Effect of intravenous fluid therapy for acute alcohol intoxication on length of time from arrival at the emergency department until awakening: A prospective observational cohort study.

Aim: To evaluate the association of intravenous fluid (IVF) therapy on the length of time from arrival at the emergency department (ED) until awakening in cases of acute alcohol intoxication. Methods: This single-center, prospective, observational study was conducted in the ED of the Self-Defense Forces Central Hospital during October 1, 2018 to July 31, 2019. Patients with 1,000 mL bolus of lactated Ringer's solution and those without bolus were compared. The primary outcome was the length of time until awakening. Secondary outcomes were the length of stay in the ED and occurrence of conditions requiring extra care. Predictors of the occurrence of any event requiring extra care were identified. Results: We included 201 patients, of whom 109 received IVF and 92 did not. No significant difference existed in the baseline characteristics between the groups. The median length of time until awakening did not significantly differ between the groups (P = 0.77). Multivariable regression analysis adjusted by age, sex, hemoglobin, blood alcohol concentration, and initial Glasgow Coma Scale (GCS) score demonstrated that the regression coefficient of IVF for length of time until awakening was -9.55 (95% confidence interval [CI], -36.2 to 17.2). Hemoglobin (regression coefficient, 10.1; 95% CI, 0.38-19.9) and initial GCS score (regression coefficient, -7.51; 95% CI, -10.8 to -4.21) were significantly associated with length of time. Conclusion: IVF therapy was not associated with the length of time until awakening in patients with acute alcohol intoxication in the ED. Routine IVF administration was unnecessary.

Differential expression of myosin heavy chain isoforms type II in skeletal muscles of polar and black bears.

In this study, the pattern of myosin heavy chain (MHC) isoforms expression in skeletal muscles of the trunk, forelimb and hindlimb in Polar Bear (PB) Ursus maritimus; American Black Bear (AmBB), Ursus americanus and Asian Black Bear (AsBB), Ursus thibetanus was analysed by immunohistochemistry and SDS-PAGE. Results showed that slow (MHC-I) and fast (MHC-II) isoforms exist in muscles of bears. Type II fibres were classified further into Type IIa and IIx in PB but not in AsBB and AmBB. The distribution of Type I and Type II fibres in the trunk, forelimb and hindlimb varied based on muscle type and animal species. The proportions of Type I fibres formed approximately one-third of muscle composition in PB (trunk, 32.0%; forelimb, 34.7%; hindlimb, 34.5%) and a half in both AsBB and AmBB whereas Type IIa and IIx formed approximately two-third in PB (trunk, 68.0%; forelimb, 65.3%; hindlimb, 65.5%) and a half of Type II in both AmBB and AsBB. PB is a good swimmer, lives in Arctic Ocean on slippery ice catching aquatic mammals such as seals and is larger in size compared to the medium sized AmBB (living in forest) and AsBB (arboreal). The results suggest that in bears, there is greater diversity in MHC isoforms II, being expressed in selected fast contracting skeletal muscles in response to variety of environments, weight bearing and locomotion.

Incidence and Risk Factors of Immediate Hypersensitivity Reactions and Immunization Stress-Related Responses With COVID-19 mRNA Vaccine.

BACKGROUND: With the implementation of mass vaccination campaigns against COVID-19, the safety of vaccine needs to be evaluated. OBJECTIVE: We aimed to assess the incidence and risk factors for immediate hypersensitivity reactions (IHSR) and immunization stress-related responses (ISRR) with the Moderna COVID-19 vaccine. METHODS: This nested case-control study included recipients who received the Moderna vaccine at a mass vaccination center, Japan. Recipients with IHSR and ISRR were designated as cases 1 and 2, respectively. Controls 1 and 2 were selected from recipients without IHSR or ISRR and matched (1 case: 4 controls) with cases 1 and cases 2, respectively. Conditional logistic regression analysis was used to identify risk factors associated with IHSR and ISRR. RESULTS: Of the 614,151 vaccine recipients who received 1,201,688 vaccine doses, 306 recipients (cases 1) and 2478 recipients (cases 2) showed 318 events of IHSR and 2558 events of ISRR, respectively. The incidence rates per million doses were estimated as IHSR: 266 cases, ISRR: 2129 cases, anaphylaxis: 2 cases, and vasovagal syncope: 72 cases. Risk factors associated with IHSR included female, asthma, atopic dermatitis, thyroid diseases, and a history of allergy; for ISRR, the risk factors were younger age, female, asthma, thyroid diseases, mental disorders, and a history of allergy and vasovagal reflex. CONCLUSION: In the mass vaccination settings, the Moderna vaccine can be used safely owing to the low incidence rates of IHSR and anaphylaxis. However, providers should be aware of the occurrence of ISRR. Although recipients with risk factors are associated with slightly increased risks of IHSR and ISRR, this is not of sufficient magnitude to warrant special measures regarding their vaccination.

Ryanodine receptors mediate high intracellular Ca2+ and some myocyte damage following eccentric contractions in rat fast-twitch skeletal muscle.

Eccentric contractions (ECC) facilitate cytosolic calcium ion (Ca2+) release from the sarcoplasmic reticulum (SR) and Ca2+ influx from the extracellular space. Ca2+ is a vital signaling messenger that regulates multiple cellular processes via its spatial and temporal concentration ([Ca2+]i) dynamics. We hypothesized that 1) a specific pattern of spatial/temporal intramyocyte Ca2+ dynamics portends muscle damage following ECC and 2) these dynamics would be regulated by the ryanodine receptor (RyR). [Ca2+]i in the tibialis anterior muscles of anesthetized adult Wistar rats was measured by ratiometric (i.e., ratio, R, 340/380 nm excitation) in vivo bioimaging with Fura-2 pre-ECC and at 5 and 24 h post-ECC (5 × 40 contractions). Separate groups of rats received RyR inhibitor dantrolene (DAN; 10 mg/kg ip) immediately post-ECC (+DAN). Muscle damage was evaluated by histological analysis on hematoxylin-eosin stained muscle sections. Compared with control (CONT, no ECC), [Ca2+]i distribution was heterogeneous with increased percent total area of high [Ca2+]i sites (operationally defined as R ≥ 1.39, i.e., ≥1 SD of mean control) 5 h post-ECC (CONT, 14.0 ± 8.0; ECC5h: 52.0 ± 7.4%, P < 0.01). DAN substantially reduced the high [Ca2+]i area 5 h post-ECC (ECC5h + DAN: 6.4 ± 3.1%, P < 0.01) and myocyte damage (ECC24h, 63.2 ± 1.0%; ECC24h + DAN: 29.1 ± 2.2%, P < 0.01). Temporal and spatially amplified [Ca2+]i fluctuations occurred regardless of DAN (ECC vs. ECC + DAN, P > 0.05). These results suggest that the RyR-mediated local high [Ca2+]i itself is related to the magnitude of muscle damage, whereas the [Ca2+]i fluctuation is an RyR-independent phenomenon.

Snakebite and local envenomation by Boiruna maculata treated without antivenom.

BACKGROUND: When snake breeders are bitten by rare snakes, deciding whether to administer snake antivenom can be challenging. CASE PRESENTATION: A 50-year-old man was bitten on the right finger by Boiruna maculata. The next day, his right upper limb exhibited pronounced local manifestations of envenomation. At the first consultation, a dark purple bleeding spot and a necrotic site were present under the fang marks at the bitten finger and his affected limb showed extensive swelling and redness. Snake antivenom was not administered because it was difficult to identify the snake and obtain the antivenom. We performed the pressure immobilization technique to his limb. The patient's symptoms peaked in severity on the second day of illness. He was discharged with marked improvement. CONCLUSIONS: We have experienced a case of snakebite envenomation by Boiruna maculata.

Long-term physical inactivity exacerbates hindlimb unloading-induced muscle atrophy in young rat soleus muscle.

This study investigated the effects of long-term physical inactivity in adolescent on subsequent hindlimb unloading-induced muscle atrophy in rat soleus muscle. First, 3-wk-old male Wistar rats were assigned to an age-matched control (n = 6) or a physical inactivity (n = 8) group. Rats in the physical inactivity group were housed in narrow cages with approximately half the usual floor space for 8 wk to limit range of movement. Whole body energy consumption was measured, and the blood, organs, femoral bone, and hindlimb muscles were removed. We found that long-term physical inactivity did not affect the metabolic and physiological characteristics of growing rats. Then, fifty-six 3-wk-old male Wistar rats were assigned randomly into control (n = 28) and physical inactivity (n = 28) groups. After 8 wk, the rats in both groups underwent hindlimb unloading. The soleus muscles were removed before unloading (0 day), and 1, 3, and 7 days after unloading (n = 7 for each). Although the soleus muscle weight was significantly decreased after 7 days of hindlimb unloading in both groups, the decrease was drastic in the inactive group. A significant interaction between inactivity and unloading (P < 0.01) was observed according to the 4-hydroxynonenal-conjugated protein levels and the histone deacetylase 4 (HDAC4) and NF-κB protein levels. HDAC4 and NF-κB p65 protein levels in the physical inactivity group increased significantly 1 day after hindlimb unloading, along with the mRNA levels of their downstream targets myogenin and muscle RING finger protein 1 (MuRF1). Subsequent protein ubiquitination was upregulated by long-term physical inactivity (P < 0.05).NEW & NOTEWORTHY Long-term physical inactivity exacerbates hindlimb unloading-induced disuse muscle atrophy in young rat soleus muscles, possibly mediated by oxidative stress-induced protein ubiquitination via HDAC4- and NF-κB p65-induced MuRF1 mRNA upregulation.

Sex-specific differences in rat soleus muscle signaling pathway responses to a bout of horizontal and downhill running.

Males and females of many species, including humans, exhibit different muscle responses and adaptations to exercise stress; however, the molecular mechanisms that underlie these changes are poorly understood. Therefore, the present study assessed sex-related differences in intracellular signaling pathway responses to bouts of horizontal or downhill running in rat soleus muscles. Age-matched male and female Wistar rats (10 weeks old, n = 18/group) were either rested (control group) or subjected to an either a bout of horizontal (22 m/min, 20 min, 0° incline) or downhill (16 m/min, 10 min, - 16% incline) treadmill running. Soleus muscle samples were collected both prior to and immediately after exercise (n = 6/group). Intramuscular signaling responses to each type of exercise were determined via real-time (RT) PCR and western blot analyses. Although mTOR signaling (mTOR/S6K1/S6) responses to both horizontal and downhill exercise were found to be similar in both sexes, ERK phosphorylation levels were found to be significantly higher in male than in female rats after downhill exercise. Similarly, heat shock protein (Hsp) 72 and myostatin protein expression levels were both found to be significantly altered after downhill exercise: Hsp levels increased in male and decreased in female rats, whereas myostatin increased in female but decreased in male rats. Thus, the results of the present study suggest that downhill exercise may elicit sex-specific differential changes to Hsp72 expression, ERK phosphorylation, and myostatin-signaling activation in female compared with those in male rat soleus muscles. Further study is required to confirm these findings and to determine the way in which they impact sex-specific differences in exercise-induced muscle adaptations.

Age-related changes in histone modification in rat gastrocnemius muscle.

Changes in histone acetylation and methylation status with aging affect gene expression and phenotype in several tissues; however, age-related changes in histone modification in the skeletal muscle have not been elucidated yet. This study investigated age-related global changes in histone modification in rat gastrocnemius muscle. Male Wistar rats (n = 28) were assigned to one of four age groups (n = 7 per group) corresponding to different life stages: 3 months old (3-mo; young), 6 months old (adult), 12 months old (12-mo; middle-aged), and 24 months old (24-mo; old). The gastrocnemius muscle was removed and global histone modification (acetylation and tri-methylation) at K9 and K27 was evaluated by western blotting. Relative muscle mass decreased in the 12- and 24-mo rats accompanied with reduction in type IIb myosin heavy chain isoforms and Myh4 (MHC IIB) mRNA expression. Histone H3 acetylation decreased in an age-dependent manner, with lower levels in 12- and 24-mo groups than in the 3-mo group. K9 and K27 acetylation decreased with age. Although there was no significant change in K27 tri-methylation, K9 tri-methylation showed an age-dependent decline. Histone modification status (acetylation at K9 and K27 and tri-methylation at K9) was positively associated with relative gastrocnemius muscle weight, the percentage of type IIb myosin heavy chain isoform, myosin heavy chain type IIb protein expression, and the level of Myh4 mRNA. Thus, global histone H3 methylation and acetylation decrease with age, and the latter might be associated with age-related muscle atrophy of rat gastrocnemius muscle.

Impact of different temperature stimuli on the expression of myosin heavy chain isoforms during recovery from bupivacaine-induced muscle injury in rats.

Limited information exists regarding the impact of different temperature stimuli on myosin heavy chain (MyHC) expression in skeletal muscle during recovery from injury. Therefore, this experiment investigated the impact of both cold and heat exposure on the MyHC isoform profile in the rat soleus during recovery from injury. Male Wistar rats were randomly divided into control, bupivacaine-injected (BPVC), BPVC with icing, and BPVC with heat stress groups. Muscle injury was induced by intramuscular injection of bupivacaine into soleus muscles of male Wistar rats. Icing treatment (0°C for 20 min) was performed immediately after the injury. Intermittent heat stress (42°C for 30 min on alternating days) was carried out during 2-14 days after bupivacaine injection. In response to injury, a transient increase in developmental, IId/x, and IIb MyHC isoforms, as well as various types of hybrid fibers, followed by the recovery of the MyHC profile toward the control level, was noted in the regeneration of the soleus. The restoration of the MyHC profile in the regenerating muscle at whole-muscle and individual myofiber levels was partially delayed by icing but facilitated by heat stress. In addition, the application of repeated heat stress promoted the recovery of soleus muscle mass toward the control level following injury. We conclude that compared with acute and immediate cold (icing) treatment, chronic and repeated heat stress may be a more appropriate treatment for the enhancement of both normalization of the MyHC profile and restoration of muscle mass following injury. NEW & NOTEWORTHY Cold exposure (icing), but not heat exposure, has been well accepted as a first-aid treatment for accidental and/or sports-related injuries. However, recent evidence suggests the negative impact of icing treatment on skeletal muscle regeneration following injury. Here, we demonstrated that acute/immediate icing treatment delayed the restoration of the myosin heavy chain (MyHC) profile, but intermittent hyperthermia, repeated for several days, facilitated the recovery of both muscle mass and the MyHC profile in the regeneration of skeletal muscle following injury.

Exercise preconditioning attenuates hind limb unloading-induced gastrocnemius muscle atrophy possibly via the HDAC4/Gadd45 axis in old rats.

The mechanisms involved in unloading-induced skeletal muscle loss may be age-specific, and the evidence for exercise preconditioning-induced protection against disuse muscle atrophy in aged rats is limited. Therefore, in this study, we investigated age-related differences in the activation of the HDAC4/Gadd45α pathway following hindlimb unloading (HU). We also assessed the protective effect of preconditioning exercise on this pathway in young and old rat gastrocnemius muscle. Three-month-old (young, n = 18) and 24-month-old (old, n = 18) male Wistar rats were assigned to the following groups: control group (n = 6), seven days of HU group (n = 6), and a bout of exercise preconditioning prior to HU (Ex+HU) group (n = 6). Rats of both ages in the Ex + HU group ran continuously on a motor-driven treadmill (0° slope, 20 m/min, 15 min) prior to HU. The gastrocnemius muscles were removed after 7 days of HU and analyzed for protein content and mRNA expression. Gastrocnemius muscle weight was significantly higher in the Ex+HU group than in the HU group of old rats, but not in young rats. Levels of HDAC4 protein and mRNA were significantly increased in the old HU group. However, the increase was significantly suppressed in the old Ex+HU group. Moreover, the protective effect of exercise preconditioning had a positive effect on Gadd45α mRNA and protein levels only in the old Ex+HU group. No exercise preconditioning-related protection was observed in the young rats. Our data indicated that a single bout of preconditioning exercise prior to HU may exert a protective effect in disuse muscle atrophy in old rats and that these effects may be partially mediated by the HDAC4/Gadd45α axis.

Sex differences in forkhead box O3a signaling response to hindlimb unloading in rat soleus muscle.

We tested the hypothesis that there are sex differences in hindlimb unloading-induced activation of the forkhead box subfamily O3a (FoxO3a) signaling pathway in rat soleus muscle. Age-matched male and female Wistar rats were subjected to hindlimb unloading, and the soleus muscle was removed before or 1 or 7 days after unloading. Female rats showed greater percent changes in relative soleus muscle weight than males. FoxO3a phosphorylation was lower in females than in males and was associated with higher levels of protein ubiquitination 7 days after unloading. Heat shock protein 72 (Hsp72) levels were lower in female rats and increased in males during unloading. Female rats showed slightly higher myostatin levels, which showed a non-significant decline in male rats following unloading. Thus, males and females show different responses to the FoxO3a/ubiquitin-proteasome pathway following hindlimb unloading in rat soleus muscle, which may be associated with differences in Hsp72 expression and myostatin signaling.

Characteristics of Muscle Fiber-Type Distribution in Moles.

Moles are a strictly fossorial Soricomorpha species and possess a suite of specialized adaptations to subterranean life. However, the contractile function of skeletal muscles in moles remains unclear. We compared muscle fiber-type distribution in two mole species (the large Japanese mole and lesser Japanese mole) with that in four other Soricomorpha species that are semi-fossorial, terrestrial, or semi-aquatic (the Japanese shrew-mole, house shrew, Japanese white-toothed shrew, and Japanese water shrew). For a single species, the fiber-type distribution in up to 38 muscles was assessed using immunohistochemical staining and/or gel electrophoresis. We found that slow and fatigue-resistant Type I fibers were absent in almost all muscles of all species studied. Although, the two methods of determining the fiber type did not give identical results, they both revealed that fast Type IIb fibers were absent in mole muscles. The fiber-type distribution was similar among different anatomical regions in the moles. This study demonstrated that the skeletal muscles of moles have a homogenous fiber-type distribution compared with that in Soricomorpha species that are not strictly fossorial. Mole muscles are composed of Type IIa fibers alone or a combination of Type IIa and relatively fast Type IIx fibers. The homogenous fiber-type distribution in mole muscles may be an adaptation to structurally simple subterranean environments, where there is no need to support body weight with the limbs, or to move at high speeds to pursue prey or to escape from predators. Anat Rec, 302:1010-1023, 2019. © 2018 Wiley Periodicals, Inc.

Effect of a combination of astaxanthin supplementation, heat stress, and intermittent reloading on satellite cells during disuse muscle atrophy.

We examined the effect of a combination of astaxanthin (AX) supplementation, repeated heat stress, and intermittent reloading (IR) on satellite cells in unloaded rat soleus muscles. Forty-nine male Wistar rats (8-week-old) were divided into control, hind-limb unweighting (HU), IR during HU, IR with AX supplementation, IR with repeated heat stress (41.0-41.5 °C for 30 min), and IR with AX supplementation and repeated heat stress groups. After the experimental period, the antigravitational soleus muscle was analyzed using an immunohistochemical technique. Our results revealed that the combination of dietary AX supplementation and heat stress resulted in protection against disuse muscle atrophy in the soleus muscle. This protective effect may be partially due to a higher satellite cell number in the atrophied soleus muscle in the IR/AX/heat stress group compared with the numbers found in the other groups. We concluded that the combination treatment with dietary AX supplementation and repeated heat stress attenuates soleus muscle atrophy, in part by increasing the number of satellite cells.

Dietary astaxanthin supplementation attenuates disuse-induced muscle atrophy and myonuclear apoptosis in the rat soleus muscle.

Extended periods of skeletal muscle disuse results in muscle atrophy and weakness. Currently, no therapeutic treatment is available for the prevention of this problem. Nonetheless, growing evidence suggests that prevention of disuse-induced oxidative stress in inactive muscle fibers can delay inactivity-induced muscle wasting. Therefore, this study tested the hypothesis that dietary supplementation with the antioxidant astaxanthin would protect against disuse muscle atrophy, in part, by prevention of myonuclear apoptosis. Wistar rats (8 weeks old) were divided into control (CT, n = 9), hindlimb unloading (HU, n = 9), and hindlimb unloading with astaxanthin (HU + AX, n = 9) groups. Following 2 weeks of dietary supplementation, rats in the HU and HU + AX groups were exposed to unloading for 7 days. Seven-day unloading resulted in reduced soleus muscle weight and myofiber cross-sectional area (CSA) by ~30 and ~47 %, respectively. Nonetheless, relative muscle weights and CSA of the soleus muscle in the HU + AX group were significantly greater than those of the HU group. Moreover, astaxanthin prevented disuse-induced increase in the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive nuclei. We conclude that astaxanthin supplementation prior to and during hindlimb unloading attenuates soleus muscle atrophy, in part, by suppressing myonuclear apoptosis.

Suppression of Myostatin Stimulates Regenerative Potential of Injured Antigravitational Soleus Muscle in Mice under Unloading Condition.

Effects of myostatin (MSTN)-suppression on the regeneration of injured skeletal muscle under unloading condition were investigated by using transgenic mice expressing a dominant-negative form of MSTN (MSTN-DN). Both MSTN-DN and wild-type (WT) mice were subjected to continuous hindlimb suspension (HS) for 6 weeks. Cardiotoxin (CTX) was injected into left soleus muscle under anesthesia 2 weeks after the initiation of HS. Then, the soleus muscles were excised following 6-week HS (4 weeks after CTX-injection). CTX-injection caused to reduce the soleus fiber cross-sectional area (CSA) in WT mice under both unloading and weight-bearing conditions, but not in MSTN-DN mice. Under unloading condition, CTX-injected muscle weight and fiber CSA in MSTN-DN mice were significantly higher than those in WT mice. CTX-injected muscle had many damaged and regenerating fibers having central nuclei in both WT and MSTN-DN mice. Significant increase in the population of Pax7-positive nuclei in CTX-injected muscle was observed in MSTN-DN mice, but not in WT mice. Evidences indicate that the suppression of MSTN cause to increase the regenerative potential of injured soleus muscle via the increase in the population of muscle satellite cells regardless of unloading conditions.

Astaxanthin intake attenuates muscle atrophy caused by immobilization in rats.

Astaxanthin is a carotenoid pigment and has been shown to be an effective inhibitor of oxidative damage. We tested the hypothesis that astaxanthin intake would attenuate immobilization-induced muscle atrophy in rats. Male Wistar rats (14-week old) were fed for 24 days with either astaxanthin or placebo diet. After 14 days of each experimental diet intake, the hindlimb muscles of one leg were immobilized in plantar flexion position using a plaster cast. Following 10 days of immobilization, both the atrophic and the contralateral plantaris muscles were removed and analyzed to determine the level of muscle atrophy along with measurement of the protein levels of CuZn-superoxide dismutase (CuZn-SOD) and selected proteases. Compared with placebo diet animals, the degree of muscle atrophy in response to immobilization was significantly reduced in astaxanthin diet animals. Further, astaxanthin supplementation significantly prevented the immobilization-induced increase in the expression of CuZn-SOD, cathepsin L, calpain, and ubiquitin in the atrophied muscle. These results support the postulate that dietary astaxanthin intake attenuates the rate of disuse muscle atrophy by inhibiting oxidative stress and proteolysis via three major proteolytic pathways.

Effects of icing or heat stress on the induction of fibrosis and/or regeneration of injured rat soleus muscle.

The effects of icing or heat stress on the regeneration of injured soleus muscle were investigated in male Wistar rats. Bupivacaine was injected into soleus muscles bilaterally to induce muscle injury. Icing (0 °C, 20 min) was carried out immediately after the injury. Heat stress (42 °C, 30 min) was applied every other day during 2-14 days after the bupivacaine injection. Injury-related increase in collagen deposition was promoted by icing. However, the level of collagen deposition in heat-stressed animals was maintained at control levels throughout the experimental period and was significantly lower than that in icing-treated animals at 15 and 28 days after bupivacaine injection. Furthermore, the recovery of muscle mass, protein content, and muscle fiber size of injured soleus toward control levels was partially facilitated by heat stress. These results suggest that, compared with icing, heat stress may be a beneficial treatment for successful muscle regeneration at least by reducing fibrosis.

Immobilization induces nuclear accumulation of HDAC4 in rat skeletal muscle.

The study described herein aimed to examine changes in HDAC4 and its downstream targets in immobilization-induced rat skeletal muscle atrophy. Eleven male Wistar rats were used, and one hindlimb was immobilized in the plantar flexion position using a plaster cast. The contralateral, non-immobilized leg served as an internal control. After 10 days, the gastrocnemius muscles were removed from both hindlimbs. Ten days of immobilization resulted in a significant reduction (-27.3 %) in gastrocnemius muscle weight. A significant decrease in AMPK phosphorylation was also observed in nuclear fractions from immobilized legs relative to the controls. HDAC4 expression was significantly increased in immobilized legs in both the cytoplasmic and nuclear fractions. Moreover, Myogenin and MyoD mRNA levels were upregulated in immobilized legs, resulting in increased Atrogin-1 mRNA expression. Our data suggest that nuclear HDAC4 accumulation is partly related to immobilization-induced muscle atrophy.

The response of apoptotic and proteolytic systems to repeated heat stress in atrophied rat skeletal muscle.

We examined the effect of repeated heat stress on muscle atrophy, and apoptotic and proteolytic regulation in unloaded rat slow- and fast-type skeletal muscles. Forty male Wistar rats (11 week-old) were divided into control (CT), hindlimb unweighting (HU), intermittent weight-bearing during HU (HU + IWB), and intermittent weight-bearing with heat stress during HU (41-41.5°C for 30 min; HU + IWB + HS) groups. The HU + IWB + HS and HU + IWB groups were released from unloading for 1 h every second day, during which the HU + IWB + HS group underwent the heating. Our results revealed that repeated bouts of heat stress resulted in protection against disuse muscle atrophy in both soleus and plantaris muscles. This heat stress-induced protection against disuse-induced muscular atrophy may be partially due to reduced apoptotic activation in both muscles, and decreased ubiquitination in only the soleus muscle. We concluded that repeated heat stress attenuated skeletal muscle atrophy via suppressing apoptosis but the response to proteolytic systems depend on the muscle phenotype.

Repeated exposure to heat stress results in a diaphragm phenotype that resists ventilator-induced diaphragm dysfunction.

Controlled mechanical ventilation (CMV) is a life-saving intervention for patients in respiratory failure. Unfortunately, prolonged mechanical ventilation (MV) results in diaphragmatic atrophy and contractile dysfunction, both of which are predicted to contribute to problems in weaning patients from the ventilator. Therefore, developing a strategy to protect the diaphragm against ventilator-induced weakness is important. We tested the hypothesis that repeated bouts of heat stress result in diaphragm resistance against CMV-induced atrophy and contractile dysfunction. Male Wistar rats were randomly divided into six experimental groups: 1) control; 2) single bout of whole body heat stress; 3) repeated bouts of whole body heat stress; 4) 12 h CMV; 5) single bout of whole body heat stress 24 h before CMV; and 6) repeated bouts of whole body heat stress 1, 3, and 5 days before 12 h of CMV. Our results revealed that repeated bouts of heat stress resulted in increased levels of heat shock protein 72 in the diaphragm and protection against both CMV-induced diaphragmatic atrophy and contractile dysfunction at submaximal stimulation frequencies. The specific mechanisms responsible for this protection remain unclear: this heat stress-induced protection against CMV-induced diaphragmatic atrophy and weakness may be partially due to reduced diaphragmatic oxidative stress, diminished activation of signal transducer/transcriptional activator-3, lower caspase-3 activation, and decreased autophagy in the diaphragm.