Prolonged fluconazole exposure leads to a shift to Candida species with decreased susceptibility in breakthrough candidemia: prospective survey of the Fungal Infection Network of Switzerland

Objectives: To compare the clinical characteristics, species distribution and antifungal susceptibility of Candida bloodstream isolates (BSI) in breakthrough (BTC) vs. non-breakthrough candidemia (NBTC) and to study the effect of prolonged vs. short fluconazole (F) exposure in BTC.Methods: Candida BSI were prospectively collected during 2004- 2006 from 27 hospitals (seven university, 20 affiliated) of the FUNGINOS network. Susceptibility to F, voriconazole (V) and caspofungin (C) was tested in the FUNGINOS mycology reference laboratory by microtitre broth dilution method with the Sensititre YeastOneTM test panel. Clinical data were collected using standardized CRFs. BTC was defined as occurring during antifungal treatment/prophylaxis of at least three days duration prior to the candidemia. Susceptibility of BSI was defined according to 2010/2011 CLSI clinical breakpoints.Results: Out of 567 candidemia episodes, 550 Candida BSI were available. Of these, 43 (7.6%) were from BTC (37/43, 86% were isolated after F exposure). 38 BTC (88.4%) and 315 NBTC (55.6%) occurred in university hospitals (P < 0.001). The majority of patients developing BTC were immunocompromised: higher proportions of haematological malignancies (62.8% in BTC vs. 47.1% in NBTC, P < 0.001), neutropenia (37.2% vs. 11.8%, P < 0.001), acute GvHD (14% vs. 0.2%, P < 0.001), immunosuppressive drugs (74.4% vs. 7.8%, P < 0.001), and mucositis (32.6% vs. 2.3%, P < 0.001) were observed. Other differences between BTC and NBTC were higher proportions of patients with central venous catheters in the 2 weeks preceding candidemia (95.3% vs. 83.4%, P = 0.047) and receiving total parenteral nutrition (62.8% vs. 35.9%, P < 0.001), but a lower proportion of patients treated with gastric proton pump inhibitors (23.3% vs. 72.1%, P < 0.001). Overall mortality of BTC and NBTC was not different (34.9% vs. 31.7%, P = 0.73), while a trend to higher attributable mortality in BTC was found (13.9% vs. 6.9%, P = 0.12). Species identification showed a majority of C. albicans in both groups (51.2% in BTC vs. 62.9% in NBTC, P = 0.26), followed by C. glabrata (18.6% vs. 18.5%), C. tropicalis (2.3% vs. 6.3%) and C. parapsilosis (7.0% vs. 4.7%). Significantly more C. krusei were detected in BTC versus NBTC (11.6% vs. 1.6%, P = 0.002). The geometric mean MIC for F, V and C between BTC and NBTC isolates was not significantly different. However, in BTC there was a significant association between duration of F exposure and the Candida spp.: >10 days of F was associated with a significant shift from susceptible Candida spp. (C. albicans, C. parapsilosis, C. tropicalis, C. famata) to non-susceptible species (C. glabrata, C. krusei, C. norvegensis). Among 21 BTC episodes occurring after £10 days of F, 19% of the isolates were non-susceptible, in contrast to 68.7% in 16 BTC episodes occurring after >10 days of F (P = 0.003).Conclusions: Breakthrough candidemia occurred more often in immunocompromised hosts. Fluconazole administered for >10 days was associated with a shift to non-susceptible Candida spp.. Length of fluconazole exposure should be taken into consideration for the choice of empirical antifungal treatment.

Inhibition of fas death signals by FLIPs.

The death receptor Fas is a member of the tumor necrosis factor receptor family; upon interaction with its ligand it efficiently activates caspases and induces apoptosis. Despite abundant Fas surface expression, however, Fas death-signals are frequently interrupted. Many viruses express antiapoptotic proteins, including caspase inhibitors, Bcl-2 homologues and death-effector-domain-containing proteins that are termed FLIPs (FLICE [Fas-associated death-domain-like IL-1beta-converting enzyme]-inhibitory proteins). Cellular homologues of these inhibitors have been identified. Cellular FLIPs structurally resemble caspase-8 except that they lack proteolytic activity. FLIPs are highly expressed in tumor cells, T lymphocytes and healthy, but not injured, myocytes; this suggests a critical role of FLIPs as endogenous modulators of apoptosis.

Rat PPARs: quantitative analysis in adult rat tissues and regulation in fasting and refeeding.

PPARs are members of the nuclear hormone receptor superfamily and are primarily involved in lipid metabolism. The expression patterns of all 3 PPAR isotypes in 22 adult rat organs were analyzed by a quantitative ribonuclease protection assay. The data obtained allowed comparison of the expression of each isotype to the others and provided new insight into the less studied PPAR beta (NR1C2) expression and function. This isotype shows a ubiquitous expression pattern and is the most abundant of the three PPARs in all analyzed tissues except adipose tissue. Its expression is especially high in the digestive tract, in addition to kidney, heart, diaphragm, and esophagus. After an overnight fast, PPAR beta mRNA levels are dramatically down-regulated in liver and kidney by up to 80% and are rapidly restored to control levels upon refeeding. This tight nutritional regulation is independent of the circulating glucocorticoid levels and the presence of PPAR alpha, whose activity is markedly up-regulated in the liver and small intestine during fasting. Finally, PPAR gamma 2 mRNA levels are decreased by 50% during fasting in both white and brown adipose tissue. In conclusion, fasting can strongly influence PPAR expression, but in only a few selected tissues.

Armazenamento de pêssegos (Prunus persica (L.) Batsch), cv. Chiripá, em atmosfera controlada

O experimento foi conduzido com o objetivo de avaliar diferentes pressões parciais de O2 e CO2 durante o armazenamento em atmosfera controlada (AC) sobre a qualidade físico-química de pêssegos, cv. Chiripá. As pressões parciais de gases avaliadas foram: 0,8kPaO2/3kPaCO2; 1kPaO2/3kPaCO2; 1kPaO2/4kPaCO2; 1kPaO2/5kPaCO2; 2kPaO2/6kPaCO2; 2kPaO2/7kPaCO2, 2kPaO2/8kPaCO2, ar/10kPaCO2 e tratamento-controle, mantido sob armazenamento refrigerado (AR). O delineamento experimental utilizado foi o inteiramente casualizado, com quatro repetições de 20 frutos. As avaliações foram realizadas após 4 e 8 semanas de armazenamento a -0,5ºC ± 0,2ºC, mais 2 dias a 20ºC. Os resultados evidenciaram que o controle de atmosfera reduz a degradação da clorofila da epiderme e a perda de peso, porém tem pouco efeito sobre a firmeza, teor de só lidos solúveis totais (SST) e acidez titulável dos frutos. A pressão parcial de 1kPa de O2, associada a 3kPa de CO2, reduz a manifestação dos sintomas de lanosidade durante 8 semanas de armazenamento. A incidência de podridões dos frutos é reduzida quando armazenados sob a condição de 2kPa de O2, associada a 8kPa de CO2. Tanto o armazenamento refrigerado quanto o armazenamento sob atmosfera controlada mantêm boa qualidade dos frutos por quatro semanas a -0,5ºC, mais 2 dias a 20ºC. Oito semanas de armazenamento em AC é um período muito prolongado para uma satisfatória manutenção da qualidade de pêssegos da cultivar Chiripá. A elevada incidência de podridões e de lanosidade são as causas que mais contribuem para a redução da qualidade de pêssegos, cv. Chiripá, durante períodos prolongados de armazenamento.

Efeito da aplicação de cianamida hidrogenada e óleo mineral na quebra de dormência e producão do pessegueiro-'Flamecrest'

Com o objetivo de aumentar a produção e qualidade de frutos do pessegueiro- 'Flamecrest', de alta exigência em frio, realizou-se um experimento no Município de Farroupilha-RS, no ano de 2000, com o uso de cianamida hidrogenada e óleo mineral. Estudou-se o efeito de duas diferentes épocas de aplicação dos tratamentos (15-7 e 2-8) sobre a brotação, floração, frutificação, produção e antecipação de colheita. Foram testados os efeitos dos seguintes tratamentos: cianamida hidrogenada (C.H.) 1,22; 2,45; 3,675 e 4,90 g de i.a.L-1 com óleo mineral (O.M.) 10 g de i.a.L-1; O.M. 10 g de i.a.L-1 isolado e testemunha (sem pulverização). Os tratamentos não anteciparam a brotação das gemas floríferas, porém C.H. 2,45 e 4,90 g de i.a.L-1 com O.M. a 10 g de i.a.L-1 proporcionaram plantas com maior brotação das gemas vegetativas. Não houve efeito marcante dos tratamentos sobre a floração e a porcentagem de frutos vingados nas duas épocas. O número de frutos raleados por planta foi superior para os tratamentos com C.H. 2,45 e 4,90 g de i.a.L-1 com O.M. 10 g de i.a.L-1 quando aplicados na segunda época. Já, para o número e massa total dos frutos colhidos, destacaram-se, na primeira época (15-7), os tratamentos com C.H. 1,22 e 3,675 g de i.a.L-1 + O.M. 10 g de i.a.L-1 e, na segunda época (2-8), os tratamentos com C.H. 2,45 e 4,90 g de i.a.L-1 + O.M. 10 g de i.a.L-1. Os tratamentos da segunda época resultaram em produções médias superiores à primeira. A massa média dos frutos não foi alterada de forma clara pelos tratamentos, assim como o teor de sólidos solúveis totais e a resistência de polpa.

Tolerância a baixas temperaturas de cultivares de abacate (Persea americana Mill.)

Em experimento realizado no Núcleo de Agronomia do Sudoeste/IAC, em Capão Bonito (SP), observou-se o comportamento de 13 cultivares de abacate com seis anos de idade: Geada, Pollock e Simmonds (raça antilhana); Antoniolli, Breda, Campinas, Ermor, Jumbo, Margarida, Ouro verde, Reis e Solano (híbridos de antilhana x guatemalense) e Fuerte (híbrido de mexicana x guatemalense) em relação às baixas temperaturas. As temperaturas do ar registradas no posto meteorológico do local foram: -2,8°C; -0,4°C; -0,2°C e -1,8°C, respectivamente, nos dias 17; 18; 20 e 21 de julho de 2000. A cultivar Fuerte mostrou-se mais tolerante às baixas temperaturas, não apresentando injúrias nas plantas nem queda de frutos; as cultivares híbridas de antilhana x guatemalense apresentaram diferenças de tolerância ao frio; enquanto as antilhanas foram severamente injuriadas.

Tratamento hidrotérmico na manutenção da qualidade pós-colheita de maracujá-amarelo

Objetivando avaliar o efeito da temperatura de imersão na manutenção da qualidade pós-colheita de frutos de maracujá-amarelo, instalou-se na FCA/UNESP este experimento, composto pelos seguintes tratamentos: T1 (testemunha); T2 (35°C por 2 horas); T3 (35°C por 4 horas); T4 (43°C por 2 horas); T5 (43°C por 4 horas); T6 (53°C por 2 horas); T7 (53°C por 4 horas), sendo os frutos mantidos em câmaras BOD a 12 ± 1 °C e 80-90% UR. A cada três dias, foram retiradas amostras dos tratamentos para as seguintes análises: Grupo destrutivo - pH, firmeza, sólidos solúveis (SS), acidez titulável (AT), relação (SS/AT), rendimento de polpa e vitamina C; e para o grupo-controle determinaram-se perda de massa e coloração da casca. Com base nos resultados obtidos, os tratamentos hidrotérmicos dos frutos, com temperaturas menores, como é o caso do T2 e T3, apresentaram frutos com menor perda de massa, melhor manutenção da coloração, boa manutenção da firmeza da casca e teores razoáveis de vitamina C, enquanto as temperaturas mais elevadas causaram danos à aparência dos frutos (queima da casca) e reduziram os teores de vitamina C na polpa.

Pós-colheita de mamão híbrido UENF/CALIMAN 01 cultivado no Rio Grande do Norte

No Brasil, foi desenvolvido um novo híbrido de mamão obtido através de melhoramento do cruzamento entre um progenitor do Grupo Formosa e um progenitor do Grupo Solo. Recentemente, os produtores de mamões do Rio Grande do Norte introduziram o cultivo desse híbrido em seus pomares: no entanto, os estudos acerca do potencial de conservação desses frutos restringem-se aos testes realizados nas próprias empresas. O presente trabalho propôs-se a avaliar a vida útil pós-colheita do mamão híbrido UENF/Caliman 01 cultivado no Estado do Rio Grande do Norte. Os frutos foram provenientes de um plantio comercial, localizado no município de Ceará-Mirim-RN. Os mamões foram colhidos no estádio de maturação I (menos de 15% da superfície da casca amarela). No galpão de embalagem, os frutos passaram por lavagem, seleção, tratamentos hidrotérmico, imersão em fungicida e cera. No laboratório da Universidade Federal Rural do Semi-Árido (Mossoró-RN), os frutos foram armazenados à temperatura de 25º C ± 2º C e umidade relativa de 55% ± 5%. Aos 0; 2; 4; 6; 8 e 10 dias de armazenamento, realizaram-se avaliações sobre as seguintes variáveis: aparência externa e interna, coloração da casca, perda de massa, firmeza, sólidos solúveis, acidez titulável, pH e açúcares. Esse híbrido apresenta características fenotípicas do Grupo Formosa, com frutos alongados, massa média de 1,28 kg, polpa com espessura de 2,74 cm, coloração vermelha e conteúdo elevado de sólidos solúveis (13,65%) e açúcares (10,53%). As variáveis de qualidade analisadas limitaram a vida útil pós-colheita do híbrido UENF/Caliman 01 em oito dias.

Theta-duality on Prym varieties and a Torelli Theorem

Let $\pi : \widetilde C \to C$ be an unramified double covering of irreducible smooth curves and let $P$ be the attached Prym variety. We prove the scheme-theoretic theta-dual equalities in the Prym variety $T(\widetilde C)=V^2$ and $T(V^2)=\widetilde C$, where $V^2$ is the Brill-Noether locus of $P$ associated to $\pi$ considered by Welters. As an application we prove a Torelli theorem analogous to the fact that the symmetric product $D^{(g)}$ of a curve $D$ of genus $g$ determines the curve.

POTENCIAIS BENEFÍCIOS DO AUMENTO DA TEMPERATURA DE ARMAZENAGEM EM ATMOSFERA CONTROLADA DE MAÇÃS ‘GALA’ TRATADAS COM 1-MCP

RESUMO O armazenamento refrigerado pode induzir o desenvolvimento de danos por frio (caracterizado pelo escurecimento de polpa) em maçãs de algumas cultivares, mesmo quando mantidas em temperatura superior ao ponto de congelamento. O presente estudo avaliou o aumento da temperatura de armazenagem de maçãs clones de ‘Gala’ sob atmosfera controlada (AC), tratadas com 1-metilciclopropeno (1-MCP), como método para redução do desenvolvimento de escurecimento da polpa e do consumo de energia durante o armazenamento. Experimentos foram conduzidos em 2011, com maçãs produzidas em Fraiburgo (armazenadas em câmaras experimentais a -0,3 e 1,2 °C, e em câmaras comerciais a 0,7 e 2 °C) e em São Joaquim (armazenadas em câmaras comerciais a 0,8; 1,4 e 1,9 °C). Frutos de todos os tratamentos foram mantidos sob AC (1,8±0,2 kPa de O2 e 2,0±0,2 kPa de CO2/UR de 91±4%), sendo que metade dos frutos de cada temperatura de armazenamento foi tratada com 1-MCP. Os frutos foram analisados após o armazenamento em AC quanto à firmeza da polpa e incidência de escurecimento da polpa, rachaduras e podridões. De maneira geral, maçãs armazenadas em temperaturas mais elevadas mantiveram melhor firmeza da polpa e apresentaram menor incidência de escurecimento da polpa rachaduras e podridões, quando não tratadas com 1-MCP. O tratamento com 1-MCP retardou a perda de firmeza de polpa e reduziu a ocorrência de escurecimento de polpa e rachaduras. O aumento da temperatura de armazenagem em câmaras comerciais de AC em Fraiburgo, de 0,7 °C para 2,0 °C resultou em economia no consumo de energia em aproximadamente 21% para ventilação do ar da câmara e 50% para refrigeração.

Estudos da eletrodeposição de metais em regime de subtensão

This work reviews recent studies of underpotential deposition (UPD) of several metals on Pt and Au substrates performed in the Grupo de Materiais Eletroquímicos e Métodos Eletroanalíticos (IQSC -- USP, São Carlos). The UPD Cu, Cd and Pb on Pt were analysed in terms of their influence in the oxygen evolution reaction. Partial blockage of surface active sites, promoted by Pb ad-atoms, resulted in a change from water to hydrogen peroxide as the final product. The Ag UPD on Pt and Au substrates was also discussed in this work. A detailed model of charge calculation for Ag monolayer was developed and confirmed by the rotating ring-disk data. The partial charge transfer in UPD studies was analysed in the Cd/Pt and Cd/Au systems and a value of 0.5 was found for the adsorption electrovalence of Cd ad-ions. The Sn/Pt UPD systems were studied from the point of view of the valences of metallic ions in solution. The deposition from Sn(IV) generates a full monolayer with a maximum occupation of approximately 40% of the surface active sites (340 µC cm-2) plus 105 µC cm-2 of Hads (half monolayer). Changing the metallic ion for Sn(II), it was possible to deposit a full monolayer (210 µC cm-2) without any detectable Hads. Finally, the effect of anions was discussed in the Zn/Pt and Zn/Au systems. Here, the hydrogen evolution reaction (her) and the hydrogen adsorption/desorption were used in order to investigate the maximum coverage of the surface with Zn ad-atoms. The full monolayer, characterised by the complete absence of Hads, was achieved only in 0.5 M HF solutions.

Tautomerism and Fragmentation of Biologically Active Hetero Atom (O, N)-Containing Acyclic and Cyclic Compounds Under Electron Ionization

In this thesis a total of 86 compounds containing the hetero atoms oxygen and nitrogen were studied under electron ionization mass spectrometry (EIMS). These compounds are biologically active and were synthesized by various research groups. The main attention of this study was paid on the fragmentations related to different tautomeric forms of 2- phenacylpyridines, 2-phenacylquinolines, 8-aryl-3,4-dioxo-2H,8H-6,7-dihydroimidazo- [2,1-c][1,2,4]triazines and aryl- and benzyl-substituted 2,3-dihydroimidazo[1,2-a]pyrimidine-5,7-(1H,6H)-diones. Also regio/stereospecific effects on fragmentations of pyrrolo- and isoindoloquinazolinones and naphthoxazine, naphthpyrrolo-oxazinone and naphthoxazino-benzoxazine derivatives were screened. Results were compared with NMR data, when available. The first part of thesis consists of theory and literature review of different types of tautomerism and fragmentation mechanisms in EIMS. The effects of tautomerism in biological systems are also briefly reviewed. In the second part of the thesis the own results of the author, based on six publications,are discussed. For 2-phenacylpyridines and 2-phenacylquinolines the correlation of different Hammett substituent constants to the relative abundances (RA) or total ion currents (% TIC) of selected ions were investigated. Although it was not possible to assign most of the ions formed unambiguously to the different tautomers, the linear fits of their RAs and % TICs can be related to changing contributions of different tautomeric forms. For dioxoimidazotriazines and imidazopyrimidinediones the effects of substituents were rather weak. The fragmentations were also found useful for obtaining structural information. Some stereoisomeric pairs of pyrrolo- and isoindoloquinazolines and regiomeric pairs of naphtoxazine derivatives showed clear differences in thir mass spectra. Some mechanisms are suggested for their fragmentations.

A cascata dos fosfoinositídeos

Inositol is a polyalcohol required for the proper formation of cell membranes. In the body, its plays an important role in the transmission of nerve impulses, its also helps in the transporting of fats within the body. In mammals, inositol exists as phosphorylated derivatives, various phosphoinositides, and in its free form. Agonist stimulated hydrolysis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is the first step in the transmembrane signalling mechanism when cells respond to external stimuli. Under control of activated phospholipase C (PLC) via G-protein, two second messengers D-myo-inositol 1,4,5-triphosphate [Ins(1,4,5)P3] and diacylglycerol are released into the cell. From Ins(1,4,5)P3, enzymatic process under phosphatases or kinases control affords subsequent inositol phosphate metabolites. During the last decade the synthesis of modified inositol phosphate derivatives has been strongly investigated. This paper reviews principal aspects about synthesis and biological functions of these biomolecules.

Determinação de arsênio em águas contaminadas usando fluorescência de raios-X por energia dispersiva

This work proposes a simple, fast and inexpensive method to determine As in natural waters, using X-ray fluorescence. 50 µL of each sample containing 100 mg L-1 of yttrium as internal standard were deposited over a 2.5 µm thickness MylarTM film. The samples were dried at 50 °C for 2 h. X-ray spectra were obtained using an EDXRF apparatus. The accuracy was determined by analyte addition/recovery and by comparison with Hydride Generation Atomic Absorption Spectrometry (HG AAS). A recovery of about 100% was obtained and the results were in good agreement with HG AAS. The method showed a relative standard deviation of 6.8% and a detection limit of 10.5 µg L-1 of As.