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Background: Transfusion-dependent thalassemia (TDT) is a severe form of beta-thalassemia, characterized by defective-globin production, resulting in a buildup of unpaired alpha globin chains. Patients with TDT can only survive if they receive safe blood transfusions regularly, which causes iron overload in their blood, which causes a variety of disorders. Cations and trace elements in TDT patients as a drug target deserve more studies., Objectives: In the present study, the cations and some trace elements were studied in TDT patients as a tool to adjust their level in the case of any disturbances., Methods: Serum calcium, magnesium, zinc, copper, and iron were measured spectrophotometrically while manganese and cobalt were measured by flameless atomic absorption spectroscopy in 100 TDT patients and compared with 35 healthy control children., Results: Patients with TDT exhibit a notable elevation in blood levels of iron, copper, copper/zinc ratio, and manganese, with a substantial reduction in serum levels of zinc, magnesium, calcium, and cobalt, as compared to the control group. These minerals have diverse associations with clinical data and transfusion frequencies. The receiver operating characteristic (ROC) analysis revealed that the elevated levels of iron, manganese, and calcium exhibit the greatest diagnostic capability, with a sensitivity and specificity of over 80 %, and a Youdin's J value of more than 0.6., Conclusion: The levels of cations and trace elements are disturbed in TDT patients. Hence, the monitoring and adjustment of the level of these minerals are important to prevent further consequences., Competing Interests: Conflict of interest The authors declare no conflicts of interest with any commercial or other affiliation on the submitted paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Novel polyepinephrine-modified NaYF 4 :Yb,Tm upconversion luminescent nanoparticles (UCNP@PEP) were prepared via the self-polymerization of epinephrine on the surfaces of the UCNPs for selective sensing of Fe 3+ inside a cell and for intracellular imaging. The proposed UCNP@PEP probe is a strong blue light emitter (λ max  = 474 nm) upon exposure to an excitation wavelength of 980 nm. The probe was used for detecting Fe 3+ owing to the complexation reaction between UCNP@PEP and Fe 3+ , resulting in reduced upconversion luminescence (UCL) intensity. The proposed probe has a detection limit of 0.2 μM and a good linear range of 1-10 μM for sensing Fe 3+ ions. Moreover, the UCNP@PEP probe displays high cell viability (90%) and is feasible for intracellular imaging. The ability of the probe to sense Fe 3+ in a human serum sample was tested and shows promising output for diagnostic purposes. The prepared UCNP@PEP probe was characterized by using UV-visible (UV-Vis) absorption spectrometry, fluorescence (FL) spectrometry, field emission scanning electron microscopy (FE-SEM), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared spectroscopy (FT-IR).

Background: Metformin-associated lactic acidosis (MALA) is a widely documented adverse event of metformin. Despite being considered one of the main causes of metabolic acidosis, the association between an anion gap and MALA diagnosis is still uncertain., Case Presentation: Cases involving six Caucasian patients with suspected MALA who were admitted to the emergency department were analysed. All these patients presented with pH values < 7.35, lactate levels > 2 mmol/L, and estimated glomerular filtration < 30 mL/min. Metformin plasma concentrations were > 2.5 mg/L in all the patients. The highest metformin concentrations were not found in the patients with the highest lactate levels. The anion gap values ranged from 12.3 to 39.3, with only two patients exhibiting values > 14., Conclusions: In patients with MALA, there is a significant variability in the anion gap values, which is not related to the level of metformin accumulation, and therefore, it is doubtful whether measuring anion gaps is useful as an approach for MALA diagnosis.

Few studies were reported on trace elements' alterations in uremic patients undergoing long-term (>24 months) hemodialysis (HD), especially by using the whole blood as the biological fluid for the measuring purpose. Our objective was to develop an improved micro-sampling inductively coupled plasma-mass spectrometry (ICP-MS) method to determine the levels of Ca, Mg, Cu, Zn, Fe, Mn, Se and Pb in uremic patients receiving long-term HD. A ICP-MS method with a modified whole blood sample preparation procedure with small volumes was established and applied for the simultaneous quantification of the various elements in uremic patients undergoing long-term HD. 124 eligible uremic patients receiving long-term HD (75 males and 49 females) and 77 healthy subjects (54 males and 23 females) were recruited and Ca, Mg, Cu, Zn, Fe, Mn, Se and Pb levels were further determined. Our results revealed that uremic patients with HD had significantly higher blood levels of Ca, Mg, Zn and Pb and lower Cu, Fe, Se and Mn concentrations than healthy controls. In conclusion, a reproducible and reliable ICP-MS method using minimal whole blood sample volume (50 μL) with a simple dilution-based preparation procedure was successfully improved, validated and applied. Uremic patients undergoing long-term HD might be at increased risk of some essential trace elements deficiency (especially for Cu, Fe and Se) or toxic trace element excess (Pb) in respect to healthy subjects. Monitoring of blood levels and supplementation of some trace elements may be indicated in uremic patients undergoing long-term HD.

Plasmonic resonance energy transfer (PRET) from a Au nanosphere (AuNS) to a quantum dot (QD) is discovered at the single particle level. A homogenous immunoassay based on this PRET is verified using a prostate specific antigen (PSA) as an example. The limit of detection of the PSA is determined to be 0.2 fM.

Magnesium sulfate (MgSO 4 ) was administered to calm competition horses. We evaluated the impact of regulatory requirements for the handling of blood samples on plasma ionized magnesium (iMg), ionized calcium (iCa), the iMg to iCa ratio, and pH. We hypothesized that iCa, iMg. and iMg/iCa would be similar among storage and collection methods. Four blood samples were collected from each of 50 horses on the same day: Group 1 - collection in a heparinized syringe and processed within hours in a clinical laboratory; Group 2 - collection into a plasma separator tube (PST) centrifuged just prior to analysis, and plasma processed as in (1); Group 3 - collection into a PST, refrigerated, shipped via overnight carrier to the United States Equestrian Federation (USEF) Equine Drug Testing and Research laboratory, centrifuged just prior to analysis, and plasma processed; and Group 4 - as in Group 3, but stored frozen at -80°C for 90 days, thawed, and plasma processed as in Group 3. Results for iMg/iCa are unit-less, adjusted iMg for potential influence of plasma protein and iCa, and highly correlated with iMg pH (r = -.933; P < 0.01). Samples processed immediately in a clinical reference laboratory had the greatest iMg/iCa. Both iMg/iCa and pH predictably decreased after freezing (P < 0.001). These data suggest that the iMg/iCa mirrors alterations in iMg regardless of storage and collection methods. This understanding can facilitate the development of a regulatory threshold for the control of the nefarious use of magnesium sulfate in competing horses, and an understanding of potential changes to iMg/iCa with storage of B samples., (© 2018 John Wiley & Sons, Ltd.)

Aim: Acute and subacute cardiotoxicity are characterized by prolongation of the corrected QT interval (QTc) and other measures derived from the QTc interval, such as QTc dispersion (QTdc) and transmural dispersion of repolarization (DTpTe). Although anthracyclines prolong the QTc interval, it is unclear whether breast cancer patients who undergo the ACT chemotherapy regimen of anthracycline (doxorubicin: A), cyclophosphamide (C) and taxane (T) may present with QTc, QTdc and DTpTe prolongation., Methods: Twenty-three consecutive patients with breast cancer were followed prospectively during ACT chemotherapy and were analyzed according to their QT measurements. QTc, QTdc and DTpTe measurements were determined by a 12-lead electrocardiogram (EKG) prior to chemotherapy (baseline), immediately after the first phase of anthracycline and cyclophosphamide (AC) treatment, and immediately after T treatment. Serum troponin and B-type natriuretic peptide (BNP) levels were also measured., Results: Compared to baseline values, the QTc interval was significantly prolonged after the AC phase (439.7 ± 33.2 ms vs. 472.5 ± 36.3 ms, p = 0.001) and after T treatment (439.7 ± 33.2 ms vs. 467.9 ± 42.6 ms, p < 0.001). Troponin levels were elevated after the AC phase (23.0 pg/mL [min-max: 6.0-85.0] vs. 6.0 pg/mL [min-max: 6.0-22.0], p < 0.001) and after T treatment (25.0 pg/mL [min-max: 6.0-80.0] vs. 6.0 pg/mL [min-max: 6.0-22.0], p < 0.001) compared to baseline values., Conclusion: In this prospective study of patients with non-metastatic breast cancer who underwent ACT chemotherapy, significant QTc prolongation and an elevation in serum troponin levels were observed.

Introduction: Microalbuminuria (MAU), a complication of diabetes, is closely related to cardiovascular events. A fragmented QRS (fQRS) in the electrocardiogram (ECG) was found to be strongly associated to cardiovascular morbidity and mortality., Objective: The aim of this study was to assess the association between a fQRS and MAU in patients with type 2 diabetes mellitus (T2DM)., Patients and Methods: One hundred and twenty-seven patients (mean age, 50.49 years; 44.01% male) with T2DM of at least six months duration and at least two urine albumin/creatinine ratios (ACRs) available were enrolled into the study between December 2015 and May 2016. All patients underwent ECG and echocardiography, and were taken blood and urine samples. Patients were divided into two groups according to presence of fQRS (group 1) or absence of fQRS (group 2)., Results: Both groups had similar baseline characteristics. MAU and glycosylated hemoglobin (HbA1c) levels and left ventricular end-diastolic diameter (LVEDd) were increased in patients with a fQRS in the ECG (p=0.002, p=0.02, and p=0.007, respectively). Univariate and multivariate logistic regression analysis showed MAU and an increased LVEDd to be independent risk factors for the presence of a fQRS in the ECG of T2DM patients., Discussion and Conclusions: In this study, a fQRS was associated to MAU. In T2DM, MAU may be related to subclinical diastolic and systolic dysfunction., (Copyright © 2017. Publicado por Elsevier España, S.L.U.)

We investigated oxidative stress markers and metal ions in patients with Alzheimer's disease (AD). The serum levels of ceruloplasmin (CER), C-reactive protein (CRP), uric acid (UA), homocysteine (Hcy), copper, iron, and zinc were determined in 125 patients with AD (mild, n = 2 8; moderate, n = 42; and severe, n = 55) and 40 healthy control (HC) participants. Compared to HC, CER and UA levels were significantly lower in moderate and severe AD groups, whereas CRP and Hcy levels were significantly higher in the severe AD group. Copper level was significantly higher in moderate and severe AD groups than the other groups. Compared to HC, iron level was significantly higher in patients with AD, whereas zinc level was significantly lower in patients with AD. In patients with AD, the severity of cognitive impairment was positively correlated with CER, UA, and zinc levels, whereas it was negatively correlated with copper level. Taken together, our findings provide a novel approach to assess AD progression.

A microfluidic droplet synthesis approach for the preparation of poly N-isopropylacrylamide protected gold nanoparticles (PNIPAm@AuNPs) was presented here. Well-dispersed PNIPAm@AuNPs could be generated within 8 min. On the basis of the aggregation-induced UV-vis adsorption intensity increasing mechanism, the PNIPAm@AuNPs-based colorimetric probe displayed high sensitivity and good selectivity for sensing copper ions. A linear calibration of relative UV-vis adsorption intensity increasing versus copper ions concentration was obtained within 5.0-750.0 μM, and the limit of detection was 2.5 μM. Furthermore, after copper ions were injected in rat, a metabolic assay was developed with the proposed probe. The results indicated that the droplet microfluidic synthesis system could provide a new way for preparation of polymer@AuNPs with good polydispersity index and showed great potential of polymer@AuNPs-based sensing probe for application in biological and clinical analysis.

Two approaches have been used in clinical evaluation the acid-base status: traditional (bicarbonate-centered) is based on the Henderson-Hasselbalch equation complemented by calculation of the anion gap, and more recent quantitative approach proposed by Stewart and Fencl. The latter method defines the three independent variables, which regulate pH. These include: the difference between the sum of charges carried by strong plasma cations and anions termed the strong ion difference - SID (decrease causes acidosis, and vice versa); the total concentration of the weak non-volatile acids [Atot] (inorganic phosphate and albumin, decrease causes alkalosis and vice versa), and pCO2. According to this approach, pH and bicarbonate are dependent variables. Their concentrations change if and only if one or more independent variables are altered.The main advantage of the Stewart-Fencl approach is the calculation of the concentration of plasma acids, which are not routinely measured. In the traditional approach, their presence is inferred from the anion gap. The correction of the value of anion gap according to the serum albumin level increases the specificity. This correction brings traditional approach closer to the Stewart-Fencl method that precisely calculates unmeasured strong anions by further adjustment of the corrected anion gap according to the serum phosphate, calcium and magnesium levels. The precise calculation of unmeasured anions is important in critically ill patients with the metabolic breakdown, where the traditional approach may overlook the presence of unmeasured anions. Consideration of the sodium-chloride difference draws the attention to acid-base disturbance caused by change of the strong ion difference.

Luminescent sensors and switches continue to play a key role in shaping our understanding of key biochemical processes, assist in the diagnosis of disease and contribute to the design of new drugs and therapies. Similarly, their contribution to the environment cannot be understated as they offer a portable means to undertake field testing for hazardous chemicals and pollutants such as heavy metals. From a physiological perspective, the Group I and II metal ions are among the most important in the periodic table with blood plasma levels of H(+), Na(+) and Ca(2+) being indicators of several possible disease states. In this review, we examine the progress that has been made in the development of luminescent probes for Group I and Group II ions as well as protons. The potential applications of these probes and the mechanism involved in controlling their luminescent response upon analyte binding will also be discussed.

Red blood cell (RBC) aging in the blood bank is characterized by the accumulation of a significant number of biochemical and morphologic alterations. Recent mass spectrometry and electron microscopy studies have provided novel insights into the molecular changes underpinning the accumulation of storage lesions to RBCs in the blood bank. Biochemical lesions include altered cation homeostasis, reprogrammed energy, and redox metabolism, which result in the impairment of enzymatic activity and progressive depletion of high-energy phosphate compounds. These factors contribute to the progressive accumulation of oxidative stress, which in turn promotes oxidative lesions to proteins (carbonylation, fragmentation, hemoglobin glycation) and lipids (peroxidation). Biochemical lesions negatively affect RBC morphology, which is marked by progressive membrane blebbing and vesiculation. These storage lesions contribute to the altered physiology of long-stored RBCs and promote the rapid clearance of up to one-fourth of long-stored RBCs from the recipient's bloodstream after 24 hours from administration. While prospective clinical evidence is accumulating, from the present review it emerges that biochemical, morphologic, and omics profiles of stored RBCs have observable changes after approximately 14 days of storage. Future studies will assess whether these in vitro observations might have clinically meaningful effects., (© 2014 AABB.)

Water-soluble carbon dots (CDs) were prepared, using a facile hydrothermal oxidation route of cyclic oligosaccharide α-CD, as carbon sources, and alkali as additives. The successful synthesis of CDs was confirmed by scanning electron microscopy (SEM), dynamic light scattering (DLS), FTIR, UV-visible absorption, and emission fluorescence. The characterizations showed that the prepared CDs are spherical and well-dispersed in water with average diameters of approximately 2 nm. These water-soluble CDs have excellent photo stability towards photo bleaching during 30 days. The obtained CDs showed a strong emission at the wavelength of 450 nm, with an optimum excitation of 360 nm. The fluorescence quenching of CDs in the presence of Fe(III) ions was used as fluorescent probes for quantifying Fe(III) ions in aqueous solution. Under optimum condition, the fluorescence intensity versus Fe(III) concentration gave a linear response, according to Stern-Volmer equation. The linearity range of the calibration curve and the limit of detection were 1.60×10(-5) to 16.6×10(-5) mol L(-1), and 6.05×10(-6) mol L(-1), respectively, which was in the range for serum analysis of Fe(III). It was concluded that the prepared CDs had a great potential as fluorescent probes for applications in analysis of Fe(III) ions in the blood serum samples, which is hardly interfered by other ions., (Copyright © 2015 Elsevier B.V. All rights reserved.)

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.

Objective: The aim of this study was to evaluate the postoperative changes in hemodynamics and biochemical indices in pediatric recipients of live-donor liver transplants (LDLT)., Methods: Hemodynamics and biochemical indices (coagulation function, electrolytes, kidney function, liver function, and blood analysis) were monitored on the day before and the 1st, 3rd, 5th, and 7th days after the procedure in 20 children who underwent LDLT from June 2006 to January 2009., Results: Compared with preoperative measurements, systolic and diastolic blood pressure and mean arterial pressure increased and prothrombin time was prolonged significantly during the first 7 days after LDLT (P < .05). Fibrinogen, platelet count, total protein, globulin, and blood magnesium decreased significantly (P < .05). Liver enzymes (aspartate transaminase [AST], alanine transaminase [ALT]) and blood sodium increased significantly; serum potassium and calcium declined on the first postoperative day (P < .05). On the 7th day, AST returned to nearly normal (P < .05) and ALT returned to the preoperative levels. Blood urea nitrogen fluctuated within the normal range (P < .05). Total and direct bilirubin decreased on the 1st day but returned to near normal levels on the 7th day (P <.001)., Conclusions: Our data demonstrated postoperative changes in hemodynamics, electrolytes, and biochemical indices in pediatric LDLT recipients. The changes in clotting factors and platelet count did not result in severe coagulation function disorder; kidney function was normal. Changes in liver enzymes and bilirubin compared with the preoperation indices were within the regulatory scope of liver and did not result in severe complications. These preliminary postoperative trends suggest that further prospective evaluation is needed., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The purpose of this study was to observe the effects of low doses of aflatoxin B1 (AFB1) on responses to common vaccines and levels of serum cations in broilers. Male broilers at 7 d of age were fed control (no AFB1), a 75 µg of AFB1/kg (75 ppb of AFB1) diet, or a 750 µg of AFB1/kg (750 ppb of AFB1) diet. The 750 ppb of AFB1 diet resulted in a temporary increase in ELISA titers against Newcastle disease virus (P = 0.014) and infectious bursal disease virus (P = 0.005) during wk 2 and 4 of exposure, respectively, compared with the control diet. Conversely, lower (P ≤ 0.01) serum protein concentrations were found in broilers under the 750 ppb AFB1 diet during wk 2 and 4. During wk 2 of exposure, lower serum levels of potassium were noted in birds under both the 75 (P = 0.037) and 750 ppb (P = 0.000) AFB1 diets compared with those under the control diet. During wk 5, higher serum magnesium (P = 0.004), and sodium (P = 0.000) under the 750 ppb AFB1 diet were found compared with the control diet. These data indicate that low dietary levels of AFB1 can temporarily increase or decrease the studied serological variables in broilers depending upon the stage of exposure.

The present experiment was carried out to investigate if levels of serum cations in broilers are modulated differently at various stages of exposure to deoxynivalenol (DON). Male broiler chicks at 7 days of age were fed a basal diet (0.27 mg of DON; 0.01 mg of zearalenone/kg), or either a low DON diet (1.68 mg of DON; 0.15 mg of zearalenone/kg) or a high DON diet (12.21 mg of DON; 1.09 mg of zearalenone/kg) produced using extracts from Fusarium graminearum cultures. Blood samples from the birds were collected during weeks 2, 4, and 5 of exposure. The high DON diet resulted in lower serum calcium levels compared to the basal diet at all the 3 sampling stages, while the low DON diet resulted in lower serum calcium levels only during weeks 2 and 5. Serum potassium levels were reduced under both the DON diets during weeks 2 and 5, while no diet-associated changes were found for serum levels of magnesium, sodium, and zinc. Under the present experimental conditions, the serum levels of calcium were consistently modulated in the broilers exposed to the DON-contaminated diets. The modulation of serum levels of potassium was, however, dependent upon the stage of exposure to DON.

A high concern for human health and safety has motivated dynamic research on the potential impact of transition metal ions and their toxic effects, thus it is very challenging to design transition-metal ion detection devices that are cost-effective, rapid and applicable to the biological milieus. Driven by the need to detect trace amounts of Fe(3+) from blood samples, we report a highly selective and ultrasensitive calix[4]arene modified silver nanoprobe for Fe(3+) recognition at the 9.4 nM level from aqueous solution with excellent discrimination against other heavy metals and biomolecules. The assembly was characterized by TEM (transmission electron microscopy), DLS (dynamic light scattering), UV-Vis, FT-IR, ESI-MS and (1)H NMR spectrometry, which demonstrate the higher binding affinity for Fe(3+). The biosensor has been successfully applied to estimate the ferric ion in human blood serum as well as in human hemoglobin.

In this work, we report a synthetic approach to a Fmoc-protected nucleoamino acid, based on L-diaminopropanoic acid, carrying the DNA nucleobase on the alpha-amino group by means of an amide bond, suitable for the solid-phase synthesis of novel nucleopeptides of potential interest in biomedicine. After ESI-MS and NMR characterization this building block was used for the assembly of a thymine-functionalized nucleopeptide, composed of nucleobase-containing L-diaminopropanoic acid moieties and underivatized L-lysine residues alternated in the backbone. Circular dichroism studies performed on the cationic nucleopeptide and adenine-containing DNA and RNA molecules suggested that the thymine-containing peptide is able to interact with both DNA and RNA. In particular, a significant conformational variation in the RNA structure was suggested by CD studies. Human serum stability assays were also conducted on the cationic nucleopeptide, which was found to be highly resistant to enzymatic degradation.

The oral adsorbent AST-120 is composed of spherical carbon particles and has an adsorption ability for certain small-molecular-weight compounds that accumulate in patients with chronic kidney disease (CKD). So far, very few compounds are known to be adsorbed by AST-120 in vivo. To examine the effect of AST-120 in vivo, we comprehensively evaluated the plasma concentrations of 146 compounds (61 anions and 85 cations) in CKD model rats, with or without four weeks of treatment with AST-120. By capillary electrophoresis with mass spectrometry, we identified 6 anions and 17 cations that were significantly decreased by AST-120 treatment. In contrast, we also identified 2 cations that were significantly increased by AST-120. Among them, 4&#160;anions, apart from indoxyl sulfate and hippurate, and 19 cations were newly identified in this study. The plasma levels of N-acetyl-neuraminate, 4-pyridoxate, 4-oxopentanoate, glycine, &#947;-guanidinobutyrate, N-&#947;-ethylglutamine, allantoin, cytosine, 5-methylcytosine and imidazole-4-acetate were significantly increased in the CKD model compared with the sham-operated group, and were significantly decreased by AST-120 treatment. Therefore, these 10 compounds could be added as uremic compounds that indicate the effect of AST-120 treatment. This study provides useful information not only for identifying the indicators of AST-120, but also for clarifying changes in the metabolic profile by AST-120 treatment in the clinical setting.

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.

In this study, online sample concentration method, which coupled field-amplified sample injection (FASI) and sweeping technology with micellar electrokinetic chromatography (MEKC), was used to detect and analyze acidic and basic components in a single run. In order to concentrate the acidic and basic components simultaneously in a single run sweeping step, a combination of successive anion- and cation-selective injections were used. Before sample loading, a rinse buffer containing 50 mM Tris buffer (pH 3) with 41% MeOH and 0.1% polyethylene oxide (PEO) was injected in order to suppress the electroosmotic flow (EOF). Sample loading of anionic components was achieved by electrokinetic injection at a negative voltage of -2.5 kV for 80 s, and then the cationic components were injected at a positive voltage of +5 kV for 120 s. Finally, sweeping with SDS micelles from the separation buffer (25 mM Tris buffer with 60 mM SDS, pH 3) was performed at a negative voltage of -20 kV. This capillary electrophoretic methodology was applied to the quantification of acidic and basic drugs in commercial tablets and in plasma samples. The precision and accuracy of the proposed method at different concentrations ranging from high, medium, to low were evaluated on spiked plasma samples. The intra and interday precision and accuracy values at three concentrations were all below 6.1%. The method was also successfully applied to monitor the tested drugs in the plasma of nine elderly cardiovascular and/or Alzheimer's disease patients after oral administration of the commercial products., (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

What begins with a failing heart, unable to sustain adequate renal perfusion and metabolic needs of the tissues it serves becomes a systemic illness whose origins are rooted in neurohormonal activation. This unwanted homeostatic stressor response, an adaptation gone awry, has pathologic consequences. It involves endocrine properties of effector hormones arising from the adrenergic and renin-angiotensin-aldosterone systems. The clinical syndrome congestive heart failure (CHF) has its symptoms and signs rooted in a hormonally mediated salt-avid state. The ensuing salt and water retention includes the expansion of the intravascular space with consequent central and systemic venous congestion that, respectively, involves the heart and lungs, the liver, gut and kidneys and ultimately the extravascular space. Other pathophysiologic outcomes contribute to a proinflammatory CHF phenotype. These include an ongoing adverse remodeling of the failing heart with lost necrotic cardiomyocytes and a consequent replacement fibrosis; wasting of soft tissues and resorption of bone; dyshomeostasis of extra- and intracellular mono- and divalent cations that contributes to the appearance of oxidative stress coupled with compromised antioxidant defenses and an immunostimulatory state with activated lymphocytes and monocytes elaborating proinflammatory cytokines. In this 2-part review, the pathophysiologic consequences associated with neurohormonal activation in CHF will first be reviewed. Next, several lines of evidence are considered that raise the hitherto unfathomable prospect for recovery from CHF, including reverse remodeling of the heart and systemic tissues.

Objectives: Autism is a developmental disorder characterized by social and emotional deficits, language impairments and stereotyped behaviors that manifest in early postnatal life. This study aims to clarify the relationship amongst absolute and relative concentrations of K+, Na+, Ca2+, Mg2+ and/or proinflammatory and proapoptotic biomarkers., Materials and Methods: Na+, K+, Ca2+, Mg2+, Na+/K+, Ca2+/Mg2+ together with IL6, TNFα as proinflammatory cytokines and caspase3 as proapoptotic biomarker were determined in plasma of 25 Saudi autistic male patients and compared to 16 age and gender matching control samples., Results: The obtained data recorded that Saudi autistic patients have a remarkable lower plasma caspase3, IL6, TNFα, Ca2+ and a significantly higher K+ compared to age and gender matching controls. On the other hand both Mg2+ and Na+ were non-significantly altered in autistic patients. Pearson correlations revealed that plasma concentrations of the measured cytokines and caspase-3 were positively correlated with Ca2+ and Ca2+/K+ ratio. Reciever Operating Characteristics (ROC) analysis proved that the measured parameters recorded satisfactory levels of specificity and sensitivity., Conclusion: Alteration of the selected measured ions confirms that oxidative stress and defective mitochondrial energy production could be contributed in the pathogenesis of autism. Moreover, it highlights the relationship between the measured ions, IL6, TNFα and caspase3 as a set of signalling pathways that might have a role in generating this increasingly prevalent disorder. The role of ions in the possible proinflammation and proapoptic mechanisms of autistics' brains were hypothesized and explained.

A simple analytical system using disposable, open-tubular ion exchange clean-up precolumns coupled in-line to capillary electrophoresis for direct injection of biological samples is presented. The clean-up precolumns were prepared from fused silica capillaries by thermally initiated layer-by-layer polymerization of poly(butadiene-maleic acid) (PBMA) directly on the capillary wall. Typically, 6 cm long precolumns with 4-layers of PBMA were used for sample pretreatment. A robust and reproducible coupling between the precolumn (75 μm ID) and the analytical capillary (50 μm ID) was achieved using an inexpensive, commercially available low dead volume union. No extra dispersion of the analyte zones was observed. Proteins and other high molecular weight compounds from biological sample matrices were retained on the cation-exchanger sites of the precolumn, which eliminated their adsorption on analytical capillary walls and ensured stable electroosmotic flow and migration times of target analytes. Unretained small inorganic cations migrated freely into the analytical capillary for separation and detection. Applicability of the sample clean-up procedure was proved by determination of major inorganic cations in blood serum and plasma samples using capillary electrophoresis with contactless conductivity detection. Separations were performed in background electrolyte solution consisting of 15 mM L-arginine, 12.5 mM maleic acid, 3 mM 18-crown-6 at pH 5.5 and repeatabilities of migration times and peak areas were below 1.5% and 7.3%, respectively. Less than 1 μL of biological sample was required for injection., (© 2010 Elsevier B.V. All rights reserved.)

Micro-electrodialysis (μED) and CE were combined for rapid pretreatment and subsequent determination of inorganic cations in biological samples. Combination of μED with CE greatly improved the analytical performance of the latter as the adsorption of high molecular weight compounds present in real samples on the inner capillary wall was eliminated. Fifty microliter of 80-fold diluted human body fluids such as plasma, serum and whole blood was used in the donor compartment of the μED system requiring less than 1 μL of the original body fluid per analysis. Inorganic cations that migrated through a cellulose acetate dialysis membrane with molecular weight cut-off value of 500 Da were collected in the acceptor solution and were then analyzed using CE-C⁴D. Baseline separation of inorganic cations was achieved in a BGE solution consisting of 12.5 mM maleic acid, 15 mM L-arginine and 3 mM 18-crown-6 at pH 5.5. Repeatability of the CE-C⁴D method was better than 0.5% and 2.5% for migration times and peak areas, respectively; limits of detection of all inorganic cations in the presence of 2 mM excess of Na(+) were around 1 μM and calibration curves were linear with correlation coefficients better than 0.998. Repeatability of the sample pretreatment procedure was calculated for six independent electrodialysis runs of artificial and real samples and was better than 11.8%. Recovery values between 96.3 and 110% were achieved for optimized electrodialysis conditions of standard solutions and real samples; lifetime of the dialysis membranes for pretreatment of real samples was estimated to 100 runs., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Dogs can be divided into two genetic groups (a minor HK phenotype and a major LK phenotype) based on erythrocyte monovalent cation concentrations, which are controlled by the putative hk and lk allelic genes. HK dogs retain Na,K-ATPase in their erythrocytes due to the high activity of the enzyme in their precursor cells, whereas total loss of reticulocyte Na,K-ATPase occurs in LK dogs. Here, we report that the levels of the lipid raft-associated membrane protein stomatin decrease in parallel with those of Na,K-ATPase during reticulocyte maturation due to its extrusion in exosomes. The stomatin content of HK reticulocytes is higher than that of LK reticulocytes, and remains in the erythrocytes at levels compatible with that in human erythrocytes. However, it is almost absent from LK erythrocytes with the lk/lk genotype; similar to the deficiency seen in human red cells with overhydrated stomatocytosis. LK erythrocytes from hk/lk genotype dogs show reduced, but not negligible, levels of stomatin. These results indicate that the erythrocyte stomatin level is a suitable genotypic marker for the HK/LK red cell phenotype, and suggests a functional association between stomatin and Na,K-ATPase. The absence of morphological abnormalities in the erythrocytes of stomatin-deficient LK dogs also confirms that stomatin deficiency and stomatocytic shape change are independent from each other.

Effective targeted drug delivery by cationic liposomes is difficult to achieve because of their rapid clearance from the blood circulation. Bolaamphiphiles that form monolayer membrane may provide vesicles with improved stability, as shown for archaeosomes. We investigated a series of bolaamphiphiles with acetylcholine head groups and systematic structural changes in their hydrophobic domain for their ability to form stable nanovesicles. Bolaamphiphiles with two aliphatic chains separated by a short amide midsection produced spherical nanovesicles ranging in diameter from 80 to 120 nm. These vesicles lost their encapsulated material within 24 hours of incubation in phosphate-buffered saline (PBS). Similar bolaamphiphiles with a longer midsection produced a mixture of fibers and more stable nanovesicles. Bolaamphiphiles with ester amide midsection produced only spherical nanovesicles that were stable during incubation in PBS for several days. Vesicles made from bolaamphiphiles with acetylcholine head groups conjugated to the aliphatic chain via the amine were less stable than vesicles made from bolaamphiphiles with head groups conjugated to the aliphatic chain via the acetyl group. Vesicles that were stable in vitro showed good stability in the blood circulation after intravenous administration to mice. These results help in elucidating the bolaamphiphile structures needed to form stable cationic vesicles for targeted drug delivery.

Background: Cryohydrocytosis is an inherited dominant hemolytic anemia characterized by mutations in a transmembrane segment of the anion exchanger (band 3 protein). Transfection experiments performed in Xenopus oocytes suggested that these mutations may convert the anion exchanger into a non-selective cation channel. The present study was performed to characterize so far unexplored ion transport pathways that may render erythrocytes of a single cryohydrocytosis patient cation-leaky., Design and Methods: Cold-induced changes in cell volume were monitored using ektacytometry and density gradient centrifugation. Kinetics, temperature and inhibitor-dependence of the cation and water movements in the cryohydrocytosis patient's erythrocytes were studied using radioactive tracers and flame photometry. Response of the membrane potential of the patient's erythrocyte membrane to the presence of ionophores and blockers of anion and cation channels was assessed., Results: In the cold, the cryohydrocytosis patient's erythrocytes swelled in KCl-containing, but not in NaCl-containing or KNO(3)-containing media indicating that volume changes were mediated by an anion-coupled cation transporter. In NaCl-containing medium the net HOE-642-sensitive Na(+)/K(+) exchange prevailed, whereas in KCl-containing medium swelling was mediated by a chloride-dependent K(+) uptake. Unidirectional K(+) influx measurements showed that the patient's cells have abnormally high activities of the cation-proton exchanger and the K(+),Cl(-) co-transporter, which can account for the observed net movements of cations. Finally, neither chloride nor cation conductance in the patient's erythrocytes differed from that of healthy donors. Conclusions These results suggest that cross-talk between the mutated band 3 and other transporters might increase the cation permeability in cryohydrocytosis.

Introduction: The traditional evaluation of acid-base status relies on the Henderson-Hasselbach equation. In 1983, an alternative approach, based on physical and chemical principles was proposed by P. Stewart. In this approach, plasma pH is determined by 3 independent variables: pCO2, Strong Ion Difference (SIDm), which is the difference between the strong cations (Na +, K +, Ca ++, Mg ++) and the strong anions (Cl-, lactate) and total plasma concentration of nonvolatile weak acids (ATot), mainly inorganic phosphate and albumin. Bicarbonate is considered a dependent variable. The aim of this study was to evaluate the acid-base status using both perspectives, physical chemical and traditional approach., Material and Methods: We studied 35 patients (24 M; 11F) on hemodiafiltration, mean age was 67,2+/-15,7, 8+/-19,2 kg. We analyzed plasma chemistry including pH, pCO2, HCO3-, base excess and Na+, K+, Cl-, Ca++, Mg++, lactate and SIDm. The SID estimated (SIDe) was calculated by Figge's formula (1000 x 2.46E-11 x pCO2 / (10-pH) + Album gr/dl x (0.123 x pH-0.631) + P in mmol/l x (0.309 x pH-0.469) and Gap of the SID as the difference SIDm-SIDe., Results: pH preHD was 7,36+/-0,08 and pH posHD 7,44+/-0,08 (p < 0.001). There was no significant differences between pCO2 pre and pos-HD. HCO3 - and base excess increased during the session (p < 0.001). SIDm decreased from 46,2+/-2,9 preHD to 45+/-2,3 mEq/l postHD (p < 0.05). On the opposite, SIDe increased from 38,5+/-3,8 to 42,9+/-3,1 mEq/l (p < 0.001). The Gap Anion descended from 18,6+/-3,8 preHD to 12,8+/-2,8 mEq/l mEq/l postHD (p < 0.001) and the Gap of the SID 7,6+/-3 to 2,1+/-2 (p < 0.001). Anion Gap correlated with the Gap-SID so much pre-HDF as pos-HDF. Delta Base excess correlated only with Delta of the Gap SID., Conclusion: Stewart-Fencl's approach does not improve characterization of acid-base status in patients on chronic HDF. In presence of normocloremia the SIDm does not reflect the alkalinizing process of the session of hemodialysis. According this approach, hemodialysis therapy can be viewed as a withdrawal of inorganic anions, especially the sulphate. These anions are replaced by OH - and secondarily for HCO3-. The approach only improves the evaluation of unmeasured anions by the Gap of the SID, without the effect of albumin and phosphate.

Purpose: Main aim of the present study was to test and show the dissolution of coatings onto Ti6Al4V pedicle screws by both in vitro and in vivo analysis., Methods: Hydroxyapatite (HA) was coated on Ti6Al4V by electrophoretic deposition (EPD). The dissolution of the coatings was tested in vitro. The coating was characterized before and after implantation via pull-out tests, X-ray diffraction (XRD) and scanning electron microscopy (SEM), respectively. The coating materials were immersed in a simulated body fluid (SBF) from 1 day to 6 weeks, in vitro, and the elemental analysis were undertaken in a calf spine, in vivo. Fourteen coated (7) and uncoated (7) Ti6Al4V pedicle screws were implanted in a calf spine for 12 weeks and the elemental concentration was analyzed using the wavelength dispersive X-ray fluorescence (WDXRF) technique., Results: The analysis of elemental concentrations by WDXRF are presented and 97% of the dissolved elements were determined as Ca, P, Ti, O and 3% of K, Na, Fe, Ni, Zn, Mg, S in total. The solubility of the coating materials increased with increasing immersion time and, interestingly, it increased substantially for reasonably longer times, for example, 6 weeks., Conclusions: Through the in vivo experiments, on the HA coated and uncoated pedicle screws implanted on a calf vertebra, the elemental concentrations by WDXRF analysis showed the Ca(%) around the pedicle screws increased by 30% after re-implantation process. The results may lead us to reconsider such ceramic coatings to test in vitro and/or in vivo for longer periods before clinical applications.

Aim: The postoperative hypocalcaemia has the higher incidence as complications related to thyroidectomy., Methods: From 1 June 2006 to 30 June 2008, we examined 492 patients operated on consecutively in our unit with a total thyroidectomy for thyroid disease. We evaluated the values of ionized calcium in all the cases, matching these with the preoperative and postoperative values of serum calcium. The pre- and postoperative (24 hours after treatment) data for ionized calcium and serum calcium were examined statistically with the Student's t-test; results with a P-value <0.05 were considered to be statistically significant., Results: Two-hundred-and-twenty-three of the 492 patients (45.2%) treated with total thyroidectomy had preoperative values of ionized calcium lower than 1.13 mmol/L (normal values 1.13-1.32 mmol/L), while the ionized calcium values were lower than 1.10 mmol/L in 154 of the 223 patients. The mean value of ionized calcium in all 223 cases was 1.04+/-0.07 mmol/L. The mean serum calcium value in these patients was 9.13+/-0.291 mg/dL (normal values 8.3-10.5 mg/dL). In the other 259 cases, the values of ionized calcium and serum calcium were 1.21+/-0.03 mmol/L and 9.1+/-0.29 mg/dL, respectively. In 75 cases on 223 with symptomatic hypocalcemia, the mean value of ionized calcium was 0.88+/-0.05 mmol/L, while, in the remaining 148 cases, the mean value was equal to 0.97+/-0.08 mmol/L (P<0.001). We compared this, in both groups, with the values of postoperative serum calcium; in the 75 cases with clinical hypocalcemia, the value of serum calcium was 7.32+/-0.35 mg/dL, while the value was equal to 8.4+/-0.34 mg/dL in the other cases (P<0.001)., Conclusions: The values of ionized calcium must not be used as marker of hypocalcemia but must be seen as a diagnostic aid linked to others laboratory values, such as serum calcium.

The strong ion gap is a derived parameter used to quantify clinically significant but unmeasured charged species in human plasma. In the general population the strong ion gap has a mean value of approximately 0.0 mEq/l, but at present no reference range exists. This severely limits its clinical application. In order to establish a reference range, a 95% confidence interval around the population mean must be calculated. As each of the variables that make up the strong ion gap have their own unique and different means and standard deviations, simple methods of pooled variance can not be used to calculate this interval. In place of a direct solution, Monte Carlo methodology was employed using known reference standard deviations to construct a large sample of a simulated population. In addition, the partial correlation between the plasma concentrations of sodium and chloride was included in the calculations. Sample sets of 20,000 were simulated, each giving a normally distributed strong ion gap. A 95% confidence interval of 3.9+/-6.4 mEq/l was derived. Depending on the degree of strong ion correlation, minima and maxima for this reference range were calculated as 3.9+/-5.1 mEq/l and 3.9+/-7.6 mEq/l respectively. Reasons for the positive bias in the mean strong ion gap result are examined briefly.

Objectives: The aim of this pilot study was to establish reference values for strong ion difference (SID) in umbilical cord blood and investigate the feasibility of evaluating fetal metabolism according to the comprehensive approach to acid-base abnormalities, based on Stewart's physiochemical theory., Study Design: A prospective observational study. Women who underwent an elective cesarean section at term (n=40) were compared to women who completed a normal spontaneous delivery at term (n=40). The primary outcome was the establishment of normal values for SID in the umbilical cord vein. We also compared acid-base variables in the umbilical vein between the groups., Results: The apparent SID in the umbilical vein was 34.61+/-3.92 mequiv./L after normal delivery and 35.98+/-2.56 mequiv./L after elective cesarean section (the effective SID is 37.43+/-1.93 and 38.29+/-2.38 mequiv./L, respectively). The pH values were similar in both groups, but the pCO(2) was significantly higher and the plasma principal weak acids (albumin and phosphate) were significantly lower after cesarean sections., Conclusions: SID enables a comprehensive approach to acid-base abnormalities in the neonate, making it a potential additional tool for evaluating fetal acid-base status.

The hereditary stomatocytoses (HSt) are a diverse group of conditions. Common features include hemolytic anemia, a red cell cation leak and morphological changes, but the severity of the condition can vary enormously. We have previously shown that one form of HSt (cryohydrocytosis), where the monovalent cation leak is increased at low temperature, results from amino acid substitutions in the membrane domain of band 3 (anion exchanger 1, SLC4A1). These substitutions appear to convert band 3 from an anion exchanger into a cation channel. More recently we found that over-hydrated hereditary stomatocytosis (OHSt) results from amino acid substitutions in Rh-associated glycoprotein (RhAG), a putative gas channel protein. Both band 3 and RhAG associate in the red cell membrane to form a macrocomplex that is thought to be involved in red cell gas exchange. In this paper I will review the data that has been published so far on the molecular basis of HSt. I will mention other similar conditions that cause either a cation leak or stomatocytosis or both, and consider the mechanisms of red cell shape change and permeability.

Silicone elastomer substrates were irradiated with acceleration voltages ranging from 3 to 9 kV and doses ranging from 1 x 10(14) to 2.5 x 10(15) ions cm(-2) by the simultaneous use of oxygen cluster and monomer (O(2) CM) ion beams, and then soaking in CaCl(2) solution. The apatite-forming ability of the substrates was examined using a metastable calcium phosphate solution that had 1.5 times the ion concentrations of normal simulated body fluid (1.5SBF). Silicon oxide clusters (SiO(x)) were formed at the silicone elastomer surfaces and the hydrophilicity of the substrates was remarkably improved by the irradiation. The irradiated silicone elastomer substrates formed apatite in 1.5SBF, whereas unirradiated ones did not. These results suggest that irradiation using O(2) CM ion beams is effective for inducing an apatite-forming ability on silicone elastomer substrates.

Between-breed genetic variation for muscle and meat quality traits was determined at eight weeks of age in 34 lines of purebred commercial broiler and layer lines and traditional breeds (categories) of chickens. Between-breed genetic variation for plasma ion concentrations and element concentration in muscle dry matter and ash were determined. Plasma from broilers had higher concentrations of Na+, K+, Mg++, total and free Ca++ and lower free:total Ca++ than plasma from layer and traditional lines. Muscle from broilers contained more Na and higher concentrations of K, Mg and Ca per mg of ash but not of dry matter compared with layer and traditional lines. In comparison with layer and traditional lines, broiler genotypes were over three times heavier, their plasma creatine kinase activity (CK), a marker of muscle tissue damage, was higher, their breast muscle colour was lighter (L*) and less red (a*) and yellow (b*) in appearance, the initial and final pH of their muscles were lower, the pH change was higher and their breast muscle was more tender. Thus, genetic selection for broiler traits has markedly altered cation regulation in muscle cells and may be associated with changes in muscle cell function and the development of pathology and meat quality problems.

Background: Cystic fibrosis (CF) is one of the most common fatal autosomal recessive disorders in the Caucasian population caused by mutations of gene for the cystic fibrosis transmembrane conductance regulator (CFTR). New experimental therapeutic strategies for CF propose a diet supplementation to affect the plasma membrane fluidity and to modulate amplified inflammatory response. The objective of this study was to evaluate the efficacy of 5-methyltetrahydrofolate (5-MTHF) and vitamin B12 supplementation for ameliorating cell plasma membrane features in pediatric patients with cystic fibrosis., Methodology and Principal Findings: A single arm trial was conducted from April 2004 to March 2006 in an Italian CF care centre. 31 children with CF aged from 3 to 8 years old were enrolled. Exclusion criteria were diabetes, chronic infections of the airways and regular antibiotics intake. Children with CF were supplemented for 24 weeks with 5-methyltetrahydrofolate (5-MTHF, 7.5 mg /day) and vitamin B12 (0.5 mg/day). Red blood cells (RBCs) were used to investigate plasma membrane, since RBCs share lipid, protein composition and organization with other cell types. We evaluated RBCs membrane lipid composition, membrane protein oxidative damage, cation content, cation transport pathways, plasma and RBCs folate levels and plasma homocysteine levels at baseline and after 24 weeks of 5-MTHF and vitamin B12 supplementation. In CF children, 5-MTHF and vitamin B12 supplementation (i) increased plasma and RBC folate levels; (ii) decreased plasma homocysteine levels; (iii) modified RBC membrane phospholipid fatty acid composition; (iv) increased RBC K(+) content; (v) reduced RBC membrane oxidative damage and HSP70 membrane association., Conclusion and Significance: 5-MTHF and vitamin B12 supplementation might ameliorate RBC membrane features of children with CF., Trial Registration: ClinicalTrials.gov NCT00730509.

The post-feeding alkaline tide (elevated blood pH and HCO3-) has been well characterised in air-breathing animals, but to date this phenomenon has only been demonstrated in one piscine species, a marine elasmobranch. We have investigated the acid-base and ion regulatory responses of a freshwater teleost to voluntary feeding as well as to involuntary filling of the stomach via an indwelling gastric intubation tube. One group of rainbow trout (Oncorhynchus mykiss) were fed a 1% body mass ration of homogenised food via the gastric intubation tube. Another group fed voluntarily on a 1% body mass ration. Blood samples were taken via dorsal aortic catheters from fish in both groups before feeding and over the subsequent 72 h. Trout fed via the gastric intubation tube exhibited post-prandial metabolic alkalosis of the blood (pH and plasma HCO3- increases of up to approximately 0.2 pH units and 3 mmol l(-1), respectively), that was more than twofold greater than the voluntary feeding fish, and took three times as long to recover (72 versus 24 h). Arterial PCO2 was unchanged in both groups indicating that freshwater trout do not retain CO2 to compensate for a post-prandial alkaline tide. Although excretion of HCO3- to the water increased post-prandially, NH4+ excretion followed a similar pattern, such that net acid equivalent fluxes were unaffected. Thus, sites other than the gills or kidney must be responsible for recovery of blood acid-base status, with intestinal HCO3- secretion being a likely candidate. In addition, fish fed via the gastric intubation tube experienced a large (17 mmol l(-1)) but acute (6 h) drop in plasma chloride and a very large (53%) and long lasting decline in plasma magnesium concentration, that were absent in voluntarily feeding fish. These results further indicate a potentially important role for neuro-endocrine mediated mechanisms when fish feed voluntarily, in promoting the earlier initiation of compensatory responses that regulate blood ion levels and acid-base status. This aspect should also be considered when interpreting studies on other aspects of post-prandial physiology, where force feeding by gavage is commonly used in preference to voluntary feeding.

The role of the central nervous system (CNS) in the control of hydrosaline homeostasis has been strikingly demonstrated by several studies. Our laboratory recently showed that centrally administered insulin produced a dose-related increase in the urinary output of sodium, which was abolished by bilateral renal denervation, nitric oxide synthase inhibition and cerebroventricular streptozotocin administration in rats. Recent studies have shown that hyperinsulinemia induces subtle derangements of intracellular insulin-insulin receptor trafficking and insulin metabolism, which are associated with an impairment of insulin signaling. The long-term effect of high insulin levels on the periventricular region could alter insulin signaling, which in turn, may modify the central natriuretic and cardiovascular effects of this peptide. In order to evaluate this hypothesis, we investigated the effects of 7-day i.c.v. insulin administration on tubular handling and blood pressure in conscious, unrestrained rats and their controls, randomly assigned to one of two separate groups: (a) i.c.v. 0.15M NaCl-injected (n=7) and (b) i.c.v. 126.0 ng insulin-injected rats (n=7). In the current study, there were no significant differences between the blood pressure, daily tap water intake and serum sodium, potassium, lithium and creatinine levels in control i.c.v. 0.15M NaCl-injected rats, compared with the insulin-treated group. Conversely, there was a significant decrease in the daily solid rat chow intake (Co: 16.4+/-3.5 g vs. Ins: 10.3+/-2.6g, P=0.003) in 7-day long-term insulin-treated rats, compared with the control group. We confirmed that centrally administered insulin produced a substantial increase in the urinary output of Na+, Li+ and K+, and that the response was significantly enhanced in long-term i.c.v. insulin pre-treated animals, when compared with controls (fractional sodium excretion (FE(Na)) from basal: 0.047+/-0.18% to Ins-treated: 0.111+/-0.035%, P=0.001). Additionally, we demonstrated that insulin-induced natriuresis occurred by increasing fractional proximal (FEP(Na)) from basal (16.8+/-2.6% to Ins-treated: 26.7+/-2.8%, P=0.001) and post-proximal sodium excretion (FEPP(Na)) from basal (0.37+/-0.03% to Ins-treated: 0.42+/-0.05%, P=0.043), despite a decreased Na(+) filtered load and rat food intake. The current data suggest that centrally injected insulin maintain its CNS ability to amplify neuronal hypotensive and natriuretic pathways that counteract the known peripheral antinatriuretic effects of insulin.

We tested the influence of magnesium, zinc and copper upon the montelukast (MK, antagonist of cysteinyl leukotriene receptor type 1) effect in experimentally-induced thermoalgesia. We worked on 5 groups of 10 adults, each Wistar rats, that received: group I-control; group II: MK (10 mg/kg) unique administration; group III: MgCl2 (1 mM/kg/day) i.p., 3 days and MK (10 mg/kg) unique administration on the 3rd day; group IV: ZnCl2, (0.1 mM/kg/day), i.p., 3 days and MK (10 mg/kg) unique administration on the 3rd day; group V: copper acetate (0.05 mM/kg/day), i.p., 3 days and MK (10 mg/kg) unique administration on the 3rd day. We determined the thermoalgesic sensitivity (TS) using a tail flick analgesia meter, initially, 3 days after daily cation administration and 3 hours after MK administration. Our data show that MK has a statistically significant reduction of TS vs control group (3.76 +/- 1.04 s vs 1.81 +/- 0.98 s, p < 0.05). Copper and magnesium administration do not significantly change the MK effect to decrease TS. The co-administration of zinc and MK statistically significantly increased the TS of the group that received only MK (2.51 +/- 0.21 s vs 3.76 +/- 1.04 s, p < 0.05). Animals that received only cations (in the above mentioned doses) did not significantly change TS.

Our objective was to examine the effects of dietary cation-anion difference (DCAD) with different concentrations of dietary crude protein (CP) on performance and acid-base status in early lactation cows. Six lactating Holstein cows averaging 44 d in milk were used in a 6 x 6 Latin square design with a 2 x 3 factorial arrangement of treatments: DCAD of -3, 22, or 47 milliequivalents (Na + K - Cl - S)/100 g of dry matter (DM), and 16 or 19% CP on a DM basis. Linear increases with DCAD occurred in DM intake, milk fat percentage, 4% fat-corrected milk production, milk true protein, milk lactose, and milk solids-not-fat. Milk production itself was unaffected by DCAD. Jugular venous blood pH, base excess and HCO3(-) concentration, and urine pH increased, but jugular venous blood Cl- concentration, urine titratable acidity, and net acid excretion decreased linearly with increasing DCAD. An elevated ratio of coccygeal venous plasma essential AA to nonessential AA with increasing DCAD indicated that N metabolism in the rumen was affected, probably resulting in more microbial protein flowing to the small intestine. Cows fed 16% CP had lower urea N in milk than cows fed 19% CP; the same was true for urea N in coccygeal venous plasma and urine. Dry matter intake, milk production, milk composition, and acid-base status did not differ between the 16 and 19% CP treatments. It was concluded that DCAD affected DM intake and performance of dairy cows in early lactation. Feeding 16% dietary CP to cows in early lactation, compared with 19% CP, maintained lactation performance while reducing urea N excretion in milk and urine.

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

In addition to paCO(2), Stewart's acid base model takes into account the influence of albumin, inorganic phosphate, electrolytes and lactate on acid-base equilibrium. It allows a comprehensive and quantitative analysis of acid-base disorders. Particularly simultaneous and mixed metabolic acid-base disorders, which are common in critically ill patients, can be assessed. Stewart's approach is therefore a valuable tool in addition to the customary acid-base approach based on bicarbonate or base excess. However, some chemical aspects of Stewart's approach remain controversial.

Sperm of the three-spined stickleback Gasterosteus aculeatus display a prolonged motility in the presence of ovarian fluid. The ovarian fluid prolongs sperm motility in freshwater from approximately 1 min to several hours, a trait that possibly gives the stickleback its unusual ability to spawn in waters of all salinities. The aim of the study was to look for factor(s) within the ovarian fluid responsible for prolonging sperm motility as well as to investigate the possible biological importance of the ovarian fluid under natural conditions. To that end, we measured the ionic content (Na(+), Cl(-), Ca(2+) and K(+)) of the ovarian fluid and prepared ionic artificial ovarian fluids. We also prepared a mannitol solution with the same osmolality as the ovarian fluid in order to distinguish between the ionic and osmotic effect. We found that the ionic artificial fluids were equally effective as the natural ovarian fluid in prolonging sperm motility and survival over a range of concentrations, whereas the mannitol solution was far less effective. By insertion of natural ovarian fluid or ovarian fluid from which macromolecules had been removed by ultra filtration in nests it was found that macromolecules help by retaining ions. We also found that ovarian fluid in water, at concentrations as low as 0.75 and 1.56%, prolonged sperm motility and that the concentration of ions (Na(+)) present in the nest 15 min after spawning corresponded to at least 3% ovarian fluid. Previous fertilisation experiments have shown that it takes at least 15 min for stickleback sperm to fertilise all eggs in a batch. This indicates that the role of ovarian fluid in prolonging the sperm motility is biologically relevant and that the effect is exerted by the fluid's ionic content.

In this work, the tissue/blood partition coefficients of seven human tissues were calculated using a nonlinear regression analysis. The dataset contained 80 structurally diverse compounds distributing into the brain, kidney, muscle, lung, liver, heart, and fat, whose acidic and basic properties were also considered by introducing the three possible forms of the compound in the human body (neutral, cationic, and anionic forms). A total of 248 data points were there in the training set (eq 5: r = 0.877, s = 0.352; eq 6: r = 0.869, s = 0.362) and 49 data points in the testing set (eq 5: r = 0.844, s = 0.342; eq 6: r = 0.860, s = 0.311). It was also concluded that the same state (neutral, cation, and anion) of a compound has essentially identical partition coefficients between the same tissue composition and the blood in these tissues. Only the different content of the three tissue compositions (lipid, protein, and water) lead to the different partition coefficient in different tissues, which offered a significant conclusion for the drug's distribution research.