Parathyroid hormone radioimmunoassay (RIA), specific for mid-region of the PTH molecule, has been proven to be extremely useful for the differential diagnosis of abnormal calcium metabolism. Recently, we developed a highly sensitive RIA for PTH, consisting of PTH antiserum (CH9), 125I labelled Tyr42 hPTH (43-68) and synthetic hPTH (1-84) as standard. This RIA cross-reacted with mid-region and carboxyl terminals of PTH. The within-assay and between-assay coefficients of variation were less than 4.6% and less than 8.6%, respectively. The limit of detection was 50pg/ml. The levels of serum calcium, serum phosphate, serum creatinine, Tmpo4/GFR and creatinine clearance (Ccr) in normal healthy volunteers aged 20 to 50 years remained almost constant and showed 9.24 +/- 0.34mg/dl (mean +/- SD, n = 242), 3.34 +/- 0.38mg/dl (n = 242), 0.870 +/- 0.121mg/dl (n = 242), 3.20 +/- 0.54mg/dl GF (n = 189) and 103 +/- 17ml/min (n = 137), respectively. All healthy volunteers (n = 326) had measurements of PTH in the blood. From 20 to 50 years, normal PTH mean was 374 +/- 97pg/ml (+/- SD, n = 237) and ranged from 180-568pg/ml, and from 60 to 80 years it was 471 +/- 133pg/ml (n = 34) and ranged from 205-737pg/ml. Since we found that PTH was markedly elevated above normal when Ccr was below 40ml/min, and PTH was very significantly correlated with the reciprocal of Ccr (r = 0.8996, P less than 0.001) using a multivariate analysis, all of the patients whose Ccr was higher than 40ml/min were selected and examined in the following studies. Serum PTH values completely separated patients with surgically proven primary hyperparathyroidism (1 degree HPT) from malignant associated hypercalcemia (MAH), and patients with idiopathic hypoparathyroidism (IHP) from pseudohypoparathyroidism (PHP), both of which were diagnosed by Ellsworth-Howard test. PTH values in all of the patients with 1 degree HPT (n = 23) were above normal, but those with MAH (n = 6) were below the normal or lower normal range. PTH values in patients with PHP (n = 7) showed above normal, while those with IHP (n = 5) were below the normal range. PTH was normalized in post operative status in all patients after parathyroidectomy (n = 6). These results indicate that this PTH RIA is extremely useful for the differential diagnosis in diseases with calcium abnormalities.
In vivo antiherpesvirus effects of 1-,-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (brovavir) were tested in two mouse model infections with herpes simplex virus type 1 (HSV-1) strains which showed different degrees of virulence in mice. Successful efficacies of oral and intraperitoneal (i.p.) treatments with brovavir were demonstrated in both intracerebral and i.p. infections with the HSV-1 WT-51 strain of moderate virulence. However, only weak or modest effects of brovavir were observed against the two model infections with a highly virulent strain, HSV-1 VR-3. Brovavir was not effective in reducing mortality of mice infected i.p. with HSV-1 KOS, which exhibited the highest virulence in mice among HSV-1 strains used when inoculated i.p. However, the drug had a significant effect on intracerebral infection with the KOS strain. Efficacies of oral treatment with brovavir were almost equal to those of i.p. administration in the model infections. After intracerebral inoculation, the VR-3 strain grew in brains of mice at a higher rate than the WT-51 strain. By oral treatment with 50 mg of brovavir per kg twice daily, replication of the WT-51 strain in the brains was markedly suppressed and was eliminated after transient elevation of the titer. Growth of the VR-3 strain in the brains was simply delayed by the drug treatment. Thus, the antiviral efficacy of brovavir in mice was affected by the degree of virulence of the challenge virus strain used for infection.1-,-D-Arabinofuranosyl-E-5-(2-bromovinyl)uraciI (brovavir) is one of the most promising antiherpesviral agents under investigation (7). Previously, we showed in vivo antiviral activity of brovavir in mice infected with herpes simplex virus type 1 (HSV-1) (6). The in vivo effect was almost equivalent to that of E-5-(2-bromovinyl)-2'-deoxyuridine. However, therapeutic efficacies of the antiherpesviral bromovinyl nucleosides we observed were not as marked as those shown by Reefschlager et al.
SUMMARY: 22‐oxa‐calcitriol (OCT), a vitamin D analogue, suppresses parathyroid hormone (PTH) secretion and has less calcaemic activity than 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3] in vivo. In this study, we evaluated the effect of OCT on PTH secretion in vitro using human hyperplastic parathyroid tissue obtained during surgery for advanced renal hyperparathyroidism and normal bovine parathyroid glands to compare the effects of 1,25(OH)2D3. 22‐oxa‐calcitriol suppressed PTH secretion by nodular hyperplastic parathyroid tissue and normal bovine tissue in a dose dependent manner, the same as 1,25(OH)2D3. We showed the additive effect of extracellular calcium level on suppression of PTH secretion by OCT and 1,25(OH)2D3. These results suggest that OCT suppresses PTH secretion, the same as 1,25(OH)2D3 not only in normal parathyroid cells but also on hyperplastic parathyroid cells.
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