In vivo measurement of the absorption of strontium in the rumen and small intestine of sheep as an index of calcium absorption capacity.

In the present study, a method was developed for determining the alimentary tract Ca absorption capacity of ruminant animals by measuring the absorption rate of Sr after the administration of an oral dose of strontium chloride acting as a tracer analogue of Ca. A close correlation between the absorption rates of the two tracers was observed upon simultaneous administration of an oral dose of stable Sr and radioactive calcium (r 0·98). The Ca absorption capacity of the rumen and small intestine was determined separately by either directing the solution into the rumen or by diverting it into the post-ruminal tract by vasopressin-induced closure of the ruminoreticular groove. The animals were treated with 1α-hydroxyvitamin D3 administered via subcutaneously implanted mini-osmotic pumps. The effect of elevated plasma 1,25-dihydroxycholecalciferol concentrations on the Ca absorption capacity of the alimentary tract was then determined. An increased rate of Sr absorption was observed in both the rumen and small intestine of sheep after treatment, although it is unclear whether the rumen possesses the same vitamin D-dependent Ca absorption pathway as the small intestine.

Association between cadmium and calcium uptake and distribution during the moult cycle of female shore crabs, Carcinus maenas: an in vivo study.

Net influxes into the haemolymph and tissue distribution of 45Ca and 109Cd were studied in vivo in female Carcinus maenas at different moult stages. Net influxes of 45Ca and 109Cd from water were higher in postmoult (A and B) C. maenas than in C3- and C4-intermoult crabs and the net influx of calcium was higher in C3-intermoult crabs than in C4-intermoult crabs. The net influxes of 45Ca and 109Cd increased in postmoult C. maenas with decreasing external calcium concentrations at constant salinity. At all external calcium concentrations a significant correlation existed between 45Ca and 109Cd accumulated in the haemolymph of individual animals. In vivo exposure of postmoult C. maenas to external lanthanum decreased the 45Ca and 109Cd uptake rates to 30 and 10%, respectively, of the control values. About 30% of injected 109Cd were found in the midgut gland, 10-20% in the gills and only a few (1-2) percent was lost to the seawater 24 h after injection. No major variations in tissue distribution of 109Cd were observed between moult stages in these tissues. Premoult crabs retained more cadmium in the haemolymph 24 h after injection than other moult stages, and postmoult crabs retained more in muscle. Between 20 and 40% of the injected 45Ca were excreted to the water, while only a few percent of the injected 45Ca were found in the soft tissues 24 h after injection. Large moult stage variations, however, were observed in the tissue distribution of internalised 45Ca. This study demonstrates that cadmium and calcium uptakes are elevated in postmoult C. maenas. The results indicate that cadmium and calcium in this stage are taken up via Ca2+-channels located in the apical membrane of gill epithelium cells. When internalised, however, cadmium and calcium are metabolised in fundamentally different ways, determined by the chemical properties and biological significance of the two metals.

Augmented platelet calcium uptake in response to serotonin stimulation in patients with major depression measured using Mn2+ influx and 45Ca2+ uptake.

There is an augmented platelet intracellular calcium response to serotonin stimulation in major depression. The role that calcium influx has in this process is not known. The objective of this study was to determine platelet calcium influx in response to serotonin by two methods, Mn2+ influx and 45Ca2+ uptake, in order to observe if the uptake response to serotonin was augmented in major depression by comparing the response to normal controls. The use of the two methods of calcium influx showed that serotonin stimulates calcium uptake into platelets. Furthermore, patients with major depression have significantly augmented platelet calcium uptake in response to serotonin. The interesting finding was that calcium uptake into platelets is biphasic, occurring immediately and after five minutes. These results may support the two pool model for calcium oscillations within cells whereby extracellular calcium is needed for intracellular calcium release, and for replenishment of depleted stores once intracellular calcium is released.

Absorption of calcium as the carbonate and citrate salts, with some observations on method.

Calcium supplement use has increased and there is confusion about the relative absorbability of various sources. Absorbability of calcium from the carbonate and citrate salts was compared at 300 mg and 1000 mg calcium loads, ingested as part of a light breakfast meal. Absorption was measured at the high load both by tracer appearance in serum and by the absorptive increment in urinary calcium, and at the low load by the tracer method only. Subjects were 37 healthy adult men and women, studied as outpatients, and each tested on both salts at the same load. Mean tracer absorption (+/- SD) for both salts combined was 36.0% at the 300 mg load and 28.4% at the 1000 mg load. In both experiments the observed mean difference in absorption between salts was very small. By the tracer method the within-subject difference (carbonate less citrate) was +3.3% +/- 1.2% of the ingested dose (mean +/- SEM; P < 0.05) at the high load, and at the low load, 3.6% +/- 2.7% (NS). Combining the two experiments yielded zero difference between sources. By the urinary calcium increment method, the mean difference between salts at the 1000 mg load was 1.8 +/- 4.1 mg (NS). Side-by-side comparisons of the two methods revealed that the tracer method was 3 times more sensitive than the urinary increment method. We conclude that, when taken with food, calcium from the carbonate salt is fully as absorbable as from the citrate, and that the urinary increment method is not sufficiently sensitive to be useful in comparing sources in free-living subjects.

Cerebral calcium fluxes and calcium homeostasis in the rat: a minimal model.

Disturbance of calcium homeostasis and unregulated increase in intracellular calcium have been implicated in cell damage and cell death in the central nervous system in particular. To determine the specific pathway(s) of cerebral Ca transport of importance in a pathophysiological situation, we have measured long term Ca flux in brain in vivo in rat, and developed a kinetic model incorporating physiologically relevant pathways of cerebral Ca transport. 45Ca was injected into a tail vein in conscious rats. Plasma 45Ca was monitored up to 4 days post-injection and 45Ca uptake determined in samples of cerebrospinal fluid (CSF) and at several sites of brain at euthanasia. Uptake of the tracer by tissues peaked after 1 h, isotopic equilibration taking longer. The uptake at hippocampus was the highest. Computer simulation of the kinetics of the plasma, CSF and tissue data was performed using a compartmental model, which included two subcompartments (intra- and extra-cellular) and two pathways from plasma to the brain: directly across the blood-brain barrier and via CSF, which included a delay. The analysis based on this model enabled estimation of the fractional rates of transport of Ca to cerebral and noncerebral tissues across all the barriers of the model.

One-hour test for estimating intestinal absorption of calcium by using stable strontium as a marker.

Intestinal absorption of calcium is a relevant marker in a broad spectrum of diseases; however, its determination in clinical practice is difficult. Our aim was to design a simple test for this based on stable strontium (88Sr). The correlation between the intestinal absorption of simultaneously administered 45Ca and 88Sr was investigated in patients with various disorders of the bone and calcium metabolism. The area under the curve for the period 0-60 min after dosing (AUC0-60 in mmol.L-1.min), being a representative measure of intestinal absorption, showed a close correlation between both elements (r = 0.90, P < 0.001). Moreover, the measure of agreement in classifying the patients as low, intermediate, or high absorbers was high (kappa = 0.80). We conclude that a test based on measuring AUC0-60 of strontium is a fast and inexpensive way to obtain reliable information about the level of intestinal calcium absorption.

Intestinal malabsorption of 45calcium in young Gy mice, a second model for X-linked hypophosphatemia.

X-linked hypophosphatemia, a common metabolic bone disease in humans and mice (the Hyp and Gy mutations), is characterized by decreased plasma phosphate, decreased renal tubular reabsorption of phosphate, rickets, and osteomalacia. The question of whether intestinal malabsorption of calcium contributes to the bone disease is controversial. Intestinal absorption of 45Ca was studied in three different mouse colonies: Gy on B6C3H background, Hyp on B6C3H background, and Hyp on C57BL/6J background, all at 4 weeks of age. The duodenum was isolated by sutures, and 45Ca in a 150 mM NaCl and 2 mM CaCl2 solution at pH 7.2 was injected into the lumen. Absorption was measured by the amount of 45Ca remaining in the lumen and by the plasma isotope level. The Gy and Hyp mice of both sexes significantly malabsorbed 45Ca at 4 weeks of age compared to normal littermates. Following the 4 week study, intestinal absorption was measured at 2, 7-8, and 12 weeks of age in normal and Gy mice on the B6C3H background. At 2 and 7-8 weeks of age, the Gy males significantly malabsorbed 45Ca compared to their normal littermates. Serum 1,25-dihydroxyvitamin D was not significantly altered in Gy males at 4 weeks of age. This suggests the possibility of resistance of the intestine to stimulation. Malabsorption of calcium in young Gy and Hyp mice may exacerbate the low mineralization in their rachitic bone disease.

Interrelations of radiocalcium absorption tests and their clinical relevance.

Intestinal absorption of radiocalcium from an oral test dose was measured in 84 patients with various disorders of bone and calcium metabolism. In each subject, five different methods were used to assess intestinal absorption and the estimates obtained were compared inter- and intra-individually. The whole-body counting technique was chosen as reference method and as a basis for comparison of the other four estimates. Plasma levels of radiocalcium after oral administration seem to provide a simple and rapid test which may serve its purpose in various clinical situations. Fractional intestinal calcium absorption can be assessed equally well by the whole-body counting technique, the double-isotope method or the double-isotope deconvolution technique, since these methods yield comparable results. The deconvolution technique additionally provides a quantitative description of the absorptive process of calcium with respect to time.

Changes in plasma calcium and in radiocalcium kinetics after termination of 5-week infusions of synthetic parathyroid peptide in dogs.

Nine dogs were infused at constant rates with the synthetic parathyroid peptide hPTH 1-34 (initially sc) to produce consistent hypercalcaemia. Over the final week, the infusions were iv. Radioisotopic tracers were injected iv 30 days (5 dogs) and 2 days (9 dogs) before the infusions were suddenly terminated. In 5 dogs, complete urine collections were obtained via a bladder catheter over 8 h beginning 2 h before stopping the infusions. Cessation of treatment caused small rises in the urinary Ca: creatinine ratio. Plasma calcium levels fell by a mean of 0.44 mmol/l, of which total urine calcium excretion only accounted for 55%. Immediately after the PTH infusions were stopped, consistent but transient increases were seen in the ratio of 'new' 47Ca to 'old' 45Ca label, suggesting inflow of 40Ca of high 47Ca specific activity from a fairly rapidly exchangeable bone pool. These data confirm and extend previous evidence that the immediate response of the calcium equilibrium between bone and bloodstream to rapid changes in plasma PTH concentrations in the supra-physiological range is paradoxical relative to the classical later response.

[Biokinetics of osteotropic radiopharmaceuticals in metabolic osteopathy--comparison of 47Ca and 99mTc-methylene-diphosphonate (MDP)]. / Biokinetik osteotroper Radiopharmaka bei metabolischen Osteopathien--Vergleich von 47Ca und 99mTc-Methylen-Diphosphonat (MDP).

Plasma clearance and osseous accumulation rates of 99mTc methylene diphosphonate (MDP) in the lumbar spine were measured in 11 patients with osteoporosis (OP), 7 patients with hyperparathyroidism (HPT), 4 patients with osteomalacia (OM) and in 3 patients (N) who were studied to exclude metabolic bone disease. The findings in 19 patients were compared with the results of 47Ca kinetics. The plasma elimination of 99mTc-MDP during the first hour after application was normal in almost all the patients. The 99mTc-MDP accumulation rates in the lumbar spine were raised in patients with HPT and OM (p less than or equal to 0.01) and normal in patients with OP and N (p greater than 0.05). 47Ca kinetics were disturbed in most of the patients with metabolic bone disease, with minimal deviations in OP. The comparison of 99mTc-MDP accumulation rates with the results of 47Ca kinetics revealed significant correlations with exchangeable bone and soft tissue calcium. The correlations with total calcium turnover and calcium accretion were poor. Only half of the patients had equal results of 99mTc-MDP accumulation rates and bone calcium accretion rates. It is concluded that the 99mTc-MDP uptake by bone is an index of bone metabolism presumably of the organic matrix, whereas 47Ca kinetics represent the mineral metabolism of bone.

[Decrease of intestinal absorption of 47-calcium in chronic alcoholism]. / Diminution de l'absorption intestinale de 47-calcium dans l'alcoolisme chronique.

Intestinal 47-calcium absorption has been studied in 34 chronic alcoholics, 17 of whom were cirrhotics (group A) and 17 non-cirrhotics (group B). These patients were compared with 44 normal subjects (group C). In group C, the 47Ca 2 h plasma % of the dose showed a significant negative correlation to the total body weight (p less than 0.001) and a positive correlation with the serum albumin (p less than 0.05). The mean intestinal absorption of 47Ca expressed as 2 h plasma % of the dose multiplied by total body weight was 131 +/- SD 52 in group A and 136 +/- SD 71 in group B. These two means are significantly low (p less than 0.001 and p less than 0.002 respectively) in relation to that found in group C (168 +/- SD 32). These results suggest that intestinal calcium absorption is diminished in chronic alcoholism even in the absence of hepatic cirrhosis.

Intestinal absorption of 47Ca in elderly patients with osteoporosis, Paget's disease and osteomalacia. Effects of calcitonin, oestrogen and vitamin D2.

The intestinal absorption of 47Ca was studied in elderly patients. A standard dose of 10 muCi of 47Ca was given orally. The radioactivity was measured in the plasma, and expressed as percentage of the administered dose per litre plasma. As a control group served 12 patients aged 60-80 years, hospitalized for observation for various reasons, receiving no medical treatment and not suffering from any known metabolic bone diseases or other metabolic pathological conditions. Results of kinetic curves demonstrate in elderly patients a decreased absorption with maximum specific activity in plasma reached at 120 min, when compared to data from the literature referring to a group of young people with a mean age of 35 years. Oestrogen treatment, given as ethinyl oestradiol 10 mug once daily per os for 10 days proved to increase 47Ca absorption as was demonstrated in 2 patients with osteoporosis. The effect of calcitonin (160 MRC units given 45 min before the test) on calcium absorption, in 5 patients with Paget's disease or osteoporosis appears as biphasic: in the first hour depressing calcium absorption and then in the second and third hours increasing the absorption, suggesting a hyperparathyroid state secondary to the calcitonin effect. The vitamin D2 treatment proved to increase calcium absorption.

[Modeling calcium-45 metabolism in tissue, taking into account the structure and hemodynamics of the capillary system]. / Modelirovanie obmena kal'tsiia-45 v tkani, uchityvaiushchee strukturu i gemodinamiku kapilliarnoi sistemy

The accumulation of Ca-45 in the tissues and the degree of its desorption during the perfusion in the sufficiently extensive limits does not depend upon the rate of the perfused solution and is the function of the perfused solution volume. Taking into account strong dependence of the volume rate of filling the capillaries with the solution upon the capilliary radii (r-4) one may come to the conclusion that Ca-45 saturation of the paracapillary spaces in the wide capillaries occurs much sooner than in the narrow ones. As a result of developing these postulates, we have got the formulae which associates these two functions. It is shown that according to the theory the accumulation and desorption processes are interrelated and may be calculated.