Muscle strength, quantity and quality and muscle fat quantity and their association with oxidative stress in patients with facioscapulohumeral muscular dystrophy: Effect of antioxidant supplementation.

The purpose of this study was to identify causes of quadriceps muscle weakness in facioscapulohumeral muscular dystrophy (FSHD). To this aim, we evaluated quadriceps muscle and fat volumes by magnetic resonance imaging and their relationships with muscle strength and oxidative stress markers in adult patients with FSHD (n = 32) and healthy controls (n = 7), and the effect of antioxidant supplementation in 20 of the 32 patients with FSHD (n = 10 supplementation and n = 10 placebo) (NCT01596803). Compared with healthy controls, the dominant quadriceps strength and quality (muscle strength per unit of muscle volume) were decreased in patients with FSHD. In addition, fat volume was increased, without changes in total muscle volume. Moreover, in patients with FSHD, the lower strength of the non-dominant quadriceps was associated with lower muscle quality compared with the dominant muscle. Antioxidant supplementation significantly changed muscle and fat volumes in the non-dominant quadriceps, and muscle quality in the dominant quadriceps. This was associated with improved muscle strength (both quadriceps) and antioxidant response. These findings suggest that quadriceps muscle strength decline may not be simply explained by atrophy and may be influenced also by the muscle intrinsic characteristics. As FSHD is associated with increased oxidative stress, supplementation might reduce oxidative stress and increase antioxidant defenses, promoting changes in muscle function.

A randomized controlled trial to determine whether beta-hydroxy-beta-methylbutyrate and/or eicosapentaenoic acid improves diaphragm and quadriceps strength in critically Ill mechanically ventilated patients.

BACKGROUND: Intensive care unit acquired weakness is a serious problem, contributing to respiratory failure and reductions in ambulation. Currently, there is no pharmacological therapy for this condition. Studies indicate, however, that both beta-hydroxy-beta-methylbutyrate (HMB) and eicosapentaenoic acid (EPA) increase muscle function in patients with cancer and in older adults. The purpose of this study was to determine whether HMB and/or EPA administration would increase diaphragm and quadriceps strength in mechanically ventilated patients. METHODS: Studies were performed on 83 mechanically ventilated patients who were recruited from the Medical Intensive Care Units at the University of Kentucky. Diaphragm strength was assessed as the trans-diaphragmatic pressure generated by supramaximal magnetic phrenic nerve stimulation (PdiTw). Quadriceps strength was assessed as leg force generated by supramaximal magnetic femoral nerve stimulation (QuadTw). Diaphragm and quadriceps thickness were assessed by ultrasound. Baseline measurements of muscle strength and size were performed, and patients were then randomized to one of four treatment groups (placebo, HMB 3 gm/day, EPA 2 gm/day and HMB plus EPA). Strength and size measurements were repeated 11 days after study entry. ANCOVA statistical testing was used to compare variables across the four experimental groups. RESULTS: Treatments failed to increase the strength and thickness of either the diaphragm or quadriceps when compared to placebo. In addition, treatments also failed to decrease the duration of mechanical ventilation after study entry. CONCLUSIONS: These results indicate that a 10-day course of HMB and/or EPA does not improve skeletal muscle strength in critically ill mechanically ventilated patients. These findings also confirm previous reports that diaphragm and leg strength in these patients are profoundly low. Additional studies will be needed to examine the effects of other anabolic agents and innovative forms of physical therapy. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01270516. Registered 5 January 2011, https://clinicaltrials.gov/ct2/show/NCT01270516?term=Supinski&draw=2&rank=4 .

Sarcopenia, oxidative stress and inflammatory process in muscle of cirrhotic rats - Action of melatonin and physical exercise.

Sarcopenia is one of the most common features of cirrhosis, contributing to morbidity and mortality in this population. We aimed to evaluate the effect of melatonin (MLT) and exercise (EX) on the quadriceps muscle in rats with biliary cirrhosis induced by bile duct ligation (BDL). We used 48 males (mean weight = 300 g), divided into eight groups. A 20 mg/Kg MLT dose was administered via i.p. (1 x daily), and the EX, the animals were set to swim in couples for 10 min each day. Upon completion, blood, liver, and quadriceps samples were taken for analysis. In the liver enzymes analysis and comet assay results, a reduction was observed in the groups treated with MLT with/or EX comparing to the BDL group. In the evaluation of substances that react to thiobarbituric acid (TBARS), nitric oxide levels (NO), and tumor necrosis factor-alpha levels (TNF-α), there was a significant increase in the BDL group and a reduction in the treated groups. In the activity of the superoxide dismutase enzyme (SOD) and interleukin-10 levels (IL-10) concentrations, there was a significant increase in the treated groups of the BDL group. Histological analysis revealed muscle hypotrophy in the BDL group in comparison with the control group (CO) and increased muscle mass in the treated groups. There was an increase in weight gain and phase angle in the groups treated with MLT with/or EX comparing to the BDL group. We suggest that treatments may contribute to the reduction of muscle changes in cirrhotic patients.

Resveratrol-induced remodelling of myocellular lipid stores: A study in metabolically compromised humans.

In non-athletes, insulin sensitivity correlates negatively with intramyocellular lipid (IMCL) content. In athletes, however, a pattern of benign IMCL storage exists, which is characterized by lipid storage in type I muscle fibres, in small and numerous lipid droplets (LDs) preferable coated with PLIN5, without affecting insulin sensitivity. Administration of resveratrol has been promoted for its beneficial effects on glucose homeostasis. We observed that 30 days of oral resveratrol administration (150 mg/day) in metabolically compromised individuals showed a 33% increase in IMCL (placebo vs. resveratrol; 0.86 ± 0.090 AU vs. 1.14 ± 0.11 AU, p = 0.003) without impeding insulin sensitivity. Thus, the aim of the present study was to examine if a resveratrol-mediated increase in IMCL content, in metabolically compromised individuals, changes the LD phenotype towards the phenotype we previously observed in athletes. For this, we studied IMCL, LD number, LD size, subcellular distribution and PLIN5 coating in different fibre types using high-resolution confocal microscopy. As proof of concept, we observed a 2.3-fold increase (p = 0.038) in lipid accumulation after 48 h of resveratrol incubation in cultured human primary muscle cells. In vivo analysis showed that resveratrol-induced increase in IMCL is predominantly in type I muscle fibres (placebo vs. resveratrol; 0.97 ± 0.16% vs. 1.26 ± 0.09%; p = 0.030) in both the subsarcolemmal (p = 0.016) and intermyofibrillar region (p = 0.026) and particularly in PLIN5-coated LDs (p = 0.024). These data indicate that administration of resveratrol augments IMCL content in metabolically compromised individuals towards a LD phenotype that mimics an 'athlete like phenotype'.

Heterogeneity in insulin-stimulated glucose uptake among different muscle groups in healthy lean people and people with obesity.

AIMS/HYPOTHESIS: It has been proposed that muscle fibre type composition and perfusion are key determinants of insulin-stimulated muscle glucose uptake, and alterations in muscle fibre type composition and perfusion contribute to muscle, and consequently whole-body, insulin resistance in people with obesity. The goal of the study was to evaluate the relationships among muscle fibre type composition, perfusion and insulin-stimulated glucose uptake rates in healthy, lean people and people with obesity. METHODS: We measured insulin-stimulated whole-body glucose disposal and glucose uptake and perfusion rates in five major muscle groups (erector spinae, obliques, rectus abdominis, hamstrings, quadriceps) in 15 healthy lean people and 37 people with obesity by using the hyperinsulinaemic-euglycaemic clamp procedure in conjunction with [2H]glucose tracer infusion (to assess whole-body glucose disposal) and positron emission tomography after injections of [15O]H2O (to assess muscle perfusion) and [18F]fluorodeoxyglucose (to assess muscle glucose uptake). A biopsy from the vastus lateralis was obtained to assess fibre type composition. RESULTS: We found: (1) a twofold difference in glucose uptake rates among muscles in both the lean and obese groups (rectus abdominis: 67 [51, 78] and 32 [21, 55] µmol kg-1 min-1 in the lean and obese groups, respectively; erector spinae: 134 [103, 160] and 66 [24, 129] µmol kg-1 min-1, respectively; median [IQR]) that was unrelated to perfusion or fibre type composition (assessed in the vastus only); (2) the impairment in insulin action in the obese compared with the lean group was not different among muscle groups; and (3) insulin-stimulated whole-body glucose disposal expressed per kg fat-free mass was linearly related with muscle glucose uptake rate (r2 = 0.65, p < 0.05). CONCLUSIONS/INTERPRETATION: Obesity-associated insulin resistance is generalised across all major muscles, and is not caused by alterations in muscle fibre type composition or perfusion. In addition, insulin-stimulated whole-body glucose disposal relative to fat-free mass provides a reliable index of muscle glucose uptake rate.

Quadriceps Weakness After Single-Shot Adductor Canal Block: A Multivariate Analysis of 1,083 Primary Total Knee Arthroplasties.

BACKGROUND: Adductor canal blocks (ACBs) are commonly employed in multimodal pain control for total knee arthroplasty (TKA) and minimize motor blockade compared with femoral nerve blocks. Quadriceps weakness may be associated with ACBs. The purpose of this study was to quantify the prevalence of clinically relevant quadriceps weakness after a single-shot ACB and to identify the factors that are associated with its diagnosis. METHODS: The study group consisted of 1,083 retrospectively reviewed consecutive TKAs that were performed with ACBs at an academic hip and knee center. Quadriceps weakness was quantified with a standardized rating system during the initial physical therapy evaluation, and 23 potential covariates were analyzed. RESULTS: The prevalence of quadriceps weakness was 9%. Increasing the dose of the ACB anesthetic per unit of body mass index (BMI) increased the probability of quadriceps weakness by 5.0 times (95% confidence interval [CI], 1.9 to 13.3; p = 0.001). The highest probability of quadriceps weakness (52.9%) was associated with women who received the highest anesthetic dose per unit of BMI and an epinephrine extender but no corticosteroid extender. CONCLUSIONS: The optimal volume of local anesthetic in ACBs to maintain pain control while minimizing quadriceps weakness has not yet been defined. Our observation that quadriceps weakness was associated with increasing doses of ACB anesthetic per unit of BMI suggests that more than traditional structural canal-fill parameters (i.e., filling the distal aspect of the adductor canal without spreading to the femoral triangle) should be considered when choosing injectates and injectate volumes for ACBs. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Comparison between subarachnoid morphine and femoral nerve block for analgesia after knee ligament reconstruction: a randomized clinical trial / Comparação entre morfina subaracnoidea e bloqueio do nervo femoral para analgesia após reconstrução ligamentar de joelho: estudo clínico randomizado

Abstract Background and objectives There are no consensus of the ideal technique to provide analgesia in knee ligament reconstructions. The aim of this study was to compare the intensity of postoperative pain in these patients under different modalities of analgesia. Method Randomized and controlled clinical trial of patients undergoing reconstruction of the Anterior Cruciate Ligament (ACL) with flexor tendons between December 2013 and 2014. All patients underwent spinal anesthesia and rescue analgesia with tramadol. The groups C, M, R0,375 and R0,25 was compared with only the previously described technique, subarachnoid morphine (100░µg), or Femoral Nerve Block (BNF) with 25░mL of 0.375% ropivacaine and 0.25%, respectively. Pain intensity at 6, 12 and 24░hours, age, sex, rescue analgesia, adverse reactions and satisfaction were evaluated. Results Among the 83 eligible patients, a predominance of males (85.7%) was observed, between 28 and 31 years. The group C requested more opioid (27.3%) than the other groups, without significance when compared. There were no significant differences in pain intensity at 6, 12 and 24░hours. There was a higher incidence of urinary retention in the M group (23.8%) than in the R0,375 (0%) and prolonged quadriceps motor block in the R0,375 group (30%) than in the M and C groups (0%), with statistical significance (p░<░0.05). Conclusion There was no difference in the intensity of postoperative pain in patients submitted to ACL reconstruction with flexor tendons under the analgesic modalities evaluated, despite the predominance of urinary retention in the M group and motor block in the R0,375 group.

Resumo Justificativa e objetivos Não há consenso sobre qual é a técnica ideal para prover analgesia em reconstruções ligamentares de joelho. Objetivou‐se comparar a intensidade da dor pós‐operatória desses pacientes sob diferentes modalidades de analgesia. Método Ensaio clínico randomizado e controlado de pacientes submetidos à reconstrução do ligamento cruzado anterior com tendões flexores entre dezembro de 2013 e 2014. Todos os pacientes foram submetidos a raquianestesia e analgesia de resgate com tramadol. Compararam‐se os grupos C, M, R0,375 e R0,25; aos quais se ofertou apenas a técnica anteriormente descrita, morfina subaracnóidea (100 µg) ou bloqueio de nervo femoral com 25 mL de ropivacaína 0,375% e 0,25%, respectivamente. Avaliou‐se intensidade da dor em 6, 12 e 24 horas, idade, sexo, analgesia de resgate, reações adversas e satisfação. Resultados Entre os 83 pacientes elegíveis, observou‐se predomínio do sexo masculino (85,7%) entre 28 e 31 anos. O Grupo C solicitou mais opioide (27,3%) do que os demais grupos, sem significância quando comparados. Não houve diferenças significativas na intensidade da dor em 6, 12 e 24 horas. Houve maior incidência de retenção urinária no Grupo M (23,8%) do que no R0,375 (0%) e de bloqueio motor prolongado do quadríceps no Grupo R0,375 (30%) do que nos Grupos M e C (0%), com significância estatística (p< 0,05). Conclusão Não houve diferença na intensidade da dor pós‐operatória nos pacientes submetidos à reconstrução de ligamento cruzado anterior com tendões flexores sob as modalidades analgésicas avaliadas, apesar do predomínio de retenção urinária no Grupo M e bloqueio motor no Grupo R0,375.

[Comparison between subarachnoid morphine and femoral nerve block for analgesia after knee ligament reconstruction: a randomized clinical trial]. / Comparação entre morfina subaracnoidea e bloqueio do nervo femoral para analgesia após reconstrução ligamentar de joelho: estudo clínico randomizado.

BACKGROUND AND OBJECTIVES: There is no consensus of the ideal technique to provide analgesia in knee ligament reconstructions. The aim of this study was to compare the intensity of postoperative pain in these patients under different modalities of analgesia. METHOD: Randomized and controlled clinical trial of patients undergoing reconstruction of the anterior cruciate ligament (ACL) with flexor tendons between December 2013 and 2014. All patients underwent spinal anesthesia and rescue analgesia with tramadol. The Groups C, M, R0,375 and R0,25 were compared with only the previously described technique, subarachnoid morphine (100 µg) or femoral nerve block with 25 mL of 0.375% ropivacaine and 0.25%, respectively. Pain intensity at 6, 12 and 24hours, age, sex, rescue analgesia, adverse reactions and satisfaction were evaluated. RESULTS: Among the 83 eligible patients, a predominance of males (85.7%) was observed, between 28 and 31 years. The Group C requested more opioid (27.3%) than the other groups, without significance when compared. There were no significant differences in pain intensity at 6, 12 and 24hours. There was a higher incidence of urinary retention in the Group M (23.8%) than in the R0,375 (0%) and prolonged quadriceps motor block in the R0,375 Group (30%) than in the M and C Groups (0%), with statistical significance (p < 0.05). CONCLUSION: There was no difference in the intensity of postoperative pain in patients submitted to anterior cruciate ligament reconstruction with flexor tendons under the analgesic modalities evaluated, despite the predominance of urinary retention in the M Group and motor block in the R0,375 Group.

Aerobic exercise induces tumor suppressor p16INK4a expression of endothelial progenitor cells in human skeletal muscle.

Aerobic exercise induces oxidative stress and DNA damage, nevertheless, lowers cancer incidence. It remains unclear how genetic stability is maintained under this condition. Here, we examined the dynamic change of the tumor suppressor p16INK4a in cells of skeletal muscle among young men following 60-min of aerobic cycling at 70% maximal oxygen consumption (V̇O2max). Rg1 (5 mg, an immunostimulant ginsenoside) and placebo (PLA) were supplemented 1 h before exercise. Data from serial muscle biopsies shows unchanged p16INK4a+ cells after exercise followed by a considerable increase (+21-fold) in vastus lateralis muscle 3 h later. This increase was due to the accumulation of endothelial progenitor cells (p16INK4a+/CD34+) surrounding myofibers and other infiltrated nucleated cells (p16INK4a+/CD34-) in necrotic myofibers. During the Rg1 trial, acute increases of p16INK4a+ cells in the muscle occurred immediately after exercise (+3-fold) and reversed near baseline 3 h later. Rg1 also lowered IL-10 mRNA relative to PLA 3 h after exercise. Post-exercise increases in VEGF mRNA and CD163+ macrophages were similar for PLA and Rg1 trials. Conclusion: The marked increases in p16INK4a protein expression of endothelial progenitor cells in skeletal muscle implicates a protective mechanism for maintaining genetic stability against aerobic exercise. Rg1 accelerates resolution of the exercise-induced stress response.

Muscle contractile properties of cancer patients receiving chemotherapy: Assessment of feasibility and exercise effects.

BACKGROUND: This pilot trial explores the feasibility of measuring muscle contractile properties in patients with cancer, effects of exercise during chemotherapy on muscle contractile properties and the association between changes in contractile muscle properties and perceived fatigue. METHOD: Patients who received (neo)adjuvant chemotherapy for breast or colon cancer were randomized to a 9-12 week exercise intervention or a waitlist-control group. At baseline and follow-up, we measured knee extensor strength using maximal voluntary contraction (MVC), contractile muscle properties of the quadriceps muscle using electrical stimulation, and perceived fatigue using the Multidimensional Fatigue Inventory. Feasibility was assessed by the proportion of patients who successfully completed measurements of contractile muscle properties. Exercise effects on muscle contractile properties were explored using linear regression analyses. Between-group differences >10% were considered potentially relevant. Pearson correlation (rp ) of changes in contractile muscle properties and changes in perceived fatigue was calculated. RESULTS: Twenty two of 30 patients completed baseline and follow-up assessments. Measurements of contractile properties were feasible except for muscle fatigability. We found a potentially relevant between-group difference in the rate of force development favoring the intervention group (1192 N/s, 95% CI = -335; 2739). Change in rate of force development was negatively correlated with change in perceived general (rp  = -0.54, P = .04) and physical (rp  = -0.59, P = .02) fatigue. CONCLUSION: Chemotherapy induces a decrease in the rate of force development, which may reflect a larger loss in type II muscle fibers. This may be attenuated with (resistance) exercise. The increase in the rate of force development was related to a decrease in perceived fatigue.

Influence of muscle oxygenation and nitrate-rich beetroot juice supplementation on O2 uptake kinetics and exercise tolerance.

We tested the hypothesis that acute supplementation with nitrate (NO3-)-rich beetroot juice (BR) would improve quadriceps muscle oxygenation, pulmonary oxygen uptake (V˙O2) kinetics and exercise tolerance (Tlim) in normoxia and that these improvements would be augmented in hypoxia and attenuated in hyperoxia. In a randomised, double-blind, cross-over study, ten healthy males completed two-step cycle tests to Tlim following acute consumption of 210 mL BR (18.6 mmol NO3-) or NO3--depleted beetroot juice placebo (PL; 0.12 mmol NO3-). These tests were completed in normobaric normoxia [fraction of inspired oxygen (FIO2): 21%], hypoxia (FIO2: 15%) and hyperoxia (FIO2: 40%). Pulmonary V˙O2 and quadriceps tissue oxygenation index (TOI), derived from multi-channel near-infrared spectroscopy, were measured during all trials. Plasma [nitrite] was higher in all BR compared to all PL trials (P < 0.05). Quadriceps TOI was higher in normoxia compared to hypoxia (P < 0.05) and higher in hyperoxia compared to hypoxia and normoxia (P < 0.05). Tlim was improved after BR compared to PL ingestion in the hypoxic trials (250 ± 44 vs. 231 ± 41 s; P = 0.006; d = 1.13), with the magnitude of improvement being negatively correlated with quadriceps TOI at Tlim (r = -0.78; P < 0.05). Tlim was not improved following BR ingestion in normoxia (BR: 364 ± 98 vs. PL: 344 ± 78 s; P = 0.087, d = 0.61) or hyperoxia (BR: 492 ± 212 vs. PL: 472 ± 196 s; P = 0.273, d = 0.37). BR ingestion increased peak V˙O2 in hypoxia (P < 0.05), but not normoxia or hyperoxia (P > 0.05). These findings indicate that BR supplementation is more likely to improve Tlim and peak V˙O2 in situations when skeletal muscle is more hypoxic.

Cigarette Smoking Is Associated With Lower Quadriceps Cross-sectional Area and Attenuation in Older Adults.

INTRODUCTION: In addition to well-established links with cardiovascular and respiratory diseases, cigarette smoking may affect skeletal muscle; however, associations with quadriceps atrophy, density, and function are unknown. This study explored the associations of current and former smoking with quadriceps muscle area and attenuation as well as muscle force (assessed as knee extension peak torque) and rate of torque development-a measure of muscle power in older adults. METHODS: Data from 4469 older adults, aged 66-95 years at baseline in the Age, Gene/Environment Susceptibility-Reykjavik Study with measurements of thigh computed tomography, isometric knee extension testing, self-reported smoking history, and potential covariates were analyzed. RESULTS: Sex differences were observed in these data; therefore, our final analyses are stratified by sex. In men, both former smokers and current smokers had lower muscle area (with ß= -0.10, 95% confidence interval [CI] = -0.17 to -0.03 and ß = -0.19, 95% CI = -0.33 to -0.05, respectively) and lower muscle attenuation (ie, higher fat infiltration, ß = -0.08, 95% CI = -0.16 to -0.01 and ß = -0.17, 95% CI = -0.34 to -0.01, respectively) when compared with never smokers. Smoking status was not associated with male peak torque or rate of torque development. In women, current smoking was associated with lower muscle attenuation (ß = -0.24, 95% CI = -0.34 to -0.13) compared to never smoking. Among female smokers (current and former), muscle attenuation and peak torque were lower with increasing pack-years. CONCLUSIONS: Results suggest that cigarette smoking is related to multiple muscle properties at older age and that these relationships may be different among men and women. IMPLICATIONS: This article presents novel data, as it examined for the first time the relationship between smoking and computed tomography-derived quadriceps muscle size (cross-sectional area) and attenuation. This study suggests that current cigarette smoking is related to higher muscle fat infiltration, which may have significant health implications for the older population, because of its known association with poor physical function, falls, and hip fractures.

Femoral nerve block at time of ACL reconstruction causes lasting quadriceps strength deficits and may increase short-term risk of re-injury.

PURPOSE: To determine whether femoral nerve blockade (FNB) at the time of primary ACL reconstruction is associated with meeting isokinetic extension strength return to sport criteria near completion of physical therapy and whether FNB affects 1-year or 2-year risk of ipsilateral ACL graft rupture or contralateral native ACL injury. METHODS: Three-hundred and sixty patients (n = 244 with FNB, n = 116 no FNB) underwent primary ACL reconstruction. All patients completed rehabilitation and underwent functional strength testing towards the end of knee rehabilitation (mean 5.6 months post-surgery). Association between FNB and isokinetic extension strength limb symmetry index (LSI) (goal LSI ≥ 90% for return to sport) as well as risk of recurrent ACL injury within first or second year after surgery was evaluated. RESULTS: Ipsilateral or contralateral ACL injury within 2 years occurred in 11.2% of patients with FNB and 5.7% without FNB (p = 0.01). Patients with FNB had higher incidence of ipsilateral graft rupture within the first year after surgery but no difference in graft rupture during the second. Two-year risk of contralateral ACL injury was similar in both groups. At the time of initial testing, patients who received FNB had lower fast isokinetic extension LSI versus patients without FNB and were less likely achieve a goal ≥ 90% LSI; slow extension LSI was unaffected. CONCLUSION: Use of FNB at the time of primary ACL reconstruction can negatively affect achievement of isokinetic extension strength return to sport criteria. FNB increases risk of graft rupture within the first year after surgery but does not affect re-injury risk during the second. FNB may not be appropriate for use in patients already at high risk of ACL re-injury. LEVEL OF EVIDENCE: III.

Concentración de bupivacaína y preservación de fuerza de cuádriceps en bloqueo femoral para artroplastía total de rodilla / Bupivacaine concentration and quadriceps strength preservation in femoral nerve block for total

INTRODUCTION: The commonly used concentrations of local anesthetics (LA) for femoral nerve block (FNB) cause a significant decrease in the quadriceps strength (QS), limiting physiotherapy and determining a risk factor for patient's falls. The use of more dilute solutions could determine the preservation of motor function without impairing analgesia. METHODS: Five patients scheduled for total knee arthroplasty (TKA) received a preoperative FNB with 20 mL of bupivacaine in decreasing concentrations (0.0875%, 0.075%, 0.0625%, 0.050%, 0.0375%). Sensory block to cold in the anterior knee region, QS, surface electromyography (SEMG) of vastus lateralis (VL), vastus medialis (VM) and rectus femoris (RF) plus were recorded before and 30 minutes after the blockage. Posteriorly, the clinical data of 20 patients who underwent TKA and received a continuous femoral nerve block (CFNB) with bupivacaine in the most dilute concentration that granted sensory blockade and significantly preserved the QS in the previous analysis were retrospectively analyzed. Postoperative pain at 24 and 48 hours, morphine consumption at 24 hours, the ability to successfully perform physiotherapy on the first postoperative day (POD) and reports of falls were rescued from the patients' files. Finally, seventy-five patients that underwent TKA during 2018 who received a CFNB with a similar dilution, but using levobupivacaine, were also retrospectively analyzed. Postoperative pain, need for advanced rescue analgesia, ability to perform physiotherapy, CFNB related complications and reports of patients falls during the first 72 hours post-surgery were obtained. RESULTS: Biomechanical study: of the 5 concentrations analyzed, either 0.050% or 0.0375% bupivacaine were adequate producing sensory block and preserving 94% and 100% of the basal QS, respectively. With both concentrations, the SEMG showed a similar range of activation with respect to baseline values. Bupivacaine case series: Twenty patients undergoing TKA received a 5-8 mL/hr infusion of 0.037% bupivacaine. The average consumption of morphine at 24 hours was 3.9 (3.6) mg. The median [IQR] of dynamic postoperative pain at 24 and 48 hours was 3 [1-4] and 3 [2-5]. All patients had adequate active joint ranges at 24 hours and physiotherapy was not limited by significant motor block. No falls were reported during the stay. Levobupivacaine case series: seventy-five patients undergoing TKA received a 5-8 mL/hr infusion of 0.037% levobupivacaine. The median [IQR] of at rest (R) and dynamic (D) postoperative pain at 24, 48 and 72 hours were R24: 0 [0-3]; D24: 3 [1-5]; R48: 0 [0-2]; D48: 3 [1.5-5]; R72: 0 [0-1]; D72: 3 [1-4]. 21% of patients required adding a PCA mode to the CFNB and a 7% a morphine PCA. On POD 1, 4% of patients were not able to adequately perform rehabilitation. On POD 2 and 3, all patients had adequate active joint ranges and physiotherapy was not limited by significant motor block. There were also no falls during hospitalization. CONCLUSIONS: The use of diluted solutions of bupivacaine and levobupivacaine for CFNB may represent a good alternative for TKA postoperative analgesia while avoiding significant quadriceps paresis. Additional studies are necessary to determine the ideal concentration and administration regimen to then compare with other quadriceps sparing analgesic alternatives.

INTRODUCCIÓN: Las concentraciones habituales de anestésicos locales (AL) utilizadas para el bloqueo del nervio femoral (BNF) provocan una disminución significativa de la fuerza del cuádriceps (FC), limitando la fisioterapia y constituyendo un factor de riesgo de caídas de pacientes. El uso de soluciones más diluidas podría determinar preservación de la función motora sin perjudicar la analgesia. MÉTODOS: Cinco pacientes programados para artroplastía total de rodilla (ATR) recibieron un BNF preoperatorio con 20 mL de bupivacaína en concentraciones decrecientes (0,0875%, 0,075%, 0,0625%, 0,050%, 0,0375%). Se registró la FC, electromiografía de superficie (EMGS) de vasto lateral (VL), vasto medial (VM) y recto femoral (RF) y el bloqueo sensitivo al frío antes y 30 minutos después del bloqueo. Posteriormente, se analizó retrospectivamente 20 casos sometidos a ATR que recibieron un bloqueo continuo del nervio femoral (BCNF) con bupivacaína en la concentración más diluida que otorgó bloqueo sensitivo y preservó significativamente la fuerza basal del cuádriceps durante el análisis anterior. El dolor postoperatorio a las 24 y 48 horas, el consumo de morfina las primeras 24 horas, la capacidad de realizar con éxito la fisioterapia el primer día postoperatorio (DPO) y reporte de caídas fueron rescatados de los expedientes. Por último, también se analizó retrospectivamente un grupo de 75 pacientes sometidos a ATR durante el 2018 y que recibieron un BCNF con una dilución similar, pero de levobupivacaína. Se obtuvieron datos de dolor, requerimientos de rescate analgésico, capacidad de realizar rehabilitación, complicaciones del BCNF y reporte de caídas durante las primeras 72 horas postoperatorias. RESULTADOS: Estudio biomecánico: de las 5 concentraciones analizadas, tanto bupivacaína 0,05% como 0,0375% produjeron adecuado bloqueo sensorial preservando el 94% y el 100% de la FC, respectivamente. Con ambas concentraciones la EMGS mostró similar rango de activación respecto a valores basales. Serie de casos con bupivacaína: veinte pacientes sometidos a ATR recibieron una infusión de bupivacaína 0,037% a 5-8 mL/h. El consumo promedio de morfina a las 24 horas fue 3,9 (3,6) mg. La mediana [RIC] del dolor dinámico postoperatorio a las 24 y 48 horas fue 3 [1-4] y 3 [2-5]. Todos los pacientes tuvieron rangos articulares activos adecuados a las 24 horas y la fisioterapia no fue limitada por bloqueo motor significativo. No se registraron caídas durante la hospitalización. Serie de casos levobupivacaína: setenta y cinco pacientes sometidos a ATR recibieron una infusión de levobupivacaína 0,037% a 5-8 mL/h. La mediana [RIC] de dolor postoperatorio en reposo (R) y dinámico (D) a las 24, 48 y 72 horas fue R24: 0 [0-3]; D24: 3 [1-5]; R48: 0 [0-2]; D48: 3 [1.5-5]; R72: 0 [0-1]; D72: 3 [1-4]. Un 21% requirió agregar modo PCA al BCNF y 7% una PCA de morfina. En DPO 1, un 4% de pacientes no pudo realizar adecuadamente la rehabilitación. En DPO 2 y 3 todos los pacientes tuvieron rangos articulares activos adecuados y fisioterapia no fue limitada por bloqueo motor significativo. Tampoco se registraron caídas durante la hospitalización. CONCLUSIONES: El uso de soluciones diluidas de bupivacaína y levobupivacaína en BCNF podría representar una buena opción para analgesia postoperatoria en ATR evitando la paresia significativa del cuádriceps. Estudios adicionales son necesarios para determinar la concentración y régimen de administración ideal para luego comparar con otras alternativas analgésicas preservantes del cuádriceps.

Effects of oral contraceptive use on female sexual salivary hormones and indirect markers of muscle damage following eccentric cycling in women.

PURPOSE: To determine the effects of oral contraceptive (OC) use on salivary concentrations of testosterone, estrogen, progesterone, and its effects on the changes in indirect markers of muscle damage following eccentric cycling in women. METHODS: 10 oral contraceptive users at follicular phase (OC-FOL), 10 non-oral contraceptives users at follicular phase (NOC-FOL), and 10 non-oral contraceptives users at ovulation phase (NOC-OV) participated. Subjects performed 30 min of eccentric cycling at 90% of their maximal concentric power output (PO). Maximal voluntary isometric contraction (MVC), creatine kinase activity (CK), muscle soreness (SOR), and pain pressure threshold of vastus lateralis (PPT-VL) was assessed before, immediately after, and 24-96 h after cycling. Salivary estrogen, progesterone and testosterone concentrations were measured before, 72 and 96 h after exercise. RESULTS: No difference in estrogen levels between users and non-users was observed. Testosterone was 45% lower in OC-FOL than NOC-FOL at 96 h post-exercise (P = 0.01). Progesterone was 30.8-fold higher in NOC-OV than OC-FOL and 9.7-fold higher than NOC-FOL at 96 h post-exercise. The NOC-FOL recovered all indirect markers of muscle damage by 72 h post-exercise (P > 0.05). NOC-OV recovered MVC strength and muscle soreness (SOR and PPT-VL) by 96 h post-exercise (P > 0.05). OC-FOL did not recover baseline values of MVC, SOR, CK, and PPT-VL by 96 h. CONCLUSION: These results suggest that recovery after exercise-induced muscle damage took longer in OC-FOL, followed by NOC-OV and by NOC-FOL, respectively. Furthermore, testosterone and progesterone levels may affect recovery of indirect markers of muscle damage in women.

Testosterone therapy induces molecular programming augmenting physiological adaptations to resistance exercise in older men.

BACKGROUND: The andropause is associated with declines in serum testosterone (T), loss of muscle mass (sarcopenia), and frailty. Two major interventions purported to offset sarcopenia are anabolic steroid therapies and resistance exercise training (RET). Nonetheless, the efficacy and physiological and molecular impacts of T therapy adjuvant to short-term RET remain poorly defined. METHODS: Eighteen non-hypogonadal healthy older men, 65-75 years, were assigned in a random double-blinded fashion to receive, biweekly, either placebo (P, saline, n = 9) or T (Sustanon 250 mg, n = 9) injections over 6 week whole-body RET (three sets of 8-10 repetitions at 80% one-repetition maximum). Subjects underwent dual-energy X-ray absorptiometry, ultrasound of vastus lateralis (VL) muscle architecture, and knee extensor isometric muscle force tests; VL muscle biopsies were taken to quantify myogenic/anabolic gene expression, anabolic signalling, muscle protein synthesis (D2 O), and breakdown (extrapolated). RESULTS: Testosterone adjuvant to RET augmented total fat-free mass (P=0.007), legs fat-free mass (P=0.02), and appendicular fat-free mass (P=0.001) gains while decreasing total fat mass (P=0.02). Augmentations in VL muscle thickness, fascicle length, and quadriceps cross-section area with RET occured to a greater extent in T (P < 0.05). Sum strength (P=0.0009) and maximal voluntary contract (e.g. knee extension at 70°) (P=0.002) increased significantly more in the T group. Mechanistically, both muscle protein synthesis rates (T: 2.13 ± 0.21%·day-1 vs. P: 1.34 ± 0.13%·day-1 , P=0.0009) and absolute breakdown rates (T: 140.2 ± 15.8 g·day-1 vs. P: 90.2 ± 11.7 g·day-1 , P=0.02) were elevated with T therapy, which led to higher net turnover and protein accretion in the T group (T: 8.3 ± 1.4 g·day-1 vs. P: 1.9 ± 1.2 g·day-1 , P=0.004). Increases in ribosomal biogenesis (RNA:DNA ratio); mRNA expression relating to T metabolism (androgen receptor: 1.4-fold; Srd5a1: 1.6-fold; AKR1C3: 2.1-fold; and HSD17ß3: two-fold); insulin-like growth factor (IGF)-1 signalling [IGF-1Ea (3.5-fold) and IGF-1Ec (three-fold)] and myogenic regulatory factors; and the activity of anabolic signalling (e.g. mTOR, AKT, and RPS6; P < 0.05) were all up-regulated with T therapy. Only T up-regulated mitochondrial citrate synthase activity (P=0.03) and transcription factor A (1.41 ± 0.2-fold, P=0.0002), in addition to peroxisome proliferator-activated receptor-γ co-activator 1-α mRNA (1.19 ± 0.21-fold, P=0.037). CONCLUSIONS: Administration of T adjuvant to RET enhanced skeletal muscle mass and performance, while up-regulating myogenic gene programming, myocellular translational efficiency and capacity, collectively resulting in higher protein turnover, and net protein accretion. T coupled with RET is an effective short-term intervention to improve muscle mass/function in older non-hypogonadal men.

Effects of adductor canal block versus femoral nerve block in patients with anterior cruciate ligament reconstruction: A protocol for a systematic review and meta-analysis.

OBJECTIVE: It is reported that both adductor canal block (ACB) and femoral nerve block (FNB) are commonly used methods for postoperative analgesia in anterior cruciate ligament (ACL) reconstruction. Currently, no record has compared the efficacy of postoperative pain relief and the influence to quadriceps strength between them. This study aims to provide a protocol to compare the efficacy and safety between ACB and FNB for the postoperative analgesia of ACL reconstruction. METHODS: This study will be performed in accordance with the guideline of the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols. Online databases including PubMed, Embase, Web of Science, Cochrane Library, Wanfang database, and the Chinese National Knowledge Infrastructure database will be systematically searched from their inception up May 31, 2019. All randomized controlled trials will be included in present meta-analysis. The quality of enrolled literatures will be evaluated by using the Cochrane Collaboration Risk of bias Tool. Statistical analysis will be calculated by the Review Manager 5.3. RESULTS: This review will investigate the efficacy and safety of ACB compared with FNB in patients undergoing ACL reconstruction. The primary outcomes are visual analog scale, cumulative opioid consumption during 24 hours after surgery, numerical rating scale, and the time to first straight-leg raise. The secondary outcomes include maximal voluntary isometric contraction, stretching torque at 3, 6 months' follow-up, and adverse effects. CONCLUSION: Findings of this systematic review and meta-analysis will summarize the current evidence in postoperative analgesia for ACL reconstruction and also provide implications for clinical practice.

The redox-dependent regulation of satellite cells following aseptic muscle trauma (SpEED): study protocol for a randomized controlled trial.

BACKGROUND: Muscle satellite cells (SCs) are crucial for muscle regeneration following muscle trauma. Acute skeletal muscle damage results in inflammation and the production of reactive oxygen species (ROS) which may be implicated in SCs activation. Protection of these cells from oxidative damage is essential to ensure sufficient muscle regeneration. The aim of this study is to determine whether SCs activity under conditions of aseptic skeletal muscle trauma induced by exercise is redox-dependent. METHODS/DESIGN: Based on the SCs content in their vastus lateralis skeletal muscle, participants will be classified as either high or low respondents. In a randomized, double-blind, crossover, repeated-measures design, participants will then receive either placebo or N-acetylcysteine (alters redox potential in muscle) during a preliminary 7-day loading phase, and for eight consecutive days following a single bout of intense muscle-damaging exercise. In both trials, blood samples and muscle biopsies will be collected, and muscle performance and soreness will be measured at baseline, pre-exercise, 2 and 8 days post exercise. Biological samples will be analyzed for redox status and SCs activity. Between trials, a 4-week washout period will be implemented. DISCUSSION: This study is designed to investigate the impact of redox status on SCs mobilization and thus skeletal muscle potential for regeneration under conditions of aseptic inflammation induced by exercise. Findings of this trial should provide insight into (1) molecular pathways involved in SCs recruitment and muscle healing under conditions of aseptic skeletal muscle trauma present in numerous catabolic conditions and (2) whether skeletal muscle's potential for regeneration depends on its basal SCs content. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03711838 . Registered on 19 Oct 2018.

Apolipoprotein A-I Protects Against Pregnancy-Induced Insulin Resistance in Rats.

Objective- Insulin resistance and inflammation in pregnancy are risk factors for gestational diabetes mellitus. Increased plasma HDL (high-density lipoprotein) and apo (apolipoprotein) A-I levels have been reported to improve glucose metabolism and inhibit inflammation in animals and humans. This study asks whether increasing plasma apoA-I levels improves insulin sensitivity and reduces inflammation in insulin-resistant pregnant rats. Approach and Results- Insulin-resistant pregnant rats received intravenous infusions of lipid-free apoA-I (8 mg/kg) or saline on days 6, 9, 12, 15, and 18 of pregnancy. The rats were then subjected to a euglycemic-hyperinsulinemic clamp. Glucose uptake was increased in white and brown adipose tissue by 57±13% and 32±10%, respectively ( P<0.05 for both), and in quadriceps and gastrocnemius muscle by 35±9.7% and 47±14%, respectively ( P<0.05 for both), in the apoA-I-treated pregnant rats relative to saline-infused pregnant rats. The pregnant rats that were treated with apoA-I also had reduced plasma TNF-α (tumor necrosis factor-α) levels by 57±8.4%, plasma IL (interleukin)-6 levels by 67±9.5%, and adipose tissue macrophage content by 54±8.2% ( P<0.05 for all) relative to the saline-treated pregnant rats. Conclusions- These studies establish that apoA-I protects against pregnancy-induced insulin resistance in rats by increasing insulin sensitivity in adipose tissue and skeletal muscle and inhibiting inflammation. This identifies apoA-I as a potential target for preventing pregnancy-induced insulin resistance and reducing the incidence of gestational diabetes mellitus.

Nandrolone decanoate administration does not attenuate muscle atrophy during a short period of disuse.

BACKGROUND: A few days of bed rest or immobilization following injury, disease, or surgery can lead to considerable loss of skeletal muscle mass and strength. It has been speculated that such short, successive periods of muscle disuse may be largely responsible for the age-related loss of muscle mass throughout the lifespan. OBJECTIVE: To assess whether a single intramuscular injection of nandrolone decanoate prior to immobilization can attenuate the loss of muscle mass and strength in vivo in humans. DESIGN, SETTING AND PARTICIPANTS: Thirty healthy (22 ± 1 years) men were subjected to 7 days of one-legged knee immobilization by means of a full leg cast with (NAD, n = 15) or without (CON, n = 15) prior intramuscular nandrolone decanoate injection (200 mg). MEASURES: Before and immediately after immobilization, quadriceps muscle cross-sectional area (CSA) (by means of single-slice computed tomography (CT) scans of the upper leg) and one-legged knee extension strength (one-repetition maximum [1-RM]) were assessed for both legs. Furthermore, muscle biopsies from the immobilized leg were taken before and after immobilization to assess type I and type II muscle fiber cross-sectional area. RESULTS: Quadriceps muscle CSA decreased during immobilization in both CON and NAD (-6 ± 1% and -6 ± 1%, respectively; main effect of time P<0.01), with no differences between the groups (time × treatment interaction, P = 0.59). Leg muscle strength declined following immobilization (-6 ± 2% in CON and -7 ± 3% in NAD; main effect of time, P<0.05), with no differences between groups (time × treatment interaction, P = 0.55). CONCLUSIONS: This is the first study to report that nandrolone decanoate administration does not preserve skeletal muscle mass and strength during a short period of leg immobilization in vivo in humans.