Flashcards in Muscle 2 Deck (24):
What is the gene regulation hypothesis?
Failure of certain molecules to be localised to the muscle membrane when DGC components are absent prevents proper signalling molecules from being recruited
What is the vascular hypothesis?
NO produced in muscle cells by the neuronal form of NO synthase, nNOS, that is normally tethered to DGC by dystrobrevin and syntrophins
What happens to nNOS in DMD?
It becomes delocalised into the cytosol, reducing its stability
What is the inflammatory hypothesis?
Muscles in DMD patients exhibit coordinated activity of numerous components of a chronic inflammatory response
What is fibrosis
Abnormal and unresolvable, chronic increase in extracellular connective tissue that interferes with function, replaces contractile material, creates a physical barrier that limits efficacy of drug, cell and gene bases therapies, very difficult to reverse
What do corticosteroids do?
Maintain or decrease muscle fibre size and counter effects of chronic inflammation
Are corticosteroids pro or anti inflammatory?
Anti - slow fibrotic deposition
What are the side effects of corticosteroids?
Weight gain, fluid retention, high BP, ulcers, growth inhibition of bones
What is the benefit of using VBP15?
Lacks side effects, preserves normal bone and cardiac structure
Why does VBP15 not have side effects?
Does not activate hormonal GRE pathway
What do anabolic agents do?
Increase protein synthesis, decrease degradation, increase muscle mass
When is myostatin level increased?
Aged human muscle
What is myostatin blockade used for and where is it present?
Therapy for muscle wasting
Present in blood serum and muscle fibres
What is IGF-1?
Endogenous growth factor, important for normal muscle growth and repair
When do IGF-1 levels increase?
After injury, overload, formation or growth or new fibres
What does IGF-1 do?
Stimulates muscle cell proliferation and differentiation
What is a potential side effect of IGF-1?
Cause growth of new or pre-existing tumours
What do high systemic doses of beta agonists do?
Reverse muscle atrophy (limited effects on strength, adverse cardiac events)
What training should be avoided in DMD patients?
High resistance and eccentric exercise
What does immobilisation do for muscles in DMD patients?
Lower percentage of regenerating fibres - same total number of fibres
What does immobilisation so for LMD patients?
What does systemic and exogenous admin of IGF-1 lead to?
Systemic-enahnced oxidative status and reduced contraction induced injury
Exogenous-no increase in myofibre CSA
What is the affect of albuterol (beta agonist)?
Modest increase in strength with no side effects - increase lean body mass and decrease fat mass