Atividade antimicrobiana de flavonóides polimetoxilados isolados de frutos cítricos

Dissertação (mestrado) - Universidade Federal de Santa Catarina. Programa de Pós-Graduação em Biotecnologia.Os flavonóides polimetoxilados (FPM) são metabólitos secundários que ocorrem nas plantas do gênero Citrus e vem sendo introduzidos na dieta humana pelo avanço tecnologico na fabricação de sucos concentrados. Essas substâncias são encontradas principalmente nas cascas dos frutos que incluem princípios de resistência natural contra patógenos. Essa propriedade é, provavelmente, derivada da possibilidade de formarem complexos com proteínas solúveis e com a parede celular de microrganismos. A metilação das hidroxilas confere à molécula caráter lipofilico, o qual é também um dos parâmetros moleculares mais estudados na elaboração de novos medicamentos e pesticidas. No presente estudo, essas moléculas promissoras foram obtidas de cascas de frutos de 4 espécies de Citrus: C. limon, C. reticulata, C. aurantifolia e C. sinensis. Com o uso de hexano foram preparados extratos da cera epicuticular e extratos brutos hexânico. A partir desses extratos, foram obtidos uma cumarina e quatro flavonóides por precipitação com metanol. O processo foi monitorado por meio de cromatografia em camada delgada (CCD) e as substâncias identificadas por métodos espectroscópicos, como sendo: 6,7-dimetoxi-cumarina, 6,7,8,4'-pentametoxi-flavona, 5,6,7,8,3',4'-hexametoxi-flavona, 8-hidroxi-3,5,6,7,4'-pentametoxi-flavona e 8-hidroxi-3,5,6,7,3',4'-hexametoxi-flavona. A atividade antimicrobiana dos extratos e compostos foi estudada por dois métodos: bioautografia direta e determinação da concentração inibitória mínima (CIM). A bioautografia revelou que todos os extratos e substâncias obtidas apresentaram atividade inibitória para os fungos e as bactérias testadas. Pela CIM, constatou-se que a 6,7-dimetoxi-cumarina foi a substância mais eficiente para os fungos dermatófitos e que as flavonas 6,7,8,4'-pentametoxi-flavona e 5,6,7,8,3',4'-hexametoxi-flavona foram as mais ativas para as bactérias

Antifungal activity of schinol and a new biphenyl compound isolated from Schinus terebinthifolius against the pathogenic fungus Paracoccidioides brasiliensis

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to isolate and identify the antifungal compounds from the extracts of <it>Schinus terebinthifolius </it>(Anacardiaceae) against clinical isolates of the pathogenic fungus <it>Paracoccidioides brasiliensis</it>.</p> <p>Methods</p> <p>The hexane and dichlomethane fractions from leaves and stems of <it>S. terebinthifolius </it>were fractionated using several chromatography techniques to afford four compounds.</p> <p>Results</p> <p>The compounds isolated from <it>S. terebinthifolius </it>were identified as schinol (<b>1</b>), a new biphenyl compound, namely, 4'-ethyl-4-methyl-2,2',6,6'-tetrahydroxy[1,1'-biphenyl]-4,4'-dicarboxylate (<b>2</b>), quercetin (<b>3</b>), and kaempferol (<b>4</b>). Compounds <b>1 </b>and <b>2 </b>were active against different strains of <it>P. brasiliensis</it>, showing a minimal inhibitory concentration value against the isolate Pb B339 of 15.6 μg/ml. The isolate Pb 1578 was more sensitive to compound <b>1 </b>with a MIC value of 7.5 μg/ml. Schinol presented synergistic effect only when combined with itraconazole. The compounds isolated from S. <it>terebinthifolius </it>were not able to inhibit cell wall synthesis or assembly using the sorbitol assay.</p> <p>Conclusion</p> <p>This work reveals for the first time the occurrence of compound <b>2 </b>and discloses activity of compounds <b>1 </b>and <b>2 </b>against several clinical isolates of <it>P. brasiliensi</it>s. These results justify further studies to clarify the mechanisms of action of these compounds.</p

Antimicrobial activity of wax and hexane extracts from Citrus spp. peels

Antibacterial and antifungal properties of wax and hexane extracts of Citrus spp. peels were tested using bioautographic and microdilution techniques against three plant pathogenic fungi (Penicillium digitatum, Curvularia sp., and Colletotrichum sp.), two human pathogens (Trichophyton mentagrophytes and Microsporum canis), and two opportunistic bacteria (Escherichia coli and Staphylococcus aureus). Two polymethoxylated flavonoids and a coumarin derivative, were isolated and identified from peel extracts, which presented antimicrobial activity especially against M. canis and T. mentagrophytes: 4',5,6,7,8-pentamethoxyflavone (tangeritin) and 3',4',5,6,7,8-hexamethoxyflavone (nobiletin) from C. reticulata; and 6,7-dimethoxycoumarin (also known as escoparone, scoparone or scoparin) from C. limon

Muscle histopathology in nebulin-related nemaline myopathy : ultrastrastructural findings correlated to disease severity and genotype

Peer reviewe

Systemic infection by Spencermartinsiella sp. in a Nile crocodile (Crocodylus niloticus)

A male adult crocodile (Crocodylus niloticus) was diagnosed with systemic yeast infection. Histologically, there were extensive areas of necrosis in the lung, which were associated with a diffuse severe lympho-plasmo-histiocytic inflammatory infiltrate, with numerous multinucleated giant cells, and myriads of intralesional pseudo-hyphae and yeast like organisms within distended foveolae. Necrotic foci were also observed in the mucosa of the digestive tract, trachea, tunica intima of arteries, liver, and heart, with a marked inflammatory lympho-histiocytic infiltrate, with large numbers of epithelioid macrophages and giant cells, and intralesional and intravascular pseudo-hyphae and yeast-like organisms. Oval yeast structures with 4 to 6 μm in diameter and 5 to 8 μm thick paralleled-wall pseudo-hyphae were observed in PAS or GMS stained sections. PCR with DNA template extracted from paraffin embedded tissues amplified the D1/D2 domains of the large subunit rRNA gene, which was sequenced and found to be identical to sequences of a new species, isolated from rotting wood in Brazil, of the genus Spencermartinsiella, which its closest relative is Spencermartinsiella cellulosicola. Um crocodilo macho adulto (Crocodylus niloticus) foi diagnosticado com infecção fúngica sustêmica. Histologicamente, havia extensas áreas de necrose no pulmão, que estavam associadas com infiltrado inflamatório linfo-plasmo-histiocitário, com numerosas células gigantes multinucleadas e miríade de pseudo-hifas e organismos leveduriformes intralesionais, dentro de favéolas distendidas. Focos necróticos também foram observados na mucosa do trato digestório, traquéia, túnica íntima de artérias, fígado e coração, com acentuado infiltrado inflamatório linfo-histiocitário, com grande número de macrófagos epitelioides e células gigantes e hifas e organismos leveduriformes intralesionais e intravasculares. Cortes corados por PAS e GMS evidenciaram estruturas leveduriformes ovais com 4 a 6 μm de diâmetro e pseudo-hifas de paredes espessas e paralelas com 5 a 8 μm. PCR realizado com DNA extraído de material parafinizado amplificou os domínios D1/D2 da subunidade maior do gene rRNA, cuja sequencia foi idêntica a sequências de uma nova espécie, isolada no Brasil de madeira em decomposição, do gênero Spencermartinsiella, cuja espécie mais próxima é Spencermartinsiella cellulosicola

Clinical Utility of Circulating Tumour Cell Androgen Receptor Splice Variant-7 Status in Metastatic Castration-resistant Prostate Cancer.

Abstract Background Detection of androgen receptor splice variant-7 (AR-V7) mRNA in circulating tumour cells (CTCs) is associated with worse outcome in metastatic castration-resistant prostate cancer (mCRPC). However, studies rarely report comparisons with CTC counts and biopsy AR-V7 protein expression. Objective To determine the reproducibility of AdnaTest CTC AR-V7 testing, and associations with clinical characteristics, CellSearch CTC counts, tumour biopsy AR-V7 protein expression and overall survival (OS). Design, setting, and participants CTC AR-V7 status was determined for 227 peripheral blood samples, from 181 mCRPC patients with CTC counts (202 samples; 136 patients) and matched mCRPC biopsies (65 samples; 58 patients). Outcome measurements and statistical analysis CTC AR-V7 status was associated with clinical characteristics, CTC counts, and tissue biopsy AR-V7 protein expression. The association of CTC AR-V7 status and other baseline variables with OS was determined. Results and limitations Of the samples, 35% were CTC+/AR-V7+. CTC+/AR-V7+ samples had higher CellSearch CTC counts (median CTC; interquartile range [IQR]: 60, 19–184 vs 9, 2–64; Mann-Whitney test p Conclusions Studies reporting the prognostic relevance of CTC AR-V7 status must account for CTC counts. Discordant CTC AR-V7 results and AR-V7 protein expression in matched, same-patient biopsies are reported. Patient summary Liquid biopsies that determine circulating tumour cell androgen receptor splice variant-7 status have the potential to impact treatment decisions in metastatic castration-resistant prostate cancer patients. Robust clinical qualification of these assays is required before their routine use