Search PubMedSearch

PubMed · 1576767

Nephrocalcinosis.

Abstract

The pathogenesis of NC in VLBW infants appears to be multifactorial. The vulnerability of extreme immaturity and the underdevelopment of renal function may be the most important variables. In some ways, we view this problem as similar to that of retinopathy of prematurity. (Clearly the exposure of the retina to high partial pressures of oxygen contributes to the development of retinopathy of prematurity but other variables--some known, such as an immature retina, and others not yet defined--must be present.) Hypercalciuria is common in the VLBW infant, yet not all develop NC. Decreased glomerular filtration rate, low citrate excretion, and frequently an alkaline urine are in part due to the immaturity of renal function of these infants. The need for prolonged hyperalimentation resulting in increased oxalate excretion and the development of BPD frequently requiring diuretics that may cause phosphaturia and magnesium depletion and that may increase calcium excretion are more common in the smallest and sickest of premature infants. Even transient insults to the kidneys, such as hypoxia or hypotension or the use of nephrotoxic drugs that provoke tubular injury and cell death with the probability of crystal formation and growth by way of heterogeneous nucleation, are likely to occur more frequently in this vulnerable population.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

N D Adams, J C Rowe. 1992. Nephrocalcinosis.. https://pubmed.ncbi.nlm.nih.gov/1576767/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Effects of postmenopausal hormone replacement therapy with and without vitamin D3 on circulating levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D.

The effects of postmenopausal hormone replacement therapy (HRT) and vitamin D3 on vitamin D metabolites (25OHD and 1,25(OH)2D) were studied in a population-based prospective 1-year study. The serum concentrations of intact parathyroid hormone (PTH), calcium, and phosphate were also studied. A total of 72 women were randomized into four treatment groups: HRT group (sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate), Vit D3 group (vitamin D3 300 IU/day + calcium lactate 500 mg/day), HRT + Vit D3 group (both above) and placebo group (calcium lactate 500 mg/day). Serum samples were taken in March-April, when vitamin D formation from sunlight in Finland is minimal after the dark winter. Serum concentrations of 25OHD increased in the Vit D3 group (33.5%, P < 0. 001) and in the HRT + Vit D3 group (38.2%, P < 0.001) but had not changed significantly in the HRT and placebo groups at the 1-year follow-up examination. Serum concentrations of calcitriol (1, 25(OH)2D) increased, however, only in the HRT group (23.7%, P < 0. 05), and remained unchanged in other groups. Serum concentrations of PTH decreased by 23.2% (P < 0.05) in the placebo group, but did not change significantly in the other three groups. The concentrations of serum calcium increased in the nonhormone groups (P < 0.001), whereas serum phosphate concentrations decreased in the hormone groups (P < 0.05 and 0.001). Our results confirm the positive effect of 1 year of HRT on serum calcitriol. Vitamin D3 supplementation increased 25OHD concentrations, but did not affect calcitriol concentrations even though the initial levels were low. Interestingly, the combination of HRT and vitamin D3 did not increase serum calcitriol concentrations as much as HRT alone.

Calcium

An inhibitor of ornithine decarboxylase antagonizes superoxide generation by primed human polymorphonuclear leukocytes.

Tumor necrosis factor-alpha (TNF-alpha) induces a rapid increase in polymorphonuclear leukocyte (PMN) polyamine content which appears to be required for optimal priming of the respiratory burst. The objective of the present study was to determine whether inhibition of polyamine biosynthesis modifies PMN responses to lipopolysaccharide (LPS), granulocyte-macrophage colony-stimulating factor (GM-CSF), or granulocyte colony-stimulating factor (G-CSF). Treatment with alpha-difluoromethylornithine (DFMO), a selective inhibitor of the rate-limiting biosynthetic enzyme ornithine decarboxylase, produced dose-dependent inhibition of the respiratory burst in PMNs that were primed by these agents and subsequently activated by formyl-Met-Leu-Phe (fMLP). However, DFMO did not significantly inhibit fMLP-stimulated superoxide generation or alter the induction of PMN adhesion and interleukin-1 beta (IL-1 beta) mRNA expression by LPS or GM-CSF. Antagonism of priming by DFMO correlated with a dose-dependent attenuation of fMLP-induced intracellular Ca2+ mobilization (r > or = 0.96). Since Ca2+ plays an important role in modulating the respiratory burst in primed PMNs, this could, in part, account for the selective effects of DFMO.

Calcium

Calcium-dependent signaling pathways in T cells. Potential role of calpain, protein tyrosine phosphatase 1b, and p130Cas in integrin-mediated signaling events.

Engagement of beta1 integrin receptors initiates an increase in intracellular calcium concentrations in T cells, potentially affecting calcium-sensitive signaling pathways. The calcium-activated cysteine protease, calpain, regulates a variety of cell functions by calcium-dependent limited proteolysis. To investigate the function of calpain in T cells, we sought to determine the role of this protease in calcium-dependent signaling events. Subsequent to elevations in intracellular calcium concentrations induced by ionomycin or adherence to fibronectin, calpain activity translocated to the cytoskeletal/membrane fraction of T cells. In addition, stimulation of T cells with these agents initiated the proteolytic cleavage of protein tyrosine phosphatase 1B by calpain. Enzymatic cleavage of protein tyrosine phosphatase 1B occurs near the endoplasmic reticulum-targeting sequence and results in the generation of an enzymatically active form of the phosphatase. Furthermore, we show that both the native and the cleaved forms of protein tyrosine phosphatase 1B interact with p130(Cas) in T cells. This interaction may serve to relocate protein tyrosine phosphatase 1B to sites of focal contact resulting in potential interactions with substrates previously inaccessible to the endoplasmic reticulum-associated phosphatase. Thus, we describe a novel calcium-dependent signaling pathway in T cells that may mediate signals generated by beta1 integrin adherence to the extracellular matrix.

Calcium