Ultrastructural Changes in Skeletal Muscle of Infants with Mitochondrial Respiratory Chain Complex I Defects

BACKGROUND AND PURPOSE: The pathogenesis of mitochondrial disease (MD) involves the disruption of cellular energy metabolism, which results from defects in the mitochondrial respiratory chain complex (MRC). We investigated whether infants with MRC I defects showed ultrastructural changes in skeletal muscle. METHODS: Twelve infants were enrolled in this study. They were initially evaluated for unexplained neurodegenerative symptoms, myopathies, or other progressive multiorgan involvement, and underwent muscle biopsies when MD was suspected. Muscle tissue samples were subjected to biochemical enzyme assays and observation by transmission electron microscopy. We compared and analyzed the ultrastructure of skeletal muscle tissues obtained from patients with and without MRC I defects. RESULTS: Biochemical enzyme assays confirmed the presence of MRC I defects in 7 of the 12 patients. Larger mitochondria, lipid droplets, and fused structures between the outer mitochondrial membrane and lipid droplets were observed in the skeletal muscles of patients with MRC I defects. CONCLUSIONS: Mitochondrial functional defects in MRC I disrupt certain activities related to adenosine triphosphate synthesis that produce changes in the skeletal muscle. The ultrastructural changes observed in the infants in this study might serve as unique markers for the detection of MD.

Expressão de antígenos MHC classe I e de células CD4 e CD8 na polimiosite e dermatomiosite / MHC class I antigens, CD4 and CD8 expressions in polymyositis and dermatomyositis

Objetivo: Analisar as frequências de expressão dos antígenos de complexo principal de histocompatibilidade classe I (MHC-I) e células CD4 e CD8 no músculo esquelético na polimiosite (PM) e dermatomiosite (DM). Métodos: Estudo retrospectivo de 34 casos de PM, oito casos de DM e 29 controles com miopatias não inflamatórias. Resultados: Os antígenos MHC-I expressaram-se no sarcolema e/ou sarcoplasma em 79,4% dos casos de PM, 62,5% dos casos de DM e 27,6% dos controles (a expressão de CD4 foi observada em 76,5%, 75% e 13,8%, respectivamente). Quando os antígenos de MHC-I foram coexpressados com CD4, houve elevada suspeita de PM/DM (principalmente PM). Em 14,3% dos casos de PM/DM, observou-se a expressão isolada dos antígenos MHC-I, sem células inflamatórias. Conclusão: A expressão dos antígenos MHC-I e a positividade do CD4 podem aumentar a suspeita diagnóstica de PM/DM. Não foi observado infiltrado celular em 14,3% dos casos. .

Objective: To analyze the frequencies of the expression of major histocompatibility complex class I (MHC-I) antigens, and CD4 and CD8 cells in skeletal muscle in polymyositis (PM) and dermatomyositis (DM). Methods: This was a retrospective study of 34 PM cases, 8 DM cases, and 29 control patients with non-inflammatory myopathies. Results: MHC-I antigens were expressed in the sarcolemma and/or sarcoplasm in 79.4% of PM cases, 62.5% of DM cases, and 27.6% of controls (CD4 expression was observed in 76.5%, 75%, and 13.8%, respectively). There was a high suspicion of PM/DM (mainly PM) in participants in whom MHC-I antigens and CD4 were co-expressed. In 14.3% of PM/DM cases, we observed MHC-I antigens expression alone, without inflammatory cells. Conclusion: MHC-I antigens expression and CD4 positivity might add to strong diagnostic suspicion of PM/DM. No cellular infiltration was observed in approximately 14.3% of such cases. .

The clinical and muscular pathological features of statin-induced myopathy / 中华内科杂志

Objective To explore clinical and muscular pathological features of statin-induced myopathy.Methods Nine patients were enrolled in this study,who were diagnosed as statin-induced myopathy by muscle biopsy in Peking University First Hospital from April,2012 to October,2014.The clinical data and pathological findings were analyzed.Results The exposure time to statins varied from 4 days to 4 years in the total of 9 patients,6 males and 3 females,with the average age of 63 ± 6 (55 to 74) years old.Three patients suffered from myalgia and 6 patients complained of weakness mainly at the proximal limbs,while no symptoms occured in 3 patients.Serum creatine kinase (CK) increased in all patients with the maximum value varied from 468 to 8 000 U/L.Serum myositis antibodies were tested in 7 patients and all were negative.Electromyogram was performed in six patients with myogenic damage found in 2 patients.MRI of bilateral thigh muscle was carried out in six patients with muscle edema and mild fatty infiltration found in 2 patients.All patients underwent skeletal muscle biopsy with histochemical and immunohistochemical staining.The main muscular pathological features were muscle fiber atrophy,necrosis,regeneration and increased lipid droplets.Ragged blue fiber,cytochrome C oxidase-negative muscle fibers and decreased NADH activity were observed in some patients.MHC-Ⅰ expressed in the sarcolemma of muscle fibers at various levels.Mild C5b-9 staining was found in the endomysium,capillary and cytoplasm.Symptoms and the level of CK were improved in 7 patients after discontinuing statins or changing to another statin,while the immunosuppressive therapy were used in 2 patients and shown to be effective.Conclusions Statin induced myopathy is self-limiting in most patients,with improvement after discontinuation of statins.Few patients with autoimmune necrotic myopathy need immunosuppressive therapy.

Gene Chip Screening of Related Genes of Shenqi Compound Recipe in Preventing Diabetic Skeletal Muscle Disease / 广州中医药大学学报

Objective To investigate the correlation of diabetic skeletal muscle disease with macroangiopathy, and to explore the related genes of Shenqi Compound Recipe (SCR) in preventing and treating diabetic skeletal muscle disease by using gene chip technique, thus to reveal the molecular mechanism. Methods KKAy mice were fed with water containing nitri oxide synthase inhibitor of Nω-nitro-L-arginine methyl ester ( L-NAME) and high fat diet to induce the macroangiopathy complicated with type 2 diabetes. The experimental animals were divided into normal c57BL/GJ group, KKAy group, model group, SCR group (in the dosage of 14.4 g·kg-1·d-1) and rosiglitazone group ( in the dosage of 1.33 mg·kg-1·d-1) , 15 in each group. The medication groups were administered the corresponding agents for 8 consecutive weeks just as the modeling began. During the experiment period, blood glucose was monitored. At the end of the experiment, the abdominal aorta and skeletal muscle of mice were taken out for the observation of morphological changes, and differentially expressed genes of skeletal muscle between SCR group and model group, and between model group and KKAy group were detected by gene chip technique. Results SCR had an effect on relieving the atrophy, edema, fracture, and inflammatory changes in the skeletal muscle. There were 198 genes differentially expressed between model group and KKAy group, including 119 up-regulated genes and 79 down-regulated genes. There were 70 genes differentially expressed between SCR group and model group, including 33 up-regulated genes and 37 down-regulated genes. In the two comparison groups, 7 genes ( Celsr2, Rilpl1, Dlx6as, 2010004M13Rik, Anapc13, Gm6097, Ddx39b) showed reversed differential expression. Conclusion Diabetic skeletal muscle disease is associated with macroangiopathy. SCR has preventive effect on diabetic skeletal muscle lesion, and the mechanism may be related to the regulation of Celsr2, Rilpl1, Dlx6as, 2010004M13Rik, Anapc13, Gm6097, Ddx39b gene expression.

Influence of triamcinolone acetonide on peribulbus tissues via periocular injection / 中华实验眼科杂志

Background Triamcinolone acetonide (TA) is often used in the treatment of uveitis and fundus disease,but whether it has toxic effect to normal tissue around eyes is unclear.Objective The aim of this study was to explore the adverse and toxic effects of TA on the periorbitally normal tissue following the periocular injection.Methods Twenty-seven New Zealand albino rabbits were randomly divided into experimental group,normal saline solution group and blank control group.TA was periocularly injected twice (20 mg for each) at 1-month interval in the rabbits of the experimental group,and 0.5 ml normal saline solution was used in the same way in the rabbits of the normal saline solution group.Not any drug was used in the blank group.The rabbits were sacrificed 1 month and 2 months,3 months after the secondary injection.For the preparation of the specimens of extraocular muscles,peribulbus adipose tissue,lacrimal gland and optic nerve.Hematoxylin and eosin staining of the specimens was performed to examine the the pathological change under the optical microscope,and the ultrastructural of peribulbus tissues was observed under the transmission electron microscope.Results No statistically significant change was found in IOP among various time points and groups (Fgroup =0.952,P =0.881 ; Ftime =7.297,P =0.411).The hyphological structures and ultrastructure of extraocular muscles,peribulbus adipose tissue,lacrimal gland and optic nerve were normal in the rabbits of the normal saline solution group and the blank control group.However,the optical microscopy showed varying degrees of atrophy or dissolving in the extraocular muscle fibers,the increase of glandular epithelial cells and enlargement of nuclei in the lacrimal gland as well as visible disorder arrangement of nerve fibers,vacuoles degeneration and the decrease of glial cells in optial nerve tissue in the rabbits of the experimental group from 1 month though 3 months after the secondary injection.Under the transmission electron microscope,the muscle stripes,bright band and dark band were incompletely disappeared,and expansionary sarcoplasmic reticulum and oval nucleus at the inferior to sarolemma were seen in the extraocular muscles.In addition,swelling lacrimal gland epithelial cells,thickening nuclear membrane and more organelles were exhibited in the lacrimal gland.In the optic never tissue,uneven myelin,space between axons and myelin,lamellar separation and degeneration also were revealed in the rabbits of the experimental group after injection of TA.Peribulbus adipose tissue was near normal both by optical microscope and transmission electron microscope in the experimental group.Conclusions The periocular injection of TA dose not elevated the IOP.However,it will result in the histogical and ultrastructural damages of extraocular muscles,lacrimal gland and optic nerve.

Pathological characteristics of muscular on delayed neuropathy induced by experimental organophosthate and the treatment efficacy of Dexamethasone and Dytidine / 临床神经病学杂志

0.05).The symptom of peripheral neuropathy emerged 1 w after poisoning,the numbers of gait abnormal were 3,4 and 4 respectively in groups A,B and C,and there were no significant difference among those groups.It showed that the necrosis of segments of muscle fibers and macrophages infiltration scattering distribution were observated in the necrosis area and muscular interstition.At the end of 3 w,4 w and 8 w,there were significant differences in the area of muscular necrosis between group A and C(P

A Case of Incontinentia Pigmenti with Destructive Encephalopathy

Becker muscular dystrophy is a X-linked recessive disease with the affected gene at locus Xp21, characterized by progressive muscular weakness. Without the definite family history, it has been known that the diagnosis of this disease is almost impossible on clinical grounds alone. We reviewed the muscle pathology of two casses of genetically confirmed Becker muscular dystrophy to know the diagnositc significances of this study. The first case, a 20 year old man, is the classical one with definite family history of X-linked recessive heredity. The muscle pathology of the biceps showed dystrophic muscular changes, including increased internal nuclei, marked variation of fiber sizes and mild endomysial fibrosis. The dystrophin stain of the muscle was also confirmative for the diagnosis. The second case was a 32 year old man who has been biopsied his left vastus lateralis 5 years before this genetic diagnosis. This case is a sporadic one without the family history. The diagnosis at the time of muscle biopsy was limb-girdle muscular dystorphy or inclusion body myositis because of the typical rimmed vacuoles and marked variation of fiber sizes. The dystophin stain was not available at that time. Our conclusion is that the molecular genetic study and/or dystrophin protein test of muscle biopsy should be done in every clinically suspected patient, including limb-girdle muscular dystorphy, inclusion body myositis or rimmed vacuolar myopathies.

Clinical and pathological features of rhabdomyolysis and it caused acute renal failure: a case report / 临床神经病学杂志

Objective To investigate the etiology, pathology, pathogenesy and treatment in patient with rhabdomyolysis (RM) complicated with acute renal failure(ARF). Methods Analysis of clinical and muscle pathological data combined with literatures were made for a patient with RM-ARF.Results The patient who had experienced exercise induced RM for 5 years. Alcohol drinking and infection were led to RM with ARF for this time. There was non-special inflammatory feature in light microscope by biopsy. The principle of RM management was prevention of hypovolemia and acidification of urine. Hemodialysis (HD)was chosen for treatment of ARF and basic recovery was obtained.Conclusions The etiology of this patient may be the alcohol drinking, particularly the infection which developed on the basis of recurrent RM. Muscle biopsy is useful not only for observing the pathological features of RM, but also for differentiation of etiological factors. The HD therapy used in time may be the key to get favorable effect for this case.