RESUMO

Onychomycosis is the most common disease affecting the nail unit and accounts for at least 50% of all nail diseases. In addition, Candida albicans is responsible for approximately 70% of onychomycoses caused by yeasts. This study investigated the antifungal effect of (R) and (S)-citronellal enantiomers, as well as its predictive mechanism of action on C. albicans from voriconazole-resistant onychomycoses. For this purpose, in vitro broth microdilution and molecular docking techniques were applied in a predictive and complementary manner to the mechanisms of action. The main results of this study indicate that C. albicans was resistant to voriconazole and sensitive to the enantiomers (R) and (S)-citronellal at a dose of 256 and 32 µg/mL respectively. In addition, there was an increase in the minimum inhibitory concentration (MIC) of the enantiomers in the presence of sorbitol and ergosterol, indicating that these molecules possibly affect the integrity of the cell wall and cell membrane of C. albicans. Molecular docking with key biosynthesis proteins and maintenance of the fungal cell wall and plasma membrane demonstrated the possibility of (R) and (S)-citronellal interacting with two important enzymes: 1,3-ß-glucan synthase and lanosterol 14α-demethylase. Therefore, the findings of this study indicate that the (R) and (S)-citronellal enantiomers are fungicidal on C. albicans from onychomycoses and probably these substances cause damage to the cell wall and cell membrane of these micro-organisms possibly by interacting with enzymes in the biosynthesis of these fungal structures.

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RESUMO

Onychomycosis is the most common disease affecting the nail unit and accounts for at least 50% of all nail diseases. In addition, Candida albicans is responsible for approximately 70% of onychomycoses caused by yeasts. This study investigated the antifungal effect of (R) and (S)-citronellal enantiomers, as well as its predictive mechanism of action on C. albicans from voriconazole-resistant onychomycoses. For this purpose, in vitro broth microdilution and molecular docking techniques were applied in a predictive and complementary manner to the mechanisms of action. The main results of this study indicate that C. albicans was resistant to voriconazole and sensitive to the enantiomers (R) and (S)-citronellal at a dose of 256 and 32 µg/mL respectively. In addition, there was an increase in the minimum inhibitory concentration (MIC) of the enantiomers in the presence of sorbitol and ergosterol, indicating that these molecules possibly affect the integrity of the cell wall and cell membrane of C. albicans. Molecular docking with key biosynthesis proteins and maintenance of the fungal cell wall and plasma membrane demonstrated the possibility of (R) and (S)-citronellal interacting with two important enzymes: 1,3-ß-glucan synthase and lanosterol 14α-demethylase. Therefore, the findings of this study indicate that the (R) and (S)-citronellal enantiomers are fungicidal on C. albicans from onychomycoses and probably these substances cause damage to the cell wall and cell membrane of these micro-organisms possibly by interacting with enzymes in the biosynthesis of these fungal structures.

A onicomicose é a doença mais comum que afeta a unidade ungueal e representa pelo menos 50% de todas as doenças ungueais. Além disso, a Candida albicans é responsável por aproximadamente 70% das onicomicoses causadas por leveduras. Nesse estudo, foi investigado o efeito antifúngico dos enantiômeros (R) e (S)-citronelal, bem como seu mecanismo de ação preditivo sobre C. albicans de onicomicoses resistentes ao voriconazol. Para este propósito, foram aplicadas técnicas in vitro de microdiluição em caldo e docking molecular de forma preditiva e complementar para os mecanismos de ação. Os principais resultados deste estudo indicam que C. albicans foi resistente ao voriconazol e sensível aos enantiômeros (R) e (S)-citronelal na dose de 256 e 32 µg/mL respectivamente. Além disso, houve aumento da concentração inibitória mínima (CIM) dos enantiômeros na presença do sorbitol e do ergosterol, indicando que estas moléculas possivelmente afetem a integridade da parede e da membrana celular de C. albicans. O docking molecular com proteínas chave da biossíntese e manutenção da parede celular e da membrana plasmática fúngica, demonstraram a possibilidade do (R) e (S)-citronelal interagir com duas importantes enzimas: 1,3-ß-glucan sintase e lanosterol 14α-demetilase. Portanto, os achados desse estudo indicam que os enantiômeros (R) e (S)-citronelal são fungicidas sobre C. albicans de onicomicoses e provavelmente essas substâncias causem danos a parede e a membrana celular desses microrganismos possivelmente por interagir com as enzimas da biossíntese destas estruturas fúngicas.

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Rotation of insecticide modes of action is recommended to delay selection for insecticide resistance. In this study, larvae of Spodoptera frugiperda (J.E. Smith) were exposed alternately to spinetoram and metaflumizone with insecticidal and biological response determined. Five generations (G) were evaluated with at least 200 larvae assayed per treatment. The experiment consisted of rearing field-collected and untreated larvae (M-Control), larvae with successive applications of either metaflumizone (M-MET) or spinetoram (M-SPI), and alternation of these insecticides (M-Rotation treatment) consisting of the following treatments: G2 = exposure to SPI, G3 = exposure to MET, G4 = exposure to SPI, G5 = exposure to MET, and G6 = exposure to SPI. Four days after application, those surviving larvae were used to compose the following generations. In the G7, evaluations were made on the selected populations M-MET, M-SPI, M-Rotation, and control larvae to determine biological characteristics used to calculate the fertility life table parameters and further comparisons across treatments. The frequency of resistance was increased at rate of 49.5% and 29.2% after five generations of selection pressure with MET and SPI, respectively. However, rotation of insecticides reduced the frequency of resistance about 50% over the generations. Individuals originated from successive exposures to the insecticides exhibited delayed egg incubation, greater percentage of pupae with deformation, longer larval and pupal periods, and reduction in emergence rate and longevity of adults, suggesting adaptive costs associated with resistance.

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It was determined by the total collection of excreta method, with broilers from 22 to 32 days of age, the coefficients of apparent metabolism of dry matter, crude protein and crude energy and apparent metabolizable energy corrected for zero nitrogen balance (AMEn) of the ethanol co-products of corn: acid oil and dried distillery grains with soluble (DDGS). The DDGS and corn acid oil presented nutritional metabolization coefficients ranging from 43 to 83% and AMEn equal 2393.5 and 7859.2kcal/kg respectively, and may be food alternatives to soybean meal and soybean oil.(AU)

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RESUMO

It was determined by the total collection of excreta method, with broilers from 22 to 32 days of age, the coefficients of apparent metabolism of dry matter, crude protein and crude energy and apparent metabolizable energy corrected for zero nitrogen balance (AMEn) of the ethanol co-products of corn: acid oil and dried distillery grains with soluble (DDGS). The DDGS and corn acid oil presented nutritional metabolization coefficients ranging from 43 to 83% and AMEn equal 2393.5 and 7859.2kcal/kg respectively, and may be food alternatives to soybean meal and soybean oil.(AU)

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The authors study 24 patients with the histologic diagnosis of osteoblastoma treated from 1953 to 1996, with a mean follow-up of 33.4 months. Two were considered as a malignant osteoblastoma. Twenty-two cases were operated, and in 2 of these was performed only a selective embolization to pelvic and spine localization. It was discussed clinical and radiographic aspects and the response to treatment. It was obtained 20 good and 4 poor results.

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The authors review 15 patients with giant cell tumor of the distal part of the radius in the period from 1980 to 1993. Pain was always present. The treatment of stage 2 with marginal resection and methylmethacrylate yielded excellent result. In the treatment of stage 3 the authors emphasize the need of wide resection. In these patients the best functional results were obtained with the use of vascularized proximal epiphyseal fibular graft, preserving some painless mobility of the wrist and forearm.

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The authors studied, in the period 1990-1993, 31 patients with benign non aggressive bone lesions, surgically treated with intralesional resection followed by the introduction of hydroxyapatite. Their follow-up was two years and one month. The authors discussed the surgical indications, the operative technique employed, and the post-operative results which were considered to be good in 29 of the patients studied. Occurred complications in three patients: local infections in two and sterile fistula in one. It is concluded that the use of hydroxyapatite is a good option as substitute of the autologous bone graft.

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The authors report on 18 cases of chondromyxoid fibroma seen at the Institute of Orthopedics and Traumatology, University of São Paulo, from 1953 to 1990. A survey of the literature on chondromyxoid fibromas was conducted and radiographic analysis of all cases is presented, with a mean follow-up of 64 months. The surgical treatment employed in each case is discussed, with emphasis on the use of cement as an adjuvant. This procedure was used in 10 patients, who have been free of recurrence up to the present time.

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