Effects of photobiomodulation applied at different times on functional performance and ergogenic response of rugby athletes: Randomized clinical trial.

BACKGROUND: Photobiomodulation (PBM) is indicated to accelerate the recovery of athletes and reduce muscle damage caused by physical exercise. The objective of this study was to establish the best time to apply photobiomodulation to increase the functional performance and ergogenic response of rugby athletes. METHODS: Randomized crossover clinical trial with 18 rugby athletes of both sexes. The interventions were carried out from January to May 2019. The blood levels of creatine kinase (CK) and lactate, and performance in the Modified Star Excursion Balance Test, Single Hop Test, Triple Hop Test, Bangsbo Sprint test (BST), and Yo-Yo intermittent recovery level 1 (YoyoIR1) were evaluated. The athletes underwent two blocks of exercises with the BST and Yoyo-IR1, as well as the random application of four interventions: without application of photobiomodulation (CO), pre-exercise photobiomodulation (PBpre), PBM during the exercise interval (PBint), or post-exercise photobiomodulation (PBpos). The photobiomodulation using light-emitting diodes (850 nm, 8 J/cm2) lasted 10 min and was applied to the quadriceps, hamstrings, and triceps surae muscles. The results were compared between groups and times, and the effect size for the interventions was established. RESULTS: No differences were found between groups in CK, lactate, and performance in the functional tests between groups and times. Only the PBpre presented improved performance in the first Yoyo-1R1 test (p < 0.01), while the PBint improved in the second Yoyo-IR1 test and BST (p < 0.05). CONCLUSION: The PBM did not change muscle damage markers or performance in the functional tests. For an ergogenic response, photobiomodulation applied before exercise improves performance, which can be maintained when PBM is performed in the exercise interval.

Can pre-exercise photobiomodulation improve muscle endurance and promote recovery from muscle strength and injuries in people with different activity levels? A meta-analysis of randomized controlled trials.

Photobiomodulation therapy (PBMT) was introduced as an ergogenic aid for sport performance in healthy individuals is still controversial. The main aim of this study is to assess the potential enhancements in muscle endurance and recovery from muscle strength and injuries mediated by PBMT among individuals exhibiting diverse activity levels. Randomized controlled trials (RCT) of PBMT interventions for healthy people (both trained and untrained individuals) exercising were searched (up to January 16, 2024) in four electronic databases: Web of Science, PubMed, Scopus and Embase. Primary outcome measures included muscle endurance, muscle strength and creatine kinase (CK) levels; secondary outcome measure included Lactate dehydrogenase (LDH) levels. Subgroup analyses based on physical activity levels were conducted for each outcome measure. Thirty-four RCTs were included based on the article inclusion and exclusion criteria. Statistical results showed that PBMT significantly improved muscle endurance (standardized mean difference [SMD] = 0.31, 95%CI 0.11, 0.51, p < 0.01), indicating a moderate effect size. It also facilitated the recovery of muscle strength (SMD = 0.24, 95%CI 0.10, 0.39, p < 0.01) and CK (mean difference [MD] = -77.56, 95%CI -112.67, -42.44, p < 0.01), indicating moderate and large effect sizes, respectively. Furthermore, pre-application of PBMT significantly improved muscle endurance, recovery of muscle strength and injuries in physically inactive individuals and athletes (p < 0.05), while there was no significant benefit for physically active individuals. Pre-application of PBMT improves muscle endurance and promotes recovery from muscle strength and injury (includes CK and LDH) in athletes and sedentary populations, indicating moderate to large effect sizes, but is ineffective in physically active populations. This may be due to the fact that physically active people engage in more resistance training, which leads to a decrease in the proportion of red muscle fibres, thus affecting photobiomodulation.

Acute dose-response effect of photobiomodulation therapy on 5-km running performance in trained runners: a randomized, double-blind, placebo-controlled, crossover study.

Photobiomodulation therapy (PBMT) has been advocated as a potential intervention to improve muscle performance and recovery in the health and sports context. However, the short- and long-term effects of PBMT on endurance running performance remain under-researched and controversial. The purpose of this study was to investigate the acute dose-response effect of PBMT with light-emitting diodes (LEDs) on endurance performance and rating of perceived exertion (RPE; 6-20 Borg) during a 5-km running trial in recreational runners. In a crossover design, eighteen young adult runners (28.7 ± 7.8 years) were randomized to receive 1 of 4 PBMT conditions (placebo, 300, 900, and 1260 Joules [J]) 60 min before the 5-km running trial on four occasions, separated by a 2-wk washout period. The treatments were applied to the quadriceps, hamstrings, and gastrocnemius muscles of both legs using a device containing 200 LEDs (100 red and 100 infrared). The following variables were assessed: endurance performance (i.e. total time, mean velocity, and velocity in the split distances at the initial 200 m and every 400 m lap) and RPE in the split distances at the initial 200 m and every 400 m lap. Data normality and homogeneity were tested using Shapiro-Wilk's and Levene's tests, respectively. Differences between treatment conditions were assessed using the analysis of variance tests (one- or two-way ANOVA, depending on the comparisons), complemented by the Bonferroni post hoc test. There were significant time effects for the running velocity and RPE in the split distances (p < 0.0001), with no significant treatment-by-time interaction (running velocity, p = 0.59; RPE, p = 0.95). The mean velocity (p = 0.997), total time (p = 0.998), and total mean of the RPE (p = 0.91) were similar between treatment conditions. In conclusion, acute PBMT with LEDs at doses of 300, 900, and 1260 J is not recommended for improving endurance performance and RPE in the 5-km running trial in recreational runners.

Preventive and therapeutic vascular photobiomodulation decreases the inflammatory markers and enhances the muscle repair process in an animal model.

Photobiomodulation therapy (PBM) has shown positive effects when applied locally to modulate the inflammatory process and facilitate muscle repair. However, the available literature on the mechanisms of action of vascular photobiomodulation (VPBM), a non-invasive method of vascular irradiation, specifically in the context of local muscle repair, is limited. Thus, this study aimed to assess the impact of vascular photobiomodulation (VPBM) using a low-level laser (LLL) on the inflammatory response and the process of skeletal muscle repair whether administered prior to or following cryoinjury-induced acute muscle damage in the tibialis anterior (TA) muscles. Wistar rats (n = 85) were organized into the following experimental groups: (1) Control (n = 5); (2) Non-Injury + VPBM (n = 20); (3) Injured (n = 20); (4) Pre-VPBM + Injury (n = 20); (5) Injury + Post-VPBM (n = 20). VPBM was administered over the vein/artery at the base of the animals' tails (wavelength: 780 nm; power: 40 mW; application area: 0.04 cm2; energy density: 80 J/cm2). Euthanasia of the animals was carried out at 1, 2, 5, and 7 days after inducing the injuries. Tibialis anterior (TA) muscles were collected for both qualitative and quantitative histological analysis using H&E staining and for assessing protein expression of TNF-α, MCP-1, IL-1ß, and IL-6 via ELISA. Blood samples were collected and analyzed using an automatic hematological analyzer and a leukocyte differential counter. Data were subjected to statistical analysis (ANOVA/Tukey). The results revealed that applying VPBM prior to injury led to an increase in circulating neutrophils (granulocytes) after 1 day and a subsequent increase in monocytes after 2 and 5 days, compared to the Non-Injury + VPBM and Injured groups. Notably, an increase in erythrocytes and hemoglobin concentration was observed in the Non-Injury + VPBM group on days 1 and 2 in comparison to the Injured group. In terms of histological aspects, only the Prior VPBM + Injured group exhibited a reduction in the number of inflammatory cells after 1, 5, and 7 days, along with an increase in blood vessels at 5 days. Both the Prior VPBM + Injured and Injured + VPBM after groups displayed a decrease in myonecrosis at 1, 2, and 7 days, an increase in newly-formed and immature fibers after 5 and 7 days, and neovascularization after 1, 2, and 7 days. Regarding protein expression, there was an increase in MCP-1 after 1 and 5 days, TNF-α, IL-6, and IL-1ß after 1, 2, and 5 days in the Injured + VPBM after group when compared to the other experimental groups. The Prior VPBM + Injured group exhibited increased MCP-1 production after 2 days, in comparison to the Non-Injury + VPBM and Control groups. Notably, on day 7, the Injured group continued to show elevated MCP-1 protein expression when compared to the VPBM groups. In conclusion, VPBM effectively modulated hematological parameters, circulating leukocytes, the protein expression of the chemokine MCP-1, and the proinflammatory cytokines TNF-α and IL-1ß, ultimately influencing the inflammatory process. This modulation resulted in a reduction of myonecrosis, restoration of tissue architecture, increased formation of newly and immature muscle fibers, and enhanced neovascularization, with more pronounced effects when VPBM was applied prior to the muscle injury.

Photobiomodulation therapy moderates cancer cachexia-associated muscle wasting through activating PI3K/AKT/FoxO3a pathway.

Cancer cachexia-associated muscle wasting as a multifactorial wasting syndrome, is an important factor affecting the long-term survival rate of tumor patients. Photobiomodulation therapy (PBMT) has emerged as a promising tool to cure and prevent many diseases. However, the effect of PBMT on skeletal muscle atrophy during cancer progression has not been fully demonstrated yet. Here, we found PBMT alleviated the atrophy of myotube diameter induced by cancer cells in vitro, and prevented cancer-associated muscle atrophy in mice bearing tumor. Mechanistically, the alleviation of muscle wasting by PBMT was found to be involved in inhibiting E3 ubiquitin ligases MAFbx and MuRF-1. In addition, transcriptomic analysis using RNA-seq and GSEA revealed that PI3K/AKT pathway might be involved in PBMT-prevented muscle cachexia. Next, we showed the protective effect of PBMT against muscle cachexia was totally blocked by AKT inhibitor in vitro and in vivo. Moreover, PBMT-activated AKT promoted FoxO3a phosphorylation and thus inhibiting the nucleus entry of FoxO3a. Lastly, in cisplatin-treated muscle cachexia model, PBMT had also been shown to ameliorate muscle atrophy through enhancing PI3K/AKT pathway to suppress MAFbx and MuRF-1 expression. These novel findings revealed that PBMT could be a promising therapeutic approach in treating muscle cachexia induced by cancer.

Photobiomodulation therapy (red/NIR LEDs) reduced the length of stay in intensive care unit and improved muscle function: A randomized, triple-blind, and sham-controlled trial.

CONTEXT: Photobiomodulation therapy (PBMT) has been widely used to improve strength, fatigue resistance and increase muscle mass in healthy individuals. These effects could help critically ill patients admitted to intensive care units (ICUs) who show reduced mobility and muscle strength. ICU-acquired weakness lessens overall health and increases the patient's length of stay in the ICU. OBJECTIVE: This study evaluated the effects of PBMT using low intensity light-emitting diodes (LEDs) on the mobility and muscle strength (functional capacity) and length of stay of patients admitted to hospital ICU. METHODS: This randomized, triple-blind, sham-controlled trial was conducted in a hospital ICU. Sixty patients were randomly assigned to two equal groups: (a) PBMT and (b) Sham. PBMT was applied daily to patients until their discharge from the ICU, using a flexible neoprene array of 264 LEDs (120 at 635 nm, 1.2 mW each; 144 at 880 nm, 15 mW each) for 90s (207.36 Joules) at each site. Ten sites were located bilaterally on the thighs, legs, arms, and forearms ventrally and dorsally, 15 min totaling 2,073.6 Joules per session. Outcomes were length of stay (in h) until discharge from the ICU, muscle strength by the Medical Research Council (MRC) score and handgrip dynamometry (HGD), patient mobility by Intensive Care Unit Mobility Scale (IMS) and the Simplified Acute Physiology Score 3 (SAPS 3) for predicting mortality of patients admitted to the ICU. RESULTS: PBMT reduced the average length of stay in the ICU by ~30% (p = 0.028); increased mobility (IMS: 255% vs. 110% p = 0.007), increased muscle strength (MRC: 12% vs. -9% p = 0.001) and HGD (34% vs. -13% p < 0.001), and the SAPS3 score was similar (p > 0.05). CONCLUSION: The results suggest that daily PBMT can reduce the length of stay of ICU patients and increase muscle strength and mobility.

Comparison of Three Antagonists of Hedgehog Pathway to Promote Skeletal Muscle Regeneration after High Dose Irradiation.

The current geopolitical context has brought the radiological nuclear risk to the forefront of concerns. High-dose localized radiation exposure leads to the development of a musculocutaneous radiation syndrome affecting the skin and subcutaneous muscles. Despite the implementation of a gold standard treatment based on an invasive surgical procedure coupled with autologous cell therapy, a muscular defect frequently persists. Targeting the modulation of the Hedgehog (Hh) signaling pathway appears to be a promising therapeutic approach. Activation of this pathway enhances cell survival and promotes proliferation after irradiation, while inhibition by Cyclopamine facilitates differentiation. In this study, we compared the effects of three antagonists of Hh, Cyclopamine (CA), Vismodegib (VDG) and Sonidegib (SDG) on differentiation. A stable cell line of murine myoblasts, C2C12, was exposed to X-ray radiation (5 Gy) and treated with CA, VDG or SDG. Analysis of proliferation, survival (apoptosis), morphology, myogenesis genes expression and proteins production were performed. According to the results, VDG does not have a significant impact on C2C12 cells. SDG increases the expression/production of differentiation markers to a similar extent as CA, while morphologically, SDG proves to be more effective than CA. To conclude, SDG can be used in the same way as CA but already has a marketing authorization with an indication against basal cell cancers, facilitating their use in vivo. This proof of concept demonstrates that SDG represents a promising alternative to CA to promotes differentiation of murine myoblasts. Future studies on isolated and cultured satellite cells and in vivo will test this proof of concept.

Antioxidant effects of LEDT in dystrophic muscle cells: involvement of PGC-1α and UCP-3 pathways.

PURPOSE: Reactive oxygen species and mitochondrial dysfunction play a crucial role in the pathophysiology of Duchenne muscular dystrophy (DMD). The light-emitting diode therapy (LEDT) showed beneficial effects on the dystrophic muscles. However, the mechanisms of this therapy influence the molecular pathways in the dystrophic muscles, particularly related to antioxidant effects, which still needs to be elucidated. The current study provides muscle cell-specific insights into the effect of LEDT, 48 h post-irradiation, on oxidative stress and mitochondrial parameters in the dystrophic primary muscle cells in culture. METHODS: Dystrophic primary muscle cells were submitted to LEDT, at multiple wavelengths (420 nm, 470 nm, 660 nm and 850 nm), 0.5 J dose, and evaluated after 48 h based on oxidative stress markers, antioxidant enzymatic system and biogenesis, and functional mitochondrial parameters. RESULTS: The mdx muscle cells treated with LEDT showed a significant reduction of H2O2 production and 4-HNE, catalase, SOD-2, and GR levels. Upregulation of UCP3 was observed with all wavelengths while upregulation of PGC-1α and a slight upregulation of electron transport chain complexes III and V was only observed following 850 nm LEDT. In addition, the mitochondrial membrane potential and mitochondrial mass mostly tended to be increased following LEDT, while parameters like O2·- production tended to be decreased. CONCLUSION: The data shown here highlight the potential of LEDT as a therapeutic agent for DMD through its antioxidant action by modulating PGC-1α and UCP3 levels.

Photobiomodulation Therapy on the Treatment of Insulin Resistance: A Narrative Review.

Background: Insulin resistance (IR) is the main risk factor for the development of type 2 diabetes mellitus (DM2). Noninvasive and nonpharmacological therapies, such as exercise and diet are effective in treating IR and DM2; however, adherence to them generally is low and diminishes positive effects in the long term. Photobiomodulation therapy (PBMT) is another noninvasive and nonpharmacological therapy, which produces positive effects on mitochondrial metabolism, oxidative stress, and inflammation generally linked to IR and DM2 and may improve or attenuate the severity of these diseases. Objective: In this narrative review, we focus on the available literature related to the effects of PBMT on IR. Results: In fact, recent in vitro and in vivo studies have demonstrated improvements in IR in skeletal muscle, adipose tissue, and hepatic cells mediated by PBMT. Further, there is evidence that PBMT can potentiate exercise-induced improvement in IR through ameliorating mitochondrial dysfunction, reducing inflammation, and modulating oxidative stress. Moreover, reduced adiposity and altered gut microbiota also appear to mediate PBMT effects on IR. Conclusions: Although these results are exciting, randomized clinical trials are urgently needed to confirm the clinical relevance of PBMT in the treatment of IR. Investigation about the effects of PBMT combined with different volumes of physical exercises may also contribute significantly for those patients having difficulty to adhere to the recommended minimal exercise volume. Finally, studies on PBMT parameters (e.g., dosimetry, wavelengths, single-point vs. full-body irradiation) are also necessary for the appropriate prescription of PBMT for the treatment of IR.

Molecular and Metabolic Mechanism of Low-Intensity Pulsed Ultrasound Improving Muscle Atrophy in Hindlimb Unloading Rats.

Low-intensity pulsed ultrasound (LIPUS) has been proved to promote the proliferation of myoblast C2C12. However, whether LIPUS can effectively prevent muscle atrophy has not been clarified, and if so, what is the possible mechanism. The aim of this study is to evaluate the effects of LIPUS on muscle atrophy in hindlimb unloading rats, and explore the mechanisms. The rats were randomly divided into four groups: normal control group (NC), hindlimb unloading group (UL), hindlimb unloading plus 30 mW/cm2 LIPUS irradiation group (UL + 30 mW/cm2), hindlimb unloading plus 80 mW/cm2 LIPUS irradiation group (UL + 80 mW/cm2). The tails of rats in hindlimb unloading group were suspended for 28 days. The rats in the LIPUS treated group were simultaneously irradiated with LIPUS on gastrocnemius muscle in both lower legs at the sound intensity of 30 mW/cm2 or 80 mW/cm2 for 20 min/d for 28 days. C2C12 cells were exposed to LIPUS at 30 or 80 mW/cm2 for 5 days. The results showed that LIPUS significantly promoted the proliferation and differentiation of myoblast C2C12, and prevented the decrease of cross-sectional area of muscle fiber and gastrocnemius mass in hindlimb unloading rats. LIPUS also significantly down regulated the expression of MSTN and its receptors ActRIIB, and up-regulated the expression of Akt and mTOR in gastrocnemius muscle of hindlimb unloading rats. In addition, three metabolic pathways (phenylalanine, tyrosine and tryptophan biosynthesis; alanine, aspartate and glutamate metabolism; glycine, serine and threonine metabolism) were selected as important metabolic pathways for hindlimb unloading effect. However, LIPUS promoted the stability of alanine, aspartate and glutamate metabolism pathway. These results suggest that the key mechanism of LIPUS in preventing muscle atrophy induced by hindlimb unloading may be related to promoting protein synthesis through MSTN/Akt/mTOR signaling pathway and stabilizing alanine, aspartate and glutamate metabolism.

Exploring the ability of low-level laser irradiation to reduce myonecrosis and increase Myogenin transcription after Bothrops jararacussu envenomation.

Envenoming caused by snakebites is a very important neglected tropical disease worldwide. The myotoxic phospholipases present in the bothropic venom disrupt the sarcolemma and compromise the mechanisms of energy production, leading to myonecrosis. Photobiomodulation therapy (PBMT) has been used as an effective tool to treat diverse cases of injuries, such as snake venom-induced myonecrosis. Based on that, the aim of this study was to analyze the effects of PBMT through low-level laser irradiation (904 nm) on the muscle regeneration after the myonecrosis induced by Bothrops jararacussu snake venom (Bjssu) injection, focusing on myogenic regulatory factors expression, such as Pax7, MyoD, and Myogenin (MyoG). Male Swiss mice (Mus musculus), 6-8-week-old, weighing 22 ± 3 g were used. Single sub-lethal Bjssu dose or saline was injected into the right mice gastrocnemius muscle. At 3, 24, 48, and 72 h after injections, mice were submitted to PBMT treatment. When finished the periods of 48 and 72 h, mice were euthanized and the right gastrocnemius were collected for analyses. We observed extensive inflammatory infiltrate in all the groups submitted to Bjssu injections. PBMT was able to reduce the myonecrotic area at 48 and 72 h after envenomation. There was a significant increase of MyoG mRNA expression at 72 h after venom injection. The data suggest that beyond the protective effect promoted by PBMT against Bjssu-induced myonecrosis, the low-level laser irradiation was able to stimulate the satellite cells, thus enhancing the muscle repair by improving myogenic differentiation.

Effects of Photobiomodulation Therapy (LED 630 nm) on Muscle and Nerve Histomorphometry after Axonotmesis.

Peripheral injuries constitute a substantial clinical problem with unsatisfactory treatment. The study's objective was to analyze the effects of photobiomodulation therapy (PBMT) on median nerve regeneration and muscle recovery after axonotmesis. Twenty-four rats were randomized into three groups: control (CG), injury (IG), and LED therapy (LEDG). A 630 ± 20 nm (300-mW) LED was placed in contact with the skin. One point over the injury site was irradiated for 30 s, delivering 9 J (9 J cm-2 ). PBMT irradiation was performed once daily for 5 days followed by two-day interval and then more five consecutive days of treatment. Proximal and distal segments of the nerve and flexors muscles were removed for histomorphometric analysis using H&E staining for muscles and osmium tetroxide for nerves. The myelinated fiber and axon diameter and the myelin sheath thickness were greater in the proximal and distal nerve segments in the LEDG compared to the IG (P ≤ 0.05). The number of myelinated fibers was greater in the distal segment of the LEDG (P ≤ 0.05). The area, circumference, and diameter of the muscle fibers were larger in the LEDG than in the IG (P ≤ 0.05). The PBMT protocol used favored axonal regeneration and muscle recovery.

Specific modulation of corticomuscular coherence during submaximal voluntary isometric, shortening and lengthening contractions.

During voluntary contractions, corticomuscular coherence (CMC) is thought to reflect a mutual interaction between cortical and muscle oscillatory activities, respectively measured by electroencephalography (EEG) and electromyography (EMG). However, it remains unclear whether CMC modulation would depend on the contribution of neural mechanisms acting at the spinal level. To this purpose, modulations of CMC were compared during submaximal isometric, shortening and lengthening contractions of the soleus (SOL) and the medial gastrocnemius (MG) with a concurrent analysis of changes in spinal excitability that may be reduced during lengthening contractions. Submaximal contractions intensity was set at 50% of the maximal SOL EMG activity. CMC was computed in the time-frequency domain between the Cz EEG electrode signal and the unrectified SOL or MG EMG signal. Spinal excitability was quantified through normalized Hoffmann (H) reflex amplitude. The results indicate that beta-band CMC and normalized H-reflex were significantly lower in SOL during lengthening compared with isometric contractions, but were similar in MG for all three muscle contraction types. Collectively, these results highlight an effect of contraction type on beta-band CMC, although it may differ between agonist synergist muscles. These novel findings also provide new evidence that beta-band CMC modulation may involve spinal regulatory mechanisms.

Modulation of torque evoked by wide-pulse, high-frequency neuromuscular electrical stimulation and the potential implications for rehabilitation and training.

The effectiveness of neuromuscular electrical stimulation (NMES) for rehabilitation is proportional to the evoked torque. The progressive increase in torque (extra torque) that may develop in response to low intensity wide-pulse high-frequency (WPHF) NMES holds great promise for rehabilitation as it overcomes the main limitation of NMES, namely discomfort. WPHF NMES extra torque is thought to result from reflexively recruited motor units at the spinal level. However, whether WPHF NMES evoked force can be modulated is unknown. Therefore, we examined the effect of two interventions known to change the state of spinal circuitry in opposite ways on evoked torque and motor unit recruitment by WPHF NMES. The interventions were high-frequency transcutaneous electrical nerve stimulation (TENS) and anodal transcutaneous spinal direct current stimulation (tsDCS). We show that TENS performed before a bout of WPHF NMES results in lower evoked torque (median change in torque time-integral: - 56%) indicating that WPHF NMES-evoked torque might be modulated. In contrast, the anodal tsDCS protocol used had no effect on any measured parameter. Our results demonstrate that WPHF NMES extra torque can be modulated and although the TENS intervention blunted extra torque production, the finding that central contribution to WPHF NMES-evoked torques can be modulated opens new avenues for designing interventions to enhance WPHF NMES.

Effect of Long-Term Light Deprivation on α-Tocopherol Content in Rats during Ontogeny.

We studied the effect of long-term light deprivation which began at different stages of ontogeny on the content of α-tocopherol in rats during the first 3 months of postnatal development. In the offspring postnatally exposed to constant darkness, the level of α-tocopherol in the liver, kidneys, heart, skeletal muscles, and lungs was significantly decreased at the early stages of postnatal ontogeny (2 weeks and 1 month). In rats kept under constant darkness after birth, the content of α-tocopherol in the lungs was also reduced at the age of 1 month. The modulating effect of light deprivation on the level of α-tocopherol can be associated both with the impact of disturbed circadian rhythms and with increased content of melatonin in the body.

The Prognostic Relevance of Computed Tomography-assessed Skeletal Muscle Index and Skeletal Muscle Radiation Attenuation in Patients With Gynecological Cancer.

The evaluation of the whole skeletal muscle area at the level of the third lumbar vertebra on computed tomography (CT) scans has often detected loss of skeletal muscle mass, defined as sarcopenia, and reduced skeletal muscle radiation attenuation (SMRA) in patients with different malignancies. Baseline sarcopenia has been detected in 33.3%-51.8% of patients with advanced cervical cancer, 33.6%-50% of those with endometrial cancer, and 11%-64% of those with advanced ovarian cancer. We reviewed the literature data on the clinical relevance of CT-assessed skeletal muscle status in gynecological malignancies. Overall, baseline skeletal muscle index and SMRA have an uncertain prognostic relevance, whereas their changes during treatment usually correlate with progression-free survival and overall survival. Multicenter clinical trials are strongly warranted to assess the effects of pharmacological agents and physical exercise in the management of skeletal muscle damage in patients with gynecological cancer.

Irradiated Skeletal Muscle Cells Mimicking Those of Atypical Fibroxanthoma on Mohs Frozen Sections.

ABSTRACT: Radiation can induce changes to skeletal muscle cells that may mimic and thus be confused with cells of atypical fibroxanthoma (AFX), pleomorphic dermal sarcoma, spindle cell squamous cell carcinoma, and other spindle soft-tissue tumors. An 80-year-old White man presented for Mohs micrographic surgery of an AFX on the left lateral neck. The medical history was notable for a tongue squamous cell carcinoma 9 years before that had been treated with wide local excision, left neck dissection, and radiation to the oral cavity and left neck. Frozen sections from the first stage of Mohs did not show typical AFX, but did reveal patchy clusters of atypical spindled and epithelioid cells, some with multiple nuclei. Because of the unusual appearance of these cells, Mohs micrographic surgery was halted, and the frozen tissue block was sent for permanent pathology examination. The cells on permanent sections stained positive for desmin, revealing them to be of skeletal muscle origin (in this case damaged platysma muscle because of late postradiation changes). It is thus important for the Mohs surgeon and the consultant dermatopathologist to be aware of the unusual histologic appearance of irradiated skeletal muscle to avoid confusion with other spindle cell tumors.

Effects of photobiomodulation therapy on the local experimental envenoming by Bothrops leucurus snake.

Bothrops leucurus is the major causative agent of snakebites in Brazil's Northeast. The systemic effects of its venom are effectively neutralized by antivenom therapy, preventing bitten patients' death. However, antivenom fails in neutralizing local effects that include intense pain, edema, bleeding, and myonecrosis. Such effects can lead to irreversible sequels, representing a clinically relevant issue for which there is no current effective treatment. Herein, the effects of photobiomodulation therapy (PBMT) were tested in the local actions induced by B. leucurus venom (BLV) in mice (n = 123 animals in 20 experimental groups). A continuous emission AlGaAs semiconductor diode laser was used in two wavelengths (660 or 780 nm). Mechanical nociceptive thresholds were assessed with the electronic von Frey apparatus. Local edema was determined by measuring the increase in paw thickness. Hemorrhage was quantified by digital measurement of the bleeding area. Myotoxicity was evaluated by serum creatine kinase (CK) activity and histopathological analysis. PBMT promoted anti-hypernociception in BLV-injected mice; irradiation with the 660 nm laser resulted in faster effect onset than the 780 nm laser. Both laser protocols reduced paw edema formation, whether irradiation was performed immediately or half an hour after venom injection. BLV-induced hemorrhage was not altered by PBMT. Laser irradiation delayed, but did not prevent myotoxicity caused by BLV, as shown by a late increase in CK activity and histopathological alterations. PBMT was effective in the control of some of the major local effects of BLV refractory to antivenom. It is a potential complementary therapy that could be used in bothropic envenoming, minimizing the morbidity of these snakebite accidents.

Characterization of macrophages, giant cells and granulomas during muscle regeneration after irradiation.

Macrophages play a fundamental role in the different stages of muscle regeneration although the precise mechanisms involved are not entirely understood. Here we investigated the types of macrophages and cytokines that appeared in muscles after local gamma irradiation of mini-pigs that underwent no subsequent treatment or received three successive adipose tissue-derived stem cell (ASC) injections. Although some variability was observed among the three animals included in each study group, a general picture emerged. No macrophages appeared in control muscles from regions that had not been irradiated nor in muscles from irradiated regions derived from two animals. A third irradiated, but untreated animal, with characteristic muscle fibrosis and necrosis due to irradiation, showed invasion of M2 macrophages within small muscle lesions. In contrast, among the three ASC-treated and irradiated animals, one of them had completely recovered normal muscle architecture at the time of sampling with no invading macrophages, muscle from a second one contained mostly M1 macrophages and some M2-like macrophages whereas muscle from a third one displayed granulomas and giant cells. ASC treatment was associated with the presence of similar levels of pro-inflammatory cytokines within the two animals in the process of muscle regeneration whereas the levels of IL-4 and IL-10 expression were distinct from one animal to another. Microspectrofluorimetry and in situ hybridization revealed strong expression of TGF-ß1 and TNFα in regenerating muscle. Overall, the data confirm the critical role of macrophages in muscle regeneration and suggest the involvement of a complex network of cytokine expression for successful recovery.