Vitamin Ds Research Articles

Causal associations of 25-hydroxyvitamin D with functional gastrointestinal disorders: a two-sample Mendelian randomization study

BackgroundPrevious observational studies have shown associations between vitamin Ds and FGIDS[Including irritable bowel syndrome(IBS) and functional dyspepsia(FD)]. However, the association is controversial and the causality remains unknown. In this study, two-sample MR was cited to explore the causal effect on FGIDS caused by vitamin D level and serum 25-hydroxyvitamin D.MethodThe GWASs of vitaminD and 25-hydroxyvitamin D, with 57–99 strongly related SNPs were all obtained from UK biobank. The GWASs of IBS and FD were obtained from FinnGen biobank with respectively 187,028 and 194,071 participants involved. Fixed-effect inverse variance weighted regression was used to evaluate causal estimates. Other statistical methods such as MR Egger, weighted median estimation, maximum likelihood estimation and penalty-weighted median estimation are also used to verify the accuracy of the main results.ResultsMeasuring by the IVW method, our research indicated that no causal relationship was detected between vitamin D intake and Functional gastrointestinal disorders [IVW, OR(vitamin D-IBS) = 0.909, 95% CI 0.789–1.053, p = 0.2017); OR(vitamin D-FD) = 1.0662, 95% CI 0.9182–1.2380, p = 0.4000]. As for serum 25-hydroxyvitamin D, no causal relationship was detected on FD(IVW, OR(25-hydroxyvitamin D-FD) = 0.9635, 95% CI 0.8039–1.1546, p = 0.6869). Nevertheless, a negative causal relationship was revealed between 25-hydroxyvitamin D and IBS(IVW, OR(25-hydroxyvitamin D-IBS) = 0.832, 95% CI 0.696–0.995, p = 0.0436). Sensitive analysis supported the main findings but did not suggest bias due to pleiotropy.ConclusionsOur Mendelian randomization analyses suggest a negative causal relationship between 25-hydroxyvitamin D and IBS. For each additional SD increase of genetically determined 25-hydroxyvitamin D levels, the risk of IBS decreased by 16.8%.

Nonvitamin, Nonmineral Dietary Supplement Use in Individuals with Rheumatoid Arthritis

Background:Over-the-counter, natural productbased (nonvitamin, nonmineral) dietary supplement (NVNM DS) use is common in adults with rheumatoid arthritis (RA), a group at risk for drug-DS interactions, due to polypharmacy, but this use is underreported to health care providers. Recent dramatic changes in US sales of specific NVNM DS suggest that the prevalence and types of NVNM DS used in RA populations may also have shifted. Objectives:A study was undertaken to identify current and past use of specific NVNM DS for RA disease treatment and to examine associations between use of NVNM DS, RA pharmaceuticals, and/or vitamin or mineral (VM) DS. Methods:We developed a survey instrument to capture current and ever use of specific NVNM DS, VM DS, and RA pharmaceuticals, with 696 subjects self-reporting an RA diagnosis recruited online or in clinic for survey participation. Analyses were limited to 611 subjects reporting RA diagnosis after age 18 y and treatment with specific RA pharmaceuticals. Results:Most participants reported DS use, with current usage prevalence 49.6% (n = 303), 83.5% (n = 510), or 87.6% (n = 535) for NVNM, VM, or any DS, respectively. While not having appeared in previous RA surveys, turmeric and ginger were among the top 3 NVNM DS in current use, along with fish oil/-3 (n–3) PUFA. Concurrent NVNM DS use was reported by 48.2% (n = 243) of participants currently using RA pharmaceuticals (n = 504) and was more common in those using disease-modifying antirheumatic drugs only (no biologics). Most methotrexate users (83%)reported concurrent folate supplementation, with one-third also using turmeric, which is notable because methotrexate and turmeric have been associated with hepatotoxicity. Conclusions:Individuals with RA commonly use NVNM DS in combination with RA pharmaceuticals, including a previously undocumented but popular use of turmeric or ginger supplements with an unclear risk/benefit ratio.

PREVALENCE, ASSOCIATED FACTORS AND ROLE OF VITAMIN D AND GLUTATHIONE REDUCTASE OF PRE-ECLAMPSIA IN PREGNANT WOMEN

Introduction: In maternal and neonatal cases, preeclampsia is a multi-organ, heterogeneous pregnancy condition associated with significant morbidity and mortality. Since preeclampsia is a progressive disease, in some cases, delivery is necessary to stop the progression to the benefit of the mother and foetus. However, the need for early delivery has adverse effects on significant neonatal outcomes that are not limited to the most premature babies. The results include oxidative stress in the disease and invoke the biochemical basis for antioxidant clinical trials to prevent and treat hypertension caused by pregnancy. In the management of preeclampsia, supplementation of antioxidants along with polyunsaturated fatty acids, particularly omega-3 fatty acids, may be useful. This describes vitamin Ds potential role in the pathogenesis of preeclampsia. However, the role of vitamin D supplementation and dosing is controversial in preventing preeclampsia.
 Method: The study was carried out from March 2019 to April 2020 at Shalinitai Meghe Hospital and Research Centre using institutional-based cross-sectional study design among women whose age was greater than or equal to eighteen. Data were collected using a standardised and pretested questionnaire from 150 participants by face-to - face interview technique. Using Chemiluminiscent Immunoassay (CLIA), vitamin D estimation was performed. The behaviour of Glutathione Reductase was calculated according to the Goldberg et al 1983 procedure. To classify the factors associated with the development of preeclampsia, logistic regression analysis was used.
 Result: With a mean age of 30.28, a total of 150 participants were enrolled in the study. Evaluation of vitamin D and glutathione levels The prevalence of preeclampsia among current pregnant women attending ANC at Shalinitai Meghe Hospital was 16 with a 95 % CI. The current preeclampsia was significantly correlated with predictive variables such as the age of the respondents, current multiple pregnancy, and history of diabetes mellitus.
 Conclusion: The findings of this study showed that preeclampsia was present in a large proportion of women. For both urban and rural residents, health seeking actions towards pregnant women should be promoted, offering an opportunity to detect preeclampsia as early as possible and preventing the coming complication of preeclampsia. The role of antioxidants is controversial in the prevention of preeclampsia. Vitamin D deficiency is associated with preeclampsia in a major way. To document the role of vitamin D supplementation in the prevention of preeclampsia, further studies are required.
 Keywords: Gestational hypertension, Pre-eclampsia, Vitamin D, GSH

Vitamin D status in a multi-ethnic population of northern Norway: the SAMINOR 2 Clinical Survey.

To investigate serum 25-hydroxyvitamin D (S-25(OH)D) concentration in a multi-ethnic population of northern Norway and determine predictors of S-25(OH)D, including Sami ethnicity. Cross-sectional data from the second survey of the Population-based Study on Health and Living Conditions in Regions with Sami and Norwegian Populations (the SAMINOR 2 Clinical Survey, 2012-2014). S-25(OH)D was measured by the IDS-iSYS 25-Hydroxy Vitamin Dˢ assay. Daily dietary intake was assessed using an FFQ. BMI was calculated using weight and height measurements. Ten municipalities of northern Norway (latitude 68°-70°N). Males (n 2041) and females (n 2424) aged 40-69 years. Mean S-25(OH)D in the study sample was 64·0 nmol/l and median vitamin D intake was 10·3 µg/d. The prevalence of S-25(OH)D<30 nmol/l was 1·9 % and <50 nmol/l was 24·7 %. In sex-specific multivariable linear regression models, older age, blood sample collection in September-October, solarium use, sunbathing holiday, higher alcohol intake (in females), use of cod-liver oil/fish oil supplements, use of vitamin/mineral supplements and higher intakes of vitamin D were significantly associated with higher S-25(OH)D, whereas being a current smoker and obesity were associated with lower S-25(OH)D. These factors explained 21-23 % of the variation in S-25(OH)D. There were many modifiable risk factors related to S-25(OH)D, however no clear ethnic differences were found. Even in winter, the low prevalence of vitamin D deficiency found among participants with non-Sami, multi-ethnic Sami and Sami self-perceived ethnicity was likely due to adequate vitamin D intake.

Looking beyond linear regression and Bland-Altman plots: a comparison of the clinical performance of 25-hydroxyvitamin D tests.

The systematic evaluation of the clinical concordance of various 25-hydroxyvitamin D (25OHD) testing methods is presented. The need for this approach is raised by the discrepancies in the analytical performance of the available assays. The analytical and clinical performance of six automated 25OHD assays and an in-house liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was investigated. Leftover serum samples (n=162, SA: n=114) were analyzed and all 21 assay combinations were evaluated. The utility of Cohen's κ values was assessed by transforming them into minimum percentage agreement (MPA). McNemar's hypothesis test was employed for testing the symmetry of the disagreeing classification outcomes within each method pair. Depending on the assay method, the ratio of results classified as positive (<20 ng/mL) was 13.5%-40.0%. The percentage agreement (PA) was 74.1%-92.6%. Compared to other methods, significantly more hypovitaminosis cases were delivered by DiaSorin Liaison® 25 OH vitamin D Total (DL) and significantly fewer by IDS-iSYS 25-Hydroxy Vitamin DS (II). The strongest clinical concordance was exerted by II vs. LC-MS/MS. The κ-derived MPA showed close similarity to the PA scores. McNemar's tests confirmed the asymmetry of the disagreement in the classification in 14 method combinations. The presented approach allows the prediction of the clinical consequences of a 25OHD method transfer. Differences in the clinical classification of assay results are likely encountered when transferring to a new method, even between assays standardized according to the Vitamin D Standardization Program (VDSP) Reference Method Procedure (RMP).

Vitamin D Insufficiency Among Lactating Women in Southern Ethiopia

Serum 25(OH)D concentration and its relations with dress habits, sun seeking behavior and skin reflectance were assessed among Ethiopian lactating women (n=120). The subjects were enrolled within 2 wk of delivery in a randomized controlled vitamin D supplementation trial (NCT02210884) being implemented in Sidama Zone (7°N, 38°E), Southern Ethiopia. Baseline data from the trial, reported here, was collected from September, 2014 to January, 2015. Plasma 25(OH)D concentration was determined using the new VDSP (Vitamin D Standardization Program)certified Immunodiagnostic Systems (IDS) 25‐Hydroxy Vitamin DS EIA manual ELISA Kits. Data on demographic characteristics, dress habits and sun seeking behavior were collected using questionnaires. Skin reflectance was measured using a portable colorimeter. Mean (SD) plasma 25(OH)D concentration was 48.5(14.6) nmol/L. Values ranged from 23 nmol/L to 102 nmol/L. In more than half of the participants (55%), 25(OHD) concentrations were between 30 and &lt;50 nmol/L, which is defined as inadequate for bone and overall health. Vitamin D deficiency (&lt; 30 nmol/L) was observed in four (3.3 %) of the women. The 25(OH)D concentrations were adequate (≥ 50 nmol/L) in 41.7%. The majority of the participants (81%) reported taking precautions to avoid direct sunlight exposure. More than half (52.5%) of the participants reported covering their head and most of their body when they go outside. Mean (SD) 25(OH)D concentration was significantly lower among women that wore more coverings outdoors (45.4 nmol/L (11.4)) compared to women who wore less conservative clothes (52.2 nmol/L (16.6)). Furthermore, skin lightness was positively correlated with 25(OH)D concentrations. The 25(OH)D concentrations were negatively correlated with maternal weight and BMI. These findings provide additional evidence that the availability of abundant sunlight does not guarantee attainment of adequate vitamin D status. Conservative dress habits and avoidance of direct sunlight are possible factors that contributed to considerable vitamin D insufficiency in a population residing near the equator.Support or Funding InformationSupported by the Nutricia Research Foundation and the W3002 Multistate Project

Development and optimization of an LC‐MS/MS‐based method for simultaneous quantification of vitamin D2, vitamin D3, 25‐hydroxyvitamin D2 and 25‐hydroxyvitamin D3

Simultaneous and accurate measurement of vitamin D and 25-hydroxyvitamin D in biological samples is a barrier limiting our ability to define "optimal" vitamin D status. Thus, our goal was to optimize conditions and evaluate an LC-MS method for simultaneous detection and quantification of vitamin D(2) , vitamin D(3) , 25-hydroxyvitamin D(2) and 25-hydroxyvitamin D(3) in serum. Extraction and separation of vitamin D forms were achieved using acetone liquid-liquid extraction and by a reversed phase C8 column, respectively. Detection was performed on a triple quadrupole tandem mass spectrometer (QQQ-MS/MS) equipped with atmospheric pressure photo ionization source. The LOQs for all analytes tested were 1 ng/mL for hydroxylated molecules and 2 ng/mL for the parent vitamin Ds. RSD at lower LOQ (2 ng/mL) and in medium (80 ng/mL) and high (200 ng/mL) quality control samples did not exceed 20 and 15% CV, respectively. Accuracy of the method for determination of hydroxylated molecules was also validated using National Institutes of Standards and Technology standard samples and found to be in the range of 90.9-111.2%. In summary, a sensitive and reproducible method is reported for simultaneous quantification of vitamin D(2) , vitamin D(3) , 25-hydroxyvitamin D(2) and 25-hydroxyvitamin D(3) molecules in biological samples.

Skin Safety Evaluation of An Active Vitamin Ds Derivative Ointment (MC-903 Ointment)

Skin Safety Evaluation of An Active Vitamin Ds Derivative Ointment (MC-903 Ointment)

Vitamin-D analogues for osteoporosis

Vitamin Ds are among the drugs for osteoporosis with the longest history. Recently, novel properties are being found in vitamin Ds and new analogues are under development. Especially, ED-71 developed in Japan has advantageous actions in the osteoporosis treatment and will be used clinically soon.

Conformer-specific photoconversion of 25-hydroxytachysterol to 25-hydroxyprevitamin D3: role in the production of vitamin Ds.

The photochemical goal in the production of vitamin Ds (Vit Ds) is to maximize the conversion of the provitamins (Pros) to the previtamins (Pres) while minimizing stoichiometric losses to undesirable over-irradiation products. The last step in the syntheses, the [1,7]-sigmatropic rearrangement of the Pres to the Vits, is thermally induced. The competition between cis-trans photoisomerization and photocyclization of the Pres is known to be highly excitation-wavelength specific. It inspired Havinga's nonequilibration of excited rotamers (NEER) principle and more recent alternative explanations. In contrast, the photochemistry of tachysterol has been reported to be relatively unexceptional with Tachy --> Pre quantum yields in the 0.10-0.13 range, independent of lambdaexc. Examination of the spectrum of the 25-hydroxy derivative of tachysterol (HOTachy) reveals vibronic structure between 295 and 260 nm and a broad structureless shoulder between 330 and 295 nm. These features are consistent with absorption by at least two Tachy conformers. We show that these conformers differ dramatically in their trans-to-cis photoisomerization efficiency. The Tachy --> Pre quantum yield at 313 nm (0.42) in degassed methanol solution is substantially higher than at 254 nm (0.12). On the basis of recent theoretical predictions, it is likely that 313 nm selectively excites the cEc HOTachy conformer which gives photoisomerization much more efficiently than do the other expected conformers (cEt, most abundant, and tEt). Efficient conversion of HOPro D3 to HOPre D3 is accomplished by a two-stage 254/313-nm irradiation sequence. Use of 313 nm in the second step is preferable to previously proposed much longer wavelengths that were hardly absorbed by HOTachy.

計算化学と合成化学を駆使したビタミンＤの三次元構造活性相関

Conformational analysis of the side chain of la, 25-dihydroxyvitamin D3 [1, 25- (OH) 2D3] and its 20-epimer revealed that the spatial region occupied by the side chain of these vitamin Ds can be divided to four areas. We designed and synthesized four diastereomers at C (20) and C (22) of 22-Me-1, 25- (OH) 2D3 whose side-chain mobility is restricted in one of these four areas. We evaluated biological activities of these four compounds. These studies allowed us to propose the relationship between the spatial region of vitamin D side-chain and the activity, an active space group concept. This concept has been generally accepted as explaining the three-dimensional structure and activity relationship of almost all known vitamin D analogs. To develop this concept to the concept including vitamin D receptor (VDR) protein, we constructed three-dimensional structure of the ligand binding domain (LBD) of the VDR by the homology modeling technique and docked 1, 25- (OH) 2D3 as a ligand into the constructed VDR-LBD.

Calcitriol Directly Sensitizes Renal Tubular Cells to ATP-Depletion- and Iron-Mediated Attack

Vitamin Ds have been reported to have diverse effects on cell homeostasis, leading to suggestions that they have therapeutic applications extending beyond their traditional actions on the Ca2+/parathyroid/bone axis. As some of these potential indications carry an inherent risk of acute renal failure (ARF; eg, cancer chemotherapy and organ transplantation), the goal of this study was to assess whether vitamin Ds directly affect renal tubule injury responses. Cultured human proximal tubular (HK-2) cells were exposed to physiological or pharmacological doses of either calcitriol (D3) or a synthetic vitamin D2 analogue (19-nor) for 3 to 48 hours. Their impact on cell integrity (percent lactate dehydrogenase (LDH) release and tetrazolium dye MTT uptake) under basal conditions and during superimposed injuries (ATP depletion/Ca2+ ionophore or iron-mediated oxidant stress) were determined. As vitamin Ds can be anti-proliferative, cell outgrowth ([3H]thymidine uptake and crystal violet staining) was also tested. Finally, the action of D3 on in vivo ARF (glycerol-induced myoglobinuria) and isolated proximal tubule injury responses were assessed. D3 induced a rapid, dose-dependent increase in HK-2 susceptibility to both ATP-depletion/Ca2+-ionophore- and Fe-mediated attack without independently affecting cell integrity or proliferative responses. In contrast, D2 negatively affected only Fe toxicity and only after relatively prolonged exposure (48 hours). D3 dramatically potentiated in vivo ARF (two- to threefold increase in azotemia), suggesting potential in vivo relevance of the above HK-2 cell results. Proximal tubules, isolated from these glycerol-exposed mice, suggested that D3 can worsen tubule injury despite a parodoxic suppression of H2O2 production. In contrast, D3 had a mild negative impact on cellular energetics (depressed ATP/ADP ratios), and it accentuated plasma membrane phospholipid breakdown. The latter was observed in both glycerol-treated and control tubules, suggesting a primary role in the injury- potentiation effect of D3. Vitamins D(s) may directly, and differentially, increase proximal tubule cell susceptibility to superimposed attack. This property should be considered as new uses for these agents are defined.

Osteoporosis: intervention options

Osteoporosis is a systemic progressive disease with important clinical complications because of the fractures that arise and cause major morbidity in especially the aging postmenopausal women. Because of the relative not complex procedure of diagnosis and prediction the most important question to answer: is treatment possible? There are now a variety of treatments available for the management of osteoporosis. The inhibitors of bone resorption, which include calcium, the vitamin Ds, bisphosphonates, calcitonins and gonadal steroids have been variously shown to prevent bone loss or to reduce fractures. On the other hand bone formation stimulating agents as fluorides and in the near future parathyroid hormone and analogues must be considered also. However, randomized clinical trials with fractures as clinical endpoints are only few in number and not present for every suggested treatment. During the last 3 years it has become clear that besides estrogen, bisphosphonates and now perhaps the selective estrogen receptor modulators also show a good alternative as intervention option of postmenopausal osteoporosis. At this moment sodium fluoride is not the first choice in treatment of osteoporosis in general practice.

Isolation and identification of 24-dehydroprovitamin D3 and its photolysis to 24-dehydroprevitamin D3 in mammalian skin.

Until now it had been assumed that mammalian skin contains only one provitamin D, 7-dehydrocholesterol, that is eventually converted to vitamin D3 after the skin is exposed to sunlight. Examination by reverse phase high performance liquid chromatography of lipid extracts from young rat skin, however, led to the observation that 7-dehydrocholesterol is not the only provitamin D in rat skin. Another provitamin D, accounting for 22 +/- 3% of the total provitamin content of the skin, was resolved from 7-dehydrocholesterol, and, on the basis of ultraviolet spectrophotometry, mass spectrometry, and nuclear magnetic resonance spectrometry, was identified as 24-dehydroprovitamin D3 (cholesta-5,7,24-trien-3 beta-ol). This new cutaneous provitamin D is not unique to the rat because it was also detected in the skin of reptiles, amphibians, birds, aquatic mammals, and humans. To be certain that the cutaneous 24-dehydroprovitamin D3 was as susceptible as 7-dehydrocholesterol to ultraviolet photolysis, rat skin was exposed to ultraviolet radiation. A reverse phase high performance liquid chromatographic analysis of a lipid extract of rat skin previously exposed to ultraviolet radiation demonstrated the presence of both previtamin D3 and 24-dehydroprevitamin D3. Therefore, these observations demonstrate for the first time that mammalian skin has the capacity to produce not one but at least two different vitamin Ds.

Stereochemical configuration at C-24 of 24,25-dihydroxycholecalciferol of human origin

Vitamin Ds (cholecalciferol) is first hydroxylated in the liver to form 2.5-OH-D3 before it is further metabolized in the kidney to either l,25(OH)2Ds or to 24,25(OH)2Ds and 25 ,26(OH)2Ds, respectively. 24,25(OH)zDs is the major dihydroxy form of cholecalciferol appearing in the plasma of normal rats [ 11. It is also found in sizeable quantities in normal man and in much smaller amounts or not at all, in anephric subjects [2,3]. The stereochemical configuration of 24,25(OH)*Ds at C-24,24R or 24S, remained unknown until the tritiated metabolite was enzymatically generated by chick renal homogenates and identified with synthetic 24R,25(OH)2Ds by HPL.co-C of their 3,24, 25-Tris-TMSderivatives [4]. Similar identification of 24,25(OH)2Ds from human origin was of great interest more especially since the determination [5] of the stereochemical configuration at C-25 of 25,26(OH)*D, isolated from human plasma. This paper reports the preparation of tritiated human 24,25(OH)*Ds and its identification with 24R,25(OH)zDs in a straight-phase HPLco-C on silica of high surface area.

Intestinal Absorption of Phosphate in the Chick: Effect of Vitamin D3 and Other Parameters

The effect of various parameters, including vitamin Ds, on the intestinal absorption of T-phosphate in the chick was investigated. Translocation was determined by the in situ ligated loop technique and measurements were made of radionuclide leav ing the intestinal lumen (absorption), accumulation by scraped mucosa (in gut tissue) and that entering the blood (transferred to body). It was observed, initially, that 1ZP was rapidly translocated across all segments of the small intestine (duodenum, jejunum, ileum) and vitamin D3 positively affected the total process in each segment. Because of the ease of showing a responsiveness to vitamin D3 by the ileum, the subsequently de scribed results were obtained with this segment. In a time course experiment, it was noted that 32Paccumulation by mucosa proceeded at a more rapid rate than the release of radionuclide to blood, indicating that the latter was the limiting step. The absorptive process was saturable as shown by a study in which increasing levels of stable phosphate were present in the absorption fluid. An effect of vitamin D3 on the transfer of 32Pfrom mucosa to body was evident, as well as an effect on the uptake phase. Arsenate, EHDP and L-phenylalanine inhibited 32Ptranslocation, but primarily in the vitamin Ds-repleted chicks. This suggested, as did the study of the effect of various levels of stable phosphate, that 32Pinteracts with some intestinal component in the transport path. Since NaEGTA (a Ca-chelator) and thorough washing of the ileal lumen did not alter 32Pabsorption and mucosal uptake, it was evident that Pi was not absorbed as a coion to calcium. A direct relationship between serum Ca levels and the degree of S2Pabsorption became evident, although this correlation (r = 0.82) might be fortuitous. Vitamin D3, when given to rachitic chicks, elicited an enhanced 32Pabsorption at 16 hours; the appearance of vitamin D-dependent CaBP was evident at 12 hours. Studies on the nature of 3AP in mucosal tissue after absorption indicated that the radionuclide was largely indistinguish able from ortho-phosphate, and that only a small fraction was present as phospholipid-HP. No phosphate binder in mucosal supernatant fluid, analogous to CaBP, was detected under the specific conditions employed. J. Nutr. 103: 586-599, 1973.

Biological Activity of the Vitamin D Metabolite 1,25-Dihydroxycholecalciferol in Chickens and Rats

The biological activity of the vitamin D»metabolite 1,25-dihydroxy cholee alcif eroi was assessed in three experiments in the chick and two experiments in the rachide rat. In the official rat line test 1,25-dihydroxycholecalciferol was found to be equally an equivalent dose of cholecalciferol. Doses of 20 to 250 pmoles (0.01 to 0.10 Mg) of l,25-dihydroxy-[26,27-sH] cholecalciferol or standard amounts of cholecalciferol were fed daily to White Leghorn cockerels for 3 weeks after hatching. The following vitamin D-related responses were measured: a) the rate of growth; b) intestinal transport of test doses of Cas+ in vivo and c) in vitro; d) percentage bone ash; e) serum calcium elevation. For each of these assays the 1,25-dihydroxycholecalciferol was judged to be much active a) more active (b,d), and as active (c,e), the parent cholecalciferol, where much active is a response 2 to 4 times and more active is a response 1 to 2 times that obtained with an equivalent dose of cholecalciferol. In some instances (d,e), the relative increment of response mediated by 1,25-dihydroxycholecalciferol was greater at the low dose level (20 pmoles/day) than at a higher dose level (100 pmoles/day). The relative activity determination of 1,25-dihydroxycholecalciferol, obtained after daily administra tion, in comparison with cholecalciferol was markedly less than that previously obtained when the activity of single doses of these steroids were analyzed. A single dose of 1,25-dihydroxycholecalciferol was 4.4 ±1.1 (SE) [Science 171: 79 (1971)] times effective cholecalciferol in stimulating the intestinal absorp tion of Ca2+, and 5.5 ±1.4 (SE) [J. Biol. Chem. 247: 5728 (1972)] times effective cholecalciferol in stimulating serum Caa+ elevation. These results collectively support the concept that 1,25-dihydroxycholecalciferol is the most highly potent form of Vitamin Ds yet known. J. Nutr. 102: 1709-1718, 1972. INDEXING

Role of Vitamins in Taurine Synthesis from Sulfate by the Chick

Taurine, a compound present in the tissues of all animals, is known to arise from cystA­neas well as through the utilization of sulfate-sulfur. Sulfate, activated by the action of ATP-sulfurylase (EC 2.7.7.4) to form adenc- sinephosphosulfate (APS) and APS-kinase (EC 2.7.1.25) to form 3'-phospho- adenosine-5'-phosphosulfate (PAPS), is then transferred to a carbon acceptor by the action of a sulfotransferase (EC 2.8.2). This enzymatic pathway in vita min-deficient and control chicks was investigated to ascertain the role that vita- min-coenzymes may play in these reactions. Chicks were fed diets deficient in thiamin, riboflavin, vitamin B6,folie acid, vitamin A or vitamin Ds and the sulfate activation and sulfotransferase activities of these birds were assayed. Folie acid- and vitamin A-deficient chicks had lower ATP-sulfurylase and APS-kinase activity than the control birds. Pyridoxine was associated with sulfotransferase activity as evidenced by decreased in vitro taurine formation from PAPS. Vitamin D8- deficient chicks showed a lower rate of taurine synthesis in the liver when ad ministered 35SO4 orally, whereas no difference was observed in taurine synthesis or PAPS formation in vitro. J. Nutr. 102: 313-318, 1972.

Inhibition of the hypercalcemic action of vitamin D 3 with imidazole.

The effects of imidazole on serum calcium were examined in groups of normal and thyroparathyroidectomized (TPTX) rats given a calcium-deficient diet. The TPTX animals had been given either no treatment or vitamin D3 in doses sufficient to produce a normal or elevated serum calcium. Imidazole lowered the mean serum calcium in each group except the TPTX one which had not received any vitamin D3 and had hypocalcemia. Studies carried out in vivo with 45Ca suggested that imidazole inhibited release of calcium from skeletal tissue. Increases in serum calcium produced with vitamin D3 were further augmented with theophylline and dibutyryl 3′,5′- adenosine monophosphate. The increases in serum calcium with these two agents were diminished or prevented with imidazole. In tissue culture studies, imidazole diminished the release of 45Ca from untreated fetal rat bone as well as from bones in which resorption was stimulated by 25- hydroxycholecalciferol, dibutyryl 3′,5′-adenosine monophosphate, and parathyroid hormone....