Antirachitic factors

Edward Mellanby and the Antirachitic Factor. (With John Parascandola). Bull. Hist. Med., 51, 507-15 (1977). 

In 1918, Mellanby produced experimental rickets in dogs. In 1919, Huldschinsky ameliorated rachitic symptoms in children with ultraviolet radiation. Hess, in 1922, showed that liver oils contain the same antirachitic factor as sunlight In that same year, McCollum increased calcium deposition in rachitic rats with cod liver oil factor. In 1924. Steenbook and Hess demonstrated irradiated foods have antirachitic properties, It was in 1925 that McCollum named antirachitic factor as vitamin D. In 1931, Angus isolated crystalline vitamin D (calciferol). In 1936, Windaus isolated vitamin D3 (activated 7-dehydrocholesterol). 

The D-vitamins are a group of fat soluble materials with high antirachitic activity. Rickets is a disease of infancy caused by faulty calcium hydroxy apatite deposition in the growing bone. It was Palm 140) in 1890 who found that the disease responded favorably to irradiation of patient s food or skin by sunlight or ultraviolet light. Mellanby 113) in 1919 first reported the presence of an antirachitic factor in cod-liver oil. This discovery encouraged research on the isolation of the active principle in fish-liver oil, but the low natural concentration of the vitamin made isolation very difficult. 

Because several of the metabolites of vitamin D3 are biologically active, the molecular species of vitamin D3 which passes into the yolk cannot be determined just from measurement of antirachitic activity. Consequently, a reliable and sensitive method for determining the amount of the unchanged form of vitamin D3 would be extremely beneficial to those interested in the metabolism and other factors that influence the chicken to deposit vitamin D3 in... 

THekap cat (VET) Nutritional factor (antirachitic). Low activity in poultry. Also as rodenticide. 

A few years later Pfordte (89) adduced evidence to show that the total toxicity of crude Irradiation mixtures of ergosterol does not exceed the toxicity of equal amounts of vitamin D. Although he was able to obtain two fractions enriched In toxicity and showing very diminished antirachitic activity, the absolute toxicity was smaller by a factor of 10 or more (78, 89) than the toxlsterol described by Llnsert. Attempts to enhance the toxic activity by further purification failed. 

Lack or deficiency of a V., as a result of unbalanced nutrition, leads to charaeteristic metabolic disturbances. Complete absenee of a V. leads to avitaminosis, with typical clinical symptoms. Relative deficiency of a V. causes hypovitaminosis. Such conditions are reversible by administration of the appropriate V. Excessive intake of certain V, e.g. V.A or V.D, can lead to hypervitaminosis. Formerly, V. were named after the diseases they cured, e.g. antiscorbutic V., antirachitic V, antiberiberi factor. Not all V., however, have such a pronounced specificity, and the clinical pictures of many avitaminoses and hypovitaminoses are complex and variable. A nomenclature based on letters of the alphabet was developed simultaneously the designations A, B, C, D and E were applied in the historical order of discovery. Subscripts were applied as more refined chemical analysis revealed that the originally isolated substances were in fact complex mixtures. This was especially true for the B vitamins. Partly because of confusion over the B complex , trivial names which give an indication of the chemical structure of the V. (e.g. pyridoxine or pyiidoxol for V.B() are now preferred. 

A fat-soluble factor that counteracts the disturbance in bone development called rickets was separated from fat-soluble A by McCollum in 1922. Ultraviolet irradiation was soon found to produce antirachitic activity. Several substances are now known to have vitamin D activity, and structures have been ascertained for the more important ones. Calciferol or vitamin Ds is the principal one obtained by irradiation, while vitamin Da is the naturally occurring activated 7-dehydro-cholesterol. 

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