scholarly journals Phospholipids in artificially induced muscular dystrophy of calves

1973 ◽  
Vol 29 (2) ◽  
pp. 293-296 ◽  
Author(s):  
Ritva Poukka Evarts ◽  
Aili Oksanen

1. Phospholipds were studied in the heart muscles, skeletal muscles and livers of seven Ayrshire calves which received vitamin E-free maize oil (in filled milk) with and without supplementary α-tocopherol from 1 week old for 17 d. The calves that were not given vitamin E developed muscular dystrophy.2. Decreased amounts of cardiolipin and increased amounts of sphingomyelin were found in the skeletal muscles of vitamin E-deficient calves. There was a significant decrease of phosphatidyl choline in the livers of vitamin E-deficient calves.3. The decrease in cardiolipin concentration confirmed the electron-microscopical picture (reported elsewhere) of preferential destruction of mitochondria in muscular dystrophy of calves.

1939 ◽  
Vol 39 (6) ◽  
pp. 643-652 ◽  
Author(s):  
Archer John Porter Martin ◽  
Thomas Moore

IN an early preliminary communication we (Martin & Moore, 1936) reported that in rats maintained for prolonged periods on diets deficient in vitamin E a brown discoloration of the uterus occurred. Degeneration of the convoluted tubules of the kidneys was also found. In a more recent paper we (Martin & Moore, 1938) described a less intense discoloration in the skeletal muscles, which was localized in distribution. The muscles of the hindlegs, which displayed the paresis described by Ringsted (1935), were always noticeably discoloured. In both the uterine and leg muscles discoloration was found to be associated with muscular degeneration. The similarity of the condition in the leg muscles to the nutritional muscular dystrophy first reported by Goettsch & Pappenheimer (1931) in guinea-pigs was noted. The purpose of this communication is to give a detailed account of this work, including its most recent developments (Moore, 1939).


1968 ◽  
Vol 22 (3) ◽  
pp. 411-422 ◽  
Author(s):  
J. W. Boyd

1. Lambs fed on skim milk containing either maize oil or cod-liver oil or both were observed for signs of muscular dystrophy, changes in serum enzymes and increases in the susceptibility of red cells to haemolysis by peroxide (peroxide haemolysis).2. Four lambs fed on the milk containing cod-liver oil, and not receiving α-tocopheryl acetate injections, developed acute muscular dystrophy, but no abnormal changes occurred in peroxide haemolysis, packed cell volume or haemoglobin concentration in the blood. Marked increases occurred in the aspartate transaminase, alanine transaminase and glutamate dehydrogenase, and in lactate dehydrogenase isoenzyme activities of the serum, presumably due to leakage from the degenerating tissues. One lamb given weekly injections of 100 mg α-tocopheryl acetate remained clinically normal and maintained normal serum enzyme levels. Treatment of dystrophic animals with 200 mg α-tocopheryl acetate by injection produced prompt clinical recovery and an exponential decline in the raised serum enzyme activities.3. In the five lambs fed on the skim-milk containing maize oil, muscular dystrophy did not occur. Small but significant increases occurred, however, in serum aspartate transaminase and glutamate dehydrogenase activities. In all five animals peroxide haemolysis was greatly increased, but in only two did packed cell volume and haemoglobin values fall slightly below the lower limit of normal (mean − 2 × SD). Injections of 100–200 mg α-tocopheryl acetate neither prevented nor cured the abnormally high levels of serum enzymes and peroxide haemolysis, although a change in the diet was followed by a gradual return to normal. In one lamb given massive doses of α-tocopherol by mouth, peroxide haemolysis was not reduced. Large amounts of α-tocopherol added in vitro to erythrocytes from the lamb did, however, prevent peroxide haemolysis.4. Peroxide haemolysis did not increase in any of three lambs fed on skim milk containing both maize oil and cod-liver oil, although two of them, which were given much larger amounts of cod-liver oil than the third, developed muscular dystrophy with elevated serum enzyme levels.5. Peroxide haemolysis in lambs is evidently not a measure of vitamin E deficiency. It is suggested that increased peroxide haemolysis in lambs, like encephalomalacia in chicks, depends on the fatty acid composition of the unsaturated lipids in the diet.


2020 ◽  
Author(s):  
Thomas Taetzsch ◽  
Dillon Shapiro ◽  
Randa Eldosougi ◽  
Tracey Myers ◽  
Robert Settlage ◽  
...  

AbstractDuchenne muscular dystrophy (DMD) is characterized by progressive degeneration of skeletal muscles. To date, there are no treatments available to slow or prevent the disease. Hence, it remains essential to identify molecular factors that promote muscle biogenesis since they could serve as therapeutic targets for treating DMD. While the muscle enriched microRNA, miR-133b, has been implicated in the biogenesis of muscle fibers, its role in DMD remains unknown. To assess the role of miR-133b in DMD-affected skeletal muscles, we genetically ablated miR-133b in the mdx mouse model of DMD. In the absence of miR-133b, the tibialis anterior muscle of juvenile and adult mdx mice is populated by small muscle fibers with centralized nuclei, exhibits increased fibrosis, and thickened interstitial space. Additional analysis revealed that loss of miR-133b exacerbates DMD-pathogenesis partly by altering the number of satellite cells and levels of protein-encoding genes, including previously identified miR-133b targets as well as genes involved in cell proliferation and fibrosis. Altogether, our data demonstrate that skeletal muscles utilize miR-133b to mitigate the deleterious effects of DMD.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nizar Y. Saad ◽  
Mustafa Al-Kharsan ◽  
Sara E. Garwick-Coppens ◽  
Gholamhossein Amini Chermahini ◽  
Madison A. Harper ◽  
...  

AbstractFacioscapulohumeral muscular dystrophy (FSHD) is a potentially devastating myopathy caused by de-repression of the DUX4 gene in skeletal muscles. Effective therapies will likely involve DUX4 inhibition. RNA interference (RNAi) is one powerful approach to inhibit DUX4, and we previously described a RNAi gene therapy to achieve DUX4 silencing in FSHD cells and mice using engineered microRNAs. Here we report a strategy to direct RNAi against DUX4 using the natural microRNA miR-675, which is derived from the lncRNA H19. Human miR-675 inhibits DUX4 expression and associated outcomes in FSHD cell models. In addition, miR-675 delivery using gene therapy protects muscles from DUX4-associated death in mice. Finally, we show that three known miR-675-upregulating small molecules inhibit DUX4 and DUX4-activated FSHD biomarkers in FSHD patient-derived myotubes. To our knowledge, this is the first study demonstrating the use of small molecules to suppress a dominant disease gene using an RNAi mechanism.


2000 ◽  
Vol 295 (3) ◽  
pp. 93-96 ◽  
Author(s):  
Takashi Kimura ◽  
Masanori P Takahashi ◽  
Yoshinobu Okuda ◽  
Misako Kaido ◽  
Harutoshi Fujimura ◽  
...  

2009 ◽  
Vol 296 (3) ◽  
pp. C476-C488 ◽  
Author(s):  
Paul T. Martin ◽  
Rui Xu ◽  
Louise R. Rodino-Klapac ◽  
Elaine Oglesbay ◽  
Marybeth Camboni ◽  
...  

The cytotoxic T cell (CT) GalNAc transferase, or Galgt2, is a UDP-GalNAc:β1,4- N-acetylgalactosaminyltransferase that is localized to the neuromuscular synapse in adult skeletal muscle, where it creates the synaptic CT carbohydrate antigen {GalNAcβ1,4[NeuAc(orGc)α2, 3]Galβ1,4GlcNAcβ-}. Overexpression of Galgt2 in the skeletal muscles of transgenic mice inhibits the development of muscular dystrophy in mdx mice, a model for Duchenne muscular dystrophy. Here, we provide physiological evidence as to how Galgt2 may inhibit the development of muscle pathology in mdx animals. Both Galgt2 transgenic wild-type and mdx skeletal muscles showed a marked improvement in normalized isometric force during repetitive eccentric contractions relative to nontransgenic littermates, even using a paradigm where nontransgenic muscles had force reductions of 95% or more. Muscles from Galgt2 transgenic mice, however, showed a significant decrement in normalized specific force and in hindlimb and forelimb grip strength at some ages. Overexpression of Galgt2 in muscles of young adult mdx mice, where Galgt2 has no effect on muscle size, also caused a significant decrease in force drop during eccentric contractions and increased normalized specific force. A comparison of Galgt2 and microdystrophin overexpression using a therapeutically relevant intravascular gene delivery protocol showed Galgt2 was as effective as microdystrophin at preventing loss of force during eccentric contractions. These experiments provide a mechanism to explain why Galgt2 overexpression inhibits muscular dystrophy in mdx muscles. That overexpression also prevents loss of force in nondystrophic muscles suggests that Galgt2 is a therapeutic target with broad potential applications.


2010 ◽  
Vol 91 (1) ◽  
pp. 63-71 ◽  
Author(s):  
Adriana Pertille ◽  
Candida Luiza Tonizza de Carvalho ◽  
Cintia Yuri Matsumura ◽  
Humberto Santo Neto ◽  
Maria Julia Marques

2018 ◽  
Vol 58 (1) ◽  
pp. 133-144 ◽  
Author(s):  
Gaia Giovannelli ◽  
Giorgia Giacomazzi ◽  
Hanne Grosemans ◽  
Maurilio Sampaolesi

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