Effect of hypophysectomy on calcium transport by rat duodenum

To examine the effect of hypophysectomy on intestinal calcium absorption, studies were performed on immature rats 7, 14, and 21 days after hypophysectomy. Duodenal calcium transport was measured in vitro utilizing everted gut sacs and in vivo by a luminal perfusion technique. Hypophysectomy produced no differences in the ability of everted gut sacs to transport calcium. Similarly, when in vivo transport data were expressed on the basis of intestinal length, no significant differences were noted. However, when transport data were expressed on the basis of mucosal weight, increases in absorption and lumen-to-plasma fluxes were apparent in hypophysectomized animals. No differences were seen in plasma-to-lumen fluxes. The results indicate that when the transport data are corrected for mass of intestinal mucosa, the duodenum from hypophysectomized animals absorbs calcium more avidly due to an increase in lumen-to-plasma flux.     

The effect of calcium restriction in the diet of calcium transport in rat small intestine

1. The everted-sac technique has been used to study the time-dependent effect of low-calcium diet on calcium active transport along rat small intestine. 2. In animals maintained on standard diet active translocation of calcium was limited to proximal 10 cm of the intestine. 3. In response to calcium restriction, calcium transport in duodenum was highly stimulated after 3 days, then gradually declined and after 28 days almost disappeared. In proximal jejunum it was the highest between 7 and 21 days. In distal ileum, the transport appeared after 3 days and increased progressively until 21 days, but markedly decreased at the 28-th day. The normal pattern of calcium transport was reestablished on refeeding the animals with standard diet.     

New findings on the mechanism and regulation of intestinal calcium transport

Only in the duodenum and in the colon calcium is absorbed by a cellular 1,25 alpha-Vitamin D3-dependent transport mechanism. Calcium absorption is highest in the proximal large intestine, about ten times higher than in the duodenum or in the descending colon. 1,25 alpha-Vitamin D3 stimulates calcium transport by genomic (slow effect: synthesis of cytosolic calcium binding protein CabP and basolateral Ca-ATPase) and non-genomic action (rapid effect: transcaltachyia, liponomic effect at the brush border membrane). CabP-dependent translocation across the cytosol is thought to be rate limiting step of cellular calcium transport. However, only about 50% of calcium absorption is cellular mediated but the same amount of calcium convectively is absorbed by transepithelial water flow across the paracellular pathway (solvent drag effect). 1,25 alpha-Vitamin D3 not only activates cellular calcium absorption but also increases paracellular permeability for calcium by an unknown mechanism. However, essential steps in the cascade from the interaction of 1,25 alpha-Vitamin D3 with the specific receptor over the regulation of the synthesis of calcium binding and transporting proteins to the induction of cellular calcium transport are not as yet clearly understood. The exact feedback mechanism of synchronized calcium transport across the distinct subcellular compartments seems also to be resolved. Cellular calcium transport is not found in the jejunum or in the ileum, what can be explained by the absence of specific 1,25 alpha-Vitamin D3-dependent carrier systems in these segments. On the other hand calcium is secreted across the jejunum and ileum by an anomalous solvent drag effect. Hence, intestinal calcium metabolism seems to underlie an eneteroenteral circuit: 1,25 alpha-Vitamin D3-controlled cellular calcium absorption across the duodenum is followed by paracellular calcium secretion across the jejunum and ileum. The carrier in the proximal colon which works at the optimal level already under normal nutritional condition could be of physiological importance for the reclamation of unabsorbed dietary calcium and for the reabsorption of calcium that is secreted across the distal small intestine. Under certain pathophysiological conditions, i.e. malabsorption in proximal segments or malnutrition, calcium in addition may be conserved by the 1,25 alpha-Vitamin D3-sensitive carrier in the descending colon.(ABSTRACT TRUNCATED AT 400 WORDS)     

Intestinal transport of calcium in rat biliary cirrhosis

The characteristics of intestinal calcium transport in chronic cholestasis remain largely unknown. Using an experimental model of biliary cirrhosis in the rat, we aimed to investigate changes in calcium transport at the jejunal and ileal levels. Two methods were used: 1) uptake of 45Ca in brush border membrane vesicles and 2) measurements of transepithelial fluxes of calcium in Ussing chambers. Thirty days postsurgery, cholestatic rats presented biliary cirrhosis, with normal growth, normal daily energy, and calcium intakes, but had depressed circulating levels of 25-(OH)-vitamin D2 and 1,25-(OH)-vitamin D3. Compared with sham-operated controls, 45Ca uptake ([Ca2+] = 0.03 mmol) measured in vesicles from cholestatic rats was decreased by 3-fold in the duodenojejunum, in concordance with a lower content in brush border membrane calmodulin. Other changes in brush border membrane composition included decreases in structural proteins, microvillous enzymes, and in triglyceride content. Transepithelial fluxes of calcium measured in the ileum ([Ca2+] = 1.2 mmol) revealed in controls a net basal secretion flux (Jnet = -30.4 +/- 8.1 mmol.h-1.cm-2) that was reduced by 3-fold (p < 0.05) in vitamin D-deficient rats (Jnet = -10.4 +/- 4.8 mmol.h-1.cm-2). In response to 25-(OH)-vitamin D2 treatment, calcium uptake rates increased by 40% in the jejunum, whereas in the ileum, the secretion flux returned to basal control levels. Oral administration of taurocholate or tauroursodeoxycholate (50 mmol) depressed almost completely calcium uptake capacity in the duodenojejunum. By complexing free calcium, tauroconjugated bile acids inhibited in vitro calcium uptake proportionally to their concentration in the medium (0-40 mmol). Our data indicate that, in rat biliary cirrhosis, transport capacity of calcium in the duodenojejunum is markedly reduced in association with vitamin D deficiency and alterations in brush border membrane composition.     

Effect of nicotinic acid on cholera-induced fluid movement and unidirectional sodium fluxes in rabbit jejunum

Cholera toxin produces intestinal secretion and elevation of intestinal cyclic AMP. Nicotinic acid has been shown to prevent these responses. The effect of nicotinic acid on cholera toxin-induced secretion could be caused by decreased plasma-to-lumen flux, increased lumen-to-plasma flux, or a combination of both. The purpose of this study was to define the effects of nicotinic acid on net fluid movement and unidirectional sodium fluxes in rabbit jejunal loops exposed to cholera toxin. In the untreated animals receiving no nicotinic acid, the cholera toxin-exposed loops secreted 0.91 ml/cm/4h above the control loops receiving no cholera toxin (p < 0.01). On the other hand, pretreatment with 100 mg/kg nicotinic acid caused a striking decrease in secretion in the cholera toxin loop, so that the cholera toxin loop was not significantly different from the control loop. Unidirectional sodium fluxes in untreated animals showed that cholera toxin caused an increase in the plasma-to-lumen flux and a decrease in the lumen-to-plasma flux. Both effects were abolished by pretreating the animals with nicotinic acid. These studies indicate that nicotinic acid prevents cholera toxin-induced secretion by restoring the unidirectional fluxes to control levels.     

Regional gastrointestinal absorption of ranitidine in the rat

PURPOSE: Ranitidine absorption from isolated segments of rat small intestine (duodenum, midgut, and terminal ileum) was investigated to examine the influence of pH and 50% bile, and to determine if ranitidine is absorbed preferentially from a specific region. METHODS: Ranitidine (50 mg/kg) was administered into each segment in pH 5 or pH 7 buffer, or in 50% bile. Venous blood was collected at various times for 40 min from the right jugular vein. RESULTS: When ranitidine was administered in pH 7 buffer or in 50% bile, Cmax and AUC0-40 were significantly greater after administration into the terminal ileum compared to the duodenum and midgut. AUC0-40 was significantly greater when ranitidine was administered in pH 5 buffer or in 50% bile into the duodenum compared to the midgut. Cmax was significantly different between administration into the duodenum and midgut only when ranitidine was administered in 50% bile. Ranitidine administration in pH 5 buffer significantly decreased AUC0-40 and Cmax after administration into the midgut, and AUC0-40 after administration into the terminal ileum compared to administration with pH 7 buffer or in 50% bile. Bile had no significant effect on AUC0-40 after ranitidine administration into the duodenum and midgut compared to administration in pH 7 buffer. However, bile significantly increased AUC0-40 and Cmax after ranitidine administration into the terminal ileum compared to administration with pH 7 and pH 5 buffer. CONCLUSIONS: Results suggest that ranitidine is absorbed from the entire small intestine. However, the terminal ileum is the optimal site of gastrointestinal absorption. Furthermore, bile enhances ranitidine absorption from the terminal ileum.     

Stimulation of ileal transport of calcium by sorbitol in in situ perfused loop in rats

OBJECTIVES: The aim of this study was to study the effect of sorbitol on sodium, water and calcium fluxes in rat ileum in situ perfused loop. METHODS: Net water, sodium and calcium fluxes, and one-way calcium fluxes were measured in situ in a perfused rat ileal loop in the presence of varying concentrations of sorbital. RESULTS: High concentrations of sorbitol in perfused ileal solution induced a decrease of sodium and water fluxes and a concomitant increase of lumen to mucosa calcium flux associated with an increase of net calcium flux, using a solution containing either 8.0 or 1.25 mM calcium. These effects were independent of absolute initial values of water and sodium fluxes. They were observed in the presence of 25 mM glucose, 10 mM theophyllin or after treatment of rats with dexamethasone. CONCLUSION: These effects of sorbitol on calcium flux are not compatible with a stimulation of paracellular pathway. By contrast, they can be explained by a stimulation of transcellular calcium pathway in ileum associated with the hyperpolarisation of the cells induced by the decrease of luminal sodium concentration necessary in the presence of sorbitol to maintain unchanged osmolarity of perfusate.     

MRI of pseudoaneurysm of a brachial venous coronary bypass graft

We studied the following responses to restriction of dietary calcium and phosphorus in the growing hamster: (i) serum concentrations of calcium, inorganic phosphorus, magnesium, and vitamin D metabolites; and (ii) calcium transport by ileum. Diets fed were normal calcium with normal or low phosphorus or low calcium with normal or low phosphorus. We found serum 1 alpha,25-dihydroxycalciferol (1,25-[OH]2D) concentration did not differ significantly among the diet groups. Calcium absorption, measured as serosal/mucosal calcium concentration ratio produced by everted ileal sac, was greater in the low calcium, normal phosphorous group than in all other groups. The other groups did not differ from one another in calcium absorption. Feeding the low calcium, normal phosphorus diet increased inorganic phosphorus and magnesium but decreased calcium concentration in serum in comparison with the three other diets. Both low phosphorus diets were without effect on serum calcium, but the low calcium, low phosphorus diet increased serum inorganic phosphorus and magnesium above that of the normal calcium, low phosphorus diet. Ileal calcium absorption in hamster (i) was independent of serum 1,25-(OH)2D concentration; (ii) increased in response to low dietary calcium if dietary phosphorus was normal; and (iii) was independent of dietary calcium, if dietary phosphorus was low. Despite increased calcium absorption, serum calcium was decreased in the low calcium-normal phosphorus group as compared with all other groups. Feeding low calcium diets increased serum inorganic phosphorus and magnesium as compared with feeding the corresponding normal calcium diets (i.e., independently of whether dietary phosphorus content was normal or low). These studies demonstrate that the interrelationships between calcium absorption and vitamin D and mineral metabolism in hamster differ from other mammals.     

Yolk utilisation in the newly hatched poult

1. Routes of yolk utilisation and some aspects of intestinal digestion and absorption were determined in the hatching poult and compared to the chick. 2. Transfer from yolk to blood was observed pre-hatch and up to 72 h post-hatch. From hatch the transport pattern was similar to the chick. 3. Transport from the yolk sac into the intestine via the yolk stalk was observed up to 120 h after hatch. Secretion was initially to the proximal ileum and reflux occurred, transporting contents to the proximal small intestine and gizzard. Antiperistaltic movements increased after hatch and secretion continued for longer post-hatch than in the chick. 4. In situ uptake of glucose per unit of duodenum did not change with age, whereas uptake of methionine and oleic acid decreased with age. In contrast, in the chick glucose and methionine uptake capacity increased slightly between hatch and 7 d. 5. The lipid class distribution of intestinal contents resembled that of yolk close to hatch, however, some lipolysis was observed in the duodenum. With age the proportion of free fatty acids increased rapidly, first in the duodenum then in the ileum and finally in the caecum. Yolk in the distal small intestine close to hatch did not appear to be utilised.     

The role of the facilitating cell in the establishment of donor chimerism and transplantation tolerance

Guanylin, structurally related to the heat-stable enterotoxin of E. coli, is a 15-amino-acid peptide isolated from rat small intestine. We investigated the morphological effects of an intravenous injection of rat and human guanylin upon the rat intestine. Various doses of rat guanylin were injected intravenously in anesthetized rats. After 5, 10 and 30 min, rats were killed by intracardiac perfusion with aldehyde fixative, and specimens of the intestine were then prepared for light and electron microscopy. Intravenously injected rat guanylin rapidly induced mucus secretion from crypt goblet cells in the duodenum. About half of the crypt goblet cells secreted mucous granules by compound exocytosis within 5 min. The villus goblet cells, in contrast, were not sensitive to guanylin. Goblet cells in the jejunum were less responsive than those in the duodenum. This secretory response was rare in the ileum and colon. Human guanylin produced similar results. The mucus secretion induced by guanylin was inhibited by a prior-injection of atropine, but not hexamethonium. Moreover, guanylin induced intense edema in the mucosa and submucosa of the small intestine 5 min after the injection, which disappeared after 30 min. A prior-injection of atropine did not block the appearance of edema. In conclusion, the intravenous injection of guanylin induces two phenomena related to water movement: (1) compound exocytosis of mucous granules from crypt goblet cells in the rat duodenum and jejunum; (2) perineural, inter-epithelial and intra-epithelial edema in the rat small intestine.     

Morphological appearance of fat in the epithelial cells of different portions of the intestines in mice

Absorption of administered fat in the small intestine of mice as judged morphologically in semi-thin sections demonstrates a proximal to distal gradient, being greatest in the mid-jejunal area, but less in the duodenum and ileum. The criterion of the amount and size of fat droplets in intestinal epithelial cells, however, does not necessarily give a reliable indication of the efficiency of fat absorption in the different segments of the intestine.     

Phosphate transport in pig proximal small intestines during postnatal development: lack of modulation by calcitriol

The role of calcitriol in the intestinal absorption of inorganic phosphate (Pi) during postnatal development was studied in newborn [<1 week postpartum (pp)], suckling (3-4 weeks pp), and weaned (>6 weeks pp) control piglets (con) and piglets suffering from inherited calcitriol deficiency (def). In addition, a number of def piglets were treated with vitamin D3 (def-D3). Regardless of age, plasma calcitriol concentrations in def piglets were unphysiologically low (16-21 pg/ml) and differed significantly from those in respective con animals (60-69 pg/ml) and vitamin D3-treated def piglets (50-56 pg/ml). However, newborn and suckling def piglets had normal Ca (approximately 3.0 mmol/liter) and Pi (approximately 2.8 mmol/liter) plasma levels. Def piglets became hypocalcemic (1.9 mmol/liter) and hypophosphatemic (1.9 mmol/liter) between 4-6 weeks pp. Treatment with vitamin D3 significantly increased plasma Ca (3.2 mmol/liter) and Pi (2.7 mmol/liter) levels in weaned def animals. Regardless of calcitriol status, net Pi flux rates (active Pi absorption, as determined with the in vitro Ussing-chamber technique) from the upper small intestines was maximal at birth [170-224 nmol/(cm2 x h)] and decreased by approximately 80% during the first week of life before remaining constant [30-50 nmol/(cm2 x h)] during the following development. In weaned def piglets, net Pi flux rates were significantly lower by about 80% compared with those in con animals. Treatment of def piglets with vitamin D3 had no effect in newborn and suckling animals but reconstituted net Pi flux rates to normal values at weaning age. Age-dependent and calcitriol-mediated changes in net Pi flux rates were paralleled by respective maximum velocity values of Na+-dependent Pi uptake across the brush border membrane of the enterocytes (newborn piglets, 1.9-2.2 nmol/(mg protein 10 sec); suckling piglets, 0.4-0.6 nmol/(mg protein x 10 sec); weaned piglets, 0.7, 0.3, and 0.7 nmol/(mg protein x 10 sec) in con, def, and def-D3 animals, respectively). These findings suggest that the apical Pi uptake represents the major rate-limiting step of the overall transepithelial Pi transport. At weaning, Na+/Pi transport across the intestinal brush-border membrane is clearly stimulated by calcitriol, but no significant effects of age or calcitriol on the Km values (0.5-0.7 mmol/liter) were observed. In conclusion, our findings reveal calcitriol-independent mechanisms for active intestinal Pi absorption during the neonatal and suckling periods. The onset of the classical calcitriol-dependent mechanism for active intestinal Pi absorption does not occur until weaning.     

Effect of hydrocortisone on total body calcium in rats

Administration of 5 mg. of hydrocortisone acetate to rats every other day for 2 weeks resulted in growth retardation and weight loss as indicated by body weights of experimental animals, which averaged 33 per cent lower than those of the controls, and a significant decrease in the length of the tibiae and femurs (p less than 0.01 for treated vs controls). However, despite the smaller size of the treated animals, the values for total body calcium (TBCa) and the calcium in the tibia and femur did not differ significantly from control values. Thus, there was more calcium per unit length of bone, resulting in an increase in the skeletal density of treated rats. This finding was confirmed by x-ray examination of these bones. The net intestinal absorption of calcium (rate of initial entry) calculated from plasma levels following an oral and intravenous dose of 47Ca and 85Sr, respectively, was not significantly different in hydrocortisone-treated rats compared to controls. This would indicate that the rate of intestinal absorption of calcium is unimpaired despite the administration of massive doses and corticosteroids. When the animals were placed on a calcium-deficient diet, both TBCa and tibia and femur calcium levels were decreased. Subsequent administration and hydrocortisone did not alter the calcium values. The results of this study are compatible with the hypothesis that hydrocortisone promotes weight loss, retards growth, but inhibits the rate of bone resorption.     

The role of the parathyroids for the adaptation to a low calcium intake. 5. The long-term effect of parathyroidectomy on the adaptation to a low calcium intake in adult rats with special reference to the metabolism of vitamin D

One-year-old selectively parathyroidectomized rats showed a normalization of their plasma calcium level to above 4.1 mEq/l in 38% within 18 weeks on a normal dietary intake of calcium and inorganic phosphate but low in vitamin D. On a low level of dietary calcium, normalization did not occur in any of the parathyroidectomized animals. The conversion of 25-hydroxycholecalciferol into the active metabolite of vitamin D, 1,25-dihydroxycholecalciferol, by the kidneys was stimulated by a low dietary intake of calcium in intact animals and the accumulation of this metabolite was increased in small intestine mucosa. This adaptory increase in the level of intestinal 1,25-dihydroxycholecalciferol was not disturbed by selective parathyroidectomy, nor the synthesis by the kidneys. The synthesis reached a limit above which no further increase occurred despite the prevailing hypocalcemia possibly through an influence of the concomitant hyperphosphatemia. The renal synthesis and intestinal accumulation of 1,25-dihydroxycholecalciferol were directly related to the intestinal net absorption of dietary calcium, which we have reported on previously. Although increased, the endogenous level of 1,25-dihydroxycholecalciferol was too low to accomplish mobilization of skeletal calcium necessary for adaptation to a low calcium intake, as we have reported elsewhere. Thus, for adaptation skeletal calcium reserves must become mobilized through stimulated parathyroid activity with resulting osteoporosis. The parathyroids were found to have no direct regulatory influence upon the synthesis of 1,25-dihydroxycholecalciferol.     

Jejunal brake: inhibition of intestinal transit by fat in the proximal small intestine

Optimal absorption of fat requires adequate time of contact with the absorptive sites of the small intestine. In order to prevent steatorrhea, intestinal transit must be slowed in response to the fat that has emptied into the small intestine. Intestinal transit is known to be inhibited by fat in the ileum via the ileal brake. This response has suggested that the regulation of intestinal transit is a function of the distal small intestine. However, clinical observations suggest that the ileal brake is not the only control mechanism for intestinal transit. In short bowel patients with resection of the ileum, the proportion of fecal fat recovery remained constant even after the fat intake was increased threefold. In these patients, optimal fat absorption based on the slowing of intestinal transit must have been triggered by an inhibitory mechanism located outside of the distal small intestine. To test the hypothesis that fat in the proximal small intestine inhibited intestinal transit, we compared intestinal transit during perfusion of the proximal half of the small intestine with 0 (buffer only), 15, 30, or 60 mM oleate in dogs equipped with duodenal and mid-intestinal fistula. Intestinal transit across a 150-cm test segment (between fistulas) was measured by counting for the recovery of a radioactive marker in the output of the mid-intestinal fistula during the last 30 min of a 90-min perfusion. We found that oleate inhibited intestinal transit in a load-dependent fashion (P < 0.005). Specifically, while the mean cumulative recovery of the transit marker was 95.5% during buffer perfusion, the recovery decreased when 15 mM (64.3%), 30 mM o(54.7%), or 60 mM oleate (38.7%) was perfused into the proximal half of the small intestine. We conclude that fat in the proximal small intestine inhibits intestinal transit as the jejunal brake.     

Methods for measuring the intestinal absorption of calcium in humans (author's transl)

For the determination of intestinal absorption of calcium, the fasting (12 hours) patient receives radioactive labeled calcium (45Ca, more frequently 47Ca) by mouth. After 10, 20, 30, 60, 90, 120, 180 and 240 min, samples of venous blood are taken. The stool is also collected for three days. The determination of radiocalcium in the plasma and in the stool samples is done with a Geiger counter. This oral test provides informative results on numerous aspects of the pathophysiology of intestinal assimilation of calcium. In humans, the duodenum seems to be of the greatest importance for calcium absorption.     

Binding of enterotoxigenic Escherichia coli to isolated enterocytes and intestinal mucus

Binding of human enterotoxigenic Escherichia coli (ETEC) to the small intestine is a prerequisite for colonization and is mediated by colonization factor (CF) antigens. Coli surface antigen 6 (CS6) is considered a CF but binding to isolated enterocytes has not been established. In this study bacteria expressing CS6 were analysed for binding to enterocytes from human and rabbit small intestine, isolated using either an EDTA-containing buffer or a buffer devoid of EDTA. We found that the bacteria bound to enterocytes from rabbit ileum and human duodenum, but only when the cells had been isolated in the absence of EDTA. Pretreatment of rabbit enterocytes with meta-periodate resulted in a decreased proportion of cells with bound bacteria. Purified CS6, and for comparison other ETEC CFs, were also tested for binding to different human and rabbit mucus fractions. These analyses showed that purified CS6 bound to mucus from rabbit duodenum and ileum as well as from human duodenum, jejunum and ileum and that this binding was abolished by pretreatment of the mucus material with meta-periodate or Proteinase K. CFA/I, CS1 to CS5, CS7, CS17, putative CF (PCF) O159 (CS12), PCFO166 (CS14), and CFA/III (CS8) also bound to the rabbit mucus material although with different patterns; the binding of CS2 and CS5 was abolished by meta-periodate treatment. Thus, ETEC bacteria expressing CS6 might bind to carbohydrate-containing structure(s) in the apical membrane of isolated rabbit ileal and human duodenal enterocytes that could probably be released by EDTA treatment. In addition, CS6 and other ETEC CFs bind to component(s), in some instances protein-associated carbohydrate structures, in mucus fractions from small intestine.     

Enhancement of Ca++ uptake by lactose in the rat small intestine

In previous experiments, lactose was shown to increase the absorption of Ca++ by the small intestine of the rat and other mammals. To further investigate the mechanism of the lactose effect, Ca++ uptake was studied in everted gut sac preparations. Gut sacs from the rat ileum were preincubated with or without lactose for 45 minutes, and then the tissue uptake of 45Ca over the first 3 minutes was measured in the presence or absence of lactose. The presence of 160 mM lactose increased the initial rate of Ca++ uptake in the first minute by 64% compared to the NaCl control. The lactose effect was dependent on the presence of lactose in the preincubation medium only and not on the presence of lactose during the measurement of Ca++ uptake. Lactose increased Ca++ absorption when the Ca++ concentrations ranged from 0.1 to 10 mM. However, the magnitude of the enhancement was dependent on the lactose concentration and was reduced below 160 mM lactose. When Ca++ and lactose uptake during a 45 minute period was measured in parallel experiments, no evidence for the co-transport of lactose and Ca++ into the tissue was found. These and other data indicated that lactose is not interacting directly with Ca++ in solution but is interacting with the absorptive cells of the intestine to increase their permeability to Ca++.     

Subcellular calcium transport in failing hearts due to calcium deficiency and overload

Mitochondrial and heavy microsomal fractions were isolated from rat hearts perfused for different intervals with Ca2+-free medium, as well as from hearts reperfused with control medium after perfusion with Ca2+-free medium. Contractile failure due to intracellular calcium deficiency produced by perfusing the isolated rat hearts with Ca2+-free medium resulted in a marked decline of calcium binding and uptake activities of the mitochondrial fraction without any effect on the microsomal fraction. On the other hand, inability of the rat hearts to recover their contractile force due to intracellular calcium overload produced by reperfusion for 10 min with control medium after 5-20 min of perfusion with Ca2+-free medium was associated with decreased microsomal calcium-binding and uptake activities and increased mitochondrial calcium-binding and uptake activities. When the hearts perfused with Ca2+-free medium in the presence of low sodium (35 mM) for 5 min were reperfused with control medium, the contractile force recovered completely, and appreciable augmentation in mitochondrial calcium transport or depression in microsomal calcium transport as seen in conditions of intracellular calcium overload did not occur. These results suggest dramatic alterations in calcium-transporting properties of mitochondria and sarcoplasmic reticulum in hearts failing due to intracellular calcium deficiency and calcium overload, respectively.     

Zinc balance in adolescent females consuming a low- or high-calcium diet

There is increasing evidence that calcium intake up to the threshold amount (1480 mg/d) increases bone mass during growth. However, there is concern that such a high calcium intake may interfere with the utilization of other nutrients such as zinc, which is also important for skeletal development. The purpose of our study was to investigate the effect of long-term calcium supplementation on zinc utilization in 26 adolescent females (mean +/- SD age 11.3 +/- 0.5 y) during a 14-d period. Each day subjects consumed a metabolic diet containing 722 mg Ca and 6.3 mg Zn. Participants were randomly assigned to receive either a placebo or a calcium supplement containing 1000 mg supplemental Ca/d as calcium citrate malate. Supplementation began 15 wk before the balance period to allow for adaptation to the greater calcium intake. Mean (+/-SD) zinc balance (0.8 +/- 0.8 compared with 0.3 +/- 1.1 mg/d, P = 0.23), fecal zinc (4.3 +/- 0.6 compared with 4.7 +/- 1.4 mg/d, P = 0.27), urinary zinc (0.4 +/- 0.2 compared with 0.5 +/- 0.1 mg/d, P = 0.55), and net zinc absorption (21% compared with 15%, P = 0.33) were not significantly different between the high- and low-calcium groups. Our results suggest that increasing the recommended dietary allowance of calcium to 1500 mg/d as recommended by the National Institutes of Health consensus panel will not have adverse effects on zinc utilization in adolescent females.