A new suprasterol by photochemical reaction of 1α,25-dihydroxy-9-methylene-19-norvitamin D3.

The UV-induced photochemical reaction of 1α,25-dihydroxy-9-methylene-19-norvitamin D3 has been investigated. The pentacyclic structure of the isolated product has been unequivocally established by X-ray crystallographic analysis. The possible reaction paths of the examined photochemical transformation are discussed. Biological in vivo and in vitro tests proved that the photoproduct is devoid of calcemic activity.

Serum vitamin D metabolites in normal subjects after phototherapy.

The serum concentrations of the major vitamin D metabolites (25-hydroxyvitamin D(2 + 3) (25-OH-D), 1,25-dihydroxyvitamin D(2 + 3) (1,25-(OH)2-D), and 24,25-dihydroxyvitamin D(2 + 3) (24,25-(OH)2-D) were studied in 22 healthy male volunteers before and after one or two treatments with whole body UVB or PUVA in conventional doses. The effect of UVB was investigated in the autumn and early spring, whereas the effect of PUVA was investigated only in the autumn. The pre-treatment values of two metabolites were significantly reduced in the spring compared to the autumn level (25-OH-D: 14.0 ng/ml versus 22.0 ng/ml, P less than 0.02; and 24,25-(OH)2-D: 1.23 ng/ml versus 2.74 ng/ml, P less than 0.01), whereas the serum concentration of 1,25-(OH)2-D was not significantly reduced in the spring. After UVB, a small, but not significant, rise in all metabolites was observed in the spring, whereas virtually no changes were measured after UVB or PUVA in the autumn. We conclude that UVB and PUVA do not lead to harmful concentrations of vitamin D metabolites in the blood of healthy subjects.

Efficient photochemical formation of 1 alpha-hydroxyprevitamin D3.

Control of the band width of the irradiating light between 280 and 310 nm and of the temperature of the reaction permits formation of 1 alpha-hydroxyprevitamin D3 in yields of over 80%, at 40-60% conversion of the 1 alpha-hydroxyprovitamin D3. The procedures developed permit doubling the photochemical yield of the 1 alpha-hydroxyvitamin D3 compounds which are the major circulatory forms of vitamin D3.

Response of plasma-25-hydroxyvitamin D to ultraviolet irradiation in long-stay geriatric patients.

The response of plasma-25-hydroxyvitamin D (25[OH]D) to different exposures to ultraviolet irradiation has been studied in patients in long-stay geriatric wards. Increases sufficient to bring the plasma-25(OH)D into the normal range may be obtained with doses less than those required to produce erythema. The provision of such background irradiation may be a suitable method of preventing vitamin-D deficiency in elderly subjects who receive very little exposure to sunlight.

Identification and determination of 25-hydroxyvitamin D3 in the blood and liver of vitamin D-deficient rats irradiated with ultraviolet light.

The intestinal calcium transport activity and serum calcium and phosphorous concentrations of vitamin D-deficient rats were increased by irradiation with an ultraviolet (UV) lamp. The existence of 25-hydroxyvitamin D3(25-OH-D3) in their bloods and livers was physicochemically confirmed by high-performance liquid chromatography (HPLC), gas-liquid chromatography (GLC) and mass fragmentography, whereas the compound could not be detected in the tissues of non-irradiated rats. The results strongly suggested that vitamin D3 in vivo generated in irradiated rat skin might be normally metabolized and utilized to prevent rickets. The level of 25-OH-D3 in the tissues was determined by a HPLC method.

Relationship of 25-hydroxyvitamin D3 side chain structure to biological activity.

27-nor-25-Hydroxyvitamin D3, 26,27-bisnor-25-hydroxyvitamin D3, and 22-27-hexanor-20-hydroxyvitamin D3 and the corresponding 5,6-trans isomers have been synthesized. All compounds were tested for their ability to induce intestinal calcium transport and bone calcium mobilization in normal and anephric rats. The 27-nor- and 26,27-bisnor-25-hydroxyvitamin D3 analog are capable of stimulating intestinal calcium transport and bone calcium mobilization in normal rats but are 10 to 100 times less active than 25-hydroxyvitamin D3. Although these analogs are inactive in anephric rats, their corresponding 5,6-trans isomer are capable of stimulating both intestine and bone activity in these animals. The 22-27-hexanor-20-hydroxyvitamin D3 and its corresponding 5,6-trans isomer are incapable of stimulating either intestinal calcium transport or bone calcium mobilization. These results suggest that minor alterations in the side chain significantly decrease the biopotency of 25-hydroxyvitamin D3. Since these analogs are biologically active in normal but not in anephric animals, it appears that the kidney 1alpha-hydroxylation is necessary for activity. Since 22-27-hexanor=20-hydroxyvitamin D3 and its corresponding 5,6-trans analog are biologically inactive, it is likely that at least part of the side chain is necessary for 25-hydroxyvitamin D3 to stimulate intestinal calcium transport and bone calcium mobilization.