Potassium citrate therapy caused a sustained increase in urinary pH and potassium, and restored urinary citrate to normal levels. No significant changes occurred in urinary uric acid, oxalate, sodium or phosphorus levels. Owing to these physiological changes, uric acid solubility increased, urinary saturation of calcium oxalate decreased and the propensity for spontaneous nucleation of calcium oxalate was reduced to normal. Therefore, the Physicochemical environment of urine following treatment become less conductive to the crystallization of calcium oxalate or uric acid. Twenty six patients with uric acid nephrolithiasis with or without calcium nephrolithiasis underwent treatment and long-term preventive management (mean of 20.8 months) with potassium citrate. Urinary pH increased from acid (5.0-5.5) to normal (6.5-7.0) during treatment. During the period of preventive management, stones were not developed.
Calcium ; Calcium Oxalate ; Citric Acid ; Crystallization ; Humans ; Hydrogen-Ion Concentration ; Nephrolithiasis ; Oxalic Acid ; Phosphorus ; Potassium Citrate* ; Potassium* ; Solubility ; Uric Acid ; Urinary Calculi*

PURPOSE: We compared the biochemical and clinical presentation of gouty diathesis in patients with uric acid and calcium nephrolithiasis MATERIALS AND METHODS: We retrospectively reviewed biochemical and clinical data from 69 gouty diathesis patients(48 with uric acid stones and 21 with calcium stones) and 57 normal subjects were performed at our institution. RESULTS: Demographic similarity between two groups was a male predominance. Gouty diathesis patients in both groups showed abnormally low urinary pH(<5.5) and propensity for hyperuricemia and hypertriglyceridemia. Gouty arthritis and hyperuricemia was found in 31% and 44% of those with uric acid stones whereas 9.5% and 23.8% in those with calcium stone respectively. In control group, 1 case presented with hyperuricemia and urinary pH at 6.3. Both urinary pH and citrate increased after potassium citrate treatment in both groups. CONCLUSIONS: The two groups of gouty diathesis with either uric acid stone or calcium stones have similar biochemical and clinical features that are characteristic of primary gout. Calcium stone formation in patients with hyperuricemia or persistent acidic urine may represent a latent form of gout. Patients with calcium stones and biochemical feature of gouty diathesis may manifest primary gouty. Both groups are responsive to potassium citrate treatment.
Arthritis, Gouty ; Calcium* ; Citric Acid ; Disease Susceptibility* ; Gout ; Humans ; Hydrogen-Ion Concentration ; Hypertriglyceridemia ; Hyperuricemia ; Male ; Nephrolithiasis ; Potassium Citrate ; Retrospective Studies ; Uric Acid*

PURPOSE: Citrate is a well recognized inhibitor of the formation of calcium oxalate and calcium phosphate stones. Hypocitraturia is a common etiology of recurrent calcium nephrolithiasis, with an incidence of 19 to 63%. Potassium citrate therapy can be a useful therapeutic approach for the management of calcium nephrolithiasis. But pharmacological treatment of hypocitraturic calcium nephrolithiasis requires taking too many tablets, or numerous crystal package or liquid supplements throughout the day. This cumbersome regimen often decreases patient compliance. We administered dietary citrate via lemon juice to stone former and evaluated the change of citrate levels. MATERIALS AND METHODS: The prospective study included 7 women and 8 men with documented recurrent or multiple urinary stone disease. None of the subjects suffered from renal impairment, urinary tract infection and other metabolic disorder. Controls comprised 6 voluntary men. They had no previous stone history and no evidence of stone. Patients ingested total 1 liter of lemon juice(containing 4.0gm/L.citrate) divided at 6 hours interval without strict diet restriction. Urine specimens were obtained for urinary citrate levels after 2-3days of lemon juice therapy and compared to pre-lemon juice baseline values. RESULTS: All 15 patient showed increased urinary citrate levels during lemon juice therapy. Average urinary citrate levels increased from 146+/-109mg/day at baseline to 453+/-226mg/day during treatment(p<0.05). Urinary citrate levels during treatment increased up to those of control group(351+/-265mg/day) and did not show significant difference (p>0.05). Urinary pH increased from 5.9+/-0.4 at baseline to 6.8+/-0.6 during treatment(p<0.05). No patient complained of gastrointestinal discomforts. CONCLUSIONS: Citrate supplementation with lemon juice increased urinary citrate levels and urinary pH. Lemon juice is well tolerated dietary source of citrate and would be beneficial in the control of calcium urolithiasis.
Calcium ; Calcium Oxalate ; Citric Acid* ; Diet ; Female ; Humans ; Hydrogen-Ion Concentration ; Incidence ; Male ; Nephrolithiasis ; Patient Compliance ; Potassium Citrate ; Prospective Studies ; Tablets ; Urinary Calculi ; Urinary Tract Infections ; Urolithiasis*

PURPOSE: To study the effects of long-term treatment with potassium magnesium citrate and vitamin B-6 prophylaxis (Urikind-KM6; 1,100-mg potassium citrate, 375-mg magnesium citrate, and 20-mg pyridoxine hydrochloride/5 mL) every 8 hours over 3 years. MATERIALS AND METHODS: A total of 247 patients with recurrent idiopathic hypocitraturia with or without hyperuricosuria and randomized controls were studied prospectively for 3 years. The total patients were divided into three groups. Control group 1 consisted of 61 patients (24.7%) who had moderate to severe hypocitraturia with or without hyperuricosuria and were recurrent stone formers but discontinued prophylaxis because of drug intolerance within 1 month of therapy. Control group 2 constituted 53 patients (21.5%) who were first-time stone formers and who had mild hypocitraturia with or without hyperuricosuria and were not put on prophylactic therapy and were followed for 3.16+/-0.08 years. Control group 3 constituted 133 patients (54.8%) who were recurrent stone formers who had moderate to severe hypocitraturia with or without hyperuricosuria and were put on prophylaxis therapy and were followed for 3.16+/-0.08 years. All patients were followed up at 6-month intervals. RESULTS: Potassium magnesium citrate prophylaxis produced a sustained increase in 24-hour urinary citrate excretion from initially low values (221.79+/-13.39 mg/dL) to within normal to high limits (604.04+/-5.00 mg/dL) at the 6-month follow-up. Urinary pH rose significantly from 5.62+/-0.2 to 6.87+/-0.01 and was maintained at 6.87+/-0.01. The stone recurrence rate declined from 3.23+/-1.04 per patient per year to 0.35+/-0.47 per patient per year. CONCLUSIONS: Potassium magnesium citrate prophylaxis was effective in reducing the recurrence of calcium oxalate and phosphate urolithiasis.
Calcium Oxalate* ; Citric Acid* ; Follow-Up Studies ; Humans ; Hydrogen-Ion Concentration ; Magnesium* ; Potassium Citrate ; Potassium* ; Prospective Studies ; Pyridoxine ; Recurrence ; Urolithiasis* ; Vitamins*

PURPOSE: It has previously been reported that citrate, thiazide, allopurinol and magnesium (CTAM) have inhibitory effects on calcium oxalate crystallization, but the effects of CTAM on the matrix proteins of stones in vivo has not been studied. Using an ethylene glycol-induced urolithiasis model, we investigated the effects of CTAM on renal crystallization and the expression of osteopontin (OPN), which is an important stone matrix protein. MATERIALS AND METHODS: Adult Sprague-Dawley rats (200-250gm) were divided randomly into 6 groups of 10 rats. Group 1 was left untreated, and served as a control. Group 2 (CID group) was fed 0.8% ethylene glycol and 1% ammonium chloride (crystal-inducing diet, CID) in drinking water for 4 weeks. Groups 3, 4, 5 and 6 (CTAM groups) were fed the same CID as group 2, but were also treated with either potassium citrate or hydrochlorothiazide or allopurinol or magnesium hydroxide, for 4 weeks, respectively. We biochemically analyzed the 24-hour urine and serum samples. The renal calcium content was measured by atomic absorption. The kidneys were histologically examined for crystal deposit with HandE staining, and for OPN expression with immunohistochemical staining. RESULTS: The grade of calcium oxalate crystal deposits, and renal calcium content, were significantly decreased in the CTAM groups compared to the CID group, which also correlated with the decreased expression of OPN proteins in the kidneys of the CTAM-treated rats. CTAM were all effective in preventing calcium oxalate crystal formation, and decreasing the expression of OPN in rat kidneys. CONCLUSIONS: Our results suggest that CTAM are effective in preventing calcium oxalate stone formation, and that OPN plays an important role in calcium oxalate nephrolithiasis.
Absorption ; Administration, Oral* ; Adult ; Allopurinol* ; Ammonium Chloride ; Animals ; Calcium Oxalate* ; Calcium* ; Citric Acid* ; Crystallization ; Diet ; Drinking Water ; Ethylene Glycol ; Hand ; Humans ; Hydrochlorothiazide ; Kidney ; Magnesium Hydroxide ; Magnesium* ; Nephrolithiasis ; Osteopontin* ; Potassium Citrate ; Rats* ; Rats, Sprague-Dawley ; Urolithiasis*

Citric Acid Cycle ; Citric Acid ; Malates/metabolism* ; Citrates/metabolism* ; Aspartic Acid/metabolism*

As one of the key enzymes in cell metabolism, the activity of citrate synthase 3 (CS3) regulates the substance and energy metabolism of organisms. The protein members of CS3 family were identified from the whole genome of apple, and bioinformatics analysis was performed and expression patterns were analyzed to provide a theoretical basis for studying the potential function of CS3 gene in apple. BLASTp was used to identify members of the apple CS3 family based on the GDR database, and the basic information of CS3 protein sequence, subcellular localization, domain composition, phylogenetic relationship and chromosome localization were analyzed by Pfam, SMART, MEGA5.0, clustalx.exe, ExPASy Proteomics Server, MEGAX, SOPMA, MEME, WoLF PSORT and other software. The tissue expression and inducible expression characteristics of 6 CS3 genes in apple were determined by acid content and real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). Apple CS3 gene family contains 6 members, and these CS3 proteins contain 473-608 amino acid residues, with isoelectric point distribution between 7.21 and 8.82. Subcellular localization results showed that CS3 protein was located in mitochondria and chloroplasts, respectively. Phylogenetic analysis divided them into 3 categories, and the number of genes in each subfamily was 2. Chromosome localization analysis showed that CS3 gene was distributed on different chromosomes of apple. The secondary structure of protein is mainly α-helix, followed by random curling, and the proportion of β-angle is the smallest. The 6 members were all expressed in different apple tissues. The overall expression trend from high to low was the highest relative expression content of MdCS3.4, followed by MdCS3.6, and the relative expression level of other members was in the order of MdCS3.3 > MdCS3.2 > MdCS3.1 > MdCS3.5. qRT-PCR results showed that MdCS3.1 and MdCS3.3 genes had the highest relative expression in the pulp of 'Chengji No. 1' with low acid content, and MdCS3.2 and MdCS3.3 genes in the pulp of 'Asda' with higher acid content had the highest relative expression. Therefore, in this study, the relative expression of CS3 gene in apple cultivars with different acid content in different apple varieties was detected, and its role in apple fruit acid synthesis was analyzed. The experimental results showed that the relative expression of CS3 gene in different apple varieties was different, which provided a reference for the subsequent study of the quality formation mechanism of apple.
Citric Acid ; Malus/genetics* ; Citrate (si)-Synthase ; Phylogeny ; Citrates

Chemical investigation of fruits of Mours alba L. lead to the isolation of fifteen compounds by various chromatographies such as silica gel, Sephadex LH-20, RP-C18 column chromatography. Their structures were determined to be: 1-[5-(2-formlfuryl) methyl] dihydrogen 2-hydroxypropane-1, 2, 3-tricarboxylate 2, 3-diethyl ester (1), 1-[2-(furan-2-yl)-2-oxoethyl] pyrrolidin-2-one (2), divaricataester A (3), methyl 1-[2-(furan-2-yl)-2-oxoethyl]-5-oxopyrrolidine-2-carboxylate (4), 1-[2-(furan-2-yl)-2-oxoethyl]-5-oxopyrrolidine-2-carboxylic acid (5), L-pyroglutamic acid (6), L-pyroglutamic acid ethyl ester (7), 3-O-caffeoylquinic acid methyl ester (8), 3-O-caffeoylquinic acid ethyl ester (9), 5-O-caffeoylquinic acid methyl ester (10), 5-O-caffeoylquinic acid ethyl ester (11), 4-O-caffeoylquinic acid methyl ester (12), 4-O-caffeoylquinic acid methyl ester (13), 4-O-caffeoylquinic acid (14), 3-O-caffeoylquinic acid (15), respectively, based on the spectral analysis such as NMR, MS etc. Compounds 1-14 were isolated from this genus for the first time, among which 1 was a new compound.
Chlorogenic Acid ; isolation & purification ; Esters ; Fruit ; chemistry ; Furans ; chemistry ; isolation & purification ; Lactams ; isolation & purification ; Molecular Structure ; Morus ; chemistry ; Plants, Medicinal ; chemistry ; Pyrrolidonecarboxylic Acid ; isolation & purification ; Tricarboxylic Acids ; chemistry ; isolation & purification

OBJECTIVETo investigate the underlying metabolomic profifiling of coronary heart disease (CHD) with blood stasis syndrome (BSS).

METHODSCHD model was induced by a nameroid constrictor in Chinese miniature swine. Fifteen miniature swine were randomly divided into a model group (n=9) and a control group (n=6), respectively according to arandom number table. After 4 weeks, plasma hemorheology was detected by automatic hemorheological analyzer, indices including hematocrit, plasma viscosity, blood viscosity, rigidity index and erythrocyte sedimentation rate; cardiac function was assessed by echocardiograph to detect left ventricular end-systolic diameter (LVED), left ventricular end-diastolic diameter (LVEDd), ejection fraction (EF), fractional shortening (FS) and other indicators. Gas chromatography coupled with mass spectrometry (GC-MS) and bioinformatics were applied to analyze spectra of CHD plasma with BSS.

RESULTSThe results of hemorheology analysis showed signifificant changes in viscosity, with low shear whole blood viscosity being lower and plasma viscosity higher in the model group compared with the control group. Moreover, whole blood reduction viscosity at high shear rate and whole blood reduction viscosity at low shear rate increased signifificantly (P <0.05). The echocardiograph results demonstrated that cardiac EF and FS showed signifificant difference (P <0.05), with EF values being decreased to 50% or less. The GC-MS data showed that principal component analysis can clearly separate the animals with BSS from those in the control group. The enriched Kyoto Encyclopedia of Genes and Genomes biological pathways results suggested that the patterns involved were associated with dysfunction of energy metabolism including glucose and lipid disorders, especially in glycolysis/gluconeogenesis, galactose metabolism and adenosine-triphosphate-binding cassette transporters.

CONCLUSIONSGlucose metabolism and lipid metabolism disorders were the major contributors to the syndrome classifification of CHD with BSS.

Animals ; Coronary Angiography ; Coronary Disease ; blood ; diagnostic imaging ; metabolism ; surgery ; Disease Models, Animal ; Electrocardiography ; Gas Chromatography-Mass Spectrometry ; Hemorheology ; Metabolome ; Metabolomics ; methods ; Principal Component Analysis ; Sus scrofa ; Tricarboxylic Acids ; metabolism

The global metabolite profiles of endogenous compounds of Wistar rats from 12 to 20 weeks old were investigated to take deep insight into and get better understanding of the pathogenesis of development and aging. Plasma from Wistar rats at 12, 14, 16, 18, and 20 weeks old were analyzed using GC/TOFMS. Multivariate data analysis was then used to process the metabonomic data which indicated excellent separation between different weeks and showed that the metabolic profiles of the samples changed with age, enabling age-related metabolic trajectories to be visualized. Decreased concentrations of citric acid, cis-aconitic acid, 9-(z)-hexadecenoic acid along with increased levels of hexanedioic acid, alpha-tocopherol, 3-indole propionic acid, etc contributed to the separation. Several major metabolic pathways were identified to be involved in metabolic regulation. This suggests that GC/TOFMS-based metabonomics is a powerful alternative approach to identifying potential biomarkers and investigating the physiological developments of aging and it is important to employ suitable age-match control group in metabonomic study of physiological monitoring, drug safety assessment, and disease diagnosis, etc.
Aconitic Acid ; blood ; Adipates ; blood ; Aging ; blood ; physiology ; Animals ; Biomarkers ; blood ; Chromatography, Gas ; methods ; Citric Acid ; blood ; Indoles ; blood ; Male ; Metabolome ; Metabolomics ; Multivariate Analysis ; Palmitic Acids ; blood ; Propionates ; blood ; Rats ; Rats, Wistar ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; methods ; alpha-Tocopherol ; blood