scholarly journals Electrochemical Oxidation as a Tool for Generating Vitamin D Metabolites

Molecules ◽  
2019 ◽  
Vol 24 (13) ◽  
pp. 2369 ◽  
Author(s):  
Navarro Suarez ◽  
Thein ◽  
Kallinich ◽  
Rohn
Keyword(s):  
Vitamin D ◽  
Phase Ii ◽  
Animal Studies ◽  
Ph Value ◽  
Oxidation Products ◽  
In Vitro Test ◽  
Vitamin D Metabolites ◽  
Constant Potential

The electrochemical behavior of the vitamers cholecalciferol and ergocalciferol was investigated in order to determine whether it is possible to evaluate phase-I and phase-II metabolism of these steroids and yield metabolites that can serve as reference material. The vitamers were electrochemically-oxidized using an electrochemical system (ROXY™ EC system). The influence of pH value, solvent, and potential was evaluated. When using methanol or ethanol, the formation of artificial methoxy or ethoxy groups, respectively, was observed, while the use of acetonitrile did not show any formation of further functional groups. A neutral pH value and use of a constant potential led to the highest number of oxidation products with intensive signals. Additionally, a binding study between vitamin D and glucuronic acid as an example for phase-II conjugation was carried out. It was possible to detect adduct formation. Coupling mass spectrometry directly to electrochemistry (EC-MS) is a promising approach for generating vitamin D metabolites and/or yielding a number of metabolites without in vivo or in vitro test systems. It can support or even replace animal studies in the long-term and might be promising for yielding reference compounds.

scholarly journals Epimers of Vitamin D: A Review

2020 ◽  
Vol 21 (2) ◽  
pp. 470 ◽  
Author(s):  
Bashar Al-Zohily ◽  
Asma Al-Menhali ◽  
Salah Gariballa ◽  
Afrozul Haq ◽  
Iltaf Shah
Keyword(s):  
Vitamin D ◽  
Biological Activity ◽  
Hydroxyl Group ◽  
Vitamin D Metabolites ◽  
Dihydroxyvitamin D3 ◽  
In Vivo Models ◽  
Vitamin D Receptors ◽  
Potential Factors

In this review, we discuss the sources, formation, metabolism, function, biological activity, and potency of C3-epimers (epimers of vitamin D). We also determine the role of epimerase in vitamin D-binding protein (DBP) and vitamin D receptors (VDR) according to different subcellular localizations. The importance of C3 epimerization and the metabolic pathway of vitamin D at the hydroxyl group have recently been recognized. Here, the hydroxyl group at the C3 position is orientated differently from the alpha to beta orientation in space. However, the details of this epimerization pathway are not yet clearly understood. Even the gene encoding for the enzyme involved in epimerization has not yet been identified. Many published research articles have illustrated the biological activity of C3 epimeric metabolites using an in vitro model, but the studies on in vivo models are substantially inadequate. The metabolic stability of 3-epi-1α,25(OH)2D3 has been demonstrated to be higher than its primary metabolites. 3-epi-1 alpha, 25 dihydroxyvitamin D3 (3-epi-1α,25(OH)2D3) is thought to have fewer calcemic effects than non-epimeric forms of vitamin D. Some researchers have observed a larger proportion of total vitamin D as C3-epimers in infants than in adults. Insufficient levels of vitamin D were found in mothers and their newborns when the epimers were not included in the measurement of vitamin D. Oral supplementation of vitamin D has also been found to potentially cause increased production of epimers in mice but not humans. Moreover, routine vitamin D blood tests for healthy adults will not be significantly affected by epimeric interference using LC–MS/MS assays. Recent genetic models also show that the genetic determinants and the potential factors of C3-epimers differ from those of non-C3-epimers.Most commercial immunoassays techniques can lead to inaccurate vitamin D results due to epimeric interference, especially in infants and pregnant women. It is also known that the LC–MS/MS technique can chromatographically separate epimeric and isobaric interference and detect vitamin D metabolites sensitively and accurately. Unfortunately, many labs around the world do not take into account the interference caused by epimers. In this review, various methods and techniques for the analysis of C3-epimers are also discussed. The authors believe that C3-epimers may have an important role to play in clinical research, and further research is warranted.

Effects of 1,25- and 24,25-dihydroxycholecalciferol on parathyroid hormone release from human parathyroid cells in vitro

1984 ◽  
Vol 105 (3) ◽  
pp. 354-359 ◽  
Author(s):  
Claes Rudberg ◽  
Göran Åkerström ◽  
Henry Johansson ◽  
Sverker Ljunghall ◽  
Jan Malmaeus ◽  
...  
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Parathyroid Tissue ◽  
Vitamin D Metabolites ◽  
Hormone Release ◽  
High Doses ◽  
Parathyroid Hormone Release ◽  
Dispersed Cells

Abstract. The effects of 125-dihydroxycholecalciferol (1,25-(OH)2D3) and 24,25-dihydroxycholecalciferol (24,25-(OH)2D3) on parathyroid hormone (PTH) release from human parathyroid cells were investigated using an in vitro system of dispersed cells. The cells were obtained from 7 patients with primary hyperparathyroidism (HPT) and adenoma, 4 patients with primary HPT due to hyperplasia and 2 patients with parathyroid hyperplasia secondary to chronic renal failure. The dispersed cells were incubated in tissue culture medium at low, normal and high external calcium concentrations for 2–16 h. There was a gradual suppression of PTH release (5–55%) when the calcium concentration in the medium was increased from 0.5 to 3.0 mM, thus indicating retained regulation of hormone release. The addition of 1,25-(OH)2D3 in concentrations of 0.1 and 1 ng/ml and of 24,25-(OH)2D3 in concentrations of 1.0 and 10 ng/ml during the incubations did not further affect the amount of PTH released by the cells. The concentrations of the different vitamin D metabolites tested closely correspond to levels observed under normal physiological conditions and during treatment with high doses of vitamin D in vivo. Thus, the findings contradict the idea of any direct short-term regulatory effect of either 1,25-(OH)2D3 or 24,25-(OH)2D3 on the secretion of PTH from hyperfunctioning human parathyroid tissue.

scholarly journals The Pleiotropic Effects of Vitamin D in Gynaecological and Obstetric Diseases: An Overview on a Hot Topic

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Francesca Colonese ◽  
Antonio Simone Laganà ◽  
Elisabetta Colonese ◽  
Vincenza Sofo ◽  
Francesca Maria Salmeri ◽  
...  
Keyword(s):  
Vitamin D ◽  
Metabolic Pathways ◽  
Polycystic Ovary ◽  
Serum Levels ◽  
In Vivo Studies ◽  
Vitamin D Metabolites ◽  
Vitamin D Metabolism ◽  
Vitamin D Levels

The traditionally recognized role of vitamin D consists in the regulation of bone metabolism and calcium-phosphorus homeostasis but recently a lot of in vitro and in vivo studies recognized several “noncalcemic” effects of vitamin D metabolites. Accumulating evidence suggests that the metabolic pathways of this vitamin may play a key role in the developing of gynaecological/obstetric diseases. VDR-mediated signalling pathways and vitamin D levels seem to (deeply) affect the risk of several gynaecological diseases, such as polycystic ovary syndrome (PCOS), endometriosis, and ovarian and even breast cancer. On the other hand, since also the maternal-fetal unit is under the influence of vitamin D, a breakdown in its homeostasis may underlie infertility, preeclampsia, and gestational diabetes mellitus (GDM). According to our literature review, the relationship between vitamin D and gynaecological/obstetric diseases must be replicated in future studies which could clarify the molecular machineries behind their development. We suggest that further investigation should take into account the different serum levels of this vitamin, the several actions which arise from the binding between it and its receptor (taking into account its possible polymorphism), and finally the interplay between vitamin D metabolism and other hormonal and metabolic pathways.

scholarly journals Comparison of In Vivo (Draize Method) and In Vitro (Corrositex Assay) Dermal Corrosion Values for Selected Industrial Chemicals

2003 ◽  
Vol 22 (2) ◽  
pp. 99-107 ◽  
Author(s):  
Jody L. Stobbe ◽  
Kevin D. Drake ◽  
Kurt J. Maier
Keyword(s):  
Animal Studies ◽  
Skin Irritation ◽  
Worker Safety ◽  
In Vitro Test ◽  
Industrial Chemicals ◽  
In Vivo Test ◽  
End Point ◽  
Dermal Irritation

Skin irritation is a common occupational hazard for employees engaged in the manufacture, transport, and use of industrial chemicals. The most common method used to evaluate dermal irritation and/or corrosion has typically been in vivo tests using rabbits (Draize method). Several in vitro test methods have been developed, with Corrositex being the first to gain approval by a regulatory agency (U.S. Department of Transportation). The purpose of this study was to compare the results of in vitro (Corrositex) assays of dermal irritation/corrosion to in vivo test data for several industrial chemical formulations and to determine the predictability and usefulness of the Corrositex assay for these types of products. Twenty-four (24) formulations were qualified, categorized, and evaluated using the Corrositex method and the results compared to available animal data for each of the formulations. The Corrositex assay accurately predicted a corrosive end point in 8 (57.1%) of the 14 formulations identified as corrosive by the in vivo evaluations. Corrositex accurately predicted a noncorrosive end point for 1 (10%) of 10 formulations determined to be noncorrosive in animal studies. The Corrositex assay overpredicted the packing group for 12 (50%) of the 24 formulations, and underpredicted the packing group for 7 (29.2%) of the 24 formulations. Compared to the in vivo results, Corrositex correctly classified as corrosive or noncorrosive 37.5% of the formulations tested. A concordance of 20.8% for the packing group assignments of the evaluated formulations was calculated. The Corrositex assay did not accurately predict a corrosive end point or packing group assignment for all of the formulations used in this study. Manufacturers should assess the relevance of this method to their products prior to relying on it for compliance with hazardous material and worker safety regulations.

Effect of Mixing Bioactive Nanoceramics with a Thermosensitive Hydrogel as Bone Substitute

2012 ◽  
Vol 622-623 ◽  
pp. 1794-1798 ◽  
Author(s):  
Po Liang Lai ◽  
Ding Wei Hong ◽  
Carl Tsai Yu Lin ◽  
Lih Huei Chen ◽  
Wen Jer Chen ◽  
...  
Keyword(s):  
Animal Studies ◽  
Ph Value ◽  
Sol Gel ◽  
Degradation Process ◽  
Thermosensitive Hydrogel ◽  
Composite Gels ◽  
Bone Graft Substitutes ◽  
Sol Gel Transition

The composite of methoxy polyethylene glycol (mPEG) and poly(lactic-co- glycolic acid) (PLGA) thermosensitive hydrogel mixed with different mass raio of hydroxyapatite and β-tricalcium phosphate (β-TCP) were used as bone graft substitutes. The physical properties of a series of composite gels, including the critical micelle concentration (CMC), particle sizes, zeta potential, rheological behavior, morphology of composite gels, and sol–gel transition, were characterized in vitro. These composite gels could form a gel at body temperature and could be controlled easily at room temperature. During the in vitro degradation process, composite gels demonstrated a slight decrease in pH value, a slower degradation rate, less toxicity, and a higher cell survival rate. The biocompatibility of the composite gels was validated by hemolysis test. In vivo animal studies demonstrated both radiographic and gross bone union when the ratio of HAP/ β-TCP was 7:3.

Effect of magnesium depletion on metabolism of 25-hydroxyvitamin D in rats

1987 ◽  
Vol 253 (1) ◽  
pp. E106-E113
Author(s):  
T. O. Carpenter ◽  
D. L. Carnes ◽  
C. S. Anast
Keyword(s):  
Vitamin D ◽  
Animal Studies ◽  
Magnesium Deficiency ◽  
Hydroxylase Activity ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Magnesium Depletion ◽  
25 Hydroxyvitamin D

Resistance to vitamin D in magnesium depletion has been observed in humans and in animal studies. Variable levels of 1,25-dihydroxyvitamin D [1,25(OH)2D] have been reported in patients with magnesium depletion, and studies of vitamin D metabolism in states of magnesium depletion have not yielded consistent results. We examined effects of magnesium deprivation on circulating 1,25(OH)2D levels before and after a loading dose of 25-hydroxyvitamin D3 [25(OH)D3], on in vivo conversion of small doses of radiolabeled 25(OH)D3 to 1,25(OH)2D3 in intact rats, and on in vitro 25-hydroxyvitamin D-1 alpha-hydroxylase (1 alpha-hydroxylase) activity in rat renal mitochondria. The effects of magnesium-free media on mitochondrial 1 alpha-hydroxylase activity was examined. Magnesium depletion did not affect in vivo conversion of 25(OH)D to 1,25(OH)2D. In vitro 1 alpha-hydroxylase activity was comparable in magnesium-replete and -deplete animals and was evident in the absence of added magnesium in incubation media. Our in vivo and in vitro studies are consistent with one another and demonstrate that in the rat conversion of 25(OH)D to 1,25(OH)2D is unimpaired in magnesium deficiency. Resistance to vitamin D in magnesium depletion is likely due to the impaired skeletal responsivity to 1,25(OH)2D, as demonstrated in earlier studies.

Decellularized bone extracellular matrix in skeletal tissue engineering

2020 ◽  
Vol 48 (3) ◽  
pp. 755-764
Author(s):  
Benjamin B. Rothrauff ◽  
Rocky S. Tuan
Keyword(s):  
Tissue Engineering ◽  
Bone Regeneration ◽  
Tissue Regeneration ◽  
Animal Studies ◽  
Tumor Resection ◽  
Regenerative Capacity ◽  
Skeletal Tissue ◽  
Large Bone

Bone possesses an intrinsic regenerative capacity, which can be compromised by aging, disease, trauma, and iatrogenesis (e.g. tumor resection, pharmacological). At present, autografts and allografts are the principal biological treatments available to replace large bone segments, but both entail several limitations that reduce wider use and consistent success. The use of decellularized extracellular matrices (ECM), often derived from xenogeneic sources, has been shown to favorably influence the immune response to injury and promote site-appropriate tissue regeneration. Decellularized bone ECM (dbECM), utilized in several forms — whole organ, particles, hydrogels — has shown promise in both in vitro and in vivo animal studies to promote osteogenic differentiation of stem/progenitor cells and enhance bone regeneration. However, dbECM has yet to be investigated in clinical studies, which are needed to determine the relative efficacy of this emerging biomaterial as compared with established treatments. This mini-review highlights the recent exploration of dbECM as a biomaterial for skeletal tissue engineering and considers modifications on its future use to more consistently promote bone regeneration.

Akalzämische Vitamin-D-Analoga zeigen antifibrotische Effekte in vitro in hepatischen Sternzellen und in vivo im CCl4-Mausmodell

2019 ◽  
Author(s):  
FP Reiter ◽  
L Ye ◽  
F Bösch ◽  
R Wimmer ◽  
R Artmann ◽  
...  
Keyword(s):  
Vitamin D

Vitamin D as potential therapeutic anticancer agent

2018 ◽  
pp. 1-3
Keyword(s):  
Vitamin D ◽  
Anticancer Activity ◽  
Anticancer Agent ◽  
Antitumor Agents ◽  
Metastatic Potential ◽  
Anticancer Properties ◽  
Chemotherapy Agents

The role of vitamin D is implicated in carcinogenesis through numerous biological processes like induction of apoptosis, modulation of immune system inhibition of inflammation and cell proliferation and promotion of cell differentiation. Its use as additional adjuvant drug with cancer treatment may be novel combination for improved outcome of different cancers. Numerous preclinical, epidemiological and clinical studies support the role of vitamin D as an anticancer agent. Anticancer properties of vitamin D have been studied widely (both in vivo and in vitro) among various cancers and found to have promising results. There are considerable data that indicate synergistic potential of calcitriol and antitumor agents. Possible mechanisms for modulatory anticancer activity of vitamin D include its antiproliferative, prodifferentiating, and anti-angiogenic and apoptic properties. Calcitriol reduces invasiveness and metastatic potential of many cancer cells by inhibiting angiogenesis and regulating expression of the key molecules involved in invasion and metastasis. Anticancer activity of vitamin D is synergistic or additive with the antineoplastic actions of several drugs including cytotoxic chemotherapy agents like paclitaxel, docetaxel, platinum base compounds and mitoxantrone. Benefits of addition of vitamin D should be weighed against the risk of its toxicity.

In vitro Lipolysis as a Tool for the Establishment of IVIVC for Lipid-Based Drug Delivery Systems

2019 ◽  
Vol 16 (8) ◽  
pp. 688-697
Author(s):  
Ravinder Verma ◽  
Deepak Kaushik
Keyword(s):  
Drug Delivery ◽  
Ph Value ◽  
Electron Paramagnetic Resonance Spectroscopy ◽  
Rapid Screening ◽  
Resonance Spectroscopy ◽  
Fed State ◽  
In Vitro Lipolysis ◽  
Ph Stat

: In vitro lipolysis has emerged as a powerful tool in the development of in vitro in vivo correlation for Lipid-based Drug Delivery System (LbDDS). In vitro lipolysis possesses the ability to mimic the assimilation of LbDDS in the human biological system. The digestion medium for in vitro lipolysis commonly contains an aqueous buffer media, bile salts, phospholipids and sodium chloride. The concentrations of these compounds are defined by the physiological conditions prevailing in the fasted or fed state. The pH of the medium is monitored by a pH-sensitive electrode connected to a computercontrolled pH-stat device capable of maintaining a predefined pH value via titration with sodium hydroxide. Copenhagen, Monash and Jerusalem are used as different models for in vitro lipolysis studies. The most common approach used in evaluating the kinetics of lipolysis of emulsion-based encapsulation systems is the pH-stat titration technique. This is widely used in both the nutritional and the pharmacological research fields as a rapid screening tool. Analytical tools for the assessment of in vitro lipolysis include HPLC, GC, HPTLC, SEM, Cryo TEM, Electron paramagnetic resonance spectroscopy, Raman spectroscopy and Nanoparticle Tracking Analysis (NTA) for the characterization of the lipids and colloidal phases after digestion of lipids. Various researches have been carried out for the establishment of IVIVC by using in vitro lipolysis models. The current publication also presents an updated review of various researches in the field of in vitro lipolysis.

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