High Concentrations Of Vitamin Research Articles

Concentrations of vitamin E in various neuroanatomical regions and subcellular fractions, and the uptake of vitamin e by specific areas, of rat brain

Vitamin E concentrations were determined by high-performance liquid chromatography in different anatomical regions of the brain from 3-month-old Fischer 344 rats. Gray matter from cerebellum and cervical spinal cord contained the lowest concentrations, while gray matter from the frontal cortex and thalamus had the highest concentrations of vitamin E. Radioactive α-tocopherol injected intravenously into the rat was readily taken up by brain although the level of uptake was very low compared with the liver. The ratios of brain-to-serum radioactivities ranged from 0.011 to 0.016 depending upon the brain region. Cerebellar gray matter is characterized by a low concentration of unlabeled a-tocopherol and a high level of uptake of radioactive a-tocopherol and thus is particularly active in the metabolism of vitamin E. Concentrations of unlabeled a-tocopherol were highest in microsomal and mitochondrial fractions and were the lowest in cytosol and nuclear fractions.

Gyrate atrophy of the choroid and retina: decreased ornithine aminotransferase concentration in cultured skin fibroblasts from patients

A sensitive and convenient radioisotopic assay for ornithine aminotransferase (OAT) and an enzyme immunoassay for human ornithine aminotransferase were developed for studying decrease in activity of this enzyme in gyrate atrophy of the choroid and retina with hyperornithinemia. Picogram amounts of human OAT could be detected by the enzyme immunoassay. The OAT activity in cultured fibroblasts from two patients was 6% and 2% of that in control fibroblasts, and did not increase on addition of a high concentration of vitamin B 6. The decreased activity, assayed by enzyme immunoassay, was associated with decreased enzyme concentration, suggesting that deficiency of OAT in these patients is not due to production of a structurally altered enzyme lacking catalytic activity, but to decreased production of enzyme protein. When cells from patients were repeatedly subcultured, selective loss of both the activity and concentration of OAT was observed, without changes in activities of several other enzymes tested.

Measurement of circulating vitamin D in man

An assay for vitamin D consisting of high-pressure liquid chromatography (HPLC) and ultraviolet (UV) absorbance detection has been developed and used to measure circulating vitamin D concentrations in human subjects during summer and winter and after deliberate exposure to ultraviolet radiation. Extracts of 2–4 ml of serum were initially fractionated on silica Sep-Pak cartridges followed by reverse-phase HPLC and finally quantitated by UV-absorbance during straight-phase HPLC. Using these methods, we determined the normal range for circulating vitamin D in Boston subjects to be < 0.5 ng/ml to 25 ng/ml ( n = 30); subjects sampled during summer months had higher concentrations of vitamin D than those sampled during winter months. In subjects exposed to a single quantitative dose of ultraviolet radiation (UVR), large transient increases in circulating vitamin D 3 were observed. Concentrations rose 30–50 fold over the first days after exposure before returning to basal levels by one week.

Effect of a 6-week vitamin A-deficient diet on the sensory cells of the inner ear. Light and electron microscopic studies

Histologic studies of the inner ear in rats with chronic vitamin A deficiency have produced contradicting results. In our own electronmicroscope investigations of the inner ear of young rats after a six week vitamin A deficit diet we found a lacking of the cuticle in the outer hair cells and a subtotally lacking of the cuticle in the inner hair cells. Furthermore, we found changes in the reticular system of the intermediate zone. These morphologic changes together with the recent findings of high concentrations of vitamin A in the corti organ support the hypothesis that the acoustic sensory receptors contain or functionally depend upon vitamin A.

Vitamin A in the Blood Serum, Liver, Corpora Lutea, Placentomas and Fetal Fluids of Cows, and in the Blood Serum and Liver of Their Fetuses in the Latter Third of Pregnancy

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Plasma Retinol and Clearance in Hypervitaminosis A

Effects of mild and severe hypervitaminosis A on retinol transport and clearance were studied in mature ewes. Excessive vitamin A intake was associated with high concentrations of vitamin A in plasma and liver, with elevated serum enzymes, with decreased feed consumption and packed cell volume, and with epithelial hypcrplasia. Retinol transport in plasma increased 6- to 8-fold with excessive dietary vitamin A, was greater with mild hypervitaminosis A, and increased exponentially with vitamin A concentration in plasma. Clearance of retinol from plasma increased 2-fold with hypervitaminosis A, exhibited a greater response in the mild group, and increased linearly with vitamin A concentration in plasma. The relationship of clearance to vitamin A concentration in liver was described best by a power function. Retinol clearance represents a mechanism to maintain vitamin A concentration in plasma and may be most effective below vitamin A concentrations of 135 μg/dl plasma. With severe hypervitaminosis A, massive vitamin A accumulates in liver leading to hepatic dysfunction and a resultant decrease in retinol clearance from plasma.

Effect of large amounts of vitamin E during pregnancy and lactation

The effects of excessive intake of vitamin E during gestation and lactation on female rats and their progeny were studied. Pregnant rats receiving large doses of vitamin E (22.5 to 2252 mg/kg per day) had larger livers, higher levels of lipids and vitamin E in plasma, and higher concentrations of vitamin E in the livers than did controls. These deviations from normal were not, however, observed for all levels of supplementation. No obvious teratogenic effects were observed in the newborn young of the vitamin E-supplemented rats. Some eye abnormalities were seen in the older pups of rats given extremely high amounts of the vitamin. The survival rate, weight of the pups, and litter size were unaffected. However, the pups of the mothers who had received 500 mg of vitamin E per day (2252 mg/kg per day) during gestation and lactation had a much higher concentration of vitamin E in their livers and plasma than did controls. This study also confirmed the observation that vitamin E transfer across the placenta is negligible and that mammary transfer of this vitamin is quite efficient.

Brood-Rearing Capability of Caged Honeybees Fed Synthetic Diets

SummaryA chemically defined diet that contained 18 amino acids and 10 water-soluble vitamins supported brood rearing when it was fed to newly emerged honeybees. Another diet supplemented with cholesterol was poorly consumed and supported only low levels of brood rearing. Diet containing higher concentrations of amino acids did not support brood rearing. A diet supplemented with higher concentrations of vitamins and a salt mixture supported brood rearing, but less than a diet containing higher levels of vitamins without the salt mixture.

Effect of Diethylstilbestrol, Ascorbic Acid and Vitamin E on Serum Lipid Patterns

The effects of relatively high concentrations of vitamin C, vitamin E and diethylstilbestrol, and various combinations of cholestyramine and diethylstilbestrol on the lipid composition of chicken serum were studied. After DES injection (at concentrations as low as 1 mg. /day for 7 days), levels of triglycerides, phospholipids and cholesterol were much higher, the effect being much more pronounced in the hens. Cholestyramine caused a fourfold decrease in cholesterol in females, a 25% reduction in males. DES consistently caused a redistribution of the esterified fatty acids, increasing the percentage of oleic and reducing percentages of stearic and linoleic acids. Preparative TLC analysis of all constituents showed other variations in fatty acid composition, but there was no other common pattern of change.Vitamin E in the diet caused a significant rise in triglycerides and phospholipids in DES treated birds. When vitamins E and C were fed, triglyceride and phospholipid values decreased. Cholesterol concentration did not vary significantly. With birds receiving both vitamins, diethylstilbestrol seemed to have less effect in. causing the shift to increased percentage of oleic acid in the total esterified fatty acids.

Changes in susceptibility of normal cells to agglutination by plant lectins following modification of cell coat material

Infection of normal chick embryo, baby hamster kidney and HEp-2 cells with the nononcogenic viruses, Newcastle disease virus and Herpes simplex virus, was found to increase their susceptibility to agglutination by the plant lectins, concanavalin A and wheat germ agglutinin. Similar results were obtained following treatment of normal HEp-2 cells with anticellular serum and high concentrations of vitamin A alcohol. The agglutination reaction with concanavalin A and wheat germ agglutinin was inhibited specifically by α-methyl- d-glucopyranoside and N-acetyl-glucosamine, respectively. A temporal correlation was demonstrated between changes in cell agglutination behaviour and digestion of the cell coat material. The relationship of changes occurring in the cell coat to the observed alterations in cell agglutination behaviour was discussed with reference to the role of enzymic modification of the cell periphery as a factor in cell growth regulation.

THE USE AND ABUSE OF VITAMIN A

The grave risks resulting from the unrestricted sale of high concentrations of vitamin A make it imperative that an active curb, by appropriate legislation if necessary, be placed on the over-the-counter marketing of high potency vitamin A preparations. Physicians should be aware of the vitamin A content in the preparations they prescribe for their patients. They also should caution parents regarding the dangers of overdosage of this vitamin.

Sub-lethal autolysis: Modification of cell periphery by lysosomal enzymes

Lysosomal activation was induced in dog kidney and HEp-2 cells by treatment with anticellular serum and high concentrations (20 μg/ml) of vitamin A alcohol. The morphological changes accompanying the release of enzymes from activated lysosomes were described. Measurements of cell coat thickness by ellipsometry revealed that lysosomal enzymes released extracellularly were able to digest the coat. The scale of enzyme release was an important factor in determining the amount of coat digested. Complement-sufficient anticellular sera and high concentrations of vitamin A induced marked lysosomal activation and extensive digestion of the coat. Complement-deficient anticellular serum produced significantly less lysosomal labilization and only limited digestion of the coat. The digestion of the cell coat induced by these agents was prevented by pretreatment of the cells with either hydrocortisone or chloroquine.

Synthesis of (1,2- 3 H 2 )cholecalciferol and metabolism of (4- 14 C,1,2- 3 H 2 )- and (4- 14 C,1- 3 H)-cholecalciferol in rachitic rats and chicks.

[1,2-(3)H(2)]Cholecalciferol has been synthesized with a specific radioactivity of 508mCi/mmol by using tristriphenylphosphinerhodium chloride, the homogeneous hydrogen catalyst. With doses of 125ng (5i.u.) of [4-(14)C,1-(3)H(2)]cholecalciferol the tissue distribution in rachitic rats of cholecalciferol and its metabolites (25-hydroxycholecalciferol and peak P material) was similar to that found in chicken with 500ng doses of the double-labelled vitamin. The only exceptions were rat kidney, with a very high concentration of vitamin D, and rat blood, with a higher proportion of peak P material, containing a substance formed from vitamin D with the loss of hydrogen from C-1. Substance P formed from [4-(14)C,1,2-(3)H(2)]cholecalciferol retained 36% of (3)H, the amount expected from its distribution between C-1 and C-2, the (3)H at C-1 being lost. 25-Hydroxycholecalciferol does not seem to have any specific intracellular localization within the intestine of rachitic chicks. The (3)H-deficient substance P was present in the intestine and bone 1h after a dose of vitamin D and 30min after 25-hydroxycholecalciferol. There was very little 25-hydroxycholecalciferol in intestine at any time-interval, but bone and blood continued to take it up over the 8h experimental period. It is suggested that the intestinal (3)H-deficient substance P originates from outside this tissue. The polar metabolite found in blood and which has retained its (3)H at C-1 is not a precursor of the intestinal (3)H-deficient substance P.

Vitamin K and coumarin anticoagulants: dependence of anticoagulant effect on inhibition of vitamin K transport.

Coumarin anticoagulants inhibit the release of plasma clotting factor VII by vitamin K in liver slices from vitamin K-deficient animals without inhibition of protein synthesis. When the ratio of vitamin K to coumarin anticoagulant is kept constant, but the concentrations are increased, the inhibition disappears. This suggests that the pharmacological action of coumarin anticoagulants depends on irreversible inhibition of normal vitamin K transport to its site of action. At higher concentrations of vitamin K the inhibition can be surmounted, because vitamin K can enter the cell by an alternate route that is not inhibited by coumarin anticoagulants.

Topical Administration of Vitamin A Acid for Ichthyosiform Dermatoses and Psoriasis

Therapeutic responses to topical administration of preparations containing 0.1% to 0.3% vitamin A acid and control bases applied to contralateral areas of involvement were compared in 26 patients with psoriasis, 8 with ichthyosis vulgaris, 8 with X-linked ichthyosis, 17 with lamellar ichthyosis, and 10 with epidermolytic hyperkeratosis. Topical administration of vitamin A acid was most effective in psoriasis, lamellar ichthyosis, and epidermolytic hyperkeratosis, disorders associated with epidermal cell hyperplasia; it did not appear to be effective in ichthyosis vulgaris. Irritation with higher concentrations of vitamin A acid, which subsided rapidly when the medication was withheld, was the only adverse effect noted.

The accumulation of aurothiomalate into the rat liver cells during the damaging of lysosomes with vitamin A.

SummaryWhen the liver cells of the rat were treated with alcoholical form of vitamin A this caused the release of lysosomal acid phosphatase into the cytoplasma. Simultaneously the transportation of aurothiomalate increased notably. The too high concentrations of vitamin A, however, caused autolysis in the cells and the decrease of the accumulation of gold.

EFFECT OF WATER SOLUBLE VITAMINS AND THEIR ANALOGUES ON GROWTH OF CANDIDA ALBICANS. III. PARA-AMINOBENZOIC ACID, NICOTINIC ACID, INOSITOL AND THEIR ANALOGUES.

By using high concentrations of vitamins in biotin basal synthetic mineral medium,Candida albicans was shown to possess a partial dependency forp-aminobenzoic acid, nicotinic acid and inositol. Sodium gantrisin [N1-3,4-dimethyl-5-isoxazolyl sulfanilamide)] was growth inhibitory in the absence ofp-aminobenzoic acid and its effect was reversed byp-aminobenzoic acid. Similarly, pyridine-3-sulfonic acid was growth inhibitory to the organism in the absence of nicotinic acid and its effect was reversed by nicotinic acid. Additions of biotins, thiamine, vitamin B12, nicotinic acid,p-amino-benzoic acid and inositol to basal synthetic medium showed clear-cut growth stimulation for each vitamin. Parallel omission type experiments on the other hand, demonstrated a masking effect of one vitamin on another. Ascorbic acid, riboflavin, calcium pantothenate choline, folic acid and thioctic acid were without effect. A new procedure for the determination of microbial vitamin requirements was outlined.

The Effects of Vitamin A and Citral on Epithelial Differentiation in vitro 2. The Chick Oesophageal and Corneal Epithelia and Epidermis

ABSTRACT Differentiation of the oesophageal and corneal epithelia and epidermis of the chick embryo was studied in organ cultures in normal medium and in media containing added vitamin A and/or citral. In normal medium the oesophageal epithelium developed well for the first 6 days, but between 6 and 12 days many superficial layers of cells were sloughed and large mucous cells from the glands spread over the remaining epithelium. Vitamin A inhibited the normal stratification, and the oesophageal epithelium became pseudostratified and folded, with tall, columnar, ciliated cells and many small mucous glands. Citral inhibited the differentiation of ciliated and mucous cells and the epithelium became thicker than in normal medium. Vitamin A and citral together produced either a vitamin A or a citral effect, depending upon the relative concentrations of the two compounds. The corneal epithelium differentiated normally in the control cultures, but under the influence of additional vitamin A it remained thin and the superficial cells secreted mucus. In + citral medium the corneal epithelium became thicker than usual and the conjunctival epithelium keratinized. When both vitamin A and citral were added to the medium the corneal cultures showed a mild vitamin A effect. Skin cultures keratinized well in normal medium, but the epithelium remained thin and became mucus-secreting in response to high concentrations of vitamin A. Citral alone had little effect on epidermis, but it suppressed the vitamin A response almost completely when both compounds were added together. Citral produced changes resembling those of vitamin A deficiency in cultures of oesophagus and cornea, and it reduced the effects of added vitamin A. The results of these experiments therefore give further evidence of antagonism between vitamin A and citral. It is suggested that either deficiency of vitamin A or treatment with citral stimulates, whilst high concentrations of vitamin A inhibit, mitosis in the corneal epithelium. The results of these experiments indicate that each epithelium achieves its maximal synthesis of mucus at a characteristic concentration of vitamin A.

The enzymic reduction of naphthoquinones by reduced nicotinamide-adenine dinucleotide

1. 1. A particulate enzyme system, obtained from cell-free extracts of the H 37 Ra strain of Mycobacterium tubercolosis , catalyzes the reduction of napthoquinones (vitamin K 1 , K 2(20) , K 2(25) , K 2(45) and benzoquinones CoQ 2 , but not CoQ 10 ) by NADH 2 . The reduction of both external quinones and protein-bound K 2(45) has been demonstrated. 2. 2. The reduction of vitamin K 2(45) is inhibited by dicumarol. 3. 3. The particulate enzyme system is solubilized by Triton X-100 and by digitonin treatment. The solubilized enzyme system contains high concentrations of vitamin K 2(45) .

The Effects of Vitamin A and Citral on Epithelial Differentiation in vitro 1. The Chick Tracheal Epithelium

ABSTRACT Differentiation of the tracheal epithelium of embryonic chicks was studied in organ cultures in a normal medium and in media containing added vitamin A and citral. In normal medium, the tracheal epithelium differentiated well, but usually fewer mucous cells developed than in the intact chick. High concentrations of vitamin A alcohol inhibited the differentiation of mucous cells and favoured that of ciliated cells. Citral, in fairly low concentrations, had opposite effects: it stimulated mucus-secretion and inhibited the differentiation of ciliated cells. In higher concentrations it stimulated division of the basal cells, and the epithelium became stratified and sometimes keratinized. Vitamin A and citral added together to the culture medium produced a citral effect, which varied in intensity according to the proportions of the two compounds, but was always milder than that resulting from treatment with the same concentration of citral alone. These results suggest that citral inhibits both the natural vitamin A in the plasma and the added synthetic vitamin A, thus producing changes in the tracheal epithelium characteristic of vitamin A deficiency. The results indicate that secretion of mucus by the tracheal epithelium is maximal at a lower concentration of vitamin A than that to which it is normally exposed in the body. It is suggested that vitamin A may influence epithelial differentiation partly by affecting the mitotic rate.