Comparison of Ultrastructural Alterations in Peripheral Artery Disease Skeletal Muscle

Peripheral artery disease (PAD) is characterized by obstructed hemodynamics and claudication reducing quality of life and muscle function. A myopathy has been shown to develop in PAD patients and characterization of changes in skeletal muscle needs further elucidation. PURPOSE: To assess myofibrillar ultrastructural changes between control and stage IV PAD patients. METHODS: Twenty-six participants (13 control:13 stage IV) were recruited to take part in this cross-sectional study. The mean(±SD) age, mass, height, and BMI were 53(±11) years, 81(±22) kg, 165(±15) cm, and 30(±1.5) kg/m2. Muscle samples were collected from the gastrocnemius and prepared for transmission electron microscopy. Relative mitochondria area, average mitochondrial size, number of mitochondria/250μm2, relative myofibril area, average m-line length, number of z-discs/250μm2, mitochondria/z-disc, relative lipid droplet area, average lipid droplet size, and number of lipid droplets/250μm2 were measured and averaged for each participant using two-individual micrographs. All variables were statistically assessed using an independent t-test or Mann-Whitney U at a significance value of pRESULTS:Relative mitochondrial area (U=11.534, p2 (t=5.343, p2 (t=-1.902, p=.07) was observed. M-line lengths were shorter for stage IV PAD patients than controls (U=11.543, p2 (U=.037, p=.848). Average mitochondria/z-disc was significantly greater in controls than in stage IV PAD patients (t=5.737, pCONCLUSION:The largest changes seen in PAD skeletal muscle ultrastructure are in the mitochondria number and total mitochondria area. This decrease in mitochondria may explain altered muscle function not accounted for by hemodynamic obstructions

Acute Maltodextrin Supplementation During Resistance Exercise

PURPOSE: Most of the research investigating the ergogenic enhancing mechanisms of carbohydrate have been conducted using aerobic based exercise. Therefore, the purpose of this study was to investigate the effects of pre-exercise maltodextrin ingestion on resistance exercise performance, serum insulin, epinephrine, glucose, and muscle glycogen concentrations. METHODS: In a double blind, cross over, repeated measures design, participants completed four sets to failure at 70% of 1-RM with 45s rest on the angled leg press with or without pre-exercise maltodextrin (2g/kg) after a 3hr fast. Serum glucose, epinephrine, and insulin were assessed at baseline, 30 min post-ingestion, immediately after, and 1hr post-exercise with or without carbohydrate supplementation. Muscle glycogen was assessed from biopsy specimens sampled from the vastus lateralis before supplementation, immediately after exercise, and 1hr post exercise under both conditions. RESULTS: There was no main effect of supplement on resistance exercise performance (p=.18). Muscle glycogen concentration decreased across time for both groups (p\u3c.001). There was an interaction in serum glucose decreasing more during exercise in the carbohydrate condition (p=.026). An interaction occurred showing insulin decreased during exercise in the carbohydrate condition (p=.003). Also, there was a main effect of insulin being elevated with carbohydrate consumption (p=.027). Epinephrine was decreased across all time points after carbohydrate ingestion (p=.023). CONCLUSION: Carbohydrate supplementation before resistance exercise did not improve leg press performance to fatigue despite increased metabolic substrate availability. These results indicate that pre-exercise dietary carbohydrate will be utilized preferentially during exercise due to decreased epinephrine, decreased serum glucose, and increased insulin concentrations. However, the increases in glycolytic substrate availability will not increase exercise performance or glycogen content following 1hr of recovery

Ubiquitin Proteasome System Activity is Suppressed by Curcumin Following Exercise-Induced Muscle Damage in Human Skeletal Muscle

PURPOSE: Curcumin is a natural polyphenolic compound with antioxidant and anti-inflammatory properties. In vitro and in vivo animal studies have demonstrated that exposure to curcumin leads to dysregulation of the ubiquitin-proteasome system (UPS). However, to date, no study has investigated curcumin’s ability to influence UPS activity in a human model. Therefore, the purpose of this study was to investigate the effects of curcumin supplementation on markers of UPS activity in the presence of elevations in UPS activity due to exercise-induced muscle damage. METHODS: Twenty-three recreationally active male and female participants between the ages of 18-30 were randomized into a curcumin (CUR; n=11) or placebo (PLA; n=12) group. Both groups were instructed to consume 2 g of their respective supplement and 20 mg of piperine for 11 consecutive days. Following 8 consecutive days of supplementation, participants performed a 45 minute eccentrically-biased muscle damaging treadmill protocol at 60% VO2max. Muscle biopsies and delayed onset muscle soreness (DOMS) analyses were performed 30 minutes prior and 3, 24, 48, and 72 hours following exercise-induced muscle damage. Skeletal muscle ubiquitin, MAFbx/Atrogin-1, ubiquitin specific peptidase 19 (USP19), and chymotrypsin-like protease concentrations were measured using ELISA. A 3-way repeated measures ANOVA with pairwise comparisons was conducted with significance set at p≤0.05. RESULTS: Both groups had a significant time effect for DOMS (p \u3c .001). Pairwise comparisons indicated DOMS was significantly greater from baseline at all time points except 72 hours following muscle damage. No significant differences were found for USP19 between groups. Regardless of time, a significant main effect for condition was observed for ubiquitin (p=.016) and MAFbx/Atrogin-1 (p=.006) where CUR was significantly lower than PLA. Additionally, a significant main effect for gender was observed for MAFbx/Atrogin-1 (p=.013) where females were greater than males. A significant group x gender interaction was found for chymotrypsin-like protease (p = .049) where males had lower values with curcumin supplementation while females had slightly higher. CONCLUSION: Curcumin supplementation in humans does appear to dysregulate UPS activity in the presence of exercise-induced muscle damage. Specifically, curcumin’s ability to suppress protein ubiquination provides preliminary evidence of curcumin supplementation’s potential therapeutic role in decreasing protein degradation associated with skeletal muscle damage and perhaps other atrophic scenarios

Wnt/β-Catenin and Androgen Receptor Signaling Increase Following High Load Resistance Exercise Without Elevations in Serum/Muscle Testosterone or Androgen Receptor Content

PURPOSE: The purpose of this study was 1) to determine the effect of single bouts of volume- and intensity-equated low (LL) and high load (HL) full-body resistance exercise (RE) on AR-DNA binding, serum/muscle testosterone and dihydrotestosterone, muscle androgen receptor (AR), and AR-DNA binding and 2) to determine the effect of RE on sarcoplasmic and nucleoplasmic β-catenin concentrations in order to determine their impact on mediating AR-DNA binding in the absence/presence of serum/muscle androgen and AR protein. METHODS: In a cross-over design, ten resistance-trained males completed volume- and intensity-equated LL and HL full-body RE. Blood and muscle samples were collected at pre-, 3h-, and 24h post-exercise. Separate 2x3 factorial ANOVAs with repeated measures and pairwise comparisons with a Bonferroni adjustment were used to analyze main effects. RESULTS: No significant differences were observed in muscle AR, testosterone, dihydrotestosterone, or serum total testosterone in either condition (p \u3e.05). Serum free testosterone was significantly decreased 3h post-exercise and remained significantly less than baseline 24h post-exercise in both conditions (p.05). Moreover, sarcoplasmic β-catenin was significantly greater in HL (p.05). CONCLUSION: Increases in AR-DNA binding in response to HL indicates AR signaling may be load-dependent. Furthermore, despite the lack of increase in serum and muscle androgens or AR content following HL RE, elevations in AR-DNA binding with elevated sarcoplasmic β-catenin suggests β-catenin may be facilitating this response

Combined Blood Flow Restriction Training and Betaine Supplementation Impacts on Serum Betaine and Homocysteine Concentrations

Homocysteine (HCY) is a clinically implicated in inflammation and cardiovascular impairments. Although both betaine supplementation and acute resistance (both high-load [HL] and low-load blood flow restriction [LL-BFR]) training notably attenuate HCY concentrations, it is hitherto unknown if these independent modalities synergistically interact. PURPOSE: to determine whether a combination of betaine supplementation, as well as acute HL and/or LL-BFR training can attenuate post-exercise HCY more effectively than either isolated modality. METHODS: Eighteen recreationally trained males (25±5y) were randomized in double-blind fashion to supplement 6g/day of either betaine anhydrous (BET) or identically dosed cellulose placebo for 14-days. Subsequently, all subjects performed four standardized sets of one-leg press and two additional sets to muscular failure on both legs in a counter-balanced and crossover design. Specifically, one leg performed standard high-load (HL; 70%1RM) exercise and contralateral limb underwent BFR (LL-BFR; 20%1RM) training at 80% arterial occlusion pressure. Serum homocysteine (HCY) and betaine (BET) concentrations were analyzed before and 30-minutes post-exercise prior to quantification via ELISA and liquid chromatography-mass spectrometry, respectively. The changes in all aforementioned variables from baseline (∆HCY and ∆BET) were assessed via separate two-way mixed model ANOVA with repeated measures at a significance level of pRESULTS: Analyses failed to reveal any significant main nor interaction effects for serum ∆BET. Although no apparent main supplement nor interaction effects were observed, ∆HCY demonstrated a significant main exercise condition effect (p=.045; ηp2=.228), whereby the LL-BFR group displayed significantly greater concentrations versus HL (p=.045). CONCLUSION: While these findings ultimately do not support a betaine-resistance training synergy-mediated reduction in serum HCY, our data otherwise suggest BFR training may preferentially result in lower post-training concentrations relative to a commonly employed, high-load approach. Future research should elucidate the credence of this interpretation via additional longitudinal investigations amidst hyperhomocysteinemia-predisposed clinical populations

Impacts of Varying Blood Flow Restriction Cuff Size and Material on Arterial, Venous and Calf Muscle Pump-Mediated Blood Flow

Blood flow restriction (BFR) may become ineffective or potentially dangerous without sufficient standardization. The purpose of this investigation was therefore to (1) assess the viability of multiple sizes of a novel BFR cuff to determine arterial occlusion pressure (AOP) and (2) compare resting arterial, venous and calf muscle pump (cMP)-mediated blood flow between the aforementioned conditions and a commonly employed wide-rigid, tourniquet-style cuff. In randomized, counter-balanced, and crossover fashion, 20 apparently healthy males (18–40 years) donned a widely employed wide-rigid (WR) cuff, along with the largest (NE) and manufacturer-recommended sizes (NER) of a novel narrow-elastic cuff. Participants subsequently assessed AOP, as well as (at 80%AOP) arterial, venous, and venous cMP flow relative to baseline values via ultrasound. All analyses were performed at a significance level of p \u3c 0.05. Analyses revealed a significant condition effect for AOP (p \u3c 0.001; ηp2 = 0.907) whereby WR was significantly lower than both NE and NER; in addition, the latter two did not differ. Compared with baseline, there were no statistically significant differences between cuffs for either arterial or cMP-mediated blood flow. Unsurprisingly, no participants demonstrated venous blood flow at 80% AOP. These findings support the viability of a novel narrow-elastic BFR product, evidenced by consistent AOP acquisition and equivocal blood flow parameters

LGD-4033 and MK-677 Use Impacts Body Composition, Circulating Biomarkers, and Skeletal Muscle Androgenic Hormone and Receptor Content: A Case Report

LGD-4033, a selective androgen receptor modulator, and MK-677, a growth hormone secretagogue, are being used increasingly amongst recreationally active demographics. However, limited data exist describing their effects on health- and androgen-related biomarkers. The purpose of this case study was to determine changes in body composition and biomarkers during and after continued co-administration of LGD-4033 and MK-677. We also aimed to examine muscular strength and intramuscular androgen-associated biomarkers relative to non-users. A 25-year-old male ingested LGD-4033 (10 mg) and MK-677 (15 mg) daily for 5 weeks. Blood and body composition metrics were obtained pre-, on- and post-cycle. One-repetition maximum leg and bench press, in addition to intramuscular androgens and androgen receptor content, were analysed on-cycle. We observed pre- to on-cycle changes in body composition (body mass, +6.0%; total lean body mass, +3.1%; trunk lean body mass, +6.6%; appendicular lean body mass, +4.3%; total fat mass, +15.4%; trunk fat mass, +2.8%; and appendicular fat mass, +14.8%), bone (bone mineral content, −3.60%; area, −1.1%; and bone mineral density, −2.1%), serum lipid-associated biomarkers (cholesterol, +14.8%; triglycerides, +39.2%; low-density lipoprotein–cholesterol, +40.0%; and high-density lipoprotein–cholesterol, −36.4%), liver-associated biomarkers (aspartate aminotransferase, +95.8%; and alanine aminotransferase, +205.0%) and androgen-associated biomarkers (free testosterone, −85.7%; total testosterone, −62.3%; and sex hormone-binding globulin, −79.6%); however, all variables returned to pre-cycle values post-cycle, apart from total fat mass, appendicular fat mass, bone area, total cholesterol and low-density lipoprotein–cholesterol. Follicle-stimulating hormone was below clinical reference values on- (1.2 IU/L) and post-cycle (1.3 IU/L). Intramuscular androgen receptor (−44.6%), testosterone (+47.8%) and dihydrotestosterone (+34.4%), in addition to one-repetition maximum leg press and bench press (+39.2 and +32.0%, respectively), were different in the case subject compared with non-users. These data demonstrate that LGD-4033 and MK-677 increase several body composition parameters, whilst negatively impacting bone and several serum biomarkers. Given the sparsity of data in recreationally using demographics, further research is warranted to elucidate the acute and chronic physiological effects of these anabolic agents

Resistance Exercise-Induced Increases in Muscle Myostatin mRNA and Protein Expression Are Subsequently Decreased in Circulation in the Presence of Increased Levels of the Extracellular Matrix Stabilizing Protein Decorin

Resistance exercise (RE) activates cell signaling pathways associated with myostatin. Decorin is located in the extracellular matrix (ECM) and can block the inhibitory effect of myostatin. This study sought to determine the impact of low-load (LL) and high-load (HL) RE on myostatin mRNA and protein expression along with changes in muscle decorin and circulating follistatin. Ten resistance-trained men performed a LL (50% 1RM) and HL (80% 1RM) RE session using the angled leg press and leg extension with load and volume equated. Venous blood samples and muscle biopsies were obtained prior to and at 3h and 24h following each RE session. Muscle myostatin mRNA expression was increased at 24h post-exercise (p = 0.032) in LL and at 3h (p = 0.044) and 24h (p = 0.003) post-exercise in HL. Muscle decorin was increased at 24h post-exercise (p \u3c 0.001) in LL and HL; however, muscle myostatin was increased at 24h post-exercise (p \u3c 0.001) only in HL. For muscle Smad 2/3, no significant differences were observed (p \u3e 0.05). Serum follistatin was increased and myostatin decreased at 24h post-exercise (p \u3c 0.001) in LL and HL. Muscle myostatin gene and protein expression increased in response to HL RE. However, serum myostatin was decreased in the presence of increases in decorin in muscle and follistatin in circulation. Therefore, our data suggest a possible mechanism may exist where decorin within the ECM is able to bind to, and decrease, myostatin that might otherwise enter the circulation for activin IIB (ACTIIB) receptor binding and subsequent canonical signaling through Smad 2/3

High-Load Resistance Exercise Augments Androgen Receptor–DNA Binding and Wnt/β-Catenin Signaling without Increases in Serum/Muscle Androgens or Androgen Receptor Content

The purpose of this study was (1) to determine the effect of single bouts of volume- and intensity-equated low- (LL) and high-load (HL) full-body resistance exercise (RE) on AR-DNA binding, serum/muscle testosterone and dihydrotestosterone, muscle androgen receptor (AR), and AR-DNA binding; and, (2) to determine the effect of RE on sarcoplasmic and nucleoplasmic β-catenin concentrations in order to determine their impact on mediating AR-DNA binding in the absence/presence of serum/muscle androgen and AR protein. In a cross-over design, 10 resistance-trained males completed volume- and intensity-equated LL and HL full-body RE. Blood and muscle samples were collected at pre-, 3 h-, and 24 h post-exercise. Separate 2 × 3 factorial analyses of variance (ANOVAs) with repeated measures and pairwise comparisons with a Bonferroni adjustment were used to analyze the main effects. No significant differences were observed in muscle AR, testosterone, dihydrotestosterone, or serum total testosterone in either condition (p > 0.05). Serum-free testosterone was significantly decreased 3 h post-exercise and remained significantly less than baseline 24 h post-exercise in both conditions (p < 0.05). In response to HL, AR-DNA binding significantly increased at 3 h post-exercise (p < 0.05), whereas no significant differences were observed at any time in response to LL (p > 0.05). Moreover, sarcoplasmic β-catenin was significantly greater in HL (p < 0.05) without significant changes in nucleoplasmic β-catenin (p > 0.05). In conclusion, increases in AR-DNA binding in response to HL RE indicate AR signaling may be load-dependent. Furthermore, despite the lack of increase in serum and muscle androgens or AR content following HL RE, elevations in AR-DNA binding with elevated sarcoplasmic β-catenin suggests β-catenin may be facilitating this response

Impacts of Varying Blood Flow Restriction Cuff Size and Material on Arterial, Venous and Calf Muscle Pump-Mediated Blood Flow

Blood flow restriction (BFR) may become ineffective or potentially dangerous without sufficient standardization. The purpose of this investigation was therefore to (1) assess the viability of multiple sizes of a novel BFR cuff to determine arterial occlusion pressure (AOP) and (2) compare resting arterial, venous and calf muscle pump (cMP)-mediated blood flow between the aforementioned conditions and a commonly employed wide-rigid, tourniquet-style cuff. In randomized, counter-balanced, and crossover fashion, 20 apparently healthy males (18–40 years) donned a widely employed wide-rigid (WR) cuff, along with the largest (NE) and manufacturer-recommended sizes (NER) of a novel narrow-elastic cuff. Participants subsequently assessed AOP, as well as (at 80%AOP) arterial, venous, and venous cMP flow relative to baseline values via ultrasound. All analyses were performed at a significance level of p p p2 = 0.907) whereby WR was significantly lower than both NE and NER; in addition, the latter two did not differ. Compared with baseline, there were no statistically significant differences between cuffs for either arterial or cMP-mediated blood flow. Unsurprisingly, no participants demonstrated venous blood flow at 80% AOP. These findings support the viability of a novel narrow-elastic BFR product, evidenced by consistent AOP acquisition and equivocal blood flow parameters