A robust, reliable method to non-invasively measure in-vivo mechanical properties of large tissue areas was unavailable until the advent of a new Magnetic Resonance Imaging (MRI) technique known as Magnetic Resonance Elastography (MRE). MRE is a phase-contrast imaging technique that enables quantification of tissue mechanical properties by capturing the motion of induced shear waves via a synchronised Motion Encoding Gradient (MEG). The complex shear modulus is determined via mathematical inversion and reported as the magnitude of the complex shear modulus, |G*|, and phase angle, φ. The work reported in this thesis focuses on the development of MRE data acquisition and analysis protocols optimised to study thigh muscle mechanical properties. The protocols are subsequently applied in healthy volunteers to study natural phenomena such as contraction and ageing and interventions such as an experimental protocol to produce Exercise Induced Muscle Damage (EIMD). Methodological advances made throughout this work include moving from 2D to 3D MRE data acquisition protocols and the application of advanced inversion software to extract muscle viscoelastic properties from the acquired MRE data. Results obtained include observation of reduced muscle stiffness in 6 elderly subjects (>80 years old) compared to 4 young subjects in the Vastus Lateralis (32%), quadriceps muscle group (22%) and entire thigh cross-section (19%), higher resting stiffness of agonist quadriceps compared to antagonist hamstrings (18%) and an increase in quadriceps stiffness (40%) during a leg raise task in 11 healthy subjects. Variability in muscle group recruitment patterns during the contraction were also observed, with the phase angle of the Vastus Intermedius (VI) increasing significantly during contraction. The final experiment involved the recruitment of 20 healthy male subjects to perform an eccentric exercise protocol designed to induce EIMD. Subjects who displayed a Maximum Voluntary Contraction (MVC) force deficit of >10% were considered to have experienced EIMD. A further severe EIMD group were defined based on the presence of hyper-intense signal on T2 weighted imaging following the protocol. The T2 hyper-intensity was found to occur exclusively in the Rectus Femoris (RF) and VI muscle groups. Increased muscle stiffness was observed in the RF muscle in subjects who experienced moderate EIMD (6%). A greater increase in RF stiffness (48%) was observed in the severe EIMD group. The severe EIMD group also displayed significantly increased VI stiffness (14%). The experiments carried out provide several novel findings which can support the development of beneficial strategies to promote both healthy ageing and rehabilitation in athletes, and potentially contribute to improving muscle performance evaluation tests which will expand the opportunities for clinical applications of muscle MRE.

Unaccustomed eccentric exercise can lead to decreases in muscle force production, increases in soreness, swelling, stiffness, and discomfort. The purpose of this study was to test the dose response of pomegranate juice concentrate on serum markers of muscle permeability, inflammation, and total anti-oxidant status. To test this hypothesis, 45 healthy recreationally active males (22.3 ± 0.5 y, 73.8 ± 1.71 kg, 174.9 ± 0.9 cm) were recruited from the local Austin community for participation in this study. Subjects were disqualified from participation in the study if in the past 6 months they were engaged in an exercise training program. Subjects were placed into either the placebo group, the once-daily, or twice-daily pomegranate juice concentrate supplementation group. Subjects performed a total of 8 days of supplementation. On day 4, all subjects came to the laboratory and underwent an eccentric exercise protocol consisting of 2 minutes of downhill running at -10% grade at 7.5 mph repeated 10 times, resulting in ~20 minutes of total downhill running. Thereafter, subjects performed 50 eccentric elbow extensions each lasting 5 seconds using a weight equal to their concentric one-repetition maximum. Blood measures were made pre-exercise (baseline), and 2, 24, 48, 72, and 96 hours post exercise and analyzed for interleukin-6, creatine kinase, myoglobin, and total anti-oxidant status. Creatine kinase was significantly elevated at 96 hours post exercise, but with no significant differences between treatments. Myoglobin was significantly elevated above baseline at 2 and 96 hours, but with no differences between treatments. There was no effect for time or treatment on the total anti-oxidant status of the serum. Il-6 was significantly higher at 2 and 24 hours after exercise, but with no difference between treatments. The percent increase in interleukin-6 from baseline was significantly lower in the twice-daily POM supplementation group versus placebo (124.3 ± 9.4, 188.6 ± 16.0% of baseline; respectively) during the 2-96 hours following eccentric exercise, but no statistical difference between 1x and 2x or 1x and placebo was observed. This suggests that 8 days of supplementation with pomegranate juice concentrate twice a day significantly reduces the percent increase in a marker of inflammation (interleukin-6) during the 96 hours following eccentric exercise; however, neither supplement was different than the placebo in regards to all other measures. / text

An acute bout of unaccustomed eccentric exercise causes prolonged strength loss and delayed onset muscle soreness (DOMS) for several days. Chronic dietary supplementation with polyphenols, from pomegranates, has been shown to accelerate recovery following eccentric exercise, but the optimal dose is unknown. The purpose of this study was to determine the effect of dietary supplementation with different doses of pomegranate juice concentrate (PJC) on muscular strength, power, and soreness throughout a 96-hour time period following an acute bout of eccentric exercise. Healthy recreationally active males (n=45) were assigned to one of three treatment groups: Once-daily PJC (1x), twice-daily PJC (2x), or placebo (PLA) supplementation over a period of eight days. A 1x dose of PJC provided approximately 650 mg GAE. On day four of each treatment, subjects performed downhill running intervals (-10% grade) over a 40-minute period followed by 40 repetitions of eccentric elbow flexion at 100% of concentric 1-RM. Muscle soreness of arms and legs, maximal isometric strength of the elbow flexors (EF) and knee extensors (KE), vertical jump height (VJ[subscript height]) maximal cycling power (P[subscript max]), and 10-meter sprint velocity (V[subscript 10m]) were assessed pre-exercise and 2, 24, 48, 72, 96 hours post-exercise. Additionally, maximal instantaneous power (IP[subscript max]), maximal velocity (V[subscript max]), maximal torque (T[subscript max]), and torque at 0° (T0) were assessed on the inertial load power cycle pre-exercise and 24, 48, 72, 96 hours post-exercise. Throughout the 96-hours post-exercise, isometric EF strength was significantly higher in 1x and 2x groups as compared to PLA (main treatment effect, 83.6 ± 2.7% vs. 85.6 ± 1.9% vs. 78.4 ± 1.8%, respectively; p < 0.001). Isometric KE strength was significantly higher in 1x and 2x groups as compared to PLA (main treatment effect, 93.9 ± 1.5% vs. 91.6 ± 1.5% vs. 87.1 ± 1.8%, respectively; p < 0.001). Both VJ and V10m were significantly higher in 1x compared to PLA (main treatment effect, 99.9 ± 0.9% vs. 98.0 ± 1.0%, respectively, p = 0.037; 100.0 ± 0.8% vs. 97.8 ± 0.7%, respectively, p = 0.003). Muscle soreness and Pmax, were similar at all time points between groups. We conclude that dietary supplementation with 1x or 2x PJC results in higher isometric strength values compared to placebo for EF and KE muscles during the 96-hour period after an acute bout of eccentric exercise. / text

Muscle function after exercise-induced muscle damage has traditionally been evaluated by measures of isometric strength at a single joint angle or muscle length. The thesis investigates the effect of muscle damage on other muscle function parameters such as, isometric strength as a function of muscle length, concentric strength as a function of angular velocity, strength across muscle actions, the stretch-shortening cycle, power output, and fatigability. Study 1 The first part of this study aimed to determine how the muscle length at which strength is measured affects reductions in isometric strength following eccentric exercise-induced muscle damage. The damaging exercise protocol consisted of 100 maximal voluntary eccentric actions of the knee extensors, performed in the prone position through a range of motion from 40° to 140° (0° = full extension) at an angular velocity of 90 deg's-1. Isometric strength of the knee extensors was measured at short muscle length (10° knee flexion) and optimal length (80°). A significantly greater relative loss of strength was observed at short versus optimal muscle length (76.3 ± 2.5% vs. 82.1 ± 2.7% of pre-exercise values, P<0.05) over the seven day testing period following eccentric exercise. The second part of the study investigated isometric strength at optimal length and concentric strength at slow (30 deg's 1) and fast (180 deg's 1) angular velocities of movement. No differences were apparent in the magnitude and rate of recovery of strength across isometric (82.1 ± 2.7%) and slow (86.6 ± 2.0%) and fast (84.3 ± 1.5%) concentric muscle actions. Both the popping sarcomere hypothesis of 2 muscle damage and a failure in excitation-contraction coupling are possible explanations for the reduction in strength being affected by the muscle length at which it is measured. Both would be expected to affect strength to a greater extent at short versus optimal muscle lengths. Study 2 The second study investigated knee extensor muscle strength during isometric, concentric and eccentric muscle actions and vertical jump performance under conditions of squat jump (SJ), countermovement jump (CMJ) and drop jump (DJ). These measures were taken before, 1 hour after, and on days 1,2,3,4 and 7 following a damaging exercise protocol consisting of 100 barbell squats (10 sets x 10 reps @ 70% body mass load). Strength was significantly reduced for four days, however, no differences were observed in the magnitude or rate of recovery of isometric strength at 80° knee flexion and concentric and eccentric strength at 90 deg's'. Vertical jump performance was significantly reduced for three days and was dependent on the type of jump being performed. The relative decline in SJ performance was significantly greater than that in CMJ performance (91.6 ± 1.1% vs. 95.2 ± 1.3% of pre-exercise values, P<0.05) and the relative decline in SJ was significantly greater than that in DJ performance (91.6 ± 1.1% vs. 95.2 ± 1.4%, P<0.05). No differences were observed in the relative decline in CMJ and DJ performance (95.2 ± 1.3% vs. 95.2 ± 1.4%, P> 0.05). The stretch-shortening cycle (SSC) of muscle function is utilised in CMJ and DJ but not in SJ. The SSC has a clear purpose: to allow the final phase (concentric action) to take place with greater force or power output, as compared to the condition where the movement is initiated by a concentric action alone. 3 Utilisation of the SSC in performance seems to attenuate the detrimental performance effects of exercise-induced muscle damage. Study 3 The third and final study investigated the effects of exercise-induced muscle damage on maximal power output and knee extensor fatigability under isometric and dynamic conditions. Under isometric conditions, strength was assessed at 40° and 80° knee flexion and fatigability was assessed by a sustained 60s maximum voluntary contraction (MVC) at each joint angle. For dynamic conditions, maximum power output and fatigue were assessed during a maximal 30s cycle ergometer test. These measures were taken before, 1 hour after, and on days 1,2,3, and 7 following a damaging exercise protocol consisting of 100 eccentric squats (10 sets x 10 reps @ 80% concentric 1 RM). Isometric strength was significantly reduced (P < 0.05) for seven days but no significant differences were observed in the magnitude of strength loss and the pattern of recovery between the two joint angles. Fatigability was quantified as the slope (b) of a linear regression line fitted to the torque and power decay during the 60s MVC and the 30s cycle test, respectively. Prior to muscle damage, subjects were significantly less fatigable (P < 0.05) at 40° (b = -2.39 ± 0.26) versus 80° (b = -5.50 ± 0.72). After muscle damage, subjects became significantly less fatigable at both 40° and 80° with recovery taking three days at 401 and seven days at 80°. Before damaging exercise, a greater rate of fatigue was observed under dynamic (b = -12.75 ± 2.3) versus isometric (80°) conditions (b = -5.50 ± 0.72). Isometric and dynamic fatigue 4 followed a similar temporal pattern after damaging exercise. When the effects of muscle damage on strength at 801 and maximal power output were compared, differences in the extent of performance loss and the time course of recovery were observed. At 1 hour post-exercise, strength was affected to a greater extent (30% reduction) than power (13% reduction) and whereas strength followed a linear recovery pattern, power suffered further decrements at day 1 (18%) and day 2 (16%) before starting to recover. The results indicate that under conditions of voluntary activation muscle becomes weaker but less fatigable under isometric and dynamic conditions following exercise-induced muscle damage. The lower starting torque / power output and the slower rate of decline in torque / power output observed in post-damage fatigue curves may be a phenomenon of selective type II fibre damage. Evidence suggests that type II fibres are selectively damaged during eccentric exercise and therefore post-damage fatigue curves may be missing their contribution to performance. The different recovery patterns observed for isometric and dynamic performance may indicate an inability to maintain central motor drive during complex dynamic tasks when damage is present.

Skeletal muscle is dynamic and actively regenerates following damage or altered functional demand. Regeneration is essential for the maintenance of muscle mass and, when dysregulated as a result of disease or aging, can lead to losses in functional capacity and increased mortality. Limited data exist on the molecular mechanisms that govern skeletal muscle regeneration in humans. Therefore, the overall objective of this dissertation was to characterize early molecular alterations in human skeletal muscle to strenuous exercise known to induce a muscle regenerative response. Thirty-five subjects completed 100 eccentric (muscle lengthening) contractions (EC) of the knee extensors with one leg and muscle biopsies were taken from both legs 3 h post-EC. The sample from the non-EC leg served as the control. A well-powered transcriptomic screen and network analysis using Ingenuity Pathway software was first conducted on mRNA from the biopsy samples. Network analysis identified the transcription factor NF-kappaB (NF-kB) as a key molecular element affected by EC. Conformational qRT-PCR confirmed alterations in genes associated with NF-kappaB. A transcription factor ELISA, using nuclear extracts from EC and control muscle samples showed a 1.6 fold increase in NF-kB DNA binding activity following EC. Immunohistochemical experiments then localized the majority of NF-kB positive nuclei to cells in the interstitium, which stained positive for markers of pericyte cells and not satellite cells. To ascertain the mechanistic significance of NF-kB activation following muscle damage, in vitro analyses were carried out using a novel primary pericyte/myoblast co-culture model. Primary pericyte/myoblast co-culture experiments demonstrated that pericytes, transfected with a DNA vector designed to drive NF-kB activation, enhanced proliferation and inhibited myogenic differentiation of co-cultured skeletal muscle myoblasts. Furthermore, reduced NF-kB activation led to enhanced myogenic potential of primary pericytes. Taken together, the data in this dissertation suggest that NF-kB dependent signaling in pericytes regulates myogenic differentiation in a cell- and non-cell autonomous manner and may affect the early regenerative response following muscle damage by inhibiting differentition and promoting proliferation of muscle satellite cells.

<p> Introduction: 17β-estradiol (E2) has proposed anti-oxidant and membrane stabilizing properties that may attenuate exercise-induced damage, inflammation and alter gene expression. The purpose of this thesis was to determine if acute E2 supplementation would affect the oxidative stress, membrane damage, inflammation and global mRNA expression induced by eccentric exercise. Methods: 18 healthy young males were randomly assigned to 8 days of placebo (CON) or E2 (EXP) supplementation. Blood and muscle samples were collected at baseline (BL), following supplementation (PS), +3 hours (3H) and +48 hours (48H) after 150 single-leg eccentric contractions. Blood samples were analyzed for hormone concentration, creatine kinase (CK) activity and total antioxidant capacity (T AC). Inflammation was quantified by neutrophil and macrophage infiltration. Genes selected a priori for oxidative stress defense, membrane homeostasis and growth were analyzed with real-time RT-PCR. High density oligonucleotide based microarrays were screened for novel differences in mRNA expression. Results: A primary finding was that increased serum E2 did not affect anti-oxidant capacity, creatine kinase efflux or mRNA content of genes related to oxidative stress defence and membrane homeostasis. E2 did attenuate neutrophil infiltration into muscle but did not affect macrophage density. Microarray analysis revealed that exercise induced differential expression of 611 genes at 3H and confirmed that E2 did not affect mRNA content. Genes were manually clustered into biological categories and from this dataset the signaling pathways for RhoA and NF AT were identified as transcriptionally active. Both pathways regulate hypertrophic signaling through the AP-1 transcription factor complex. Conclusions and significance: A major contribution ofthis thesis is that E2 may affect exercise induced inflammation through mechanisms that that do not affect oxidative stress or membrane stability. Additionally, the transcriptional activation ofSTARS/RhoA/APl and NFAT/APl indicates that both are important for early repair and remodelling signaling after a single bout of unaccustomed eccentric exercise. </p> / Thesis / Doctor of Philosophy (PhD)

Purpose The purpose of this study was to describe the evidence-based research recommendations on injury prevention methods against hamstring injuries among Swedish men's elite team in football. The research-based recommendations was then to be compared with the way Swedish elite football teams work to prevent hamstrings injuries. Method First a literature search of PubMed and SPORTDiscuss was made to find the most evidence-based training methods to hamstring injuries. Then an Internet questionnaire regarding injury prevention training methods against hamstring injuries was sent to all Swedish elite football teams. The answers off the questionnaire was then compared with the research that had the most evidence based training methods to hamstring injuries. Results Research shows that the method with the most evidence is eccentric strength training. Flexibility, static stretch and core stability training is research methods that can be used to prevent hamstrings injuries but these methods lack a large validated research basis. 8 of 32 (25 %) teams answered the questionnaire. All teams indicated that they were working with injury prevention methods but the methods varied from the eccentric strength training to periodization and flexibility training. 2 of 8 teams indicated that they worked with eccentric strength training that is recommended by science as the most evidence-based training method. Conclusion The study shows that the teams partly work after what the research recommends as the most evidence-based training methods against hamstring injuries. However, the study lacks validity and further research is needed before definitive conclusions can be drawn. / Syfte Syftet med denna studie är att beskriva vilka evidensbaserade forskningsrekommendationer som finns kring skadeförebyggande träningsmetoder mot hamstringsskador hos svenska herrelitlag i fotboll. De forskningsbaserade rekommendationerna ska sedan jämföras med arbetssättet hos herrelitlagen i svensk fotboll. Metod Först gjordes en litteratursökning på databaserna PubMed och SPORTDiscuss för att hitta de mest evidensbaserade träningsmetoderna mot hamstringsskador. Sedan skickades en webbenkät angående skadeförebyggande träningsmetoder mot hamstringsskador ut till alla svenska herrelitfotbollslag. Svaren på enkäten speglades sedan mot vad forskningen rekommenderade som de mest effektiva träningsmetoderna mot hamstringsskador. Resultat Forskning visar att den metoden med mest evidens är excentrisk styrketräning. Rörelse/stretch samt bålstabilitetsträning är enligt forskningen metoder som kan användas för att förebygga hamstringsskador men dessa metoder saknar ett stort validerat forskningsunderlag. 8 av 32 (25%) föreningar besvarade enkäten. Alla föreningar angav att de arbetade med skadeförebyggande åtgärder men metoderna varierade från excentrisk styrketräning till periodisering och rörlighetsträning. 2 av 8 föreningar angav att de arbetade med excentrisk styrketräning som forskningen rekommenderar som den mest evidensbaserade träningsmetoden. Slutsats Studien visar att föreningarna delvis arbetar efter vad forskningen rekommenderar som evidensbaserade träningsmetoder mot hamstringsskador. Dock saknar studien validitet och ytterligare forskning behövs för att slutgiltiga slutsatser ska kunna dras.

Bakgrund: Besvär från akillessenan är ett vanligt problem hos såväl motionärer som elitidrottare och kan leda till båda smärta och funktionsförlust. Excentrisk träning är en vanlig behandlingsmetod i klinik, trots att evidensen är begränsad och motstridig. Syfte: Att kartlägga vilken evidens som finns för excentrisk träning som behandling av akillestendinopati. Metod: Systematisk litteraturstudie. Sökningen genomfördes i databasen PubMed. Studierna granskades med PEDro-skalan och den sammanlagda evidensen graderades enligt GRADEstud. Resultat: Litteratursökningen resulterade i att 7 studier med totalt 448 deltagare inkluderades. Studierna fick medelhög-hög kvalitet enligt PEDro. Evidensen för excentrisk träning vid 8-16 veckor var måttligt hög (+++) och vid 52 veckor mycket låg (+). Excentrisk träning hade en lägre effekt än hälinlägg och akupunktur mätt med VISA-A vid 8-16 veckor. Effekten av excentrisk träning mätt med VISA-A hade en likvärdig effekt som passiv stretch och tung långsam styrketräning vid 8-16 veckor. Vid 52 veckor var effekten mätt med VISA-A densamma av excentrisk träning som proloterapiinjektioner och tung långsam styrketräning. Konklusion: Excentrisk träning kan ha en effekt vid achillestendinopati. Effekten är densamma som eller lägre sett till poäng på VISA-A än andra behandlingsmetoder och skulle kunna bero på naturlig läkning över tid eller deltagandet i en studie. Evidensen för excentrisk träning graderades vid 8-16 respektive 52 veckor till måttligt hög (+++) och mycket låg (+). Detta grundar sig på studier av medelgod till hög kvalitet. / Background: Achilles tendon issues is a common problem among athletes on all levels. The problem can cause pain and loss of function. Eccentric exercise is a somewhat gold standard and often used in the clinical setting although the level of evidence is limited and conflicting. Objective: Map the evidence of eccentric exercise as a treatment for achilles tendinopathy. Method: A systematic review. The search was conducted in the Pubmed database. The included studies were analyzed using the PEDro scale and the evidence was graded using the GRADEstud. Results: The literature search identified 7 studies that were included with a total of 448 participants. The studies received a moderate-high quality on PEDro. The level of evidence at 8-16 weeks was moderate (+++) and at 52 weeks very low (+). Eccentric exercise had a lower effect than heel lifts and acupuncture measured with VISA-A. Eccentric exercise had a similar effect on VISA-A as passive stretch and heavy slow resistance. At 52 weeks the effect of eccentric exercise was the same as prolotherapy injections and heavy slow resistance. Conclusion: Eccentric exercise might have an effect as treatment for achilles tendinopathy, but the effect is the same or lower than other treatment options measured with VISA-A and might depend on the natural healing process or the participation in a study. The level of evidence for eccentric exercise was graded at 8-16 and 52 weeks respectively, as moderate (+++) and very low (+). This is based on studies of moderate to high quality.

No description available.

Thesis (PhD)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: Background: Understanding the contribution of divergent individual response patterns remains a key objective in identifying mechanisms of inflammation and potential factors limiting the resolution of inflammation. The purpose of this research project was to investigate downstream effects of inflammation following exercise-induced muscle damage in human subjects. Methods: For three different studies, a total of 53 untrained healthy male participants were recruited and divided into a non-exercising control (n=13) and exercise-induced muscle damage groups (n=40). The study design for the three studies was the same (with few exceptions): Downhill running (DHR) (12 x 5min bouts, 10% decline, 15 km.h-1) with blood samples taken pre, post, after 2 and 4 hours post-exercise (2h, 4h) and on days 1, 2, 3, 4 and 7 (d1-d7). Serum was analysed for creatine kinase activity (CK), myoglobin (Mb), cortisol, cytokine (TNFα, IL-1ra, IL-1β, IL-4, IL-6, IL-8, IL-10, sIL-6R), chemokine (G-CSF, MIP-1β) and adhesion factor (sICAM-1, sP-selectin) concentrations. Tissue degradation was assessed by serum matrix metalloprotease (MMP-9) and myeloperoxidase (MPO) content. White blood cell differential count was determined and the surface expression of various cluster of differentiation factors (CD11b, CD163, CD68, CD88, CD34) as well as intracellular MPO were assessed in whole bood using flow cytometry. Nuclear localization of the inflammatory mediator NFĸB in isolated perhipheral blood mononuclear cells (PBMCs) was determined using immunofluorescence microscopy. Muscle biopsies (vastus lateralis) taken at baseline, 4h, d1 and d2 were analysed for fibre type, inflammatory and stress-induced pathways (STAT3, IĸBα, p38MAPK), myogenic factors (MyoD, myogenin), neutrophil activity (MPO) and satellite cell number (Pax7). Results: Participants in the DHR group were subdivided into those with a normal recovery (DHR1) and those who developed secondary damage (DHR2). CK peaked on d1 in both subgroups (DHR1: 1512 ± 413 u.L-1, DHR2: 1434 ± 202 u.L-1) and again on d4 only in the DHR2 group (1110 ± 184 u.L-1). A similar IL-6 and IL-10 response was evident immediately post DHR in all individuals. Additional IL-6 was released in the DHR2 subgroup peaking at 4h (10.3 ± 4.2 pg.mL-1) whereas IL-10 had returned to baseline. IL-1ra (23.6 ± 8.8 pg.mL-1), CD68+ (5%) and CD163+ (3%) monocytes were significantly higher in the DHR2 subgroup. Neutrophil count at 2h (DHR1: 8.6 ± 0.8 x109 cells.L-1, DHR2: 11.4 ± 1.8 x109 cells.L-1) was significantly (p<0.02) correlated to CK activity on d4. PBMC NFĸB p65 nuclear localization was slightly less at 2h in the DHR2 compared to the DHR1 and control groups. Intramuscular STAT3 signalling and MPO were significantly higher in the DHR2 compared to the DHR1 subgroup at 4h and d2 respectively. The progenitor cell response was similar for all DHR individuals with an increase in Pax7+ SC observed at 4h (0.06 ± 0.01 Pax+ SCs/fibre) and d1 (0.07 ± 0.02 Pax+ SCs/fibre). Conclusion: Healthy young men can be divided into those with a adequate and those with a less efficient capacity to control the post damage inflammatory response. The early cytokine response, especially IL-6, seems to be a key role player in the cascade of events leading to late secondary skeletal muscle damage. / AFRIKAANSE OPSOMMING: Agtergrond: Die begrip van uiteenlopende individuele reaksie patrone, is belangrik in die identifisering van faktore asook meganismes betrokke in die ontwikkeling en resolusie van inflammasie. Die doel van hierdie navorsingsprojek was om die gevolge van oefening-geïnduseerde spierskade en inflammasie te ondersoek in menslike proefpersone. Metodiek: ‘n Totaal van 53 gesonde mans is tydens drie verskillende studies, gegroepeer in ’n kontrole (geen oefening) (n=13) en oefening geinduseerde spier skade (DHR) groep (n=40). Die uitleg van de studies was eenders (met min uitsonderings): Afdraende hardloop (12 x 5min hardloop sessies, 10% afdraende, 15km.h-1) met bloed monsters geneem voor, na, 2 ure, 4 ure (pre, post, 2h, 4h) en op dag 1, 2, 3, 4 en 7 (d1-7). Serum is ontleed vir die volgende: kreatien kinase aktiwiteit (CK), kortisol, sitokiene (TNFα, IL-1ra, IL-1β, IL-4, IL-6, IL-8, IL-10, sIL-6R), chemokien (G-CSF, MIP-1β) en adhesie molekuul (sICAM-1, sP-selectin) konsentrasies. Weefsel degradasie is vasgestel deur die teenwoordigheid van matriks metalo-protease-9 (MMP-9) en miëloperoksidase (MPO) in serum te meet. Differensiële witbloed sel (WBC) telling asook die teenwoordigheid van sekere differensiasie faktore (CD11b, CD163, CD68, CD88, CD34) op die sel oppervlak asook intrasellulêre MPO vlakke is bepaal deur gebruik te maak van vloeisitometrie. Die lokalisering van NFĸB in die selkerne van geïsoleerde bloed mononukleêre selle (PBMC) is bepaal deur fluoriserende mikroskopie. Spierbiopsies (vastus lateralis) geneem tydens rus (basislyn), na 4h, en op d1 en d2 is ontleed vir veseltipe, inflammatoriese en stresverwante faktore (STAT3, IĸBα, p38 MAPK), miogeniese faktore (myoD, myogenin), neutrofiel aktiwiteit (MPO) en aantal satelliet selle (Pax7). Resultate: Deelnemers in die DHR-groep is onderverdeel in twee groepe. Persone wat normaalweg herstel het is saam gegroepeer (DHR1) en diegene wat sekondêre skade ontwikkel het is saam gegroepeer (DHR2). CK aktiwiteit in serum het hoogtepunte bereik op d1 in beide subgroepe (DHR1: 1512 ± 413 u.L-1, DHR2: 1434 ± 202 u.L-1) en weer op d4 in die DHR2 groep (1110 ± 184 u.L-1). 'n Soortgelyke IL-6 en IL-10 reaksie is onmiddellik na oefening (in al die proefpersone) waargeneem. Addisionele IL-6 is vrygestel in die DHR2 subgroep en het ’n hoogtepunt bereik na 4h (10.3 ± 4.2 pg.mL-1), terwyl IL-10 reeds teruggekeer het na rustende waardes. IL-1ra (23.6 ± 8.8 pg.mL-1), CD68+ (5%) en CD163+ (3%) monosiete was aansienlik hoër in die DHR2 subgroep. Neutrofieltelling na 2h (DHR1: 8.6 ± 0.8 x109cells.L-1, DHR2: 11.4 ± 1.8 x109cells.L-1) het verband (p <0,02) gehou met CK-aktiwiteit op d4. In vergelyking met die DHR1 en kontrole groep was die lokalisering van NFĸB p65 in PBMC selkerne na 2h effens minder in die DHR2 subgroep. STAT3- en MPO-vlakke in die spiere was aansienlik hoër in die DHR2 subgroep as in die DHR1 subgroep na 4h en op d2 onderskeidelik. Die spierherstel proses was eenders vir alle individue wat aan die oefening deelgeneem het; 'n toename in Pax7+ Satelietselle (SC) is waargeneem na 4h (0.06 ± 0.01 Pax+ SC/spiervesel) en op d1 (0.07 ± 0.02 Pax+ SC/spiervesel). Gevolgtrekking: Gesonde jong mans kan verdeel word in diegene met 'n bevoegde en diegene met 'n minder doeltreffende vermoë om oefenings-geïnduseerde spierskade en die inflammatoriese reaksie te beheer. Die sitokien-reaksie, veral IL-6, blyk om 'n belangrike rolspeler in die ontwikkeling van sekondêre skeletspierskade te wees.