RESUMO
Vitamin D, a fat-soluble vitamin, is an important nutrient for tissue homeostasis and is recently gaining attention for its role in sarcopenia. Although several studies have focused on the role of vitamin D in muscle homeostasis, the molecular mechanism underlying its action on skeletal muscle remains unclear. This study investigated the role of vitamin D in myogenesis and muscle fiber maintenance in an immortalized mouse myogenic cell line. A high concentration of active vitamin D, 1α,25(OH)2D3, decreased the expression of myogenic regulatory factors (MRFs), myf5 and myogenin in proliferating myoblasts. In addition, high concentration of vitamin D reduced myoblast-to-myoblast and myoblast-to-myotube fusion through the inhibition of Tmem8c (myomaker) and Gm7325 (myomerger), which encode muscle-specific fusion-related micropeptides. A similar inhibitory effect of vitamin D was also observed in immortalized human myogenic cells. A high concentration of vitamin D also induced hypertrophy of multinucleated myotubes by stimulating protein anabolism. The results from this study indicated that vitamin D had both positive and negative effects on muscle homeostasis, such as in muscle regeneration and myofiber maintenance. Elderly individuals face a higher risk of falling and suffering fractures; hence, administration of vitamin D for treating fractures in the elderly could actually promote fusion impairment and, consequently, severe defects in muscle regeneration. Therefore, our results suggest that vitamin D replacement therapy should be used for prevention of age-related muscle loss, rather than for treatment of sarcopenia.
Assuntos
Fusão Celular , Desenvolvimento Muscular/efeitos dos fármacos , Mioblastos/efeitos dos fármacos , Vitamina D/antagonistas & inibidores , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Humanos , Hipertrofia , Desenvolvimento Muscular/genética , Músculo Esquelético/metabolismo , Mioblastos/metabolismo , SarcopeniaRESUMO
Fibroblast growth factor 23 (FGF23) is released primarily from osteoblasts/osteocytes in bone. In cooperation with the transmembrane protein Klotho, FGF23 is a powerful inhibitor of 1α 25OH Vitamin D Hydroxylase (Cyp27b1) and thus of the formation of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). As 1,25(OH)2D3 up-regulates intestinal calcium and phosphate absorption, the downregulation of 1,25(OH)2D3 synthesis counteracts phosphate excess and tissue calcification. FGF23 also directly inhibits renal phosphate reabsorption. Other actions of FGF23 include triggering of cardiac hypertrophy. FGF23 formation and/or release are stimulated by 1,25(OH)2D3, phosphate excess, Ca2+, PTH, leptin, catecholamines, mineralocorticoids, volume depletion, lithium, high fat diet, iron deficiency, TNFα and TGFß2. The stimulating effect of 1,25(OH)2D3 on FGF23 expression is dependent on RAC1/PAK1 induced actin-polymerisation. Intracellular signaling involved in the stimulation of FGF23 release also includes increases in the cytosolic Ca2+ concentration ([Ca2+]i) following intracellular Ca2+ release and store-operated Ca2+ entry (SOCE). SOCE is accomplished by the Ca2+ release-activated calcium channel protein 1 (Orai1) and its stimulator stromal interaction molecule 1 (STIM1). Expression of Orai1, SOCE and FGF23-formation are up-regulated by the proinflammatory transcription factor NFκB. The present brief review describes the cellular mechanisms involved in FGF23 regulation and its sensitivity to both phosphate metabolism and inflammation. The case is made that up-regulation of FGF23 by inflammatory mediators and signaling may amplify inflammation by inhibiting formation of the anti-inflammatory 1,25(OH)2D3.
Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Homeostase , Inflamação/etiologia , Fosfatos/metabolismo , Animais , Fator de Crescimento de Fibroblastos 23 , Humanos , Vitamina D/análogos & derivados , Vitamina D/antagonistas & inibidoresRESUMO
BACKGROUND & AIMS: Azacitidine (AZA) therapy has become the recommended first-line treatment for patients with high-risk myelodysplastic syndromes (MDS) and oligoblastic (<30% bone marrow blasts) acute myeloid leukemia (AML). However, improvement of the efficacy of AZA treatment remains a challenge. We retrospectively tested the hypothesis that VitD levels (25-hydroxyvitamin D3) prior to start of first-line AZA therapy are predictive of overall survival (OS) in patients diagnosed with MDS and secondary oligoblastic AML. Furthermore, the antiproliferative effects of AZA in combination with 25-hydroxyvitamin D3 and 1α,25-dihydroxyvitamin D3 were investigated in vitro. METHODS: A total of 58 patients treated at our center between 2006 and 2014 were analyzed. Serum levels of VitD were quantified using a standard, commercially available 25-hydroxyvitamin D3 chemiluminescent immunoassay. Effects on cell proliferation were assessed using tetrazolium-based MTT assays. RESULTS: Median serum VitD level prior to AZA treatment was 32.8 nM (range 11.0-101.5 nM). Patient, disease and treatment characteristics did not differ significantly between the low (≤32.8 nM; n = 29) and high (>32.8 nM; n = 29) VitD group. Estimated probability of 2-year OS in the low versus high VitD group was 14% versus 40% (P < 0.05). In multivariable analysis with OS as endpoint, adverse cytogenetics (HR 2.66, P = 0.03) and VitD (per 10 nM decrease, HR 1.68, P = 0.02) were independent predictors of worse survival. In-vitro treatment of myeloid cell lines with AZA in combination with VitD produced synergistic and additive antiproliferative effects. Addition of nanomolar VitD concentrations to AZA resulted in potentiation of AZA activity. Conversely, combination with the VitD antagonist TEI-9647 resulted in inhibition of AZA activity. CONCLUSIONS: Our study suggests that higher VitD levels were associated with a survival advantage following first-line AZA therapy. Enhanced cytotoxic effects upon combination treatment may contribute to the observed clinical effects. VitD repletion/supplementation during AZA treatment should be explored.
Assuntos
Azacitidina/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Vitamina D/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Calcitriol/análogos & derivados , Calcitriol/farmacologia , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Leucemia Mieloide Aguda/sangue , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/sangue , Estudos Retrospectivos , Resultado do Tratamento , Vitamina D/administração & dosagem , Vitamina D/antagonistas & inibidoresRESUMO
Enriching oils, such as olive oil, could be one solution to tackle the worldwide epidemic of vitamin D deficiency and to better fit with omega 3 (DHA) recommendations. However, data regarding the interactions occurring at the intestinal level between vitamin D and phenols from olive oil are scarce. We first determined the effect of polyphenols from a virgin olive oil, and a virgin olive oil enriched with DHA, on vitamin D absorption in rats. We then investigated the effects of 3 main olive oil phenols (oleuropein, hydroxytyrosol and pinoresinol) on vitamin D uptake by Caco-2 cells. The presence of polyphenols in the olive oil supplemented with DHA inhibited vitamin D postprandial response in rats (-25%, p<0.05). Similar results were obtained with a mix of the 3 polyphenols delivered to Caco-2 cells. However, this inhibitory effect was due to the presence of pinoresinol only. As the pinoresinol content can highly vary between olive oils, the present results should be taken into account to formulate an appropriate oil product enriched in vitamin D.
Assuntos
Furanos/análise , Absorção Intestinal/efeitos dos fármacos , Lignanas/análise , Azeite de Oliva/química , Vitamina D/farmacocinética , Animais , Células CACO-2 , Ácidos Docosa-Hexaenoicos/análise , Feminino , Humanos , Glucosídeos Iridoides , Iridoides/análise , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/análise , Polifenóis/análise , Ratos , Ratos Wistar , Vitamina D/antagonistas & inibidoresRESUMO
BACKGROUND AND OBJECTIVE: Increasing evidence suggests that 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ), a fat-soluble secosteroid hormone, has a positive impact on periodontal health through diverse mechanisms. The present study was aimed at investigating the effect of 1,25(OH)2 D3 on the growth of and virulence factor gene expression by the periodontopathogenic bacterium Porphyromonas gingivalis. The effect of 1,25(OH)2 D3 on P. gingivalis-mediated activation of nuclear factor kappa B (NF-κB) transcription factor in monocytes was also assessed. MATERIAL AND METHODS: A broth microdilution assay was used to determine the antibacterial activity of 1,25(OH)2 D3 . The modulation of virulence factor gene expression in P. gingivalis was assessed by quantitative reverse transcription-polymerase chain reaction. NF-κB activation was assessed using a human monocytic cell line stably transfected with a luciferase reporter containing NF-κB binding sites. RESULTS: Minimal inhibitory concentrations of 1,25(OH)2 D3 against P. gingivalis ranged from 3.125 to 6.25 µg/mL. Moreover, a partial synergistic effect was observed when 1,25(OH)2 D3 was used in association with metronidazole. 1,25(OH)2 D3 attenuated the virulence of P. gingivalis by reducing the expression of genes coding for important virulence factors, including adhesins (fimA, hagA and hagB) and proteinases (rgpA, rgpB and kgp). 1,25(OH)2 D3 dose-dependently prevented P. gingivalis-induced NF-κB activation in a monocyte model. CONCLUSION: Our study suggested that 1,25(OH)2 D3 selectively inhibits the growth of and virulence factor gene expression by P. gingivalis, in addition to attenuating NF-κB activation by this periodontopathogen. This dual action on P. gingivalis and the inflammatory response of host cells may be of particular interest with a view to developing a novel and inexpensive preventive/therapeutic strategy.
Assuntos
Expressão Gênica/efeitos dos fármacos , Monócitos/metabolismo , NF-kappa B/efeitos dos fármacos , Porphyromonas gingivalis/efeitos dos fármacos , Porphyromonas gingivalis/genética , Fatores de Transcrição/efeitos dos fármacos , Fatores de Virulência/genética , Vitamina D/antagonistas & inibidores , Adesinas Bacterianas/efeitos dos fármacos , Adesinas Bacterianas/genética , Proteínas de Bactérias/efeitos dos fármacos , Proteínas de Bactérias/genética , Linhagem Celular Tumoral/efeitos dos fármacos , Cisteína Endopeptidases/efeitos dos fármacos , Cisteína Endopeptidases/genética , Combinação de Medicamentos , Proteínas de Fímbrias/efeitos dos fármacos , Proteínas de Fímbrias/genética , Cisteína Endopeptidases Gingipaínas , Humanos , Lectinas/efeitos dos fármacos , Lectinas/genética , Metronidazol/farmacologia , Testes de Sensibilidade Microbiana , NF-kappa B/metabolismo , Peptídeo Hidrolases/efeitos dos fármacos , Peptídeo Hidrolases/genética , Porphyromonas gingivalis/metabolismo , Fatores de Transcrição/genética , Células U937/efeitos dos fármacos , Vitamina D/análogos & derivadosRESUMO
Mice lacking the renal epithelial Ca(2+) channel TRPV5 (TRPV5(-/-)) display impaired renal Ca(2+) reabsorption, hypercalciuria, and intestinal Ca(2+) hyperabsorption, due to secondary hypervitaminosis D. Using these mice, we previously demonstrated that ZK191784 acts as an intestine-specific 1,25(OH)(2) D(3) antagonist without affecting serum calcium levels. On the other hand, it acted as an agonist in the kidney and the effects of ZK191784 on bone were ambiguous. The present study was undertaken to further evaluate the effect of the vitamin D receptor antagonist on murine bone in mice lacking TRPV5. Eight-week-old female Trpv5(+/+) and Trpv5(-/-) mice were treated for 4 weeks with or without 50 µg/kg/day ZK191784. Quantitative backscattered electron imaging showed that the reduced bone matrix mineralization found in femoral bones of Trpv5(-/-) mice was partially but significantly restored upon ZK191784 treatment, just as we observed for trabecular bone thickness. This supports the significance of 1,25(OH)(2) D(3) and optimal control of Ca(2+) homeostasis for bone formation and matrix mineralization. Restoration also took place at the bone gene expression level, where 1α-hydroxylase (Cyp27b1) mRNA in femurs from ZK-treated Trpv5(-/-) mice was upregulated compared to control levels. The downregulated 24-hydroxylase (Cyp24a1) gene expression in femoral bone indicated local vitamin D resistance in the mice treated with ZK191784. Phosphate homeostasis was unaffected between the groups as shown by unaltered serum PO(4)(3-) and fibroblast growth factor (FGF) 23 as well as Fgf23 mRNA expression in bone. In conclusion, circulating 1,25(OH)(2) D(3) is important for optimal control of Ca(2+) homeostasis but also for controlled bone formation and matrix mineralization.
Assuntos
Matriz Óssea/efeitos dos fármacos , Calcificação Fisiológica/efeitos dos fármacos , Calcitriol/análogos & derivados , Canais de Cálcio/deficiência , Canais de Cátion TRPV/deficiência , Vitamina D/análogos & derivados , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/biossíntese , Animais , Calcitriol/farmacologia , Cálcio/metabolismo , Colecalciferol/sangue , Colecalciferol/metabolismo , Feminino , Fêmur/efeitos dos fármacos , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/biossíntese , Regulação da Expressão Gênica/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Camundongos , Fosfatos/sangue , Esteroide Hidroxilases/biossíntese , Vitamina D/antagonistas & inibidores , Vitamina D3 24-HidroxilaseRESUMO
Increasingly vitamin D deficiency is being associated with a number of psychiatric conditions. In particular for disorders with a developmental basis, such as autistic spectrum disorder and schizophrenia the neurobiological plausibility of this association is strengthened by the preclinical data indicating vitamin D deficiency in early life affects neuronal differentiation, axonal connectivity, dopamine ontogeny and brain structure and function. More recently epidemiological associations have been made between low vitamin D and psychiatric disorders not typically associated with abnormalities in brain development such as depression and Alzheimer's disease. Once again the preclinical findings revealing that vitamin D can regulate catecholamine levels and protect against specific Alzheimer-like pathology increase the plausibility of this link. In this review we have attempted to integrate this clinical epidemiology with potential vitamin D-mediated basic mechanisms. Throughout the review we have highlighted areas where we think future research should focus.
Assuntos
Encéfalo/metabolismo , Deficiência de Vitamina D/metabolismo , Deficiência de Vitamina D/psicologia , Vitamina D/metabolismo , Envelhecimento/patologia , Envelhecimento/fisiologia , Envelhecimento/psicologia , Animais , Encéfalo/crescimento & desenvolvimento , Encéfalo/fisiopatologia , Humanos , Vitamina D/antagonistas & inibidores , Vitamina D/uso terapêutico , Deficiência de Vitamina D/fisiopatologiaRESUMO
Oxidative catabolism of 1α,25-dihydroxyvitamin D(3) [1α,25(OH)(2)D(3)] is mediated by either CYP24A1 or CYP3A4. In this paper, we tested whether induction of CYP3A4 in the LS180 intestinal cell model enhances clearance of 1α,25(OH)(2)D(3) and blunts its hormonal effect on expression of the apical membrane calcium transport protein, TRPV6. Treatment with the hPXR agonist rifampin significantly increased CYP3A4 mRNA content and catalytic activity, but had no effect on CYP24A1 or TRPV6 mRNA content. Pre-treating cells with rifampin for 48h, prior to a 24h 1α,25(OH)(2)D(3) treatment phase, was associated with a subsequent 48% increase in the elimination of 1α,25(OH)(2)D(3) and a 35% reduction of peak TRPV6 mRNA. Introduction of the CYP3A4 inhibitor, 6',7'-dihydroxybergamottin, an active inhibitor in grapefruit juice, reversed the effects of rifampin on 1α,25(OH)(2)D(3) clearance and TRPV6 expression. Over-expression of hPXR in LS180 cells greatly enhanced the CYP3A4 responsiveness to rifampin pretreatment, and elicited a greater relative suppression of TRPV6 expression and an increase in 1α,25(OH)(2)D(3) disappearance rate, compared to vector expressed cells, following hormone administration. Together, these results suggest that induction of CYP3A4 in the intestinal epithelium by hPXR agonists can result in a greater metabolic clearance of 1α,25(OH)(2)D(3) and reduced effects of the hormone on the intestinal calcium absorption, which may contribute to an increased risk of drug-induced osteomalacia/osteoporosis in patients receiving chronic therapy with potent hPXR agonists. Moreover, ingestion of grapefruit juice in the at-risk patients could potentially prevent this adverse drug effect.
Assuntos
Adenocarcinoma/enzimologia , Neoplasias do Colo/enzimologia , Citocromo P-450 CYP3A/biossíntese , Receptores de Esteroides/fisiologia , Rifampina/farmacologia , Vitamina D/análogos & derivados , Células CACO-2 , Cálcio/metabolismo , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Indução Enzimática/efeitos dos fármacos , Indução Enzimática/fisiologia , Humanos , Receptor de Pregnano X , Receptores de Esteroides/agonistas , Vitamina D/antagonistas & inibidores , Vitamina D/fisiologiaRESUMO
OBJECTIVE: Vitamin D deficiency and polypharmacy are common in the elderly. However, knowledge on the associations between the use of specific medicines and serum 25-hydroxyvitamin D (25(OH)D) is limited. The aim of this study was to (better) define the associations between the use of specific medicines and serum 25(OH)D. METHODS: Two different cohorts (1995/1996 and 2002/2003) from the Longitudinal Aging Study Amsterdam (LASA) were used for cross-sectional analyses. LASA is based on an age and sex-stratified random sample of the Dutch older population. Study participants were aged 65-88 years in the first cohort (n = 1301) and 55-65 years in the second cohort (n = 736). Serum 25(OH)D of users of several groups of medicines were compared with levels of non-users using multiple linear regression analysis. RESULTS: Of all participants, 75.4% (first cohort) and 61.1% (second cohort) were using at least one medicine. In both cohorts, the number of medicines was associated with lower serum 25(OH)D. In the first cohort, after adjustment for confounding, users of any kind of medicine, loop diuretics and inhaled corticosteroids (only men) had respectively 4.4 nmol/l (P<0.01), 4.7 nmol/l (P = 0.04) and 7.3 nmol/l (P = 0.02) lower serum 25(OH)D than non-users. In the second cohort, the use of oral antidiabetics, calcium-channel blockers and angiotensin-converting enzyme inhibitors was associated with respectively 7.4 nmol/l (P = 0.04), 7.7 nmol/l (P = 0.01) and 7.6 nmol/l (P<0.01) lower serum 25(OH)D. CONCLUSIONS: These data show that users of several medicines have lower serum 25(OH)D than non-users. Vitamin D supplementation may be considered in patients with chronic use of medicines.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Deficiência de Vitamina D/induzido quimicamente , Vitamina D/antagonistas & inibidores , Vitamina D/biossíntese , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Preparações Farmacêuticas/sangue , Estudos Prospectivos , Vitamina D/sangue , Deficiência de Vitamina D/diagnósticoRESUMO
OBJECTIVE: To evaluate the prevalence of vitamin D deficiency, as well as factors associated with serum 25-hydroxyvitamin D [25(OH)D] levels, in children attending a pediatric rheumatology clinic, and to determine whether there was a difference in serum 25(OH)D levels and in vitamin D deficiency between children with autoimmune disorders and nonautoimmune conditions. METHODS: Cross-sectional analysis of serum 25(OH)D levels of patients between the ages of 2 and 19 years, seen between November 2008 and October 2009. RESULTS: A total of 254 patients were studied (169 autoimmune disorders, 85 nonautoimmune conditions). The mean age of study patients was 12.3 years; 67% were female and 80% were white. In the autoimmune disorders group, 23% had vitamin D deficiency [serum 25(OH)D < 20 ng/ml], and in the nonautoimmune conditions group 14% were vitamin D deficient. The average level of serum 25(OH)D was 28.6 (± 11) ng/ml (range 2 to 59). Age, ethnicity, body mass index, use of supplements, and season were significantly associated with serum levels of 25(OH)D (all p ≤ 0.02). The OR of patients with autoimmune disorders being vitamin D deficient was 2.3, in relation to patients with nonautoimmune conditions (p = 0.04). CONCLUSION: Twenty percent of patients attending a pediatric rheumatology clinic were vitamin D deficient. Patients with autoimmune disorders were more likely to be vitamin D deficient than patients with nonautoimmune conditions. Screening of serum 25(OH)D levels should be performed for patients with autoimmune disorders.
Assuntos
Doenças Reumáticas/sangue , Doenças Reumáticas/epidemiologia , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Adolescente , Criança , Pré-Escolar , Comorbidade/tendências , Estudos Transversais , Feminino , Humanos , Masculino , Obesidade/sangue , Obesidade/epidemiologia , Obesidade/etnologia , Prevalência , Grupos Raciais , Doenças Reumáticas/etnologia , Distribuição por Sexo , Vitamina D/antagonistas & inibidores , Vitamina D/sangue , Deficiência de Vitamina D/etnologiaRESUMO
Mismatches between skin pigmentation and modern lifestyle continue to challenge our naked skin. One of our responses to these challenges is the development and use of sunscreens. The management of sunscreens has to balance their protective effect against erythema, photocarcinogenesis and photoageing owing to the potential toxicity of the ultraviolet (UV) filters for humans and the environment. The protection against UV radiation offered by sunscreens was recently standardized in the European Union (EU) based on international harmonization of measurement techniques. Four different categories of sun protection have been implemented along with recommendations on how to use sunscreen products in order to obtain the labelled protection. The UV filters in sunscreens have long been authorized for use by the EU authority on the basis of data from studies on acute toxicity, subchronic and chronic toxicity, reproductive toxicity, genotoxicity, photogenotoxicity, carcinogenicity, irritation, sensitization, phototoxicity and photosensitization as well as on environmental aspects. New challenges with respect to the safety of UV filters have arisen from the banning of animal experiments for the development of cosmetics. Future debates on sunscreens are likely to focus on nanoparticles and environmental issues, along with motivation campaigns to persuade consumers to protect their skin. However, more efficient sunscreen use will also continue to raise questions on the benefit in preventing vitamin D synthesis in the skin induced by sunlight.
Assuntos
Queimadura Solar/prevenção & controle , Protetores Solares/efeitos adversos , Carcinoma de Células Escamosas/induzido quimicamente , Carcinoma de Células Escamosas/prevenção & controle , Rotulagem de Medicamentos/legislação & jurisprudência , Monitoramento de Medicamentos , Poluição Ambiental/prevenção & controle , Humanos , Ceratose Actínica/induzido quimicamente , Ceratose Actínica/prevenção & controle , Legislação de Medicamentos , Estilo de Vida , Melanoma/induzido quimicamente , Melanoma/prevenção & controle , Cooperação do Paciente , Educação de Pacientes como Assunto , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/prevenção & controle , Protetores Solares/normas , Resultado do Tratamento , Vitamina D/antagonistas & inibidoresRESUMO
BACKGROUND: we explored serum 25-hydroxyvitamin D (25[OH]D) levels and associated factors for insufficiency or deficiency in an adult human immunodeficiency virus (HIV) cohort and compared 25(OH)D levels with those in the general US population. METHODS: using baseline data from the Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN), a prospective, observational cohort study of HIV-infected adults enrolled at 7 HIV specialty clinics in 4 US cities from March 2004 to June 2006, we estimated the prevalence of vitamin D insufficiency or deficiency (defined as 25(OH)D levels <30 ng/mL), standardized by age, race, and sex. Using multiple logistic regression, we examined risk factors for vitamin D insufficiency or deficiency. RESULTS: among 672 SUN participants with baseline serum 25(OH)D determinations who were not receiving vitamin D supplements, 70.3% (95% confidence interval [CI], 68.1%-74.9%) were vitamin D insufficient or deficient, compared with 79.1% (95% CI, 76.7-81.3) of US adults. Factors associated with vitamin D insufficiency or deficiency included black race (adjusted odds ratio [aOR], 4.51; 95% CI, 2.59-7.85), Hispanic ethnicity (aOR, 2.78; 95% CI, 1.31-5.90), higher body mass index (aOR, 1.04; 95% CI, 1.00-1.09), hypertension (aOR, 1.88; 95% CI, 1.10-3.22), lack of exercise (aOR, 3.14; 95% CI, 1.80-5.47), exposure to efavirenz (aOR, 1.98; 95% CI, 1.18-3.34), higher exposure to ultraviolet light (aOR, .78; 95% CI, .71-.86), renal insufficiency (aOR, .55; 95% CI, .36-.83), and exposure to ritonavir (aOR, .56; 95% CI, .35-0.89). CONCLUSIONS: similar to findings in US adults generally, vitamin D insufficiency or deficiency is highly prevalent among HIV-infected adults and is associated with known risk factors. Observed associations of vitamin D levels with renal insufficiency and with use of ritonavir- and efavirenz-containing regimens are consistent with both HIV-related and therapy-mediated alterations in vitamin D metabolism. Clinicians should consider screening all patients for vitamin D insufficiency or deficiency.
Assuntos
Antirretrovirais/efeitos adversos , Antirretrovirais/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Deficiência de Vitamina D/induzido quimicamente , Deficiência de Vitamina D/epidemiologia , Vitamina D/antagonistas & inibidores , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Fatores de Risco , Soro/química , Estados Unidos/epidemiologia , Vitamina D/sangue , Vitamina D/metabolismoRESUMO
We report here preliminary pilot study data of the effect of sunless tanning spray with 9% [Correction added after online publication (August 24th, 2009): The concentration of Dihydroxyacetone used in the study was 9% and not 3% as previously stated] dihydroxyacetone (DHA) on 25-hydroxyvitamin D [25(OH)D] serum levels in subjects exposed to controlled amounts of UV-B radiation during April/May in Omaha, NE, 41 degrees N latitude. We found that DHA-induced melanoidins in skin act as a topical sunscreen attenuating the formation of 25(OH)D.
Assuntos
Di-Hidroxiacetona/administração & dosagem , Polímeros/administração & dosagem , Vitamina D/biossíntese , Administração Tópica , Feminino , Humanos , Projetos Piloto , Vitamina D/antagonistas & inibidoresRESUMO
INTRODUCTION: Vitamin D-binding protein (also called DBP or Gc-globulin) is recognized as a multifunctional protein involved in the action scavenger system, the transport of vitamin D sterols, and the modulation of immune and inflammatory responses. This study evaluated total serum and peritoneal concentrations of vitamin D-binding protein in women with endometriosis, known as an inflammation-associated disease. MATERIALS/METHODS: The total concentration of DBP was measured with an enzyme-linked immunosorbent assay (ELISA) using a polyclonal antibody raised in a goat immunized with human DBP. Serum and peritoneal fluid were collected from women with endometriosis (n=26) and from patients with benign gynecological conditions serving as a control group (n=17). RESULTS: In general, the vitamin D-binding protein concentration was higher in serum than in peritoneal fluid. Women with endometriosis had higher serum but lower peritoneal levels of DBP compared with the control group; however, no significance was noted. When the endometriosis group was divided with regard to severity, an insignificantly higher serum level of DBP was observed in advanced endometriosis compared with the mild form of the disease, whereas the peritoneal concentration was not dependent on disease severity. CONCLUSIONS: It is concluded that serum and peritoneal DBP concentrations are not affected in women with endometriosis; however, based on the latest published data, it is possible that both the serum and peritoneal concentrations of vitamin D-binding protein may be dependent on Gc genotype, which results in differential modulation of monocyte/macrophage activity.
Assuntos
Líquido Ascítico/química , Endometriose/sangue , Proteína de Ligação a Vitamina D/análise , Adulto , Líquido Ascítico/patologia , Calcifediol/metabolismo , Endometriose/complicações , Ensaio de Imunoadsorção Enzimática , Estudos de Avaliação como Assunto , Feminino , Humanos , Pessoa de Meia-Idade , Doença Inflamatória Pélvica/complicações , Peritônio/patologia , Peritonite/complicações , Pré-Menopausa/sangue , Pré-Menopausa/metabolismo , Soro/química , Vitamina D/antagonistas & inibidores , Vitamina D/sangue , Proteína de Ligação a Vitamina D/sangueAssuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Falência Renal Crônica/complicações , Falência Renal Crônica/metabolismo , Fósforo na Dieta , Metabolismo/fisiologia , Guias de Prática Clínica como Assunto , Vitamina D/antagonistas & inibidoresRESUMO
1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) can modulate immune responses, but whether it directly affects B cell function is unknown. Patients with systemic lupus erythematosus, especially those with antinuclear Abs and increased disease activity, had decreased 1,25(OH)(2)D(3) levels, suggesting that vitamin D might play a role in regulating autoantibody production. To address this, we examined the effects of 1,25(OH)(2)D(3) on B cell responses and found that it inhibited the ongoing proliferation of activated B cells and induced their apoptosis, whereas initial cell division was unimpeded. The generation of plasma cells and postswitch memory B cells was significantly inhibited by 1,25(OH)(2)D(3), although the up-regulation of genetic programs involved in B cell differentiation was only modestly affected. B cells expressed mRNAs for proteins involved in vitamin D activity, including 1 alpha-hydroxylase, 24-hydroxylase, and the vitamin D receptor, each of which was regulated by 1,25(OH)(2)D(3) and/or activation. Importantly, 1,25(OH)(2)D(3) up-regulated the expression of p27, but not of p18 and p21, which may be important in regulating the proliferation of activated B cells and their subsequent differentiation. These results indicate that 1,25(OH)(2)D(3) may play an important role in the maintenance of B cell homeostasis and that the correction of vitamin D deficiency may be useful in the treatment of B cell-mediated autoimmune disorders.
Assuntos
Linfócitos B/citologia , Linfócitos B/efeitos dos fármacos , Calcitriol/fisiologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Fatores Imunológicos/fisiologia , ADP-Ribosil Ciclase 1/biossíntese , Adolescente , Adulto , Idoso , Apoptose/efeitos dos fármacos , Apoptose/genética , Apoptose/imunologia , Linfócitos B/enzimologia , Linfócitos B/imunologia , Calcitriol/deficiência , Calcitriol/farmacologia , Diferenciação Celular/genética , Células Cultivadas , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Regulação para Baixo/imunologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Inibidores do Crescimento/genética , Inibidores do Crescimento/fisiologia , Humanos , Fatores Imunológicos/deficiência , Fatores Imunológicos/farmacologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/patologia , Ativação Linfocitária/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Plasmócitos/efeitos dos fármacos , Plasmócitos/patologia , Receptores de Calcitriol/biossíntese , Receptores de Calcitriol/genética , Esteroide Hidroxilases/biossíntese , Esteroide Hidroxilases/genética , Vitamina D/análogos & derivados , Vitamina D/antagonistas & inibidores , Vitamina D/sangue , Vitamina D3 24-HidroxilaseRESUMO
Clinically apparent hereditary vitamin D-resistant rickets (HVDRR) usually results from a loss of function mutation in the vitamin D receptor (VDR). We recently described a human with the classical HVDRR phenotype but normal VDR function. Hormone resistance resulted from constitutive overexpression of heterogeneous nuclear ribonucleoprotein (hnRNP) that competed with a normally functioning VDR-retinoid X receptor (RXR) dimer for binding to the vitamin D response element (VDRE). Here we describe the purification, molecular cloning, and expression of this vitamin D resistance-causing, competitive response element-binding protein (REBiP) hnRNP C1/C2. When overexpressed in vitamin D-responsive cells, cDNAs for both hnRNPC1 and hnRNPC2 inhibited VDR-VDRE-directed transactivation (28 and 43%, respectively; both p < 0.005). By contrast, transient expression of an hnRNP C1/C2 small interfering RNA increased VDR transactivation by 39% (p < 0.005). Chromatin immunoprecipitation of nucleoproteins bound to the transcriptionally active 1,25-dihydroxy vitamin D-driven CYP24 promoter revealed the presence of REBiP in vitamin D-responsive human cells and indicated that the normal pattern of 1,25-dihydroxy vitamin D-initiated cyclical movement of the VDR on and off the VDRE is legislated by competitive, reciprocal occupancy of the VDRE by hnRNP C1/C2. The temporal and reciprocal pattern of VDR and hnRNPC1/C2 interaction with the VDRE was lost in HVDRR cells overexpressing the hnRNP C1/C2 REBiP. These observations provide further evidence for the functional importance of REBiP as a component of the multiprotein complex involved in the regulation of vitamin D-mediated transcription. In particular, chromatin immunoprecipitation data suggest that, in addition to its RNA-processing functions, hnRNP C1/C2 may be a key determinant of the temporal patterns of VDRE occupancy.
Assuntos
Ribonucleoproteínas Nucleares Heterogêneas Grupo C/química , Vitamina D/antagonistas & inibidores , Sequência de Aminoácidos , Animais , Cromatina/química , Clonagem Molecular , Ribonucleoproteínas Nucleares Heterogêneas Grupo C/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas , Humanos , Dados de Sequência Molecular , Regiões Promotoras Genéticas , Ratos , Receptores de Calcitriol/genética , Raquitismo/genética , Raquitismo/metabolismo , Esteroide Hidroxilases/genética , Transcrição Gênica , Vitamina D3 24-HidroxilaseRESUMO
Vitamin D [1,25(OH)2D3] plays a crucial role in Ca2+ homeostasis by stimulating Ca2+ (re)absorption and bone turnover. The 1,25(OH)2D3 analog ZK191784 was recently developed to dissociate the therapeutic immunomodulatory activity from the hypercalcemic side effects of 1,25(OH)2D3 and contains a structurally modified side chain characterized by a 22,23-double bond, 24R-hydroxy group, 25-cyclopropyl ring, and 5-butyloxazole unit. We investigated the effect of ZK191784 on Ca2+ homeostasis and the regulation of Ca2+ transport proteins in wild-type (WT) mice and mice lacking the renal epithelial Ca2+ channel TRPV5 (TRPV5-/-). The latter display hypercalciuria, hypervitaminosis D, increased intestinal expression of the epithelial Ca2+ channel TRPV6, the Ca2+-binding protein calbindin-D(9K), and intestinal Ca2+ hyperabsorption. ZK191784 normalized the Ca2+ hyperabsorption and the expression of intestinal Ca2+ transport proteins in TRPV5-/- mice. Furthermore, the compound decreased intestinal Ca2+ absorption in WT mice and reduced 1,25(OH)2D3-dependent 45Ca2+ uptake by Caco-2 cells, substantiating a 1,25(OH)2D3-antagonistic action of ZK191784 in the intestine. ZK191784 increased renal TRPV5 and calbindin-D(28K) expression and decreased urine Ca2+ excretion in WT mice. Both 1,25(OH)2D3 and ZK191784 enhanced transcellular Ca2+ transport in primary cultures of rabbit connecting tubules and cortical collecting ducts, indicating a 1,25(OH)2D3-agonistic effect in kidney. ZK191784 enhanced bone TRPV6 mRNA levels and 1,25(OH)2D3 as well as ZK191784 stimulated secretion of the bone formation marker osteocalcin in rat osteosarcoma cells, albeit to a different extent. In conclusion, ZK191784 is a synthetic 1,25(OH)2D3 ligand displaying a unique tissue-specific profile when administered in vivo. Because ZK191784 acts as an intestine-specific 1,25(OH)2D3 antagonist, this compound will be associated with less hypercalcemic side effects compared with the 1,25(OH)2D3 analogs currently used in clinical practice.