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Biomedical subjects

R Vieth

Publications and source records attributed to R Vieth.

At least 55 records · Page 3Linked to original sources
PubMed1990

The long-term treatment of steroid osteoporosis with fluoride.

Twenty-two patients with steroid-induced osteoporosis were studied retrospectively to assess the effects on bone mass of fluoride therapy over 4 years. Thirteen of 19 patients with miscellaneous disorders and 2 with Cushing's syndrome received 1 g calcium/day, 50,000 IU vitamin D (D) weekly, and 40-60 mg/day sodium fluoride (F). Six patients with miscellaneous disorders and one with Cushing's syndrome received only Ca and vitamin D. The mean (+/- SD) cumulative dose of prednisone for fluoride-treated patients at the beginning of the study was 42 +/- 25 g, and for those patients treated with only Ca and vitamin D, 45 +/- 47 g, and during the study the cumulative dose was comparable in both groups. The bone mineral mass of the central skeleton was measured by neutron activation analysis and the results expressed as the calcium bone index (CaBI) which normalizes the results to that of young adults of the same body size (normal range 0.75-1.2). In the 13 patients with miscellaneous disorders treated with fluoride, the mean +/- SD CaBI rose from 0.65 +/- .03 to 0.75 +/- .03 after 3 years p less than 0.001) and to 0.81 +/- .11 at 4 years. Patients without fluoride had an initial mean CaBI of 0.70 +/- .08 and it was not significantly changed over 3 years, 0.68 +/- .09 and 4 years, 0.71 +/- .09. The rise in CaBI in fluoride-treated patients with steroid-induced osteoporosis including Cushing's syndrome was comparable to that of 61 patients with postmenopausal osteoporosis treated with fluoride.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Tracer kinetics and actions of oral and intraperitoneal 1,25-dihydroxyvitamin D3 administration in rats.

Tracer kinetic parameters of [3H]-1,25(OH)2D3 were calculated from data obtained following its acute oral (p.o.) or intraperitoneal (i.p.) administration. In normal rats studied after the tracer had distributed into the body, the slope and intercept of the log-serum [3H]-1,25(OH)2D3 versus time relationship were not significantly influenced by the route of administration. Pretreatment with 1,25(OH)2D3 (0.2 micrograms/100 g/day) by the same route as the tracer resulted in the following changes: in p.o. rats the serum [3H]-1,25(OH)2D3 intercept was much lower but the slope was not changed; in i.p. rats the intercept was not changed but the slope was increased. Both p.o. and i.p. treatment with 1,25(OH)2D3 lowered the weight gain and diet consumption, and increased serum calcium, kidney tissue calcium and urinary excretion of orally administered 45Ca. All the measures of bioactivity were greater in the i.p. dosed rats than in the p.o. dosed rats. We conclude that the p.o. 1,25(OH)2D3 was less potent because of diminished bioavailability due to self induction of its presystemic metabolism and inactivation.

Administration, Oral↗
PubMed1990

A simple technique to feed newborn piglets.

We describe a simple and relatively inexpensive technique for feeding conventionally reared newborn pigs. The feeding system consists of a nipple assembly and an enteral feeding bag. Piglets are weaned at 4-10 h of age and are initially bottle-fed a simulated sow's milk formula. After adaptation to the synthetic nipple and artificial milk, the piglets are placed on the semiautomatic feeding system. Piglets fed in this manner gain weight at rates comparable to sow-reared animals or animals fed via completely automated systems.

Animals↗
PubMed1990

Species differences in the binding kinetics of 25-hydroxyvitamin D3 to vitamin D binding protein.

The specific binding of 25-hydroxyvitamin D3 to its binding protein was studied in serum of the human, rhesus monkey, cow, horse, and rat. The free fraction of 25-hydroxyvitamin D3 in the rat was 0.34 +/- 0.15 pmol free/nmol total (+/- SD) and this was lower than in any of the other species (p less than 0.01). In the human, the free fraction was 1.5 +/- 0.32 pmol free/nmol total, which was higher than in any of the other species (p less than 0.001). The differences in the free fraction were mainly due to differences in dissociation constant. The relative levels of free 25-hydroxyvitamin D should be taken into account when extrapolating findings about vitamin D metabolism in animals to the human. A technical outcome of this study is that of the species tested, vitamin D binding protein from rat serum is the most suitable as a reagent component for methods used to measure total 25-hydroxyvitamin D by competitive protein binding assay.

Analysis of Variance↗
PubMed1990

Role of 25-hydroxyvitamin D3 dose in determining rat 1,25-dihydroxyvitamin D3 production.

To understand the relationships among 1) the dose of 25-hydroxyvitamin D [25(OH)D] in vivo, 2) the activity of 1-hydroxylase in renal mitochondria, and 3) the production of 1,25-dihydroxyvitamin D [1,25(OH)2D] in vivo, we gave rats different chronic or acute doses of 25-hydroxyvitamin D3 [25(OH)D3]. We followed the metabolism of intracardially administered [25-hydroxy-26,27-methyl-3H]cholecalciferol [25(OH)[3H]D3] for 24 h before killing by measuring extracts of serum by chromatography. Specific activity of 1-hydroxylase in kidney was measured at death. In rats given 0-2,000 pmol 25(OH)D3 chronically by mouth, there was a dose-dependent decline in the percent of serum radioactivity made up of 1,25-dihydroxy-[26,27-methyl-3H]cholecalciferol [1,25(OH)2[3H]D3] as well as a decline in mitochondrial 1-hydroxylase, and these correlated significantly (r = 0.83, P less than 0.001). Serum %1,25(OH)2[3H]D3 in this experiment ranged from 0.8 to 42%. A small part of this range could be accounted for by a faster metabolic clearance rate (MCR) of 1,25(OH)2D3 from rats supplemented with 25(OH)D3 (MCR, 2.12 +/- 0.10 ml/min) compared with rats restricted in vitamin D (MCR, 0.94 +/- 0.06 ml/min, P less than 0.001). The activity of 1-hydroxylase was by far the major factor determining serum %1,25(OH)2[3H]D3. When different acute doses of 25(OH)D3 were given to rats with identical specific activities of 1-hydroxylase, the resulting 1,25(OH)2D3 concentrations in serum correlated with the 25(OH)D3 dose (r = 0.99, P less than 0.001). We conclude that the behavior of 1-hydroxylase in vivo is analogous to the classic behavior in vitro of an enzyme functioning below its Michaelis constant (Km). The amount of 1-hydroxylase present in renal mitochondria determines the fraction (not simply the quantity) of 25(OH)D metabolized to 1,25(OH)2D3 in vivo.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1989

Losses of calcitriol to peritoneal dialysis bags and tubing.

Peritoneal dialysis provides a convenient means of administering calcitriol. We investigated in vitro the efficiency with which this approach would deliver the drug to patients. We used an injectable preparation of calcitriol, Calcijex (Abbott Laboratories, Montreal, Quebec, Canada), which we radiolabelled by adding radioactive 1,25-dihydroxyvitamin D3 to it. The preparation was injected into dialysis bags and drained through appropriate tubing to monitor delivery of the radiolabelled calcitriol. By 2 h after injecting calcitriol into dialysis bags, 50% of the dose was left in the fluid, by 20 h only 26% was left. The delivered drug was pure 1,25-dihydroxyvitamin D3 based on chromatographic analysis of the recovered radiochemical. To study what would happen if the drug was in the bag for a minimal length of time the calcitriol was injected immediately prior to draining the fluid. We recovered 62.9% +/- 5.2% SD of the dose from the tubing which would theoretically have entered a patient. There was no significant change in calcitriol dose delivered if the fluid was warmed to 37 degrees C prior to injecting the drug and immediate drainage of the bag.

Calcitriol↗
PubMed1988

The effect of fluoride on bone histology in postmenopausal osteoporosis depends on adequate fluoride absorption and retention.

Forty-one women with idiopathic postmenopausal osteoporosis have been followed for 2 years after initiation of sodium fluoride at 40-50 mg/day, given together with a daily calcium supplement of 1 gram and vitamin D2, at 50,000 IU weekly. Histological and histomorphometric analyses were done on bone biopsies taken prior to and after 1 year of treatment (mean 1.25 +/- 0.35 years). Thirty patients (74%) developed the histological fluoride effect of hyperosteoidosis, while the remaining 11 patients (26%) had no change from pretreatment biopsies. Hyperosteoidosis was based on increased values for osteoid volume and/or thickened osteoid with greater than 3 lamellar bands. Based on previously reported findings, this histological evidence of hypersoteoidosis within 12-18 months of initiation of therapy provides a useful predictor of ultimate satisfactory fluoride response in terms of bone mineral accretion. No increases in bone mass (measured by neutron activation analysis) were observed at the time of the posttreatment biopsy but, according to this previous work, increases are anticipated over a further 2-3 years of treatment. Factors affecting the development of hyperosteoidosis were analyzed. Hyperosteoidosis was associated with a significantly higher dose of sodium fluoride and a significantly higher level of bone fluoride retention but without significant increase in fasting serum fluoride. Results suggest that fluoride retention depends not only on fluoride dose but also on body size, renal function, and intestinal absorptions of calcium and fluoride. There were no differences in the initial investigations between patients with and without hyperosteoidosis, with respect to age, years of postmenopause, estrogen use, initial biochemistry, or initial bone histology.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
PubMed1987

Low dietary calcium reduces 25-hydroxycholecalciferol in plasma of rats.

We investigated whether dietary factors that are known to increase 1,25-(OH)2-cholecalciferol production can deplete plasma 25-OH-cholecalciferol. Plasma concentration of 25-OH-cholecalciferol, its metabolism in vivo and activities of renal mitochondrial 25-OH-cholecalciferol 1-hydroxylase (1-OHase) and 25-OH-cholecalciferol 24-hydroxylase (24-OHase) were measured in rats fed various amounts of calcium (Ca) and phosphorus (P). All diets contained 5 micrograms (200 IU) cholecalciferol per 100 g. For rats fed the "normal" diet (0.7% Ca and 1.2% P) the mean plasma 25-OH-cholecalciferol level was 11.0 +/- 0.8 nmol/L, and the mean 1-OHase activity was 30 +/- 5 fmol/(mg X min). All rats fed the low Ca (0.014%) diet had 1-OHase activities above 200 fmol/(mg X min) and undetectable plasma 25-OH-cholecalciferol levels (less than 2.5 nmol/L). The chi-square test interrelating plasma 25-OH-cholecalciferol and dietary Ca showed statistical significance (P less than 0.001). The high activity of 1-OHase that resulted from dietary Ca restriction increased utilization of 25-OH-cholecalciferol to the point of causing depletion of this metabolite in the circulation.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1987

Serum concentrations of vitamin D metabolites in Cayo Santiago rhesus macaques.

Serum 25-hydroxyvitamin D (25[OH]D), an index of vitamin D nutrition, and the calcium-regulating hormone 1,25-dihydroxyvitamin D (1,25[OH]2D) were measured in rhesus macaques of various ages. Both metabolites were much higher in monkeys than in man. For 25(OH)D there was no sex difference, and this metabolite increased with age (P greater than 0.05). The 1,25(OH)2D fell with age for males (P less than 0.02), but not for females. Pregnant or lactating females had significantly elevated 1,25(OH)2D levels (P less than 0.025).

Age Factors↗
PubMed1985

Hepatic microsomal short-chain beta-hydroxyacyl-CoA dehydrase distinct from the fatty acid elongation component: substrate specificity of the membrane-extracted enzyme.

The ability of 0.4 M KCl to extract over 80% of a short-chain beta-hydroxyacyl-CoA dehydrase from rat hepatic endoplasmic reticulum, while more than 80% of the long-chain beta-hydroxyacyl-CoA dehydrase component of the fatty acid chain elongation system remains intact, confirms the existence of more than one hepatic microsomal dehydrase. Following extraction from the microsomal membrane, the short-chain dehydrase undergoes, at least, a two-fold activation. Employing even-numbered trans-2-enoyl-CoA substrates ranging in carbon chain length from 4 to 16, the highest dehydrase specific activity of 16 mumol min-1 mg protein-1 was obtained with trans-2-hexenoyl-CoA; crotonyl-CoA was the second most active substrate, followed by 8 greater than 10 greater than 12 greater than 14 greater than 16. The specific activity of the short-chain dehydrase with trans-2-hexadecenoyl-CoA (C-16) was only 3% of that observed with the trans-2-hexenoyl-CoA. With crotonyl-CoA or beta-hydroxybutyryl-CoA as substrates, HPLC was employed to identify the products, beta-hydroxybutyryl-CoA, of the hydration reaction, or crotonyl-CoA, of the reverse dehydration reaction. It was also observed that the short-chain dehydrase catalyzed the formation of both D(-) and L(+) stereoisomers of beta-hydroxybutyryl-CoA. The equilibrium constant for the dehydrase-catalyzed reaction determined at pH 7.4 and 35 degrees C, was calculated to be 6.38 X 10(-2) M-1, while the standard free energy change was -775 cal/mol, results similar to those obtained with crystalline crotonase. Finally, based on membrane fraction marker enzymes, substrate specificity, and heat lability of the dehydrase, it was concluded that the microsomal membrane contains a short-chain beta-hydroxyacyl-CoA dehydrase which is separate from the mitochondrial crotonase.

Acetyltransferases↗
PubMed1984

Rat hepatic microsomal acetoacetyl-CoA reductase. A beta-ketoacyl-CoA reductase distinct from the long chain beta-ketoacyl-CoA reductase component of the microsomal fatty acid chain elongation system.

The present study provides evidence for a new rat liver microsomal enzyme, a short chain beta-ketoacyl (acetoacetyl)-CoA reductase, which is separate from the long chain beta-ketoacyl-CoA reductase component of the microsomal fatty acid chain elongation system. This microsomal reductase converts acetoacetyl-CoA to beta-hydroxybutyryl-CoA at a rate of 70 nmol/min/mg of protein; the enzyme has a specific requirement for NADH and appears to obtain electrons directly from the reduced pyridine nucleotide without the intervention of cytochrome b5 and its flavoprotein reductase. The apparent Km of the enzyme of the acetoacetyl-CoA was 21 microM and for the cofactor, 18 microM. The pH optimum was broad, ranging from 6.5 to 8.0. The product formed is the D-isomer of beta-hydroxybutyryl-CoA. High carbohydrate fat-free diet resulted in a small but significant (35%) increase in microsomal acetoacetyl-CoA reductase activity. The cytosol also contains this enzyme activity, measuring approximately 57% of that found in the microsomes. The mitochondrial activity which is 20-25% higher than the microsomal activity appears to be due to L-beta-hydroxyacyl-CoA dehydrogenase which converts acetoacetyl-CoA to L-beta-hydroxybutyryl-CoA. The microsomal acetoacetyl-CoA reductase activity was extracted from the microsomal membrane by 0.4 M KCl, resulting in an 8- to 10-fold purification; in addition, the long chain fatty acid elongation system was unaffected by this extraction procedure. Employing beta- hydroxyhexanoyl -CoA as a substrate, evidence is also provided for a separate dehydratase which acts on short chain substrates. Lastly, the liver microsomes had no detectable acetoacetyl-CoA synthetase or acetyl-CoA acetyltransferase activities. Hence, the possible involvement of the rat hepatic microsomal short chain beta-ketoacyl-CoA reductase, short chain beta-hydroxyacyl-CoA dehydratase, and the previously reported short chain trans-2-enoyl-CoA reductase in the hepatic utilization of acetoacetyl-CoA and in the synthesis of butyryl-CoA for hepatic lipogenesis is discussed.

Acetoacetates↗
PubMed1980

25-hydroxyvitamin D metabolism in the sheep fetus and lamb.

The metabolism of [3H]-25-hydroxyvitamin D3(3H-25-OH-D3) to [3H]-1,25-dihydroxyvitamin D3 (3H-1,25-(OH)2D)3 and [3H]24, 325 dihydroxyvitamin D3 (3H-24,25-(OH)2D3) was studied in sheep fetuses and lambs. In vivo metabolism was observed by chromatography of extracts of plasma obtained 24 hr after direct iv injection of 3H-25-OH-D3 to the fetus and lamb. The renal enzymes 25-hydroxyvitamin D-1-hydroxylase and -24-hydroxylase were determined in vitro by quantitative assay. In fetal lambs, 3H-24,25-(OH)2D3 was consistently the only detectable dihydroxyvitamin D3 metabolite; this was confirmed by the in vitro studies in which 24-hydroxylase was the only detectable enzyme. Parathyroid hormone infusion to the fetus did not stimulate 3H-1,25-(OH)2D3 production. In normal lambs fed sheep's milk or cow's milk 3H-24,25-(OH)2D3 was the only metabolite of 3H-25-OH-D3 in vivo and only 24-hydroxylase activity was detected in vitro. In lambs fed a low-calcium, vitamin D-free formula, 24-hydroxylase activity remained measurable for at least 11 days of feeding, and by that time 1-OHase activity became evident in vitro. Appreciable 3H-1,25-(OH)2D3 was not observed in plasma until 16 days of feeding with the formula. After 18 days on low-calcium, vitamin D-free formula, 1-OHase was the only detectable 25-OH-D3 metabolizing enzyme. We also studied the rates at which 3H-25-OH-D3, 3H-24,25-(OH)2D3 and 3H-1,25-(OH)2D3 disappeared from the lamb plasma compartment. Within 1 hr, 3H-1,25-(OH)2D3 fell to 50% of its initial concentration, and after 72 hr only 2% was left. In the case of 3H-25-OH-D and 3H-24,25-(OH)2D3, 50% of each metabolite was left after 7 to 10 hr and about 20% after 72 hr. The rapid disappearance of 3H-1,25-(OH)2D3 may explain the low levels or absence of this metabolite observed in the plasma of some animals shown to have renal 1-hydroxylase activity.

Animals↗
PubMedDate not supplied

Primary infantile hypomagnesaemia: outcome after 21 years and treatment with continuous nocturnal nasogastric magnesium infusion.

UNLABELLED: Primary infantile hypomagnesaemia is an infrequent cause of neonatal hypocalcaemic seizures but one that responds well to magnesium supplementation. We describe a 22-year-old male, first reported at 4 months of age, who is currently free of neurological deficit but has suffered from intermittent hypomagnesaemic tetany and chronic diarrhoea due to large oral magnesium supplements. Hypothesizing that modest hypercalcaemia might prevent the tetany, we conducted a trial of 5 microg/day 1,25(OH)2D3 over 5 days. Despite the resultant increase in calcium, he developed tetany with the reduction of magnesium intake and decline of serum magnesium from 0.63 to 0.39 mmol/l (normal >0.65 mmol/l). After 1,25(OH)2D3 was stopped and the parenteral magnesium injections suspended, 33% of his usual oral supplement was given instead by continuous nasogastric infusion and serum magnesium rose to 0.60 mmol/l. This regimen was better tolerated because of decreased gastrointestinal side-effects and freedom from parenteral injections. We observed that 1,25(OH)2D3 supplements do not promote magnesium retention nor does the resultant hypercalcaemia prevent hypomagnesaemic tetany. CONCLUSION: Continuous nocturnal nasogastric infusion may be considered in lieu of parenteral therapy in primary infantile hypomagnesaemia.

Administration, Oral↗
PubMedDate not supplied

Regulation of sodium, calcium and vitamin D metabolism in Dahl rats on a high-salt/low-potassium diet: genetic and neural influences.

1. A dietary combination of high salt and low potassium (HSLK) exacerbates hypertension in Dahl salt-sensitive (DS) rats and renders previously normotensive Dahl salt-resistant (DR) rats hypertensive. In both strains, the severity of hypertension correlates with urinary calcium loss. However, the magnitude of excretory calcium losses is significantly greater in DS rats and is potentiated by chemical sympathectomy in both strains. 2. We hypothesized that a defect in vitamin D metabolism may underlie the observed strain-dependent differences in calcium balance. 3. Arterial blood pressure (ABP), water and mineral balance and serum concentrations of 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3) and 25-hydroxyvitamin D3 (25(OH)D3) were measured in intact and chemically sympathectomized (6-hydroxydopamine; 6-OHDA) DS and DR rats after 8 weeks on a HSLK diet. 4. Chronic ingestion of this diet resulted in marked and moderate levels of hypertension in DS and DR rats, respectively. The hypertension was abated and eliminated by 6-OHDA in the DS and DR strains, respectively. Independent of treatment, DS rats had significantly higher urinary excretion of calcium and reduced intestinal absorption of the ion compared with DR rats. The DS rats had significantly higher serum levels of 1,25(OH)2 D3 and markedly lower serum levels of 25(OH)D3 than DR rats. Chemical sympathectomy tended to increase 1,25(OH)2 D3 and to decrease 25(OH)D3 levels in both strains. 5. These data indicate a genetic difference in vitamin D metabolism between DS and DR rats. The abnormally elevated levels of 1,25(OH)2 D3 in DS rats may be an appropriate compensatory response to excessive excretory calcium loss and reduced target organ sensitivity to the hormone and may, maladaptively, directly contribute to hypertension, by stimulating vascular smooth muscle contractility.

Adrenergic Agents↗