ISSN:1062-4821    

出版商:OVID    

年代:1995

数据来源: OVID

ISSN:1062-4821    

出版商:OVID    

年代:1995

数据来源: OVID

ISSN:1062-4821    

出版商:OVID    

年代:1995

数据来源: OVID

ISSN:1062-4821    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The genomic action of calcitriol is mediated through the interaction of the calcitriol receptor (VDR) with the vitamin D response elements of the target genes. Although decreased VDR concentration in renal failure could diminish the biological action of calcitriol, recent study indicates that uremic toxins could modify the VDR DNA-binding domain and inhibit the binding of the VDR to the vitamin D response elements. The latter reaction could also account for end-organ resistance in renal failure. The inhibitory action of uremic toxins has been testedin vivoby a method using gene transcription. It was demonstrated that uremic ultrafiltrate blocks calcitriol-induced chloramphenical acetyltransferase reporter constructs containing a synthetic vitamin D response element in JEG-3 cells. Taken together, the findings indicate that uremia could underlie the calcitriol resistance in renal failure. The modification of the VDR may involve Schiff base formation between lysine residues of the VDR DNA-binding domain and reactive aldehydes accumulated in uremia. This suggestion is on the basis of the finding that the VDR and other steroid receptors form Schiff bases with pyridoxal 5′-phosphate and weaken the binding of these receptors to the DNA cellulose.

ISSN:1062-4821    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Deficiency of 1,25-dihydroxyvitamin D plays an important role in the pathogenesis of secondary hyperparathyroidism. Adequate replacement of this hormone is required to normalize parathyroid gland function and restore bone homeostasis in patents with advanced renal failure. Controversy exists regarding the best method of administering 1,25-dihydroxyvitamin D. Although intial, uncontrolled clinical trials suggested the superiority of intravenous calcitriol treatment, more recent controlled investigations have shown that different routes (oral versus intravenous), frequency (daily versus intermittent) and dosing (physiologic versus pharmacologic) of calcitriol administration are equivalent. Overall, the response to calcitriol treatment depends more on the severity of secondary hyperparathyroidism and the presence of confounding variables, such as hyperphosphatemia and acquired abnormalities of parathyroid cell function, than on the method of calcitriol administration.

ISSN:1062-4821    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The activated form of vitamin D, 1,25-dihydroxyvitamin D3has not only a central role in bone and calcium metabolism, but also has important general effects on cell proliferation and differentiation. Moreover, 1,25-dihydroxyvitamin D3behaves as a paracrine factor in the immune system as it can be produced by monocytes and has potent actions on all the celluar components of the immune defence system. In recent years, this new physiological role has been studied intensively both in terms of research and with the purpose of exploiting this action in a (pre) clinical setting. Indeed, through chemical alterations of the parent molecule, new substances have been created, called vitamin D analogues. Some of these molecules share the immunological effects of the mother compound, but have decreased effects on calcium and bone metabolism. This makes them potentially useful in clinical practice as immunomodulatory drugs. In the present review, we summarize the data on the in-vitro immune effects of 1,25-dihydroxyvitamin D3and its analogues and demonstrate that these compounds have clear in-vivo immune modulating properties in the prevention of spontaneous and allergic autoimmune diseases and in the prevention of graft rejection.

ISSN:1062-4821    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Postmenopausal oestrogen dificiency is associated with the development of osteoporosis. Oestrogen therapy prevents further bone loss but does not have an anabolic effect. The only treatment with an anabolic effect on bone is intermittent parathyroid hormone treatment. Oestrogens have a direct action on the parathyroid to increase parathyroid homone gene expression and parathyroid hormone secretion. They, exert this effect at doses that are too low to cause the uterotrophic effect of oestradiol. Osteoporotic patients have a decreased parathyroid hormone secretory response to changes in serum calcium, supporting the experimental data that oestrogens have a direct effect on the parathyroid. The value of parathyroid hormone treatment is limited by the need for parenteral therapy. The ability of oestrogens to increase parathyroid hormone secretion suggests that the intermittent administration of oestrogen analogues, at doses that exert no effects on breast tissue and the uterus, would be the optimal treatment for osteoporosis.

ISSN:1062-4821    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Plasma ionized calcium is the major determinant of parathyroid hormone (PTH) secretion. The minute-to-minute secretory response of the parathyroids to changes in plasma ionized calcium is described by the calcium/PTH concept, but the detailed mechanism is not yet well understood. The recent cloning of a calcium-sensing receptor in the plasma membrane of the parathyroid cells will probably yield important information concerning the mechanisms by which calcium and other ions control the parathyroid function. It is likely that autocrine and paracrine factors also participate in the regulation of PTH secretion. PTH, chromogranin A, chromogranin A-related peptides and endothelin-1 have been suggested as autocrine factors. More documentation is needed on the impact of these factors in the physiology of the parathyroid gland. In-vivo investigations of the parathyroid function are difficult to interpret because of the complexity of the PTH secretory response to hypo- and hypercalcaemia. Rate dependency and the ability of the parathyroids to sense the direction of changes in calcium make the existing models for investigating the calcium/PTH relationship inappropriate.In vitro,the models are compromised by a rapid drop in the expression of the calcium-sensing receptor of the cultured parathyroid cells. We, therefore, recommend caution when using the calcium/PTH concept in clinical or experimental investigations.

ISSN:1062-4821    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Markers of bone formation determined in serum include alkaline phosphatase, bone-specific alkaline phosphatase, osteocalcin [bone γ-carboxyglutamic acid peptide (BGP)] and procollagen type I carboxyterminal propeptide. Recently, advances have been made in the immunoassary of bone-specific alkaline phosphatase. This is a marker for osteoblastic activity; it is very stable and is not primarily dependent on kidney function because it is degraded in the liver. BGP is not specific for bone formation because it increases in serum during bed rest (which involves increased bone resportion), and it is not stable. Furthermore, the elimination of BGP is dependent on glomerular filtration rate. Procollagen type I carboxyterminal propeptide is not as sensitive as bone-specific alkaline phosphatase because it increases less in women after the menopause. Urinary pyridinoline and deoxypyridinoline determined by high-performance liquid chromatography are regarded as the best methods for measuring bone resorption. These might be replaced by type I collagen crosslinked N-telopeptide or CrossLaps in the future in laboratories not equipped with a high-performance liquid chromatography system. Serum markers of bone resorption are currently under investigation. An immunoassay for the tartrate-resistant acid phosphatase in serum should be a very promising tool for the quantification of bone resorption.

ISSN:1062-4821    

出版商:OVID    

年代:1995

数据来源: OVID