Influence of a pore-forming agent on swelling, network parameters, and permeability of poly(ethylene glycol)-crosslinked poly(methyl vinyl ether-co-maleic acid) hydrogels:Application in transdermal delivery systems

We characterized hydrogels, prepared from aqueous blends of poly(methyl vinyl ether-co-maleic acid) (PMVE/MA) and poly(ethylene glycol) (PEG 10,000 Daltons) containing a pore-forming agent (sodium bicarbonate, NaHCO ). Increase in NaHCO content increased the equilibrium water content (EWC) and average molecular weight between crosslinks (M ) of hydrogels. For example, the %EWC was 731, 860, 1109, and 7536% and the M was 8.26, 31.64, 30.04, and 3010.00 × 10 g/mol for hydrogels prepared from aqueous blends containing 0, 1, 2, and 5% w/w of NaHCO , respectively. Increase in NaHCO content also resulted in increased permeation of insulin. After 24 h, percentage permeation was 0.94, 3.68, and 25.71% across hydrogel membranes prepared from aqueous blends containing 0, 2, and 5% w/w of NaHCO , respectively. Hydrogels containing the pore-forming agent were fabricated into microneedles (MNs) for transdermal drug delivery applications by integrating the MNs with insulin-loaded patches. It was observed that the mean amount of insulin permeating across neonatal porcine skin in vitro was 20.62% and 52.48% from hydrogel MNs prepared from aqueous blends containing 0 and 5% w/w of NaHCO . We believe that these pore-forming hydrogels are likely to prove extremely useful for applications in transdermal drug delivery of biomolecules. © 2012 Wiley Periodicals, Inc.

Gastroretentive Extended-Release Floating Granules Prepared Using a Novel Fluidized Hot Melt Granulation (FHMG) Technique

The objective of this work was to investigate the feasibility of using a novel granulation technique, namely, fluidized hot melt granulation (FHMG), to prepare gastroretentive extended-release floating granules. In this study we have utilized FHMG, a solvent free process in which granulation is achieved with the aid of low melting point materials, using Compritol 888 ATO and Gelucire 50/13 as meltable binders, in place of conventional liquid binders. The physicochemical properties, morphology, floating properties, and drug release of the manufactured granules were investigated. Granules prepared by this method were spherical in shape and showed good flowability. The floating granules exhibited sustained release exceeding 10 h. Granule buoyancy (floating time and strength) and drug release properties were significantly influenced by formulation variables such as excipient type and concentration, and the physical characteristics (particle size, hydrophilicity) of the excipients. Drug release rate was increased by increasing the concentration of hydroxypropyl cellulose (HPC) and Gelucire 50/13, or by decreasing the particle size of HPC. Floating strength was improved through the incorporation of sodium bicarbonate and citric acid. Furthermore, floating strength was influenced by the concentration of HPC within the formulation. Granules prepared in this way show good physical characteristics, floating ability, and drug release properties when placed in simulated gastric fluid. Moreover, the drug release and floating properties can be controlled by modification of the ratio or physical characteristics of the excipients used in the formulation.

Soluciones hipertónicas en trauma craneoencefálico: revisión sistemática de la literatura

El traumatismo craneoencefálico, es la epidemia silenciosa de nuestra época, que genera gastos en salud, en países como Estados Unidos, cercanos a los 60 billones de dólares anuales, y cerca de 400 billones en rehabilitación de los discapacitados. El pilar del manejo médico del trauma craneoencefálico moderado o severo, es la osmoterapia, principalmente con sustancias como el manitol y las soluciones hipertónicas. Se realizó la revisión de 14 bases de datos, encontrando 4657754 artículos, quedando al final 40 artículos después de un análisis exhaustivo, que se relacionaban con el manejo de la hipertensión endocraneana y terapia osmótica. Resultados: Se compararon diferentes estudios, encontrando gran variabilidad estos, sin homogenización en los análisis estadísticos, y la poca rigurosidad no permitieron, la recolección de datos y la comparación entre los diferentes estudios, no permitió realizar el meta-análisis y por esto se decidió la realización de una revisión sistemática de la literatura. Se evidenció principalmente tres cosas: la primera es la poca rigurosidad con la que se realizan los estudios clínicos; la segunda, es que aún falta mucha más investigación principalmente, la presencia de estudios clínicos aleatorizados multicéntricos, que logren dar una sólida evidencia y que genere validez científica que se requiere, a pesar de la evidencia clara en la práctica clínica; la tercera es la seguridad para su uso, con poca presencia de complicaciones para las soluciones salinas hipertónicas.

DESCRIPCIÓN DEL ESTADO ÁCIDO BASE POR MODELO DE STEWART EN PACIENTES POSTOPERATORIO DE TRASPLANTE HEPÁTICO

Introducción: Los pacientes en postoperatorio de trasplante hepático presentan múltiples cambios hemodinámicos y alteraciones hidroelectrolíticas que generan cambios en el estado ácido base. El presente trabajo, busca describir el comportamiento ácido base en pacientes pos trasplante hepático, a través del análisis del modelo de Stewart, enfocado en la búsqueda etiológica de cada trastorno y planteando posibles formas de optimizar el manejo en Cuidado Intensivo (CI). Metodología: Estudio observacional, descriptivo histórico de los gases arteriales de los pacientes en post operatorio de trasplante hepático por cualquier causa, interpretados por método de Stewart. Se realizó con el universo de pacientes ingresados en el año 2014 en la Fundación Santa Fe de Bogotá. Resultados: Ingresaron en total 24 pacientes al estudio, entre el 1 de enero al 31 de septiembre de 2014. La mediana de pH fue de 7.36 con un valor mínimo de 7.05 y el máximo de 7.49. El 41% de los pacientes al ingreso a cuidado intensivo tenían lactato normal (menor a 2), y el 88% tenían niveles de albumina bajos. El trastorno electrolítico más común fue hipercloremia (58%), seguido de hipomagnesemia (25%). Conclusiones. El análisis de gases arteriales por el modelo de Stewart permite realizar un diagnóstico de un trastorno específico y adicionalmente, permite buscar la etiología del trastorno. Esta serie de casos mostró que el 95% de los pacientes tenían algún trastorno metabólico al ingreso, siendo el más frecuente la acidosis metabólica (66%).

Evidence for systemic spread of the potentially zoonotic intestinal spirochaete Brachyspira pilosicoli in experimentally challenged laying chickens

Brachyspira pilosicoli is a potentially zoonotic anaerobic intestinal spirochaete that is one of several species causing avian intestinal spirochaetosis. The aim of this study was to develop a reproducible model of infection in point-of-lay chickens and compare the virulence of two strains of B. pilosicoli in a model using experimentally challenged laying chickens. Seventeen-week-old commercial laying chickens were experimentally challenged by oral gavage with either B. pilosicoli strain B2904 or CPSp1, following an oral dose of 10 % sodium bicarbonate to neutralize acidity in the crop. Approximately 80 % of the chickens became colonized and exhibited increased faecal moisture content, reduced weight gain and delayed onset of lay. Tissues sampled at post-mortem examination were analysed to produce a quantitative output on the number of spirochaetes present and hence, the extent of colonization. The liver and spleen were colonized, and novel histopathology was observed in these tissues. The infection model we report here has potential use in studies to improve our understanding of the mechanisms by which Brachyspira elicit disease in poultry and in testing novel intervention strategies.

Intake, water consumption, ruminal fermentation, and stress response of beef heifers fed after different lengths of delays in the daily feed delivery time

Four rumen-fistulated Holstein heifers (134 +/- 1 kg initial BW) were used in a 4 x 4 Latin square design to determine the effects of delaying daily feed delivery time on intake, ruminal fermentation, behavior, and stress response. Each 3-wk experimental period was preceded by 1 wk in which all animals were fed at 0800 h. Feed bunks were cleaned at 0745 h and feed offered at 0800 h (T0, no delay), 0900 (T1), 1000 (T2), and 1100 (T3) from d1 to 21 with measurements taken during wk 1 and 3. Heifers were able to see each other at all times. Concentrate and barley straw were offered in separate compartments of the feed bunks, once daily and for ad libitum intake. Ruminal pH and saliva cortisol concentrations were measured at 0, 4, 8, and 12 h postfeeding on d 3 and 17 of each experimental period. Fecal glucocorticoid metabolites were measured on d 17. Increasing length of delay in daily feed delivery time resulted in a quadratic response in concentrate DMI (low in T1 and T2; P = 0.002), whereas straw DMI was greatest in T1 and T3 (cubic P = 0.03). Treatments affected the distribution of DMI within the day with a linear decrease observed between 0800 and 1200 h but a linear increase during nighttimes (2000 to 0800 h), whereas T1 and T2 had reduced DMI between 1200 and 1600 h (quadratic P = 0.04). Water consumption (L/d) was not affected but decreased linearly when expressed as liters per kilogram of DMI (P = 0.01). Meal length was greatest and eating rate slowest in T1 and T2 (quadratic P <= 0.001). Size of the first meal after feed delivery was reduced in T1 on d 1 (cubic P = 0.05) and decreased linearly on d 2 (P = 0.01) after change. Concentrate eating and drinking time (shortest in T1) and straw eating time (longest in T1) followed a cubic trend (P = 0.02). Time spent lying down was shortest and ruminating in standing position longest in T1 and T2. Delay of feeding time resulted in greater daily maximum salivary cortisol concentration (quadratic P = 0.04), which was greatest at 0 h in T1 and at 12 h after feeding in T2 (P < 0.05). Daily mean fecal glucocorticoid metabolites were greatest in T1 and T3 (cubic P = 0.04). Ruminal pH showed a treatment effect at wk 1 because of increased values in T1 and T3 (cubic P = 0.01). Delaying feed delivery time was not detrimental for rumen function because a stress response was triggered, which led to reduced concentrate intake, eating rate, and size of first meal, and increased straw intake. Increased salivary cortisol suggests that animal welfare is compromised.

Functional analysis of a novel missense NBC1 mutation and of other mutations causing proximal renal tubular acidosis

Mutations in the Na+-HCO3- cotransporter NBC1 cause severe proximal tubular acidosis (pRTA) associated with ocular abnormalities. Recent studies have suggested that at least some NBC1 mutants show abnormal trafficking in the polarized cells. This study identified a new homozygous NBC1 mutation (G486R) in a patient with severe pRTA. Functional analysis in Xenopus oocytes failed to detect the G486R activity due to poor surface expression. In ECV304 cells, however, G486R showed the efficient membrane expression, and its transport activity corresponded to approximately 50% of wild-type (WT) activity. In Madin-Darby canine kidney (MDCK) cells, G486R was predominantly expressed in the basolateral membrane domain as observed for WT. Among the previously identified NBC1 mutants that showed poor surface expression in oocytes, T485S showed the predominant basolateral expression in MDCK cells. On the other hand, L522P was exclusively retained in the cytoplasm in ECV304 and MDCK cells, and functional analysis in ECV304 cells failed to detect its transport activity. These results indicate that G486R, like T485S, is a partial loss of function mutation without major trafficking abnormalities, while L522P causes the clinical phenotypes mainly through its inability to reach the plasma membranes. Multiple experimental approaches would be required to elucidate potential disease mechanism by NBC1 mutations.

Mechanisms underlying the long-term regulation of NHE3 by parathyroid hormone

The activity of the Na(+)/H(+) exchanger NHE3 is regulated by a number of factors including parathyroid hormone (PTH). In the current study, we used a renal epithelial cell line, the opossum kidney (OKP) cell, to elucidate the mechanisms underlying the long-term effects of PTH on NHE3 transport activity and expression. We observed that NHE3 activity was reduced 6 h after addition of PTH, and this reduction persisted almost unaltered after 24 h. The decrease in activity was associated with diminished NHE3 cell surface expression at 6, 16, and 24 h after PTH addition, total cellular NHE3 protein at 16 and 24 h, and NHE3 mRNA abundance at 24 h. The lower levels of NHE3 mRNA were associated to a small, but significant, decrease in mRNA stability. Additionally, by analyzing the rat NHE3 gene promoter activity in OKP cells, we verified that the regulatory region spanning the segment -152 to +55 was mildly reduced under the influence of PTH. This effect was completely abolished by the presence of the PKA inhibitor KT 5720. In conclusion, long-term exposure to PTH results in reduction of NHE3 mRNA levels due to a PKA-dependent inhibitory effect on the NHE3 promoter and a small reduction of mRNA half-life, and decrease in the total amount of protein which is preceded by endocytosis of the apical surface NHE3. The decreased NHE3 expression is likely to be responsible for the reduction of sodium, bicarbonate, and fluid reabsorption in the proximal tubule consistently perceived in experimental models of PTH disorders.

Induced alkalosis and caffeine supplementation : effects on 2,000-m rowing performance

Introduction: The purpose of this investigation was to determine the effect of ingested caffeine, sodium bicarbonate, and their combination on 2,000-m rowing performance, as well as on induced alkalosis (blood and urine pH and blood bicarbonate concentration [HCO3 -]), blood lactate concentration ([La-]), gastrointestinal symptoms, and rating of perceived exertion (RPE). Methods: In a double-blind, crossover study, 8 well-trained rowers performed 2 baseline tests and 4 × 2,000-m rowing-ergometer tests after ingesting 6 mg/kg caffeine, 0.3 g/kg body mass (BM) sodium bicarbonate, both supplements combined, or a placebo. Capillary blood samples were collected at preingestion, pretest, and posttest time points. Pairwise comparisons were made between protocols, and differences were interpreted in relation to the likelihood of exceeding the smallest-worthwhile- change thresholds for each variable. A likelihood of >75% was considered a substantial change. Results: Caffeine supplementation elicited a substantial improvement in 2,000-m mean power, with mean (± SD) values of 354 ± 67 W vs. placebo with 346 ± 61 W. Pretest [HCO3 -] reached 29.2 ± 2.9 mmol/L with caffeine + bicarbonate and 29.1 ± 1.9 mmol/L with bicarbonate. There were substantial increases in pretest [HCO3 -] and pH and posttest urine pH after bicarbonate and caffeine + bicarbonate supplementation compared with placebo, but unclear performance effects. Conclusions: Rowers' performance in 2,000-m efforts can improve by ~2% with 6 mg/kg BM caffeine supplementation. When caffeine is combined with sodium bicarbonate, gastrointestinal symptoms may prevent performance enhancement, so further investigation of ingestion protocols that minimize side effects is required. ABSTRACT FROM AUTHOR

Effects of acute alkalosis and acidosis on performance

Ingestion of agents that modify blood buffering action may affect high-intensity performance. Here we present a meta-analysis of the effects of acute ingestion of three such agents - sodium bicarbonate, sodium citrate and ammonium chloride - on performance and related physiological variables (blood bicarbonate, pH and lactate). A literature search yielded 59 useable studies with 188 observations of performance effects. To perform the mixed- model meta-analysis, all performance effects were converted into a percentage change in mean power and were weighted using standard errors derived from exact p-values, confidence limits (CLs) or estimated errors of measurement. The fixed effects in the meta-analytic model included the number of performance-test bouts (linear), test duration (log linear), blinding (yes/no), competitive status (athiete/nonathlete) and sex (male/female). Dose expressed as buffering mmoL/kg/body mass (BM) was included as a strictly proportional linear effect interacted with all effects except blinding. Probabilistic inferences were derived with reference to thresholds for small and moderate effects on performance of 0.5% and 1.5%, respectively. Publication bias was reduced by excluding study estimates with a standard error >2.7%. The remaining 38 studies and 137 estimates for sodium bicarbonate produced a possibly mod- erate performance enhancement of 1.7% (90% CL ± 2.0%) with a typical dose of 3.5mmoL/kg/BM (-0.3g/kgIBM) in a single 1-minute sprint, following blinded consumption by male athletes. In the 16 studies and 45 estimates for sodium citrate, a typical dose of l.SmmoL/kgIBM (-0.5gIkgJBM) had an unclear effect on performance of 0.0% (±1.3%), while the five studies and six estimates for ammonium chloride produced a possibly moderate impairment of 1.6% (±1.9%) with a typical dose of 5.5mmoL/kgIBM (-0.3glkg/BM). Study and subject characteristics had the following modifying small effects on the enhancement of performance with sodium bicarbonate: an increase of 0.5% (±0.6%) with a 1 mmoL/kg/BM increase in dose; an increase of 0.6% (±0.4%) with five extra sprint bouts; a reduction of 0.6% (±0.9%) for each 10-fold increase in test duration (e.g. 1-10 minutes); reductions of 1.1% (± 1 .1%) with nonathletes and 0.7% (±1.4%) with females. Unexplained variation in effects between research settings was typically ± 1.2%. The only noteworthy effects involving physiological variables were a small correlation between performance and pre-exercise increase in blood bicarbonate with sodium bi- carbonate ingestion, and a very large correlation between the increase in blood bicarbonate and time between sodium citrate ingestion and exercise. The approximate equal and opposite effects of sodium bicarbonate and am- monium chloride are consistent with direct performance effects of pH, but sodium citrate appears to have some additional metabolic inhibitory effect. Important future research includes studies of sodium citrate ingestion several hours before exercise and quantification of gastrointestinal symptoms with sodium bicarbonate and citrate. Although individual responses may vary, we recommend ingestion of 0.3-0.5 glkg/BM sodium bicarbonate to improve mean power by 1.7% (±2.0%) in high-intensity races of short duration. ABSTRACT FROM AUTHOR

Estudos hidroquímicos da água produzida de um determinado campo de petróleo da bacia potiguar

Waste generated during the exploration and production of oil, water stands out due to various factors including the volume generated, the salt content, the presence of oil and chemicals and the water associated with oil is called produced water. The chemical composition of water is complex and depends strongly on the field generator, because it was in contact with the geological formation for thousands of years. This work aims to characterize the hydrochemical water produced in different areas of a field located in the Potiguar Basin. We collected 27 samples from 06 zones (400, 600, 400/600, 400/450/500, 350/400, A) the producing field called S and measured 50 required parameter divided between physical and chemical parameters, cations and anions. In hydrochemical characterization was used as tools of reasons ionic calculations, diagrams and they hydrochemical classification diagram Piper and Stiff diagram and also the statistic that helped in the identification of signature patterns for each production area including the area that supplies water injected this field for secondary oil recovery. The ionic balance error was calculated to assess the quality of the results of the analysis that was considered good, because 89% of the samples were below 5% error. Hydrochemical diagrams classified the waters as sodium chloride, with the exception of samples from Area A, from the injection well, which were classified as sodium bicarbonate. Through descriptive analysis and discriminant analysis was possible to obtain a function that differs chemically production areas, this function had a good hit rate of classification was 85%

Effect of insulin-like growth factor-1 during in vitro oocyte maturation and in vitro culture of bovine embryos

Avaliaram-se o efeito do IGF-I na maturação in vitro (MIV) (experimento I) e no desenvolvimento embrionário (DE) (experimento II) de oócitos bovinos fecundados in vitro, quanto às taxas de clivagem (TC), de blastocistos (TB) e de eclosão (TE). Para MIV, complexos cumulus-oócitos imaturos foram cultivados em meio TCM-199 suplementado com HEPES, bicarbonato e piruvato de sódio, aditivos, soro fetal bovino (meio B-199) e gonadotrofinas 14U/ml de PMSG e 7U/ml de hCG). Para o desenvolvimento embrionário, os oócitos/zigotos foram cultivados em meio B-199 com células epiteliais do oviduto bovino em suspensão sob óleo de silicone. As condições de cultivo in vitro para ambos os experimentos seguiram os tratamentos: 1- meio B-199 + 200 ng/ml IGF-I; 2- B-199 + 100 ng/ml IGF-I; 3- B-199 + 50 ng/ml IGF-I; 4- B-199 + 10 ng/ml IGF-I; 5- B-199 + 0 ng/ml IGF-I. Todas as culturas foram realizadas a 38,5° C em atmosfera com 5% de CO2 e os dados foram analisados pelo teste do qui-quadrado. No experimento I, não houve diferença (P>0,05) entre os tratamentos quanto às TC, TB e TE, quando o meio de MIV foi suplementado com IGF-I. No experimento II, a adição de IGF-I ao meio de DE resultou em aumento na TC (P<0,05) mas não influenciou a TB e a TE. A adição de 200 ng/ml de IGF-I ao meio DE melhorou a TC (71,1%) quando comparada com a TC dos grupos de 100 ng/ml de IGF-I (57,6%) ou controle (56,7%), entretanto não houve diferença quando comparada com a dos grupos de 50 ng/ml (69,4%) ou 10 ng/ml (73,1%) de IGF-I. Não houve efeito benéfico na adição de 10 a 200 ng/ml de IGF-I nos meios de MIV e de DE com relação ao desenvolvimento de embriões produzidos a partir de oócitos maturados e fecundados in vitro.

Efeitos das fontes e níveis de sódio, cloro e potássio e da relação (Na + K)/Cl, sobre o desempenho e características do plasma sangüíneo de poedeiras comerciais

Dois experimentos foram realizados para estudar os efeitos da relação (Na + K)/Cl na dieta de poedeiras comerciais no final do ciclo de postura, pela adição de bicarbonato de sódio (NaHCO3), cloreto de sódio (NaCl), cloreto de potássio (KCl) e cloreto de amônia (NH4Cl), avaliando-se os parâmetros produtivos e características do plasma sangüíneo. O primeiro experimento envolveu cinco tratamentos: 0,30% de NaCl; 0,30% de NaCl + 0,95% de NaHCO3; 0,38% de KCl + 0,67% de NaHCO3; 0,38% de KCl + 1,62% de NaHCO3; e 0,38% de KCL + 2,56% de NaHCO3. A relação (Na + K)/Cl foi, respectivamente, 3,46; 4,46; 4,46; 5,46; e 6,46. O segundo experimento envolveu quatro tratamentos: 0,30% NaCl; 0,47% de NaHCO3 + 0,19 de NH4Cl; 1,17% NaHCO3 + 0,19% de NH4Cl; e 1,88% de NaHCO3 + 0,19% de NH4Cl. A relação (Na + K)/Cl foi 3,46; 4,46; 5,46; e 6,46, respectivamente. No primeiro experimento, o maior consumo alimentar foi observado nas aves alimentadas com dietas contendo 0,30% de NaCl. As aves que consumiram KCl apresentaram melhor conversão alimentar. Foi observado aumento no fósforo e pH do plasma sangüíneo. Aves que receberam dietas em que a relação (Na +K)/Cl foi de 5,46 apresentaram maiores níveis de fósforo no plasma sangüíneo. O aumento do pH no plasma sangüíneo foi observado em aves que receberam dietas com relações de (Na + K)/Cl de 4,46 e 6,46. No segundo experimento, o peso do ovo diminuiu com o aumento do NaHCO3 da dieta.

Fontes de Sódio e Relação Sódio: Cloro para Frangos de Corte

Foram utilizados 2.880 pintos de corte, para avaliar os efeitos de diferentes fontes de sódio (Na+) e relações sódio:cloro (Na+:Cl-) na ração. As aves receberam ração e água ad libtum. O delineamento experimental foi inteiramente casualizado, com quatro tratamentos e seis repetições. O ganho de peso, consumo de ração, conversão alimentar e mortalidade não foram influenciados (p>0,05) pela substituição da fonte tradicional de Na e pelas diferentes relações Na:Cl. A umidade da cama foi afetada pela fonte e níveis de Na na ração. Os resultados mostraram que pode-se utilizar o NaHCO3 como fonte parcial à exigência de Na para frangos de corte de 1 a 47 dias de idade.

Efeito de diferentes níveis de bicarbonato de sódio em dietas com bagaço de cana-de-açúcar auto-hidrolisado sobre a degradação in situ do milho e farelo de algodão

The objective of this work was to evaluate the buffering effect of sodium bicarbonate (NaHCO3), used in the levels of: 0, 0.7, 1.4 and 2.1% of dry matter, on the in situ degradation of corn and cottonseed meal. A diet with 60% autohidrolised sugar bagasse (BAH) and 40% of concentrate was used, plus urea, minerals and limestone. The rations was calculated to allow 300g of daily gain. After 20 days of adaptation to the treatment (levels of NaHCO3), 5g of each feed was incubated in the rumen of four bovines for 3, 6, 12, 24 and 48 hours, using naylon bag with size of 7,5 x 17,5 cm with pores of 36 micras. A randomized blocks design with four treatment (levels of NaHCO3) were used. The buffer affected the in situ dry matter degradation, whose means were 49.68; 63,10; 67,71; and 60,85% and 25.89; 30.88; 33.48 and; 31.02% for the corn and cottonseed meal, respectively. The level of 1.4% of NaHCO3 provided the highest value of degradability, which did not differ from the 0.7% and 2.1% levels, for the corn. The degradability of protein was not affected by the treatments.