AGE cross-linking on type I collagen and elastin results in increased stiffness. AGEs are also known to increase synthesis of type III collagen that forms the granulation tissue. AGEs on laminin result in reduced binding to type IV collagen in the basement membrane, reduced polymer elongation and reduced binding of heparan sulfate proteoglycan. Impaired NO synthesis
Nitric oxide is known as an important stimulator of cell proliferation, maturation and differentiation. Thus, nitric oxide increases fibroblast proliferation and thereby collagen production in wound healing. Also, L-arginine and nitric oxide are required for proper cross linking of collagen fibers, via proline, to minimize scarring and maximize the tensile strength of healed tissue. Endothelial cell specific nitric oxide synthase (EcNOS) is activated by the pulsatile flow of blood through vessels. Nitric oxide produced by EcNOS, maintains the diameter of blood vessels and proper blood flow to tissues. In addition to this, nitric oxide also regulates angiogenesis, which plays a major role in wound healing. Thus, diabetic patients exhibit reduced ability to generate nitric oxide from L-arginine. Reasons that have been postulated in the literature include accumulation of nitric oxide synthase inhibitor due to high glucose associated kidney dysfunction and reduced production of nitric oxide synthase due to ketoacidosis observed in diabetic patients and pH dependent nature of nitric oxide synthase.Structural and functional changes in fibroblasts
Diabetic ulcer fibroblasts show various morphological differences compared to fibroblasts from age matched controls.
Resistant ovary syndrome, previously known as Savage syndrome, is a cause of ovarian failure that can lead to secondary amenorrhea. Resistant ovaries result from a functional disturbance of the gonadotropin receptors in the ovarian follicles. It may be a cause of primary or secondary amenorrhea and is resistant to exogenous gonadotropin stimulation. Diagnosis of this condition requires that the patient has a normal 46,XX karyotype, normal secondary sexual characteristics, elevated plasma follicle-stimulating hormone and luteinizing hormone – in the menopausal range – and that normal, multiple follicles are seen on ovarian biopsy. Spontaneous reversal of the receptor resistance may occur. == References ==