Umbilical cord fluoride serum levels may not reflect fetal fluoride status.

OBJECTIVE: To evaluate the reliability of fluoride levels in the umbilical cord as reflecting neonate fluoride status. DESIGN: Prospective study of fluoride levels of pregnant women at term and their neonates. SETTING: Delivery room and maternity unite of Hadassah Hospital Mount Scopus. PATIENTS: Fluoride serum levels were determined in the sera of 20 women with normal pregnancies at term, during delivery, in the corresponding mixed cord sera and neonatal sera at 24 hours after delivery. RESULTS: The mean maternal fluoride serum level was 0.0303 microgram/ml (SD 9.015), mean cord fluoride serum level 0.0183 microgram/ml (SD 0.012), and mean neonatal fluoride serum 0.0380 microgram/ml (SD 0.016). CONCLUSION: The significantly (p < 0.001) low mixed cord serum levels of fluoride as compared with neonatal and maternal serum levels may be explained by placental sequestration of fluoride. It is suggested that cord serum fluoride levels to not reflect fetal fluoride status.

Vitamin D in Paget's disease of bone.

The role of vitamin D metabolism in Paget's disease of bone has not been well defined. Serum levels of the main, circulating vitamin D metabolites were measured in 23 patients with Paget's disease. Values of 25(OH)D3 and 24,25(OH)2D3 were within the normal range in most (more than 90%) of the subjects. 1,25(OH)2D3 was increased in 11 (48%) patients. Markedly elevated levels (93-298 pg/ml) were found in five patients. In a subgroup of patients with high 1,25(OH)2D3, the mean serum alkaline phosphatase activity was insignificantly higher, while serum calcium, phosphorous, and kidney function were the same as in a subgroup with normal 1,25(OH)2D3. 1,25(OH)2D3 levels were not affected by treatment with either calcitonin or etidronate disodium. Serum 1,25(OH)2D3 levels may be increased in a subset of patients with Paget's disease of bone.

Studies of normal and prematurely ruptured human amniotic membranes: low calcium and magnesium in prematurely ruptured membranes.

Prematurely ruptured amniotic membranes at term, and membranes from normal term pregnancies were studied. The membranes were analyzed for neutral sugars, hexosamines, sialic acid, uronic acid, DNA, RNA, cholesterol, phospholipids, calcium, magnesium, sodium and potassium. The only significant difference found between the normal and the prematurely ruptured membranes was a significantly lower concentration of calcium and magnesium in the latter group. (Calcium 0.32 +/- 0.07, vs. 0.24 +/- 0.07, p less than 0.05; Magnesium 0.30 +/- 0.19 vs. 0.15 +/- 0.04, p less than 0.05; in mg/100 mg protein). The possible metabolic effects of low calcium and magnesium may be of relevance to the pathogenesis of premature rupture of the amniotic membranes.

Calcium and hypoxic injury in the renal medulla of the perfused rat kidney.

To study the interaction between calcium and the medullary hypoxic lesions found in isolated perfused rat kidneys, the acute effects of high extracellular calcium upon renal function and morphology were evaluated in kidneys perfused with cell-free medium at a total calcium concentration of 8 to 9 mg/dl (controls), 13 to 14 and 19 to 20 mg/dl (high Ca++). High Ca++ increased hypoxic damage to medullary thick ascending limbs from 58.2 +/- 4.0% of tubules in controls to 80.2 +/- 4.0% (P less than 0.005) in the deepest area of the outer medulla. Morphological changes in the cortex were minimal. The increase in damage to medullary thick limbs induced by high Ca++ was prevented by the calcium channel blocker verapamil. Addition of the calcium ionophore A23187 to controls reproduced the effects of high Ca++ with an increase in the proportion of damaged thick limbs to 92.1 +/- 4.1% (P less than 0.001 vs. controls). Addition of equimolar amounts of magnesium chloride did not reproduce the effect of high calcium perfusions. When transport activity was reduced with ouabain, high calcium perfusions were no longer associated with structural damage. In kidneys perfused with a medium enriched with amino acids, the proportion of tubules with severe, irreversible damage increased from 12 +/- 3 to 43 +/- 10% (P less than 0.01) after high calcium perfusion, and to 75 +/- 12% (P less than 0.001) after perfusion with the calcium ionophore. High extracellular and intracellular calcium appear to act in concert with hypoxia to increase the susceptibility of the renal medulla to injury by mechanisms potentially operative in hypercalcemic and ischemic nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Medical treatment of primary hyperparathyroidism: effects on parathormone and vitamin D metabolites.

A 63-year-old woman was treated medically for primary hyperparathyroidism because of a recent myocardial infarction. She received propranolol alone or combined with either cimetidine, calcitonin or disodium etidronate (EHDP). The treatment did not affect the elevated serum parathormone or urinary cyclic AMP levels, nor did it correct the elevated serum 1,25(OH)2D and the decreased serum 24,25(OH)2D levels in this patient. Propranolol combined with either cimetidine or with EHDP (600 mg/day) caused a mild decrease in the serum calcium level which, however, remained within the hypercalcemic range. Following surgery all parameters returned to normal. We conclude that the above medical regimens were incapable of correcting the hyperparathyroid condition in this patient.

Vitamin D3 metabolites in amniotic fluid in relation with maternal and fetal sera in term pregnancies.

The concentration of 25-hydroxyvitamin D3 (25(OH)D3), 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) were determined in amniotic fluid, fetal cord serum and maternal serum in 26 cases of elective cesarean sections at term. All the women had a normal pregnancy and did not get any vitamin D fortified preparations. The samples were collected during December 1982-April 1983, at 37-40 weeks of pregnancy. The respective levels (+/- S.D.) of 25(OH)D3, 24,25(OH)2D3 and 1,25(OH)2D3 in maternal serum were: 18.03 +/- 10.8 ng/ml, 1.473 +/- 1.562 ng/ml and 36 +/- 21.5 pg/ml; in fetal cord serum: 13.15 +/- 8.3 ng/ml, 0.9 +/- 0.76 ng/ml and 29.2 +/- 18.55 pg/ml and in amniotic fluid: 0.732 +/- 0.508 ng/ml, 0.212 +/- 0.104 ng/ml and 14.3 +/- 10.0 pg/ml. The levels of the three metabolites in maternal and fetal cord serum were not statistically different. There was a statistically significant correlation between maternal and fetal serum levels of 25(OH)D3 and 24,25(OH)2D3 (r = 0.79, p less than 0.01 and r = 0.743, p less than 0.01 respectively). No significant correlation was found in 1,25(OH)2D3 levels between maternal and fetal cord sera. This lack of correlation may well be in agreement with the recent findings of Kouppala, et al. who demonstrated that the fetus contributes to its own pool of 1,25(OH)2D3. A significant difference was found between maternal serum and amniotic fluid levels of the three metabolites. A statistically significant difference was also found between fetal serum levels of 25(OH)D3 and 24,25(OH)2D3 and amniotic fluid levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Fluoride concentration in amniotic fluid and fetal cord and maternal plasma.

Fluoride concentrations were determined in plasma of 50 pregnant women, 44 samples of amniotic fluid and fetal cord blood of 29 fetuses at various stages of normal pregnancies, from an area with a relatively low water fluoride (less than 0.5 ppm) content. The mean concentrations of fluoride from maternal plasma, cord plasma and amniotic fluid (+/- S.D.) were 0.033 +/- 0.003, 0.028 +/- 0.005 and 0.017 +/- 0.003 ppm, respectively. Maternal and fetal plasma fluoride concentrations did not differ significantly. In the older age group fetal cord plasma fluoride concentration was significantly lower than maternal plasma levels (0.012 +/- 0.08 ppm vs. 0.023 +/- 0.001, respectively; p less than 0.05). Amniotic fluid fluoride levels were significantly higher at term than in midtrimester pregnancy, 0.017 +/- 0.0018 vs. 0.010 +/- 0.009 ppm (P less than 0.05), respectively. This higher concentration may imply higher fetal urinary excretion of fluoride at term due to the lower sequestration of fluoride as the process of bone calcification is more complete.

Increased placental concentrations of 25-hydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 in pregnant rats treated with human chorionic gonadotropin.

Pregnant rats were injected intrajugularly with 2500 i.u. human chorionic gonadotropin (HCG) toward the end of gestation (days 18-19) and 7.0 pmoles of tritiated 25-hydroxyvitamin D3 [( 3H]25(OH)D3) the following day. They were sacrificed ten to 24 hours later. [3H]25(OH)D3 and the in vivo produced [3H]24,25-dihydroxyvitamin D3 [( 3H]24,25(OH)2D3) in lipid extracts from maternal serum, kidneys, placenta and fetal tissues were separated by Sephadex LH-20 chromatography, and high performance liquid chromatography (HPLC). HCG treatment of pregnant rats increased significantly 25(OH)D3 levels in the placenta and kidneys and 24,25(OH)2D3 level in the placenta. Fetal metabolites levels were unaffected by HCG treatment. Serum and kidney levels of 25(OH)D3 and 24,25(OH)2D3 in pregnant rats were significantly lower than in non-pregnant rats. Serum and kidney levels of both metabolites in non-pregnant female rats treated with HCG did not differ from the untreated controls. HCG may, therefore, be involved in regulation of fetoplacental vitamin D metabolism.

Low serum 24,25 dihydroxyvitamin D in Duchenne muscular dystrophy.

Levels of serum 24,25(OH)2D3 (0.69 +/- 0.17 ng/ml) were lower in DMD patients than in age-matched controls (2.13 +/- 0.15 ng/ml). Circulating levels of 1,25(OH)2D3 and 25(OH)D3 were within the accepted normal range. Bearing in mind the proposed pathophysiologic role of calcium in DMD and the influence of vitamin D metabolites on muscle ATP and protein synthesis, as well as on sarcoplasmic reticulum calcium transport and muscle mitochondrial calcium content, the above findings of low or deficient 24,25(OH)2D3 levels in DMD could be meaningful from the etiologic and therapeutic points of view.

Maternal-fetal transfer of aminophylline.

Ten women with normal pregnancies who underwent an elective cesarean section received orally 200 mg of aminophylline every 6 hours for 24 - 36 hours prior to surgery. The levels of aminophylline and caffeine were measured in maternal and cord sera and in amniotic fluids. The mean level of aminophylline (+/- SD) in maternal serum was 10.4 +/- 1.74 micrograms/ml, and in cord serum 11.2 +/- 1.25 micrograms/ml. The mean aminophylline level in amniotic fluids was 8.2 +/- 1.42 micrograms/ml. The serum aminophylline levels were within the therapeutic level range. Caffeine levels in those specimens ranged between traces to 6 micrograms/ml which correspond to the normal dietary range.

Vitamin D3 metabolites in rat epididymis: high 24,25-dihydroxy vitamin D3 levels in the cauda region.

Normal male rats received six subcutaneous injections of 8.0 pmoles of tritiated 25-hydroxy vitamin D3 ([3H]25(OH)D3) or one intrajugular injection of 8.0 pmoles of high specific radioactivity [3H]-25(OH)D3. Lipid extracts of several tissues including the reproductive organs were subjected to sephadex LH-20 chromatography to determine the tissue distribution of the injected material and of the in vivo produced dihydroxylated cholecalciferol metabolites. The nature of the putative 25(OH)D3 and the 24,25-dihydroxy vitamin D3 (24,25(OH)2D3) from epididymis tissue was confirmed by high performance liquid chromatography (HPLC). The epididymis levels of 24,25(OH)2D3 were considerably higher in the cauda epididymis compared to kidney and caput epididymis levels. The other metabolites levels in this tissue were similar to those determined in the kidneys. The amounts of the three metabolites found in all other tissues were well below the cauda epididymis or kidney levels. The findings suggest a possible physiological role for 24,25(OH)2D3 in the epididymis, and are also consistent with data of others which indicated a possible action of 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) in rat reproductive tissues.

Incidence of acetaminophen in donated blood.

Acetaminophen levels were determined in 1,176 sera separated from donated blood. The analysis was performed by both a colorimetric method and by high performance liquid chromatography. 6.12% of the samples contained acetaminophen levels ranging from 18 to 58 microgram/ml. The possible clinical significance of such a high incidence of this drug among healthy blood donors is discussed.

Applicability and significance of salicylate screening in sera of voluntary blood donors: evaluation of two analytical methods.

Salicylate concentrations in 3819 sera of apparently healthy voluntary blood donors were determined in view of the significance of this drug in the induction of allergic reactions and its possible interference in platelet function. Two hundred and ninety-five sera were found by a modified colorimetric determination to contain salicylates. The colorimetric determination was compared with a high performance liquid chromatography (HPLC) analysis of salicylate-containing sera. Drug concentrations detected were mostly in the range of 20-100 mg/l. Such concentrations have been reported to evoke allergic reactions and to affect the haemostatic action of platelets.

Presence of aspirin in blood units.

2,655 blood units collected from healthy voluntary donors selected according to the criteria of the International Society of Blood Transfusion were tested for the presence of aspirin. This drug was found in 6% of the samples at concentrations ranging from 10 to 200 microgram/ml. The clinical implications of these findings are discussed. We also report a case of allergic reaction which could probably be related to the transfusion of blood containing aspirin.

Glucosamine-labelled envelope proteins of Escherichia coli K-12. I. Electrophoretic studies and partial fractionation of phenol-soluble proteins.

Hydrophobic envelope proteins were extracted by phenol from a glucosamine- and leucine-requiring mutant of Escherichia coli K-12 (E-110). Three protein fractions labelled with D-[1-14C]glucosamine and L-[4,5-3H]leucine were obtained by electrophoretic separation. Envelopes were isolated from cells labelled with D-[1-14C]glucosamine--HCL and acid hydrolyzed. At least 68% of the radioactivity was recovered as glucosamine and glucose with no random distribution of label. Fingerprinting of pronase digests of glucosamine-labelled proteins showed four radioactive spots associated with peptides. The glycoproteins were pronase- and trypsin-sensitive and had apparent molecular weights of 11 000 (fast mobility), 35 000 (intermediate mobility) and 62 000 (slow mobility) as estimated by sodium dodecyl sulfate-polyacrylamide disc electrophoresis. The two heavier fractions were labelled with meso-diamino[1,7-14C2]pimelic acid, while orth[32P]phosphate was not incorporated into any fraction. The glucosamine radioactivity of the fast fraction underwent rapid changes upon a chase with non-radioactive glucosamine. Using a Sephadex LH-20 column, the radioactive proteins were separated from the phenol and subsequently fractionated on a DEAE-cellulose column. The DEAE-cellulose fractions were distinct from each other in the number and composition of protein bands, when analyzed by sodium dodecyl sulfate-polyacrylamide disc electrophoresis. Radioactive bands with intermediate and fast electrophoretic mobilities were found in separate DEAE-cellulose fractions.