Extent In Muscle Research Articles

Strain-dependent shear properties of human adipose tissue in vivo

IntroductionHuman adipose tissue (fat) deforms substantially under normal physiological loading and during impact. Thus, accurate data on strain-dependent stiffness of fat is essential for the creation of accurate biomechanical models. Previous studies on ex vivo samples reported human fat to be nonlinear and viscoelastic. When static compression is combined with magnetic resonance (MR) elastography (an imaging technique used to measure viscoelasticity in vivo), the large deformation properties of tissues can be determined. Here, we use magnetic resonance elastography to quantify fat shear modulus in vivo under increasing compressive strain and compare it to the underlying passive gluteal muscle. MethodsThe right buttocks of ten female participants were incrementally compressed at four levels while MR elastography (50 Hz) and mDixon images were acquired. Maps of tissue shear modulus (G*) were reconstructed from the MR elastography phase images. Tissue strain was estimated from registration of deformed and undeformed mDixon images. Linear mixed models were fit to the natural logarithm of the compressive strain and shear modulus data for each tissue. ResultsShear modulus increased in an exponential relationship with compressive strain in fat: Gfat*=748.5*Cyy−1.18Pa, and to a lesser extent in muscle: Gmuscle*=956.4*Cyy−0.36Pa. The baseline (undeformed) stiffness of fat was significantly lower than that of muscle (mean G*fat = 752 Pa, mean G*muscle = 1000 Pa, paired samples t-test, t = −4.24, p = 0.001). However, fat exhibited a significantly higher degree of strain dependence (characterised by the exponent of the curve, t = −6.47, p = 0.0001). ConclusionStatic compression of human adipose tissue results in an increase in apparent viscoelastic shear modulus (stiffness), in an exponentially increasing relationship. The relationships defined here can be used in the development of physiologically realistic computational models for impact, injury and biomechanical modelling.

Thermoneutral housing increases the obesogenic phenotype of mice, while some effects of exercise are reduced

Introduction: Mice are extensively used to investigate the molecular foundations of obesity and the beneficial effect of exercise training (ET). Mice are most often housed at ambient temperature, ~22°C, which is below their thermoneutral environment (~30°C). Mild cold stress at ambient temperature accelerates mouse metabolic rate and may confound translation of results to humans. Aiming to determine the metabolic adaptations of ET in an obesogenic environment, we hypothesized that thermoneutral housing would increase adiposity during high-fat feeding. Moreover, thermoneutral housing would blunt the effects of ET by relieving the added cold stress. Methods: After temperature acclimatization (3 weeks, 22°C vs. 30°C), C57BL/6J mice (n=68, ♀, Age: 11 weeks) were dual-housed for 8 weeks receiving a chow diet or a 60%E high-fat diet (HFD). HFD mice were then separated into two additional groups with access to voluntary wheel running for another 8 weeks. Metabolic parameters were measured using magnetic resonance imaging, indirect calorimetry, glucose tolerance tests, and maximal running capacity on treadmill. Brown and white adipose tissues and gastrocnemius muscle mRNA and protein content were analyzed using qPCR and immunoblotting analyses, respectively. Results: In chow-fed mice, thermoneutral housing decreased metabolic rate (VO2), fasting plasma glucose, and thermogenic genes in adipose tissue depots, without changes in skeletal muscle mitochondrial protein content compared to 22°C. In HFD mice, thermoneutral housing increased fat mass, induced glucose intolerance, and fasting plasma insulin levels compared to 22°C housing. This was despite decreased food intake and metabolic rate compared to HFD mice housed at 22°C. ET mice improved the exercise capacity and glucose tolerance independent of housing temperature. Interestingly, while ET at 30°C prevented further fat gain during the intervention, ET at 22°C decreased fat mass. Moreover, only ET at 22°C increased the metabolic rate during the active phase. Gene expression responded similarly to ET independent of housing temperature in adipose tissue depots. ET induced GLUT4, peroxiredoxin 2 and pyruvate dehydrogenase protein content to a lesser extent in muscle at 30°C housing. Conclusion: Adaptations to diet-induced obesity and ET in mice critically depend upon housing temperature. Our findings underscore housing temperature as a key consideration in research related the beneficial effect of exercise in an obesogenic environment. Disclosure of funding: SHR is supported by the Lundbeck Foundation and Independent Research Fund Denmark. LS and EAR are supported by the Novo Nordisk Foundation and Independent Research Fund Denmark. IK is supported by the Novo Nordisk Foundation. 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.

Integrated biomarker response in signal crayfish Pacifastacus leniusculus exposed to diphenhydramine

Diphenhydramine (DPH) is a pharmaceutical with multiple modes of action, primarily designed as an antihistamine therapeutic drug. Among antihistamines, DPH is a significant contaminant in the environment, frequently detected in surface waters, sediments, and tissues of aquatic biota. In the present study, signal crayfish Pacifastacus leniusculus was used as a model organism because of their prominent ecological roles in freshwater ecosystems. The biochemical effects were investigated in crayfish exposed to the environmental (low: 2 μg L−1), ten times elevated (medium: 20 μg L−1), and the sublethal (high: 200 μg L−1) nominal concentrations of DPH in water for 96 h. Lipid peroxidation, antioxidant enzyme activities, and acetylcholinesterase activity were assessed as toxicological biomarkers in crayfish hepatopancreas, gills, and muscles. Low and medium DPH exposure caused imbalances only in glutathione-like enzyme activities. Integrated biomarker response showed the absolute DPH toxicity effects on all tested tissues under high exposure. This study identified that high, short-term DPH exposure induced oxidative stress in crayfish on multiple tissue levels, with the most considerable extent in muscles.

Clinical diagnosis and surgical treatment of cervical spondylosis with distal upper extremity amyotrophy

Objective To summarize the clinical features of cervical spondylosis with distal upper extremity amyotrophy; and further analyze the clinical efficacy of cervical anterior decompression and fusion on cervical spondylosis with distal upper extremity amyotrophy. Methods Thirty cases of cervical spondylosis with distal upper extremity amyotrophy were analyzed retrospectively from June 2006 to June 2015. nineteen males and eleven females with an average age of 55.20±9.08 years (41 to 72 years) were included. The preoperative course was 1 to 108 months with a median of 6 months. The muscle extent of the affected group, the segmentation and location of spinal canal stenosis, and the results of neurophysiological examination were analyzed. The muscular strength recovery of atrophic muscles was evaluated by Manual Muscle Testing (MMT), and the clinical satisfaction was assessed at the last followed up. Results The muscles involved in patients of cervical spondylosis with distal upper extremity amyotrophy are mainly the thenar muscle (17 cases, 56.7%), interosseous muscle (15 cases, 50.0%), and shypothenar muscles (13 cases, 43.3%). Most cases of imaging findings showed multi-segmental degeneration, of which C5, 6 (24 cases, 80.0%), C6,7 (21 cases, 70.0%) segments were most common, and the types of anterior compression: 23 segments (33.5%) of the central type, 37 segments (54.4%) of the lateral-central type, and 8 segments (11.8%) of the foramen type. Neuroelectrophysiological examination showed that cervical spinal cord anterior horn cells or nerve root damage, the most commonly involved segments of C7, C8, T1(18 cases, 60.0%). The average follow-up time was 36.8 months. At the last follow-up, MMT assessment showed that thirteen patients (43.3%) in this group had muscle strength recovery for more than one grade at the last follow-up. The average clinical satisfaction was 73.4%. Conclusion The clinical diagnosis of cervical spondylosis with distal upper extremity amyotrophy requires a combination of clinical symptoms, imaging findings and neurophysiological examination results for comprehensive judgment. Cervical anterior decompression and fusion can effectively prevent the progression of cervical spondylosis in distal upper extremity amyotrophy patients, and some patients can get a good muscle recovery. Key words: Cervical vertebrae; Spinal cord compression; Muscular atrophy; Spinal fusion

Effect of TMS coil orientation on the spatial distribution of motor evoked potentials in an intrinsic hand muscle.

Previous reports on the relationship between coil orientation and amplitude of motor evoked potential (MEP) in transcranial magnetic stimulation (TMS) did not consider the effect of electrode arrangement. Here we explore this open issue by investigating whether TMS coil orientation affects the amplitude distribution of MEPs recorded from the abductor pollicis brevis (APB) muscle with a bi-dimensional grid of 61 electrodes. Moreover, we test whether conventional mono- and bipolar montages provide representative MEPs compared to those from the grid of electrodes. Our results show that MEPs with the greatest amplitudes were elicited for 45° and 90° coil orientations, i.e. perpendicular to the central sulcus, for all electrode montages. Stimulation with the coil oriented at 135° and 315°, i.e. parallel to the central sulcus, elicited the smallest MEP amplitudes. Additionally, changes in coil orientation did not affect the spatial distribution of MEPs over the muscle extent. It has been shown that conventional electrodes with detection volume encompassing the APB belly may detect representative MEPs for optimal coil orientations. In turn, non-optimal orientations were identified only with the grid of electrodes. High-density electromyography may therefore provide new insights into the effect of coil orientation on MEPs from the APB muscle.

Biotransformation of 8:2 polyfluoroalkyl phosphate diester in gilthead bream (Sparus aurata)

Polyfluoroalkyl phosphate esters (PAPs) are high production volume surfactants used in the food contact paper and packaging industry. PAPs may transform to persistent perfluoroalkyl carboxylic acids (PFCAs) under biotic conditions, but little is known about their fate and behavior in aquatic organisms. Here we report for the first time on the uptake, tissue distribution, and biotransformation of 8:2 polyfluoroalkyl phosphate diester (8:2 diPAP) in fish. Gilt-head bream (Sparus aurata) were dosed via the diet (8:2 diPAP at 29μg/g) for 7days, during which time 8:2 diPAP and its transformation products were monitored in plasma, liver, muscle, gills, bile and brain. 8:2 diPAP tended to accumulate in liver, plasma and gills, and to a lesser extent in muscle, bile and brain. Several transformation products (observed previously in other organisms) were also observed in most tissues and biofluids, including both saturated and unsaturated fluorotelomer acids (8:2 FTCA, 8:2 FTUCA, 7:3 FTCA), and perfluorooctanoic acid (PFOA). 8:2 FTCA was the major metabolite in all tissues/biofluids, except for bile, where PFOA occurred at the highest concentrations. Unexpectedly high PFOA levels (up to 3.7ng/g) were also detected in brain. Phase 2 metabolites, which have been reported in fish following exposure to fluorotelomer alcohols, were not observed in these experiments, probably due to their low abundance. Nevertheless, the detection of PFOA indicates that exposure to PAPs may be an indirect route of exposure to PFCAs in fish.

Obesity-induced discrepancy between contractile and metabolic phenotypes in slow- and fast-twitch skeletal muscles of female obese Zucker rats.

A clear picture of skeletal muscle adaptations to obesity and related comorbidities remains elusive. This study describes fiber-type characteristics (size, proportions, and oxidative enzyme activity) in two typical hindlimb muscles with opposite structure and function in an animal model of genetic obesity. Lesser fiber diameter, fiber-type composition, and histochemical succinic dehydrogenase activity (an oxidative marker) of muscle fiber types were assessed in slow (soleus)- and fast (tibialis cranialis)-twitch muscles of obese Zucker rats and compared with age (16 wk)- and sex (females)-matched lean Zucker rats (n = 16/group). Muscle mass and lesser fiber diameter were lower in both muscle types of obese compared with lean animals even though body weights were increased in the obese cohort. A faster fiber-type phenotype also occurred in slow- and fast-twitch muscles of obese rats compared with lean rats. These adaptations were accompanied by a significant increment in histochemical succinic dehydrogenase activity of slow-twitch fibers in the soleus muscle and fast-twitch fiber types in the tibialis cranialis muscle. Obesity significantly increased plasma levels of proinflammatory cytokines but did not significantly affect protein levels of peroxisome proliferator-activated receptors PPARγ or PGC1α in either muscle. These data demonstrate that, in female Zucker rats, obesity induces a reduction of muscle mass in which skeletal muscles show a diminished fiber size and a faster and more oxidative phenotype. It was noteworthy that this discrepancy in muscle's contractile and metabolic features was of comparable nature and extent in muscles with different fiber-type composition and antagonist functions.NEW & NOTEWORTHY This study demonstrates a discrepancy between morphological (reduced muscle mass), contractile (shift toward a faster phenotype), and metabolic (increased mitochondrial oxidative enzyme activity) characteristics in skeletal muscles of female Zucker fatty rats. It is noteworthy that this inconsistency was comparable (in nature and extent) in muscles with different structure and function.

Greater inadvertent muscle damage in direct anterior approach when compared with the direct superior approach for total hip arthroplasty

We wished to quantify the extent of soft-tissue damage sustained during minimally invasive total hip arthroplasty through the direct anterior (DA) and direct superior (DS) approaches. In eight cadavers, the DA approach was performed on one side, and the DS approach on the other, a single brand of uncemented hip prosthesis was implanted by two surgeons, considered expert in their surgical approaches. Subsequent reflection of the gluteus maximus allowed the extent of muscle and tendon damage to be measured and the percentage damage to each anatomical structure to be calculated. The DA approach caused substantially greater damage to the gluteus minimus muscle and tendon when compared with the DS approach (t-test, p = 0.049 and 0.003, respectively). The tensor fascia lata and rectus femoris muscles were damaged only in the DA approach. There was no difference in the amount of damage to the gluteus medius muscle and tendon, piriformis tendon, obturator internus tendon, obturator externus tendon or quadratus femoris muscle between approaches. The posterior soft-tissue releases of the DA approach damaged the gluteus minimus muscle and tendon, piriformis tendon and obturator internus tendon. The DS approach caused less soft-tissue damage than the DA approach. However the clinical relevance is unknown. Further clinical outcome studies, radiographic evaluation of component position, gait analyses and serum biomarker levels are necessary to evaluate and corroborate the safety and efficacy of the DS approach. Cite this article: Bone Joint J 2016;98-B1036-42.

Changes in the expression of splicing factor transcripts and variations in alternative splicing are associated with lifespan in mice and humans.

SummaryDysregulation of splicing factor expression and altered alternative splicing are associated with aging in humans and other species, and also with replicative senescence in cultured cells. Here, we assess whether expression changes of key splicing regulator genes and consequent effects on alternative splicing are also associated with strain longevity in old and young mice, across 6 different mouse strains with varying lifespan (A/J, NOD.B10Sn‐H2b/J, PWD.Phj, 129S1/SvlmJ, C57BL/6J and WSB/EiJ). Splicing factor expression and changes to alternative splicing were associated with strain lifespan in spleen and to a lesser extent in muscle. These changes mainly involved hnRNP splicing inhibitor transcripts with most changes more marked in spleens of young animals from long‐lived strains. Changes in spleen isoform expression were suggestive of reduced cellular senescence and retained cellular proliferative capacity in long‐lived strains. Changes in muscle isoform expression were consistent with reduced pro‐inflammatory signalling in longer‐lived strains. Two splicing regulators, HNRNPA1 and HNRNPA2B1, were also associated with parental longevity in humans, in the InCHIANTI aging study. Splicing factors may represent a driver, mediator or early marker of lifespan in mouse, as expression differences were present in the young animals of long‐lived strains. Changes to alternative splicing patterns of key senescence genes in spleen and key remodelling genes in muscle suggest that correct regulation of alternative splicing may enhance lifespan in mice. Expression of some splicing factors in humans was also associated with parental longevity, suggesting that splicing regulation may also influence lifespan in humans.

Sepsis attenuates the anabolic response to skeletal muscle contraction.

Electrically stimulated muscle contraction is a potential clinical therapy to treat sepsis-induced myopathy; however, whether sepsis alters contraction-induced anabolic signaling is unknown. Polymicrobial peritonitis was produced by cecal ligation and puncture (CLP) in male C57BL/6 mice and time-matched, pair-fed controls (CON). At ∼24 h post-CLP, the right hindlimb was electrically stimulated via the sciatic nerve to evoke maximal muscle contractions, and the gastrocnemius was collected 2 h later. Protein synthesis was increased by muscle contraction in CON mice. Sepsis suppressed the rate of synthesis in both the nonstimulated (31%) and stimulated (57%) muscle versus CON. Contraction of muscle in CON mice increased the phosphorylation of mTORC1 (mammalian target of rapamycin [mTOR] complex 1) substrates S6K1 (70-kd ribosomal protein S6 kinase 1) Thr (8-fold), S6K1 ThrSer (7-fold) and 4E-BP1 Ser (11-fold). Sepsis blunted the contraction-induced phosphorylation of S6K1 Thr (67%), S6K1 ThrSer (46%), and 4E-BP1 Ser (85%). Conversely, sepsis did not appear to modulate protein elongation as eEF2 Thr phosphorylation was decreased similarly by muscle contraction in both groups. Mitogen-activated protein kinase signaling was discordant following contraction in septic muscle; phosphorylation of extracellular signal-regulated kinase ThrTyr and p38 ThrTyr was increased similarly in both CON and CLP mice, while sepsis prevented the contraction-induced phosphorylation of JNK ThrTyr and c-JUN Ser. The expression of interleukin 6 and tumor necrosis factor α (TNF-α) mRNA in muscle was increased by sepsis, and contraction increased TNF-α to a greater extent in muscle from septic than CON mice. Injection of the mTOR inhibitor Torin2 in separate mice confirmed that contraction-induced increases in S6K1 and 4E-BP1 were mTOR mediated. These findings demonstrate that resistance to contraction-induced anabolic signaling occurs during sepsis and is predominantly mTORC1-dependent.

Lead in Shrimp Litopenaeus vannamei Boone in Sublethal Concentrations

Determination of the accumulation and elimination of sublethal lead (Pb) in different shrimp tissues may be useful as an indicator of uptake and elimination characteristics of this metal. Aquaculture ponds are particularly influenced by Pb contamination, where aquatic animals may acquire the metal through adsorption to exoskeletons or gills from the surrounding water. Cationic Pb is accumulated preferentially in the nonedible fraction of shrimp, followed by exoskeleton, and to a minor extent in muscle. Lead contents in different tissues were lower than metal levels in exoskeleton. However, the presence of Pb in sediment due to purging may exert adverse consequences on shrimp as bottom feeders.

Lifelong training preserves some redox-regulated adaptive responses after an acute exercise stimulus in aged human skeletal muscle

Several redox-regulated responses to an acute exercise bout fail in aged animal skeletal muscle, including the ability to upregulate the expression of antioxidant defense enzymes and heat shock proteins (HSPs). These findings are generally derived from studies on sedentary rodent models and thus may be related to reduced physical activity and/or intraspecies differences as opposed to aging per se. This study, therefore, aimed to determine the influence of age and training status on the expression of HSPs, antioxidant enzymes, and NO synthase isoenzymes in quiescent and exercised human skeletal muscle. Muscle biopsy samples were obtained from the vastus lateralis before and 3 days after an acute high-intensity-interval exercise bout in young trained, young untrained, old trained, and old untrained subjects. Levels of HSP72, PRX5, and eNOS were significantly higher in quiescent muscle of older compared with younger subjects, irrespective of training status. 3-NT levels were elevated in muscles of the old untrained but not the old trained state, suggesting that lifelong training may reduce age-related macromolecule damage. SOD1, CAT, and HSP27 levels were not significantly different between groups. HSP27 content was upregulated in all groups studied postexercise. HSP72 content was upregulated to a greater extent in muscle of trained compared with untrained subjects postexercise, irrespective of age. In contrast to every other group, old untrained subjects failed to upregulate CAT postexercise. Aging was associated with a failure to upregulate SOD2 and a downregulation of PRX5 in muscle postexercise, irrespective of training status. In conclusion, lifelong training is unable to fully prevent the progression toward a more stressed muscular state as evidenced by increased HSP72, PRX5, and eNOS protein levels in quiescent muscle. Moreover, lifelong training preserves some (e.g., CAT) but not all (e.g., SOD2, HSP72, PRX5) of the adaptive redox-regulated responses after an acute exercise bout. Collectively, these data support many but not all of the findings from previous animal studies and suggest parallel aging effects in humans and mice at rest and after exercise that are not modulated by training status in human skeletal muscle.

The changes of healthy adults delayed onset muscle soreness 31P-MR spectroscopy and correlation between serum creatine kinase and soreness index

Objective To analyse quadriceps metabolic changings in 31P-MRS of healthy volunteers with delayed onset muscle soreness (DOMS) and its relationship with creatine kinase (CK),pain index.Methods Ten healthy volunteers,who conducted a motion model to induce DOMS.Serum creatine kinase (CK) concentration,muscle soreness (DOMS),and 31 P-MRS were taken immediately before and at 0 hours,1 day,2 days,3 days,5 days,7 days after exercise to elucidate the extent of muscle damage.31P-MRS observation indexes included the peak areas of Pi,PCr,ATP and the ratio of Pi/PCr.Repeated measures ANOVA(analysis of variance)was used for 31P-MRS observation indexes of each time.Correlation between serum CK concentration and 31P-MRS observation indexes was assessed with Spearman rank correlation analysis.Results The peak area of Pi,Pi/PCr ratio and CK concentrations gradually increased after exercise,and reached their maximum(0.33 ±0.04 and 0.27 ± 0.03) in 24-48 hours after exercise in time consistency.After exercise,the peak areas of PCr and ATP could be reduced compared with before exercise,24 h after gradually returned to the pre-exercise leve(0.28 ±0.05 and 1.22 ±0.04).CK were significantly clcvated above baseline for 72 hours post-exercise [(483 ± 229)U/L],24 hours after exercise serum CK was significantly increased and reached the peak [(577 ± 223)U/L].One week after exercise CK gradually returned to pre-exercise level [(86 ± 30) U/L] (P ＞ 0.05).The CK showed significant positive correlations with Pi (r =0.631,P ＜ 0.01) and Pi/PCr (r =0.614,P ＜ 0.01).Respectively,the CK showed no correlation with PCr(r =0.044,P ＞ 0.05) and ATP (r =0.188,P ＞ 0.05).The indexes of exercise-induced sore-pain showed positive correlation with Pi (r =0.762,P ＜ 0.05),Pi/PCr (r =0.758,P ＜ 0.05) and Pi/ATP(r =0.616,P ＜0.05).Conclusions 31P-MRS could effectively assess skeletal muscle metabolites after DOMS variation,31P-MRS and serological markers,aching pain index capable of DOMS comprehensive evaluation is very helpful for the movement to provide scientific basis for training and guidance. Key words: Muscle fatigue; Creatine kinase; Pain measurement; Magnetic resonance spectroscopy

Time to task failure influences the postural alteration more than the extent of muscles fatigued

The aim of this study was to compare the effects of unilateral and bilateral muscle fatigue on monopedal postural control. Nineteen subjects completed bilateral fatiguing contractions and unilateral fatiguing contractions of the quadriceps femoris until the torque output for both exercises dropped below 30% of the measured peak torque (the time to task failure was measured) for three consecutive contractions (independently measured for each leg). Postural control was evaluated by using a force platform which recorded center of foot pressure (COP) and was measured before and after the completion of both fatiguing tasks. Spatio-temporal COP parameters were used to evaluate postural control. The unilateral contractions affected monopedal postural control more than the bilateral fatiguing contractions (p<0.05). Moreover, the time to task failure was significantly longer for the unilateral contractions than for the bilateral contractions (p<0.05). The greater alteration of postural control for the unilateral fatiguing contractions compared to the bilateral fatiguing contractions could be related to a longer time to task failure which could provoke greater disturbances of the postural system in terms of sensory input and motor output.

Hemostasis in patients with acute kidney injury secondary to acute liver failure

Acute kidney injury (AKI) occurs in over half of patients with acute liver failure. Despite prolonged prothrombin times and thrombocytopenia, continuous renal replacement therapy circuits frequently develop clots during patient treatment. Here we assessed factors contributing to this by measuring coagulation parameters (standard coagulation tests, pro- and anticoagulant factors, thromboelastography, and thrombin generation) in 20 consecutive patients with acute liver failure; mean age 42 years. Within 48 h, 10 had developed stage 3 AKI and 9 required continuous renal replacement therapy, of whom 2 had frequent circuit clots. The patients with stage 3 AKI were found to have significantly lower platelet counts and levels of factor V and the natural anticoagulants antithrombin, Protein C and Protein S, but increased extrinsic pathway activation and von Willebrand factor levels. Tissue factor levels were greater in those with stage 3 AKI, as was microparticle activity. Although patients with acute liver failure and advanced AKI requiring continuous renal replacement therapy have an even more marked thrombocytopenia and more prolonged extrinsic pathway activation, this was not associated with increased bleeding. Thus, more frequent circuit clots during continuous renal replacement therapy appear to be due to a combination of increased tissue factor and microparticle release, endothelial activation, and reduction in natural anticoagulants.

Training Effects on Skeletal Muscle Calcium Handling in Human Chronic Heart Failure

Patients with chronic heart failure (CHF) typically complain about skeletal muscle fatigue. In rat experiments, reduced intracellular calcium release seems to be related to fatigue development in normal skeletal muscle but not in muscle from rats with CHF. We therefore hypothesize that training may not improve intracellular calcium cycling to the same extent in muscles from patients with CHF compared with healthy controls (HC). Thirteen HC and 11 CHF patients performed 6 wk of unilateral knee extensor endurance training. Computed tomographic examinations of the thigh and biopsies of vastus lateralis were obtained bilaterally before and after the training period. Peak power of the trained leg was 10% and 14% greater than that in the untrained leg in HC and CHF, respectively. For the HC, training resulted in a higher Ca2+ release rate and a lower leak in the trained leg associated with a tendency of increased ryanodine receptor (RyR) content with reduced phosphorylation level. In the trained leg of CHF patients, RyR content was reduced without associated changes of either Ca2+ leak or release rate. Training in HC has an effect on Ca2+ leak and release of the sarcoplasmic reticulum, but in CHF patients, training is achieved without such changes. Thus, calcium handling seems not to be the site of decreased exercise tolerance in CHF.

Hepatic Expression of Long‐Chain Acyl‐CoA Synthetase 3 is Upregulated in Hyperlipidemic Hamsters

Members of the mammalian long-chain acyl-CoA synthetase (ACSL) family are key enzymes for cellular fatty acid metabolism that catalyze the initial step in activation of long-chain fatty acids. However, the specificity of individual isoforms of ACSL to the lipid metabolic process is not well studied. In addition, the regulation of expression of individual ACSL isoforms under hyperlipidemic conditions is largely unknown. We cloned the hamster ACSL3 cDNA coding region and generated specific antibodies recognizing the ACSL3 protein. We next observed the changes in ACSL3 mRNA and protein expression in hamsters fed a standard chow diet or a high fat and high cholesterol (HFHC) diet. HFHC feeding significantly increased ACSL3 mRNA and protein expression in liver and to a lesser extent in muscle but not in adipose, brain, heart, or testis. Additionally, ACSL3 mRNA abundance was differentially regulated by the nutritional status in different tissues with liver, muscle, and adipose being the most sensitive tissues. Importantly, the hepatic ACSL3 mRNA expression pattern in response to fasting and refeeding in hyperlipidemic hamsters differed from that observed in normal chow-fed hamsters. Together, these results provide the first in vivo evidence of altered regulation of hepatic ACSL3 expression under hyperlipidemic conditions and suggest important regulatory roles for this enzyme in lipid metabolism.

Deficiency of the Bax gene attenuates denervation-induced apoptosis

Apoptosis has been implicated in mediating denervation-induced muscle wasting. In this study we determined the effect of interference of apoptosis on muscle wasting during denervation by using mice genetically deficient in pro-apoptotic Bax. After denervation, muscle wasting was evident in both wild-type and Bax(-/-) muscles but reduction of muscle weight was attenuated in Bax(-/-) mice. Apoptotic DNA fragmentation increased in wild-type denervated muscles whereas there was no statistical increase in DNA fragmentation in denervated muscles from Bax(-/-) mice. Mitochondrial AIF and Smac/DIABLO releases and Bcl-2, p53 and HSP27 increased whereas XIAP and MnSOD decreased to a similar extent in muscles from wild-type and Bax(-/-) mice following denervation. Mitochondrial cytochrome c release was elevated in denervated muscles from wild-type mice but the increase was suppressed in muscles from Bax(-/-) mice. Increases in caspase-3 and -9 activities and oxidative stress markers H(2)O(2), MDA/4-HAE and nitrotyrosine were all evident in denervated muscles from wild-type mice but these changes were absent in muscles from Bax(-/-) mice. Moreover, ARC increased exclusively in denervated Bax(-/-) muscle. Our data indicate that under conditions of denervation, pro-apoptotic signalling is suppressed and muscle wasting is attenuated when the Bax gene is lacking. These findings suggest that interventions targeting apoptosis may be valuable in ameliorating denervation-associated pathologic muscle wasting in certain neuromuscular disorders that involve partial or full denervation.

The use of intra‐operative endo‐anal ultrasound in perianal disease

Endoanal ultrasound (EAUS) has demonstrated high sensitivity and specificity for the structural imaging of anorectal pathology. This study prospectively assessed the impact of intra-operative EAUS on the surgical management of perianal disease. EAUS was performed prior to and after examination under anaesthesia (EUA) in a consecutive series of patients with perianal disease. The impact of EAUS on the surgery performed was identified. Forty-three procedures have been performed in 38 patients (21 male, 17 female; mean age 42.7 years, range 6-76 years) over a three year period. Pathologies encountered were fistula-in-ano (42%), fissure-in-ano (26%), complicated perianal sepsis (16%) and carcinoma (5%). No specific abnormality was identified in 5 symptomatic patients (12%). Four patients with fissures had undergone previous sphincterotomy. In 22 cases (51.2%) the EAUS findings affected the surgical management (extent of muscle above a fistula 9 cases, extent of sphincterotomy 7 cases, site of sepsis identified 2 cases, exclusion of sepsis 2 cases, assessment of cancer resectability 1 case, biopsy of intersphincteric lesion 1 case). Intra-operative EAUS accurately identifies perianal disease and influences the surgical procedure performed. While not essential, it is a useful adjunct especially in recurrent perianal sepsis, undiagnosed anorectal pain and anal fissure.

Dietary manipulation of pro- and macroglycogen in porcine skeletal muscle.

The aim of the study was to investigate how feeding-induced changes in muscle glycogen stores affect the ratio of between the glycogen pools, pro- and macroglycogen. Pro- and macroglycogen content were determined in longissumus muscle from slaughter pigs subjected to a feeding strategy known to reduce total glycogen stores. Furthermore, early postslaughter glycolysis of the two glycogen forms was determined. The feeding strategy involved a diet (GLYRED diet) with a low digestible carbohydrate (5%)/high fat (18%) content, which was fed to the pigs the last 3 wk before harvest. A control group was fed a standard pig diet (49% digestible carbohydrate/5% fat). Total glycogen was reduced by 48 micromol/g dry weight (d.w.) in GLYRED pigs during the 3-wk feeding period. This was mainly due to a reduction in macroglycogen of 42 micromol/g d.w. During postmortem glycolysis the proglycogen appeared to be degraded in favor of macroglycogen. Moreover, total glycogen was degraded to a larger extent in muscle from the control pigs compared with muscle from GLYRED pigs. This difference was due to a significantly greater degradation of proglycogen in the control pigs. In conclusion, the results support earlier studies suggesting that proglycogen and macroglycogen are different glycogen pools that have different functions. Furthermore, the results show that the muscle glycogen pools can be manipulated through diet and that proglycogen is degraded in favor of macroglycogen under the anaerobic conditions postmortem.