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Corneal nerve homeostasis is essential for the functional integrity of the ocular surface. Vitamin D deficiency (VDD) and vitamin D receptor knockout (VDR KO) have been found to reduce corneal nerve density in diabetic mice. This is the first study to comprehensively examine the influence of vitamin D on nerve regeneration following corneal epithelial injury in diabetic mice. Corneal nerve regeneration was significantly retarded by diabetes, VDR KO, and VDD, and it was accelerated following topical 1,25 Vit D and 24,25 Vit D administration. Furthermore, topical 1,25 Vit D and 24,25 Vit D increased nerve growth factor, glial cell line-derived neurotropic factor, and neurotropin-3 protein expression, and it increased secretion of GDNF protein from human corneal epithelial cells. CD45+ cells and macrophage numbers were significantly decreased, and vitamin D increased CD45+ cell and macrophage recruitment in these wounded diabetic mouse corneas. The accelerated nerve regeneration observed in these corneas following topical 1,25 Vit D and 24,25 Vit D administration may be related to the vitamin D-stimulated expression, secretion of neurotrophic factors, and recruitment of immune cells.

There is an increased demand for comprehensive analysis of vitamin D metabolites. This is a major challenge, especially for 1α,25-dihydroxyvitamin D [1α,25(OH)2VitD], because it is biologically active at picomolar concentrations. 4-Phenyl-1,2,4-triazoline-3,5-dione (PTAD) was a revolutionary reagent in dramatically increasing sensitivity of all diene metabolites and allowing the routine analysis of the bioactive, but minor, vitamin D metabolites. A second generation of reagents used large fixed charge groups that increased sensitivity at the cost of a deterioration in chromatographic separation of the vitamin D derivatives. This precludes a survey of numerous vitamin D metabolites without redesigning the chromatographic system used. 2-Nitrosopyridine (PyrNO) demonstrates that one can improve ionization and gain higher sensitivity over PTAD. The resulting vitamin D derivatives facilitate high-resolution chromatographic separation of the major metabolites. Additionally, a liquid-liquid extraction followed by solid-phase extraction (LLE-SPE) was developed to selectively extract 1α,25(OH)2VitD, while reducing 2- to 4-fold ion suppression compared with SPE alone. LLE-SPE followed by PyrNO derivatization and LC/MS/MS analysis is a promising new method for quantifying vitamin D metabolites in a smaller sample volume (100 µL of serum) than previously reported methods. The PyrNO derivatization method is based on the Diels-Alder reaction and thus is generally applicable to a variety diene analytes.

Systemic sclerosis (SSc) is an often fatal disease characterized by autoimmunity and inflammation, leading to widespread vasculopathy and fibrosis. Lysophosphatidic acid (LPA), a bioactive phospholipid in serum, is generated from lysophospholipids secreted from activated platelets in part by the action of lysophospholipase D (lysoPLD). Sphingosine 1-phosphate (S1P), a member of the bioactive lysophospholipid family, is also released from activated platelets. Because activated platelets are a hallmark of SSc, we wanted to determine whether subjects with SSc have altered serum lysophospholipid levels or lysoPLD activity. Lysophospholipid levels were measured using mass spectrometric analysis. LysoPLD activity was determined by quantifying choline released from exogenous lysophosphatidylcholine (LPC). The major results were that serum levels of arachidonoyl (20:4)-LPA and S1P were significantly higher in SSc subjects versus controls. Furthermore, serum LPA:LPC ratios of two different polyunsaturated phospholipid molecular species, and also the ratio of all species combined, were significantly higher in SSc subjects versus controls. No significant differences were found between other lysophospholipid levels or lysoPLD activities. Elevated 20:4 LPA, S1P levels and polyunsaturated LPA:LPC ratios may be markers for and/or play a significant role in the etiology of SSc and may be future pharmacological targets for SSc treatment.

Osteoporosis is a serious public health problem, and dietary interventions may potentially be helpful in preventing this disorder. The purpose of this study was to determine the effects of a low sodium diet on bone metabolism in postmenopausal women. This was a longitudinal study to determine the effects of a low sodium (2-g/day) diet on bone. Forty postmenopausal African–American and Caucasian women were enrolled in a 2-g/day sodium diet for 6 months. Sodium and calcium excretion, bone turnover, and calcitropic hormones (intact parathyroid hormone (PTH) and 1,25 dihydroxyvitamin D) were measured before and 6 months after the intervention. In women who had baseline sodium excretions equal to or greater than the average sodium intake in the United States (≥3.4g/day), the low sodium diet resulted in significant decreases in sodium excretion (P = 0.01), in calcium excretion (P = 0.01), and in a biomarker of bone turnover, aminoterminal propeptide of type I collagen (P = 0.04). However, there were no significant changes in calcitropic hormones, including intact PTH (P = 0.97) or 1,25 dihydroxyvitamin D (P = 0.49) with the low sodium diet. These findings suggest that in postmenopausal women with sodium intakes ≥3.4g/day, a low sodium diet may have benefits for skeletal health. [ABSTRACT FROM AUTHOR]