Objective
To evaluate relationships between vitamin D, proteinuria, and disease activity in pediatric systemic lupus erythematosus (SLE) and juvenile dermatomyositis (JDM).
Study design
Multiple linear regression was used to associate subject-reported race, sunscreen use, and vitamin D intake with physician-assessed disease activity and serum 25-hydroxyvitamin D [25(OH)D] in subjects with pediatric SLE (n = 37) or JDM (n = 21). Serum 25(OH)D was correlated with urinary vitamin D binding protein/creatinine ratio (DBP/C) and other indicators of proteinuria.
Results
Serum 25(OH)D levels in subjects with SLE were inversely associated with the natural log of urinary DBP/C (r = −0.63, p < 0.001) and urine protein to creatinine ratio (r = −0.60, p<0.001), with an adjusted mean 10.9 (95% CI 5.1, 16.8) ng/mL decrease in 25(OH)D for those with proteinuria. Excluding subjects with proteinuria, serum 25(OH)D levels were inversely associated with disease activity in JDM, but not in SLE. Overall, 66% of all subjects were taking concurrent corticosteroids, but this was not associated with 25(OH)D levels.
Conclusions
Low serum 25(OH)D in patients with SLE is associated with proteinuria and urinary DBP. Vitamin D deficiency is associated with disease activity in patients with JDM and SLE; this relationship in SLE may be confounded by proteinuria.
To evaluate gender differences in salt-induced hypertension, female and male Dahl salt-sensitive rats were fed high (8.0% NaCl, HS) and low (0.3% NaCl, LS) salt diets. During a 3-week treatment period, blood pressure was significantly elevated in both female and male HS groups compared to their respective LS groups. The blood pressure and 4 week mortality rate of the female HS group, however, were significantly lower than those of the male HS group. Renal and aortic blood flows were reduced in male rats on HS diet compared to the LS group, while, in females, renal blood flow was elevated and aortic flow was maintained while on HS diet. Plasma prostaglandin E2 and prostacyclin levels were higher in females than males and unaffected by diet. In contrast, plasma nitric oxide levels were reduced by HS, regardless of gender. In isolated aortic rings, HS diet caused a smaller elevation in the stimulated norepinephrine release ratio in female rats than in males. Thus, salt-induced hypertension is associated with a reduction in levels of nitric oxide regardless of gender. Plasma prostaglandin E2 and prostacyclin levels were higher in females. Taken together, the higher plasma prostaglandin levels and reduced sympathetic activity in females may be contributing factors in their lower blood pressure and reduced mortality.
Vitamin D hormone (1,25-dihydroxyvitamin D) is involved in innate immunity and induces host defense peptides in epithelial cells, suggesting its involvement in mucosal defense against infections. Chlamydia trachomatis is a major cause of bacterial sexually transmitted disease worldwide. We tested the hypothesis that the vitamin D endocrine system would attenuate chlamydial infection. Vitamin D receptor knock-out mice (VDR−/−) and wild-type mice (VDR+/+) were infected with 103 inclusion forming units of Chlamydia muridarum and cervical epithelial cells (HeLa cells) were infected with C. muridarum at multiplicity of infection 5:1 in the presence and absence of 1,25-dihydroxyvitamin D3.VDR−/− mice exhibited significantly higher bacterial loading than wild-type VDR+/+ mice (P<0.01) and cleared the chlamydial infection in 39 days, compared with 18 days for VDR+/+ mice. Monocytes and neutrophils were more numerous in the uterus and oviduct of VDR−/− mice than in VDR+/+ mice (P< 0.05) at d 45 after infection. Pre-treatment of HeLa cells with 10nM or 100nM 1,25-dihydroxyvitamin D3 decreased the infectivity of C. muridarum (P< 0.001). Several differentially expressed protein spots were detected by proteomic analysis of chlamydial-infected HeLa cells pre-treated with 1,25-dihydroxyvitamin D3. Leukocyte elastase inhibitor (LEI), an anti-inflammatory protein, was up-regulated. Expression of LEI in the ovary and oviduct of infected VDR+/+ mice was greater than that of infected VDR−/− mice. We conclude that the vitamin D endocrine system reduces the risk for prolonged chlamydial infections through regulation of several proteins and that LEI is involved in its anti-inflammatory activity.
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