Rachitic

Vitamin D3 was effective in enhancing duodenal As+S absorption in rachitic chicks. 

Plaquet et al. (PI) found in the urine of rachitic children peptides consisting of proline, hydroxyproline, and glycine, which they believed to be the products of collagen degradation. Two similar peptides containing considerable amounts of proline and hydroxyproline were isolated from the urine of a patient with rheumatoid arthritis by Mechanic et al. (Ml). One of these peptides consisted of three proline, two hydroxyproline, and nine glutamic acid residues, the second one consisted of four proline, four hydroxyproline, and one glutamic acid residues. The N-terminal amino acid in the first peptide was demonstrated to be hydroxyproline. 

Ergosterol CjgH OH, a trebly unsaturated alcohol, is derived from the same ring system. It is produced in relatively large amounts by fungi, in particular by yeast, and on irradiation it is isomerised to the anti-rachitic vitamin, vitamin-D (Windaus). 

The key experiments leading to the identification of vitamin D were those of Mellanby (1918-1919) using puppies. When they were fed on bread, skimmed milk, linseed oil, yeast (to give B vitamins), and orange juice (vitamin C) the puppies developed rickets. When cod-liver oil and/or butter were added, rickets was prevented. The distinction between the effects of vitamin A and the anti-rachitic factor was aided by the sensitivity of vitamin A to oxidation. Aerated (oxidized) cod-liver oil no longer cured xerophthalmia but its anti-rachitic properties were unaffected (McCollum, 1922). 

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). 

Dixit, P. K. Quantitative histochemistry of cartilage. Alkaline phosphatase and glucose-6-phosphate dehydrogenase activity in different zones of rachitic rat cartilage during healing. Calc. Tiss. Res. JO, 49-57 (1972). 

The relationship of serum calcium and phosphate with rickets was discovered by Howland and Kramer [10]. They found that blood from normal rats could mineralize rachitic rat cartilage, whereas blood from rachitic rats could not. They also provided evidence that a low serum calcium and phosphate status caused rickets. Orr etal. [11] demonstrated that UV irradiation stimulated calcium absorption. This study was largely unappreciated for 30 years until Nicolaysen and Eeg-Larsen [12] and Schachter and Rosen [13] demonstrated evidence for vitamin D-induced intestinal absorption of calcium by an active transport process. 

There are a number of rachitic syndromes that do not respond to normal amounts of vitamin D ... 

Osteocalcin is induced in osteoblasts by calcitriol, and circulating osteocalcin can be used as an index of calcitriol action and metabolic bone disease. In rachitic children, the plasma concentration of osteocalcin is lower than in controls, and rises on therapy, remaining high until there is radiological evidence of cure. However, plasma osteocalcin can be undetectably low in normal subjects with adequate vitamin D status, so this does not provide a useful indication of deficiency (Greig et al., 1989). 

Vitamin D is necessary in the diet for the prevention of rickets, a disease involving malformation of the bones and unsatisfactory development of the teeth. There are several substances with anti-rachitic activity. The form that occurs in oils from fish livers is called vitamin Dg it has the following chemical structure ... 

Shapiro I. M. and Boyde A. (1984) Microdissection-elemental analysis of the mineralizing growth cartilage of the normal and rachitic chick. Metabolic Bone Dis. 5, 317-326. 

Rachitic rosaiy, 582 RAC protein, 905 Radicals damage from ascorbic acid and, 626 vitamin E, 631,632 forrnation, 829... 

Lauriola AL, Taugeriui A, Lodi A, Gamberini MR, Testa MR, Orziucolo C, De Sauctis V, Vullo C. Rachitic rosary iu a well chelated thalassaemic patient with primary amenorrhea (patient report). J Pediatr Endocrinol Metab 1998 ll(Suppl 3) 979-80. 

The anti-rachitic factors resulting from the ultraviolet irradiation of cholesterol (40) and ergosterol (41) namely vitamin Dj (42) cholecalciferol and Dj, ergocalciferol (43) respectively are important dietary materials the chemistry of which was only elucidated by the investigations of many chemists (ref.41). Vitamin Dj is most easily derived by semi-synthesis from cholesterol through formation firstly of 7-dehydrocholesterol by reaction with N-bromosuccinimide followed by dehydrobromination with collidine. Ultraviolet light irradiation affords previtamin Dj which is thermally isomerised to the endo compound shown and thence to the exo... 

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