Administration of TGF-ß Inhibitor Mitigates Radiation-induced Fibrosis in a Mouse Model.

BACKGROUND: Radiation-induced fibrosis is a long-term adverse effect of external beam radiation therapy for cancer treatment that can cause pain, loss of function, and decreased quality of life. Transforming growth factor beta (TGF-ß) is believed to be critical to the development of radiation-induced fibrosis, and TGF-ß inhibition decreases the development of fibrosis. However, no treatment exists to prevent radiation-induced fibrosis. Therefore, we aimed to mitigate the development of radiation-induced fibrosis in a mouse model by inhibiting TGF-ß. QUESTION/PURPOSES: Does TGF-ß inhibition decrease the development of muscle fibrosis induced by external beam radiation in a mouse model? METHODS: Twenty-eight 12-week-old male C57BL/6 mice were assigned randomly to three groups: irradiated mice treated with TGF-ßi, irradiated mice treated with placebo, and control mice that received neither irradiation nor treatment. The irradiated mice received one 50-Gy fraction of radiation to the right hindlimb before treatment initiation. Mice treated with TGF-c (n = 10) received daily intraperitoneal injections of a small-molecule inhibitor of TGF-ß (1 mg/kg) in a dimethyl sulfoxide vehicle for 8 weeks (seven survived to histologic analysis). Mice treated with placebo (n = 10) received daily intraperitoneal injections of only a dimethyl sulfoxide vehicle for 8 weeks (10 survived to histologic analysis). Control mice (n = 8) received neither radiation nor TGF-ß treatment. Control mice were euthanized at 3 months because they were not expected to exhibit any changes related to treatment. Mice in the two treatment groups were euthanized 9 months after radiation, and the quadriceps of each thigh was sampled. Masson's trichome stain was used to assess muscle fibrosis. Slides were viewed at 10 × magnification using bright-field microscopy, and in a blinded fashion, five representative images per mouse were used to quantify fibrosis. The mean ± SD fibrosis pixel densities in the TGF-ßi and radiation-only groups were compared using Mann-Whitney U tests. The ratio of fibrosis to muscle was calculated using the mean fibrosis per slide in the TGF-ßi group to standardize measurements. Alpha was set at 0.05. RESULTS: The mean (± SD) percentage of fibrosis per slide was greater in the radiation-only group (1.2% ± 0.42%) than in the TGF-ßi group (0.14% ± 0.09%) (odds ratio 0.12 [95% CI 0.07 to 0.20]; p < 0.001). Among control mice, mean fibrosis was 0.05% ± 0.02% per slide. Mice in the radiation-only group had 9.1 times the density of fibrosis as did mice in the TGF-ßi group. CONCLUSION: Our study provides preliminary evidence that the fibrosis associated with radiation therapy to a quadriceps muscle can be reduced by treatment with a TGF-ß inhibitor in a mouse model. CLINICAL RELEVANCE: If these observations are substantiated by further investigation into the role of TGF-ß inhibition on the development of radiation-induced fibrosis in larger animal models and humans, our results may aid in the development of novel therapies to mitigate this complication of radiation treatment.

Thermographic response resulting from strength training: A preliminary study

INTRODUCTION: Exercise induces modifications in thermal homeostasis. The type of exercise may have a specific impact on skin temperature (Tsk). OBJECTIVE: To analyze and compare the behavior of Tsk in a resistance training between men and women and monitor the thermal recovery response. MATERIAL AND METHODS: Sixteen male and female adults (24.56±3.22 years old) underwent a resistance circuit training session. They performed 3 sets of 12 repetitions with 70-80% 1 RM for lat pulldown, leg press, and biceps arm curl exercises. Thermograms were taken in anterior and posterior body view at rest, 20min, and 24h after training. Tsk was measured in the body regions of interest corresponding to the brachial biceps, quadriceps, and upper back. ANOVA with Tukey's post hoc test was used to analyze Tsk changes among moments, and independent samples t-test was used to compare Tsk between males and females. RESULTS: At rest, women showed Tsk significantly lower than men. There was no significant Tsk change 20min after exercise. However, Tsk increased 24h after exercise in the upper back for men compared with baseline and in quadriceps for women compared with baseline and 20min after exercise (p < 0.05). CONCLUSION: The Tsk of women at rest is lower than that of men. A resistance circuit training session does not significantly change Tsk 20min after exercise, but it increases Tsk 24h after training in the upper back for men and quadriceps for women

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Low-Intensity Electrical Stimulation to Improve the Neurological Aspect of Weakness in Individuals with Chronic Anterior Cruciate Ligament Lesion.

PURPOSE: This study is aimed at investigating the effect of low-intensity electrical stimulation on the voluntary activation level (VA) and the cortical facilitation/inhibition of quadriceps in people with chronic anterior cruciate ligament lesion. METHODS: Twenty former athletes with unilateral ACL deficiencies (ACL group) and 20 healthy subjects (healthy control group) participated in the study. The quadriceps VA level, motor-evoked potential (MEP), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) elicited by transcranial magnetic stimulation were tested before and after 30 minutes of low-intensity electrical stimulation (ES). RESULTS: Before ES, the quadriceps VA in the ACL lesion legs of the ACL group was lower compared to the legs of the healthy control group (P < 0.05). The MEP sizes in the ACL lesion legs and the healthy control were not significantly different. The ACL lesion legs showed lower SICI and higher ICF compared to the healthy control group (P < 0.05). After ES, the quadriceps VA level increased and the SICI-ICF was modulated only in the ACL lesion legs (P < 0.05) but not in the healthy controls. CONCLUSIONS: Low-intensity ES can normalize the modulation of intracortical inhibition and facilitation, thereby ameliorating the activation failure in individuals with ACL lesion.

Immediate responses of multi-focal low level laser therapy on quadriceps in knee osteoarthritis patients.

Low-level laser therapy (LLLT) applying on knee osteoarthritis (OA) patients has shown positive outcomes in analgesic effect and functional recovery. However, few studies applied such therapy on large area of quadriceps muscle in these patients. The aim of this study was to evaluate immediate effect of multi-focal LLLT on quadriceps of knee OA patients in pain and functional performance. Fifty-one participants with knee OA were enrolled and evaluated before (T1) and immediately after intervention (T2) by knee joint pain in numeric rating scale (NRS), walking speed, timed five-chair stands, and quadriceps strength by isokinetic dynamometer. Intervention with two multi-focal Gallium-Aluminum-Arsenide laser devices, each device with 36 laser diodes (wavelength 808 ± 10 nm, continuous, mean power 50 mW, 30 minutes), applied simultaneously over bilateral quadriceps with a total dose of 180 J for each thigh. The multi-focal LLLT significantly improved knee joint pain as measured by the NRS (54% reduction), timed five-chair stands, and walking speed (P < .05). Knee extensor strength also increased in terms of peak torque and force of concentric and eccentric contraction as measured by isokinetic dynamometer (P < .05). In conclusion, single-session multi-focal LLLT on quadriceps in knee OA patients has immediate beneficial effect on knee pain reduction, quadriceps strengthening and functional performance recovery. Long-term effect requires further investigation. Multi-focal LLLT on quadriceps might serve as an alternative non-invasive treatment option in these patients.

Radiation-induced muscle fibrosis rat model: establishment and valuation.

BACKGROUND: Lack of animal model of radiation induced muscle fibrosis, this study aimed to establish such a model by using 90 Gy single dose irradiation to mimic clinical relevance and also to explore the potential post-irradiation regenerative mechanism. METHODS: SD rats were randomly divided into dose investigation groups and time gradient groups. Group1-6 were irradiated with a single dose of 65Gy, 70Gy, 75Gy, 80Gy, 85Gy and 90Gy respectively, and the degree of rectus femoris fibrosis in the irradiated area was detected at 4 weeks after irradiation. Group 7-9 were irradiated with a single dose of 90Gy, and the results were detected 1, 2, 4, and 8 weeks after irradiation. Then the general condition of rats was recorded. Masson staining was used to detect muscle fibrosis. The ultrastructure of muscles was observed by electron microscope, and the expression changes of satellite cell proliferation and differentiation related genes were detected by quantitative real-time-PCR. RESULTS: A single dose of 90Gy irradiation could cause muscle fibrosis in rats. As time goes on, the severity of muscle fibrosis and the expression of TGF- ß1 increased. Significant swelling of mitochondria, myofilament disarrangement and dissolution, obvious endothelial cell swelling, increased vascular permeability, decrease of blood cell, deposition of fibrosis tissue around the vessel could be found compared with the control group. At around the 4th week, the expressions of Pax7, Myf5, MyoD, MyoG, Mrf4 increased. CONCLUSION: Irradiation of 90Gy can successfully establish the rat model of radiation-induced muscle fibrosis. This model demonstrated that regenerative process was initiated by the irradiation only at an early stage, which can serve a suitable model for investigating regenerative therapy for post-radiation muscle fibrosis.

Effects of Ablation (Radio Frequency, Cryo, Microwave) on Physiologic Properties of the Human Vastus Lateralis.

OBJECTIVE: Ablative treatments can sometimes cause collateral injury to surrounding muscular tissue, with important clinical implications. In this study, we investigated the changes in muscle physiology of the human vastus lateralis when exposed to three different ablation modalities: radiofrequency ablation, cryoablation, and microwave ablation. METHODS: We obtained fresh vastus lateralis tissue biopsy specimens from nine patients (age range: 29-73 years) who were undergoing in vitro contracture testing for malignant hyperthermia. Using leftover waste tissue, we prepared 46 muscle bundles that were utilized in tissue baths before and after ablation. RESULTS: After ablation with all the three modalities, we noted dose-dependent sustained reductions in peak force (strength of contraction), as well as transient increases in baseline force (resting muscle tension). But, over the subsequent 3-h recovery period, peak force improved and the baseline force consistently recovered to below its preablation levels. CONCLUSION: The novel in vitro methodologies we developed to investigate changes in muscle physiology after ablation can be used to study a spectrum of ablation modalities and also to make head-to-head comparisons of different ablation modalities. SIGNIFICANCE: As the role of ablative treatments continues to expand, our findings provide unique insights into the resulting changes in muscle physiology. These insights could enhance the safety and efficacy of ablations and help individuals design and develop novel medical devices.

Improvement of Performance and Reduction of Fatigue With Low-Level Laser Therapy in Competitive Cyclists.

Evidence indicates that low-level laser therapy (LLLT) minimizes fatigue effects on muscle performance. However, the ideal LLLT dosage to improve athletes'performance during sports activities such as cycling is still unclear. Therefore, the goal of this study was to investigate the effects of different LLLT dosages on cyclists'performance in time-to-exhaustion tests. In addition, the effects of LLLT on the frequency content of the EMG signals to assess fatigue mechanisms were examined. Twenty male competitive cyclists participated in a crossover, randomized, double-blind, placebo-controlled trial. They performed an incremental cycling test to exhaustion (on day 1) followed by 4 time-to-exhaustion tests (on days 2-5) at their individual maximal power output. Before each time-to-exhaustion test, different dosages of LLLT (135, 270, and 405 J/thigh, respectively) or placebo were applied at the quadriceps muscle bilaterally. Power output and muscle activation from both lower limbs were recorded throughout the tests. Increased performance in time-to-exhaustion tests was observed with the LLLT-135 J (∼22 s; P < .01), LLLT-270 J (∼13 s; P = .03), and LLLT-405 J (∼13 s; P = .02) compared to placebo (149 ± 23 s). Although LLLT-270 J and LLLT-405 J did not show significant differences in muscle activation compared with placebo, LLLT-135 J led to an increased high-frequency content compared with placebo in both limbs at the end of the exhaustion test (P ≤ .03). In conclusion, LLLT increased time to exhaustion in competitive cyclists, suggesting this intervention as a possible nonpharmacological ergogenic agent in cycling. Among the different dosages, LLLT-135 J seems to promote the best effects.

Effects of low-level laser therapy applied before or after plyometric exercise on muscle damage markers: randomized, double-blind, placebo-controlled trial.

Promising effects of phototherapy on markers of exercise-induced muscle damage has been already demonstrated in constant load or isokinetic protocols. However, its effects on more functional situations, such as plyometric exercises, and when is the best moment to apply this treatment (pre- or post-exercise) remain unclear. Therefore, the purpose of this study was to investigate the effect of low-level laser therapy (LLLT) before or after plyometric exercise on quadriceps muscle damage markers. A randomized, double-blinded, placebo-controlled trial was conducted with 24 healthy men, 12 at pre-exercise treatment group and 12 at post-exercise treatment group. Placebo and LLLT (810 nm, 200 mW per diode, 6 J per diode, 240 J per leg) were randomly applied on right/left knee extensor muscles of each volunteer before/after a plyometric exercise protocol. Muscular echo intensity (ultrasonography images), soreness (visual analogue scale - VAS), and strength impairment (maximal voluntary contraction - MVC) were assessed at baseline, 24, 48, and 72 h post-exercise. Legs treated with LLLT before or after exercise presented significantly smaller increments of echo intensity (values up to 1 %) compared to placebo treatments (increased up to ∼7 %). No significant treatment effect was found for VAS and MVC, although a trend toward better results on LLLT legs have been found for VAS (mean values up to 30 % lesser than placebo leg). In conclusion, LLLT applied before or after plyometric exercise reduces the muscle echo intensity response and possibly attenuates the muscle soreness. However, these positive results were not observed on strength impairment.

Effects of photobiomodulation on the fatigue level in elderly women: an isokinetic dynamometry evaluation.

Aging is responsible by a series of morphological and functional modifications that lead to a decline of muscle function, particularly in females. Muscle tissue in elderly people is more susceptible to fatigue and, consequently, to an increased inability to maintain strength and motor control. In this context, therapeutic approaches able of attenuating muscle fatigue have been investigated. Among these, the photobiomodulation demonstrate positive results to interacts with biological tissues, promoting the increase in cell energy production. Thus, the aim of this study was to investigate the effects of photobiomodulation (808 nm, 250 J/cm(2), 100 mW, 7 J each point) in the fatigue level and muscle performance in elderly women. Thirty subjects entered a crossover randomized double-blinded placebo-controlled trial. Photobiomodulation was delivered on the rectus femoris muscle of the dominant limb immediately before the fatigue protocol. In both sessions, peripheral muscle fatigue was analyzed by surface electromyography (EMG) and blood lactate analysis. Muscle performance was evaluated using an isokinetic dynamometer. The results showed that photobiomodulation was able of reducing muscle fatigue by a significant increase of electromyographic fatigue index (EFI) (p = 0.047) and decreasing significantly lactate concentration 6 min after the performance of the fatigue protocol (p = 0. 0006) compared the placebo laser session. However, the photobiomodulation was not able of increasing muscle performance measured by the isokinetic dynamometer. Thus, it can be conclude that the photobiomodulation was effective in reducing fatigue levels. However, no effects of photobiomodulation on muscle performance was observed.

Immediate effects of low-intensity laser (808 nm) on fatigue and strength of spastic muscle.

The cerebrovascular accident (CVA), high-impact disease II, affects the basic functions of the limbs, leading to changes of sensory, language, and motor functions. The search for resources that minimize the damage caused by this disease grows every day. The clinical use of low-intensity laser therapy (LILT) has provided major breakthroughs in the treatment of muscular disorders and prevention of muscle fatigue. Thus, the objective of the present study is to analyze the answers and immediate adaptations of the rectus femoris and vastus medialis of spastic hemiparetic patients, facing the increase in peak torque and triggering muscle fatigue, after application of LILT. Double-blind clinical trials were conducted with 15 volunteers post-CVA with spasticity, of both genders, between 40 and 80 years old. To this end, the volunteers went through three consecutive stages of rating (control, placebo, and laser). All performed tests of isometric contraction on the patient's hemiparetic side. Significant differences were observed with regard to the increase in muscle performance (p = 0.0043) and the reduction in blood lactate concentration (p < 0.0001) of the post-LILT muscles. The LILT (diode laser, l100 mW 808 nm, 4.77 J/cm(2)/point, 40 s/AP) can be employed during and after spastic muscle-strengthening exercises, contributing to the improvement of motor function of the patient. After application of LILT, we found increased torque as well as decreased in lactate level in patients with spasticity.

Phototherapy in skeletal muscle performance and recovery after exercise: effect of combination of super-pulsed laser and light-emitting diodes.

Recent studies with phototherapy have shown positive results in enhancement of performance and improvement of recovery when applied before exercise. However, several factors still remain unknown such as therapeutic windows, optimal treatment parameters, and effects of combination of different light sources (laser and LEDs). The aim of this study was to evaluate the effects of phototherapy with the combination of different light sources on skeletal muscle performance and post-exercise recovery, and to establish the optimal energy dose. A randomized, double-blinded, placebo-controlled trial with participation of 40 male healthy untrained volunteers was performed. A single phototherapy intervention was performed immediately after pre-exercise (baseline) maximum voluntary contraction (MVC) with a cluster of 12 diodes (4 of 905 nm lasers-0.3125 mW each, 4 of 875 nm LEDs-17.5 mW each, and 4 of 670 nm LEDs-15 mW each- manufactured by Multi Radiance Medical™) and dose of 10, 30, and 50 J or placebo in six sites of quadriceps. MVC, delayed onset muscle soreness (DOMS), and creatine kinase (CK) activity were analyzed. Assessments were performed before, 1 min, 1, 24, 48, 72, and 96 h after eccentric exercise protocol employed to induce fatigue. Phototherapy increased (p < 0.05) MVC was compared to placebo from immediately after to 96 h after exercise with 10 or 30 J doses (better results with 30 J dose). DOMS was significantly decreased compared to placebo (p < 0.05) with 30 J dose from 24 to 96 h after exercise, and with 50 J dose from immediately after to 96 h after exercise. CK activity was significantly decreased (p < 0.05) compared to placebo with all phototherapy doses from 1 to 96 h after exercise (except for 50 J dose at 96 h). Pre-exercise phototherapy with combination of low-level laser and LEDs, mainly with 30 J dose, significantly increases performance, decreases DOMS, and improves biochemical marker related to skeletal muscle damage.

Effects of pre- or post-exercise low-level laser therapy (830 nm) on skeletal muscle fatigue and biochemical markers of recovery in humans: double-blind placebo-controlled trial.

OBJECTIVES: The purpose of this study was to investigate the effect of low-level laser therapy (LLLT) before and after exercise on quadriceps muscle performance, and to evaluate the changes in serum lactate and creatine kinase (CK) levels. METHODS: The study was randomized, double blind, and placebo controlled. PATIENTS: A sample of 27 healthy volunteers (male soccer players) were divided into three groups: placebo, pre-fatigue laser, and post-fatigue laser. The experiment was performed in two sessions, with a 1 week interval between them. Subjects performed two sessions of stretching followed by blood collection (measurement of lactate and CK) at baseline and after fatigue of the quadriceps by leg extension. LLLT was applied to the femoral quadriceps muscle using an infrared laser device (830 nm), 0.0028 cm(2) beam area, six 60 mW diodes, energy of 0.6 J per diode (total energy to each limb 25.2 J (50.4 J total), energy density 214.28 J/cm(2), 21.42 W/cm(2) power density, 70 sec per leg. We measured the time to fatigue and number and maximum load (RM) of repetitions tolerated. Number of repetitions and time until fatigue were primary outcomes, secondary outcomes included serum lactate levels (measured before and 5, 10, and 15 min after exercise), and CK levels (measured before and 5 min after exercise). RESULTS: The number of repetitions (p=0.8965), RM (p=0.9915), and duration of fatigue (p=0.8424) were similar among the groups. Post-fatigue laser treatment significantly decreased the serum lactate concentration relative to placebo treatment (p<0.01) and also within the group over time (after 5 min vs. after 10 and 15 min, p<0.05 both). The CK level was lower in the post-fatigue laser group (p<0.01). CONCLUSIONS: Laser application either before or after fatigue reduced the post-fatigue concentrations of serum lactate and CK. The results were more pronounced in the post-fatigue laser group.

Acute effects of light emitting diodes therapy (LEDT) in muscle function during isometric exercise in patients with chronic obstructive pulmonary disease: preliminary results of a randomized controlled trial.

Patients with chronic obstructive pulmonary disease (COPD) are susceptible to early muscle fatigue. Light-emitting diodes therapy (LEDT) has been used to minimize muscle fatigue in athletes and healthy subjects. The aim of this study is to investigate the acute effects of LEDT on muscle fatigue and perception of effort in patients with COPD during isometric endurance test of the quadriceps femoris (QF). Ten patients (VEF1 50 ± 13% of predicted) underwent a single LEDT and sham application, 48 h apart, in a randomized crossover design. The LEDT and sham were applied in three localized areas of the QF (rectus femoris, vastus lateralis, and vastus medialis). Before and after exposure to LEDT and sham, the patients performed an isometric endurance test (60 % of the maximum voluntary isometric contraction), until the limit of tolerance concomitant to surface electromyography recording (median frequency as mean outcome). The slope obtained from linear regression analysis of the median frequency (MF) over endurance time was also used as an endurance index. Endurance time increased significantly after exposure to LEDT (from 26 ± 2 to 53 ± 5 s) as compared to sham (from 23 ± 3 to 30 ± 4 s) (F = 64, P = 0.0001). A greater decline in MF was observed during isometric endurance test after sham, compared to LEDT (F = 14.6, P = 0.004). The slope of the MF over time was lower post-LEDT compared to post-sham (-0.7 ± 0.3 vs. -1.5 ± 0.8; P = 0.004). The dyspnea score corrected for endurance time was lower post-LEDT (P = 0.008) but similar for fatigue both post-LEDT and post-sham. A single application of LEDT minimizes muscle fatigue and increases isometric endurance time.

Effects of low level laser therapy (808 nm) on physical strength training in humans.

Recent studies have investigated whether low level laser therapy (LLLT) can optimize human muscle performance in physical exercise. This study tested the effect of LLLT on muscle performance in physical strength training in humans compared with strength training only. The study involved 36 men (20.8±2.2 years old), clinically healthy, with a beginner and/or moderate physical activity training pattern. The subjects were randomly distributed into three groups: TLG (training with LLLT), TG (training only) and CG (control). The training for TG and TLG subjects involved the leg-press exercise with a load equal to 80% of one repetition maximum (1RM) in the leg-press test over 12 consecutive weeks. The LLLT was applied to the quadriceps muscle of both lower limbs of the TLG subjects immediately after the end of each training session. Using an infrared laser device (808 nm) with six diodes of 60 mW each a total energy of 50.4 J of LLLT was administered over 140 s. Muscle strength was assessed using the 1RM leg-press test and the isokinetic dynamometer test. The muscle volume of the thigh of the dominant limb was assessed by thigh perimetry. The TLG subjects showed an increase of 55% in the 1RM leg-press test, which was significantly higher than the increases in the TG subjects (26%, P = 0.033) and in the CG subjects (0.27%, P < 0.001). The TLG was the only group to show an increase in muscle performance in the isokinetic dynamometry test compared with baseline. The increases in thigh perimeter in the TLG subjects and TG subjects were not significantly different (4.52% and 2.75%, respectively; P = 0.775). Strength training associated with LLLT can increase muscle performance compared with strength training only.

A comparison of monopolar and bipolar recording techniques for examining the patterns of responses for electromyographic amplitude and mean power frequency versus isometric torque for the vastus lateralis muscle.

The purpose of the present study was to compare monopolar and bipolar recording techniques for the patterns of responses and mean values for absolute and normalized electromyographic (EMG) amplitude and mean power frequency (MPF) versus isometric torque for the vastus lateralis muscle. Ten healthy men (mean+/-S.D. age=23.6+/-3.0 years; body weight=80.9+/-15.6 kg) volunteered to perform submaximal to maximal isometric muscle actions of the dominant leg extensors. Monopolar and bipolar surface EMG signals were detected simultaneously from the vastus lateralis with an eight-channel linear electrode array. The results indicated that in 70-80% of the cases, monopolar and bipolar recording techniques resulted in the same patterns of responses for absolute and normalized EMG amplitude and MPF versus isometric torque. There were, however, differences between the two techniques for mean absolute EMG amplitude and MPF values, but not for the normalized values. Thus, these results supported the practice of normalization, and suggested that comparisons can be made between monopolar and bipolar recording methods for the patterns of responses and mean values for normalized (but not absolute) EMG amplitude and MPF versus isometric torque.