Osteomalacia in a hemodialysis patient receiving an active vitamin D sterol

Background. The role of vitamin D in the body's ability to fight influenza and URI's may be dependent on regulation of specific cytokines that participate in the host inflammatory response. The aim of this study was to test the hypothesis that vitamin D can influence intracellular signaling to regulate the production of cytokines.Subjects and Methods. This study was a 3-month prospective placebo-controlled trial of vitamin D3 supplementation in ambulatory adults [Li-Ng et al., 2009]. 162 volunteers were randomized to receive either 50 μg/d(2000 IU) of vitamin D3 or matching placebo. 25(OH)D and the levels of 10 different cytokines (IL-2, 4, 5, 6, 8, 10, 13, GM-CSF, IFN-γ, TNF-α) were measured in the serum of participants at baseline and the final visit. There were 6 drop-outs from the active vitamin D group and 8 from the placebo group.Results. In the active vitamin D group, we found a significant median percent decline in levels of GM-CSF (−62.9%,P<.0001), IFN-γ(−38.9%,P<.0001), IL-4 (−50.8%,P=.001), IL-8 (−48.4%,P<.0001), and IL-10 (−70.4%,P<.0001). In the placebo group, there were significant declines for GM-CSF (−53.2%,P=.0007) and IFN-γ(−34.4%,P=.0011). For each cytokine, there was no significant difference in the rate of decline between the two groups. 25(OH)D levels increased in the active vitamin D group from a mean of64.3±25.4 nmol/L to88.5±23.2 nmol/L.Conclusions. The present study did not show that vitamin D3 supplementation changed circulating cytokine levels among healthy adults.

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Dynamic changes in calcium and phosphate plasma concentrations in the patients on peritoneal dialysis

Vojnosanitetski pregled ◽

10.2298/vsp0601027j ◽

2006 ◽

Vol 63 (1) ◽

pp. 27-30

Author(s):

Natasa Jovanovic ◽

Mirjana Lausevic ◽

Biljana Stojimirovic

Keyword(s):

Vitamin D ◽

Renal Failure ◽

Peritoneal Dialysis ◽

End Stage Renal Disease ◽

Calcium Concentration ◽

Phosphate Binders ◽

Active Vitamin ◽

Active Vitamin D ◽

Stage Renal Disease ◽

End Stage

Background/Aim. The disturbances of active forms of vitamin D synthesis and disturbances in calcium and posphate metabolism develop early in chronic renal failure, when creatinine clearance is about 30 ml/min. Chronic hemodialysis and peritoneal dialysis only partially correct the biochemical environment of patients on chronic renal replacement therapy because of end-stage renal disease. These dialysis modalities can?t significantly affect the endocrine disturbances of chronic renal failure and they have minimal modulatory effect. The management of disturbed calcium (Ca) and phosphate (P) metabolism and the maintainance of Ca ? P product below 4.4 mmol/l thanks to the use of dialysate solutions with the appropriate calcium concentration and the careful dosage of phosphate binders, calcium and active vitamin D metabolits, are extremely important for the prevention of renal osteodystrophy, secondary hyperparathyroidism as well as low-bone turnover disease. The aim of the study was to analyze the plasma levels of calcium, phosphate, albumin, alkaline phosphatase and parathormon (PTH) in 58 patients who were treated with continuous ambulatory peritoneal dialysis (CAPD) from March to August 2003. The use of phosphate binders and the substitution with active vitamin D metabolits were also analyzed. Methods. We examined 58 patients, 30 males and 28 female, mean-age 52 years (range, 26-78 years), affected by end-stage renal disease of the different leading cause. The average time on peritoneal dialysis program was 20 months (2-66 months). Most of the patients were treated by CAPD, while only few of them performed automatic, cyclic or intermittent peritoneal dialysis. Most of the patients used a dialysate with 1.75 mmol/l calcium concentration. Results. The study showed that our patients on chronic CAPD program during several months had normal calcemia, phosphatemia and the level of alkaline phosphatase, and that they had Ca ? P product in the recommended range. PTH serum level ranged from 16 to 490 pg/l in our patients. Conclusion. The study showed that a balanced diet and a correct dosage of phosphate binders, as well as a careful substitution with active vitamin D metabolits render a good control of calcium and phosphate serum balance, as well as an effective prevention of renal osteodystrophy development in the patients on chronic peritoneal dialysis treatment.

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Inflammation- and Gut-Homing Macrophages, Engineered to De Novo Overexpress Active Vitamin D, Promoted the Regenerative Function of Intestinal Stem Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22179516 ◽

2021 ◽

Vol 22 (17) ◽

pp. 9516

Author(s):

Yi Xu ◽

David J. Baylink ◽

Huynh Cao ◽

Jeffrey Xiao ◽

Maisa I. Abdalla ◽

...

Keyword(s):

Stem Cells ◽

Vitamin D ◽

De Novo ◽

Chronic Inflammatory Disease ◽

Intestinal Stem Cells ◽

Intestinal Epithelial ◽

Active Vitamin ◽

Gut Inflammation ◽

Epithelial Regeneration ◽

Active Vitamin D

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gut. Available drugs aim to suppress gut inflammation. These drugs have significantly delayed disease progression and improved patients’ quality of life. However, the disease continues to progress, underscoring the need to develop novel therapies. Aside from chronic gut inflammation, IBD patients also experience a leaky gut problem due to damage to the intestinal epithelial layer. In this regard, epithelial regeneration and repair are mediated by intestinal stem cells. However, no therapies are available to directly enhance the intestinal stem cells’ regenerative and repair function. Recently, it was shown that active vitamin D, i.e., 1,25-dihydroxyvitamin D or 1,25(OH)2D, was necessary to maintain Lgr5+ intestinal stem cells, actively cycling under physiological conditions. In this study, we used two strategies to investigate the role of 1,25(OH)2D in intestinal stem cells’ regenerative function. First, to avoid the side effects of systemic high 1,25(OH)2D conditions, we used our recently developed novel strategy to deliver locally high 1,25(OH)2D concentrations specifically to inflamed intestines. Second, because of the Lgr5+ intestinal stem cells’ active cycling status, we used a pulse-and-chase strategy via 5-bromo-2′-deoxyuridine (BrdU) labeling to trace the Lgr5+ stem cells through the whole epithelial regeneration process. Our data showed that locally high 1,25(OH)2D concentrations enhanced intestinal stem cell migration. Additionally, the migrated cells differentiated into mature epithelial cells. Our data, therefore, suggest that local delivery of high 1,25(OH)2D concentrations is a promising strategy to augment intestinal epithelial repair in IBD patients.

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