Implication of AMPK in glucose-evoked modulation of Na,K-ATPase

Background and aims: Na,K-ATPase is an integral membrane protein that maintains the gradients of Na+ and K+, using the energy of ATP hydrolysis, maintaining the ionic gradients that allow electrical activity to occur. It has been demonstrated that, in pancreatic β-cells, Na,K-ATPase is regulated by glucose and that this phenomenon is impaired in glucose intolerant subjects. However, the mechanism underlying glucose-induced modulation of Na,K-ATPase is still unclear. The AMP-activated protein kinase (AMPK) is a molecular key player in energy homeostasis, providing exquisite sensitivity to small changes in intracellular AMP levels and thus to intracellular [ATP]/[ADP] ratio, that is known to activate protein regulatory pathways. Since in pancreatic β-cell, glucose has marked effects on oxidative metabolism and total intracellular ATP and AMP levels, the involvement of AMPK in the cascade of events regulating Na,K-ATPase regulation in pancreatic β-cells was postulated. The aim of this work was to evaluate the putative role of AMPK in the glucose-evoked regulation of Na,K-ATPase activity in the pancreatic β-cell. Materials and methods: Pancreatic -cells from normal (control) or glucose-intolerant Wistar rats (GIR) were isolated and cultured (48h). Cell batches were pre-incubated (30min) with 2.1mM glucose to reach basal activity. Afterwards cells were challenged to 8.4mM glucose for 20min, in the presence or absence of AMPK agonists (AICAR) and antagonists (compound C; CC). ATPase activity was assessed in intact cells by colorimetric quantification of Pi formed in 30min. Na,K-ATPase activity was calculated by the difference between the activities obtained in the absence and in presence the of 1mM ouabain. Results: In basal conditions the activity of Na,K-ATPase from normal and GIR pancreatic β-cell was similar (0.184±0.030 and 0.186±0.020 molPi/min/mgProt, respectively). Challenging the control β-cells with glucose 8.4mM evoked a 62% reduction of Na,K-ATPase activity whereas in GIR β-cells a significantly lower inhibition (40%) was observed. The addition of AICAR 1mM abolished glucose-induced Na,K-ATPase inhibition (0,166±0.011 molPi/min/mg). In control β-cell, the addition of CC 10 μM had no effect on glucose-induced inhibition of Na,K-ATPase. In the contrary, in GIR β-cells it significantly potentiated glucose-evoked inhibition of Na,K-ATPase reaching values similar to that observed in the controls (66%). Conclusions: The AMPK agonist AICAR counteracts the inhibitory action of glucose on Na,K-ATPase of control β-cells whereas CC amplified the glucose-induced inhibition of Na,K-ATPase in GIR β-cells. These results suggest that AMPK plays a central role in the cascade of events underlying glucose-induced modulation of Na,K-ATPase and that the defect must be upstream of AMPK. Finally, abnormal glucose-induced regulation of Na,K-ATPase occurs prior to overt type 2 diabetes and might be a feature in the disease development

Abnormal regulation of Na,K-ATPase in Glucose Intolerant Rats.

Introduction: Glucose is the most important physiological insulin secretagogue. However, the mechanisms underlying glucose-induced insulin release are not fully understood. The role of electrogenic systems such as ionic pumps, to these events remains essentially uninvestigated. Na,K-ATPase, responsible for maintaining Na+ and K+ gradients across the plasma membrane and generates a net outward current, thus changes in its activity may contribute to the early ionic events regulating insulin secretion (Therien and Blostein, 2000). Objective: The aim of this work was to evaluate the regulation of Na,K-ATPase activity by glucose in intact -cells of normal and glucose intolerant (GI) rats and its putative contribution to the regulation of insulin secretion. Material and Methods: Pancreatic -cells, from normal or control or GI rats, were isolated and cultured (48h). Cell batches were pre-incubated (30min) with 2mM glucose to reach basal. Afterwards cells were challenged with glucose in the interval 0-11mM for 60min, for dose-dependence evaluation, or with 8mM glucose for 5-120min, for time-dependence evaluation. ATPase activity was assessed in intact cells by colorimetric quantification of Pi formed in 30min. Na,K-ATPase activity was calculated by the difference between the activities obtained in the absence and in presence the of 1mM ouabain (Costa et al., 2009). Results: In β-cells from normal rats, glucose induced a bimodal regulation of Na,K-ATPase. In the absence of glucose, Na,K-ATPase activity was 0.056±0.015 U/mg. Stimulation with 2mM glucose induced an increase of Na,K-ATPase activity of ~4 fold whereas for [glucose] above 2mM it was observed a significant inhibition of Na,K-ATPase activity (0.061±0.013, 0.080±0.009 and 0.064±0.005 U/mg for 5.6, 8.4 and 11mM glucose, respectively, compared to 0.188±0.035 U/mg observed in 2mM G; n=3-8). β-cells from GI rats does not present this profile; in the absence of glucose, Na,K-ATPase activity was 0.202±0.036 U/mg and no significant differences from this value were observed with the other glucose concentration tested. Addicionally, in β-cells from normal rats, glucose (8mM) induced a time-dependent inhibition, with a biphasic profile, of Na,K-ATPase - it was observed a decrease in the pump activity between 0 and 20min stimulation where it reached a minimum value (77%). For incubation periods over 20min, the pump activity slowly and partially recovered (54%, 55% and 52%, for 30, 60 and 120min, respectively; n=7). In β-cells from GI animals, an less accentuated decrease of Na,K-ATPase activity between 0 ans 20min was also observed (34%), and is not observed further recover in activity. Conclusions: This work demonstrates there Na,K-ATPase is strictly regulated by glucose in pancreatic β-cell. This regulation is unpaired in GI animals. Na,K-ATPase contribution to glucose-induced ionic events and insulin secretion might be relevant and must be explored as a possible therapeutic target in TD2 . 1. Therien AG, Blostein R (2000) Mechanisms of sodium pump regulation. Am J Physiol Cell Physiol 279:C541-C566 2. Costa AR, Real J, Antunes CM, Cruz-Morais J (2009) A new approach for determination of Na,K-ATPase activity: application to intact pancreatic beta-cells. In Vitro Cell Dev Biol Ani

The Relevance of Digital Infographics in Online Newspapers

In the more developed societies online newspapers have already reached a very high degree of notoriety. The newspaper, besides being a product of the journalistic domain, is also the product of the visual domain. Due to the incorporation of new technologies and of different visual trends, substantial changes in consolidated models of newspaper design have been seen that originated a growth in the importance of the image that the newspaper has in the web. It was from this context that emerged the research described in this article. An analysis of the technique used in a specific aspect of the essential graphics in this model of communication: infographics, was carried out. To that purpose, a study of infographics in web journalism was performed, in order to determine its essencial elements

A propósito del género Paralcamenes Bolívar 1909 (Orth. Acridoidea)

En el año 1909 describió D. Ignacio Bolívar el género Paralcamenes, con P. camposi nov. sp. como genotipo, sobre un ejemplar macho procedente de Posorja, Ecuador, que le comunicara su colector el Profesor Francisco Campos. Tiempo después, Hebard (1924-25), describe Colpolopha camposi nov. sp. sobre una hembra de igual localidad que el insecto nominado por Bolívar y que le fuera enviado también por el precitado entomólogo ecuatoriano.Peer reviewe

STOCK-FLOW CONSISTENT (SFC) AS A SUITABLE APPROACH TO MODELING THE NEW DEVELOPMENTALIST FRAMEWORK

This paper explores the theoretical bases of New Developmentalism, highlighting its core propositions. Evaluates the first effort of mathematical proposition of a New Developmentalist prototype model. It explores how the integration of the current model with a version using the Stock-Flow Consistent approach would look like and how this methodology could help to solve some gaps left behind. Finally, a projection for a new research agenda using sectoral and microeconomic details is pointed out as a possible work front.This paper explores the theoretical bases of New Developmentalism, highlighting its core propositions. Evaluates the first effort of mathematical proposition of a New Developmentalist prototype model. It explores how the integration of the current model with a version using the Stock-Flow Consistent approach would look like and how this methodology could help to solve some gaps left behind. Finally, a projection for a new research agenda using sectoral and microeconomic details is pointed out as a possible work front

The effect of musical practice on speech recognition in quiet and noisy situations

BACKGROUND: auditory training improves the perception of complex acoustic signals as well as the perception of speech. AIM: to verify if auditory training, through the practice of music, has an influence on the ability to recognize speech in quiet and noisy situations. METHOD: participants of this study were 55 individuals, with no musical experience (non-musicians) and 45 professional musicians who had been playing at military bands for at least 5 years (musicians). All of the participants were male right-handed military volunteers, with normal hearing thresholds and with ages varying between 25 and 40 years. Using the Portuguese Sentence Lists (LSP) test, sentence recognition threshold was investigated in quiet (SRTQ) and in noise (SRTN). Based on the obtained data, the signal/noise ratio (S/N) was calculated. The sentences and noise (fixed to 65 dB HL) had a monoaural presentation using headphones. RESULTS: when comparing the performances of both groups, the statistical analysis pointed no significant difference between the mean values obtained for the SRTQ. However, a statistically significant difference was verified between the mean values obtained for the S/N ratio. CONCLUSION: in a quiet situation, musicians and non-musicians had similar performances. However, in the noise situation, musicians presented better performances, indicating that musical practice is an activity that improves the ability of speech recognition when in a noisy environment.TEMA: o treinamento auditivo melhora a percepção de sinais acústicos complexos como a fala. OBJETIVO: verificar se o treinamento auditivo proporcionado pela prática musical é um fator que exerce influência na habilidade de reconhecer a fala no silêncio e no ruído. MÉTODO: participaram do estudo 55 indivíduos sem experiência musical (não músicos) e 45 indivíduos que atuavam como músicos profissionais em bandas militares há, no mínimo, 5 anos (músicos). Todos os voluntários eram militares, do sexo masculino, destros, normo-ouvintes e com idades variando entre 25 e 40 anos. Utilizando o teste Listas de Sentenças em Português (LSP), realizou-se a pesquisa do limiar de reconhecimento de sentenças no silêncio (LRSS) e do limiar de reconhecimento de sentenças no ruído (LRSR), a partir do qual foi calculada a relação sinal/ruído (S/R). As sentenças e o ruído (fixo a 65 dB NA) foram apresentados monoauralmente, por fones auriculares. RESULTADOS: ao serem comparados os desempenhos dos grupos estudados, a análise estatística dos resultados não evidenciou diferença significante entre os valores médios obtidos para os LRSS. No entanto, foi constatada diferença estatisticamente significante entre os valores médios obtidos para as relações S/R. CONCLUSÃO: no silêncio, músicos e não músicos apresentaram desempenhos semelhantes, porém, em tarefas de reconhecimento de sentenças apresentadas diante de ruído competitivo, músicos apresentaram melhores desempenhos, indicando que a prática musical é uma atividade que melhora a habilidade de reconhecimento da fala, quando esta ocorre diante de ruído.Universidade Federal de Santa MariaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUniversidade Federal de Santa Maria Departamento de Otorrino-FonoaudiologiaUNIFESP, EPMSciEL

Effects of Mitomycin C in Early Conjunctival Inflammation after Pterygium Surgery

Purpose: The purpose of this study was to compare inflammatory events and graft characteristics 1 month and 6 months after conjunctival limbal autograft (CLAU) with and without intraoperative mitomycin C (MMC). Methods: This study included 69 eyes of 69 patient’s eyes with pterygium. Clinical data concerning patient demography, preoperative examination including pterygium morphology, recurrence clinical assessment, and complications after CLAU with (MMC+) and without (MMC-) intraoperative MMC were all registered at 1 month and 6 months after surgery. Results: Thirty-five eyes were included in MMC+ and 34 in MMC-. Preoperative data were similar in both groups (Student’s t test and Fisher’s exact test; p > 0.05). Thirty-four (49.6%) eyes in the whole sample showed at least one inflammatory complication at 1 month after surgery. MMC- group showed a significantly higher number of cases with complications (p 0.05; Chi2 test). Pyogenic granuloma developed at the surgical site in three eyes (4.37%), two of those granulomas were at the MMC- group (p > 0.05). Tendency for recurrences was significantly different between both groups (p = 0.0001; Fisher’s exact test) at the end of 6 months. Thirteen (38%) eyes showed recurrence in MMC- and no cases were displayed in MMC+. Presence of at least 1 inflammatory event was only seen in 16 (23%) cases, all of them in MMC-. Specifically, 15 (44%) eyes showed hyperemia and one (3%) eye presented conjunctival hemorrhages. No new cases of pyogenic granuloma or graft contraction were seen at this time point in both groups. Hyperemia was the only specific event with significant differences between MMC- and MMC+ (p = 0.0001; Fisher’s exact test) at 6 months after surgery. Conclusion: The eyes receiving intraoperative MMC after CLAU seem to present less hyperemia and graft contraction after surgery than those that did not receive MMC as an adjuvant factor. Intraoperative MMC could be associated with a lower recurrence rates.Postprint (author's final draft

Advanced Control for Energy Management of Grid-Connected Hybrid Power Systems in the Sugar Cane Industry

This work presents a process supervision and advanced control structure, based on Model Predictive Control (MPC) coupled with disturbance estimation techniques and a finite-state machine decision system, responsible for setting energy productions set-points. This control scheme is applied to energy generation optimization in a sugar cane power plant, with non-dispatchable renewable sources, such as photovoltaic and wind power generation, as well as dispatchable sources, as biomass. The energy plant is bound to produce steam in different pressures, cold water and, imperiously, has to produce and maintain an amount of electric power throughout each month, defined by contract rules with a local distribution network operator (DNO). The proposed predictive control structure uses feedforward compensation of estimated future disturbances, obtained by the Double Exponential Smoothing (DES) method. The control algorithm has the task of performing the management of which energy system to use, maximize the use of the renewable energy sources, manage the use of energy storage units and optimize energy generation due to contract rules, while aiming to maximize economic profits. Through simulation, the proposed system is compared to a MPC structure, with standard techniques, and shows improved behavior.Ministerio de Economía y Competitividad CNPq401126/2014-5Ministerio de Economía y Competitividad CNPq303702/2011-7Ministerio de Economía y Competitividad DPI2016-78338-

Chemical composition and anti-diabetic properties of Cytisus multiflorus

Bakground and aims: The interest on plants with potential medicinal properties has been increasing worldwide. In the Iberian Peninsula there are some endemic species known by the population for their pharmacologic activity with valorization potential that have not been yet characterized. The white Spanish broom (Cytisus multiflorus) is described as having anti-diabetic effect [1] and in a preliminary the hypoglycemic and hyper-insulinemic effect of an aqueous extract has been shown [2]. The aim of this work was to fractionate and analyse the composition of the aqueous extract of C. multiflorus flowering parts and evaluate its potential as an anti-diabetic agent. Materials and methods: The aqueous extract was primarily fractionated by SPE using water:methanol (W:Me) eluent (a 10% step-wise gradient W:Me from 100:0 to 0:100) followed by high performance liquid chromatography with diode array detector (HPLC-DAD). The most relevant fraction were analysed by LC-MS to determine the chemical composition. Total fenol content was determined by a modified Folin-Ciocalteau method and the anti-oxidant activity was evaluated by the DPPH mehod. Finally, the hipoglicemic potential was evaluated in vivo using glucose intolerant rats (GIR). Results: Eleven fractions of the bulk extract were obtained. Seven of these fractions (10, 30, 40, 50, 60, 70 e 80% Me) were found to have a relevant compounds, mostly flavonoid compounds, namely, rutin (50, 60 and 70% Me fractions), ferrulic acid (30% Me), referred as having hypoglicemic effect. The fractions obtained with 50 and 70% Me showed the highest content in phenol equivalents and the highest anti-oxidant effect were found in the 50 and 60% Me fractions. The 30 and 60% Me fraction had no effect on the post-prandial glicemia. Conclusions: The 30, 50, 60 and 70% Me fractions, due to their chemical composition and anti-oxidant effects were the most promising to have anti-diabetic effect. However, the 30 and 60% Me were found to be ineffective. The 50% Me fraction showed both a high content of flavonoid compounds and the highest anti-oxidant power which suggest that it may constitute the most promising one. The anti-diabetic properties of this fraction should be investigated. [1] Camejo-Rodrigues J. et al. (2003). J. Ethnopharmacol, 89, 199-209 [2] Célia M. Antunes, Laurinda R. Areias, Inês P. Vieira, Ana C. Costa, M. Teresa Tinoco, & Júlio Cruz-Morais (2009). Rev. Fitoterapia 9 (Supl.1): 91

Recognition of speech in noise and relations with suppression of otoacoustic emissions and the acoustic reflex

Subjects presenting difficulties in understanding speech with competing sounds may have absence of otoacoustic emission suppression and the acoustic reflex. AIM: To study the performance of the efferent auditory system in normal hearing subjects complaining of difficulties to understand speech in noise. MATERIAL AND METHODS: A prospective study comprising 50 normal-hearing subjects aged from 19 to 32 years, reporting difficulties with speech recognition in noise (with complaints - WC) or not (with no complaints - WNC). Distortion product evoked otoacoustic emissions (DPOAEs) were tested at frequencies from 1500 to 6000 Hz.The contralateral acoustic reflex (CAR) was investigated from 500 to 4000 Hz. RESULTS: Groups differed statistically as to the occurrence of CAR in the left ear at 4000 Hz. At 1500 Hz, there was a statistically significant effect - absence of DPOAEs in the WC group in the right ear. In left ears, absence of DPOAE suppression was higher in the WC at 1500 Hz and 2000 Hz. CONCLUSION: An association between self-reported difficulties in discriminating speech in noise and the absence of contralateral acoustic reflex at 4000 Hz in the left ear was observed; there was also absence of the suppression effect of DPOAEs, especially at middle frequencies in both ears.Pessoas com dificuldade para compreensão de fala com som competitivo podem apresentar ausência do efeito de supressão das emissões otoacústicas e do reflexo acústico. OBJETIVO: Estudar o desempenho do sistema auditivo eferente em indivíduos normo-ouvintes com queixa de reconhecer a fala na presença de ruído. MATERIAL E MÉTODO: Estudo prospectivo, com amostra composta por 50 voluntários, com idades entre 19 e 32 anos, normo-ouvintes, que referiram (com queixa-CQ) ou não (sem queixa-SQ) dificuldade de compreender a fala no ruído. As emissões otoacústicas evocadas produto de distorção (EOAEPDs) foram testadas nas frequências de 1500 a 6000Hz. O reflexo acústico contralateral (RAC) foi pesquisado nas frequências de 500 a 4000Hz. RESULTADOS: Os grupos diferiram estatisticamente quanto à ocorrência de RAC nas orelhas do lado esquerdo na frequência de 4000Hz. Na frequência de 1500 Hz nas orelhas do lado direito constatou-se predomínio estatisticamente significante da ausência do efeito de supressão das EOAEPDs no grupo CQ. Nas orelhas do lado esquerdo, a ausência do efeito de supressão das EOAEPDs foi maior no grupo CQ em 1500Hz e 2000Hz. CONCLUSÃO: Em normo-ouvintes com autorrelato de dificuldade de reconhecer a fala na presença de ruído verificou-se: ausência de supressão das EOAEPDs nas frequências médias em ambas as orelhas e ausência de reflexo acústico contralateral em 4000Hz na orelha esquerda.UNIFESPUFSM Departamento de FonoaudiologiaUNIFESPSciEL