Low-Level Photobiomodulation Therapy Modulates H2O2 Production, TRPC-6, and PGC-1α Levels in the Dystrophic Muscle.

Objective: This study evaluated photobiomodulation therapy (PBMT) effects on the factors involved in mitochondrial biogenesis, on the mitochondrial respiratory complexes, and on the transient receptor potential canonical channels (such as TRPC-1 and TRPC-6) in in vitro (mdx muscle cells) and in vivo studies (gastrocnemius muscle) from mdx mice, the dystrophin-deficient model of Duchenne muscular dystrophy (DMD). Background: There is no successful treatment for DMD, therefore demanding search for new therapies that can improve the muscle role, the quality of life, and the survival of dystrophic patients. Methods: The dystrophic primary muscle cells received PBMT at 0.6 J and 5 J, and the dystrophic gastrocnemius muscle received PBMT at 0.6 J. Results: The dystrophic muscle cells treated with PBMT (0.6 J and 5 J) showed no cytotoxicity and significantly lower levels in hydrogen peroxide (H2O2) production. We also demonstrated, for the first time, the capacity of PBMT, at a low dose (0.6 J), in reducing the TRPC-6 content and in raising the peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) content in the dystrophic gastrocnemius muscle. Conclusions: PBMT modulates H2O2 production, TRPC-6, and PGC-1α content in the dystrophic muscle. These results suggest that laser therapy could act as an auxiliary therapy in the treatment of dystrophic patients.

Effectiveness of electrotherapy for the treatment of orofacial pain: A systematic review and meta-analysis.

OBJECTIVE: Summarize the evidence from randomized controlled trials and controlled trials that examined the effectiveness of electrotherapy in the treatment of patients with orofacial pain. DATA SOURCE: Medline, Embase, CINAHL PLUS with Full text, Cochrane Library Trials, Web of Science, and Scopus. REVIEW METHODS: A data search (last update, July 1, 2022) and a manual search were performed (October 5, 2022). Trials involving adults with orofacial pain receiving electrotherapy compared with any other type of treatment were included. The main outcome was pain intensity; secondary outcomes were mouth opening and tenderness. The reporting was based on the new PRISMA Guidelines. RESULTS: From the electronics databases and manual search 43 studies were included. Although this study was open to including any type of orofacial pain, only studies that investigated temporomandibular disorders were found. The overall quality of the evidence for pain intensity was very low. Although the results should be carefully used, transcutaneous electric nerve stimulation therapy showed to be clinically superior to placebo for reducing pain after treatment (2.63 [-0.48; 5.74]) and at follow-up (0.96 [-0.02; 1.95]) and reduce tenderness after treatment (1.99 [-0.33; 4.32]) and at follow-up (2.43 [-0.24; 5.10]) in subjects with mixed temporomandibular disorders. CONCLUSION: The results of this systematic review support the use of transcutaneous electric nerve stimulation therapy for patients with mixed temporomandibular disorders to improve pain intensity, and tenderness demonstrating that transcutaneous electric nerve stimulation is superior to placebo. There is inconsistent evidence supporting the superiority of transcutaneous electric nerve stimulation against other therapies.

Photobiomodulation Therapy for Attenuating the Dystrophic Phenotype of Mdx Mice.

This study analyzed photobiomodulation therapy (PBMT) effects on regenerative, antioxidative, anti-inflammatory and angiogenic markers in the dystrophic skeletal muscle of mdx mice, the experimental model of Duchenne muscular dystrophy (DMD), during the acute phase of dystrophy disease. The following groups were set up: Ctrl (control group of normal wild-type mice; C57BL/10); mdx (untreated mdx mice); mdxPred (mdx mice treated with prednisolone) and mdxLA (mdx mice treated with PBMT). The PBMT was carried out using an Aluminum Gallium Arsenide (AIGaAs; IBRAMED® laserpulse) diode, 830 nm wavelength, applied on the dystrophic quadriceps muscle. The mdxLA group showed a degenerative and regenerative area reduction simultaneously with a MyoD level increase, ROS production and inflammatory marker reduction and up-regulation in the VEGF factor. In addition, PBMT presented similar effects to prednisolone treatment in most of the parameters analyzed. In conclusion, our results indicate that PBMT in the parameters selected attenuated the dystrophic phenotype of mdx mice, improving skeletal muscle regeneration; reducing the oxidative stress and inflammatory process; and up-regulating the angiogenic marker.

Effects of Creatine Supplementation on Renal Function: A Systematic Review and Meta-Analysis.

Creatine supplements are intended to improve performance, but there are indications that it can overwhelm liver and kidney functions, reduce the quality of life, and increase mortality. Therefore, this is the first systematic review and meta-analysis study that aimed to investigate creatine supplements and their possible renal function side effects. After evaluating 290 non-duplicated studies, 15 were included in the qualitative analysis and 6 in the quantitative analysis. The results of the meta-analysis suggest that creatine supplementation did not significantly alter serum creatinine levels (standardized mean difference = 0.48, 95% confidence interval 0.24-0.73, P = .001, I2 = 22%), and did not alter plasma urea values (standardized mean difference = 1.10, 95% confidence interval 0.34-1.85, P = .004, I2 = 28%). The findings indicate that creatine supplementation does not induce renal damage in the studied amounts and durations.

High-fat diet suppresses the positive effect of creatine supplementation on skeletal muscle function by reducing protein expression of IGF-PI3K-AKT-mTOR pathway.

High-fat (HF) diets in combination with sedentary lifestyle represent one of the major public health concerns predisposing to obesity and diabetes leading to skeletal muscle atrophy, decreased fiber diameter and muscle mass with accumulation of fat tissue resulting in loss of muscle strength. One strategy to overcome the maleficent effects of HF diet is resistance training, a strategy used to improve muscle mass, reverting the negative effects on obesity-related changes in skeletal muscle. Together with resistance training, supplementation with creatine monohydrate (CrM) in the diet has been used to improve muscle mass and strength. Creatine is a non-essential amino acid that is directly involved in the cross-bridge cycle providing a phosphate group to ADP during the initiation of muscle contraction. Besides its antioxidant and anti-inflammatory effects CrM also upregulates IGF-1 resulting in hyperthophy with an increase in muscle function. However, it is unknown whether CrM supplementation during resistance training would revert the negative effects of high-fat diet on the muscle performance. During 8 weeks we measured muscle performance to climb a 1.1m and 80° ladder with increasing load on trained rats that had received standard diet or high-fat diet, supplemented or not with CrM. We observed that the CrM supplementation up-regulated IGF-1 and phospho-AKT protein levels, suggesting an activation of the IGF1-PI3K-Akt/PKB-mTOR pathway. Moreover, despite the CrM supplementation, HF diet down-regulated several proteins of the IGF1-PI3K-Akt/PKB-mTOR pathway, suggesting that diet lipid content is crucial to maintain or improve muscle function during resistance training.

Effects of beta-hydroxy-beta-methyl butyrate in muscle regeneration of rats / Efeitos do beta-hidroxi-beta-metil-butirato na regeneração muscular de ratos / Efectos de beta-hidroxi-beta-metilbutirato en la regeneración muscular de ratas

ABSTRACT Introduction: Studies have shown that beta-hydroxy-beta-methyl butyrate (HMB) supplementation increases muscle strength and mass. Objective: To evaluate the effect of HMB supplementation on the muscle regeneration process in young and sedentary rats. Methods: Twenty-four male Wistar rats two months old were divided into two groups: lesion (LE) and supplemented (S), and evaluated in two moments - seven days (LE7; S7, n=6) and 21 days (LE21; S21, n=6). The right tibialis anterior muscle was subjected to cryolesion in all animals. After the injury, the LE group remained in the vivarium without any intervention. Group S received HMB calcium supplementation diluted in water by gavage (320 mg/kg/weight per day). The injury tibialis anterior (ITA), the tibialis anterior (TA), and the left soleus (SOL) muscles were removed, weighted and divided transversally into two parts, one for the analysis of the cross-sectional area (CSA) and the area of inflammation/regeneration and the other part to measure the muscular glycogen concentration. Data were evaluated using the SAS program considering mean and standard deviation. For analysis of variance the ANOVA test was used followed by the Tukey-HSD test (p≤0.05). Results: The ITA muscle weight was higher in S21 compared to S7 (p<0.05). The groups LE21 and S21 presented greater CSA of muscle fibers area and smaller ITA regeneration/inflammation area (p<0.05) when compared with the LE7 and S7 groups. There was an increase in muscle glycogen levels in S7 group compared to LE7 and S21 groups for TA and SOL (p<0.01), as well as in S21 group compared to LE21 for SOL (p<0.05). Conclusion: HMB did not influence the muscle regeneration process and did not favor anabolic activity in the different muscular fibers of young sedentary rats. Level of Evidence II; Therapeutic studies - Investigation of treatment results.

RESUMO Introdução: Estudos demonstram que a suplementação de beta-hidroxi-beta-metil-butirato (HMB) aumenta a força e a massa muscular. Objetivo: Avaliar o efeito da suplementação com HMB no processo de regeneração muscular em ratos jovens e sedentários. Métodos: Foram utilizados 24 ratos Wistar machos com dois meses de idade, divididos nos grupos lesão (LE) e suplementado (S) e avaliados em dois momentos, em sete dias (LE7; S7, n = 6) e em 21 dias (LE21; S21, n = 6). O músculo tibial anterior direito foi submetido à criolesão em todos os animais. Após a lesão, o grupo LE permaneceu no biotério sem nenhum tipo de intervenção. O grupo S recebeu suplementação de cálcio HMB em pó diluído em água por meio de gavagem (320 mg/kg/peso por dia). Os músculos tibial anterior lesado (TAL), tibial anterior (TA) e sóleo (SOL) esquerdo foram retirados, pesados e divididos transversalmente em duas partes, sendo uma destinada à análise da área de corte transversal (ACT) e da área de inflamação/regeneração e a outra parte para medir a concentração de glicogênio muscular. A avaliação dos dados foi realizada por meio do programa SAS, considerando média e desvio padrão. Para análise de variância usou-se o teste ANOVA, seguido do teste de Tukey-HSD (p ≤ 0,05). Resultados: O peso do músculo TAL foi maior no S21 em comparação com o S7 (p < 0,05). Os grupos LE21 e S21 apresentaram maior ACT de fibras musculares e menor área de regeneração/inflamação do TAL (p < 0,05), quando comparados com os grupos LE7 e S7. Observou-se aumento nos níveis de glicogênio muscular no grupo S7 com relação a LE7 e S21 para TAE e SOL (p < 0,01), assim como no grupo S21 em comparação com LE21 no SOL (p < 0,05). Conclusão: O HMB não influenciou o processo de regeneração muscular e não favoreceu a atividade anabólica nos diferentes tipos de fibras musculares de ratos jovens e sedentários. Nível de Evidência II, Estudos terapêuticos - Investigação dos resultados do tratamento.

RESUMEN Introducción: Los estudios han demostrado que el beta-hidroxi-beta-metilbutirato (HMB) suplementario aumenta la fuerza y la masa muscular. Objetivo: Evaluar el efecto del HMB suplementario en el proceso de regeneración muscular en ratas jóvenes y sedentarias. Métodos: Se utilizaron 24 ratas Wistar machos con dos meses de edad, divididas en los grupos lesión (LE) y suplementario (S) y evaluados en dos momentos, en siete días (LE7; S7, n = 6) y en 21 días (LE21; S21, n = 6). El músculo tibial anterior derecho fue sometido a la criolesión en todos los animales. Después de la lesión, el grupo LE se mantuvo en el vivero sin ninguna intervención. El grupo S recibió calcio HMB suplementario diluido en agua por medio de alimentación forzada (320 mg/kg/peso al día). Los músculos tibial anterior lesión (TAL), tibial anterior (TA) y sóleo (SOL) izquierdo fueron retirados, pesados y divididos transversalmente en dos partes, siendo una destinada al análisis del área de corte transversal (ACT) y del área de inflamación/regeneración y otra parte para medir la concentración de glucógeno muscular. La evaluación de los datos se realizó a través del programa SAS, considerando media y desviación estándar. Para el análisis de varianza se utilizó la prueba ANOVA, seguida de la prueba de Tukey-HSD (p ≤ 0,05). Resultados: El peso del músculo TAL fue mayor en el grupo S21 en comparación con el S7 (p < 0,05). Los grupos LE21 y S21 tuvieron mayor ACT de fibras musculares y menor área de regeneración/inflamación del TAL (p < 0,05) en comparación con los grupos LE7 y S7. Se observó un aumento en los niveles de glucógeno muscular en el grupo S7 con relación a LE7 y S21 para TA y SOL (p < 0,01), así como en el grupo S21 en comparación con LE21 en el SOL (p < 0,05). Conclusión: HMB no influyó el proceso de regeneración muscular y no favoreció la actividad anabólica en los diferentes tipos de fibras musculares de ratas jóvenes y sedentarias. Nivel de Evidencia II, Estudios terapéuticos - Investigación de los resultados del tratamiento.

Low-Level Laser Therapy (LLLT) in Dystrophin-Deficient Muscle Cells: Effects on Regeneration Capacity, Inflammation Response and Oxidative Stress.

The present study evaluated low-level laser therapy (LLLT) effects on some physiological pathways that may lead to muscle damage or regeneration capacity in dystrophin-deficient muscle cells of mdx mice, the experimental model of Duchenne muscular dystrophy (DMD). Primary cultures of mdx skeletal muscle cells were irradiated only one time with laser and analyzed after 24 and 48 hours. The LLLT parameter used was 830 nm wavelengths at 5 J/cm² fluence. The following groups were set up: Ctrl (untreated C57BL/10 primary muscle cells), mdx (untreated mdx primary muscle cells), mdx LA 24 (mdx primary muscle cells - LLLT irradiated and analyzed after 24 h), and mdx LA 48 (mdx primary muscle cells - LLLT irradiated and analyzed after 48 h). The mdx LA 24 and mdx LA 48 groups showed significant increase in cell proliferation, higher diameter in muscle cells and decreased MyoD levels compared to the mdx group. The mdx LA 48 group showed significant increase in Myosin Heavy Chain levels compared to the untreated mdx and mdx LA 24 groups. The mdx LA 24 and mdx LA 48 groups showed significant increase in [Ca2+]i. The mdx group showed significant increase in H2O2 production and 4-HNE levels compared to the Ctrl group and LLLT treatment reduced this increase. GSH levels and GPx, GR and SOD activities increased in the mdx group. Laser treatment reduced the GSH levels and GR and SOD activities in dystrophic muscle cells. The mdx group showed significant increase in the TNF-α and NF-κB levels, which in turn was reduced by the LLLT treatment. Together, these results suggest that the laser treatment improved regenerative capacity and decreased inflammatory response and oxidative stress in dystrophic muscle cells, indicating that LLLT could be a helpful alternative therapy to be associated with other treatment for dystrophinopathies.

Evaluation of muscle regeneration in aged animals after treatment with low-level laser therapy / Avaliação da regeneração muscular em animais idosos após tratamento com laser de baixa intensidade

BACKGROUND: The aging process and its associated morphophysiological changes trigger a reduction in the regenerative ability of the satellite cells, a reduction of vascular tissue and an increase in the production of fibroblasts, developing a cellular environment unfavorable for muscle regeneration. OBJECTIVE: The aim of this study was to evaluate the effect of low-level laser therapy on the muscle regeneration of old experimental rat models after contusion. METHOD: A total of 25 old rats,18 months old, were divided into three groups: control group (CT) without treatment; injury group (IN) with muscle contusion and without treatment and laser group (LA) with contusion and low-level laser therapy, 830 nm, 30 mW e 4 J/cm². The no invasive contusion was induced in the Tibialis Anterior muscle and the samples were collected after 7 and 21 treatment sessions. The muscle was evaluated by Light Microscopy and Immunoblotting. RESULTS: After 21 days of treatment there was a significant reduction in the areas of inflammation/regeneration of the LA 21 group compared to IN 21 group. The cross-sectional area of the fibers in regeneration was not statistically different between the groups. Molecular analysis showed that the content of MyoD was statistically reduced in the IN 21 group compared to the CT group. The Myogenin content was increased in the IN 21 group compared to the CT group. Ultimately, the content of TGF-β1 on the IN 21 group was higher when compared to the CT group. CONCLUSION: Considering the parameters used, the laser therapy demonstrated to be effective for muscle regeneration in old rats, however only through its anti-inflammatory effect.

CONTEXTUALIZAÇÃO: O processo de envelhecimento e suas consequentes alterações morfofisiológicas desencadeiam redução da habilidade regenerativa das células satélites, redução da vascularização tecidual e aumento da produção de fibroblastos, desenvolvendo-se um ambiente celular desfavorável para a regeneração muscular. OBJETIVO: Avaliar o efeito do tratamento com laser de baixa intensidade sobre a regeneração muscular de modelos experimentais idosos após contusão. MÉTODO: Foram utilizados 25 ratos machos, com 18 meses de idade, divididos em três grupos: grupo controle (CT), sem intervenção; grupo lesão (LE), com contusão muscular e sem tratamento e grupo laser (LA), com contusão muscular e tratado com laser de baixa intensidade, 830 nm, 30 mW e 4 J/cm². A contusão foi realizada no músculo tibial anterior, e as amostras coletadas após sete e 21 sessões de tratamento. O músculo foi designado às técnicas de Microscopia de Luz e Immunoblotting. RESULTADOS: Após 21 dias de tratamento, houve redução significativa na área de inflamação/regeneração no grupo LA 21 comparado ao grupo LE 21. Na área de secção transversal das fibras em processo de regeneração, não houve diferença estatística entre os grupos LA e LE. A análise molecular evidenciou que o conteúdo de MyoD apresentou redução significativa no grupo LE 21 em relação ao CT. O conteúdo de Miogenina exibiu aumento no LE 21 comparado ao CT e, por fim, o conteúdo de TGF-β1 do grupo LE 21 aumentou em relação ao grupo CT. CONCLUSÃO: Para os parâmetros utilizados, o laser demonstrou eficácia na regeneração muscular em animais idosos somente por meio do seu efeito anti-inflamatório.

Evaluation of muscle regeneration in aged animals after treatment with low-level laser therapy.

BACKGROUND: The aging process and its associated morphophysiological changes trigger a reduction in the regenerative ability of the satellite cells, a reduction of vascular tissue and an increase in the production of fibroblasts, developing a cellular environment unfavorable for muscle regeneration. OBJECTIVE: The aim of this study was to evaluate the effect of low-level laser therapy on the muscle regeneration of old experimental rat models after contusion. METHOD: A total of 25 old rats,18 months old, were divided into three groups: control group (CT) without treatment; injury group (IN) with muscle contusion and without treatment and laser group (LA) with contusion and low-level laser therapy, 830 nm, 30 mW e 4 J/cm². The no invasive contusion was induced in the Tibialis Anterior muscle and the samples were collected after 7 and 21 treatment sessions. The muscle was evaluated by Light Microscopy and Immunoblotting. RESULTS: After 21 days of treatment there was a significant reduction in the areas of inflammation/regeneration of the LA 21 group compared to IN 21 group. The cross-sectional area of the fibers in regeneration was not statistically different between the groups. Molecular analysis showed that the content of MyoD was statistically reduced in the IN 21 group compared to the CT group. The Myogenin content was increased in the IN 21 group compared to the CT group. Ultimately, the content of TGF-ß1 on the IN 21 group was higher when compared to the CT group. CONCLUSION: Considering the parameters used, the laser therapy demonstrated to be effective for muscle regeneration in old rats, however only through its anti-inflammatory effect.

Immediate effects of bilateral grade III mobilization of the talocrural joint on the balance of elderly women.

OBJECTIVE: The purpose of this study was to evaluate the immediate effects of a single treatment session of bilateral grade III mobilization of the talocrural joint on the balance of elderly women. METHODS: Thirty-two elderly women (age, 65-80 years) with low physical activity levels completed balance evaluation using baropodometry, the Functional Reach Test and the Timed Up and Go Test, and plantar flexion and dorsiflexion range of motion (ROM), before and immediately after the mobilization (n = 16) or sham (n = 16). Each subject was submitted to a total of twelve 30-second grade III mobilizations, 6 for each ankle, in a single treatment session. RESULTS: No significant difference was found for intragroup and intergroup comparisons in the balance of elderly women during the following evaluations: Functional Reach Test (P = .851), Timed Up and Go Test (P = .653), anteroposterior oscillation with eyes opened (P = .333) and with eyes closed (P = .652), and mediolateral oscillation with eyes opened (P = .486) and with eyes closed (P = .602). In addition, no significant difference was observed in right (P = .881) and left (P = .060) plantar flexion ROM and in right (P = .540) and left (P = .341) dorsiflexion ROM. CONCLUSION: The results of this study suggest that a single session of bilateral grade III mobilization of the talocrural joint does not immediately improve balance and ROM in elderly women with low physical activity levels.

Primary nerve repair by muscle autografts prepared with local anesthetic.

We evaluated the usefulness of muscle autografts obtained immediately after graft preparation with lidocaine injections for primary nerve repair. The right sciatic nerve of adult Wistar rats was sectioned, and muscle grafts obtained 15 min or 24 h after lidocaine injection were used to repair a gap 1.5 cm long. Axon and fiber diameters, as well as myelin thickness, decreased to similar extents for grafts of both time intervals. The G-ratios in the distal stumps of both groups were not different from controls, indicating that regenerated axons had a proper level of myelination. The ultrastructural appearance of the neuromuscular junctions was similar to that of normal samples. These results indicate that there are no restrictions to the use of a muscle graft for primary nerve repair, immediately after lidocaine injection, since the nerve regeneration was comparable to that observed with this type of graft used 24 h after being prepared.