ALL naturalists, with, as far as I know, a single exception, believe that the several domestic breeds of the rabbit are descended from the common wild species with hair loss treatment sacrificed to the gods, and, as he prescribes their multiplication, they were probably at this early period domesticated in China. T hey are mentioned by several of the classical writers. In
Gervaise Markham writes, "You shall not, as in other cattell, looke to their shape, but to their richnesse, hair loss elect your buckes, the largest and goodliest conies you can get; and for the richnesse of the skin, that is accounted the richest which hath the equallest mixture of blacke and white hair together, yet the blacke rather shadowing the white; the furre should be hair thicke, deepe, smooth, and shining; ... they are of body much fatter and larger, and, when another skin is worth two or three pence, they are worth two shillings." From this full description we see that silver-grey rabbits existed in England at this period; and what is far more important, we see that the breeding or selection of rabbits was then carefully attended to. Aldrovandi, in 1637, describes, on the authority of several old writers (as Scaliger.
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This is of some clinical importance, since an antiinflammatory pharmaceutical preparation rich in SOD ("orgotein") is used in veterinary medicine and recently has been shown to be both effective and apparently safe in the treatment of various inflammatory lesions in man. Catalase has also been may be at least partially dependent upon interference with active oxygen metabolism in phagocytes.
Further, peroxidase release from eosinophils may playa similar role in inhibition of the inflammatory response (201) while the antioxidant properties of ceruloplasmin may also give this compound antiinflammatory properties.(21,128).
An illustrative (albeit circumstantial) model for the role of superoxide in rheumatoid arthritis can be postulated as follows: Granulocytes tend to be concentrated at sites of active rheumatic disease, presumably in response to the presence of immune complexes and other Agents such as ectopic SOD may interfere with this process by destroying active oxygen species or increasing peroxide fluxes, thus interfering with one or more of the mechanisms detailed above and in Figure 4.
Since SOD is one of the most substrate-specific enzymes known, at first sight its efficacy in rheumatoid arthritis and other lesions strongly implies a role for active oxygen species in such diseases and a role for superoxide-destroying agents in their treatment. However, there are serious problems with such an assumption. For example, the course of action of SOD as an inflammatory agent often bears no apparent relationship to its serum levels (1,185) and the "denatured" enzyme still possesses significant antiinflammatory properties. 185 Feel (51) even ably questions the specific role of the protein in destroying superoxide.
With this caution, active oxygen species may play a significant role in the etiology of other inflammatory lesions in man, For example, SOD is reported to be effective in the treatment of lupus erythematosis,(43,158) and unique light-activated, superoxide-dependent lymphocyte clastogenic factors present in the serum of patients with lupus and other collagen diseases may account for some of the photosensitivity of this group of disorders.(157-159). Both direct and indirect production of active oxygen species may also have a role in the pathophysiology of gout and other hyperuricemic syndromes. of active species of oxygen by phagocytes (203,204) and may protect cycloepoxigenase from autooxidation.(131) The effectiveness of SOD in the treatment of urate-induced inflammatory disease in Dalmations suggests a role for superoxide in this lesion.(138).
free radical involvement in inflammation and neuronal injury is circumstantial and has not been proven conclusively.