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1.

Background

Candida parapsilosis may acquire resistance to echinocandins, a fact that prompts the search for new therapeutic options.

Aims

The present study aimed to evaluate the in vitro activity of antifungal agents, alone and in combination, against four groups of C. parapsilosis strains: (1) echinocandin-susceptible (ES) clinical isolates (MIC ≤ 2 μg/ml), (2) anidulafungin-resistant strains (MIC ≥ 8 μg/ml), (3) caspofungin-resistant strains (MIC ≥ 8 μg/ml), and (4) micafungin-resistant strains (MIC ≥ 8 μg/ml).

Methods

Antifungal interactions were evaluated by a checkerboard micro-dilution method. The determination of the MIC to each drug for every isolate according to the Clinical and Laboratory Standards Institute documents M27 (2017) and M60 (2017) was also done.

Results

The echinocandins-resistant (ER) strains showed higher MICs to the tested antifungals than the ES strains, except for amphotericin B, for which the ER groups remained susceptible.

Conclusions

Most combinations showed indifferent interactions. The use of monotherapy still seems to be the best option. As resistance to echinocandins is an emergent phenomenon, further studies are required to provide clearer information on the susceptibility differences between strains to these antifungal agents.  相似文献   
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Four derivatives of an α,β-amyrin mixture were synthesized by acylation with appropriate anhydrides. The structures of the compounds were confirmed by means of IR and (1)H and (13)C NMR. The compounds were screened for cytotoxic activity using four human tumor cell lines (HL-60, MDAMB-435, SF-295 and HCT-8) and normal peripheral blood mononuclear cells (PBMC). 3-O-Carboxymaleinate of α,β-amyrin (3a/3b) were found to be the only active compounds of the series (high cytotoxicity), showing IC(50) values ranging from 1.8 to 3μM. In PBMC, 3a/3b were not toxic, suggesting selectivity for tumor cells. To better understand the mechanism of action involved in the cytotoxicity of 3a/3b, HL-60 cells treated with 3a/3b were examined for morphological changes, DNA fragmentation, cell cycle perturbation, externalization of phosphatidylserine and activation of caspases 3/7, with doxorubicin serving as the positive control. The results indicate that the cytotoxicity of 3a/3b involves the induction of cell death by apoptosis.  相似文献   
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Objective: To compare the thermic response to a meal between men and women of varied body composition and to determine whether adrenergic amines extracted from citrus aurantium (CA) induce an increase in metabolic rate and enhance the thermic response to the meal. Research Methods and Procedures: In 30 healthy weight‐stable subjects (17 women, 13 men; BMI: 20 to 42 kg/m2), body composition was determined by bioimpedance analysis followed by resting energy expenditure for 20 minutes, and the thermic effect of food (TEF) of a 1.7‐MJ, 30‐gram protein meal was determined intermittently for 300 minutes by indirect calorimetry. In a subset of 22 subjects, the TEFs of CA alone and when added to the same 1.7‐MJ meal were determined. Blood pressure and pulse before and throughout the studies and catecholamine excretion were determined. Results: TEF was significantly lower in women than men (152 ± 7 vs. 190 ± 12 kJ and 8.8 ± 0.4% vs. 11.0 ± 0.7% of meal), independently of age and magnitude of adiposity. The thermic response to CA alone was higher in men, but, when added to the meal, CA increased TEF only in women and to values no longer different from men. CA had no effect on blood pressure and pulse rate but increased epinephrine excretion by 2.4‐fold. Discussion: A 20% lower TEF in women suggests a diminished sympathetic nervous system response to meals, because with CA, TEF increased by 29% only in women. However, this acute response may not translate into a chronic effect or a clinically significant weight loss over time.  相似文献   
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Bacteriophage phi29 requires scaffolding protein to assemble the 450 x 540 A prolate prohead with T = 3 symmetry end caps. In infections with a temperature-sensitive mutant scaffolding protein, capsids assemble predominantly into 370 A diameter isometric particles with T = 3 symmetry that lack a head-tail connector. However, a few larger, 430 A diameter, particles are also assembled. Cryo-electron microscopy shows that these larger particles are icosahedral with T = 4 symmetry. The prolate prohead, as well as the two isometric capsids with T = 3 and T = 4 symmetry, are composed of similar pentamers and differently skewed hexamers. The skewing of the hexamers in the equatorial region of proheads and in the T = 4 isometric particles reflects their different environments. One of the functions of the scaffolding protein, present in the prohead, may be to stabilize skewed hexamers during assembly.  相似文献   
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In this study, the amino acid sequence and anti‐inflammatory effect of Bauhinia bauhinioides (BBL) lectin were evaluated. Tandem mass spectrometry revealed that BBL possesses 86 amino acid residues. BBL (1 mg/kg) intravenously injected in rats 30 min prior to inflammatory stimuli inhibited the cellular edema induced by carrageenan in only the second phase (21% – 3 h, 19% – 4 h) and did not alter the osmotic edema induced by dextran. BBL also inhibited carrageenan peritoneal neutrophil migration (51%), leukocyte rolling (58%) and adhesion (68%) and the neutrophil migration induced by TNF‐α (64%). These effects were reversed by the association of BBL with galactose, demonstrating that the carbohydrate‐binding domain is essential for lectin activity. In addition, BBL reduced myeloperoxidase activity (84%) and TNF‐α (68%) and IL1‐β (47%) levels. In conclusion, the present investigation demonstrated that BBL contains highly homologous isolectins, resulting in a total of 86 amino acid residues, and exhibits anti‐inflammatory activity by inhibiting neutrophil migration by reducing TNF‐α and IL1‐β levels via the lectin domain. Copyright © 2015 John Wiley & Sons, Ltd.  相似文献   
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Summary Elytrosporangium (Greek Elytron, pod), a new genus of Actinomycetales from soil, placed in the family ActinoplanaceaeCouch, and its type species,E. brasiliense, are described. The main characteristic of the new genus is the production, in the substratal mycelium, of pod-shaped sporangia (merosporangia) with non-motile, globose, subglobose, to more or less cylindrical sporangiospores in chains. In addition, aerial mycelium with spores in chains, as inStreptomyces, is produced.
Zusammenfassung Elytrosporangium (griechisch: Elytron, Schote) eine neue Gattung von Actinomycetels des Bodens wird hier zusammen mit der ArttypeE. brasiliense beschrieben. Das Hauptmerkmal der genannten Gattung ist die Erzeugung von Sporangien in Schotenform (Merosporangien) im vegetativen Myzel. Die Sporangien bilden sich sowohl am Ende von Haupthyphen als auch in kleinen seitlichen Zweigen, einzeln oder als Trauben, von zwei bis fünf. Die Sporangiosporen bilden eine Kette, die Basale mehr oder weniger zylindrisch und die übrigen fast kugelförmig. Luftmyzel mit Ketten von Konidien können erzeugt werden wie inStreptomyces. Wir betrachten die beschriebene Gattung als zur Familie Actinoplanaceae gehörend.Die Arttype wurde isoliert von Bodenproben welche gesammelt wurden in einen Bodenprofil von 45 cm Tiefe in Verfolg des Programms einer Mikrobiologischen Prospektion des Bodens im Nordosten von Brasilien welches IMUR gemeinsam mit anderen brasilianischen wissenschaftlichen Körperschaften ausführt.

Sumário Elytrosporangium (grego Elytron, vágem), um novo gênero de Actinomycetales do solo é descrito, juntamente com sua espécie tipo,E. brasiliense, A principal característica do gênero em foco é a produção de esporângios em forma de vágem (merosporângios), no micélio vegetativo. Os esporângios formam-se tanto na extremidade de hifas principais como na de pequenos ramos laterais, isoladamente ou em cachos de dois a cinco.Os esporangiosporos constituem uma cadeia, os basais sendo mais ou menos cilíndricos e os demais globosos ou subglobosos.Um micélio aéreo exibindo cadeias de conídios pode ser produzido, como emStreptomyces.Consideramos o gênero em causa como integrante da familia Actinoplanaceae. A espécie tipo foi isolada de amostra de solo coletada num perfil, a 45 cm de profundidade, como decorrência de programa de prospecção microbiológica dos solos do Nordeste do Brasil que o IMUR vem desenvolvendo em colaboração com entidades científicas brasileiras.


IMUR, Publ. no. 467.  相似文献   
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The MDJ1/LON locus is conserved among pathogenic dimorphic fungi. We have mapped using DNase I footprinting and mobility shift assays three putative heat shock elements and one AP-1 binding domain (ARE) in the 5' intergenic region shared by PbMDJ1and PbLON (ML) from Paracoccidioides brasiliensis. The region bearing an ARE-like towards PbLON also has an opposite skn-1-like element. We studied genetically and pathogenically distinct isolates Pb18 and Pb3, where ML is polymorphic and the number of elements detected was higher. The functionality of the elements was suggested by the stimulatory response of both genes to heat shock and oxidative stress. Co-regulation occurred upon heat shock from 36 to 42 degrees C and, only in Pb3, also during mycelium to yeast transformation (26-36 degrees C). In Pb18, PbMDJ1 seemed to be preferentially expressed in yeast. Our study might help understand regulation of genes involved in fungal adaptation to the host.  相似文献   
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