Electrically stimulated sartorius neosphincter: Canine model of activation and skeletal muscle transformation

1990 ◽  
Vol 77 (2) ◽  
pp. 208-213 ◽  
Author(s):  
R. I. Hallan ◽  
N. S. Williams ◽  
M. R. E. Hutton ◽  
M. Scott ◽  
M. A. Pilot ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Canine Model ◽  
Muscle Transformation

Duchenne muscular dystrophy gene therapy in the canine model

2018 ◽  
Author(s):  
◽  
Kasun Kodippili
Keyword(s):  
Skeletal Muscle ◽  
Gene Therapy ◽  
Animal Model ◽  
Duchenne Muscular Dystrophy ◽  
Sarcoplasmic Reticulum ◽  
Muscular Dystrophy ◽  
Canine Model ◽  
Disease Pathogenesis ◽  
Preclinical Treatment ◽  
Expression And Activity

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Duchenne muscular dystrophy (DMD) is a devastating muscle wasting disease caused by loss of function mutations in the dystrophin gene, resulting in the absence of dystrophin, a structural protein in muscle. DMD is the most common form of inherited muscle disease in childhood, with an incidence of 1 in 5000 live male births worldwide. The dystrophin-null mdx mouse has been the most widely used animal model for DMD research over the last 30 years. Dystrophin-deficient DMD dogs have also gained prominence as a highly relevant preclinical animal model due to their high phenotypic homology to human DMD patients. Preclinical treatment studies in these dogs are expected to better inform and guide clinical trials in human patients. However, there are still significant gaps in our understanding of the disease pathogenesis and gene therapy in the canine model. The goals of my dissertation work were to establish reagents and methodologies to study preclinical treatment in the canine model, and subsequently characterize the disease pathogenesis and gene therapy in DMD dogs. To this end, I first characterized 65 epitope-specific human dystrophin monoclonal antibodies for their reactivity in canine skeletal and cardiac muscle by both immunofluorescence (IF) staining and western blot. I found species-specific, tissue-specific and assay-specific patterns of reactivity in these antibodies. Importantly, out of the 65 antibodies that I characterized, I recognized 15 antibodies that worked well for canine tissue on both IF staining and western blot, which are recommended for DMD research in the canine model. ... Dystrophin-independent gene therapy for DMD takes advantage of disease-modifying genes that are either structural and/or functional homologues of dystrophin, or alternative targets that are involved in disease pathogenesis. One such alternative target gene is the sarcoplasmic reticulum calcium ATPase 2a (SERCA2a), a pump that transports calcium ions from the cytoplasm into the sarcoplasmic reticulum. I show that SERCA2a expression and activity are impaired, and that calcium homeostasis is dysregulated in DMD dog skeletal muscle. Furthermore, gene therapy with human SERCA2a restored expression and activity of the pump, and improved several aspects of muscle function and histopathology in DMD dog skeletal muscle. In summary, this dissertation work advances our knowledge of the disease pathogenesis and gene therapy prospects in the canine model of DMD, a highly relevant and valuable preclinical DMD model.

scholarly journals Lipid-induced insulin resistance does not impair insulin access to skeletal muscle

2015 ◽  
Vol 308 (11) ◽  
pp. E1001-E1009 ◽  
Author(s):  
Cathryn M. Kolka ◽  
Joyce M. Richey ◽  
Ana Valeria B. Castro ◽  
Josiane L. Broussard ◽  
Viorica Ionut ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acids ◽  
Free Fatty Acids ◽  
Fold Increase ◽  
Canine Model ◽  
Hepatic Insulin Resistance ◽  
Lipid Infusion ◽  
Peripheral Insulin Resistance ◽  
Induce Insulin Resistance

Elevated plasma free fatty acids (FFA) induce insulin resistance in skeletal muscle. Previously, we have shown that experimental insulin resistance induced by lipid infusion prevents the dispersion of insulin through the muscle, and we hypothesized that this would lead to an impairment of insulin moving from the plasma to the muscle interstitium. Thus, we infused lipid into our anesthetized canine model and measured the appearance of insulin in the lymph as a means to sample muscle interstitium under hyperinsulinemic euglycemic clamp conditions. Although lipid infusion lowered the glucose infusion rate and induced both peripheral and hepatic insulin resistance, we were unable to detect an impairment of insulin access to the lymph. Interestingly, despite a significant, 10-fold increase in plasma FFA, we detected little to no increase in free fatty acids or triglycerides in the lymph after lipid infusion. Thus, we conclude that experimental insulin resistance induced by lipid infusion does not reduce insulin access to skeletal muscle under clamp conditions. This would suggest that the peripheral insulin resistance is likely due to reduced cellular sensitivity to insulin in this model, and yet we did not detect a change in the tissue microenvironment that could contribute to cellular insulin resistance.

scholarly journals The use of autologous skeletal muscle-derived cells as a sling in the treatment of induced stress urinary incontinence, an experimental study

2021 ◽  
Author(s):  
Bassem S Wadie ◽  
Haytham Aamer ◽  
Sherry Khater ◽  
Mahmoud Gabr
Keyword(s):  
Skeletal Muscle ◽  
Urinary Incontinence ◽  
Stress Urinary Incontinence ◽  
Muscle Biopsy ◽  
Culture Medium ◽  
Biceps Femoris ◽  
Canine Model ◽  
Polyglycolic Acid ◽  
Urethral Pressure ◽  
Skeletal Muscle Biopsy

Introduction & hypothesis: This is an experimental pre-clinical study testing for the applicability of autologous skeletal muscle derived cells as a seeded sling for the treatment of Stress urinary incontinence in canine model. Methods: 10 Mongrel dogs: In 4, skeletal muscle biopsy was harvested from Biceps Femoris. 1 month later, incontinence was induced in 8 dogs through surgical disruption of the pubourethral ligaments. Muscle biopsy was incubated in medium and after expansion for 8 weeks, Muscle derived cells were collected. Polyglycolic acid scaffold was immersed in culture medium, coated with matrigel and cells were seeded. The sling was placed suburethral in 8 dogs; 2 of which were cell-seeded and 4 had the scaffold only. Urethral pressure measurement was done at baseline and 2 weeks after insertion of the sling. The urethra with its surrounding was harvested 4 weeks after sling insertion for histopathology. 2 dogs were considered as control, in which no urethrolysis or insertion of slings was carried out. Results: Urethral pressure shows increase of maximum urethral pressure during static measurement in all dogs with a scaffold inserted. The increase ranged from 5-40 centimeter water (Median: 23 cmH20). Histopathology shows significant periurethral proliferation of skeletal muscles in 4 dogs with cell-seeded scaffold, as demonstrated by Desmin. This was maximum in dogs numbers 1and 2. This was not the case in the 4 dogs that had Polyglycolic acid sling only. Conclusion: The use of skeletal muscle-seeded scaffold is a practical technique with preserved integrity of histological differentiation in canine model at short term.

Quantitation of skeletal muscle necrosis using 99Tcm-pyrophosphate with SPECT in a canine model

1990 ◽  
Vol 11 (2) ◽  
pp. 143-150 ◽  
Author(s):  
T-C. K. YIP ◽  
S. HOULE ◽  
G. HAYES ◽  
I. FORREST ◽  
L. NELSON ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Canine Model ◽  
Muscle Necrosis

Muscle transformation of the sartorius muscle in a canine model

1997 ◽  
Vol 40 (11) ◽  
pp. 1321-1327 ◽  
Author(s):  
Harald R. Rosen ◽  
Guido Dorner ◽  
Wolfgang Feil ◽  
Gerald Zöch ◽  
Karl Renner ◽  
...  
Keyword(s):  
Canine Model ◽  
Sartorius Muscle ◽  
Muscle Transformation

scholarly journals The Use of Autologous Skeletal Muscle Derived Cells as a Sling in the Treatment of Induced Stress Urinary Incontinence, An Experimental Study in Dogs

2021 ◽  
Author(s):  
Bassem S Wadie ◽  
Haytham G Aamer ◽  
Sherry M Khater ◽  
Mahmoud M Gabr
Keyword(s):  
Skeletal Muscle ◽  
Muscle Biopsy ◽  
Skeletal Muscles ◽  
Culture Medium ◽  
Canine Model ◽  
Polyglycolic Acid ◽  
Urethral Pressure ◽  
Histological Differentiation ◽  
Skeletal Muscle Biopsy ◽  
Induced Stress

Abstract Introduction:This is an experimental pre-clinical study, testing the applicability of autologous skeletal muscle derived cells as a treatment of SUI in canine modelMethods:10 Mongrel dogs included. Skeletal muscle biopsy was harvested in 4. 1 month later, incontinence was induced in 8 dogs through urethrolysis. Muscle biopsy was incubated and expanded for 8 weeks. Muscle derived cells were collected and covered a Polyglycolic acid (PGA) scaffold immersed in culture medium and coated with matrigel to be used as a sling. Placed suburethral in 8 dogs; 4 had cell- seeded and 4 had scaffold only. Urethral pressure (UP) measurement was done at baseline 2 &6 weeks after sling insertion. The urethra was harvested 4 weeks after sling insertion for histopathology.Results:UP shows increase of maximum urethral pressure during static measurement in all dogs with a scaffold inserted. The increase ranged from 5-40 cmH20 Histopathology shows significant periurethral proliferation of skeletal muscles in 4 dogs with cell-seeded scaffold. This was maximum in dogs # 1& 2. This was not the case in the 4 dogs that had sling only.Conclusion: Use of skeletal muscle –seeded PGA scaffold is a practical technique with preserved integrity of histological differentiation in canine model.

The remodelling of skeletal muscle for indefatigable hemodynamic work

1991 ◽  
Vol 69 (2) ◽  
pp. 230-237 ◽  
Author(s):  
J. N. K. Odim ◽  
C. Li ◽  
C. Desrosiers ◽  
R. C.-J. Chiu ◽  
P. J. O'Brien ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Pulse Train ◽  
Therapeutic Potential ◽  
Low Frequency ◽  
Myosin Isoforms ◽  
Cardiac Assist ◽  
Cardiac Assist Devices ◽  
Fast Twitch ◽  
Train Stimulation ◽  
Muscle Transformation

Skeletal muscle possesses inherent plasticity of gene expression. Low frequency pulse-train stimulation can remodel the biochemical machinery that confers physiological expression and fatigue resistance approaching that of the myocardium. This fatigue-resistant muscle can generate sufficient force to meet the power requirements for useful cardiac work. This ultimate goal is currently being pursued in models of cardiomyoplasty and muscle-powered cardiac assist devices. In this article, we review the three major subcellular systems subserving canine skeletal muscle transformation and compare them to those of cardiac muscle. The magnitude of the problem of clinical heart failure and the feasibility of fatigue-resistant skeletal muscle joining the therapeutic armamentarium are addressed. The adaptation and transformation of fast-twitch skeletal muscle in response to chronic electrical stimulation augers therapeutic potential as an endogenous, readily available power source for myocardial assistance. The basis mechanisms of skeletal muscle fatigue require elucidation to gain a complete and thorough understanding of how to manipulate this property to provide continuous hemodynamic work.Key words: muscle transformation, pulse-train stimulation, cardiomyoplasty, counterpulsation, cardiac assist, myosin isoforms, sarcoplasmic reticulum ATPase, myofibrillar ATPase.

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