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1.
Arch Anim Nutr ; 73(1): 44-51, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31274343

RESUMO

The study evaluated the effects of different doses of 25-hydroxyvitamin D3 (25(OH)D3) on growth performance, immune function and antioxidative capacity in piglets. In a 21-d trial, 35 weaned pigs were divided into five groups and diets were supplemented with 5.5 (control), 43.0, 80.5, 118.0 and 155.5 µg 25(OH)D3/kg, respectively. No treatment effects were observed for average daily gain, average daily feed intake and feed to gain ratio. Increasing dietary 25(OH)D3 levels increased serum 25(OH)D3 concentrations linearly (p < 0.01), decreased the frequency of CD3+CD4+ and CD3+CD8+ T cells (p < 0.01), and the serum level of complement component 3 (p < 0.05). Supplementation of 80.5 and 118.0 µg 25(OH)D3/kg enhanced the activity of serum glutathione peroxidase (p < 0.05) and addition of 43.0 µg 25(OH)D3/kg increased the malondialdehyde concentration (p < 0.05). Overall, feeding high-dose 25(OH)D3 to weaned pigs partly improved immune functions and the antioxidative capacity.


Assuntos
Antioxidantes/metabolismo , Calcifediol/metabolismo , Imunidade Inata/imunologia , Sus scrofa/fisiologia , Vitaminas/metabolismo , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Calcifediol/administração & dosagem , Dieta/veterinária , Suplementos Nutricionais/análise , Imunidade Inata/efeitos dos fármacos , Sus scrofa/crescimento & desenvolvimento , Sus scrofa/imunologia , Vitaminas/administração & dosagem , Desmame
2.
J Steroid Biochem Mol Biol ; 194: 105435, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31352023

RESUMO

Factors that can modify the bioavailability of orally administered vitamin D are not yet widely known. Ergosterol is a common fungal sterol found in food which has a chemical structure comparable to that of vitamin D. This study aimed to investigate the effect of ergosterol on vitamin D metabolism. Therefore, 36 male wild type-mice were randomly subdivided into three groups (n = 12) and received a diet containing 25 µg vitamin D3 and either 0 mg (control), 2 mg or 7 mg ergosterol per kg diet for 6 weeks. To elucidate the impact of ergosterol on hepatic hydroxylation of vitamin D, human hepatoma cells (HepG2) were treated with different concentrations of ergosterol. Concentrations of vitamin D3 and 25-hydroxyvitamin D3 (25(OH)D3) in cells, livers and kidneys of mice and additionally 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) in serum were quantified by LC-MS/MS. The concentration of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in serum was analyzed by commercially-available enzyme immuno assay. The concentrations of cholesterol and triglycerides were analyzed in livers of mice by photometric assays. Analyses revealed that mice receiving 7 mg/kg ergosterol with their diet had 1.3-, 1.7- and 1.5-times higher concentrations of vitamin D3 in serum, liver and kidney, respectively, than control mice (P < 0.05), whereas no significant effects were observed in mice fed 2 mg/kg ergosterol. The hydroxylation of vitamin D remained unaffected by dietary ergosterol, since the concentration of 25-hydroxyvitamin D3 in serum and tissues and the concentrations of 1,25(OH)2D3 and 24,25(OH)2D3 in serum were not different between the three groups of mice. The lipid concentrations in liver were also not affected by dietary ergosterol. Data from the cell culture studies showed that ergosterol did not influence the conversion of vitamin D3 to 25(OH)D3. To conclude, ergosterol appears to be a modulator of vitamin D3 concentrations in the body of mice, without modulating the hydroxylation of vitamin D3 in liver.


Assuntos
Colecalciferol/farmacologia , Ergosterol/farmacologia , Vitaminas/farmacologia , 24,25-Di-Hidroxivitamina D 3/sangue , 24,25-Di-Hidroxivitamina D 3/metabolismo , Animais , Calcifediol/sangue , Calcifediol/metabolismo , Colecalciferol/sangue , Colecalciferol/farmacocinética , Células Hep G2 , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Vitaminas/sangue , Vitaminas/farmacocinética
3.
Arch Anim Nutr ; 73(4): 271-286, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31192703

RESUMO

To investigate the effects of maternal 25-hydroxycholecalciferol (25OHD3) supplementation during lactation on nutrient digestibility and milk composition of sows and gut bacterial metabolites and their metabolites in the hindgut of suckling piglets, 24 Large White × Landrace sows were assigned randomly to one of two dietary treatments (Diet ND: 2000 IU vitamin D3/kg feed; Diet 25-D: 50 µg 25OHD3/kg feed). The experiment began on d 107 of gestation and continued until weaning on d 21 of lactation. Maternal 25OHD3 supplementation increased (p < 0.05) total litter weight gain during lactation. Milk fat content, immunoglobulin G level on d 21 of lactation and 25OHD3 concentration on d 7, 14, and 21 of lactation were higher (p < 0.05) in sows fed with 25OHD3. Apparent total tract digestibility of dietary calcium was higher (p < 0.05) in 25-D sows than ND sows. With respect to fatty-acid profile, C16:0 and saturated fatty acids in milk were higher (p < 0.05), but C20:4n-6, the ratios of monounsaturated fatty acids to saturated fatty acids and polyunsaturated fatty acids to saturated fatty acids were lower (p < 0.05) in 25-D sows than ND sows. 25OHD3 supplementation increased the mRNA expressions of acetyl-CoA carboxylase α and fatty-acid synthase in the mammary gland of lactating sows. For gut bacterial metabolites, concentration of butyrate in the caecal digesta was higher (p < 0.05) in piglets suckling 25-D sows than piglets suckling ND sows. In conclusion, 25OHD3 supplementation in maternal diets changed dietary calcium digestibility, milk composition and milk fatty-acid profile of lactating sows and altered gut bacterial metabolites in the hindgut of suckling piglets.


Assuntos
Calcifediol/metabolismo , Digestão/fisiologia , Ácidos Graxos/metabolismo , Microbioma Gastrointestinal/fisiologia , Leite/química , Sus scrofa/fisiologia , Vitaminas/metabolismo , Ração Animal/análise , Animais , Animais Lactentes , Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Calcifediol/administração & dosagem , Dieta/veterinária , Suplementos Nutricionais/análise , Digestão/efeitos dos fármacos , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Intestino Grosso/fisiologia , Lactação , Fenômenos Fisiológicos da Nutrição Materna , Leite/efeitos dos fármacos , Nutrientes/metabolismo , Sus scrofa/microbiologia , Vitaminas/administração & dosagem
4.
Poult Sci ; 98(11): 6108-6116, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31222260

RESUMO

The study aimed to examine the effects of 25-hydroxycholecalciferol (25-OH-D3) on reproductive performance and livability in broiler breeder hens. Hens at age of 26 wk were continued on restricted rations (R) or allowed ad libitum feeding (Ad) to 60 wk of age. Ad-feed intake greatly impaired egg production and hens' livability. The survival rate in both R- and Ad-hens was improved (86.7 vs.78.9% and 48.2 vs.29.1%, respectively) as was egg production in R-hens (P < 0.05) by inclusion of 69 µg 25-OH-D3/kg feedin the basal diet. Sudden death (SD) was the cause of hen mortality; hens died earlier with heavier BW and greater absolute and relative abdominal fat weights than surviving hens. Interestingly, feed intake of SD hens became less than that of surviving hens after 37 and 42 wk in Ad- and R-groups, respectively, and led to a progressive decline in SD hen BW with a ratio (relative to surviving hens of the same age) equaled 1 around 34 to 38 wk in Ad-groups and 52 to 53 wk in R-groups. Supplementation of 25-OH-D3 ameliorated untoward changes of heart and respiratory rate of Ad-survivors after 29 wk (P < 0.05), but had no significant effects on SD AD-hens. In contrast to the surviving counterparts, all SD hens experienced persistently higher respiratory rates in conjunction with declining heart rates (P < 0.05), suggesting compromised cardiac function as the cause of SD, in which hens increased heart and respiratory rate for more blood and oxygen supply to meet the need for rapid BW gain and/or adiposity in response to Ad-feed intake or due to genetically better feed efficiency even under R-feed intake. As the cardiorespiratory derangements advanced, compromised cardiac function ultimately led to heart failure and sudden death despite spontaneous reductions in feed intake and BW loss in all SD hens. Provision of 69 µg 25-OH-D3/kg feed is an effective and practical method to improve livability in broiler breeder hens.


Assuntos
Calcifediol/metabolismo , Galinhas/fisiologia , Longevidade/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Vitaminas/metabolismo , Ração Animal/análise , Animais , Calcifediol/administração & dosagem , Dieta/veterinária , Suplementos Nutricionais/análise , Feminino , Vitaminas/administração & dosagem
5.
Poult Sci ; 98(11): 5679-5690, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31222321

RESUMO

Coccidiosis penalizes calcium (Ca), phosphorus (P), and fat-soluble vitamin status, as well as bone mineralization in broiler chickens. We hypothesized that dietary vitamin D (VitD) supplementation in the form of 25-hydroxycholecalciferol (OHD), compared to cholecalciferol (D3), would improve bone mineralization in broilers receiving marginally deficient Ca/P diets, with more pronounced effects during malabsorptive coccidiosis. In a 2 VitD source × 2 Ca/P levels × 2 levels of infection factorial experiment (n = 6 pens per treatment, 6 birds/pen), Ross 308 broilers were assigned to an Aviagen-specified diet supplemented with 4,000 IU/kg of either OHD or D3 between days 11 and 24 of age. The diet contained adequate (A; 8.7:4.4 g/kg) or marginally deficient (M; 6.1:3.1 g/kg) total Ca and available (av)P levels. At day 12 of age, birds were inoculated with water (C) or 7,000 Eimeria maxima oocysts (I). Pen performance was measured over 12 days post-infection (pi). One bird per pen was assessed for parameters of bone mineralization and intestinal histomorphometric features (day 6 and 12 pi), as well as E. maxima replication and gross lesions of the small intestine (day 6 pi). There was no interaction between infection status and Ca/avP level on bone mineralization. Bone breaking strength (BS), ash weight (AW), and ash percentage (AP) were highest in broilers fed the OHD-supplemented A diets irrespective of infection status. Eimeria maxima infection impaired (P < 0.05) ADG and FCR pi; Ca and P status at day 6 pi; OHD status, BS, AW, and AP at day 12 pi; and intestinal morphology at day 6 and 12 pi. A- compared to M-fed broilers had higher BS, AW, and AP at day 6 pi, and AW at day 12 pi. VitD source affected only OHD status, being higher (P < 0.001) for OHD- than D3-fed broilers at day 6 and 12 pi. In conclusion, offering OHD and adequate levels of Ca and P improved bone mineralization, with no effect on performance. Dietary D3 and OHD supplemented at 4,000 IU/kg had similar effects on coccidiosis-infected and uninfected broilers, which led to the rejection of our hypothesis.


Assuntos
Cálcio/deficiência , Galinhas/fisiologia , Colecalciferol/metabolismo , Fósforo/deficiência , Vitaminas/metabolismo , Ração Animal/análise , Animais , Calcifediol/administração & dosagem , Calcifediol/metabolismo , Calcificação Fisiológica/efeitos dos fármacos , Cálcio na Dieta/análise , Galinhas/crescimento & desenvolvimento , Colecalciferol/administração & dosagem , Coccidiose/parasitologia , Coccidiose/veterinária , Dieta/veterinária , Suplementos Nutricionais/análise , Eimeria/fisiologia , Intestinos/efeitos dos fármacos , Intestinos/fisiologia , Fósforo na Dieta/análise , Doenças das Aves Domésticas/parasitologia , Vitaminas/administração & dosagem
6.
Nutrients ; 11(5)2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31064117

RESUMO

Hypovitaminosis D is becoming a notable health problem worldwide. A consensus exists among several different medical societies as to the need for adequate levels of vitamin D for bone and general health. The correct method by which to restore normal vitamin D levels is still a matter of debate. Although cholecalciferol remains the most commonly distributed form of vitamin D supplementation worldwide, several drugs with vitamin D activity are available for clinical use, and making the correct selection for the individual patient may be challenging. In this narrative review, we aim to contribute to the current knowledge base on the possible and appropriate use of calcifediol-the 25-alpha-hydroxylated metabolite-in relation to its chemical characteristics, its biological properties, and its pathophysiological aspects. Furthermore, we examine the trials that have aimed to evaluate the effect of calcifediol on the restoration of normal vitamin D levels. Calcifediol is more soluble than cholecalciferol in organic solvents, due to its high polarity. Good intestinal absorption and high affinity for the vitamin-D-binding protein positively affect the bioavailability of calcifediol compared with cholecalciferol. In particular, orally administered calcifediol shows a much shorter half-life than oral cholecalciferol. Most findings suggest that oral calcifediol is about three- to five-fold more powerful than oral cholecalciferol, and that it has a higher rate of intestinal absorption. Accordingly, calcifediol can be particularly useful in treating diseases associated with decreased intestinal absorption, as well as obesity (given its lower trapping in the adipose tissue) and potentially neurological diseases treated with drugs that interfere with the hepatic cytochrome P-450 enzyme system, resulting in decreased synthesis of calcifediol. Up to now, there has not been enough clinical evidence for its use in the context of osteoporosis treatment.


Assuntos
Calcifediol/uso terapêutico , Deficiência de Vitamina D/tratamento farmacológico , Osso e Ossos/metabolismo , Calcifediol/metabolismo , Cálcio/metabolismo , Cálcio/farmacocinética , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Humanos
7.
Nutrients ; 11(5)2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31036792

RESUMO

Salmon have been widely publicized as a good dietary source of vitamin D, but recent data points to large variation in vitamin D content and differences between wild and farmed salmon. We aimed to: (1) investigate the content of vitamin D in Atlantic salmon (Salmo salar) in wild species caught in two different waters, (2) perform a 12-week feeding trial in farmed Salmo salar with 270-1440 µg vitamin D3/kg feed (4-20 times maximum level in the EU) and (3) conduct a review for the published data on the content of vitamin D in salmonids. Content of vitamin D3 in the fillet from wild salmon caught in the Baltic Sea and the North Sea was significantly different (p < 0.05), being 18.5 ± 4.6 µg/100 g and 9.4 ± 1.9 µg/100 g, respectively. In the farmed salmon the content ranged from 2.9 ± 0.7 µg vitamin D3/100 g to 9.5 ± 0.7 µg vitamin D3/100 g. Data from 2018 shows that farmed salmon contained 2.3-7.3 µg vitamin D3/100 g. Information on the content of vitamin D in wild and farmed salmonids is very limited, which calls for further research to ensure a sustainable production of salmon with adequate vitamin D.


Assuntos
Animais Selvagens , Aquicultura , Calcifediol/química , Carne/análise , Animais , Composição Corporal , Calcifediol/metabolismo , Humanos , Músculo Esquelético , Salmo salar/crescimento & desenvolvimento
8.
Arch Biochem Biophys ; 666: 16-21, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30926433

RESUMO

25-Hydroxyvitamin D3 3-epimerase catalyzes the 3ß â†’ 3α epimerization of 25-hydroxyvitamin D3 (25(OH)D3) producing 3-epi-25-hydroxyvitamin D3 (3-epi-25(OH)D3). 3-Epi-25(OH)D3 is one of the most abundant forms of vitamin D present in the serum. It can be converted to 3-epi-1α,25-dihydroxyvitamin D3 by CYP27B1 which generally displays lower biological activity than 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). The 25(OH)D3 3-epimerase has been poorly characterized to date and the gene encoding it has not been identified. The 3-epimerase has been reported to be present in the microsomal fraction of cells, including liver cells, and to use NADPH as cofactor. It can also act on 1,25(OH)2D3 and 24,25(OH)2D3 forming the 3α-epimers. In this study we have characterized the activity of the 25(OH)D3 3-epimerase in rat and human liver microsomes, using 25(OH)D3 as substrate and HPLC to analyze product formation. For both rat and human liver microsomes the preferred cofactor was NADH, with the rat enzyme displaying a 6-fold greater catalytic efficiency (Vmax/Km) for NADH over that for NADPH. No activity was observed with oxidized cofactor, either NAD+ or NADP+. This was unexpected since the initial step in the epimerization, predicted to be the oxidation of the 3ß-OH to a ketone, would require oxidized cofactor. The rat 3-epimerase in microsomes gave a Km for 25(OH)D3 of 14 µM. The reverse reaction, conversion of 3-epi-25(OH)D3 to 25(OH)D3, was catalyzed by both rat and human liver microsomes but at lower rates than the forward reaction. In conclusion, both rat and human 25-hydroxyvitamin D3 3-epimerase catalyze the reversible interconversion of 25(OH)D3 and 3-epi-25(OH)D3, and use NADH as the preferred cofactor. The lack of requirement for exogenous NAD+ suggests that the enzyme has a tightly bound NAD+ in its active site that is released only upon its reduction.


Assuntos
Calcifediol/metabolismo , Microssomos Hepáticos/enzimologia , Racemases e Epimerases/metabolismo , Animais , Catálise , Feminino , Humanos , Cinética , Masculino , NAD/metabolismo , NADP/metabolismo , Ratos , Ratos Wistar
9.
Metab Brain Dis ; 34(2): 527-535, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30604028

RESUMO

Growing evidence support the role of vitamin D in brain function and behavior. This study investigated the relationship between 25-hydroxyvitamin D3 [25(OH)D3] levels, biochemical profile and symptoms of depression and anxiety in healthy individuals. Symptoms of depression were assessed by the Beck Depression Inventory (BDI) and anxiety was evaluated with the State-Trait Anxiety Inventory (STAI). Our sample included 36 individuals, mostly women 27(75%), 36.39 ± 9.72 years old, non-smokers 31(86.1%), body mass index of 26.57 ± 3.92 kg/m2, 27.95 ± 7.50% body fat. Participants were divided into those with 25(OH)D3 levels lower than 40 ng/mL (mean 28.16 ± 7.07) and equal or higher than 40 ng/mL (mean 53.19 ± 6.32). Those with lower 25(OH)D3 had higher levels of triacylglycerol, triacylglycerol/high density lipoprotein (HDL) ratio, high glucose and homeostatic model assessment of insulin resistance (HOMA-IR) index. No changes were observed in sociodemographic variables, body composition, inflammatory parameters and cortisol. Additionally, in the groups with low and high 25(OH)D3 levels, STAI state, STAI trait and BDI scores were not statistically different. Levels of 25(OH)D3 were inversely and independently associated with glucose and HOMA-IR, but not associated with triacylglycerol, depression and anxiety scores. Lower levels of 25(OH)D3 were associated with dysfunction in glucose metabolism but not with depression and anxiety in healthy individuals.


Assuntos
Transtornos de Ansiedade/metabolismo , Ansiedade/metabolismo , Calcifediol/metabolismo , Depressão/metabolismo , Adulto , Transtorno Depressivo/complicações , Transtorno Depressivo/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Deficiência de Vitamina D/complicações , Vitaminas/metabolismo
10.
Poult Sci ; 98(3): 1127-1133, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30325457

RESUMO

This study was conducted to identify the effects of 25-OH cholecalciferol supplementation to turkeys on the immune cells parameters, fecal coccidial oocyst shedding, macrophage nitric oxide production, T regulatory cell cytokine production, and production parameters during a coccidial challenge. A total of 200 1-day-old turkey poults were supplemented with 27.5, 55, 82.5, or 110 µg/kg 25-OH cholecalciferol and challenged or not challenged with coccidial oocysts in a 4 × 2 factorial set up of treatments. Birds fed 110 µg/kg of 25-OH cholecalciferol and infected with coccidial oocyst had 41% lower (P < 0.05) fecal oocyst and 53% higher (P < 0.05) macrophage nitric oxide production than the birds fed 27.5 µg/kg of 25-OH cholecalciferol and infected with coccidial oocyst at 5 d post-coccidial infection. Birds fed 82.5 µg/kg 25-OH cholecalciferol and infected with coccidial oocyst had 5-fold higher (P < 0.05) IL-1 mRNA amounts than the birds fed 27.5 µg/kg of 25-OH cholecalciferol and infected with coccidial oocyst. Birds fed 110 µg/kg 25-OH cholecalciferol and infected with coccidial oocyst had 5.3-fold higher (P < 0.05) IL-10 mRNA amounts than the birds fed 27.5 µg/kg of 25-OH cholecalciferol and infected with coccidial oocyst at 5 d post-coccidial infection. CD4+CD25+ cells from birds fed 110 µg of 25-OH cholecalciferol and infected with coccidial oocyst had 12-fold higher (P < 0.05) IL-10 mRNA than that from the birds fed 27.5 µg/kg of 25-OH cholecalciferol and infected with coccidial oocyst. In conclusion, supplementing birds with 101 µg/kg 25-OH cholicalciferol decreases coccidial oocyst shedding in the feces and could be a nutritional strategy to reduce the coccidial infection and spread in turkeys.


Assuntos
Calcifediol/metabolismo , Eimeria/fisiologia , Linfócitos T Reguladores/metabolismo , Perus/imunologia , Vitaminas/metabolismo , Ração Animal/análise , Animais , Proteínas Aviárias/metabolismo , Calcifediol/administração & dosagem , Citocinas/metabolismo , Dieta/veterinária , Suplementos Nutricionais/análise , Fezes/parasitologia , Oocistos/fisiologia , Distribuição Aleatória , Linfócitos T Reguladores/parasitologia , Perus/fisiologia , Vitaminas/administração & dosagem
11.
J Cosmet Dermatol ; 18(2): 671-676, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30070012

RESUMO

OBJECTIVES: The immunological aspects of inflammatory acne are still incompletely understood, so this study aimed to investigate the possible role of IL-17 and 25 hydroxycholecalciferol (25(OH)D3) in the disease pathogenesis and progression. MATERIALS AND METHODS: Across-sectional study has been conducted on 135 patients with active acne vulgaris of various severities and 150 matched controls. ELISA assays of serum and tissue levels of IL-17 and 25(OH)D3, also immunohistochemical and Western blotting demonstration of the expression patterns of lesional IL-17 in comparison with control group, were performed. RESULTS: The mean serum levels of IL-17 were 544.2 pg/mL ± 477.4 SD and 42.2 pg/mL ± 8.1 SD for acne patients and controls, respectively, with significantly higher levels among the patient group (P < 0.05). Higher IL-17 expression levels in active acne lesions when compared with its level in healthy skin of the controls. The mean serum levels of 25(OH)D3 among patients and controls were 33.3 ng/mL ± 9.7 SD and 51.7 ng/mL ± 2.7 SD, respectively, with significantly lower levels among the patient group (P < 0.05). There were significantly negative correlations between IL-17 and 25(OH)D3 levels (P < 0.001 for both). CONCLUSIONS: Deficiency of vitamin D3 accompanied with higher IL-17 in an inverse pattern may have a possible role in active acne vulgaris.


Assuntos
Acne Vulgar/imunologia , Calcifediol/sangue , Interleucina-17/sangue , Pele/patologia , Deficiência de Vitamina D/imunologia , Acne Vulgar/sangue , Acne Vulgar/diagnóstico , Adulto , Biomarcadores/sangue , Biomarcadores/metabolismo , Biópsia , Calcifediol/metabolismo , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Interleucina-17/imunologia , Interleucina-17/metabolismo , Masculino , Índice de Gravidade de Doença , Pele/imunologia , Deficiência de Vitamina D/sangue , Adulto Jovem
12.
J Steroid Biochem Mol Biol ; 186: 161-168, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30367940

RESUMO

Three 23-hydroxylated vitamin D3 derivatives, which are metabolites of 25-hydroxyvitamin D3 produced by CYP24A1 and a related diastereomer, were efficiently synthesized. Each C23 hydroxy unit was constructed by the Claisen condensation reaction with ethyl acetate or the Grignard reaction with 2-methylallymagnesium chloride. Stereochemistry at the C23 position was determined by a modified Mosher's method. The triene structures were constructed by the Wittig-Horner reaction utilizing the A-ring phosphine oxide moiety.


Assuntos
Calcifediol/metabolismo , Di-Hidroxicolecalciferóis/síntese química , Hidroxicolecalciferóis/síntese química , Calcifediol/análogos & derivados , Técnicas de Química Sintética , Di-Hidroxicolecalciferóis/química , Hidroxicolecalciferóis/química , Estereoisomerismo , Vitamina D3 24-Hidroxilase/metabolismo
13.
Mol Cell Biochem ; 450(1-2): 105-112, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29909574

RESUMO

Vitamin D3 deficiency was found to be tightly linked to many health problems including metabolic syndrome, cancer, cardiovascular diseases, and type 2 diabetes mellitus. In our study, we tested the possible antidiabetic effects of one of vitamin D3 analogs, alfacalcidol, solely or in a combination with metformin on type 2 diabetic rats. Type 2 diabetic model rats were induced by feeding high-fat diet for 4 weeks followed by intraperitoneal injection of streptozotocin. In addition to the control group, the diabetic rats were divided into four groups: untreated, metformin-treated, alfacalcidol-treated, and combination-treated group (metformin + alfacalcidol) for 4 weeks. The level of fasting blood glucose, fasting serum insulin, homeostatic model of insulin resistance, serum lipid profile, liver enzymes, calcium, phosphorus, and 25-hydroxyvitamin D3 were also determined. Besides, sterol regulatory element binding protein-1c (SREBP-1c) and vitamin D receptors (VDR) gene expression at mRNA and protein levels were evaluated. The level of significance was fixed at P ≤ 0.05 for all statistical tests. Alfacalcidol, solely or combined with metformin, significantly ameliorated glucose homeostasis and lipid profile parameters (P < 0.001) with a neutral effect on calcium and phosphorus levels. Significant downregulation of mRNA expression of SREBP-1c in the liver, white as well as brown adipose tissues (P < 0.001) and different patterns of mRNA expression of VDR gene in pancreas and white adipose tissue were observed in rats treated with alfacalcidol solely or in combination with metformin. Vitamin D3 analogs can modulate glucose parameters and lipid metabolism in a diabetic rat model and it provides additional protective effects when combined with metformin.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Regulação da Expressão Gênica/efeitos dos fármacos , Hidroxicolecalciferóis/farmacologia , Fígado/metabolismo , Receptores de Calcitriol , Animais , Calcifediol/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Masculino , Metformina/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de Calcitriol/agonistas , Receptores de Calcitriol/biossíntese , Proteína de Ligação a Elemento Regulador de Esterol 1/biossíntese
14.
J Steroid Biochem Mol Biol ; 188: 23-28, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30553931

RESUMO

Calcitroic acid, the excretory form of vitamin D, is the terminal product of a 5-step pathway catalyzed by CYP24A1, commencing with C24-hydroxylation of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). Catabolism of 25-hydroxyvitamin D3 (25-OH-D3) proceeds via analogous steps culminating in calcioic acid; however this C23-truncated acid has not been reported in the circulation. It has recently been shown that 24,25-dihydroxyvitamin D3 (24,25-(OH)2D3) is an important factor in optimal bone fracture healing acting via an effector molecule FAM57B2 to produce lactosylceramide. Administration of 24,25-(OH)2D3 was found to restore normal fracture repair in Cyp24a1-/- mice devoid of 24,25-(OH)2D3. We set out to study the multi-step catabolism of D3 metabolites in vivo using LC-MS/MS methods in vehicle or 24,25-(OH)2D3-treated mice. Vehicle-treated Cyp24a1+/- mice possessed normal levels of serum 24,25-(OH)2D3 (7 ng/mL) and 25-OH-D3-26,23-lactone (4 ng/mL). We also detected 24-oxo-25-OH-D3 (3 ng/mL) and 24-oxo-23,25-(OH)2D3 (0.4 ng/mL); which were not detectable in vehicle-treated Cyp24a1-/- mice. In 24,25-(OH)2D3-treated Cyp24a1+/- mice, serum 24,25-(OH)2D3 rose to 200 ng/mL while 25-OH-D3-26,23-lactone remained unchanged in comparison to vehicle-treated Cyp24a1+/- mice Concentration of serum 24-oxo-25-OH-D3 and 24-oxo-23,25-(OH)2D3 rose by 10-fold, when Cyp24a1+/- mice were treated with 24,25-(OH)2D3 Calcioic acid was increased to 0.030 ng/mL for 24,25-(OH)2D3-treated Cyp24a1+/- mice. In 24,25-(OH)2D3-treated Cyp24a1-/- mice, serum 24,25-(OH)2D3 rose further to a striking 830 ng/mL due to lack of catabolism of the 24,25-(OH)2D3 dose. Serum 1,25-(OH)2D3 levels were suppressed in 24,25-(OH)2D3-treated Cyp24a1+/- and Cyp24a1-/- mice. Circulating 1,24,25-(OH)3D3 rose from 73 pg/mL to 106 pg/mL when Cyp24a1+/- mice were treated with 24,25-(OH)2D3. While undetectable in vehicle-treated Cyp24a1-/- mice, 1,24,25-(OH)3D3 rose unexpectedly to 153 pg/mL in 24,25-(OH)2D3-treated nulls suggesting conversion of 24,25-(OH)2D3 to 1,24,25-(OH)3D3 via 1-hydroxylation. Taken together, amplification of 24,25-(OH)2D3 catabolism by exogenous doses of this metabolite have enabled detection of downstream C24-oxidation pathway products in vivo, including calcioic acid; and provides a platform for studying alternative routes of vitamin D metabolism that may occur in pathological states including hypervitaminosis D and idiopathic infantile hypercalcemia caused by mutations of CYP24A1.


Assuntos
Calcifediol/sangue , Calcitriol/análogos & derivados , Vitamina D/análogos & derivados , Vitaminas/uso terapêutico , Animais , Calcifediol/metabolismo , Calcitriol/sangue , Calcitriol/metabolismo , Cromatografia Líquida , Feminino , Camundongos , Oxirredução , Espectrometria de Massas em Tandem , Vitamina D/administração & dosagem , Vitamina D/metabolismo , Vitamina D/uso terapêutico , Vitaminas/administração & dosagem , Vitaminas/metabolismo
15.
Protein Eng Des Sel ; 31(10): 375-387, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30566669

RESUMO

Attempts to create novel ligand-binding proteins often focus on formation of a binding pocket with shape complementarity against the desired ligand (particularly for compounds that lack distinct polar moieties). Although designed proteins often exhibit binding of the desired ligand, in some cases they display unintended recognition behavior. One such designed protein, that was originally intended to bind tetrahydrocannabinol (THC), was found instead to display binding of 25-hydroxy-cholecalciferol (25-D3) and was subjected to biochemical characterization, further selections for enhanced 25-D3 binding affinity and crystallographic analyses. The deviation in specificity is due in part to unexpected altertion of its conformation, corresponding to a significant change of the orientation of an α-helix and an equally large movement of a loop, both of which flank the designed ligand-binding pocket. Those changes led to engineered protein constructs that exhibit significantly more contacts and complementarity towards the 25-D3 ligand than the initial designed protein had been predicted to form towards its intended THC ligand. Molecular dynamics simulations imply that the initial computationally designed mutations may contribute to the movement of the helix. These analyses collectively indicate that accurate prediction and control of backbone dynamics conformation, through a combination of improved conformational sampling and/or de novo structure design, represents a key area of further development for the design and optimization of engineered ligand-binding proteins.


Assuntos
Engenharia de Proteínas , Proteínas/genética , Proteínas/metabolismo , Sequência de Aminoácidos , Calcifediol/metabolismo , Cristalografia por Raios X , Ligantes , Simulação de Dinâmica Molecular , Ligação Proteica , Estrutura Secundária de Proteína , Proteínas/química , Especificidade por Substrato
16.
Clin Biochem ; 61: 23-27, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30130523

RESUMO

BACKGROUND: vitamin D deficiency in children is still a global health problem. Measuring free 25-hydroxyvitamin D concentrations could provide a better estimate of the vitamin D status than total 25-hydroxyvitamin D (25(OH)D) levels. OBJECTIVE: To assess the relationship between measured free vitamin D (m-f25(OH)D) and calculated free 25(OH)D (c-f25(OH)D), total 25(OH)D, intact parathyroid hormone (iPTH) and other markers of phosphocalcic metabolism. To establish serum m-f25(OH)D concentrations corresponding to a total 25(OH)D > 50 nmol/L which is accepted as vitamin D-sufficiency status in children. DESIGN: Prospective cohort study. SETTING: January and February 2017 in a Mediterranean population. PATIENTS: healthy children. MEASUREMENTS: m-f25(OH)D and vitamin D binding protein (VDBP) by ELISA. Free 25(OH)D was calculated using the formula described by Bikle. RESULTS: m-f25(OH)D directly correlated with total 25(OH)D (r:0.804,p < .001), serum calcium (r:0.26,p:0.035), and c-f25(OH)D (r:0.553,p:0.016); and inversely with iPTH (r:-0.374, p:0.002), alkaline phosphatase (r:-0.28, p:0.026), and age (r:-0.289, p:0.018). Total 25(OH)D correlated with the same parameters as m-f25(OH)D except for serum calcium. However, c-f25(OH)D correlated only with total 25(OH)D and VDBP, both included in the calculation formula. Multiple regression analysis showed that m-f25(OH)D variations were independently explained by calcium (ß:0.156, p:0.026) and total 25(OH)D (ß:0.043, p < .001). The optimal m-f25(OH)D cut-off for discriminating between insufficient and sufficient total 25(OH)D was >9.8 pmol/L (Area Under Curve (AUC): 0.897 (95% confidence interval (CI): (0.798-0.958); p < .001; sensitivity:72.7% (95%CI: 49.8-89.3); specificity: 95.5% (95%CI: 84.5-99.4)). CONCLUSIONS: Directly measured free vitamin D correlated better with markers of phosphocalcic metabolism than total 25(OH)D and c-f25(OH)D in a population of healthy children.


Assuntos
Doenças Assintomáticas , Calcifediol/sangue , Fenômenos Fisiológicos da Nutrição Infantil , Estado Nutricional , Deficiência de Vitamina D/sangue , Proteína de Ligação a Vitamina D/sangue , Adolescente , Biomarcadores/sangue , Calcifediol/química , Calcifediol/deficiência , Calcifediol/metabolismo , Cálcio/sangue , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Hospitais Universitários , Humanos , Masculino , Ambulatório Hospitalar , Hormônio Paratireóideo/sangue , Estudos Prospectivos , Valores de Referência , Sensibilidade e Especificidade , Solubilidade , Deficiência de Vitamina D/diagnóstico , Proteína de Ligação a Vitamina D/metabolismo
17.
Meat Sci ; 143: 60-68, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29715661

RESUMO

This study investigated the effects of synthetic and natural sources of vitamin D biofortification in pig diets on pork vitamin D activity and pork quality. One hundred and twenty pigs (60 male, 60 female) were assigned to one of four dietary treatments for a 55 d feeding period. The dietary treatments were (1)50 µg vitamin D3/kg of feed; (2)50 µg of 25-hydroxvitamin D3/kg of feed (25-OH-D3); (3)50 µg vitamin D2/kg of feed; (4)50 µg vitamin D2-enriched mushrooms/kg of feed (Mushroom D2). The pigs offered the 25-OH-D3 diet exhibited the highest (P < 0.001) serum total 25-hydroxyvitamin D concentration and subsequently exhibited the highest (P < 0.05) Longissimus thoracis (LT) total vitamin D activity. Mushroom D2 and 25-OH-D3 supplementation increased pork antioxidant status. The vitamin D2-enriched mushrooms improved (P < 0.05) pig performance, carcass weight and LT colour. In conclusion, 25-OH-D3 is the most successful source for increasing pork vitamin D activity, while Mushroom D2 may be a new avenue to improve animal performance and pork quality.


Assuntos
Agaricales/química , Fenômenos Fisiológicos da Nutrição Animal , Antioxidantes/administração & dosagem , Calcifediol/administração & dosagem , Qualidade dos Alimentos , Carne/análise , Músculo Esquelético/metabolismo , 25-Hidroxivitamina D 2/sangue , Agaricales/crescimento & desenvolvimento , Agaricales/metabolismo , Animais , Antioxidantes/análise , Antioxidantes/metabolismo , Calcifediol/análise , Calcifediol/sangue , Calcifediol/metabolismo , Colecalciferol/administração & dosagem , Colecalciferol/análise , Colecalciferol/metabolismo , Cruzamentos Genéticos , Ergocalciferóis/administração & dosagem , Ergocalciferóis/análise , Ergocalciferóis/metabolismo , Feminino , Alimentos Fortificados/análise , Humanos , Irlanda , Masculino , Músculo Esquelético/crescimento & desenvolvimento , Valor Nutritivo , Pigmentos Biológicos/análise , Pigmentos Biológicos/biossíntese , Distribuição Aleatória , Sus scrofa , Ganho de Peso
18.
Curr HIV Res ; 16(2): 167-173, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29807518

RESUMO

BACKGROUND: Vitamin D is an immunomodulator, and its deficiency is associated with Tuberculosis (TB) infection. Bronchoalveolar lavage fluid (BALF) is a rich milieu of macrophages that form the first line of defense against invading TB bacilli. As there is an increased prevalence of vitamin D deficiency in TB and human immunodeficiency virus-1 (HIV-1) subjects, we intend exploring the possibility of a localized deficiency of vitamin D metabolites in BALF of these patients. OBJECTIVE: The primary objective was to assess the level of 25D3 in serum and BALF of subjects and look for a significant difference among patients and controls. The secondary objective was to find a correlation between serum and BALF 25D3 levels. METHODS: We performed a cross-sectional study with subjects divided into four groups: Controls (group 1), HIV positive without active TB (group 2), active TB without HIV (group 3), and HIV-TB coinfection (group 4). BALF and serum 25D3 levels were compared between the groups. RESULTS: Among the 149 (an immunomodulator) successive subjects enrolled, there were 40 subjects in group 1 (HIV-TB-), 48 in group 2 (HIV+TB-), 37 in group 3 (HIV-TB+), and 24 in group 4 (HIV+TB+). Females constituted 31.6% of the study subjects. In groups 3 and 4, there were significantly lower serum 25D3 levels compared to group 1 (p-value group 3: 0.002; group 4: 0.012). In groups 2, 3, and 4, there were significantly lower BALF 25D3 levels compared to group 1 (p-value group 2: 0.000; group 3: 0.000; group 4: 0.001). There was a significant correlation between serum and BALF 25D3 levels (Spearman's rank correlation coefficient 0.318, p-value = 0.0001). CONCLUSION: Lower levels of serum and BALF 25D3 were observed in HIV, TB, and HIV-TB coinfected patients. Localized deficiency of vitamin D metabolites might be associated with increased vulnerability to TB infection.


Assuntos
Líquido da Lavagem Broncoalveolar , Calcifediol/metabolismo , Infecções por HIV/epidemiologia , Infecções por HIV/metabolismo , Tuberculose/epidemiologia , Adulto , Biomarcadores , Contagem de Linfócito CD4 , Calcifediol/sangue , Coinfecção , Estudos Transversais , Feminino , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Centros de Atenção Terciária
19.
Oxid Med Cell Longev ; 2018: 6468234, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29743982

RESUMO

Objectives: Nordic walking (NW) is relatively new and popular type of physical exercise with less studied effects than other sports activities. The aim of the study was to analyze possible changes in somatic indices, oxidant and antioxidant status, interleukins, and calcidiol levels in middle-aged women after a 12-week NW training program. Study Design: In this study, we examined the effects of NW training on selected measures and changes in body weight, fat mass, and calcidiol levels. Methods: The study group consisted of 13 women (46 ± 4.2 years), who took part in trainings. Before and after the training program, some anthropometric indices were determined and selected biochemical parameters were measured in blood. Results: NW training led to a significant decrease of the total body mass and fat mass and to an increase in lean body mass (p < 0.05). It also contributed to a significant increase in total antioxidative status (TAS) and calcidiol levels (p < 0.05). Before training, a reverse correlation between IL-6 and total oxidative capacity (TOC) levels (p < 0.05) was found, while after training between IL-6 and calcidiol levels (p ≤ 0.001). Conclusions: 12-week NW training undertaken by premenopausal women not only has a positive effect on body composition but also on the plasma antioxidative capacity.


Assuntos
Composição Corporal , Peso Corporal , Oxirredução , Caminhada , Adulto , Antropometria , Índice de Massa Corporal , Calcifediol/metabolismo , Feminino , Humanos , Interleucina-6/metabolismo , Pessoa de Meia-Idade
20.
Diabet Med ; 35(7): 972-979, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29608221

RESUMO

AIMS: To measure total 25-hydroxyvitamin D levels in women in mid-pregnancy who participated in the Belfast centre of the Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) observational study, and to investigate the associations between levels of 25-hydroxyvitamin D and markers of gestational diabetes mellitus and lipid biomarkers. METHODS: A total of 1585 pregnant women had serum samples available for measurement. Participants were recruited from the Royal Jubilee Maternity Hospital, Belfast, Northern Ireland, at 24-32 weeks' gestation, as part of the HAPO study. 25-hydroxyvitamin D concentrations were measured using liquid chromatography tandem mass spectrometry. Glucose, C-peptide and lipid levels were previously analysed in a central laboratory. Statistical analysis was performed. RESULTS: The median (interquartile range) 25-hydroxyvitamin D concentration during pregnancy was 38.6 (24.1-60.7) nmol/l, with 65.8% of women being vitamin D-deficient (≤50 nmol/l). In regression analysis, the association between maternal 25-hydroxyvitamin D and fasting plasma glucose levels approached significance [regression coefficient -0.017 (95% CI -0.034 to 0.001); P=0.06], and a significant positive association was observed between maternal 25-hydroxyvitamin D and ß-cell function [1.013 (95% CI 1.001 to 1.024); P=0.031]. Maternal 25-hydroxyvitamin D level was positively associated with HDL [0.047 (95% CI 0.021 to 0.073) P≤ 0.001] and total cholesterol [0.085 (95% CI 0.002 to 0.167); P=0.044] in regression analysis. CONCLUSIONS: These results indicate a high prevalence of vitamin D deficiency during pregnancy, which requires identification and treatment; however, only weak associations were observed between 25-hydroxyvitamin D level and markers of glucose and insulin metabolism. This would suggest that these are of doubtful clinical significance.


Assuntos
Glicemia/metabolismo , Peptídeo C/metabolismo , Colesterol/metabolismo , Diabetes Gestacional/metabolismo , Complicações na Gravidez/metabolismo , Deficiência de Vitamina D/metabolismo , Vitamina D/análogos & derivados , 25-Hidroxivitamina D 2/metabolismo , Adolescente , Adulto , Calcifediol/metabolismo , Cromatografia Líquida , Diabetes Gestacional/epidemiologia , Dieta , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Irlanda do Norte , Gravidez , Complicações na Gravidez/epidemiologia , Segundo Trimestre da Gravidez , Terceiro Trimestre da Gravidez , Espectrometria de Massas em Tandem , Vitamina D/metabolismo , Deficiência de Vitamina D/epidemiologia , Adulto Jovem
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