Search

Low levels of vitamin D in maternal and cord blood have been associated with neonatal sepsis. This study assessed the association of vitamin D metabolites (25(OH)D, 3-epi-25(OH)D3, and 24,25(OH)2D3) levels in maternal and cord blood with newborn sepsis evaluation in Nigerian mother–infant dyads. Maternal and cord blood from 534 mothers and 536 newborns were processed using liquid chromatography-tandem mass spectrometry. Spearman correlation was used to compare continuous variables, Mann–Whitney for dichotomous variables, and Kruskal–Wallis for two or more groups. High cord percent 3-epi-25(OH)D3 levels were positively associated with newborn evaluation for sepsis (p = 0.036), while maternal and cord 25(OH)D and 24,25(OH)2D3 levels were not. Being employed was positively associated with maternal and newborn 3-epi-25(OH)D3 concentrations (p = 0.007 and p = 0.005, respectively). The maternal 3-epi-25(OH)D3 and percent 3-epi-25(OH)D3 were positively associated with vaginal delivery (p = 0.013 and p = 0.012, respectively). Having a weight-for-age Z-score ≤ −2 was positively associated with newborn percent 3-epi-25(OH)D3 levels (p = 0.004), while a weight-for-length Z-score ≤ −3 was positively associated with maternal and newborn percent 3-epi-25(OH)D3 levels (p = 0.044 and p = 0.022, respectively). Our study highlights the need to further investigate the biological role of 3-epi-25(OH)D3 and its clinical significance in fetal growth and newborn outcome. [ABSTRACT FROM AUTHOR]

Clinical and preclinical studies have provided conflicting data on the postulated beneficial effects of vitamin D in patients with prostate cancer. In this opinion piece, we discuss reasons for discrepancies between preclinical and clinical vitamin D studies. Different criteria have been used as evidence for the key roles of vitamin D. Clinical studies report integrative cancer outcome criteria such as incidence and mortality in relation to vitamin D status over time. In contrast, preclinical vitamin D studies report molecular and cellular changes resulting from treatment with the biologically active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (calcitriol) in tissues. However, these reported changes in preclinical in vitro studies are often the result of treatment with biologically irrelevant high calcitriol concentrations. In typical experiments, the used calcitriol concentrations exceed the calcitriol concentrations in normal and malignant prostate tissue by 100 to 1000 times. This raises reasonable concerns regarding the postulated biological effects and mechanisms of these preclinical vitamin D approaches in relation to clinical relevance. This is not restricted to prostate cancer, as detailed data regarding the tissue-specific concentrations of vitamin D metabolites are currently lacking. The application of unnaturally high concentrations of calcitriol in preclinical studies appears to be a major reason why the results of preclinical in vitro studies hardly match up with outcomes of vitamin D-related clinical studies. Regarding future studies addressing these concerns, we suggest establishing reference ranges of tissue-specific vitamin D metabolites within various cancer entities, carrying out model studies on human cancer cells and patient-derived organoids with biologically relevant calcitriol concentrations, and lastly improving the design of vitamin D clinical trials where results from preclinical studies guide the protocols and endpoints within these trials. [ABSTRACT FROM AUTHOR]

The active vitamin D metabolites, 25-hydroxyvitamin D3 (25D3) and 1,25-dihydroxyvitamin D3 (1,25D3), are produced by successive hydroxylation steps and play key roles in several cellular processes. However, alternative metabolic pathways exist, and among them, the 4-hydroxylation of 25D3 is a major one. This study aims to investigate the structure–activity relationships of 4-hydroxy derivatives of 1,25D3. Structural analysis indicates that 1,4α,25(OH)3D3 and 1,4β,25(OH)3D3 maintain the anchoring hydrogen bonds of 1,25D3 and form additional interactions, stabilizing the active conformation of VDR. In addition, 1,4α,25D3 and 1,4β,25D3 are as potent as 1,25D3 in regulating the expression of VDR target genes in rat intestinal epithelial cells and in the mouse kidney. Moreover, these two 4-hydroxy derivatives promote hypercalcemia in mice at a dose similar to that of the parent compound. [ABSTRACT FROM AUTHOR]

(1) Background: Vitamin D supplementation after type 1 diabetes mellitus (T1DM) onset has led to conflicting results on beta-cell preservation. Aim: This paper presents a systematic review to verify whether randomized prospective controlled trials (RCTs) demonstrate that improved vitamin D status confers protection on T1DM. (2) Methods: A systematic review was conducted up until 18 January 2024 according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching MEDLINE, MEDLINE In-Process, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials, using keywords "vitamin D", "type 1 diabetes", and "children". (3) Results: Following the above-mentioned search process, 408 articles in PubMed and 791 in Embase met inclusion criteria. After removing duplicates, 471 articles remained. After exclusion criteria, 11 RCTs remained. Because of major heterogeneity in design and outcomes, no meta-analyses were conducted, allowing only for qualitative analyses. There was no strong evidence that vitamin D supplementation has lasting effects on beta-cell preservation or glycemic control in new-onset T1DM. (4) Conclusions: More rigorous, larger studies are needed to demonstrate whether vitamin D improves beta-cell preservation or glycemic control in new-onset T1DM. Because T1DM may cause osteopenia, it is advisable that patients with new onset T1DM have adequate vitamin D stores. [ABSTRACT FROM AUTHOR]

Liquid chromatography/tandem mass spectrometry is firmly established today as the gold standard technique for analysis of vitamin D, both for vitamin D status assessments as well as for measuring complex and intricate vitamin D metabolic fingerprints. While the actual mass spectrometry technology has seen only incremental performance increases in recent years, there have been major, very impactful changes in the front‐ and back‐end of MS‐based vitamin D assays; for example, the extension to new types of biological sample matrices analyzed for an increasing number of different vitamin D metabolites, novel sample preparation techniques, new powerful chemical derivatization reagents, as well the continued integration of high resolution mass spectrometers into clinical laboratories, replacing established triple‐quadrupole instruments. At the same time, the sustainability of mass spectrometry operation in the vitamin D field is now firmly established through proven analytical harmonization and standardization programs. The present review summarizes the most important of these recent developments. [ABSTRACT FROM AUTHOR]

In current clinical practice, a thorough understanding of vitamin D metabolism is in high demand both for patients with various diseases and for healthy individuals. Analytical techniques that provide simultaneous measurement of multiple metabolites are preferred. Herein, the development of an HPLC-DMS-MS/MS method for the quantitation of vitamin D compounds (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3, 24,25(OH)2D3, and D3) in serum is described. The selected sample preparation procedure based on the combination of liquid–liquid and solid-phase extraction, which excluded a lengthy derivatization step, was compared with other common approaches. Sensitivity was increased through the implementation of differential ion mobility separation. The proposed assay allowed us to determine the low abundant 1,25(OH)2D3 with the detection limit of 10 pg/mL. The validation study showed good linearity (r2 > 0.99), a wide analytical range (2.5–75 ng/mL for 25(OH)D3), and acceptable precision (<7%) for all metabolites. The recovery ranged from 71% to 93% and the matrix effect from 0.80 to 0.95 depending on the metabolite; accuracy determination was performed using DEQAS controls. [ABSTRACT FROM AUTHOR]

Recent research activities have provided new insights in vitamin D metabolism in various conditions. Furthermore, substantial progress has been made in the analysis of vitamin D metabolites and related biomarkers, such as vitamin D binding protein. Liquid chromatography tandem mass spectrometric (LC–MS/MS) methods are capable of accurately measuring multiple vitamin D metabolites in parallel. Nevertheless, only 25(OH)D and the biologically active form 1,25(OH)2D are routinely measured in clinical practice. While 25(OH)D remains the analyte of choice for the diagnosis of vitamin D deficiency, 1,25(OH)2D is only recommended in a few conditions with a dysregulated D metabolism. 24,25(OH)2D, free and bioavailable 25(OH)D, and the vitamin D metabolite ratio (VMR) have shown promising results, but technical pitfalls in their quantification, limited clinical data and the lack of reference values, impede their use in clinical practice. LC–MS/MS is the preferred method for the measurement of all vitamin D related analytes as it offers high sensitivity and specificity. In particular, 25(OH)D and 24,25(OH)2D can accurately be measured with this technology. When interpreted together, they seem to provide a functional measure of vitamin D metabolism beyond the analysis of 25(OH)D alone. The determination of VDBP, free and bioavailable 25(OH)D is compromised by unresolved analytical issues, lacking reference intervals and insufficient clinical data. Therefore, future research activities should focus on analytical standardization and exploration of their clinical value. This review provides an overview on established and new vitamin D related biomarkers including their pathophysiological role, preanalytical and analytical aspects, expected values, indications and influencing conditions. [ABSTRACT FROM AUTHOR]

Introduction: Our aim is to study the correlation between vitamin D metabolites and osteoporosis in rheumatoid arthritis (RA) by ultra-high-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS). At the same time, other influencing factors and serum biomarkers of osteoporosis in patients with RA were studied. Materials and methods: Patients with RA admitted from January 2020 to December 2020 were selected at our hospital. The subjects were divided into the normal bone mineral density (BMD), osteopenia, and osteoporosis groups. The differences of vitamin D (VD) metabolites among groups were compared. The Pearson correlation coefficient was used to analyze the relationship between BMD and various parameters. The relationship between BMD and influencing factors was studied by a multiple linear regression equation. Results: A total of 287 patients with RA were included. RA patients with 25-hydroxy vitamin D [25(OH)D] deficiency accounted for 43.63% and 25(OH)D insufficient levels accounted for 31.37%. There were 31 cases (10.80%) in the normal BMD group, 161 cases (56.10%) in the osteopenia group, and 95 cases (33.10%) in the osteoporosis group. The BMD of L1-4 (T- score) was negatively correlated with age (P < 0.05), course of disease (P < 0.05), and erythrocyte sedimentation rate (ESR) (P < 0.05), and positively correlated with 25(OH)D3 (P < 0.05). The multiple linear regression model results showed that age and 25(OH)D3 were independent predictors of BMD; this explained 22.11% of the total variation. Conclusions: VD deficiency and insufficient are common in RA patients. RA patients can be appropriately supplemented with VD. VD3 may be a better choice. [ABSTRACT FROM AUTHOR]

The determination of vitamin D metabolites as status marker or for diagnostic purposes is almost entirely conducted from blood serum or plasma. Other biological matrices, however, have also interested researchers, for two main reasons: (1) alternative matrices may allow non-invasive sampling, permit easier sample transfer and require less demanding storage conditions; and (2) the levels of vitamin D metabolites in other body compartments may further aid the understanding of vitamin D metabolism and function. Thus, the development of reliable and efficient sample preparation protocols for sample matrices other than serum/plasma, which will remove potential interferences and selectively extract the targeted metabolites, is of great importance. This review summarizes sample preparation methods for measurement of vitamin D metabolites using liquid chromatography-(tandem)mass spectrometry in more than ten different human tissues, including hair, saliva, adipose tissue, brain and others. [ABSTRACT FROM AUTHOR]

During the past 40 years, the National Institute of Standards and Technology (NIST) has developed over 180 natural matrix Standard Reference Materials® (SRMs) for the determination of trace organic constituents in environmental, clinical, food, and dietary supplement matrices. A list of the Top Ten SRMs intended for organic analysis was identified based on selection criteria including analytical challenge to assign certified values, challenges in material preparation, novel matrices, longevity, widespread use, and unique design concept or intended use. The environmental matrix SRMs include air particulate matter, marine sediment, mussel tissue, and human serum with the focus on contaminants such as polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), chlorinated pesticides, and polybrominated diphenyl ethers (PBDEs). Human serum and plasma SRMs for clinical diagnostic markers including vitamin D metabolites represent clinical analysis, whereas infant formula, multivitamin/multielement tablets, and Ginkgo biloba constitute the food and dietary supplement matrices on the list. Each of the SRMs on the Top Ten list is discussed relative to the selection criteria and significance of the material, and several overall lessons learned are summarized. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency significantly correlates with the severity of SARS-CoV-2 infection. Molecular docking-based virtual screening studies predict that novel vitamin D and related lumisterol hydroxymetabolites are able to bind to the active sites of two SARSCoV-2 transcription machinery enzymes with high affinity. These enzymes are the main protease (Mpro) and RNA-dependent RNA polymerase (RdRP), which play important roles in viral replication and establishing infection. Based on predicted binding affinities and specific interactions, we identified 10 vitamin D3 (D3) and lumisterol (L3) analogs as likely binding partners of SARSCoV-2 Mpro and RdRP and, therefore, tested their ability to inhibit these enzymes. Activity measurements demonstrated that 25 (OH)L3, 24(OH)L3, and 20(OH)7DHC are the most effective of the hydroxymetabolites tested at inhibiting the activity of SARSCoV-2 Mpro causing 10%-19% inhibition. These same derivatives as well as other hydroxylumisterols and hydroxyvitamin D3 metabolites inhibited RdRP by 50%-60%. Thus, inhibition of these enzymes by vitamin D and lumisterol metabolites may provide a novel approach to hindering the SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Vitamin D Binding Protein (VDBP), also well-known as Gc-globulin, is a plasma protein which acts as a carrier molecule for vitamin D and its metabolites. This multifunctional glycoprotein is a member of the albumin superfamily of binding proteins. It is predominantly synthesized as a single long chain glycoprotein in the liver. VDBP helps in vitamin D metabolites transport, control bone development, binds actin monomers and fatty acids and prevents their polymerization; which might be harmful in circulatory system. A less defined role in modulating immune and inflammatory response is also known. VDBP plays an important role in protection of microcirculation, inflammation, infection and also known to have antiviral and antitumoral activity. Recent studies documented its use as a early marker for diagnosis of chronic kidney disease. This review discusses the multifunctional characters of VDBP in spectra of diseases with emphasis on its use as marker for diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Background: Vitamin D deficiency is diagnosed by total serum 25-hydroxyvitamin D (25(OH)D) concentration and is associated with poor health and increased mortality; however, some populations have low 25(OH) D concentrations without manifestations of vitamin D deficiency. The Vitamin D Metabolite Ratio (VMR) has been suggested as a superior indicator of vitamin D status. Therefore, VMR was determined in a population with type 2 diabetes at high risk for vitamin D deficiency and correlated with diabetic complications. Research design and methods: Four hundred sisty patients with type 2 diabetes (T2D) were recruited, all were vitamin D3 supplement naive. Plasma concentration of 25-hydroxyvitamin D3 (25(OH)D3) and its metabolites 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) and its epimer, 3-epi-25-hydroxyvitamin D3 (3-epi-25(OH)D3), were measured by LC-MS/MS analysis. VMR-1 was calculated as a ratio of 24,25(OH)2D3:25(OH)D3; VMR-2 as a ratio of 1,25(OH)2D3:25(OH)D3; VMR-3 was calculated as a ratio of 3-epi-25(OH)D3: 25(OH)D3. Results: An association means that there were significant differences between the ratios found for those with versus those without the various diabetic complications studied. VMR-1 was associated with diabetic retinopathy (p = 0.001) and peripheral artery disease (p = 0.012); VMR-2 associated with hypertension (p < 0.001), dyslipidemia (p < 0.001), diabetic retinopathy (p < 0.001), diabetic neuropathy (p < 0.001), coronary artery disease (p = 0.001) and stroke (p < 0.05). VMR-3 associated with hypertension (p < 0.05), dyslipidemia (p < 0.001) and coronary artery disease (p < 0.05). Conclusions: In this cross sectional study, whilst not causal, VMR-2 was shown to be the superior predictor of diabetic and cardiovascular complications though not demonstrative of causality in this cross-sectional study population over VMR-1, VMR-3 and the individual vitamin D concentration measurements; VMR-2 associated with both microvascular and cardiovascular indices and therefore may have utility in predicting the development of diabetic complications. [ABSTRACT FROM AUTHOR]

Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aims: Vitamin D measurement is a composite of vitamin D2 (25(OH)D2) and D3 (25(OH)D3) levels, and its deficiency is associated with the development of type 2 diabetes (T2DM) and diabetic complications; vitamin D deficiency may be treated with vitamin D2 supplements. This study was undertaken to determine if vitamin D2 and D3 levels differed between those with and without T2DM in this Middle Eastern population, and the relationship between diabetic microvascular complications and vitamin D2 and vitamin D3 levels in subjects with T2DM. Methods: Four hundred ninety-six Qatari subjects, 274 with and 222 without T2DM participated in the study. Plasma levels of total vitamin D2 and D3 were measured by LC-MS/MS analysis. Results: All subjects were taking vitamin D2 and none were taking D3 supplements. Vitamin D2 levels were higher in diabetics, particularly in females, and higher levels were associated with hypertension and dyslipidemia in the diabetic subjects (p < 0.001), but were not related to diabetic retinopathy or nephropathy. Vitamin D3 levels measured in the same subjects were lower in diabetics, particularly in females (p < 0.001), were unrelated to dyslipidemia or hypertension, but were associated with retinopathy (p < 0.014). Neither vitamin D2 nor vitamin D3 were associated with neuropathy. For those subjects with hypertension, dyslipidemia, retinopathy or neuropathy, comparison of highest with lowest tertiles for vitamin D2 and vitamin D3 showed no difference. Conclusions: In this Qatari cohort, vitamin D2 was associated with hypertension and dyslipidemia, whilst vitamin D3 levels were associated with diabetic retinopathy. Vitamin D2 levels were higher, whilst vitamin D3 were lower in diabetics and females, likely due to ingestion of vitamin D2 supplements. [ABSTRACT FROM AUTHOR]

The demand for measurement of vitamin D metabolites for clinical diagnosis and to advance our understanding of the role of vitamin D in human health has significantly increased in the last decade. New developments in technologies employed have enabled the separation and quantification of additional metabolites and interferences. Also, developments of immunoassays have changed the landscape. Programmes and materials for assay standardisation, harmonisation and the expansion of the vitamin D external quality assurance scheme (DEQAS) with the provision of target values as measured by a reference measurement procedure have improved standardisation, quality assurance and comparability of measurements. In this article, we describe developments in the measurement of the commonly analysed vitamin D metabolites in clinical and research practice. We describe current analytical approaches, discuss differences between assays, their origin, and how these may be influenced by physiological and experimental conditions. The value of measuring metabolites beyond 25 hydroxyvitamin D (25(OH)D), the marker of vitamin D status, in routine clinical practice is not yet confirmed. Here we provide an overview of the value and application of the measurement of 1,25 dihydroxyvitamin D, 24,25 dihydroxyvitamin D and free 25OHD in the diagnosis of patients with abnormalities in vitamin D metabolism and for research purposes. [ABSTRACT FROM AUTHOR]

Objective: The relationship between fertilization rates and 1,25-dihydroxyvitamin D (1,25(OH)2D3), 25-hydroxyvitamin D2 (25(OH)D2), 25-hydroxyvitamin D3 (25(OH)D3), 24,25-dihydroxyvitamin D (24,25(OH)2D3), and 25-hydroxy-3epi-Vitamin D3 (3epi25(OH)D3) concentrations in age and weight matched women with and without PCOS was studied. Methods: Fifty nine non-obese women, 29 with PCOS, and 30 non-PCOS undergoing IVF, matched for age and weight were included. Serum vitamin D metabolites were taken the menstrual cycle prior to commencing controlled ovarian hyperstimulation. Results: Vitamin D metabolites did not differ between PCOS and controls; however, 25(OH)D3 correlated with embryo fertilization rates in PCOS patients alone (p = 0.03). For all subjects, 3epi25(OH)D3 correlated with fertilization rate (p < 0.04) and negatively with HOMA-IR (p < 0.02); 25(OH)D2 correlated with cleavage rate, G3D3 and blastocyst (p < 0.05; p < 0.009; p < 0.002, respectively). 24,25(OH)2D3 correlated with AMH, antral follicle count, eggs retrieved and top quality embryos (G3D3) (p < 0.03; p < 0.003; p < 0.009; p < 0.002, respectively), and negatively with HOMA-IR (p < 0.01). 1,25(OH)2D3 did not correlate with any of the metabolic or embryo parameters. In slim PCOS, 25(OH)D3 correlated with increased fertilization rates in PCOS, but other vitamin D parameters did not differ to matched controls. Conclusion: 3epi25(OH)D3, 25(OH)D2, and 24,25(OH)2D3, but not 1,25(OH)2D3, were associated with embryo parameters suggesting that vitamin D metabolites other than 1,25(OH)2D3 are important in fertility. [ABSTRACT FROM AUTHOR]

ABSTRACT: Most trials of vitamin D supplementation have shown no benefits on bone mineral density (BMD), although severe vitamin D deficiency causes osteomalacia, which is associated with profound BMD deficits. Recently, the ViDA‐BMD study from New Zealand demonstrated a threshold of baseline 25‐hydroxyvitamin D (25OHD; 30 nmol/L) below which vitamin D supplementation did benefit BMD. We have now reexamined data from a similar trial in Aberdeen to determine whether a baseline 25OHD threshold of 30 nmol/L is also observed in that database. The Aberdeen study recruited 305 postmenopausal women in late winter and randomized them to receive placebo, vitamin D 400 IU/d, or vitamin D 1000 IU/d over 1 year. As previously reported, BMD loss at the hip was reduced by vitamin D 1000 IU/d only, and there was no significant treatment effect of either dose at the lumbar spine. In the present analysis, when the trial participants were grouped according to whether their baseline 25OHD was ≤30 nmol/L or above this threshold, significant treatment effects were apparent at both the spine and hip in those with baseline 25OHD ≤30 nmol/L, but no significant effects were apparent in those with baseline 25OHD above this level. There was evidence of a similar threshold for effects on parathyroid hormone, but no groups showed changes in bone turnover markers during the study. It is concluded that vitamin D supplements only increase bone density in adults with nadir 25OHD ≤30 nmol/L. This moves us further toward a trial‐based definition of vitamin D deficiency in adults with adequate calcium intakes and suggests that supplement use should be targeted accordingly. Future trials of vitamin D supplementation should focus on individuals with 25OHD concentrations in this range. © 2018 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Serum vitamin D metabolite levels are of interest as biomarkers for vitamin D status, which has influence on numerous body functions and pathologies. The determination of vitamin D metabolite levels by liquid chromatography/mass spectrometry (LC/MS) is challenging due to their low concentrations and relatively low ionization efficiencies. Three ionization sources, dielectric barrier discharge ionization (DBDI), atmospheric pressure chemical ionization (APCI), and electrospray ionization (ESI), were compared regarding achievable limits of detection and occurring matrix effects. The latter were mainly caused by phospholipids. Therefore, in addition to a conventional solid phase extraction (SPE) stationary phase, a material for selective removal of phospholipids was examined. The selective removal of phospholipids significantly reduced observed matrix effects, especially when ESI was applied. Achievable limits of detection and observed matrix effects were lowest for APCI and with some limitations, also for DBDI.Graphical abstract [ABSTRACT FROM AUTHOR]

The effect of exposure to different UVb compact lamps on the vitamin D status of growing bearded dragons (Pogona vitticeps) was studied. Forty-two newly hatched bearded dragons (<24 h old) were allocated to six treatment groups ( n = 7 per group). Five groups were exposed to different UVb compact lamps for two hours per day, with a control group not exposed to UVb radiation. At 120 days of age, blood samples were obtained and concentrations of 25( OH)D3, Ca, P and uric acid were determined. In addition, plasma 25( OH)D3 concentration was determined in free-living adult bearded dragons to provide a reference level. Only one treatment resulted in elevated levels of 25( OH)D3 compared to the control group (41.0 ± 12.85 vs. 2.0 ± 0.0 nmol/L). All UVb-exposed groups had low 25( OH)D3 plasma levels compared to earlier studies on captive bearded dragons as well as in comparison with the free-living adult bearded dragons (409 ± 56 nmol/L). Spectral analysis indicated that all treatment lamps emitted UVb wavelengths effective for some cutaneous vitamin D synthesis. None of these lamps, under this regime, appeared to have provided a sufficient UVb dose to enable synthesis of plasma 25( OH)D3 levels similar to those of free-living bearded dragons in their native habitat. [ABSTRACT FROM AUTHOR]

Background: High levels of fibroblast growth factor-23 (FGF23) are associated with mortality. In chronic kidney disease (CKD), FGF23 levels rise as renal function declines. We analyzed the contribution of laboratory values to the variance of FGF23 levels in relationship to a curve of expected FGF23 levels for a given GFR.Methods: Following approval by the research ethics boards, we measured FGF23, CysC eGFR, creatinine, urea, albumin, calcium, phosphate, vitamin D metabolites, PTH, alkaline phosphatase, CRP, and venous gases in 141 pediatric CKD patients (45, 37, 32, 13 and 14 CKD stages I, II, III, IV, and V, respectively). Data were expressed as median (25th, 75th percentile).Results: FGF23 correlated significantly with CysC, CysC eGFR, PTH, 1.25 (OH)2 vitamin D, phosphate, and pH. The correlation of the latter three remained significant in the multivariate analysis. We calculated a formula for the expected FGF23 value for a given level of eGFR which reads Y = 1295 * e-0.07247*X + 38.35. Deviation by more than 20% from the curve also depended on phosphate, 1.25 (OH)2 vitamin D and pH.Conclusions: Our data emphasize the importance of phosphate and 1.25 (OH)2 vitamin D levels. The impact of acidosis on FGF23 warrants further studies. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the effects of the supplementation of vitamin D on the growth, vitamin D metabolites, and osteocalcin secretion in juvenile Siberian sturgeon ( Acipenser baerii). A 90-day growth trial was conducted with juvenile Siberian sturgeon (initial body weight 3.47 ± 0.14 g) fed seven isonitrogenous and isoenergetic practical diets (45% CP and 13% lipid) containing 60 (basal diet), 240, 450, 880, 1670, 3300, or 1.0 × 10 IU/kg feed (D60~D 1.0 × 10) vitamin D. The results showed that weight gain and specific growth rate increased as the dietary vitamin D levels increased from 450 to 3300 IU/kg ( P < 0.05). The fish fed with D1670 and D3300 diets had higher crude lipid and ash levels than the fish fed the D60 diet ( P < 0.05). The fish fed D880, D1670, or D3300 diets had higher 25-OH-D and 1,25-(OH)-D levels than the fish fed the D60 diet ( P < 0.05). The fish fed D880, D1670, D3300, or D1.0 × 10 diets had higher osteocalcin levels than the fish fed the D60 diet ( P < 0.05). Based on the broken line method analysis of weight gain and osteocalcin, the dietary vitamin D requirement of juvenile Siberian sturgeon was estimated to be 1683.30 and 1403.27 IU/kg per diet, respectively. [ABSTRACT FROM AUTHOR]

Vitamin D and its metabolites are lipophilic molecules with low aqueous solubility and must be transported bound to plasma carrier proteins, primarily to vitamin D binding protein (DBP). The biological functions of vitamin D metabolites are intimately dependent on the protein, hence the importance of determining their affinity for DBP. In this study, we developed a novel procedure for measuring the kinetic and equilibrium constants of human-DBP with vitamin D and three metabolites: 1,25-dihydroxyvitamin D [1,25(OH)D], 25-hydroxyvitamin D (25OHD) and 24,25-dihydroxyvitamin D [24,25(OH)D] by surface plasmon resonance (SPR). At the same time, five different analogues, synthetized in our laboratory, were evaluated in order to compare the affinity values with the metabolites. Real-time SPR measurements showed that 25OHD and 24,25(OH)D had higher affinity (0.3 μM) than 1,25(OH)D (5 μM), with the higher affinity of 25OHD and 24,25(OH)D due to dissociation constants 1 order of magnitude slower. In the case of the analogues, the affinity values were lower, with 1-hydroxy-25-nitro-vitamin D (NO-446), structurally closer to 1,25(OH)D, showing the highest value with a K of 50 μM. (24R)-1,25-dihydroxyvitamin-24-buthyl-28-norvitamin D (Bu-471) and (24R)-1,25-dihydroxyvitamin-24-phenyl-28-norvitamin D (Ph-491), structurally similar, had affinities of 180 and 170 μM, respectively. (22R,23E)-1-hydroxy-22-ethenyl-25-methoxy-23-dehydrovitamin D (MeO-455) and 1-hydroxy-20(R)-[5(S)-(2,2-dimethyltetrahydropyran-5-yl)]-22,23-dinor vitamin D (Oxan-429) had affinities of 310 and 100 μM, respectively. The binding of the metabolites and analogues was reversible allowing the rapid capture of data for replicates. The kinetic and equilibrium data for both the metabolites and the analogues fitted to the Langmuir model describing a 1:1 interaction. [ABSTRACT FROM AUTHOR]

Copyright of Biosalud is the property of Universidad de Caldas and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The National Institute of Standards and Technology administers quality assurance programs devoted to improving measurements of nutrients and related metabolites in foods, dietary supplements, and serum and plasma samples. These programs have been developed in collaboration with the National Institutes of Health to assist measurement communities in their efforts to achieve accurate results that are comparable among different laboratories and over time. Targeted analytes include micronutrients, botanical markers, nutritional elements, contaminants, fatty acids, and vitamin D metabolites. [ABSTRACT FROM AUTHOR]

Chronic liver disease ( CLD) and several related extrahepatic manifestations such as hepatic osteodystrophy are associated with deficiency of vitamin D, which has therefore been suggested as therapeutic target. Vitamin D undergoes hepatic 25-hydroxylation, rendering the liver critical to the metabolic activation of this vitamin. Vitamin D deficiency is highly prevalent in CLD patients, and vitamin D levels are inversely related to the severity of CLD. Declining levels of carrier proteins such as albumin and vitamin D-binding protein might also be critical in CLD. Intervention studies report improvements of CLD following supplementation, and benefits to health outcomes in particular with respect to hepatitis C virus infection have recently been documented. Content:We discuss vitamin D sources, functions and metabolism with a focus on the inherent complications of analytical measurements, such as the interference of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D C-3 epimers. Global discrepancies in the definition of optimal serum 25-hydroxyvitamin D levels are covered, and the prevalence of vitamin D deficiency in CLD is reviewed. We also address the functional mechanisms underlying this deficiency, and refer to associations between genetic variation in vitamin D metabolism and CLD. Lastly, we consider the health implications of a vitamin D deficiency in CLD and consider therapeutic options. Summary Herein, we focus on the epidemiological and functional relationships between vitamin D deficiency and CLD, followed by a discussion of the potential implications for therapeutic interventions. [ABSTRACT FROM AUTHOR]

Both in ankylosing spondylitis (ASP) and psoriatic arthritis (PsA), osteopenia is present in one-third of women and men, whereas osteoporosis mainly affects men, even in their 30 s. Subclinical gut inflammation has been described in patients with AS or PsA. Joint involvement also occurs with other gastrointestinal diseases such as celiac disease. We tested the hypothesis, whether elevated serum levels of human anti-tissue-transglutaminase-IgA (htTG) are associated with changes in disease activity, vitamin D metabolism and bone mineral density (BMD) in patients with ASP and PsA. In a cross-sectional study, we evaluated both biochemical markers of bone turnover, BMD and htTG in 76 patients with ASP and 120 patients with PsA. A reduction of BMD in lumbar spine was determined both in ASP (42.7%) and in PsA (57.3%). Furthermore, a significantly higher prevalence of htTG was detected only in ASP (14/76). ASP patients with negative htTG status have significant higher 25-vitamin D3 levels. ASP patients with positive htTG status are younger. A positive htTG status entails the risk of a bad vitamin D supply, which should be considered in young patients since this constellation favors a reduction in bone density. The coincidence of ASP along with detection of htTG and clinically asymptomatic celiac disease as an accessory source of inflammation with a negative influence on the bone metabolism is also conceivable. Clinicians need to be aware of patients younger than 45 years with ASP, which have important implications for the correct treatment and vitamin D supplementation. [ABSTRACT FROM AUTHOR]

In 2 women with distal renal tubular acidosis and osteomalacia, alkali treatment cured the bone disease and was accompanied by marked increases in the serum 1,25 dihydroxyvitamin D concentration, without a significant change in the 25-hydroxyvitamin D concentration. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aim: To provide reference data of biochemical markers of bone turnover and vitamin D metabolites for children and young adults. Methods: Blood samples were taken from 176 healthy Dutch children and young adults (age range 7.6–25.3 years) to assess serum calcium, alkaline phosphatase, inorganic phosphate, osteocalcin, collagen type I cross-linked N-telopeptide, N-terminal propeptide of type I procollagen , 25-hydroxyvitamin D[sub 3] , and 1,25-dihydroxyvitamin D[sub 3] levels. Cross-linked telopeptide of type I collagen and carboxy-terminal propeptide of type I procollagen were assessed in 286 subjects (age range 1.4–25.3 years). Results: Calcium and vitamin D levels were independent of age. The peak concentrations for collagen type I cross-linked N-telopeptide, cross-linked telopeptide of type I collagen, carboxy-terminal propeptide of type I procollagen, N-terminal propeptide of type I procollagen, alkaline phosphatase, and osteocalcin were found during puberty, in girls approximately 2.5 years earlier than in boys. Strong correlations were found between the markers of bone turnover, while no correlation was found between the markers of bone turnover and bone mineral density measured by dual-energy X-ray absorptiometry. Conclusions: Single measurements of bone markers cannot predict bone density. Reference data according to gender, age, and Tanner stage are given which allow calculating standard deviation scores adjusted for age and gender.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The brain's supply with vitamin D is poorly understood. Therefore, the present study aimed to determine 25-hydroxy vitamin D3 (25(OH)D) and 24,25-dihydroxy vitamin D (24,25(OH)2D3) in serum and cerebrospinal fluid (CSF) from individuals with intact and disturbed brain-CSF-barrier (BCB) function. In 292 pairs of serum and CSF samples the vitamin D metabolites were measured with liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). CSF/serum ratios (QALB, Q25(OH)D, Q24,25(OH)2D3) were calculated. Median (IQR) serum concentrations of 25(OH)D and 24,25(OH)2D3 were 63.8 (43.4–83.9) nmol/L and 4.2 (2.2–6.2) nmol/L. The CSF concentrations of both metabolites accounted for 3.7 and 3.3% of the respective serum concentrations. Serum 25(OH)D correlated inversely with Q25(OH)D and Q24,25(OH)2D3 implying a more efficient transport of both metabolites across the BCB when the serum concentration of 25(OH)D is low. In patients with BCB dysfunction, the CSF concentrations and the CSF/serum ratios of both vitamin D metabolites were higher than in individuals with intact BCB. The CSF concentrations of 25(OH)D and 24,25(OH)2D3 depend on BCB function and the respective serum concentrations of both metabolites. Higher vitamin D metabolite concentrations in CSF of patients with impaired BCB function may be due to passive diffusion across the BCB. [ABSTRACT FROM AUTHOR]

The active metabolites of vitamin D3 (D3) and lumisterol (L3) exert a variety of antiaging and photoprotective effects on the skin. These are achieved through immunomodulation and include anti-inflammatory actions, regulation of keratinocytes proliferation, and differentiation programs to build the epidermal barrier necessary for maintaining skin homeostasis. In addition, they induce antioxidative responses, inhibit DNA damage and induce DNA repair mechanisms to attenuate premature skin aging and cancerogenesis. The mechanism of action would involve interaction with multiple nuclear receptors including VDR, AhR, LXR, reverse agonism on RORα and -γ, and nongenomic actions through 1,25D3-MARRS receptor and interaction with the nongenomic binding site of the VDR. Therefore, active forms of vitamin D3 including its canonical (1,25(OH)2D3) and noncanonical (CYP11A1-intitated) D3 derivatives as well as L3 derivatives are promising agents for the prevention, attenuation, or treatment of premature skin aging. They could be administrated orally and/or topically. Other forms of parenteral application of vitamin D3 precursor should be considered to avoid its predominant metabolism to 25(OH)D3 that is not recognized by CYP11A1 enzyme. The efficacy of topically applied vitamin D3 and L3 derivatives needs further clinical evaluation in future trials. [ABSTRACT FROM AUTHOR]

(1) Background: Vitamin D, a well-established regulator of calcium and phosphate metabolism, also has immune-modulatory functions. An uncontrolled immune response and cytokine storm are tightly linked to fatal courses of COVID-19. The present retrospective study aimed to inves-tigate vitamin D status markers and vitamin D degradation products in a mixed cohort of 148 hospitalized COVID-19 patients with various clinical courses of COVID-19. (2) Methods: The serum concentrations of 25(OH)D3, 25(OH)D2, 24,25(OH)2D3, and 25,26(OH)2D3 were determined by a validated liquid-chromatography tandem mass-spectrometry method in leftover serum samples from 148 COVID-19 patients that were admitted to the University Hospital of the Medical Uni-versity of Graz between April and November 2020. Anthropometric and clinical data, as well as outcomes were obtained from the laboratory and hospital information systems. (3) Results: From the 148 patients, 34 (23%) died within 30 days after admission. The frequency of fatal outcomes did not differ between males and females. Non-survivors were significantly older than survivors, had higher peak concentrations of IL-6 and CRP, and required mechanical ventilation more frequently. The serum concentrations of all vitamin D metabolites and the vitamin D metabolite ratio (VMR) did not differ significantly between survivors and non-survivors. Additionally, the need for res-piratory support was unrelated to the serum concentrations of 25(OH)D vitamin D and the two vitamin D catabolites, as well as the VMR. (4) Conclusion: The present results do not support a relevant role of vitamin D for the course and outcome of COVID-19. [ABSTRACT FROM AUTHOR]

25-hydroxycholecalciferol (25OHD) and 1,25-dihydroxycholecalciferol (1,25(OH)D) at physiological concentrations exerted direct effects on Ca fluxes in cultured vitamin D-deficient chick soleus muscle and myoblasts. Isotopic desaturation curves of soleus muscle prelabeled withCa indicated that the action of 25OHD is localized in a slow-exchangeable Ca pool where it stimulates net Ca uptake. On the other hand, the predominant effects of 1,25(OH)D consist in an increase of the rate constant of Ca efflux of this pool and in an increase of net Ca uptake in a fast-exchangeable pool. 24,25-dihydroxycholecalciferal proved to be inactive on both Ca uptake and efflux. In addition, 1,25(OH)D significantly increasedCa labeling of cultured chick myoblasts. These effects were accompanied by changes in the growth and differentiation of the cultures. The results suggest a direct involvement in vivo of 25OHD and 1,25(OH)D on muscle cellular calcium. [ABSTRACT FROM AUTHOR]

The effect of the vitamin D metabolites 1,25 dihydroxyvitamin D (100 pg/ml) and 25-hydroxyvitamin D (30 ng/ml) on hepatic production ofH-25 hydroxyvitamin D was investigated using rachitic liver perfusions and homogenates. 1,25 dihydroxyvitamin D inhibited hepaticH-25 hydroxyvitamin D production in the liver perfusion (3.6 ± 0.4 vs 2.0 ± 0.5 pmol/liver, P<0.05) and in liver homogenates (11.9 ± 0.6 vs 10.1 ± 0.4 pmol/g liver protein/3 h, P<0.02). Inhibition was time and dose dependent. 25-hydroxyvitamin D inhibited production in liver homogenates (11.9 ± 0.6 vs 9.2 ± 0.1 pmol/g liver protein/3 h, P<0.05) but not in the intact liver (3.6 ± 0.4 vs 3.4 ± 0.5 pmol/liver). The data indicate that 1,25 dihydroxyvitamin D is able to feedback regulate the production of its precursor, 25-hydroxyvitamin D. Although 25-hydroxyvitamin D also inhibits its own production in liver homogenates, it failed to alter total production in the intact liver, suggesting that this metabolite may require immediate access to the vitamin D 25-hydroxylase, located on the microsomes and mitochondria, to induce inhibition. [ABSTRACT FROM AUTHOR]

The effects of selected vitamin D metabolites and analogs on bone collagen synthesis in vitro were examined in organ cultures of neonatal mouse calvarial bone. The incorporation of [H]proline into the collagenase-digestible fraction of newly synthesized protein was progressively inhibited by 1α,25-dihydroxyvitamin D (1α,25-(OH)D) (10 M to 10 M) in 24-h cultures, and incorporation into noncollagen protein was also blunted at the higher doses employed. The synthetic analog 1α-hydroxyvitamin D (1α-OHD) was almost 300-fold less potent an inhibitor of collagen synthesis than was 1α,25(OH)D, and the natural metabolites 25-hydroxyvitamin D (25OHD) and 24R,25-dihydroxyvitamin D (24R,25(OH)D), 1000-fold less potent, although the dose-response curve for each of these compounds was not parallel with that for 1α,25(OH)D. The 24S,25(OH)D enantiomer was four-fold less potent than 24R,25-(OH)D or 25OHD, and vitamin D showed less than 2% the activity of 25OHD. The responses were unaffected by the substitution of 0.4% bovine albumin for 5% horse serum in the medium, and no stimulation of collagen synthesis was observed in response to 25-hydroxylated metabolites between 2×10 and 2×10 M or in cultures treated for up to 96 h with 24R,25(OH)D (2×10M). The overall results emphasize the similarity of the structural requirements for the inhibition of matrix synthesis and the stimulation of resorption by active vitamin D metabolites in bone. In addition, these studies support the importance of the 1-hydroxyl function to the biologic activity of vitamin D in the skeleton. [ABSTRACT FROM AUTHOR]

The hypophosphatemic male mouse (Hyp/y), the proposed model for human vitamin D-resistant rickets (VDRR), is characterized by chronic hypophosphatemia, dwarfism, and rachitic and osteomalacic bone lesions. We have reported that treatment of Hyp/y mice with phosphate salts (Pi) heals rickets but does not correct the defective endosteal bone mineralization. In an attempt to cure osteomalacia, mutant male animals were treated with Pi combined with 25-hydroxyvitamin D (25OHD, 1 µg/kg/day), 24,25-dihydroxyvitamin D [24,25(OH)D, 0.5 µg/kg/day], or 1,25-dihydroxyvitamin D [1,25(OH)D, 0.05-0.25 µg/kg/day] infused constantly for 3 weeks. The biochemical and skeletal effects of treatment were assessed by analytical methods and bone histomorphometry. The results show that only 1,25(OH)D produced a dose-dependent elevation of serum calcium and phosphorus, and greatly improved bone mineralization at doses high enough to increase serum calcium and phosphorus concentrations within or above the normal range. Better improvement of bone mineralization was obtained when Pi was combined to 1,25(OH)D. In conjunction with the correction of hypocalcemia, Pi+1,25(OH)D suppressed the stimulation of bone turnover induced by Pi supplementation. The results show that, as in VDRR children, 1,25(OH)D produces beneficial effects on bone lesions in Hyp/y mice, mainly through enhancement of mineral availability. However, the persistence of osteomalacia despite correction of serum mineral concentrations suggests that there is a specific bone cell resistance to mineral and/or hormonal influences in Hyp/y mice. [ABSTRACT FROM AUTHOR]

Adult male rats were fed a diet containing 0.15% calcium, 0.3% phosphorus, and either 100, 50, or 20 mg of prednisolone per kg of diet. All these levels of prednisolone led to osteopenia, decreased intestinal absorption of calcium, slightly lower serum calcium and phosphorus, and a decreased level of serum 1,25-dihydroxyvitamin D. Exogenous parenteral 1,25-dihydroxyvitamin D corrected steroid-induced changes in serum calcium and phosphorus, but could not completely correct the low intestinal calcium transport; nor did it prevent the development of osteopenia. The prednisolone-induced osteopenia seems at least in part to be caused by impaired intestinal calcium transport. The impaired calcium transport may be the result of low levels of 1,25-dihydroxyvitamin D and a direct effect of presnisolone on the intestine. [ABSTRACT FROM AUTHOR]

The present study was undertaken to test the in vitro action of aluminum on bone phosphatase activities and the possible interaction of this metal with parathyroid hormone (bPTH) or vitamin D dihydroxymetabolites [1,25- and 24,25(OH)D). Three-day-old rat calvaria were incubated for 24 h with one of the following: bPTH at 5×10M, 1,25-or 24,25(OH)D at 2.5×10M, Al at concentrations ranging from 3×10M to 6×10M, or their corresponding solvents. Al effects were also investigated when the medium phosphate or calcium concentrations were modified. In some experiments, Al was added simultaneously with bPTH or one of the vitamin D metabolites at the beginning of the 24 h incubation. At the end of all incubations, acid and alkaline phosphatase activities were measured in bone cytoplasmic extract. The results show that: (a) When compared to the value found in half calvaria incubated in a control medium, the bone acid and alkaline phosphatase content is significantly higher in paired halves incubated with Al (3×10M to 1.5×10M) as well as with bPTH, 1,25-, or 24,25(OH)D and sharply decreased with higher Al concentrations (6×10M). (b) The Al effect on phosphatase activities is modified in a free phosphate or a free calcium medium. (c) The presence of Al at 1.5×10M or 6×10M significantly decreases the bPTH or 1,25(OH)D-induced stimulation of bone phosphatase activities. (d) A similar interaction could not be found between Al and 24,25-(OH)D. [ABSTRACT FROM AUTHOR]

Weanling rats were given a vitamin D-deficient diet containing 1.4% calcium and 1.0% phosphorus. After 4 weeks these deficient animals were injected for 7 days with selected doses of one of the following vitamin D metabolites: 25(OH)D, 1,25(OH)D, 24,25(OH)D, 25,26(OH)D or the ethanol vehicle. A vitamin D-replete group was placed on the same diet but injected with 50 IU of vitamin D once a week for the entire 5-week period. By the use of a modified Ussing chamber [1], the measurements of calcium fluxes into and from the rat calvaria were possible. These data enabled the apparent mineral solubilities to be derived. After 5 weeks on this diet the vitamin D-deficient rats had low levels of serum calcium (1.41 mM) and decreased mineral solubility when compared to the vitamin D-replete group. The apparent solubility of the bone mineral increased toward the vitamin D-replete level in calvaria from vitamin D metabolite-treated rats. However, these changes did not directly reflect the alterations in the level of serum calcium. At any given dose level, 1,25(OH)D was the most effective metabolite in increasing serum calcium. In fact, the high dose (250 pmoles/day) was hypercalcemic. Next in effectiveness was 25(OH)D. These two metabolites were equally effective in increasing mineral solubility. At a 10 times higher dose, the 24,25(OH)D metabolite was able to normalize serum calcium and improve but not normalize mineral solubility. At the high dose (260 pmoles/day), the 25,26(OH)D metabolite caused no effect on mineral solubility and minimal increases in serum calcium. [ABSTRACT FROM AUTHOR]

We compared the effects of four vitamin D metabolites, 1α,25 dihydroxy vitamin D (1α,25(OH)D), 1α hydroxy vitamin D (1αOH D), 25 hydroxy vitamin D (25 OH D), and 24R,25 dihydroxy vitamin D (24R,25(OH)D) on resorption and collagen synthesis in fetal rat bone maintained in organ culture. Resorption was quantitated by measuring the release of previously incorporatedCa from long bone shafts of 19-day fetal rats, and collagen synthesis was assessed by measuring the incorporation ofH-proline into collagenase digestible protein (CDP) in calvaria from 21-day fetal rats. All four compounds stimulated bone resorption and inhibited collagen synthesis, but 1α,25(OH)D was approximately 1000 times more potent in both organ culture systems. Although the differences were small among the other three compounds, the order of potency was 1αOH D>25 OH D≧24R,25(OH)D. These results suggest that the receptor for 1α25(OH)D in both bone resorbing and bone forming cells has similar affinities for several vitamin D metabolites. [ABSTRACT FROM AUTHOR]

Results from in vitro works suggest that 1,25- and 24,25-dihydroxyvitamin D (1,25-(OH)D and 24,25-(OH)D) act on bone via different mechanisms. The present investigation was performed to study the effect of these two metabolites and of their precursor 25-hyxdroxyvitamin D (25-(OH)D) on bone cAMP content in vitro. Rats' paired half calvaria were incubated under sterile conditions with one vitamin D derivative (10 to 10 M) or with ethanol (0.005 ml for 15 min to 24 h in 1 ml medium containing 0, 0.2, 1, 2, or 3 mM calcium. In some experiments: (a) cycloheximide (10M) was added simultaneously with the vitamin D metabolites; (b) 1-84 bPTH (5 × 10 M) was added for 5 or 15 min at the end of the 24 h incubation. Calvaria were immersed in 1 ml TCA 5% 4°C and homogenized. The cAMP was extracted with diethylether and measured by a competitive protein binding assay. Results bring further evidence for a particular effect of low doses of 24,25-(OH)D (10 to 10M) and of 25-(OH)D (10 to 10M) on bone, different from that of 1,25-(OH)D: cAMP content was higher in 24,25-(OH)D- or 25-(OH)D-treated and lower in 1,25-(OH)D-treated calvaria than in ethanol-treated ones with 1 mM calcium. The 1,25-(OH)D effect persisted in calcium-free medium whereas 25-(OH)D and 24,25-(OH)D effects could not be observed with 0 mM nor with 3 mM calcium. The required duration of the preincubation (over 1 h) as well as the inhibitory action of cycloheximide may suggest an involvement of protein synthesis in the vitamin D metabolites effects. Neither 1,25-(OH)D nor 24,25-(OH)D affected the PTH-induced increase in bone cAMP content. [ABSTRACT FROM AUTHOR]

The in vitro effects of vitamin D metabolites, parathyroid extract (PTE), purified parathyroid hormone (bPTH), vitamin A, and heparin on acid and alkaline phosphatases in rat or mouse calvaria in culture were investigated. Results show that: (a) when compared to values found in half calvaria incubated for 24 h in control medium, the bone acid and alkaline phosphatase content is significantly higher in paired halves incubated with PTE (1 USP/ml), bPTH (4×10M), heparin (5 USP/ml), vitamin A (23 USP/ml), 25-(OH)D (2.5×10 to 2.5×10M), 24,25-(OH)D, and 1,25(OH)D (2.5×10 to 2.5×10M); (b) the presence of 24,25-(OH)D at low concentrations in the incubation medium decreases significantly the PTE, bPTH, vitamin A, or heparin induced stimulation of the phosphatase activities. This interaction is also observed when measuring β glucuronidase and glucose-6-phosphatase activities andCa release from previously labeled mouse calvaria; (c) a similar activity could not be found with 1,25-(OH)D suggesting that 24,25-(OH)D may have a specific role in bone metabolism. [ABSTRACT FROM AUTHOR]

Serum concentrations of 25-hydroxyvitamin D [25(OH)D], 24,25-dihydroxyvitamin D [24,25(OH)D], and 1α,25-dihydroxyvitamin D [1α,25(OH)D] were measured in ten cadmium (Cd)-exposed subjects and five non exposed subjects. The Cd-exposed subjects were divided into two groups according to serum 1α,25(OH)D levels. No significant differences for 25(OH)D were found between the Cd-exposed group with low or normal serum 1α,25(OH)D and the non exposed group. The concentrations of 24,25(OH)D were the lowest in the Cd-exposed group with low serum 1α,25(OH)D, highest in the non exposed group, and significantly lower in the Cd-exposed group with normal serum 1α,25(OH)D than in the non exposed group. Renal function was much worse in the Cd-exposed group with low serum 1α,25(OH)D than in the group with normal serum 1α,25(OH)D. These findings indicate that Cd initially disturbs hydroxylation from 25(OH)D to 24,25(OH)D and then disturbs hydroxylation from 25(OH)D to 1α,25(OH)D. The decrease of serum 24,25(OH)D and 1α,25(OH)D in Cd-exposed subjects is not due to a decrease of the serum 25(OH)D level. [ABSTRACT FROM AUTHOR]

The effects of a partially purified aqueous extract of Solanum malacoxylon (SM) leaves and of an SM extract incubated with ruminal fluid (RF) prior to administration on intestinal phosphate and calcium absorption in rachitic rats were compared with 1α, 25-dihydroxy-vitamin D[1α,25-(OH)-D] using a duodenal loop in situ method. The time course responses elicited by both extracts were qualitatively similar to that of 1α, 25-(OH)-D. However, a single dose of SMRF was significantly more effective in stimulatingP absorption than an equivalent dose of SM. Part of this difference can be accounted for by incomplete saturation of the phosphate transport system with the level of SM employed. Treatment with rumen potentiated the effects of SM onCa absorption to a lesser extent. Extraction of SMRF with nonpolar organic solvents and purification of the lipid extract by chromatography on Silica Gel G thin-layer plates and on Sephadex LH-20 columns yield two fractions which promote intestinalP absorption. The bioactive fraction eluting first from the Sephadex LH-20 column migrates similarly as 1α,25-(OH)-D. The greater effectiveness of SMRF extracts on intestinal phosphate and calcium absorption may be tentatively attributed to the release of 1α,25-(OH)-D from the corresponding glycoside, shown previously to be present in SM, and to steroid modification during incubation with rumen. [ABSTRACT FROM AUTHOR]

Samples of CSF and plasma were obtained simultaneously from 46 adult patients who had no endocrine disorders and were undergoing routine diagnostic lumbar puncture because of suspected or proved prolapse of a disc. Concentrations of 25-OHD, 24,25(OH)D and 1,25(OH)D were measured. The samples were purified by column chromatography and fractionated by HPLC. In the appropriate fractions the vitamin D metabolites were measured by PBA, and cytoreceptor assay. The results were as follows (median, range in brackets): 25-OHD in CSF 8.3 ng/ml (2.0-24.8), in plasma 14.5 ng/ml (7.0-36.0). 24,25(OH)D in CSF 1.8 ng/ml (0.3-4.6) and 2.5 ng/ml (0.4-4.7) in plasma. 1.25(OH) D in CSF 25.0 pg/ml (2.2-39.0) and 31.0 pg/ml (10.1-55.0) in plasma. The correlations between plasma and CSF concentrations were as follows: 25-OHD r=0.479 ( P<0.001); 24,25(OH)D r=0.815 ( P<0.001) and for 1.25(OH)D r=0.497 ( P<0.001). Our findings showed vitamin D metabolites to be present in human CSF. [ABSTRACT FROM AUTHOR]

Caffeine has been cited as a risk factor for osteoporosis in humans. In rats, caffeine increases calcium absorption and excretion and raises parathyroid hormone (iPTH) levels. This study investigated the effect of chronic caffeine administration on bone histomorphometry and serum markers of bone mineral metabolism. Twenty-seven male Sprague Dawley rats weighing approximately 300 g were divided into three groups: Group A (n=8) served as controls, Group B (n=9) received 2.5 mg/100 g caffeine in their drinking water, and Group C (n=10) received 10 mg/100 g body weight caffeine in their drinking water. Animals were bled serially for the 8 week study period: Ionized calcium was measured from tail vein blood and serum iPTH and osteocalcin (BGP) from orbital sinus blood. All three groups received two doses of tetracycline for bone histomorphometry which was performed on a right tibial section from each animal. Ionized calcium was not different among the three groups at any time point. No alteration in serum iPTH levels was demonstrated except for day 56 when the high-dose group (C) showed a raised level (mean=59.1, SE=±8.9 pg/ml ( P<0.05). By week 8 Group C showed a failure to gain weight compared with Group A. Group C mean weight=384.0±6.6 g, Group A 427.4±10.8 g ( P<0.005). Serum BGP was significantly increased in Group C compared with control ( P<0.001). No differences in bone histomorphometry were observed among the three groups. We conclude that although chronic caffeine administration in the rat may slightly increase bone turnover as evidenced by the BGP increase, bone histomorphometry was not altered. This makes the role of caffeine by itself doubtful as an etiological factor for osteoporosis. [ABSTRACT FROM AUTHOR]

The biochemical parameters of bone mineral metabolism in patients with nonhypercalcemic malignancy have not been extensively investigated. Therefore, a group of 29 such patients with different types of malignancy was studied. Ten patients received corticosteroids. In the entire group, serum ionized calcium (Ca2+), bone gla protein (BGP), 25-hydroxyvitamin D (25OHD), and 1,25-dihydroxyvitamin D (1,25(OH)2D) were all lower than in age-matched controls, and carboxy-terminal parathyroid hormone (CPTH) was higher. Although both corticosteroid- and noncorticosteroid-treated patients had decreased BGP values, the corticosteroid-treated patients had lower BGP levels than those not on steroids (4.24 +/- 0.70 SE vs. 11.50 +/- 2.20 ng/ml; P less than 0.005). Patients on corticosteroids had lower 1,25(OH)2D values than controls (18.81 +/- 2.71 vs. 27.83 +/- 1.17 pg/ml; P less than 0.01), whereas those not on corticosteroids had normal 1,25(OH)2D values. These results suggest that patients with nonhypercalcemic malignancy have nutritional vitamin-D deficiency and secondary hyperparathyroidism with perhaps corticosteroid-induced suppression of serum 1,25(OH)2D and BGP. The decreased levels of serum BGP in the nonsteroid-treated patients suggest, in addition, a defect in osteoblast function. [ABSTRACT FROM AUTHOR]

Bone gla protein, the vitamin K-dependent protein synthesized by osteoblasts and measured in blood by radioimmunoassay, has been used as an index of the rate of bone turnover. The relationship of bone gla protein with other markers of bone mineral metabolism was determined in 31 untreated postmenopausal women with the osteoporotic syndrome. In addition to serum osteocalcin (BGP) we measured parathyroid hormone (PTH) (carboxyl and mid-molecule fragments), 25(OH)D, alkaline phosphatase, estradiol (E2), estrone (E1), dietary calcium intake, 24 hour urinary calcium excretion, and bone mineral density by CT scan of the lumbar vertebrae. Significant osteopenia was present on CT in untreated postmenopausal osteoporotic women (bone density in 18 out of 31 was below the critical value of 60 mg/cm3). Serum BGP correlated positively with CT scan (r + 0.647, P less than 0.001). CT and age were negatively correlated (r - 0.661, P less than 0.001) while CT and E2 showed a positive correlation (r + 0.554, P less than 0.01). Unexpectedly, BGP and age revealed a significant negative correlation (r - 0.421, P less than 0.05). These findings suggest a state of low bone turnover in this group with untreated postmenopausal osteoporosis. [ABSTRACT FROM AUTHOR]

The relative roles of 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D (1,25-(OH)2D) and 24,25-dihydroxyvitamin D (24,25-(OH)2D) in bone mineralization are largely unknown. Young vitamin D depleted rats were fed increasing amounts of vitamin D and grouped radiologically in accordance with the rat line test. They ranged from severely rachitic to normal. Radiology was correlated with serum levels of 25-OHD, 1,25-(OH)2D, 24,25-(OH)2D, ionized calcium, magnesium, and phosphate, with bone histology, and with the total mineral content of the animals. Serum 1,25-(OH)2D rose in a linear fashion to supranormal values during bone healing and correlated with the radiological degree of rickets. Serum 25-OHD was below detection limit in the most rachitic and low in the radiologically normal rats, whereas 24,25-(OH)2D was low in all groups. These two metabolites showed no correlation with the radiologic, histologic or biochemical parameters. In rachitic rats, 1,25-(OH)2D appears to play a major role in bone healing and possibly exerts a direct effect on bone cells. It cannot be ruled out, however, that the effect is mediated through a rise in serum levels of calcium and phosphorus, although signs of bone healing were seen in the presence of a subnormal calcium X phosphorus product. Initiation of mineralization can take place with unmeasurable 25-OHD, and 24,25-(OH)2D seems to be without importance. [ABSTRACT FROM AUTHOR]

The effects of i.v. 1,25-dihydroxycholecalciferol (DHCC) on blood pressure and insulin sensitivity were studied in 7 patients on maintenance hemodialysis and compared with 7 healthy controls. Three days after discontinuing oral 1,25-DHCC, the dialysis patients were evaluated by glucose clamp studies to quantitate insulin sensitivity, with (+D) and without (−D) a prior single dose of i.v. 1,25-DHCC at 2μg/m. Blood pressure was measured just before the glucose studies. During −D studies, the patients were hypertensive (mean arterial blood pressure 108±2 mmHg, controls 84±4 mmHg, P<0.02) and insulin resistant (insulin sensitivity index 7.5±0.4 mg/kg·min per μU per ml, controls 14.2±0.7, P<0.01) i.v. 1,25-DHCC significantly reduced the mean arterial blood pressure (96±3 mmHg, P<0.05) and increased insulin sensivity (10.9±0.5 mg/kg·min per μU per ml, P<0.02) in the dialysis patients. I. V. 1,25-DHCC did not change blood pressure and insulin sensitivity in the control subjects. During −D studies, serum concentrations of 1,25-DHCC were significantly lower in patients than controls ( P<0.02). Serum 1,25-DHCC during the +D studies increased to supraphysiological levels in both patients and controls. Serum concentrations of intact parathyroid hormone, total and ionized calcium, magnesium, potassium, urea nitrogen and creatinine were not different between the +D and −D studies in either the dialysis patients or the controls. These results suggest that pharmacological doses of 1,25-DHCC may have therapeutic value in the treatment of hypertension and insulin resistance in dialysis patients. [ABSTRACT FROM AUTHOR]