Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CITRATES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 469 records · Page 26Linked to original sources
PubMed2006

Sodium citrate 4% locking solution for central venous dialysis catheters--an effective, more cost-efficient alternative to heparin.

BACKGROUND: Thrombosis of the central venous haemodialysis catheter compromises dialysis adequacy and catheter survival. Heparin containing catheter-locking solution has been associated with bleeding, interferes with INR (prothrombin time/international normalized ratio) measurements and is costly. Sodium citrate has been used successfully as a catheter-locking solution, but long-term experience with its use as the exclusive locking solution has not been published. METHODS: Our haemodialysis unit converted to locking all central venous haemodialysis catheters with sodium citrate 4% instead of heparin 10 000 U/ml. A retrospective analysis compared the outcomes of the year prior and after the conversion. Flow-related catheter exchange rate, prevalence of INR assay interference, tissue plasminogen activator (rt-PA) utilization rate, rate of bacteraemias and annual cost of locking agent were examined. RESULTS: During the study period, 30 925 and 37 139 catheter days were identified during the heparin and citrate years, respectively. The rate of flow-related catheter exchange was not different during the two periods (1.81 vs 1.88 per 1000 catheter days, P = 0.89). Falsely elevated INR values were eliminated with citrate and the rate of rt-PA treatments was similar during the two periods (4.1 vs 3.23 per 1000 catheter days respectively, P = 0.07). The number of bacteraemias was similar during the two periods (0.77 vs 0.94 per 1000 catheter days respectively, P = 0.36) There was an 85% reduction in the costs associated with catheter-locking therapy during the citrate period. CONCLUSIONS: The pharmaco-economic benefits of sodium citrate 4% are well supported by this analysis. Furthermore, citrate offers several clinical advantages over concentrated heparin: citrate lock avoids heparin-associated bleeding complications, improves reliability of INR assays and provides an effective alternative for patients with suspected or confirmed heparin-induced thrombocytopenia.

Aged↗
PubMed2000

Fever of unknown origin: prospective comparison of [18F]FDG imaging with a double-head coincidence camera and gallium-67 citrate SPET.

Gallium-67 citrate is currently considered as the tracer of first choice in the diagnostic workup of fever of unknown origin (FUO). Fluorine-18 2'-deoxy-2-fluoro-D-glucose (FDG) has been shown to accumulate in malignant tumours but also in inflammatory processes. The aim of this study was to prospectively evaluate FDG imaging with a double-head coincidence camera (DHCC) in patients with FUO in comparison with planar and single-photon emission tomography (SPET) 67Ga citrate scanning. Twenty FUO patients underwent FDG imaging with a DHCC which included transaxial and longitudinal whole-body tomography. In 18 of these subjects, 67Ga citrate whole-body and SPET imaging was performed. The 67Ga citrate and FDG images were interpreted by two investigators, both blinded to the results of other diagnostic modalities. Forty percent (8/20) of the patients had infection, 25% (5/20) had auto-immune diseases, 10% (2/20) had neoplasms and 15% (3/20) had other diseases. Fever remained unexplained in 10% (2/20) of the patients. Of the 20 patients studied, FDG imaging was positive and essentially contributed to the final diagnosis in 11 (55%). The sensitivity of transaxial FDG tomography in detecting the focus of fever was 84% and the specificity, 86%. Positive and negative predictive values were 92% and 75%, respectively. If the analysis was restricted to the 18 patients who were investigated both with 67Ga citrate and FDG, sensitivity was 81% and specificity, 86%. Positive and negative predictive values were 90% and 75%, respectively. The diagnostic accuracy of whole-body FDG tomography (again restricted to the aforementioned 18 patients) was lower (sensitivity, 36%; specificity, 86%; positive and negative predictive values, 80% and 46%, respectively). 67Ga citrate SPET yielded a sensitivity of 67% in detecting the focus of fever and a specificity of 78%. Positive and negative predictive values were 75% and 70%, respectively. A low sensitivity (45%), but combined with a high specificity (100%), was found in planar 67Ga imaging. Positive and negative predictive values were 100% and 54%, respectively. It is concluded that in the context of FUO, transaxial FDG tomography performed with a DHCC is superior to 67Ga citrate SPET. This seems to be the consequence of superior tracer kinetics of FDG compared with those of 67Ga citrate and of a better spatial resolution of a DHCC system compared with SPET imaging. In patients with FUO, FDG imaging with either dedicated PET or DHCC should be considered the procedure of choice.

Adult↗
PubMed1992

Regulation of ATP-citrate lyase at transcriptional and post-transcriptional levels in rat liver.

The amounts of ATP-citrate lyase in liver cytosol began to increase at 12 hours after refeeding a high-carbohydrate diet and further increased until 48 hours. The amounts of the ATP-citrate lyase mRNA began to increase at 6 hours and reached to a maximum level at 12 hours, followed by decrease to a very low level until 48 hours. The elevated amount of the ATP-citrate lyase mRNA reflected on the increase of ATP-citrate lyase content in the first 24 hours, but these two parameters were not paralleled thereafter. The transcriptional activity of ATP-citrate lyase gene in nuclei of rat liver began to increase at 4 hours and further increased to reach a maximum level of 24 fold at 12 hours, maintaining a high level of 17 fold until 48 hours. The elevation of transcriptional activity of ATP-citrate lyase gene preceded the increase of ATP-citrate lyase mRNA content in the liver cytosol by 2 hours, and its increasing pattern was similar to changes of mRNA content until 12 hours. However, while the transcriptional activity remained at a high level until 48 hours, the ATP-citrate lyase mRNA concentration in the cytosol decreased after 12 hours.

ATP Citrate (pro-S)-Lyase↗
PubMed1993

Role of glutamate dehydrogenase reaction in the control of citrate pool in yeast.

1. Role of NADP-glutamate dehydrogenase in the depletion of citrate was analyzed using permeabilized yeast cells. 2. Citrate was converted to 2-oxoglutarate, which was then metabolized to glutamate by NADP-glutamate dehydrogenase in the presence of ammonium ion. 3. Formation of 2-oxoglutarate plus glutamate was in good agreement with the concentration of citrate decreased. Glutamate formation can be a good indicator of the depletion of citrate, because 70% of the citrate decreased was converted to glutamate. 4. Glycolytic activity was closely correlated with the decrease in citrate under the in situ conditions. 5. NADP-glutamate dehydrogenase increased in anaerobically grown yeast cells. 6. An effective depletion of citrate by increased synthesis of NADP-glutamate dehydrogenase can explain the lowered mechanism of citrate causing glycolytic stimulation under the anaerobic growth conditions of yeast.

Candida↗
PubMed1996

Changes in citrate concentration in the mouse uterus with experimentally-induced adenomyosis.

Components of the uterine fluid in mice with experimentally-induced adenomyosis and in controls were examined by proton nuclear magnetic resonance spectroscopy. One of the components was markedly different in mice with adenomyosis. As this component was estimated to be citrate by comparison with authentic samples (standard spectrum), its levels in uterine fluid, uterine tissue and blood were determined by enzymatic analysis. The fluid obtained from the uterus with adenomyosis showed significantly lower concentration of citrate than that from normal uterus. However, the uterine tissue concentration was significantly higher in the experimental mice with adenomyosis. There was no difference in the blood citrate level between the experimental and the control groups. Since adenomyosis was induced by chronic hyperprolactinemia, the change of citrate level in the uterus with this lesion might imply some effects of prolactin (PRL) on metabolism and/or secretion of citrate. However, in normal mice, no significant change was demonstrated in uterine citrate concentration after short-term experimental modulation of the circulating PRL level. Thus, it is unlikely that PRL can regulate directly citrate metabolism in the uterus, indicating some other cause for changes in citrate level accompanying the development of adenomyosis.

Animals↗
PubMed1995

Arthropod venom citrate inhibits phospholipase A2.

Citrate has been identified as a major component of honey bee (Apis mellifera) venom by gas liquid chromatography-mass spectrometry. A citrate concentration of 9% was found for dried bee venom by a coupled enzyme assay, aconitase-isocitric dehydrogenase. A liquid honey bee venom would contain 140 mM citrate concentration (if the solids content were 30%). Bee venom phospholipase was inhibited at a 43% level with a citrate concentration of 20 mM and calcium ion at 3 mM with the enzyme assay. Citrate was also found in the venoms of bumble bee, Bombus fervidus, 7%; yellow jacket, Vespula maculifrons, 4%; scorpion, Centruroides sculpturatus, 8%; tarantula, Grammastola cala, 8% and brown recluse spider venom gland extract, Loxoceles reclusa, 1.5% based on dried venom solids. Citrate may serve as an endogenous inhibitor of divalent metal ion-dependent enzymes in arthropod venoms as described by Francis et al. (1992, Toxicon 30, 1239-1246). Many arthropod venoms contain calcium-dependent phospholipases. A direct effect of citrate as a venom component may be possible. The presence of citrate in venoms must be considered in research on receptors, ion channels and divalent ion-dependent toxins.

Aconitate Hydratase↗
PubMed1988

Site-directed mutagenesis of citrate synthase; the role of the active-site aspartate in the binding of acetyl-CoA but not oxaloacetate.

Asp-362, a potential key catalytic residue of Escherichia coli citrate synthase (citrate oxaloacetate-lyase [pro-3S)-CH2COO- ----acetyl-CoA), EC 4.1.3.7) has been converted to Gly-362 by oligonucleotide-directed mutagenesis. The mutant gene was completely sequenced, using a series of synthetic oligodeoxynucleotides spanning the structural gene to confirm that no additional mutations had occurred during genetic manipulation. The mutant gene was expressed in M13 bacteriophage and produced a protein which migrated in an identical manner to wild-type E. coli citrate synthase on SDS-polyacrylamide gels and which cross-reacted with E. coli citrate synthase antiserum. The mutant gene was subsequently recloned into pBR322 for large scale purification of the protein, and the resulting plasmid, pCS31, used to transform the citrate synthase deletion strain, W620. The mutant enzyme purified in an analogous manner to wild-type E. coli citrate synthase and expressed less than 2% of wild-type enzyme activity. The activity of the partial reactions catalysed by citrate synthase was similarly affected suggesting that this residual activity may be due to contaminating wild-type enzyme activity. The mutant citrate synthase retains a high-affinity NADH-binding site consistent with the protein preserving its overall structural integrity. Oxaloacetate binding to the protein is unaffected by the Asp-362 to Gly-362 mutation. Binding of the acetyl-CoA analogue, carboxymethyl-CoA, could not be detected in the mutant protein indicating that the lack of catalytic competence is due primarily to the inability of the protein to bind the second substrate, acetyl-CoA.

Acetyl Coenzyme A↗
PubMed1981

The role of the cyclic AMP-dependent protein kinase in the glucagon-stimulated phosphorylation of ATP-citrate lyase.

We have examined the mechanism whereby glucagon stimulates the phosphorylation of ATP-citrate lyase in intact rat hepatocytes. Purified ATP-citrate lyase is phosphorylated in vitro by the catalytic subunit of the cyclic AMP-dependent protein kinase, in a reaction wherein 2-3 mol phosphate/mol lyase are incorporated, at an initial rate that approaches that observed for mixed histone. This reaction is completely abolished by the protein kinase inhibitor protein. Limited tryptic digestion of ATP-citrate lyase phosphorylated in vitro by the cyclic AMP-dependent protein kinase yields a pattern of 32P-labeled peptides, indistinguishable from those observed in parallel digests of lyase isolated from 32P-labeled, glucagon-stimulated hepatocytes. Phosphorylase b kinase catalyzes the incorporation of 1 mol phosphate/mol lyase, albeit at less than 1/160 the rate observed for phosphorylase b. The phosphorylation of purified ATP-citrate lyase is also catalyzed by homogenates of hepatocytes. This reaction is stimulated by cyclic AMP. At 30 degrees C, in the presence of maximally stimulating concentrations of cyclic AMP, the addition of excess protein kinase inhibitor protein inhibits the phosphorylation of ATP-citrate lyase by 67%. Thus, hepatocytes contain both cyclic AMP-dependent and cyclic AMP-independent ATP-citrate lyase kinase activities. Pretreatment of hepatocytes with glucagon (10(-8) M for 2 min) prior to homogenization results in activation of an endogenous hepatocyte ATP-citrate lyase kinase, as well as histone kinase and phosphorylase b kinase; the glucagon-stimulated increment in lyase kinase (and histone kinase) is observed only when homogenates are assayed in the absence of added cyclic AMP, and is completely abolished by an excess of the protein kinase inhibitor protein. We conclude that the glucagon-stimulated phosphorylation of ATP-citrate lyase in intact hepatocytes is catalyzed directly by the cyclic AMP-dependent protein kinase.

ATP Citrate (pro-S)-Lyase↗
PubMed1994

Limited risk of kidney stone formation during long-term calcium citrate supplementation in nonstone forming subjects.

The physiological and physicochemical effects of long-term calcium citrate supplementation (25 mmol. calcium per day) were assessed in 7 normal premenopausal women. Calcium citrate increased urinary calcium from 3.27 +/- 0.42 mmol. per day (standard deviation) before treatment to 5.16 +/- 0.75 mmol. per day after 1-month of treatment (p < 0.0125). After 3 months of treatment urinary calcium decreased from the 1-month value to 4.54 +/- 0.67 mmol. per day (p < 0.0125) but remained higher than the pretreatment value (p < 0.0125). Fractional intestinal calcium absorption and serum 1,25-dihydroxyvitamin D levels decreased marginally at 1 month of calcium citrate therapy, from 0.457 +/- 0.092 to 0.374 +/- 0.035 (p < 0.05) and from 103 +/- 7 to 77 +/- 14 pmol./l. (p < 0.05), respectively. After 3 months of treatment fractional intestinal calcium absorption decreased further to 0.341 +/- 0.061 (p < 0.0125 compared to pretreatment), whereas serum 1,25-dihydroxyvitamin D remained unchanged at 82 +/- 14 pmol./l. Calcium citrate treatment decreased urinary phosphorus levels significantly from 18.9 +/- 3.3 to 15.0 +/- 2.5 mmol. per day (p < 0.0125) and 14.0 +/- 2.5 mmol. per day (p < 0.05) at 1 and 3 months, respectively. Mean urinary oxalate decreased by 15 to 20% and urinary citrate increased marginally during treatment. Urinary saturation of calcium oxalate and brushite did not change during calcium citrate therapy, except at 1 month when the saturation of calcium oxalate increased marginally. The inhibitory activity of urine against spontaneous nucleation of calcium oxalate and brushite (formation product) did not change during treatment. In conclusion, long-term calcium citrate supplementation in normal subjects does not increase the propensity for crystallization of calcium salts in the urine. This protective effect is probably due to the attenuated increase in urinary calcium excretion (from a decrease in fractional intestinal calcium absorption), a decrease in urinary phosphorus and an increase in urinary citrate.

Adult↗
PubMed1982

Mitochondrial aspartate aminotransferase and the effect of testosterone on citrate production in rat ventral prostate.

Mitochondrial aspartate transamination was investigated as a major source of oxalacetate for citrate synthesis in rat ventral prostate. Citrate accumulation was measured in isolated mitochondria incubated with acetyl coenzyme A and various combinations of amino acids. Aspartate plus alpha ketoglutarate in the presence of acetyl coenzyme A resulted in significant citrate accumulation. Neither aspartate nor alpha ketoglutarate alone resulted in any significant citrate accumulation. Aspartate and alpha ketoglutarate use was comparable to glutamate and citrate production. The results indicated the presence of a mitochondrial aspartate aminotransferase. Castration (3 days) caused a significant decrease in citrate production from aspartate plus alpha ketoglutarate as well as a decrease in mitochondrial AAT activity in prostate although no effect on kidney activity occurred. A single injection of 1 mg. testosterone propionate to castrate rats significantly increased prostate mitochondrial AAT activity within 24 hours while MDH activity was unaltered. A double reciprocal plot indicated that testosterone might regulate the level of mitochondrial AAT in prostate. Ventral prostate also contain a uniquely high level of endogenous aspartate. These studies indicate that aspartate might be the major 4-carbon source of oxalacetate for citrate synthesis. Also testosterone possibly regulated prostate citrate production by its effect on the level of mitochondrial AAT activity.

Animals↗
PubMed1975

Renal metabolism of citrate.

Our studies on renal handling of citrate have shown that: (1) citrate enters renal tubular cells from luminal fluid (reabsorption) and peritubular blood; (2) reabsorption becomes maximal, i.e., Tm-limited, at filtered loads 7 to 8 times the normal; (3) administration of malate stimulates net renal production of citrate, leading to release into urine (net secretion) and into peritubular blood; (4) acute metabolic alkalosis, induced while plasma citrate levels are above normal, depressess net citrate reabsorption, stimulates citrate release into peritubular blood and abolishes overall renal uptake of citrate; (5) essentially all citrate extracted by the kidney is converted to CO2 at endogenous circulating levels. This contribution is 15 per cent of the total renal CO2 production and is independent of chronic alterations in acid-base balance.

Acidosis↗
PubMed1988

[Regional anticoagulation with citrate in hemodialysis in patients with a high risk for hemorrhage].

During haemodialysis in the patient at high risk for bleeding, heparin cannot be safely used to prevent clotting in the dialysis assembly. Among numerous procedures proposed to reduce the risk for bleeding, Pinnick et al. (N Engl J Med, 308: 258, 1983) proposed the use of citrate as the sole anticoagulant. Citrate toxicity and efficiency were studied during 44 haemodialyses carried out in thirteen patients with a high risk for bleeding or with active bleeding. Three patients had hepatic failure. Two types of citrate solution were used, the trisodium form of citrate (102 mmol.l-1 citrate) or the monosodium form (306 mmol.l-1 citrate). The solutions were infused with a calibrated, pressure insensitive pump, before the dialysis unit at a flow rate of 600 ml.h-1 and 200 ml.h-1 respectively. Sufficient citrate was infused to maintain a clotting time of the blood line and dialyser of more than 18 min. Standard 10% calcium chloride was infused at a constant rate of 7 mg.min-1 into the blood being returned to the patient. The patients were dialysed for 4 h for each haemodialysis with a single-pass system. The dialyses were uncomplicated; no active bleeding was noted. The patient's clotting time was significantly reduced during haemodialysis (18.1 +/- 8.9 min to 14.5 +/- 6.3 min; p less than 0.001). Two-hundred and twenty serum citrate levels were measured. Only nine were above the toxic value of 2 mmol.l-1. No clinical evidence of a decrease in ionized calcium was found: there was no change in the corrected QT intervals and blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2003

Competition between transferrin and the serum ligands citrate and phosphate for the binding of aluminum.

A key issue regarding the speciation of Al(3+) in serum is how well the ligands citric acid and phosphate can compete with the iron transport protein serum transferrin for the aluminum. Previous studies have attempted to measure binding constants for each ligand separately, but experimental problems make it very difficult to obtain stability constants with the accuracy required to make a meaningful comparison between these ligands. In this study, effective binding constants for Al-citrate and Al-phosphate at pH 7.4 have been determined using difference UV spectroscopy to monitor the direct competition between these ligands and transferrin. The analysis of this competition equilibrium also includes the binding of citrate and phosphate as anions to apotransferrin. The effective binding constants are 10(11.59) for the 1:1 Al-citrate complexes and 10(14.90) for the 1:2 Al-citrate complexes. The effective binding constant for the 1:2 Al-phosphate complex is 10(12.02). No 1:1 Al-phosphate complex was detected. Speciation calculations based on these effective binding constants indicate that, at serum concentrations of citrate and phosphate, citrate will be the primary low-molecular-mass ligand for aluminum. Formal stability constants for the Al-citrate system have also been determined by potentiometric methods. This equilibrium system is quite complex, and information from both electrospray mass spectrometry and difference UV experiments has been used to select the best model for fitting the potentiometric data. The mass spectra contain peaks that have been assigned to complexes having aluminum:citrate stoichiometries of 1:1, 1:2, 2:2, 2:3, and 3:3. The difference UV results were used to determine the stability constant for Al(H(-1)cta)-, which was then used in the least-squares fitting of the potentiometric data to determine stability constants for Al(Hcta)+, Al(cta), Al(cta)2(3-), Al(H(-1)cta)(cta)(4-), Al2(H(-1)cta)2(2-), and Al3(H(-1)cta)3(OH)(4-).

Algorithms↗
PubMed1983

Alteration of hepatic glucocorticoid receptor stability and nuclear binding in vitro by citrate.

Citrate greatly stabilized rat hepatic unbound glucocorticoid receptors in cell-free conditions at 4 degrees C with optimal effectiveness at 5-15 mM. Control receptors were inactivated at 4 degrees C with a half-life of less than 12 h. However, in the presence of 10 mM-citrate, unbound receptors were almost completely stabilized for 48 h at 4 degrees C. Citrate at a concentration of 1-2 mM yielded half-maximal stabilization. The stabilizing effect of citrate was rather specific, as succinate, alpha-oxoglutarate, oxaloacetate, malate and pyruvate had no apparent stabilizing action. Citrate stabilized receptors over a wide range of H+ concentrations, with complete protection between pH 6.5 and 8.5. In addition, citrate appeared to have a significant effect on glucocorticoid-receptor complex activation into a nuclear binding form. Thus 5-10 mM-citrate enhanced nuclear binding, with optimal activation achieved at 10 mM concentration. As analysed by sucrose-density-gradient centrifugation and DEAE-cellulose chromatography, no apparent change was observed in the physical characteristics of the glucocorticoid receptor in the presence of citrate.

Animals↗
PubMed1992

Effect of citrate on plasma aluminium concentration and aluminium excretion in the rat.

1. Plasma aluminium concentration and urinary aluminium excretion were monitored for 4.5 h in rats after the administration of 25 micrograms or 800 micrograms of aluminium as an intravenous bolus, either as aluminium chloride or as aluminium citrate (i.e. aluminium chloride together with sodium citrate). 2. Immediately after the bolus aluminium administration, the plasma aluminium concentration was higher in the groups given aluminium chloride than in those which received aluminium citrate, although the difference was significant (P < 0.05) only for the 25 micrograms dose. This difference between aluminium chloride and citrate indicates that the citrate form has a higher volume of distribution (i.e. is able to leave the plasma). The calculated volume of distribution for the 25 micrograms of aluminium chloride (17.5 ml) was similar to the plasma volume of the rats used (15 ml). 3. In experiments in vitro, the ultrafilterability of aqueous solutions of aluminium chloride and aluminium citrate were compared. Only 1.05 +/- 0.09% of the aluminium chloride solution was ultrafilterable (aluminium concentration 28,200 +/- 730 ng/ml), whereas 97.3 +/- 2.4% of the aluminium citrate was ultrafilterable (aluminium concentration 42,000 +/- 370 ng/ml). When the filterability of aluminium in plasma was examined, the aluminium chloride ultrafilterability was identical with that in aqueous solution (1.06 +/- 0.13%, aluminium concentration 19,800 +/- 2956 ng/ml), but the aluminium citrate was 79.8 +/- 7.1% ultrafilterable (aluminium concentration 10,125 +/- 591 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗
PubMed2002

Testosterone and prolactin regulation of metabolic genes and citrate metabolism of prostate epithelial cells.

The control and alteration of key regulatory enzymes is a determinant of the reactions and pathways of intermediary metabolism in mammalian cells. An important mechanism in the metabolic control is the hormonal regulation of the genes associated with the transcription and the biosynthesis of these key enzymes. The secretory epithelial cells of the prostate gland of humans and other animals possess a unique citrate-related metabolic pathway regulated by testosterone and prolactin. This specialized hormone-regulated metabolic activity is responsible for the major prostate function of the production and secretion of extraordinarily high levels of citrate. The key regulatory enzymes directly associated with citrate production in the prostate cells are mitochondrial aspartate aminotransferase, pyruvate dehydrogenase, and mitochondrial aconitase. Testosterone and prolactin are involved in the regulation of the corresponding genes associated with these enzymes (which we refer to as "metabolic genes"). The regulatory regions of these genes contain the necessary response elements that confer the ability of both hormones to control gene transcription. In this report, we describe the role of protein kinase c (PKC) as the signaling pathway for the prolactin regulation of the metabolic genes in prostate cells. Testosterone and prolactin regulation of these metabolic genes (which are constitutively expressed in all mammalian cells) is specific for these citrate-producing cells. We hope that this review will provide a strong basis for future studies regarding the hormonal regulation of citrate-related intermediary metabolism. Most importantly, altered citrate metabolism is a persistent distinguishing characteristic (decreased citrate production) of prostate cancer (PCa) and also (increased citrate production) of benign prostatic hyperplasia (BPH). An understanding of the role of hormonal regulation of metabolism is essential to understanding the pathogenesis of prostate disease. The relationships described for the regulation of prostate cell metabolism provides insight into the mechanisms of hormonal regulation of mammalian cells in general.

Animals↗
PubMed2002

Effects of sildenafil citrate (viagra) on cardiac repolarization and on autonomic control in subjects with chronic heart failure.

BACKGROUND: Cases of sudden death associated with sildenafil citrate use have been reported in men with coronary artery disease. The aim of this study was to investigate the drug's effect on cardiac repolarization and sinus autonomic and vascular control in men with mild chronic heart failure (CHF; New York Heart Association classification II). Changes in these variables could predispose patients to malignant ventricular arrhythmias. METHOD: We measured QT dispersion, the QT-RR slope, and the index of QT variability (QTVI) and analyzed spectral power of RR and systolic blood pressure variability in 10 men with dilated cardiomyopathy and in 10 control subjects after administration of a single 50-mg oral dose of sildenafil citrate or placebo at rest (not followed with any attempt at intercourse). RESULTS: In both groups, oral sildenafil citrate decreased the systolic blood pressure (P <.05) and increased the heart rate (P <.05). In subjects with CHF, it also increased the QT-RR (P <.001) and QTVI (from -0.45 +/- 0.07 to -0.27 +/- 0.07; P <.001), but in controls, it increased the QTVI (from -1.20 +/- 0.08 to -0.78 +/-.014; P <.001). In these subjects and controls, oral sildenafil citrate induced a significant reduction in high frequency, expressed in absolute power (subjects with CHF: from 4.04 +/- 0.14 to 3.43 +/- 0.16 natural logarithm ms2; P <.001; controls: from 5.61 +/- 0.44 to 4.98 +/- 0.32 natural logarithm ms2; P <.05) and in normalized units (P <.05). In subjects with CHF but not in controls, it also significantly increased the low frequency to high frequency ratio (from 1.3 +/- 0.12 to 1.89 +/- 0.16; P <.001) and low frequency expressed in normalized units (P <.05). Sildenafil citrate caused no significant changes in the QT interval or dispersion. CONCLUSION: These findings indicate that, in men with heart failure, sildenafil citrate reduces vagal modulation and increases sympathetic modulation, probably through its reflex vasodilatory action. The autonomic system changes induced with sildenafil citrate could alter QT dynamics. Both changes could favor the onset of lethal ventricular arrhythmias. At the dose usually taken for erectile dysfunction, sildenafil citrate has no direct effect on cardiac repolarization (QT interval or dispersion).

Administration, Oral↗
PubMed1997

Probing the origin of acetyl-CoA and oxaloacetate entering the citric acid cycle from the 13C labeling of citrate released by perfused rat hearts.

We present a strategy for simultaneous assessment of the relative contributions of anaplerotic pyruvate carboxylation, pyruvate decarboxylation, and fatty acid oxidation to citrate formation in the perfused rat heart. This requires perfusing with a mix of 13C-substrates and determining the 13C labeling pattern of a single metabolite, citrate, by gas chromatography-mass spectrometry. The mass isotopomer distributions of the oxaloacetate and acetyl moieties of citrate allow calculation of the flux ratios: (pyruvate carboxylation)/(pyruvate decarboxylation), (pyruvate carboxylation)/(citrate synthesis), (pyruvate decarboxylation)/(citrate synthesis) (pyruvate carboxylation)/(fatty acid oxidation), and (pyruvate decarboxylation)/(fatty acid oxidation). Calculations, based on precursor-product relationship, are independent of pool size. The utility of our method was demonstrated for hearts perfused under normoxia with [U-13C3](lactate + pyruvate) and [1-13C]octanoate under steady-state conditions. Under these conditions, effluent and tissue citrate were similarly enriched in all 13C mass isotopomers. The use of effluent citrate instead of tissue citrate allows probing substrate fluxes through the various reactions non-invasively in the intact heart. The methodology should also be applicable to hearts perfused with other 13C-substrates, such as 1-13C-labeled long chain fatty acid, and under various conditions, provided that assumptions on which equations are developed are valid.

Acetyl Coenzyme A↗