Serum Creatine Kinase Activity Research Articles

Postanesthetic rhabdomyolysis in 7 warmblood horses.

To describe the clinical findings, outcomes, and muscle histopathology in warmblood horses that developed severe rhabdomyolysis in the perianesthetic period despite remaining stable while under general anesthesia. 7 warmblood horses, 6 geldings and 1 mare, with a median age of 9 years (range, 4 to 18 years) and median weight of 615 kg (range, 550 to 703 kg). Records from the Valberg Neuromuscular Diagnostic Laboratory and Michigan State University were reviewed (2016 to 2023) to identify warmbloods with postanesthetic myopathy (PAM). Warmblood horses with no history of myopathy developed PAM after remaining stable while under general anesthesia. Five of 7 horses were in regular work prior to anesthesia, and activity level was unknown in 2 horses. Time to standing in recovery was prolonged, 3 horses were euthanized due to persistent recumbency, and rhabdomyolysis recurred in 4 horses 5 to 11 days after anesthesia, with 1 surviving. Horses had muscle stiffness, pain, and sweating and struggled to remain standing. As PAM developed, serum creatine kinase activity and lactate concentrations (12 ± 7 mmol/L; n = 5) were markedly increased. At necropsy, histopathology revealed complete glycogen depletion (5 of 7), acute myodegeneration (6 of 7), and chronic active myodegeneration of representative skeletal muscle samples. A semimembranosus biopsy obtained 14 days after anesthesia from the survivor had rare glycogen-depleted fibers. Warmblood horses are susceptible to fatal PAM characterized by acute myodegeneration, lactic acidosis, and muscle glycogen depletion that occurs up to 11 days after anesthesia. In horses with delayed recovery after anesthesia, monitoring for 2 weeks after anesthesia, including assessment of serum creatine kinase activity and blood lactate, could potentially improve outcomes.

Neosporosis in 21 adult dogs, 2010-2023.

Limited information is available regarding the clinical features, treatment, and prognosis of neosporosis in adult dogs. Describe the clinical signs, laboratory findings, magnetic resonance imaging (MRI) findings, treatment and outcome in adult dogs (>6 months) diagnosed with neosporosis based on consistent clinical signs and positive serology (titer ≥1 : 800) at a referral hospital in Sydney, Australia. Twenty-one client-owned dogs. Retrospective case series of affected dogs between 2010 and 2023. Survival times were determined from onset of clinical signs to date of death or censoring. Clinical signs varied, and were indicative of generalized myopathy (6 dogs), multifocal intracranial disease (7 dogs), myelopathy (4 dogs), polyneuropathy (2 dogs) and single cases of focal myopathy and cerebellar disease. Serum creatine kinase activity was markedly increased (median, 3369 U/L) in most dogs. The most common MRI abnormalities were multifocal intracranial abnormalities (7/13 dogs) and muscle changes (5/13 dogs) whereas T2-weighted cerebellar abnormalities (2/13 dogs) and cerebellar atrophy (1/13) were less common. Treatment response was complete (resolution to normal) in 8 dogs, incomplete (persistent neurological deficits) in 6 dogs, but there was minimal response in 7 dogs. Thirteen dogs (62%) were alive after 6 months and 12 dogs (57%) alive after 1 year. Relapse was common, with 4 dogs experiencing at least 1 relapse event during the follow-up period. Adult-onset neosporosis is uncommon and has variable clinical presentations. Treatment response also is variable, and relapse can occur, even among patients that respond completely to initial treatment.

Construct validity of PROMIS pain interference, fatigue, and physical function as patient-reported outcomes in adults with idiopathic inflammatory myopathies: An international study from the OMERACT myositis working group

BackgroundValidated patient-reported outcome measures to assess disease impact in patients with adult idiopathic inflammatory myopathies (IIMs) are needed. The objective of this study was to assess the construct validity of PROMIS Pain Interference, Fatigue, and Physical Function measures in comparison with core disease activity measures. MethodsAdults with IIM, excluding inclusion body myositis, from OMERACT Myositis Working Group (MWG) clinic sites completed PROMIS Short Form v1.0—Pain Interference 6a, PROMIS Short Form v1.0—Fatigue 7a, and PROMIS Short Form v2.0—Physical Function 8b measures. Core disease activity measures including patient and physician global disease activity assessments, manual muscle testing, serum creatine kinase activity, and Health Assessment Questionnaire Disability Index (HAQ-DI) were simultaneously assessed. To evaluate construct validity, a priori hypotheses for the expected correlations between PROMIS measures, age, and core disease measures were determined by >70 % agreement among MWG members and were compared against observed Pearson's correlations. Internal consistency of items and floor or ceiling effects for the PROMIS measures were also assessed. Subgroup analysis according to IIM subtype (dermatomyositis vs. non-dermatomyositis IIM) was performed. Results135 adults with IIM from 5 countries across North America, Europe, Asia, and Australia were included. For construct validity, a priori hypotheses were confirmed for 5 of 6 (83 %) PROMIS Pain Interference, 4 of 5 (80 %) PROMIS Fatigue, and 3 of 4 (75 %) PROMIS Physical Function correlations. Internal consistency was high for each PROMIS measure (Cronbach's alpha >0.9). Ceiling effects were observed only for PROMIS Pain Interference, with low/no pain in 29 % of patients. Subgroup analysis between dermatomyositis (n = 65) and non-dermatomyositis (n = 70) subtypes demonstrated similar correlations between PROMIS measures and disease activity measures. ConclusionsPROMIS Short Form v1.0—Pain Interference 6a, PROMIS Short Form v1.0—Fatigue 7a, and PROMIS Short Form v2.0—Physical Function 8b measures demonstrate strong construct validity when compared to core disease activity measures in IIM, with consistent results across IIM subtypes. These findings support the use of these selected PROMIS measures to assess core domains of interest for measuring life impact in IIMs.

Creatine Kinase-MM/Proto-oncogene Tyrosine-Protein Kinase Receptor as a Sensitive Indicator for Duchenne Muscular Dystrophy Carriers.

Duchenne muscular dystrophy (DMD), a lethal X-linked recessive genetic disease, is characterized by progressive muscle wasting which will lead to premature death by cardiorespiratory complications in their late twenties. And 2.5-19% DMD carriers that also suffer from skeletal muscle damage or dilated cardiomyopathy when diagnosed as soon as possible is meaningful for prenatal diagnosis and advance warning for self-health. The current DMD carrier screening mainly relies on detecting serum creatine kinase activity, covering only 50-70% DMD carriers which will cause many false negatives and require the discovery of highly effective biomarker and simple detection procedure for DMD carriers. In this article, we have compiled a comprehensive summary of all documented biomarkers associated with DMD and categorized them based on their expression patterns. We specifically pinpointed novel DMD biomarkers, previously unreported in DMD carriers, and conducted further investigations to explore their potential. Compared to creatine kinase activity alone in DMD carriers, creatine kinase-MM can improve the specificity from 73 to 81%. And our investigation revealed another promising protein: proto-oncogene tyrosine-protein kinase receptor (RET). When combined with creatine kinase-MM (creatine kinase-MM/RET ratio), it significantly enhances the specificity (from 81 to 83%) and sensitivity (from71.4 to 93%) of detecting DMD carriers in serum. Moreover, we successfully devised an efficient method for extracting RET from dried blood spots. This breakthrough allowed us to detect both creatine kinase-MM and RET using dried blood spots without compromising the detection rate.

Investigating skeletal muscle biomarkers for the early detection of Australian myotoxic snake envenoming: an animal model pilot study

Introduction Myotoxicity is an important toxidrome that can occur with envenoming from multiple Australian snake types. Early antivenom administration is an important strategy to reduce the incidence and severity of myotoxicity. The current gold standard biomarker, serum creatine kinase activity, does not rise early enough to facilitate early antivenom administration. Several other skeletal muscle biomarkers have shown promise in other animal models and scenarios. The aim of this study was to examine the predictive values of six skeletal muscle biomarkers in a rat model of Australian snake myotoxicity. Methods Sprague-Dawley rats were anaesthetised and administered either Pseudechis porphyriacus (red-bellied black snake) or Notechis scutatus (tiger snake) venom, or normal saline via intramuscular injection. Blood samples were collected. Assays were performed for serum creatine kinase skeletal muscle troponin-I concentration, skeletal muscle troponin-C concentration, myoglobin activity, skeletal muscle myosin light chain-1 concentration, and creatine kinase-MM activity. Serum markers were plotted against time, with comparison of area under the concentration (or activity)-time curve. The predictive values of six skeletal muscle biomarkers were examined using receiver operating characteristic curves. Results There was no difference in area under the serum creatine kinase activity-time curve between venom and control groups. Serum creatine kinase-MM activity rose early in the venom treated rats, which had a significantly greater area under the serum activity-time curve. No difference in area under the serum concentration-time curve was demonstrated for the other biomarkers. Creatine kinase-MM activity had a superior predictive values than creatine kinase activity at 0–4 hours and 0–10 hours after venom administration, as indicated by area under the receiver operating characteristic curves (95 per cent confidence intervals) of 0.91 (0.78–1.00) and 0.88 (0.73–1.00) versus 0.79 (0.63–0.95) and 0.66 (0.51–0.80). Discussion The limitations of serum creatine kinase activity in early detection of myotoxicity were demonstrated in this rat model. Conclusion Serum creatine kinase-MM activity was superior for early detection of Australian myotoxic snake envenoming.

Benefits of Puerarin on Metabolic Syndrome and Its Associated Cardiovascular Diseases in Rats Fed a High-Fat/High-Sucrose Diet.

Metabolic syndrome (MetS) is a cluster of risk factors for cardiovascular diseases (CVDs) that has become a global public health problem. Puerarin (PUE), the principal active compound of Pueraria lobata, has the effects of regulating glucose and lipid metabolism and protecting against cardiovascular damage. This study aimed to investigate whether dietary supplementation with PUE could ameliorate MetS and its associated cardiovascular damage. Rats were randomly divided into three groups: the normal diet group (NC), the high-fat/high-sucrose diet group (HFHS), and the HFHS plus PUE diet group (HFHS-PUE). The results showed that PUE-supplemented rats exhibited enhanced glucose tolerance, improved lipid parameters, and reduced blood pressure compared to those on the HFHS diet alone. Additionally, PUE reversed the HFHS-induced elevations in the atherogenic index (AI) and the activities of serum lactate dehydrogenase (LDH) and creatine kinase (CK). Ultrasonic evaluations indicated that PUE significantly ameliorated cardiac dysfunction and arterial stiffness. Histopathological assessments further confirmed that PUE significantly mitigated cardiac remodeling, arterial remodeling, and neuronal damage in the brain. Moreover, PUE lowered systemic inflammatory indices including C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and systemic immune-inflammation index (SII). In conclusion, dietary supplementation with PUE effectively moderated metabolic disorders, attenuated systemic inflammation, and minimized cardiovascular damage in rats with MetS induced by an HFHS diet. These results provide novel insights into the potential benefits of dietary PUE supplementation for the prevention and management of MetS and its related CVDs.

Local and systemic responses to repeated gluteal muscle microbiopsies in mature sedentary horses

We aimed to test the hypothesis that repeated muscle collections would impact mitochondrial function, antioxidant status, and markers of inflammation and muscle damage. Twenty-six horses (8 geldings, 18 mares; mean ± SD 9.5 ± 3.5 y) had gluteus medius muscle biopsy samples collected at: 0 and 24h (n=7); 0 and 6h (n = 6); 0, 6, and 12h (n=7); or 0, 6, 12, and 24h (n=6). Blood was collected from all horses every 6h for 72h, starting 24h prior to the 0h muscle collection. Data were analyzed using mixed linear models. Muscle integrative (per mg tissue) electron transfer capacity of complex II decreased (P=0.004) and intrinsic (relative to citrate synthase (CS) activity) LEAK increased (P<0.03) from 0 to 6h but both returned to 0h levels by 12h. Activity of CS was greater at 0 than 12 and 24h (P≤0.02). Serum creatine kinase (CK) activity was similar from -24 through 0h but increased in all horses at 6h and remained elevated through 48h (P<0.05) though not above reference ranges. Whole blood superoxide dismutase activity fluctuated throughout the 72-h collection period (P=0.03) and serum cortisol concentration displayed a circadian pattern (P<0.0001) but neither were altered by muscle collections. No other variable, including muscle mitochondrial capacities and function, blood and muscle antioxidant status and concentrations of select cytokines, and serum amyloid A, differed by time or muscle collection. Repeated gluteal collections had limited short-term or no effect on physiological markers in unstressed, mature horses except serum CK activity, which should be interpreted with caution during repeated tissue collections.

Impact of curcumin supplementation on exercise performance and muscle damage after a soccer match: a double-blind placebo-controlled cross-over study.

Curcumin ingestion can mitigate muscle damage, soreness, and inflammation following a laboratory-based eccentric exercise. Similar effects were observed in recent field-based studies wherein responses were evaluated after a soccer match. However, various potential confounding factors, such as matching opponent skill levels and daily training conditions, may have influenced the outcomes. In the present study, we investigated whether curcumin intake ameliorates changes in muscle damage markers following a soccer match while controlling for the potential confounding factors. Fifteen collegiate athletes were tested in a randomized, double-blind, cross-over manner. They were recruited from the same college soccer team and thus followed the same daily training regimen and competition levels. Furthermore, athletes positioning during matches were counterbalanced. They consumed either 180mg/day of curcumin or a placebo starting 1h before the match and continuing for 2days after a match (two 45-min plays and a 15-min half-time). Muscle soreness, jump performance (including countermovement jump and rebound jump index), and inflammatory and muscle damage markers (high-sensitive C-reactive protein, serum creatine kinase activity, and urinary N-terminal fragment of titin concentration) were evaluated before and after the match. The washout period between matches was set at 1week. After the match, all markers showed similarity between the placebo and curcumin conditions (all P > 0.208). These findings indicate that ingesting 180mg/day of curcumin may not expedite recovery from muscle damage elicited by soccer matches in collegiate soccer players.

Effects of Dietary Calcium Lactate Supplementation on Laying Performance, Blood Index, Shinbone Quality, Jejunal Immunity, and Egg Quality of Aged Laying Hens

This study aimed to verify the potential of calcium lactate for the performance, blood index, shinbone quality, jejunal immunity, and egg quality of aged laying hens. A total of 360 62-week-old Hy-Line Brown laying hens were randomly divided into four treatments, with six replicates and 15 chickens per replicate. Experimental groups were fed with 0.25%, 0.5%, and 1.0% calcium lactate to substitute limestone in the control group (maintaining the same amount of calcium). The feeding trial lasted for 12 weeks. The laying rate and daily egg mass of laying hens fed the diets supplemented with calcium lactate was increased relative to those of the control group. The dietary addition of calcium lactate for laying hens enhanced the eggshell ratio, eggshell thickness, eggshell strength, and albumen height of eggs, and the addition level of 0.5% had the best effect. Dietary calcium lactate increased the number of red blood cells, corpuscular hemoglobin, mononuclear leucocytes and basophilic granulocytes, and decreased heterophils in the blood of laying hens. The activities of serum alanine transaminase and creatine kinase in laying hens was reduced by the dietary addition of calcium lactate. Calcium lactate supplementation in diets increased the serum calcium and phosphorus contents of laying hens. The dietary inclusion of calcium lactate increased the contents of IgA, IgG, lysozyme, and sIgA in the jejunal mucosa, and the 0.5% addition level worked best, but the IL-2 content decreased. The addition of 0.5% calcium lactate to the diet reduced the maximal force of the shinbone and increased the work required for shinbone rupture in laying hens. In conclusion, the dietary addition of calcium lactate improved the performance and egg quality of laying hens, probably by its positive effects on body health, intestinal digestible ability, calcium bioavailability, and jejunal mucosal immunity. The optimum amount of calcium lactate in the diet of laying hens is recommended to be 0.5%.

Common Markers of Muscle Damage Are Associated with Divergent Gene Expression Patterns after Eccentric Contractions.

Unaccustomed eccentric (ECC) exercise evokes exercise-induced muscle damage (EIMD). Soreness, strength loss, and serum creatine kinase (CK) are often used to quantify EIMD severity. However, changes in these markers are not fully understood mechanistically. To test the hypothesis that muscle damage markers are associated with unique molecular processes, we correlated gene expression responses with variation in each marker post-ECC. Vastus lateralis biopsies were collected from 35 young men 3 h post-ECC (10 sets of 10 maximal eccentric contractions; contralateral leg [CON] as control). Maximal isometric strength, soreness, and serum CK activity were assessed 24 h preexercise and every 24 h for 5 d post-ECC. Strength was also measured 10 min post-ECC. Over the 5 d after ECC, average peak strength loss was 51.5 ± 20%; average soreness increased from 0.9 ± 1.9 on a 100-mm visual analog scale to 39 ± 19; serum CK increased from 160 ± 130 to 1168 ± 3430 U·L -1 . Muscle RNA was used to generate gene expression profiles. Partek Genomics Suite correlated peak values of soreness, strength loss, and CK post-ECC with gene expression in ECC (relative to paired CON) using Pearson linear correlation ( P < 0.05) and repeated-measures ANOVA used to detect influence of ECC. After ECC, 2677 genes correlated with peak soreness, 3333 genes with peak strength loss, and 3077 genes with peak CK. Less than 1% overlap existed across all markers (16/9087). Unique genes included 2346 genes for peak soreness, 3032 genes for peak strength loss, and 2937 genes for peak CK. The largely unique molecular pathways associated with common indirect markers of EIMD indicate that each marker of "damage" represents unique mechanistic processes.

Inclusion of guanidinoacetic acid in a low metabolizable energy diet improves broilers growth performance by elevating energy utilization efficiency through modulation serum metabolite profile.

This study was aimed to explore the elevating energy utilization efficiency mechanism for the potentially ameliorative effect of guanidinoacetic acid (GAA) addition on growth performance of broilers fed a low metabolizable energy (LME) diet. A total of 576 d old broilers were randomly allocated to one of the six treatments: a basal diet (normal ME, positive control, PC), or an LME diet (50 kcal/kg reduction in ME, negative control, NC) supplemented with 0.02%, 0.04%, 0.06%, and 0.08% GAA from 1 to 42 d of age, respectively. The GAA fortification in LME diet linearly or quadratically dropped (P < 0.05) the feed conversion ratio (FCR) from 22 to 42 and 1 to 42 d of age, abdominal fat rate on day 42, serum alanine aminotransferase (ALT) on day 21, and serum creatinine (CREAN) on days 21 and 42, elevated (P < 0.05) breast muscle rate and leg muscle rate on day 42, serum creatine kinase (CK) on days 21 and 42, as well as alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) on day 21. The dietary optimal GAA levels were 0.03%-0.08% based on the best-fitted quadratic models (P < 0.03) of the above parameters. Thus, the PC, LME, and 0.04% GAA-LME groups were selected for further analysis. Serum essential amino acids (EAA) tryptophan, histidine and arginine, non-essential amino acids (NEEA) serine, glutamine and aspartic acid were significantly decreased (P < 0.05), compared to PC diet by LME or 0.04% GAA-LME diet. 0.04% GAA-LME group reversed (P < 0.05) the reduction of arginine, 3-methyhistidine, and 1-methylhistidine by LME diet. Besides, six birds at 28 d of age from LME and 0.04% GAA-LME groups were selected for energy utilization observation in calorimetry chambers. The results demonstrated that 0.04% GAA-LME group significantly improved (P < 0.05) the ME intake (MEI) and net energy (NE) compared to the LME diet. Overall, these findings suggest that 0.04% GAA is the ideal dose of broilers fed the LME diet, which can significantly improve the growth performance and carcass characteristics by modulation of creatine metabolism through elevating serum CK activity and arginine concentration.

Protective Effect of Dihydromyricetin Against ExerciseInduced Muscle Damage and Its Mechanism

Objective To investigate the protective effect of dihydromyricetin (DHM) against exercise-induced muscle damage (EIMD) in mice and its potential mechanism.Methods Adult male C57BL/6J mice were randomly divided into control group (CG), exercise group (EG), and exercise + 100 mg/kg weight ·d DHM (DHM) group. The intervention lasted for four weeks, during which the animals in the EG and DHM groups were subjected to exercise training for 1 h per day. The day after the training, a 90-min treadmill exercise (slope: 0 and speed: 18 m/min) was conducted in both EG and DHM groups. Samples of blood and gastrocnemius muscles were harvested from the three groups 24 h after the exercise, followed by the measurement of serum creatine kinase (CK) and lactate dehydrogenase (LDH) activities, total superoxide dismutase (T-SOD) activity, malondialdehyde (MDA), and skeletal muscle mitochondrial enzyme complex I and II activities. Histological changes in the skeletal muscle were observed by transmission electron microscopy, and the protein expressions of mitochondrial function-related pathways were detected by Western blotting.Results Skeletal muscle morphological changes and mitochondrial damage were alleviated in the DHM group compared to those in the EG. The activities of EIMD markers CK and LDH and the level of lipid peroxidation were notably repressed and the serum T-SOD activity was enhanced after DHM intervention. Western blotting demonstrated that the expressions of sirtuin type 3 (SIRT3), estrogen-related receptor alpha, and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha in the skeletal muscle of mice increased after the DHM intervention.Conclusion DHM can relieve EIMD in mice, possibly by promoting the recovery of the mitochondrial structure and function in the skeletal muscle of mice after high-intensity exercise via the activation of the SIRT3 signaling pathway.

The Association of Serum Calprotectin with Fitness Indicators and Biochemical Markers in High-Level Athletes: A Continuous Dynamic Monitoring during One Competitive Season.

Twenty professional male water polo players (median age: 28 (22-42)) were included in this study. Serum creatine kinase activity was determined by the automated photometric UV method. The concentrations of calprotectin, C-reactive protein, and myoglobin were measured using an automated immunoturbidimetric method, while an automated immunochemistry method was employed for interleukin-6, troponin I, and cortisol determination. Tests of repeated strength, maximal strength, and static strength were used to evaluate physical activity. Serum calprotectin concentrations expressed in median and IQR were significantly different: T1: 2.92 g/mL (2.47; 3.86); T2: 2.35 g/mL (1.26; 2.87); T3: 2.27 g/mL (1.60; 3.27); and T4: 1.47 g/mL (1.04; 2.85) (p = 0.004). Cortisol concentration and CK activity showed significant changes among phases (p = 0.049 and p = 0.014, respectively). Each physical activity examined showed a significant seasonal decrease (all p values were 0.001). Calprotectin serum concentration and indicators of muscular injury, inflammation, and physical activity were found to be correlated during particular stages of the seasonal examination. Calprotectin values determined throughout one competitive season decreased as training intensity among water polo players increased. Serum calprotectin concentrations and indicators were related to biochemical markers of inflammation and muscle damage.

Early functional and morphological changes of calf muscles in delayed onset muscle soreness (DOMS) assessed with 7T MRI

BackgroundTo assess morphological and functional alterations of the skeletal muscle in exercise-induced delayed onset muscle soreness (DOMS) using 7 Tesla (T) magnetic resonance imaging (MRI). MethodsDOMS was induced in 16 volunteers performing an eccentric exercise protocol of the calf muscles of one randomized leg. 7 T MRI including T1w- (0.18×0.18×1mm3), T2w-images (0.2×0.2×2mm3), T2-maps (0.5×0.5×5mm3), and susceptibility weighted imaging (SWI, 0.7×0.7×0.7 mm3) were acquired at baseline, directly (t1) and 60 hours (t2) after the exercise. T2 signal intensity (SI), T2 values [ms], T1 SI and SWI were assessed in the medial (MG) and lateral gastrocnemius muscle (LG) and in the soleus muscle (SM). In addition, the serum creatine kinase (CK) activity, range of motion (ROM) of the ankle, calf circumference, and muscle soreness were assessed at each time point. ResultsDirectly after exercise (t1), T2 SI (p=0.04) and T2 values (p=0.03) increased significantly in the LG. No changes of SI and T2 values for MG and SM were present at t1. At t2, T2 SI and T2 values of LG (p=0.001, p=0.02) and MG (p=0.04, p=0.03) increased significantly compared to baseline. T1 SI did not change in any muscle at any time point. In SWI, no signs of intramuscular signal drop could be detected. Clinical parameters confirmed the induction of DOMS, with a significant increase of CK (p=0.03), muscle soreness (p<0.001), calf circumference (p=0.001), and respective a decrease of ROM (p=0.04). Conclusions7 T MRI has the potential to visualize microstructural muscle damage immediately after an exercise that induces DOMS. No changes in susceptibility which could, for example, reflect micro-hemorrhage, could be detected with SWI immediately after exercise or in DOMS. Ultra-high field MRI may potentially be used in sports medicine to monitor intramuscular structural changes, allowing for modification of training intensity or to implement appropriate therapeutic strategies.

Accidental monensin poisoning in goats

Sodium monensin is the most frequently used ionophore as a growth promoter in ruminant diets. It has numerous benefits; however its toxic effects have also been observed in several animal species. Naturally occurring cases have not yet been reported in goats. This study describes an outbreak of accidental poisoning, characterizing its clinical, laboratory and pathological findings. Thirty-seven of 40 Anglo Nubian goat kids became intoxicated after receiving a diet that was erroneously supplemented with sodium monensin. They ingested an estimated toxic dose between 25 and 39 mg/kg BW. Clinical evolution was monitored (n = 27), followed by serum creatine kinase (CK) and aspartate aminotransferase (AST) activities measurements, and blood gas analysis. Postmortem examinations were performed between 1 and 8 days of evolution (n = 14). Clinical signs began 5 h after ingestion and included reticuloruminal hypomotility, lethargy, anorexia, tachycardia, cardiac arrhythmia, wet cough, pulmonary and tracheal crackles, and serous nasal discharge. The morbidity and lethality rates were 92.5 and 62.1%, respectively. CK and AST activities increased, reaching median values of 10,860 and 1596 U/L, respectively; the hyperchloremic metabolic acidosis was mild. The lesions were characterized by degeneration and necrosis of the cardiac and skeletal muscles, pulmonary congestion and edema, and passive liver congestion. The kids essentially developed cardiomyopathy with left and right congestive heart failures. Unlike in other ruminant species, skeletal muscle functional disability was infrequent. It can be concluded that monensin is toxic to goats and should be used with caution in their diet.

Monensin toxicosis in a dog with initial apparent recovery followed by severe relapse

AbstractThis case report describes successful intensive care management of a toxic myopathy in a 7‐month‐old, female, entire springer spaniel secondary to presumed monensin intoxication. The dog was seen chewing a monensin capsule, and was subsequently presented to the local veterinary practice with generalised weakness, ataxia, hypersalivation and pyrexia. Intravenous lipid emulsion‐activated charcoal and intensive fluid therapy were administered. Bloodwork identified a marked increase in serum creatine kinase activity (226,554 iu/L; reference range: 0–400 iu/L). The patient was discharged the following day after initial hospitalisation, with a complete resolution of clinical signs. Five days after exposure, a rapid deterioration required veterinary assessment at the referral hospital. The patient recovered and was discharged after 9 days of hospitalisation. This case report describes recurrence of clinical signs of monensin toxicosis after initial improvement. However, with aggressive emergency care, symptomatic therapy and intense monitoring, a positive outcome was achieved.

A fat- and sucrose-enriched diet causes metabolic alterations in mdx mice.

Duchenne muscular dystrophy (DMD), a progressive muscle disease caused by the absence of functional dystrophin protein, is associated with multiple cellular, physiological, and metabolic dysfunctions. As an added complication to the primary insult, obesity/insulin resistance (O/IR) is frequently reported in patients with DMD; however, how IR impacts disease severity is unknown. We hypothesized a high-fat, high-sucrose diet (HFHSD) would induce O/IR, exacerbate disease severity, and cause metabolic alterations in dystrophic mice. To test this hypothesis, we treated 7-wk-old mdx (disease model) and C57 mice with a control diet (CD) or an HFHSD for 15 wk. The HFHSD induced insulin resistance, glucose intolerance, and hyperglycemia in C57 and mdx mice. Of note, mdx mice on CD were also insulin resistant. In addition, visceral adipose tissue weights were increased with HFHSD in C57 and mdx mice though differed by genotype. Serum creatine kinase activity and histopathological analyses using Masson's trichrome staining in the diaphragm indicated muscle damage was driven by dystrophin deficiency but was not augmented by diet. In addition, markers of inflammatory signaling, mitochondrial abundance, and autophagy were impacted by disease but not diet. Despite this, in addition to disease signatures in CD-fed mice, metabolomic and lipidomic analyses demonstrated a HFHSD caused some common changes in C57 and mdx mice and some unique signatures of O/IR within the context of dystrophin deficiency. In total, these data revealed that in mdx mice, 15 wk of HFHSD did not overtly exacerbate muscle injury but further impaired the metabolic status of dystrophic muscle.

Hexavalent chromium inhibits myogenic differentiation and induces myotube atrophy

Hexavalent chromium [Cr(VI)] is extensively used in many industrial processes. Previous studies reported that Cr(VI) exposures during early embryonic development reduced body weight with musculoskeletal malformations in rodents while exposures in adult mice increased serum creatine kinase activity, a marker of muscle damage. However, the impacts of Cr(VI) on muscle differentiation remain largely unknown. Here, we report that acute exposures to Cr(VI) in mouse C2C12 myoblasts inhibit myogenic differentiation in a dose-dependent manner. Exposure to 2 μM of Cr(VI) resulted in delayed myotube formation, as evidenced by a significant decrease in myotube formation and expression of muscle-specific markers, such as muscle creatine kinase (Mck), Myocyte enhancer factor 2 (Mef2), Myomaker (Mymk) and Myomixer (Mymx). Interestingly, exposure to 5 μM of Cr(VI) completely abolished myotube formation in differentiating C2C12 cells. Moreover, the expression of key myogenic regulatory factors (MRFs) including myoblast determination protein 1 (MyoD), myogenin (MyoG), myogenic factor 5 (Myf5), and myogenic factor 6 (Myf6) were significantly altered in Cr(VI)-treated cells. The inhibitory effect of Cr(VI) on myogenic differentiation was further confirmed in freshly isolated mouse satellite cells, a stem cell population essential for adult skeletal muscle regeneration. Furthermore, Cr(VI) exposure to fully differentiated C2C12 myotubes resulted in a decrease in myotube diameter, which was exacerbated upon co-treatment with dexamethasone. Together, our results demonstrate that Cr(VI) inhibits myogenic differentiation and induces myotube atrophy in vitro.

Effect of chronic heat stress on the carbonylation of glycolytic enzymes in breast muscle and its correlation with the growth performance of broilers

Chronic heat stress has detrimental effects on the growth performance of broilers, and the potential mechanism is under exploration. In this study, the protein carbonyl modification was introduced to glycolytic enzymes to evaluate its relationship with the growth performance of heat-stressed (HS) broilers. A total of 144 male 28-day-old broilers were assigned to 3 treatments: the normal control group (NC, raised at 22°C with free access to feed and water), the HS group (raised at 32°C with free access to feed and water), and the pair-fed group (PF, raised at 22°C with an amount of feed equal to that consumed by the HS group on a previous day). Results showed that heat stress decreased the average daily growth, increased the feed-to-gain ratio (F/G), decreased breast muscle rate, and increased abdominal fat rate compared with the NC and PF groups (P < 0.05). Higher cloacal temperature and serum creatine kinase activity were found in the HS group than those of the NC and PF groups (P < 0.05). Heat stress increased the contents of carbonyl, advanced glycation end-products, malonaldehyde, and the activities of catalase, glutathione peroxidase, and total antioxidant capacity compared with the NC and PF groups (P < 0.05). Heat stress increased the contents of glucose and lactate, declined the glycogen content, and lowered the relative protein expressions of pyruvate kinase muscle type, lactate dehydrogenase A type (LDHA), and citrate synthase compared to those of the NC group (P < 0.05). In contrast to the NC and PF groups, heat stress intensified the carbonylation levels of phosphoglucomutase 1, triosephosphate isomerase 1, β-enolase, and LDHA, which were positively correlated with the F/G (P < 0.05). These findings demonstrate that heat stress depresses growth performance on account of oxidative stress and glycolysis disorders. It further increases the carbonylation of glycolytic enzymes, which potentially correlates with the F/G by disturbing the mode of energy supply of broilers.

Renal functional and structural alterations induced by intramuscular injection of Bothrops leucurus venom

Acute kidney injury (AKI) is the main cause of death from Bothrops snakebite. Although many studies have investigated the nephrotoxicity induced by other Bothrops species, no study has assessed the renal alterations induced by intramuscular (i.m.) injection of Bothrops leucurus venom. In this study, we evaluated the nephrotoxicity induced by B. leucurus venom by analyzing renal function and histology. Wistar rats were submitted to i. m. injection of B. leucurus venom or saline and divided into two groups: Control group (C), rats submitted to i. m. injections of saline, and B. leucurus group (Bl), rats submitted to i. m. injections of B. leucurus venom (1 mg/kg). After venom or saline injection, serum and urine were collected to measure creatinine, albumin, sodium, and potassium levels. The glomerular filtration rate (GFR), urinary flow urinary, creatinine/serum creatinine ratio, and albuminuria-urinary creatinine ratio were determined. All rats were euthanized 72 h following the injections, and the kidneys were removed for histology and immunohistochemical studies. B. leucurus experimental envenoming was accompanied by an increase of 236% in serum creatine kinase activity in the Bl group. The weights of the right and left kidneys were, respectively, 26 and 22% higher in rats of the Bl group than in control rats. Regarding renal function, the Bl group showed a decrease of 37% in GFR compared to control group. The rats of the Bl group also presented increased cortical (8.20 ± 1.35) and medullar (6.17 ± 2.00) tubulointerstitial lesion area when compared to control group (0.02 ± 0.00) (1.20 ± 0.73), respectively. The number of macrophages was also higher in the renal cortex (6.66 ± 0.06) and medulla (1.22 ± 0.10) of rats from the Bl group when compared to control rats (1.04 ± 0.55), (0.65 ± 0.10), respectively. Our results indicate that B. leucurus venom promoted significant histological and functional renal alterations following intramuscular inoculation, which simulates the majority of snakebites observed in the clinical practice.