Binding properties of plasma vitamin D-binding protein and intestinal 1,25-dihydroxyvitamin D3 receptor in piglets with pseudo-vitamin D-deficiency rickets, type I: Treatment effects with pharmacological doses of vitamin D3

1990 ◽  
Vol 282 (2) ◽  
pp. 326-332 ◽  
Author(s):  
R. Kaune ◽  
B. Schroeder ◽  
J. Harmeyer
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Vitamin D3 ◽  
Plasma Vitamin ◽  
Type I ◽  
D3 Receptor ◽  
Vitamin D Binding Protein ◽  
Binding Properties ◽  
Dihydroxyvitamin D3 ◽  
Deficiency Rickets

Studies of the Porcine Intestinal Calcitriol Receptor in Pseudo-Vitamin D Deficiency Rickets Type I

1990 ◽  
Vol 79 (4) ◽  
pp. 409-414 ◽  
Author(s):  
B. Schröder ◽  
R. Kaune ◽  
J. Harmeyer
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Rate Constant ◽  
Clinical Symptoms ◽  
Binding Capacity ◽  
Relative Molecular Mass ◽  
Type I ◽  
Binding Properties ◽  
Deficiency Rickets ◽  
And Control

1. Calcitriol (1,25-dihydroxyvitamin D3) concentrations in plasma of humans and pigs with pseudo-vitamin D deficiency rickets type I (PVDRI) have been reported to be significantly lower than in normal subjects and animals. Sometimes, however, calcitriol concentrations are relatively high in these subjects and animals (50–80 pmol/l) and nevertheless clinical symptoms of rickets develop. We have studied whether or not the development of rachitic lesions in piglets with PVDRI is due to altered binding properties of the intestinal calcitriol receptor in addition to the defective renal production of calcitriol. PVDRI piglets with clinical and biochemical symptoms of rickets (hypocalcaemia, increased activity of alkaline phosphatase) and with calcitriol concentrations in plasma of 83.7 ± 4.2 pmol/l (n = 7) were used. They were compared with unaffected piglets with normal calcitriol concentrations (178.0 ± 17.7 pmol/l, n = 9). 2. The equilibrium dissociation constant (Kd) of the receptor in the PVDRI piglets (0.31 ± 0.05 nmol/l) and in control piglets (0.33 ± 0.05 nmol/l) and the maximum binding capacity (Bmax.) (674 ± 103 and 719 ± 122 fmol/mg of protein, respectively) were not different (n = 9). 3. The association rate constant (kass) at 4°C [0.15 × 107 and 0.24 × 107 (mol/l)−1 min−1] and the dissociation rate constant (kdiss) (0.40 × 10−3 and 0.48 × 10−3 min−1; half-life of dissociation = 24.1 and 28.9 h, respectively) were also not different between diseased and control piglets. 4. No differences between PVDRI and control piglets were also found for the relative molecular mass (47 500 and 47700, respectively) and the Stokes' radius (3.04 and 3.05 nm, respectively) of the calcitriol receptor. 5. It is concluded that the intestinal calcitriol receptor of this animal model functions normally and that changes in binding properties and concentration of the intestinal calcitriol receptor do not contribute to the development of rachitic lesions in PVDRI piglets.

1, 25-Dihydroxyvitamin D Suppresses TNFα-Mediated NF-κB Activation in K562 and Human CD34+ Cells and Promotes Recovery of Erythroid Colony Formation in Human CD34+ Cells

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2097-2097
Author(s):  
Michelle Levine ◽  
Jee-Yeong Jeong ◽  
Nancy Berliner ◽  
Gary J. Vanasse
Keyword(s):  
Vitamin D ◽  
Signaling Pathways ◽  
Vitamin D Deficiency ◽  
Vitamin D3 ◽  
Nuclear Translocation ◽  
K562 Cells ◽  
T Test ◽  
Dihydroxyvitamin D3 ◽  
Human Cd34 ◽  
Cd34 Cells

Abstract Abstract 2097 Anemia of inflammation (AI) has been widely associated with chronic rheumatologic, infectious, and cardiovascular disorders and comprises one-third of cases of anemia in the elderly. Although the antimicrobial peptide hepcidin is felt to be the prime regulator of AI, emerging evidence supports the premise that subsets of AI may be mediated via hepcidin-independent inflammatory pathways, such as those modulated by tumor necrosis factor alpha (TNFα), that directly suppress erythropoiesis. A better understanding of the pathophysiology of anemia subtypes is necessary if we are to develop more effective targeted, oral therapies for patients with inflammatory anemia. Our recent analysis of elderly participants in the Third National Health and Nutrition Examination Survey (NHANES III) revealed that vitamin D deficiency was strongly associated with AI in this population, with this subgroup exhibiting a rate of vitamin D deficiency nearly twice that of similarly aged non-anemic individuals. In the current study we aimed to evaluate whether vitamin D treatment may ameliorate TNFα-mediated erythroid colony suppression in humans. Human bone marrow-derived CD34+ cells from 3 healthy adults were first cultured in methylcellulose medium containing IL-3 (10ng/ml), EPO (1U/ml), SCF (50ng/ml) in the presence or absence of TNFα (25 ng/ml) and increasing doses of 1, 25-dihydroxyvitamin D3 [calcitriol, (0.01-1nM)], and erythroid burst-forming units (BFU-E) measured on day 14. The percentage of BFU-E colonies was reduced by 50% at day 14 in the presence of 25ng/ml TNFα (p < 0.01, t-test). TNFα-mediated suppression of erythropoiesis was reversed by the addition of vitamin D3 in a dose-dependent manner, with 1nM vitamin D3 resulting in a 50% recovery of BFU-E colony numbers at day 14 (p < 0.05, t-test). Vitamin D3 alone exhibited no significant effect on BFU-E formation at all concentrations tested. Based on studies showing that vitamin D receptor may serve as a negative regulator of NF-κB transcriptional activity, we next investigated whether vitamin D3 may alter TNFα-induced NF-κB activation in both K562 and human CD34+ cells. K562 cells pre-incubated with 1nM vitamin D3 for 3, 24, 48 and 72 hours were treated with 5 ng/ml TNFα for 30 minutes, and NF-κB activity in nuclear fraction was determined by an ELISA-format oligonucleotide binding assay. TNFα treatment alone markedly increased the oligonucleotide binding activity of the NF-κB p65 subunit, which was completely blocked by co-incubation with competitor oligonucleotide, confirming the assay specificity. Pre-incubation with vitamin D3 for 3 – 48 hours showed little effect on TNFα-mediated NF-κB activation, but pre-incubation for 72 hours resulted in suppression of TNFα-induced NF-κB activity by 46% (p < 0.02, t-test). Under similar conditions, human CD34+ cells pre-incubated with 1 nM vitamin D3 for 48 hours and 72 hours exhibited 38% and 84% suppression of TNFα-induced NF-κB activity, respectively (p < 0.01 for both conditions, t-test). Reduced NF-κB activity was correlated with the decreased nuclear translocation of NF-κB in K562 cells with no significant changes in IκB degradation, suggesting that vitamin D3 regulates the NF-κB nuclear translocation independent of IκB. Western analysis of whole cell lysates from both K562 and human CD34+ cells using antibodies recognizing known TNFα-associated signaling pathways revealed robust increases in phospho-p38, phospho-JNK, and phospho-ERK1/2 in response to TNFα stimulation compared with control, with no inhibition of these signaling pathways noted in response to vitamin D3 treatment at all doses tested, suggesting that vitamin D3 does not inhibit these TNFα-induced signaling cascades. Our study indicates that 1, 25-dihydroxyvitamin D3 significantly ameliorates TNFα-mediated suppression of erythroid colony development in human CD34+ cells via mechanisms that involve modulation of NF-κB signaling pathways and supports the design of future clinical trials examining whether vitamin D3 supplementation may prove to be an effective therapy for subgroups of patients with TNFα-mediated inflammatory anemia. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Laboratory Parameters of Bone Metabolism in Premature Infants and Children Born Using In Vitro Fertilization

2021 ◽  
Vol 20 (6) ◽  
pp. 103-110
Author(s):  
Natalya A. Natalya A. Druzhinina ◽  
Dinara R. Merzlyakova ◽  
Gulnaz A. Vakhitova ◽  
Zilia А. Shangareeva ◽  
Aliya R. Khabibullina ◽  
...  
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Bone Metabolism ◽  
Vitamin D Deficiency ◽  
Premature Infants ◽  
Type I Collagen ◽  
Plasma Vitamin ◽  
Type I ◽  
Premature Babies ◽  
Low Weight

Aim. To study the indicators of bone metabolism in premature babies born naturally and children born with IVF. Material and methods. The premature babies’ study was conducted, they were divided into 4 groups: depending on the method of birth and weight: 1st-children born with IVF, with very low weight; the second group – similar to the first, but children with extremely low weight; the third – children with very low weight, born naturally, with ; the fourth – similar to the 3rd, but with extremely low weight. The level of calcium, parathyroid hormone, calcitonin and C-terminal telopeptides of type I collagen was determined. Results and discussion. Diagnosis of vitamin D deficiency is possible only by measuring certain biochemical parameters, primarily the levels of its metabolites in the blood. Clinical symptoms of vitamin D deficiency in the form of rickets, osteomalacia, osteoporosis and extra-skeletal manifestations as a result of this vitamin deficiency occur over a long period of time. The most informative indicator of the body’s vitamin D supply is the content of calcidiol [25 (OH)D] in both serum and blood plasma. Vitamin D deficiency was detected in more than half (67.7±4.8%) of premature newborns in the first year of life. It seemed that in premature babies born in different ways, vitamin D deficiency was noted in 8 %, insufficiency – in 67.7 %, and the normal content in 27.5 %. In children at an early age, there is a violation of bone metabolism (an increase in the level of calcium, parathyroid hormone, calcitonin, on the one hand, and a decrease in the C-terminal telopeptides of type I collagen, on the other). These changes were associated with the weight of children, while aggressive disorders were noted in children with extremely low weight. In premature infants (with a body weight of less than 1500 g), monitoring of the level of vitamin D in the blood and C-terminal telopeptides of type 1 collagen should be recommended. Conclusion. Bone modeling has a great advantage due to the analysis of the blood serum biomarkers levels in premature infants, it enables to establish the features of osteogenesis.

scholarly journals Markers Indicating Body Vitamin D Stores and Responses of Liver and Adipose Tissues to Changes in Vitamin D Intake in Male Mice

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1391
Author(s):  
Mikis Kiourtzidis ◽  
Julia Kühn ◽  
Corinna Brandsch ◽  
Anja-Christina Baur ◽  
Monika Wensch-Dorendorf ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D3 ◽  
Rapid Decline ◽  
Plasma Vitamin ◽  
Vitamin D Status ◽  
Male Mice ◽  
Adipose Tissues ◽  
Dihydroxyvitamin D3 ◽  
Hydroxyvitamin D ◽  
Vitamin D Intake

Circulating 25-hydroxyvitamin D (25(OH)D) is regarded as the most reliable biomarker of vitamin D status. However, limited data exist concerning the suitability of 25(OH)D as an indicator of body vitamin D stores and the ability of adipose tissue to mobilize vitamin D. In the first study, in which male mice received different vitamin D3 doses for three weeks, we found strong linear response relationships between vitamin D3 intake and levels of vitamin D3 in the plasma (p < 0.001), liver (p < 0.001) and adipose tissues (p < 0.001), and strong positive correlations between plasma and tissue stores of vitamin D3 (p < 0.001). Plasma levels of 25(OH)D3 and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) showed weak or no correlations with tissue vitamin D3 stores. Data from a second study demonstrate a strong and rapid response of plasma 25(OH)D3 in vitamin D3-treated mice with a low vitamin D status. Additionally, mice fed a vitamin D-free diet showed a strong and rapid decline in vitamin D3 in the liver, whereas the decline in different adipose tissues was distinctly lower than that in the liver. To conclude, tissue stores of vitamin D3 were best reflected by plasma vitamin D3. In contrast to the liver, adipose tissues responded less sensitively to an absence of vitamin D intake.

Vitamin D3 metabolism in a pig strain with pseudo vitamin D-deficiency rickets, type I

1987 ◽  
Vol 115 (3) ◽  
pp. 345-352 ◽  
Author(s):  
Reinhard Kaune ◽  
Johein Harmeyer
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Type I ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Before And After ◽  
25 Hydroxyvitamin D ◽  
Deficiency Rickets ◽  
Clinical Healing

Abstract. Vitamin D metabolism was studied in the 'Hannover Pig', a strain which suffers from pseudo vitamin D-deficiency rickets, type I. Animals of this strain are known to be devoid of renal 25-hydroxyvitamin D3-1α-hydroxylase and -24-hydroxylase activities. Pigs with florid rickets and hypocalcaemia were treated with single im injections of 0.25 to 1.25 mg of vitamin D3, doses that have been shown in previous studies to be effective in producing transient healing of rachitic symptoms. The levels of vitamin D3 and its most relevant physiological metabolites in plasma were estimated at intervals before and after this vitamin D3 treatment. Vitamin D3 rose from 14.8 ± 8.1 to 364 ± 190 nmol/l (mean ± sd) 2 to 3 days post injectionem, 25-hydroxyvitamin D3 from 131.0 ± 46.2 to 1068 ± 160 nmol/l within 7 days post injectionem. The 1α,25-dihydroxyvitamin D3 concentration in plasma was elevated from 73.9 ± 25.0 to 281 ± 168 pmol/l 2 to 3 days post injectionem and declined continually from that time. 24R,25-dihydroxyvitamin D3 and 25S,26-dihydroxyvitamin D3 levels after treatment showed different responses in different animals being either elevated or unchanged. Clinical healing of the pigs with these doses of vitamin D3 was attributed to the transient rise of 1α,25-dihydroxyvitamin D3 in plasma. It was assumed that 1α,25-dihydroxyvitamin D3 synthesis takes place under these circumstances in extrarenal tissues.

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