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Biomedical subjects

F Bronner

Publications and source records attributed to F Bronner.

At least 55 records · Page 3Linked to original sources
PubMed1987

Intestinal calcium absorption: mechanisms and applications.

Calcium absorption from the intestine involves two sets of events. One, a saturable transcellular process is regulated by vitamin D via its molecular product, the calcium-binding protein (CaBP, MW = 8800). This transcellular movement is largely confined to the proximal portion of the intestine. The second process is nonsaturable, occurs throughout the length of the intestine and is paracellular. Evidence in support of these statements is discussed, with emphasis on kinetic considerations. It is proposed that CaBP acts as a ferry, amplifying the intracellular movement of calcium by a factor of about 60, thereby enabling transcellular calcium transport to reach the measured values of Vm = 22 mumol/h per gram (wet) duodenum, with Km = 3.9 mM. The transcellular process is subject to down-regulation and is influenced by functional or nutritional factors such as age or calcium intake. The nonsaturable process, on the other hand, is not directly influenced by these or related events. Vitamin D therapy alters active calcium transport, but may lead to undesirable effects at other target organs, e.g., kidney or bone. An increase in calcium intake is the simplest method for increasing the amount absorbed. Future research may show whether paracellular pathway alterations are a practical approach to changing the amount of calcium absorbed by the nonsaturable process.

Animals↗
PubMed1987

[A statistical model for interpreting the antibiogram].

Up to now, to interpret antibiotic susceptibility tests, the common practice has been to use: first, breakpoints without any quantitative justification, secondly, concordance curves between the different measurement techniques; these are not well adapted to the heterogeneous character of bacterial populations. We hereby propose another method: it is based on a global data analysis for each bacterial species, each antibiotic family and each measurement technique. So, we have drawn up a new model for the interpretation, both global and data-processed; it is based on qualifying classes, which are obtained and interpreted by hierarchical ascendent classification, principal components analysis, and comparison with pharmacological data. It can be used by any biologist. What is more, justified breakpoints with a numerical risk and quality control are defined. There are also some additional uses: evaluation of the effect of new antibiotics, standardization of new measurement techniques, detection of the emergence of new bacterial resistance in patients, guidance for research into unknown resistance mechanisms and characters.

Computers↗
PubMed1986

An analysis of intestinal calcium transport across the rat intestine.

Kinetic analysis of transmural calcium transport, as evaluated by in situ intestinal loops, has confirmed the existence of two transport processes, a saturable, transcellular one that is regulated by vitamin D and predominates in the proximal intestine and a nonsaturable process similar in intensity throughout the intestine. Transport data obtained from everted sac experiments are kinetically consistent with events in the in situ loop. Analysis of the three component steps making up the saturable process, i.e., entry across the brush-border membrane, intracellular diffusion, and extrusion across the basolateral membrane, indicates that intracellular diffusion is likely to be the limiting step. Active calcium transport varies directly and proportionately with the content of calcium-binding protein (CaBP), a specific molecular expression of the action of vitamin D. Since CaBP is a cytosolic protein, it may act to facilitate calcium diffusion, a proposition advanced by Kretsinger, Mann, and Simmons and supported here quantitatively. We calculate that the rate of intracellular calcium diffusion in the absence of CaBP is only approximately 1/70 of what is found in the vitamin D-replete cell. Similar considerations have led to the proposal that calcium moved by the nonsaturable process travels largely via the paracellular route. The kinetic parameters derived here, i.e., Vm = 22 mumol X h-1 X g (wt wt-1, Km = 3.9 mM, and a nonsaturable rate of 0.16/h, can be used to predict calcium absorption data as determined in previously published balance experiments.

Aging↗
PubMed1986

Localization of vitamin D-dependent active Ca2+ transport in rat duodenum and relation to CaBP.

Vitamin D-replete (+D) and vitamin D-deficient (-D) rats received by intraperitoneal injection varying amounts of 1,25-dihydroxyvitamin D3, and 4 h (+D) or 9 h (-D) later everted duodenal sacs were prepared to evaluate active calcium transport, i.e., the amount of calcium found in the serosal fluid. At the same time, duodenal calcium-binding protein (CaBP) content was measured. Calcium transport was a close positive function of CaBP content. It was not detectable when CaBP content was zero and increased linearly without plateauing as CaBP content increased to 100 nmol calcium bound/g mucosa. Trifluoperazine (TFP) inhibited active calcium transport in a concentration-dependent manner. Experiments using vesicles prepared from brush-border or basolateral membranes indicated that TFP inhibited the calcium-extrusion process, with virtually no effect on calcium entry. It is concluded that vitamin D exerts its major regulation of active calcium transport in the rat duodenum via CaBP on transport steps beyond brush-border entry.

Animals↗
PubMed1985

Saturable and nonsaturable copper and calcium transport in mouse duodenum.

Duodenal copper and calcium absorption was evaluated in 30-day-old normal male Swiss mice by an in situ loop procedure. For both ions, the 90-min absorption values yielded a curve that was resolvable into a hyperbolic (saturable) and a linear (nonsaturable) function. The two ions differed, however, in total absorption and the relative importance of the two functions. For copper, the maximum saturable component of transepithelial movement (Jmax) was 127 +/- 2.4 (SE) pmol in 90 min, the apparent half-saturation constant of the saturable process (Kt) was 4.3 +/- 0.7 microM, and the slope of the nonsaturable function was 0.011 +/- 0.006. Thus, when luminal copper equaled plasma copper (approximately equal to 15 microM), only 8% was absorbed, nearly all of which was by the saturable component. For calcium, on the other hand, Jmax was 4.8 +/- 0.1 mumol, the Kt was 27 +/- 2 mM, and the slope was 0.10 +/- 0.01. At luminal calcium concentrations equal to the inorganic plasma calcium (1 mM), calcium absorption was 75%, but only 80% of that was moved by the saturable process. The findings suggest the existence of separate transport mechanisms for copper and calcium.

Animals↗
PubMed1984

Role of intestinal calcium absorption in plasma calcium regulation of the rat.

Transmural calcium movement in the intestine involves both saturable and nonsaturable components, with the saturable movement subject to regulation by vitamin D and indirectly by parathyroid hormone. Under conditions of high-calcium intake, calcium absorption due to the saturable component is minimized and the numerical value of the nonsaturable component can equal that found in vitamin D-deficient or parathyroidectomized (PTX) animals on similar calcium intakes. Yet in PTX animals intestinal calcium represents a larger proportion of the calcium inflow into the central pool, and PTX animals are less able to regulate their plasma calcium than hormonally intact animals. This demonstrates that intestinal calcium input in the rat can be classified as a signal disturbing (raising) the plasma calcium.

Absorption↗
PubMed1984

Regulation of calcium metabolism in streptozotocin-induced diabetes.

Sixty-nine-day-old female Wistar rats that had been made diabetic 9 days earlier by an intraperitoneal injection of streptozotocin were studied by a combination radioisotope and balance technique that evaluates calcium absorption, excretion, and bone calcium deposition and resorption rates. Streptozotocin-induced diabetes was associated with a marked drop in calcium absorption and a threefold rise in urinary calcium excretion, changes that greatly exceeded the expected effects from the hyperphagia and increased calcium intake of the experimental animals. Bone calcium deposition was halved in the diabetic rats, with bone resorption unchanged and equal to the deposition rate. As a result, the bone and body calcium balances were zero in the experimental animals. To maintain plasma calcium near normal under these circumstances, the diabetic animals turned over their skeletal calcium in relationship to the central pool much more rapidly than the controls. Although the skeleton in the normal animals serves as both storehouse and regulator of the plasma calcium, in short-term streptozotocin-induced diabetes there is no calcium storage in bone, with the skeleton only playing the role of regulator of calcium homeostasis.

Animals↗
PubMed1983

Calcium uptake by isolated rat intestinal cells.

Intestinal cells were isolated by a combination of mechanical and enzymatic means, and their calcium uptake was assayed by a rapid filtration procedure. Calcium uptake was a time- and concentration-dependent process that was markedly elevated at 25 and 37 degrees C, as compared to 0 degree C. Cells isolated from rat duodenum exhibited higher uptakes than cells from jejunum, which in turn took up more calcium than cells from the ileum. Duodenal cells from vitamin D-deficient animals took up less calcium than cells from vitamin D-replete cells. In vivo vitamin D repletion with 1,25-dihydroxyvitamin D3 raised calcium uptake by duodenal cells from treated animals toward that of cells from replete rats. Furthermore, calcium uptake by duodenal cells from vitamin D-deficient animals approximated that of ileal cells from replete rats. These findings with isolated cells parallel prior findings of tissue calcium transport and suggest that cellular calcium uptake may be related to the saturable component of intestinal calcium absorption. Isolated intestinal cells may therefore constitute one experimental model for the study of transcellular calcium transport.

Animals↗
PubMed1983

Developmental changes in the mechanisms of duodenal calcium transport in the rat.

Duodenal calcium transport was resolved into a saturable and a nonsaturable process by means of an in situ ligated loop procedure applied to Wistar rats at 3, 12, 19, 24, 30, 40, 60, 110, and 150 days of age. All postweaning animals were males that had been placed on a 1.5% calcium, 1.5% phosphorus semisynthetic diet. Duodenal calcium-binding protein (CaBP) levels were determined at all ages. The newborn rat had no saturable transport component and no CaBP. Its nonsaturable component was very high. With increasing age the saturable component and CaBP varied biphasically, increasing steeply until the animals were about 35 days old; thereafter, each decreased to low but detectable values. The nonsaturable component, on the other hand, decreased in near-linear fashion in the first 35 days; in animals beyond that age it remained invariant. The difference in age dependence between the saturable and nonsaturable components may be considered to constitute additional evidence for the existence of the two transport processes. CaBP and the saturable transport process were highly correlated, further proof that both are vitamin D dependent. Histological studies have revealed the presence of many vacuoles in the intestinal cells of the very young rats; these vacuoles were absent in rats older than 35 days. It is suggested that these vacuoles may be implicated in a pinocytosislike nonsaturable transport that is superimposed on the nonsaturable, non-vitamin D-dependent calcium transport found in all enterocytes.

Aging↗
PubMed1983

Duodenal and ileal calcium absorption in the rat and effects of vitamin D.

An in situ ligated loop procedure was applied to dissect transmural calcium transport in the intestine into two components, a saturable and a nonsaturable process. The existence of two such processes was confirmed in the duodenum, but ileal calcium transport was devoid of the saturable component. There was a small saturable component in the upper jejunum. The level of CaBP, the vitamin D-dependent cytosolic calcium-binding protein (Mr, approximately or equal to 9,000), corresponded to the magnitude of the saturable component. No CaBP was detected in the ileum. Vitamin D dependence of the saturable component was established by inducing it in the duodenum of vitamin D-deficient animals following intraperitoneal injection of 1,25-dihydroxyvitamin D3. In these same animals, conversely, the ileum did not respond to exogenous 1,25-dihydroxyvitamin D3. This confirms the absence in the ileum of the saturable component of transmural calcium movement and the fact that the nonsaturable component is not vitamin D dependent. Everted sac experiments also showed that duodenal sacs from vitamin D-replete or -repleted animals transported calcium against a chemical gradient, whereas ileal sacs did not. Vitamin D regulation of intestinal calcium absorption thus occurs only in the proximal intestine, even though calcium is absorbed down its chemical gradient all along the small intestine.

Animals↗
PubMed1982

Characterization of calcium binding to brush-border membranes from rat duodenum.

The Ca2+-binding properties of isolated brush-border membranes at physiological ionic strength and pH were examined by rapid Millipore filtration. A comprehensive analysis of the binding data suggested the presence of two types of Ca2+-binding sites. The high-affinity sites, Ka = (6.3 +/- 3.3) X 10(5) M-1 (mean +/- S.E.M.), bound 0.8 +/- 0.1 nmol of Ca2+/mg of protein and the low-affinity sites, Ka = (2.8 +/- 0.3) X 10(2) M-1, bound 33 +/- 3.5 nmol of Ca2+/mg of protein. The high-affinity site exhibited a selectivity for Ca2+, since high concentrations of competing bivalent cations were required to inhibit Ca2+ binding. The relative effectiveness of the competing cations (1 and 10 mM) for the high-affinity site was Mn2+ approximately equal to Sr2+ greater than Ba2+ greater than Mg2+. Data from the pH studies, treatment of the membranes with carbodi-imide and extraction of phospholipids with aqueous acetone and NH3 provided evidence that the low-affinity sites were primarily phospholipids and the high-affinity sites were either phosphoprotein or protein with associated phospholipid. Two possible roles for the high-affinity binding sites are suggested. Either high-affinity Ca2+ binding is involved with specific enzyme activities or Ca2+ transport across the luminal membrane occurs via a Ca2+ channel which contains a high-affinity Ca2+-specific binding site that may regulate the intracellular Ca2+ concentration and gating of the channel.

Animals↗
PubMed1982

The molecular nature of 1,25-(OH)2-D3-induced calcium-binding protein biosynthesis in the rat.

Exogenous 1,25-(OH)2-D3, administered to vitamin D-replete animals on a high calcium diet, induces biosynthesis of the duodenal, cytosolic calcium-binding protein (CaBP) in less than 2 h. This process can be blocked by simultaneously administered cycloheximide, but not by actinomycin D. In vitamin D-replete animals on a low Ca diet, on the other hand, 1,25-(OH)2-D3 administration leads to new CaBP synthesis only after about 7 h; this process can be blocked by actinomycin D. In vitamin D-deficient animals on a high calcium diet who have no CaBP, treatment with 1,25-(OH)2-D3 induces CaBP formation in congruent to 8 h; this process is known to be blocked by actinomycin D. Thus in D-replete animals on a low calcium diet and in D-deficient animals, CaBP biosynthesis proceeds by a transcriptional route, whereas in D-replete animals on a high calcium diet the rapid response appears to be posttranscriptional. This finding points to the possibility of a more rapid regulatory action of vitamin D than previously reported and how vitamin D might function in the D-replete state.

Animals↗
PubMed1982

Molecular and transport effects of 1,25-dihydroxyvitamin D3 in rat duodenum.

The saturable component of transmural calcium transport in rat duodenum is transcellular, dependent on vitamin D, and can be evaluated by in situ gut loops or everted sacs. Vitamin D action at the molecular level can be studied by analyzing the response in terms of calcium-binding protein (CaBP; Mr congruent to 9000) biosynthesis to exogenous 1,25-dihydroxyvitamin D3 (1,25-(OH)2-D3). In vitamin D-replete animals, the CaBP response occurs within 1 h of intraperitoneal injection when the animals have been fed a high-calcium diet (III), but in 7 h if the animals have been fed a low-calcium diet(I). The latter response appears to be transcriptional, whereas the former seems posttranscriptional. In vitamin D-deficient animals, exogenous 1,25-(OH)2-D3 evokes a CaBP response that occurs 7-8 h after treatment and is transcriptional in nature. Calcium uptake by isolated duodenal cells can be stimulated by prior in vivo treatment with 1,25-(OH)2-D3. Peak response times parallel those found with CaBP biosynthesis, i.e., 3 h in cells from vitamin D-replete animals fed diet III, 7 h in cells from vitamin D-replete animals fed diet I, and 12 h in cells from vitamin D-deficient animal. Cycloheximide treatment appears to inhibit these responses. Moreover, everted sacs from vitamin D-replete animals fed diets III and I show an early and a delayed transport response, respectively. Studies with brush border membrane vesicles prepared from rat duodenum have shown calcium uptake to be vitamin D-dependent. Part of this uptake involves binding to the inner aspect of the membrane and may involve a high-affinity CaBP. Thus a major component of the action of vitamin D in stimulating calcium transport appears to involve protein synthesis. The time and molecular nature of these responses depend on the calcium intake and vitamin D status of the animals. A model of calcium movement through the intestinal cell is included.

Animals↗