[Calcitonin concentration in the cerebrospinal fluid in patients with medullary thyroid carcinoma--passing of calcitonin through the blood-brain barrier].
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Biomedical subjects
Publications and source records attributed to K Fukuo.
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Calcitonin (CT) was measured by RIA in samples of plasma and cerebrospinal fluid (CSF) obtained simultaneously from 27 normal volunteers and 8 patients with medullary thyroid carcinoma to examine the extent of penetration of CT across the blood-brain barrier. CT concentrations in plasma and CSF were 68.2 +/- 25.1 pg/ml (mean +/- SD; range, less than 25-110) and 38.5 +/- 12.1 pg/ml (range, less than 25-56), respectively, in normal subjects and 5,650 +/- 4,120 pg/ml (range, 980-21,100) and 36.1 +/- 11.1 pg/ml (range, less than 25-45), respectively, in patients with medullary thyroid carcinoma. No significant difference was observed in the mean concentrations of CT in CSF from normal subjects and that from patients with medullary thyroid carcinoma. The concentration of CT in CSF from patients with medullary thyroid carcinoma was only 0.05-2.5% the concentration of CT in plasma. Moreover, there was no significant correlation between the concentrations of CT in plasma and CSF from normal subjects, from patients with medullary thyroid carcinoma, or when normal and patient groups were combined. It is concluded that penetration of CT from blood in CSF is minimal.
A simple technique for measuring urine calcitonin (CT) was established using a sensitive radioimmunoassay (RIA) system for plasma human calcitonin (hCT). To extract urinary CT, urine samples were fractioned by gel chromatography on a column (0.8 x 20 cm) of Bio Gel P-2. Recovery of synthetic (1-32)hCT was 86.1 +/- 6.2% and the intra- and inter-assay coefficients of variation in RIA were 5.9 and 8.2%, respectively. Dilution curves of the urinary CT after gel-filtration were parallel with the standard curve. In 11 patients with medullary carcinoma of the thyroid (MCT), the CT levels of the urine (in ng/mg Cr) were 3.4 to 20.8 times higher than those of the plasma (in ng/ml), and a significant positive correlation (r = 0.93, P less than 0.001) was obtained between the urinary and plasma levels of CT in these 11 patients. In 32 normal subjects, the CT levels of the urine (in pg/mg Cr) were only 0.41 to 5.1 times of those of the plasma (in pg/ml), and a weak positive correlation (r = 0.408, P less than 0.05) was obtained between these two levels. However, urinary CT level in normal subjects apparently reflected a rise in endogenous plasma hCT in response to calcium infusion (4 mg/kg B.W. for 1 min) and that of exogenous plasma CT when synthetic (1-32)hCT (500 micrograms for 1 min) was injected intravenously. Following gel filtration on a Bio Gel P-30 1.5 x 80 cm column, larger molecular forms of CT than (1-32)hCT were found in the urine not only patients with MCT but also of normal subjects after infusion of calcium or synthetic (1-32)hCT. It is concluded that measurement of urine CT is useful not only for diagnosis of MCT but also for evaluating CT metabolism in normal subjects.
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We studied the relation between cholesteryl-ester transfer activity (CETA) and abdominal aortic calcification in elderly subjects. Compared with 10 young healthy subjects (mean +/- S.D. age, 27 +/-2 years) and to 26 elderly subjects without abdominal aortic calcification (79 +/- 7 years), 16 elderly patients with abdominal aortic calcification (82 +/- 6 years) had significantly lower levels of serum CETA. However, there were no differences in the levels of serum lipids and apolipoproteins, including total cholesterol, triglycerides, high density lipoprotein cholesterol, low density lipoprotein cholesterol and apolipoproteins A-I, A-II, B, C-II and E, between the two elderly groups. When the two groups of elderly subjects were considered together, the level of serum CETA did not correlate significantly with any lipids and apolipoproteins. These results provide evidence that CETA may prevent the development of aortic calcification in normolipidemic elderly people.
As elastase is known to affect cell functions in various cell systems, its effects on the functions of control and 12-O-tetradecanoylphorbol 13-acetate (TPA)-treated chondrocytes in vitro were examined. Pretreatment of chondrocytes with TPA (10(-8) M) for 48 h significantly enhanced DNA synthesis, inhibited glycosaminoglycan (GAG) synthesis and inhibited the increase in ornithine decarboxylase (ODC) activity in response to parathyroid hormone (PTH) relative to values in control cultures. Addition of elastase (1, 10 and 50 ng/ml) for 24 h partially inhibited the de-differentiated phenotypes induced by TPA such as the decreased synthesis of GAG and decreased response of ODC activity to PTH without affecting the DNA synthesis. Moreover, elastase significantly increased both the basal level of cyclic AMP and that on PTH treatment of TPA-pretreated cells. These results suggested that elastase partially restored the differentiated phenotypes of de-differentiated chondrocytes probably through its effect in increasing the level of intracellular cyclic AMP.
The purpose of this study was to evaluate the long-term efficacy and tolerability of pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, in elderly patients with hypercholesterolemia. Pravastatin was administered for 12 months at a mean final dose of 9.9 mg/d to 208 elderly patients (mean [+/- SD] age, 70 +/- 7 years) with levels of total serum cholesterol greater than 5.69 mmol/L. The mean total cholesterol level was significantly decreased from 6.85 +/- 0.80 mmol/L to 5.59 +/- 0.70 mmol/L after 3 months, and this decrease was maintained thereafter. A similar change was observed in the mean serum level of low-density lipoprotein cholesterol. Although the mean serum level of high-density lipoprotein cholesterol in all the patients did not change significantly, the level in 34 patients with a value lower than 1.03 mmol/L was significantly increased after 3 months and thereafter. The serum level of triglycerides in all patients was significantly decreased after 3 months and thereafter and the decrease was more marked in 101 patients with levels greater than 1.73 mmol/L. In 168 elderly patients receiving 10 mg/d of pravastatin, there were significant negative correlations between the percent decrease in total cholesterol and both baseline total serum cholesterol level (r = -.354, P < 0.001) and age (r = -.208, P = 0.007). No serious side effects were observed. These results indicate that long-term administration of pravastatin is beneficial in the treatment of hypercholesterolemia in elderly patients.