Sodium nitroprusside has leishmanicidal activity independent of iNOS

Abstract: INTRODUCTION: Leishmaniasis is a zoonotic disease caused by protozoa of the genus Leishmania . Cutaneous leishmaniasis is the most common form, with millions of new cases worldwide each year. Treatments are ineffective due to the toxicity of existing drugs and the resistance acquired by certain strains of the parasite. METHODS: We evaluated the activity of sodium nitroprusside in macrophages infected with Leishmania (Leishmania) amazonensis . Phagocytic and microbicidal activity were evaluated by phagocytosis assay and promastigote recovery, respectively, while cytokine production and nitrite levels were determined by ELISA and by the Griess method. Levels of iNOS and 3-nitrotyrosine were measured by immunocytochemistry. RESULTS: Sodium nitroprusside exhibited in vitro antileishmanial activity at both concentrations tested, reducing the number of amastigotes and recovered promastigotes in macrophages infected with L. amazonensis . At 1.5µg/mL, sodium nitroprusside stimulated levels of TNF-α and nitric oxide, but not IFN-γ. The compound also increased levels of 3-nitrotyrosine, but not expression of iNOS, suggesting that the drug acts as an exogenous source of nitric oxide. CONCLUSIONS: Sodium nitroprusside enhances microbicidal activity in Leishmania -infected macrophages by boosting nitric oxide and 3-nitrotyrosine.

Sodium serum levels in hypoalbuminemic adults at general medical wards

Hypoalbuminemia may cause interstitial edema and hemodilution, which we hypothesized may influence serum sodium levels. Our purpose was to compare serum sodium levels of hospitalized adults with or without hypoalbuminemia. All sodium and albumin serum levels of 142 adults hospitalized at general medical wards over a six-month period were searched at a University Hospital mainframe computer. Relevant laboratory data and clinical details were also registered. Hypoalbuminemia was defined by serum albumin concentration < 3.3 g/dl Fisher, Mann-Whitney, and Student's t tests were applied to compare groups with or without hypoalbuminemia. Ninety-nine patients, classified as hypoalbuminemic, had lower blood hemoglobin (10.68 ± 2.62 vs. 13.54 ± 2.41), and sodium (135.1 ± 6.44 vs. 139.9 ± 4.76mEq/l) and albumin (2.74 ± 0.35 vs. 3.58 ± 0.28g/dl) serum levels than non-hypoalbuminemic (n=43). Pearson's coefficient showed a significant direct correlation between albumin and sodium serum levels (r=0.40) and between serum albumin and blood hemoglobin concentration (r=0.46). Our results suggest that hypoalbuminemic adults have lower serum sodium levels than those without hypoalbuminemia, a phenomenon that may be at least partially attributed to body water retention associated with acute phase response syndrome.

Influence of physical exercise and sodium intake on arterial pressure and cardiac hypertrophy in rats

Evidence shows that cardiac hypertrophy (CH) is a risk factor for many cardiovascular diseases. Several stimuli may cause CH-like manifestations and promote volume or pressure overload. Exercise-induced cardiac hypertrophy is an expected adaptation to regular exercise training. Salt intake has been shown to be the most important determinant of blood pressure in different populations. The purpose of the present work was to verify the influence of physical exercise and sodium intake on the blood pressure and myocardium. The study was performed on 36 rats divided into six groups: Group I (diet without salt overload), Group II (diet without salt overload and swimming), Group III (diet with 2.5% NaCl solution and swimming), Group IV (diet with 5% NaCl solution and swimming), Group V (diet with 2.5% NaCl solution without exercise), Group VI (diet with 5% NaCl solution without exercise). The arterial pressure was significantly lower in Group I when compared with Group IV. The ratio of cardiac mass/body mass was increased in Groups III and IV. In conclusion, there was evidence that exercise training and NaCl intake promotes arterial hypertension and cardiac hypertrophy.

Bowel preparation for colonoscopy: comparison of mannitol and sodium phosphate. Results of a prospective randomized study

METHOD: Eighty patients were prospectively randomized for precolonoscopic cleansing either with 750 ml of 10% mannitol (Group M) or 180 ml of a sodium phosphate preparation (Group NaP). Laboratory examinations before and after preparation on all patients included hemoglobin, hematocrit, sodium, potassium, phosphorous, calcium and serum osmolarity. A questionnaire was used to assess undesirable side effects and patient tolerance to the solution. The quality of preparation was assessed by the endoscopist who was unaware of the solution employed. RESULTS: Statistically significant changes were verified in serum sodium, phosphorous, potassium and calcium between the two groups, but no clinical symptoms were observed. There were no significant differences in the frequency of side effects studied. Six of the eight patients in Group NaP who had taken mannitol for a previous colonoscopy claimed better acceptance of the sodium phosphate solution. The endoscopic-blinded trial reported excellent or good bowel preparation in 85% prepared with sodium phosphate versus 82.5% for mannitol (p=0.37). CONCLUSIONS: Quality of preparation and frequency of side effects was similar in the two solutions. The smaller volume of sodium phosphate necessary for preparation seems to be related to its favorable acceptance. Nevertheless, the retention of sodium and phosphate ions contraindicates the use of sodium phosphate in patients with renal failure, cirrhosis, ascites, and heart failure.

Design of bio-inspired ionic liquids for protein stabilisation

Ionic Liquids (ILs) consist in organic salts that are liquid at/or near room temperature. Since ILs are entirely composed of ions, the formation of ion pairs is expected to be one essential feature for describing solvation in ILs. In recent years, protein - ionic liquid (P-IL) interactions have been the subject of intensive studies mainly because of their capability to promote folding/unfolding of proteins. However, the ion pairs and their lifetimes in ILs in P-IL thematic is dismissed, since the action of ILs is therefore the result of a subtle equilibrium between anion-cation interaction, ion-solvent and ion-protein interaction. The work developed in this thesis innovates in this thematic, once the design of ILs for protein stabilisation was bio-inspired in the high concentration of organic charged metabolites found in cell milieu. Although this perception is overlooked, those combined concentrations have been estimated to be ~300 mM among the macromolecules at concentrations exceeding 300 g/L (macromolecular crowding) and transient ion-pair can naturally occur with a potential specific biological role. Hence the main objective of this work is to develop new bio-ILs with a detectable ion-pair and understand its effects on protein structure and stability, under crowding environment, using advanced NMR techniques and calorimetric techniques. The choline-glutamate ([Ch][Glu]) IL was synthesized and characterized. The ion-pair was detected in water solutions using mainly the selective NOE NMR technique. Through the same technique, it was possible to detect a similar ion-pair promotion under synthetic and natural crowding environments. Using NMR spectroscopy (protein diffusion, HSQC experiments, and hydrogen-deuterium exchange) and differential scanning calorimetry (DSC), the model protein GB1 (production and purification in isotopic enrichment media) it was studied in the presence of [Ch][Glu] under macromolecular crowding conditions (PEG, BSA, lysozyme). Under dilute condition, it is possible to assert that the [Ch][Glu] induces a preferential hydration by weak and non-specific interactions, which leads to a significant stabilisation. On the other hand, under crowding environment, the [Ch][Glu] ion pair is promoted, destabilising the protein by favourable weak hydrophobic interactions , which disrupt the hydration layer of the protein. However, this capability can mitigates the effect of protein crowders. Overall, this work explored the ion-pair existence and its consequences on proteins in conditions similar to cell milieu. In this way, the charged metabolites found in cell can be understood as key for protein stabilisation.

Exchange rate pressure in Angola

The objective of this work is to develop an operational tool to analyze exchange rate pressure in the context of Angola. The Angolan economy exhibits a number of relevant characteristics: a closed financial account, a partially controlled current account, a highly dollarized economy and exports (oil) price determined in World markets. These features have a direct effect on the demand of foreign currency and motivate their inclusion in the specification of a model for Angola. The model provides the rational for a measure of an exchange market rate pressure (EMP) index that contains exports changes, imports changes, the foreign interest rate and inflation and the change in foreign reserves corrected for a measure dollarization. The empirical performance new measure is comparable (slightly better) to the performance of the EMP indexes obtained in Eichengreen Rose and Wyplosz (1994) and Klassen and Jager (2011).

Chlorite Dismutase from perchlorate reducing bacteria. A potential biocatalyst to eliminate chlorinated species from polluted water resources and industrial wastes

Magnetospirillum (M.) sp. strain Lusitani, a perchlorate reducing bacteria (PRB), was previously isolated from a wastewater treatment plant and phylogenetic analysis was performed to classify the isolate. The DNA sequence of the genes responsible for perchlorate reduction and chlorite dismutation was determined and a model was designed based on the physiological roles of the proteins involved in the pcr-cld regulon. Chlorite dismutase (Cld) was purified from Magnetospirillum sp. strain Lusitani cells grown in anaerobiosis in the presence of perchlorate. The protein was purified up to electrophoretic grade using HPLC techniques as a 140 kDa homopentamer comprising five ~28 kDa monomers. Steady-state kinetic studies showed that the enzyme follows a Michaelis-Menten model with optimal pH and temperature of 6.0 and 5°C, respectively. The average values for the kinetic constants KM and Vmax were respectively 0.56 mM and 10.2 U, which correspond to a specific activity of 35470 U/mg and a turnover number of 16552 s-1. Cld from M. sp. strain Lusitani is inhibited by the product chloride, but not by dioxygen. Inhibition constants KiC= 460 mM and KiU= 480 mM indicated that sodium chloride is a weak mixed inhibitor of Cld, with a slightly stronger competitive character. The X-ray crystallography structure of M. sp. strain Lusitani Cld was solved at 3.0 Å resolution. In agreement with cofactor content biochemical analysis, the X-ray data showed that each Cld monomer harbors one heme b coordinated by a histidine residue (His188), hydrogen-bonded to a conserved glutamic acid residue (Glu238). The conserved neighboring arginine residue (Arg201) important for substrate positioning, was found in two different conformations in different monomers depending on the presence of the exogenous ligand thiocyanate. UV-Visible and CW-EPR spectroscopies were used to study the effect of redox agents, pH and exogenous ligands on the heme environment.

Sodium chloride added to transport water and physiological responses of Matrinxã Brycon amazonicus (Teleost: Characidae)

The addition of salt to the water has been used to mitigate stress and improve survival in fishes. This study investigated the effects of sodium chloride (0.0, 1.0, 3.0 and 6.0 g/l) on levels of plasma cortisol, glucose, tryacilglycerol, total protein, hematocrit, hemoglobin, erythrocyte number, liver glycogen and lipid, and muscle lipid in adult matrinxã(Brycon amazonicum) after a 4-h transport and during a 96-h recovery period. Fish were sampled before and after transport, and 24 and 96 h of the recovery period. Plasma cortisol was higher than initial condition immediately after transportation, except in fish transported in 3.0 and 6.0 g/l of salt. A similar pattern was observed for blood glucose but fish transported in water with 0.0, 1.0 and 3.0 g/l of salt needed more than 24 h to return to the initial condition. Liver glycogen was lower after transport in fish not exposed to salt. Hemoglobin, erythrocyte number, total plasma protein and liver lipid did not change during the experiment but hematocrit was lower after transport in all treatments and returned to pre-transport values in 24 h. Reductions of muscle lipid and plasma tryacilglycerol were observed during the recovery period in fish from all treatments. The results show that 6.0 g/l NaCl added to the transport water reduce the stress responses and a 96-h recovery period is needed if no salt is used to mitigate the stress.

Ion exchange dependent electroactive phase content and electrical properties of poly(vinylidene fluoride)/Na(M)Y composites

Different metal-ion exchanged NaY zeolite, Na(M)Y, were used to prepare poly(vinylidene fluoride) based composites by solvent casting and melting crystallization. The effect of different metal ion-exchanged zeolites on polymer crystallization and electrical properties was reported. Cation-framework interactions and hydration energy of the cations determined that K+ is the most efficient exchanged ion in NaY zeolite, followed by Cs+ and Li+. The electroactive phase crystallization strongly depends on the ions present in the zeolite, leading to variations of the surface energy characteristics of the Na(M)Y zeolites and the polymer chain ability of penetration in the zeolite. Thus, Na(Li)Y and NaY induces the complete electroactive -phase crystallization of the crystalline phase of PVDF, while Na(K)Y only induces it partly and Na(Cs)Y is not able to promote the crystallization of the electroactive phase. Furthermore, different ion size/weigh and different interaction with the zeolite framework results in significant variations in the electrical response of the composite. In this way, iinterfacial polarization effects in the zeolite cavities and zeolite-polymer interface, leads to strong increases of the dielectric constant on the composites with lightest ions weakly bound to the zeolite framework. Polymer composite with Na(Li)Y show the highest dielectric response, followed by NaY and Na(K)Y. Zeolite Na(Cs)Y contribute to a decrease of the dielectric constant of the composite. The results show the relevance of the materials for sensor development.

Light-distortion analysis as a possible indicator of visual quality after refractive lens exchange with diffractive multifocal intraocular lenses

METHODS: Refractive lens exchange was performed with implantation of an AT Lisa 839M (trifocal) or 909MP (bifocal toric) IOL, the latter if corneal astigmatism was more than 0.75 diopter (D). The postoperative visual and refractive outcomes were evaluated. A prototype light-distortion analyzer was used to quantify the postoperative light-distortion indices. A control group of eyes in which a Tecnis ZCB00 1-piece monofocal IOL was implanted had the same examinations. RESULTS: A trifocal or bifocal toric IOL was implanted in 66 eyes. The control IOL was implanted in 18 eyes. All 3 groups obtained a significant improvement in uncorrected distance visual acuity (UDVA) (P < .001) and corrected distance visual acuity (CDVA) (P Z .001). The mean uncorrected near visual acuity (UNVA) was 0.123 logMAR with the trifocal IOL and 0.130 logMAR with the bifocal toric IOL. The residual refractive cylinder was less than 1.00 D in 86.7% of cases with the toric IOL. The mean light-distortion index was significantly higher in the multifocal IOL groups than in the monofocal group (P < .001), although no correlation was found between the light-distortion index and CDVA. CONCLUSIONS: The multifocal IOLs provided excellent UDVA and functional UNVA despite increased light-distortion indices. The light-distortion analyzer reliably quantified a subjective component of vision distinct from visual acuity; it may become a useful adjunct in the evaluation of visual quality obtained with multifocal IOLs.

Silicon nanowire arrays coupled with cobalt phosphide spheres as low-cost photocathodes for efficient solar hydrogen evolution

We demonstrate the first example of silicon nanowire array photocathodes coupled with hollow spheres of the emerging earth-abundant cobalt phosphide catalysts. Compared to bare silicon nanowire arrays, the hybrid electrodes exhibit significantly improved photoelectrochemical performance toward the solar-driven H2 evolution reaction.

Interrelationship between partition behavior of organic compounds and proteins in aqueous dextran-Polyethylene glycol and Polyethylene glycol-sodium sulfate two-phase systems

Partition behavior of adenosine and guanine mononucleotides was examined in aqueous dextran-polyethylene glycol (PEG) and PEG-sodium sulfate two-phase systems. The partition coefficients for each series of mononucleotides were analyzed as a functions of the number of phosphate groups and found to be dependent on the nature of nucleic base and on the type of \ATPS\ utilized. It was concluded that an average contribution of a phosphate group into logarithm of partition coefficient of a mononucleotide cannot be used to estimate the difference between the electrostatic properties of the coexisting phases of ATPS. The data obtained in this study were considered together with those for other organic compounds and proteins reported previously, and the linear interrelationship between logarithms of partition coefficients in dextran-PEG, PEG-Na2SO4 and PEG-Na2SO4-0.215 M NaCl (all in 0.01 M Na- or K/Na-phosphate buffer, pH 7.4 or 6.8) was established. Similar relationship was found for the previously reported data for proteins in Dex-PEG, PEG-600-Na2SO4, and PEG-8000-Na2SO4 ATPS. It is suggested that the linear relationships of the kind established in \ATPS\ may be observed for biological properties of compounds as well.

Gas exchange during exercise in different evolutional stages of chronic Chagas' heart disease

OBJECTIVE: To compare gas exchange at rest and during exercise in patients with chronic Chagas' heart disease grouped according to the Los Andes clinical/hemodynamic classification. METHODS: We studied 15 healthy volunteers and 52 patients grouped according to the Los Andes clinical/hemodynamic classification as follows: 17 patients in group IA (normal electrocardiogram/echocardiogram), 9 patients in group IB (normal electrocardiogram and abnormal echocardiogram), 14 patients in group II (abnormal electrocardiogram/echocardiogram, without congestive heart failure), and 12 patients in group III (abnormal electrocardiogram/echocardiogram with congestive heart failure). The following variables were analyzed: oxygen consumption (V O2), carbon dioxide production (V CO2), gas exchange rate (R), inspiratory current volume (V IC), expiratory current volume (V EC), respiratory frequency, minute volume (V E), heart rate (HR), maximum load, O2 pulse, and ventilatory anaerobic threshold (AT). RESULTS: When compared with the healthy group, patients in groups II and III showed significant changes in the following variables: V O2peak, V CO2peak, V ICpeak, V ECpeak, E, HR, and maximum load. Group IA showed significantly better results for these same variables as compared with group III. CONCLUSION: The functional capacity of patients in the initial phase of chronic Chagas' heart disease is higher than that of patients in an advanced phase and shows a decrease that follows the loss in cardiac-hemodynamic performance.

The effects of sodium hypochlorite against selected drinking water-isolated bacteria in planktonic and sessile states

Chlorine is the most commonly used agent for general disinfection, particularly for microbial growth control in drinking water distribution systems. The goals of this study were to understand the effects of chlorine, as sodium hypochlorite (NaOCl), on bacterial membrane physicochemical properties (surface charge, surface tension and hydrophobicity) and on motility of two emerging pathogens isolated from drinking water, Acinetobacter calcoaceticus and Stenotrophomonas maltophilia. The effects of NaOCl on the control of single and dual-species monolayer adhered bacteria (2 h incubation) and biofilms (24 h incubation) was also assessed. NaOCl caused significant changes on the surface hydrophobicity and motility of A. calcoaceticus, but not of S. maltophilia. Planktonic and sessile S. maltophilia were significantly more resistant to NaOCl than A. calcoaceticus. Monolayer adhered co-cultures of A. calcoaceticus-S. maltophilia were more resilient than the single species. Oppositely, dual species biofilms were more susceptible to NaOCl than their single species counterparts. In general, biofilm removal and killing demonstrated to be distinct phenomena: total bacterial viability reduction was achieved even if NaOCl at the higher concentrations had a reduced removal efficacy, allowing biofilm reseed. In conclusion, understanding the antimicrobial susceptibility of microorganisms to NaOCl can contribute to the design of effective biofilm control strategies targeting key microorganisms, such as S. maltophilia, and guarantying safe and high-quality drinking water. Moreover, the results reinforce that biofilms should be regarded as chronic contaminants of drinking water distribution systems and accurate methods are needed to quantify their presence as well as strategies complementary/alternative to NaOCl are required to effectively control the microbiological quality of drinking water.

Energía Eólica en Argentina: una cuestión estratégica hacia la Economía del Hidrógeno. Wind Energy in Argentina: a strategic subject towards the Hydrogen Economy.

Identificación/caracterización del problema: El abastecimiento energético en base a fuentes no tradicionales o recursos no renovables es un tema altamente estratégico en las agendas de los Estados. El petróleo se está agotando y las existencias no alcanzarán para abastecer el consumo mundial.Esto ha llevado a Gobiernos a implementar alternativas de producción energética basadas en fuentes no tradicionales, tales como el Hidrógeno (H2), lo cual creará una Economía basada en el Hidrógeno.Argentina cuenta con una matriz energética dependiente en un 90 por ciento del petróleo y con reservas certificadas de petróleo y gas natural para 8,6 y 9,4 años respectivamente. Sin duda, los desafíos próximos serán: a) crear las herramientas necesarias para minimizar una potencial crisis energética en el corto plazo, y b) desarrollar políticas energéticas que articulen su autoabastecimiento e inserción en la Economía del Hidrógeno. Dado que Argentina cuenta con uno de los recursos renovables más importantes del mundo, "el viento", tiene condiciones inmejorables para obtener Hidrógeno (H2) por electrólisis del agua, utilizando energía eléctrica proveniente de fuentes renovables como la eólica (EE). Es por ello que apostar al desarrollo local del H2 basado en la EE nos ofrecerá como país, un rol estratégico en la futura Economía del Hidrógeno.Objetivo General: Identificar la actual Matriz Energética Argentina y reconocer los factores limitantes y oportunidades para la diversificación de la misma, utilizando la Energía Eólica (EE) como pilar hacia la Economía del Hidrógeno (Econo-H2). El fin último será esbozar herramientas de política energética e instrumentos regulatorios pertinentes, que sirvan de base para la formulación de una macro política energética.Metodología de Investigación: Se utilizarán técnicas de análisis de la siguiente información:a) Documental (textos, artículos, información periodística)b) Técnica, Legal y administrativa) Oral (Declaraciones oficiales-privadas y entrevistas)d) Visual (imágenes, gráficos y mapas)e) Datos (cronológicos, estadísticos y geográficos)Resultados esperados: La formulación de herramientas de política energética y de instrumentos regulatorios pertinentes, que sirvan de base para la formulación de una macro política energética que considere la Energía Eólica (EE) como un pilar fundamental para la diversificación de la matriz energética actual. Asimismo se reflexionará sobre la importancia de asociar la EE a la producción masiva del hidrógeno (H2) para la inserción y proyección futura de la Argentina hacia la Economía del Hidrógeno.Importancia del Proyecto: Argentina ha ratificado el protocolo de Kioto y forma parte de la Johannesburg Renewable Energy Coalition (JREC), por la cual ha asumido compromisos para fijar políticas nacionales de incentivo para el desarrollo de uso de energías renovables.Sin embargo, y a pesar de una serie de iniciativas y leyes promulgadas relacionadas a uso de energías renovables, hasta la fecha, no se ha logrado cumplir con metas concretas.Consideramos que uno de los factores fundamentales que ha dificultado esto, se basa en la ausencia de una política de Estado de mediano y largo plazo que incluya a las energías renovables como un objetivo concreto y un sistema de instrumentos y planes complementarios que acompañen dicha política.