Plasma levels of calcium and of parathyroid hormone (PTH) were comparable in the mothers at delivery and in nonpregnant controls; magnesium was decreased (P < 0.001) in maternal blood; and phosphate (P < 0.001), 1,25-dihydroxyvitamin D (1,25(OH)2D) (P < 0.001), and calcitonin (CT) (P < 0.01) were raised. Cord levels of calcium (P < 0.01), magnesium (P < 0.05), and CT (P < 0.01) were higher, and PTH (P < 0.01) was lower than in the maternal blood. Levels of 25(OH)D, 1,25(OH)2D, and 24,25(OH)2D lower in fetal than in maternal blood (P < 0.01) and significant linear correlations between the vitamin D metabolites examined in mothers and neonates (P < 0.001) are consistent with a diffusion barrier across the placenta and/or different affinities of binding proteins. Plasma levels of 25(OH)D and 24,25(OH)2D were significantly related (P < 0.01), suggesting precursor product type, relationships. Levels of 1,25(OH)2D higher in arterial than in venous umbilical blood (P = 0.06, sign test; P < 0.005, paired t test) suggest that the fetus participates in the synthesis of 1,25(OH)2D. Maternal PTH was significantly related to the arteriovenous difference of 1,25(OH)2D levels (P < 0.01) in cord blood, and it possibly enhances the synthesis of 1,25(OH)2D during the final stage of fetal development.

A B S T R A C T Modifications ofthe plasma level of im

Effects of intravenously administered human calcitonin gene-related peptides (hCGRP) I and II on regional blood flow and gastric acid secretion were examined in barbiturate-anesthetized rabbits. Blood flow was measured by injection of radioactively labeled microspheres at 0, 10, 20, 30, and 60 min. hCGRP I and II and vehicle were infused intravenously in five rabbits in rising doses of 0.01 (0-10th min), 0.03 (11-20th min), and 0.1 microgram.kg-1.min-1 (21-30th min). hCGRP I and II increased gastric blood flow dose dependently. Moreover, hCGRP I raised regional conductance (inverse of vascular resistance) in the stomach, duodenum, heart, brain, and skeletal muscle. As a result of the increased total peripheral conductance the mean arterial pressure was reduced, but the cardiac output remained unchanged. hCGRP II increased blood flow and conductance selectively in the stomach and the pancreas. The total peripheral conductance and mean arterial pressure remained unchanged. Apparently, hCGRP II exerts a more localized effect on the stomach than hCGRP I. hCGRP I and II did not affect basal gastric acid secretion. Pentagastrin-stimulated acid secretion was increased by 28% with hCGRP I (0.025 micrograms.kg-1.min-1) and decreased by 27% with hCGRP II (0.025 micrograms.kg-1.min-1). The inverse effect of hCGRP I and II and the parallel stimulation of blood flow brought about with hCGRP I and II indicate a different mode of action of the peptides on gastric blood flow and gastric acid secretion.

The increase of plasma 1,25-dihydroxyvitamin D (1,25(OH)2D) in response to Ca restriction has been suggested to be essentially mediated by parathyroid hormone (PTH). In this study, we have assessed the influence of variations in calcium intake on plasma 1,25(OH)2D in pair-fed sham-operated (sham) and in hypocalcemic hypoparathyroid rats after thyroparathyroidectomy (TPTX). In sham rats, plasma 1,25(OH)2D increased from 189 +/- 16 to 486 +/- 41 pM when dietary calcium was inreased from 1.2% Ca to 0.2% Ca. This increase was associated with an increase in plasma PTH level. In TPTX rats, plasma 1,25(OH)2D increased from 112 +/- 9 to 332 +/- 36 pM when dietary calcium was decreased. In this case, the increase was not associated with a rise in plasma PTH level nor with an increase in urinary cyclic AMP. When TPTX rats were infused chronically with PTH (60 U/day), plasma 1,25(OH)2D was 62 +/- 9 pM when the 1.2% Ca diet was given and 281 +/- 45 pM with the 0.2% Ca diet. These reults confirm that the thyroparathyroid glands influence plasma 1,25(OH)2D but they also provide evidence for a PTH-independent response of plasma 1,25(OH)2D to Ca restriction.

Nine patients with Paget's disease were treated with 200 U (15 nmol) synthetic salmon calcitonin (sCT) intranasally (in)/day for 12 months. Five of them had received im or in sCT therapy for 1-4 yr up to 0.5-5 yr before this study. Low titer antibodies to sCT were detected in the serum of three of these five patients, but not in the four patients who had not received prior sCT therapy. After 2 months of in sCT administration, four of the former group, but none of the latter group, had antibodies to sCT. After 12 months of treatment, antibodies to sCT were found in all patients who had received sCT earlier and in three of the four patients who had not. The half-maximal inhibition of [125I]sCT binding ranged from 44-284 pmol/L sCT. In a cultured human breast cancer cell line (T47D) cAMP production was stimulated by sCT (EC50, 70 pmol/L). cAMP production stimulated by sCT (5 pmol/L) was reduced to 6-20% of the control value in the presence of serum from patients which inhibited [125I]sCT binding by more than 50% in a dilution of 1:50 or greater. In patients with lower titer antibodies cAMP production was not inhibited. Serum alkaline phosphatase activity was transiently lowered to 79 +/- 6% (+/- SE) of basal levels in the patients who had earlier received sCT (P greater than 0.1), while sustained reduction to between 66 +/- 2% and 84 +/- 6% of basal levels (P less than 0.05) occurred in the patients who had not been treated with sCT previously. In conclusion, reexposure to sCT of five patients with Paget's disease caused secondary antibody responses and clinical resistance.