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Biomedical subjects

F Bronner

Publications and source records attributed to F Bronner.

At least 19 recordsLinked to original sources
PubMed1996

1,25-Dihydroxycholecalciferol regulates rat intestinal calbindin D9k posttranscriptionally.

To determine whether calbindin D9k (CaBP) is subject to posttranscriptional control, 6-wk-old Sprague Dawley-derived rats were fed one of three purified diets, 1.5% Ca and 3.0% Ca, mostly as carbonate, and 2.9% Ca, mostly as gluconate. Two weeks later, 5-cm segments of duodenum, jejunum, ileum, cecum and colon were obtained and analyzed for CaBP and CaBP-mRNA. Analysis of the steady-state distribution of CaBP-mRNA and of CaBP revealed a statistically significant (r = 0.95; P < 0.01) linear relationship between CaBP-mRNA and CaBP. When, however, animals that had been fed the 1.5% Ca diet received by intrajugular injection 1.2 nmol 1,25-dihydroxycholecalciferol [1.25-(OH)2-D3] and their CaBP-mRNA and CaBP were analyzed as a function of time after 1,25-(OH)2-D3 administration, the kinetic response of the two molecules differed. The CaBP-mRNA increased linearly by approximately 68% for 4 h after administration and then declined over the next 6 h to a concentration below the preinjection value. Thus, appearance and disappearance of CaBP-mRNA approximated 17% x h(-1). The CaBP, however, increased steeply to 80% above preinjection concentration until 2 h postinjection, i.e., at a rate of 40% x h(-1). Thereafter, CaBP decreased to 35% above the preinjection value between 5 and 10 h postinjection (2.5% x h(-1)). These findings are consistent with a 1,25-(OH)2-D3-mediated posttranscriptional regulation of CaBP concentrations, because the 1,25-(OH)2-D3-mediated increase in CaBP-mRNA is not reflected in an immediately changed CaBP level.

Animals↗
PubMed1995

Calcium solubility, intestinal sojourn time and paracellular permeability codetermine passive calcium absorption in rats.

To investigate the nonsaturable, paracellular pathway of intestinal Ca absorption, the luminal contents of 12-cm segments of the intestine of 8-wk-old male Sprague-Dawley rats were analyzed for pH, sojourn time and soluble and insoluble Ca over a 24-h period. The rats had been fed one of two high Ca diets for 2 wk: 1.5% Ca (diet group 3a) and 3.1% (diet group 5a). The pH of the small intestine increased from < 6.6 to > 8.0 from duodenum to ileum; transit time increased from 2.5 min in the duodenum to 58 min in the distal ileum, with the entire ileum accounting on the average for 74% of the transit time of 3 h. The amount of Ca solubilized throughout the intestine was 32 +/- 3.3 mumol in diet group 3a and 53 +/- 5.3 mumol in diet group 5a, i.e., 2.7% and 2.0% of the total luminal Ca. Because absorption by diet group 3a was 1.45 +/- 0.23 mmol/d and that by diet group 5a was 2.50 +/- 0.18 mmol/d, the amounts absorbed were 45.3 and 47.1 times greater than present in the lumen in soluble form at any one time. Thus, over a 24-h period, an average of 3.2% (46.2/1440) of the soluble Ca present in the lumen at any time was absorbed per min. Calculations involving the gradient between luminal and plasma Ca show that the rate of Ca diffusion from lumen to blood is < 2% of what it would be if the paracellular path were unrestricted. Thus, intestinal sojourn time, Ca solubility and mucosal permeability to Ca are factors that determine the rate of passive Ca absorption.

Animals↗
PubMed1995

Calcium homeostasis--an old problem revisited.

This article proposes a novel model of calcium homeostasis, based on the concept of a series of bone calcium-binding sites of varying calcium affinities. When an i.v. Ca load is administered to mammals, it is rapidly (t1/2 < 1 min) dispersed into a volume equivalent to the extracellular fluid. Thereafter the calcium concentration drops monoexponentially with a t1/2 of tens of minutes. When a negative Ca load is administered, as by EDTA injection, the return to the preinjection plasma Ca level, [Cas], occurs also mono-exponentially at the same rate as restoration after a positive load. The numerical value of the rate can be arrived at by taking into account the fraction of cardiac output (5%) that is directed to the skeleton. Acute regulation is brought about by controlling access to subpopulations of the Ca binding sites, whose average Km determines [Cas]. Osteoblasts, when active and extended, block low-affinity binding sites; osteoclasts, when active and extended, block high-affinity sites. Exposure of sites is brought about when bone cells respond by rapid shape changes, osteoblasts rounding up in response to parathyroid hormone (PTH) or vitamin D, osteoclasts rounding up in response to calcitonin. These shape changes are the first steps in the cascade of events that lead to bone formation and resorption, but acute regulation need not involve the latter steps of a cascade. The model accounts for the changes in the response times to Ca loads that have been observed in older animals or those deprived of PTH, calcitonin or vitamin D.

Animals↗
PubMed1994

Calcium and osteoporosis.

Skeletal size and mass are genetically programmed. Optimum skeletal size can be attained if the nutrient supply, ie, calcium, is ample, but the age-dependent decrease in skeletal mass that begins in the third decade cannot be arrested by adequate calcium intake alone. The decrease in skeletal mass is primarily caused by the age-dependent decrease in gonadal hormones. The dramatic drop in hormones in menopause is associated with a sharp decrease in trabecular bone and a slower decrease in cortical bone. In men this decrease is gradual. Replacement therapy with gonadal hormones can markedly slow this decrease in bone mass, provided calcium intake is adequate. Soluble forms of calcium are preferred to ensure adequate calcium absorption. Vitamin D supplementation beyond the recommended dietary allowance does not appear beneficial in osteoporosis, but may be so in cases of senile hyperparathyroidism. Calculations based on bone calcium turnover indicate that the recommended dietary allowance for calcium is adequate for boys and men, but is insufficient for adolescent girls. Calcium intake by women is probably too low to slow bone calcium turnover to its programmed minimum. Adequate calcium intake in childhood and adolescence is essential to attain the optimal bone mass and size.

Bone and Bones↗
PubMed1994

Compartmental analysis of calcium metabolism in very-low-birth-weight infants.

The calcium metabolism of 13 very-low-birth-weight infants fed a high-calcium diet was evaluated by means of stable isotope kinetic and balance studies. The studies used orally and i.v. administered stable isotopes, and the kinetic data were evaluated with the aid of a sequential, three-compartment model. The infants (postmenstrual age 33 +/- 1 wk, weight 1.34 +/- 0.03 kg) had higher bone calcium deposition rates (160 +/- 7 mg.kg-1.d-1 or 4.00 +/- 0.18 mmol.kg-1.d-1) than those previously reported for either older children or adults. Furthermore, when analyzed as a function of net calcium absorption, bone calcium deposition rates increased markedly and significantly as net calcium absorption increased (r = 0.70, p < 0.01), whereas in older individuals, bone calcium deposition is a relatively invariant function of absorption. A relatively smaller response of bone calcium removal to calcium absorption was found for the very-low-birth-weight infants in this study (r = -0.39, p = 0.18), whereas in adults, bone calcium removal constitutes the major regulatory response. It is suggested that the calcium kinetic results in the very-low-birth-weight infants reflect the high rate of bone growth typical of the third trimester of gestation.

Adult↗
PubMed1993

Nutrient bioavailability, with special reference to calcium.

The term "bioavailability" attempts to include in a single concept the effect of a sequence of metabolic events, i.e., digestibility, solubilization, absorption, organ uptake and release, enzymatic transformation, secretion and excretion. Each of these events is difficult to measure experimentally, and, with the possible exception of digestibility and solubilization, all are age-dependent and subject to nutritional and hormonal controls. In the case of calcium, the body's demand increases and then decreases with age; it also increases with pregnancy and lactation. Age, pregnancy and lactation each affect the regulatable component of the intestinal absorption of calcium. The passive component of calcium absorption is a function of the amount of calcium solubilized and of intestinal transit time. Inasmuch as digestibility and solubilization of calcium are very difficult to determine separately, even a reliable measure of calcium absorption includes a measure of uncertainty. If one wishes to include in the term "calcium bioavailability" rates of net deposition in bone, as well as rates of excretion from the body, quantitative information on calcium pool size, turnover and the effects thereon of age, sex, endocrine and nutritional status are needed. In the case of other nutrients, rates of enzymatic transformation and organ utilization need also to be taken into account. It will therefore require major research programs before the term "bioavailability" of a nutrient can become a quantitative concept useful for clinical, nutritional or managerial evaluation and counseling.

Animals↗
PubMed1993

Solubility and intestinal transit time limit calcium absorption in rats.

Six-week-old male rats were placed on two high calcium regimens: one with calcium carbonate and monobasic calcium phosphate, with calcium content increased via calcium carbonate; and another with calcium phosphate and calcium gluconate, with calcium gluconate the source of increased calcium. Animals fed the gluconate-containing diets absorbed 29% of the ingested calcium over the entire calcium intake range, whereas those fed the calcium carbonate diets absorbed 25% over an intake range of 225 to 450 mg Ca/d, but at calcium intakes above 450 mg Ca/d their absorption reached a plateau at approximately 109 mg/d. Active calcium transport decreased with increased calcium intake in both the calcium carbonate- and calcium gluconate-fed groups. Nonsaturable transport was unchanged as a result of increasing calcium intake and did not differ among the diet groups. Because the absorptive processes were unaffected by the calcium source, events in the lumen must have been responsible for the observed differences. Because phosphate is nearly 18 times more soluble than carbonate, very little calcium of calcium carbonate origin can have been solubilized in the presence of phosphate and this, we conclude, accounts for the limit on calcium absorption observed in diets high in calcium carbonate. Moreover, when intake is expressed as soluble calcium, absorption approaches 50%, the value expected when intestinal transit time (approximately 3 h) is multiplied by 16%/h, the experimental value of nonsaturable absorption.

Animals↗
PubMed1992

Modulation of bone calcium-binding sites regulates plasma calcium: an hypothesis.

A new model of calcium (Ca) homeostasis is proposed. It is based on the kinetics of restoration of the plasma Ca level following positive or negative Ca loads in animals of different endocrine status. As others, we can account for the kinetics of plasma Ca restoration as being the result of a very rapid dilution of Ca into extracellular water (t1/2 less than 1 minute) and an uptake or release by bone (t1/2 = 14-80 minutes) that occurs as the fraction of cardiac output directed to bone is partially cleared of or repleted with Ca. In this model, bone surfaces have Ca-binding sites that demonstrate a range of affinities and whose average Km determines the plasma Ca level. Acute regulation is brought about by controlling access to subpopulations of Ca binding sites in bone, comprising the extremes of high and low affinity. Osteoblasts, when active and extended, block the low affinity sites, and osteoclasts, when active and extended, block the high affinity sites. Exposure of low- or high-affinity sites is brought about when these cells respond to hormonal signals by contraction, parathyroid hormone (PTH), and vitamin D leading to osteoblast, and calcitonin to osteoclast, contraction. These reciprocal cell shape changes are the first in a cascade of metabolic events that lead to bone formation and resorption, as well as changes in the number or affinity of the binding sites. The model also accounts for the prolongation of the response time to Ca loads in animals deprived of PTH, calcitonin, or vitamin D.

Animals↗
PubMed1992

Net calcium absorption in premature infants: results of 103 metabolic balance studies.

Net calcium absorption was evaluated in 103 low-birth-weight preterm infants by a 72-h balance technique. At birth the infants had a mean (+/- SE) gestational age of 30.9 +/- 0.2 wk and weighed 1.43 +/- 0.03 kg. When tested 3 wk later, their net calcium absorption averaged 58 +/- 1% with an intake of 80 +/- 2 mg Ca.kg body wt-1.d-1. Of the 103 infants, 58 had been fed low-birth-weight formulas supplemented with vitamin D. The remainder received banked human milk, of whom 34 were supplemented with vitamin D and calcium; 11 infants received no supplementation. Calcium absorption in the four subgroups did not differ significantly, with neither vitamin D supplementation nor supplementation with vitamin D and calcium affecting percent absorption significantly. Net calcium absorption was a linear function of intake (40-130 mg Ca.kg body wt-1.d-1) with a zero intercept. Because vitamin D supplementation did not increase net calcium absorption, it is concluded that in preterm low-birth-weight infants calcium absorption proceeds by a nonsaturable route, with the transcellular, vitamin D-regulated mechanism not yet expressed.

Calcium↗
PubMed1992

Bone and calcium homeostasis.

The principal repository of calcium is bone. Calcium enters bone largely via the trabeculae, with the rate of calcium clearance by bone approximating 50 percent. Calcium enters bone as an ion in solution, but undergoes a phase change to a solid as soon as in contact with the bone surfaces. Calcium removal from and redistribution in bone is mediated by the bone cells, principally osteoblasts and osteoclasts. Calcium enters the body via intestinal absorption, a transport process that is the vectorial result of a saturable and an non-saturable step. Calcium leaves the body in the urine and stool, with a circulating calcium ion having one chance in about four of being lost via excretion. Ions like lead can compete with calcium at the sites of calcium deposition and transport. Their rate in the body should therefore parallel that of calcium, but may be modified by differing binding affinities or interactions with specific sites and molecules.

Animals↗
PubMed1992

Microdistribution of lead in bone: a new approach.

A knowledge of the microdistribution of lead in bone is important in order to understand the mechanisms for accumulation and release of lead. The availability of the synchrotron x-ray microscope for sensitive measurements of bone content and distribution of lead provides a valuable tool which, when combined with kinetic, balance, and tissue measurements, can lead to better evaluation of lead toxicity. It may also provide the basis for the development of a suitable model of how lead behaves in the human body. An outline of an experimental protocol for exploitation of the x-ray microscope is given, along with synchrotron x-ray microscope measurements of the distribution of gallium in rat bone that demonstrate the feasibility of the experimental approach.

Animals↗
PubMed1991

A human periodontal ligament fibroblast clone releases a bone resorption inhibition factor in vitro.

The conditioned media (CM) obtained from three lines of cloned human periodontal ligament (PDL) cells were analyzed to determine whether they altered the parathyroid hormone (PTH)-stimulated resorption rates (45Ca release) in 48-hour cultures of 45Ca-labeled rat long bones. One PDL cell line, PDL-5, produced a heat-resistant factor in its CM that inhibited the PTH-stimulated resorption by 43.8 +/- 9.7 (SE) percent (p less than or equal to 0.02), whereas the CM from the other cell lines were without statistically significant effect. The CM from the PDL-5 line did not diminish organ culture viability, as determined by 3H-thymidine incorporation, and did not enhance or diminish the resorption-inhibiting activity of calcitonin added to the PTH-stimulated cultures. The addition of CM from PDL-5 did not alter the bone-resorbing effect of interleukin-1 (IL-1). These results indicate that CM from PDL-5 inhibits only the PTH-induced and not the IL-1-mediated resorption processes, whose mechanisms are therefore likely to differ.

Analysis of Variance↗