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1.
Mycoses ; 64(6): 616-623, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33555073

RESUMO

BACKGROUND: The genus Blastobotrys consists of at least 20 species. Disease in humans has been reported with B adeninivorans, B raffinosifermentans, B proliferans and B serpentis, mostly in immunocompromised patients and those with cystic fibrosis. OBJECTIVE: We report a lung infection secondary to B raffinosifermentans in a cystic fibrosis patient successfully treated with isavuconazole and review the literature of invasive infections caused this genus. We also evaluated clinical isolates in our laboratory for species identification and antifungal susceptibility. METHODS: Phylogenetic analysis was performed on a collection of 22 Blastobotrys isolates in our reference laboratory, and antifungal susceptibility patterns were determined for nine clinically available antifungals against 19 of these isolates. RESULTS: By phylogenetic analysis, 21 of the 22 isolates in our collection were identified as B raffinosifermentans and only 1 as B adeninivorans. Most were cultured from the respiratory tract, although others were recovered from other sources, including CSF and blood. Isavuconazole, caspofungin and micafungin demonstrated the most potent in vitro activity, followed by amphotericin B. In contrast, fluconazole demonstrated poor activity. The patient in this case responded to isavuconazole treatment for breakthrough infection due to B raffinosifermentans that was cultured from pleural fluid while on posaconazole prophylaxis post-bilateral lung transplantation for cystic fibrosis. CONCLUSIONS: Blastobotrys species are rare causes of infections in humans and primarily occur in immunocompromised hosts. In our collection, the majority of isolates were identified as B raffinosifermentans. To our knowledge, this is the first report of successful treatment of such an infection with isavuconazole.


Assuntos
Fibrose Cística/complicações , Nitrilas/uso terapêutico , Pneumonia , Piridinas/uso terapêutico , Saccharomycetales , Triazóis/uso terapêutico , Adulto , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Fibrose Cística/microbiologia , Feminino , Fluconazol/uso terapêutico , Genes Fúngicos , Humanos , Terapia de Imunossupressão/efeitos adversos , Testes de Sensibilidade Microbiana , Micoses/complicações , Micoses/tratamento farmacológico , Filogenia , Pneumonia/tratamento farmacológico , Pneumonia/microbiologia , Pneumonia/patologia , Saccharomycetales/genética , Saccharomycetales/isolamento & purificação , Saccharomycetales/patogenicidade
2.
J Transl Med ; 18(1): 205, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32430070

RESUMO

The COVID-19 pandemic has become the leading societal concern. The pandemic has shown that the public health concern is not only a medical problem, but also affects society as a whole; so, it has also become the leading scientific concern. We discuss in this treatise the importance of bringing the world's scientists together to find effective solutions for controlling the pandemic. By applying novel research frameworks, interdisciplinary collaboration promises to manage the pandemic's consequences and prevent recurrences of similar pandemics.


Assuntos
Pesquisa Biomédica/organização & administração , Infecções por Coronavirus/epidemiologia , Prestação Integrada de Cuidados de Saúde/organização & administração , Emergências , Necessidades e Demandas de Serviços de Saúde , Pandemias , Pneumonia Viral/epidemiologia , Betacoronavirus/patogenicidade , Pesquisa Biomédica/métodos , COVID-19 , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , Prestação Integrada de Cuidados de Saúde/métodos , História do Século XXI , Humanos , Comunicação Interdisciplinar , Estudos Interdisciplinares , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Saúde Pública/história , Saúde Pública/normas , SARS-CoV-2
3.
Anticancer Agents Med Chem ; 19(17): 2140-2153, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31736448

RESUMO

BACKGROUND: Green synthesis of silver nanoparticles (AgNPs) is limited to produce AgNPs with only relatively low concentrations, and is unsuitable for large-scale productions. The use of Myrtus communis (MC) leaf methanolic extract (rich in hydrolyzable tannins) has been recommended to resolve the issues related to the aggregation of nanoparticles at high concentrations of silver ions with added facet of antioxidant properties. METHODS: The produced highly concentrated MC-AgNPs were characterized by using imaging and spectroscopic methods. Subsequently, antioxidant, anticancer and antifungal activities of the nanoparticles were evaluated. RESULTS: The thermogravimetric analysis and energy dispersive spectroscopy quantitative results suggested that the nanoparticles are biphasic in nature (bio-molecule + Ag0) and layered in structure, suggesting the formation of nanoparticles through a different mechanism than those described in the literature. MC-AgNPs showed greater scavenging activity of nitric oxide and iron (II) chelating ability than the extract. It also showed good reducing power compared to the standard antioxidant. Remarkable anticancer activity of MC-AgNPs (IC50 = 5.99µg/mL) was found against HCT-116 (human colon carcinoma) cell lines after 24h exposure with a therapeutic index value 2-fold higher than the therapeutic index of standard doxorubicin. Furthermore, distinct antifungal activity (MIC = 4µg/mL) was found against Candida krusei. CONCLUSION: The current method outperforms the existing methods because it produces a large amount of multifunctional nanoscale hybrid materials more efficiently using natural sources; thus, it may be used for diverse biomedical applications.


Assuntos
Antifúngicos/farmacologia , Antioxidantes/farmacologia , Candida/efeitos dos fármacos , Nanopartículas/química , Prata/farmacologia , Antifúngicos/química , Antioxidantes/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Íons/química , Íons/farmacologia , Testes de Sensibilidade Microbiana , Oxirredução , Prata/química
4.
Bioorg Med Chem ; 23(7): 1481-91, 2015 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-25740636

RESUMO

In order to find new azole antifungals, we have recently designed a series of triazole alcohols in which one of the 1,2,4-triazol-1-yl group in fluconazole structure has been replaced with 4-amino-5-aryl-3-mercapto-1,2,4-triazole motif. In this paper, we focused on the structural refinement of the primary lead, by removing the amino group from the structure to achieve 5-aryl-3-mercapto-1,2,4-triazole derivatives 10a-i and 11a-i. The in vitro antifungal susceptibility testing of title compounds demonstrated that most compounds had potent inhibitory activity against Candida species. Among them, 5-(2,4-dichlorophenyl)triazole analogs 10h and 11h with MIC values of <0.01 to 0.5µg/mL were 4-256 times more potent than fluconazole against Candida species.


Assuntos
Antifúngicos/síntese química , Fluconazol/análogos & derivados , Fluconazol/síntese química , Triazóis/síntese química , Antifúngicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Fluconazol/farmacologia , Células Hep G2 , Humanos , Testes de Sensibilidade Microbiana , Triazóis/farmacologia
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