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PubMed1963

Studies on the mode of action of excess of vitamin A. VII. Changes in the fine structure of erythrocytes during haemolysis by vitamin A.

Rabbit erythrocytes have been haemolysed by treatment with vitamin A alcohol and the sequence of changes in the fine structure of the cells during lysis has been investigated by phase contrast microscopy of intact cells and electron microscopy of thin sections. The initial effect of the vitamin, which occurs within 1 minute, is the production of cells of bizarre appearance which have a greatly increased surface area relative to untreated cells. Large indentations appear in the surfaces of the cells, and vacuoles are formed from the indentations by a process that resembles micropinocytosis. The cells then become spherical and loss of haemoglobin begins as breaks appear in the membranes of some cells; finally, ghosts are produced that are no longer spherical but still contain numerous vacuoles. These observations support the thesis that one site of action of vitamin A is at lipoprotein membranes.

Animals↗
PubMedDate not supplied

Vitamin K epoxide reductase complex subunit 1 (VKORC1): the key protein of the vitamin K cycle.

Vitamin K epoxide, a by-product of the carboxylation of blood coagulation factors, is reduced to vitamin K by an enzymatic system possessing vitamin K epoxide reductase (VKOR) activity. This system is the target of coumarin-derived drugs widely used in thrombosis therapy and prophylaxis. Recently, the key protein of the VKOR system has been identified. The human VKORC1 gene maps to chromosome 16 and consists of 3 exons encoding a 163-amino acid integral ER membrane protein with three or four predicted transmembrane alpha- helices. Expression of human VKORC1 in Spodoptera frugiperda (Sf9) cells and in Pichia pastoris results in enhanced VKOR activity over low endogenous constitutive levels. Sequence based search methods reveal that human VKORC1 belongs to a large family of homologous genes found in vertebrates, insects, plants, protists, archea, and bacteria. All orthologs share five completely conserved amino acids, including two cysteines found in a tetrapeptide motif presumably required for redox function. The recent discovery of the VKORC1 gene has initiated renewed interest in understanding VKOR activity. Analysis of VKORC1 protein structure and function will be crucial in understanding the VKOR catalytic mechanism, how anticoagulant drugs modulate VKOR activity, and the role of VKORC1 in downstream physiological and pathological pathways.

Amino Acid Sequence↗
PubMed1986

Interpretations of requirements for thiamin, riboflavin, niacin-tryptophan, and vitamin E plus comments on balance studies and vitamin B-6.

Data from the long-term projects sponsored by the Food and Nutrition Board to determine the requirements for thiamin, riboflavin, niacin-tryptophan, and vitamin E are utilized to effect an opinion regarding the recommended dietary allowances for these vitamins. Based upon data obtained during these and subsequent research projects, comments on balance studies, changes in tissue lipids, and the requirements for vitamin B-6 are included. The possibility that antioxidants may have an effect on delaying oncogenesis is discussed.

Animals↗
PubMed1992

Effects of timing and dose of vitamin A on tissue retinol concentrations and antibody production in the previously vitamin A-depleted rats.

The effect of retinol repletion in previously vitamin A-depleted Lewis rats on antibody production to pneumococcal polysaccharide (SSS-III) was studied. When vitamin A-depleted rats were given either 0.35 mumol (0.1 mg) or 5.2 mumol (1.5 mg) retinol, plasma retinol became normal within 8 h. Liver and lymphoid-organ retinol concentrations were normalized by 1 d after repletion with 5.2 mumol but not 0.35 mumol retinol. Antibody production to SSS-III was compared after administering 5.2 mumol retinol either as a divided dose (half given 4 d before and half given on the day of immunization) or as a single dose concurrent with immunization. Vitamin A-depleted rats produced very little SSS-III-specific antibody. The divided dose of retinol consistently restored anti-SSS-III production whereas the single concurrent dose was less effective despite equal effects on tissue retinol concentrations. Interestingly, normalization of plasma retinol was not always a good predictor of the immune response to pneumococcal polysaccharide.

Animals↗
PubMed1993

A priming dose of oral vitamin A given to preschool children may extend protection conferred by a subsequent large dose of vitamin A.

A randomized trial tested whether a priming dose of vitamin A would extend the protection of a subsequent 60,000-micrograms retinol equivalent (RE) oral dose. Seventy-five xerophthalmic and 74 age- and neighborhood-matched non-xerophthalmic preschool children were randomized to one of three oral regimens of vitamin A, receiving peanut oil only (Group A), 7500 micrograms RE (Group B) or 60,000 micrograms RE (Group C), followed in all instances by 60,000 micrograms RE 1 wk later. Serum retinol was measured 2, 4, 6 and 12 mo following the second dose by technicians unaware of the children's treatment status. Among xerophthalmic children, mean values differed across treatment groups at 2 mo (C > A) and tended to be different at 12 mo (C > A and B > A). Among non-xerophthalmic children mean retinol concentrations differed across treatment groups at 6 mo, but not in a consistent way (A > C > B), and at 12 mo (C > A and B > A). Xerophthalmic children reverted to biochemical deficiency faster than non-xerophthalmic children. A small or large priming dose may extend the protection conferred by a 60,000-micrograms RE dose, supporting the use of repeated, spaced doses of vitamin A for treating xerophthalmia. Similar retinol concentrations in Groups B and C at 12 mo suggest the 60,000-micrograms RE prophylactic dose currently recommended by the World Health Organization need not be increased.

Administration, Oral↗
PubMed1995

Supplementing ferrets with canthaxanthin affects the tissue distributions of canthaxanthin, other carotenoids, vitamin A and vitamin E.

To study the effects of canthaxanthin supplementation on the tissue distribution of canthaxanthin, other carotenoids, vitamin A and vitamin E, 26 spayed female ferrets (2 mo of age) were used. Ferrets were assigned to receive a commercial ferret diet and a gavage of canthaxanthin [50 mg/(kg body wt.d)] or a gavage of placebo beadlets (0 mg canthaxanthin) 5 d/wk. Serum canthaxanthin concentrations in the canthaxanthin-fed group increased from 0 at baseline to 37.76 +/- 5.34 nmol/L trans and 77.10 +/- 12.60 nmol/L cis canthaxanthin at 12 mo. Further accumulation of canthaxanthin did not occur with continuous dosing. After 2 y of receiving canthaxanthin beadlets by gavage, the ferrets did not show a detectable concentration of canthaxanthin in the eyes, nor did they have clinical signs of toxicity. Canthaxanthin concentrations were highest in liver, with high concentrations also seen in fat, lung and small intestine. The sum of alpha and beta-carotene concentrations detected in livers was significantly higher in the canthaxanthin-fed group than in the placebo-fed group, but not significantly higher when individual carotenes were compared. However, alpha-tocopherol concentrations in the livers and lungs and lutein/zeaxanthin in the fats of the ferrets fed canthaxanthin were significantly lower than in those fed the placebo. Retinoid concentrations in tissues of the ferrets fed canthaxanthin were not different from those of the placebo-fed group. The effects of canthaxanthin supplementation on other antioxidants and vitamin A nutrients demonstrate either a synergistic or antagonistic relationship, depending on the specific tissue assayed.

Adipose Tissue↗
PubMed2001

A randomised, double masked, clinical trial of high dose vitamin A and vitamin E supplementation after photorefractive keratectomy.

AIM: To evaluate the effect of a high dose vitamin A and E supplementation on corneal re-epithelialisation time, visual acuity and haze following photorefractive keratectomy (PRK). METHODS: Two groups of 20 patients who underwent myopic PRK were supplemented with either 25 000 IU retinol palmitate and 230 mg alpha tocopheryl nicotinate or a placebo. Clinical outcomes were evaluated up to 360 days. RESULTS: In the vitamin treated group, re-epithelialisation time was significantly faster (p = 0.029) and haze incidence was reduced (p = 0.035), especially for high myopic corrections (p = 0.043). This group also reported a significantly better uncorrected visual acuity (p = 0.043). CONCLUSIONS: High dose vitamin A and E oral supplementation may accelerate re-epithelialisation time and may reduce corneal haze formation after PRK.

Adult↗
PubMed2006

Vitamin D receptor polymorphisms in hypocalcemic vitamin D-resistant rickets carriers.

BACKGROUND/AIMS: Hypocalcemic vitamin D-resistant rickets (HVDRR) is a rare autosomal recessive disorder characterized by severe rickets, hypocalcemia, secondary hyperparathyroidism, elevated levels of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], and occasionally, alopecia. In most cases, the disease is associated with mutations in the gene of the vitamin D receptor (VDR), the mediator of 1,25(OH)(2)D(3) action. The apparently healthy HVDRR heterozygotes express both normal and mutant VDR alleles, and they present higher levels of 1,25(OH)(2)D(3) than their respective controls. Because VDR function, except for the disease-causative mutations, might be influenced by the presence of certain polymorphisms, we investigated the distribution of four common VDR polymorphisms--BsmI, ApaI, TaqI and FokI--in HVDRR carriers compared with their respective controls. METHODS: Sixty-seven relatives of 2 HVDRR patients, all members of an extended Greek kindred, were included in the study. VDR allelic polymorphisms were assessed by restriction fragment length polymorphisms after specific polymerase chain reaction amplification. RESULTS: The distribution of genotypic and allelic frequencies differed between HVDRR carriers and their respective controls regarding BsmI and TaqI polymorphisms. The bb genotype and the T allele (presence of BsmI and absence of TaqI polymorphisms) were less frequent in the HVDRR carrier group than in the control group in a statistically significant manner (p = 0.029 and p = 0.025, respectively). CONCLUSIONS: Our findings showed that the apparently healthy HVDRR carriers present a different distribution of BsmI and TaqI VDR polymorphisms than their controls, suggesting that further investigation of the HVDRR carrier population may elucidate the implication of VDR alleles in VDR function and the vitamin D endocrine system.

Adolescent↗
PubMed1979

Effects of maternal administration of endoxan, vitamin A and vitamin B12 on the development of the fetal spinal cord of the albino mouse.

The effects of maternal administration of endoxan, vitamin A and vitamine B12 were studied on the cervical fetal spinal cord of the albino mouse. Endoxan caused dorsal and ventral herniation of the spinal cord, chromatolysis and degeneration of the neuroblasts together with neuroglial proliferation. Vitamin A and B12 resulted in an increase in the surface areas of both grey and white matter and an increase in the volume of the neuroblasts. The possible mechanisms concerned were discussed.

Abnormalities, Drug-Induced↗
PubMed1980

Comparative histological study of the effects of high calcium diet and vitamin D supplements on epiphyseal plates of vitamin-D-deficient chicks.

A comparative histological and microradiographic study of the tibial epiphyseal plates of chickens raised on: (1) a vitamin-D-deficient diet; (2) a vitamin-D-deficient diet supplemented with cholecalciferol, and (3) a vitamin-D-deficient diet to which extra calcium had been added, has revealed that a high-calcium diet did not normalize the epiphyseal plates completely. However, it restored the normal length and chondrocyte arrangement to the proliferative zone. The degenerative zone became elongated and this seems to be related to the hypophosphataemic condition which has developed as a result of the special diet.

Animals↗
PubMed2004

Prediction of vitamin A, vitamin E, selenium and zinc status of periparturient dairy cows using blood sampling during the mid dry period.

Vitamins A and E, and the trace elements selenium (Se) and zinc (Zn) are essential for the health and performance of dairy cows. Their concentrations often decrease around calving and extra supplementation is sometimes recommended at that time. However, the need for this varies, for example depending on quantity and quality of feedstuffs in the diet. The aim of this study was to measure the concentrations of serum vitamin A (S-vit A) and vitamin E (S-vit E), plasma Se (P-Se) and serum Zn (S-Zn) in blood samples taken at several time points from one month before to one month after calving, and to evaluate if a blood sample taken during the mid dry period can accurately predict the blood concentration at calving and early lactation. Dairy cows on 3 different feeding regimens during the dry period were included in the study. A significant decrease in the concentrations of S-vit A and S-vit E, and S-Zn, was observed at calving, and P-Se was significantly lower during the dry period and at calving than in early lactation. The blood concentrations of S-vit E and P-Se in the mid dry period significantly predicted the occurrence of values considered marginal or deficient at the time of calving. The data indicate that a mid dry period concentration of > or = 5.4 mg/l of S-vit E and > or = 0.09 mg/l of P-Se will result in a 90% chance that the cow stays above marginal levels at calving given that a feed of the same quality is offered.

Animals↗
PubMed1977

A case of idiopathic hypoparathyroidism and dietary vitamin D deficiency: the requirement for calcium and vitamin D for bone, but not renal responsiveness to PTH.

A patient with concurrent idiopathic hypoparathyroidism and dietary vitamin D deficiency was studied. Acute renal responsiveness to PTH was demonstrated by immediate increases in urinary cyclic AMP and phosphorus excretion. An impaired bone response to sustained PTH administration was demonstrated by absence of significant increases in serum calcium or urine hydroxyproline during 3 days of PTH administration. Skeletal responsiveness was restored either by raising the initial serum calcium with constant calcium infusion or by raising serum 25-OH-D levels to normal by administration of 1,000 units vitamin D daily. These results extend to the human, animal observations which suggest that vitamin D is required for the skeletal but not for the renal actions of parathyroid hormone.

Bone Resorption↗
PubMed2000

Bone mineral density increases with vitamin D repletion in patients with coexistent vitamin D insufficiency and primary hyperparathyroidism.

Two hundred and twenty-nine consecutive subjects, 202 women and 27 men, referred for evaluation of osteoporosis or low bone mineral density (BMD) had serum measurements of immunoreactive PTH (iPTH) and 25-hydroxyvitamin D (25OHD) performed. Fifteen individuals (mean age +/- SE, 75+/-2.4 yr) had depressed serum 25OHD (<15 pg/mL) and concomitantly elevated (>65 pg/mL) iPTH levels. After successful treatment of vitamin D insufficiency in all subjects, iPTH remained inappropriately high or frankly elevated in 5, describing a 2.2% prevalence rate of coexistent primary hyperparathyroidism and vitamin D insufficiency in our population. Despite persistent primary hyperparathyroidism, normalization of serum 25OHD levels in these 5 subjects increased their BMD at an annual rate of 6.3% and 8.2% in spine and hip, respectively. Our results suggest that coexistent vitamin D insufficiency can obscure the diagnosis of primary hyperparathyroidism and, when treated effectively, can result in substantial short-terms gains in BMD despite persistence of the inappropriate production of PTH.

Aged↗
PubMed2000

Ataxia with vitamin E deficiency: biochemical effects of malcompliance with vitamin E therapy.

To prevent neuronal damage, patients with ataxia with isolated vitamin E deficiency need lifelong supplementation with high doses of vitamin E. Short interruptions of therapy, such as occur in malcompliance, do not lead to clinical symptoms. However, the authors show that even short withdrawals may cause a prolonged decrease of the total radical trapping capacity of plasma; its major contributors, such as urate and sulfhydryl groups, fail to compensate for the missing vitamin E.

Adolescent↗
PubMed2005

Treatment of malabsorption vitamin D deficiency myopathy with intramuscular vitamin D.

A nearly 5 year-old boy presented with proximal muscle weakness, reduced muscle bulk, a positive Gower sign and Trendelenburg gait. He was known to have cholestatic liver disease. Investigations revealed markedly low serum total calcium, elevated alkaline phosphatase, very low serum 25-hydroxyvitamin D, and radiographs consistent with active rickets despite the ongoing administration of a water-soluble preparation of vitamin D. Only i.v. calcitriol acutely corrected the hypocalcemia, despite trying several oral preparations, suggesting that malabsorption secondary to chronic liver disease was the cause of his rickets. Intramuscular calciferol quickly corrected his muscle weakness and X-ray findings. Myopathy secondary to vitamin D deficiency is an uncommon diagnosis in children. Intermittent calciferol is an inexpensive and practical treatment for vitamin D deficiency, especially if associated with malabsorption.

Child, Preschool↗
PubMed1989

Concentrations of vitamin D-binding protein and vitamin D metabolites in plasma of patients with liver cirrhosis.

Plasma levels of vitamin D-binding protein (DBP) and vitamin D metabolites in patients with decompensated and compensated liver cirrhosis were assayed. Plasma levels of DBP in the decompensated group were significantly lower than those in the compensated group, but both were lower than the normal range. The plasma levels of 25-hydroxyvitamin D (25-OH-D) and 1 alpha,25-dihydroxyvitamin D [1,25(OH)2D] in the compensated group were within the respective normal ranges, whereas both values in the decompensated group were significantly lower than those in the compensated group. Most of 25-OH-D (higher than 96%) was confirmed to be circulated as a bound form with DBP in the plasma of not only the compensated but also the decompensated group. When vitamin D2 was given to the decompensated group, a significant increase of 1,25(OH)2D levels in the plasma could not be observed while 25-OH-D levels were increased. On the other hand, the administration of 1 alpha-hydroxyvitamin D3 (1 alpha-OH-D3) to the decompensated group caused a significant increase in the plasma levels of 1,25(OH)2D. Therefore, we suggest that the administration of 1 alpha-OH-D3 is useful for the treatment of bone disease induced by liver cirrhosis.

Calcifediol↗
PubMedDate not supplied

[Effect of vitamin D3, arginine, and a biologically active complex from Serratula coronata on free radical oxidation of lipids in vitamin D deficiency].

Lipid free-radical oxidation (LFRO) on the D-deficient model with the animal administration per os by vitamin D3 (cholecalciferol), specimen from Serratula coronata plant, containing low molecular weight biological sterol--20-hydroxyecdysone (ecdysterone) was investigated. As well influence of arginine as one of the amino acid components of the specimen from Serratula coronata was investigated. The LFRO in the blood serum, liver microsomal and mitochondrial fractions were characterize by measured of the chemiluminescence kinetic parameters. Vitamin D3, the specimen from Serratula coronata plant and arginine displayed some antioxidant (AO) properties as was established. On the basis of the received experimental data the series of their antioxidizing activity: vitamin D3 = drug from Serratula coronata > arginine were offered. The possible mechanism of the 20-hydroxyecdysone and arginine participation on LFRO maybe in free-radical reactions breaking via hydroxy and amino groups in structure of their molecules.

Animals↗
PubMed2006

[Elevated plasma concentration of homocysteine, low level of vitamin B6, pyridoxal, and vitamin D insufficiency in patients with hip fracture: a possible explanation for detrimental cross-link pattern in bone collagen].

Impaired bone quality has been proposed as a cause of increased bone fragility in osteoporosis. Collagen crosslinking is a candidate for determining the material properties of bone. Collagen cross-links are of two types; lysyl oxidase (LOX) and lysyl hydroxylase (PLOD1; LH1, PLOD2; LH2b) controlled cross-links, and advanced glycation end products, pentosidine. Homocysteine and vitamin B(6) (pyridoxal) are also regulatory factors of collagen crosslinking. Recently, we reported that in the femoral neck fracture cases, not only reduced enzymatic cross-links in old osteon and increased pentosidine in both young and old osteons from cortical and cancellous bone, but also higher plasma homocysteine and lower pyridoxal levels were evident compared with the controls (Osteoporos Int 2006. Calcif Tissue Int, 2006). In this review, we describe that mildly hyperhomocysteinemia, and vitamin B(6) or vitamin D insufficiency are crucial determinants of detrimental crosslinking of bone collagen in patients with hip fracture.

Aged↗