Implications of vitamin D deficiency in pregnancy and lactation.

Vitamin D is an essential fat soluble vitamin and a key modulator of calcium metabolism in children and adults. Because calcium demands increase in the third trimester of pregnancy, vitamin D status becomes crucial for maternal health, fetal skeletal growth, and optimal maternal and fetal outcomes. Vitamin D deficiency is common in pregnant women (5-50%) and in breastfed infants (10-56%), despite the widespread use of prenatal vitamins, because these are inadequate to maintain normal vitamin D levels (>or=32 ng/mL). Adverse health outcomes such as preeclampsia, low birthweight, neonatal hypocalcemia, poor postnatal growth, bone fragility, and increased incidence of autoimmune diseases have been linked to low vitamin D levels during pregnancy and infancy. Studies are underway to establish the recommended daily doses of vitamin D in pregnant women. This review discusses vitamin D metabolism and the implications of vitamin D deficiency in pregnancy and lactation.

1,25(OH)2 vitamin d inhibits foam cell formation and suppresses macrophage cholesterol uptake in patients with type 2 diabetes mellitus.

BACKGROUND: Cardiovascular disease is the leading cause of death among those with diabetes mellitus. Vitamin D deficiency is associated with an increased risk of cardiovascular disease in this population. To determine the mechanism by which vitamin D deficiency mediates accelerated cardiovascular disease in patients with diabetes mellitus, we investigated the effects of active vitamin D on macrophage cholesterol deposition. METHODS AND RESULTS: We obtained macrophages from 76 obese, diabetic, hypertensive patients with vitamin D deficiency (25-hydroxyvitamin D <80 nmol/L; group A) and 4 control groups: obese, diabetic, hypertensive patients with normal vitamin D (group B; n=15); obese, nondiabetic, hypertensive patients with vitamin D deficiency (group C; n=25); and nonobese, nondiabetic, nonhypertensive patients with vitamin D deficiency (group D; n=10) or sufficiency (group E; n=10). Macrophages from the same patients in all groups were cultured in vitamin D-deficient or 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] -supplemented media and exposed to modified low-density lipoprotein cholesterol. 1,25(OH)(2)D(3) suppressed foam cell formation by reducing acetylated or oxidized low-density lipoprotein cholesterol uptake in diabetic subjects only. Conversely, deletion of the vitamin D receptor in macrophages from diabetic patients accelerated foam cell formation induced by modified LDL. 1,25(OH)(2)D(3) downregulation of c-Jun N-terminal kinase activation reduced peroxisome proliferated-activated receptor-gamma expression, suppressed CD36 expression, and prevented oxidized low-density lipoprotein-derived cholesterol uptake. In addition, 1,25(OH)(2)D(3) suppression of macrophage endoplasmic reticulum stress improved insulin signaling, downregulated SR-A1 expression, and prevented oxidized and acetylated low-density lipoprotein-derived cholesterol uptake. CONCLUSIONS: These results identify reduced vitamin D receptor signaling as a potential mechanism underlying increased foam cell formation and accelerated cardiovascular disease in diabetic subjects.

Analysis of responses to valerian root extract in the feline pulmonary vascular bed.

OBJECTIVES: This study was undertaken to investigate pulmonary vascular response to valerian (Valeriana officinalis) in the feline pulmonary vasculature under constant flow conditions. DESIGN: In separate experiments, the effects of NG-L-nitro-L-arginine methyl ester (L-NIO), a nitric oxide synthase inhibitor, glibenclamide, an adenosine triphosphate (ATP)-sensitive potassium (K+) channel blocker, meclofenamate, a nonselective cyclooxygenase (COX) inhibitor, bicuculline, a GABA(A) receptor antagonist, and saclofen, a GABA(B) antagonist, were investigated on pulmonary arterial responses to various agonists in the feline pulmonary vascular bed. These agonists included valerian, muscimol, a GABA(A) agonist, SKF-97541 a GABA(B) agonist, acetylcholine (ACh), and bradykinin, both inducers of nitric oxide synthase, arachidonic acid, a COX substrate, and pinacidil, an ATP-sensitive K+ channel activator, during increased tone conditions induced by the thromboxane A2 mimic, U46619. SETTINGS/LOCATION: Laboratory investigation. SUBJECTS: Mongrel cats of either gender. INTERVENTIONS: Injections of the abovementioned agonists and antagonists were given. OUTCOME MEASURES: Baseline pulmonary tone, responses to the agonists, and responses to the agonists after injections of antagonists were all measured via a pulmonary catheter transducer and recorded. RESULTS: Valerian root extract is a potent smooth muscle dilator in the feline pulmonary vascular bed. The vasodilatory effects of valerian root extract were unchanged after the administration of L-NIO, glibenclamide, and meclofenamate. These effects were ablated, however, by both saclofen and bicuculline. The ability of saclofen and bicuculline to modulate the dilatory effects of valerian root extract was not statistically different. CONCLUSIONS: The vasodilatory effects of valerian root extract are mediated by a nonselective GABA mechanism.