Twenty-Four Percent of Wildland Firefighters Reach Critical Levels of Serum Creatine Kinase During 80-Hour Critical Training.

INTRODUCTION: Wildland firefighters (WLFFs) must undergo a 2-wk critical training (CT) period prior to deployment to the field. This stress may result in clinical risks, including severe muscle damage and rhabdomyolysis. We aimed to document the effects of WLFFs' CT on physiologic markers of muscle damage and soreness. METHODS: Two interagency hotshot crews (n=25) were followed during spring 2022 for 80 h of training. Activity counts as well as records of upper-body (US) and lower-body (LS) muscle soreness were collected daily. Body weight (BW) and skinfold measurements were recorded on Day 1 (D1) and D11 to estimate body fat (BF) and lean body weight (LBW). Blood was collected on D1 and D11 to measure muscle and liver damage markers. RESULTS: Critical training resulted in significant elevations in creatine kinase (CK) (216.9±57.4 U/L vs 5166.4±1927.8 U/L, P=0.017) and lactate dehydrogenase (LDH) (175.5±4.0 IU/L vs 340.0±42.6 IU/L, P=0.001) despite no significant changes in BW, BF, LBW, cortisol, or testosterone. Main effects of time were seen in US and LS, peaking on D11 (US: 5.2±0.4 cm, P<0.001; LS: 5.5±0.4 cm, P<0.001). Those who spent the most minutes with activity counts of >1500 counts/min showed the greatest increase in CK and LDH. CONCLUSIONS: These data suggest that WLFFs undergo significant physiologic stressors, resulting in muscle soreness and damage during CT, with 6 of the 25 subjects reaching critical levels of serum CK. It appears that much of the muscle damage and soreness occurred because of unaccustomed WLFF job-specific tasks.

Immune-mediated necrotizing myopathy (NAM) related to SARS-Cov-2 infection: a case report.

BACKGROUND: There is a growing body of evidence that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) or COVID-19 infection is associated with the development of autoimmune diseases. A recent systematic review reported that the new-onset autoimmune disorders during or after COVID-19 infection included inflammatory myopathies such as immune-mediated necrotizing myopathies. CASE PRESENTATION: We described a 60-year-old man diagnosed with COVID-19 infection and later presented with a two-week history of myalgia, progressive limb weakness, and dysphagia. He had a Creatinine Kinase (CK) level of more than 10,000 U/L, was strongly positive for anti-signal recognition particle (SRP) and anti-Ro52 antibody, and a muscle biopsy revealed a paucity-inflammation necrotizing myopathy with randomly distributed necrotic fibers, which was consistent with necrotizing autoimmune myositis (NAM). He responded well clinically and biochemically to intravenous immunoglobulin, steroids and immunosuppressant and he was able to resume to his baseline. CONCLUSION: SARS-CoV-2 may be associated with late-onset necrotizing myositis, mimicking autoimmune inflammatory myositis.

A randomized controlled trial investigating the effect of transport duration and age at transport on surplus dairy calves: Part II. Impact on hematological variables.

Surplus dairy calves often arrive at veal and dairy-beef rearing facilities with health and blood metabolite level abnormalities, which can affect their welfare and performance, predisposing them to future health challenges. The objective of this randomized controlled trial was to investigate the effects of transport duration and age at the time of transport on blood parameters in surplus dairy calves following 6, 12, or 16 h of continuous road transportation. All surplus calves from 5 commercial dairy farms in Ontario were enrolled and examined daily before transport (n = 175). On the day of transportation, calves were weighed, blood sampled, and randomly assigned to 6, 12, or 16 h of transportation. Blood samples were then collected immediately after transportation, as well as 24, 48, and 72 h thereafter. Serum was analyzed at a provincial diagnostic laboratory for nonesterified fatty acids (NEFA), ß-hydroxybutyric acid (BHBA), creatine kinase (CK), cholesterol, and haptoglobin. In addition, blood gas and electrolyte values were also assessed at the time of sample collection. Mixed models with repeated measures were used to assess the effects of transport duration, breed, sex, transfer of passive immunity status, weight before transportation, and age at transportation on blood parameters. Immediately following transportation, NEFA and BHBA were greater for calves transported for 12 h (Δ = 0.22 mmol/L NEFA, 95% CI = 0.15 to 0.30; Δ = 0.04 mmol/L BHBA, 95% CI = 0.02 to 0.06) and 16 h (Δ = 0.35 mmol/L NEFA, 95% CI = 0.27 to 0.42; Δ = 0.10 mmol/L BHBA, 95% CI = 0.08 to 0.11) compared with calves transported for 6 h. Glucose was lower immediately following transportation in calves transported for 16 h compared with 6 h (Δ = -15.54 mg/dL, 95% CI = -21.54 to -9.54). In addition, pH and HCO3- were lower in calves transported for 12 (Δ = -0.09 pH, 95% CI = -0.13 to -0.05; Δ = -1.59 mmol/L HCO3-, 95% CI = -2.61 to -0.56) and 16 h (Δ = -0.07 pH, 95% CI = -0.12 to -0.03; Δ = -1.95 mmol/L HCO3-, 95% CI = -2.95 to -0.95) compared with calves transported for 6 h. Calves transported between 15 and 19 d of age had a higher concentration of cholesterol and CK (Δ = 0.27 mmol/L cholesterol; 37.18 U/L CK) compared with 2- to 6-d-old calves, and calves 12 to 14 d old had greater reduction in HCO3- (Δ = -0.92 mmol/L) compared with 2- to 6-d-old calves. These findings show that transporting calves for long distances results in lower glucose concentration and suboptimal energy status, and that this effect varies based on the calf's age.

Effect of Sodium Bicarbonate Supplementation on Muscle Performance and Muscle Damage: A Double Blind, Randomized Crossover Study.

Sodium bicarbonate (NaHCO3) has been used as an ergogenic substance during high-intensity exercises. Therefore, the aim of the present study was to investigate the effects of NaHCO3 supplementation on external and internal load parameters during isokinetic exercise in trained subjects. Ten subjects were tested on two occasions: after ingesting 0.3 g.kg-1 of body mass of NaHCO3 or placebo. Maximum voluntary isometric contraction was performed before and after a dynamic protocol consisting of 10 series of 10 movements of flexion/extension of the knee extensors at 120° s-1 at an interval of 60 s between series. Outcomes considered were: peak torque (isokinetic dynamometry), blood lactate and creatine concentration (CK), analysis of perceptions of effort (OMNI scale), pain (visual analog scale) and recovery (scale raging 6 to 20). Performance was assessed using peak torque values. Muscle damage was assessed prior and 24 h post exercise. The subjective perceptions of effort, pain and recovery were assessed at different times and the internal load of the session was assessed 30 min post-effort. Although significant reductions in peak torque were noted both in isometric (NaHCO3:-29.11 ± 22.95%, Placebo: -23.51 ± 15.23%; p = 0.38) and isokinetic strength (NaHCO3:-23.0 ± 13.9%, Placebo:-19.6 ± 9.1%; p = 0.09), there was no effect of supplementation on performance (p > 0.05). The blood CK concentrations (NaHCO3: pre:225.3 ± 135.9 U/L, post: 418.4 ± 318.4 U/L; Placebo: pre:238 ± 94.03 U/L, post:486 ± 336.6 U/L) increased after protocol (p = 0.005), however, without differences between conditions. In conclusion, the NaHCO3 did not attribute benefits in performance or in parameters related to the internal load of exercise.

Elevated level of creatine phosphokinase in newborn: Clinical significance and association with congenital muscle diseases.

OBJECTIVES: To establish the normal Creatine phosphokinase (CPK) range in newborns of all 3 modes of delivery and prove that high CPK level in neonates is not specific a indicator for muscular pathology. METHODS: This is a prospective cohort study that is conducted in King Abdulaziz Medical City and King Abdullah Specialized Children Hospital in Riyadh and included 504 term neonates who were born between March 2021 and August 2021. Two hundred and fifty three were males and 251 were females. Data and consents were managed and collected using 2 coordinators. RESULTS: Duration of the second stage of labor, age on the first CPK test and fetal gestational age were significantly correlated with CPK values (r=0.197, r=-0.234, r=0.274, respectively). The normal ranges for each delivery type were 334 U/L-2667U/L in normal spontaneous vaginal delivery, 265U/L-1182U/L in elective cesarean section, and 223U/L-3082 U/L in emergency cesarean section. CONCLUSION: The CPK was elevated in all neonates in all 3 modes of deliveries. An elevated levels of CPK in neonates is not a specific indicator for any congenital muscular pathology.

Amisulpride steady-state plasma concentration and adverse reactions in patients with schizophrenia: a study based on therapeutic drug monitoring data.

The aim of the study was to evaluate the reference range of amisulpride for Chinese patients with schizophrenia and to assess its possible influencing factors based on therapeutic drug monitoring information. The relative adverse reactions of patients induced by amisulpride were also systematically investigated. A total of 425 patients with schizophrenia were assessed, including Positive and Negative Syndrome Scales, Treatment Emergent Symptom Scale, blood routine examination, hepatorenal function, lipids, hormones, as well as myocardial enzymes at baseline, and following treatment with amisulpride for 8 weeks. The steady-state plasma concentration of amisulpride was assayed using two-dimensional liquid chromatography. At the same dose, the amisulpride plasma concentration of patients combined with clozapine was higher than that without clozapine. The therapeutic reference range of amisulpride can be defined as 230.3-527.1 ng/ml for Chinese patients with schizophrenia. The potential side effects appear to be associated with significantly increased levels of LDH, CK, creatine kinase isoenzyme (CK-MB), TC and decreased level of E 2 , relative to the amisulpride plasma concentration. These findings could provide individualized medication and reduce the adverse effects of amisulpride for Chinese patients with schizophrenia.

Psychophysiological Stress Markers During Preseason Among Elite Female Soccer Players.

ABSTRACT: Botelho, R, Abad, CCC, Spadari, RC, Winckler, C, Garcia, MC, and Guerra, RLF. Psychophysiological stress markers during preseason among elite female soccer players. J Strength Cond Res 36(6): 1648-1654, 2022-This study aimed to investigate changes and correlations between mood states and various physiological stress markers after a 7-week preseason period among elite female soccer players. Twenty-four elite female soccer players participated in this study (26.4 ± 3.7 years). Their internal training load, mood states, day and evening salivary testosterone and cortisol concentrations, blood creatine kinase concentration (CK), and heart rate variability (HRV) were assessed during the first week of preseason (PRE), and again 7 weeks after a systematic training period (END). After the preseason, there were significant increases in subject negative mood scales (p ≤ 0.03; Effect Size [ES] > 0.60), total mood scores (p = 0.01; QI = 100/0/0; ES = 1.32), day and evening testosterone and cortisol concentrations (p ≤ 0.03; ES > 0.54), and CK concentrations (p = 0.01; QI = 100/0/0; ES = 1.54). Correlations were found between cortisol and tension (r = 0.53 and 0.60; p ≤ 0.02), cortisol and confusion (r = 0.75; p = 0.01), and cortisol and the LF/HF index of HRV (r = -0.52; p = 0.04). Mood states (except vigor), salivary testosterone, and cortisol concentrations, as well as CK, showed significant changes after a 7-week systematic training system. The cortisol was the factor most highly related to various mood states (including tension and confusion), and with the HRV indices. Coaches and researchers can use these data to design, monitor, and control soccer training programs, in particular throughout the preseason period.

Attenuation of isoprenaline-induced myocardial infarction by Rheum turkestanicum.

BACKGROUND: Oxidative stress plays a major role in the pathogenesis of myocardial infarction. This study evaluated the cardioprotective effects of the hydroalcoholic extract of Rheum turkestanicum on isoprenaline-induced myocardial infarction (MI) in Wistar rats. METHODS: In this study, we used liquid chromatography-mass spectrometry to determine the active compounds present in the extract. Thirty rats were divided to 5 groups (6 rats in each group). The extract was administered orally at the doses of 100 and 300 mg/kg body weight and then a subcutaneous injection of isoprenaline (85 mg/kg) was administered on the 8th and 9th days. Serum levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and creatinine kinase (CPK) were measured using standard commercial kits. Serum activities of superoxide dismutase, catalase, and cardiac levels of thiol and lipid peroxidation were also determined. Hematoxylin and eosin were used for histopathological staining. RESULTS: Phytochemical analysis revealed the presence of 24 compounds in the hydro-ethanolic extract of R. turkestanicum. Isoprenaline increased malondialdehyde (4.002 ± 0178, P < 0.001) while decreased thiol content (101.7 ± 6.186, P < 0.001). Moreover, reduced activities of superoxide dismutase (139 ± 10.88, P < 0.001) and catalase (2.812 ± 0.215, P < 0.001), and elevated levels of LDH (1245 ± 62.28, P < 0.001), CPK (898 ± 23.06, P < 0.001) and CK-MB (697 ± 50.22, P < 0.001) were observed. Pretreatment with the R. turkestanicum extract significantly reduced cardiac markers and increased thiol content as well as the activity of antioxidant enzymes. The extract attenuated the histopathological changes induced by isoprenaline. CONCLUSION: According to the obtained results, R. turkestanicum may be an appropriate candidate to reduce isoprenaline-induced MI through modulation of oxidative stress. Administration of the extract attenuated cardiac enzymes following isoprenaline administration. The cardioprotective action of the extract can be attributed to the bioactive antioxidant ingredients of R. turkestanicum. To identify the precise mechanisms, further investigations are required.

Muscle pain and muscle weakness in COVID19 patients: Cross-talk with statins - Preliminary results.

BACKGROUND: Muscle pain and muscle weakness, common symptoms among statin-treated patients, may worsen with COVID-19 infection. AIMS: The aim of the paper was to find out if concomitant COVID-19 infections increase the frequency of specific side effects of statins such as muscle pain and muscle weakness. METHOD: A total of 66 patients diagnosed with COVID-19 without comorbidities participated in the study. The patients were divided into two groups: statin-users who had not experienced adverse effects of statins in the past (statin group (SG)) and patients who had not used any drugs in the past six months (control group (CG)). The severity of muscle pain and creatinine kinase (CK) activity was evaluated in each patient, and muscle weakness was confirmed by a dynamometer test (grip strength on both hands). RESULTS: In SG, muscle pain was more common and it was characterized by a high level of intensity. Muscle weakness occurred more frequently in the SG and it was more frequent compared to CG. The CK parameter was observed to be higher in the SG compared to the CG and was often associated with the severity of muscle pain in the range of moderate to severe. CONCLUSIONS: Our study indicates that COVID-19 is associated with the higher risk of occurrence of typical statin-related side effects, especially with more advanced age, which should be considered in future trials and treatments.

Effects of photobiomodulation and deep water running in patients with chronic non-specific low back pain: a randomized controlled trial.

Photobiomodulation therapy (PBM) is often used to treat musculoskeletal disorders such as chronic non-specific low back pain (NSCLBP) as it can have positive effects on biomarkers-creatine kinase (CK) and serum cortisol levels-related to stress caused by physical exercise, such as deep water running (DWR) or by pain. The aim of this study was to evaluate the effects of the combination of PBM and aquatic exercise (DWR) on the intensity of pain, disability, 6-min walk test adapted (6WTA), and on cortisol and creatine kinase (CK) levels in a population with NSCLBP. The participants were allocated into three groups: TGPBM (Photobiomodulation and Training Group), TGPLA (Placebo Photobiomodulation and Training Group), and the GPBM (Photobiomodulation Group). Information regarding anthropometric data, blood pressure, and heart rate were collected, and the questionnaires were applied: IPAQ-Short Form, Oswestry Disability Index, and the Visual Analog Scale for Pain. The submaximal exercise test (6WTA) was performed. Blood was collected for analysis of cortisol and CK levels. The training sessions were performed twice a week, for 4 weeks. In the intragroup comparisons, there were statistically significant changes in the TGPBM and GPBM groups in the outcomes pain intensity, disability (reductions in both groups), and in cortisol (increased in the TGPBM and reduced in the GPBM); in the TGPLA group, there was a statistically significant reduction only in the outcome of pain intensity. In the intergroup comparison, in the comparison between TGPBM and TGPLA, there was a statistically significant difference in the level of cortisol, as well as in the comparison between TGPBM and GPBM, in which there was a statistically significant difference for this same outcome (cortisol) and for the 6WTA outcome. The effects of the combination of PBM and aquatic exercise have positive effects on reducing pain intensity, disability, and cortisol levels, but its effects on other variables (6WTA and CK) are too small to be considered significant. Trial registration number: NCT03465228-April 3, 2019; retrospectively registered (ClinicalTrials.gov).

Acute physiological and perceptual responses to a netball specific training session in professional female netball players.

The 24 h responses to professional female netball-specific training were examined. British Superleague players (n = 14) undertook a 90-min on-court training session incorporating key movement, technical, and scenario-specific match-play drills. Perceptual (mood, fatigue, soreness), neuromuscular (countermovement jump peak power output [PPO], PPO relative to mass [PPOrel], jump height [JH]), endocrine (salivary cortisol [C], testosterone [T] concentrations) and biochemical (creatine kinase concentrations [CK]) markers were assessed at baseline (immediately before; Pre), and immediately, two and 24 hours after (+0h, +2h, +24h) training. Session (sRPE) and differential (dRPE) ratings of perceived exertion were recorded at +0h. Identification of clear between time-point differences were based on the 95% confidence interval (CI) for mean differences relative to baseline values not overlapping. At +0h, C (raw unit mean difference from baseline; 95% CI: 0.16; 0.06 to 0.25 µg·dl-1), T (32; 20 to 45 pg⋅ml-1), CK (39; 28 to 50 u·L-1), PPOrel (2.4; 0.9 to 3.9 W·kg-1) and PPO (169; 52 to 286 W) increased. At +2h, fatigue (15; 7 to 24 AU), CK (49; 38 to 60 u·L-1), and soreness (14; 3 to 25 AU) increased, while T (-24; -37 to -11 pg⋅ml-1) and mood (-20; -27 to -12 AU) reduced. At +24h, CK increased (25; 13 to 36 u·L-1) whereas PPOrel (-1.6; -3.2 to -0.1 W·kg-1) and JH (-0.02; -0.03 to -0.08 m) reduced. Responses were variable specific, and recovery of all variables did not occur within 24h. The residual effects of the prior stimulus should be accounted for in the planning of training for professional female netball players.

Relationship between infrared thermography and muscle damage markers in physically active men after plyometric exercise.

Plyometric training has been used in several sports and fitness programs to improve jumping ability and explosive strength, both in individual and team sports. Eccentric muscle actions, such as those performed during plyometric jumps, induce muscle damage and consequently a rise in skin temperature (Tsk). Thus, the purpose of this study is to assess the response of infrared thermography measurement as an indirect marker of muscle damage after a protocol of plyometric jumps in physically active subjects. Therefore, for the aim of this study ten male subjects with no previous experience in plyometric training participated in the research (age 22.5 ± 3.3 years, weight 71.7 ± 11.0 kg, height 171.1 ± 5.3 cm, and fat mass 15.5 ± 4.7%). To assess the muscle damage, countermovement jump (CMJ), creatine kinase (CK), delayed-onset muscle soreness (DOMS) and infrared thermography (IRT) were measured at 24, 48, and 72 h after plyometric exercise. The acute exercise protocol of plyometric jumps induced muscle damage, as shown by the CK and DOMS (24 and 48 h, p < 0.05) but no statistical difference was shown between the moments analyzed in Tsk (warm zone). Nevertheless, when comparing baseline to 48h, a moderate effect was found in the Tsk (warm zone) for anterior right thigh (ES = 1.1) and posterior left thigh (ES = 0.9) and large effect was found for anterior left thigh (ES = 1.4) and posterior right thigh (ES = 1.3). A moderate effect in the Tsk (warm zone) was found for posterior right and left thigh (ES = 0.9 and ES = 1.1, respectively) when comparing baseline to 72h of IRT. These results suggest that a plyometric jumping session alters CK and DOMS, as well as the thigh's skin temperature in an evident way, bringing up a possible relation with markers of muscle damage.

Genetic polymorphisms in CYP19A1 and ESR1 are associated with serum CK activity after prolonged running in men.

This study aimed to clarify 1) the influence of genetic polymorphisms in the cytochrome P450 aromatase gene (CYP19A1) on circulating estradiol levels in men and 2) whether estrogen-related genetic polymorphisms, such as the CYP19A1 rs936306 and estrogen receptor-α (ESR1) rs2234693 polymorphisms, predict exercise-induced serum creatine kinase (CK) activity, which is an index of skeletal muscle membrane disruption. Serum estradiol levels were examined in young men (n = 167). In a different cohort, serum CK activity was analyzed in a 2-day ultramarathon race: baseline, after the first day, and after the second day (114 males and 25 females). Genetic polymorphisms in CYP19A1 rs936306 C/T and ESR1 rs2234693 T/C were analyzed using the TaqMan SNP Genotyping Assay. Male subjects with the TT genotype of the CYP19A1 polymorphism exhibited significantly higher serum estradiol levels than the C allele carriers. Male runners had significantly higher postrace serum CK activity than female runners. The change in the CK activity during the ultramarathon race was significantly lower in male subjects with the CYP19A1 TT genotype than in those with the CC + CT genotypes and was correlated with the number of C alleles in ESR1 rs2234693 in male subjects. Furthermore, the genotype scores of these two polymorphisms were significantly correlated with changes in serum CK activity during race (r = -0.279, P = 0.003). The results of this study suggest that genetic polymorphisms in CYP19A1 rs936306 influence serum estradiol levels in men, and genetic polymorphisms in CYP19A1 and ESR1 are associated with serum CK activity in men.NEW & NOTEWORTHY Men with the TT genotype of the CYP19A1 polymorphism exhibited higher circulating estradiol levels than the TC + CC genotype. The TT genotype in the CYP19A1 polymorphism and the C allele of the ESR1 polymorphism, an allele increasing ESR1 expression, were associated with low serum CK activity after the ultramarathon. A combination of these polymorphisms was correlated with changes in the serum CK activity. Therefore, estrogen-related genetic polymorphisms partially predict exercise-induced muscle damage, that is, skeletal muscle membrane disruption.

Assessment of serum CK-MM level as a bioindicator for work-related musculoskeletal injuries among Emergency hospital workers.

Musculoskeletal disorders (MSDs) are considered a growing problem among healthcare personnel, especially service workers. The emergency room (ER) service workers are highly exposed to work-related risk factors which predispose them to MSDs. A cross-sectional study was performed on 78 ER workers. Full medical and occupational histories were taken. The Standardized Nordic Questionnaire (SNQ) was used for the assessment of musculoskeletal symptoms. Clinical examination was done with special emphasis on the locomotors system, and serum levels of muscle enzymes, including creatine kinase (CK) and creatine kinase isoenzyme (CK-MM), were measured. The study aims to detect the prevalence of occupational musculoskeletal disorders (MSDs) among ER workers at University hospitals, and assessment of CK-MM as a biomarker used in the early detection of MSDs. We found that 71.8% of the participants were complaining of musculoskeletal disorder in the last 7 days before the study, while only 34.6% were complaining of musculoskeletal disorder in the last 12 months before the study. The knee joint was the most commonly affected site in the past 7 days, by 39.7%. On the other hand, the highest prevalent disorder in the last 12 months was for the ankle joint (17.9%) with significantly high levels of serum CK-MM. In conclusion, musculoskeletal injuries are a common complaint among healthcare occupations, especially among ER service workers that need regular health education and ergonomic training programs. Monitoring of serum CK-MM level with cut-off value 90 ng\ml could be used as a novel approach for the early detection of work-related musculoskeletal disorders.

ROS and iron homeostasis dependent ferroptosis play a vital role in 5-Fluorouracil induced cardiotoxicity in vitro and in vivo.

5-Fluorouracil (5-FU) was a key chemotherapeutic agent in the treatment of different solid tumors. However, cardiotoxicity was included among the therapeutic strategies of 5-FU. The molecular mechanism of cardiotoxicity induced by 5-FU remains unclear. The aim of the study was to investigate whether ferroptosis was involved in 5-FU-induced cardiotoxicity in vivo and in vitro. The in vivo cardiotoxicity model was induced by intraperitoneal injection of 5-FU at the dose of 15, 30, 60 mg/kg for 7 days. Body weight, general condition and plasma enzyme activities of the mice were observed to evaluate heart function. In addition, HE staining, MASSON staining and TEM technology was used. Western-blot analysis were performed to evaluate the protein level of iron transport, iron storage and reactive oxygen species (ROS) of ferroptosis. In H9c2 cardiomyocyte cells, cell viability, generation of ROS, mitochondrial activity and cellular Fe2+ levels were measured. The in vivo results showed that 5-FU significantly impaired cardiac function and structure. The serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels were significantly increased in 5-FU group. HE and MASSON staining showed that 5-FU caused structural injuries. In addition, 5-FU increased the level of ferroptosis markers involving malonaldehyde (MDA) and Fe2+ content. Ferrostatin-1 (Fer-1) was an aromatic amine that specifically binds with lipid ROS and protects cells against lipid peroxidation. Furthermore, 5-FU markedly induced ferroptosis in H9c2 cardiomyocyte cells, which mainly embodied as declined cell vitality, accumulated iron, elevated lipid peroxides. Conversely, inhibition of ferroptosis by Fer-1 completely abolished 5-FU-induced effects. Both in vivo and in vitro experiments indicated that 5-FU increased the expression of ferroptosis, mainly by reducing the expression of glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1), but enhancing the expression of transferrin receptor 1 (TfR1). In conclusion, the present study suggested that ROS and iron homeostasis dependent ferroptosis played a vital role in 5-FU induced cardiotoxicity.

Ursolic acid increases strength in mdx mice model and may decrease fibrosis deposition by tgf-ß downregulation / El ácido ursólico aumenta la resistencia en el modelo de ratones mdx y podría disminuir la deposición de fibrosis mediante la regulación decreciente de tgf-ß

SUMMARY: Dystrophin disfunction results in sarcolemma destabilization, leading muscle cell damage by continuous degeneration cycles and limited regeneration. In muscle dystrophy, caused by dystrophin dysfunction, inflammation, necrosis and fibrosis are pathophysiological muscle function loss characteristics. As a genetic disease, this muscle dystrophy has no cure, however, advances in drug therapy using glucocorticoids can decrease the disease progression. Subsequently, alternative therapies were studied, such as ursolic acid (UA), that inhibits muscle atrophy and increases muscle mass and strength. Herein, we used 10 mg/kg daily supplementation in mdx mice for 4 weeks to evaluate serum creatine phosphokinase (CPK), muscle strength (Kondziela test), muscular organization (histology) and expression of fibrosis related genes (TGF-ß, TNF-α, mstn and ostn). UA supplementation increased muscle morphological organization, motor strength and decreased muscular TGF-ß expression. Altogether, the gene expression profile, histological organization and strength could suggest that UA treatment did not stop the fibrogenesis but decreased its progress.

RESUMEN: La disfunción de la distrofina resulta en la desestabilización del sarcolema, llevando al daño de las células musculares por ciclos continuos de degeneración y regeneración limitada. En la distrofia muscular, debido a la disfunción de la distrofina, la inflamación, la necrosis y la fibrosis, son características fisiopatológicas de la pérdida de la función muscular. Como enfermedad genetica no es possible remediar esta distrofia muscular, sin embargo, los avances en la terapia de medicamentos con glucocorticoides pueden disminuir la progresión de la enfermedad. Se estudiaron terapias alternativas, como el ácido ursólico (UA), que inhibe la atrofia muscular y aumenta la masa y la fuerza muscular. En este estudio, utilizamos una suplementación diaria de 10 mg / kg en ratones mdx durante 4 semanas para evaluar la creatina fosfoquinasa (CPK) sérica, la fuerza muscular (prueba de Kondziela), la organización muscular (histología) y la expresión de genes relacionados con la fibrosis (TGF-ß, TNF- α, mstn y ostn). La suplementación con AU aumentó la organización morfológica muscular, la fuerza motora y la disminución de la expresión muscular de TGF-ß. El perfil de expresión génica, la organización histológica y la fuerza simultáneamente podrían sugerir que el tratamiento con AU no detuvo la fibrogénesis sino que disminuyó su progreso.

Sex differences in the involvement of skeletal and cardiac muscles in myopathic Ano5-/- mice.

Limb-girdle muscular dystrophy R12 (LGMD-R12) is caused by recessive mutations in the Anoctamin-5 gene (ANO5, TMEM16E). Although ANO5 myopathy is not X-chromosome linked, we performed a meta-analysis of the research literature and found that three-quarters of patients with LGMD-R12 are males. Females are less likely to present with moderate to severe skeletal muscle and/or cardiac pathology. Because these sex differences could be explained in several ways, we compared males and females in a mouse model of LGMD-R12. This model recapitulates the sex differences in human LGMD-R12. Only male Ano5-/- mice had elevated serum creatine kinase after exercise and exhibited defective membrane repair after laser injury. In contrast, by these measures, female Ano5-/- mice were indistinguishable from wild type. Despite these differences, both male and female Ano5-/- mice exhibited exercise intolerance. Although exercise intolerance of male mice can be explained by skeletal muscle dysfunction, echocardiography revealed that Ano5-/- female mice had features of cardiomyopathy that may be responsible for their exercise intolerance. These findings heighten concerns that mutations of ANO5 in humans may be linked to cardiac disease.

[Anti-mitochondrial M2 antibody-positive myositis preceded by heart failure and cardiac conduction disturbance. A case report].

A 69-year-old man visited our hospital complaining of fatigue in the lower extremities while walking. The patient had a two-year history of congestive heart failure and received a permanent artificial pacemaker implantation for sick sinus syndrome. Physical examination revealed proximal muscle weakness and exaggerated lumbar lordosis. Serum creatine kinase level was 1,455 U/l. The atrophies of the paraspinal muscles at thoracic to lumbar spine levels, rectus abdominis and soleus muscles were detected on computed tomography. Muscle biopsy showed mild to moderate variability in muscle fiber size with regenerating and necrotic muscle fibers. Mononuclear cell infiltration was not found. HLA-ABC expression was minimum. After anti-mitochondrial M2 antibody was detected, administration of oral prednisolone resulted in improvements in muscle strength and serum creatine kinase level. Based on the clinical course, examination and clinical findings, the patient was diagnosed as anti-mitochondrial M2 antibody positive myositis. Anti-mitochondrial M2 positive myositis is not only difficult to diagnose by muscle biopsy, but can also be preceded or complicated by fatal cardiac complications.