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FRONTIERS IN PHYSIOLOGY > Muscle 2 > Flashcards

Flashcards in Muscle 2 Deck (24):
1

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

2

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

3

What happens to nNOS in DMD?

It becomes delocalised into the cytosol, reducing its stability

4

What is the inflammatory hypothesis?

Muscles in DMD patients exhibit coordinated activity of numerous components of a chronic inflammatory response

5

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

6

What do corticosteroids do?

Maintain or decrease muscle fibre size and counter effects of chronic inflammation

7

Are corticosteroids pro or anti inflammatory?

Anti - slow fibrotic deposition

8

What are the side effects of corticosteroids?

Weight gain, fluid retention, high BP, ulcers, growth inhibition of bones

9

What is the benefit of using VBP15?

Lacks side effects, preserves normal bone and cardiac structure

10

Why does VBP15 not have side effects?

Does not activate hormonal GRE pathway

11

What do anabolic agents do?

Increase protein synthesis, decrease degradation, increase muscle mass

12

When is myostatin level increased?

Aged human muscle

13

What is myostatin blockade used for and where is it present?

Therapy for muscle wasting

Present in blood serum and muscle fibres

14

What is IGF-1?

Endogenous growth factor, important for normal muscle growth and repair

15

When do IGF-1 levels increase?

After injury, overload, formation or growth or new fibres

16

What does IGF-1 do?

Stimulates muscle cell proliferation and differentiation

17

What is a potential side effect of IGF-1?

Cause growth of new or pre-existing tumours

18

What do high systemic doses of beta agonists do?

Reverse muscle atrophy (limited effects on strength, adverse cardiac events)

19

What training should be avoided in DMD patients?

High resistance and eccentric exercise

20

What does immobilisation do for muscles in DMD patients?

Lower percentage of regenerating fibres - same total number of fibres

21

What does immobilisation so for LMD patients?

No improvement

22

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

23

What is the affect of albuterol (beta agonist)?

Modest increase in strength with no side effects - increase lean body mass and decrease fat mass

24

What things block myostatin?

GASP-1, follistatin