT increased muscle strength and endurance in some of the muscles tested and were well tolerated in most patients. Our findings suggest that supervised resistance training may be considered in the management of patients with LGMD2 and BMD.

S65 Raised CK Levels in Severe Asthmatics Admitted to the Critical Care Unit- A Retrospective Cohort Analysis

<h3>Introduction and Aims</h3> Acute severe asthma is a life threatening condition. Mechanical ventilation may be indicated in about third of asthmatics admitted to the intensive care unit and has a mortality rate of 8%.¹ Several reports have identified elevated CK levels during an episode of acute severe asthma. Intense muscular workload during an acute episode and drugs such as steroids, anaesthetic induction agents, aminophylline and salbutamol are all implicated in raising plasma CK levels. Our aim was to retrospectively evaluate the CK levels and clinical implications in patients with acute severe asthma, who were admitted to our intensive care unit. <h3>Methods</h3> This was a retrospective survey of all asthmatics admitted to intensive care unit between October 2009 and July 2011. Patient’s case notes were screened to identify demographics and clinical details. <h3>Results</h3> Thirty asthmatics with 37 admissions were identified. Three patients had multiple admissions. Mean age was 37 and two third were female. Twelve patients had CK levels performed as part of clinical management. Seven patients (58%) had CK levels ≤320 IU/ml and 5 patients (42%) had CK levels ≥320 IU/ml. Patients with raised CK levels had more intubations, ICU days and hospital days. IV aminophyline and IV salbutamol infusions were more frequent in patients with raised CK levels. The elevated CK was noted on average 1.8 days after the admission (Table 1). Three patients with raised CK levels had severe renal failure with evidence of myoglobinuria. Statistical analysis is not performed due to small number of patients. <h3>Discussions</h3> Acute severe asthmatics may develop raised CK levels with evidence of myoglobinuria and subsequent renal failure. The exact mechanisms are not fully explored. Intravenous beta₂-agonists with combination of IV aminophylline may be a contributory factor. Prospective studies are needed to evaluate the path ophysiological mechanisms and clinical implications. <h3>References</h3> McFadden ER Am J Respir Crit Care Med 2003. Pathologyharmony.co.uk (for reference range).

Whole body vibration is a safe exercise training method and induces no impaired alterations on rat plasma parameters

Whole body vibration (WBV) has been regarded as an exercise training method and as a non-pharmacological supportive treatment option appearing to be efficient for chronic disease conditions, such as bone disorders and cardio-respiratory fitness. Since, data on the safety and efficacy of vibration on plasma parameters are lacking, therefore, it was decided to assess the effects of WBV on the plasma parameters in adult male Wistar rat model. Male Wistar rats, weighing 140–180 g, were divided into control and the vibration group. Vibration training consisted of vertical sinusoidal whole body vibration for 8 weeks, followed by blood collection. The vibrated rats weighed more than the control group (approximately 14% more). Plasma CK, E2 and IL-6 levels were significantly higher in the vibration group compared with the controls. The mean of Vit. D level was 15% higher; hsCRP level was 11% lower and IL-6 level was 32% higher in the vibration group. No difference was observed for other selected plasma parameters. The potential effects of physiological responses of WBV on several physiological systems are without deteriorations in plasma parameters.

Pharmacologically activating the pyruvate dehydrogenase complex protects against statin‐induced myopathy in rodent muscle

Statin myopathy decreases Akt and FOXO phosphorylation, increases mRNA expression of FOXO gene targets PDK4, MAFbx and cathepsin-L and reduces muscle glycogen use in rodent skeletal muscle (Mallinson et al 2009). We hypothesised that increasing carbohydrate flux by pharmacologically activating the pyruvate dehydrogenase complex (PDC) would reduce statin myopathy by increasing Akt phosphorylation and thereby blunting the upregulation of FOXO gene targets. Female Wistar Hanover rats were administered (oral gavage) vehicle (CON, n=9), 88 mg.kg−1.d−1 simvastatin (SIM, n=8) or 88 mg.kg−1.d−1simvastatin and 40 mg.kg−1.d−1 DCA (SIM+DCA, n=9) for 12 d, after which the biceps muscle was collected. Compared to CON, SIM increased fibre necrosis and plasma CK levels (p<0.05) and reduced PDC activity (p<0.05), Akt (p<0.05) and FOXO1 (p<0.05) phosphorylation. MAFbx (p<0.001), cathepsin-L (p<0.001) and PDK4 (p<0.01) mRNA, were also elevated along with proteasome activity (p<0.05). SIM+DCA markedly reduced fibre necrosis and plasma CK concentration (p<0.01), whilst concomitantly increasing PDC activity (p<0.05) and decreasing MAFbx (p<0.001), cathepsin-L (p<0.001) and PDK4 (p<0.01) mRNA expression and proteasome activity (p=0.08). PDC activation reduced statin myopathy and catabolic gene expression, but independently of statin mediated reductions in Akt and FOXO1 phosphorylation.

Danon disease: intrafamilial phenotypic variability related to a novel LAMP‐2 mutation

Danon disease is an X-linked lysosomal disorder, characterized by hypertrophic cardiomyopathy, skeletal myopathy and mental retardation. We report a family with a novel mutation, in which the mother and her three sons were affected with various clinical presentations. A massive hypertrophy of the left ventricle was the predominant feature in the three male patients, with different degrees of severity of cardiac symptoms, from isolated palpitations to cardiac failure and sudden death. Muscle pain and weakness were also variable, but constantly associated with increased plasma CK levels. Finally, the male patients had variable degree of a mental retardation. The mother had an attenuated phenotype, limited to a mild hypertrophic cardiomyopathy with premature ventricular contractions diagnosed during her 40's. Microscopy examination of skeletal muscle biopsy, performed in the youngest patient, demonstrated atrophic myofibers with intracytoplasmic vacuoles suggesting lysosomal glycogen storage disease. Immunohistochemistry analyses in muscle specimen showed no detectable Lysosomal-Associated Membrane Protein-2 (LAMP-2), in keeping with the diagnosis of Danon disease. However, a very low expression of a shortened LAMP-2 protein could be evidenced by Western-blot in the patient's fibroblasts. Molecular investigations identified a novel splicing mutation (IVS6 + 1delG) in the LAMP-2 gene. This case report highlights the intrafamilial variability of Danon disease phenotype. In this case, morphological examination of muscle biopsy, showing lysosomal storage myopathy, and immunohistochemistry analyses can provide key elements for orienting etiologic investigations.

The effect of water immersion on the recovery of team-sport-specific exercise

Introduction: The purpose of the present study was to examine the effects of two hydrotherapy techniques, cold water immersion (CWI) and contrast-water therapy (CWT), on the recovery of team-sport-specific exercise tests following muscle-damaging exercise. Methods: Seven male, team-sport players (mean±SD age: 21±2 y, body mass:76.8±7.2 kg) completed a preliminary familiarisation trial for three team-sport-specific exercise tests (TESTS), which included an all-out 30-m sprint test, two agility T-tests (left and right) and a vertical jump test. Three experimental trials were subsequently carried out, each separated by one week, using a counter-balanced cross-over design. On each visit a resting fingertip blood sample and a rating of perceived muscle soreness (PMS) was collected. Participants then performed the TESTS, followed by a 5-min rest period. A repeated sprint exercise (RSE) protocol was then performed to induce muscle damage, which comprised of 15 × 30-m sprints with a 10-m deceleration zone. Sprints were separated by 1 min. A second fingertip blood sample and PMS score was collected immediately after the RSE and a second set of TESTS were performed 10 min after the RSE. Participants then received either CWI, CWT or no water immersion (CON). The next day (24–28 h later) a final fingertip blood sample and PMS score was collected and a final set of TESTS were completed. Results and conclusion: There were no changes in plasma CK over time and no significant interaction effects between the three intervention groups (P > 0.05). The PMS increased from baseline to 24–28 h in the CON group (P 0.05). The PMS was significantly higher for CON compared with CWT after 24–28 h (P 0.05). There were no significant differences in performance during the TESTS between the three intervention groups across any of the three time points (pre RSE, post RSE or after 24–28 h; P > 0.05). These data suggest that the RSE may not have induced sufficient muscle damage to increase plasma CK levels, which may explain why the recovery interventions did not have a significant effect on performance of the TESTS. However, the differences in PMS changes indicate that hydrotherapy may be effective in suppressing the perception of muscle soreness when biochemical and performance markers are unchanged.

Muscle Fiber Type And Blood Oxidative Stress Following Muscle Damaging Strength Exercise

Acute participation in high intensity strength type exercise elicits a transient blood oxidative stress. Factors underlying the oxidative stress magnitude, however, are poorly understood. There is a rationale to suspect that muscle fiber type composition may influence the magnitude of the blood oxidative stress response to acute strength training. PURPOSE: To determine whether muscle fiber type correlates to the magnitude of blood oxidative stress following acute strength type exercise. METHODS: Eleven college aged males performed muscle damaging strength exercise which involved 3 sets of 50 eccentric-action repetitions at a rate of 30 degrees/second. Heparinized blood plasma samples taken Pre, Post, 24 hours, 48 hours, 72 hours, and 96 hours post muscle damaging exercise were assayed for comparison of muscle damage (creatine kinase - CK, and lactate dehydrogenase - LDH) and oxidative stress biomarkers (uric acid - UA, Ferric Reducing Antioxidant Power - FRAP, Trolox-Equivalent Antioxidant Capacity - TEAC, lipid hydroperoxides - LOOH, and protein carbonyls - PC). Muscle biopsies were taken of the vastus lateralis prior to the muscle damaging exercise protocol and subsequently assayed to determine the relative percentage of slow and fast type muscle fibers. Relationships between oxidative stress, muscle damage, and muscle fiber type were examined. RESULTS: A mixed fiber composition existed (Type I = 36.2 +/- 4.7%, Type IIa = 34.3 +/- 3.1, Type IIx = 29.53 +/- 2.73%; p = 0.366). Plasma CK levels peaked 24-96 hours post exercise (214%, p = 0.002) while LDH levels peaked between Post and 96 hours post (18%, p = 0.012). No elevation in Pre-to-immediately-Post sample oxidative stress biomarkers was observed. An elevation in plasma PC existed, however, 24, 48, 72, and 96 hours (p = 0.032) post strength exercise, with a peak response of 126% (p = 0.012) above baseline. No statistically significant correlations existed between muscle fiber composition and elevations in plasma markers for oxidative stress or muscle damage. CONCLUSIONS: A fiber type - oxidative stress relationship did not exist following muscle damaging strength type exercise. Further study is needed to determine whether a fiber type-oxidative stress relationship exists in individuals with fast or slow muscle fiber type predominance.

Spinal and bulbar muscular atrophy: Skeletal muscle pathology in male patients and heterozygous females

Spinal and bulbar muscular atrophy (SBMA) is an adult form of X-linked motor neuron disease caused by an expansion of a CAG repeat sequence in the first exon of the androgen receptor (AR) gene. Nuclear accumulation of mutant AR with expanded polyglutamines in motor neurons is a major pathogenic mechanism. To characterize muscle involvement in SBMA the skeletal muscle biopsies of 8 SBMA patients and 3 female carriers were studied. Six of 8 SBMA patients showed myogenic changes together with the neurogenic atrophy in their muscle biopsy. Myopathic abnormalities did not correlate with disease duration and were more prominent in the muscle of patients with an higher degree of disability. In all patients plasma CK levels were more elevated than what usually occurs in denervative diseases. Both neurogenic and myopathic changes were also observed in female carriers. Here we suggest that myopathic changes in SBMA muscle are not only related to denervation and that muscle satellite cells may have a role in the pathogenesis of muscle damage.

High plasma creatine kinase: review of the literature and proposal for a diagnostic algorithm

The condition of persistently high plasma CK levels is frequently encountered in asymptomatic patients with normal neurological examination. This condition may be the unique manifestation of several neuromuscular disorders, whose diagnosis is now possible using new diagnostic techniques. However, even if these patients are intensely investigated, specific diagnoses are not always forthcoming. Because of the lack of a widely accepted diagnostic protocol, hyperCKaemia in asymptomatic subjects is a potentially difficult clinical problem. In this paper we review the literature on conditions associated with variations in plasma CK levels and the literature on investigations carried out in asymptomatic persons with high CK to identify neuromuscular diseases. In the light of these data, and the deliberations of a working group of the Italian Association of Myology, we propose a diagnostic algorithm to guide the diagnostic work-up of persons presenting with persistently high levels of plasma CK. This algorithm has been discussed and approved by the Committee of the Italian Association of Myology.

The role of muscle damage in muscle remodeling: No pain, no gain?

Skeletal muscle is a dynamic tissue that responds adaptively to both the nature and intensity of muscle use. This study tested the hypothesis that a damaging bout of exercise is pre-requisite for muscle hypertrophy. Although this hypothesis has been widely accepted, there is surprisingly scant evidence that muscle damage, accompanied by an inflammatory response, is a necessary precursor to muscle hypertrophy. Subjects were divided into two experimental populations: (PT) pre-trained (n=7) and (NA) naïve (n=7). Muscle damage was avoided in the pre-trained group by a 3 week gradual “ramp-up” program before both groups were subjected to an 11 week high force eccentric cycle ergometry program (20min, 3x/week). Work totals throughout the 11 week session were the same for both groups. The naïve group experienced damage, whereas the pre-trained group did not, as indicated by: >5 times higher plasma CK levels and self reporting of perceived soreness, fatigue and exertion. The observed increase in mean cross sectional area (and total muscle volume) was significant for both groups (p<0.01) but not different between groups (NA=7.0% and PT=6.1%). Strength increases were also observed for all subjects in the study (PT=20% and NA=24% improvement) again, no significant difference was found between the groups. Independent of any initial muscle damage, muscle volume increases and quadriceps strength increases were found to be the same for both groups indicating that a damaging bout may not be a prerequisite to muscle hypertrophy. Arizona Technology and Research Initiative Fund.