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1.
Cancer Res ; 69(4): 1439-47, 2009 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-19208842

RESUMO

Experimental evidence suggests that vitamin D has anticarcinogenic properties; however, a nested case-control study conducted in a population of male Finnish smokers found that higher 25-hydroxyvitamin D [25(OH)D], the best indicator of vitamin D status as determined by the sun and diet, was associated with a significant 3-fold increased risk for pancreatic cancer. We conducted a nested case-control study in the Prostate, Lung, Colorectal, and Ovarian Screening Trial cohort of men and women 55 to 74 years of age at baseline to test whether prediagnostic serum 25(OH)D concentrations were associated with pancreatic cancer risk. Between 1994 and 2006, 184 incident cases of pancreatic adenocarcinoma occurred (follow-up to 11.7 years). Two controls (n = 368) who were alive at the time the case was diagnosed were selected for each case and matched by age, race, sex, and calendar date of blood draw (to control for seasonal variation). We calculated odds ratios (OR) and 95% confidence intervals (95% CI) using conditional logistic regression, adjusting for smoking and body mass index. Vitamin D concentrations were not associated with pancreatic cancer overall (highest versus lowest quintile, >82.3 versus <45.9 nmol/L: OR, 1.45; 95% CI, 0.66-3.15; P trend = 0.49). However, positive associations were observed among subjects with low estimated annual residential solar UBV exposure, but not among those with moderate to high annual exposure (P interaction = 0.015). We did not confirm the previous strong positive association between 25(OH)D and pancreatic cancer; however, the increased risk among participants with low residential UVB exposure is similar.


Assuntos
Adenocarcinoma/epidemiologia , Calcifediol/sangue , Neoplasias Colorretais/secundário , Neoplasias Pulmonares/secundário , Neoplasias Ovarianas/secundário , Neoplasias Pancreáticas/epidemiologia , Neoplasias da Próstata/secundário , Vitamina D/sangue , Adenocarcinoma/complicações , Idoso , Estudos de Coortes , Neoplasias Colorretais/patologia , Suplementos Nutricionais , Feminino , Humanos , Incidência , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/patologia , Neoplasias Ovarianas/patologia , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/complicações , Neoplasias da Próstata/patologia , Fatores de Risco , Fatores Socioeconômicos , Luz Solar , Deficiência de Vitamina D/epidemiologia
2.
Breastfeed Med ; 1(1): 27-35, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17661558

RESUMO

OBJECTIVE: Improve vitamin D status in lactating women and their recipient infants, and measure breast milk calcium concentration [Ca] as a function of vitamin D regimen. DESIGN/METHODS: Fully breastfeeding mothers were randomized at 1 month postpartum to 2000 (n = 12) or 4000 (n = 13) IU/day vitamin D for 3 months to achieve optimal vitamin D status [serum 25(OH)D > or =32 ng/mL (80 nmol/L)]. Breast milk [Ca], maternal and infant serum 25(OH)D and serum Ca, and maternal urinary Ca/Cr ratio were measured monthly. RESULTS: Mothers were similar between groups for age, race, gestation, and birth weight. 25(OH)D increased from 1 to 4 months in both groups (mean +/- SD): +11.5 +/- 2.3 ng/mL for group 2000 (p = 0.002) and +14.4 +/- 3.0 ng/mL for group 4000 (p = 0.0008). The 4000 IU/day regimen was more effective in raising both maternal and infant serum levels and breast milk antirachitic activity than the 2000 IU/day regimen. Breast milk [Ca] fell with continued lactation through 4 months in the 2000 and 4000 IU groups. Decline in breast milk [Ca] was not associated with vitamin D dose (p = 0.73) or maternal 25(OH)D (p = 0.94). No mother or infant experienced vitamin D-related adverse events, and all laboratory parameters remained in the normal range. CONCLUSION: High-dose vitamin D was effective in increasing 25(OH)D levels in fully breastfeeding mothers to optimal levels without evidence of toxicity. Breast milk [Ca] and its decline in both groups during 1 to 4 months were independent of maternal vitamin D status and regimen. Both the mother and her infant attained improved vitamin D status and maintained normal [Ca].


Assuntos
Cálcio/metabolismo , Fenômenos Fisiológicos da Nutrição do Lactente/fisiologia , Fenômenos Fisiológicos da Nutrição Materna/fisiologia , Leite Humano/química , Vitamina D/administração & dosagem , Vitamina D/sangue , Adulto , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/sangue , Conservadores da Densidade Óssea/metabolismo , Cálcio/sangue , Cálcio/urina , Creatinina/urina , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Lactente , Recém-Nascido , Lactação/metabolismo , Necessidades Nutricionais , Estado Nutricional , Estudos Prospectivos , Vitamina D/análogos & derivados , Vitamina D/metabolismo , Deficiência de Vitamina D/prevenção & controle
3.
Endocrinology ; 145(8): 3804-12, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15265826

RESUMO

Hyp-mice exhibit abnormal regulation of 25-hydroxyvitamin D [25(OH)D]-1alpha-hydroxylase activity. Previous observations suggest such aberrant modulation is posttranscriptional. To investigate this possibility further, we examined whether hyp-mice manifest abnormal translation of 25(OH)D-1alpha-hydroxylase mRNA. We compared phosphate, parathyroid, and calcitonin effects on renal 25(OH)D-1alpha-hydroxylase protein as well as mRNA and enzyme activity in normal and hyp-mice. We assayed protein by Western blots, mRNA by real-time RT-PCR, and enzyme activity by measuring 1,25-dihydroxyvitamin D production. Although phosphate-depleted mice exhibited enhanced enzyme function, with significantly increased mRNA and protein expression, hyp-mice comparably increased mRNA but failed to augment enzyme activity, concordant with an inability to increase protein expression. PTH stimulation increased mRNA and protein expression as well as enzyme activity in normal mice but in hyp-mice, despite effecting mRNA enhancement, did not increment enzyme function or protein. The inability of hypophosphatemia and PTH to increase 25(OH)D-1alpha-hydroxylase activity and protein expression in hyp-mice was not universal because calcitonin stimulation was normal, suggesting proximal convoluted tubule localization of the defect. These data, in accord with absent undue enhancement of protein expression in hyp-mice treated with protease inhibitors, establish that abberrant regulation of vitamin D metabolism results from abnormal translational activity.


Assuntos
25-Hidroxivitamina D3 1-alfa-Hidroxilase/metabolismo , Hipofosfatemia Familiar/enzimologia , Rim/enzimologia , Biossíntese de Proteínas , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/análise , Animais , Calcitonina/farmacologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hormônio Paratireóideo/farmacologia , Fósforo/sangue , Inibidores de Proteases/farmacologia , Vitamina D/metabolismo
4.
J Bone Miner Res ; 18(3): 434-42, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12619927

RESUMO

The hyp mouse exhibits abnormal metabolic/hormonal regulation of renal 25(OH)D-1alpha-hydroxylase activity. Whether this results from aberrant transcriptional regulation of the 1alpha-hydroxylase gene, CYP27B1, remains unknown. To investigate this possibility, we compared phosphate and parathyroid hormone effects on renal proximal convoluted tubule and thyrocalcitonin effects on proximal straight tubule enzyme activity and mRNA expression in normal and hyp mice. We assayed 25(OH)D-1alpha-hydroxylase activity by measuring 1,25(OH)2D production and mRNA by ribonuclease protection. Phosphate-depleted mice exhibited a 3-fold increment of 25(OH)D-1alpha-hydroxylase activity compared with normals, whereas hyp mice displayed no enhanced enzyme function. Phosphate-depleted mice concurrently displayed a 2-fold increase in mRNA transcripts; in contrast, despite failure to alter enzyme activity, hyp mice exhibited a similar increment in mRNA transcripts. Parathyroid hormone stimulation of normal mice increased 25(OH)D-1alpha-hydroxylase activity 10-fold, while eliciting only a 2-fold increment in hyp mouse enzyme function. This disparity occurred despite increments of mRNA transcripts to comparable levels (22.2 +/- 3.5- vs. 19.9 +/- 1.8-fold). The dissociation between phosphate- and parathyroid hormone-mediated transcriptional activity and protein function was not universal. Thus, thyrocalcitonin stimulation of normal and hyp mice resulted in comparable enhancement of mRNA transcripts and enzyme activity. These observations indicate that abnormal regulation of vitamin D metabolism in hyp mice occurs in the proximal convoluted tubule and results, not from aberrant transcriptional regulation, but from a defect in translational or post-translational activity.


Assuntos
Hipofosfatemia/enzimologia , Biossíntese de Proteínas , Processamento de Proteína Pós-Traducional , Cromossomo X , Animais , Calcitonina/farmacologia , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Ligação Genética , Hipofosfatemia/genética , Camundongos , Camundongos Endogâmicos C57BL , Hormônio Paratireóideo/farmacologia , Esteroide Hidroxilases/genética , Esteroide Hidroxilases/metabolismo , Vitamina D3 24-Hidroxilase
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