Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 8.625
Filtrar
1.
Anticancer Res ; 39(9): 4795-4803, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519581

RESUMO

BACKGROUND/AIM: To determine the mechanism of vitamin D3-induced modulation of antioxidant-related factors in endometrial cancer, we investigated their role in apoptosis of human endometrial cancer cells exposed to vitamin D3 Materials and Methods: The survival rate of human endometrial cancer cells was estimated after treatment with activated vitamin D3 Reactive oxygen species (ROS) levels were measured using flow cytometry. The levels of VDR, Trx, TXNIP and apoptosis-related proteins were investigated using western blotting and immunocytochemistry in human tissues. RESULTS: Treatment with D3 induced apoptotic cell death and cell-cycle arrest by increasing ROS concentration. Vitamin D3 inhibited proliferation of human endometrial cancer cells. It regulated intracellular ROS concentration in endometrial cancer cells via increased TXNIP expression. CONCLUSION: Antioxidant regulation via TXNIP is an important cell death mechanism in human endometrial cancer, and occurs via induction by vitamin D3.


Assuntos
Antioxidantes/metabolismo , Proteínas de Transporte/metabolismo , Neoplasias do Endométrio/metabolismo , Tiorredoxinas/metabolismo , Vitamina D/análogos & derivados , Apoptose/efeitos dos fármacos , Biomarcadores , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/patologia , Feminino , Humanos , Imuno-Histoquímica , Oxirredução/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Vitamina D/farmacologia
2.
Niger J Clin Pract ; 22(9): 1201-1207, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31489854

RESUMO

Background: The presence of vitamin D, and parathyroid hormone receptors has been demonstrated in the vascular endothelium. Variations in vitamin D, and parathyroid hormone levels may affect coronary flow and cause the coronary slow-flow phenomenon (CSF). Methods: We enrolled 93 patients who had undergone coronary angiography and had near-normal coronary arteries. Blood samples were taken to determine the calcium, phosphorus, 25-hydroxy vitamin D, and parathyroid hormone levels. Vitamin D deficiency was defined as a serum 25-hydroxy vitamin D level of less than 20 ng/mL. We divided the study population into two groups according to thrombolysis in myocardial infarction frame count (TFC) levels. Results: Patients with TFC ≤27 were in the control group (n = 39), and those with TFC >27 were in the CSF group (n = 54). 25-Hydroxy vitamin D levels were similar in both groups: 17.5 [3.3-36.1] ng/ml in the CSF group and 15.2 [5.3-34] ng/ml in the control group (P = 0.129). When we analyzed TFC for each of the coronary arteries, we found a weak negative correlation between vitamin D level and TFC of the right coronary artery in the CSF group (r = -0.314, P = 0.021). Parathyroid hormone levels were similar in both groups: 48 [16-140] pg/ml in the CSF group and 52 [25-125] pg/ml in the control group (P = 0.297). Conclusion: The study failed to demonstrate a relationship between serum parathyroid hormone level and CSF. However, a weak negative correlation was found between vitamin D level and TFC of the right coronary artery.


Assuntos
Circulação Coronária/fisiologia , Vasos Coronários/diagnóstico por imagem , Fenômeno de não Refluxo , Hormônio Paratireóideo/sangue , Deficiência de Vitamina D/diagnóstico , Vitamina D/análogos & derivados , Idoso , Calcifediol/sangue , Cálcio/sangue , Angiografia Coronária , Vasos Coronários/fisiopatologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio , Fósforo/sangue , Vitamina D/sangue , Deficiência de Vitamina D/sangue
3.
Medicine (Baltimore) ; 98(34): e16733, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441845

RESUMO

Lower circulating vitamin D is common in older adults and may be a potential reversible risk factor for cardiovascular disease (CVD) in older adults, however, presented controversial results.Database was searched update to February 2018. Key data were extracted from eligible studies. Dose-response meta-analysis were conducted for synthesizing data from eligible studies.A total of 13 eligible studies involving 21,079 participants were included in this meta-analysis. Person with lower 25-hydroxyvitamin D status (25 (OH)D level <50 nmol/L) appeared to have higher mortality of CVD in older adults (RR = 1.54, 95% CI 1.24-1.91). Furthermore, a significantly higher mortality of CVD in older adults was observed for the deficient (<25 nmol/L; RR = 1.47, 95% CI 1.15-1.81) and insufficient (25-50 nmol/L; RR = 1.16, 95% CI 1.04-1.27) categories of 25 (OH)D, compared to the reference category of >75 nmol/L. Additionally, decrease of 10 nmol/L 25-hydroxyvitamin D was associated with a 7% incremental in the risk of CVD mortality in older adults.Considering these promising results, circulating vitamin D is associated with CVD mortality increment in older adults.


Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Vitamina D/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia
4.
Zhonghua Nei Ke Za Zhi ; 58(9): 673-679, 2019 Sep 01.
Artigo em Chinês | MEDLINE | ID: mdl-31461819

RESUMO

Objective: To examine associations of 25-hydroxyvitamin D [25(OH)D] concentrations with sex hormone levels and cardiovascular risk factors. Methods: A total of 697 male subjects were obtained from the thyroid disorders, lodine status and diabetes: a national epidemiological survey-2014 (TIDE) research--Henan sub-center survey through multistage stratified cluster random sampling from December 2015 to March 2016. The associations between 25(OH)D and sex hormones or cardiovascular risk factors were analyzed by linear regression analyses. Results: The age of the subjects was (46.6±15.9) years (19-85 years). Proportions of vitamin D deficient, vitamin D intermediate and vitamin D optimal were 9.3%, 13.1% and 77.6%, respectively. More subjects with vitamin D deficient were in urban area than in rural area (13.3% vs. 5.7%, P=0.001). After fully adjusting for age, residence area, economic status, education, body mass index, waist circumference, homeostasis model assessment of insulin resistance (HOMA-IR), hypertension, diabetes, triglyceride, high-density lipoproteincholesterol, total cholesterol, low-density lipoprotein cholesterol and uric acid, linear regression analyses showed that every 25 nmol/L increase in 25(OH)D levels increased lg FT(FT=free testosterone) by 0.013ng/L (ß=0.013, P=0.036), lg DHT (DHT=dihydrotestosterone) by 0.030 ng/L (ß=0.030, P=0.019), and lg AD (AD=androstenedione) by 0.019 µg/L (ß=0.019, P=0.008). After fully adjusting for age, residence area, economic status and education, every 25 nmol/L increase in 25(OH)D levels lowered glycosylated hemoglobin A1c (HbA1c) by 0.051% (ß=-0.051, P=0.027). Conclusions: Higher 25(OH)D concentrations in men were associated with higher FT, DHT, AD and lower HbA1c levels.


Assuntos
Doenças Cardiovasculares , Hormônios Esteroides Gonadais/sangue , Deficiência de Vitamina D , Vitamina D/análogos & derivados , Vitamina D/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etnologia , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/etiologia , Feminino , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Fatores de Risco , População Rural , População Urbana , Adulto Jovem
5.
JAMA ; 322(8): 736-745, 2019 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-31454046

RESUMO

Importance: Few studies have assessed the effects of daily vitamin D doses at or above the tolerable upper intake level for 12 months or greater, yet 3% of US adults report vitamin D intakes of at least 4000 IU per day. Objective: To assess the dose-dependent effect of vitamin D supplementation on volumetric bone mineral density (BMD) and strength. Design, Setting, and Participants: Three-year, double-blind, randomized clinical trial conducted in a single center in Calgary, Canada, from August 2013 to December 2017, including 311 community-dwelling healthy adults without osteoporosis, aged 55 to 70 years, with baseline levels of 25-hydroxyvitamin D (25[OH]D) of 30 to 125 nmol/L. Interventions: Daily doses of vitamin D3 for 3 years at 400 IU (n = 109), 4000 IU (n = 100), or 10 000 IU (n = 102). Calcium supplementation was provided to participants with dietary intake of less than 1200 mg per day. Main Outcomes and Measures: Co-primary outcomes were total volumetric BMD at radius and tibia, assessed with high resolution peripheral quantitative computed tomography, and bone strength (failure load) at radius and tibia estimated by finite element analysis. Results: Of 311 participants who were randomized (53% men; mean [SD] age, 62.2 [4.2] years), 287 (92%) completed the study. Baseline, 3-month, and 3-year levels of 25(OH)D were 76.3, 76.7, and 77.4 nmol/L for the 400-IU group; 81.3, 115.3, and 132.2 for the 4000-IU group; and 78.4, 188.0, and 144.4 for the 10 000-IU group. There were significant group × time interactions for volumetric BMD. At trial end, radial volumetric BMD was lower for the 4000 IU group (-3.9 mg HA/cm3 [95% CI, -6.5 to -1.3]) and 10 000 IU group (-7.5 mg HA/cm3 [95% CI, -10.1 to -5.0]) compared with the 400 IU group with mean percent change in volumetric BMD of -1.2% (400 IU group), -2.4% (4000 IU group), and -3.5% (10 000 IU group). Tibial volumetric BMD differences from the 400 IU group were -1.8 mg HA/cm3 (95% CI, -3.7 to 0.1) in the 4000 IU group and -4.1 mg HA/cm3 in the 10 000 IU group (95% CI, -6.0 to -2.2), with mean percent change values of -0.4% (400 IU), -1.0% (4000 IU), and -1.7% (10 000 IU). There were no significant differences for changes in failure load (radius, P = .06; tibia, P = .12). Conclusions and Relevance: Among healthy adults, treatment with vitamin D for 3 years at a dose of 4000 IU per day or 10 000 IU per day, compared with 400 IU per day, resulted in statistically significant lower radial BMD; tibial BMD was significantly lower only with the 10 000 IU per day dose. There were no significant differences in bone strength at either the radius or tibia. These findings do not support a benefit of high-dose vitamin D supplementation for bone health; further research would be needed to determine whether it is harmful. Trial Registration: ClinicalTrials.gov Identifier: NCT01900860.


Assuntos
Densidade Óssea/efeitos dos fármacos , Colecalciferol/administração & dosagem , Suplementos Nutricionais , Vitaminas/administração & dosagem , Absorciometria de Fóton , Administração Oral , Idoso , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Análise de Elementos Finitos , Resistência à Flexão , Humanos , Masculino , Pessoa de Meia-Idade , Rádio (Anatomia)/anatomia & histologia , Rádio (Anatomia)/diagnóstico por imagem , Tíbia/anatomia & histologia , Tíbia/diagnóstico por imagem , Falha de Tratamento , Vitamina D/análogos & derivados , Vitamina D/sangue
6.
Cochrane Database Syst Rev ; 7: CD008873, 2019 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-31348529

RESUMO

BACKGROUND: Vitamin D supplementation during pregnancy may be needed to protect against adverse pregnancy outcomes. This is an update of a review that was first published in 2012 and then in 2016. OBJECTIVES: To examine whether vitamin D supplementation alone or in combination with calcium or other vitamins and minerals given to women during pregnancy can safely improve maternal and neonatal outcomes. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register (12 July 2018), contacted relevant organisations (15 May 2018), reference lists of retrieved trials and registries at clinicaltrials.gov and WHO International Clinical Trials Registry Platform (12 July 2018). Abstracts were included if they had enough information to extract the data. SELECTION CRITERIA: Randomised and quasi-randomised trials evaluating the effect of supplementation with vitamin D alone or in combination with other micronutrients for women during pregnancy in comparison to placebo or no intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently i) assessed the eligibility of trials against the inclusion criteria, ii) extracted data from included trials, and iii) assessed the risk of bias of the included trials. The certainty of the evidence was assessed using the GRADE approach. MAIN RESULTS: We included 30 trials (7033 women), excluded 60 trials, identified six as ongoing/unpublished trials and two trials are awaiting assessments.Supplementation with vitamin D alone versus placebo/no interventionA total of 22 trials involving 3725 pregnant women were included in this comparison; 19 trials were assessed as having low-to-moderate risk of bias for most domains and three trials were assessed as having high risk of bias for most domains. Supplementation with vitamin D alone during pregnancy probably reduces the risk of pre-eclampsia (risk ratio (RR) 0.48, 95% confidence interval (CI) 0.30 to 0.79; 4 trials, 499 women, moderate-certainty evidence) and gestational diabetes (RR 0.51, 95% CI 0.27 to 0.97; 4 trials, 446 women, moderate-certainty evidence); and probably reduces the risk of having a baby with low birthweight (less than 2500 g) (RR 0.55, 95% CI 0.35 to 0.87; 5 trials, 697 women, moderate-certainty evidence) compared to women who received placebo or no intervention. Vitamin D supplementation may make little or no difference in the risk of having a preterm birth < 37 weeks compared to no intervention or placebo (RR 0.66, 95% CI 0.34 to 1.30; 7 trials, 1640 women, low-certainty evidence). In terms of maternal adverse events, vitamin D supplementation may reduce the risk of severe postpartum haemorrhage (RR 0.68, 95% CI 0.51 to 0.91; 1 trial, 1134 women, low-certainty evidence). There were no cases of hypercalcaemia (1 trial, 1134 women, low-certainty evidence), and we are very uncertain as to whether vitamin D increases or decreases the risk of nephritic syndrome (RR 0.17, 95% CI 0.01 to 4.06; 1 trial, 135 women, very low-certainty evidence). However, given the scarcity of data in general for maternal adverse events, no firm conclusions can be drawn.Supplementation with vitamin D and calcium versus placebo/no interventionNine trials involving 1916 pregnant women were included in this comparison; three trials were assessed as having low risk of bias for allocation and blinding, four trials were assessed as having high risk of bias and two had some components having a low risk, high risk, or unclear risk. Supplementation with vitamin D and calcium during pregnancy probably reduces the risk of pre-eclampsia (RR 0.50, 95% CI 0.32 to 0.78; 4 trials, 1174 women, moderate-certainty evidence). The effect of the intervention is uncertain on gestational diabetes (RR 0.33,% CI 0.01 to 7.84; 1 trial, 54 women, very low-certainty evidence); and low birthweight (less than 2500 g) (RR 0.68, 95% CI 0.10 to 4.55; 2 trials, 110 women, very low-certainty evidence) compared to women who received placebo or no intervention. Supplementation with vitamin D and calcium during pregnancy may increase the risk of preterm birth < 37 weeks in comparison to women who received placebo or no intervention (RR 1.52, 95% CI 1.01 to 2.28; 5 trials, 942 women, low-certainty evidence). No trial in this comparison reported on maternal adverse events.Supplementation with vitamin D + calcium + other vitamins and minerals versus calcium + other vitamins and minerals (but no vitamin D)One trial in 1300 participants was included in this comparison; it was assessed as having low risk of bias. Pre-eclampsia was not assessed. Supplementation with vitamin D + other nutrients may make little or no difference in the risk of preterm birth < 37 weeks (RR 1.04, 95% CI 0.68 to 1.59; 1 trial, 1298 women, low-certainty evidence); or low birthweight (less than 2500 g) (RR 1.12, 95% CI 0.82 to 1.51; 1 trial, 1298 women, low-certainty evidence). It is unclear whether it makes any difference to the risk of gestational diabetes (RR 0.42, 95% CI 0.10 to 1.73) or maternal adverse events (hypercalcaemia no events; hypercalciuria RR 0.25, 95% CI 0.02 to 3.97; 1 trial, 1298 women,) because the certainty of the evidence for both outcomes was found to be very low. AUTHORS' CONCLUSIONS: We included 30 trials (7033 women) across three separate comparisons. Our GRADE assessments ranged from moderate to very low, with downgrading decisions based on limitations in study design, imprecision and indirectness.Supplementing pregnant women with vitamin D alone probably reduces the risk of pre-eclampsia, gestational diabetes, low birthweight and may reduce the risk of severe postpartum haemorrhage. It may make little or no difference in the risk of having a preterm birth < 37 weeks' gestation. Supplementing pregnant women with vitamin D and calcium probably reduces the risk of pre-eclampsia but may increase the risk of preterm births < 37 weeks (these findings warrant further research). Supplementing pregnant women with vitamin D and other nutrients may make little or no difference in the risk of preterm birth < 37 weeks' gestation or low birthweight (less than 2500 g). Additional rigorous high quality and larger randomised trials are required to evaluate the effects of vitamin D supplementation in pregnancy, particularly in relation to the risk of maternal adverse events.


Assuntos
Resultado da Gravidez , Vitamina D/administração & dosagem , Vitaminas/administração & dosagem , Cálcio na Dieta/administração & dosagem , Diabetes Gestacional/prevenção & controle , Suplementos Nutricionais , Feminino , Humanos , Pré-Eclâmpsia/prevenção & controle , Gravidez , Complicações na Gravidez/prevenção & controle , Nascimento Prematuro/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Vitamina D/análogos & derivados
7.
J Zoo Wildl Med ; 50(2): 421-426, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31260209

RESUMO

For many reptile species, adequate ultraviolet B (UVB) radiation is essential for proper calcium metabolism. In this study, the effects of UVB radiation on calcium metabolism were evaluated in green sea turtles (Chelonia mydas). 25-Hydroxyvitamin D, parathyroid hormone (PTH), and ionized calcium (iCa) were measured in juvenile (n = 18, 9 indoor, 9 outdoor) and adult (n = 8, 4 indoor, 4 outdoor) turtles. All animals were fed an identical diet. Outdoor animals had access to unfiltered sunlight, whereas indoor animals were housed under artificial lighting without UVB. Mean values for 25-hydroxyvitamin D for the outdoor and indoor groups were 34.33 ± 7.98 nmol/L and 7.11 ± 1.69 nmol/L for juveniles and 73.25 ± 30.34 nmol/L and 14.0 ± 11.52 nmol/L for adults respectively. Mean values for iCa for the outdoor and indoor groups were 0.98 ± 0.07 mmol/L and 0.99 ± 0.06 mmol/L for juveniles and 1.18 ± 0.22 mmol/L and 0.97 ± 0.18 mmol/L for adults respectively. UVB exposure (P < 0.001) and age (P < 0.001) had a significant effect on 25-hydroxyvitamin D as well as a significant interaction between the two variables (P = 0.008), with highest values in adult outdoor turtles. There was a significant interaction between age group and UVB status for iCa (P = 0.036), with greater values in older outdoor turtles. 25-Hydroxyvitamin D and total calcium were positively correlated, rs = 0.39, P = 0.042. iCa and calcium-to-phosphorus ratios were also positively correlated, rs = 0.42, P = 0.027. These results suggest that UVB exposure is an important source of 25-hydroxyvitamin D for green sea turtles and has significant effects on calcium metabolism in this species. PTH values in this study were near the minimum limits of detection and suggest that current mammalian-based PTH assays are not valid for reptiles.


Assuntos
Cálcio/sangue , Hormônio Paratireóideo/sangue , Tartarugas/sangue , Raios Ultravioleta , Vitamina D/análogos & derivados , Envelhecimento , Animais , Animais de Zoológico , Feminino , Abrigo para Animais , Masculino , Vitamina D/sangue
8.
Hum Genet ; 138(10): 1155-1169, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31342140

RESUMO

Vitamin D inadequacy, assessed by 25-hydroxyvitamin D [25(OH)D], affects around 50% of adults in the United States and is associated with numerous adverse health outcomes. Blood 25(OH)D concentrations are influenced by genetic factors that may determine how much vitamin D intake is required to reach optimal 25(OH)D. Despite large genome-wide association studies (GWASs), only a small portion of the genetic factors contributing to differences in 25(OH)D has been discovered. Therefore, knowledge of a fuller set of genetic factors could be useful for risk prediction of 25(OH)D inadequacy, personalized vitamin D supplementation, and prevention of downstream morbidity and mortality. Using PRSice and weights from published African- and European-ancestry GWAS summary statistics, ancestry-specific polygenic scores (PGSs) were created to capture a more complete set of genetic factors in those of European (n = 9569) or African ancestry (n = 2761) from three cohort studies. The PGS for African ancestry was derived using all input SNPs (a p value cutoff of 1.0) and had an R2 of 0.3%; for European ancestry, the optimal PGS used a p value cutoff of 3.5 × 10-4 in the target/tuning dataset and had an R2 of 1.0% in the validation cohort. Those with highest genetic risk had 25(OH)D that was 2.8-3.0 ng/mL lower than those with lowest genetic risk (p = 0.0463-3.2 × 10-13), requiring an additional 467-500 IU of vitamin D intake to maintain equivalent 25(OH)D. PGSs are a powerful predictive tool that could be leveraged for personalized vitamin D supplementation to prevent the negative downstream effects of 25(OH)D inadequacy.


Assuntos
Grupo com Ancestrais do Continente Africano/genética , Grupo com Ancestrais do Continente Europeu/genética , Genética Populacional , Padrões de Herança , Herança Multifatorial , Polimorfismo de Nucleotídeo Único , Vitamina D/análogos & derivados , Estudos de Coortes , Bases de Dados Genéticas , Suplementos Nutricionais , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Raios Ultravioleta , Vitamina D/sangue
9.
Georgian Med News ; (290): 96-100, 2019 May.
Artigo em Russo | MEDLINE | ID: mdl-31322523

RESUMO

The article discusses the role of vitamin D in the development of skin pathology - in particular, psoriasis and acne. In some publications the results of vitamin D sufficiency in patients with these diseases are cited, but there is still insufficient information to draw definitive conclusions about the role of vitamin D in their development. The aim of the study was to assess the role of vitamin D in psoriasis and acne development. The case-control study involved 66 people, including 20 patients with psoriasis (group 1), 20 with acne (group 2) and 26 healthy individuals (control group). All participants in the study were determined the level of plasma vitamin 25 (OH)D; in patients with psoriasis PASI index to determine the severity of the disease was calculated. Vitamin 25(OH)D deficiency was detected in a significant majority of patients with skin diseases, and its average plasma level in each group was significantly lower than in the control group. There was a correlation between vitamin 25(OH)D deficiency and psoriasis severity. In patients with psoriasis and acne, vitamin D preparations should be included in the treatment complex to increase the effectiveness of therapy.


Assuntos
Acne Vulgar/sangue , Psoríase/sangue , Deficiência de Vitamina D/sangue , Vitamina D/sangue , Acne Vulgar/complicações , Acne Vulgar/tratamento farmacológico , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Psoríase/complicações , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Vitamina D/análogos & derivados , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/tratamento farmacológico , Vitaminas/uso terapêutico
10.
Chem Pharm Bull (Tokyo) ; 67(7): 609-619, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31257315

RESUMO

To develop potent ligands for the vitamin D receptor (VDR), we designed and synthesized a series of vitamin D analogues with and without 22-alkyl substituents. These analogues exhibited agonistic, partial agonistic, or antagonistic activity. To elucidate the mechanism of action of the analogues, we conducted crystal structure analyses of the ligand-binding domain (LBD) of VDR complexed with the analogues. The VDR-LBD/agonist complex exhibited precise interactions, which clearly explained VDR agonism. The VDR-LBD/partial agonist complex showed two conformers (agonist and antagonist binding conformers) in a single crystal, demonstrating that partial agonism could be explained by the sum of the agonistic and antagonistic activities. Antagonist binding to the VDR-LBD structure was elucidated using both crystal structure analysis and in-solution structural analyses with the small-angle X-ray scattering (SAXS)-molecular dynamics (MD) and hydrogen/deuterium exchange coupled with mass spectrometry (HDX-MS) methods. Several antagonist-binding structures were detected. We found that the antagonist binding structures differed depending on the structure of the antagonist itself, and those structures clearly explained the VDR antagonism. Furthermore, the apo VDR-LBD structure without the ligand in the ligand-binding pocket was revealed and found to have an entrance to accommodate the ligand. Thus we elucidated the mechanisms of action of agonists, partial agonists, and antagonists based on structural changes (differences) in the receptor protein induced by ligand binding.


Assuntos
Ligantes , Receptores de Calcitriol/metabolismo , Sítios de Ligação , Cristalografia por Raios X , Humanos , Simulação de Dinâmica Molecular , Conformação Proteica em alfa-Hélice , Domínios Proteicos , Receptores de Calcitriol/agonistas , Receptores de Calcitriol/antagonistas & inibidores , Vitamina D/análogos & derivados , Vitamina D/metabolismo
11.
Lakartidningen ; 1162019 May 15.
Artigo em Sueco | MEDLINE | ID: mdl-31192381

RESUMO

Systematic reviews and meta-analyses have shown that there is little justification for vitamin D supplements to prevent infections, cancer and cardiovascular disease. Despite the limited evidence of effectiveness, the total number of ordered serum 25-hydroxyvitamin D (25(OH)D) tests has increased considerably in recent years. There seems to be an overuse of this test that does not provide meaningful benefit for patients. A passive introduction of new tests leads generally to a slow initiation of value-based diagnostics, as well as overuse and underuse of diagnostic tests. In this study, in Region Östergötland, we applied a ¼Choosing wisely« model that reversed a rising trend of 25(OH)D tests and reduced the number of unnecessary tests. The findings point to the need for strategic plans for introducing new analyses and approaches to counteract misuse of laboratory diagnostics. We recommend ¼Choosing wisely« models for the introduction of new analyses to facilitate appropriate laboratory diagnostics and to counteract long-term overuse.


Assuntos
Análise Química do Sangue/normas , Atenção Primária à Saúde/normas , Utilização de Procedimentos e Técnicas/normas , Vitamina D/análogos & derivados , Análise Química do Sangue/estatística & dados numéricos , Humanos , Atenção Primária à Saúde/estatística & dados numéricos , Utilização de Procedimentos e Técnicas/estatística & dados numéricos , Suécia , Procedimentos Desnecessários/normas , Procedimentos Desnecessários/estatística & dados numéricos , Vitamina D/sangue
12.
BMC Infect Dis ; 19(1): 532, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31208362

RESUMO

BACKGROUND: There is controversy regarding the relative influence of 'exogenous' versus 'endogenous' factors on the risk of progression from latent tuberculosis infection to active tuberculosis (TB) disease in children. METHODS: We conducted a cross-sectional analysis to identify risk factors for active tuberculosis in QuantiFERON®-TB Gold (QFT-G)-positive children aged 6-13 years attending 18 schools in Ulaanbaatar, Mongolia. Children underwent clinical and radiological screening for active tuberculosis, and data relating to potential risk factors for disease progression were collected by questionnaire and determination of serum 25-hydroxyvitamin D (25[OH]D) concentrations. Risk ratios were calculated using generalized estimating equations with adjustment for potential confounders. RESULTS: 129/938 (13.8%) QFT-positive children were diagnosed with active tuberculosis. Risk of active tuberculosis was independently associated with household exposure to pulmonary TB (adjusted risk ratio [aRR] 2.40, 95% CI 1.74 to 3.30, P < 0.001), month of sampling (adjusted risk ratio [aRR] for March-May vs. June-November 3.31, 95% CI 1.63 to 6.74, P < 0.001; aRR for December-February vs. June-November 2.53, 95% CI 1.23 to 5.19, P = 0.01) and active smoking by the child (aRR 5.23, 95% CI 2.70 to 10.12, P < 0.001). No statistically significant independent association was seen for age, sex, socio-economic factors, presence of a Bacillus Calmette-Guérin (BCG) scar, tobacco exposure or vitamin D status. CONCLUSIONS: Household exposure to active TB, winter or spring season and active smoking were independently associated with risk of active tuberculosis in QFT-positive children. Our findings highlight the potentially high yield of screening child household contacts of infectious index cases for active tuberculosis in low- and middle-income countries.


Assuntos
Tuberculose Latente/epidemiologia , Tuberculose Pulmonar/epidemiologia , Adolescente , Criança , Estudos Transversais , Progressão da Doença , Feminino , Testes Hematológicos/métodos , Humanos , Tuberculose Latente/diagnóstico , Masculino , Programas de Rastreamento , Mongólia/epidemiologia , Mycobacterium bovis , Razão de Chances , Fatores de Risco , Fumar , Inquéritos e Questionários , Tuberculose Pulmonar/diagnóstico , Vitamina D/análogos & derivados , Vitamina D/sangue
13.
N Engl J Med ; 381(6): 520-530, 2019 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-31173679

RESUMO

BACKGROUND: Observational studies support an association between a low blood 25-hydroxyvitamin D level and the risk of type 2 diabetes. However, whether vitamin D supplementation lowers the risk of diabetes is unknown. METHODS: We randomly assigned adults who met at least two of three glycemic criteria for prediabetes (fasting plasma glucose level, 100 to 125 mg per deciliter; plasma glucose level 2 hours after a 75-g oral glucose load, 140 to 199 mg per deciliter; and glycated hemoglobin level, 5.7 to 6.4%) and no diagnostic criteria for diabetes to receive 4000 IU per day of vitamin D3 or placebo, regardless of the baseline serum 25-hydroxyvitamin D level. The primary outcome in this time-to-event analysis was new-onset diabetes, and the trial design was event-driven, with a target number of diabetes events of 508. RESULTS: A total of 2423 participants underwent randomization (1211 to the vitamin D group and 1212 to the placebo group). By month 24, the mean serum 25-hydroxyvitamin D level in the vitamin D group was 54.3 ng per milliliter (from 27.7 ng per milliliter at baseline), as compared with 28.8 ng per milliliter in the placebo group (from 28.2 ng per milliliter at baseline). After a median follow-up of 2.5 years, the primary outcome of diabetes occurred in 293 participants in the vitamin D group and 323 in the placebo group (9.39 and 10.66 events per 100 person-years, respectively). The hazard ratio for vitamin D as compared with placebo was 0.88 (95% confidence interval, 0.75 to 1.04; P = 0.12). The incidence of adverse events did not differ significantly between the two groups. CONCLUSIONS: Among persons at high risk for type 2 diabetes not selected for vitamin D insufficiency, vitamin D3 supplementation at a dose of 4000 IU per day did not result in a significantly lower risk of diabetes than placebo. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; D2d ClinicalTrials.gov number, NCT01942694.).


Assuntos
Colecalciferol/uso terapêutico , Diabetes Mellitus Tipo 2/prevenção & controle , Suplementos Nutricionais , Estado Pré-Diabético/tratamento farmacológico , Vitaminas/uso terapêutico , Administração Oral , Idoso , Colecalciferol/administração & dosagem , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/sangue , Fatores de Risco , Falha de Tratamento , Vitamina D/análogos & derivados , Vitamina D/sangue , Vitaminas/administração & dosagem
14.
Rev Assoc Med Bras (1992) ; 65(5): 691-698, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31166447

RESUMO

BACKGROUND: Hypovitaminosis D is considered a global public health issue. Knowledge of its true dimensions will allow us to design interventions and plan preventive measures that can have a significant impact on human health. OBJECTIVES: The aim of this study was to evaluate the prevalence of hypovitaminosis D, defined as a serum 25-hydroxyvitamin D concentration < 30 ng/ml, in postmenopausal women around the world, as well as to identify the potential associated factors. METHODS: A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses recommendations. Specific search terms were consulted in Medline, Excerpta Medica, and Latin-American and Caribbean Health Sciences Literature databases, with no restriction for the year or language of publication. RESULTS: Of 451 studies initially identified, 32 were selected for analysis. Collectively, those 32 studies evaluated 21,236 postmenopausal women, of whom 16,440 (77.4%) had serum 25-hydroxyvitamin D concentrations < 30 ng/ml. The reported prevalence of hypovitaminosis D ranged from 29% (in the United States) to 99.4% (in China). In six of the studies, the prevalence was above 90%. CONCLUSIONS: If the criterion is the 30 ng/ml cut-off point, the majority of postmenopausal women in the world could be classified as having hypovitaminosis D. Among the studies evaluated, the lowest prevalence reported was nearly 30%. Neither latitude, region of the world, nor laboratory methodology were found to be associated with the prevalence of hypovitaminosis D.


Assuntos
Pós-Menopausa/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , Feminino , Humanos , Prevalência , Fatores de Risco , Vitamina D/análogos & derivados , Vitamina D/sangue
15.
Orthopedics ; 42(3): 158-162, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31099881

RESUMO

The authors' main objective was to demonstrate the confounding effect of combining subgroup data, specifically race, on the prevalence of vitamin D deficiency in adolescent idiopathic scoliosis (AIS). This was a retrospective chart review. Vitamin D deficiency was defined as 25-hydroxyvitamin D (25[OH]D) less than 20 ng/mL. Data were compared between white patients and black and Hispanic patients. Vitamin D status in girls with AIS was also compared with that in girls without AIS who had a history of fracture and with the medical literature to determine if deficiency in AIS was equal to or greater than other cohorts. Mean age was 13.9±2.3 years for the white girls with AIS (n=221) and 13.6±2.2 years for pooled non-whites (n=134). Significant racial differences were found that biased interpretation of the total pooled cohort. Mean 25(OH)D was 27.9±8.5 ng/mL for white girls with AIS vs 21.9±10.3 ng/mL for non-whites (P<.0001). Deficiency was present in 13.1% of white girls vs 47.8% of non-white girls (P<.0001). Compared with girls with fractures and with the published literature, the race-matched deficiency rates were not abnormally high in girls with AIS. Prevalence of deficiency was greater in non-whites with AIS than in whites. However, percent deficiency was not greater in girls with AIS than in race-matched cohorts without AIS. Without separating data by race, interpretation of vitamin D status can be confounded. [Orthopedics. 2019; 42(3):158-162.].


Assuntos
Grupos de Populações Continentais/estatística & dados numéricos , Escoliose/epidemiologia , Deficiência de Vitamina D/epidemiologia , Adolescente , Criança , Feminino , Florida/epidemiologia , Humanos , Estudos Retrospectivos , Vitamina D/análogos & derivados , Vitamina D/sangue
16.
BMC Infect Dis ; 19(1): 366, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31039752

RESUMO

BACKGROUND: Independent of HIV infection, extrapulmonary TB (EPTB) risk is increased in women, persons of black race or foreign birth, and by genetic variants in vitamin D receptor (VDR), interleukin-1 beta (IL-1ß), and toll-like receptor (TLR)-2; functional correlates are unclear. We evaluated macrophage expression of VDR, TLR2, cathelicidin, and TNF-α, and production of IL-1ß in HIV-seronegative persons with previous EPTB, previous pulmonary TB, latent M. tuberculosis infection, and uninfected TB contacts. Persons with previous pleural TB were excluded due to enhanced immune responses at the site of disease. METHODS: Macrophages were stimulated with TLR-2 agonist M. tuberculosis lipoprotein (LpqH), live and gamma-irradiated M. tuberculosis. RESULTS: M. tuberculosis - infected macrophages from persons with previous EPTB had increased VDR expression (29.17 relative value unit increase in median expression vs. uninfected contacts, after adjusting for foreign-born status; P = 0.02). Macrophages from persons with previous EPTB had a 38.88 µg/mL increase in median IL-1ß production after stimulation with LpqH compared to uninfected contacts (P = 0.01); the effect was similar (44.99 µg/mL) but not statistically significant after controlling for foreign-born status. Median 25-hydroxyvitamin D levels were low but not significantly different between groups. CONCLUSIONS: There was increased macrophage expression of VDR after stimulation with live M. tuberculosis in persons with previous extrapulmonary TB. If post-treatment VDR expression reflects expression prior to disease, it may identify persons at risk for extrapulmonary TB.


Assuntos
Macrófagos/metabolismo , Mycobacterium tuberculosis/fisiologia , Receptores de Calcitriol/metabolismo , Tuberculose/patologia , Adulto , Idoso , Proteínas de Bactérias/imunologia , Estudos de Casos e Controles , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , Feminino , Raios gama , Expressão Gênica , Humanos , Interleucina-1beta/análise , Macrófagos/citologia , Macrófagos/microbiologia , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/efeitos da radiação , Receptores de Calcitriol/genética , Receptor 2 Toll-Like/agonistas , Tuberculose/imunologia , Vitamina D/análogos & derivados , Vitamina D/sangue
17.
N Engl J Med ; 380(22): 2136-2145, 2019 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-31116917

RESUMO

BACKGROUND: Bariatric surgery results in weight loss and health improvements in adults and adolescents. However, whether outcomes differ according to the age of the patient at the time of surgery is unclear. METHODS: We evaluated the health effects of Roux-en-Y gastric bypass in a cohort of adolescents (161 patients enrolled from 2006 through 2012) and a cohort of adults (396 patients enrolled from 2006 through 2009). The two cohorts were participants in two related but independent studies. Linear mixed and Poisson mixed models were used to compare outcomes with regard to weight and coexisting conditions between the cohorts 5 years after surgery. The rates of death and subsequent abdominal operations and selected micronutrient levels (up to 2 years after surgery) were also compared between the cohorts. RESULTS: There was no significant difference in percent weight change between adolescents (-26%; 95% confidence interval [CI], -29 to -23) and adults (-29%; 95% CI, -31 to -27) 5 years after surgery (P = 0.08). After surgery, adolescents were significantly more likely than adults to have remission of type 2 diabetes (86% vs. 53%; risk ratio, 1.27; 95% CI, 1.03 to 1.57) and of hypertension (68% vs. 41%; risk ratio, 1.51; 95% CI, 1.21 to 1.88). Three adolescents (1.9%) and seven adults (1.8%) died in the 5 years after surgery. The rate of abdominal reoperations was significantly higher among adolescents than among adults (19 vs. 10 reoperations per 500 person-years, P = 0.003). More adolescents than adults had low ferritin levels (72 of 132 patients [48%] vs. 54 of 179 patients [29%], P = 0.004). CONCLUSIONS: Adolescents and adults who underwent gastric bypass had marked weight loss that was similar in magnitude 5 years after surgery. Adolescents had remission of diabetes and hypertension more often than adults. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases; ClinicalTrials.gov number, NCT00474318.).


Assuntos
Derivação Gástrica , Obesidade Mórbida/cirurgia , Perda de Peso , Adolescente , Adulto , Fatores Etários , Índice de Massa Corporal , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Feminino , Ferritinas/sangue , Derivação Gástrica/mortalidade , Hemoglobina A Glicada/análise , Humanos , Hipertensão/complicações , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/sangue , Obesidade Mórbida/complicações , Obesidade Mórbida/mortalidade , Distribuição de Poisson , Indução de Remissão , Reoperação/estatística & dados numéricos , Vitamina D/análogos & derivados , Vitamina D/sangue , Adulto Jovem
18.
Wei Sheng Yan Jiu ; 48(3): 352-373, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31133118

RESUMO

OBJECTIVE: To explore the relationship between serum 25-hydroxyvitamin D(25-OH-D), parathyroid hormone(PTH) and calcium levels and hyperglycemia. METHODS: Based on the previously studies, 621 eligible subjects were selected in this research. Demographic data, lifestyle information, history of disease and medication were collected. Height, weight and blood pressure were measured. Fasting blood glucose(FBG), 25-OH-D, PTH, calcium, phosphorus of all subjects were determined. RESULTS: Compared with participants with 25-OH-D<10.0 µg/L, those with 25-OH-D between 10.0 µg/L and 19.9 µg/L and ≥20.0 µg/L had lower FBG levels and prevalence of hyperglycemia(all P<0.001). The FBG levels and prevalence of hyperglycemia were not significantly different between individuals with PTH≥65.0 ng/L and PTH<65.0 ng/L. Individuals with calcium level≤2.03 mmol/L or ≥2.54 mmol/L had higher FBG levels than those with moderate calcium level(2.03-2.54 mmol/L), however, the prevalence of hyperglycemia increased with the elevation of the calcium level. The adjusted Logistic analysis showed the risks of hyperglycemia in participants with 25-OH-D between 10.0 µg/L and 19.9 µg/L, and ≥20.0 µg/L were 0.467 times(95%CI 0.311-0.703, P<0.001), 0.402 times(95%CI 0.205-0.790, P=0.008) as that in people with 25-OH-D<10.0 µg/L, respectively. The individuals with serum calcium≥2.54 mmol/L was 1.884 times(95%CI 1.272-2.791, ) as likely to have hyperglycemia as the median calcium level 2.03-2.54 mmol/L(P=0.001). CONCLUSION: Vitamin D deficiency and the elevated serum calcium levels may increase the risk of hyperglycemia.


Assuntos
Hiperglicemia , Cálcio , Humanos , Hormônio Paratireóideo , Vitamina D/análogos & derivados
19.
Int Braz J Urol ; 45(3): 621-628, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31063279

RESUMO

PURPOSE: To investigate the relationship between 25-hydroxyvitamin D (25 (OH) D) levels and acquired premature ejaculation (PE). MATERIALS AND METHODS: A total of 97 patients with acquired PE and 64 healthy men as a control group selected from volunteers without PE attending our Andrology Outpatient Clinic between November 2016 and April 2017 were included the study. All patients were considered to have acquired PE if they fulfilled the criteria of the second Ad Hoc International Society for Sexual Medicine Committee. Premature ejaculation diagnostic tool questionnaires were used to assessment of PE and all participants were instructed to record intravaginal ejaculatory latency time. Vitamin D levels were evaluated in all participants using high performance liquid chromatography method included in the study. RESULTS: Compared to men without PE, the patients with acquired PE had significantly lower 25 (OH) D levels (12.0 ± 4.5 ng/mL vs. 18.2 ± 7.4 ng/mL, p < 0.001). In the logistic regression analysis, 25 (OH) D was found to be an independent risk factor for acquired PE, with estimated odds ratios (95% CI) of 0.639 (0.460-0.887, p = 0.007) and the area under curve of the ROC curve of 25 (OH) D diagnosing acquired PE was 0.770 (95% CI: 0.695 to 0.844, p < 0.001). The best cut-off value was 16 ng/mL with a sensitivity of 60.9%, specificity of 83.5%, PPV of 70.9%, and NPV of 76.4% to indicate acquired PE. CONCLUSIONS: This study demonstrates that lower vitamin D levels are associated with the acquired PE. The result of our study showed that the role of serum vitamin D levels should be investigate in the etiology of acquired PE. Perhaps supplementation of vitamin D in men with acquired PE will ameliorate the sexual health of these patients.


Assuntos
Ejaculação Precoce/sangue , Ejaculação Precoce/etiologia , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Vitamina D/análogos & derivados , Adulto , Estudos de Casos e Controles , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Fatores de Risco , Inquéritos e Questionários , Testosterona/sangue , Vitamina D/sangue , Adulto Jovem
20.
Onderstepoort J Vet Res ; 86(1): e1-e5, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-31038320

RESUMO

Canine babesiosis is a virulent infection of dogs in South Africa caused principally by Babesia rossi. Hypovitaminosis D has been reported in a wide range of infectious diseases in humans and dogs, and low vitamin D status has been associated with poor clinical outcomes. However, the relationship between vitamin D status and canine babesiosis has not been investigated. The objective of this study was to examine the relationship between the presence and severity of B. rossi infection and vitamin D status of infected dogs. Owners with dogs with a confirmed diagnosis of B. rossi infection and of healthy control dogs were invited to enrol onto the study. Vitamin D status was assessed by measurement of serum concentrations of the major circulating vitamin D metabolite, 25-hydroxyvitamin D (25[OH]D). Dogs with babesiosis (n = 34) had significantly lower mean serum 25(OH)D concentrations than healthy dogs (n = 24) (37.76 ± 21.25 vs. 74.2 ± 20.28 nmol/L). The effect of babesiosis on serum 25(OH)D concentrations was still significant after adjusting for any effect of age, body weight and sex. There was a negative relationship between serum 25(OH)D concentrations and disease severity in dogs with babesiosis. Serum concentrations of creatinine and alanine aminotransferase and time to last meal were not associated with serum 25(OH)D concentrations in dogs with babesiosis. In conclusion, dogs with Babesia rossi infections had lower serum 25(OH)D concentrations than healthy dogs. The inverse correlation between 25(OH)D concentrations and the clinical severity score indicate that hypovitaminosis D might be a helpful additional indicator of disease severity.


Assuntos
Babesiose/sangue , Doenças do Cão/sangue , Vitamina D/análogos & derivados , Animais , Estudos de Casos e Controles , Cães , Feminino , Masculino , Estudos Prospectivos , África do Sul , Vitamina D/sangue
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA