Muscle Fiber Necrosis Research Articles

Modeling of rabbit femoral artery occlusion by high-intensity focused ultrasound

One of the effective methods of artery and vein occlusion used in experimental studies and in clinical practice for certain diseases is local exposure of vessels to high-intensity focused ultrasound (HIFU). The wide use of this method in our country is limited by the lack of appropriate domestic equipment. At the Peter the Great St. Petersburg Polytechnic University, in the Laboratory of Ultrasound Technologies of the Center for Advanced Research, a stand for HIFU effects on various biological objects has been developed. There is no experience in using this device in angiology yet. The purpose of our research was to study the possibility of using Medusa 008, a high-tech mobile medical device designed for ultrasound diagnosis and personalized HIFU therapy, to model vascular occlusion and stop blood flow during irradiation. Materials and methods. The object of the study is the femoral artery of a rabbit. The source of HIFU is Medusa 008, the high-tech mobile medical device designed for ultrasound diagnostics and personalized HIFU-therapy with radiation frequency of 2 MHz (prototype). The following irradiation modes were used in the research: irradiation duration - 50 ms, pause between exposures – 10 ms, number of pulses – 20, 30, 40. The following energy values corresponded to these modes: 58 J, 87 J, 116 J. Irradiation of the femoral artery of an anesthetized rabbit was performed percutaneously. We used ultrasound to visualize the arteries and measure the blood flow velocity. According to ultrasound data, after HIFU irradiation, blood flow in the artery stopped. The factor contributing to arterial occlusion is the cessation of blood flow during irradiation. A histological examination of the area of the irradiated artery revealed structural changes in all layers of the vascular wall. Results. HIFU irradiation with intensity of 87 and 116 J has a significant dose-dependent destructive effect on the muscular arterial wall. The more intense damaging irradiation (116 J) causes smooth muscle cell necrosis. The time of direct influence on the vessel wall structures did not exceed 3 sec. During the experiment, we found that HIFU in the used modes causes temperature increase up to 45–60 оC, which is enough for thermal damage of cells in the irradiation zone. Conclusion. Thus, as a result of the above experiments, it was shown that Medusa 008, the high-tech mobile medical device designed for ultrasound diagnostics and personalized HIFU-therapy can be used to simulate vascular occlusion.

Novel Antiarrhythmic and Cardioprotective Effects of Brilliant Blue G

In this study, we investigated the effects of the purinergic P2X7 receptor antagonist brilliant blue G (BBG) on cardiac arrhythmia and myocardial injury induced by intravenously (i.v.) administered epinephrine in anesthetized rats. We also examined the possible involvement of beta-adrenergic receptors or cholinergic mechanisms in the effects of BBG. Sprague-Dawley rats were treated with epinephrine (10 μg/kg, i.v.). Brilliant blue G (100 mg/kg) was intraperitoneally (i.p.) administered thirty minutes prior to i.v. epinephrine. The effects of pretreatment with propranolol (2 mg/kg, i.p.) or atropine (2 mg/kg, i.v.) given prior to BBG and epinephrine were examined. The control group received saline. Moreover, the effects of only BBG on electrocardiogram (ECG) parameters were investigated. Results showed that compared with the saline control, BBG caused significant bradycardia (from 405.8 ± 1.18 to 239.4 ± 6.69 beats/min), increased RR interval (from 0.149 ± 0.002 to 0.254± 0.007 sec) and PR interval (from 0.051 ± 0.0008 to 0.059 ± 0.0004 sec), increased R wave amplitude (from 0.238 ± 0.019 to 0.548 ± 0.009 mv), and shortened QTc interval (from 0.169 ± 0.006 to 0.141 ± 0.003 sec) over 15 minutes after of BBG administration. BBG did not cause cardiac arrhythmia. Meanwhile, epinephrine produced significant bradycardia (209.8 ± 28.78 vs. 405.8 ± 1.18 beats/min), increased PR interval, prolonged the QRS complex, shortened QTc interval, decreased R wave amplitude and induced ventricular tachycardia. Brilliant blue G given prior to epinephrine increased heart rate and completely suppressed the epinephrine-induced ventricular arrhythmia. The inhibitory effect of BBG on the arrhythmia caused by epinephrine was prevented by atropine. In contrast the epinephrine induced arrhythmia was completely suppressed with propranolol and BBG. The histopathological study showed that epinephrine caused necrosis and apoptosis of cardiac muscle cells, degeneration of cardiac muscle fibers, and interstitial haemorrhages. These changes were markedly prevented by BBG alone, propranolol/BBG and to a less extent by atropine/BBG pretreatment. The study provided the first evidence for a cardioprotective and anti-arrhythmogenic actions for BBG against epinephrine-induced arrhythmia and myocardial damage, and suggested that cholinergic mechanisms are involved in its anti-arrhythmogenic action.

Myotendinopathy of Unknown Etiology in Broiler Breeder Males.

This case series describes an emerging and ongoing lameness condition observed in broiler breeder males in flocks owned by a broiler integrator in the United States between February 2021 and April 2023. The lameness is characterized by an upright, penguin-like posture and gait. Affected flocks are typically 12-22 wk of age at presentation, but birds with similar stance and gross lesions can be observed as early as 1 day of age. Male mortality associated with this condition ranges from 0.01% to 6% per flock. The condition is infrequently observed in pullets from the female line but has not been observed in males (sex slips) from the female line. On postmortem examination, affected birds have bilateral hemorrhage due to a tearing of the iliotibialis muscles and fascia. In one case, a higher proportion of affected birds had unilateral lesions concurrently with broken legs or severe inguinal vaccine reaction. In this case, the affected leg was the weight-bearing leg. Histopathology confirmed the presence of hemorrhage in fascial sheaths surrounding major muscles, in addition to muscle fiber necrosis, edema, fibroplasia, and dissociation of tendon collagen. Bacteriology, histopathology, and clinical presentation identified no factors that were suggestive of an infectious etiology for this condition. No etiology has been established, but a suggested pathogenesis involves excessive biomechanical force resulting in tendon structural stress, leading to separation of tendon collagen fibers and associated muscle fiber stretching, separation, necrosis, and hemorrhage. The condition has been reported in multiple genetic lines, but the role of inheritance in the condition has not been fully evaluated.

Research Note: Chicken breast muscle satellite cell function: effect of expression of CNN1 and PHRF1

The Wooden Breast myopathy results in the necrosis and fibrosis of breast muscle fibers in fast-growing heavy weight meat-type broiler chickens. Myogenic satellite cells are required to repair and regenerate the damaged muscle fibers. Using Genome Wide Association, candidate genes affected with Wooden Breast have been previously reported. The effect of these genes on satellite cell proliferation, differentiation, and the synthesis of lipids by satellite cells is unknown. Satellite cells isolated from the pectoralis major muscle from commercial Ross 708 broilers and a Randombred chicken (RBch) line were used. Expression of calponin 1 (CNN1) and PHD and ring fingers domains 1 (PHRF1) were knocked down by silent interfering RNA to determine their effect on satellite cell-mediated proliferation, differentiation, and lipid accumulation. CNN1 and PHRF1 affected satellite cell activity and lipid accumulation in both lines. Proliferation was reduced in the Ross 708 and RBch lines by knocking down the expression of both genes, and differentiation was affected with a line and treatment interaction when gene expression was reduced at the beginning of proliferation. During differentiation lipid accumulation was decreased with knocking down the expression of CNN1 and PHRF1. Both CNN1 and PHRF1 have not been reported previously in skeletal muscle and further research is required to determine their effect on satellite cell-mediated growth and regeneration of the pectoralis major (breast) muscle.

Apelin stimulation of the vascular skeletal muscle stem cell niche enhances endogenous repair in dystrophic mice.

Impaired skeletal muscle stem cell (MuSC) function has long been suspected to contribute to the pathogenesis of muscular dystrophy (MD). Here, we showed that defects in the endothelial cell (EC) compartment of the vascular stem cell niche in mouse models of Duchenne MD, laminin α2-related MD, and collagen VI-related myopathy were associated with inefficient mobilization of MuSCs after tissue damage. Using chemoinformatic analysis, we identified the 13-amino acid form of the peptide hormone apelin (AP-13) as a candidate for systemic stimulation of skeletal muscle ECs. Systemic administration of AP-13 using osmotic pumps generated a pro-proliferative EC-rich niche that supported MuSC function through angiocrine factors and markedly improved tissue regeneration and muscle strength in all three dystrophic mouse models. Moreover, EC-specific knockout of the apelin receptor led to regenerative defects that phenocopied key pathological features of MD, including vascular defects, fibrosis, muscle fiber necrosis, impaired MuSC function, and reduced force generation. Together, these studies provide in vivo proof of concept that enhancing endogenous skeletal muscle repair by targeting the vascular niche is a viable therapeutic avenue for MD and characterized AP-13 as a candidate for further study for the systemic treatment of MuSC dysfunction.

Anti-SAE dermatomyositis: clinical and histologic characteristics from a monocentric Italian cohort.

Multiple myositis-specific antibodies have been identified, each associated with different clinical subsets of dermatomyositis (DM). Anti-SAE associated DM is considered the least studied subset. Our study aimed to evaluate the clinical and histological characteristics of DM patients with anti-SAE antibodies. As reference, patients with anti-Mi2 antibodies associated DM, representing a well-characterised subset, were analysed. We recorded data from our DM cohort in the INflammatory MYositis REgistry (INMYRE). Patients were divided into two groups: those positive for anti-SAE and those positive for anti-Mi2 antibodies. Clinical characteristics, including skin, muscle, and extra-muscular involvements, were recorded. Available muscle biopsies were compared between the two groups. Of 92 DM patients, 10 (10.9%) were positive for anti-SAE and 17 (18.5%) for anti-Mi2. Anti-SAE positive DM patients showed classic DM findings but were characterised by a higher prevalence of skin itching (60% vs. 11.8%, p<0.01), shawl sign (40% vs. 5.9%, p<0.05) and lung involvement (30% vs. 0%, p<0.05) compared to anti-Mi2 positive patients. Furthermore, anti-SAE positive DM patients showed lower creatine kinase levels than those with anti-Mi2 (median [IQR]: 101 [58-647] vs. 1984 [974-3717], p<0.05) and a lower percentage of muscle fibre degeneration and necrosis (1.5%±1.7 vs. 5.9%±3.2, p<0.05) in muscle biopsies. No other differences were observed. Anti-SAE DM represents a disease subset characterised by classic cutaneous involvement often associated with itching, less severe muscle involvement, but potential pulmonary involvement that should always be investigated in these patients.

Non-purulent myositis caused by direct invasion of skeletal muscle tissue by Leptospira in a hamster model.

Myalgia is a common symptom of Leptospira infection in humans. Autopsies have reported that muscle tissue shows degeneration and necrosis of the myofibers and infiltration of inflammatory cells composed mainly of macrophages and lymphocytes. It remains unclear whether Leptospira directly infects the muscle and how the infiltrating inflammatory cells are involved in muscle fiber destruction. This study evaluated the relationship between histopathological changes and leptospiral localization in the muscle tissue of a hamster model. The influence of macrophages in skeletal muscle injury was also investigated, using selective depletion of macrophages by administration of liposomal clodronate. Hamsters infected subcutaneously with Leptospira interrogans serovar Manilae strain UP-MMC-SM showed myositis of the thighs adjacent to the inoculated area beginning at 6 days post-infection. The myositis was non-purulent and showed sporadic degeneration and necrosis of muscle fibers. The degeneration of myofibers was accompanied by aggregations of macrophages. Immunofluorescence staining revealed leptospires surrounding the damaged muscle fibers. Subcutaneous injection of formalin-killed Leptospira or intraperitoneal injection of live Leptospira caused no myositis in hamster thighs. Liposomal clodronate treatment in infected hamsters reduced macrophage infiltration in muscle tissue without impacting bacterial clearance. Muscle necrosis was still observed in the infected hamsters treated with liposomal clodronate, and there was no significant change in serum creatine kinase levels compared to those in animals treated with liposomes alone. Our findings suggest that leptospiral invasion of muscle tissue from an inoculation site leads to the destruction of muscle fibers and causes non-purulent myositis, whereas the infiltrating macrophages contribute less to muscle destruction.

A Highly Rare Autoimmune Disease — IMNM

A new subtype of myositis syndrome, immune-mediated necrotizing myopathy (IMNM), was initially explained in 2004. It manifests as symmetrical proximal muscular weakness in the extremities fairly quickly, with no obvious inflammatory infiltrate and significant muscle fiber necrosis and regeneration. According to the specific autoantibodies in patients, Anti-HMGCR+, anti-SRP+, and antibody-negative IMNM are the three subtypes of IMNM. which are characterized by subtle differences in pathogenesis, clinical manifestations, and therapeutic approaches. The aim of this review is to sort out most of the current studies on IMNM, to provide detailed explanations of their pathogenesis, diagnostic techniques and therapeutic approaches, and to summarize some of the protein molecules and structures that may play a key role in myopathogenesis. We hope that this will help to deepen the understanding of IMNM pathogenesis and optimize therapeutic strategies.

Multietiological abortion induced by Brucella melitensis and Chlamydophila abortus in a sheep fetus

In this case, multietiological abortion due to Brucella melitensis (B. melitensis) and Chlamydophila abortus (C. abortus) agents was defined in a sheep abortion. An aborted sheep fetus submitted to Konya Veterinary Control Institute (KVCI) from a sheep farm in Nigde province in Brucella spp. presence was determined by bacterial isolation method and confirmed by slide agglutination test with monospecific A and M sera. C. abortus was detected by real time PCR and immunohistochemistry (IHC) methods. In histopathological examinations, in the lung; hyperemia, hemorrhage and bronchopneumonia, In the heart; in the placenta with degeneration and necrosis of heart muscle cells; hyperemia, hemorrhage, edema, necrosis and mononuclear cell infiltrations were observed. In this study, it was emphasized that in the fight against sheep abortions, multi-etiological abortions involving more than one factor should be taken into consideration, as well as an etiological agent, and it would be appropriate to use multidisciplinary diagnostic methods to determine the abortion factors, thus contributing to the prevention of abortions, which is still an important problem in sheep breeding.

Extracellular vesicles derived from human ESC–MSCs target macrophage and promote anti-inflammation process, angiogenesis, and functional recovery in ACS-induced severe skeletal muscle injury

BackgroundAcute compartment syndrome (ACS) is one of the most common complications of musculoskeletal injury, leading to the necrosis and demise of skeletal muscle cells. Our previous study showed that embryonic stem cells-derived mesenchymal stem cells (ESC–MSCs) are novel therapeutics in ACS treatment. As extracellular vesicles (EVs) are rapidly gaining attention as cell-free therapeutics that have advantages over parental stem cells, the therapeutic potential and mechanisms of EVs from ESC–MSCs on ACS need to be explored.MethodIn the present study, we examined the protective effects in the experimental ACS rat model and investigated the role of macrophages in mediating these effects. Next, we used transcriptome sequencing to explore the mechanisms by which ESC–MSC-EVs regulate macrophage polarization. Furthermore, miRNA sequencing was performed on ESC–MSC-EVs to identify miRNA candidates associated with macrophage polarization.ResultsWe found that intravenous administration of ESC–MSC-EVs, given at the time of fasciotomy, significantly promotes the anti-inflammation process, angiogenesis, and functional recovery of muscle in ACS. The beneficial effects were associated with ESC–MSC-EVs affecting macrophage polarization by delivering various miRNAs which regulate NF-κB, JAK/STAT, and PI3K/AKT pathways. Our data further illustrate that ESC–MSC-EVs mainly modulate macrophage polarization via the miR-21/PTEN, miR-320a/PTEN, miR-423/NLRP3, miR-100/mTOR, and miR-26a/TLR3 axes.ConclusionTogether, our results demonstrated the beneficial effects of ESC–MSC-EVs in ACS, wherein the miRNAs present in ESC–MSC-EVs regulate the polarization of macrophages.

Successful treatment of seronegative immune‐mediated necrotizing myopathy developing during pregnancy: A case report and literature review

AbstractImmune‐mediated necrotizing myopathy (IMNM) is an idiopathic inflammatory myopathy characterized by limb weakness, markedly elevated serum creatine kinase (CK), and muscle fiber necrosis without lymphocytic infiltration. Here, we present a case of IMNM that developed during pregnancy. The patient was treated immediately with systemic corticosteroids, and muscle weakness and serum CK levels were improved without adverse effects on the pregnancy. As there are only a few reports of IMNM during pregnancy, the clinical course and treatment of IMNM during pregnancy are discussed with a review of the literature.

Comprehensive transcriptomic analysis and machine learning reveal unique gene expression profiles in patients with immune-mediated necrotizing myopathy.

Immune-mediated necrotizing myopathy (IMNM) is an autoimmune myopathy characterized by severe proximal weakness and muscle fiber necrosis, yet its pathogenesis remains unclear. So far, there are few bioinformatics studies on underlying pathogenic genes and infiltrating immune cell profiles of IMNM. Therefore, we aimed to characterize differentially expressed genes (DEGs) and infiltrating cells in IMNM muscle biopsy specimens, which may be useful for elucidating the pathogenesis of IMNM. Three datasets (GSE39454, GSE48280 and GSE128470) of gene expression profiling related to IMNM were obtained from the Gene Expression Omnibus database. Data were normalized, and DEG analysis was performed using the limma package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of DEGs were performed using clusterProfiler. The CIBERSORT algorithm was performed to identify infiltrating cells. Machine learning algorithm and gene set enrichment analysis (GSEA) were performed to find distinctive gene signatures and the underlying signaling pathways of IMNM. DEG analysis identified upregulated and downregulated in IMNM muscle compared to the gene expression levels of other groups. GO and KEGG analysis showed that the pathogenesis of IMNM was notable for the under-representation of pathways that were important in dermatomyositis and inclusion body myositis. Three immune cells (M2 macrophages, resting dendritic cells and resting natural killer cells) with differential infiltration and five key genes (NDUFAF7, POLR2J, CD99, ARF5 and SKAP2) in patients with IMNM were identified through the CIBERSORT and machine learning algorithm. The GSEA results revealed that the key genes were remarkably enriched in diverse immunological and muscle metabolism-related pathways. We comprehensively explored immunological landscape of IMNM, which is indicative for the research of IMNM pathogenesis.

Morphological and functional changes in the skeletal muscles of the hind limbs in rats under enforced anaerobic physical exertion and allogeneic biomaterial application

Exhausting physical activity leads to sarcomere overstrain, destruction of the cell membrane, hydrolysis of structural proteins, thus, resulting in irreversible damage to muscle fibers. Allogeneic biomaterial (AB) is applied to regenerate various tissues and organs. The aim of the study was to identify morphofunctional features of the skeletal muscle tissue after physical exertion and under AB application. Material and methods. This experimental study involved male Wistar rats. Anaerobic physical exertion was simulated using the Porsolt test with a load equal 10 % of the body weight for 30 days. After training, animals of the main group (n = 10) were injected AB suspension: 4 ml of a 0.2 % solution into the muscles of the fore and hind limbs totally. Animals of the control group (n = 10) received physiological saline into similar zones. Tolerant load was investigated in 5 and 21 days after injection. Then the animals were withdrawn from the experiment, and muscles of the hind limbs were studied histologically, the total number, the average cross-sectional area of muscle fibers, and the number of necrotic fibers were measured. Results. In 5 and 21 days animals from the control group manifested dystrophic changes in muscle fibers: type III, IV contractures, microcirculation disorders, mosaic necrosis of muscle fibers, inflammatory cell infiltration, and a decreased tolerant load. In 21 days fibrosis was detected. The AB introduction provided rhabdomyogenesis as soon as in 5 days. Inflammatory cell infiltration decreased, the polygonality of muscle fiber profiles was restored, and edematous phenomena were leveled. There was hyperplasia of muscle fibers, a decreased number of necrotic muscle fibers, inhibited fibrosis, and an increased tolerant load. AB further biodegraded. Conclusion. AB contributed to the reduced manifestations of dystrophic changes in muscle fibers, strengthened actoprotective mechanism, and restored physical activity in the early stages.

Association between intracerebral hemorrhage and cholesterol levels, and molecular mechanism underlying low cholesterol inhibiting autophagy in cerebral arterial smooth muscle cells leading to cell necrosis

BackgroundAn association between cholesterol and intracerebral hemorrhage (ICH) has been reported, but the mechanism is unclear. MethodsIn this cross-sectional study, participants aged 50–75 years were selected using multistage stratified cluster sampling. All samples completed a questionnaire (age, gender, medication, etc.) and were examined (blood lipid, height, blood pressure, etc.) for risk factors. Multivariable logistic regression was used to analyze the association between cholesterol levels and ICH risk, after adjusting for age, smoking, hypertension, and other factors. We cultured rat cerebral artery smooth muscle cells at different cholesterol concentrations. The autophagy pathway was identified by transcriptome sequencing. The results were then validated using real-time polymerase chain reaction and western blot. ResultsWe included 39,595 patients, among whom 286 had ICH. The study showed that a low level of low-density lipoprotein cholesterol (LDL-C) was a risk factor of ICH (odds ratio 2.912, 95% confidence interval 1.460–5.806; P = 0.002). Cell experiments showed that lower cholesterol levels could significantly induce rat cerebral artery smooth muscle cell necrosis. In low-cholesterol groups, expression of the autophagy marker LC3 protein was significantly decreased and p62 protein was significantly increased. In western blot and comparison with the control group, the low cholesterol PI3K/Akt/mTOR signaling pathway was significantly activated in the autophagy pathway, resulting in its inhibition, which in turn led to smooth muscle cell death. ConclusionLow cholesterol levels may inhibit autophagy through PI3K/Akt/mTOR signaling and induce arterial smooth muscle cell necrosis, thereby increasing the risk of ICH.

Anti-SRP antibody-associated necrotizing myopathy: 2 clinical cases

Necrotizing myopathies are a subtype of autoimmune myopathies characterized by muscle fiber necrosis with minimal infiltration by inflammatory cells on muscle biopsy. This group of myopathies is defined by flaccid palsies due to prima‑ ry skeletal muscle damage as well as extramuscular manifestations such as fever, rash, arthritis, Raynaud’s syndrome and interstitial lung disease. The presence of anti-SRP antibodies is associated with rapidly progressive refractory myositis predominantly affecting limb muscles and axial muscles.Objective of the work is to analyze the course of severe, refractory to several lines of immunosuppressive therapies anti-SRP associated necrotizing myopathy and to highlight an adequate treatment regime.Necrotizing myopathy was suspected in patients aged 39 and 56 years with rapidly progressive flaccid tetraparesis on the basis of clinical and anamnestic data, the results of needle electromyography and muscle magnetic resonance imaging, as well as the analysis of myositis-specific and myositis-associated autoantibodies. In both cases, a rapid development of atrophies, marked muscle weakness in the limbs, without involvement of the bulbar musculature, was observed. To achieve effective control of the disease progression, several lines of therapy were required: glucocorticosteroids, intravenous immunoglobulins, methotrexate and rituximab. Our observations are consistent with those in the literature.Our observations illustrate the clinical course of severe myopathy associated with anti-SRP antibodies. Early initiation of aggressive immunosuppression is crucial to control the disease progression. Treatment and rehabilitation allow achieving significant improvement of the patient’s condition.

Skeletal muscle regeneration at different phases of the menstrual cycle

INTRODUCTION: The effect of estrogen on muscle function and recovery from damage has been studied, but the effects of estrogen fluctuations during the menstrual cycle on muscle regeneration remain inconclusive. PURPOSE: The purpose of this study was to examine the effects of menstrual cycle phases on muscle regeneration after electrically stimulated muscle damage. We hypothesized that muscle damage during the late follicular (LF) phase results in better muscle regeneration as compared to muscle damage during the early follicular (EF) phase. METHODS: 23 premenopausal females (21.3±2 yrs) were recruited and split into two groups, EF and LF. After menstrual cycle tracking and phase confirmation, subjects underwent 200 electrically stimulated eccentric muscle contractions one week after providing a muscle biopsy. 7 days after inducing muscle damage, the subjects reported to give a final biopsy. Sections from muscle samples were stained for markers of laminin, dystrophin, satellite cells (SCs; Pax7), nuclei, total macrophages (CD68), and anti-inflammatory macrophages (CD206/CD68). Data for SCs, and %CD206+CD68+ cells are presented as mean±SD, and damaged fibers and CD206+CD68+ cells/fiber are presented as median±interquartile range. RESULTS: Electrical stimulation caused muscle fiber necrosis (0.005±0.018 damaged fiber/fiber, p=0.0002) as measured by the laminin-containing and dystrophin-deficient fibers. There was no difference between EF and LF groups for the number of damaged fibers (p=0.055) Muscle damage resulted in ~200% increase in the total number of CD68+ macrophages (p=0.008), and ~ 40% increase in the number of SCs (p=0.001) in both groups. However, there was no significant difference between EF and LF groups for the change in total macrophages per fiber (p=0.07) or SCs/fiber (p=0.25) in response to electrically stimulated muscle damage. Anti-inflammatory macrophages increased by about 104%±127 in EF and 240%±390 in LF group, but the difference between groups was not significant (p=0.39). A comparison of the proportion of anti-inflammatory macrophages per total macrophages before and one week after muscle damage did not show any time effect (p=0.25), which could indicate the regenerative and anti-inflammatory state of skeletal muscle one week after damage. CONCLUSION: Contrary to our hypothesis, our data indicate that skeletal muscle regeneration is not affected by different phases of the menstrual cycle. However, this finding is limited to only some of the markers of regeneration one week after muscle damage. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Rhabdomyolysis caused by interaction between rosuvastatin and vadadustat: a case report

BackgroundRhabdomyolysis is a potentially life-threatening disease caused by melting or necrosis of skeletal muscle cells and leakage of muscle components into the bloodstream. It has been reported that the interaction of the HMG-CoA reductase inhibitor rosuvastatin with the renal anemia drug vadadustat increases the blood concentration of rosuvastatin in vitro. In this study, we report a case of suspected rhabdomyolysis caused by the drug interaction of rosuvastatin and vadadustat in clinical practice.Case presentationA 62-year-old male with medical records of hypertension, myocardial infarction, chronic renal failure, renal anemia, dyslipidemia, and alcoholic liver disease. The patient had been diagnosed with chronic kidney disease (CKD) at the Department of Nephrology, and treated by outpatient care with renal support therapy for the past two years. On X-63 day, his prescription was rosuvastatin (10 mg/day) and a continuous erythrocyte-stimulating agent, epoetin beta pegol (genetical recombination, 100 μg). X-Day 0, blood tests revealed creatine phosphokinase (CPK) 298 U/L, serum creatinine (SCr) 5.26 mg/dL, and hemoglobin (Hb) 9.5 g/dL; thus, the prescription was changed from epoetin beta pegol 100 μg to vadadustat 300 mg/day. On X + day 80, a prescription for a diuretic (azosemide 15 mg/day) was added for swelling of the lower extremities. On X + day 105, we found CPK 16,509 U/L, SCr 6.51 mg/dL, and Hb 9.5 g/dL. The patient was diagnosed as rhabdomyolysis and hospitalized. After hospitalization, rosuvastatin and vadadustat were discontinued and we administered intravenous fluids. Thereafter, CPK and SCr values of the patient improved. On X + day 122, CPK improved to 29 U/L, SCr to 2.6 mg/dL, and Hb to 9.6 g/dL, and he was discharged on X + day 124. At discharge, rosuvastatin 2.5 mg/day was resumed. A blood test on X + day 133 showed CPK 144 U/L and SCr 4.2 mg/dL.ConclusionWe experienced a case of rhabdomyolysis caused by drug interactions between rosuvastatin and vadadustat.

Antioxidant activity of raw and cooked onions in rabbit doe nutrition

The aim of this research is to examine how raw and cooked onions affect some antioxidant enzymes and some tissues in female rabbits. Twenty-four female albino rabbits weighing (1-1.5 Kg), (5-6 months age), non-pregnant, were used for the experiment, and they were divided into three groups for a duration of 28 days. A 20 g/kg raw onion and same amount of cooked onion were added to the second and third groups’ diets respectively for comparison of results with control groups without any addition of onion. Results showed that diets supplemented with raw and cooked onion significantly increased the superoxide dismutase (SOD) activity. The cooked onion group showed normal and no pathological changes in liver, kidney, and heart tissues, while liver tissues of both control and raw onion groups suffered extreme congestion in the central veins of the liver lobules and in kidney tissues of only control rabbits, developed hemorrhagic foci was observed. In the control and raw onion groups, the heart tissue showed the development of hemorrhagic foci and necrosis in the heart muscle fibers. In conclusion, both raw and cooked onions boosted the activity of SOD enzyme, but the cooked onions showed to be more effective than raw at protecting liver, kidney, and heart tissues against cell necrosis caused by oxidative processes.

Effects of Triheptanoin on Mitochondrial Respiration and Glycolysis in Cultured Fibroblasts from Neutral Lipid Storage Disease Type M (NLSD-M) Patients

Neutral lipid storage disease type M (NLSD-M) is an ultra-rare, autosomal recessive disorder that causes severe skeletal and cardiac muscle damage and lipid accumulation in all body tissues. In this hereditary pathology, the defective action of the adipose triglyceride lipase (ATGL) enzyme induces the enlargement of cytoplasmic lipid droplets and reduction in the detachment of mono- (MG) and diglycerides (DG). Although the pathogenesis of muscle fiber necrosis is unknown, some studies have shown alterations in cellular energy production, probably because MG and DG, the substrates of Krebs cycle, are less available. No tests have been tried with medium-chain fatty acid molecules to evaluate the anaplerotic effect in NLSD cells. In this study, we evaluated the in vitro effect of triheptanoin (Dojolvi®), a highly purified chemical triglyceride with seven carbon atoms, in fibroblasts obtained from five NLSD-M patients. Glycolytic and mitochondrial functions were determined by Seahorse XF Agylent Technology, and cellular viability and triglyceride content were measured through colorimetric assays. After the addition of triheptanoin, we observed an increase in glycolysis and mitochondrial respiration in all patients compared with healthy controls. These preliminary results show that triheptanoin is able to induce an anaplerotic effect in NLSD-M fibroblasts, paving the way towards new therapeutic strategies.

Effects of thermal stress and mechanistic target of rapamycin and wingless-type mouse mammary tumor virus integration site family pathways on the proliferation and differentiation of satellite cells derived from the breast muscle of different chicken lines

Satellite cells (SCs) are muscle stem cells responsible for muscle hypertrophic growth and the regeneration of damaged muscle. Proliferation and differentiation of the pectoralis major (p. major) muscle SCs are responsive to thermal stress in turkeys, which are, in part, regulated by mechanistic target of rapamycin (mTOR) and Frizzled7 (Fzd7)-mediated wingless-type mouse mammary tumor virus integration site family/planar cell polarity (Wnt/PCP) pathways in a growth dependent-manner. It is not known if chicken p. major SCs respond to thermal stress in a manner similar to that of turkey p. major SCs. The objective of the current study was to investigate the effects of thermal stress and mTOR and Wnt/PCP pathways on the proliferation, differentiation, and expression of myogenic transcriptional regulatory factors in SCs isolated from the p. major muscle of a current modern commercial (MC) broiler line as compared to that of a Cornish Rock (BPM8) and Randombred (RBch) chicken line in the 1990s. The MC line SCs had lower proliferation and differentiation rates and decreased expression of myoblast determination factor 1 (MyoD) and myogenin (MyoG) compared to the BPM8 and RBch lines. Heat stress (43°C) increased proliferation and MyoD expression in all the cell lines, while cold stress (33°C) showed a suppressive effect compared to the control temperature (38°C). Satellite cell differentiation was altered with heat and cold stress in a cell line-specific manner. In general, the differentiation of the MC SCs was less responsive to both heat and cold stress compared to the BPM8 and RBch lines. Knockdown of the expression of either mTOR or Fzd7 decreased the proliferation, differentiation, and the expression of MyoD and MyoG in all the cell lines. The MC line during proliferation was more dependent on the expression of mTOR and Fzd7 than during differentiation. Thus, modern commercial meat-type chickens have decreased myogenic activity and temperature sensitivity of SCs in an mTOR- and Fzd7-dependent manner. The decrease in muscle regeneration will make modern commercial broilers more susceptible to the negative effects of myopathies with muscle fiber necrosis requiring satellite cell-mediated repair.