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Background: Loading interventions have become a predominant treatment strategy for tendinopathy, and positive clinical outcomes and tendon tissue responses may depend on the exercise dose and load magnitude. Purpose/Hypothesis: The purpose was to investigate if the load magnitude influenced the effect of a 12-week loading intervention for patellar tendinopathy in the short term (12 weeks) and long term (52 weeks). We hypothesized that a greater load magnitude of 90% of 1 repetition maximum (RM) would yield a more positive clinical outcome, tendon structure, and tendon function compared with a lower load magnitude of 55% of 1 RM when the total exercise volume was kept equal in both groups. Study Design: Randomized clinical trial; Level of evidence, 1. Methods: A total of 44 adult participants with chronic patellar tendinopathy were included and randomized to undergo moderate slow resistance (MSR group; 55% of 1 RM) or heavy slow resistance (HSR group; 90% of 1 RM). Function and symptoms (Victorian Institute of Sport Assessment–Patella questionnaire [VISA-P]), tendon pain during activity (numeric rating scale [NRS]), and ultrasound findings (tendon vascularization and swelling) were assessed before the intervention, at 6 and 12 weeks during the intervention, and at 52 weeks from baseline. Tendon function (functional tests) and tendon structure (ultrasound and magnetic resonance imaging) were investigated before and after the intervention period. Results: The HSR and MSR interventions both yielded significant clinical improvements in the VISA-P score (mean ± SEM) (HSR: 0 weeks, 58.8 ± 4.3; 12 weeks, 70.5 ± 4.4; 52 weeks, 79.7 ± 4.6) (MSR: 0 weeks, 59.9 ± 2.5; 12 weeks, 72.5 ± 2.9; 52 weeks, 82.6 ± 2.5), NRS score for running, NRS score for squats, NRS score for preferred sport, single-leg decline squat, and patient satisfaction after 12 weeks, and these were maintained after 52 weeks. HSR loading was not superior to MSR loading for any of the measured clinical outco

The present study explores the methods to determine human in vivo protein-specific myofibrillar and collagenous connective tissue protein fractional synthesis and breakdown rates. We found that in human myofibrillar proteins, the protein-bound tracer disappearance method to determine the protein fractional breakdown rate (FBR) (via 2 H2 O ingestion, endogenous labeling of 2 H-alanine that is incorporated into proteins, and FBR quantified by its disappearance from these proteins) has a comparable intrasubject reproducibility (range: 0.09-53.5%) as the established direct-essential amino acid, here L-ring-13 C6 -phenylalanine, incorporation method to determine the muscle protein fractional synthesis rate (FSR) (range: 2.8-56.2%). Further, the determination of the protein breakdown in a protein structure with complex post-translational processing and maturation, exemplified by human tendon tissue, was not achieved in this experimentation, but more investigation is encouraged to reveal the possibility. Finally, we found that muscle protein FBR measured with an essential amino acid tracer prelabeling is inappropriate presumably because of significant and prolonged intracellular recycling, which also may become a significant limitation for determination of the myofibrillar FSR when repeated infusion trials are completed in the same participants.

Muscle contractures are a common complication to cerebral palsy (CP). The purpose of this study was to evaluate whether individuals with CP carry specific gene variants of important structural genes that might explain the severity of muscle contractures. Next-generation-sequencing (NGS) of 96 candidate genes associated with muscle structure and metabolism were analyzed in 43 individuals with CP (Gross Motor Function classification system [GMFCS] I, n=10; GMFCS II, n=14; GMFCS III, n=19) and four control participants. In silico analysis of the identified variants was performed. The variants were classified into four categories ranging from likely benign (VUS0) to highly likely functional effect (VUS3). All individuals with CP were classified and grouped according to their GMFCS level: Statistical comparisons were made between GMFCS groups. Kruskal-Wallis tests showed significantly more VUS2 variants in the genes COL4 (GMFCS I-III; 1, 1, 5, respectively [p < .04]), COL5 (GMFCS I-III; 1, 1, 5 [p < .04]), COL6 (GMFCS I-III; 0, 4, 7 [p < .003]), and COL9 (GMFCS I-III; 1, 1, 5 [p < .04]), in individuals with CP within GMFCS Level III when compared to the other GMFCS levels. Furthermore, significantly more VUS3 variants in COL6 (GMFCS I-III; 0, 5, 2 [p < .01]) and COL7 (GMFCS I-III; 0, 3, 0 [p < .04]) were identified in the GMFCS II level when compared to the other GMFCS levels. The present results highlight several candidate gene variants in different collagen types with likely functional effects in individuals with CP.

INTRODUCTION: Valid length measurements of the different segments of the Achilles tendon are needed in order to investigate if differential elongation of the Achilles tendon takes place after rupture. The purpose of this paper was to present data concerning the accuracy and reliability of an ultrasound measurement of the free part of the Achilles tendon.METHODS: Both legs of 19 non-injured subjects were examined by magnetic resonance imagining (MRI) and ultrasound. The length from the distal tip of the soleus muscle to the tendon insertion on the calcaneus was measured by three independent ultrasound examiners. Repeated ultrasound measurements were performed and compared with MRI measurements. Intra-rater and inter-rater reliability and the agreement between MRI and ultrasound were determined. Data were evaluated using the intraclass correlation coefficient (ICC), the standard error of the measurement (SEM) and the minimal detectable change (MDC).RESULTS: The measurement showed excellent intra-rater reliability (ICC = 0.94 (95% confidence interval (CI): 0.91-0.96), SEM = 5 mm and MDC = 13 mm) and inter-rater reliability (ICC = 0.96 (95% CI: 0.93-0.97), SEM = 4 mm and MDC = 11 mm). On average, ultrasound measurements exceeded the MRI measurements by 2 mm (non-significant), resulting in a measurement error of 5%.CONCLUSIONS: The ultrasound measurement of the free part of the Achilles tendon showed good reliability and accuracy. For comparison between groups of non-injured subjects, differences of > 5 mm can be detected. For repeated assessment of individual subject differences ≥ 13 mm can be detected.FUNDING: none.TRIAL REGISTRATION: Institutional Review Board of Zealand, Denmark, Ref. no: SJ-318.

The aging process of tendon tissue is associated with decreased collagen content and increased risk for injuries. An essential factor in tendon physiology is transforming growth factor-ß1 (TGF-ß1), which is presumed to be reduced systemically with advanced age. The aim of this study was to investigate whether human serum from elderly donors would have an inhibiting effect on the expression of collagen and collagen-related genes as well as on cell proliferative capacity in tendon cells from young individuals. There was no difference in systemic TGF-ß1 levels in serum obtained from young and elderly donors, and we found no difference in collagen expression when cells were subjected to human serum from elderly versus young donors. In addition, tendon cell proliferation was similar when culture medium was supplemented with serum of different donor age. These findings suggest that factors such as the cell intrinsic capacity or the tissue-specific environment rather than systemic circulating factors are important for functional capacity throughout life in human tendon cells.

Oral contraceptive (OC) treatment has an inhibiting effect on protein synthesis in tendon and muscle connective tissue. We aimed to investigate whether OC influence myofibrillar protein turnover in young women. OC-users (24±2 years; Lindynette® n=7, Cilest® n=4) and non-OC-users (controls, 24±4 years n=12) performed one-legged kicking exercise. The next day, the myofibrillar protein fractional synthesis rate (FSR) was measured using stable isotopic tracers ((13)C-proline) while the subjects were fed standardized nutrient drinks. Simultaneously, a marker for myofibrillar protein breakdown, 3-methyl-histidine (3-MH), was measured in the interstitial fluid of the vastus lateralis. Measurements were performed in both legs. In general, myofibrillar protein FSR was lower in OC-users (two-way analysis of variance, P<0.05), although the difference seemed to depend on the OC type. Interstitial 3-MH in the skeletal muscle was not different between groups and did not vary by OC type. Exercise did not change myofibrillar protein FSR or 3-MH concentrations. Serum androstenedione and bioavailability of testosterone were lower in OC-users. In conclusion, the results indicate that the use of OC has an inhibiting effect on myofibrillar protein synthesis and the magnitude of the effect may depend on the type of OC. In contrast, there was no effect of OC on myofibrillar protein breakdown in the fed state., Oral contraceptive (OC) treatment has an inhibiting effect on protein synthesis in tendon and muscle connective tissue. We aimed to investigate whether OC influence myofibrillar protein turnover in young women. OC-users (24±2 years; Lindynette® n=7, Cilest® n=4) and non-OC-users (controls, 24±4 years n=12) performed one-legged kicking exercise. The next day, the myofibrillar protein fractional synthesis rate (FSR) was measured using stable isotopic tracers ((13)C-proline) while the subjects were fed standardized nutrient drinks. Simultaneously, a marker for myofibrillar protein breakdown, 3-methyl-histidine (3-MH), was measured in the interstitial fluid of the vastus lateralis. Measurements were performed in both legs. In general, myofibrillar protein FSR was lower in OC-users (two-way analysis of variance, P<0.05), although the difference seemed to depend on the OC type. Interstitial 3-MH in the skeletal muscle was not different between groups and did not vary by OC type. Exercise did not change myofibrillar protein FSR or 3-MH concentrations. Serum androstenedione and bioavailability of testosterone were lower in OC-users. In conclusion, the results indicate that the use of OC has an inhibiting effect on myofibrillar protein synthesis and the magnitude of the effect may depend on the type of OC. In contrast, there was no effect of OC on myofibrillar protein breakdown in the fed state.

Muscle protein turnover following resistance exercise and amino acid availability are relatively well described. By contrast, the beneficial effects of different sources of intact proteins in relation to exercise need further investigation. Our objective was to compare muscle anabolic responses to a single bolus intake of whey or casein after performance of heavy resistance exercise. Young male individuals were randomly assigned to participate in two protein trials (n = 9) or one control trial (n = 8). Infusion of l-[1-(13)C]leucine was carried out, and either whey, casein (0.3 g/kg lean body mass), or a noncaloric control drink was ingested immediately after exercise. l-[1-(13)C]leucine-labeled whey and casein were used while muscle protein synthesis (MPS) was assessed. Blood and muscle tissue samples were collected to measure systemic hormone and amino acid concentrations, tracer enrichments, and myofibrillar protein synthesis. Western blots were used to investigate the Akt signaling pathway. Plasma insulin and branched-chain amino acid concentrations increased to a greater extent after ingestion of whey compared with casein. Myofibrillar protein synthesis was equally increased 1-6 h postexercise after whey and casein intake, both of which were higher compared with control (P < 0.05). Phosphorylation of Akt and p70(S6K) was increased after exercise and protein intake (P < 0.05), but no differences were observed between the types of protein except for total 4E-BP1, which was higher after whey intake than after casein intake (P < 0.05). In conclusion, whey and casein intake immediately after resistance exercise results in an overall equal MPS response despite temporal differences in insulin and amino acid concentrations and 4E-BP1., Muscle protein turnover following resistance exercise and amino acid availability are relatively well described. By contrast, the beneficial effects of different sources of intact proteins in relation to exercise need further investigation. Our objective was to compare muscle anabolic responses to a single bolus intake of whey or casein after performance of heavy resistance exercise. Young male individuals were randomly assigned to participate in two protein trials (n = 9) or one control trial (n = 8). Infusion of l-[1-(13)C]leucine was carried out, and either whey, casein (0.3 g/kg lean body mass), or a noncaloric control drink was ingested immediately after exercise. l-[1-(13)C]leucine-labeled whey and casein were used while muscle protein synthesis (MPS) was assessed. Blood and muscle tissue samples were collected to measure systemic hormone and amino acid concentrations, tracer enrichments, and myofibrillar protein synthesis. Western blots were used to investigate the Akt signaling pathway. Plasma insulin and branched-chain amino acid concentrations increased to a greater extent after ingestion of whey compared with casein. Myofibrillar protein synthesis was equally increased 1-6 h postexercise after whey and casein intake, both of which were higher compared with control (P < 0.05). Phosphorylation of Akt and p70(S6K) was increased after exercise and protein intake (P < 0.05), but no differences were observed between the types of protein except for total 4E-BP1, which was higher after whey intake than after casein intake (P < 0.05). In conclusion, whey and casein intake immediately after resistance exercise results in an overall equal MPS response despite temporal differences in insulin and amino acid concentrations and 4E-BP1.

Collagen is the predominant structural protein in tendons and ligaments, and can be controlled by hormonal changes. In animals, injections of insulin-like growth factor I (IGF-I) has been shown to increase collagen synthesis in tendons and ligaments and to improve structural tissue healing, but the effect of local IGF-I administration on tendon collagen synthesis in human has not been studied. The purpose of this study was to study whether local injections of IGF-I would have a stimulating effect on tendon collagen synthesis. Twelve healthy nonsmoking men [age 62 ± 1 years (mean ± SEM), BMI 27 ± 1] participated. Two injections of either human recombinant IGF-I (0.1 mL Increlex©) or saline (control) into each patellar tendon were performed 24-h apart, respectively. Tendon collagen fractional synthesis rate (FSR) was measured by stable isotope technique in the hours after the second injection. Simultaneously, interstitial peritendinous (IGF-I) and [procollagen type I N-terminal propeptide (PINP)], as a marker for type I collagen synthesis, were determined by microdialysis technique. Tendon collagen FSR and PINP were significantly higher in the IGF-I leg compared with the control leg (P < 0.05). In conclusion, local IGF-I administration can directly enhance tendon collagen synthesis both within and around the human tendon tissue., Collagen is the predominant structural protein in tendons and ligaments, and can be controlled by hormonal changes. In animals, injections of insulin-like growth factor I (IGF-I) has been shown to increase collagen synthesis in tendons and ligaments and to improve structural tissue healing, but the effect of local IGF-I administration on tendon collagen synthesis in human has not been studied. The purpose of this study was to study whether local injections of IGF-I would have a stimulating effect on tendon collagen synthesis. Twelve healthy nonsmoking men [age 62 ± 1 years (mean ± SEM), BMI 27 ± 1] participated. Two injections of either human recombinant IGF-I (0.1 mL Increlex©) or saline (control) into each patellar tendon were performed 24-h apart, respectively. Tendon collagen fractional synthesis rate (FSR) was measured by stable isotope technique in the hours after the second injection. Simultaneously, interstitial peritendinous (IGF-I) and [procollagen type I N-terminal propeptide (PINP)], as a marker for type I collagen synthesis, were determined by microdialysis technique. Tendon collagen FSR and PINP were significantly higher in the IGF-I leg compared with the control leg (P < 0.05). In conclusion, local IGF-I administration can directly enhance tendon collagen synthesis both within and around the human tendon tissue.

Muscle protein turnover following resistance exercise and amino acid availability are relatively well described. By contrast, the beneficial effects of different sources of intact proteins in relation to exercise need further investigation. Our objective was to compare muscle anabolic responses to a single bolus intake of whey or casein after performance of heavy resistance exercise. Young male individuals were randomly assigned to participate in two protein trials (n = 9) or one control trial (n = 8). Infusion of l-[1-(13)C]leucine was carried out, and either whey, casein (0.3 g/kg lean body mass), or a noncaloric control drink was ingested immediately after exercise. l-[1-(13)C]leucine-labeled whey and casein were used while muscle protein synthesis (MPS) was assessed. Blood and muscle tissue samples were collected to measure systemic hormone and amino acid concentrations, tracer enrichments, and myofibrillar protein synthesis. Western blots were used to investigate the Akt signaling pathway. Plasma insulin and branched-chain amino acid concentrations increased to a greater extent after ingestion of whey compared with casein. Myofibrillar protein synthesis was equally increased 1-6 h postexercise after whey and casein intake, both of which were higher compared with control (P <0.05). Phosphorylation of Akt and p70(S6K) was increased after exercise and protein intake (P <0.05), but no differences were observed between the types of protein except for total 4E-BP1, which was higher after whey intake than after casein intake (P <0.05). In conclusion, whey and casein intake immediately after resistance exercise results in an overall equal MPS response despite temporal differences in insulin and amino acid concentrations and 4E-BP1.

The purpose of this study was to test the hypothesis that remodeling of skeletal muscle extracellular matrix (ECM) is involved in protecting human muscle against injury. Biopsies were obtained from medial gastrocnemius muscles after a single bout of electrical stimulation (B) or a repeated bout (RB) 30 d later, or 30 d after a single stimulation bout (RBc). A muscle biopsy was collected from the control leg for comparison with the stimulated leg. Satellite cell content, tenascin C, and muscle regeneration were assessed by immunohistochemistry; real-time PCR was used to measure mRNA levels of collagens, laminins, heat-shock proteins (HSPs), inflammation, and related growth factors. The large responses of HSPs, CCL2, and tenascin C detected 48 h after a single bout were attenuated in the RB trial, indicative of protection against injury. Satellite cell content and 12 target genes, including IGF-1, were elevated 30 d after a single bout. Among those displaying the greatest difference vs. control muscle, ECM laminin-ß1 and collagen types I and III were elevated ~6- to 9-fold (P

Disproportionate growth of musculoskeletal tissue is a major cause of morbidity in both acromegalic (ACRO) and GH-deficient (GHD) patients. GH/IGF1 is likely to play an important role in the regulation of tendon and muscle collagen. We hypothesized that the local production of collagen is associated with the level of GH/IGF1.

Purpose. Tendon structures have been studied for decades, but over the last decade, methodological development and renewed interest for metabolic, circulatory and tissue protein turnover in tendon tissue has resulted in a rising amount of investigations. Method. This paper will detail the various modern investigative techniques available to study tendons. Results. There are a variety of investigative methods available to study the correlations between mechanics and biology in tendons. Conclusion. The available methodologies not only allow for potential insight into physiological and pathophysiological mechanisms in tendon tissue, but also, to some extent, allow for more elaborate studies of the intact human tendon. Read More: http://informahealthcare.com/doi/full/10.1080/09638280701785403, Purpose. Tendon structures have been studied for decades, but over the last decade, methodological development and renewed interest for metabolic, circulatory and tissue protein turnover in tendon tissue has resulted in a rising amount of investigations. Method. This paper will detail the various modern investigative techniques available to study tendons. Results. There are a variety of investigative methods available to study the correlations between mechanics and biology in tendons. Conclusion. The available methodologies not only allow for potential insight into physiological and pathophysiological mechanisms in tendon tissue, but also, to some extent, allow for more elaborate studies of the intact human tendon. Read More: http://informahealthcare.com/doi/full/10.1080/09638280701785403

Muscle mass accretion is accomplished by heavy-load resistance training. The effect of light-load resistance exercise has been far more sparsely investigated with regard to potential effect on muscle size and contractile strength. We applied a resistance exercise protocol in which the same individual trained one leg at 70% of one-repetition maximum (1RM) (heavy load, HL) while training the other leg at 15.5% 1RM (light load, LL). Eleven sedentary men (age 25 +/- 1 yr) trained for 12 wk at three times/week. Before and after the intervention muscle hypertrophy was determined by magnetic resonance imaging, muscle biopsies were obtained bilaterally from vastus lateralis for determination of myosin heavy chain (MHC) composition, and maximal muscle strength was assessed by 1RM testing and in an isokinetic dynamometer at 60 degrees /s. Quadriceps muscle cross-sectional area increased (P < 0.05) 8 +/- 1% and 3 +/- 1% in HL and LL legs, respectively, with a greater gain in HL than LL (P < 0.05). Likewise, 1RM strength increased (P < 0.001) in both legs (HL: 36 +/- 5%, LL: 19 +/- 2%), albeit more so with HL (P < 0.01). Isokinetic 60 degrees /s muscle strength improved by 13 +/- 5% (P < 0.05) in HL but remained unchanged in LL (4 +/- 5%, not significant). Finally, MHC IIX protein expression was decreased with HL but not LL, despite identical total workload in HL and LL. Our main finding was that LL resistance training was sufficient to induce a small but significant muscle hypertrophy in healthy young men. However, LL resistance training was inferior to HL training in evoking adaptive changes in muscle size and contractile strength and was insufficient to induce changes in MHC composition., Muscle mass accretion is accomplished by heavy-load resistance training. The effect of light-load resistance exercise has been far more sparsely investigated with regard to potential effect on muscle size and contractile strength. We applied a resistance exercise protocol in which the same individual trained one leg at 70% of one-repetition maximum (1RM) (heavy load, HL) while training the other leg at 15.5% 1RM (light load, LL). Eleven sedentary men (age 25 +/- 1 yr) trained for 12 wk at three times/week. Before and after the intervention muscle hypertrophy was determined by magnetic resonance imaging, muscle biopsies were obtained bilaterally from vastus lateralis for determination of myosin heavy chain (MHC) composition, and maximal muscle strength was assessed by 1RM testing and in an isokinetic dynamometer at 60 degrees /s. Quadriceps muscle cross-sectional area increased (P < 0.05) 8 +/- 1% and 3 +/- 1% in HL and LL legs, respectively, with a greater gain in HL than LL (P < 0.05). Likewise, 1RM strength increased (P < 0.001) in both legs (HL: 36 +/- 5%, LL: 19 +/- 2%), albeit more so with HL (P < 0.01). Isokinetic 60 degrees /s muscle strength improved by 13 +/- 5% (P < 0.05) in HL but remained unchanged in LL (4 +/- 5%, not significant). Finally, MHC IIX protein expression was decreased with HL but not LL, despite identical total workload in HL and LL. Our main finding was that LL resistance training was sufficient to induce a small but significant muscle hypertrophy in healthy young men. However, LL resistance training was inferior to HL training in evoking adaptive changes in muscle size and contractile strength and was insufficient to induce changes in MHC composition.

Udgivelsesdato: 2006-Sep, Synergic action of nitric oxide (NO) and prostaglandins (PG) in the regulation of muscle blood flow during exercise has been demonstrated. In the present study, we investigated whether these vasodilators also regulate local blood flow, flow heterogeneity, and glucose uptake within the exercising skeletal muscle. Skeletal muscle blood flow was measured in seven healthy young men using near-infrared spectroscopy and indocyanine green and muscle glucose uptake using positron emission tomography and 2-fluoro-2-deoxy-D-[(18)F]glucose without and with local blockade of NO and PG at rest and during one-legged dynamic knee-extension exercise. Local blockade was produced by infusing nitro-L-arginine methyl ester and indomethacin directly in the muscle via a microdialysis catheter. Blood flow and glucose uptake were measured in the region of blockade and in two additional regions of vastus lateralis muscle 1 and 4 cm away from the infusion of blockers. Local blockade during exercise at 25 and 40 watts significantly decreased blood flow in the infusion region and in the region 1 cm away from the site of infusion but not in the region 4 cm away. During exercise, muscle glucose uptake did not show any regional differences in response to blockade. These results show that NO and PG synergistically contribute to the local regulation of blood flow in skeletal muscle independently of muscle glucose uptake in healthy young men. Thus these vasodilators can play a role in regulating microvascular blood flow in localized regions of vastus lateralis muscle but do not influence regional glucose uptake. The findings suggest that local substrate uptake in skeletal muscle can be regulated independently of regional changes in blood flow.

Udgivelsesdato: 2005-Sep, Both tendon and peritendinous tissue show evidence of metabolic activity, but the effect of acute exercise on substrate turnover is unknown. We therefore examined the influence of acute exercise on glucose uptake in the patellar and quadriceps tendons during dynamic exercise in humans. Glucose uptake was measured in five healthy men in the patellar and quadriceps tendons and the quadriceps femoris muscle at rest and during dynamic knee-extension exercise (25 W) using positron emission tomography and [18F]-2-fluoro-2-deoxy-D-glucose ([18F]FDG). Glucose uptake index was calculated by dividing the tissue activity with blood activity of [18F]FDG. Exercise increased glucose uptake index by 77% in the patellar tendon (from 0.30 +/- 0.09 to 0.51 +/- 0.16, P = 0.03), by 106% in the quadriceps tendon (from 0.37 +/- 0.15 to 0.75 +/- 0.36, P = 0.02), and by 15-fold in the quadriceps femoris muscle (from 0.31 +/- 0.11 to 4.5 +/- 1.7, P = 0.005). The exercise-induced increase in the glucose uptake in neither tendon correlated with the increase in glucose uptake in the quadriceps muscle (r = -0.10, P = 0.87 for the patellar tendon and r = -0.30, P = 0.62 for the quadriceps tendon). These results show that tendon glucose uptake is increased during exercise. However, the increase in tendon glucose uptake is less pronounced than in muscle and the increases are uncorrelated. Thus tendon glucose uptake is likely to be regulated by mechanisms independently of those regulating skeletal muscle glucose uptake.