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1.
Shokuhin Eiseigaku Zasshi ; 61(2): 53-57, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32336709

RESUMO

Considerable amounts of processed foods contain vitamin D (ergocalciferol (D2) and cholecalciferol (D3)) as food additives. For field surveys on food additives, the analytical method for vitamin D should be well-validated. However, the current official method in Japan cannot separately determine the concentrations of D2 and D3, whereas the method for the Standard Tables of Food Composition in Japan 2015 (STFC method) can. Therefore, in this study, we verified the applicability of the STFC method to processed foods. During the course of this research, we added some improvements to the original method. Spike and recovery experiments using vegetable juice, soymilk, and corn flakes as food matrices showed that the recovery rates (relative standard deviation) of D2 and D3 were 103-112% (4.7-12.6%) and 102-109% (2.4-21.8%), respectively, at the estimated method limit of quantification (EMLOQ) level; and 100-110% (4.0-7.4%) and 102-105% (3.8-4.8%), respectively, at 10 times the EMLOQ level. These results indicated that accuracy and precision of the modified STFC method were enough to determine dietary D2 and D3 as endogenous nutrients and/or food additives, and suggested that this method is appropriate for analyzing vitamin D concentrations in processed foods.


Assuntos
Colecalciferol/análise , Ergocalciferóis/análise , Análise de Alimentos/normas , Vitaminas/análise , Japão
2.
Aging Clin Exp Res ; 32(1): 41-48, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30784012

RESUMO

BACKGROUND: Vitamin D inadequacy is common in institutionalized post-menopausal women who are at the highest risk for osteoporotic fracture. AIM: To evaluate efficacy and safety of ergocalciferol 40,000 versus 100,000 IU per week for 12 weeks for vitamin D inadequacy in institutionalized postmenopausal women. METHOD: A randomized double-blinded placebo-controlled trial was conducted in 94 institutionalized subjects with baseline 25(OH)D levels < 30 ng/mL. Subjects were randomized to receive ergocalciferol 40,000 (standard dose) or ergocalciferol 100,000 IU (high dose) per week. Serum 25(OH)D levels, calcium, phosphate, handgrip strength, time up and go (TUG) test and quality of life by EQ-5D-5L were measured at baseline and 12 weeks after randomization. RESULTS: Of the 94 subjects enrolled, 85 subjects completed the study. Subjects in the high dose group had higher mean 25(OH)D levels than subjects in the standard group (51.73 ± 19.35 and 34.5 ± 9.12, p < 0.001). More subjects in the high dose group (90.9%) achieved optimal 25(OH)D levels (> 30 ng/mL) than those in the standard group (65.9%), p = 0.007. In a subgroup analysis of subjects with vitamin D deficiency (< 20 ng/mL, n = 44) and severe vitamin D deficiency (< 10 ng/mL, n = 9), more subjects in the high dose group achieved optimal 25(OH)D levels than those in the standard group (88% and 100% versus 47.4% and 16.7% with p of 0.007 and 0.018, respectively). There were no differences in handgrip strength, TUG, EQ-5D-5L and adverse events between groups. DISCUSSION/CONCLUSIONS: Subjects who received high dose ergocalciferol achieved more optimal 25(OH)D levels than those who received standard dose. High dose ergocalciferol is preferred to optimize 25(OH)D levels in subjects with severe vitamin D deficiency.


Assuntos
Ergocalciferóis/administração & dosagem , Deficiência de Vitamina D/tratamento farmacológico , Vitaminas/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Força da Mão , Humanos , Pós-Menopausa , Qualidade de Vida , Deficiência de Vitamina D/sangue
3.
Food Chem ; 309: 125738, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-31706679

RESUMO

In the present study, the impact of ultraviolet (UV)-C treatment and ultrafine grinding on the conversion of ergosterol to vitamin D2, physiochemical properties, and antioxidant properties of shiitake and Jew's ear was assessed. After exposure to UV-C, vitamin D2 contents of both the mushroom samples has increased significantly (p < 0.05). Whereas, ultrafine grinding along with UV-C treatment has a synergistic effect on bioconversion of ergosterol to vitamin D2 and this effect is more prominent in low dose UV-C irradiation groups (2 kJ/m2). Ultrafine grinding significantly (p < 0.05) improved the water holding capacity (WHC), water solubility index (WSI) and polysaccharide dissolution rate (PDR). However, UV-C treatment led to insignificant changes in the physiochemical properties of mushroom samples. A significant improvement was also observed in the antioxidant profiles especially tannin contents of mushrooms followed by the ultrafine grinding and UV-C treatment.


Assuntos
Agaricales/metabolismo , Agaricales/efeitos da radiação , Antioxidantes/metabolismo , Ergocalciferóis/metabolismo , Ergosterol/metabolismo , Cogumelos Shiitake/metabolismo , Cogumelos Shiitake/efeitos da radiação , Agaricales/química , Antioxidantes/química , Biotransformação , Ergocalciferóis/química , Ergosterol/química , Cogumelos Shiitake/química , Raios Ultravioleta
4.
Ann Biol Clin (Paris) ; 77(6): 693-696, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31859648

RESUMO

Several hyperthyroidism misdiagnoses cases have been recently described due to biotin intake. Biotin used in immuno-analysis assays which rely on biotin/streptavidin binding properties. In these assays, high plasmatic biotin levels can lead to major analytical interferences resulting in falsely higher (competition tests) or falsely reduced determinations (for sandwiches assays). We performed a simulation test of biotin intake with patient's samples. We studied the effect of biotin on cardiac troponin I and total vitamin D (D2+D3) assays that are using biotin-streptavidin binding on Dimension EXL®. Increasing doses of biotin were added (28 samples for each parameter) before the assays. The results evidenced a significant negative interference of biotin on cardiac troponin I determinations for concentrations of 100 ng/mL and above, with a total loss of signal for higher biotin additions. Such interference may lead to inappropriate therapeutic decisions. Positive interferences were observed on total vitamin D (D2+D3) with less impact for therapeutic decisions.


Assuntos
Ligação Competitiva , Biotina/metabolismo , Testes Diagnósticos de Rotina , Hipertireoidismo/diagnóstico , Estreptavidina/metabolismo , Troponina I/análise , Vitamina D/análise , Adulto , Artefatos , Biotina/administração & dosagem , Biotina/efeitos adversos , Colecalciferol/análise , Colecalciferol/sangue , Doença das Coronárias/sangue , Doença das Coronárias/diagnóstico , Erros de Diagnóstico , Testes Diagnósticos de Rotina/instrumentação , Testes Diagnósticos de Rotina/métodos , Testes Diagnósticos de Rotina/normas , Ergocalciferóis/análise , Ergocalciferóis/sangue , Humanos , Hipertireoidismo/sangue , Imunoensaio/instrumentação , Imunoensaio/métodos , Miocárdio/química , Miocárdio/metabolismo , Troponina I/sangue , Troponina I/metabolismo , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico
5.
Nutrients ; 11(11)2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31731605

RESUMO

Vitamin D (VitD) insufficiency is common in multiple sclerosis (MS). VitD has possible anti-inflammatory effects on the immune system. The ratio between VitD metabolites in MS patients and the severity of the disease are suggested to be related. However, the exact effect of the bone-derived hormone fibroblast-growth-factor-23 (FGF23) and VitD binding protein (VDBP) on this ratio is not fully elucidated yet. Therefore, the aim is to study differences in total, free, and bioavailable VD metabolites and FGF23 between MS patients and healthy controls (HCs). FGF23, vitD (25(OH)D), active vitD (1,25(OH)2D), inactive 24,25(OH)D, and VDBP were measured in 91 MS patients and 92 HCs. Bioavailable and free concentrations were calculated. No difference in FGF23 (p = 0.65) and 25(OH)D/24.25(OH)2D ratio (p = 0.21) between MS patients and HCs was observed. Bioavailable 25(OH)D and bioavailable 1.25(OH)2D were lower (p < 0.01), while VDBP concentrations were higher in MS patients (p = 0.02) compared with HCs, specifically in male MS patients (p = 0.01). In conclusion, FGF23 and 25(OH)D/24.25(OH)2D did not differ between MS patients and HCs, yet bioavailable VitD concentrations are of potential clinical relevance in MS patients. The possible immunomodulating role of VDBP and gender-related differences in the VD-FGF23 axis in MS need further study.


Assuntos
25-Hidroxivitamina D 2/sangue , Ergocalciferóis/sangue , Fatores de Crescimento de Fibroblastos/sangue , Esclerose Múltipla/sangue , Vitamina D/análogos & derivados , Adulto , Disponibilidade Biológica , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/etiologia , Proteína de Ligação a Vitamina D/sangue
6.
Nutrients ; 11(10)2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31614966

RESUMO

Vitamin D2 deficiency is one of the most common micronutrient insufficiencies among children. Few foods, mainly those derived from animal sources, naturally contain this vitamin. The basidiomycete mushroom Pleurotus ostreatus could be used as an innovative and sustainable ingredient for food fortification with vitamin D2. This study was aimed at exploring children's acceptance of a whole-cereal-based product (breadsticks) combined with increasing concentrations of P. ostreatus powder rich in vitamin D2. The food neophobia trait (fear of trying unfamiliar and new food) on sample acceptability was also investigated. One hundred and three children (47 girls and 56 boys, aged 9-11 years) were recruited, and breadstick-liking was studied in relation to gender and neophobic traits. Results showed that the samples enriched in vitamin D2 were well accepted by children even if liking decreased with increasing concentration of mushroom powder. Generally, neophilic subjects gave higher liking scores compared with the neophobic ones, especially for the modified samples. New, well-accepted fortified products could be developed using an adequate concentration of mushroom powder to deal with the increasing vitamin D2 deficiency among children.


Assuntos
Ergocalciferóis/administração & dosagem , Alimentos Fortificados , Pleurotus/química , Paladar , Grãos Integrais/química , Criança , Ergocalciferóis/química , Feminino , Humanos , Masculino
7.
PLoS One ; 14(9): e0214349, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31527864

RESUMO

This study aimed to assess the renopreventive effect of enalapril and/or paricalcitol on streptozotocin (STZ) diabetes-induced nephropathy and to elucidate their mechanisms of action through investigation of the effects on renal oxidative stress, antioxidant defense system and expressions of TNF-α, p53, caspase-3, and Bcl-2. Diabetes mellitus was induced in fasting male Wistar rats by single intraperitoneal injection of STZ (45 mg /kg b.w.) dissolved in citrate buffer (pH 4.5). Ten days after STZ injection, the diabetic rats were treated with enalapril (25 mg/l of drinking water) and/or paricalcitol (8 µg/kg b.w. per os) dissolved in 5% DMSO daily for 4 weeks. The obtained data revealed that the treatment of diabetic Wistar rats with enalapril and/or paricalcitol led to significant decreases in the elevated serum urea, uric acid, creatinine, sodium and potassium levels; thereby reflecting the improvement of the impaired kidney function. The deteriorated kidney lipid peroxidation, GSH content and GST and catalase activities in diabetic rats were significantly ameliorated as a result of treatment with enalapril and/or paricalcitol. The elevated fasting and post-prandial serum glucose levels and the lowered serum insulin and C-peptide levels were also improved. The treatment with enalapril and paricalcitol in combination was the most potent in decreasing the elevated serum glucose levels. Moreover, the treatment of diabetic rats successfully prevented the diabetes-induced histopathological deleterious changes of kidney and islets of Langerhans of pancreas. In association, the immunohistochemically detected pro-inflammatory cytokine, TNF-α, and apoptotic mediators, p53 and caspase-3, were remarkably decreased in kidney of diabetic rats as a result of treatment while the expression of anti-apoptotic protein Bcl-2 was increased. Based on these findings, it can be concluded that enalapril and paricalcitol alone or in combination can prevent STZ diabetes-induced nephropathy through amelioration of the glycemic state and antioxidant defense system together with the suppression of oxidative stress, inflammation and apoptosis. However, the treatment of diabetic rats with enalapril and paricalcitol in combination has no further significant improvement effects on renal function and damage when compared with enalapril or paclitaxel treated diabetic groups.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/tratamento farmacológico , Enalapril/farmacologia , Ergocalciferóis/farmacologia , Rim/efeitos dos fármacos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Apoptose , Caspase 3/genética , Caspase 3/metabolismo , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Enalapril/uso terapêutico , Ergocalciferóis/uso terapêutico , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Rim/metabolismo , Masculino , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
8.
Life Sci ; 234: 116755, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31415769

RESUMO

AIMS: Vitamin D and its receptor, vitamin D receptor (VDR), have renoprotection effect against diabetic nephropathy (DN). But the exact mechanism has not been fully elucidated. Epoxyeicosatrienoic acids (EETs) are cytochrome P450 (CYP) epoxygenase-derived metabolites of arachidonic acid, protecting against diabetes and DN. Herein, we hypothesized that activation of VDR attenuated high glucose-induced cellular injury in renal tubular epithelial cells partially through up-regulating CYP2J5 expression. MAIN METHODS: Streptozotocin (STZ) was injected to induce diabetic in wild type and Vdr-/- mice. The effects of VDR knockout and an activator of VDR, paricalcitol, on the renal injury were detected. In vitro, a murine kidney proximal tubule epithelial cell line BU.MPT induced by high glucose were treated with or without paricalcitol (30 mM) for 12 h or 24 h. KEY FINDINGS: The expression of CYP2J5 was significantly decreased both in wild type and Vdr-/- diabetic mice induced by STZ. The STZ-induced kidney architecture damage and apoptosis rate in Vdr-/- mice were more severe. In vitro, high glucose treatment strongly reduced the CYP2J5 expression and the synthesis of 14,15-EET in BU.MPT cells. Supplement of 14,15-EET significantly reduced the lactate dehydrogenase (LDH) release induced by high glucose in BU.MPT cells. Furthermore, treatment with paricalcitol attenuated cellular injury and restored the expression of CYP2J5 reduced by high glucose in BU.MPT cells. SIGNIFICANCE: We conclude that activation of VDR attenuates high glucose-induced cellular injury partially dependent on CYP2J5 in murine renal tubule epithelial cells and paricalcitol may represent a potential therapy for DN.


Assuntos
Sistema Enzimático do Citocromo P-450/genética , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/etiologia , Ergocalciferóis/farmacologia , Túbulos Renais Proximais/efeitos dos fármacos , Receptores de Calcitriol/agonistas , Animais , Linhagem Celular , Sistema Enzimático do Citocromo P-450/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/patologia , Ergocalciferóis/uso terapêutico , Deleção de Genes , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , Masculino , Camundongos , Camundongos Knockout , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo
9.
Nutr Hosp ; 36(Spec No3): 3-7, 2019 Aug 27.
Artigo em Espanhol | MEDLINE | ID: mdl-31368328

RESUMO

Introduction: Vitamin D is an essential nutrient whose deficiency has been associated with the risk of various chronic diseases such as osteoporosis, hypertension, cardiovascular disease, diabetes, some types of cancer and even overweight and obesity. Although vitamin D can be synthesized at the skin from exposure to sunlight, this source is not always sufficient to meet the needs. For example, the use of sunscreen or the low exposition to the sunlight limits the syntheses. In fact, studies have found that at least half of the Spanish population has vitamin D deficits. Therefore, the dietary contribution is fundamental. Although there are different foods fortified in this vitamin, few products are natural source of it, as fatty fish and eggs. However, according to different studies carried out in the Spanish population, there is a low consumption of this food group. In this way, it would be advisable to promote egg consumption among the population, since this food, in addition to having many nutrients, contains a high amount of vitamin D, which contributes to avoid the appearance of deficiencies and the consequences health consequences that this implies.


Assuntos
Colecalciferol/administração & dosagem , Ovos , Ergocalciferóis/administração & dosagem , Deficiência de Vitamina D/dietoterapia , Vitaminas/administração & dosagem , Colecalciferol/biossíntese , Colecalciferol/sangue , Ergocalciferóis/sangue , Ergocalciferóis/metabolismo , Humanos , Política Nutricional , Espanha/epidemiologia , Luz Solar , Vitamina D/biossíntese , Vitamina D/sangue , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologia
10.
BMJ ; 366: l4673, 2019 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-31405892

RESUMO

OBJECTIVE: To investigate whether vitamin D supplementation is associated with lower mortality in adults. DESIGN: Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: Medline, Embase, and the Cochrane Central Register from their inception to 26 December 2018. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials comparing vitamin D supplementation with a placebo or no treatment for mortality were included. Independent data extraction was conducted and study quality assessed. A meta-analysis was carried out by using fixed effects and random effects models to calculate risk ratio of death in the group receiving vitamin D supplementation and the control group. MAIN OUTCOME MEASURES: All cause mortality. RESULTS: 52 trials with a total of 75 454 participants were identified. Vitamin D supplementation was not associated with all cause mortality (risk ratio 0.98, 95% confidence interval 0.95 to 1.02, I2=0%), cardiovascular mortality (0.98, 0.88 to 1.08, 0%), or non-cancer, non-cardiovascular mortality (1.05, 0.93 to 1.18, 0%). Vitamin D supplementation statistically significantly reduced the risk of cancer death (0.84, 0.74 to 0.95, 0%). In subgroup analyses, all cause mortality was significantly lower in trials with vitamin D3 supplementation than in trials with vitamin D2 supplementation (P for interaction=0.04); neither vitamin D3 nor vitamin D2 was associated with a statistically significant reduction in all cause mortality. CONCLUSIONS: Vitamin D supplementation alone was not associated with all cause mortality in adults compared with placebo or no treatment. Vitamin D supplementation reduced the risk of cancer death by 16%. Additional large clinical studies are needed to determine whether vitamin D3 supplementation is associated with lower all cause mortality. STUDY REGISTRATION: PROSPERO registration number CRD42018117823.


Assuntos
Suplementos Nutricionais , Mortalidade , Vitamina D/administração & dosagem , Colecalciferol/administração & dosagem , Ergocalciferóis/administração & dosagem , Humanos , Neoplasias/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
EBioMedicine ; 45: 393-407, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31303501

RESUMO

BACKGROUND: Recent studies have revealed that vitamin D deficiency may increase the risk of Alzheimer's disease, and vitamin D supplementation may be effective strategy to ameliorate the neurodegenerative process in Alzheimer's disease patients. Paricalcitol (PAL), a low-calcemic vitamin D receptor agonist, is clinically used to treat secondary hyperparathyroidism. However, the potential application of PAL for treating neurodegenerative disorders remains unexplored. METHODS: The APP/PS1 mice were intraperitoneally injected with PAL or vehicle every other day for 15 weeks. The ß-amyloid (Aß) production was confirmed using immunostaining and enzyme linked immunosorbent assay. The underlying mechanism was verified by western blot and immunostaining in vivo and in vitro. FINDINGS: Long-term PAL treatment clearly reduced ß-amyloid (Aß) generation and neuronal loss in APP/PS1 transgenic mouse brains. PAL stimulated the expression of low-density lipoprotein receptor-related protein 1 (LRP1) possibly through inhibiting sterol regulatory element binding protein-2 (SREBP2); PAL also promoted LRP1-mediated ß-site APP cleavage enzyme 1 (BACE1) transport to late endosomes, thus increasing the lysosomal degradation of BACE1. Furthermore, PAL diminished 8-hydroxyguanosine (8-OHdG) generation in neuronal mitochondria via enhancing base excision repair (BER), resulting in the attenuation of calpain-1-mediated neuronal loss. INTERPRETATION: The present data demonstrate that PAL can reduce Aß generation through accelerating BACE1 lysosomal degradation and can inhibit neuronal loss through suppressing mitochondrial 8-OHdG generation. Hence, PAL might be a promising agent for treating Alzheimer's disease. FUND: This study was financially supported by the Natural Science Foundation of China (U1608282).


Assuntos
Doença de Alzheimer/tratamento farmacológico , Secretases da Proteína Precursora do Amiloide/genética , Ácido Aspártico Endopeptidases/genética , Ergocalciferóis/farmacologia , Neurônios/efeitos dos fármacos , 8-Hidroxi-2'-Desoxiguanosina/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/genética , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Calpaína/genética , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Proteína-1 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Lisossomos/efeitos dos fármacos , Lisossomos/genética , Camundongos , Camundongos Transgênicos , Mitocôndrias/metabolismo , Neurônios/patologia , Oligopeptídeos/genética , Presenilina-1/genética , Proteólise/efeitos dos fármacos
13.
Int Urol Nephrol ; 51(7): 1261-1270, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31161518

RESUMO

OBJECTIVE: To evaluate monthly percentage changes of intact parathyroid hormone (iPTH) and other major bone marker levels in patients with secondary hyperparathyroidism (SHPT) undergoing hemodialysis (HD) and receiving paricalcitol. METHODS: A total of 493 (F/M 244/249) adult patients with SHPT who were undergoing HD in 22 HD units and receiving paricalcitol treatment, with iPTH > 300 mg/mL, adjusted serum levels of calcium (Ca) < 10.2 mg/dL, and serum levels of inorganic phosphorus (iP) < 6 mg/dL were included in this multi-center, national, prospective, observational study. Data regarding efficacy, safety, and adverse events of paricalcitol treatment were collected during a 12-month follow-up period through monthly visits along with serum iPTH, Ca, iP, alkaline phosphatase (ALP) and other required biochemistry tests as necessary. Mortality data until 6 months after the end of the study were also investigated. RESULTS: The mean age was 58.3 ± 15.8 years and the mean duration of HD was 6.2 ± 5.5 years, respectively. As of 12th month, mean iPTH values decreased from 646 ± 424 pg/mL to 473 ± 387 pg/mL (p < 0.001); no statistically significant changes were observed in Ca levels (p > 0.05). Serum ALP levels also significantly decreased (p = 0.001) and serum phosphorus levels significantly increased (p < 0.001) during the study observation period. Reasons for early terminations were being lost to follow-up (n = 119, 24.1%), hyperphosphatemia (iP > 6 mg/dL, n = 108, 21.9%), low iPTH levels (iPTH < 150 mg/dL, n = 97, 19.7%), and withdrawal of consent (n = 41, 8.3%). In total 32 patients (6.5%) were prematurely terminated the study with hypercalcemia (Ca > 10.2 mg/dL). 46.9% of those hypercalcemic patients had other anomalies with iP and iPTH levels along with hypercalcemia. CONCLUSION: Paricalcitol treatment, resulted in successful iPTH control. In approximately 6.5% of the patients paricalcitol treatment was discontinued since Ca levels reached > 10.2 mg/dL in those patients. No unfavorable effects on serum phosphorus and Ca-phosphorus (Ca × P) product were observed.


Assuntos
Ergocalciferóis , Hiperparatireoidismo Secundário , Falência Renal Crônica/terapia , Diálise Renal , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/efeitos adversos , Cálcio/sangue , Monitoramento de Medicamentos/métodos , Ergocalciferóis/administração & dosagem , Ergocalciferóis/efeitos adversos , Feminino , Humanos , Hiperparatireoidismo Secundário/sangue , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/prevenção & controle , Falência Renal Crônica/epidemiologia , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fósforo/sangue , Estudos Prospectivos , Diálise Renal/efeitos adversos , Diálise Renal/métodos , Turquia/epidemiologia
14.
J Steroid Biochem Mol Biol ; 192: 105407, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31201925

RESUMO

24,25(OH)2D and the 25OHD/24,25(OH)2D ratio have recently been shown to be useful for screening for hypercalcemia caused by CYP24A1 mutations. However, no population-based data on 24,25(OH)2D have been published for Chinese populations, and few studies evaluated the sources of variation on 24,25(OH)2D levels and the 25OHD/24,25(OH)2D ratio. Hence, in 2018, we enrolled 1211 apparently healthy adults without systematic diseases from six representative cities in China (Beijing, Dongying, Guiyang, Urumqi, Shenzhen, and Qiqihar). 24,25(OH)2D and 25OHD levels were measured using isotope dilution liquid chromatography tandem mass spectrometry. Multiple regression analysis showed that sex contributed the most to variations in 24,25(OH)2D, 25OHD, and 25OHD/24,25(OH)2D (rp= -0.255, -0.253, and 0.141, respectively), and age also contributed to variations in 25OHD but not 24,25(OH)2D or 25OHD/24,25(OH)2D. Men had significantly higher 24,25(OH)2D and 25OHD levels than women, but had significantly lower 25OHD/24,25(OH)2D values. Individuals from Dongying had the highest 24,25(OH)2D and 25OHD values, whereas individuals from Urumqi had the lowest values. The median(2.5-97.5%) values for 24,25(OH)2D, 25OHD, and 25OHD/24,25(OH)2D were 1.2(0.36-2.65) ng/mL, 18.9(8.6-32.5) ng/mL, and 16.0 (9.8-30.8), respectively. 24,25(OH)2D was significantly correlated with 25OHD (r = 0.838, p <  0.001), and 25OHD/24,25(OH)2D was significantly negatively correlated with 24,25(OH)2D (r = -0.758, P < 0.001) and 25OHD (r = -0.310, P < 0.001). In conclusion, in this nationwide, multicenter, cross-sectional study, we evaluated the levels of 24,25(OH)2D and the 25OHD/24,25(OH)2D ratio in the Chinese population. Sex contributed the most to variations in 24,25(OH)2D, 25OHD, and 25OHD/24,25(OH)2D.


Assuntos
Biomarcadores/sangue , Ergocalciferóis/sangue , Deficiência de Vitamina D/sangue , Vitamina D/análogos & derivados , Adulto , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Prevalência , Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/epidemiologia
16.
Nutrients ; 11(5)2019 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-31035488

RESUMO

BACKGROUND: Epidemiological studies have suggested a survival benefit for hemodialysis patients on paricalcitol or calcitriol, but nutritional vitamin D supplementation of patients already on vitamin D receptor (VDR) activators is controversial. METHODS: This observational retrospective cohort study was conducted with prospectively collected data from all consecutive patients with chronic kidney disease (CKD) who underwent hemodialysis under routine clinical practice conditions for two years. RESULTS: Of the 129 patients, 89 were treated with calcidiol, paricalcitol, and/or calcitriol. The patients with any vitamin D formulation had higher serum concentrations of 25-hydroxy vitamin D and fibroblast growth factor-23 and tended to have higher mortality rates (42% vs. 25%, p = 0.07). On subgroup analysis, any calcidiol treatment or calcidiol combined with paricalcitol associated with significantly higher mortality rates than no treatment (47% and 62.5%, p = 0.043 and 0.008, respectively). The association between calcidiol/paricalcitol treatment and elevated mortality remained significant after adjusting for age, sex, diabetes, C-reactive protein, and hemodialysis vintage. Any calcidiol and calcidiol/paricalcitol treatment exhibited a dose-response relationship with mortality (p for trend: 0.002 and 0.005, respectively). CONCLUSIONS: These data draw attention to the hitherto unexplored safety of calcidiol supplementation in patients on hemodialysis, especially in those already on vitamin D. Until clinical trials demonstrate the safety and efficacy of this approach, caution should be exercised when prescribing these patients ≥0.5 calcidiol mg/month.


Assuntos
Calcifediol/efeitos adversos , Calcifediol/uso terapêutico , Diálise Renal , Idoso , Calcifediol/administração & dosagem , Ergocalciferóis/administração & dosagem , Ergocalciferóis/efeitos adversos , Ergocalciferóis/uso terapêutico , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D , Vitaminas/administração & dosagem , Vitaminas/efeitos adversos , Vitaminas/farmacologia
17.
Drug Des Devel Ther ; 13: 999-1009, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30992658

RESUMO

Background: The elevated calcium and phosphorus levels in patients undergoing hemodialysis may increase the risk of all-cause mortality. Paricalcitol, as a new vitamin D receptor activator (VDRA), seemed to be effective in reducing the calcium and phosphorus levels. Objectives: The aim of this study was to compare the efficacy and safety of paricalcitol with other VDRAs in patients undergoing hemodialysis. Methods: PubMed, Embase, and Web of Science database were systematically reviewed. Selection criteria: Studies that focused on the use of paricalcitol for hemodialysis patients were eligible for inclusion. Data collection and analysis: Two independent investigators performed the literature search, data extraction, and assessment of methodological quality. The outcomes were expressed with standard mean difference (SMD), HR, or risk ratio (RR) with 95% CI. Results: Thirteen studies involving 112,695 patients were included in this meta-analysis. Among these studies, four studies were cohort studies and nine studies were randomized controlled trials (RCTs). For cohort studies, they were regarded as being of high quality; for RCTs, only one was classified as being at low risk of bias; and the remaining eight studies were at being unclear risk of bias. Compared with other VDRAs, paricalcitol significantly improved the overall survival (HR =0.86, 95% CI: 0.80, 0.92; P<0.001) and reduced the intact parathyroid hormone (iPTH) (SMD =-0.53, 95% CI: -0.90, -0.17; P=0.004). Paricalcitol offered similar effect with other VDRAs in the control of calcium (SMD =0.32, 95% CI: -0.04, 0.67; P=0.078) and phosphorus (SMD =0.06, 95% CI: -0.26, 0.37; P=0.727) levels. However, the serum change in calcium phosphate product was greater in the paricalcitol group than in the other VDRA group (SMD =2.13, 95% CI: 0.19, 4.07; P=0.031). There was no significant difference in the incidence of adverse events between the two groups (RR =1.02, 95% CI: 0.93, 1.12; P=0.674). Conclusion: Paricalcitol was crucial in reducing the mortality in patients undergoing hemodialysis. Moreover, both paricalcitol and other VDRAs were effective in control of the serum iPTH, calcium, and phosphorus levels. Given the potential limitations in this study, more prospective large-scale, well-conducted RCTs are needed to confirm these findings.


Assuntos
Ergocalciferóis/efeitos adversos , Ergocalciferóis/uso terapêutico , Hiperparatireoidismo/prevenção & controle , Falência Renal Crônica/terapia , Diálise Renal , Estudos de Coortes , Ergocalciferóis/administração & dosagem , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
Am J Physiol Renal Physiol ; 316(5): F1068-F1077, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30864841

RESUMO

Acute kidney injury (AKI) is a common complication of sepsis characterized by a rapid degradation of renal function. The effect of vitamin D on AKI remains poorly understood. Here, we showed that vitamin D receptor (VDR) activation protects against lipopolysaccharide (LPS)-induced AKI by blocking renal tubular epithelial cell apoptosis. Mice lacking VDR developed more severe AKI than wild-type (WT) control mice after LPS treatment, which was manifested by marked increases in body weight loss and accumulation of serum blood urea nitrogen and creatinine as well as the magnitude of apoptosis of tubular epithelial cells. In the renal cortex, LPS treatment led to more dramatic downregulation of Bcl-2, more robust induction of p53-upregulated modulator of apoptosis (PUMA) and miR-155, and more severe caspase-3 activation in VDR knockout mice compared with WT control mice. Conversely, paricalcitol pretreatment markedly prevented LPS-induced AKI. Paricalcitol ameliorated body weight loss, attenuated serum blood urea nitrogen and creatinine accumulation, blocked tubular cell apoptosis, prevented the suppression of Bcl-2, and reversed PUMA and miR-155 induction and caspase-3 activation in LPS-treated WT mice. In HK2 cells, LPS induced PUMA and miR-155 by activating NF-κB, whereas 1,25(OH)2D3 blocked PUMA and miR-155 induction by repressing NF-κB activation. Both PUMA and miR-155 target Bcl-2 to promote apoptosis; namely, PUMA inhibits Bcl-2 activity, whereas miR-155 promotes Bcl-2 mRNA degradation and inhibits Bcl-2 protein translation. Collectively, these data provide strong evidence that LPS induces tubular cell apoptosis via upregulating PUMA and miR-155, whereas vitamin D/VDR signaling protects against AKI by blocking NF-κB-mediated PUMA and miR-155 upregulation.


Assuntos
Lesão Renal Aguda/prevenção & controle , Apoptose/efeitos dos fármacos , Ergocalciferóis/farmacologia , Túbulos Renais Proximais/efeitos dos fármacos , Lipopolissacarídeos , Receptores de Calcitriol/agonistas , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/metabolismo , Lesão Renal Aguda/patologia , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Modelos Animais de Doenças , Humanos , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Células RAW 264.7 , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Transdução de Sinais , Proteínas Supressoras de Tumor/metabolismo
19.
G Ital Nefrol ; 36(1)2019 Feb.
Artigo em Italiano | MEDLINE | ID: mdl-30758155

RESUMO

BACKGROUND: Left ventricular hypertrophy (LVH) is common in renal transplant recipients (RTRs), and persistent secondary hyperparathyroidism (SHPT) is considered to be one of the main causes of its pathogenesis. In this study we evaluated if the control of SHPT with paricalcitol is associated with a reduction of LVH in RTRs. METHODS: For this purpose we selected 24 RTRs with LVH and SHPT. Secondary hyperparathyroidism was defined as PTH levels 1.5 times higher than the high normal limits, while LVH was defined as a left ventricular mass index (LVMi) >95g/m2 in females, and >115g/m2 in males. Treatment with paricalcitol started at mean dose of 1µg/day and lasted 18 months. The dose of paricalcitol was reduced to 1µg on the other day when serum calcium was >10.5mg/dl and/or fractional excretion of calcium was >0.020%; administration was temporarily stopped when serum calcium was >11 mg/dl. RESULTS: At follow-up PTH levels decreased from 198 ± 155 to 105 ± 43pg/ml, and LVMi decreased from 134 ± 21 to 113 ± 29g/m2; the presence of LVH decreased from 100% at baseline to 54% at F-U. Serum calcium levels showed a modest and not significant increase. Renal function was stable in all patients. CONCLUSIONS: Secondary hyperparathyroidism seems to play an important role in the development and maintenance of LVH and its correction with paricalcitol has a favorable impact on its progression.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Ergocalciferóis/uso terapêutico , Hiperparatireoidismo Secundário/tratamento farmacológico , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Transplante de Rim , Adulto , Idoso , Conservadores da Densidade Óssea/administração & dosagem , Cálcio/urina , Esquema de Medicação , Ergocalciferóis/administração & dosagem , Feminino , Seguimentos , Humanos , Hiperparatireoidismo Secundário/sangue , Hiperparatireoidismo Secundário/complicações , Hiperparatireoidismo Secundário/diagnóstico , Hipertrofia Ventricular Esquerda/diagnóstico , Hipertrofia Ventricular Esquerda/etiologia , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fatores Sexuais , Fatores de Tempo
20.
J Steroid Biochem Mol Biol ; 189: 204-209, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30710745

RESUMO

Inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease have been linked to vitamin D-deficiency. Using a dextran sodium sulphate (DSS)-induced model of IBD we have shown previously that mice raised on vitamin D-deficient diets from weaning have lower serum 25-hydroxyvitamin D (25OHD) levels and develop more severe colitis compared to vitamin D-sufficient counterparts. We have also shown in vitro that immune responses to 25OHD may depend on 'free' rather than total serum concentrations of 25OHD. To investigate the possible effects of free versus total 25OHD on anti-inflammatory immune responses in vivo we have studied DSS-induced colitis in wild type C57BL/6 mice raised from weaning on diets containing vitamin D2 (D2) or vitamin D3 (D3) only (both 1000 IU/kg feed). 25OHD2 has lower binding affinity for the vitamin D binding protein than 25OHD3 which results in higher levels of free 25OHD2 relative to free 25OHD3 in mice raised on a D2-only diet. Total serum 25OHD concentrations, measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS), showed that D2 mice had significantly lower levels of 25OHD than D3 mice (6.85 ± 2.61 nmol/L vs. 49.16 ± 13.8 nmol/L for D2 and D3 respectively). Despite this, direct ELISA measurement showed no difference in free serum 25OHD levels between D2 and D3 mice (13.62 ± 2.26 pmol/L vs. 14.11 ± 2.24 pmol/L for D2 and D3 respectively). Analysis of DSS-induced colitis also showed no difference in weight loss or disease progression between D2 and D3 mice. These data indicate that despite D2-fed mice being vitamin D-deficient based on serum total 25OHD concentrations, these mice showed no evidence of increased inflammatory colitis disease relative to vitamin D-sufficient D3 mice. We therefore propose that free, rather than total serum 25OHD, may be a better marker of immune responses to vitamin D in vivo.


Assuntos
25-Hidroxivitamina D 2/sangue , Calcifediol/sangue , Deficiência de Vitamina D/sangue , Vitaminas/sangue , Animais , Colecalciferol/administração & dosagem , Colecalciferol/sangue , Colite/sangue , Ergocalciferóis/administração & dosagem , Ergocalciferóis/sangue , Masculino , Camundongos Endogâmicos C57BL , Vitamina D/análogos & derivados , Vitamina D/sangue
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