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Biomedical subjects

M F Holick

Publications and source records attributed to M F Holick.

At least 109 records · Page 6Linked to original sources
PubMed1994

Epidermis and serum protect retinol but not retinyl esters from sunlight-induced photodegradation.

Sunlight-induced photodegradation of retinyl esters and retinol in human skin, blood and cultured keratinocytes was investigated. Using high-performance liquid chromatography with an extraction method that avoided saponification, the analysis of human foreskin (Caucasian) showed that levels of retinyl esters and retinol were approximately 3.5 and 5.0 times higher, respectively, in the epidermis than in the dermis. Upon irradiation by sunlight, a significant reduction in epidermal retinyl esters was observed in both summer and winter. However, epidermal retinol, dermal retinol and dermal retinyl esters did not show statistically significant reductions. When serum from volunteers who had taken a large dose of retinyl palmitate to elevate serum retinyl esters was exposed to sunlight, the retinyl esters in the serum rapidly disappeared after 10 min of exposure--similar to the photodegradation seen for retinyl palmitate in an organic solvent. While retinol in an organic solvent rapidly photodegraded similar to serum retinyl palmitate, serum retinol slowly declined upon sunlight irradiation. When cultured keratinocytes that took-up 3H-retinol and thereafter contained 3H-retinyl esters and 3H-retinol were exposed to sunlight, 80% of the 3H-retinyl esters disappeared upon sunlight irradiation whereas only about 20% of the 3H-retinol did so. These results suggest that the epidermis, serum and keratinocytes selectively protect retinol from sunlight-induced photodegradation. It is most likely that serum retinol-binding protein and cellular retinol-binding protein protect retinol, a vital epithelial growth factor, from photodegradation.

Blood↗
PubMed1993

Kinetic and thermodynamic studies of the conversion of previtamin D3 to vitamin D3 in human skin.

The thermoisomerization of previtamin D3 to vitamin D3 is the last step in the synthesis of vitamin D3 in human skin. Kinetic and thermodynamic studies of this reaction in human skin and an organic solvent revealed that not only the equilibrium of the reaction was shifted in favor of vitamin D3 formation in human skin (equilibrium constant K at 37 degrees C = 11.44) compared to hexane (K = 6.15), but also the rate of the reaction was increased by more than 10-fold in human skin (T1/2 at 37 degrees C = 2.5 h) when compared to hexane (T1/2 = 30 30 h). This extraordinarily fast reaction rate was also confirmed in vitro in chicken skin and in vivo in human subjects. The enthalpy change for the reaction determined by the van't Hoff plot was delta H degree = -21.58 kJ mol-1 in human skin and delta H degree = -15.60 kJ mol-1 in hexane. Arrhenius plots showed that the activation energies for both the forward and the reverse reactions were lower in human skin (Ea1 = 71.05 kJ mol-1 and Ea2 = 92.63 kJ mol-1) than in hexane (Ea1 = 84.90 kJ mol-1 and Ea2 = 100.5 kJ mol-1). Activation parameters for the reaction in human skin and in hexane were also reported. Subcellular fractionation of human epidermal tissue revealed that most epidermal 7-dehydrocholesterol and previtamin D3 were in the membrane fraction, while only 20% were in the cytosol. The interaction of previtamin D3 with intracellular lipids and/or proteins in skin may be responsible for the increased vitamin D3 formation rate in the skin.

Adult↗
PubMed1993

High fiber diets slow bone turnover in young men but have no effect on efficiency of intestinal calcium absorption.

Dietary fiber reduces the absorption of dietary calcium from a meal, but its impact on calcium kinetics is unknown. We therefore evaluated the effects of a high fiber diet on calcium balance and kinetics and on calcium-regulating hormones. Seven young men each participated in two 23-d experiments. In the low fiber period the controlled diet provided 6.5 g fiber/d and 530 mg calcium/d. In the high fiber period fiber was increased to 31.3 g/d and calcium to 586 mg/d by substituting high fiber cereal. Measured between d 7 and 12 of each period, the high fiber diet significantly lowered the apparent absorption of calcium (from 60.6 +/- 23.8% to 37.1 +/- 26.5%) and reduced calcium balance, although balance remained positive overall. Fiber had no effect on serum total or ultrafiltrable calcium, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D or parathyroid hormone concentrations measured on d 1, 7, 12 and 20. Calcium kinetics was studied between d 17 and 23 by administering oral 44Ca and intravenous 42Ca to fasting subjects. Fractional absorption of calcium in the fasting state was unaffected by fiber. However, during the high fiber period, subjects had significantly lower bone accretion, resorption and turnover rates, and calcium flow to bone from the exchangeable pool than during the low fiber period. We conclude that the fiber-induced reduction in calcium absorption slowed down bone calcium turnover but did not increase the efficiency of intestinal absorption.

Adult↗
PubMed1992

Hypervitaminosis D associated with drinking milk.

BACKGROUND: Vitamin D has been added to milk in the United States since the 1930s to prevent rickets. We report the unusual occurrence of eight cases of vitamin D intoxication that appear to have been caused by excessive vitamin D fortification of dairy milk. METHODS: Medical records were reviewed and a dietary questionnaire was sent to eight patients who had unexplained hypervitaminosis D. Vitamin D analyses with high-performance liquid chromatography were performed on samples of the patients' serum, the dairy milk they drank, and the vitamin D concentrate added to the milk. RESULTS: All eight patients drank milk produced by a local dairy in amounts ranging from 1/2 to 3 cups (118 to 710 ml) daily. All had elevated serum 25-hydroxyvitamin D concentrations (mean [+/- SD], 731 +/- 434 nmol per liter [293 +/- 174 ng per milliliter]). Six of the eight patients had elevated serum vitamin D3 concentrations. Of the eight patients, seven had hypercalcemia and one had hypercalciuria but normocalcemia (mean serum calcium, 3.14 +/- 0.51 mmol per liter [12.6 +/- 2.1 mg per deciliter]). Analysis of the dairy's vitamin D-fortified milk revealed concentrations of vitamin D3 (cholecalciferol) that ranged from undetectable to as high as 232,565 IU per quart (245,840 IU per liter). An analysis of the concentrate that was used to fortify the milk, labeled as containing vitamin D2 (ergocalciferol), revealed that it contained vitamin D3. CONCLUSIONS: Hypervitaminosis D may result from drinking milk that is incorrectly and excessively fortified with vitamin D. Milk that is fortified with vitamin D must be carefully monitored.

Adult↗
PubMed1992

The vitamin D content of fortified milk and infant formula.

BACKGROUND: The fortification of milk and infant formula with vitamin D has had an important role in eliminating rickets in children and osteomalacia in adults. A recent outbreak of vitamin D intoxication caused by drinking milk fortified with excess vitamin D has led to questions about the level of vitamin D in milk from other producers. METHODS: We used high-performance liquid chromatography to measure vitamin D in samples of 13 brands of milk with various fat contents and 5 brands of infant formula purchased at random from local supermarkets in five Eastern states. RESULTS: Only 12 (29 percent) of the 42 samples of the 13 brands of milk and none of the 10 samples of the 5 brands of infant formula contained 80 to 120 percent of the amount of vitamin D stated on the label. Twenty-six of the 42 milk samples (62 percent) contained less than 80 percent of the amount claimed on the label. No vitamin D was detected in 3 of the 14 samples of skim milk tested (lower limit of assay, 4.7 IU per quart [5.0 IU per liter]). One milk sample labeled as containing vitamin D2 (ergocalciferol) contained vitamin D3 (cholecalciferol). Seven of the 10 samples of infant formula contained more than 200 percent of the amount stated on the label; the sample with the highest concentration contained 419 percent of the stated amount. None of the samples of infant formula contained less than the amount stated. CONCLUSIONS: Milk and infant-formula preparations rarely contain the amount of vitamin D stated on the label and may be either underfortified or overfortified. Since both underfortification and overfortification are hazardous, better monitoring of the fortification process is needed.

Animals↗
PubMed1992

Collisionally induced dissociation in the study of A-ring hydroxylated vitamin D type compounds.

Collisionally induced dissociation (CID) is often used to determine the structure of ions based on comparison with the CID spectra of known ions. The latter are generated from judiciously selected compounds taking into account basic principles of ion chemistry. We report here on the use of this approach toward determination of the site of A-ring hydroxylation of vitamin D. Although not intrinsically an aromatic compound, vitamin D gives rise in its mass spectrum to an aromatic methylstyryl cation at m/z 118. A-ring hydroxylated metabolites of vitamin D would thus incorporate the extra OH group on the ion at m/z 118, shifting it to m/z 134. The position of substitution of the extra OH group on a metabolite could then be ascertained by comparing the CID spectrum of its m/z 134 fragment to those of the four possible (hydroxymethyl)styryl cations generated from synthesized authentic compounds. Because of their propensity to polymerize, these cations were generated in situ via the McLafferty rearrangement of the corresponding (hydroxyphenyl)ethanols. For optimum differentiation of isomeric ions, preparation of permethylated derivatives of vitamin D was necessary. The validity of the hypothesis was verified using 1,25-dihydroxy-vitamin D3 as a test compound. This method provides a viable approach for the characterization of A-ring hydroxylated metabolites of vitamin D as well as for related aromatic compounds.

Binding Sites↗
PubMed1992

Clothing prevents ultraviolet-B radiation-dependent photosynthesis of vitamin D3.

Photoprotection of the skin is mainly a function of clothing, although the effectiveness of the latter against UV-B solar radiation (wavelengths 290-320 nm) has not been measured in vivo. Since UV-B mediates the cutaneous formation of vitamin D3, we examined the attenuation of that photosynthetic reaction by the commonly used fabrics cotton, wool, and polyester in black and white colors. Direct transmission of UV-B was attenuated the most by black wool (98.6% of incident irradiance) and the least by white cotton (47.7%). None of the fabrics allowed the photoproduction of previtamin D3 from 7-dehydrocholesterol irradiated in vitro with up to 40 min of simulated sunlight or the elevation of serum vitamin D3 after irradiation with approximately one minimal erythema dose (MED) of UV-B in volunteers wearing jogging garments made of these fabrics. Increasing the whole body irradiation dose to six MEDs still failed to produce a serum vitamin D3 response in garment-clad subjects. Regular (seasonal) street clothing also prevented an elevation of the vitamin D3 in response to UV-B radiation. We conclude that clothing prevents or significantly impairs the formation of vitamin D3 after photostimulation with up to six MEDs of UV-B.

Adult↗
PubMed1992

Evolutionary biology and pathology of vitamin D.

There is mounting evidence that essentially all fungi, plants and animals living on earth produce provitamin D. It is likely that once exposed to sunlight, these provitamins are converted to previtamin D. It is unclear why fungi, phytoplankton, zooplankton and plants have the capacity to produce such large quantities of provitamin D. It is likely, however, that provitamin D and possibly vitamin D play an important biologic role in these organisms. Buchala and Schmid found, for example, that vitamin D3 promoted adventitious root development. It may be that provitamin D has a more fundamental function in lower life forms. Provitamin D and its photoproducts have UV absorption spectra that overlap with the ultraviolet absorption spectra from ultraviolet radiation-sensitive macromolecules including DNA, RNA and proteins. Thus, provitamin D and photoisomers could serve as a photon sink, and therefore, act as a natural sunscreen to protect lower life forms from the damaging effects of the high energy ultraviolet radiation that they are exposed to. It is more clear, however, that amphibians, reptiles, birds, mammals and humans all require vitamin D and that the vitamin D must be metabolized to 1,25(OH)2D3 before it can carry-out its physiologic functions on calcium and bone metabolism. The intense research activities during the past decade on the antiproliferative and differentiation activities of 1,25(OH)2D3 has opened a new chapter for this vitamin/hormone. 1,25(OH)2D3 and its analogs are being developed for the treatment of psoriasis, breast cancer, and leukemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Prediagnostic serum levels of 1,25-dihydroxyvitamin D and malignant melanoma.

A prospective nested case-control study of the relationship between prediagnostic serum levels of 1,25-dihydroxyvitamin D and subsequent development of malignant melanoma was done to test the hypothesis that increased levels are protective. Serum from 23 cases of malignant melanoma that developed between 1975 and 1987 in donors to the Washington County, Maryland serum bank was assayed along with that from 46 matched controls. There were no demonstrable differences among controls by sex, age, smoking or use of multivitamin supplements. The mean serum levels of 1,25-dihydroxyvitamin D were only 5% lower among cases than controls, a difference that could easily have occurred by chance.

Adolescent↗
PubMed1992

[Preparation of milligram quantity of vitamin D3 isomers by a two-step high performance liquid chromatographic method].

The preparation of milligram quantities of three vitamin D3 isomers, previtamin D3, lumisterol3 and tachysterol3, were carried out in a laboratory scale first by irradiating 7-dehydrocholesterol in a phototherapy chamber equipped with UVB lamps, followed by using a two-step high performance liquid chromatography (HPLC) with a semi-preparative normal phase column and an analytical reverse-phase column. The final products obtained were identified by UV spectrophotometry and HPLC. According to the detection limits for the three isomers, no contamination with any other isomers was detected in the previtamin D3, lumisterol3 and tachysterol3 preparations, except that a very small amount of vitamin D3, constituting no more than 0.25% of the product, was found in previtamin D3 preparation.

Cholecalciferol↗
PubMed1991

Photoaffinity labeling of human serum vitamin D binding protein and chemical cleavages of the labeled protein: identification of an 11.5-kDa peptide containing the putative 25-hydroxyvitamin D3 binding site.

In this paper, we describe photoaffinity labeling and related studies of human serum vitamin D binding protein (hDBP) with 25-hydroxyvitamin D3 3 beta-3'-[N-(4-azido-2-nitrophenyl)amino]propyl ether (25-ANE) and its radiolabeled counterpart, i.e., 25-hydroxyvitamin D3 3 beta-3'-[N-(4-azido-2-nitro-[3,5-3H]phenyl)amino]propyl ether (3H-25-ANE) (Ray et al., 1986, 1991). We have carried out studies to demonstrate that (1) 25-ANE competes with 25-OH-D3 for the binding site of the latter in hDBP and (2) 3H-25-ANE is capable of covalently labeling the hDBP molecule when exposed to UV light. Treatment of a sample of purified hDBP, labeled with 3H-25-ANE, with BNPS-skatole produced two Coomassie Blue stained peptide fragments, and the majority of the radioactivity was associated with the smaller of the two peptide fragments (16.5 kDa). On the other hand, cleavage of the labeled protein with cyanogen bromide produced a peptide (11.5 kDa) containing most of the covalently attached radioactivity. Considering the primary amino acid structure of hDBP, this peptide fragment (11.5 kDa) represents the N-terminus through residue 108 of the intact protein. Thus, our results tentatively identify this segment of the protein containing the binding pocket for 25-OH-D3.

Affinity Labels↗