State protection under collective damping and diffusion

In this paper we provide a recipe for state protection in a network of oscillators under collective damping and diffusion. Our strategy is to manipulate the network topology, i.e., the way the oscillators are coupled together, the strength of their couplings, and their natural frequencies, in order to create a relaxation-diffusion-free channel. This protected channel defines a decoherence-free subspace (DFS) for nonzero-temperature reservoirs. Our development also furnishes an alternative approach to build up DFSs that offers two advantages over the conventional method: it enables the derivation of all the network-protected states at once, and also reveals, through the network normal modes, the mechanism behind the emergence of these protected domains.

Equivalence between hot tensile and creep testing data for Kanthal A1 alloy

Hot tensile and creep tests were carried out on Kanthal A1 alloy in the temperature range from 600 to 800 degrees C. Each of these sets of data were analyzed separately according to their own methodologies, but an attempt was made to find a correlation between them. A new criterion proposed for converting hot tensile data to creep data, makes possible the analysis of the two kinds of results according to usual creep relations like: Norton, Monkman-Grant, Larson-Miller and others. The remarkable compatibility verified between both sets of data by this procedure strongly suggests that hot tensile data can be converted to creep data and vice-versa for Kanthal A1 alloy, as verified previously for other metallic materials.

Enantioselective analysis of praziquantel and trans-4-hydroxypraziquantel in human plasma by chiral LC-MS/MS: Application to pharmacokinetics

A simple enantioselective method for the determination of praziquantel (PZQ) and trans-4-hydroxypraziquantel (4-OHPZQ) in human plasma was developed and validated by high-performance liquid chromatography/mass spectrometry. The plasma samples were prepared by liquid-liquid extraction using a mixture of methyl-tert-butylether/dichloromethane (2:1, v/v) as extraction solvent. The direct resolution of PZQ and 4-OHPZQ enantiomers was performed on a Chiralpak AD column using hexane-isopropanol (75:25, v/v) as the mobile phase. Diazepam was used as internal standard. The method described here is simple and reproducible. The quantitation limit of 1.25 ng/ml for each PZQ enantiomer and of 12.5 ng/ml for each 4-OHPZQ enantiomer permits the use of the method in studies investigating the kinetic disposition of a single dose of 1.5g racemic PZQ. Enantioselectivity in the kinetic disposition of PZQ and 4-OHPZQ was observed in the clinical study. with the demonstration of a higher proportion of the (+)-(S)-PZQ and (-)-(R)-4-OHPZQ enantiomers in plasma. (C) 2009 Elsevier B.V. All rights reserved.

Synthesis of indole derivatives by domino hydroformylation/indolization of 2-nitrocinnamaldehydes

The present work furnishes an innovative preparation of substituted indoles based on tandem hydroformylation, where the chemo- and the regio-selectivities are good, so the yield of the reaction. The novelty has been established in the four-step transformation of substituted alpha nitrocinnamaldehydes into desired indoles in a one-pot reaction. Under hydroformylation reaction conditions we have been able to trigger off a cascade of reactions, which gave substituted indoles in high yields. Useful intermediates are prepared by using this technique for the synthesis of well-known biologically active molecules. (C) 2008 Elsevier B.V. All rights reserved.

Simultaneous Analysis of Tramadol, O-Desmethyltramadol, and N-Desmethyltramadol Enantiomers in Rat Plasma by High-Performance Liquid Chromatography-Tandem Mass Spectrometry: Application to Pharmacokinetics

Tramadol (T) is available as a racemic mixture of (+)-trans-T and (-)-trans-T. The main metabolic pathways are O-demethylation and N-demethylation, producing trans-O-desmethyltramadol (M1) and trans-N-desmethyltramadol (M2) enantiomers, respectively. The analgesic effect of T is related to the opioid activity of (+)-trans-T and (+)-M1 and to the monoaminergic action of (+/-)-trans-T. This is the first study using tandem mass spectrometry as a detection system for the simultaneous analysis of trans-T, M1, and M2 enantiomers. The analytes were resolved on a Chiralpak (R) AD column using hexane: ethanol (95.5:4.5, v/v) plus 0.1% diethylamine as the mobile phase. The quantitation limits were 0.5 ng/ml for trans-T and M1 and 0.1 ng/ml for M2. The method developed and validated here was applied to a pharmacokinetic study in rats. Male Wistar rats (n = 6 at each time point) received a single oral dose of 20 mg/kg racemic trans-T. Blood samples were collected up to 12 h after drug administration. The kinetic disposition of trans-T and M2 was enantioselective (AUC((+)/(-)) ratio = 4.16 and 6.36, respectively). The direction and extent of enantioselectivity in the pharmacokinetics of trans-T and M2 in rats were comparable to data previously reported for healthy volunteers, suggesting that rats are a suitable model for enantioselective studies of trans-T pharmacokinetics. Chirality 23: 287-293, 2011. (C) 2010 Wiley-Liss, Inc.

Metformin pharmacokinetics in nondiabetic pregnant women with polycystic ovary syndrome

The use of metformin throughout gestation by pregnant women with polycystic ovary syndrome (PCOS) significantly reduces the number of first trimester spontaneous abortions and the rate of occurrence of gestational diabetes. The objective of this study was to investigate the pharmacokinetics and the placental transfer of metformin in pregnant women with PCOS. Eight pregnant women with PCOS taking 850 mg metformin every 12 h during the third trimester of pregnancy were evaluated. Maternal blood samples were collected at steady state during the dose interval (0-12 h). Maternal and umbilical cord blood samples were also obtained at delivery. Metformin plasma concentrations were analyzed by high-performance liquid chromatography, and pharmacokinetic parameters were determined using a non-compartmental model. Data are reported as median and minimum and maximum values. Metformin pharmacokinetic parameters were: t(A1/2), 3.8 (2.8-5.4) h; t(max), 2.0 (0.5-3.0) h; C(max), 1.4 (0.5-2.1) mg/L; C(mean), 0.5 (0.2-0.9) mg/L; AUC(0-12), 6.4 (1.1-9.2) mg h/L; Cl/f, 105 (60-274) L/h; Vd/f, 551 (385-1173) L; median fluctuation, 89 (79-95)%. Umbilical/maternal metformin plasma concentration ratios were 0.7 (0.4-1.3). Metformin oral clearance (Cl/f) had increased in our patients relative to nonpregnant healthy volunteers or diabetic patients. Therefore, lower plasma metformin concentrations were observed for nondiabetic pregnant women with PCOS. Future studies should be conducted to demonstrate the therapeutic efficacy of metformin during pregnancy. Caution is warranted as umbilical/maternal metformin plasma concentrations ratios of around 0.7 require metformin dosage adjustment.

Albendazole-praziquantel interaction in healthy volunteers: kinetic disposition, metabolism and enantioselectivity

center dot Pharmacokinetic interactions between albendazole and praziquantel are based on plasma concentrations of the enantiomeric mixture of both drugs with contradictory data, although the antiparasitic activity arises from (-)-(R)-praziquantel and (+)-albendazole sulfoxide. WHAT THIS STUDY ADDS center dot The pharmacokinetic interaction between albendazole and praziquantel is enantioselective. Praziquantel increased the plasma concentrations of (+)-albendazole sulfoxide more than those of (-)-albendazole sulfoxide and the administration of albendazole did not change the kinetic disposition of (+)-(S)-praziquantel, but increased the plasma concentration of (-)-(R)-praziquantel. AIM This study investigated the kinetic disposition, metabolism and enantioselectivity of albendazole (ABZ) and praziquantel (PZQ) administered alone and in combination to healthy volunteers. METHODS A randomized crossover study was carried out in three phases (n = 9), in which some volunteers started in phase 1 (400 mg ABZ), others in phase 2 (1500 mg PZQ), and the remaining volunteers in phase 3 (400 mg ABZ + 1500 mg PZQ). Serial blood samples were collected from 0-48 h after drug administration. Pharmacokinetic parameters were calculated using a monocompartmental model with lag time and were analyzed using the Wilcoxon test; P < 0.05. RESULTS The administration of PZQ increased the plasma concentrations of (+)-ASOX (albendazole sulphoxide) by 264% (AUC 0.99 vs. 2.59 mu g ml-1 h), (-)-ASOX by 358% (0.14 vs. 0.50 mu g ml-1 h) and albendazole sulfone (ASON) by 187% (0.17 vs. 0.32 mu g ml-1 h). The administration of ABZ did not change the kinetic disposition of (+)-(S)-PZQ (-)-(R)-4-OHPZQ or (+)-(S)-4-OHPZQ, but increased the plasma concentration of (-)-(R)-PZQ by 64.77% (AUC 0.52 vs. 0.86 mu g ml-1 h). CONCLUSIONS The pharmacokinetic interaction between ABZ and PZQ in healthy volunteers was demonstrated by the observation of increased plasma concentrations of ASON, both ASOX enantiomers and (-)-(R)-PZQ. Clinically, the combination of ABZ and PZQ may improve the therapeutic efficacy as a consequence of higher concentration of both active drugs. On the other hand, the magnitude of this elevation may represent an increased risk of side effects, requiring, certainly, reduction of the dosage. However, further studies are necessary to evaluate the efficacy and safety of this combination.

Lipopolysaccharide from Escherichia coli prevents indomethacin-induced gastric damage in rats: role of non-protein sulfhydryl groups and leukocyte adherence

To investigate the role of non-protein sulfhydryl groups (NP-SH) and leukocyte adhesion in the protective effect of lipopolysaccharide (LPS) from Escherichia coli against indomethacin-induced gastropathy. Male Wistar rats were divided into four groups: saline, LPS, saline + indomethacin and LPS + indomethacin, with six rats in each group. Rats were pretreated with LPS (300 mu g/kg, by intravenous) or saline. After 6 h, indomethacin was administered (20 mg/kg, by gavage). Three hours after treatments, rats were killed. Macroscopic gastric damage, gastric NP-SH concentration, myeloperoxidase (MPO) activity and mesenteric leukocyte adhesion (intravital microscopy) were assessed. Statistical analysis was performed using one-way analysis of variance followed by the Newman-Keuls test. Statistical significance was set at P < 0.05. LPS reduced the gastric damage, gastric MPO activity and increased gastric NP-SH concentration in indomethacin-induced gastropathy. LPS alone increased gastric NP-SH when compared to saline. Indomethacin increased leukocyte adhesion when compared to the saline, and LPS reduced indomethacin-induced leukocyte adhesion. In addition, LPS alone did not change leukocyte adhesion, when compared to the saline. LPS protective effect against indomethacin-induced gastropathy is mediated by an increase in the NP-SH and a decrease in leukocyte-endothelial adhesion.

Stereoselective Analysis of Labetalol in Human Plasma by LC-MS/MS: Application to Pharmacokinetics

Labetalol is clinically available as a mixture of two racemates (four stereoisomers). The stereoisomer (R,R) has as main activity the beta(1)-antagonism and the stereoisomer (S,R) is highly selective for the alpha(1) adrenoceptor and is responsible for most of the alpha-blocker activity. In the present investigation, a method for the analysis of labetalol stereoisomers in human plasma was developed and applied to pharmacokinetic studies. Plasma samples (0.5 ml) were extracted with methyl tert-butyl ether at pH 9.5. The four labetalol stereoisomers were analyzed by LC-MS/MS on a Chirobiotic (R) V column using a mobile phase consisting of methanol, acetic acid, and diethylamine, with a recovery of more than 90% for all four. The quantitation limit was 0.5 ng/ml and linearity was observed at 250 ng/ml plasma for each stereoisomer. Studies of precision and accuracy presented coefficients of variation and percentage inaccuracy of less than 15%, indicating that the method is precise and accurate. The method was applied to the study of the kinetic disposition of labetalol over a period of 12 h after oral administration of a single 100 mg dose to a hypertensive pregnant woman. The clinical study revealed stereoselectivity in the pharmacokinetics of labetalol, with a lower plasma proportion for the active stereoisomers (R,R)-labetalol and (S,R)-labetalol. The stereoselectivity observed after oral administration is due to the hepatic metabolism and the first pass effect, with an AUC((R,R))/AUC((S,S)) ratio of 0.5. Chirality 21:738-744, 2009. (C) 2008 Wiley-Liss, Inc.

O diagnóstico da linguagem e a linguagem do diagnóstico : uma perspectiva pragmática

A teoria dos atos de fala, de John Austin, apresenta a linguagem a partir de uma perspectiva pragmática, ou seja, quando os signos têm um compromisso com a produção de realidades, de mundo e de sujeitos. A linguagem possui – nessa perspectiva – força de criação. Em sintonia com os estudos da pragmática da linguagem, defenderemos a ideia que uma classificação não é mera descrição neutra acerca dos fatos, e Ian Hacking será a ponte entre a linguagem (enquanto fonte de produção de mundo) e as classificações (como produtoras de sujeitos). Para esse autor, as classificações tanto transformam quanto são transformadas. Elas, de diversas formas, interagem entre si, com os sujeitos, com as instituições, com os saberes, enfim, com tudo aquilo a que faz referência. A partir de uma revisão, análise e composição bibliográfica, o trabalho se dedicará a produzir um elo entre a problemática da linguagem-ato, tal como postulada por John Austin, e o caráter produtor de realidade das classificações. Dentre as classificações, daremos importância particular ao diagnóstico (enquanto uma espécie de estudo de caso na teoria dos enunciados) e seus efeitos pragmáticos, a partir dos elementos que lhe dão força de eficácia e existência em nosso mundo contemporâneo, tendo em vista o aumento do número e da proliferação de categorias nosológicas no corpo social. Trataremos, em particular, as classificações da medicina psiquiátrica. Abordaremos, por um lado, as condições que contribuem na emergência e na potência de um diagnóstico e, por outro, seus efeitos. Dentre os efeitos que daremos importância, encontramos a formação de novos sujeitos e modos de vida. Sendo assim, tanto as condições de eficácia de um enunciado quanto seus efeitos são estendidos à noção de diagnóstico enquanto uma classificação numa condição sociohistórica particular.

Prevalência e fatores associados à infecção pelo M. tuberculosis entre agentes comunitários de saúde

Introdução: A tuberculose é uma doença milenar e que, ainda hoje, constitui grave problema de saúde pública em todo o mundo. Objetivo: Estimar a prevalência e os fatores associados à infecção latente pelo MTB entre Agentes Comunitários de Saúde atuantes na rede básica de saúde de Municípios prioritários para o controle de TB – Cuiabá/MT, Manaus/AM, Salvador/BA e Vitória/ES. Métodos: Estudo de corte transversal no qual os dados foram coletados através de questionário, composto de questões abertas e fechadas sobre características pessoais; informações a respeito da tuberculose; utilização de medidas preventivas, etc. Aplicou-se prova tuberculínica, com leitura após 48-72h por enfermeiros treinados, considerando como ponte de corte positivo 5 e 10 mm de enduração. A análise múltipla foi feita por meio de regressão logística hierarquica. Foram incluídas no modelo as variáveis que mostraram associação com desfecho com p<0,1. Permaneceram no modelo as variáveis independentes que mantiveram associação com desfecho após ajuste (p<0,05). Este estudo obteve aprovação do Comitê de Ética em Pesquisa com seres humanos do Centro de Ciências da Saúde da Universidade Federal do Espírito Santo, n° de registro CEP-07/2010 e das Secretarias Municipais de Saúde, por meio de uma Carta de Apresentação. Resultados: 322 Agentes Comunitários de Saúde (ACS) aceitaram participar voluntariamente do estudo por meio da assinatura do Termo de Consentimento Livre e Esclarecido. Destes, 10 não compareceram para leitura, sendo estes considerados como perdas, além do que um indivíduo foi excluído pelo fato do teste rápido para HIV ter resultado positivo, perfazendo uma amostra final de 311 participantes. Ainda em relação aos ACS triados, a positividade a Prova Tuberculínica, levando-se em consideração o ponto de corte ao teste de 10 mm e de 5 mm de enduração, foi de 37,30% (IC95%: 0,31-0,42) e de 57,88% (IC95%: 0,52-0,63), respectivamente.Conclusões: Faz-se necessário um programa de realização de Prova Tuberculínica, de rotina, combinado com intervenções para reduzir o risco de transmissão nosocomial, bem como a realização de outros estudos para avaliar a eficácia de novos testes para detecção de tuberculose latente.

Pólipos de pregas vocais e alterações estruturais mínimas: lesões associadas?

Pólipos são lesões comuns de pregas vocais. O fonotrauma é o principal fator relacionado com o início desta lesão. A associação entre pólipos de pregas vocais e alterações estruturais mínimas de cobertura mucosa (sulco vocal, cisto epidermóide, ponte de mucosa, microdiafragma laríngeo e vasculodisgenesia) foi pouco estudada na literatura, por isso o objetivo deste trabalho foi quantificar e analisar essa associação. FORMA DE ESTUDO: Clínico retrospectivo. MATERIAL E MÉTODOS: Realizamos um estudo retrospectivo com 68 pacientes, idade média de 39,5 anos, operados de pólipo de pregas vocais no período entre janeiro de 1999 e maio de 2003. Procuramos analisar a presença de pólipo de pregas vocais e as possíveis AEMC associadas no levantamento realizado. RESULTADOS: A presença de AEMC associada ao pólipo ocorreu em 16 (23,5%) pacientes, sendo que em 8 (50%) pacientes o achado foi o sulco vocal (7 sulco estria e 1 sulco bolsa). Em 4 (25%) pacientes o achado foi o cisto de prega vocal, em 2 (12,5%) pacientes a ponte mucosa, em 1 (6,25%) a vasculodisgenesia e em 1 (6,25%) paciente o microdiafragma laríngeo. A AEMC era contralateral ao pólipo de prega vocal em 11 pacientes. Dos sulcos, 6 (75%) eram contralaterais e dos cistos, 3 (75%) eram contralaterais ao pólipo. CONCLUSÃO: A associação entre pólipos de pregas vocais e alterações estruturais mínimas de cobertura mucosa é relativamente freqüente, 23,5% em nosso estudo. A exploração cuidadosa de ambas pregas vocais é essencial no intraoperatório das cirurgias de exérese de pólipo na procura destas alterações estruturais associadas.

A Política Externa da Alemanha após a reunificação

Análise das opções abertas à Alemanha no período após a reunificação, enfatizando seu papel internacional, seu protagonismo comunitário e sua função de ponte entre a Europa Ocidental e a Eurásia.

Planning Considerations for Tourism in the Minho-Lima Region (Northwest Portugal)

In administering their territories, most local municipalities aim to preserve their natural, historical and ethnographical resources while simultaneously using them to increase revenue and employment. In order to efficiently promote the products and services available and attract tourists, decision makers, private and public, need to know and incorporate tourists’ preferences in their marketing strategies. In this chapter we illustrate the use of stated preferences as an instrument to identify national and foreign tourists’ preferences regarding the products and services that the touristic destination of the Minho-Lima region (Northwest Portugal) should offer. As a starting point, we have taken the three general groups of touristic resources mentioned above as attributes. We take Ponte de Lima, a municipality in this region that has a strong cultural tourism potential as an example to identify possible future tourism scenarios for this territory. We believe the previously identified methodology can be a valuable instrument in the identification of the strengths and weaknesses of the selected territory and, thus, support the decision making process behind its future tourist development and marketing strategies.

Emergência da Bioquímica Interacção das culturas química e biológica

Em primeiro lugar, definiremos o âmbito da disciplina de bioquímica. Veremos assim como, à medida que a química orgânica se tornava na química dos compostos de carbono, houve necessidade de criar um novo ramo de química que se dedicasse, quer ao estudo dos constituintes e processos do organismo a química fisiológica , quer à interacção de diferentes áreas de investigação (química orgânica, fisiologia e biologia). Foi desta convergência que a bioquímica emergiu, nos finais do século XIX. Seguiremos depois o desenvolvimento das ideias e conceitos de fotossíntese, oxidação, respiração e fermentação, cujo esclarecimento forneceu a base química da função celular; e, ainda, como o estudo destes fenómenos da vida foi retardado, quer pela oposição dos químicos à participação de uma entidade biológica a levedura na química da fermentação, quer pelo esquecimento a que Pasteur votou a química, apesar de ter identificado a função da levedura, perdendo a descoberta das enzimas, força vital da fermentação e ponte de ligação entre a química e a biologia. Foi esta interacção entre as culturas química e biológica que permitiu demonstrar a unidade da natureza em todos os aspectos do crescimento celular e funções das plantas, animais e microorganismos. O nosso objectivo é mostrar os esforços desenvolvidos na explicação dos fenómenos biológicos nos organismos vivos e a permeabilidade da biologia, da medicina e da agricultura a conceitos e métodos químicos. No decorrer destes esforços, houve uma complexa e contínua interacção entre química e biologia, na qual se envolveram muitos cientistas de diferente formação.