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1.
Eur J Appl Physiol ; 121(12): 3551-3559, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34542671

ABSTRACT

PURPOSE: To investigate the effects of cross-education (CE) exercise on strength and performance at 10 and 24 weeks post anterior cruciate ligament (ACL) surgery. METHODS: Design: randomised controlled trial. N = 44 ACL-reconstruction patients, randomly-allocated into: CE: strength training of the non-operative limb, or CON: sham exercise of upper limb stretching. Each patient underwent standardised ACL rehabilitation, plus 8 weeks of thrice weekly CE or CON, commencing at 2 weeks post surgery. The primary outcome was quadriceps peak force (QPF) of the ACL-reconstructed limb at 10 weeks post surgery. Secondary measures were hamstrings peak force (HPF), rate of force development (RFD) and International Knee Documentation Committee score (IKDC) at 10 and 24 weeks; QPF and hop for distance (HOP) at 24 weeks post surgery. RESULTS: CE significantly attenuated the decline in QPF of the ACL-reconstructed limb at 10 weeks compared to CON (16.6% decrease vs. 32.0%, respectively); that advantage was not retained at 24 weeks. A training effect was observed in the trained limb for HPF and QPF, which was retained at 24 weeks. No significant differences were observed for IKDC, HOP, RFD, or HPF of the reconstructed limb. Inter-limb symmetry (ILS) ranged from 0.78 to 0.89 and was not significantly different between groups. CONCLUSION: High-intensity CE strength training attenuated the post-operative decline in QPF and should be considered in early-phase ACL rehabilitation. ILS data showed good symmetry, but it masked significantly inferior performance between groups and should be used with caution. TRIAL REGISTRATION NUMBER: NCT02722876.


Subject(s)
Anterior Cruciate Ligament Reconstruction/rehabilitation , Muscle Strength/physiology , Resistance Training , Adult , Female , Humans , Male
2.
Arch Phys Med Rehabil ; 98(9): 1842-1851, 2017 09.
Article in English | MEDLINE | ID: mdl-28366821

ABSTRACT

OBJECTIVE: To evaluate the methodologic quality of resistance training interventions for the management of knee osteoarthritis. DATA SOURCES: A search of the literature for studies published up to August 10, 2015, was performed on MEDLINE (OVID platform), PubMed, Embase, and Physiotherapy Evidence Database databases. Search terms associated with osteoarthritis, knee, and muscle resistance exercise were used. STUDY SELECTION: Studies were included in the review if they were published in the English language and met the following criteria: (1) muscle resistance training was the primary intervention; (2) randomized controlled trial design; (3) treatment arms included at least a muscle conditioning intervention and a nonexercise group; and (4) participants had osteoarthritis of the knee. Studies using preoperative (joint replacement) interventions with only postoperative outcomes were excluded. The search yielded 1574 results. The inclusion criteria were met by 34 studies. DATA EXTRACTION: Two reviewers independently screened the articles for eligibility. Critical appraisal of the methodology was assessed according to the principles of resistance training and separately for the reporting of adherence using a specially designed scoring system. A rating for each article was assigned. DATA SYNTHESIS: There were 34 studies that described a strength training focus of the intervention; however, the principles of resistance training were inconsistently applied and inadequately reported across all. Methods for adherence monitoring were incorporated into the design of 28 of the studies, but only 13 reported sufficient detail to estimate average dose of exercise. CONCLUSIONS: These findings affect the interpretation of the efficacy of muscle resistance exercise in the management of knee osteoarthritis. Clinicians and health care professionals cannot be confident whether nonsignificant findings are because of the lack of efficacy of muscle resistance interventions, or occur through limitations in treatment prescription and patient adherence. Future research that seeks to evaluate the effects of muscle strength training interventions on symptoms of osteoarthritis should be properly designed and adherence diligently reported.


Subject(s)
Exercise Therapy/methods , Osteoarthritis, Knee/therapy , Resistance Training/methods , Exercise Therapy/psychology , Humans , Muscle Strength , Osteoarthritis, Knee/psychology , Patient Compliance , Treatment Outcome
3.
Calcif Tissue Int ; 98(5): 426-37, 2016 May.
Article in English | MEDLINE | ID: mdl-26686693

ABSTRACT

UNLABELLED: Vitamin D is important for skeletal muscle health and deficiency is associated with clinical neuromuscular symptoms of poor strength and gait. Supplementation can independently increase muscle strength in chronically deficient populations. However, the regulatory role of vitamin D on neuromuscular remodelling and adaptation subsequent to exercise conditioning or injury has not been systematically reviewed. OBJECTIVE: to systematically review the available evidence of the role of vitamin D on neuromuscular remodelling following exercise conditioning, exercise- or experimentally induced injury. We searched Medline (OVID platform), PubMed, Embase and Web of Science for randomised controlled trials (RCTs) including measures of neuromuscular function, injury and/or inflammation; a physiologically stressful intervention involving exercise conditioning, exercise- or experimentally induced injury and; vitamin D supplementation. Nine RCTs met the inclusion criteria. Significant heterogeneity of methodological approaches and outcomes meant that meta-analysis of data was limited. Qualitative findings indicated that vitamin D may be an effective accelerant of neuromuscular remodelling in animal models (24-140 % improved recovery vs. control); the effects in humans are inconclusive and likely influenced by baseline vitamin D and supplementation strategy. Results of the meta-analyses indicated no effect of vitamin D supplementation on muscle strength adaptation following resistance training [standardised mean difference (SMD): 0.74, P = 0.42] or muscle damage (SMD: -0.03, P = 0.92), although inflammatory markers were elevated in the latter (SMD: 0.56, P = 0.04). Data from animal models offer promising and plausible mechanisms for vitamin D as an agent for neuromuscular adaptation. Further high-quality research is needed to offer clearer insight into the influential role of vitamin D in human populations.


Subject(s)
Exercise/physiology , Muscle Strength/drug effects , Muscle, Skeletal/drug effects , Muscle, Skeletal/injuries , Vitamin D/pharmacology , Adaptation, Physiological/drug effects , Animals , Dietary Supplements , Humans
4.
Eur J Appl Physiol ; 115(4): 837-47, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25476745

ABSTRACT

PURPOSE: Females are known to exhibit a greater risk of ACL injury compared to males. Lower explosive hamstrings-to-quadriceps (H/Q) force ratio in the first 150 ms from activation onset could reflect an impaired capacity for knee joint stabilisation and increased risk of ACL injury. However, the explosive H/Q force ratio has not been compared between the sexes. METHODS: The neuromuscular performance of untrained males and females (20 of each) was assessed during a series of isometric knee flexor and extensor contractions, specifically explosive and maximum voluntary contractions of each muscle group. Force, in absolute terms and normalised to body mass, and surface EMG of the hamstrings and quadriceps were recorded. Hamstrings force was expressed relative to quadriceps force to produce ratios of explosive H/Q force and H/Q maximum voluntary force (MVF). For the explosive contractions, agonist electromechanical delay (EMD) and agonist neural activation were also assessed. RESULTS: The H/Q MVF ratio was greater in males (56 %) than females (50 %; P < 0.001). However, the explosive H/Q force ratio was similar between the sexes at each time point (25-150 ms) from activation onset. Explosive hamstrings, but not quadriceps, force relative to body mass was greater for males compared to females. There were no sex differences in EMD or agonist activation for either of the muscle groups. CONCLUSIONS: The lack of a sex difference in early phase isometric explosive H/Q force ratio suggests other factors might be more important in determining the substantially higher knee injury rates of females.


Subject(s)
Isometric Contraction , Leg/physiology , Ligaments, Articular/physiology , Muscle, Skeletal/physiology , Adult , Female , Humans , Male , Sex Factors
5.
J Appl Physiol (1985) ; 118(5): 604-12, 2015 Mar 01.
Article in English | MEDLINE | ID: mdl-25539942

ABSTRACT

ß-Alanine (BA) supplementation improves human exercise performance. One possible explanation for this is an enhancement of muscle contractile properties, occurring via elevated intramuscular carnosine resulting in improved calcium sensitivity and handling. This study investigated the effect of BA supplementation on in vivo contractile properties and voluntary neuromuscular performance. Twenty-three men completed two experimental sessions, pre- and post-28 days supplementation with 6.4 g/day of BA (n = 12) or placebo (PLA; n = 11). During each session, force was recorded during a series of knee extensor contractions: resting and potentiated twitches and octet (8 pulses, 300 Hz) contractions elicited via femoral nerve stimulation; tetanic contractions (1 s, 1-100 Hz) via superficial muscle stimulation; and maximum and explosive voluntary contractions. BA supplementation had no effect on the force-frequency relationship, or the force responses (force at 25 and 50 ms from onset, peak force) of resting or potentiated twitches, and octet contractions (P > 0.05). Resting and potentiated twitch electromechanical delay and time-to-peak tension were unaffected by BA supplementation (P > 0.05), although half-relaxation time declined by 7-12% (P < 0.05). Maximum and explosive voluntary forces were unchanged after BA supplementation. BA supplementation had no effect on evoked force responses, implying that altered calcium sensitivity and/or release are not the mechanisms by which BA supplementation influences exercise performance. The reduced half-relaxation time with BA supplementation might, however, be explained by enhanced reuptake of calcium, which has implications for the efficiency of muscle contraction following BA supplementation.


Subject(s)
Muscle Relaxation/drug effects , Muscle Relaxation/physiology , Muscle, Skeletal/drug effects , Muscle, Skeletal/physiology , beta-Alanine/administration & dosage , Adult , Calcium/metabolism , Dietary Supplements , Double-Blind Method , Electric Stimulation/methods , Electromyography/methods , Exercise/physiology , Humans , Isometric Contraction/drug effects , Isometric Contraction/physiology , Knee/physiology , Knee Joint/drug effects , Knee Joint/metabolism , Knee Joint/physiology , Male , Muscle Contraction/drug effects , Muscle Contraction/physiology , Muscle Fatigue/drug effects , Muscle Fatigue/physiology , Muscle, Skeletal/metabolism , Rest/physiology
6.
J Sport Rehabil ; 23(3): 235-43, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24622423

ABSTRACT

CONTEXT: Autologous chondrocyte implantation (ACI) aims to restore hyaline cartilage. Traditionally, ACI rehabilitation is prescribed in a concurrent (CON) format. However, it is well known from studies in asymptomatic populations that CON training produces an interference effect that can attenuate strength gains. Strength is integral to joint function, so adopting a nonconcurrent (N-CON) approach to ACI rehabilitation might improve outcomes. OBJECTIVE: To assess changes in function and neuromuscular performance during 48 wk of CON and N-CON physical rehabilitation after ACI to the knee. SETTING: Orthopedic Hospital NHS Foundation Trust. DESIGN: Randomized control, pilot study. PARTICIPANTS: 11 patients (9 male, 2 female; age 32.3 ± 6.6 y; body mass 79.3 ±10.4 kg; time from injury to surgery 7.1 ± 4.9 mo [mean ± SD]) randomly allocated to N-CON:CON (2:1). INTERVENTIONS: Standardized CON and N-CON physiotherapy that involved separation of strength and cardiovascular-endurance conditioning. MAIN OUTCOME MEASURES: Function in the single-leg-hop test, patient-reported outcomes (Knee injury and Osteoarthritis Outcome Score [KOOS], International Knee Documentation Committee subjective questionnaire [IKDC]), and neuromuscular outcomes of peak force (PF), rate of force development (RFD), electromechanical delay (EMD), and sensorimotor performance (force error [FE]) of the knee extensors and flexors of the injured and noninjured legs, measured presurgery and at 6, 12, 24, and 48 wk postsurgery. RESULTS: Factorial ANOVAs with repeated measures of group by leg and by test occasion revealed significantly superior improvements for KOOS, IKDC, PF, EMD, and FE associated with N-CON vs. CON rehabilitation (F(1.5,13.4 GG) = 3.7-4.7, P < .05). These results confirm increased peak effectiveness of N-CON rehabilitation (~4.5-13.3% better than CON over 48 wk of rehabilitation). N-CON and CON showed similar patterns of improvement for single-leg-hop test and RFD. CONCLUSIONS: Nonconcurrent strength and cardiovascular-endurance conditioning during 48 wk of rehabilitation after ACI surgery elicited significantly greater improvements to functional and neuromuscular outcomes than did contemporary concurrent rehabilitation.


Subject(s)
Osteoarthritis, Knee/rehabilitation , Osteoarthritis, Knee/surgery , Physical Endurance/physiology , Adult , Autografts , Chondrocytes/transplantation , Female , Humans , Male , Muscle Strength/physiology , Outcome Assessment, Health Care/methods , Physical Therapy Modalities , Pilot Projects , Recovery of Function , Resistance Training , State Medicine
7.
Eur J Sport Sci ; 14(3): 233-41, 2014.
Article in English | MEDLINE | ID: mdl-23688197

ABSTRACT

The effects of flexibility conditioning on neuromuscular and sensorimotor performance were assessed near to full knee extension (25°). Eighteen males who were randomly assigned into two groups underwent eight weeks (three-times per week) of flexibility conditioning (hip region/knee flexor musculature; dominant limb) involving either proprioceptive neuromuscular facilitation (PNF) (n=9) or passive stretching (PASS) (n=9). Both modes of flexibility conditioning are popular within contemporary exercise and clinical settings and have demonstrated efficacy in improving range of motion. The contralateral limb and a prior 'no exercise' condition were used as controls. The PNF and PASS modes of conditioning improved passive hip flexibility to a similar extent (mean 19.3% vs. baseline, intervention limb, p<0.01) but did not alter knee flexor strength (overall mean 309.6±81 N) or sensorimotor performance (force and positional errors: 2.3±8.2% and 0.48±7.1%). Voluntary and magnetically evoked electromechanical delays (EMDV and EMDE, respectively) were increased but to a greater extent following PASS compared to PNF (PASS: 10.8% and 16.9% lengthening of EMDV and EMDE, respectively vs. PNF: 3.2% and 6.2%, p<0.01).The attenuated change to electromechanical delay (EMD) performance during PNF conditioning suggests a preserved capability for rapid muscle activation, which is important in the maintenance of dynamic joint stability. That PNF was also equally efficacious in flexibility conditioning would suggest that this mode of flexibility training should be used over passive to help preserve dynamic joint stability capabilities at this extended and vulnerable joint position.


Subject(s)
Muscle Stretching Exercises/methods , Muscle, Skeletal/physiology , Proprioception/physiology , Psychomotor Performance/physiology , Adolescent , Adult , Humans , Male , Range of Motion, Articular/physiology , Young Adult
8.
Med Sci Sports Exerc ; 46(5): 963-72, 2014.
Article in English | MEDLINE | ID: mdl-24126965

ABSTRACT

INTRODUCTION: Explosive neuromuscular performance refers to the ability to rapidly increase force in response to neuromuscular activation. The lower explosive force production of the hamstrings relative to the quadriceps could compromise knee joint stability and increase the risk of anterior cruciate ligament injury. However, the time course of the rise in explosive force of the hamstrings and quadriceps from their initial activation, and thus the explosive hamstrings-to-quadriceps (H/Q) force ratio, has not been documented. METHODS: The neuromuscular performance of 20 untrained males was assessed during a series of isometric knee flexion and extension contractions, with force and surface EMG of the hamstrings and quadriceps recorded during explosive and maximum voluntary contractions. Hamstrings force was expressed relative to quadriceps force to produce hamstring-to-quadriceps ratios of explosive H/Q force and H/Q maximum voluntary force. For the explosive contractions, agonist electromechanical delay (EMD), agonist and antagonist neural activation were assessed. RESULTS: The quadriceps was 79% stronger than the hamstrings, but quadriceps explosive force was up to 480% greater than the hamstrings from 25 to 50 ms after first activation. Consequently, the explosive H/Q force ratio was very low at 25 and 50 ms (0%-17%) and significantly different from H/Q maximum voluntary force ratio (56%). Hamstrings EMD was 95% greater than quadriceps EMD (44.0 vs 22.6 ms), resulting in a 21-ms later onset of force in the hamstrings that appeared to explain the low explosive H/Q force ratio in the early phase of activation. CONCLUSIONS: Prolonged hamstrings EMD appears to impair early phase (0-50 ms) explosive force production relative to the quadriceps and may render the knee unstable and prone to anterior cruciate ligament injury during this period.


Subject(s)
Isometric Contraction/physiology , Muscle Strength/physiology , Muscle, Skeletal/physiology , Quadriceps Muscle/physiology , Adult , Anterior Cruciate Ligament Injuries , Biomechanical Phenomena , Electromyography , Humans , Joint Instability/physiopathology , Knee Joint/physiopathology , Male , Risk Factors , Thigh , Torque , Young Adult
9.
Appl Physiol Nutr Metab ; 38(1): 21-6, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23368824

ABSTRACT

This study investigated the effects of hypohydration by fluid restriction on voluntary and evoked indices of neuromuscular performance at a functional joint angle. Measures of static volitional peak force (2-3-s maximal muscle actions) and evoked peak twitch force, electromechanical delay, and rate of force development were obtained from the knee extensors (30° knee flexion) of 10 males (age, 24 (4) years; height, 1.76 (0.10) m; body mass, 78.7 (9.13) kg (mean (SD))) prior to and immediately following 24 h of (i) euhydration (EU) and (ii) hypohydration (HYP). Neuromuscular performance was also assessed in response to a fatiguing task (3 × 30-s maximal static knee extensions) following each condition. Repeated-measures ANOVAs showed that HYP was associated with a significant 2.1% loss in body mass (p < 0.001) and a 7.8% reduction in volitional peak force (p < 0.05). Following fatigue, data indicated statistically similar levels of impairment to volitional peak force (11.6%, p < 0.01) and rate of force development (21.0%, p < 0.01) between conditions (EU; HYP). No changes to any other indices of performance were observed. The substantive hypohydration-induced deficits to muscle strength at this functional joint angle might convey a decreased performance capability and should be considered by the hypohydrated athlete. Whilst hypohydration did not affect fatigue-related performance of the knee extensors, the additive changes associated with lower baseline levels of strength performance (7.8%) and fatigue (11.6%) coupled with slower rate of muscle force production (from 0-100 ms) following fatigue may present significant challenges to the maintenance of dynamic knee joint stability, particularly at this vulnerable joint position.


Subject(s)
Dehydration/physiopathology , Knee Joint/physiopathology , Muscle Contraction/physiology , Muscle Fatigue/physiology , Muscle, Skeletal/physiopathology , Physical Endurance/physiology , Adult , Analysis of Variance , Body Height/physiology , Body Mass Index , Body Weight/physiology , Electromyography/methods , Humans , Male , Reference Values , Young Adult
10.
Eur J Appl Physiol ; 113(4): 905-9, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23001003

ABSTRACT

The aims of this study were (1) to investigate the relationship between self-perception of effort and task duration in an intermittent isometric fatigue trial (IIF) and (2) to evaluate the capability of two assessment paradigms (perceived exertion; perceived task duration) to reflect changes in IIF intensity. Fifteen participants performed two IIF tasks of the knee extensors at intensities of 60 and 70 % of daily peak force, each separated by 48-72 h. Ordering of the tasks was counter-balanced and participants were blinded to the precise intensity of each IIF. A category-ratio scale (CR-10) and visual analogue scale were used during each IIF task to record measures of perceived exertion and perceived task duration, respectively. Measures were recorded at 10 % intervals across the relative duration of each IIF task. Pearson product-moment correlation coefficients revealed strong positive correlations (r > 0.99; p < 0.01) between completed task duration and both perceptual scales at the two IIF intensities. Separate two-way repeated measures ANOVAs of CR-10 and perceived task duration responses revealed significant main effects for time only (F [2.2,30.1] = 126.8; p < 0.001; F [2.6,36.8] = 117.2; p < 0.001, CR-10 and perceived task duration, respectively). The results suggest that perceived exertion and perceived task duration are equally effective predictors of IIF end-point. However, neither measure was sufficiently responsive to discriminate between 10 % changes in exercise intensity.


Subject(s)
Exercise , Isometric Contraction , Muscle Fatigue , Muscle, Skeletal/physiology , Time Perception , Adult , Analysis of Variance , Cross-Over Studies , England , Humans , Male , Muscle Strength , Muscle, Skeletal/innervation , Time Factors , Young Adult
11.
J Sports Sci ; 30(10): 1015-24, 2012.
Article in English | MEDLINE | ID: mdl-22574708

ABSTRACT

This study examined the concurrent effects of exercise-induced muscle damage and superimposed acute fatigue on the neuromuscular activation performance of the knee flexors of nine males (age: 26.7 ± 6.1 years; height 1.81 ± 0.05 m; body mass 81.2 ± 11.7 kg [mean±s]). Measures were obtained during three experimental conditions: (i) 'fatigue-muscle damage', involving acute fatiguing exercise performed on each assessment occasion plus a single episode of eccentric exercise performed on the first occasion and after the fatigue trial; (ii) 'fatigue', involving the fatiguing exercise only; and (iii) 'control' consisting of no exercise. Assessments were performed prior to (pre) and at 1 h, 24 h, 48 h, 72 h, and 168 h relative to the muscle damaging eccentric exercise. Repeated-measures analyses of variance (ANOVAs) showed that muscle damage elicited reductions of up to 38%, 24% and 65% in volitional peak force, electromechanical delay and rate of force development compared to baseline and controls, respectively (F ([10, 80]) = 2.3 to 4.6; P < 0.05) with further impairments (6.2% to 30.7%) following acute fatigue (F ([2, 16]) = 4.3 to 9.1; P < 0.05). By contrast, magnetically-evoked electromechanical delay was not influenced by muscle damage and was improved during the superimposed acute fatigue (∼14%; F ([2, 16]) = 3.9; P < 0.05). The safeguarding of evoked muscle activation capability despite compromised volitional performance might reveal aspects of capabilities for emergency and protective responses during episodes of fatigue and antecedent muscle damaging exercise.


Subject(s)
Athletic Injuries/physiopathology , Knee Joint/physiopathology , Muscle Fatigue/physiology , Muscle, Skeletal/injuries , Adult , Athletic Injuries/blood , Creatine Kinase/blood , Electromyography , Exercise/physiology , Humans , Male , Muscle Strength/physiology , Muscle, Skeletal/physiopathology , Young Adult
12.
Exp Physiol ; 97(5): 618-29, 2012 May.
Article in English | MEDLINE | ID: mdl-22308163

ABSTRACT

The purpose of the study was to investigate sex-related differences in explosive muscular force production, as measured by electromechanical delay (EMD) and rate of force development (RFD), and to examine the physiological mechanisms responsible for any differences. The neuromuscular performance of untrained males (n = 20) and females (n = 20) was assessed during a series of isometric knee extension contractions; explosive and maximal voluntary efforts, as well as supramaximal evoked twitches and octets (eight pulses at 300 Hz). Evoked and voluntary EMD were determined from twitch and explosive contractions. The RFD was recorded over consecutive 50 ms time windows from force onset during evoked and explosive contractions, and normalized to maximal strength. Neuromuscular activity during explosive voluntary contractions was measured with EMG of the superficial knee extensors normalized to maximal M-wave. Muscle size (thickness) and muscle-tendon unit (MTU) stiffness were assessed using ultrasonic images of the vastus lateralis at rest and during ramped contractions. Males and females had similar evoked and voluntary EMD. Males were 33% stronger (P < 0.001) and their absolute RFD was 26-56% greater (all time points P < 0.05) compared with females. Muscle size (P < 0.001) and absolute MTU stiffness were also greater for males (P < 0.05). However, normalized RFD was similar for both sexes during the first 150 ms of the explosive voluntary contractions (P > 0.05). This was consistent with the similar normalized twitch and octet RFD, MTU stiffness and agonist EMG (all P > 0.05). When differences in maximal strength were accounted for, the evoked capacity of the knee extensors for explosive force production and the ability to utilize that capacity during explosive voluntary contractions was similar for males and females.


Subject(s)
Isometric Contraction/physiology , Muscle Contraction/physiology , Electromyography , Female , Humans , Knee/physiology , Male , Muscle, Skeletal/physiology , Sex Characteristics , Young Adult
13.
J Sports Sci ; 30(2): 217-25, 2012.
Article in English | MEDLINE | ID: mdl-22126366

ABSTRACT

The effects of serial episodes of fatigue and recovery on volitional and magnetically evoked neuromuscular performance of the knee flexors were assessed in 20 female soccer players during: (i) an intervention comprising 4 × 35 s maximal static exercise, and (ii) a control condition. Volitional peak force was impaired progressively (-16% vs. baseline: 235.3 ± 54.7 to 198.1 ± 38.5 N) by the fatiguing exercise and recovered to within -97% of baseline values following 6 min of rest. Evoked peak twitch force was diminished subsequent to the fourth episode of exercise (23.3%: 21.4 ± 13.8 vs. 16.4 ± 14.6 N) and remained impaired at this level throughout the recovery. Impairment of volitional electromechanical delay performance following the first episode of exercise (25.5%: 55.3 ± 11.9 vs. 69.5 ± 24.5 ms) contrasted with concurrent improvement (10.0%: 24.5 ± 4.7 vs. 22.1 ± 5.0 ms) in evoked electromechanical delay (P < 0.05), and this increased disparity between evoked and volitional electromechanical delay remained during subsequent periods of intervention and recovery. The fatiguing exercise provoked substantial impairments to volitional strength and volitional electromechanical delay that showed differential patterns of recovery. However, improved evoked electromechanical delay performance might identify a dormant capability for optimal muscle responses during acute stressful exercise and an improved capacity to maintain dynamic joint stability during critical episodes of loading.


Subject(s)
Exercise/physiology , Knee Joint/physiology , Muscle Contraction/physiology , Muscle Fatigue/physiology , Muscle Strength/physiology , Muscle, Skeletal/physiology , Soccer/physiology , Adult , Athletic Performance , Electromyography , Female , Humans , Physical Endurance , Rest , Stress, Physiological , Task Performance and Analysis , Volition , Young Adult
14.
J Mol Biol ; 373(4): 891-902, 2007 Nov 02.
Article in English | MEDLINE | ID: mdl-17897672

ABSTRACT

The ADAMTS (a disintegrin-like and metalloproteinase domain with thrombospondin type I motifs) family of proteases plays a role in pathological conditions including arthritis, cancer, thrombotic thrombocytopenic purpura and the Ehlers-Danlos type VIIC and Weill-Marchesani genetic syndromes. Here, we report the first crystal structures for a member of the ADAMTS family, ADAMTS-1. Originally cloned as an inflammation-associated gene, ADAMTS-1 has been shown to be involved in tissue remodelling, wound healing and angiogenesis. The crystal structures contain catalytic and disintegrin-like domains, both in the inhibitor-free form and in complex with the inhibitor marimastat. The overall fold of the catalytic domain is similar to related zinc metalloproteinases such as matrix metalloproteinases and ADAMs (a disintegrin and metalloproteinases). The active site contains the expected organisation of residues to coordinate zinc but has a much larger S1' selectivity pocket than ADAM33. The structure also unexpectedly reveals a double calcium-binding site. Also surprisingly, the previously named disintegrin-like domain showed no structural homology to the disintegrin domains of other metalloproteinases such as ADAM10 but is instead very similar in structure to the cysteine-rich domains of other metalloproteinases. Thus, this study suggests that the D (for disintegrin-like) in the nomenclature of ADAMTS enzymes is likely to be a misnomer. The ADAMTS-1 cysteine-rich domain stacks against the active site, suggesting a possible regulatory role.


Subject(s)
ADAM Proteins/chemistry , Disintegrins/chemistry , ADAM Proteins/genetics , ADAM Proteins/metabolism , ADAMTS1 Protein , Binding Sites , Calcium/metabolism , Catalytic Domain , Crystallography, X-Ray/methods , Disintegrins/genetics , Disintegrins/metabolism , Humans , Metalloendopeptidases/chemistry , Metalloendopeptidases/genetics , Metalloendopeptidases/metabolism , Models, Molecular , Protein Binding , Protein Structure, Secondary , Protein Structure, Tertiary
15.
Eur J Appl Physiol ; 100(4): 469-78, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17468881

ABSTRACT

Neuromuscular performance capabilities, including those measured by evoked responses, may be adversely affected by fatigue; however, the capability of the neuromuscular system to initiate muscle force rapidly under these circumstances is yet to be established. Sex-differences in the acute responses of neuromuscular performance to exercise stress may be linked to evidence that females are much more vulnerable to anterior cruciate ligament injury than males. Optimal functioning of the knee flexors is paramount to the dynamic stabilisation of the knee joint, therefore the aim of this investigation was to examine the effects of acute maximal intensity fatiguing exercise on the voluntary and magnetically-evoked electromechanical delay in the knee flexors of males and females. Knee flexor volitional and magnetically-evoked neuromuscular performance was assessed in seven male and nine females prior to and immediately after: (1) an intervention condition comprising a fatigue trial of 30-s maximal static exercise of the knee flexors, (2) a control condition consisting of no exercise. The results showed that the fatigue intervention was associated with a substantive reduction in volitional peak force that was greater in males compared to females (15.0, 10.2%, respectively, P < 0.01) and impairment to volitional electromechanical delay in females exclusively (19.3%, P < 0.05). Similar improvements in magnetically-evoked electromechanical delay in males and females following fatigue (21%, P < 0.001), however, may suggest a vital facilitatory mechanism to overcome the effects of impaired voluntary capabilities, and a faster neuromuscular response that can be deployed during critical times to protect the joint system.


Subject(s)
Exercise/physiology , Knee Joint/physiology , Muscle Fatigue/physiology , Muscle, Skeletal/physiology , Neuromuscular Junction/physiology , Adult , Anterior Cruciate Ligament Injuries , Biomechanical Phenomena , Electromyography , Female , Humans , Magnetics , Male , Muscle Contraction/physiology , Muscle, Skeletal/innervation , Sex Characteristics , Time Factors , Volition/physiology
17.
Bioorg Med Chem Lett ; 14(9): 2249-52, 2004 May 03.
Article in English | MEDLINE | ID: mdl-15081018

ABSTRACT

Modification of imidazo[1,2-a]pyridine CDK inhibitors lead to identification of less lipophilic imidazo[1,2-b]pyridazine series of CDK inhibitors. Although several equivalent compounds from these two series have similar structure and show similar CDK activity, the SAR of the two series differs significantly. Protein inhibitor structure determination has confirmed differences in binding mode and given some understanding of these differences in SAR. Potent and selective imidazo[1,2-b]pyridazine inhibitors of CDK2 have been identified, which show >1 microM plasma levels following a 2mg/kg oral dose to mice.


Subject(s)
Cyclin-Dependent Kinases/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Pyridazines/chemistry , Pyridazines/pharmacology , Animals , Enzyme Inhibitors/blood , Enzyme Inhibitors/chemistry , Mice , Models, Molecular , Pyridazines/blood
18.
Structure ; 12(1): 75-84, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14725767

ABSTRACT

Human thymidine phosphorylase (HTP), also known as platelet-derived endothelial cell growth factor (PD-ECGF), is overexpressed in certain solid tumors where it is linked to poor prognosis. HTP expression is utilized for certain chemotherapeutic strategies and is also thought to play a role in tumor angiogenesis. We determined the structure of HTP bound to the small molecule inhibitor 5-chloro-6-[1-(2-iminopyrrolidinyl) methyl] uracil hydrochloride (TPI). The inhibitor appears to mimic the substrate transition state, which may help explain the potency of this inhibitor and the catalytic mechanism of pyrimidine nucleotide phosphorylases (PYNPs). Further, we have confirmed the validity of the HTP structure as a template for structure-based drug design by predicting binding affinities for TPI and other known HTP inhibitors using in silico docking techniques. This work provides the first structural insight into the binding mode of any inhibitor to this important drug target and forms the basis for designing novel inhibitors for use in anticancer therapy.


Subject(s)
Models, Molecular , Protein Binding , Protein Folding , Pyrrolidines/chemistry , Thymidine Phosphorylase/metabolism , Uracil/analogs & derivatives , Uracil/chemistry , Crystallization , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Humans , Protein Structure, Tertiary , Pyrrolidines/pharmacology , Uracil/pharmacology
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