摘要:

Acidosis had long been thought to influence the bone mineral; however, there was little direct evidence to support this impression. When neonatal mouse calvariae are cultured for 3 hours in medium with a reduced bicarbonate concentration, a model of acute metabolic acidosis, there is net calcium efflux from bone in addition to a net influx of protons into bone lessening the magnitude of the acidosis. The protons appear to exchange for sodium and potassium on the bone surface. In these acute experiments, the calcium efflux appears to be due to mobilization of carbonated apatite through an alteration in the physicochemical driving forces for bone accretion and dissolution. In more chronic cultures (greater than 48 hours) metabolic acidosis induces calcium efflux by stimulating osteoclastic bone resorption and inhibiting osteoblastic bone formation. When calvariae are cultured acutely in medium with an elevated partial pressure of carbon dioxide, a model of respiratory acidosis, there is also calcium efflux, but at the same decrement in pH the magnitude is far less than that observed during metabolic acidosis. There does not appear to be any measurable influx of protons into bone, and during chronic cultures there is no measurable calcium efflux. Thus, acidosis influences the bone mineral; however, for the same decrement in pH there is a marked difference in the response of bone to models of metabolic and respiratory acidosis.

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Over the past year, there have been major advances in the descriptive analysis of the extracellular matrix in the kidney. Several aspects of the interaction of matrix molecules with renal and, in particular with glomerular cells via specific integrin receptors, have also been studied. Most results on cell-matrix interactions have been obtained by in vitro investigations of glomerular mesangial cells in two-dimensional culture. The regulation of matrix formation and degradation has been shown to involve the concerted action of several soluble factors, notably transforming growth factor-(3, as well as the effects of nonsoluble matrix components themselves, such as collagens and proteoglycans. The mediation of such complex interactions between cells, matrix, and cytokines is facilitated by the tightly regulated expression of cell surface receptors, eg, cytokine receptors and integrins of the (31 series, which bind specific matrix molecules. New results have yielded more insight into the regulation not only of matrix formation but also of the specific interactions between cells and matrix and of the modulation of cytokine activity by matrix molecules. Using experimental rat models and transgenic mouse models of kidney disease, the first in vivo findings using immunohistochemistry and mRNA analysis have confirmed that major changes occur in the expression of matrix molecules, integrins, and cytokines in the process of glomerular inflammation. With the advent of specific modulators of the bioactivity of ligands and receptors, it is hoped that more information will be forthcoming on the functional relevance of various components of the cell-matrix-cytokine crosstalk in the normal and injured kidney.

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Recent advances in our understanding of the regulation of parathyroid hormone secretion in vivo and in vitro are reviewed. The use of assays specific for immunoreactive intact parathyroid hormone has greatly improved our capacity to study parathyroid hormone dynamics in vivo. Such studies have emphasized the steep, inverse sigmoidal relationship between circulating intact parathyroid hormone and serum ionized Ca2+concentrations, which can be modulated in a reciprocal fashion by 1,25 dihydroxyvitamin D. The use of the intact assay has also revealed additional complexities in the control of parathyroid hormone dynamics in vivo, including circadian and pulsatile patterns in parathyroid hormone as well as hysteresis and rate dependence in the relationship between intact parathyroid hormone levels and Ca2+. Studies in vitro have emphasized the role of a putative, extracellular Ca2+receptor in regulating parathyroid function that is coupled by one or more G proteins to intracellular second messengers and parathyroid hormone secretion. Finally, the regulation of parathyroid hormone gene expression by extracellular Ca2+and 1,25 dihydroxyvitamin D has been clarified at a molecular level by the description of specific motifs in the upstream region of the parathyroid hormone gene that mediate binding of specific inhibitory nuclear factors.

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

It has become increasingly evident that clear-cut disturbances of bone and mineral metabolism develop early in renal failure. Among these disturbances, hyperparathyroidism is well documented and is usually asymptomatic at that early stage. It is now accepted that early therapy using phosphate restriction, through diet and calcium-containing phosphate binders, and la-hydroxylated vitamin D analogues is an effective means of preventing or even reversing hyperparathyroidism in early renal failure. The response to these therapies is both functional (reduced parathyroid hormone secretion) and structural (prevention of parathyroid gland hyperplasia). Parathyroid hyperplasia is largely irreversible; prevention is therefore important and can be achieved initially by a combination of diet and calcium-containing phosphate binders, with later addition of calcitriol or alfacalcidol if parathyroid hormone control cannot be achieved or sustained.

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Recent progress in cellular and molecular biology has had a great impact on our understanding of parathyroid hormone-vitamin D physiology and of the pathogenesis of secondary hyperparathyroidism in chronic renal failure and made possible the development of new therapeutic approaches for management of bone disease in dialysis patients. Management of parathyroid hyperplasia by calcitriol pulse therapy is one example. Suppression of parathyroid hyperfunction by other vitamin D analogues was also proposed, and some of these analogues are now under clinical trial. Further, percutaneous ethanol injection into hyperplastic parathyroid glands under ultrasonographic guidance has become the choice practical procedure under certain clinical settings and can be an effective alternate to surgical parathyroidectomy. In this article, we review selected and pertinent progress in the pathogenesis and management of secondary hyperparathyroidism and parathyroid hyperplasia, major causes of morbidity in chronic dialysis patients, emphasizing the important contributions made by laboratory research and critical clinical observations.

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Phosphate retention plays a major role in the pathogenesis of hyperparathyroidism at all stages of renal insufficiency. Dietary phosphate restriction is mandatory only for adults and is not advised for children because of the recommended diet allowance. Dietary restriction is usually not sufficient, and phosphate binders are almost always necessary when the glomerular filtration rate falls below 40 mL/min. Because long-term administration of aluminum phosphate binders is associated with risk of aluminum intoxication despite the use of so-called “safe doses,” alternative phosphate binders should be used. Magnesium hydroxide and carbonate can be used only for dialysis patients because a low dialysate magnesium concentration is necessary to prevent the hazards of hypermagnesemia. Therefore, the major alternative is the use of alkaline salts of calcium. The most recently proposed salt, acetate, has a higher phosphate-binding capacity than carbonate but exposes patients to the same incidence of hypercalcemia despite the use of half the dose of elemental calcium. These salts should be taken with meals in order to complex more dietary phosphate and decrease calcium absorption and therefore the risk of hypercalcemia. Oral calcium alone, without 1aOH-vitamin D3derivatives, can prevent hyperphosphatemia and hyperparathyroidism in most uremic patients before dialysis and in about half of the patients dialyzed with a dialysate calcium of 1.5 to 1.65 mmol/L. 1αOH-vitamin D3derivatives, which increase intestinal absorption of phosphate, should be used only when hyperphosphatemia has been prevented by oral calcium and diet and when plasma parathyroid hormone levels increase above three times the upper limit of normal. To decrease hypercalcemic risk, patients should be given 1αOH-vitamin D3derivatives, preferably at night, as an intermittent bolus (intravenous or oral). In dialysis patients, the dialysate concentration of calcium may have to be further decreased in order to prevent hypercalcemia when high doses of oral calcium are necessary to control hyperphosphatemia.

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Secondary hyperparathyroidism remains the predominant histologic lesion in pediatric patients undergoing regular dialysis, but recent evidence indicates that the regulation of parathyroid hormone secretion by calcium does not differ substantially between patients with osteitis fibrosa and subjects with normal renal function. Growth retardation and skeletal deformities are major findings in pediatric patients with renal osteodystrophy, and alterations in vitamin D metabolism and insulin-like growth factor almost certainly contribute to these findings. Avoidance of aluminum-containing medications and the introduction of intermittent calcitriol therapy provide newer approaches to the effective management of secondary hyperparathyroidism in pediatric patients with end-stage renal disease.

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID