Muscle Enzymes Research Articles

Clinical Characteristics of Anti-Synthetase Syndrome: Analysis from the CLASS project.

Anti-synthetase syndrome (ASSD) is a rare systemic autoimmune rheumatic disease (SARD) with significant heterogeneity and no shared classification criteria. We aimed to identify clinical and serological features associated with ASSD that may be suitable for inclusion in the data-driven classification criteria for ASSD. We utilized a large, international, multi-center "Classification Criteria for Anti-synthetase Syndrome" (CLASS) project database, which includes both ASSD patients and controls with mimicking conditions, namely SARDs and/or interstitial lung disease (ILD). The local diagnoses of ASSD and controls were confirmed by project team members. We employed univariable logistic regression and multivariable Ridge regression to evaluate clinical and serological features associated with an ASSD diagnosis in a randomly selected subset of the cohort. Our analysis included 948 ASSD cases and 1077 controls. Joint, muscle, lung, skin, and cardiac involvement were more prevalent in ASSD than in controls. Specific variables associated with ASSD included arthritis, diffuse myalgia, muscle weakness, muscle enzyme elevation, ILD, mechanic's hands, secondary pulmonary hypertension due to ILD, Raynaud phenomenon, and unexplained fever. In terms of serological variables, Jo-1 and non-Jo-1 anti-synthetase autoantibodies, antinuclear antibodies with cytoplasmic pattern, and anti-Ro52 autoantibodies were associated with ASSD. In contrast, isolated arthralgia, dysphagia, electromyography/MRI/muscle biopsy findings suggestive of myopathy, inflammatory rashes, myocarditis, and pulmonary arterial hypertension did not differentiate between ASSD and controls or were inversely associated with ASSD. We identified key clinical and serological variables associated with ASSD, which will help clinicians and offer insights into the development of data-driven classification criteria for ASSD.

Prompt response to rituximab in a patient with resistant polymyositis with complications of dysphagia and dysphonia: a case report

Introduction and importance: Polymyositis is an inflammatory process, primarily affecting proximal muscles, characterized by elevated muscle enzymes and distinctive electromyography patterns. Case presentation: The authors present a case of a 33-year-old male patient experiencing complications of polymyositis, including pharyngeal and laryngeal involvement leading to dysphagia and dysphonia. Steroids and intravenous immunoglobulin (IVIG) therapy proved ineffective. Subsequently, rituximab was administered, resulting in significant improvement in dysphagia, dysphonia, and proximal muscles within 3 days of the initial rituximab dose. Additionally, there was a remarkable decrease in creatine phosphokinase (CPK) levels. Clinical discussion: Immune-mediated myopathies (IMM) are rare diseases characterized by muscle inflammation and weakness. This case of probable polymyositis, diagnosed through clinical features and elevated CPK, was complicated by the patient’s lack of response to glucocorticoids and IVIG therapy. Remarkably, rituximab treatment led to rapid improvement in muscle strength and symptoms, highlighting its potential effectiveness in refractory cases of polymyositis. Conclusions: Primary treatment for cases of polymyositis typically involves the use of glucocorticoids. However, approximately half of the patients do not respond adequately to corticosteroids alone. Alternatives, in such cases, encompass IVIG therapy and rituximab.

Disease characteristics and medications use in idiopathic inflammatory myopathy: a multi-center prospective observational study of decentralized remote vs. traditional clinic enrollment.

Idiopathic Inflammatory Myopathies (IIM) are rare and characterized by heterogeneous manifestations and clinical trajectories. Utilizing tele-research methods has the potential to improve participant recruitment and advance the understanding of the disease. We aimed to evaluate disease characteristics in IIM patients throughout the U.S. and compare these parameters between patients recruited remotely through mobile application or website vs those recruited locally in myositis clinics. "Myositis Patient Centered Tele-Research" (My PACER) is a multicentre prospective observational study of U.S. IIM subjects, competitively recruited through traditional in-person clinic visits (Center-Based Cohort [CBC]), and remotely using mobile application or website and social media (Tele-Research Cohort [TRC]). Data collection comprised baseline demographic and clinical variables, encompassing symptoms, organ involvement, diagnostic tests results and medication use. The study included 120 IIM patients, 82 in the TRC and 38 in the CBC. The average age was 55 ± 13.4, 75% females and 81% Caucasians. Both cohorts exhibited similar demographic characteristics. Overall, 41% dermatomyositis, 27% polymyositis, 23% anti-synthetase syndrome, and 9% necrotizing myositis patients were enrolled, with comparable subtypes prevalence among cohorts (p= 0.85). The groups demonstrated similarities in multiple clinical factors, including muscle enzymes, diagnostic delay, employment status, various patient and physician-reported outcomes, functional tests, and the frequency of abnormal findings in chest CT, pulmonary function tests, and electromyography. TRC patients received biologics and csDMARDs more frequently (p< 0.001 and p= 0.013, respectively). Tele-research recruitment yielded a patient cohort resembling traditionally recruited patients demographically and clinically, indicating its effectiveness for robust and diverse patient recruitment in clinical studies.

The Effect of the Species Source of Muscle and/or Digestive Enzymes on the Utilization of Fish Protein Hydrolysates as a Dietary Protein Source in First Feed for Larval Walleye (Sander vitreus).

Fish protein hydrolysates used in larval diets have been prepared from a variety of fish species, with different enzymes used to hydrolyze the protein. This study's objectives were to determine the effect of the dietary inclusion of fish muscle hydrolysates obtained from species-specific muscle/enzymes-versus hydrolysates produced from muscle/enzymes of a different species-on the growth performance, survival, skeletal development, intestinal peptide uptake, and muscle-free amino acid (FAA) composition of larval Walleye (Sander vitreus). Eight protein products were obtained for this study, comprising an unhydrolyzed and hydrolyzed product from each combination of muscle/enzymes from Walleye and Nile tilapia (Oreochromis niloticus). Four diets were produced, and the dietary protein was provided in a 50/50 ratio of unhydrolyzed and hydrolyzed protein from the respective muscle/enzyme combination. Four groups were fed one of the corresponding formulated diets, and two groups of larvae, fed a commercial starter diet and Artemia, respectively, served as reference groups. Larval Walleye fed the diet containing protein produced with the species-specific muscle and enzymes had a significantly higher weight after the study-30% higher than any other group. A significant interaction effect between muscle and enzyme sources on the growth of Walleye larvae was observed. The species-specific combination also led to a significant increase in postprandial FAA and indispensable amino acid concentrations in muscle. No significant differences were observed between the hydrolysate-fed groups in survival, deformity occurrence, or peptide uptake. Each hydrolysate-based diet significantly reduced skeletal deformities and survival compared to the commercial diet. The results of this study suggest that species-specific muscles and enzymes produce a more optimal dietary protein source for larval fish than non-species-specific products. Further research should focus on improving the physical properties of the formulated diets to reduce possible leaching of hydrolyzed protein and improve the survival of fish larvae.

A case report on congenital hypothyroidism and alpha thalassemia in children with anemia and muscle damage as the main manifestation.

This study reports the first case of congenital hypothyroidism (CH) and alpha thalassemia in a child in China, with anemia and muscle damage as the main manifestations. Analyzing and studying this case is of great significance in reducing missed and misdiagnosed CH and will provide a clinical strategy for treating these patients. Child, female, 2 years and 7 months old, the child appeared dispirited, had poor appetite, shallow complexion, reduced activities with anemia, elevated muscle enzymes, height, and growth retardation. The child was diagnosed with CH with alpha thalassemia. The patient was treated with levothyroxine sodium and anemia correction. The children's current spirit, appetite, red face, normal limb activity, physical development, and intelligence were significantly better than those of normal children of the same age. CH with alpha thalassemia, especially anemia and muscle damage as the main manifestations, has not been reported. Administration of levothyroxine sodium is effective in correcting anemia in patients with CH and alpha thalassemia. Due to CH and alpha thalassemia, there are no specific symptoms and they are prone to missed diagnosis and misdiagnosis. Therefore, patients with anemia and elevated muscle enzyme levels should be routinely tested for thyroid function to diagnose them early and provide proper treatment to avoid negative consequences.

Atypical Facio-Scapulo-Humeral Dystrophy with facial sparing: a case report

Facio-Scapulo-Humeral Dystrophy (FSHD) is an autosomal dominant and third most common inherited muscular dystrophy. Typical phenotype of FSHD initially affects the muscles of the face and upper arm. Atypical FSHD refers to genetically confirmed FSHD with phenotypic variations. Scapulo-Humeral Dystrophy (SHD) is the most common atypical form of FSDH characterized by no facial muscle weakness on clinical examination, while other signs remain consistent with FSHD. We report a 31-year-old male who presented with foot drop and had an unexpected presentation as SHD. Provisional diagnosis of SHD was based on careful medical history, physical examination findings, modest rise in muscle enzymes, and needle electromyography findings of myopathy. Muscle biopsy suggested dystrophic changes which supported the diagnosis of FSHD with facial sparing. Rehabilitation plan included patient and family counseling/education, lifestyle modifications, energy conservation strategies, right ankle foot orthosis, and therapeutic exercises with regular follow-up for monitoring of the disease.

ASM is a therapeutic target in dermatomyositis by regulating the differentiation of naive CD4 + T cells into Th17 and Treg subsets

BackgroundThis study aims to investigate the involvement of acid sphingomyelinase (ASM) in the pathology of dermatomyositis (DM), making it a potential therapeutic target for DM.MethodsPatients with DM and healthy controls (HCs) were included to assess the serum level and activity of ASM, and to explore the associations between ASM and clinical indicators. Subsequently, a myositis mouse model was established using ASM gene knockout and wild-type mice to study the significant role of ASM in the pathology and to assess the treatment effect of amitriptyline, an ASM inhibitor. Additionally, we investigated the potential treatment mechanism by targeting ASM both in vivo and in vitro.ResultsA total of 58 DM patients along with 30 HCs were included. The ASM levels were found to be significantly higher in DM patients compared to HCs, with median (quartile) values of 2.63 (1.80–4.94) ng/mL and 1.64 (1.47–1.96) ng/mL respectively. The activity of ASM in the serum of DM patients was significantly higher than that in HCs. Furthermore, the serum levels of ASM showed correlations with disease activity and muscle enzyme levels. Knockout of ASM or treatment with amitriptyline improved the severity of the disease, rebalanced the CD4 T cell subsets Th17 and Treg, and reduced the production of their secreted cytokines. Subsequent investigations revealed that targeting ASM could regulate the expression of relevant transcription factors and key regulatory proteins.ConclusionASM is involved in the pathology of DM by regulating the differentiation of naive CD4 + T cells and can be a potential treatment target.

The Effect of High Intensity Ultrasound on the Quality and Shelf Life of Tilapia (Oreochromis niloticus) Muscle

It has been documented that the shelf life of fishery products is extremely reduced due to microbial development and its endogenous biochemistry. For this reason, food technologists around the world are researching how to reduce the main processes that lead to spoilage. Recently, high-intensity ultrasound (HIU) has had different applications in the food industry because the cavitation effect can inhibit or reduce microbial development as well as cause conformational changes in muscle enzymes. Therefore, in this study, HIU was applied for 30, 60, and 90 min to the tilapia (Oreochromis niloticus) fillet, and subsequently, it was stored on ice for 20 days. During this period, samples were taken every 5 days (day 0, 5, 10, 15, and 20), and moisture content, pH, total volatile base (TVB-N), non-protein nitrogen (NPN), texture, electrophoresis, color, and microbiological analyses (mesophiles and psychrophiles) were determined. No significant changes (p ≥ 0.05) were observed in the moisture content, pH, and the L* parameter, while a significant decrease (p &lt; 0.05) in TVB-N (from 29.67 to 15.09), NPN (from 0.39 to 0.27%), and texture (from 4.88 to 2.69 N) were found. On the other hand, an increase (p &lt; 0.05) in a* (from 2.02 to 4.27) and b* (from 10.66 to 12.45) parameters, as well as total mesophile count (from 2.48 to 6.52 log CFU/g) were detected due to the application of ultrasound. The results suggest that the application of this treatment represents a viable alternative to increase the shelf life and quality of tilapia fillets stored on ice.

BIOCHEMICAL INDICATORS OF MILITARY BLOOD ON THE ISCHEMIC AND DENERVATION PROCESS IN MUSCLES AFTER A MINE-EXPLOSIVE INJURYS

The injuries received are accompanied by massive damage to the soft tissues of the limbs, main vessels and nerves, and the development of compartment syndrome. Violation of muscle function in the case of a limb injury can be both a consequence of denervation — as a result of damage to peripheral nerves, and ischemia with subsequent necrosis and fibrosis — as a result of direct or indirect damage to muscles, «tenotomy syndrome» — in case of traumatic damage to tendons and muscles yams, with the simultaneous combination of denervation and ischemia. Markers for assessing the state of muscle tissue — levels of Na+, K+ and Ca++ electrolytes, indicators of kidney function (urea, creatinine); glucose and the products of its transformations — lactate (lacticacid) and pyruvate (pyruvic acid) and, finally, muscle enzymes, namely creatine kinase (CK) and lactate dehydrogenase (LDH). Objective. To study the biochemical indicators of blood (activity of energy metabolism enzymes and electrolyte content) of military personnel with ischemic contracture and muscle denervation after a mine-explosive injury. Methods. The blood serum of 45 people, who were divided into IV groups, was analyzed. The average age of patients of the II group was 33.75 ± 3.46; III — 37 ± 3.66; IV — 35.86 ± 2.35. The results. The activity of LDH and CK and the content of electrolytes Na+, K+, Ca++ were determined in blood serum. Conclusions. LDH plays a key role in lactate metabolism and maintenance of energy balance in skeletal muscle. Its increased activity indicates the presence of hypoxia due to ischemic contracture of the limb and damage to peripheral nerves. KK enzyme protects cell membranes from damage. The tendency to decrease the activity of CC is a negative sign that reflects the initial process of destruction of the cell membranes of muscles damaged by a mine-explosive injury. The obtained results can be used to determine the severity of pathological processes in patients after traumatic damage to peripheral nerves and ischemic contracture, as well as when assessing the expediency of surgical intervention.

An unusual presentation of dermatomyositis: dermatomyositis sine dermatitis presenting with rapidly progressive myositis

Dermatomyositis sine dermatitis (DMSD) is a rare variant of dermatomyositis where progressive muscle weakness presents without the characteristic rash but with muscle histology of dermatomyositis. A 55-year-old woman presented with progressive severe proximal limb, neck, pharyngeal and respiratory muscle weakness, without dermatologic manifestations. Elevated muscle enzymes and myopathic electromyogram pointed towards inflammatory myositis while the muscle biopsy confirmed DMSD. Her condition improved with steroids, intravenous immunoglobulin, methotrexate, and rituximab. This case emphasises the necessity of maintaining a high index of suspicion for dermatomyositis, even when a classic skin rash is absent and the criticality of early aggressive treatment. Anti-NXP-2 antibody positivity could indicate severe disease.

FROM DERMATOMYOSITIS SINE DERMATITIS TO A COMPLETE FORM OF JUVENILE DERMATOMYOSITIS: AN INTRIGUING CASE REPORT!

Although rare, juveniledermatomyositis (JD) is the mostcommoninflammatorymyopathy in children. It is a vasculopathycategorizedintoclassical and non-classicalsubtypes, the latter includingamyopathicdermatomyositis (DM) and dermatomyositis (DM) withoutdermatitis. DM sine dermatitisis a rarelydescribedphenotype, representing an atypicalformwith no classiccutaneous manifestations, complicatingdiagnosis, and isthereforeidentified on the basis of well-defined diagnostic criteria.In this article, we report the case of a twelve-year-oldchildpresentingwith muscle weakness and myalgias one monthprior to admission. Clinicalexaminationrevealed a progressive myogenic syndrome withdysphagia to solids, with no other multi-visceralinvolvement or signs of severity. Mucocutaneousexaminationwaspoor, revealingonlyleukokeratosis of the leftlateralborder of the tongue, with no otherassociated skin signs. Muscle enzymes wereelevated. A myositis-specificautoantibodyassayrevealed a positive anti-NXP2. Electromyographyshowed a diffuse emyogenic syndrome. MRI of the lowerlimbsshowed diffuse hypersignal in the muscle tissue. A diagnosis of dermatomyositis sine dermatitiswas made, and treatmentwasinitiatedwith oral prednisone 2 mg/kg/day, combinedwithsubcutaneous Methotrexate 25 mg/week. In the absenceimprovementafter 5 months of treatment, weswitched to mycophenolatemofetil (MMF) at a dose of 600 mg/m² twicedaily, with good progression.Afterlosinghissight and stoppingtreatment for a long time, the patient returnedaftertwoyearswith a full clinicalpicture of juveniledermatomyositis, withsevere muscle weakness and skin signs. This time, given the severity of the disease, ourtherapeuticapproachwas to switch to third-line treatmentwithinfliximab 5 mg/kg biotherapyadministered at specificintervals, with good improvement.

Decreased Peripheral Blood Natural Killer Cell Count in Untreated Juvenile Dermatomyositis Is Associated with Muscle Weakness.

Juvenile Dermatomyositis (JDM) is the most common inflammatory myopathy in pediatrics. This study evaluates the role of Natural Killer (NK) cells in Juvenile Dermatomyositis (JDM) pathophysiology. The study included 133 untreated JDM children with an NK cell count evaluation before treatment. NK cell subsets (CD56low/dim vs. CD 56bright) were examined in 9 untreated children. CD56 and perforin were evaluated in situ in six untreated JDM and three orthopedic, pediatric controls. 56% of treatment-naive JDM had reduced circulating NK cell counts, designated "low NK cell". This low NK group had more active muscle disease compared to the normal NK cell group. The percentage of circulating CD56low/dim NK cells was significantly lower in the NK low group than in controls (0.55% vs. 4.6% p < 0.001). Examination of the untreated JDM diagnostic muscle biopsy documented an increased infiltration of CD56 and perforin-positive cells (p = 0.023, p = 0.038, respectively). Treatment-naive JDM with reduced circulating NK cell counts exhibited more muscle weakness and higher levels of serum muscle enzymes. Muscle biopsies from treatment-naive JDM displayed increased NK cell infiltration, with increased CD56 and perforin-positive cells.

Characterised intron retention profiles in muscle tissue of idiopathic inflammatory myopathy subtypes

ObjectivesIdiopathic inflammatory myopathies (IIMs) are a group of heterogeneous autoimmune diseases. Intron retention (IR) serves as an important post-transcriptional and translational regulatory mechanism. This study aims to identify changes in...

Correlation between acute muscle damage and oxidative protection enzymes during different aerobic exercises

Different types of aerobic exercise can cause different disorders of homeostasis. This cross-over experiment aimed to determine the muscle fatigue and the antioxidative protection of female basketball players following a load caused by three different aerobic-type exercises (low-intensity continuous, high-intensity continuous, and high-intensity interval training). Twelve female basketball players (age 17.7±4.3 years; weight 67.3±9.8 kg; height 178.0±7.4 cm) voluntarily participated in the study. A wash-out period of 7 days between single sessions of different training was provided. Venous blood was drawn right before and immediately after each exercise session. The parameters that were analyzed are markers of muscle damage and enzymes of antioxidant protection. As a marker of muscle damage, myoglobin (F=2.884; p=0.065) and lactates (F=5.254; p=0.008) have higher values and statistically significant differences between training types. Creatinine shows higher values after each training session (F=4.053; p=0.022). Results of enzyme activity for oxidative protection show statistically significant differences between groups for catalase (F=5.811; p=0.005) with different types of training intervention. At the beginning of the preparatory period, parameters of acute muscle damage values are high. During the season, in response to different types of training, those parameters decrease in response to the body's adaptation to exercise-induced stress. Training leads to maintenance of physiological balance in the body and oxidative stress is not a necessary phenomenon of high aerobic training load. The inclusion of antioxidant protection enzymes decreases as the body adapts to a certain type of exercise.

Treatment and nursing care of a patient diagnosed with malignant hyperthermia after general anesthesia: a case report.

Malignant hyperthermia (MH), characterized by severe myoclonus, pyrexia, tachycardia, hypertension, elevated muscle enzymes, and hypercapnia, often occurs in patients with congenital deformities or genetic disorders. Although the reported incidence rate is as low as 1:5000 to 1:100,000, patients with MH exhibit rapid aggravation and an elevated mortality rate. Thus, MH is associated with substantial perioperative risk. Successful treatment of patients with MH largely depends on early diagnosis and timely effective treatment. This clinical report provides a detailed description of a patient with newly diagnosed MH who developed a rapid rise in body temperature, end-tidal carbon dioxide, and heart rate during maxillary osteotomy. After successful rescue, the patient recovered smoothly during the postoperative period, indicating the importance of intraoperative monitoring, early diagnosis, effective treatment, and postoperative monitoring. This case is expected to serve as a reference for future interventions and healthcare practices in managing other patients with MH.

Skeletal muscle PGC-1α remodels mitochondrial phospholipidome but does not alter energy efficiency for ATP synthesis.

Exercise training is thought to improve the mitochondrial energy efficiency of skeletal muscle. Some studies suggest exercise training increases the efficiency for ATP synthesis by oxidative phosphorylation (OXPHOS), but the molecular mechanisms are unclear. We have previously shown that exercise remodels the lipid composition of mitochondrial membranes, and some of these changes could contribute to improved OXPHOS efficiency (ATP produced by O2 consumed or P/O). Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) is a transcriptional co-activator that coordinately regulates exercise-induced adaptations including mitochondria. We hypothesized that increased PGC-1α activity is sufficient to remodel mitochondrial membrane lipids and promote energy efficiency. Mice with skeletal muscle-specific overexpression of PGC-1α (MCK-PGC-1α) and their wildtype littermates were used for this study. Lipid mass spectrometry and quantitative PCR were used to assess muscle mitochondrial lipid composition and their biosynthesis pathway. The abundance of OXPHOS enzymes was determined by western blot assay. High-resolution respirometry and fluorometry analysis were used to characterize mitochondrial bioenergetics (ATP production, O2 consumption, and P/O) for permeabilized fibers and isolated mitochondria. Lipidomic analyses of skeletal muscle mitochondria from wildtype and MCK-PGC-1α mice revealed that PGC-1α increases the concentrations of cone-shaped lipids such as phosphatidylethanolamine (PE), cardiolipin (CL), and lysophospholipids, while decreases the concentrations of phosphatidylcholine (PC), phosphatidylinositol (PI) and phosphatidic acid (PA). However, while PGC-1α overexpression increased the abundance of OXPHOS enzymes in skeletal muscle and the rate of O2 consumption (JO2), P/O values were unaffected with PGC-1α in permeabilized fibers or isolated mitochondria. Collectively, overexpression of PGC-1α promotes the biosynthesis of mitochondrial PE and CL but neither PGC-1α nor the mitochondrial membrane lipid remodeling induced in MCK-PGC-1α mice is sufficient to increase the efficiency for mitochondrial ATP synthesis. These findings suggest that exercise training may increase OXPHOS efficiency by a PGC-1α-independent mechanism, and question the hypothesis that mitochondrial lipids directly affect OXPHOS enzymes to improve efficiency for ATP synthesis.

A Complex Case of Colchicine-Induced Myopathy and Polyarticular Gout in a Patient with Chronic Kidney Disease

Colchicine, a medication commonly used for the treatment of gout and other inflammatory conditions, is known to cause various adverse effects, including myopathy. We present a case of colchicine-induced myopathy in a 58-year-old male with a history of gout. The patient developed progressive muscle weakness after initiating colchicine therapy. Prompt discontinuation of colchicine resulted in resolution of symptoms and normalization of muscle enzyme levels. This case underscores the importance of recognizing colchicine-induced myopathy and prompt discontinuation of the medication to prevent further complications and report also highlights the challenges and considerations in managing a patient with multiple comorbidities and the importance of close follow-up and ongoing monitoring. Keywords: Colchicine, Myopathy, Gout, Adverse effects, Muscle weakness

Effect of sex and milk replacer with or without supplemental carnitine and arginine on growth characteristics, carcass, and meat quality of artificially reared low-birth weight pigs.

This study compared milk replacer either remaining unsupplemented (CON) or supplemented with 0.5g L-carnitine plus 16.7g L-arginine/kg (CarArg) and fed to 48 low-birth weight (L-BtW) artificially reared piglets (24 per group) from days 7 to 28 of age. Eight farrowing series were needed to complete the study. On day 28, the lightest piglets were slaughtered, and the heaviest pigs were weaned. The heaviest pigs were weaned on day 28 and offered free access to a starter (weaning to 25kg body weight [BW]), grower (25 to 60kg BW), and finisher diet (60 to 96kg BW on day 170 of age). After euthanization on days 28 and 170, blood was sampled for assessment of serum metabolite and hormone concentrations, and the semitendinosus muscle (STM) was weighed, and later subjected to enzyme activity analysis and assessment of myofiber characteristics. In the 170-d-old pigs carcass and meat quality traits were assessed. Growth data were analyzed accordingtoatwo-way analysis of variance (ANOVA), with dietary treatment and farrowing series as fixed effects, while remaining data were analyzed with dietary treatment, sex, their interaction, and farrowing series as main factors. Dietary treatments affected (P ≤ 0.049) muscle enzyme activity at both day 28, with greater citrate synthase (CS) and LDH activities and lower HAD:CS ratio in STM light portion, and lower LDH:CS ratio in STM dark portion, and 170 of age with lower HAD:CS ratio. In the starter period, CarArg pigs had greater average daily gain (P = 0.021) and average daily feed intake (P = 0.010). At slaughter, these pigs had lower (P = 0.013) glucose and greater (P = 0.022) urea serum concentrations. However, supplementing the milk replacer with carnitine and arginine had no long-term effects on growth performance, carcass composition, and meat quality of L-BtW pigs. In addition, muscle morphology and myofiber-related properties remained unaffected by the supplementation.

Clinical characteristics and genetic analysis of six children with carnitine palmitoyltransferase 2 deficiency.

To investigate the clinical characteristic and genetic variants of children with carnitine palmitoyltransferase 2 (CPT2) deficiency. The clinical and genetic data of 6 children with CPT2 deficiency were retrospectively analyzed. The blood acylcarnitines and genetic variants were detected with tandem mass spectrometry and whole-exon gene sequencing, respectively. There were 4 males and 2 females with a mean age of 32 months (15 d-9 years) at diagnosis. One case was asymptomatic and with normal laboratory test results, 2 had delayed onset, and 3 were of infantile type. Three cases were diagnosed at neonatal screening, and 3 cases presented with clinical manifestations of fever, muscle weakness, and increased muscle enzymes. Five children presented with decreased free carnitine and elevated levels of palmitoyl and octadecenoyl carnitines. CPT2 gene variants were detected at 8 loci in 6 children (4 harboring biallelic mutations and 2 harboring single locus mutations), including 3 known variants (p.R631C, p.T589M, and p.D255G) and 5 newly reported variants (p.F352L, p.R498L, p.F434S, p.A515P, and c.153-2A>G). It was predicted by PolyPhen2 and SIFT software that c.153-2A>G and p.F352L were suspected pathogenic variants, while p.R498L, p.F434S and p.A515P were variants of unknown clinical significance. The clinical phenotypes of CPT2 deficiency are diverse. An early diagnosis can be facilitated by neonatal blood tandem mass spectrometry screening and genetic testing, and most patients have good prognosis after a timely diagnosis and treatment.

Endocannabinoid remodeling in murine cachexic muscle associates with catabolic and metabolic regulation

Muscle degeneration is a common feature in cancer cachexia that cannot be reversed. Recent advances show that the endocannabinoid system, and more particularly cannabinoid receptor 1 (CB1), regulates muscle processes, including metabolism, anabolism and regenerative capacity. However, it is unclear whether muscle endocannabinoids, their receptors and enzymes are responsive to cachexia and exercise. Therefore, this study investigated whether cachexia and exercise affected muscle endocannabinoid signaling, and whether CB1 expression correlated with markers of muscle anabolism, catabolism and metabolism. Male BALB/c mice were injected with PBS (CON) or C26 colon carcinoma cells (C26) and had access to wheel running (VWR) or remained sedentary (n = 5–6/group). Mice were sacrificed 18 days upon PBS/tumor cell injection. Cachexic mice exhibited a lower muscle CB1 expression (−43 %; p < 0.001) and lower levels of the endocannabinoid anandamide (AEA; −22 %; p = 0.044), as well as a lower expression of the AEA-synthesizing enzyme NAPE-PLD (−37 %; p < 0.001), whereas the expression of the AEA degrading enzyme FAAH was higher (+160 %; p < 0.001). The 2-AG-degrading enzyme MAGL, was lower in cachexic muscle (−34 %; p = 0.007), but 2-AG and its synthetizing enzyme DAGLβ were not different between CON and C26. VWR increased muscle CB1 (+25 %; p = 0.005) and increased MAGL expression (+30 %; p = 0.035). CB1 expression correlated with muscle mass, markers of metabolism (e.g. p-AMPK, PGC1α) and of catabolism (e.g. p-FOXO, LC3b, Atg5). Our findings depict an emerging role of the endocannabinoid system in muscle physiology. Future studies should elaborate how this translates into potential therapies to combat cancer cachexia, and other degenerative conditions.