Characteristics of the vitamin D binding protein in different species.
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Biomedical subjects
Publications and source records attributed to R Bouillon.
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An acute rise or decrease in parathyroid hormone (PTH) secretion was found in 30 patients, dialyzed with, respectively, low (5 mg/100 ml) or high (7.5 mg/100 ml) calcium concentration. The percentage changes were, respectively, +35% and -47% when a N-terminal antiserum measuring predominantly the glandular PTH was used. Only relatively small changes, respectively, +3% and -17%, were found using a C-terminal antiserum which detects preferentially smaller PTH fragments. Predialysis serum PTH concentration increases significantly with increasing duration of repetitive hemodialysis treatment using an intermediate (6 and 6.4 mg/100 ml) concentration of calcium in the dialysate. No such increase could be found in two other groups of patients treated with high-calcium (7.5 mg/100 ml) dialysis. Moreover, a significant but temporary decrease in predialysis serum PTH concentration occurred two months after a rise in dialysate calcium concentration from 6 to 7.5 mg/100 ml. Treatment with pharmacologic doses of vitamin D3 in selected patients (renal osterdystrophy or children) always resulted in a definite suppression of serum PTH concentration during 14 treatment periods in ten patients. After cessation of vitamin D3 treatment, serum PTH concentration returned to high levels in four out of five patients. These data fail to confirm the long-term involution of secondary hyperparathyroidism using high-calcium dialysis. Vitamin D treatment, however, results in a much more pronounced decrease in serum PTH concentrations, but sustained therapy is necessary.
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In 20 female patients treated for 2 to 37 years (mean :12) with anticonvulsant drugs, low serum levels of 25-hydroxy-vitamin D (25-OH-D; 6.4 +/- 3.2 ng/ml M +/- SD), relative hypocalcemia (9.2 +/- 0.4 mg/100 ml) and high levels of parathyroid hormone (PTH 277 +/- 165 pg/ml) were found compared to an age-matched control group (respectively 8.6 +/- 3.2 ng/ml, 9.6 +/- 0.3 mg/100 ml and 183 +/- 95 pg/ml) living in the same psychiatric clinic. A significant negative correlation was found between total duration of treatment and either serum 25-OH-D or serum calcium. After treatment with an oral vitamin D3 supplement (2000 IU/day) for 3 weeks, the serum 25-OH-D levels, although increased, remained lower than normal in the epileptic group and neither hypocalcemia nor their secondary hyperparathyroidism were corrected. These data confirm the occurrence of vitamin D deficiency in patients treated with anticonvulsant drugs resulting in hypocalcemia and secondary hyperparathyroidism.
In two patients with chronic renal failure, extensive renal osteodystrophy, and vascular calcifications, treatment with high doses of vitamin D3 and aluminum hydroxide was followed by healing of the osteodystrophy and marked resolution of the vascular calcifications. The importance of adequate serum phosphate control during this treatment is stressed. It is postulated that the presence of pathologic bone that was rendered more avid for mineral by the action of vitamin D contributed to the disposal of calcium and phosphorus derived from the calcified vessels and from a positive external balance.
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The activated form of vitamin D(3), 1alpha,25(OH)(2)D(3), not only plays a central role in bone and calcium metabolism but has also potent antiproliferative and prodifferentiating effects. Moreover, the combined presence of 25(OH)D(3)-1alpha-hydroxylase as well as the vitamin D receptor in several tissues introduced the idea of a paracrine role for 1alpha,25(OH)(2)D(3). By introducing chemical modifications into the flexible parent molecule 1alpha,25(OH)(2)D(3), a whole generation of vitamin D analogs was created. Due to a clear dissociation of the antiproliferative and prodifferentiating effects from calcemic effects, these analogs can be used not only for the treatment of bone disorders but also for non-classical applications.
Parameters of fibrinolysis, including euglobulin fibrinolytic activity, tissue-type plasminogen activator (t-PA) antigen, plasminogen activator inhibitor (PA-inhibitor) activity, and plasmin-alpha 2-antiplasmin complex (PAP) were studied in 62 patients (35 women and 27 men; ages 53 +/- 16 years) with either insulin-dependent (IDDM) or noninsulin-dependent (NIDDM) diabetes mellitus. Compared to a control group of similar age (n = 57), the diabetic patients had a significantly lower mean euglobulin fibrinolytic activity (1.2 +/- 0.7 vs. 1.7 +/- 1.1 ng/ml, p less than 0.01) but significantly higher mean t-PA antigen (15.7 +/- 8.4 vs. 6.6 +/- 2.9 ng/ml, p less than 0.001) and PA-inhibitor activity (2.6 +/- 1.3 vs. 1.5 +/- 0.7 IU/ml, p less than 0.001) levels. Significant univariate correlations were observed between PA-inhibitor activity and age (r = 0.32, p less than 0.05), diastolic blood pressure (r = 0.42, p less than 0.01) and euglobulin fibrinolytic activity (r = -0.40, p less than 0.01). In multivariate analysis, only body mass index (positively) and euglobulin fibrinolytic activity (negatively) remained significantly related to PA-inhibitor activity in the total diabetic population as well as in the NIDDM group. The only parameter in the IDDM group significantly related to PA-inhibitor activity was diastolic blood pressure. These results suggest that PA-inhibitor plays a role in the regulation of fibrinolysis in diabetes patients and that factors like obesity and hypertension may be related to reduced fibrinolysis via PA-inhibitor levels.
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A review of human parathyroid hormone measurements is presented. Although parathyroid hormone was among the first hormones to be measured with the radioimmunoassay technique in 1963, there are even now still many pitfalls in both the technical aspects and clinical applicability of this assay. The main reasons for these difficulties are presented: firstly the complex intra- and extraglandular metabolism of parathyroid hormone results in the heterogeneity of the hormone in serum; secondly, the scarceness of pure human parathyroid hormone delays the development of a complete homologous human assay. The existing assays however have, despite their limitations, enormously contributed to our knowledge of parathyroid hormone secretion in both the normal state and in disease. The clinical applicability of these assays is reviewed and future technical improvements are suggested.