Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 132
Filtrar
1.
Am J Physiol Heart Circ Physiol ; 314(4): H753-H765, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29351464

RESUMO

Vitamin D deficiency is linked to pathogenesis of many diseases including cardiovascular, cancer, and various eye diseases. In recent years, important roles for vitamin D in regulation of immune function, inflammation, angiogenesis, and aging have been demonstrated. Thus, vitamin D and its analogs have been evaluated for the treatment of various types of cancer and chronic diseases. We have previously shown that the active form of vitamin D [1,25(OH)2D3] is a potent inhibitor of angiogenesis. This activity is consistent with the important role proposed for vitamin D and its analogs in the mitigation of tumor growth through inhibition of angiogenesis. Here, we review the important nutritional value of vitamin D and the abnormalities linked to its deficiency. We will explore its potential role as a regulator of angiogenesis and vascular cell function and the role vitamin D receptor (VDR) expression plays in these activities during vascular development and neovascularization. Our studies have established an important role for 1,25(OH)2D3 and VDR in the regulation of perivascular supporting cell function. In addition, the interaction of 1,25(OH)2D3 and VDR is essential for these activities and inhibition of neovascularization. Delineating the signaling pathways involved and identification of genes that are the target of 1,25(OH)2D3 regulation in vascular cells will allow us to identify novel pathways that are targets for regulation of vascular function and angiogenesis.


Assuntos
Calcitriol/metabolismo , Doenças Cardiovasculares/metabolismo , Neovascularização Fisiológica , Receptores de Calcitriol/metabolismo , Doenças Retinianas/metabolismo , Neovascularização Retiniana , Vasos Retinianos/metabolismo , Deficiência de Vitamina D/metabolismo , Animais , Calcitriol/deficiência , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/fisiopatologia , Humanos , Doenças Retinianas/epidemiologia , Doenças Retinianas/patologia , Doenças Retinianas/fisiopatologia , Vasos Retinianos/patologia , Vasos Retinianos/fisiopatologia , Fatores de Risco , Transdução de Sinais , Deficiência de Vitamina D/epidemiologia
2.
J Bone Miner Res ; 33(1): 16-26, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28686309

RESUMO

We hypothesized that adaptation to calcium supply demands of pregnancy and lactation do not require calcitriol. Adult Cyp27b1 null mice lack calcitriol and have hypocalcemia, hypophosphatemia, and rickets. We studied wild-type (WT) and null sister pairs raised on a calcium-, phosphorus-, and lactose-enriched "rescue" diet that prevents hypocalcemia and rickets. Bone mineral content (BMC) increased >30% in pregnant nulls, declined 30% during lactation, and increased 30% by 4 weeks post-weaning. WT showed less marked changes. Micro-CT revealed loss of trabecular bone and recovery in both genotypes. In lactating nulls, femoral cortical thickness declined >30%, whereas endocortical perimeter increased; both recovered to baseline after weaning; there were no such changes in WT. Histomorphometry revealed a profound increase in osteoid surface and thickness in lactating nulls, which recovered after weaning. By three-point bend test, nulls had a >50% decline in ultimate load to failure that recovered after weaning. Although nulls showed bone loss during lactation, their milk calcium content was 30% lower compared with WT. Serum parathyroid hormone (PTH) was markedly elevated in nulls at baseline, reduced substantially in pregnancy, but increased again during lactation and remained high post-weaning. In summary, pregnant Cyp27b1 nulls gained BMC with reduced secondary hyperparathyroidism, implying increased intestinal calcium delivery. Lactating nulls lost more bone mass and strength than WT, accompanied by increased osteoid, reduced milk calcium, and worsened secondary hyperparathyroidism. This implies suboptimal intestinal calcium absorption. Post-weaning, bone mass and strength recovered to baseline, whereas BMC exceeded baseline by 40%. In conclusion, calcitriol-independent mechanisms regulate intestinal calcium absorption and trabecular bone metabolism during pregnancy and post-weaning but not during lactation; calcitriol may protect cortical bone during lactation. © 2017 American Society for Bone and Mineral Research.


Assuntos
25-Hidroxivitamina D3 1-alfa-Hidroxilase/deficiência , Reabsorção Óssea/patologia , Osso e Ossos/patologia , Calcitriol/deficiência , Cálcio/metabolismo , Lactação/metabolismo , Leite/química , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/metabolismo , Animais , Biomarcadores/sangue , Densidade Óssea , Remodelação Óssea , Reabsorção Óssea/diagnóstico por imagem , Osso e Ossos/diagnóstico por imagem , Calcitriol/sangue , Cálcio/sangue , Feminino , Regulação da Expressão Gênica , Tamanho da Ninhada de Vivíparos , Glândulas Mamárias Animais/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Reprodução , Microtomografia por Raio-X
3.
J Immunol ; 199(12): 3952-3958, 2017 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-29109124

RESUMO

The vitamin D receptor participates in the control of IgE class-switch recombination in B cells. The physiologic vitamin D receptor agonist, 1,25(OH)2D3 (calcitriol), is synthesized by the essential enzyme 25-hydroxyvitamin D3-1α-hydroxylase (CYP27B1), which can be expressed by activated immune cells. The role of endogenous calcitriol synthesis for the regulation of IgE has not been proven. In this study, we investigated IgE-responses in Cyp27b1-knockout (KO) mice following sensitization to OVA or intestinal infection with Heligmosomoides polygyrus Specific Igs and plasmablasts were determined by ELISA and ELISpot, Cyp27b1 expression was measured by quantitative PCR. The data show elevated specific IgE and IgG1 concentrations in the blood of OVA-sensitized Cyp27b1-KO mice compared with wild-type littermates (+898 and +219%). Accordingly, more OVA-specific IgG1-secreting cells are present in spleen and fewer in the bone marrow of Cyp27b1-KO mice. Ag-specific mechanisms are suggested as the leucopoiesis is in general unchanged and activated murine B and T lymphocytes express Cyp27b1 Accordingly, elevated specific IgE concentrations in the blood of sensitized T cell-specific Cyp27b1-KO mice support a lymphocyte-driven mechanism. In an independent IgE-inducing model, i.e., intestinal infection with H. polygyrus, we validated the increase of total and specific IgE concentrations of Cyp27b1-KO compared with wild-type mice, but not those of IgG1 or IgA. We conclude that endogenous calcitriol has an impact on the regulation of IgE in vivo. Our data provide genetic evidence supporting previous preclinical and clinical findings and suggest that vitamin D deficiency not only promotes bone diseases but also type I sensitization.


Assuntos
25-Hidroxivitamina D3 1-alfa-Hidroxilase/fisiologia , Calcitriol/imunologia , Switching de Imunoglobulina , Imunoglobulina E/sangue , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/deficiência , Animais , Linfócitos B/imunologia , Medula Óssea/imunologia , Calcitriol/biossíntese , Calcitriol/deficiência , Feminino , Helmintíase Animal/imunologia , Imunoglobulina E/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Enteropatias Parasitárias/imunologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Nematospiroides dubius/imunologia , Especificidade de Órgãos , Ovalbumina/imunologia , Receptores de Calcitriol/fisiologia , Baço/imunologia , Linfócitos T/imunologia , Deficiência de Vitamina D/imunologia
4.
Biomed Pharmacother ; 95: 1033-1039, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28922720

RESUMO

Breast cancer is one of the most common malignancies and bone is the commonest site of distant metastases. Evidences indicate that adequate supply of vitamin D will decrease the morbidity and mortality of breast cancer. However, the main role of vitamin D deficiency in breast cancer bone metastases remains unclear. In this study, the relationship between vitamin D and breast cancer bone metastases were evaluated. Results showed that 1,25(OH)2D3 can not only inhibit the proliferation, migration and invasion of breast cancer cell TM40D in vitro, but also attenuate the breast cancer cell TM40D-induced bone destruction in vivo, whose underlying mechanism was at least partially through decreasing the number of the osteoclasts. To our knowledge, this is the first to use 1-alpha-hydroxylase [1α(OH)ase] knockout mice which characterized vitamin D deficiency to establish the breast cancer bone metastases model. Based on this model, we also found that vitamin D deficiency will accelerate the osteolytic lesions, and 1,25(OH)2D3 supplement will restrain osteolytic lesions. Therefore, these findings suggest that vitamin D has the potential capacity to be a therapeutic agent for the breast cancer bone metastases.


Assuntos
Neoplasias Ósseas/secundário , Osso e Ossos/patologia , Calcitriol/deficiência , Neoplasias Mamárias Animais/patologia , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/metabolismo , Animais , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Remodelação Óssea , Osso e Ossos/diagnóstico por imagem , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Modelos Animais de Doenças , Feminino , Camundongos , Invasividade Neoplásica , Osteólise/complicações , Osteólise/patologia , Fosfatase Ácida Resistente a Tartarato/metabolismo , Microtomografia por Raio-X
5.
Braspen J ; 32(2): 160-164, abr.-jun. 2017.
Artigo em Português | LILACS | ID: biblio-848204

RESUMO

Introdução: Doenças autoimunes afetam cerca de 7% da população mundial, chegando a ser consideradas um problema de saúde pública. Além do importante papel relacionado à homeostase óssea, estudos atuais têm relacionado a hipovitaminose D com várias doenças autoimunes, pois o calcitriol possui diversas atividades no corpo humano, entre elas imunomoduladores, visto que os linfócitos T e B possuem o receptor de ligação de vitamina D. O objetivo desta pesquisa é avaliar os níveis de vitamina D e realizar a classificação mediante o resultado da avaliação. Método: Estudo do tipo transversal descritivo, por meio de revisão de prontuários, sendo selecionados um grupo de pacientes com doenças autoimunes, avaliando os níveis séricos de 25-OH-Vit.D, 1,25-(OH)2-Vit.D3 e PTH molécula inteira. Resultados: O número de prontuários coletados foi de 384 pacientes, 275 do sexo masculino (71,61%) e 109 do sexo feminino (28,39%), com idade média de 43,9±11,8 anos. A prevalência de hipovitaminose D no grupo avaliado foi de 89,06%, sendo classificados em níveis deficiente e insuficiente cerca de 13,5% e 75,5%, respectivamente. Aproximadamente 82% dos pacientes apresentaram níveis de 1,25-hidroxivitamina2D3 dentro dos valores de referência, porém este não é considerado um bom parâmetro de avaliação, em razão de possuir um curto tempo de meia-vida e sofrer influência dos níveis séricos de cálcio e paratormônio. Em relação aos níveis de paratormônio PTH, foi observado que todos pacientes estão dentro dos valores de referência (15,0 ­ 65,0 pg/ml). Conclusão: Foi demonstrado que os pacientes com doenças autoimunes analisados apresentam um nível evidente de hipovitaminose D, o que pode ser considerado um agravante à autoimunidade.(AU)


Introduction: Autoimmune diseases affect about 7% of the world, coming to be considered a public health problem. Besides the important role related to bone homeostasis, recent studies have related vitamin D deficiency with several autoimmune diseases because calcitriol has several activities in the human body, including immunomodulators, as the T and B lymphocytes have the vitamin D receptor binding. The objective of this research is to assess the levels of vitamin D and perform the classification by the evaluation result. Methods: Study of descriptive cross-sectional through chart review and selected a group of patients with autoimmune diseases, evaluating serum levels of 25-OH-Vit.D, 1,25- (OH) 2 Vit.D3 and PTH entire molecule. Results: The number of records was collected from 384 patients, 275 were male (71.61%) and 109 females (28.39%) with a mean age of 43.9±11.8 years. The prevalence of vitamin D deficiency in the studied group was of 89.06% when classified as deficient and insufficient levels about 13.5% and 75.5% respectively. Approximately 82% of patients had levels of 1,25-hidroxivitamina2D3 within the reference values, but this is not considered a good parameter to assess, due to have a short half-life and be influenced by serum calcium levels and parathyroid hormone. Related to the levels of parathyroid hormone PTH was observed that all patients are within the reference range (15.0 - 65.0 pg / ml). Conclusion: It has been demonstrated that patients with autoimmune diseases analyzed present one evident level of vitamin D deficiency, which can be regarded as an aggravating autoimmunity.(AU)


Assuntos
Humanos , Doenças Autoimunes , Deficiência de Vitamina D/etiologia , Calcitriol/deficiência , Registros Médicos , Epidemiologia Descritiva , Estudos Transversais
6.
Exp Clin Transplant ; 14(6): 606-616, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27934558

RESUMO

Fibroblast growth factor 23 is likely to be the most important regulator of phosphate homeostasis, which mediates its functions through fibroblast growth factor receptors and the coreceptor Klotho. In addition to reducing expression of the sodium-phosphate cotransporters NPT2a and NPT2c in the proximal tubules, fibroblast growth factor 23 inhibits renal 1α-hydroxylase and stimulates 24-hydroxylase and appears to reduce parathyroid hormone secretion in short-term studies. Fibroblast growth factor 23 synthesis and secretion by osteocytes and osteoblasts are upregulated through 1,25-dihydroxyvitamin D3 and through an increased dietary phosphate intake. Recent studies have indicated that a low-protein diet and calcium deficiency reduce circulating fibroblast growth factor 23 levels, but magnesium deficiency increases fibroblast growth factor levels. Drugs such as phosphate binders, bisphosphonate, and estrogens have various effects on circulating fibroblast growth factor 23 levels. The high cardiovascular disease event rates and mortality associated with elevated levels of this hormone may be due to various effects on the cardiovascular system, including left ventricular hypertrophy, arterial stiffness, vascular calcifications, endothelial dysfunction, and increased levels of inflammatory markers. In addition, elevated levels of this hormone may contribute to mineral bone metabolism disorders and to patient and allograft survival after renal transplant. Here, we discuss the effects of fibroblast growth factor 23 on adverse renal, bone, and cardiovascular outcomes after kidney transplant.


Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias , Aloenxertos , Calcitriol/deficiência , Doenças Cardiovasculares/mortalidade , Distúrbio Mineral e Ósseo na Doença Renal Crônica , Fatores de Crescimento de Fibroblastos/química , Fatores de Crescimento de Fibroblastos/fisiologia , Humanos , Hipercalcemia , Hipofosfatemia
7.
Clin Transplant ; 30(10): 1347-1359, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27532453

RESUMO

Observation that 1,25-Dihydroxyvitamin-D3 has an immunomodulatory effect on innate and adaptive immunity raises the possible effect on clinical graft outcome. Aim of this study was to evaluate the correlation of biopsy-proven acute rejection, CMV infection, BKV infection, with 1,25-Dihydroxyvitamin-D3 deficiency and the benefit of calcitriol supplementation before and during the transplantation. Risk factors and kidney graft function were also evaluated. All RTRs received induction therapy with basiliximab, cyclosporine, mycophenolic acid, and steroids. During the first year, the incidence of BPAR (4% vs 11%, P=.04), CMV infection (3% vs 9%, P=.04), and BKV infection (6% vs 19%, P=.04) was significantly lower in users compared to controls. By multivariate Cox regression analysis, 1,25-Dihydroxyvitamin-D3 deficiency and no calcitriol exposure were independent risk factors for BPAR (HR=4.30, P<.005 and HR=3.25, P<.05), for CMV infection (HR=2.33, P<.05 and HR=2.31, P=.001), and for BKV infection (HR=2.41, P<.05 and HR=2.45, P=.001). After one year, users had a better renal function: eGFR was 62.5±6.7 mL/min vs 51.4±7.6 mL/min (P<.05). Only one user developed polyomavirus-associated nephropathy vs 15 controls. Two users lost their graft vs 11 controls. 1,25(OH)2-D3 deficiency circulating levels increased the risk of BPAR, CMV infection, BKV infection after kidney transplantation. Administration of calcitriol is a way to obtain adequate 1,25(OH)2-D3 circulating levels.


Assuntos
Calcitriol/deficiência , Infecções por Citomegalovirus/etiologia , Rejeição de Enxerto/etiologia , Transplante de Rim , Infecções por Polyomavirus/etiologia , Complicações Pós-Operatórias/etiologia , Deficiência de Vitamina D/complicações , Administração Oral , Adulto , Idoso , Biomarcadores/sangue , Calcitriol/sangue , Calcitriol/uso terapêutico , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/prevenção & controle , Feminino , Seguimentos , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/prevenção & controle , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/epidemiologia , Infecções por Polyomavirus/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/tratamento farmacológico , Vitaminas/uso terapêutico
8.
IUBMB Life ; 68(6): 445-51, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27080220

RESUMO

1,25-Dihydroxyvitamin D3 [1,25(OH)2 D3 ] has recently been shown to have immunomodulatory property. This study aimed to investigate the expression and potential role of 1,25(OH)2 D3 in the pathogenesis of diabetic retinopathy (DR) in the Uygur population. Blood samples were obtained from 22 patients with proliferative DR (PDR), 29 patients with nonproliferative DR (NPDR), and 24 normal controls. ELISA was performed to estimate the serum levels of 1,25(OH)2 D3 . Peripheral blood mononuclear cells (PBMCs) were cultured with or without 1,25(OH)2 D3 in the presence of anti-CD3 and anti-CD28 antibodies to detect the secretion of cytokines and cell proliferation. The FACS cytometric bead array system was used to analyze cytokine levels in the serum and culture supernatants. The Cell Counting Kit was used to determine the rate of cell proliferation. In this study, we found that the patients with PDR showed a decreased serum level of 1,25(OH)2 D3 and increased production of IFN-γ, TNF-α, IL-6, and IL-17A, by anti-CD3 and anti-CD28 antibodies activated PBMCs. Furthermore, 1,25(OH)2 D3 significantly inhibited the proliferation of PBMCs, as well as the secretion of IFN-γ, TNF-α, IL-6, and IL-17A. Overall, our findings suggest a potential protective effect of 1,25(OH)2 D3 in DR, whereas supplementation with 1,25(OH)2 D3 might be an effective strategy for preventing the development of DR. © 2016 IUBMB Life, 68(6):445-451, 2016.


Assuntos
Calcitriol/deficiência , Diabetes Mellitus Tipo 2/metabolismo , Retinopatia Diabética/etiologia , Adulto , Idoso , Calcitriol/sangue , Calcitriol/farmacologia , Estudos de Casos e Controles , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , China , Citocinas/sangue , Feminino , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Deficiência de Vitamina D/complicações
9.
J Steroid Biochem Mol Biol ; 164: 344-352, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-26361014

RESUMO

Animal models show that vitamin D deficiency may have severe consequences for skeletal health. However, most studies have been performed in young rodents for a relatively short period, while in older adult rodents the effects of long-term vitamin D deficiency on skeletal health have not been extensively studied. Therefore, the first aim of this study was to determine the effects of long-term vitamin D deficiency on bone structure, remodeling and mineralization in bones from older adult mice. The second aim was to determine the effects of long-term vitamin D deficiency on mRNA levels of genes involved in vitamin D metabolism in bones from older adult mice. Ten months old male C57BL/6 mice were fed a diet containing 0.5% calcium, 0.2% phosphate and 0 (n=8) or 1 (n=9) IU vitamin D3/gram for 14 months. At an age of 24 months, mice were sacrificed for histomorphometric and micro-computed tomography (micro-CT) analysis of humeri as well as analysis of CYP27B1, CYP24 and VDR mRNA levels in tibiae and kidneys using RT-qPCR. Plasma samples, obtained at 17 and 24 months of age, were used for measurements of 25-hydroxyvitamin D (25(OH)D) (all samples), phosphate and parathyroid hormone (PTH) (terminal samples) concentrations. At the age of 17 and 24 months, mean plasma 25(OH)D concentrations were below the detection limit (<4nmol/L) in mice receiving vitamin D deficient diets. Plasma phosphate and PTH concentrations did not differ between both groups. Micro-CT and histomorphometric analysis of bone mineral density, structure and remodeling did not reveal differences between control and vitamin D deficient mice. Long-term vitamin D deficiency did also not affect CYP27B1 mRNA levels in tibiae, while CYP24 mRNA levels in tibiae were below the detection threshold in both groups. VDR mRNA levels in tibiae from vitamin D deficient mice were 0.7 fold lower than those in control mice. In conclusion, long-term vitamin D deficiency in older adult C57BL/6 mice, accompanied by normal plasma PTH and phosphate concentrations, does not affect bone structure, remodeling and mineralization. In bone, expression levels of CYP27B1 are also not affected by long-term vitamin D deficiency in older adult C57BL/6 mice. Our results suggest that mice at old age have a low or absent response to vitamin D deficiency probably due to factors such as a decreased bone formation rate or a reduced response of bone cells to 25(OH)D and 1,25(OH)2D. Older adult mice may therefore be less useful for the study of the effects of vitamin D deficiency on bone health in older people.


Assuntos
Calcificação Fisiológica/genética , Calcitriol/deficiência , Úmero/metabolismo , Osteogênese/genética , Tíbia/metabolismo , Deficiência de Vitamina D/metabolismo , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/metabolismo , Animais , Densidade Óssea , Calcitriol/sangue , Família 24 do Citocromo P450/genética , Família 24 do Citocromo P450/metabolismo , Regulação da Expressão Gênica , Úmero/anatomia & histologia , Rim/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hormônio Paratireóideo/sangue , Fosfatos/sangue , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Tíbia/anatomia & histologia , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/genética
10.
Endocrinol Nutr ; 62(7): 300-5, 2015.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-26138703

RESUMO

OBJECTIVE: Despite the high prevalence of chronic kidney disease in the elderly population, few data are available on the frequency of secondary hyperparathyroidism in the Spanish population affected by this problem. We undertook a study on this issue in patients attending the internal medicine departments in our area. DESIGN AND METHODS: An observational, cross-sectional survey performed at internal medicine departments on 415 patients with stage 3 and 4 chronic kidney disease. Clinical history and risk factors were collected using a standardized protocol. Serum creatinine, phosphate, calcium, intact parathormone (PTH) and 25-hydroxy-cholecalciferol (25-OH-vitD) levels were measured in all patients. RESULTS: Among stage 3 patients, 62.9% had PTH levels ≥70pg/mL and 32.7% levels ≥110pg/mL. Median PTH level in stage 4 patients was 120pg/mL (p <0.001), and 77.9% of these patients had PTH ≥70pg/mL (p <0.001) and 54.1% ≥110pg/mL (p=0.015). Adequate 25-hydroxy-cholecalciferol levels were found in only 7.2% of stage 3 patients and 4.1% of stage 4 patients. Only 7.2% of stage 3 patients had hyperphosphatemia, as compared to 25.4% of stage 4 patients (p <0.001). CONCLUSIONS: Hyperparathyroidism is a common complication of stage 3 and 4 chronic kidney disease which is not associated to detectable changes in serum calcium and phosphate levels. It is therefore advisable to measure PTH levels in all patients with decreased glomerular filtration rate.


Assuntos
Hiperparatireoidismo Secundário/epidemiologia , Insuficiência Renal Crônica/complicações , Idoso , Calcitriol/sangue , Calcitriol/deficiência , Cálcio/sangue , Estudos Transversais , Feminino , Taxa de Filtração Glomerular , Departamentos Hospitalares , Humanos , Hiperparatireoidismo Secundário/sangue , Hiperparatireoidismo Secundário/etiologia , Medicina Interna , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fósforo/sangue , Prevalência , Fatores de Risco , Índice de Gravidade de Doença , Espanha/epidemiologia , Inquéritos e Questionários
11.
J Neuroimmunol ; 279: 20-4, 2015 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-25669995

RESUMO

Vitamin D deficiency is associated with increased susceptibility to multiple sclerosis (MS) and increased disease activity. Vitamin D is a potent immunomodulator but the effects of vitamin D treatment on T cell memory have not been explored. We studied the effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on T cell memory in MS patients (n = 10) and healthy controls (n = 10). In vitro treatment of PBMC cultures with 1,25(OH)2D3, led to a decrease in the proportion of effector memory T cells with an increase in naïve T cells, compared to vehicle in both groups. Further studies to unravel the mechanism of this effect and to understand its long-term implications are required.


Assuntos
Calcitriol/deficiência , Esclerose Múltipla/patologia , Linfócitos T/imunologia , Linfócitos T/patologia , Deficiência de Vitamina D/patologia , Adulto , Antígenos CD/metabolismo , Calcitriol/farmacologia , Células Cultivadas , Feminino , Citometria de Fluxo , Humanos , Técnicas In Vitro , Masculino , Esclerose Múltipla/imunologia , Receptores CXCR3/metabolismo , Estatísticas não Paramétricas , Linfócitos T/efeitos dos fármacos , Deficiência de Vitamina D/imunologia
12.
J Cell Physiol ; 230(6): 1189-98, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25204635

RESUMO

Asthma in the pediatric population remains a significant contributor to morbidity and increasing healthcare costs. Vitamin D3 insufficiency and deficiency have been associated with development of asthma. Recent studies in models of adult airway diseases suggest that the bioactive Vitamin D3 metabolite, calcitriol (1,25-dihydroxyvitamin D3 ; 1,25(OH)2 D3 ), modulates responses to inflammation; however, this concept has not been explored in developing airways in the context of pediatric asthma. We used human fetal airway smooth muscle (ASM) cells as a model of the early postnatal airway to explore how calcitriol modulates remodeling induced by pro-inflammatory cytokines. Cells were pre-treated with calcitriol and then exposed to TNFα or TGFß for up to 72 h. Matrix metalloproteinase (MMP) activity, production of extracellular matrix (ECM), and cell proliferation were assessed. Calcitriol attenuated TNFα enhancement of MMP-9 expression and activity. Additionally, calcitriol attenuated TNFα and TGFß-induced collagen III expression and deposition, and separately, inhibited proliferation of fetal ASM cells induced by either inflammatory mediator. Analysis of signaling pathways suggested that calcitriol effects in fetal ASM involve ERK signaling, but not other major inflammatory pathways. Overall, our data demonstrate that calcitriol can blunt multiple effects of TNFα and TGFß in developing airway, and point to a potentially novel approach to alleviating structural changes in inflammatory airway diseases of childhood.


Assuntos
Remodelação das Vias Aéreas/efeitos dos fármacos , Asma/metabolismo , Calcitriol/deficiência , Citocinas/metabolismo , Miócitos de Músculo Liso/metabolismo , Deficiência de Vitamina D/metabolismo , Proliferação de Células/efeitos dos fármacos , Matriz Extracelular/metabolismo , Humanos , Músculo Liso/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
13.
Curr Opin Endocrinol Diabetes Obes ; 21(6): 431-6, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25354043

RESUMO

PURPOSE OF REVIEW: Current data clearly support an interaction of vitamin D with cells of the immune system apart from its regulatory role in calcium homeostasis. The discovery that immune cells express the vitamin D receptor and are capable of metabolizing circulating 25-hydroxyvitamin D into its active form, 1,25-dihydroxyvitamin D, has revolutionized the field and suggested a regulatory role on both the innate and adaptive immune systems. RECENT FINDINGS: Of particular interest with respect to infectious diseases, 1,25-dihydroxyvitamin D has been shown to trigger the production of antimicrobial peptides with a direct pathogen-killing capacity. Interestingly, pathogen-derived components influence the key players in the vitamin D metabolizing pathway, further supporting such an interaction. SUMMARY: Here, we review the potential mechanisms of vitamin D in promoting the innate immune response against infectious agents and discuss the possible implications for such a response in the prevention of or the intervention in various infectious diseases.


Assuntos
Doenças Autoimunes/imunologia , Calcitriol/uso terapêutico , Doenças Transmissíveis/imunologia , Transdução de Sinais/imunologia , Linfócitos T/imunologia , Deficiência de Vitamina D/imunologia , Imunidade Adaptativa/efeitos dos fármacos , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/prevenção & controle , Calcitriol/deficiência , Calcitriol/fisiologia , Doenças Transmissíveis/tratamento farmacológico , Humanos , Imunidade Inata/efeitos dos fármacos , Receptores de Calcitriol/efeitos dos fármacos , Receptores de Calcitriol/imunologia , Transdução de Sinais/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Vitamina D/análogos & derivados , Vitamina D/uso terapêutico , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/tratamento farmacológico , Vitaminas/uso terapêutico
14.
J Allergy Clin Immunol ; 134(2): 342-9, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24698317

RESUMO

BACKGROUND: Cigarette smoke (CS) plays a role in the exacerbation of chronic rhinosinusitis (CRS); however, the mechanism for this is unknown. We hypothesize that CS impairs human sinonasal epithelial cell (HSNEC) conversion of 25(OH)D3 (25VD3) to 1,25-dihydroxyvitamin D3 (1,25VD3) and, furthermore, that supplementation with 1,25VD3 will reverse smoke-induced inflammatory responses by HSNECs. OBJECTIVE: We sought to determine the effect of CS on vitamin D3 (VD3) levels, conversion, and regulation of CS-induced inflammation in control subjects and patients with CRS. METHODS: Blood and sinus tissue explants were collected at the time of surgery from control subjects, patients with chronic rhinosinusitis without nasal polyps, and patients with chronic sinusitis with nasal polyps (CRSwNP). Expression of VD3 metabolizing enzymes were measured by using RT-PCR. Primary HSNECs were cultured from tissue explants. 25VD3 with and without cigarette smoke extract (CSE) was used to examine conversion of 25VD3 to 1,25VD3, as well as HSNEC production of proinflammatory cytokines. RESULTS: CS exposure was associated with reduced circulating and sinonasal 25VD3 levels in all groups compared with those seen in CS-naive, disease-matched counterparts. CS exposure decreased expression of CYP27B1 and was especially pronounced in patients with CRSwNP. CSE impairs control HSNEC conversion of 25VD3. HSNECs from patients with CRSwNP also demonstrate an intrinsic reduction in conversion of 25VD3 to 1,25VD3. Exogenous 1,25VD3 reduces CSE-induced cytokine production by HSNECs. CONCLUSIONS: Exposure to CS is associated with reduced 25VD3 levels and an impaired ability of HSNECs to convert 25VD3 to 1,25VD3. Addition of 1,25VD3 reduces the proinflammatory effects of CS on HSNECs. Impaired VD3 conversion by CS exposure represents a novel mechanism through which CS induces its proinflammatory effects.


Assuntos
Calcitriol/deficiência , Rinite/metabolismo , Sinusite/metabolismo , Fumaça , Tabaco/química , Deficiência de Vitamina D/metabolismo , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/metabolismo , Adulto , Idoso , Calcifediol/metabolismo , Calcitriol/farmacologia , Estudos de Casos e Controles , Doença Crônica , Misturas Complexas/isolamento & purificação , Misturas Complexas/farmacologia , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/complicações , Pólipos Nasais/metabolismo , Pólipos Nasais/patologia , Cultura Primária de Células , Mucosa Respiratória/citologia , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/metabolismo , Rinite/complicações , Rinite/patologia , Sinusite/complicações , Sinusite/patologia , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/patologia
15.
Int J Oncol ; 44(5): 1625-33, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24626468

RESUMO

The secosteroidal hormone 1,25-dihyroxyvitamin D [1,25(OH)(2)D(3)] and its receptor, the vitamin D receptor (VDR), are crucial regulators of epidermal proliferation and differentiation. However, the effects of 1,25(OH)(2)D(3)-directed signaling on oral keratinocyte pathophysiology have not been well studied. We examined the role of 1,25(OH)(2)D(3) in regulating proliferation and differentiation in cultured oral keratinocytes and on the oral epithelium in vivo. Using lentiviral-mediated shRNA to silence VDR, we generated an oral keratinocyte cell line with stable knockdown of VDR expression. VDR knockdown significantly enhanced proliferation and disrupted calcium- and 1,25(OH)(2)D(3)-induced oral keratinocyte differentiation, emphasizing the anti-proliferative and pro-differentiation effects of 1,25(OH)(2)D(3) in oral keratinocytes. Using vitamin D(3)-deficient diets, we induced chronic vitamin D deficiency in mice as evidenced by decreased serum 25-hydroxyvitamin D (25OHD) concentrations. The vitamin D-deficient mice manifested increased proliferation of the tongue epithelium, but did not develop any morphological or histological abnormalities in the oral epithelium, suggesting that vitamin D deficiency alone is insufficient to alter oral epithelial homeostasis and provoke carcinogenesis. Immunohistochemical analyses of human and murine oral squamous cell carcinomas showed increased VDR expression. Overall, our results provide strong support for a crucial role for vitamin D signaling in oral keratinocyte pathophysiology.


Assuntos
Calcitriol/farmacologia , Queratinócitos/metabolismo , Boca/citologia , Receptores de Calcitriol/genética , Deficiência de Vitamina D/patologia , Vitaminas/farmacologia , Animais , Calcitriol/deficiência , Carcinoma de Células Escamosas/metabolismo , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Epiderme/metabolismo , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Neoplasias Bucais/metabolismo , Transdução de Sinais/efeitos dos fármacos
16.
Curr Osteoporos Rep ; 12(1): 74-81, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24488588

RESUMO

In this commentary, we focus on common 'downstream' links of vitamin D between muscle and bone health. Both direct and indirect effects of 1,25 dihydroxyvitamin D (1,25(OH)D) link the mutual age-related decline in muscle function and bone density, independent of physical activity. Changes in calcium absorption associated with vitamin D deficiency affect both muscle and bone mass. The age-related decline in vitamin D receptor expression and 1,25(OH)D activity impact on proinflammatory cytokines such as tumor necrosis factor -α and interleukin-6 in skeletal muscle and vitamin D deficiency appears to enhance both bone marrow adipogenesis and intramuscular adipose tissue impacting as reduced functionality in both skeletal tissues. Controversial findings on the role of 1,25(OH)D on skeletal muscle may relate to differences in vitamin D receptor expression throughout different stages of muscle cell differentiation. Prolonged vitamin D insufficiency in the elderly is associated with reductions in both bone mineral density and type 2 muscle fibers with the outcomes of skeletal fragility in combination with reduced muscle power, leading to increased risk of falls and fracture.


Assuntos
Densidade Óssea/fisiologia , Calcitriol/deficiência , Fibras Musculares de Contração Rápida/metabolismo , Força Muscular/fisiologia , Músculo Esquelético/metabolismo , Sarcopenia/metabolismo , Deficiência de Vitamina D/metabolismo , Acidentes por Quedas , Idoso , Doenças Ósseas Metabólicas , Calcitriol/metabolismo , Fraturas Ósseas , Humanos , Fibras Musculares de Contração Rápida/fisiologia , Músculo Esquelético/fisiopatologia , Sarcopenia/fisiopatologia , Deficiência de Vitamina D/fisiopatologia
17.
Curr Vasc Pharmacol ; 12(2): 294-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23713873

RESUMO

The synthesis of 1α,25-dihydroxyvitamin D3 (Calcitriol) takes place mostly in the kidneys through the action of 1α-hydroxylase (CYP27B1) which converts 25(OH)D into 1,25(OH)2D3. Renal production of calcitriol is stimulated by PTH, low calcium and low phosphate and it is reduced by high phosphate and FGF23. Binding of 1α,25-dihydroxyvitamin D3 to its receptor (VDR) causes gut absorption of calcium and phosphate, decrease in PTH synthesis, stimulation of FGF23. At the bone level calcitriol suppresses pre-osteoblasts and activates mature osteoblasts. VDR is present in a large variety of cells that do not have any direct role in the regulation of mineral metabolism. Calcitriol regulates immune and inflammatory response, cell turnover, cell differentiation, Renin production, reduces proteinuria and others. In patients with Chronic Kidney Disease (CKD) there is a decrease in calcitriol that is apparent at early stages of renal disease; this is probably due to the elevation of FGF23 which is present since very early stage of CKD. In CKD stage, 3-4 moderate doses of calcitriol are effective to control secondary hyperparathyroidism and observational studies suggest that calcitriol therapy increases survival and slows the progression of renal disease as long as phosphate and calcium levels are controlled. Calcitriol (0.5 µg calcitriol twice per week) has been effective in decreasing proteinuria in patients with IgA nephropathy. In dialysis patients, the administration of calcitriol reduces serum PTH levels but it is also known that high doses of calcitriol are associated with hypercalcemia and worse control of hyperphosphatemia. In kidney transplant patients, the administration of calcitriol, 0.5 µg/48h prevents bone mass loss during the first few months after transplantation.


Assuntos
Calcitriol/uso terapêutico , Calcitriol/deficiência , Humanos , Hiperparatireoidismo Secundário/tratamento farmacológico , Rim/efeitos dos fármacos , Transplante de Rim , Minerais/metabolismo , Diálise Renal , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/mortalidade
18.
Rev. chil. pediatr ; 84(6): 672-680, dic. 2013. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-703291

RESUMO

Introducción: La hipocalcemia es un hallazgo infrecuente en los pacientes atendidos en los servicios de urgencia pediátricos. El raquitismo se puede presentar como una hipocalcemia crónica la mayoría de las veces asintomática, sin embargo, algunos pacientes presentan tetanias hipocalcémica. Objetivo: Presentar el caso clínico de una niña con raquitismo hipocalcémico, cuyo diagnóstico fue tardío. Caso clínico: Prescolar de 2 años 5 meses con alteración en la marcha, mal incremento ponderal, espasmos musculares y signos de raquitismo activo. Los exámenes revelaron hipocalcemia severa, normofosfemia, fosfatasa alcalina y PTH elevada y niveles normales de 25 hidroxivitamina D. Se manejó con calcio y calcitriol, y se diagnosticó raquitismo vitamina D dependiente tipo I. Conclusión: Los síntomas y signos clásicos de raquitismo, así como la hipocalcemia, deben hacernos plantear hoy en día el diagnóstico de raquitismo. Un mejor conocimiento de esta patología permitirá evitar el retraso en el diagnóstico y un tratamiento más oportuno.


Introduction: Hypocalcemia is rare in patients attending pediatric emergency services. Rickets can present as a chronic hypocalcemia often asymptomatic, poor growth rate, psychomotor delay and bone abnormalities, but some patients may present tetanic seizures. Although its incidence has decreased, a resurgence of rickets has been described. Objective: To present a case of a child with hypocalcemic rickets, whose diagnosis was delayed. Case report: Preschool of 2,4 years old with gait disturbance, poor growth rate, muscle spams and signs of active rickets. Laboratory results showed hypocalcemia, normophosphemia, alkaline phosphatase, high PTH and normal 25-hydroxyvitamin D levels. She received treatment with calcium and calcitriol and had a good response; Vitamin D dependent rickets type I was diagnosed. Conclusion: Classics signs and symptoms of rickets, as hypocalcemic manifestations, should lead us today to diagnose rickets. Better knowledge of this disease will avoid retarded diagnosis and give a suitable treatment.


Assuntos
Humanos , Feminino , Pré-Escolar , Hipocalcemia/diagnóstico , Raquitismo/diagnóstico , Evolução Clínica , Cálcio/administração & dosagem , Calcitriol/administração & dosagem , Calcitriol/deficiência , Diagnóstico Diferencial , Hipocalcemia/tratamento farmacológico , Raquitismo/tratamento farmacológico
19.
Clin Calcium ; 23(10): 1437-43, 2013 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-24076641

RESUMO

Vitamin D dependency was first termed for patients resembling vitamin D-deficiency but require high doses of vitamin D administration. Now this disease is known to be caused by defective conversion of 25OHD to 1,25 (OH) 2D, which is termed vitamin D-dependent rickets type 1 or 1α-hydroxylase deficiency, or by end-organ unresponsiveness to 1,25 (OH) 2D, which is called vitamin D-dependent rickets type 2 or hereditary vitamin D-resistant rickets. Recent advance in the molecular analysis of these diseases revealed variety in the presentation and in the inheritance patterns. Molecular diagnosis would be preferable for some atypical cases for adequate therapy.


Assuntos
Raquitismo/etiologia , Deficiência de Vitamina D/complicações , Vitamina D/metabolismo , Calcitriol/deficiência , Humanos , Mutação/genética , Raquitismo/diagnóstico , Raquitismo/tratamento farmacológico , Raquitismo/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA