Lifespan Analysis of Dystrophic mdx Fast-Twitch Muscle Morphology and Its Impact on Contractile Function

Duchenne muscular dystrophy is caused by the absence of the protein dystrophin from skeletal muscle and is characterized by progressive cycles of necrosis/regeneration. Using the dystrophin deficient mdx mouse model, we studied the morphological and contractile chronology of dystrophic skeletal muscle pathology in fast-twitch Extensor Digitorum Longus muscles from animals 4–22 months of age containing 100% regenerated muscle fibers. Catastrophically, the older age groups lost ∼80% of their maximum force after one eccentric contraction (EC) of 20% strain with the greatest loss of ∼92% recorded in senescent 22-month-old mdx mice. In old age groups, there was minimal force recovery ∼24% after 120 min, correlated with a dramatic increase in the number and complexity of branched fibers. This data supports our two-phase model where a “tipping point” is reached when branched fibers rupture irrevocably on EC. These findings have important implications for pre-clinical drug studies and genetic rescue strategies.

A Novel Incremental Iterative Force Recovery Method for Second-Order Beam-Column Elements in Plastic Hinge Analysis of Steel Frames

This paper is concerned with an incremental iterative force recovery method in the second-order plastic hinge analysis of steel frames mainly modelled by a single element per member. Second-order beam-column elements are preferred in the direct analysis of steel frames due to their high accuracy and efficiency. However, formulations of these elements are complicated, and therefore they may have a problem of getting element force recovery in inelastic analysis. To overcome this difficulty, a novel incremental iterative force recovery method for second-order beam-column elements is proposed to perform plastic hinge analysis. The proposed method is derived more strictly and has good performance. Also, the section assemblage approach and the refined plastic hinge method are adopted in this study to consider the gradual degradation of section stiffness in the plastic hinge analysis. To verify the accuracy, efficiency and robustness of the proposed method, several benchmark examples are analyzed by the proposed method and compared with solutions reported by early researchers.

Lifespan analysis of dystrophic mdx fast-twitch muscle morphology and its impact on contractile function

ABSTRACTDuchenne muscular dystrophy is caused by the absence of the protein dystrophin from skeletal muscle and is characterized by progressive cycles of necrosis/regeneration. Using the dystrophin deficient mdx mouse model we studied the morphological and contractile chronology of dystrophic skeletal muscle pathology in fast twitch EDL muscles from animals 4-22 months of age containing 100% regenerated muscle fibers. Catastrophically, the older age groups lost ∼80% of their maximum force after one eccentric contraction of 20% strain, with the greatest loss ∼93% recorded in senescent 22 month old mdx mice. In old age groups there was minimal force recovery ∼24% after 120 minutes, correlated with a dramatic increase in the number and complexity of branched fibers. This data supports our two-stage model where a “tipping point” is reached when branched fibers rupture irrevocably on eccentric contraction. These findings have important implications for pre-clinical drug studies and genetic rescue strategies.

Force degradation and staining of aesthetic chain elastics when submitted to different phytotherapic rinses / Degradação forçada e coloração de elásticos de cadeia estética quando submetidos a diferentes enxaguamentos fitoterápicos

The objective of this study was to evaluate the color (∆E*) and the degradation of the strength of chain elastics when submitted to different rinses. Forty segments of aesthetics chain elastics (American Orthodontics) were maintained extended in distilled water at 37°C. The elastics (n=10) were immersed twice a day for 60 seconds each in the following solutions: Chlorhexidine Gluconate; Grapefruit essential oil; Ginger and distilled water. The readings were performed in the following times: initial, 24 hours, 7, 14, 21, and 28 days using universal testing machine and spectrophotometer. The force degradation data were analyzed by mixed models for repeated measurements in time, and the data from ∆E* were evaluated by Kruskal Wallis and Dunn and Friedmann and Nemenyi (α=5%). Except for the group immersed in Ginger, there was a significant decrease in force degradation after 24 hours (p0.05); after 7 days there was force recovery for all solutions. For ∆E* it was found that there was no statistically significant difference between the solutions for most of the time. However, after 28 days Chlorhexidine showed less ∆E* than the other solutions. It is concluded that the time in which the elastic chain is stretched influences the degradation of strength; immersions in rinses with the exception of ginger solution degrade the strength after 24 hours and; there is color change for all solutions after 28 days.

Muscle Precursor Cells Enhance Functional Muscle Recovery and Show Synergistic Effects With Postinjury Treadmill Exercise in a Muscle Injury Model in Rats

Background: Skeletal muscle injuries represent a major concern in sports medicine. Cell therapy has emerged as a promising therapeutic strategy for muscle injuries, although the preclinical data are still inconclusive and the potential clinical use of cell therapy has not yet been established. Purpose: To evaluate the effects of muscle precursor cells (MPCs) on muscle healing in a small animal model. Study Design: Controlled laboratory study. Methods: A total of 27 rats were used in the study. MPCs were isolated from rat (n = 3) medial gastrocnemius muscles and expanded in primary culture. Skeletal muscle injury was induced in 24 rats, and the animals were assigned to 3 groups. At 36 hours after injury, animals received treatment based on a single ultrasound-guided MPC (105 cells) injection (Cells group) or MPC injection in combination with 2 weeks of daily exercise training (Cells+Exercise group). Animals receiving intramuscular vehicle injection were used as controls (Vehicle group). Muscle force was determined 2 weeks after muscle injury, and muscles were collected for histological and immunofluorescence evaluation. Results: Red fluorescence–labeled MPCs were successfully transplanted in the site of the injury by ultrasound-guided injection and were localized in the injured area after 2 weeks. Transplanted MPCs participated in the formation of regenerating muscle fibers as corroborated by the co-localization of red fluorescence with developmental myosin heavy chain (dMHC)–positive myofibers by immunofluorescence analysis. A strong beneficial effect on muscle force recovery was detected in the Cells and Cells+Exercise groups (102.6% ± 4.0% and 101.5% ± 8.5% of maximum tetanus force of the injured vs healthy contralateral muscle, respectively) compared with the Vehicle group (78.2% ± 5.1%). Both Cells and Cells+Exercise treatments stimulated the growth of newly formed regenerating muscles fibers, as determined by the increase in myofiber cross-sectional area (612.3 ± 21.4 µm2 and 686.0 ± 11.6 µm2, respectively) compared with the Vehicle group (247.5 ± 10.7 µm2), which was accompanied by a significant reduction of intramuscular fibrosis in Cells and Cells+Exercise treated animals (24.2% ± 1.3% and 26.0% ± 1.9% of collagen type I deposition, respectively) with respect to control animals (40.9% ± 4.1% in the Vehicle group). MPC treatment induced a robust acceleration of the muscle healing process as demonstrated by the decreased number of dMHC-positive regenerating myofibers (enhanced replacement of developmental myosin isoform by mature myosin isoforms) (4.3% ± 2.6% and 4.1% ± 1.5% in the Cells and Cells+Exercise groups, respectively) compared with the Vehicle group (14.8% ± 13.9%). Conclusion: Single intramuscular administration of MPCs improved histological outcome and force recovery of the injured skeletal muscle in a rat injury model that imitates sports-related muscle injuries. Cell therapy showed a synergistic effect when combined with an early active rehabilitation protocol in rats, which suggests that a combination of treatments can generate novel therapeutic strategies for the treatment of human skeletal muscle injuries. Clinical Relevance: Our study demonstrates the strong beneficial effect of MPC transplant and the synergistic effect when the cell therapy is combined with an early active rehabilitation protocol for muscle recovery in rats; this finding opens new avenues for the development of effective therapeutic strategies for muscle healing and clinical trials in athletes undergoing MPC transplant and rehabilitation protocols.