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PubMed1996

The inhibitory activity of some citrate analogues upon calcium crystalluria: observations using an improved urine evaporation technique.

The ability of three compounds, all similar in chemical structure to citric acid, to decrease calcium crystalluria has been measured. The measurements were made in normal human urine at 37 degrees C and compared with the crystal-decreasing power of citric acid when measured in the same way and in the same urine samples. One of the compounds tested, phosphocitric acid, was more potent than citric acid in inhibiting calcium oxalate crystal precipitation. At higher concentrations it also proved more effective against calcium phosphate. A urine evaporation method was used to carry out the crystal inhibition tests after modification to improve its precision.

Calcium Oxalate↗
PubMed1989

Reduction of dietary phosphorus absorption by phosphorus binders. A theoretical, in vitro, and in vivo study.

Antacids used to decrease phosphorus absorption in patients with renal failure may be toxic. To find more efficient or less toxic binders, a three-part study was conducted. First, theoretical calculations showed that phosphorus binding occurs in the following order of avidity: Al3+ greater than H+ greater than Ca2+ greater than Mg2+. In the presence of acid (as in the stomach), aluminum can therefore bind phosphorus better than calcium or magnesium. Second, in vitro studies showed that the time required to reach equilibrium varied from 10 min to 3 wk among different compounds, depending upon solubility in acid and neutral solutions. Third, the relative order of effectiveness of binders in vivo was accurately predicted from theoretical and in vitro results; specifically, calcium acetate and aluminum carbonate gel were superior to calcium carbonate or calcium citrate in inhibiting dietary phosphorus absorption in normal subjects. We concluded that: (a) inhibition of phosphorus absorption by binders involves a complex interplay between chemical reactions and ion transport processes in the stomach and small intestine; (b) theoretical and in vitro studies can identify potentially better in vivo phosphorus binders; and (c) calcium acetate, not previously used for medical purposes, is approximately as efficient as aluminum carbonate gel and more efficient as a phosphorus binder than other currently used calcium salts.

Acetates↗
PubMed1985

Effects of divalent cations on the interaction of platelets with tumor cells: aggregation and perfusion studies with two homologous human systems.

The effects of chelation of divalent cations in the interaction of platelets and tumor cells has been studied in a homologous human system using human platelet-rich plasma and two tumor cell lines of human origin: SKNMC (neuroblastoma) cells, which cause platelet aggregation by an adenosine diphosphate-dependent mechanism, and U87MG (glioblastoma) cells, which function by a thrombin-dependent mechanism. When added at zero time, citrate 14 mmol/L completely abolished aggregation in heparinized (5 U/ml) platelet-rich plasma by either cell line, but the degree of inhibition was reduced by later addition of the chelating agent. Calcium citrate 8 mmol/L reduced by only 10%, indicating that citrate anion was not responsible for the inhibition. Addition of Ca++ or Mg++ alone or in combination at concentrations up to 1.5 mmol/L did not reverse the inhibition. Addition of higher concentrations of Ca++ (2 mmol/L) caused immediate clotting, whereas concentrations of Mg++ up to 6 mmol/L were without effect. Inhibition could be reversed by washing the platelets free of citrate and resuspending in heparinized platelet-rich plasma. Aggregation by either cell line was inhibited by EDTA and EGTA. In the Baumgartner perfusion apparatus, platelet interaction with subendothelium was increased about 50-fold in the presence of SKNMC cells, but this effect was also abolished after addition of citrate. After addition of U87MG cells to heparinized PRP, there was a 400-fold increase in platelet interaction with subendothelium, and complex thrombi containing red cells, white cells, and fibrin were formed. This stimulation was reduced to control levels by addition of citrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Platelets↗
PubMed2006

Effect of potential renal acid load of foods on urinary citrate excretion in calcium renal stone formers.

The aim of this study was to investigate the influence of the potential renal acid load (PRAL) of the diet on the urinary risk factors for renal stone formation. The present series comprises 187 consecutive renal calcium stone patients (114 males, 73 females) who were studied in our stone clinic. Each patient was subjected to an investigation including a 24-h dietary record and 24-h urine sample taken over the same period. Nutrients and calories were calculated by means of food composition tables using a computerized procedure. Daily PRAL was calculated considering the mineral and protein composition of foods, the mean intestinal absorption rate for each nutrient and the metabolism of sulfur-containing amino acids. Sodium, potassium, calcium, magnesium, phosphate, oxalate, urate, citrate, and creatinine levels were measured in the urine. The mean daily PRAL was higher in male than in female patients (24.1+/-24.0 vs 16.1+/-20.1 mEq/day, P=0.000). A significantly (P=0.01) negative correlation (R=-0.18) was found between daily PRAL and daily urinary citrate, but no correlation between PRAL and urinary calcium, oxalate, and urate was shown. Daily urinary calcium (R=0.186, P=0.011) and uric acid (R=0.157, P=0.033) were significantly related to the dietary intake of protein. Daily urinary citrate was significantly related to the intakes of copper (R=0.178, P=0.015), riboflavin (R=0.20, P=0.006), piridoxine (R=0.169, P=0.021) and biotin (R=0.196, P=0.007). The regression analysis by stepwise selection confirmed the significant negative correlation between PRAL and urinary citrate (P=0.002) and the significant positive correlation between riboflavin and urinary citrate (P=0.000). Urinary citrate excretion of renal stone formers (RSFs) is highly dependent from dietary acid load. The computation of the renal acid load is advisable to investigate the role of diet in the pathogenesis of calcium stone disease and it is also a useful tool to evaluate the lithogenic potential of the diet of the individual patient.

Acids↗
PubMed1990

Inhibitory effect of different anticoagulants on gamma-glutamyl transpeptidase activity.

Increased gamma-glutamyl transpeptidase (GGT) levels have been observed in patients with several types of liver diseases. However, since GGT activity can be inhibited or increased by several substances, the interpretation of these increased levels should be made with caution. The present study was designed to determine plasma GGT activity in blood samples obtained from 24 adult volunteers (13 males and 11 females aged 20 to 40 years) with the use of three different anticoagulants, i.e., ethylenediaminetetraacetic acid (EDTA), calcium fluoride and calcium citrate, and to compare it with GGT activity in serum obtained from the same blood samples. Serum GGT activity was significantly higher than plasma GGT activity (P less than 0.001) and significantly higher in men than in women (P less than 0.05), though plasma GGT activity was similar for both sexes.

Adult↗
PubMed2006

[Urinary citrate excretion in children with calcium urolithiasis].

UNLABELLED: Citrate is thought to be one of the most important inhibitor of calcium salts crystallization in the urine. Therefore, an assessment of urinary citrate excretion is an integral element of metabolic evaluation in urolithiasis. The reported incidence of urolithiasis associated with hypocitraturia varies from 10% to 63%. The purpose of the study was to assess urinary citrate excretion in children with calcium urolithiasis living in region of Lublin. The study comprised 60 children (34 boys and 26 girls) aged 4.3-18 years. In 36 of them, calcium oxalate urolithiasis was diagnosed by spectrophotometry. In the remaining children, an assessment of stone composition was impossible. However, in all children, stones were radiopaque. Hypercalciuria (HC) and mild hyperoxaluria (HOx) were diagnosed in 23 and 16 children, respectively. In the remaining 21 children urolihiasis was classified as idiopathic. The controls were 35 healthy age- and gender-matched children. Urinary citrate excretions were assessed by enzymatic method in 24-hour urine specimens and expressed as citrate/creatinine ratios (Cit/Cr). Decreased Cit/Cr were observed in 9 (15%) children with calcium urolithiasis. However, there was no significant difference between the mean Cit/ Cr in children with calcium urolithiasis and controls (410 +/- 207 mg/g vs 385 +/- 144 mg/g). There was also no significant difference between the mean Cit/ Cr in children with HC and controls. Similarly, the mean Cit/Cr did not differ significantly between children with HOx and controls. However, the lowest mean Cit/Cr was revealed in children with HOx (306 +/- 161 mg/g). CONCLUSIONS: In most children with calcium urolithiasis urinary citrate excretion was normal. However, in some children with urolithiasis, detection of hypocitraturia allows to explain pathogenesis of stone formation and to carry on a causative prophylaxis.

Adolescent↗
PubMed1996

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

Increasing emphasis is being placed on optimizing calcium intake during growth as a way to enhance peak bone mass. Although some studies in adults have shown that high calcium intake may negatively affect magnesium utilization, few data are available regarding the interaction of calcium and magnesium in healthy children. The purpose of our study was to measure the effect of calcium intake on magnesium balance in 26 adolescent girls (mean age 11.3 y) during a 14-d period. Subjects ate a controlled basal diet containing 667 mg Ca and 176 mg Mg. In addition to the basal diet, subjects were randomly assigned in a double-blind fashion to consume 1000 mg elemental Ca/d as calcium citrate malate or a placebo. Magnesium use did not differ between the low-calcium and high-calcium groups as measured by absorption (50% compared with 55%), urinary excretion (70 compared with 74 mg/d), and fecal excretion (88 compared with 79 mg/d). Accordingly, magnesium balance was not different in subjects consuming 667 or 1667 mg Ca/d and averaged 21 mg Mg/d for the whole study group. Magnesium balance was significantly correlated with magnesium intake (r = 0.511, P = 0.008) and magnesium absorption (r = 0.723, P < 0.001). Prediction intervals from the regression of magnesium balance on intake indicated that the current recommended dietary allowance of magnesium would result in magnesium balance > or = 8.5 mg/d in 95% of the girls. This value appears consistent with long-term accretion rates needed to account for the expansion of the total-body magnesium pool during growth. In summary, our observations support the adequacy of the current recommended dietary allowance for magnesium and indicate that alterations in magnesium utilization should not be anticipated in adolescent females consuming a high-calcium diet.

Absorption↗
PubMed1996

Some aspects of citrate metabolism in renal-stone patients from northeastern Thailand.

In our previous nephrolithiasis studies in the northeast region of Thailand, hypokaliurea and hypocitraturia were the 2 most commonly encountered metabolic abnormalities. This led us to believe that people prone to forming renal-stones in this area were in a state of potassium depletion, a condition which probably caused the low urinary excretion of citrate. Further studies on some aspects of citrate metabolism in these subjects were carried out. Two groups of adult male subjects were included in the study protocol. Group 1 consisted of 20 urban dwellers who were used as normal controls, and group 2 was comprised of 36 renal-stone patients residing in rural villages outside the municipal area. Fasting clotted venous blood and one 24-hour urine specimens were collected and analyzed for creatinine, citrate, calcium, phosphate, magnesium, sodium, potassium, chloride, bicarbonate and uric acid. Values for: creatinine and citrate clearances, the filtered load of citrate and the tubular reabsorption of citrate were then calculated. The results showed that, for both groups, the concentrations of most of the above parameters were within the normal ranges both serum and urine. An exception to this was that the levels of serum potassium and of urinary excretions of sodium, potassium and citrate in people in group 2 were significantly less than those in group 1 (p < 0.005, p < 0.001, p < 0.001 and p < 0.0001, respectively). With respect to citrate metabolism, while the serum citrate levels and the filtered load of citrate were not different between the 2 groups, the average percentage of renal tubular reabsorption of group 2 (95 +/- 1.1%) increased significantly (P < 0.0001)in comparison to group 1 (85 +/- 1.6%). Moreover when results from both groups were combined, a significant negative correlation between the renal tubular reabsorption of citrate and the urinary excretion of potassium was clearly seen (r = 0.4001, p < 0.007). Our data suggests that potassium depletion may affect the renal tubular cells in some manner which, consequently, causes an increase in renal tubular reabsorption of citrate. The final outcome of these changes in these renal stone subjects was hypocitraturia.

Adult↗
PubMed1984

The role of citrate in determining the activity of calcium ions in human semen.

The concentrations of calcium and citrate in 52 samples of human semen obtained from 10 donors were 11.07 +/- 0.41 (mean +/- SEM) and 27.2 +/- 1.62 mM, respectively, and were strongly correlated (r = + 0.79). The pH of the semen was 7.65 +/- 0.069. All 3 parameters varied significantly between the donors (P less than 0.001 in each case), but the activity of calcium ions measured with a calcium electrode was 0.24 +/- 0.022 mM (n = 45) and did not vary significantly between donors. The expected activity of calcium ions was calculated on the hypothesis that the chelation of calcium by citrate could explain the discrepancy between the concentration and the activity of the ion. The result was 0.57 +/- 0.043 mM (n = 52). It was concluded that chelation by citrate could be the most important factor in determining the low activity of Ca++ in semen.

Calcium↗
PubMed2003

Interaction of dietary calcium and protein in bone health in humans.

Protein has both positive and negative effects on calcium balance, and the net effect of dietary protein on bone mass and fracture risk may be dependent on the dietary calcium intake. In addition to providing substrate for bone matrix, dietary protein stimulates the production of insulin-like growth factor-1 (IGF-1), a factor that promotes osteoblast-mediated bone formation. Protein also increases urinary calcium losses, by several proposed mechanisms. Increasing calcium intake may offset the negative impact of dietary protein on urinary calcium losses, allowing the favorable effect of protein on the IGF-1 axis to dominate. Several, although not all, studies are either compatible with or support this hypothesis. Protein supplements significantly reduced bone loss in elderly hip-fracture patients in a study in which both the protein and control groups received supplemental calcium. In an observational study, total protein intake was positively associated with favorable 3-y changes in femoral neck and total body bone mineral density in volunteers who received supplemental calcium citrate malate and vitamin D, but not in volunteers taking placebos. In conclusion, an adequate calcium intake may help promote a favorable effect of dietary protein on the skeleton in older individuals.

Aged↗
PubMedDate not supplied

Mathematical model to estimate risk of calcium-containing renal stones.

BACKGROUND/AIMS: Astronauts exposed to microgravity during the course of spaceflight undergo physiologic changes that alter the urinary environment so as to increase the risk of renal stone formation. This study was undertaken to identify a simple method with which to evaluate the potential risk of renal stone development during spaceflight. METHOD: We used a large database of urinary risk factors obtained from 323 astronauts before and after spaceflight to generate a mathematical model with which to predict the urinary supersaturation of calcium stone forming salts. RESULT: This model, which involves the fewest possible analytical variables (urinary calcium, citrate, oxalate, phosphorus, and total volume), reliably and accurately predicted the urinary supersaturation of the calcium stone forming salts when compared to results obtained from a group of 6 astronauts who collected urine during flight. CONCLUSIONS: The use of this model will simplify both routine medical monitoring during spaceflight as well as the evaluation of countermeasures designed to minimize renal stone development. This model also can be used for Earth-based applications in which access to analytical resources is limited.

Calcium↗
PubMed1993

Acute biochemical variations induced by four different calcium salts in healthy male volunteers.

Calcium (Ca) supplements have positive effects in growing children, reduce bone loss in late-postmenopausal women with a low calcium diet and, in association with vitamin D3 supplements, may reduce non-vertebral fracture rates in elderly women. However, for many formulated pharmaceutical products their relative beneficial effects have not been conclusively established. We have compared the acute (6 h) metabolic responses following oral administration of two preparations of calcium gluconolactate and carbonate (CG and CG'), tricalcium phosphate (TCP) and calcium citrate (CC), given on separate occasions in each of 10 healthy young male volunteers. The subjects fasted overnight for 12 h and continued to fast during the experimental procedure. A 1000 mg dose of each Ca salt was ingested at weekly intervals. Blood was drawn after 30, 60, 90, 120, 180, 240, 300 and 360 min for measurement of serum Ca, phosphorus (P), parathyroid hormone (PTH) and whole plasma calcitonin (iCT). All Ca supplements induced significant (+6.4% to +8.1%; p < 0.01) increases in Ca and significant suppression of PTH (-37.4% to -57.4%; p < 0.01). Comparison of response curves revealed significantly (p < 0.01) more marked Ca increase and PTH suppression with CC than with the other three Ca salts. CG' and CC induced marginal decreases in serum P and the overall curve of P variations was different for TCP compared with CG, CG' and CC. No significant variation of iCT was recorded during the test.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Changes in serum calcium fractions and citrate concentrations during massive blood transfusions and cardiopulmonary bypass.

Total serum calcium, its fractions and serum citrate concentrations were measured in children receiving massive blood transfusion for scoliosis surgery, and in other children undergoing open heart surgery with cardiopulmonary bypass. During scoliosis surgery, although up to 100% of blood volume was replaced, and no additional calcium salts were infused, serum ionized calcium concentration remained within normal limits, provided that infusion rates of blood did not exceed 30 ml kg-1 h-1. During cardiopulmonary bypass, in which citrate-containing blood priming solutions were used, serum ionized calcium concentrations decreased markedly during perfusion associated with extremely high serum citrate concentrations. Serum ionized calcium concentrations returned to normal by the end of bypass, but serum citrate concentrations remained five times the normal concentration 5 h after bypass.

Adolescent↗
PubMed1996

Calcium modulation of adrenocorticotropin levels in women--a clinical research center study.

In vitro calcium modulation of anterior pituitary hormone secretion has been well described. In addition, several investigations performed in human subjects have documented modulation of the circulating levels of pituitary hormones by supraphysiological calcium concentrations. Recent data from our laboratory document the existence of an extracellular calcium-sensing receptor that is thought to mediate the effects of variations in extracellular calcium on the secretion of PTH and calcitonin. We have also demonstrated the presence of this receptor in pituitary-derived, ACTH-secreting AtT-20 cells as well as in the anterior pituitary of rats and mice. In the present study we investigated the effect on anterior pituitary hormone levels of variations in serum calcium within the physiological range. We serially measured serum levels of ionized calcium (Cai), ACTH, cortisol, TSH, and PRL during 90-min iv infusions (on separate days) of calcium, citrate, and dextrose in 10 healthy women with a mean age of 55 +/- 5 yr. During the calcium infusion, the serum Cai level increased significantly from 4.32 +/- 0.10 mg/dL at baseline to 4.86 +/- 0.08 mg/dL at completion (P = 0.002), and this change was accompanied by a significant increment in the serum ACTH level from 9.87 +/- 1.32 to 16.31 +/- 2.84 pg/mL (P = 0.0008). There was no change in the serum ACTH level during the citrate infusion despite significant decrements in serum Cai, nor were there changes in either Cai or ACTH during the dextrose infusion. Finally, changes in Cai did not alter TSH or PRL levels. In summary, our dynamic studies are the first to demonstrate an increase in baseline serum ACTH levels in response to physiological increments in Cai (i.e. increments within the normal range). This effect was specific for increments and not decrements in serum Cai and was selective for ACTH, as TSH and PRL levels did not change with any of the infusions.

Adrenocorticotropic Hormone↗
PubMed2000

Citrate utilization by homo- and heterofermentative lactobacilli.

Citrate utilization by several homo- and heterofermentative lactobacilli was determined in Kempler and McKay and in calcium citrate media. The last medium with glucose permitted best to distinguish citrate-fermenting lactobacilli. Lactobacillus rhamnosus ATCC 11443, Lactobacillus zeae ATCC 15820 and Lactobacillus plantarum ATCC 8014 used citrate as sole energy source, whereas in the other strains, glucose and citrate were cometabolized. Some lactobacilli strains produced aroma compounds from citrate. Citrate transport experiments suggested that all strains studied presented a citrate transport system inducible by citrate. The levels of induction were variable between several strains. Dot blot experiment showed that lactobacilli do not present an equivalent plasmid coding for citrate permease.

Acetoin↗
PubMed1997

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.

Absorption↗
PubMed2001

Rethinking the role of urinary magnesium in calcium urolithiasis.

BACKGROUND AND PURPOSE: The role of magnesium in urinary stone formation remains undefined. In vivo, magnesium inhibits stone formation in hyperoxaluric rats, and small clinical studies suggest a protective effect of magnesium supplementation in calcium oxalate stone formers. We performed a retrospective review of more than 7,000 stone patients to see if there is a relation between urinary magnesium and other stone risk variable constituents. MATERIALS AND METHODS: A national database of stone formers categorized by residential ZIP code was queried, and, using strict inclusion criteria, 2,147 patients having pure calcium oxalate stones were identified. There were 1,912 (89%) eumagnesuric (43-246 mg/24 hours) and 235 (11%) hypomagnesuric (<43 mg/24 hours) patients. RESULTS: Patients with decreased urinary magnesium excretion had significantly less daily urine excretion of citrate, calcium, oxalate, uric acid, and sodium than the eumagnesuric group (p < 0.0001). Stone recurrence was slightly more common in the hypomagnesuric group, although the difference was not statistically significant. The percentage of patients voiding <1 L of urine per day was significantly higher in the hypomagnesuric group. In the eumagnesuric group, males outnumbered females 2:1, whereas hypomagnesuric patients showed a female predominance of 1.4:1. CONCLUSION: The beneficial effects of urinary magnesium on stone formation may be less than previously reported. The role of oral magnesium supplementation and the subsequent increase in urinary magnesium in calcium urinary stone formation remains unknown. Our data suggest that its effect on or interaction with citrate may be influential on urinary citrate concentrations. If magnesium has a protective effect, it may work through pathways that enhance citrate excretion.

Calcium Oxalate↗