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biopharmaceuticals biochemistry and biotecnology - Walsh G.

Walsh G. biopharmaceuticals biochemistry and biotecnology - John Wiley & Sons, 2003. - 572 p.
ISBN 0-470-84327-6
Download (direct link): biochemistryandbiotechnology2003.pdf
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Insulin-like growth factor-1 (IGF-1) Certain forms of dwarfism, type II diabetes, kidney disease,
growth hormone insensitivity, cachexia, amyotrophic lateral
sclerosis, peripheral neuropathy
Epidermal growth factor (EGF) Wound healing, skin ulcers
Platelet-derived growth factor Diabetic ulcers, wound healing
(PDGF)
Transforming growth factor-b Bone healing, skin ulcers, detached retinas
(TGF-b)
Fibroblast growth factors (FGFs) Soft tissue ulcers, wound healing
Neurotrophic factors (NTs) Mainly conditions caused by/associated with neurodegeneration,
including peripheral neuropathies, amyotrophic lateral sclerosis
and neurodegenerative diseases of the brain
influence disrupts the normal healing process. Such influences can include diabetes, malnutrition, rheumatoid arthritis and ischaemia (inadequate flow of blood to any part of the body). Elderly people are particularly susceptible to developing chronic wounds, often resulting in the necessity for hospitalization. Ulceration (particularly of the limbs or extremities) associated with old age, diabetes, etc. remains the underlying cause of up to 50% of all amputations carried out in the USA.
The fluid exuded from a fresh or acute wound generally exhibits high levels of various growth factors (as determined by bioassay or immunoassay analysis). In contrast, the concentration of
GROWTH FACTORS 279
Table 7.3. Various types of ulcers along with their underlying cause. An ulcer may simply be described as a break or cut in the skin or membrane lining the digestive tract which fails to heal. The damaged area may then become inflamed
Ulcer category Description
Decubitus ulcer Ulcer due to continuous pressure exerted on a particular area of
(e.g. bed sores, pressure sores) skin; often associated with bed-ridden patients
Diabetic ulcers Ulcers (e.g. ‘diabetic leg’) caused by complications of diabetes
Varicose ulcers Due to defective circulation, sometimes associated with varicose
veins
Rodent ulcers An ulcerous cancer (basal cell carcinoma), usually affecting the
face
Peptic ulcers Ulcer of the digestive tract, caused by digestion of the mucosa by
acid and pepsin; may occur in e.g. the duodenum (duodenal
ulcer), or the stomach (gastric ulcer)
such mitogens present in chronic wounds is usually several-fold lower. Direct (topical) application of exogenous growth factors results in accelerated wound healing in animals. While some encouraging results have been observed in human trials, the overall results obtained thus far have been disappointing. Having said this, one such factor (rPDGF) has been approved for topical administration on diabetic ulcers, as described later. Future studies may well also focus on application of a cocktail of growth factors instead of a single such factor to a wound surface.
A greater understanding of wound physiology and biochemistry may also facilitate greater success in future trials. It has been established, for example, that the fluid exuded from chronic wounds harbours high levels of proteolytic activity (almost 200-fold higher than associated with acute wounds). Failure of mitogens to stimulate wound healing thus may be due, in part, to their rapid proteolytic degradation (and/or the degradation of growth factor receptors present on the surface of susceptible cells). Identification of suitable protease inhibitors, and their application in conjunction with exogenous growth factor therapy, may improve clinical results recorded in the future.
INSULIN-LIKE GROWTH FACTORS (IGFs)
The insulin-like growth factors (also termed ‘somatomedins’), constitute a family of two closely related (small) polypeptides: insulin-like growth factor 1 (IGF-1) and insulin-like growth factor 2 (IGF-2). As the names suggest, these growth factors bear a strong structural resemblance to insulin (or, more accurately, proinsulin). Infusion of IGF-1 decreases circulating levels of insulin and glucagon, increases tissue glucose uptake and inhibits hepatic glucose export. IGFs display pluripotent activities, regulating the growth, activation, differentiation (and maintenance of the differentiated state) of a wide variety of cell and tissue types (discussed later). The full complexity and variety of their biological activities are only now beginning to be appreciated.
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