Characterization of acid-base status in maintenance hemodialysis: physicochemical approach

Acidosis is a common and deleterious aspect of maintenance dialysis. Traditionally, it is considered to be an elevated anion gap acidosis caused by the inability to excrete nonvolatile anions. Stewart`s approach made it possible to identify real determinants of the acid-base status and allowed quantification of the components of these disturbances, especially the unmeasured anions. We performed a cross-sectional study to identify and quantify each component of acidosis in hemodialysis maintenance patients. Sixty-four maintenance hemodialysis patients and 14 controls were enrolled in this study. Gasometrical and biochemical analysis were performed before the midweek dialysis session. Quantitative physicochemical analysis was carried out using the Stewart methodology. Hemodialysis patients were found to have mild acidemia (mean pH: 7.33 +/- 0.06 versus 7.41 +/- 0.05) secondary to metabolic acidosis (serum bicarbonate: 18.8 +/- 0.26 versus 25.2 +/- 0.48 mEq/l). The metabolic acidosis was due to retention of unmeasured anions (6.5 +/- 0.29 versus 3.1 +/- 0.62 mEq/l), hyperchloremia (105.1 +/- 0.5 versus 101.8 +/- 0.7 mEq/l), and hyperphosphatemia (5.90 +/- 0.19 versus 3.66 +/- 0.14 mg/dl). Compared with control values, the unmeasured anions and hyperchloremia had a similar acidifying effect (3.4 and 3.3 mEq/l), corresponding to almost 90% of the metabolic acidosis. Unmeasured anions and hyperchloremia are important components of acidosis in maintenance hemodialysis, in addition to phosphorus. Future studies to determine the etiology and consequences of hyperchloremic acidosis are warranted.

Evolutive physicochemical characterization of diabetic ketoacidosis in adult patients admitted to the intensive care unit

Purpose: The aim of this study was to characterize the first 48-hour evolution of metabolic acidosis of adult patients with diabetic ketoacidosis admitted to the intensive care unit. Materials and Methods: We studied 9 patients retrieved from our prospective collected database, using the physicochemical approach to acid-base disturbances. Results: Mean (SD) age was 34 (13) years; mean (SD) Acute Physiology and Chronic Health Evaluation II score was 16 (10); mean (SD) blood glucose level on admission was 480 (144) mg/dL; mean (SD) pH was 7.17 (0.18); and mean (SD) standard base excess was -16.8 (7.7) mEq/L. On admission, a great part of metabolic acidosis was attributed to unmeasured anions (strong ion gap [SIG], 20 +/- 10 mEq/L), with a wide range of strong ion difference (41 +/- 10 mEq/L). During the first 48 hours of treatment, 297 +/- 180 IU of insulin and 9240 +/- 6505 mL of fluids were used. Metabolic improvement was marked by the normalization of pH, partial correction of standard base excess, and a reduction of hyperglycemia. There was a significant improvement of SIG (7.6 +/- 6.2 mEq/L) and a worsening of strong ion difference acidosis (36 +/- 5 mEq/L) in the first 24 hours, with a trend toward recuperation between 24 and 48 hours (38 +/- 6 mEq/L). Conclusion: Initial metabolic acidosis was due to SIG, and the treatment was associated with a significant decrease of SIG with an elevation of serum chloride above the normal range. (C) 2011 Elsevier Inc. All rights reserved.

Effect of chloride dialysate concentration on metabolic acidosis in aintenance hemodialysis patients

Hyperchloremia is one of the multiple etiologies of metabolic acidosis in hemodialysis (HD) patients. The aim of the present study was to determine the influence of chloride dialysate on metabolic acidosis control in this population. We enrolled 30 patients in maintenance HD program with a standard base excess (SBE) ≤2 mEq/L and urine output of less than 100 mL/24 h. The patients underwent dialysis three times per week with a chloride dialysate concentration of 111 mEq/L for 4 weeks, and thereafter with a chloride dialysate concentration of 107 mEq/L for the next 4 weeks. Arterial blood was drawn immediately before the second dialysis session of the week at the end of each phase, and the Stewart physicochemical approach was applied. The strong ion gap (SIG) decreased (from 7.5 ± 2.0 to 6.2 ± 1.9 mEq/L, P = 0.006) and the standard base excess (SBE) increased after the use of 107 mEq/L chloride dialysate (from -6.64 ± 1.7 to -4.73 ± 1.9 mEq/L, P < 0.0001). ∆SBE was inversely correlated with ∆SIG during the phases of the study (Pearson r = -0.684, P < 0.0001) and there was no correlation with ∆chloride. When we applied the Stewart model, we demonstrated that the lower concentration of chloride dialysate interfered with the control of metabolic acidosis in HD patients, surprisingly, through the effect on unmeasured anions.

Descripción del estado acido base en pacientes con quemaduras térmicas agudas: serie de casos

Introducción: Los pacientes con lesiones térmicas presentan alteraciones fisiológicas complejas que hacen difícil la caracterización del estado ácido-base y así mismo alteraciones electrolíticas e hipoalbuminemia que pudieran estar relacionados con un peor pronóstico. Se ha estudiado la base déficit (BD) y el lactato, encontrando una gran divergencia en los resultados. Por lo anterior, el análisis físico-químico del estado ácido-base podría tener un rendimiento superior a los métodos tradicionales. Metodología: Se realizó el análisis de una serie de casos de 15 pacientes mayores de 15 años, con superficie corporal quemada mayor al 20% que ingresaron a una unidad de cuidado intensivo (UCI) de quemados, dentro de las siguientes 48 horas del trauma. Para el análisis se utilizaron tres métodos distintos: 1) método convencional basado en la teoría de Henderson-Hasselbalch, 2) anión-gap (AG) y anión-gap corregido por albúmina, 3) análisis físico-químico del estado ácido-base según la teoría de Stewart modificado por Fencl y Figge. Resultados: Por el método de Henderson-Hasselbalch, 8 pacientes cursaron con acidosis metabólica, 4 pacientes con una BD leve, 5 pacientes con una BD moderada y 5 pacientes con una BD severa. El AG resultó menor a 16 mmol/dl en 10 pacientes, pero al corregirlo por albumina sólo 2 pacientes cursaron con AG normal. La diferencia de iones fuertes (DIF) se encontraba anormalmente elevada en la totalidad de los pacientes. Conclusión:El análisis del AG corregido por albumina y el análisis físico-químico del estado ácido-base, podrían tener mayor rendimiento al identificar las alteraciones metabólicas de estos pacientes.

New analytical LC-mass spectrometry methodologies for the quali-quantitative determination of natural substances and drugs in complex matrices

This thesis reports an integrated analytical and physicochemical approach for the study of natural substances and new drugs based on mass spectrometry techniques combined with liquid chromatography. In particular, Chapter 1 concerns the study of Berberine a natural substance with pharmacological activity for the treatment of hepatobiliary and intestinal diseases. The first part focused on the relationships between physicochemical properties, pharmacokinetics and metabolism of Berberine and its metabolites. For this purpose a sensitive HPLC-ES-MS/MS method have been developed, validated and used to determine these compounds during their physicochemical properties studies and plasma levels of berberine and its metabolites including berberrubine(M1), demethylenberberine(M3), and jatrorrhizine(M4) in humans. Data show that M1, could have an efficient intestinal absorption by passive diffusion due to a keto-enol tautomerism confirmed by NMR studies and its higher plasma concentration. In the second part of Chapter 1, a comparison between M1 and BBR in vivo biodistribution in rat has been studied. In Chapter 2 a new HPLC-ES-MS/MS method for the simultaneous determination and quantification of glucosinolates, as glucoraphanin, glucoerucin and sinigrin, and isothiocyanates, as sulforaphane and erucin, has developed and validated. This method has been used for the analysis of functional foods enriched with vegetable extracts. Chapter 3 focused on a physicochemical study of the interaction between the bile acid sequestrants used in the treatment of hypercholesterolemia including colesevelam and cholestyramine with obeticolic acid (OCA), potent agonist of nuclear receptor farnesoid X (FXR). In particular, a new experimental model for the determination of equilibrium binding isotherm was developed. Chapter 4 focused on methodological aspects of new hard ionization coupled with liquid chromatography (Direct-EI-UHPLC-MS) not yet commercially available and potentially useful for qualitative analysis and for “transparent” molecules to soft ionization techniques. This method was applied to the analysis of several steroid derivatives.

A patient presenting with metabolic acidosis despite severe vomiting—correct diagnosis by use of the physical-chemical approac

We describe the case of a 28-year-old otherwise healthy woman who presents to our emergency department with nausea for 2 days and severe vomiting for 1 day. She has no history of travel, and her medical history is unremarkable. The physical examination shows a soft and nontender abdomen. Laboratory examinations reveal the presence of significant metabolic alkalosis despite the severe vomiting of the patient. Hypochloremic alkalosis would be expected to be present in this patient. We explain how to correctly identify the rare cause of metabolic acidosis present in this patient using the physicochemical approach (Stewarts approach) for the analysis of human acid-base disorders.

Sensory evaluation and physicochemical optimisation of soy-based desserts using response surface methodology

The objective of this study was to develop a dessert that contains soy protein (SP) (1%, 2%, 3%) and guava juice (GJ) (22%, 27%, 32%) using Response Surface Methodology (RSM) as the optimisation technique. Water activity, physical stability, colour, acidity, pH, iron, and carotenoid contents were analysed. Affective tests were performed to determine the degree of liking of colour, creaminess, and acceptability. The results showed that GJ increased the values of redness, hue angle, chromaticity, acidity, and carotenoid content, while SP reduced water activity. Optimisation suggested a dessert containing 32% GJ and 1.17% SP as the best proportion of these components. This sample was considered a source of fibres, ascorbic acid, copper, and iron and garnered scores above the level of `slightly liked` for sensory attributes. Moreover, RSM was shown to be an adequate approach for modelling the physicochemical parameters and the degree of liking of creaminess of desserts. (C) 2010 Elsevier Ltd. All rights reserved.

Nanotechnology and antioxidant therapy: An emerging approach for neurodegenerative diseases

The efficacy, cellular uptake and specific transport of dietary antioxidants to target organs, tissues and cells remains the most important setback for their application in the treatment of oxidative-stress related disorders and in particular in neurodegenerative diseases, as brain targeting remains a still unsolved challenge. Nanotechnology based delivery systems can be a solution for the above mentioned problems, specifically in the case of targeting dietary antioxidants with neuroprotective activity. Nanotechnology-based delivery systems can protect antioxidants from degradation, improve their physicochemical drug-like properties and in turn their bioavailability. The impact of nanomedicine in the improvement of the performance of dietary antioxidants, as protective agents in oxidative- stress events, specifically through the use of drug delivery systems, is highlighted in this review as well as the type of nanomaterials regularly used for drug delivery purposes. From the data one can conclude that the research combining (dietary) antioxidants and nanotechnology, namely as a therapeutic solution for neurodegenerative diseases, is still in a very early stage. So, a huge research area remains to be explored that hopefully will yield new and effective neuroprotective therapeutic agents in a foreseeable future.

Lipids under stress - a lipidomic approach for the study of mood disorders

The emerging field of lipidomics has identified lipids as key players in disease physiology. Their physicochemical diversity allows precise control of cell structure and signaling events through modulation of membrane prop- erties and trafficking of proteins. As such, lipids are important regulators of brain function and have been implicated in neurodegenerative and mood disorders. Importantly, environmental chronic stress has been associated with anxiety and depression and its exposure in rodents has been extensively used as a model to study these diseases. With the accessibility to modern mass- spectrometry lipidomic platforms, it is now possible to snapshot the extensively interconnected lipid network. Here, we review the fundamentals of lipid biology and outline a framework for the interpretation of lipidomic studies as a new approach to study brain pathophysiology. Thus, lipid profiling provides an exciting avenue for the identification of disease signatures with important implications for diagnosis and treatment of mood disorders.

iLOGP: A Simple, Robust, and Efficient Description of n-Octanol/Water Partition Coefficient for Drug Design Using the GB/SA Approach.

The n-octanol/water partition coefficient (log Po/w) is a key physicochemical parameter for drug discovery, design, and development. Here, we present a physics-based approach that shows a strong linear correlation between the computed solvation free energy in implicit solvents and the experimental log Po/w on a cleansed data set of more than 17,500 molecules. After internal validation by five-fold cross-validation and data randomization, the predictive power of the most interesting multiple linear model, based on two GB/SA parameters solely, was tested on two different external sets of molecules. On the Martel druglike test set, the predictive power of the best model (N = 706, r = 0.64, MAE = 1.18, and RMSE = 1.40) is similar to six well-established empirical methods. On the 17-drug test set, our model outperformed all compared empirical methodologies (N = 17, r = 0.94, MAE = 0.38, and RMSE = 0.52). The physical basis of our original GB/SA approach together with its predictive capacity, computational efficiency (1 to 2 s per molecule), and tridimensional molecular graphics capability lay the foundations for a promising predictor, the implicit log P method (iLOGP), to complement the portfolio of drug design tools developed and provided by the SIB Swiss Institute of Bioinformatics.

Impact of biological and environmental variabilities on biological monitoring: an approach using toxicokinetic models

Biological monitoring of occupational exposure is characterized by important variability, due both to variability in the environment and to biological differences between workers. A quantitative description and understanding of this variability is important for a dependable application of biological monitoring. This work describes this variability,using a toxicokinetic model, for a large range of chemicals for which reference biological reference values exist. A toxicokinetic compartmental model describing both the parent compound and its metabolites was used. For each chemical, compartments were given physiological meaning. Models were elaborated based on physiological, physicochemical, and biochemical data when available, and on half-lives and central compartment concentrations when not available. Fourteen chemicals were studied (arsenic, cadmium, carbon monoxide, chromium, cobalt, ethylbenzene, ethyleneglycol monomethylether, fluorides, lead, mercury, methyl isobutyl ketone, penthachlorophenol, phenol, and toluene), representing 20 biological indicators. Occupational exposures were simulated using Monte Carlo techniques with realistic distributions of both individual physiological parameters and exposure conditions. Resulting biological indicator levels were then analyzed to identify the contribution of environmental and biological variability to total variability. Comparison of predicted biological indicator levels with biological exposure limits showed a high correlation with the model for 19 out of 20 indicators. Variability associated with changes in exposure levels (GSD of 1.5 and 2.0) is shown to be mainly influenced by the kinetics of the biological indicator. Thus, with regard to variability, we can conclude that, for the 14 chemicals modeled, biological monitoring would be preferable to air monitoring. For short half-lives (less than 7 hr), this is very similar to the environmental variability. However, for longer half-lives, estimated variability decreased. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resource: tables detailing the CBTK models for all 14 chemicals and the symbol nomenclature that was used.] [Authors]

Origin of needle fibre calcite (NFC) : a geochemical approach

ABSTRACTNeedle fibre calcite (NFC) is one of the most widespread habits of pedogenic calcite. It is a monocrystal of calcite, in the shape of a needle, with a diameter of one micron and a length between 4 and 103 times its width. NFC occurs in soils with different macroscopic and microscopic morphologies. Macroscopically, two main habits of NFC exist: "cotton ball'Mike clusters and as "powder" coating on pebbles inside the soil. It can also act as nucleation sites for precipitation of calcite cements of purely physicochemical origin (LCC - Late Calcitic Cement). Although many studies have been conducted on needle fibre calcite, its origin remains a subject of debate. The NFC having never been reproduced in the laboratory whatever the considered approach, the processes responsible for its precipitation as a so particular morphology remain unexplained. The shift between the length orientation of the needle crystal and the normal axis of calcite growth (c-axis) is also unresolved.Samples taken in two soils observed in quarries (Villiers and Savagnier) in the Swiss Jura Mountains are used to investigate the processes involved in the formation of these calcite crystals in pedogenic environments. Three groups of microscopic morphologies are distinguished: (i) simple needles (SN), (ii) simple needles with overgrowths (SNO), and (iii) simple needles with nanofibres (SNN), nanofibres being either organic or mineral in nature. These groups correspond to different stages in the formation and evolution of NFC.Comparison of carbon and oxygen isotope compositions of NFC with LCC, in relationship with the composition of the carbonate host rock (CHR), and the carbon isotope signature of dissolved inorganic carbon (DIC) from the soil waters, indicates that both NFC and LCC are precipitated in isotopic equilibrium with the soil solution. Similar Ô13C and Ô180 values of the elongated NFC and the rhombohedral calcite crystals of the LCC suggest that the precipitation of these different calcite habits is not due to changes in physicochemical conditions. The growth of NFC crystals inside an organic mould formed by the fungal hyphae could explain the formation of calcite ciystals in the shape of a needle in isotopic equilibrium with the local environment.Strontium and calcium isotope compositions of the three microscopic groups of NFC and LCC were also studied, in order to determine the origin of calcium (Ca2+) entrapped in the calcite lattice and to elucidate the processes responsible for the precipitation of NFC. The 87Sr/86Sr ratio of the SN is closer to the 87Sr/86Sr ratio of the carbonate host rock than the LCC, SNO, and SNN. This could be another clue for the formation of SN inside fungal hyphae, because fungi are known to dissolve the rocks to release and translocate through their hyphae nutrients necessary for their growth. SN and SNN are depleted in Sr and enriched in ^Ca compared to the LCC. In the context of Villiers quarry, where the two ciystal shapes precipitate at similar temperature (in a range of 0,6°C), such variations are the result of a slower precipitation rate of NFC, which is inconsistent with a purely physicochemically precipitated elongate crystal.Finally, NFC is enriched in major and trace elements (i.e. Fe, Zn, Cu, and Mo) compared to the LCC. This enrichment is ascribed to modification in precipitation processes between the NFC and LCC. Right now, it is not possible to preclude the influence of the particular shape of NFC or the biological influence. REEs are not fractionated in NFC, contrary to LCC. Thus, NFC does not precipitate from a percolation solution circulating downward the soil, which should lead to the fractionation of the REEs. As explained above, fungi, are able to dissolve and translocate nutrients. This kind of processes allows releasing elements in the soil solution without fractionation and could explain the particular chemical signature of NFC regarding the REEs.The geochemical approach to investigate the origin of NFC presented in this study does not allow providing direct clues to the fungal origin of NFC, but brings several new insights in the understanding of the formation of such a particular mineral, calcite needles, by precluding definitively their physicochemical origin.RESUMELa calcite en aiguilles (NFC) est l'une des formes les plus ubiquiste de calcite pédogénique. Il s'agit d'un monocrystal de calcite d'un diamètre d'un micron et d'une longueur 4 à 102 fois supérieure à sa largeur. A l'échelle macroscopique, la NFC a été observée sous deux principaux aspects : l'une « cotonneuse » et l'autre formant un mince croûte autour des graviers du sol. La NFC peut également servir de support à la nucléation de ciments secondaires précipités de manière purement physico-chimique (LCC). Malgré les nombreuses études menées sur la NFC, son origine demeure encore inconnue. A ce jour, aucune expérience en laboratoire n'a permis de créer de la calcite en aiguilles, et ce, quelque soit l'approche abordée. Par conséquent, les processus précis responsables de la précipitation calcite avec une telle morphologie restent inconnus. Le décalage existant entre l'axe d'allongement des aiguilles de calcite et l'axe normal de croissance de la calcite (axe c) reste inexpliqué.Des échantillons de NFC, LCC, roche mère, eau de pluie des différents horizons du sol ont été prélevés principalement au front de deux carrières de graviers, ainsi que dans un profil de sol adjacent à ces carrières, dans le but de mieux comprendre les processus à l'origine de la précipitation de calcite en forme d'aiguille. Trois micro-morphologies ont été distinguées: les aiguilles simples (SN), les aiguilles simples avec surcroissances calcitiques (SNO) et enfin les aiguilles simples avec nanofibres (SNN), celles-ci pouvant être de minérales ou organiques. Ces groupes, d'après nos résultats et les études antérieures pourraient correspondre à différentes étapes de formation de la calcite en aiguilles.Dans un premier temps, la comparaison des signatures isotopiques de la calcite en aiguilles, du LCC, de la roche mère et du carbone inorganique dissout dans la solution du sol (CID) indique que la NFC, tout comme le LCC, précipite en équilibre avec la solution du sol. Les valeurs similaires en Ô13C et δ180 de cristaux de calcite allongés (NFC) et rhombohédriques (LCC) formés dans un même milieu suggère que ces différences morphologiques ne peuvent pas être attribuées à des modifications purement physico-chimiques. La croissance de NFC à l'intérieur d'un moule organique comme les hyphes de champignons semble être la seule hypothèse plausible permettant d'expliquer la formation de monocrystaux allongés de calcite en équilibre avec leur environnement.La composition isotopique en strontium (Sr) et calcium (Ca) des LCC et des trois micro¬morphologies de la NFC ont été étudiées également, afin de déterminer l'origine du Ca2+ présent dans le réseau cristallin de la calcite en aiguilles, ainsi que les processus responsables de la formation de NFC. Les valeurs du rapport 87Sr/86$r de la forme SN sont les plus proches de celles de la roche mère par rapport aux formes SNN et SNO et du LCC. Ceci pourrait être un nouvel indice de l'implication des champignons dans la précipitation de calcite en aiguilles, puisqu'ils sont connus pour avoir la capacité de dissoudre les roches afin de libérer les nutriments nécessaires à leur croissance, ainsi que de les transloquer par leurs hyphes. De plus, les formes SN et SNN sont appauvries en Sr et enrichies en "Ca, comparativement au LCC. Dans le sol étudié, tous les carbonates de calcium précipitent à la même température, par conséquent, de telles variations sont dues à un taux de précipitation plus lent de SN et SNN, ce qui est contradictoire avec l'hypothèse physico-chimique. Pour finir, la NFC est enrichie en certains éléments majeurs et traces (i.e. Fe, Zn, Cu et Mo) par rapport au LCC. Ceci peut être attribué à différents processus de formation entre la NFC et le LCC. Pour le moment il est impossible d'exclure l'influence de la forme particulière de la NFC ou celle du champignon. Les terres rares (REEs) ne sont pas fractionnées dans la NFC, contrairement au LCC. Ceci peut être expliqué par le fait que la NFC précipite à partir d'une solution qui n'a pas percolé à travers le sol. Les champignons en dissolvant les roches mettent en solution éléments sans les fractionner. L'approche géochimique de l'étude de la calcite en aiguilles ne permets pas de produire des preuves directes sur sa potentielle origine fongique, mais permet de mieux comprendre comment un minéral aussi singulier que la NFC peut se former. D'autre pare cette étude permets d'exclure définitivement l'hypothèse physico-chimique de l'origine de la calcite en aiguilles

Indomethacin solubility estimation in 1,4-dioxane + water mixtures by the extended hildebrand solubility approach

Extended Hildebrand Solubility Approach (EHSA) was successfully applied to evaluate the solubility of Indomethacin in 1,4-dioxane + water mixtures at 298.15 K. An acceptable correlation-performance of EHSA was found by using a regular polynomial model in order four of the W interaction parameter vs. solubility parameter of the mixtures (overall deviation was 8.9%). Although the mean deviation obtained was similar to that obtained directly by means of an empiric regression of the experimental solubility vs. mixtures solubility parameters, the advantages of EHSA are evident because it requires physicochemical properties easily available for drugs.

Fish crackers development from minced fish and starch: an innovative approach to a traditional product

This study aimed to develop sensory acceptable, high nutritional value fish crackers that could be kept at room temperature for 180 days. Minced fish of different low-value species was the raw material employed to produce two types of fish crackers: a) the traditional keropok cracker, which was expanded by deep frying; and b) a low-fat fish cracker, expanded by microwave cooking. The protein content of the fried fish crackers (FFCs) and that of the microwaved fish crackers (MFCs) were high (10.86 and 14.70%, respectively). The essential amino acid contents of the two types of fish cracker were above the FAO requirements for adults, and the lysine content was above the requirements for children. Sensory analysis, performed by adult panelists, resulted in a general level of acceptability of 90% for the MFCs and of 97% for the FFCs. Vacuum packaging maintained microbiological and physicochemical properties for a storage period of 180 days at room temperature.