vendex and Inflammation

We examined the effect of curcumin (CUR) ingestion before or after exercise on changes in muscle damage and inflammatory responses after exercise. We conducted two parallel experiments with different CUR ingestion timings using a double-blind crossover. In Exp. 1, ten healthy men ingested 180 mg d

Topics: Adult; Biomarkers; Creatine Kinase; Cross-Over Studies; Curcumin; Dietary Supplements; Double-Blind Method; Eating; Elbow; Exercise; Humans; Inflammation; Interleukin-8; Isometric Contraction; Male; Muscle, Skeletal; Myalgia; Range of Motion, Articular; Torque

Protease supplementation has been purported to reduce the damaging effects of eccentric exercise and accelerate recovery of muscle function, possibly by regulating inflammation.. To determine the effectiveness of protease supplementation in attenuating eccentric exercise-induced skeletal muscle damage and inflammation.. After standard physical and hemodynamic assessment and fasting venous blood samples, subjects performed isokinetic extension/flexion of the quadriceps group on a Biodex isokinetic dynamometer at 60°·s(-1), followed by VO2max testing. Subjects were randomly assigned to consume 5.83 g daily of either a cellulose placebo (N = 15; 22.27 ± 3.33 yr, 71.17 ± 2.91 inches, 179.4 ± 24.05 lb, 50.55 ± 5.66 mL·kg(-1)·min(-1)) or a proteolytic supplement containing fungal proteases, bromelain, and papain (N = 14; 22.85 ± 5.9 yr, 70.0 ± 2.67 inches, 173.11 ± 29.94 lb, 49.69 ± 6.15 mL·kg(-1)·min(-1)) for a period of 21 d. After the supplementation period, subjects donated blood samples before performing a 45-min downhill (-17.5%) treadmill protocol at 60% of VO2max. An additional four blood draws and three muscle function tests were performed during the next 48 h. Blood was analyzed using standard hematology and clinical chemistry, enzyme-linked immunosorbent assay, and bead array. Blood data were analyzed using multivariate analysis of variance (MANOVA) with repeated measures, whereas Biodex data were analyzed using a MANOVA on %Δ values.. Significant group differences (T1-T3, P = 0.033; T1-T4, P = 0.043) and another strong trend (T1-3 h, P = 0.055) were observed for flexion (peak torque %Δ at 60°·s(-1)) indicating higher force production in the protease group. Significant group × time interactions (P < 0.05) were observed, including elevations in circulating eosinophils and basophils in the protease group coinciding with lower levels of serum cyclooxygenase 2, interleukin 6, and interleukin 12 in this group.. Protease supplementation seems to attenuate muscle strength losses after eccentric exercise by regulating leukocyte activity and inflammation.

Topics: Administration, Oral; Adolescent; Adult; Basophils; Creatine Kinase; Cyclooxygenase 2; Dietary Supplements; Dinoprost; Dinoprostone; Double-Blind Method; Eosinophils; Exercise; Humans; Immunoglobulins; Inflammation; Interleukins; Leukocyte Count; Male; Muscle Strength; Muscle, Skeletal; Neutrophils; Peptide Hydrolases; Quadriceps Muscle; Recovery of Function; Superoxide Dismutase; Torque; Young Adult

Previous studies indicate that exercise-induced muscle damage may be attenuated when protein is included in a carbohydrate recovery supplement. This study was designed to examine systemic indices of muscle damage, inflammation, and recovery of muscle function, following strenuous exercise, with ingestion of either carbohydrate alone or a carbohydrate-protein mixture. Seventeen highly trained volunteers participated in 2 trials in a randomized order, separated by approximately 9 weeks. Each trial involved 90 min of intermittent shuttle-running, either with ingestion of a 9% sucrose solution during and for 4 h after (1.2 g.kg-1 body mass.h-1) or with the same solution plus 3% whey protein isolate (0.4 g.kg-1 body mass.h-1). Blood was sampled throughout and 24 h after each trial to determinate the systemic indices of muscle damage and inflammation. An isokinetic dynamometer was used to establish reliable baseline measurements of peak isometric torque for knee and hip flexors and extensors, which were then followed-up at 4-, 24-, 48-, and 168-h postexercise. The exercise protocol resulted in significantly elevated variables indicative of muscle damage and inflammation, while peak isometric torque was immediately reduced by 10%-20% relative to baseline, across all muscle groups tested. However, none of these responses varied in magnitude or time-course between the treatments, or between participants' first and second trials. The addition of whey protein isolate to a dietary carbohydrate supplement ingested during and for 4 h following strenuous exercise did not attenuate systemic indices of muscle damage or inflammation, nor did it restore muscle function more rapidly than when the carbohydrate fraction was ingested alone.

Topics: Administration, Oral; Adult; Beverages; Biomarkers; C-Reactive Protein; Creatine Kinase, MM Form; Cross-Over Studies; Dietary Sucrose; Exercise; Humans; Inflammation; Inflammation Mediators; Interleukins; L-Lactate Dehydrogenase; Lower Extremity; Male; Milk Proteins; Muscle Contraction; Muscle Strength; Muscle, Skeletal; Muscular Diseases; Myoglobin; Pain; Pain Measurement; Recovery of Function; Single-Blind Method; Time Factors; Torque; Whey Proteins; Young Adult

We studied five young healthy volunteers who performed a "damage protocol" consisting of 240 (24 sets x 10 repetitions/set) maximal isokinetic eccentric muscle contractions (30 degrees/s) on each leg one week apart. Biopsies were taken from the vastus lateralis on two occasions. Two biopsies were taken from within the same muscle 24h following the damage protocol. On a second occasion a single biopsy was taken from the contralateral leg at 24h following the same damage protocol. Biopsies at all three sites showed Z-band disruption, much greater (i.e., approximately 14-fold) than is typically observed in resting biopsies, with no significant differences (ANOVA) according to site location (within legs or between legs). The within-leg coefficient of variation (CV) was, however, 41 +/- 30%, and the between-leg CVs were 57 +/- 36% and 68 +/- 36%. Macrophage cells were also detected within the muscle, and cell numbers were not statistically different between biopsy sites. However, the within-biopsy CV = 52 +/- 19% and the between-biopsy CVs of 34 +/- 24% and 48 +/- 27%. We conclude that eccentric contraction-induced Z-band streaming and inflammatory cell response, as detected in muscle biopsy samples from humans, is highly variable with a CV of 40-70%.

Topics: Adult; Biopsy, Needle; Cell Count; Exercise; Female; Humans; Inflammation; Macrophages; Male; Muscle Contraction; Muscle, Skeletal; Torque

The frank loss of a large volume of skeletal muscle (i.e., volumetric muscle loss [VML]) can lead to functional debilitation and presents a significant problem to civilian and military medicine. Current clinical treatment for VML involves the use of free muscle flaps and physical rehabilitation; however, neither are effective in promoting regeneration of skeletal muscle to replace the tissue that was lost. Toward this end, skeletal muscle tissue engineering therapies have recently shown great promise in offering an unprecedented treatment option for VML. In the current study, we further extend our recent progress (Machingal et al., 2011, Tissue Eng; Corona et al., 2012, Tissue Eng) in the development of tissue engineered muscle repair (TEMR) constructs (i.e., muscle-derived cells [MDCs] seeded on a bladder acellular matrix (BAM) preconditioned with uniaxial mechanical strain) for the treatment of VML. TEMR constructs were implanted into a VML defect in a tibialis anterior (TA) muscle of Lewis rats and observed up to 12 weeks postinjury. The salient findings of the study were (1) TEMR constructs exhibited a highly variable capacity to restore in vivo function of injured TA muscles, wherein TEMR-positive responders (n=6) promoted an ≈61% improvement, but negative responders (n=7) resulted in no improvement compared to nonrepaired controls, (2) TEMR-positive and -negative responders exhibited differential immune responses that may underlie these variant responses, (3) BAM scaffolds (n=7) without cells promoted an ≈26% functional improvement compared to uninjured muscles, (4) TEMR-positive responders promoted muscle fiber regeneration within the initial defect area, while BAM scaffolds did so only sparingly. These findings indicate that TEMR constructs can improve the in vivo functional capacity of the injured musculature at least, in part, by promoting generation of functional skeletal muscle fibers. In short, the degree of functional recovery observed following TEMR implantation (BAM+MDCs) was 2.3×-fold greater than that observed following implantation of BAM alone. As such, this finding further underscores the potential benefits of including a cellular component in the tissue engineering strategy for VML injury.

Topics: Animals; Disease Models, Animal; Extracellular Matrix; Inflammation; Male; Muscle, Skeletal; Prosthesis Implantation; Rats; Rats, Inbred Lew; Recovery of Function; Regeneration; Sus scrofa; Tissue Engineering; Tissue Scaffolds; Torque; Urinary Bladder; Wound Healing

The overexpression of tumor necrosis factor (TNF)-α leads to systemic as well as local loss of bone and cartilage and is also an important regulator during fracture healing. In this study, we investigate how TNF-α inhibition using a targeted monoclonal antibody affects fracture healing in a TNF-α driven animal model of human rheumatoid arthritis (RA) and elucidate the question whether enduring the anti TNF-α therapy after trauma is beneficial or not.. A standardized femur fracture was applied to wild type and human TNF-α transgenic mice (hTNFtg mice), which develop an RA-like chronic polyarthritis. hTNFtg animals were treated with anti-TNF antibody (Infliximab) during the fracture repair. Untreated animals served as controls. Fracture healing was evaluated after 14 and 28 days of treatment by clinical assessment, biomechanical testing and histomorphometry.. High levels of TNF-α influence fracture healing negatively, lead to reduced cartilage and more soft tissue in the callus as well as decreased biomechanical bone stability. Blocking TNF-α in hTNFtg mice lead to similar biomechanical and histomorphometrical properties as in wild type.. High levels of TNF-α during chronic inflammation have a negative impact on fracture healing. Our data suggest that TNF-α inhibition by an anti-TNF antibody does not interfere with fracture healing.

Topics: Animals; Antibodies, Monoclonal; Arthritis; Arthritis, Rheumatoid; Bone Nails; Bony Callus; Disease Models, Animal; Female; Femoral Fractures; Fracture Fixation, Internal; Fracture Healing; Humans; Inflammation; Infliximab; Mice; Mice, Transgenic; Stress, Mechanical; Torque; Tumor Necrosis Factor-alpha; Weight-Bearing

This study compared the effect of immediate versus delayed massage-like compressive loading (MLL) on peak isometric torque recovery and inflammatory cell infiltration after eccentric exercise (EEX).. Eighteen skeletally mature New Zealand White rabbits were instrumented with peroneal nerve cuffs for the stimulation of hindlimb tibialis anterior muscles. After a bout of EEX, rabbits were randomly assigned to an MLL protocol (0.5 Hz, 10 N, 15 min) that started immediately post-EEX, 48 h post-EXX, or no-MLL control and performed for four consecutive days. A torque-angle (T-Θ) relationship was obtained for 21 joint angles pre- and post-EEX and after four consecutive days of MLL or no-MLL. Muscle wet weights and immunohistochemical sections were obtained after final treatments.. EEX produced an average 51% ± 13% decrease in peak isometric torque output. The greatest peak torque recovery occurred with the immediate application of MLL. There were differences in torque recovery between immediate and delayed MLL (P = 0.0012), immediate MLL and control (P < 0.0001), and delayed MLL and control (P = 0.025). Immunohistochemical analysis showed 39.3% and 366.0% differences in the number of RPN3/57 and CD11b-positive cells between immediate (P = 0.71) and delayed MLL (P = 0.12). The area under the T-Θ curve showed a difference for immediate (P < 0.0001) and delayed (P = 0.0051) MLL as compared with control. Exercise produced an average 10° ± 0.2° rightward shift from preexercise peak isometric torque angle. Control, immediate MLL, and delayed MLL produced an average leftward angular shift from the postexercise angle (P = 0.28, P = 0.03, and P = 0.47, respectively).. Post-EEX, immediate MLL was more beneficial than delayed MLL in restoring muscle function and in modulating inflammatory cell infiltration. These findings invite similar human studies to make definitive conclusions on optimal timing of massage-based therapies.

Topics: Animals; Biomechanical Phenomena; Female; Immunohistochemistry; Inflammation; Leukocytes; Linear Models; Massage; Muscle, Skeletal; Neutrophil Infiltration; Physical Conditioning, Animal; Rabbits; Random Allocation; Recovery of Function; ROC Curve; Torque; Weight-Bearing

Mutations in the DYSF gene, encoding dysferlin, cause muscular dystrophies in man. We compared 4 dysferlinopathic mouse strains: SJL/J and B10.SJL-Dysf(im)/AwaJ (B10.SJL), and A/J and B6.A-Dysf(prmd)/GeneJ (B6.A/J). The former but not the latter two are overtly myopathic and weaker at 3 months of age. Following repetitive large-strain injury (LSI) caused by lengthening contractions, all except B6.A/J showed ~40% loss in contractile torque. Three days later, torque in SJL/J, B10.SJL and controls, but not A/J, recovered nearly completely. B6.A/J showed ~30% torque loss post-LSI and more variable recovery. Pre-injury, all dysferlinopathic strains had more centrally nucleated fibers (CNFs) and all but A/J showed more inflammation than controls. At D3, all dysferlinopathic strains showed increased necrosis and inflammation, but not more CNFs; controls were unchanged. Dystrophin-null DMD(mdx) mice showed more necrosis and inflammation than all dysferlin-nulls. Torque loss and inflammation on D3 across all strains were linearly related to necrosis. Our results suggest that (1) dysferlin is not required for functional recovery 3 days after LSI; (2) B6.A/J mice recover from LSI erratically; (3) SJL/J and B10.SJL muscles recover rapidly, perhaps due to ongoing myopathy; (4) although they recover function to different levels, all 4 dysferlinopathic strains show increased inflammation and necrosis 3 days after LSI.

Topics: Animals; Disease Models, Animal; Dysferlin; Histocytochemistry; Inflammation; Macrophages; Membrane Proteins; Mice; Mice, Inbred Strains; Mice, Transgenic; Muscle Contraction; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Dystrophies, Limb-Girdle; Necrosis; Torque

We studied the response of dysferlin-null and control skeletal muscle to large- and small-strain injuries to the ankle dorsiflexors in mice. We measured contractile torque and counted fibers retaining 10-kDa fluorescein dextran, necrotic fibers, macrophages, and fibers with central nuclei and expressing developmental myosin heavy chain to assess contractile function, membrane resealing, necrosis, inflammation, and myogenesis. We also studied recovery after blunting myogenesis with X-irradiation. We report that dysferlin-null myofibers retain 10-kDa dextran for 3 days after large-strain injury but are lost thereafter, following necrosis and inflammation. Recovery of dysferlin-null muscle requires myogenesis, which delays the return of contractile function compared with controls, which recover from large-strain injury by repairing damaged myofibers without significant inflammation, necrosis, or myogenesis. Recovery of control and dysferlin-null muscles from small-strain injury involved inflammation and necrosis followed by myogenesis, all of which were more pronounced in the dysferlin-null muscles, which recovered more slowly. Both control and dysferlin-null muscles also retained 10-kDa dextran for 3 days after small-strain injury. We conclude that dysferlin-null myofibers can survive contraction-induced injury for at least 3 days but are subsequently eliminated by necrosis and inflammation. Myogenesis to replace lost fibers does not appear to be significantly compromised in dysferlin-null mice.

Topics: Animals; Cumulative Trauma Disorders; Dextrans; Disease Models, Animal; Dysferlin; Fluoresceins; Inflammation; Macrophages; Male; Membrane Proteins; Mice; Mice, Knockout; Muscle Contraction; Muscle Development; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Dystrophies, Limb-Girdle; Necrosis; Recovery of Function; Time Factors; Torque

To assess the biologic basis of massage therapies, we developed an experimental approach to mimic Swedish massage and evaluate this approach on recovery from eccentric exercise-induced muscle damage using a well-controlled animal model.. Tibialis anterior muscles of six New Zealand White rabbits were subjected to one bout of damaging, eccentric contractions. One muscle was immediately subjected to cyclic compressive loads, and the contralateral served as the exercised control.. We found that commencing 30 min of cyclic compressive loading to the muscle, immediately after a bout of eccentric exercise, facilitated recovery of function and attenuated leukocyte infiltration. In addition, fiber necrosis and wet weight of the tissue were also reduced by compressive loading.. We conclude that subjecting muscle to compressive loads immediately after exercise leads to an enhanced recovery of muscle function and attenuation of the damaging effects of inflammation in the rabbit model. Although these observations suggest that skeletal muscle responds to cyclic compressive forces similar to those generated by clinical approaches, such as therapeutic massage, further research is needed to assess the translational efficacy of these findings.

Topics: Adaptation, Physiological; Animals; Biomechanical Phenomena; Female; Inflammation; Lower Extremity; Massage; Models, Animal; Muscle, Skeletal; Physical Conditioning, Animal; Rabbits; Stress, Physiological; Torque

It has been reported that exercise with eccentric contractions can induce damage and inflammation in human muscle tissue, the severity of which depends on the duration and the intensity of exercise. Platelet activating factor (PAF) is a potent inflammatory mediator implicated in a series of pathophysiological conditions. We sought to investigate the relationship between PAF and eccentric exercise induced muscle damage. Thirteen healthy, recreationally active male subjects (27.5+/-3.78 year) performed 36 maximum voluntary eccentric contractions on a motorized muscle dynamometer using the elbow flexor muscles of the non-dominant arm. Venous blood samples were collected immediately before and after exercise at 2, 24, 48, 72 and 96 h. PAF was isolated, purified and determined by a platelet aggregation assay. Serum levels of creatine kinase (CK), lactate dehydrogenase (LDH), C-reactive protein (CRP) and complement C3 (C3), plasma level of fibrinogen and whole blood level of leukocytes (and their subsets) were determined. Established indicators of muscle damage as maximum isometric torque (MIT), range of motion (ROM), relaxed arm angle (RANG), flexed arm angle (FANG), arm circumference (CIRC) and muscle soreness were also measured at the same time points. PAF, leukocytes, CK and LDH were elevated after exercise, while other biochemical parameters such as CRP, C3 and fibrinogen were unchanged. We also observed an inverse association between PAF and MIT and ROM, as well as a positive association with other markers of muscle injury, i.e. CK, LDH, FANG and CIRC (all P's<0.05). Our findings may imply a role for PAF in the mechanism of eccentric exercise induced muscle damage.

Topics: Adult; C-Reactive Protein; Complement C3; Creatine Kinase; Elbow Joint; Exercise; Fibrinogen; Humans; Inflammation; L-Lactate Dehydrogenase; Leukocyte Count; Male; Muscle Contraction; Muscle, Skeletal; Platelet Activating Factor; Torque

Low-intensity pulsed ultrasound (LIPUS) has been shown to accelerate fracture healing in both animal models and clinical trials, but the mechanism of action remains unclear. In fracture healing, various consecutive cellular reactions occurred until repair. We investigated whether the advanced effects of LIPUS depended on the duration and timing of LIPUS treatment in a rat closed femoral fracture model to determine the target of LIPUS in the healing process. Sixty-nine Long-Evans male rats that have bilateral closed femoral fractures were used. The right femur was exposed to LIPUS (30 mW/cm2 spatial and temporal average [SATA], for 20 minutes/day), and the left femur was used as a control. Rats were divided into four groups according to timing and duration of treatment (Ph-1, days 1-8; Ph-2, days 9-16; Ph-3, days 17-24; throughout [T], days 1-24 after the fracture). Animals were killed on day 25. After radiographs and microfocus X-ray computed tomography (muCT) tomograms were taken, the hard callus area (HCA), bone mineral content (BMC) at the fracture site, and mechanical torsion properties were measured, and histological analysis was conducted. Interestingly, the maximum torque of the LIPUS-treated femur was significantly greater than that of the controls in all groups without any changes in HCA and BMC. The multiviewing of three-dimensional (3D) muCT reconstructions and histology supported our findings that the partial LIPUS treatment time was able to accelerate healing, but longer treatment was more effective. These results suggest that LIPUS acts on some cellular reactions involved in each phase of the healing process such as inflammatory reaction, angiogenesis, chondrogenesis, intramembranous ossification, endochondral ossification, and bone remodeling.

Topics: Animals; Bone Density; Bone Remodeling; Bony Callus; Femoral Fractures; Fracture Healing; Fractures, Closed; Imaging, Three-Dimensional; Inflammation; Male; Neovascularization, Physiologic; Osteogenesis; Pliability; Rats; Stress, Mechanical; Tomography, X-Ray Computed; Torque; Ultrasonic Therapy

The purpose of this study was to determine whether a post-exercise cryotherapy protocol could facilitate recovery of elbow flexor strength and reduce the severity of delayed onset muscle soreness following eccentric exercise. Eight resistance-trained males (23 +/- 3 yr) performed 64 eccentric elbow flexions with each arm. One arm was subjected to five, 20 minute immersions in a 5 +/- 1 degree C ice-water bath interspersed by 60 minute rest periods. The non-immersed arm served as the control. A main effect for time was observed for all dependent variables (p < 0.05). Isometric torque (mean SE) decreased from a pre-exercise value of 87.9 +/- 4.5 Nm to 65.2 +/- 4.5 Nm immediately post-exercise. Isokinetic torque at 60 and 300 degrees x s(-1) decreased from 71.0 +/- 3.5 NM and 48.4 +/- 2.8 Nm to 55.8 +/- 3.3 Nm and 39.8 +/- 3.1 Nm, respectively. All torque measures returned to pre-test levels by 72 h. Muscle soreness peaked 48 h post-exercise and was evident until 120 h. Limb volume increased by 200 +/- 18 ml immediately post-exercise (p < 0.05) but was not significantly elevated thereafter. No significant difference between the immersed and control arms were observed for any variable. The result suggest that the use of cryotherapy immediately following damaging eccentric exercise may not provide the same therapeutic benefits commonly attributed to cryotherapy following traumatic muscle injury.

Topics: Adult; Analysis of Variance; Arm; Cryotherapy; Exercise; Exercise Test; Humans; Ice; Inflammation; Male; Muscle, Skeletal; Pain; Torque

Exercise-induced muscle damage is characterized by histological changes, like Z-line streaming, inflammatory response and decreased muscle function reflected in a prolonged decline in maximal isometric muscle strength after eccentric work. It is assumed that force decrement is mainly related to the amount of structural damage. However, the relationship between number of eccentric contractions, magnitude of structural damage and force decrement is not very well documented. Therefore we studied the effect of an increasing number of both isometric and eccentric (forced lengthening) contractions on histological parameters of muscle damage and maximal isometric force in an experimental in situ rat model. Tibialis anterior muscles of male Wistar rats were subjected to an increasing number of either isometric or eccentric contractions and were examined for histological markers of muscle damage. The present study shows that muscle damage increases progressively with the number of forced lengthening contractions. Maximal isometric torque was found to decline after both types of exercise. However, the decline after forced lengthening exercise was more pronounced. Only a weak relationship between percentage of histological muscle damage and isometric torque after forced lengthening contractions was found. The findings of the present study suggest that the decline in muscle force after eccentric exercise may partly be attributed to other factors than structural damage.

Topics: Analysis of Variance; Animals; Electric Stimulation; Hindlimb; Inflammation; Isometric Contraction; Male; Muscle Fatigue; Muscle, Skeletal; Peroneal Nerve; Physical Exertion; Rats; Rats, Wistar; Regression Analysis; Torque