Cholecalciferol plasma concentrations

There seems to be no metabolic control exerted on hepatic 25-hydroxylase and so all of the available cholecalciferol is converted. Hydroxylation in the kidney however is an important control point being regulated by PTH, and indirectly therefore by calcium and phosphate concentrations. Stimulation of la-hydroxylase by PTH is via a cyclic AMP (cAMP) -dependent mechanism and longer-term regulation of the activity of this enzyme is via induction mediated by other hormones such as oestrogens, cortisol and growth hormone. Typically, the plasma concentration of 1,25 dihydroxy vitamin D is in the range 20-60 ng/1, that is approximately 1000-times lower than that of its precursor. 

Sunlight is not strictly essential for cutaneous synthesis of cholecalciferol, because UV-B penetrates clouds reasonably well complete cloud cover reduces the available intensity by about 50%. It also penetrates light clothing. However, low-intensity irradiation (below 20 ml per cm in vitro) does not result In significant photolysis of 7-dehydrocholesterol to previtamin D. Acute whole-body exposure to UV-B irradiation below 18 ml per cm does not result in any detectable increase in plasma cholecalciferol or calcidiol. In temperate regions (beyond about 40°N or S), the intensity of UV-B is below this threshold in winter, so there is unlikely to be any significant cutaneous synthesis of the vitamin in winter, and plasma concentrations of calcidiol show a marked seasonal variation in temperate regions (Holick, 1995 see Table 3.2). 

A number of studies have suggested that the cholecalciferol content of human mUk is inadequate to meet the requirements of hreast-fed infants without exposure to sunlight, especially during the winter, when the mother s reserves of the vitamin are low. Infant formulae normally provide 10 /xg of cholecalciferol per day, and a similar amount is recommended for hreast-fed infants. Supplements of 10 /xg per day are also recommended for children between 3 months and 3 years, because of the relatively high requirement during the phase of maximum bone development and the limited exposure to sunlight in temperate regions. Such supplements maintain the plasma concentration of calcidiol above 20 mnol per L. 

Calcium is the major mineral component of bone and normal repair and remodelling of bone is reliant on an adequate supply of this mineral. Calcium uptake in the gut, loss through the kidneys and turnover within the body are controlled by hormones, notably PTH and 1,25 dihydroxy cholecalciferol (1,25 DHCC or 1,25 dihydroxy vitamin D3 or calcitriol). Refer to Figure 8.12 for a summary of the involvement of PTH and vitamin D3 in controlling plasma calcium concentration. These two major hormones have complementary actions to raise plasma calcium concentration by promoting uptake in the gut, reabsorption in the nephron and bone resorption. Other hormones such as thyroxine, sex steroids and glucocorticoids (e.g. cortisol) influence the distribution of calcium. 

Vitamin D hormone is derived from vitamin D (cholecalciferol). Vitamin D can also be produced in the body it is formed in the skin from dehydrocholesterol during irradiation with UV light. When there is lack of solar radiation, dietary intake becomes essential, cod liver oil being a rich source. Metaboli-cally active vitamin D hormone results from two successive hydroxylations in the liver at position 25 ( calcifediol) and in the kidney at position 1 ( calci-triol = vit. D hormone). 1-Hydroxylation depends on the level of calcium homeostasis and is stimulated by parathormone and a fall in plasma levels of Ca or phosphate. Vit D hormone promotes enteral absorption and renal reabsorption of Ca and phosphate. As a result of the increased Ca + and phosphate concentration in blood, there is an increased tendency for these ions to be deposited in bone in the form of hydroxyapatite crystals. In vit D deficiency, bone mineralization is inadequate (rickets, osteomalacia). Therapeutic Liillmann, Color Atlas of Pharmacology... 

Boron stimulated growth in Vitamin Dj-deflcient chicks. Supplemental dietary boron alleviated or corrected cholecalciferol dehciency-induced elevations in plasma glucose concentrations in chicks (Hunt 1994). There is no need to supplement the diets of laying hens with boron, provided that basal diets contained about 11 mg B/kg ration (Qin and Klandorf 1991). 

Colloidal systems can be divided into lyophilic and lyophobic systems. Lyophilic colloids have a strong affinity with the dispersion medium by which a solvation shell around the particle is formed. This process is called solvation and if the dispersion medium is water it is called hydration. A polysaccharide dissolved in water is an example of a lyophilic colloidal system. The solvation shell is formed by hydrogen bonds between the hydroxyl groups of the polymer molecules and the water molecules. Pharmaceutical examples are solutions of dextran, used as plasma expanders. Micelles are also lyophilic colloids. Example of such a system is the aqueous cholecalciferol oral mixture (Table 18.15). In these preparations, a lipophilic fluid is dissolved in an aqueous medium by incorporating it in micelles. Because this type of colloids falls apart on dilution to concentrations below the CMC, they are also known as association colloids. Lyophobic colloids have no affinity with the dispersion medium. Thus, in this type of colloids no solvation shell is formed around the particles. An example of lyophobic particles are colloidal gold particles (with a diameter of 1 nm - 1 pm) dispersed in water. There are no... 

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