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A dialysate containing a calcium concentration of 1.75 mmol/L has been the standard in CAPD for a long time. This concentration was chosen to achieve a positive calcium balance to suppress hyperparathyroidism. In the measurement of peritoneal calcium mass transfer, conflicting results have been published, with positive and negative calcium balances reported. These differences have been explained by differences in the filtration rate, and a negative correlation between the filtration rate and the peritoneal calcium mass transfer can be found. Whereas nearly all patients in this study had a negative calcium balance using a glucose solution of 3.86%, a wide variation was found for the 1.36% glucose solution. There were several patients who had a positive calcium balance despite a positive filtration rate. The explanation for this finding lay in differences in serum concentrations of calcium, and especially differences in the size of the total exchangeable calcium pool that contains the plasma calcium compartment. A negative correlation between peritoneal calcium balance and the size of the total exchangeable calcium pool could be demonstrated. This finding may explain the differences in the peritoneal calcium flux reported in the literature. As an enlargement of the exchangeable calcium pool correlates with the progression of vascular calcification, therapeutic efforts should be directed toward prevention of an enlargement of this pool.

Calcium balances performed on 519 individuals from birth to 30 years of age, derived from 34 published reports, were pooled by age group and the relationship between intake and balance for each group was compared at both extremes of the intake range. At all ages, from infancy through the young adult years, balance values tended to flatten and become constant at higher intakes, while at lower intakes balance was invariably highly correlated with intake. Threshold intakes and balances were estimated by fitting the data to a two-component, split, linear-regression model. The threshold values at which balance no longer rose with intake exceeded the US recommended dietary allowances for calcium for all the age groups concerned.

Twelve adult female patients and 16 children who had undergone augmentation cystoplasty at least 2 years previously were studied to assess calcium balance and skeletal mineralisation. The serum and 24-h urinary calcium levels were measured and arterial blood gas analysis was performed in all patients. In children, skeletal mineralisation was assessed by serial study of their growth charts, comparing their growth centiles before and after cystoplasty. In adults, skeletal mineralisation was assessed by dual photon absorptiometry (DPA). As previously reported, all patients had a metabolic acidosis, usually with respiratory compensation. Serum and 24-h urinary calcium levels were all within the normal range. Growth charts of the 6 children with colocystoplasties showed an average of 20% reduction in growth potential in 3 of them. Growth charts in the 10 children with ileocystoplasties did not show any change in growth pattern. DPA bone scans in adults were all normal. These results suggest that if calcium is mobilised from bone in patients with a cystoplasty as a result of the metabolic acidosis, then it is reabsorbed from the bladder by the gut segment after an ileocystoplasty; colonic segments are less efficient than ileal segments, however, so that after a colocystoplasty skeletal demineralisation or a reduction in growth potential is more likely.

Calcium flux and mode of uptake were investigated in an underground dwelling mole-rat, Cryptomys damarensis, fed diets of varying Ca content. The amount of dietary Ca positively influenced the amounts ingested, absorbed and retained. The linear relationship between ingested and absorbed Ca was significantly (P less than 0.001) correlated, implying that this process is nonsaturable. When mole-rats were fed a diet low in Ca, apparent fractional absorption of Ca was high (85.88%). This increased still further when the diet was changed to a food of greater Ca content (96.13%, carrots; 96.97%, gemsbok cucumber). Mineral homeostasis is regulated at the intestinal level in most mammals. Regardless of dietary Ca content, uptake of 45Ca (examined via the everted gut sac technique) was passive, confirming that absorption is via a nonsaturable process. Plasma Ca concentrations were not tightly regulated, yet when fed the diet with the highest Ca content, mole-rats were not hypercalcemic. Regardless of diets, Ca apparent fractional retention was positive, and approached physiological maxima (greater than 97%). Cryptomys damarensis, in using highly efficient modes of mineral uptake and retention, is therefore capable of fully exploiting the limited food resources of their arid ecotope.

1. An equivalent circuit model of the R15 bursting neuron in Aplysia has been combined with a fluid compartment model, resulting in a model that incorporates descriptions of most of the membrane ion channels that are known to exist in the somata of R15, as well as providing a Ca2+ balance on the cell. 2. A voltage-activated, calcium-inactivated Ca2+ current (denoted the slow inward current ISI) was sufficient to produce bursting activity without invoking any other calcium-dependent currents (such as a nonspecific cation current, INS, or a calcium-activated K+ current, IK,Ca). Furthermore, many characteristics of a typical R15 burst could be simulated, such as a parabolic variation in interspike interval, the depolarizing afterpotential (DAP), and the progressive decrease in the undershoots of spikes during a burst. 3. The dynamic activity of R15 was analyzed by separately characterizing two different temporal domains; the fast dynamics associated with action potentials and the slow dynamics associated with low-amplitude oscillations lasting tens of seconds ("slow waves"). The slow dynamics were isolated by setting the Na+ conductance (gNa) to zero and then studied by the use of a system of equations reduced to two variables: intracellular concentration of Ca2+ and membrane potential. The fixed point of the system was located at the intersection of the nullclines for these two variables. A stability analysis of the fixed point was then used to determine whether a given set of parameters would produce slow-wave activity. 4. If the reduced model predicted slow-wave oscillations for a given set of parameters with gNa set to zero, then bursting activity was observed for the same set of parameters in the full model with gNa reset to its control value. However, for certain sets of parameters with gNa at its usual value, the full model exhibited bursting activity because of a slow oscillation produced by the activation of INS by action potentials. This oscillation resulted from an interaction between the fast and slow dynamics that the reduced model alone could not predict and was not observed when gNa was subsequently set to zero. If gNS was also set to zero, this discrepancy disappeared.(ABSTRACT TRUNCATED AT 400 WORDS)

The nature and mechanism of calcium complexation with human serum components in the presence of silicone rubber were assessed in in vitro model experiments. Silicone rubber samples were incubated for 67 h in serum of both physiologic calcium concentrations and induced hypercalcemic levels. Physiologic calcium incubation decreased the intrinsic and nth binding site association constants by factors of 2 and 4, respectively, from initial serum values. Incubation with silicone rubber did not change the association constants. Hypercalcemia incubation lowered the intrinsic and nth binding site association constants by 39 and 61%, respectively. Polymer incubation increased the intrinsic association constant and decreased the number of binding sites by a factor of 2. With initial binding site association constants unperturbed by incubation and Hill coefficients equivalent to 1, complexation was non-cooperative and binding sites were considered to be identical and independent. Both Scatchard and Hill plots show nonlinearity for the polymer incubation case giving two distinct linear regions. This is indicative of cooperative binding for incubation with polymer; the Hill coefficient for the physiologic calcium concentration range was 0.97, while the coefficient for the hypercalcemic calcium range was 6.

We suggested that calcium may be an important determinant of peak bone mass. For further elucidation, calcium balances in adolescent females with different calcium intakes (270-1637 mg/d), and a 2-y intervention study of calcium supplementation were performed. Hereditary influences on bone status were also evaluated by comparing subjects' and parents' bone mass. The main determinant of calcium balance was calcium intake; net calcium absorption increased with intake and urinary calcium did not change. Adolescent females retained 200-500 mg Ca/d, suggesting that inadequate calcium intake may translate into inadequate calcium retention and a reduction in peak bone mass. There was a more pronounced increase in bone mass over time in the calcium-supplemented group (1640 mg Ca/d) than in the control group (750 mg Ca/d), but the differences between bone mass measurements were not statistically significant, possibly because of a type II error. By the age of 16 y daughters had accumulated 90-97% of the bone mass of their premenopausal mothers.

In postmenopausal osteoporotics, malabsorption of calcium is associated with reduced levels of serum 1,25-dihydroxyvitamin D. Metabolic studies have shown that calcium absorption can be normalized and calcium balance improved after administration of oral doses of synthetic 1,25-dihydroxyvitamin D3 (Rocaltrol) 0.25 micrograms twice daily. Further studies performed at two centers compared the effect of Rocaltrol 0.25 micrograms twice daily versus placebo on vertebral fracture rates in osteoporotics. A significant reduction in vertebral fracture rates was seen at the end of 1 year. Those patients who continued on Rocaltrol for a second and third year showed a progressive decrease in vertebral fractures. Rocaltrol, administered at a dose of 0.25 micrograms twice daily, seldom causes hypercalcuria or hypercalcemia in osteoporotic patients on a typical calcium intake of 700 to 800 mg/d. Careful measurements of renal function over a period of 3 years in patients treated with Rocaltrol, 0.25 micrograms twice daily, showed no deterioration in renal function. These data suggest that 1,25-dihydroxyvitamin D3 is a useful therapy in the management of patients with postmenopausal osteoporosis, particularly those who have malabsorption of calcium. We found that it improves calcium balance, reduces the vertebral fracture rate, and is safe to use provided that the dietary calcium is monitored and does not exceed 800 mg/d.

The effects of sulfur-containing amino acids (SAA) and potassium (K) on urinary excretion and retention of calcium (Ca) of 27 young Japanese women were studied. A basal diet low in protein level (50 g per day) was fortified by meat or soy protein isolate (SPI) to a protein level of 100 g per day, and effects of addition of apple to these high protein diets, and addition of SAA and/or potassium (K) to the high SPI diet, especially on urinary Ca excretion, were studied. The addition of meat which increased protein intake to 100 g caused the increase in apparent absorption and urinary excretion of Ca with increased excretion of urinary sulfur (S), phosphate, ammonia, and titratable acids (TA), whereas addition of SPI did not. The addition of apple to high meat diet decreased absorption and urinary excretion of Ca. Urinary Ca, S, K, ammonia, and TA excretion increased by the addition of SAA to high SPI diet in a manner similar to the meat diet. Consequently, SAA-supplemented diet had a significantly negative effect on Ca retention. In SPI+SAA,K diet period, urinary K excretion markedly increased, and increments in urinary Ca, ammonia, and TA excretion were reversed. These changes observed in SPI+SAA, K diet period were similar to those by adding apple to meat diet without any effect on Ca absorption. The results suggest that the hypercalciuria induced by high meat diet is mainly caused by high content of SAA and may be reversed by the ingestion of K-rich foodstuffs, and soy protein does not induce hypercalciuria because of it contains less SAA than animal protein.

The response of calciotropic hormones and bone turnover to exercise and immobilization was examined by the measurement of calcium balance, bone turnover indexes, levels of parathyroid hormone, nephrogenous adenosine 3',5'-cyclic monophosphate (cAMP), and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] weekly for 6 wk in three groups of rats: control, exercise trained, and immobilized. Early in the experiment, increases were observed in excretion of urinary calcium, hydroxyproline, and in serum alkaline phosphatase after both exercise and immobilization. It was not until the latter part of the experimental period that changes were observed in nephrogenous cAMP and intestinal absorption efficiency of calcium. In the fasting state, the exercise group had a drop in serum calcium and phosphate and a rise in nephrogenous cAMP and serum 1,25(OH)2D3 compared with the control group. The exercised animals experienced an increase in bone mass, whereas the immobilized animals had a decline in bone mass. Thus exercise stimulates bone growth, resulting in an increased demand for minerals that is satisfied by an increase in serum 1,25(OH)2D3 levels and increased intestinal absorption of calcium. The increase in calcium absorption suppresses parathyroid hormone production (nephrogenous cAMP) in the exercised animal. Immobilization resulted in increased bone resorption that suppressed parathyroid hormone, nephrogenous cAMP, and the intestinal absorption of calcium.

Rats, age 28 days, experiencing tail suspension in modified metabolic cages for 1, 2, and 3 wk were compared with littermate controls. Food and water consumption, urinary and fecal Ca excretion, and serum Ca were measured; hearts, fore- and hindlimb bones, skulls, and mandibles were removed for determination of wet, dry, and ash weights and Ca concentration and for histological examination. Weight gain and Ca intake and excretion were the same for both groups; both displayed net Ca gain. Suspended rats had significantly lower wet, dry, and ash weights of femora and tibiae. Dry weights of the humeri and radii/ulnae were moderately higher, and the skull and mandible dry and ash weights were significantly higher in suspended than in control rats. Cortical thickness of the femur, but not humerus, was less in suspended rats. The data are consistent with the hypothesis that bone growth is influenced by the cardiovascular changes associated with tail suspension.

Furosemide, a potent natriuretic agent, is well known to increase urinary calcium excretion. We study the effects of long term administration of furosemide on the calcium balance, renal function and histopathological changes of the kidneys and the parathyroid glands in the rat. Furosemide (20 mg/kg) was administered 3-4 times per week for 62 weeks intraperitoneally in 10 male rats. The same volume of normal saline was administered intraperitoneally in 9 male rats as control. All were given with standard diet (CE-2) and deionized water. While urinary calcium and creatinine were measured every 1-4 weeks, serum calcium and creatinine were measured in the first week and at the end of examination. 24 hours urinary excretion of calcium was elevated to two to three folds (a significant increase over the control: p less than 0.01) after the furosemide loading, though serum calcium and creatinine levels remained as in control. Despite a marked hypercalciuria in the furosemide loaded rats, there was no evidence of stone formation in the kidney or in the urinary tract. On histopathological examination renal parenchyma showed some pyelonephritic changes but without evidence of crystal formation, while no significant change was noted in the parathyroid glands. Based on these data we concluded that in our model, 1) there was a significant calcium loss in the absence of any change in the serum calcium, but 2) this hypercalciuria alone was not lithogenic, and 3) parathyroid glands showed no discernible secondary morphological changes.(ABSTRACT TRUNCATED AT 250 WORDS)