筋収縮後の再酸素化実験に関する研究

博甲第38号生命システム科学博士県立広島大

Extraocular Muscle Imbalance and Outcomes of Scleral Buckling Surgery for Primary Rhegmatogenous Retinal Detachment

Objective: The objective was to study the muscle imbalance, restrictive motility in unlike gazes and the outcomes of the scleral buckling surgery for rhegmatogenous retinal detachment. Study design: Prospective follow-up study Settings and duration: The study was conducted at Al-Shifa Trust Eye Hospital Rawalpindi from Aug 2015 to Jan 2016. Methodology: The patients were checked prior to surgery and two follow up visits were done afterwards. Thorough history was taken along with full orthoptic assessment and ocular motility in all four main gazes including elevation, depression, adduction and abduction. Vision, type and position of explants, site of detachment, and risk factors of detachment were also observed. Results: A total of 48 eyes of 46 patients were taken. Mean age of the study participants was 37.16±20.37 years. Horizontal, vertical and combined deviations were observed in study population. Exo deviation was most common deviation among patients. Most reported risk factors of retinal detachment included trauma, pseudophakia, aphakia and myopia. Motility limitations of all four gazes was observed and it was found out that after buckling the squint and restriction is been increased up till two months. Conclusion: Ocular restriction among the patients was observed over a period of 2 months and it depicted that encircling with sclera buckling elicited an increase in restrictive ocular motility from pre-operative to 1 week and 2 months after surgery

HDAC4 preserves skeletal muscle structure following long-term denervation by mediating distinct cellular responses

BACKGROUND: Denervation triggers numerous molecular responses in skeletal muscle, including the activation of catabolic pathways and oxidative stress, leading to progressive muscle atrophy. Histone deacetylase 4 (HDAC4) mediates skeletal muscle response to denervation, suggesting the use of HDAC inhibitors as a therapeutic approach to neurogenic muscle atrophy. However, the effects of HDAC4 inhibition in skeletal muscle in response to long-term denervation have not been described yet. METHODS: To further study HDAC4 functions in response to denervation, we analyzed mutant mice in which HDAC4 is specifically deleted in skeletal muscle. RESULTS: After an initial phase of resistance to neurogenic muscle atrophy, skeletal muscle with a deletion of HDAC4 lost structural integrity after 4 weeks of denervation. Deletion of HDAC4 impaired the activation of the ubiquitin-proteasome system, delayed the autophagic response, and dampened the OS response in skeletal muscle. Inhibition of the ubiquitin-proteasome system or the autophagic response, if on the one hand, conferred resistance to neurogenic muscle atrophy; on the other hand, induced loss of muscle integrity and inflammation in mice lacking HDAC4 in skeletal muscle. Moreover, treatment with the antioxidant drug Trolox prevented loss of muscle integrity and inflammation in in mice lacking HDAC4 in skeletal muscle, despite the resistance to neurogenic muscle atrophy. CONCLUSIONS: These results reveal new functions of HDAC4 in mediating skeletal muscle response to denervation and lead us to propose the combined use of HDAC inhibitors and antioxidant drugs to treat neurogenic muscle atrophy

A histochemical study of the red and white muscle fibers Part III. Activity of the diphosphopyridine nucleotide diaphorase and triphosphopyridine nucleotide diaphorase in muscle fibers

From the histochemical study of DPN and TPN diaphorase on the striated muscles of the cats, the following results were obtained. 1. M. gastrocnemius, which belongs to the white muscle by naked eye, consists of three types of muscle fibers distinguished by the DPN diaphorase staining: namely, the small muscle fibers, i. e., the red muscle fibers show a moderate activity, being stained pink, while the large muscle fibers, i. e., the white muscle fibers show a low activity, being stained faint pink. The. third type of muscle fibers: namely, the medium fibers are stained pale pink and show the enzymatic activity intermediate between the red and white muscle fibers. 2. M. soleus, belonging to the red muscle by naked eye, consists of three types of fibers distinguished by the DPN-diaphorase staining, i. e., the red muscle fibers are stained pink, medium fibers pale pink, and a few white muscle fibers faint pink. The diameters of these three types of muscle fibers in M. soleus are almost the same. 3. From the staining pattern of TPN-diaphorase in M. gastrocnemius and M. soleus, the three types of muscle fibers can be distinguished by TPN-diaphorase activity, namely, the red muscle fibers show a high TPN-diaphorase activity, being stained purple, while, the white muscle fibers a low activity, being stained pale pink. The medium fibers are stained pink and show a moderate enzymatic activity intermediate between the red and white muscle fibers. 4. The TPN-diaphorase activity is higher than the DPN-diaphorase activity in the striated muscle, but it is less active than the TPN-diapborase activity in the kidney. However, the activity of DPN-diaphorase in the striated muscle is quite lower than that of the kidney.</p

Accumulation of muscle ankyrin repeat protein transcript reveals local activation of primary myotube endcompartments during muscle morphogenesis

The characteristic shapes and positions of each individual body muscle are established during the process of muscle morphogenesis in response to patterning information from the surrounding mesenchyme. Throughout muscle morphogenesis, primary myotubes are arranged in small parallel bundles, each myotube spanning the forming muscles from end to end. This unique arrangement potentially assigns a crucial role to primary myotube end regions for muscle morphogenesis. We have cloned muscle ankyrin repeat protein (MARP) as a gene induced in adult rat skeletal muscle by denervation. MARP is the rodent homologue of human C-193 (Chu, W., D.K. Burns, R.A. Swerick, and D.H. Presky. 1995. J. Biol. Chem. 270:10236-10245) and is identical to rat cardiac ankyrin repeat protein. (Zou, Y., S. Evans, J. Chen, H.-C. Kuo, R.P. Harvey, and K.R. Chien. 1997. Development. 124:793-804). In denervated muscle fibers, MARP transcript accumulated in a unique perisynaptic pattern. MARP was also expressed in large blood vessels and in cardiac muscle, where it was further induced by cardiac hypertrophy. During embryonic development, MARP was expressed in forming skeletal muscle. In situ hybridization analysis in mouse embryos revealed that MARP transcript exclusively accumulates at the end regions of primary myotubes during muscle morphogenesis. This closely coincided with the expression of thrombospondin-4 in adjacent prospective tendon mesenchyme, suggesting that these two compartments may constitute a functional unit involved in muscle morphogenesis. Transfection experiments established that MARP protein accumulates in the nucleus and that the levels of both MARP mRNA and protein are controlled by rapid degradation mechanisms characteristic of regulatory early response genes. The results establish the existence of novel regulatory muscle fiber subcompartments associated with muscle morphogenesis and denervation and suggest that MARP may be a crucial nuclear cofactor in local signaling pathways from prospective tendon mesenchyme to forming muscle and from activated muscle interstitial cells to denervated muscle fibers

Monitoring muscle fatigue following continuous load changes

Department of Human Factors EngineeringPrevious studies related to monitoring muscle fatigue during dynamic motion have focused on detecting the accumulation of muscle fatigue. However, it is necessary to detect both accumulation and recovery of muscle fatigue in dynamic muscle contraction while muscle load changes continuously. This study aims to investigate the development and recovery of muscle fatigue in dynamic muscle contraction conditions following continuous load changes. Twenty healthy males conducted repetitive elbow flexion and extension using 2kg and 1kg dumbbell, by turns. They performed the two tasks of different intensity (2kg intensity task, 1kg intensity task) alternately until they felt they could no longer achieve the required movement range or until they experienced unacceptable biceps muscle discomfort. Meanwhile, using EMG signal of biceps brachii muscle, fatigue detections were performed from both dynamic measurements during each dynamic muscle contraction task and isometric measurements during isometric muscle contraction right before and after each task. In each of 2kg and 1kg intensity tasks, pre, post and change value of EMG amplitude (AEMG) and center frequency were computed respectively. They were compared to check the validity of the muscle fatigue monitoring method using Wavelet transform with EMG signal from dynamic measurements. As a result, a decrease of center frequency in 2kg intensity tasks and an increase of center frequency in 1kg intensity tasks were detected. It shows that development and recovery of muscle fatigue were detected in 2kg and 1kg intensity tasks, respectively. Also, the tendency of change value of center frequency from dynamic measurements were corresponded with that from isometric measurements. It suggests that monitoring muscle fatigue in dynamic muscle contraction conditions using wavelet transform was valid to detect the development and recovery of muscle fatigue continuously. The result also shows the possibility of monitoring muscle fatigue in real-time in industry and it could propose a guideline in designing a human-robot interaction system based on monitoring user's muscle fatigue.clos

Denervation does not induce muscle atrophy through oxidative stress

Denervation leads to the activation of the catabolic pathways, such as the ubiquitin-proteasome and autophagy, resulting in skeletal muscle atrophy and weakness. Furthermore, denervation induces oxidative stress in skeletal muscle, which is thought to contribute to the induction of skeletal muscle atrophy. Several muscle diseases are characterized by denervation, but the molecular pathways contributing to muscle atrophy have been only partially described. Our study delineates the kinetics of activation of oxidative stress response in skeletal muscle following denervation. Despite the denervation-dependent induction of oxidative stress in skeletal muscle, treatments with anti-oxidant drugs do not prevent the reduction of muscle mass. Our results indicate that, although oxidative stress may contribute to the activation of the response to denervation, it is not responsible by itself of oxidative damage or neurogenic muscle atrophy

A nitric oxide synthase transgene ameliorates muscular dystrophy in mdx mice.

Dystrophin-deficient muscles experience large reductions in expression of nitric oxide synthase (NOS), which suggests that NO deficiency may influence the dystrophic pathology. Because NO can function as an antiinflammatory and cytoprotective molecule, we propose that the loss of NOS from dystrophic muscle exacerbates muscle inflammation and fiber damage by inflammatory cells. Analysis of transgenic mdx mice that were null mutants for dystrophin, but expressed normal levels of NO in muscle, showed that the normalization of NO production caused large reductions in macrophage concentrations in the mdx muscle. Expression of the NOS transgene in mdx muscle also prevented the majority of muscle membrane injury that is detectable in vivo, and resulted in large decreases in serum creatine kinase concentrations. Furthermore, our data show that mdx muscle macrophages are cytolytic at concentrations that occur in dystrophic, NOS-deficient muscle, but are not cytolytic at concentrations that occur in dystrophic mice that express the NOS transgene in muscle. Finally, our data show that antibody depletions of macrophages from mdx mice cause significant reductions in muscle membrane injury. Together, these findings indicate that macrophages promote injury of dystrophin-deficient muscle, and the loss of normal levels of NO production by dystrophic muscle exacerbates inflammation and membrane injury in muscular dystrophy

Muscle force is determined also by muscle relative position: isolated effects

Effects on force of changes of the position of extensor digitorum longus muscle (EDL) relative to surrounding tissues were investigated in rat. Connective tissue at the muscle bellies of tibialis anterior (TA), extensor hallucis longus (EHL) and EDL was left intact, to allow myofascial force transmission. The position of EDL muscle was altered, without changing EDL muscle–tendon complex length, and force exerted at proximal and distal tendons of EDL as well as summed force exerted at the distal tendons of TA and EHL muscles (TA+EHL) were measured. Proximal and distal EDL forces as well as distal TA+EHL force changed significantly on repositioning EDL muscle.\ud \ud These muscle position–force characteristics were assessed at two EDL lengths and two TA+EHL lengths. It was shown that changes of muscle force with length changes of a muscle is the result of the length changes per se, as well as of changes of relative position of parts of the muscle. It is concluded that in addition to length, muscle position relative to its surroundings co-determines isometric muscle force.\ud \ud Keywords: Intermuscular and extramuscular connective tissue; Myofascial force transmission; Rat m. extensor digitorum longus (EDL); Sarcomere length; Muscle relative positio