Altered functional connectivity and network excitability in a model of cortical dysplasia.

Focal cortical dysplasias (FCDs) are malformations of cortical development that often result in medically refractory epilepsy, with a greater incidence in the pediatric population. The relationship between the disturbed cortical morphology and epileptogenic activity of FCDs remains unclear. We used the BCNU (carmustine 1-3-bis-chloroethyl-nitrosourea) animal model of cortical dysplasia to evaluate neuronal and laminar alterations and how these result in altered activity of intracortical networks in early life. We corroborated the previously reported morphological anomalies characteristic of the BCNU model, comprising slightly larger and rounder neurons and abnormal cortical lamination. Next, the neuronal activity of live cortical slices was evaluated through large field-of-view calcium imaging as well as the neuronal response to a stimulus that leads to cortical hyperexcitability (pilocarpine). Examination of the joint activity of neuronal calcium time series allowed us to identify intracortical communication patterns and their response to pilocarpine. The baseline power density distribution of neurons in the cortex of BCNU-treated animals was different from that of control animals, with the former showing no modulation after stimulus. Moreover, the intracortical communication pattern differed between the two groups, with cortexes from BCNU-treated animals displaying decreased inter-layer connectivity as compared to control animals. Our results indicate that the altered anatomical organization of the cortex of BCNU-treated rats translates into altered functional networks that respond abnormally to a hyperexcitable stimulus and highlight the role of network dysfunction in the pathophysiology of cortical dysplasia.

Home physical exercise improves functional mobility and quality of life in the elderly: A CONSORT-prospective, randomised controlled clinical trial.

AIMS: To test the hypothesis of a semi-supervised home physical exercise programme that is likely to improve the functional mobility and quality of life (QOL) of elderly in the community. METHODS: This trial included elderly adults (88% female) aged 60 years or older and who were sedentary and without cognitive decline. The participants were randomly assigned to an intervention group (IG, home physical exercise and sleep hygiene) and a control group (CG, sleep hygiene). The International Questionnaire on Physical Activity, mental state mini-exam, World Health Organization Quality of Life Instrument-Older Adults Module (WHOQOL-OLD) and the Timed Up and Go (TUG) tests were conducted before and after the 12-week intervention period. RESULTS: The study was concluded with 125 elderly participants. Anthropometric data were indicative of pre-obesity, with a mean body mass index of 27.3 ± 4, a low-income socio-economic profile (78% ≤ 2 SM) and low schooling rates (76% ≤ 3 years of study). Most of the elderly (87%) were considered physically active with IPAQ > 150 min/week. The group of elderly people who performed the home physical exercise programme showed a significant improvement in functional mobility according to the time of execution of the TUG test before (9.1 ± 2) and after (7.1 ± 1) with an average reduction of 2 ± 1 s (P < .01). The difference in the QOL of the elderly who participated in the exercise protocol was also observed, verified through the WHOQOL-OLD global score, which presented an initial score of 85 ± 10, changing to 90.4 ± 9 after the intervention. CONCLUSION: Semi-supervised physical home exercise is safe and effective in improving the functional mobility and QOL of sedentary elderly people in the community.

A novel application of microwave-assisted extraction of polyphenols from brewer's spent grain with HPLC-DAD-MS analysis.

This paper reports a novel application of microwave-assisted extraction (MAE) of polyphenols from brewer's spent grains (BSG). A 2(4) orthogonal composite design was used to obtain the optimal conditions of MAE. The influence of the MAE operational parameters (extraction time, temperature, solvent volume and stirring speed) on the extraction yield of ferulic acid was investigated through response surface methodology. The results showed that the optimal conditions were 15 min extraction time, 100 °C extraction temperature, 20 mL of solvent, and maximum stirring speed. Under these conditions, the yield of ferulic acid was 1.31 ± 0.04% (w/w), which was fivefold higher than that obtained with conventional solid-liquid extraction techniques. The developed new extraction method considerably reduces extraction time, energy and solvent consumption, while generating fewer wastes. HPLC-DAD-MS analysis indicated that other hydroxycinnamic acids and several ferulic acid dehydrodimers, as well as one dehydrotrimer were also present, confirming that BSG is a valuable source of antioxidant compounds.

Analysis of cardamonin by square wave voltammetry.

INTRODUCTION: Several biochemical studies have already shown that cardamonin has health promoting properties, such is in agreement with typical characteristics of chalcones. Although being a very promising compound for the nutraceutical field there is a lack of studies concerning its electroanalytical properties. OBJECTIVE: To develop an electroanalytical methodology for the quantification of cardamonin in cardamom. METHODOLOGY: Cardamonin was analysed electrochemically by means of a hanging mercury drop electrode (HMDE) using square wave voltammetry (SWV). It was extracted from cardamom spice and quantified thereafter using the standard additions method to overcome matrix effects. RESULTS: A limit of detection (LOD) of 0.15 mg/L and good linearity (r² = 0.9998) were obtained. Decoction using ethanol as the extraction solvent appears to be the simplest extraction technique. Spectrophotometric analysis (maximum absorbance peak was found in ethanol at 344 nm with a value of molar extinction coefficient of (2.8 ± 0.1) × 104 L mol⁻¹ cm⁻¹) and mass spectrometry analysis by electrospray in the positive ion mode were also performed. CONCLUSION: Cardamonin was detected voltammetrically. The LOD and limit of quantification (LOQ) of the proposed voltammetric methodology are adequate for trace analysis of this compound in several phytochemical matrices.

Application of gas-diffusion microextraction to the analysis of free and bound acetaldehyde in wines by HPLC-UV and characterization of the extracted compounds by MS/MS detection.

In wines, the presence of high levels of acetaldehyde (AA) not only is responsible for undesirable characteristic odours but can also cause health adverse effects. Such sensorial activity of AA can be overcome by adding sulphites during winemaking, due to the formation of adducts between AA and sulphites, which lower the sensorial impact of AA. Nevertheless, bound AA can be released during wine storage; therefore, the knowledge of its total amount can be important to estimate the long-term wine quality. The proposed methodology is based on the extraction of AA from wines using gas-diffusion microextraction and determination by liquid chromatography. Free and bound forms of AA could be differentiated and determined using an alkaline hydrolysis step to dissociate the sulphites-AA adducts. This methodology was successfully applied to different wine types, with free AA values ranging between 5 and 26 mg L(-1) and total form between 154 and 906 mg L(-1). Bound AA was above 90% of the total content determined for all samples analysed, and higher amounts were obtained for white wines (around 98%). Other carbonyl compounds were also identified in the extracts using mass spectrometry.

Increased sensitivity of anodic stripping voltammetry at the hanging mercury drop electrode by ultracathodic deposition.

An improved approach to the anodic stripping voltammetric (ASV) determination of heavy metals, using the hanging mercury drop electrode (HMDE), is reported. It was discovered that using very cathodic accumulation potentials, at which the solvent reduction occurs (overpotential deposition), the voltammetric signals of zinc(II), cadmium(II), lead(II) and copper(II) increase. When compared with the classical methodology a 5 to 10-fold signal increase is obtained. This effect is likely due to both mercury drop oscillation at such cathodic potentials and added local convection at the mercury drop surface caused by the evolution of hydrogen bubbles.

Novel application of square-wave adsorptive-stripping voltammetry for the determination of xanthohumol in spent hops.

This paper reports the development of a novel electrochemical assay for xanthohumol (XN) by square-wave adsorptive-stripping voltammetry (SWAdSV) with a hanging mercury drop electrode. The method showed good repeatability (CV < 2%) and linearity (between 10 and 250 µg L(-1)), as well as suitable limits of detection (2.6 µg L(-1)) and quantification (8.8 µg L(-1)). The method was applied for the quantification of this compound in spent hops, and the results obtained were compared with the HPLC-UV method. XN contents determined by the SWAdSV method were 16 ± 1 and 100 ± 4 µg L(-1) for aqueous and methanolic extracts, respectively. The developed new methodology considerably reduces the analysis time, approximately from 25 min (HPLC-UV method) to 7 min, enabling a high sample throughput. In addition, the detection and quantification limits were approximately 5-fold lower than those obtained with the chromatographic method.

Controlling voltammetric responses by electrode modification; using adsorbed acetone to switch graphite surfaces between adsorptive and diffusive modes.

Graphite is a highly versatile electrode substrate material but the recorded voltammetric response is regularly complicated by varying degrees of adsorption of the analyte to the surface leading to voltammetry which is complex to analyse. We report how through the pre-adsorption of acetone the electro-activity of the substrate is unhindered but adsorption of an electro-active species is effectively blocked, hence the experimentalist is able to readily tailor the electrode so as to effectively switch the adsorption of the analyte 'on' or 'off'.

Isolation of phenolic compounds from hop extracts using polyvinylpolypyrrolidone: characterization by high-performance liquid chromatography-diode array detection-electrospray tandem mass spectrometry.

The aim of the present work was the development of a suitable methodology for the separation and determination of phenolic compounds in the hop plant. The developed methodology was based on the sample purification by adsorption of phenolic compounds from the matrix to polyvinylpolypyrrolidone (PVPP) and subsequent desorption of the adsorbed polyphenols with acetone/water (70:30, v/v). At last, the extract was analyzed by HPLC-DAD and HPLC-ESI-MS/MS. The first phase of this work consisted of the study of the adsorption behavior of several classes of phenolic compounds (e.g. phenolic acids, flavonols, and flavanols) by PVPP in model solutions. It has been observed that the process of adsorption of the different phenolic compounds to PVPP (at low concentrations) is differentiated, depending on the structure of the compound (number of OH groups, aromatic rings, and stereochemistry hindrance). For example, within the phenolic acids class (benzoic, p-hydroxybenzoic, protocatechuic and gallic acids) the PVPP adsorption increases with the number of OH groups of the phenolic compound. On the other hand, the derivatization of OH groups (methylation and glycosylation) resulted in a greatly diminished binding. The use of PVPP revealed to be very efficient for adsorption of several phenolic compounds such as catechin, epicatechin, xanthohumol and quercetin, since high adsorption and recovery values were obtained. The methodology was further applied for the extraction and isolation of phenolic compounds from hops. With this methodology, it was possible to obtain high adsorption values (>or=80%) and recovery yield values (>or=70%) for the most important phenolic compounds from hops such as xanthohumol, catechin, epicatechin, quercetin and kaempferol glycosides, and in addition it allows the identification of about 30 phenolic compounds by HPLC-DAD and HPLC-ESI-MS/MS.

Fundamentals and health benefits of xanthohumol, a natural product derived from hops and beer.

In recent years, there has been a growing interest in phenolic compounds and their presumed role in the prevention of various degenerative diseases, such as cancer and cardiovascular diseases. Xanthohumol, a prenylated chalcone from hops and beer, is among the phenolic compounds which have received the most attention in recent years. This compound has a range of interesting biological properties that may have therapeutic utility. Based on the health-promoting properties of xanthohumol, the production of a beer enriched in this substance would be of huge interest to the brewing industry, for the benefits this could bring to consumer's health. This paper reviews recent and important data with respect to the health benefits or biological activities of xanthohumol and beer. In addition, an overview of the chemistry and biotechnological aspects of xanthohumol is presented.

[Alpha-1 antitrypsin deficiency: diagnosis and treatment]. / Deficiência de alfa-1 antitripsina: diagnóstico e tratamento.

Alpha-1 antitrypsin deficiency is a recently identified genetic disease that occurs almost as frequently as cystic fibrosis. It is caused by various mutations in the SERPINA1 gene, and has numerous clinical implications. Alpha-1 antitrypsin is mainly produced in the liver and acts as an antiprotease. Its principal function is to inactivate neutrophil elastase, preventing tissue damage. The mutation most commonly associated with the clinical disease is the Z allele, which causes polymerization and accumulation within hepatocytes. The accumulation of and the consequent reduction in the serum levels of alpha-1 antitrypsin cause, respectively, liver and lung disease, the latter occurring mainly as early emphysema, predominantly in the lung bases. Diagnosis involves detection of low serum levels of alpha-1 antitrypsin as well as phenotypic confirmation. In addition to the standard treatment of chronic obstructive pulmonary disease, specific therapy consisting of infusion of purified alpha-1 antitrypsin is currently available. The clinical efficacy of this therapy, which appears to be safe, has yet to be definitively established, and its cost-effectiveness is also a controversial issue that is rarely addressed. Despite its importance, in Brazil, there are no epidemiological data on the prevalence of the disease or the frequency of occurrence of deficiency alleles. Underdiagnosis has also been a significant limitation to the study of the disease as well as to appropriate treatment of patients. It is hoped that the creation of the Alpha One International Registry will resolve these and other important issues.

Deficiência de alfa-1 antitripsina: diagnóstico e tratamento / Alpha-1 antitrypsin deficiency: diagnosis and treatment

A deficiência de alfa-1 antitripsina é um distúrbio genético de descoberta recente e que ocorre com freqüência comparável à da fibrose cística. Resulta de diferentes mutações no gene SERPINA1 e tem diversas implicações clínicas. A alfa-1 antitripsina é produzida principalmente no fígado e atua como uma antiprotease. Tem como principal função inativar a elastase neutrofílica, impedindo a ocorrência de dano tecidual. A mutação mais freqüentemente relacionada à doença clínica é o alelo Z, que determina polimerização e acúmulo dentro dos hepatócitos. O acúmulo e a conseqüente redução dos níveis séricos de alfa-1 antitripsina determinam, respectivamente, doença hepática e pulmonar, sendo que esta se manifesta principalmente sob a forma de enfisema de aparecimento precoce, habitualmente com predomínio basal. O diagnóstico envolve a detecção de níveis séricos reduzidos de alfa-1 antitripsina e a confirmação fenotípica. Além do tratamento usual para doença pulmonar obstrutiva crônica, existe atualmente uma terapia específica com infusão de concentrados de alfa-1 antitripsina. Essa terapia de reposição, aparentemente segura, ainda não teve a eficácia clínica definitivamente comprovada, e o custo-efetividade também é um tema controverso e ainda pouco abordado. Apesar da sua importância, não existem dados epidemiológicos brasileiros a respeito da prevalência da doença ou da freqüência de ocorrência dos alelos deficientes. O subdiagnóstico também tem sido uma importante limitação tanto para o estudo da doença quanto para o tratamento adequado dos pacientes. Espera-se que a criação do Registro Internacional de Alfa-1 venha a resolver essas e outras importantes questões.

Alpha-1 antitrypsin deficiency is a recently identified genetic disease that occurs almost as frequently as cystic fibrosis. It is caused by various mutations in the SERPINA1 gene, and has numerous clinical implications. Alpha-1 antitrypsin is mainly produced in the liver and acts as an antiprotease. Its principal function is to inactivate neutrophil elastase, preventing tissue damage. The mutation most commonly associated with the clinical disease is the Z allele, which causes polymerization and accumulation within hepatocytes. The accumulation of and the consequent reduction in the serum levels of alpha-1 antitrypsin cause, respectively, liver and lung disease, the latter occurring mainly as early emphysema, predominantly in the lung bases. Diagnosis involves detection of low serum levels of alpha-1 antitrypsin as well as phenotypic confirmation. In addition to the standard treatment of chronic obstructive pulmonary disease, specific therapy consisting of infusion of purified alpha-1 antitrypsin is currently available. The clinical efficacy of this therapy, which appears to be safe, has yet to be definitively established, and its cost-effectiveness is also a controversial issue that is rarely addressed. Despite its importance, in Brazil, there are no epidemiological data on the prevalence of the disease or the frequency of occurrence of deficiency alleles. Underdiagnosis has also been a significant limitation to the study of the disease as well as to appropriate treatment of patients. It is hoped that the creation of the Alpha One International Registry will resolve these and other important issues.

Characterization of monomeric and oligomeric flavan-3-ols from barley and malt by liquid chromatography-ultraviolet detection-electrospray ionization mass spectrometry.

The pattern of the monomeric and oligomeric flavan-3-ols for 10 barley varieties and the corresponding malts were identified and quantified using high-performance liquid chromatography-ultraviolet detection-electrospray ion trap mass spectrometry. The Folin-Ciocalteau and the vanillin spectrophotometric assays were used for the assessment of the total polyphenol and total flavan-3-ol content, respectively, and the antioxidant activity was determined as the 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity and the ferricyanide reducing power. Catechin and prodelphinidin B3 were respectively the major monomeric and dimeric flavan-3-ols. Moreover, prodelphinidin B3 was shown to be the main contributor for the radical scavenging activity both for barley and malt.

Detection and quantification of provitamin D2 and vitamin D2 in hop (Humulus lupulus L.) by liquid chromatography-diode array detection-electrospray ionization tandem mass spectrometry.

In this work, ergosterol and ergocalciferol were identified for the first time in hop. In addition, in this article, a simple and reliable analytical methodology for analysis of these compounds in different commercial forms of hop is presented. The performance of the method was assessed by the evaluation of parameters such as absolute recovery (higher than 70%), repeatability (lower than 3 %), linearity ( r(2) > 0.9988) and limits of detection (ranging from 0.034 for ergocalciferol to 0.058 mg/L for ergosterol) and quantification (ranging from 0.113 for ergocalciferol to 0.195 mg/L for ergosterol). On the basis of standard additions applied with the optimized procedure and high-performance liquid chromatography with diode array detection, it appears that the Nugget hop plant (crop 2006) contains 1.84 +/- 0.09 microg/g of ergosterol and 1.95 +/- 0.05 microg/g of ergocalciferol. The identity of the compounds was confirmed by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry in the positive ion mode. The presence of ergosterol here reported should have great potential for the assessment of hop as related to the fungal contamination proportion and hence the quality of this raw material.

Correlation of malt quality parameters and beer flavor stability: multivariate analysis.

Malt is known to have an impact on beer flavor stability mainly due to the presence of antioxidants. In this study, five barley varieties were malted at industrial and micro scale, and quality parameters of the resulting malts were measured (diastatic power, friability, beta-glucan content, antiradical power, reducing power, lipoxygenase activity, and nonenal potential) and correlated with the sensory data obtained for the corresponding fresh and forced aged beers. A statistical strategy using multiple linear regressions was applied to explore relationships between the malt chemical parameters and beer sensory data, showing antiradical power as the major contribution of malt to beer flavor stability. Additionally, the measured antiradical power, which is well correlated with the polyphenolic content, was found to be very similar for malt and barley, emphasizing the key role of barley endogenous polyphenols.

Analysis of xanthohumol and isoxanthohumol in different hop products by liquid chromatography-diode array detection-electrospray ionization tandem mass spectrometry.

An analytical methodology based on the sample extraction with methanol/formic acid by ultra-sonication and subsequent analysis by high-performance liquid chromatography with diode array detection is proposed for the determination of xanthohumol (XN) and isoxanthohumol (IXN) in different hop products. The identity of the compounds was confirmed by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry in positive ion mode. The performance of the method was assessed by the evaluation of parameters such as absolute recovery, repeatability, linearity and limits of detection and quantitation. This methodology was applied to investigate the impact of the extraction process of the hop products on the amount of xanthohumol and isoxanthohumol. The ethanolic extract revealed to be the hop product richest in xanthohumol (3.75+/-0.05 g/100 g) relatively to the pellets (0.62+/-0.01 g/100 g) and supercritical CO2 extract (0.089+/-0.001 g/100 g).

Electroanalytical determination of paroxetine in pharmaceuticals.

Electroanalytical methods based on square-wave adsorptive-stripping voltammetry (SWAdSV) and flow-injection analysis with SWAdSV detection (FIA-SWAdSV) were developed for the determination of paroxetine (PRX). The methods were based on the reduction of PRX at a mercury drop electrode at -1.55V versus Ag/AgCl, in a borate buffer of pH 8.8, and the possibility of accumulating the compound at the electrode surface. Because the presence of dissolved oxygen did not interfere significantly with the analysis, it was also possible to determine PRX using FIA-SWAdSV. This method enables analysis of up to 120 samples per hour at reduced costs. Both methods developed were validated and successfully applied to the quantification of PRX in pharmaceutical products.

Electroanalytical study of the antidepressant sertraline.

A flow injection square wave cathodic stripping voltammetric method has been developed for the determination of sertraline in a pharmaceutical preparation. The method shows linearity between peak current intensity and sertraline concentration for the interval between 0.20 x 10(-6) and 1.20 x 10(-6) mol L(-1). Limits of detection and quantification were found to be 1.5 x 10(-7) and 5.0 x 10 (-7) mol L(-1), respectively. Up to 70 samples per hour can be analysed with a good precision (R.S.D. = 2.5%). The proposed method was successfully applied to the determination of sertraline in a commercial product. In the voltammetric determination of sertraline in flow, a high sample rate is obtained at reduced costs, opening the possibility to compete with the chromatographic methods generally used for this analysis.

Electroanalytical study of fluvoxamine.

Fluvoxamine (FVX) can be reduced at a mercury-drop electrode, with a maximum peak current intensity being obtained at a potential of -0.7 V vs. Ag/AgCl, in an aqueous electrolyte solution of pH 2. The compound was determined in a pharmaceutical product and in spiked human serum by square-wave adsorptive-stripping voltammetry (SWAdSV) after accumulation at the electrode surface, under batch conditions. Because the presence of dissolved oxygen did not interfere significantly with the analysis, it was also possible to determine FVX in the pharmaceutical product by use of a flow-injection analysis (FIA) system with SWAdSV detection. The methods developed were validated and successfully applied to the quantification of FVX in a pharmaceutical product. Recoveries between 76 and 89% were obtained in serum analysis. The FIA-SWAdSV method enabled analysis of up to 120 samples per hour at reduced cost, implying the possibility of competing with the chromatographic methods usually used for this analysis.

Automatic flow system with voltammetric detection for diacetyl monitoring during brewing process.

Diacetyl can be determined by adsorptive stripping voltammetry after derivatization with o-phenylenediamine. The method may be applicable to the determination of diacetyl in different foods, being a good alternative to other analytical methods. In this work an on-line automated analytical system for diacetyl determination in beer is described. A hanging mercury drop electrode voltammetric flow detector was used, and the analyte was determined without the traditional deoxygenation procedure. The method was successfully applied to the determination of diacetyl during beer fermentation and in the final product. The automation strategy used was based on a flow network similar to those used in multicommutated flow systems, with a pervaporation unit used for diacetyl separation. The developed system was tested in real conditions in the monitoring of brewing processes. The results obtained were similar to those obtained with the usual GC-ECD methodology in the 5-600 ppb range. The analytical rate of the developed method is about 12 determinations/h.