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1.
J Steroid Biochem Mol Biol ; 175: 138-145, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28161533

RESUMO

Vitamin D deficiency is common in patients with chronic obstructive pulmonary disease (COPD), yet a comprehensive analysis of environmental and genetic determinants of serum 25-hydroxyvitamin D (25[OH]D) concentration in patients with this condition is lacking. We conducted a multi-centre cross-sectional study in 278 COPD patients aged 41-92 years in London, UK. Details of potential environmental determinants of vitamin D status and COPD symptom control and severity were collected by questionnaire, and blood samples were taken for analysis of serum 25(OH)D concentration and DNA extraction. All participants performed spirometry and underwent measurement of weight and height. Quadriceps muscle strength (QS) was measured in 134 participants, and sputum induction with enumeration of lower airway eosinophil and neutrophil counts was performed for 44 participants. Thirty-seven single nucleotide polymorphisms (SNP) in 11 genes in the vitamin D pathway (DBP, DHCR7, CYP2R1, CYP27B1, CYP24A1, CYP27A1, CYP3A4, LRP2, CUBN, RXRA, and VDR) were typed using Taqman allelic discrimination assays. Linear regression was used to identify environmental and genetic factors independently associated with serum 25(OH)D concentration and to determine whether vitamin D status or genetic factors independently associated with % predicted forced expiratory volume in one second (FEV1), % predicted forced vital capacity (FVC), the ratio of FEV1 to FVC (FEV1:FVC), daily inhaled corticosteroid (ICS) dose, respiratory quality of life (QoL), QS, and the percentage of eosinophils and neutrophils in induced sputum. Mean serum 25(OH)D concentration was 45.4nmol/L (SD 25.3); 171/278 (61.5%) participants were vitamin D deficient (serum 25[OH]D concentration <50nmol/L). Lower vitamin D status was independently associated with higher body mass index (P=0.001), lower socio-economic position (P=0.037), lack of vitamin D supplement consumption (P<0.001), sampling in Winter or Spring (P for trend=0.006) and lack of a recent sunny holiday (P=0.002). Vitamin D deficiency associated with reduced % predicted FEV1 (P for trend=0.060) and % predicted FVC (P for trend=0.003), but it did not associate with FEV1:FVC, ICS dose, QoL, QS, or the percentage of eosinophils or neutrophils in induced sputum. After correction for multiple comparisons testing, genetic variation in the vitamin D pathway was not found to associate with serum 25(OH)D concentration or clinical correlates of COPD severity. Vitamin D deficiency was common in this group of COPD patients in the UK, and it associated independently with reduced % predicted FEV1 and FVC. However, genetic variation in the vitamin D pathway was not associated with vitamin D status or severity of COPD.


Assuntos
Doença Pulmonar Obstrutiva Crônica/epidemiologia , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos Transversais , Sistema Enzimático do Citocromo P-450/sangue , Sistema Enzimático do Citocromo P-450/genética , Proteínas de Ligação a DNA/sangue , Proteínas de Ligação a DNA/genética , Eosinófilos/metabolismo , Eosinófilos/patologia , Feminino , Regulação da Expressão Gênica , Humanos , Londres/epidemiologia , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/sangue , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Neutrófilos/patologia , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/sangue , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética , Prevalência , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/genética , Grupos Raciais , Receptores de Calcitriol/sangue , Receptores de Calcitriol/genética , Receptores de Superfície Celular/sangue , Receptores de Superfície Celular/genética , Testes de Função Respiratória , Índice de Gravidade de Doença , Fatores de Transcrição/sangue , Fatores de Transcrição/genética , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/genética
2.
J Steroid Biochem Mol Biol ; 175: 88-96, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-27825992

RESUMO

Vitamin D deficiency is common in children with asthma, and it associates with poor asthma control, reduced forced expiratory volume in one second (FEV1) and increased requirement for inhaled corticosteroids (ICS). Cross-sectional studies investigating the prevalence, determinants and clinical correlates of vitamin D deficiency in adults with asthma are lacking. We conducted a multi-centre cross-sectional study in 297 adults with a medical record diagnosis of ICS-treated asthma living in London, UK. Details of potential environmental determinants of vitamin D status, asthma control and medication use were collected by questionnaire; blood samples were taken for analysis of serum 25(OH)D concentration and DNA extraction, and participants underwent measurement of weight, height and fractional exhaled nitric oxide concentration (FeNO), spirometry and sputum induction for determination of lower airway eosinophil counts (n=35 sub-group). Thirty-five single nucleotide polymorphisms (SNP) in 11 vitamin D pathway genes (DBP, DHCR7, RXRA, CYP2R1, CYP27B1, CYP24A1, CYP3A4 CYP27A1, LRP2, CUBN, VDR) were typed using Taqman allelic discrimination assays. Linear regression was used to identify environmental and genetic factors independently associated with serum 25(OH)D concentration, and to determine whether vitamin D status was independently associated with Asthma Control Test (ACT) score, ICS dose, FeNO, forced vital capacity (FVC), FEV1 or lower airway eosinophilia. Mean serum 25(OH)D concentration was 50.6nmol/L (SD 24.9); 162/297 (54.5%) participants were vitamin D deficient (serum 25(OH)D concentration <50nmol/L). Lower vitamin D status was associated with higher body mass index (P=0.014), non-White ethnicity (P=0.036), unemployment (P for trend=0.012), lack of vitamin D supplement use (P<0.001), sampling in Winter or Spring (P for trend <0.001) and lack of a recent sunny holiday abroad (P=0.030), but not with potential genetic determinants. Vitamin D status was not found to associate with any marker of asthma control investigated. Vitamin D deficiency is common among UK adults with ICS-treated asthma, and classical environmental determinants of serum 25(OH)D operate in this population. However, in contrast to studies conducted in children, we found no association between vitamin D status and markers of asthma severity or control.


Assuntos
Asma/epidemiologia , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Administração por Inalação , Adolescente , Corticosteroides/uso terapêutico , Adulto , Idoso , Antiasmáticos/uso terapêutico , Asma/sangue , Asma/complicações , Asma/tratamento farmacológico , Índice de Massa Corporal , Estudos Transversais , Sistema Enzimático do Citocromo P-450/sangue , Sistema Enzimático do Citocromo P-450/genética , Proteínas de Ligação a DNA/sangue , Proteínas de Ligação a DNA/genética , Eosinófilos/metabolismo , Eosinófilos/patologia , Feminino , Regulação da Expressão Gênica , Humanos , Londres/epidemiologia , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/sangue , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Masculino , Pessoa de Meia-Idade , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/sangue , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética , Grupos Raciais , Receptores de Calcitriol/sangue , Receptores de Calcitriol/genética , Receptores de Superfície Celular/sangue , Receptores de Superfície Celular/genética , Testes de Função Respiratória , Índice de Gravidade de Doença , Fatores de Transcrição/sangue , Fatores de Transcrição/genética , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/tratamento farmacológico
3.
Indian J Biochem Biophys ; 46(1): 73-8, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19374257

RESUMO

Bilirubin above a threshold level is toxic to human system and is excreted in urinary and through gastrointestinal tract. The role of bilirubin as antioxidant is debatable. This paper aims at elucidating the role of bilirubin as an antioxidant in neonatal jaundice patients. It is observed that bilirubin up to 6 mg/dl in blood acts as an antioxidant and above 12.5 mg/dl is strongly prooxidant. Phototherapy is the accepted therapeutic management of neonatal jaundice and has been shown to enhance the oxidative stress. Approaches have been taken to formulate a herbal medication which will reduce bilirubin level in the neonates without inducing additional damages. The ethanolic extract of sweet lime peel, administered orally at a dose of 72 microg is found to reduce the oxidative stress in erythrocytes of phenylhydrazine-induced jaundiced rats treated with phototherapy.


Assuntos
Antioxidantes/uso terapêutico , Bilirrubina/metabolismo , Citrus aurantiifolia , Icterícia Neonatal/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Animais , Antioxidantes/metabolismo , Bilirrubina/sangue , Bilirrubina/química , Biliverdina/sangue , Feminino , Glucosefosfato Desidrogenase/metabolismo , Humanos , Recém-Nascido , Icterícia Neonatal/induzido quimicamente , Peroxidação de Lipídeos , Masculino , Oxidantes/sangue , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/sangue , Fosfogluconato Desidrogenase/metabolismo , Ratos , Ratos Wistar , Superóxidos/metabolismo , Transcetolase/metabolismo
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