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2.
J Midwifery Womens Health ; 67(4): 442-447, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35403807

RESUMO

INTRODUCTION: Up to 40% of patients report depression or anxiety symptoms in pregnancy; feelings of increased stress are nearly universal. Antepartum stress is linked to adverse outcomes including preterm birth, low birthweight, postpartum depression, and maternal self harm. Unfortunately, limited treatment options exist, and patients are often hesitant to initiate medications prenatally. Thus, the development of efficacious nonpharmacologic interventions is crucial. This pilot study investigated the feasibility and impact of an application (app)-based mindfulness practice, begun in the first trimester, on maternal stress and pregnancy outcomes. METHODS: The study enrolled patients prior to 15 weeks' gestation and followed them prospectively through birth. Patients were provided with a free subscription to Expectful, a commercially available prenatal mindfulness app, and asked to complete daily meditations. Patients completed the Perceived Stress Scale (PSS) self-assessment at 15 weeks and 28 weeks. PSS scores and pregnancy outcomes were compared with a historical control group of pregnant people who did not use the app. RESULTS: Of 68 patients approached, 59 consented to enrollment. Of these, 21 used the app, with an average use of 170 minutes (range, 1.3-1315 min). The average PSS score was significantly lower in the app group at 28 weeks. Additionally, the change in PSS score for app users was greater compared with that of the historical control between enrollment and 28 weeks (-6.3 vs -0.95, P = .0008). Pregnancy outcomes were similar for app users and the historical control. DISCUSSION: Our recruitment rate suggests pregnant patients are eager for a nonmedication intervention to decrease stress. However, adherence after enrollment was limited. For a subset of motivated patients, an app-based mindfulness practice significantly reduced perceived stress between the second and third trimesters compared with non-app users. Prenatal mindfulness apps represent an important low-intervention, low-cost, highly accessible tool for managing perinatal mood and stress.


Assuntos
Meditação , Atenção Plena , Nascimento Prematuro , Ansiedade/prevenção & controle , Feminino , Humanos , Recém-Nascido , Projetos Piloto , Gravidez , Estresse Psicológico/prevenção & controle
3.
Metabol Open ; 12: 100143, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34755103

RESUMO

INTRODUCTION: Several studies have reported the importance of vitamin D status to musculoskeletal health in populations of older adults. Here we report relationships between circulating serum 25(OH)D and musculoskeletal health in a community cohort of UK adults in midlife and investigate whether environmental (dietary intake, use of supplements) and/or genetic factors (4 SNPs previously related to vitamin D status) play more significant roles in determining vitamin D status in this population. METHODS: Participants were recruited from the Hertfordshire Cohort Study, an established longitudinal cohort study of community dwelling adults and were seen at baseline and follow up 9-12 years later. Lumbar spine and total femur BMD were measured at baseline using a Hologic QDR 4500 instrument. Osteoarthritis (OA) was defined by radiographs of the knees graded according to Kellgren & Lawrence at both time points. Serum 25(OH)D concentrations were measured using a DiaSorin Liaison chemiluminescent assay. Genotyping of 4 SNPs previously associated with 25(OH)D values were assessed: (rs12785878 (DHCR7), rs10741657 (CYP2R1) and rs6013897 (CYP24A1)) and a fourth SNP (rs4588), described as "a near-perfect proxy (i.e. substitute) for rs2282679 on the GC gene". RESULTS: 820 subjects (397 men, 423 women) participated at baseline, and 339 of these 820 subjects (164 men; 175 women) participated in a follow up study of OA progression. The median (IQR) age of participants at baseline was 64.0 (61.8-66.5) and 65.5 (63.3-67.6) for men and women respectively. Median circulating levels of 25(OH)D were 44.6 (35.0-63.0) nmol/L and 41.3 (29.8-53.5) nmol/L in men and women respectively. Circulating 25(OH)D was strongly associated with season of blood testing (p < 0.001). The greatest variance in a model of vitamin D status that included the four SNPs measured, season, and whether participants reported taking vitamin D supplements was explained by season of assay (17.9% men; 15.8% women). Higher femoral neck BMD was observed in men with higher baseline vitamin D status, after adjustment for age, season, BMI, smoker status, alcohol consumption, physical activity and social class (p = 0.01). Associations between 25(OH)D and BMD in women were not statistically significant in this population. There were no associations between circulating 25(OH)D and radiographic knee OA at either time point after adjustment for confounders and for duration of follow-up. CONCLUSION: Circulating 25(OH)D levels were generally lower than is recommended in community dwelling adults in midlife, with marked seasonal variation observed, but relationships with reported vitamin D supplementation were weaker. Circulating 25(OH)D was directly associated with hip BMD in men but relationships with BMD in women and radiographic OA were not seen in this sample.

4.
J Dent Educ ; 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34338323

RESUMO

PURPOSE/OBJECTIVE: The work of faculty, staff, and students is driven by their alignment with an institution's vision and purpose, as set forth in its strategic plan. Any plan that calls for innovative growth must address certain aspects of organizational culture as roadblocks to success and should foster relationship building to achieve long-standing progress. This demonstration project investigates a method for effecting change through a Small Group Initiative (SGI). METHODS: Representatives from faculty and staff were selected by purposive sampling, placed into eight groups of six, and one member of each group was made a facilitator to participate in or facilitate monthly structured discussion-based meetings for a 1-year time period. Participants read one chapter a month of 12: The Elements of Great Managing, which corresponds to the Gallup Q12 Employee Engagement survey that each participant completed at the beginning and end of the program. RESULTS: Findings indicate an overall increase in participant levels of employee engagement and increased levels of personal ownership in regard to the strategic plan after participating in the SGI. CONCLUSIONS: Many other institutional efforts aimed at the advancement of school-wide vision and employee engagement can be cumbersome to implement and require a substantial allocation of resources. The SGI, however, requires minimal resources, limited infringement on regular activity, and minimal direct cost to implement. These factors suggest that the SGI could be tailored to meet specific needs of leadership and may have broad-based applicability across various academic settings.

5.
Am J Infect Control ; 47(9): 1157-1159, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30904371

RESUMO

Therapeutic ultrasound (US) is commonly used in the rehabilitation of soft tissue injuries including wounds. US heads and coupling gel come into direct contact with patient skin, increasing the risk for health care-associated infections owing to cross contamination. In this study, nearly 80% of Staphylococcus aureus placed on US heads in gel survived for 1 hour, with survival of 3 days possible in other types of organic matter.


Assuntos
Equipamentos e Provisões/microbiologia , Fômites/microbiologia , Géis , Viabilidade Microbiana , Staphylococcus aureus/fisiologia , Ultrassonografia/instrumentação , Humanos
6.
Child Psychiatry Hum Dev ; 47(4): 618-26, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26429569

RESUMO

Preschool identification of and intervention for psychiatric symptoms has the potential for lifelong benefits. However, preschool identification of thought disorder, a symptom associated with long term risk for social and cognitive dysfunction, has received little attention with previous work limited to examining preschoolers with severe emotional and behavioral dysregulation. Using story-stem methodology, 12 children with ADHD and 12 children without ADHD, ages 4.0-6.0 years were evaluated for thought disorder. Thought disorder was reliably assessed (Cronbach's alpha = .958). Children with ADHD were significantly more likely than children without ADHD to exhibit thought disorder (75 vs 25 %; Fischer's Exact Test = .0391). Thought disorder can be reliably assessed in preschool children and is present in preschool children with psychiatric illness including preschool children with ADHD. Thought disorder may be identifiable in preschool years across a broad range of psychiatric illnesses and thus may be an appropriate target of intervention.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Atenção/fisiologia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Criança , Pré-Escolar , Transtornos Cognitivos/complicações , Feminino , Humanos , Masculino
7.
Clin Interv Aging ; 8: 69-74, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23378749

RESUMO

BACKGROUND: Depression is common in elderly stroke survivors and has been associated with systemic inflammation. We aimed to investigate an elderly population of Swedish stroke patients for evidence of sustained peripheral inflammation 18 months post-stroke and to identify if inflammation is associated with post-stroke depression at 18 months post-stroke. METHODS: The Barthel Index was used to measure the level of impairment in activities of daily living at 3 days post-stroke. Serum concentrations of inflammation markers, ie, C-reactive protein and white cell count, were measured in 149 stroke patients (mean age 81 ± 5.33 years, 35% male) at 18 months post-stroke, and a comparison was made with an age-matched sample of elderly Swedish individuals who had not suffered a stroke. At the same visit, clinical depression was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised criteria. Severity of depression was assessed using the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: Mean C-reactive protein and white cell count levels in stroke patients were significantly elevated at 18 months post-stroke compared with population probands. Disability scores were associated with MADRS depression scores, but C-reactive protein and white cell count were not. CONCLUSION: We found evidence for a sustained peripheral inflammatory response at 18 months post-stroke. C-reactive protein and white cell count were not associated with depression in this study.


Assuntos
Depressão/epidemiologia , Transtorno Depressivo Maior/epidemiologia , Inflamação/epidemiologia , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa , Comorbidade , Depressão/sangue , Depressão/diagnóstico , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/diagnóstico , Avaliação da Deficiência , Feminino , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Contagem de Leucócitos , Masculino , Gravidade do Paciente , Fatores Sexuais , Suécia , Fatores de Tempo
8.
J Stroke Cerebrovasc Dis ; 22(7): e124-35, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23149149

RESUMO

BACKGROUND: The association between stroke and depression is well established and has been suggested to be bidirectional. Systemic immune activation, hypothalamic-pituitary-adrenal axis hyperactivity, physiologic changes in the perfusion of blood vessels, the downregulation of neurotrophic factors, and apoptosis and necrosis of neuronal, glial, and endothelial cells have been frequently implicated in this relationship. A better understanding of the biology of poststroke depression could be important for enhancing clinical management. We review the currently available biologic markers of stroke-associated depressive illness (i.e., neurophysiologic, neuroendocrine, immunologic, and neuroimaging markers as well as neurotrophic factors). METHODS: Search strategies included the electronic databases PubMed, PsycINFO, EMBASE, CINAHL, the Cochrane Library, and Proquest Dissertations (all records through June 2012), the reference lists of retrieved articles, the reference list of relevant reviews, and direct contact with authors of retrieved articles for any additional unpublished data. RESULTS: Thirty-three papers fulfilled the criteria for inclusion. We detected moderate effects for high postdexamethasone cortisol levels (odds ratio [OR] 3.28; 95% confidence interval [CI] 1.28-8.39; P = .01), lower serum brain-derived neurotrophic factor levels (standardised mean difference [SMD] -0.52; 95% CI -0.84 to -0.21; P = .001), smaller amygdala volumes (SMD -0.45; 95% CI -0.89 to -0.02; P = .04), and a small effect for overall brain perfusion reduction (SMD -0.35; 95% CI -0.64 to -0.06; P = .02), respectively, to poststroke depression. CONCLUSIONS: Cortisol-lowering therapies and those that increase blood flow and neurotrophic factors represent promising novel therapeutics for depression subtypes and may reduce the risk of depression in stroke patients.


Assuntos
Encéfalo/fisiopatologia , Depressão/etiologia , Transtorno Depressivo/etiologia , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Acidente Vascular Cerebral/complicações , Depressão/fisiopatologia , Transtorno Depressivo/fisiopatologia , Humanos , Neuroimagem , Acidente Vascular Cerebral/fisiopatologia
9.
Food Nutr Res ; 562012.
Artigo em Inglês | MEDLINE | ID: mdl-22509143

RESUMO

BACKGROUND: Elderly stroke survivors have been reported to be at risk of malnutrition and depression. Vitamin B-related metabolites such as methylmalonic acid and homocysteine have been implicated in depression. OBJECTIVE: We conducted a study exploring the relationship between homocysteine and post-stroke depression. DESIGN: THREE METHODOLOGIES WERE USED: Observational cohort study of elderly Swedish patients (n=149) 1.5 years post-stroke, assessed using Diagnostic and Statistical Manual of Mental Disorders, Montgomery Åsberg Depression Rating Scale and serum blood levels of methylmalonic acid and homocysteine. RESULTS: Homocysteine significantly correlated with depressive symptomatology in stroke survivors (ß=0.18*). Individuals with abnormal levels of methylmalonic acid and homocysteine were almost twice more likely to show depressive symptomatology than those with normal levels (depressive symptoms 22%; no depressive symptoms 12%). Comparison of methylmalonic acid and homocysteine levels with literature data showed fewer stroke survivors had vitamin deficiency than did reference individuals (normal range 66%; elevated 34%). CONCLUSIONS: Homocysteine is significantly associated with depressive symptomatology in elderly Swedish stroke survivors.

10.
Am J Clin Nutr ; 93(3): 628-35, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21228264

RESUMO

BACKGROUND: Metabolic consequences of vitamin D deficiency have become a recent research focus. Maternal vitamin D status is thought to influence musculoskeletal health in children, but its relation with offspring metabolic risk is not known. OBJECTIVE: We aimed to examine the association between maternal vitamin D status and anthropometric variables, body composition, and cardiovascular risk markers in Indian children. DESIGN: Serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured at 28-32 wk gestation in 568 women who delivered at Holdsworth Memorial Hospital, Mysore, India. Anthropometric variables, glucose and insulin concentrations, blood pressure, and fasting lipid concentrations were measured in the offspring at 5 and 9.5 y of age. Muscle-grip strength was measured by using a hand-held dynamometer at age 9.5 y. Arm-muscle area was calculated as a measure of muscle mass. Fasting insulin resistance was calculated by using the homeostasis model assessment equation. RESULTS: Sixty-seven percent of women had vitamin D deficiency [serum 25(OH)D concentration <50 nmol/L]. At ages 5 and 9.5 y, children born to vitamin D-deficient mothers had smaller arm-muscle area in comparison with children born to mothers without deficiency (P < 0.05). There was no difference in grip strength between offspring of women with and without vitamin D deficiency. At 9.5 y, children of vitamin D-deficient mothers had higher fasting insulin resistance than did children of nondeficient women (P = 0.04). There were no associations between maternal vitamin D status and other offspring risk factors at either age. CONCLUSION: Intrauterine exposure to low 25(OH)D concentrations is associated with less muscle mass and higher insulin resistance in children.


Assuntos
Composição Corporal , Doenças Cardiovasculares/epidemiologia , Fenômenos Fisiológicos da Nutrição Materna , Estado Nutricional , Deficiência de Vitamina D/epidemiologia , 25-Hidroxivitamina D 2/sangue , Adulto , Pesos e Medidas Corporais , Doenças Cardiovasculares/sangue , Criança , Desenvolvimento Infantil , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Índia/epidemiologia , Resistência à Insulina , Masculino , Força Muscular , Gravidez , Terceiro Trimestre da Gravidez/sangue , Fatores de Risco , Deficiência de Vitamina D/sangue
11.
Int J Epidemiol ; 38(6): 1681-8, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19564248

RESUMO

BACKGROUND: Maternal vitamin D status in pregnancy has been postulated to have important effects on intrauterine development. UVB radiation is not commonly measured but is the prime determinant of circulating 25-hydroxyvitamin-D [25-(OH)D] and is highly dependent on regional weather including cloud cover, ozone and sunshine hours. METHODS: Using linear regression we described the relationship between estimated ambient-erythemal ultraviolet (eUV) exposure in Oxford (1990-95) and total hours of sunshine and month in order to forecast eUV in nearby regions, whilst adjusting for regional variations in weather. The forecast was validated with empirical data collected from Cornwall and then predicted for the Avon region. Total 98-day prenatal ambient-eUV was then predicted in 355 expectant mothers in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort and its relationship with maternal vitamin D status was determined. RESULTS: Estimated ambient-eUV was strongly associated with measured ambient-eUV (r(2) = 0.989) with a near 1:1 prediction for the validation data set [beta = 0.99, 95% confidence interval (CI) 0.913, 1.067 r(2) = 0.980]; strong seasonal associations were observed between eUV in the last trimester of pregnancy and maternal serum 25-(OH)D concentrations (r(2) = 0.40). CONCLUSION: This technique of prediction could be applied to existing cohorts allowing the relationship between maternal vitamin D status and the health of the offspring to be studied via instrumental variable analysis.


Assuntos
Estado Nutricional , Terceiro Trimestre da Gravidez/sangue , Raios Ultravioleta , Vitamina D/sangue , Estudos de Coortes , Exposição Ambiental , Feminino , Humanos , Modelos Lineares , Estudos Longitudinais , Fenômenos Fisiológicos da Nutrição Materna , Valor Preditivo dos Testes , Gravidez , Estações do Ano , Reino Unido , Vitamina D/análogos & derivados
12.
Am J Kidney Dis ; 53(5): 856-65, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19393473

RESUMO

BACKGROUND: Kidney transplantation is associated with an increased risk of bone fracture and rapid loss of bone mineral density after kidney transplantation. STUDY DESIGN: Randomized controlled trial. SETTING & PARTICIPANTS: Patients were randomly assigned to treatment (n = 46) or control (no treatment; n = 47) groups. Patients were stratified according to parathyroid hormone level and sex. Those with parathyroid hormone level less than 150 pg/mL were excluded. INTERVENTION: The treatment and control groups received pamidronate, 1 mg/kg, perioperatively and then at 1, 4, 8, and 12 months or no treatment, respectively. All received calcium (500 mg) and vitamin D (400 units) daily. Immunosuppression was cyclosporine and prednisolone, with no difference in dosing between the 2 groups. OUTCOMES & MEASUREMENTS: Bone mineral density was evaluated by means of dual-energy x-ray absorptiometry of the lumbar spine and hip at baseline and 3, 6, 12, and 24 months, with the primary end point at 1 year of percentage of change in bone mineral density from baseline. Clinical fractures were recorded and also evaluated by means of spinal radiographs at baseline and 1 and 2 years. RESULTS: Pamidronate protected bone mineral density at the lumbar spine; bone mineral density increased by 2.1% in the treatment group and decreased by 5.7% in the control group at 12 months (P = 0.001). Protection was also seen in Ward's area of the hip (P = 0.002) and the total hip (P = 0.004). There was no difference in femoral neck bone mineral density loss between the 2 groups. Fracture rates in the treatment and control groups were 3.3% and 6.4% per annum, respectively. LIMITATIONS: This study was not powered to detect differences in fracture rates. CONCLUSION: Pamidronate protects against posttransplantation bone loss at the lumbar spine and Ward's area of the hip.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Reabsorção Óssea/tratamento farmacológico , Difosfonatos/uso terapêutico , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Absorciometria de Fóton , Adolescente , Adulto , Idoso , Conservadores da Densidade Óssea/administração & dosagem , Reabsorção Óssea/sangue , Reabsorção Óssea/etiologia , Difosfonatos/administração & dosagem , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , GTP Fosfo-Hidrolases , Humanos , Masculino , Pessoa de Meia-Idade , Pamidronato , Hormônio Paratireóideo/sangue , Complicações Pós-Operatórias , Radioimunoensaio , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
13.
J Clin Endocrinol Metab ; 91(7): 2612-7, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16670168

RESUMO

CONTEXT: Vitamin D deficiency, common in South Asians, is a risk factor for metabolic syndrome, type 2 diabetes, and ischemic heart disease. Vitamin D receptor (VDR) activation depends on activated vitamin D [1,25-dihydroxyvitamin D (1,25(OH)(2)D)] concentration, reflecting opposing actions of 25-hydroxyvitamin D-1alpha-hydroxylase [1-alpha(OH)ase] for formation and 25(OH)D-24-hydroxylase [24(OH)ase] for catabolism. We previously reported that circulating 1,25(OH)(2)D contributed to determination of VDR-protein levels and VDR genotype was a determinant of both VDR mRNA and VDR-protein in South Asians. OBJECTIVE: We hypothesized that chewing betel nut, an addictive habit common throughout South Asian communities, contributes to hypovitaminosis-D by modulating the enzymes regulating circulating 1,25(OH)(2)D concentration. DESIGN: Peripheral blood mononuclear cell (PBMC) 1-alpha(OH)ase and 24(OH)ase mRNA concentrations were measured and examined in relation to cross-sectional data on the vitamin-D axis, diet, smoking, and betel usage, including PBMC VDR-RNA and VDR-protein content in a pilot study of 33 healthy British Bangladeshis. RESULTS: PBMC 24(OH)ase mRNA correlated positively and serum 1,25(OH)(2)D negatively with betel quids per day (r = 0.49, P = 0.006 and r = -0.486, P = 0.006, respectively). Independent determinants for 24(OH)ase included betel quids per day (P < 0.0001) and serum 25-OHD (P = 0.024). Independent determinants for serum 1,25(OH)(2)D were gender, smoking, and betel quids per day. PBMC 1-alpha(OH)ase mRNA correlated inversely with VDR mRNA (r = -0.44; P = 0.013); its independent determinants were serum 1,25(OH)(2)D and VDR TaqI and BsmI polymorphisms (P = 0.03-0.0001). CONCLUSIONS: Betel chewing is a more powerful independent determinant of increased 24(OH)ase expression and of decreased serum calcitriol than serum 25-OHD, supporting the hypothesis that this habit could aggravate the effects of vitamin-D deficiency.


Assuntos
Areca/efeitos adversos , Leucócitos Mononucleares/enzimologia , Estado Nutricional , Deficiência de Vitamina D/enzimologia , Vitamina D/sangue , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , Adulto , Idoso , Bangladesh/etnologia , Calcifediol/sangue , Calcitriol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Esteroide Hidroxilases/genética , Reino Unido , Vitamina D3 24-Hidroxilase
14.
Am J Clin Nutr ; 82(3): 517-22, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16155262

RESUMO

BACKGROUND: Although hypovitaminosis D has been suggested to increase the risk of heart disease, its relation to components of the fasting lipid profile has not been clarified for specific ethnic groups. OBJECTIVE: The objective was to determine the relation of circulating 25-hydroxyvitamin D [25(OH)D] concentrations to fasting lipid concentrations in South Asian subjects at risk of hypovitaminosis D. DESIGN: The present study was conducted in 170 British Bangladeshi adults, 69 men and 101 women, from east London who were free of known diabetes or chronic disorders. Vitamin D repletion was assessed by measuring fasting serum 25(OH)D concentrations. Fasting lipid profiles were measured as part of a study of the risk factors for type 2 diabetes and ischemic heart disease, which included hypovitaminosis D. RESULTS: A univariate analysis showed that total cholesterol, LDL cholesterol, and both apolipoprotein (apo) A-I and apo B concentrations correlated directly with serum 25(OH)D concentrations. However, a multiple regression analysis, which included all the documented risk factors for diabetes and ischemic heart disease, showed that the 25(OH)D concentration (vitamin D status) was an independent predictor of increasing apo A-I concentrations (standardized coefficient beta = 0.3; P < 0.001) but not of fasting lipid concentrations. CONCLUSIONS: In this study of British South Asians, the data showed a positive relation of fasting apo A-I concentrations to serum 25(OH)D concentrations, independent of glycemia and other dietary, anthropometric, and lifestyle risk factors for type 2 diabetes and ischemic heart disease after multiple regression analyses. Subjects with hypovitaminosis D are likely to have an increased risk of ischemic heart disease independent of their increased risk of type 2 diabetes.


Assuntos
Apolipoproteína A-I/sangue , Colesterol/sangue , Deficiência de Vitamina D/sangue , Vitamina D/análogos & derivados , Adulto , Idoso , Análise de Variância , Apolipoproteínas B/sangue , Bangladesh/etnologia , LDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etnologia , Diabetes Mellitus Tipo 2/etiologia , Jejum/sangue , Feminino , Humanos , Lipídeos/sangue , Londres , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/sangue , Isquemia Miocárdica/etnologia , Isquemia Miocárdica/etiologia , Análise de Regressão , Fatores de Risco , Vitamina D/sangue , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/etnologia
16.
Nephron Physiol ; 94(4): p62-73, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12972708

RESUMO

BACKGROUND: New 'non-calcaemic' analogues of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) are entering the clinical arena and some of them have been shown to have differential effects in bone. This may have a bearing on the evolution of bone lesions in uraemic patients receiving vitamin D therapies. A potential mechanism for differential effects of analogues lies in their target cell inactivation. METHODS: Using a human osteoblastic cell line, MG-63, three analogues, 22-oxacalcitriol (OCT), 19-nor-1,25-dihydroxyvitamin D2 (paricalcitol) and 1alpha,25-dihydroxydihydrotachysterol2(1,25(OH)2DHT2), were compared with 1,25(OH)2D3 for (1) their affinity for the vitamin D receptor (VDR) by competitive displacement of tritiated 1,25(OH)2D3 from calf thymus VDR; (2) effects on 24-hydroxylase mRNA expression using comparative RT-PCR, and (3) rates of metabolism, using high performance liquid chromatography, over a 24-hour time course. RESULTS: Relative VDR-binding affinities (IC50) were 1,25(OH)2D3 (100%), OCT (25%), paricalcitol (14%) and 1,25(OH)2DHT2 (0.3%). A > or =3-fold increase in 24-hydroxylase mRNA expression was observed for all compounds at 2 h peaking at 7- to 8-fold above control levels by 12 h, with no significant difference between the analogues and 1,25(OH)2D3. Differences in their rates of metabolism were observed [calculated t(1/2) values = OCT (1.2 h) > paricalcitol (2.3 h) > 1,25(OH)2D3 (2.6 h) > 1,25(OH)2DHT2 (3.4 h)], with OCT having a significantly shorter half-life. CONCLUSION: In MG-63 cells these analogues up-regulate 24-hydroxylase mRNA expression with similar potency, in each case accelerating ligand inactivation, despite significant differences in VDR affinity. VDR affinity did not correspond to either 24-hydroxylase mRNA expression or the rates of ligand disappearance, suggesting cellular metabolism is one of several factors that determine the analogue specificity of these agents in bone.


Assuntos
Calcitriol/análogos & derivados , Calcitriol/farmacologia , Sistema Enzimático do Citocromo P-450/biossíntese , Osteoblastos/efeitos dos fármacos , Osteoblastos/enzimologia , Esteroide Hidroxilases/biossíntese , Animais , Calcitriol/metabolismo , Bovinos , Linhagem Celular , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Di-Hidrotaquisterol/química , Di-Hidrotaquisterol/metabolismo , Ergocalciferóis/metabolismo , Ergocalciferóis/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Hidroxilação/efeitos dos fármacos , Oxigenases de Função Mista/metabolismo , Osteoblastos/química , Ligação Proteica/efeitos dos fármacos , Receptores de Calcitriol/metabolismo , Esteroide Hidroxilases/genética , Esteroide Hidroxilases/metabolismo , Timo/química , Timo/enzimologia , Timo/metabolismo , Vitamina D3 24-Hidroxilase
17.
Diabetes ; 51(7): 2294-300, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12086963

RESUMO

Associations have been reported between vitamin D receptor (VDR) gene polymorphisms, type 1 diabetes, insulin secretion, and the insulin resistance syndrome. As VDR polymorphisms have no known functional significance, these findings may implicate a variant of the VDR gene or a locus in linkage disequilibrium with the VDR. We have examined VDR mRNA and VDR protein levels in relation to VDR polymorphisms (41 Bangladeshi subjects) and analyzed insulin secretory capacity (143 Bangladeshi subjects), allowing for other known determinants. Peripheral blood mononuclear cells (PBMCs) from subjects who had been genotyped for BsmI, ApaI, TaqI, and FokI VDR restriction fragment length polymorphisms were used for both total VDR mRNA quantitation (using TaqMan) and measurement of VDR protein levels (using a specific micro-immunoassay). Stepwise multiple regression analyses were used (to P < 0.05) to analyze the data. For the insulin secretion index, the best-fit model (n = 143, P < 0.0001) gave age (P = 0.002), TaqI (P < 0.0001), and BMI (P = 0.001) as independent determinants; with the inclusion of VDR mRNA and VDR protein levels, VDR mRNA was the sole independent determinant (n = 41, P = 0.024). However, the best-fit model for VDR mRNA (P = 0.004) gave FokI (P = 0.044) and TaqI (P = 0.04) genotypes and insulin secretory capacity (P = 0.042) as independent determinants. For VDR protein levels, the best-fit model (P = 0.006) gave TaqI genotype (P = 0.005) and circulating 1,25-dihydroxyvitamin-D levels (P = 0.03) as independent determinants. In conclusion, these studies confirm an association between VDR polymorphisms and insulin secretory capacity and demonstrate the VDR genotype to be a significant determinant of VDR mRNA and VDR protein levels in PBMCs, providing functional support to previously described genetic associations with the VDR gene. Furthermore, VDR expression has been shown to be a determinant of insulin secretory capacity.


Assuntos
Insulina/metabolismo , RNA Mensageiro/genética , Receptores de Calcitriol/genética , Vitamina D/sangue , Adulto , Bangladesh/etnologia , Genótipo , Humanos , Insulina/sangue , Secreção de Insulina , Receptores de Calcitriol/metabolismo , Valores de Referência , Análise de Regressão , Estados Unidos
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