Farnesol is a sesquiterpene alcohol that modulates cell-to-cell communication in Candida albicans. In recent years, several studies have shown that this molecule presents inhibitory effects against non-albicans Candida species, Paracoccidioides brasiliensis and bacteria. The present study aimed at determining the effect of farnesol on the growth of strains of the Cryptococcus neoformans species complex, through microdilution assays. In addition, the effect of farnesol on the synthesis of phospholipase and protease - important virulence-associated enzymes - by C. neoformans and Cryptococcus gattii was also investigated. A total of 36 strains were studied, out of which 20 were from veterinary sources, 8 were from human cases and 8 were from a reference collection. The minimum inhibitory concentrations (MICs) were determined in accordance with the M27-A3 protocol as described by the CLSI and farnesol was tested at a concentration range of 0.29-150 μM. Phospholipase and protease activities were evaluated through growth on egg yolk agar and spectrophotometry, respectively, after pre-incubating the strains at different farnesol concentrations (MIC/4, MIC/2 and MIC). It was observed that farnesol presents an inhibitory activity against C. neoformans and C. gattii (MIC range: 0.29-75.0 μM). Although farnesol did not significantly alter phospholipase activity, a tendency to decrease this activity was observed. Concerning protease, no statistically significant differences were observed when comparing the production before and after pre-incubation at different farnesol concentrations. Based on these findings, it can be concluded that farnesol has in vitro inhibitory activity against C. neoformans and C. gattii, but has little impact on the production of the analyzed virulence factors.
The Cryptococcus neoformans species complex contains the most important agents of fungal meningoencephalitis. Therapeutic choices are limited and issues related to toxicity and resistance to antifungals have been described. The present study evaluated the inhibitory effect of the antifolate combinations sulfamethoxazole-trimethoprim (SMX/TMP) and sulfadiazine-pyrimethamine (SDZ/PYR) against planktonic cells and biofilms of C. neoformans and C. gattii. The influence of the antifolate combinations on the amphotericin minimum inhibitory concentration (MIC) of planktonic cells was also investigated. In addition, the effect of these combinations on the cellular ergosterol content of planktonic cells was studied. Strains of C. neoformans (n = 15) and C. gattii (n = 15) obtained from environmental or clinical sources were evaluated by the broth microdilution method. SMX/TMP and SDZ/PYR showed antifungal activity against free living cells and sessile cells of Cryptococcus spp. Moreover, planktonic cells showed increased susceptibility to amphotericin B after pre-incubation with sub-inhibitory concentrations of SMX/TMP or SDZ/PYR. The drug combinations SMX/TMP and SDZ/PYR were able to prevent the biofilm formation and showed inhibitory effect against mature biofilms of both species. Additionally, the study showed that antifolate drugs reduced the ergosterol content in C. neoformans and C. gattii planktonic cells. Our results highlight the antifungal potential of antifolate drugs.
This study evaluated in vitro interactions of antituberculosis drugs and triazoles against Histoplasma capsulatum. Nine drug combinations, each including an antituberculosis drug (isoniazid, pyrazinamide, or ethambutol) plus a triazole (itraconazole, fluconazole, or voriconazole), were tested against both growth forms of H. capsulatum. Stronger synergistic interactions were seen in isoniazid or pyrazinamide plus triazoles for the mold form and ethambutol plus voriconazole for the yeast-like form. Further studies should evaluate these combinations in vivo.Previously we demonstrated the inhibitory effect of some antituberculosis drugs alone or combined with antifungals against the pathogen Coccidioides posadasii (5, 6). Stronger synergistic interactions were seen in the combinations including ethambutol (ETB) plus triazoles as well as pyrazinamide (PZA) plus itraconazole (ITR). Based on these results, the purpose of this study was to investigate the effect of these combinations against the dimorphic pathogen Histoplasma capsulatum var. capsulatum-the etiological agent of American histoplasmosis, regarded as the most frequent systemic fungal infection worldwide (1, 7) and an important opportunistic infection among AIDS patients (7,8,13,14). The emergence of resistance to fluconazole (FLC) as a cause of failure during treatment of histoplasmosis in patients with AIDS indicates a need for studies seeking new therapeutic options for this mycosis (13).A total of 18 strains of Histoplasma capsulatum var. capsulatum (henceforth called H. capsulatum) isolated in Brazil were included in the study. Most of the strains were recovered from AIDS patients with histoplasmosis and were isolated from bone marrow puncture (n ϭ 10) and peripheral blood (n ϭ 6). Two strains isolated from cutaneous ulcers of domestic felines with disseminated histoplasmosis were also tested. The strains belong to the fungal collection of the Specialized Medical Mycology Center (CEMM) of the Federal University of Ceará, Brazil. All procedures were performed inside a biosafety level 3 laboratory.For macrobroth testing, inoculum preparation was carried out as described by Li et al. (9) with minor modifications. First, the H. capsulatum strains were grown on brain heart infusion agar (BHI; BD Diagnostics) at 28°C for 7 days. Sterile 0.9% saline was added to the agar slant, and the cultures were gently scraped with cotton swabs. The suspensions were read at 530 nm and adjusted to 90 to 95% transmittance. The suspension was then diluted 1:10 with RPMI 1640 medium (Sigma Chemical Co.) containing L-glutamine and without sodium bicarbonate and buffered to pH 7.0 with 0.165 M MOPS (morpholinepropanesulfonic acid; Sigma Chemical Co.) to obtain an inoculum of approximately 0.5 ϫ 10 3 to 2.5 ϫ 10 4 CFU ⅐ ml Ϫ1 . Inoculum preparation for microbroth tests was performed as described by Brilhante et al (3). The suspensions were diluted with RPMI medium buffered to pH 7.0 with MOPS to obtain an inoculum of approximately 0.5 ϫ 10 3 to 2.5 ϫ 10 4 CFU ⅐ ml Ϫ1 . The densit...
RESUMOAs enteroparasitoses são problemas de saúde pública associadas às condições socioeconômicas, principalmente pela falta de conhecimento de bons hábitos sanitários da população. Nesse ínterim, o presente trabalho objetivou a analisar prevalência de enteroparasitas em amostras fecais provenientes de pacientes da rede pública e privada da Região Metropolitana de Fortaleza -CE. A pesquisa se caracteriza em um estudo transversal, conduzido no período de abril/2014 a novembro/2016, com indivíduos provenientes da área metropolitana de Fortaleza, de ambos os sexos e diferentes faixas etárias. Do total de 6.596 amostras fecais analisadas de pacientes, 840 (12,73%) apresentaram-se positivas para diversas formas parasitárias, prevalecendo os protozoários, as espécies Endolimax nana (55,14%), Entamoeba coli (21,33%) e Giardia lamblia (13,95%) foram as mais frequentes. Seguido de nematelmintos como Ascaris lumbricoides (1,32%), Trichocephalus trichiurus (0,66%), Enterobius vermiculares (0,33%) e os platelmintos foram Hymenolepis nana (0,66%), Fasciola hepatica (0,11%) e Taenia sp. (0,11%). O número de casos positivos analisados nesta pesquisa, induz à necessidade da elaboração de políticas públicas, além de programas de educação e conscientização, principalmente para as populações carentes, com o intuito de amenizar a incidência e os impactos causados por enteroparasitoses.Palavras-chave: Protozoário; Helminto; Fezes. ABSTRACTPrevalence of parasitic diseases in the metropolitan region of Fortaleza in Ceará. Parasitic diseases are public health problems associated with socioeconomic conditions, mainly due to a lack of knowledge of good sanitary habits of a population. In this context, the present study aimed to analyze the prevalence of parasitic diseases in fecal samples from patients of the public and private network of the Metropolitan Region of Fortaleza -Ce. The research is characterized as a cross-sectional study, carried out from April 2014 to November 2016, with individuals from the metropolitan region of Fortaleza, of both sexes and different age groups. From the total of 6,596 fecal samples analyzed, 840 (12.73%) were positive for several parasite forms, with the prevalence of protozoa, Endolimax nana (55.14%), Entamoeba coli (21.33%) and Giardia lamblia (13.95%) were the most frequent. It was followed by nematelmines such as Ascaris lumbricoides (1.32%), Trichocephalus trichiurus (0.66%), Enterobius vermicularis (0.33%) and flatworms were Hymenolepis nana (0.66%), Fasciola hepatica (0.11%) and Taenia sp. (0.11%). The number of positive cases analyzed in this research leads to the need for public policies, as well as education and awareness programs, especially for the poor people in order to reduce the incidence and impacts caused by parasitic diseases.
O câncer de colo do útero é considerado um problema de saúde pública no Brasil e no mundo. Sua incidência vem regredindo nos últimos anos, porém, a taxa de mortalidade ainda permanece alta. A doença se caracteriza pelo desenvolvimento de tumores a partir de alterações celulares na cérvice uterina, que podem ter início com uma simples lesão de baixo grau, ou até mesmo progredir lentamente até atingir estágios mais avançados da doença, tais como as de caráter maligno. O trabalho teve como objetivo investigar a incidência de laudos com diagnóstico compatível ao ASC-US entre os laudos citológicos alterados e não alterados em um Laboratório da rede privada de Anatomia Patológica, localizado na cidade de Fortaleza, Ce. O<strong> </strong>estudo é do tipo descritivo, transversal, retrospectivo, onde foi avaliada a frequência de laudos citopatológicos com resultados equivalentes a ASC-US, usando como banco de dados os registros do laboratório privado durante os anos de 2016 e 2017. Os resultados obtidos: a frequência de exames citopatológicos com diagnóstico de ASC-US foi de 33,58%, entre o total de exames alterados, e de 3,29 considerando o valor total de citologias analisadas. Tais resultados se assemelham aos encontrados em estudo realizado no Serviço Integrado Tecnológico em Citologia do INCA, onde dentre os exames com alterações, 44,7% eram ASC-US e entre todos os exames processados apenas 2,59% dos resultados se referiam ao ASC-US. Conclui-se que a prevalência de células escamosas atípicas de significado indeterminado (ASC-US), no laboratório, foi de 3,29%, não ultrapassando os 5% recomendados no sistema Bethesda.
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