Foundations 2 Week 3 part 1

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Foundations 2 Week 3 part 1
2013-09-30 14:53:08

Foundations 2 Week 3 part 1
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  1. What is PDGF? What form does it have?  What does it do?
    • Platelet Derived Growth Factor is a potent mitogen that plays a significant role in angiogenesis.
    • It may be homodimeric (PDGF-AA, BB, CC, DD) or heterodimeric (PDGF-AB).  
    • PDGF binds α-α, α-ß, or ß-ß transmembrane tyrosine kinase receptors.
    • Upon injury, PDGF is released at the wound by degranulating platelets
  2. What is Regranex?
    (generic name = becaplermin topical) A topical gel that uses a PDGF-derived growth factor to treat ulcers.
  3. What is PRP?
    • Platelet Rich Plasma (it has higher concentrations of platelets than normal plasma).
    • It has been used in wound therapy.
  4. What do growth factors do?
    Growth factors can cause mitosis (mitogens), migration, differentiation, and gene regulation.
  5. How do growth factors signal?
    • Growth factors work through autocrine and paracrine secretion (ie, over short distances).
    • They affect cellular functions through cell receptors.
  6. Describe TGF-ßs.
    • The Transforming Growth Factor ß superfamily plays important roles in development, homeostasis, disease, and repair.
    • The superfamily includes TGF-ß 1, 2, &3, bone morphogenetic proteins, Mullerian inhibiting substance, nodals, inhibins, and activins.
  7. How do TGF-ß1, TGF-ß2, and TGF-ß3 signal?
    • TGF-ß1-3 bind to receptor complexes, consisting of a type I and a type II receptor.
    • The receptors are serine-threonine kinases which activate intracellular signaling complexes.
    • They have been shown to be mitogenic for fibroblasts, stimulate extracellular matrix proteins, and stimulate integrins.  Most other cells are inhibited.
  8. Where is TFG-ß produced?
    TFG-ß is produced by platelets, leukocytes, macrophages, fibroblasts, and keratinocytes (basically, all the cells involved in wound repair).
  9. What role do the TGF-ß proteins play in scar formation?
    • TGF-ß1-2 promote angiogenesis, collagen production, and attract inflammatory cells.
    • TGF-ß3 is an antagonist to TGF-ß1 and 2, and promotes scarless healing.
  10. Describe VEGF
    • Vascular Endothelial Growth Factor includes VEGF-A,B,C,D,E and placenta growth factor (PLGF).
    • These bind tyrosine kinase receptors VEGFR-1,2,&3.
  11. How have VEGFs been used in therapy?
    • Topical VEGF therapy accelerates wound healing.
    • Anti-VEGF antibodies are used to treat malignancy and macular degeneration, but have been suggested to lead to wound healing complications (WHCs).
  12. What are FGFs?
    Fibroblast growth factors are are heparin-binding proteins that stimulate proliferation of many cell types, except for FGF7 (keratinocyte growth factor) which only stimulates epithelial cells.
  13. What are EGFs?
    • Epidermal Growth Factors are mitogens that bind to EGFR/ErbB1, HER2/ErbB2, HER3/ErbB3, and HER4/ErbB4.  
    • They are involved in keratinocyte migration, fibroblast function, and formation of granulation tissue during wound healing.
  14. Which is NOT a TGFb family member? Activin, BMP-1, Inhibin, TGF-α
  15. TGF-ß1-deficient mice show...
    Late-stage wound repair impairment
  16. What does topical becaplermin contain?
    Recombinant PDGF
  17. Which cell type primarily produce PDGF at wound sites, and at what phase of healing?
    Platelets, Degranulation at hemostasis
  18. Avotermin, a recombinant human transforming growth factor ß3 was developed for the treatment of what?
  19. PDGF exert their functions by binding to how many types of transmembrane receptor?
  20. True or False, Topical VEGF therapy acelerates wound healining in experimental diabetic wounds?
  21. What are growth factors?
    Polypeptides that stimulate proliferation and migration.
  22. Latency-associated peptide-bound TGF-ß is inactive, True or False?
    True. It becomes active after being cleaved.
  23. TGF-ß is mitogenic for all of the following, except what? Karatinocytes, Fibroblasts, T-cells, Macrophages
  24. EGF has been implicated in what?
    Keratinocyte migration
  25. OSU8-1 has been associated with what?
    HB-EGF shedding
  26. What molecule can be phosphorylated by active TGF-ß-a binding to TGF-ß-R?
  27. True or false, PDGF-R is a serine-threonine kinase?False.
    PDGF-R is a tyrosine kinase
  28. What are VEGF receptors?
    Tyrosine kinases
  29. What is PRP?
    Platelet rich plasma, a platelet concentrate used in wound therapy.
  30. What does FGF-heparin interaction do?
    Stabilizes FGF against thermal denaturation and proteolysis
  31. What is the major problem with the use of topical becaplermin in chronic wound treatments?
    Malignancies remote to the site of operation.
  32. Name the mitotic phase:
  33. Name the mitotic phase:
  34. Name the phase: