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PubMed1999

Rat stomach ECL-cell histidine decarboxylase activity is suppressed by ergocalciferol but unaffected by parathyroid hormone and calcitonin.

The ECL cells are peptide hormone-producing cells, rich in histamine and chromogranin A (CGA)-derived peptides, that operate under the control of gastrin. Gastrin and the ECL cells form a functional unit, the gastrin-ECL-cell axis. The aims of the present study were to examine (1) if calcitonin (CT), parathyroid hormone (PTH) and vitamin D affect the gastrin-ECL-cell axis (by measuring the activity of the histamine-forming enzyme, histidine decarboxylase (HDC), and the expression of HDC mRNA and CGA mRNA in the ECL cells), and (2) if activation of the gastrin-ECL-cell axis affects the parathyroid glands (by measuring plasma PTH and mRNA expression). We also examined the possibility that the oxyntic mucosa harbours vitamin D receptors. Fasted rats received intravenous infusion of PTH and CT with or without gastrin. PTH raised the blood Ca2+ concentration, whereas CT infusion lowered it. Plasma PTH rose in response to CT, while serum gastrin remained unaffected. ECL-cell HDC was activated by gastrin but not by CT and PTH. Five daily subcutaneous injections of large amounts of ergocalciferol raised the blood Ca2+ concentration, while reducing the oxyntic mucosal HDC activity and the expression of HDC and CGA mRNA. The serum gastrin concentration was not affected. The findings are in line with the idea that the gastrin-ECL-cell axis can be suppressed by vitamin D or by vitamin D-dependent mechanisms. Western blot analysis revealed the presence of vitamin D receptor immunoreactivity and reverse transcription PCR detected vitamin D receptor gene expression in the rat oxyntic mucosa. Hypergastrinemia was induced by daily peroral treatment with the H+/K+-ATPase inhibitor, omeprazole, for 2 weeks or by continuous subcutaneous infusion of gastrin for 7 days. Elevated serum gastrin concentration was associated with increased HDC activity and increased HDC and CGA mRNA expression in the oxyntic mucosa. There was no elevation of plasma PTH or PTH mRNA expression in the parathyroid gland.

Animals↗
PubMed1985

Vitamin D metabolism in patients intoxicated with ergocalciferol.

Vitamin D metabolites were measured on admission in eight patients intoxicated with ergocalciferol (serum calcium 3.01-4.05 mmol/l) and also during the subsequent 2 months in six of the eight. Serum concentrations of 25-hydroxyergocalciferol, on admission, were grossly elevated in all patients (range 583-1843 nmol/l). Serum calcium concentration was related significantly only to the concentration of 25-hydroxyergocalciferol (P = 0.003). Concentrations of 25-hydroxyergocalciferol in serum were significantly related to those of calciferol (P = 0.004). Elevated initial concentrations of 1,25-dihydroxycalciferol, mainly as 1,25-dihydroxyergocalciferol, were found in seven of the eight patients (range 179-313 pmol/l). It is suggested that the hypercalcaemia in these patients may be explained by the action of 25-hydroxyergocalciferol at high concentration in competing for 1,25-dihydroxycalciferol receptors, thus exerting a biological effect per se, and also by increasing the synthesis of 1,25-dihydroxycalciferol through a mass-action effect on the renal 1 alpha-hydroxylase.

25-Hydroxyvitamin D 2↗
PubMed2001

Diminished and erratic absorption of ergocalciferol in adult cystic fibrosis patients.

BACKGROUND: Osteoporosis diminishes the quality of life in adults with cystic fibrosis (CF). Vitamin D deficiency resulting from malabsorption may be a factor in the etiology of low bone mineral density (BMD) in patients with CF. OBJECTIVE: Absorption of oral ergocalciferol (vitamin D2) and the consequent response of 25-hydroxyvitamin D in 10 adults with CF and exocrine pancreatic insufficiency was compared with that of 10 healthy control subjects. DESIGN: In this pharmacokinetic study, CF patients and control subjects were pair-matched on age, sex, and race. Each subject consumed 2500 microg oral vitamin D2 with a meal. The CF group also took pancreatic enzymes that provided > or = 80000 U lipase. Blood samples were obtained at baseline and at 5, 10, 24, 30, and 36 h after vitamin D2 consumption to measure serum vitamin D2 and 25-hydroxyvitamin D concentrations. RESULTS: Vitamin D2 concentrations in all subjects were near zero at baseline. CF patients absorbed less than one-half the amount of oral vitamin D2 that was absorbed by control subjects (P < 0.001). Absorption by the CF patients varied greatly; 2 patients absorbed virtually no vitamin D2. The rise in 25-hydroxyvitamin D in response to vitamin D2 absorption was significantly lower over time in the CF group than in the control group (P = 0.0012). CONCLUSIONS: Vitamin D2 absorption was significantly lower in CF patients than in control subjects. These results may help explain the etiology of vitamin D deficiency in CF patients, which may contribute to their low BMD.

Administration, Oral↗
PubMed1975

Effects of massive doses of ergocalciferol plus cholesterol on pregnant rats and their offspring.

Ergocalciferol (320,000 or 480,000 IU/kg) plus cholesterol (60 mg/kg) in olive oil solution was administered daily on 1, 2, or 4 consecutive days to pregnant rats from 9,10, 14, or 18 of gestation. The control animals received only olive oil. Disseminated lesions of metastic calcinosis were found in various tissues, in the coronary arteries and myocardium, in the media of the abnormal aorta, in the lung and pleura, in the gastoinstestinal tract, and in the kidney. This is in contrast to the atherosclerosis described in nonpregnant rats fed a similiar diet. A significant decline in maternal weight as well as a high rate of morbidity and mortality was observed. In mothers killed on day 22 of pregnancy, fetal and placental growths appeared significantly retarded suggesting a direct effect of the steroid or its more active metabolite, 1,25-dihydroxycholecalciferol, on the fetus or the trophoblastic tissue. Fetal bone lesionsassociated with a generalized retardation of ossification, placental edema, or calcification accompanied by a loss of the normal structure of the placenta and degenerative manifestation at this level were observed. Moreover, we noted a striking alteration of the fetal face in 33-39% of experimental fetuses, called by us carnival fetuses.

Abnormalities, Drug-Induced↗
PubMed1982

Relative biopotency of dietary ergocalciferol and cholecalciferol and the role of and requirement for vitamin D in rainbow trout (Salmo gairdneri).

A growth assay was conducted for six consecutive 28-day periods by using triplicate groups of 110 rainbow trout with an average initial body weight of 3.0 g. Ergocalciferol (vitamin D2 or D2) and cholecalciferol (vitamin D3 or D3) were included to provide levels of 200, 400 and 800 iu/kg in a semipurified casein, gelatin diet. Further treatments with 0 vitamin D and 1600 IU/kg of D3 were also included. The resulting growth curves were significant for parallelism. Statistical analysis showed that D3 was 3.27 times as potent as D2 (limits 2.33 to 4.58). The dietary requirement for D3 was found to be in excess of 800 iu/kg of diet. Vitamin D-deficient fish showed no change in bone ash but exhibited clinical manifestations of tetany with no hypocalcemia. A complete absence of tetany was seen only in the groups fed 800 and 1600 IU of D3 per kilogram. None of the levels of D2 used were sufficient to completely alleviate symptoms of this disorder. These studies of rainbow trout provide evidence that vitamin D is required for the normal functioning of white muscle without altering the calcium content of the plasma or epaxial musculature.

Animals↗
PubMed1988

Evidence that discrimination against ergocalciferol by the chick is the result of enhanced metabolic clearance rates for its mono- and dihydroxylated metabolites.

Studies on the discrimination between ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3) by chickens have led to conflicting conclusions. To investigate this problem in more detail, radiolabeled vitamin D and vitamin D metabolites were administered intravenously, which allowed determination of their relative plasma clearance rates. The study involved three groups of adult male chickens (five per group). Birds in group 1 were co-dosed with [3H]vitamin D2 and [3H]vitamin D3. Birds in group 2 were co-dosed with [3H]25-dihydroxyvitamin D2 and [3H]25-dihydroxyvitamin D3 and birds in group 3 were co-dosed with [3H]1,25-dihydroxyvitamin D3 and [3H]1,25-dihydroxyvitamin D2. The results indicated that the plasma turnover rate of [3H]vitamin D2 is 1.5 times faster than that of [3H]vitamin D3. Plasma turnover of the 25-hydroxylated metabolites differed, with [3H]25-dihydroxyvitamin D2 clearing faster (11 times) than [3H]25-dihydroxyvitamin D3. The largest difference appeared in the 1,25-dihydroxyvitamin D2 turnover rates with 1,25-dihydroxyvitamin D2 clearing approximately 33 times faster then [3H]1,25-dihydroxyvitamin D3. These data, therefore, indicate that discrimination against vitamin D2 sterols in the chick occurs primarily between steps in the metabolism of vitamin D and not at the point of metabolism or excretion of the parent vitamin.

25-Hydroxyvitamin D 2↗
PubMed1989

Effects of ergocalciferol supplementation on the concentration of vitamin D and its metabolites in human milk.

The effect of maternal ergocalciferol (vitamin D2) supplementation on the concentrations of vitamin D, 25-hydroxyvitamin D (25-OH-D), 24R,25-dihydroxyvitamin D [24,25-(OH)2D], and 1 alpha,25-dihydroxyvitamin D [1,25-(OH)2D] in their milk was studied. Vitamin D2, D3, 25-OH-D2 and 25-OH-D3 were simultaneously determined by high performance liquid chromatography, and the determination of 24,25-(OH)2D and 1,25-(OH)2D was performed by competitive protein binding assay and radioreceptor assay, respectively, after separation of the D2 and D3 compounds. After healthy lactating mothers had received a daily oral dose of vitamin D2 (1,200 IU/d) for 4 wk, the concentrations of vitamin D2, D3 and the metabolites were determined in their plasma and milk. Although the plasma levels of 25-OH-D2 were significantly increased, the increase in milk was relatively small. On the other hand, the increase of vitamin D2 levels in milk was greater than that of 25-OH-D2 in milk after supplementation. The levels of 1,25-(OH)2D in milk was lower after 5 wk of lactation than after 1 wk of lactation, regardless of maternal vitamin D2 supplementation. When total antirachitic activities in milk were calculated, only a very slight increase was observed as a result of supplementation.

24,25-Dihydroxyvitamin D 3↗
PubMed2004

Ergocalciferol promotes in vivo differentiation of keratinocytes and reduces photodamage caused by ultraviolet irradiation in hairless mice.

BACKGROUND: Ergocalciferol (VD(2)) is usually administered orally and it is metabolized to produce its biologically active metabolites in the liver and kidney. Active vitamin D is a well-known potent regulator of cell growth and differentiation. PURPOSE: Active vitamin D such as 1,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) prevents photodamage, including wrinkles and morphologic alterations. However, its clinical and cosmetic use is limited because of its potent, associated effect on calcium metabolism. We examined the efficacy of vitamin D analogues with few adverse effects for preventing skin photodamage. METHOD: Topical application of VD(2) to hairless mouse dorsal skin, and exposure to solar-simulating ultraviolet (UV) radiation at a dose of 10.8 J/cm(2) (UVA) were performed for 15 weeks, five times a week on weekdays. At the end of the final irradiation, histological and analytical studies were performed. RESULTS: Topical application of VD(2) significantly prevented wrinkle formation and abnormal accumulation of extracellular matrix components. In addition, VD(2) suppressed excessive secretion of IL-6 induced by UV irradiation in cultured human normal keratinocytes, in a dose-dependent manner. CONCLUSION: VD(2) promoted keratinocytes differentiation in the epidermis and showed diverse physiological effects, the same as the active form of VD(3). The results suggested that the suppression of skin photodamage involved the promotion of keratinocytes differentiation and suppression of IL-6 secretion induced by exposure to UV. Topical application of VD(2) may become an effective means to suppress solar UV-induced human skin damage.

Administration, Cutaneous↗
PubMedDate not supplied

[Toxic action of ergocalciferol in strontium rickets].

Tests conducted on albino rats of the Wistar line demonstrated that introduction of large doses of ergocalciferol (vitamin D2) to animals kept on a strontium-rich diet exhibiting signs of rickets brings about the development in them of specific manifestations of the D-vitamin activity, viz. rising level of calcium, strontium and inorganic phosphorus in the blood serum, lowering of the alkaline phosphatase activity and a greater degree of the soft tissues calcification.

Animals↗
PubMed1988

Vitamin D-deficiency in the elderly: treatment with ergocalciferol and hydroxylated analogues of vitamin D3.

The purpose of the present work was to study the effect of vitamin D and its metabolites in correcting hypovitaminosis D in the elderly. Thirty elderly people (mean age 78.4 years) participated in this study. They all had low serum levels of 25-hydroxyvitamin D (25-OH-D), of 24,25-dihydroxyvitamin D [24,25(OH)2D] and of 1,25-dihydroxyvitamin D [1,25(OH)2D]. These low levels did not increase in nine subjects after oral administration of vitamin D2 (3,000 IU/day for 12 weeks). However, administration of 1 alpha-hydroxyvitamin D3 (1 alpha-OH-D3) to 12 other subjects (0.5 micrograms/day for 8 weeks) led to a significant increase in the serum levels of 1,25(OH)2D. The other vitamin D metabolite levels remained unchanged. A significant increase in the levels of all three main vitamin D metabolites was obtained following administration of 25-hydroxyvitamin D3 (25-OH-D3) to a third group of nine subjects (25 micrograms/day for 1 week). These results suggest that vitamin D nutrition in elderly people insufficently exposed to the sun could be maintained by regular administration of 25-OH-D, whereas the administration of native vitamin D (ergocalciferol) in the doses used was inadequate for vitamin D nutrition.

24,25-Dihydroxyvitamin D 3↗
PubMed1976

Combined assays for vitamins A, D (ergocalciferol), and E in multivitamin preparations with separation by reversed-phase partition chromatography.

A rapid method was developed whereby vitamins A, D (ergocalciferol), and E in multivitamin products are measured in a common assay sample. The method depends on reversed-phase partition chromatography by which the vitamin alcohols are eluted in separate fractions from a column. Vitamins A and E are then determined by their UV absorption, while vitamin D is measured colorimetrically with an antimony trichloride reagent. The column consists of diatomaceous earth impregnated with dimethyl polysiloxane, with n-heptane as the immobile solvent, and 90% methanol followed by 95% methanol as the mobile solvents. Vitamins A and D elute in that order in the 90% methanol, and finally vitamin E elutes in the 95% methanol fraction. The method is widely applicable to various types of multivitamin and vitamin-mineral products including oil-based, water-based, and dry formulations.

Alkalies↗
PubMed1980

Determination of potential content of vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) in gelatin-coated beadlets, oil-based mixtures, and multivitamin tablet and capsule formulations.

A high-performance liquid chromatographic procedure was used to determine routinely the potential vitamin D content in raw materials and multivitamin formulations. The method employs a microparticulate silica column to separate vitamin D from its degradation products as well as other fat-soluble vitamins. Sample preparation is simple, and the chromatographic time is less than 20 min when progesterone is added to the injection mixture as an internal standard. Replicate analyses of complex multivitamin formulations demonstrate precision with a relative standard deviation of less than 4%. Spiked placebos typically show 98--100% recovery and a linear chromatographic response. The use of bulk drug as a working reference standard is recommended for the determination of the potential vitamin D concentration in pharmaceutical multivitamin preparations.

Capsules↗
PubMed1983

Synthesis of [10S(19)-3H]-dihydrotachysterol2 from ergocalciferol and preliminary investigations into its metabolic fate in rats.

Dihydrotachysterol2 (DHT2), a 5,6-trans derivative of vitamin D2, is very successfully used in the treatment of hypoparathyroidism and renal osteodystrophy. However, the metabolism and the action of DHT2 are poorly understood. Investigations into metabolism of DHT2 start at the synthesis of the radioactively labelled compound. This paper deals with a two-step synthesis of [10S(19)-3H]-dihydrotachysterol2 from vitamin D2. Vitamin D2 can be converted into 5,6-trans vitamin D2 by iodination under irradiation and by triplet-sensitized isomerization. The first method led to unwanted side-reaction products which were difficult to separate from 5,6-trans vitamin D2. Triplet-sensitized isomerization yielded merely 5,6-trans vitamin D2 which could be separated from the residual starting material by chromatography on silica gel and recrystallization. [10S](19)-3H]-Dihydrotachysterol2 with a specific radioactivity of 56 kCi/mol was prepared from 5,6-trans vitamin D2 via partial, homogeneous catalytic reduction of the 10S(19) double bond with tritium gas. It was purified by high-performance liquid chromatography (h.p.l.c.) and characterized by chromatography and ultra-violet absorption spectrophotometry. The biological usefulness of the material was demonstrated in rats following intragastric administration. Blood was collected after 24 and 48 h and fractionation of serum lipids on h.p.l.c. showed 5 peaks of radioactivity.

Animals↗
PubMed1978

High-performance liquid chromatography determination of potential content of vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) in resins, oils, dry concentrates and multivitamin formulations.

The determination of potential vitamin D concentrations in raw materials and in multivitamin formulations by high-performance liquid chromatography is reported. Simple experimental conditions allow the rapid separation of the vitamins from their respective pro- and pre-vitamins, from their irradiation side-products and from some of their overirradiation products. Vitamin extraction is performed directly from dry concentrates, tablets and capsules, without saponification; all procedures are carried out at room temperature so as to preserve the ratio of vitamin D and pre-vitamin D present in the prepatation. The relative standard deviation is less than 1.5%.

Cholecalciferol↗