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1.
Am J Physiol Renal Physiol ; 317(4): F967-F977, 2019 10 01.
Article in English | MEDLINE | ID: mdl-31390232

ABSTRACT

We studied sex differences in response to high K+ (HK) intake on thiazide-sensitive cation (Na+ and K+) excretion in wild-type (WT) and ANG II receptor subtype 1a (AT1aR) knockout (KO) mice. Renal clearance experiments were performed to examine Na+-Cl- cotransporter (NCC) activity on mice fed with control and HK (5% KCl, 7 days) diets. Hydrochlorothiazide (HCTZ)-induced changes in urine volume, glomerular filtration rate, absolute Na+ and K+ excretion, and fractional excretion were compared. HK-induced changes in NCC, Na+/H+ exchanger isoform 3 (NHE3), and ENaC expression were examined by Western blot analysis. In WT animals under the control diet, HCTZ-induced cation excretion was greater in female animals, reflecting larger increases in Na+ excretion, since there was little sex difference in HCTZ-induced K+ excretion. Under the HK diet, the sex difference in HCTZ-induced cation excretion was reduced because of larger increments in K+ excretion in male animals. The fraction of K+ excretion was 57 ± 5% in male WT animals and 36 ± 4% in female WT animals (P < 0.05), but this difference was absent in AT1aR KO mice. NCC abundance was higher in female animals than in male animals but decreased by similar fractions on HK diet. NHE3 abundance decreased, whereas cleaved forms of γ-ENaC increased, with HK in all groups; these changes were similar in male and female animals and were not significantly affected by AT1aR ablation. These results indicate that, with the HK diet, male animals display greater distal Na+ delivery and greater activation of K+ secretion mechanisms, all suggesting a more powerful male adaptation to HK intake.


Subject(s)
Cations/urine , Diuretics/pharmacology , Electron Transport Complex II/metabolism , Hydrochlorothiazide/pharmacology , Kidney/metabolism , Potassium/pharmacology , Animals , Female , Glomerular Filtration Rate , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Potassium/urine , Receptor, Angiotensin, Type 1/genetics , Receptor, Angiotensin, Type 1/metabolism , Sex Characteristics , Sodium-Hydrogen Exchanger 3/metabolism , Sodium-Potassium-Chloride Symporters/metabolism , Urodynamics
2.
Am J Kidney Dis ; 74(3): 320-327, 2019 09.
Article in English | MEDLINE | ID: mdl-31005371

ABSTRACT

RATIONALE & OBJECTIVE: The discovery of sodium storage without concurrent water retention suggests the presence of an additional compartment for sodium distribution in the body. The osmoregulatory role of this compartment under hypotonic conditions is not known. STUDY DESIGN: Experimental interventional study. SETTING & PARTICIPANTS: Single-center study of 12 apparently healthy men. INTERVENTION: To investigate whether sodium can be released from its nonosmotic stores after a hypotonic fluid load, a water-loading test (20mL water/kg in 20 minutes) was performed. OUTCOMES: During a 240-minute follow-up, we compared the observed plasma sodium concentration ([Na+]) and fluid and urine cation excretion with values predicted by the Barsoum-Levine and Nguyen-Kurtz formulas. These formulas are used for guidance of fluid therapy during dysnatremia, but do not account for nonosmotic sodium stores. RESULTS: 30 minutes after water loading, mean plasma [Na+] decreased 3.2±1.6 (SD) mmol/L, after which plasma [Na+] increased gradually. 120 minutes after water loading, plasma [Na+] was significantly underestimated by the Barsoum-Levine (-1.3±1.4mmol/L; P=0.05) and Nguyen-Kurtz (-1.5±1.5mmol/L; P=0.03) formulas. In addition, the Barsoum-Levine and Nguyen-Kurtz formulas overestimated urine volume, while cation excretion was significantly underestimated, with a cation gap of 57±62 (P=0.009) and 63±63mmol (P=0.005), respectively. After 240 minutes, this gap was 28±59 (P=0.2) and 34±60mmol (P=0.08), respectively. LIMITATIONS: The compartment from which the mobilized sodium originated was not identified, and heterogeneity in responses to water loading was observed across participants. CONCLUSIONS: These data suggest that healthy individuals are able to mobilize osmotically inactivated sodium after an acute hypotonic fluid load. Further research is needed to expand knowledge about the compartment of osmotically inactivated sodium and its role in osmoregulation and therapy for dysnatremias. FUNDING: This investigator-initiated study was partly supported by a grant from Unilever Research and Development Vlaardingen, The Netherlands B.V. (MA-2014-01914).


Subject(s)
Body Fluids/chemistry , Cations/urine , Sodium/blood , Water/administration & dosage , Adolescent , Adult , Body Fluids/metabolism , Cations/metabolism , Humans , Male , Sodium/metabolism , Water/metabolism , Water-Electrolyte Balance , Young Adult
3.
Anal Sci ; 35(3): 295-300, 2019 Mar 10.
Article in English | MEDLINE | ID: mdl-30393239

ABSTRACT

An analytical method for concurrent analysis of inorganic anions and cations has been developed using a capillary electrophoresis (CE)-capacitively coupled contactless conductivity detector (C4D) system. Although hydrodynamic and electrokinetic injection techniques have been widely used in CE, we employed a capillary filling method (CFM) for the analysis of inorganic ions. The procedure is relatively simple and has the advantage that CMF does not require pressure control and vial exchange. Three anions (chloride, sulfate, nitrate) and five cations (ammonium, potassium, sodium, magnesium, calcium) were successfully separated and detected at ppm levels within 80 s using a 9 mM histidine/15 mM malic acid (pH 3.6) containing 50 mM N-dodecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate as background electrolyte. Applying this analytical condition, the electroosmotic flow is negligible and anions and cations were migrated concurrently to different polarities according to their electrophoretic mobility. Obtained raw data showed stepwise increases in detected conductivity due to the migration of sample components, which expresses as peak profiles by differentiation of electropherograms. The RSD values of the peak area and migration times for the anions and cations were satisfactory and were less than 5.15 and 2.04%, respectively. The developed method was applied for the analysis of inorganic anions and cations in commercial mineral waters, tap water, urine, and exhaled breath condensate. These results indicate that the CE-C4D system with CFM is suitable for the rapid analysis of inorganic anions and cations in various samples.


Subject(s)
Anions/analysis , Cations/analysis , Conductometry/methods , Drinking Water/chemistry , Electrophoresis, Capillary/methods , Mineral Waters/analysis , Anions/urine , Breath Tests , Cations/urine , Conductometry/instrumentation , Electric Conductivity , Electrophoresis, Capillary/instrumentation , Humans
4.
World J Urol ; 34(12): 1685-1691, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27027645

ABSTRACT

PURPOSE: To identify and quantify toxic urinary cations in male patients with bladder pain syndrome/interstitial cystitis versus male controls, to compare them in symptomatic patients to those significantly improved, and to evaluate cytotoxicity of these cations to cultured urothelial cells to determine whether Tamm-Horsfall protein (THP) can neutralize the cations. METHODS: Isolation of cationic fraction (CFs) was achieved by solid phase extraction on urine specimens of 51 male patients with IC and 33 male controls. C18 reverse-phase high-performance liquid chromatography was used to profile and quantify cationic metabolites. Major CF peaks were identified by liquid chromatography-tandem mass spectrometry. HTB-4 urothelial cells were used to determine the cytotoxicity of CFs, individual metabolites, and of metabolite mixture with THP of patient versus THP of control subject. RESULTS: CF content was significantly higher in patients compared to controls (p < 0.001). Patients had higher levels of modified nucleosides, amino acids, and their derivatives compared to controls. Cytotoxicity for control versus patient mean (SEM) percent was 1.7 (2.9) % versus 63.0 (3.7) %, respectively, (p < 0.001). Cytotoxicity of metabolites was reduced in the presence of THP of control compared to THP of patient (p < 0.001). CONCLUSIONS: Patients with IC had significantly higher levels of cationic metabolites with higher cytotoxicity compared to controls. THP of these patients had reduced ability to sequester cytotoxicity of cationic metabolites. Patients who significantly improved on therapy had the same levels and toxicity of cationic metabolites as symptomatic males, suggesting that these cations may be the cause of epithelial dysfunction in IC.


Subject(s)
Cations/urine , Cystitis, Interstitial/urine , Urinary Bladder/metabolism , Adult , Biomarkers/urine , Cells, Cultured , Chromatography, Liquid , Cystitis, Interstitial/pathology , Humans , Male , Middle Aged , Tandem Mass Spectrometry , Urinalysis , Urinary Bladder/pathology , Urothelium/pathology
5.
Electrophoresis ; 36(16): 1962-8, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25752683

ABSTRACT

A computer-controlled hydrodynamic sample introduction method has been proposed for short-capillary electrophoresis. In the method, the BGE flushes sample from the loop of a six-way sampling valve and is carried to the injection end of the capillary. A short pressure impulse is generated in the electrolyte stream at the time when the sample zone is at the capillary, leading to injection of the sample into the capillary. Then the electrolyte flow is stopped and the separation voltage is turned on. This way of sample introduction does not involve movement of the capillary and both of its ends remain constantly in the solution during both sample injection and separation. The amount of sample introduced to the capillary is controlled by the duration of the pressure pulse. The new sample introduction method was tested in the determination of ammonia, creatinine, uric acid, and hippuric acid in human urine. The determination was performed in a capillary with an overall length of 10.5 cm, in two BGEs with compositions 50 mM MES + 5 mM NaOH (pH 5.1) and 1 M acetic acid + 1.5 mM crown ether 18-crown-6 (pH 2.4). A dual contactless conductivity/UV spectrometric detector was used for the detection.


Subject(s)
Electrophoresis, Capillary/methods , Urinalysis/methods , Ammonium Compounds/urine , Cations/urine , Creatinine/urine , Electric Conductivity , Electrophoresis, Capillary/instrumentation , Equipment Design , Humans , Limit of Detection , Linear Models , Pressure , Reproducibility of Results , Spectrophotometry, Ultraviolet , Urinalysis/instrumentation
6.
Analyst ; 139(13): 3469-75, 2014 Jul 07.
Article in English | MEDLINE | ID: mdl-24842842

ABSTRACT

The significance of metals in life and their epidemiological effects necessitate the development of a direct, efficient, and rapid method of analysis. The matrix assisted laser desorption/ionization technique is on the horns of a dilemma of metal analysis as the conventional matrixes have high background in the low mass range. An organic salt, NEDC (N-naphthylethylenediamine dihydrochloride), is applied as a matrix for identification of metal ions in the negative ion mode in the present work. Sixteen metal ions, Ba(2+), Ca(2+), Cd(2+), Ce(3+), Co(2+), Cu(2+), Fe(3+), Hg(2+), K(+), Mg(2+), Mn(2+), Na(+), Ni(2+), Pb(2+), Sn(2+) and Zn(2+), in the form of their chloride-adducted clusters were systematically tested. Mass spectra can provide unambiguous identification through accurate mass-to-charge ratios and characteristic isotope patterns. Compared to ruthenium ICP standard solution, tris(2,2'-bipyridyl)dichlororuthenium(ii) (C30H24N6Cl2Ru) can form organometallic chloride adducts to discriminate from the inorganic ruthenium by this method. After evaluating the sensitivity for Ca, Cu, Mg, Mn, Pb and Zn and plotting their quantitation curves of signal intensity versus concentration, we determined magnesium concentration in lake water quantitatively to be 5.42 mg L(-1) using the standard addition method. There is no significant difference from the result obtained with ICP-OES, 5.8 mg L(-1). Human urine and blood were also detected to ascertain the multi-metal analysis ability of this strategy in complex samples. At last, we explored its applicability to tissue slice and visualized sodium and potassium distribution by mass spectrometry imaging in the normal Kunming mouse brain.


Subject(s)
Brain Chemistry , Ethylenediamines/chemistry , Lakes/analysis , Metals/analysis , Metals/blood , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Adult , Animals , Cations/analysis , Cations/blood , Cations/urine , Chlorides/chemistry , Female , Humans , Metals/urine , Mice , Young Adult
7.
Anal Chim Acta ; 761: 178-85, 2013 Jan 25.
Article in English | MEDLINE | ID: mdl-23312329

ABSTRACT

A novel assay of chromium(III) ion based on upconversion fluorescence resonance energy transfer was designed and established. Lysine-capped NaYF(4):Yb/Er upconversion nanoparticles (UCNPs) and dimercaptosuccinic acid-capped gold nanoparticles (AuNPs) were used as the energy donor and acceptor, respectively. They were bound together via electrostatic interaction, resulting in the quenching of the fluorescence of UCNPs by AuNPs. Chromium(III) ions can specifically and strongly interact with dimercaptosuccinic acid that was modified on the surface of AuNPs, leading to the separation of AuNPs from UCNPs and the recovery of fluorescence of UCNPs. The fluorescence recovery of UCNPs showed a good linear response to Cr(3+) concentration in the range of 2-500 nM with a detection limit of 0.8 nM. This method was further applied to determine the levels of Cr(3+) in urine. Compared with other fluorescence methods, current method displayed very high sensitivity and signal-to-noise ratio because of the excitation of near-infrared that can eliminate autofluorescence, providing a promising examination of biological samples for the diagnostic purposes.


Subject(s)
Cations/urine , Chromium/urine , Fluorescence Resonance Energy Transfer/methods , Nanoparticles/chemistry , Gold/chemistry , Humans , Limit of Detection , Lysine/chemistry , Nanoparticles/ultrastructure , Signal-To-Noise Ratio , Succimer/chemistry
8.
Nutr J ; 11: 39, 2012 Jun 07.
Article in English | MEDLINE | ID: mdl-22676161

ABSTRACT

BACKGROUND: The finding reported in a previous paper - alkalization of urine facilitates uric acid excretion - is contradictory to what one might expect to occur: because food materials for the alkalization of urine contain fewer purine bodies than those for acidification, less uric acid in alkaline urine should have been excreted than in acid urine. To make clear what component of uric acid excretion mechanisms is responsible for this unexpected finding, we simultaneously collected data for the concentration of both creatinine and uric acid in serum as well as in urine, in order to calculate both uric acid and creatinine clearances. METHODS: Within the framework of the Japanese government's health promotion program, we made recipes which consisted of protein-rich and less vegetable-fruit food materials for H + -load (acidic diet) and others composed of less protein and more vegetable-fruit rich food materials (alkaline diet). This is a crossover study within some limitations. Healthy female students, who had no medical problems at the regular physical examination provided by the university, were enrolled in this consecutive 5-day study for each test. From whole-day collected urine, total volume, pH, organic acid, creatinine, uric acid, titratable acid and all cations (Na+,K+,Ca2+,Mg2+,NH4+) and anions (Cl-,SO42-,PO4-) necessary for the estimation of acid-base balance were measured. In the early morning before breakfast of the 1st, 3rd and 5th experimental day, we sampled 5 mL of blood to estimate the creatinine and uric acid concentration in serum. RESULTS AND DISCUSSION: Urine pH reached a steady state 3 days after switching from ordinary daily diets to specified regimens. The amount of acid generated ([SO42-] + organic acid - gut alkali)was linearly related with the excretion of acid (titratable acid + [NH4+] - [HCO3-]), indicating that H + in urine is generated by the metabolic degradation of food materials. Uric acid and excreted urine pH retained a linear relationship, as reported previously. Among the five factors which are associated with calculating clearances for both uric acid and creatinine, we identified a conspicuous difference between acidic and alkaline diets in the uric acid concentration in serum as well as in urine; uric acid in the serum was higher in the acidic group than in the alkaline group, while uric acid in the urine in the acidic group was lower than that in the alkaline group. These changes of uric acid in acidic urine and in serum were reflected in the reduction of its clearance. From these observations, it is considered that uric acid may be reabsorbed more actively in acidic urine than in alkaline urine. CONCLUSION: We conclude that alkalization of urine by eating nutritionally well-designed alkaline -prone food is effective for removing uric acid from the body.


Subject(s)
Acid-Base Equilibrium , Diet , Feeding Behavior , Uric Acid/urine , Anions/blood , Anions/urine , Cations/blood , Cations/urine , Creatinine/blood , Creatinine/urine , Cross-Over Studies , Female , Fruit , Humans , Hydrogen-Ion Concentration , Specimen Handling , Uric Acid/blood , Young Adult
9.
Electrophoresis ; 31(14): 2319-27, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20564266

ABSTRACT

In this study, the usefulness of noncovalently coated capillaries with layers of charged polymers is investigated to obtain global electrophoretic profiles of urinary metabolites covering a broad range of different compound classes in a highly repeatable way. Capillaries were coated with a bilayer of polybrene (PB) and poly(vinyl sulfonate) (PVS), or with a triple layer of PB, dextran sulfate (DS) and PB. The bilayer and triple layer coatings were evaluated at acidic (pH 2.0) and alkaline (pH 9.0) separation conditions, thereby providing separation conditions for basic and acidic compounds. A representative metabolite mixture and spiked urine samples were used for the evaluation of the four CE methods. Migration time repeatability (RSD<2%) and plate numbers (N, 100,000-400,000) were similar for the test compounds in all CE methods, except for some multivalent ions that may exhibit adsorption to oppositely charged coatings. The analysis of cationic compounds with the PB-DS-PB CE method at low pH (i.e. after the EOF time) provided a larger separation window and number of separated peaks in urine compared to the analysis with the PB-PVS CE method at low pH (i.e. before the EOF time). Approximately, 600 molecular features were detected in rat urine by the PB-DS-PB CE-MS method whereas about 300 features were found with the PB-PVS CE-MS method. This difference can be attributed to reduced comigration of compounds with the PB-DS-PB CE-MS method and a related decrease of ion suppression. With regard to the analysis of anionic compounds by CE-MS, in general analyte responses were significantly lower than that for cationic compounds, most probably due to less efficient ionization and to ion suppression effects caused by the background electrolyte. Hence, further optimization is required for the sensitive CE-MS analysis of anionic compounds in body fluids. It is concluded that the selection of a CE method for profiling of cationic metabolites in urine depends on the purpose of the study. For high-throughput analyses, the PB-PVS CE-MS method is favored whereas the PB-DS-PB CE-MS method provides a more information-rich metabolic profile, but at the cost of prolonged analysis time.


Subject(s)
Anions/urine , Cations/urine , Electrophoresis, Capillary/methods , Metabolome , Metabolomics/methods , Animals , Mass Spectrometry/methods , Rats , Urine/chemistry
10.
Am J Vet Res ; 70(1): 149-55, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19119961

ABSTRACT

OBJECTIVE: To determine correlations between dietary cation anion difference (DCAD) and urine pH, urine specific gravity, and blood pH in goats. ANIMALS: 24 crossbred goat wethers. PROCEDURES: Goats were randomly assigned to 1 of 4 DCAD groups (-150, -75, 0, or +75 mEq/kg of feed) and fed pelleted feed and ground hay for 7 days. The diet was then supplemented with ammonium chloride to achieve the assigned DCAD of each group for 7 days. Urine was obtained for pH and specific gravity measurements at hours -3 to -1, 1 to 3, 5 to 7, 9 to 11, and 13 to 15 relative to the morning feeding. Blood pH was determined on alternate days of the study period. RESULTS: Goats in the -150 and -75 mEq/kg groups had a urine pH of 6.0 to 6.5 two days after initiation of administration of ammonium chloride, and urine pH decreased to < 6.0 by day 7. Goats in the 0 mEq/kg group had a urine pH from 6.0 to 6.5 on day 5, whereas urine pH in goats in the +75 mEq/kg group remained > 6.5 throughout the trial. Urine specific gravity differed only between the -150 mEq/kg and the -75 mEq/kg groups. Blood pH in the -150 mEq/kg group was significantly lower than that in the other groups. CONCLUSIONS AND CLINICAL RELEVANCE: Goats in the 0 mEq/kg DCAD group had a urine pH of 6.0 to 6.5 five days after intitiation of feeding the diet, and that pH was maintained through day 7, without significant reduction in blood pH. This may serve as a target for diet formulation for the prevention of urolithiasis.


Subject(s)
Ammonium Chloride/administration & dosage , Goat Diseases/metabolism , Urolithiasis/veterinary , Animals , Anions/urine , Cations/urine , Goat Diseases/blood , Goat Diseases/prevention & control , Goat Diseases/urine , Goats , Hydrogen-Ion Concentration , Male , Random Allocation , Specific Gravity , Urine/chemistry , Urolithiasis/blood , Urolithiasis/metabolism , Urolithiasis/prevention & control , Urolithiasis/urine
11.
J Sep Sci ; 31(12): 2260-4, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18563755

ABSTRACT

CE with capacitively coupled contactless conductivity detection (C(4)D) was used to determine waste products of the nitrogen metabolism (ammonia and creatinine) and of biogenic inorganic cations in samples of human urine. The CE separation was performed in two BGEs, consisting of 2 M acetic acid + 1.5 mM crown ether 18-crown-6 (BGE I) and 2 M acetic acid + 2% w/v PEG (BGE II). Only BGE II permitted complete separation of all the analytes in a model sample and in real urine samples. The LOD values for the optimized procedure ranged from 0.8 microM for Ca(2+) and Mg(2+) to 2.9 microM for NH(4)(+) (in terms of mass concentration units, from 7 microg/L for Li(+) to 102 microg/L for creatinine). These values are adequate for determination of NH(4)(+), creatinine, Na(+), K(+), Ca(2+) and Mg(2+) in real urine samples.


Subject(s)
Ammonia/urine , Creatinine/urine , Electrophoresis, Capillary/methods , Cations/urine , Electric Conductivity , Electrophoresis, Capillary/statistics & numerical data , Humans , Polyethylene Glycols , Reproducibility of Results , Solutions
12.
J Nutr ; 138(4): 718-24, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18356326

ABSTRACT

High dietary protein intake generates endogenous acid production, which may adversely affect bone health. Alkaline potassium citrate (Kcit)(2) may contribute to the neutralization of the protein-induced metabolic acidosis. We investigated the impact of 2 levels of protein intake and Kcit supplementation on acid-base metabolism and bone status in rats. Two-month-old Wistar male rats were randomly assigned to 4 groups (n = 30 per group). Two groups received a normal-protein content (13%) (NP) or a high-protein (HP) content diet (26%) for 19 mo. The 2 other groups received identical diets supplemented with Kcit (3.60%) (NPKcit and HPKcit). Rats were pair-fed based on the ad libitum intake of the HP group. At 9, 16, and 21 mo of age, 10 rats of each group were killed. The HP diet induced a metabolic acidosis characterized by hypercalciuria, hypermagnesuria, and hypocitraturia at all ages. Kcit supplementation neutralized this effect, as evidenced by decreased urinary calcium and magnesium excretion by the HPKcit rats. Femoral bone mineral density, biomechanical properties, bone metabolism biomarkers (osteocalcin and deoxypyridinoline), and plasma insulin-like growth factor 1 levels were not affected by the different diets. Nevertheless, at 21 mo of age, calcium retention was reduced in the HP group. This study suggests that lifelong excess of dietary protein results in low-grade metabolic acidosis without affecting the skeleton, which may be protected by an adequate calcium supply.


Subject(s)
Acid-Base Equilibrium/drug effects , Bone Density/drug effects , Dietary Proteins/administration & dosage , Dietary Proteins/pharmacology , Potassium Citrate/administration & dosage , Potassium Citrate/pharmacology , Animals , Anions/urine , Biomarkers , Biomechanical Phenomena , Body Weight , Calcium/metabolism , Cations/urine , Dietary Supplements , Drug Administration Schedule , Drug Therapy, Combination , Male , Rats , Rats, Wistar
13.
Urology ; 69(4 Suppl): 9-16, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17462486

ABSTRACT

The urothelium plays a pivotal role as a barrier between urine and its solutes and the underlying bladder. Bladder surface mucus is a critical component of this function. The biologic activity of mucus that imparts this barrier function is generated by the highly anionic polysaccharide components (eg, glycosaminoglycans), which are extremely hydrophilic and trap water at the outer layer of the umbrella cell. This trapped water forms a barrier at the critical interface between urine and the bladder. The result is a highly impermeable urothelium that serves as a key protective barrier for the bladder interstitium. In interstitial cystitis (IC), disruption of the urothelial barrier may initiate a cascade of events in the bladder, leading to symptoms and disease. Specifically, epithelial dysfunction leads to the migration of urinary solutes, in particular, potassium, that depolarize nerves and muscles and cause tissue injury. Exogenous heparinoids can restore the barrier function of the urothelium and thus successfully treat patients with IC. Groups of patients who have been given a diagnosis of IC, chronic prostatitis, and urethritis have been shown to have IC by virtue of their shared potassium sensitivity. It would seem, therefore, that mucous deficiency may be present throughout the lower urinary tract. If one is to rename these diseases, perhaps it is best to do so in reference to a shared loss of epithelial barrier function. A name such as lower urinary dysfunctional epithelium would incorporate all of these diseases under a single pathophysiologic process. As a result of these discoveries, a new paradigm for diagnosis and treatment is emerging.


Subject(s)
Cystitis, Interstitial/etiology , Prostatitis/etiology , Urethritis/etiology , Urothelium/physiopathology , Animals , Bacterial Adhesion , Biological Transport , Cations/urine , Cystitis, Interstitial/pathology , Female , Glycosaminoglycans/chemistry , Glycosaminoglycans/physiology , Heparinoids/pharmacology , Heparinoids/therapeutic use , Humans , Hydrophobic and Hydrophilic Interactions , Male , Mucoproteins/physiology , Mucus/chemistry , Mucus/physiology , Pentosan Sulfuric Polyester/pharmacology , Permeability , Potassium/adverse effects , Potassium/metabolism , Prostatitis/pathology , Protamines/pharmacology , Rabbits , Urea/metabolism , Urethritis/pathology , Urine/chemistry , Uromodulin , Urothelium/drug effects
14.
J Hum Hypertens ; 21(5): 387-92, 2007 May.
Article in English | MEDLINE | ID: mdl-17301826

ABSTRACT

Genetic variability in the ADD1 (Gly460Trp) and ADD2 (C1797T) subunits of the cytoskeleton protein adducin plays a role in the pathogenesis of hypertension, possibly via changes in intracellular cation concentrations. ADD2 1797CC homozygous men have decreased erythrocyte count and hematocrit. We investigated possible association between intra-erythrocyte cations and the adducin polymorphisms. In 259 subjects (mean age 47.7 years), we measured intra-erythrocyte Na(+) [iNa], K(+) [iK] and Mg(2+) [iMg], serum cations and adducin genotypes. Genotype frequencies (ADD1: GlyGly 61.5%, Trp 38.5%; ADD2: CC 80.4%, T 19.6%) complied with Hardy-Weinberg proportions. In men, ADD2 CC homozygotes (n=100) compared to T-carriers (n=23) had slightly lower iK (85.8 versus 87.5 mmol/l cells; P=0.107), higher iMg (1.92 versus 1.80 mmol/l cells; P=0.012), but similar iNa (6.86 versus 6.88 mmol/l cells; P=0.93). In men, iK, iMg and iNa did not differ according to ADD1 genotypes. In men, iK (R(2)=0.128) increased with age and serum Na(+), but decreased with serum total calcium and the daily intake of alcohol. iMg (R(2)=0.087) decreased with age, but increased with serum total calcium. After adjustment for these covariates (P

Subject(s)
Calmodulin-Binding Proteins/genetics , Cations/metabolism , Erythrocyte Membrane/genetics , Erythrocyte Membrane/metabolism , Polymorphism, Genetic/genetics , Adult , Belgium/epidemiology , Biomarkers/blood , Biomarkers/urine , Blood Pressure/genetics , Calcium/blood , Calcium/urine , Cations/blood , Cations/urine , Female , Genetic Predisposition to Disease , Genotype , Humans , Hypertension/genetics , Hypertension/metabolism , Hypertension/physiopathology , Magnesium/blood , Magnesium/urine , Male , Middle Aged , Phenotype , Potassium/blood , Potassium/urine , Regression Analysis , Research Design , Sensitivity and Specificity , Sex Factors , Sodium/blood , Sodium/urine
15.
Talanta ; 74(2): 255-64, 2007 Nov 30.
Article in English | MEDLINE | ID: mdl-18371638

ABSTRACT

The measurement of sodium ion concentration in urine can provide diagnostic information and guide therapy. Unfortunately, neutral-carrier-based ion-selective electrodes show a large positive drift and loss in selectivity in undiluted urine. The extraction of electrically neutral lipids from the urine into the sensing membrane was suggested as the main source of the drift, loss of selectivity and the consequent incorrect concentration readings. In this work, (i) solvent-solvent extraction, (ii) membrane-immobilized solvent extraction and (iii) solid phase extraction were used to remove interfering compounds from urine samples. The "cleaned" urine samples were subsequently analyzed using a calixarene (sodium ionophore X)-based, solid-contact, sodium-selective electrode in a flow-through manifold. The solid-contact sodium sensors had excellent stability in cleaned urine and an acceptable bias compared to commercial clinical analyzers.


Subject(s)
Chemistry, Clinical/methods , Ion-Selective Electrodes , Lipids , Membranes, Artificial , Polymers/chemistry , Sodium/urine , Calibration , Cations/urine , Chemistry, Clinical/instrumentation , Chemistry, Clinical/standards , Humans , Lipids/isolation & purification , Lipids/urine , Reference Standards , Sensitivity and Specificity , Solid Phase Extraction , Solutions , Solvents/chemistry
16.
Eur J Cardiovasc Prev Rehabil ; 12(4): 355-62, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16079643

ABSTRACT

OBJECTIVES: To determine any differences in the urinary excretion and dietary intake of sodium, potassium, magnesium and calcium intake in three South African ethnic groups, and to assess whether the blood pressure-cation association varies according to ethnic status. DESIGN: A cross-sectional study of 325 black, white and mixed-ancestry men and women, conveniently sampled in Cape Town. Twenty-four-hour urine samples were collected on three separate occasions for assessment of urinary electrolytes, and three 24-h dietary recalls for the corresponding urine collection times were administered by two trained fieldworkers. Para-amino benzoic acid was used as a marker of the completeness of urine collection. RESULTS: Mean urinary sodium values equate to a daily salt (sodium chloride) intake of 7.8, 8.5 and 9.5 g in black, mixed-ancestry and white individuals, respectively. In normotensive individuals, black and mixed-ancestry subjects had significantly lower median urinary sodium concentrations than white subjects, but these differences were not evident between black and white hypertensive subjects. No ethnic differences were found for urinary potassium, except for mixed-ancestry normotensive individuals having a lower excretion than white normotensive individuals. Urinary magnesium excretion did not differ across ethnic groups. In both normotensive and hypertensive individuals, urinary calcium concentrations differed between all three groups, with black subjects having the lowest values, approximately less than half those of white subjects. CONCLUSION: White normotensive subjects in Cape Town have higher habitual intakes of sodium, but also higher calcium intakes than their black and mixed-ancestry counterparts. Dietary differences may contribute to ethnic-related differences in blood pressure.


Subject(s)
Calcium, Dietary/administration & dosage , Calcium, Dietary/urine , Magnesium/administration & dosage , Magnesium/urine , Potassium, Dietary/administration & dosage , Potassium, Dietary/urine , Sodium, Dietary/administration & dosage , Sodium, Dietary/urine , Adult , Age Distribution , Aged , Antihypertensive Agents/therapeutic use , Biomarkers/urine , Black People/statistics & numerical data , Cations/administration & dosage , Cations/urine , Cross-Sectional Studies , Eating , Electrolytes/metabolism , Female , Humans , Hypertension/drug therapy , Hypertension/ethnology , Hypertension/metabolism , Male , Middle Aged , Predictive Value of Tests , Sex Distribution , South Africa/ethnology , White People/statistics & numerical data
17.
Am J Vet Res ; 63(7): 1053-60, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12118668

ABSTRACT

OBJECTIVE: To determine whether plasma, urine, and fecal electrolyte and mineral concentrations differ between clinically normal horses and Thoroughbreds with recurrent exertional rhabdomyolysis (RER) after consumption of diets varying in cation-anion balance. ANIMALS: 5 Thoroughbred mares with RER and 6 clinically normal mixed-breed mares. PROCEDURE: Each of 3 isocaloric diets designated as low, medium, and high on the basis of dietary cation-anion balance (DCAB) values of 85, 190, and 380, respectively, were fed to horses for 14 days. During the last 72 hours, 3 horses with RER and 3 control horses had daily urine and fecal samples obtained by total 24-hour collection. Remaining horses had urine samples collected daily by single catheterization. RESULTS: For each diet, no differences existed between horses with RER and control horses in plasma pH, electrolyte concentrations, and creatine kinase activity or in urine pH and renal fractional excretion (FE) values. Plasma pH, strong ion difference, bicarbonate and total carbon dioxide concentrations, and base excess decreased and plasma chloride and ionized calcium concentrations increased with decreasing DCAB. Urine pH decreased with decreasing DCAB. The FE of chloride and phosphorus were greatest for horses fed the low diet. The FE values for all electrolytes exept magnesium did not differ between urine samples obtained by single catheterization and total 24-hour collection. Daily balance of calcium, phosphorus, sodium, chloride, and potassium did not differ significantly among horses fed the various diets. CONCLUSIONS: In clinically normal horses and in horses with RER, the DCAB strongly affects plasma and urine pH and the FE of sodium, potassium, chloride, and phosphorus.


Subject(s)
Electrolytes/blood , Electrolytes/urine , Horse Diseases/blood , Horse Diseases/urine , Rhabdomyolysis/veterinary , Animal Feed , Animals , Anions/blood , Anions/urine , Blood Chemical Analysis/veterinary , Cations/blood , Cations/urine , Diet , Feces/chemistry , Female , Horses , Hydrogen-Ion Concentration , Rhabdomyolysis/blood , Rhabdomyolysis/urine , Urinalysis/veterinary
18.
Fresenius J Anal Chem ; 370(4): 426-8, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11495068

ABSTRACT

A new ion chromatographic (IC) technique has been developed for the determination of inorganic cations in biological fluids with direct sample injection. This involved the use of a mixed zwitterionic-micelle/electrolyte solution as an eluent. The proteins in the sample became bound to the zwitterionic micelles in the eluent and were thus eliminated from the column. The cations were separated by cation exchange. This method is ideal for the online, simultaneous determination of common inorganic cations (Na+, NH4+, K+, Mg2+, and Ca2+) in urine and serum samples. Such an application was demonstrated experimentally. Non-suppressed conductivity was used for analyte detection. The detection limits obtained using this IC system were 2.94, 5.22, 34.9, 32.6, and 56.7 microg/L for Na+, NH4+, K+, Mg2+, and Ca2+, respectively.


Subject(s)
Cations/analysis , Cations/blood , Cations/urine , Chromatography, High Pressure Liquid , Electric Conductivity , Humans , Indicators and Reagents , Micelles , Proteins/chemistry , Solubility , Solvents
19.
Anal Chem ; 73(14): 3199-205, 2001 Jul 15.
Article in English | MEDLINE | ID: mdl-11476216

ABSTRACT

Ionophore-free ion exchanger electrodes were found to exhibit quite a high selectivity for the creatininium ion; however, measurements in diluted urine samples revealed large emf drifts. Potentiometric, chromatographic, NMR, and mass spectrometric evidence did not reveal any major cationic interfering agents, and anionic interfering agents cannot trivially explain the consistently positive emf drifts. Ultrafiltration of urine samples showed that the interfering agents have molecular weights below 1000 u. The drifts are apparently caused by electrically neutral lipophilic compounds of low molecular weight that are easily extracted into organic phases. Follow-up experiments showed that p-cresol and cholesterol cause no significant emf responses but that coproporphyrin, phosphatidylserine, taurocholic acid, cholic acid, phosphatidylethanolamine, and octanoic acid cause positive emf drifts of the type that was observed with the urine samples. The extent of the responses and the response time depend not only on the specific compound but also on the cation in the sample solution. These results suggest that the emf drifts are due to extraction of such natural lipids into the organic membrane phase where they interact in an ionophore-like fashion with the analyte and interfering ions. Changes in the potentiometric selectivities after contact with natural lipids support this interpretation. The same effect of natural lipids is also expected for ionophore-based electrodes. Indeed, exposure of a valinomycin-based electrode to a methylene chloride extract of urine resulted in a significant reduction of the Na+ discrimination, increasing log Kpot(K,Na) from -3.9 to -3.1.


Subject(s)
Creatinine/urine , Ion-Selective Electrodes , Lipids/urine , Membranes, Artificial , Cations/urine , Humans , Ionophores/chemistry , Lipids/chemistry , Potentiometry/methods , Valinomycin/chemistry
20.
Acta Cardiol ; 56(3): 163-8, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11471929

ABSTRACT

BACKGROUND: The relationship between cation intake and blood pressure (BP) in populations with specific dietary habits such as a low fat intake, remains unclear. A low fat intake has been prevalent during human evolution. METHODS: The average of 6 BP readings and heart rate (HR) recordings has been calculated. Dietary intake was measured using the 24 h recall-method. A 24 h urine sample was collected. RESULTS: A highly significant correlation was found between the sodium/potassium ratio (Na/K), after adjustment for age, weight, height, heart rate, alcohol intake and sex and systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP). The same applies to the sodium/creatinine (Na/Cr) and potassium/creatinine (K/Cr) ratios, with a positive correlation for Na/Cr and a negative one for K/Cr. The partial regression coefficient was in absolute value about 4-5 times greater for K/Cr than for Na/Cr. Age correlates highly significantly and independently with both SBP and DBP. CONCLUSION: If a Na/K ratio of 1 is considered optimal, by achieving that goal mean SBP could be reduced by about 6 mm Hg and mean DBP by 3 mm Hg in this normotensive population.


Subject(s)
Blood Pressure/physiology , Cations/administration & dosage , Cations/urine , Diet, Fat-Restricted , Adolescent , Adult , Aged , Anthropometry , China , Cholesterol/blood , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Creatinine/urine , Diet Surveys , Female , Health Status , Heart Rate/physiology , Humans , Life Style , Male , Middle Aged , Potassium/urine , Random Allocation , Regression Analysis , Sodium/urine , Triglycerides/blood
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