After direct superior rectus muscle injection of BtA in rabbit eyes, we examined the ultrasructural changes of the muscles from 1 day to 8 weeks after injection. The most profound changes seen at electron microxcopic levels after BtA injedtion were early vacuolization of the sarcoplasmic structure, extensive damage of myofibril, degeneration of the postjunctional fold and widening of the synaptic cleft. Myofiber changes were reversible with no apparent long-term consequence. However, most of the degenerations of myoneuronal junction were still present in 8 weeks post-injedtion. Comparing myotoxic effects according to rabbit age, the botulinum toxin seems to make more severe histologic damage in the fibers of the two-month old than six-month old or older. AchE activity of injection group is mildly decrease in number of positive fibers rather than control group, which was not statistically significant in the quantitative analysis. In conclusion the early vacuolization and degeneration of the sarcoplasmic structure, and degeneration of the postjunctional folds after toxin injection in the muscles are most likely due to a direct myotoxic effect of BtA.
Botulinum Toxins* ; Botulinum Toxins, Type A ; Muscles ; Myofibrils

The effects of unilateral sciatic neurectomy on gastrocnemius muscle were studied in adult male rats. The morphological changes of both gastrocnemius muscles were observed by light and electron microscopy. Western blot analysis was performed to study the protein expression. Following the denervation, the affected muscle weights decreased significantly than normal. And the denervation led to a significant reduction in the area and diameter of muscle fibers on light microscopy. The affected muscle fibers showed the decreasing in size and the irregularity of myofibrilar arrangement on electron microscopy. On transverse view, the area of affected muscle fibers were smaller than normal. Their myofibrils were smaller and very irregular in size. The thin and thick myofilaments were not regular and partially lost. Mitochondria between myofibrils and subsarcolemmal area in affected muscle fibers were damaged and partially lost. The sacoplasmic reticulum and T-tubules were mostly lost and irregular. Some satellite cells were observed adjacent the muscle fiber, but they were inactive morphologically. On longitudinal view, most of myofibrils in affected muscle fibers were lost generally or partially although the their most sarcomeres were regularly arranged. Z line and myofilaments were lost partially and were partially irregularly arranged. The loss of thin myofilaments was more than that of thick myofilaments. Much debris of cell organelles were scattered among myofibrils. The expression of MyoD and myogenin were decrease significantly and the expression of p-mTOR and p-FOXO1 were decreased, too. On the other hand, MuRF1 was increased significantly. Taken together, the main effect of gastrocnemius muscle by sciatic neurectomy is the atrophy as a result of the loss of myofilaments and cell organelles through the decrease of protein synthesis and the increase of protein degradation.
Adult ; Animals ; Atrophy ; Blotting, Western ; Denervation ; Hand ; Humans ; Light ; Male ; Microscopy ; Microscopy, Electron ; Mitochondria ; Muscle, Skeletal ; Muscles ; Myofibrils ; Myogenin ; Organelles ; Proteolysis ; Rats ; Reticulum ; Sarcomeres ; Sciatic Nerve ; Weights and Measures

Muscle wasting is commonly seen in patients with sepsis as a consequence of the catabolic response in skeletal muscle. Muscle wasting can occur in cases that have an imbalance between degradation and synthesis of muscle proteins. Although decrements in the synthesis of muscle proteins may contribute to sepsis-induced muscle wasting, it has been recognized that increments in its degradation play a more essential role in muscle wasting. Muscle wasting in sepsis patients has some significant clinical consequences such as reduced ambulation and exercise tolerance, and an increased risk for pulmonary and thromboembolic complications. Several mechanisms have been proposed for sepsis-induced muscle wasting. Increased proteolysis via the ubiquitin-proteasome pathway and the calpains system is one of the principal mechanisms of muscle wasting induced by sepsis. Calpains are activated by calcium, which increases in patients with sepsis. The activation of the calpains system disrupts the sarcomere of the myofibrils, resulting in the release of myofilaments that are subsequently ubiquitinated and degraded by the 26S proteasome complex. Recent studies have suggested that transcriptional factors such as NF-kappaB and FoxO, and the apoptosis and autophagy-lysosome pathways may also be involved in sepsis-induced muscle wasting. This review briefly summarizes the contribution of these mechanisms of muscle wasting in patients with sepsis and the possible therapeutic agents to treat it.
Apoptosis ; Atrophy ; Calcium ; Calpain ; Exercise Tolerance ; Humans ; Muscle Proteins ; Muscle, Skeletal ; Muscles ; Myofibrils ; NF-kappa B ; Proteasome Endopeptidase Complex ; Proteolysis ; Sarcomeres ; Sepsis ; Ubiquitin ; Walking

A 12-year-old girl presented with a ciliary body mass that measured approximately 13 X 10 mm in size. The tumor was excised through cyclectomy. The light microscopic apprearance resembled neurogenic neoplasm such as neurofibroma or schwannoma. However, some tumor cells included fasciculus which is a characteristic feature of myogenic tumor. Immunohistochemistry assay and electron microscopic examination revealed smooth muscle nature including myofilaments with dense bodies and established the diagnosis as mesectodermal leiomyoma in the ciliary body. To our best knowledge, our patient is the youngest among the ciliary body leiomyoma cases ever reported.
Child ; Ciliary Body* ; Diagnosis ; Female ; Humans ; Immunohistochemistry ; Leiomyoma* ; Muscle, Smooth ; Myofibrils ; Neurilemmoma ; Neurofibroma

PURPOSE: Doxorubicin has an effect of permanently removing muscle after direct injection into the eyelid for treatment of blepharospasm. However, the major dilemma of this attractive treatment is the necrosis of skin overlying the orbicularis oculi muscle. This study was to evaluate whether liposome-encapsulated doxorubicin (Doxil R ) and dimethyl sulfoxide (DMSO) could decrease the incidence and severity of the skin necrosis. METHODS: 0.5, 1, 2 mg of doxorubicin, Doxil and a combination of doxorubicin with DMSO were injected into eyelids of rabbits, respectively. Animals were examined daily on onset, duration, and the size of skin necrosis after each injection. For the evaluation of functional change of muscle after doxorubicin injection, EMG study was conducted and the eyelids were examined histologically and the amount of muscle loss were measured by means of a NIH image analysis program. Electronmicroscopic morphology was also assessed. RESULTS: Doxil decreased the duration and size of skin necrosis, incidence of ectropion, and delayed the onset of skin necrosis markedly. Doxil was more effective in the protection of skin from necrosis than a combination of doxorubicin and DMSO. Compared with free doxorubicin, doxil had 79.2% of myectomy effect. Although doxil was less effective in myectomy than free doxorubicin, excellent myectomy effect was functionally proved on EMG study. A combination of DMSO and doxorubicin had 84.1% of myectomy effect compared with doxorubicin alone but the difference was not significant. In electronmicroscopic study, loss of Z-disc and I-band and segmental disorganization of myofibrills were observed in all three groups. CONCLUSIONS: Both Doxil and a combination of doxorubicin and DMSO improved safety of doxorubicin chemomyectomy by prevention of skin necrosis. Doxil 1.0 mg was most effective in protection of skin from necrosis.
Animals ; Blepharospasm ; Dimethyl Sulfoxide* ; Doxorubicin* ; Ectropion ; Eyelids* ; Incidence ; Myofibrils ; Necrosis ; Rabbits ; Skin*

Childhood onset nemaline myopathy, first described in 1963 by Shy, et al and Conen, et al, is rare congenital myopathy, characterized by nonprogressive or slowly progressive muscle weakness associated with rod-like structures in muscle fibers, often with dysmorphic features. This myopathy was confirmed by muscle biopsy. The light microscopic features noted generally small round fibers that showed variation in size and occasional internal nuclei and characteristic rod bodies that could be demonstrated in the longitudinal sections stained with modified Gomori trichrome stain. Electromicroscopically there were accumulations of numerous irregular electron dense materials scattered between the myofibrils, particularly under the sarcolemma and enlargement and streamimg of the Z disk. We report a case of childhood onset nemaline myopathy in Korea in a 7 year- old boy who had nonprogressive muscle weakness of the limbs with a waddling gait.
Biopsy ; Extremities ; Gait ; Humans ; Korea ; Male ; Muscle Weakness ; Muscular Diseases ; Myofibrils ; Myopathies, Nemaline* ; Sarcolemma

PURPOSE: We'd like to evaluate the relationship between the degree of cardiac damage and that of cardiac function according to the total injected dose of doxorubicin. METHODS: 12 rabbits(body weight : 2.0-3.2 kg) were used and 30 mg/m2/week of doxorubicin hydrochloride was injected intravenously. The cardiac function was checked under anesthesia, after which the thorax was opened and cardiac samples were evaluated with light and electron microscopics. RESULTS: Regardless of total injected dose of doxorubicin, there was no difference between the general appearance, sizes and thickness of both atria and ventricles of doxorubicin injected rabbits and those of normal control. The rabbits with total cumulative dose <180 mg/m2 showed no differences with the rabbits of normal control in the cardiac histology. The rabbits with cumulative doses of 210 mg/m2 had an increased number of vacuoles in the interspaces of the myofibrils and glucogen granules in myocytes. The rabbits with the cumulative dose of 240 mg/m2 had focal necrosis and degeneration of myocytes with fibrous cells infiltration. The rabbits with cumulative doses of 300 mg/m2 demonstrated severe and diffuse degenerations with markedly decreased numbers of myocytes and increased intracellular vacuoles. All the rabbits with total cumulative doses <240 mg/m2 showed no difference in the aortic pressure, left ventricular(LV) maximal dP/dt and left ventricular end diastolic pressure(LVEDP) compared to normal control. The rabbit with total cumulative doses of 300 mg/m2 showed no difference in the aortic pressure and LV maximal dP/ dt, but revealed significantly elevated LVEDP compared to normal control. CONCLUSION: These results showed doxorubicin induced cardiotoxicity is dose related and may be certain at total cumulative dose >200 mg/m2, although cardiac function is normal.
Anesthesia ; Arterial Pressure ; Doxorubicin* ; Muscle Cells ; Myofibrils ; Necrosis ; Rabbits* ; Thorax ; Vacuoles ; Ventricular Function, Left*

To elucidate the effects of dimethyl sulfoxide on of myocardial and endothelial cells in culture, the cells were exposed to 10% dimethyl sulfoxide in culture medium for 1 hour at 48 hours after cell isolation. The general morphology and the cytochemical reaction of marker enzymes for mitochondria and Golgi complexes were investigated. The results were summarized as follows 1. DMSO induced elongation and narrowing of the cells and increase of mitochondrial reaction in myocardial cells. 2. DMSO induced destruction and disruption of myofibrils in myocardial cells resulting in increase of contractile activities. 3. In the endothelial cells, DMSO suppressed proliferative activities but thiamine pyrophosphatase reactions were enhanced indicating increase of Golgi complex activity. 4. DMSO seemed to hamper with the adhesiveness and motility of the endothelial cells causing the decrease of the number of cells in vitro.
Adhesiveness ; Cell Separation ; Dimethyl Sulfoxide* ; Endothelial Cells* ; Golgi Apparatus ; In Vitro Techniques ; Mitochondria ; Myofibrils ; Thiamine Pyrophosphatase

The authors studied one case with rhabdomyolysis associated with acute renal failure, which followed acute CO intoxication. Oliguria, hyperkalemia developed within one day of rhabdomyolysis on left extremities. During the first three days of hospitalization, rapid increase in serum BUN, serum creatinine and serum muscle enzymes (CPK, LDH, GPT, GOT) were noted. Renal failure was controlled by artifiral kidney. Several areas of increased uptake of technetium-99m DP were noticed on bone scan. Electron microscopic examinations of biopsied muscle consist of disarrangement of myofibrils, loss or destruction of Z-line, difficulties in distinguishing A-band from I-band, and swelling of mitochondrias. These findings suggest that acute CO poising may be followed by severe muscle destruction and renal damage.
Acute Kidney Injury* ; Creatinine ; Extremities ; Hospitalization ; Hyperkalemia ; Kidney ; Mitochondria ; Myofibrils ; Oliguria ; Poisoning* ; Renal Insufficiency ; Rhabdomyolysis*

Light and electron microscopic obserbations of developing heart wall of zebrafish, which has been recently used for developmental studies of many organs, were performed. Heart tissue was obtained from adult and 24, 48 and 72 hour embryos of zebrafish. Heart wall of adult zebrafish was composed of 3 typical layers, endocardium, myocardium and epicardium, as ones of other vertebrates. Heart wall of 24 hour embryo was composed of primitive myocytes. Myofibrils in myocytes at this period was found as assembly of myofilaments, 500~1,000 nm sized and 5~10 layered. Heart of 48 hour embryo has ventricle and atrium. Ventricular wall of was composed of endocardium, myocardium and incomplete epicardium. Atrial wall at 48 hour embryo was composed of endocardium and myocardium. Development of myocytes in ventricle was earlier than those of atrium, and myofibrils with Z disc were found first at 48 hour embryo. Heart wall of 72 hour embryo was morphologically similar to that of 48 hour embryo, but development of myocytes was more progressed. Specific atrial granules of 100~200 nm size appeared very rarely at 24 hour embryo and its numbers increased gradually at 48 and 72 hour embryos in myocytes of atrium as well as the ventricle. Specific atrial granules were consider as ones containing atrial natriuretic peptide (ANP).
Adult ; Embryonic Structures ; Endocardium ; Heart* ; Humans ; Muscle Cells ; Myocardium ; Myofibrils ; Pericardium ; Vertebrates ; Zebrafish*