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PubMed1994

[In vitro effect of citrate and phosphates on calcium transport in the rat ileum].

OBJECTIVES AND METHODS: The effect of the presence of phosphates or citrate on ileal calcium (Ca) absorption was studied by using rat ileum mounted in a Ussing chamber. RESULTS: Mucosa-to-serosa and serosa-to-mucosa undirectional fluxes were not modified by mucosal addition of 2.8 mM Na phosphate or 2.0 mM Na citrate to Krebs-Ringer-bicarbonate buffer containing 1.25 mM CaCl2. However, 50 mM Na citrate induced a significant and similar increase of both unidirectional Ca fluxes, leading to no modification of net Ca flux. This high citrate concentration was associated with a significant increase of tissue conductance and no alteration of zona adherens and tight junction as observed by electron microscopy. CONCLUSIONS: Thus in the absence of any Ca gradient along the epithelium, even at high concentration, citrate did not induced modification of ileal Ca absorption.

Animals↗
PubMed1994

Urinary citrate, bone resorption and intestinal alkali absorption in stone formers with fasting hypercalciuria.

Reduced citrate in urine and increased fasting excretion of calcium are abnormalities frequently reported in stone forming (SF) patients. Increased dietary acid (or reduced alkali) introduction or absorption may be a potential cause of both these pathological findings. To test this hypothesis, we studied 64 SF patients (32 with fasting hypercalciuria (FH) and 32 without FH (NFH)). After a basal evaluation for nephrolithiasis, while on a 500 mg calcium diet, they were evaluated for: (1) daily intestinal alkali absorption (IAA), by urinary electrolyte excretion; (2) basal concentrations of PTH, calcitonin (CT) and 1,25(OH)2-VitD; (3) oral calcium load for evaluation of changes in calcium and hydroxyproline urinary excretions; (4) intestinal calcium absorption (18 patients), with double curve analysis (stable Sr as tracer); and (5) changes in citrate excretion after an alkali load (50 mEq of a mixture of calcium gluconate, lactate and carbonate) in 10 patients. The results demonstrated: (1) FH stone formers had reduced citrate excretion and lower mean IAA levels than NFH stone formers; (2) FH stone formers also had higher bone resorption levels with lower PTH and higher CT levels; (3) IAA levels were related to both citrate excretion and bone turnover indices; and (4) the increases in citrate excretion after oral alkali load were strictly related to basal IAA values (index of alkali absorption and/or generation after oral load), demonstrating that a different absorptive capacity of alkali rather than a different dietary content may underlie these metabolic abnormalities.

Adult↗
PubMed1994

[Effect of urine alkalization on excretion of renal citrate and degree of urine saturation with calcium oxalate in patients with calcium-oxalate urolithiasis and in healthy subjects].

The aim of the study was to compare the renal citrate excretion and the degree of urine saturation with calcium oxalate in patients with active calcium oxalate urolithiasis and in healthy subjects under basal conditions and after alkalization. There were 20 women before menopause with calcium stone disease aged 33.5 +/- 7.1 in the first group and 20 healthy women aged 32.3 +/- 7.6 in the second one. Sodium bicarbonate was administrated intravenously in a dose 16.8 g during 2 h. 24h excretion of calcium, magnesium and citrate, the degree of urine saturation with calcium oxalate and pH of urine before and after alkalization were evaluated. Hypocitraturia occurred in 45% of patients under basal conditions. The degree of urine saturation with calcium oxalate was significantly higher in women with nephrolithiasis (p < 0.01). A significant increase of citrate excretion (p < 0.001) and a decrease of calcium excretion (p < 0.05) after alkalization took place in both groups. The degree of urine saturation with calcium oxalate decreased significantly in patients with urolithiasis and in healthy subjects. During acute alkalosis, induced by sodium bicarbonate, increase of citrate excretion was observed in patients with urolithiasis in spite of hypocitraturia under basal conditions. This indicates that kidney function following alkalization is normal in "stone kidney". Significantly decreased saturation of urine with calcium oxalate was due to the decrease of calcium excretion and the increase of citrate excretion. In conclusion, the results show that the use of alkalizing factors in prevention of recurrent calcium urolithiasis is justifiable.

Adult↗
PubMed1993

Uptake of iron from ferric-citrate in the cyanobacteria Synechocystis PCC6803.

Iron is an essential element for bacterial growth. Its intracellular concentration is mainly controlled at the uptake level, which is mediated by iron-dicitrate transport in various prokaryotes. We report here that the cyanobacterium Synechocystis PCC6803 takes up iron from ferric citrate. This process is dependent of the iron:citrate ratio, with a better efficiency for the highest concentration of citrate. The iron-citrate complex is the substrate of this active uptake, inhibited in part by the uncoupler FCCP. Iron starvation activates this uptake. These data suggest the existence of a specific ferric citrate receptor on the cyanobacterial membrane.

Biological Transport, Active↗
PubMedDate not supplied

[Regulation of citrate synthese in bacteria: Comparison of the action of various effectors on the enzymes of Rhodospirillum rurbum and Bacillus stearothermophilus].

A comparative study of the citrate synthases purified from the facultatively photosynthetic bacterium Rhodospirillum rubrum (Gram negative) and the thermophile Bacillus stearothermophilus (Gram positive) was made. The citrate synthase from R. rubrum was activated by KCl (6-fold at 0.1 M KCl) and, less effectively, by NaCl and NH4Cl. Its molecular weight was about 300,000. The enzyme was strongly inhibited by NADH, and this inhibition was counteracted by AMP. The citrate synthase from B. stearothermophilus was little affected by KCl, NaCl and NH4Cl, all of which activated by about 25% at 0.1 M. Its molecular weight was ca 100,000. The enzyme was not affected by NADH or AMP. Both citrate synthases were insensitive to alpah-oxoglutarate concentrations up to 5 mM, and were inhibited by ATP; the B. stearothermophilus enzyme was more strongly inhibited than the R. rubrum enzyme. In both cases the ATP inhibition was strictly competitive towards acetyl-CoA and non-competitive towards oxaloacetate. Both enzymes, in spite of the peculiar physiological properties of their bacterial sources, followed the close correlation between the properties of the citrate synthase and the taxonomical position of the microorganism, proposed by Weitzman and his co-workers.

Animals↗
PubMed1993

Citrate versus heparin anticoagulation in chronic haemodialysis patients.

Anticoagulation with citrate at a rate of 0.68 mM/min in combination with a calcium and magnesium-free dialysate and i.v. supplementation of calcium and magnesium at rates of 0.18 mM/min and 0.08 mM/min respectively, was compared with low-dose heparin. The heparin dose was a loading dose of 2500 IU and a sustaining infusion of 750-1250 IU/h; or a loading dose of 1250 IU and a sustaining infusion of 500-750 IU/h until 1 h before the end of the dialysis if the patient was taking concomitantly coumarin anticoagulation for a Goretex shunt. Six chronic haemodialysis patients changed from heparin to citrate anticoagulation because they reported bleeding between dialyses. Heparin, after 2 h dialysis, induced a significant 10% prolongation of each patient's whole-blood activated clotting time (WBACT) as compared to the predialysis value; while the WBACT at the dialyser outlet was less than 3% prolonged as compared to the patient's WBACT. However, after 2 h citrate the patient's WBACT was not prolonged but the WBACT at the dialyser outlet was 20-100% longer, indicating a better anticoagulation of the extracorporeal system without systemic effects. With heparin the shunt pressure time (SPT), i.e. the time needed to stop bleeding from the puncture sites of the Goretex shunts, was 12 of 28 times 20 min or more. Citrate reduced these episodes by 75%. Thus citrate should be considered for chronic haemodialysis patients who are at risk of bleeding because of the concomitant use of anticoagulants.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1977

Regulation of citrate transport and pyruvate dehydrogenase in rat kidney cortex mitochondria by bicarbonate.

1. Bicarbonate increased citrate and 2-oxoglutarate accumulation when rat kidney cortex mitochondria were incubated with pyruvate or L(-)-palmitoyl carnitine in the presence of L-malate. 2. Bicarbonate stimulated the exit of citrate from mitochondria. The Km for bicarbonate was 13.5 mM and the Vmax was 0.59 nmol/min/mg of protein at 10 degrees. 3. The bicarbonate-stimulated exit of citrate from the mitochondria was prevented by inhibitors of the tricarboxylate, dicarboxylate, and phosphate transport systems. 4. The activity of pyruvate dehydrogenase was significantly increased by preincubation of rat kidney mitochondria with bicarbonate. This bicarbonate-induced activation was not observed in presence of inhibitors of citrate transport. Bicarbonate did not activate pyruvate dehydrogenase in rat heart mitochondria. Bicarbonate had no effect on pyruvate dehydrogenase activity in either broken mitochondria or whole tissue preparations. 5. The mechanism of this activation is discussed in the light of the known regulatory properties of pyruvate dehydrogenase, pyruvate carboxylase, and citrate synthase.

Animals↗
PubMed1997

[Cost-effectiveness analysis of preventive treatment of urinary lithiasis recurrence using potassium citrate].

OBJECTIVE: This study evaluated two possible alternatives of potassium citrate administration-granulate (liquid) and tablet (wax matrix)-versus treatment with diet and/or fluid to prevent recurrence of urinary lithiasis. METHODS: The cost-effectiveness of the alternative modalities were analyzed using data from the studies conducted by Barceló (1993), Pak (1985) and Preminger (1985). The variables utilized for effectiveness were 'avoided relapse' and 'avoided intervention'. Since the data from the foregoing studies did not make any distinction between the two alternative forms of potassium citrate administration, the incidence of side effects and the dropout rate were included. These data were obtained from the studies conducted by Barceló (1993). Campoy (1994) and Conte (1994). RESULTS/CONCLUSION: Potassium citrate is effective in the prevention of recurrence of urinary lithiasis; relapses and interventions were significantly avoided. Both forms of potassium citrate are similarly effective and the only differences found were in regard to the side effects and the dropout rate; however, further studies are warranted to determine the possible differences with more precision. Potassium citrate in granulated form in much more cost-effective than the diet and fluid regimen than the tablet alternative, with a difference significantly in favor of the former in the order of 8:1. Price was the most important variable and therefore it is important to determine the appropriate dosage since it will influence the cost-effectiveness ratio and the allocation of resources.

Clinical Trials as Topic↗
PubMed1999

Action potential conduction block of nerves in vitro by potassium citrate, potassium tartrate and potassium oxalate.

OBJECTIVES: Potassium salts in desensitising formulations are believed to act by blocking nerve conduction. The aim of this study was to assess the ability of some organic potassium salts to block action potential conduction and to compare their effects with potassium chloride and potassium nitrate. MATERIALS AND METHOD: Potassium citrate, oxalate or tartrate were added to Krebs' solutions to raise the potassium concentration to 8-64 mM. The test solutions were applied to rat spinal nerves in a bath while monitoring the compound action potentials evoked by electrical stimulation. RESULTS: All potassium salts attenuated the compound action potential in a dose-dependent manner. There were no significant differences between the effects of potassium tartrate and potassium citrate solutions (p>0.1) which caused significantly greater compound action potential attenuation than the same concentrations of potassium oxalate (p<0.05). On the basis of the potassium ion concentration required to cause 50% attenuation of the compound nerve action potential, the relative potencies of the potassium salts were: citrate = tartrate> oxalate>chloride =nitrate. CONCLUSION: Potassium citrate and potassium tartrate were more effective than other potassium salts in blocking nerve conduction and may be more effective dentinal desensitising agents.

Action Potentials↗
PubMed2000

Long-term follow-up of stone formers treated with a low dose of sodium potassium citrate.

We evaluated the clinical efficacy of long-term preventive treatment with a single evening dose of alkaline citrate. Information was collected from the files of 52 recurrent stone formers prescribed a daily intake of 3.75-5 g of sodium potassium citrate (SPC; 14-18 mmol of citrate). The annual and cumulative rates of stone formation and the rate of recurrence were compared before and during the treatment. A comparison was also made between the patients with (Group R) and without (Group NR) recurrent stone formation during treatment in terms of urine composition and previous history of the disease. For all patients who started the treatment, the number of stones was smaller during treatment (period tT) than during a period of the same length immediately before treatment (period tB), but greater than the number formed during a corresponding period immediately after the diagnosis (period tA). Via questionnaire we found low treatment compliance, with only 62% of the patients reporting consistent taking of their medication (Group T). The patients in Group T had a smaller cumulated number of stones during period tT than that during periods tA and tB, but the Kaplan-Meier curve of the fraction of patients remaining stone-free during treatment was almost identical to that recorded in 446 recurrent stone formers without medical treatment. No significant differences were recorded in terms of relevant pretreatment urinary risk factors between Groups T(R) and T(NR), but numerically higher values of calcium oxalate (CaOx) supersaturation and calcium/citrate quotients were observed in Group T(R). When 9 patients with a daily intake of SPC and a citrate excretion below 2.5 mmol/day were compared with 16 hypocitraturic patients only given drinking advice, the cumulated percentages of patients without recurrent stone formation in the 2 groups after 3 years were 44% and 48%, respectively. Although the number of patients in this study was small, our results indicate poor long-term protection from recurrent calcium stone formation when a single evening dose of only 3.75-5 g of SPC was taken. The rate of stone formation was apparently slightly reduced, but the fraction of patients free of recurrence was no different from that in patients without medical treatment.

Citrates↗
PubMed1996

Density-matrix calculations of the 1.5 T citrate signal acquired with volume-localized STEAM sequences.

Citrate detection and quantitation with proton spectroscopic methods are of current interest as potential tools in the diagnosis and staging of prostate cancer. The stimulated echo acquisition mode (STEAM) sequence is a commonly used volume-localization method for detecting citrate signal. Since the 1H citrate resonance at clinically available field strengths arises from a strongly coupled two-spin system, the 90 degrees RF pulses and localizing gradients used in STEAM sequences result in a complicated dependence of signal intensity on timing intervals and gradient amplitudes. The density-matrix formalism has been applied to arrive at a general solution to this problem. Citrate-signal properties at 1.5 T for different gradient localization schemes are examined with the solution. Optimal interpulse delays, deleterious gradient balances, zero-quantum oscillations with mixing time, and a low-frequency, large-amplitude oscillation with echo time are identified for signals acquired with the standard disposition of gradients in STEAM. The generality of the solution also allows for an examination of non-standard gradient disposition schemes for enhancing citrate signal and for quantifying the sensitivity of such approaches to both field inhomogeneities and off-resonance effects.

Citric Acid↗
PubMed1975

[99mTc-sulfur-rhenium colloid and 111In-indium citrate in bone-marrow scintigraphy].

Bone marrow scinitigraphy using 111In-Indium-citrate and 99mTc-sulfur rhenium colloid was compared with each other in 6 male and 3 female patients. Our results in all patients were in favour of 111In-citrate which caused a better delineation of morphological details than 99mTc-sulfur rhenium colloid did. In the first days after intravenous administration of 111In-citrate, radioindium accumulated markedly in the pudendal region, this finding being more distinct in male patients than in female ones. On account of these results a considerable radiation dose has to be assumed in bone marrow scinitigraphy using 111In-citrate as long as the absorbed dose from 111In has not been estimated under consideration of the radioindium accumulation in the pudendal region. 111In-citrate should be applied in bone marrow scanning only exceptionally and 99mTc-sulfur rhenium colloid be preferred in the routine diagnostics of bone marrow.

Adult↗
PubMed1997

Removal of the outer lines of the citrate multiplet in proton magnetic resonance spectra of the prostatic gland by accurate timing of a point-resolved spectroscopy pulse sequence.

Proton MR spectra of a healthy human prostatic gland show a major signal for citrate appearing as an AB-type multiplet. After application of multipulse localization sequences, the outer lines of this multiplet often appear with dispersion line shapes disturbing the baseline and interfering with proper quantification of citrate itself and other nearby resonances. Based upon analytical descriptions of the time evaluation of an AB spin system during a point resolved spectroscopy (PRESS) pulse sequence (90x-tau 1-180y-tau 2-180y-t), equations were derived representing the intensity of the absorption and dispersion line shape of the outer lines of the citrate multiplet at the top of echo t = tau 2-tau 1. From these equations, it was calculated that the outer lines of citrate can be removed almost completely using a PRESS pulse sequence with tau 1 = 11 ms and tau 2 = 60 ms. The theoretical description was confirmed by the almost complete disappearance of the two outer citrate resonances in in vitro and in vivo proton MR spectra acquired with this pulse sequence timing.

Citric Acid↗
PubMed1998

Effects of dietary supplementation with aluminum and citrate on iron metabolism in the rat.

The metabolism of iron (Fe) has been shown to interact with that of aluminum (Al) in relation to intestinal absorption, transport in the blood plasma, and the induction of lipid peroxidation and cellular damage. Also, dietary supplementation with citrate has been shown to increase the absorption of both metals and, in the presence of high intakes of Fe and Al, leads to excessive accumulation of both metals in the body. In this study, the likely interaction between Al and internal Fe metabolism was investigated using rats fed diets that were either deficient, sufficient, or loaded with Fe, with or without the addition of Al and sodium citrate. These diets commenced when the rats were 4 wk old and were continued for 9-11 wk. At that time, Fe metabolism as assessed by measurement of organ uptake of 59Fe and 125I-transferrin, after iv injection of transferrin labeled with both isotopes, plus measurement of tissue concentrations of nonheme Fe and Al. The Fe-deficient diet and Fe-loaded diet led to states of Fe deficiency and Fe overload in the rats, and supplementation of the diet with Al increased Al levels in the kidneys, liver, and femurs, but, generally, only when the diet also contained citrate. Neither Al nor citrate supplementation of the diet had any effect on nonheme Fe concentrations in the liver, kidney, or brain, or on the uptake of 59Fe or 125I-transferrin by liver, kidney, brain, or spleen. Only with the femurs was a significant effect observed: increased 59Fe uptake in association with increased Al intake. Therefore, using this animal model, there was little evidence for interaction between Fe and Al metabolism, and no support was obtained for the hypothesis that dietary supplementation with Fe and citrate can lead to excessive Fe absorption and deposition in the tissues.

Aluminum↗
PubMed1986

Effects of clomiphene citrate on cytosolic estradiol and progesterone receptor concentrations in secretory endometrium.

Cytosolic estradiol and progesterone receptor concentrations were measured in luteal phase endometrial biopsy samples obtained from 12 anovulatory or oligoovulatory women on clomiphene citrate therapy and from 40 normal control subjects. Clomiphene citrate treatment (250 to 750 mg per cycle) decreased both endometrial estradiol and progesterone receptor concentrations. Estradiol receptor levels were nondetectable in seven tissue samples and progesterone receptor levels in four samples from the 12 subjects given clomiphene citrate compared to nondetectable estradiol receptor concentrations in one tissue sample and progesterone receptor concentrations in two samples from the 40 normal control subjects. In histologically dated endometrium, mean estradiol receptor concentrations on days 20 to 23 and progesterone receptor levels on days to 24 to 27 were lower than the values observed in the comparable dated endometrium of normal ovulatory women. Steroid receptor concentrations correlated negatively with the duration of clomiphene citrate therapy, which implies a time-dependent suppressive effect of clomiphene citrate on measurable cytosolic estradiol and progesterone receptor concentrations during the luteal phase of the cycle.

Adult↗
PubMed1989

Fentanyl citrate analgesia during labor.

Fentanyl citrate is a potent short-acting narcotic reported to cause less nausea and sedation than morphine or meperidine hydrochloride. The purpose of this prospective investigation was to determine whether a safe but adequate intrapartum dosing schedule is possible. A total of 137 women with uncomplicated term pregnancies were offered a standard intravenous dose (50 mcg or 100 mcg hourly as needed) of fentanyl citrate during active labor. Temporary analgesia and mild sedation were apparent in each case. The cumulative dose varied in accordance with maternal needs (mean, 140 +/- 42 micrograms; range, 50 mcg to 600 micrograms). Apart from a brief decrease in fetal heart rate variability that lasted 30 minutes, no worrisome pattern was apparent from exposure to fentanyl citrate. Pediatric examinations were performed without knowledge of analgesic therapy on infants exposed to fentanyl citrate and those not exposed to analgesics. No differences were found in frequencies of newborn depressed respirations, low Apgar scores, or neurologic and adaptive capabilities at two hours and 24 hours postnatally. With the use of the described dosing schedule, fentanyl citrate was helpful during labor and did not cause immediate or prolonged hazards to the mother and unborn infant.

Adaptation, Physiological↗
PubMed1989

Effects of clomiphene citrate on episodic luteinizing hormone secretion throughout the menstrual cycle.

Pituitary luteinizing hormone secretory dynamics (pulse frequency and amplitude) were evaluated in eight normal women administered clomiphene citrate or placebo. After 5 days of treatment clomiphene citrate was found to increase mean luteinizing hormone secretion by increasing the amount of pituitary luteinizing hormone released per pulse. No change in pituitary luteinizing hormone interpulse interval was found in the follicular phase of the cycle, although a faster pulse frequency in the luteal phase was found after clomiphene citrate when compared with placebo. No differences were found in the luteal phase (pulse frequency, amplitude, and mean luteinizing hormone level) after clomiphene citrate versus placebo in the volunteers. These data suggest that the principal mechanism of action of clomiphene citrate is an increase in the concentration of hypothalamic gonadotropin releasing hormone into the hypothalamic-pituitary portal circulation, with a resultant increase in pituitary luteinizing hormone secretion.

Adult↗
PubMed1990

Luteal insufficiency: correlation between endometrial dating and integrated progesterone output in clomiphene citrate-induced cycles.

Midluteal phase endometrium was histologically dated with midcycle luteinizing hormone surge time in 29 cycles from 10 parous women during untreated cycles (control) and treatment with clomiphene citrate 50 mg and 150 mg daily on days 5 through 9. Integrated progesterone output for 7 days after luteinizing hormone surge calculated from the daily plasma progesterone levels was 66.6 +/- 9.8 ng/ml in the control group compared with 117.5 +/- 18.6 ng/ml for clomiphene citrate 50 mg treatment and 152.1 +/- 11 ng/ml for clomiphene citrate 150 mg treatment (p less than or equal to 0.05). Only one cycle (clomiphene citrate 150 mg) had an out-of-phase endometrium and a significantly reduced integrated progesterone output of 28 ng/ml. All other cycles showed synchronous endometrial maturation. We conclude that luteal insufficiency as a result of clomiphene citrate treatment in ovulatory women is infrequent and is more likely to be a result of functional outcome of a relative lack of luteal phase progesterone output.

Adult↗