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Combination Efficacy of Voriconazole and Amphotericin B in the Experimental Disease in Immunodeficient Mice Caused by Fluconazole-resistant Cryptococcus neoformans

SILVA, Eriques Goncalves; PAULA, Claudete Rodrigues; DIAS, Amanda Latercia Tranches; CHANG, Marilene Rodrigues; RUIZ, Luciana da Silva; GAMBALE, Valderez; PRATES, Renato Araujo; RIBEIRO, Martha Simoes
Fonte: SPRINGER Publicador: SPRINGER
Tipo: Artigo de Revista Científica
Português
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66.33%
The therapeutic efficacy of amphotericin B and voriconazole alone and in combination with one another were evaluated in immunodeficient mice (BALB/c-SCID) infected with a fluconazole-resistant strain of Cryptococcus neoformans var. grubii. The animals were infected intravenously with 3 x 10(5) cells and intraperitoneally treated with amphotericin B (1.5 mg/kg/day) in combination with voriconazole (40 mg/kg/days). Treatment began 1 day after inoculation and continued for 7 and 15 days post-inoculation. The treatments were evaluated by survival curves and yeast quantification (CFUs) in brain and lung tissues. Treatments for 15 days significantly promoted the survival of the animals compared to the control groups. Our results indicated that amphotericin B was effective in assuring longest-term survival of infected animals, but these animals still harbored the highest CFU of C. neoformans in lungs and brain at the end of the experiment. Voriconazole was not as effective alone, but in combination with amphotericin B, it prolonged survival for the second-longest time period and provided the lowest colonization of target organs by the fungus. None of the treatments were effective in complete eradication of the fungus in mice lungs and brain at the end of the experiment.; FAPESP; Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); CNPq

In vitro sensitivity of Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis Brazilian isolates to meglumine antimoniate and amphotericin B

ZAULI-NASCIMENTO, Rogeria C.; MIGUEL, Danilo C.; YOKOYAMA-YASUNAKA, Jenicer K. U.; PEREIRA, Ledice I. A.; OLIVEIRA, Milton A. Pelli de; RIBEIRO-DIAS, Fatima; DORTA, Miriam L.; ULIANA, Silvia R. B.
Fonte: WILEY-BLACKWELL PUBLISHING, INC Publicador: WILEY-BLACKWELL PUBLISHING, INC
Tipo: Artigo de Revista Científica
Português
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76.29%
Resistance of Leishmania parasites to specific chemotherapy has become a well-documented problem in the Indian subcontinent in recent years but only a few studies have focused on the susceptibility of American Leishmania isolates. Our susceptibility assays to meglumine antimoniate were performed against intracellular amastigotes after standardizing an in vitro model of macrophage infection appropriate for Leishmania (Viannia) braziliensis isolates. For the determination of promastigote susceptibility to amphotericin B, we developed a simplified MTT-test. The sensitivity in vitro to meglumine antimoniate and amphotericin B of 13 isolates obtained from Brazilian patients was determined. L. (V.) braziliensis isolates were more susceptible to meglumine antimoniate than Leishmania (Leishmania) amazonensis. EC(50), EC(90) and activity indexes (calculated over the sensitivity of reference strains), suggested that all isolates tested were susceptible in vitro to meglumine antimoniate, and did not show association with the clinical outcomes. Isolates were also uniformly susceptible in vitro to amphotericin B.; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP); Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Voriconazole, Combined with Amphotericin B, in the Treatment for Pulmonary Cryptococcosis Caused by C. neoformans (Serotype A) in Mice with Severe Combined Immunodeficiency (SCID)

Silva, Eriques Goncalves; Paula, Claudete Rodrigues; Baroni, Francisco de Assis; Gambale, Walderez
Fonte: SPRINGER; DORDRECHT Publicador: SPRINGER; DORDRECHT
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
66.33%
Cryptococcosis is a subacute or chronic systemic mycosis with a cosmopolitan nature, caused by yeast of the genus Cryptococcus neoformans. The model of systemic cryptococcosis in mice with severe combined immunodeficiency (SCID) is useful for immunological and therapeutic study of the disease in immunodeficient hosts. Amphotericin B, fluconazole and flucytosine are the drugs most commonly used to treat cryptococcosis. Voriconazole is a triazole with high bioavailability, large distribution volume, and excellent penetration of the central nervous system. The objective of this study was to evaluate treatment with amphotericin B (AMB), voriconazole (VRC), and AMB, used in combination with VRC, of experimental pulmonary cryptococcosis in a murine model (SCID). The animals were inoculated intravenously (iv) with a solution containing 3.0 x 10(5) viable cells of C. neoformans ATCC 90112, (serotype A). Treatments were performed with amphotericin B (1.5 mg/kg/day), voriconazole (40.0 mg/kg/day) and AMB (1.5 mg/kg/day) combined with VRC (40.0 mg/kg/day); began 1 day after the initial infection; were daily; and lasted 15 days. Evaluations were performed using analysis of the survival curve and isolation of yeast in the lung tissue. There was a significant increase in survival in groups treated with AMB combined with VRC...

Nefrotoxicidade associada à anfotericina B em pacientes de baixo risco; Amphotericin B-related nephrotoxicity in low-risk patients

Berdichevski, Roberto Herz
Fonte: Universidade Federal do Rio Grande do Sul Publicador: Universidade Federal do Rio Grande do Sul
Tipo: Dissertação Formato: application/pdf
Português
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66.4%
Introdução: A anfotericina B é a droga de escolha para o tratamento de doenças fúngicas severas, estando associada, no entanto, a alta incidência de nefrotoxicidade. O uso de anfotericinas modificadas está associado a elevado custo. Em grupos de baixo risco o uso de sobrecarga hidrossalina pode ser suficiente para evitar perda severa de função renal. Métodos: Foram estudados prospectivamente pacientes internados em hospital universitário, com idade superior a 12 anos, e que estavam dentro das primeiras 24 horas de uso de anfotericina B. Foram excluídos pacientes em centros de terapia intensiva e que estivessem em uso de drogas vasoativas. Solução salina 0,9% (500 ml) foi infundida antes e após a anfotericina B. Foram coletados exames na inclusão e no término do tratamento. A dosagem de creatinina sérica foi repetida após 30 dias do término do tratamento. Resultados: Foram estudados 48 pacientes. A média de elevação da creatinina sérica foi de 0,3 (0,18-0,41) mg/dl., representando um decréscimo médio de 25 (12,8-36,9) ml/min na depuração de creatinina endógena (DCE). Insuficiência renal aguda (IRA), definida pela elevação maior do que 50% da creatinina basal, ocorreu em 15 pacientes (31,3%). Pacientes que utilizaram antibióticos e aqueles em status pós-quimioterapia ou submetidos a transplante de medula óssea foram os que apresentaram maior risco de desenvolverem IRA. A creatinina e a DCE após 30 dias do término do tratamento não diferiram de seus valores basais. Conclusão: Em pacientes de baixo risco...

Amphotericin B mediates killing in Cryptococcus neoformans through the induction of a strong oxidative burst

Sangalli-Leite, Fernanda; Scorzoni, Liliana; Cecilia Mesa-Arango, Ana; Casas, Celia; Herrero, Enrique; Mendes Giannini, Maria José Soares; Luis Rodriguez-Tudela, Juan; Cuenca-Estrella, Manuel; Zaragoza, Oscar
Fonte: Elsevier B.V. Publicador: Elsevier B.V.
Tipo: Artigo de Revista Científica Formato: 457-467
Português
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76.24%
We studied the effects of Amphotericin B (AmB) on Cryptococcus neoformans using different viability methods (CFUs enumeration, XTT assay and propidium iodide permeability). After 1 h of incubation, there were no viable colonies when the cells were exposed to AmB concentrations >= 1 mg/L. In the same conditions, the cells did not become permeable to propidium iodide, a phenomenon that was not observed until 3 h of incubation. When viability was measured in parallel using XTT assay, a result consistent with the CFUs was obtained, although we also observed a paradoxical effect in which at high AmB concentrations, a higher XTT reduction was measured than at intermediate AmB concentrations. This paradoxical effect was not observed after 3 h of incubation with AmB, and lack of XTT reduction was observed at AmB concentrations higher than 1 mg/L. When stained with dihydrofluorescein, AmB induced a strong intracellular oxidative burst. Consistent with oxidative damage, AmB induced protein carbonylation. Our results indicate that in C. neoformans, Amphotericin B causes intracellular damage mediated through the production of free radicals before damage on the cell membrane, measured by propidium iodide uptake. (C) 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Amphotericin B Microemulsion Reduces Toxicity and Maintains the Efficacy as an Antifungal Product

Damasceno, Bolivar P. G. L.; Dominici, Victor A.; Urbano, Isabel A.; Silva, Joso A.; Araujo, Ivonete B.; Santos-Magalhaes, Nereide S.; Silva, Amanda K. A.; Medeiros, Aldo C.; Oliveira, Anselmo Gomes de; Egito, E. Socrates T.
Fonte: Amer Scientific Publishers Publicador: Amer Scientific Publishers
Tipo: Artigo de Revista Científica Formato: 290-300
Português
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76.44%
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); Amphotericin B remains the drug of choice for the treatment of most of the systemic fungal infections in immunodeficient patients. Because of the high incidence of adverse drug reactions the clinical use of Amphotericin B is rather limited. To reduce its toxicity new drug delivery systems has been suggested. Nevertheless, these carriers present several technological drawbacks that impair the development of a marketable product. The aim of this work was to develop an Amphotericin B microemulsion in order to increase its efficacy and decrease its toxicity compared to Fungizon (TM), the widely know inexpensive micellar system of Amphotericin B. Amphotericin B loaded microemulsion showed an average size close to 300 nm by photon correlation spectroscopy. In the UV spectrum, the observation of the monomeric peak at 405 nm, which was independent of the sample dilution, revealed that the Amphotericin B molecules were strongly and individually bound to the microemulsion droplets. The new microemulsion formulation had the same efficacy than Fungizon (TM) against C. albicans. Concerning toxicity, Amphotericin B loaded microemulsion showed lower toxicity against human red blood cells compared to the commercial product. Taken together...

Structural Properties Induced by the Composition of Biocompatible Phospholipid-Based Microemulsion and Amphotericin B Association

Franzini, Cristina Maria; Pestana, Kelly Christina; Molina, Eduardo Ferreira; Scarpa, Maria Virginia; Tabosa do Egito, Eryvaldo Socrates; Oliveira, Anselmo Gomes de
Fonte: Amer Scientific Publishers Publicador: Amer Scientific Publishers
Tipo: Artigo de Revista Científica Formato: 350-359
Português
Relevância na Pesquisa
66.38%
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); Anionic microemulsions (MEs) containing soya phosphatidylcholine, Tween-20, sodium oleate as surfactant, and cholesterol as oil phase were investigated as drug carriers for amphotericin B. Depending on the composition of the microemulsion, various structures, which differently interact with amphotericin B, can be formed. The nanostructured systems were characterized by photon correlation spectroscopy, rheological behavior, and polarized light microscopy. The results reveal that the droplet diameters increased with amphotericin B incorporation for all ranges of surfactant and oil phase. For both amphotericin B-unloaded and amphotericin B-loaded microemulsions, the profile of the oil droplet diameter decreased with increasing the surfactant concentration, demonstrating the stabilizing effect of the surfactant. The increase in the oil phase proportions led to the growth of the droplet diameter, clearly demonstrating the limit of the surfactant organization in the oil-water interface. The amphotericim B incorporation into microemulsion increased with the fraction volume of the oil phase and the surfactant concentration reaching a plateau at high contents. This profile could be quantitatively analyzed by the framework of the pseudo-phase model that considers the amphotericim B distribution between the oil and the aqueous phases. The rheological analysis showed a pseudoplastic behavior with little thixotropic characteristic. Under polarized light...

Microdilution procedure for antifungal susceptibility testing of Paracoccidioides brasiliensis to amphotericin B and itraconazole

Takahagi-Nakaira, E.; Sugizaki, M. F.; Peracoli, M. T. S.
Fonte: Universidade Estadual Paulista (UNESP), Centro de Estudos de Venenos e Animais Peçonhentos (CEVAP) Publicador: Universidade Estadual Paulista (UNESP), Centro de Estudos de Venenos e Animais Peçonhentos (CEVAP)
Tipo: Artigo de Revista Científica Formato: 718-731
Português
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66.33%
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Processo FAPESP: 02/12462-4; Processo FAPESP: 03/12743-0; In vitro tests employing microdilution to evaluate fungal susceptibility to antifungal drugs are already standardized for fermentative yeasts. However, studies on the susceptibility of dimorphic fungi such as Paracoccidioides brasiliensis employing this method are scarce. The present work introduced some modifications into antifungal susceptibility testing from the European Committee on Antimicrobial Susceptibility Testing (EUCAST), concerning broth medium and reading time, to determine minimal inhibitory concentration (MIC) of amphotericin B and itraconazole against Paracoccidioides brasiliensis. Yeast-like cells of P. brasiliensis (Pb18 strain) were tested for susceptibility to amphotericin B and itraconazole in RPMI 1640 medium, supplemented with 2% glucose and nitrogen source and incubated at 35 degrees C. The MIC of amphotericin B and itraconazole against Pb18 were respectively 0.25 mu g/mL and 0.002 mu g/mL. The results of minimal fungicidal concentration (MFC) showed that amphotericin B at 0.25 mu g/mL or higher concentrations displayed fungicidal activity against Pb18 while itraconazole at least 0.002 mu g/mL has a fungistatic effect on P. brasiliensis. In conclusion...

Oil-in-water lecithin-based microemulsions as a potential delivery system for amphotericin B

Pestana, K. C.; Formariz, T. P.; Franzini, C. M.; Sarmento, V. H. V.; Chiavacci, L. A.; Scarpa, M. V.; Egito, E. S. T.; Oliveira, Anselmo Gomes de
Fonte: Elsevier B.V. Publicador: Elsevier B.V.
Tipo: Artigo de Revista Científica Formato: 253-259
Português
Relevância na Pesquisa
76.17%
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); In this work the structural features of microemulsions (MEs) containing the pharmaceutical biocompatible Soya phosphatidylcholine/Tween 20 (1:1) as surfactant (S), Captex(TM) 200 as oil phase (0), and phosphate buffer 10mM, pH 7.2 as aqueous phase (W) were Studied. Systems obtained with different proportions of the components were described by pseudo-ternary phase diagrams in order to characterize the microemulsions studied here. MEs were prepared with and without the polyene antifungal drug amphotericin B (AmB). The maximum AmB incorporation into the ME system was dependent on both the oil phase and surfactant proportions with 6.80 and 5.7 mg/mL in high contents, respectively. The incorporation of AmB into the ME systems significantly increased the profile of the droplet size of the ME for all ranges of surfactant proportions used in the formulations. The microstructures of the system were characterized by dynamic light scattering (DLS) and theological behavior. The DLS results showed that the size of the oil droplets increases 4.6-fold when AmB is incorporated into the ME system. In all cases the increase in the proportion of the oil phase of the ME leads to a slight increase in the diameter of the oil droplets of the system. Furthermore...

It only takes one to do many jobs: Amphotericin B as antifungal and immunomodulatory drug

Mesa-Arango, Ana C.; Scorzoni, Liliana; Zaragoza, Oscar
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
66.33%
Amphotericin B acts through pore formation at the cell membrane after binding to ergosterol is an accepted dogma about the action mechanism of this antifungal, and this sentence is widely found in the literature. But after 60 years of investigation, the action mechanism of Amphotericin B is not fully elucidated. Amphotericin B is a polyene substance that is one of the most effective drugs for the treatment of fungal and parasite infections. As stated above, the first mechanism of action described was pore formation after binding to the ergosterol present in the membrane. But it has also been demonstrated that AmB induces oxidative damage in the cells. Moreover, amphotericin B modulates the immune system, and this activity has been related to the protective effect of the molecule, but also to its toxicity in the host. This review tries to provide a general overview of the main aspects of this molecule, and highlight the multiple effects that this molecule has on both the fungal and host cells. © 2012 Mesa-Arango, Scorzoni and Zaragoza.

Influence of the Freeze-Drying Process on the Physicochemical and Biological Properties of Pre-heated Amphotericin B Micellar Systems

Siqueira, Scheyla D. V. S.; Silva-Filho, Miguel A.; Silva, Christian A.; Araujo, Ivonete B.; Silva, Acarilia E.; Fernandes-Pedrosa, Matheus F.; Oliveira, Anselmo Gomes de; Egito, E. Socrates T.
Fonte: Springer Publicador: Springer
Tipo: Artigo de Revista Científica Formato: 612-619
Português
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76.16%
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); The moderate heat treatment of amphotericin B (AmB) in its micellar form (M-AmB) results in superaggregates (H-AmB) that present a substantially lower toxicity and similar activity. The aim of this work was to evaluate the H-AmB behavior after a freeze-drying process. H-AmB and M-AmB micelles were evaluated before and after freeze-drying concerning their physicochemical and biological properties by spectrophotometry and activity/toxicity assay, respectively. Four concentrations of M-AmB and H-AmB were studied aiming to correlate their aggregation state and the respective biological behavior: 50 mg L-1, 5 mg L-1, 0.5 mg L-1, and 0.05 mg L-1. Then, potassium leakage and hemoglobin leakage from red blood cells were used to evaluate the acute and chronic toxicity, respectively. The efficacy of M-AmB and H-AmB formulations was assessed by potassium leakage from Candida albicans and by the broth microdilution method. After heating, in addition to an evident turbidity, a slight blueshift from 327 to 323 nm was also observed at the concentrations of 50 and 5 mg L-1 for H-AmB. Additionally, an increase in the absorbance at 323 nm at the concentration of 0.5 mg L-1 was detected. Concerning the toxicity...

Radiometric detection of metabolic activity of Paracoccidioides brasiliensis and its susceptibility to amphotericin B and diethylstilbestrol

Camargo,Edwaldo E.; Sato,Maria K.; Del Negro,Gilda M. B.; Lacaz,Carlos da Silva
Fonte: Instituto de Medicina Tropical Publicador: Instituto de Medicina Tropical
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/10/1987 Português
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Paracoccidioidomycosis (South American blastomycosis) is a systemic disease, strikingly more frequent in males, caused by the dimorphic fungus Paracoccidioides brasiliensis. A radiometric assay system has been applied to study the metabolic activity and the effect of drugs on this fungus "in vitro". The Y form of the yeast, grown in liquid Sabouraud medium was inoculated into sterile reaction vials containing the 6B aerobic medium along with 2.0 μCi of 14C-substrates. Control vials, prepared in the same way, contained autoclaved fungi. To study the effects of amphotericin B (AB) (0.1 and 10 μg/ml) and diethylstilbestrol (DSB) (1.0, 5.0 and 10 μg/ml) extra controls with live fungi and no drug were used. All vials were incubated at 35°C and metabolism measured daily with a Bactec instrument. 14CO2 production by P. brasiliensis was slow and could be followed for as long as 50 days. AB at 10mg/ml and DSB at 5 μg/ml inhibited the metabolism and had a cidal effect on this fungus. The results with DSB might explain the low incidence of the disease in females. This technique shows promise for studying metabolic pathways, investi gating more convenient 14C-substrates to expedite radiometric detection and for monitoring the effects of other drugs and factors on the metabolism of P. brasiliensis "in vitro".

Mutants with heteroresistance to amphotericin B and fluconazole in Candida

Claudino,A.L.R.; Peixoto Junior,R.F.; Melhem,M.S.C.; Szeszs,M.W.; Lyon,J.P.; Chavasco,J.K.; Franco,M.C.
Fonte: Sociedade Brasileira de Microbiologia Publicador: Sociedade Brasileira de Microbiologia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/12/2009 Português
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66.4%
Several studies have reported the occurrence of infections caused by Candida yeasts as well as the increasing prevalence of non albicans species. The aim of the present work is focused on the obtaining of heteroresistance to amphotericin B and fluconazole in Candida species using two distinct methodologies: selection and induction. Resistant samples were obtained by selective pressure using a medium with fluconazole for growth, followed by growth in a medium with amphotericin B. The selective pressure was also created beginning with growth in amphotericin B medium followed by growth in fluconazole medium. Concomitantly, samples were submitted to the induction of resistance through cultivation in increasing concentrations of fluconazole, followed by cultivation in increasing concentrations of amphotericin B. Subsequently, the induction began with amphotericin B followed by fluconazole. Three samples resistant to fluconazole and amphotericin B were obtained, two by induction (C. glabrata and C. tropicalis) and one by selection (C. tropicalis). Both C. tropicalis originated from the same wild sample. After successive transfers for drug free medium, only the sample obtained by selection was able to maintain the resistance phenotype. These results suggest that the phenotype of heteroresitance to fluconazole and amphotericin B can be produced by two methodologies: selection and induction.

Microdilution procedure for antifungal susceptibility testing of Paracoccidioides brasiliensis to amphotericin b and itraconazole

Takahagi-Nakaira,E; Sugizaki,MF; Peraçoli,MTS
Fonte: Centro de Estudos de Venenos e Animais Peçonhentos - CEVAP, Universidade Estadual Paulista - UNESP Publicador: Centro de Estudos de Venenos e Animais Peçonhentos - CEVAP, Universidade Estadual Paulista - UNESP
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2009 Português
Relevância na Pesquisa
66.33%
In vitro tests employing microdilution to evaluate fungal susceptibility to antifungal drugs are already standardized for fermentative yeasts. However, studies on the susceptibility of dimorphic fungi such as Paracoccidioides brasiliensis employing this method are scarce. The present work introduced some modifications into antifungal susceptibility testing from the European Committee on Antimicrobial Susceptibility Testing (EUCAST), concerning broth medium and reading time, to determine minimal inhibitory concentration (MIC) of amphotericin B and itraconazole against Paracoccidioides brasiliensis. Yeast-like cells of P. brasiliensis (Pb18 strain) were tested for susceptibility to amphotericin B and itraconazole in RPMI 1640 medium, supplemented with 2% glucose and nitrogen source and incubated at 35°C. The MIC of amphotericin B and itraconazole against Pb18 were respectively 0.25 µg/mL and 0.002 µg/mL. The results of minimal fungicidal concentration (MFC) showed that amphotericin B at 0.25 µg/mL or higher concentrations displayed fungicidal activity against Pb18 while itraconazole at least 0.002 µg/mL has a fungistatic effect on P. brasiliensis. In conclusion, our results showed that the method employed in the present study is reproducible and reliable for testing the susceptibility of P. brasiliensis to antifungal drugs.

Multicenter evaluation of a new disk agar diffusion method for susceptibility testing of filamentous fungi with voriconazole, posaconazole, itraconazole, amphotericin B, and caspofungin

Espinel-Ingroff, A.; Arthington-Skaggs, B.; Iqbal, N.; Ellis, D.; Pfaller, M.; Messer, S.; Rinaldi, M.; Fothergill, A.; Gibbs, D.; Wang, A.
Fonte: Amer Soc Microbiology Publicador: Amer Soc Microbiology
Tipo: Artigo de Revista Científica
Publicado em //2007 Português
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76.25%
The purpose of this study was to correlate inhibition zone diameters, in millimeters (agar diffusion disk method), with the broth dilution MICs or minimum effective concentrations (MECs) (CLSI M38-A method) of five antifungal agents to identify optimal testing guidelines for disk mold testing. The following disk diffusion testing parameters were evaluated for 555 isolates of the molds Absidia corymbifera, Aspergillus sp. (five species), Alternaria sp., Bipolaris spicifera, Fusarium sp. (three species), Mucor sp. (two species), Paecilomyces lilacinus, Rhizopus sp. (two species), and Scedosporium sp. (two species): (i) two media (supplemented Mueller-Hinton agar [2% dextrose and 0.5 µg/ml methylene blue] and plain Mueller-Hinton [MH] agar), (ii) three incubation times (16 to 24, 48, and 72 h), and (iii) seven disks (amphotericin B and itraconazole 10-µg disks, voriconazole 1- and 10-µg disks, two sources of caspofungin 5-µg disks [BBL and Oxoid], and posaconazole 5-µg disks). MH agar supported better growth of all of the species tested (24 to 48 h). The reproducibility of zone diameters and their correlation with either MICs or MECs (caspofungin) were superior on MH agar (91 to 100% versus 82 to 100%; R, 0.71 to 0.93 versus 0.53 to 0.96 for four of the five agents). Based on these results...

Cryptococcus neoformans-Cryptococcus gattii Species Complex: an International Study of Wild-Type Susceptibility Endpoint Distributions and Epidemiological Cutoff Values for Amphotericin B and Flucytosine

Espinel-Ingroff, A.; Chowdhary, A.; Cuenca-Estrella, M.; Fothergill, A.; Fuller, J.; Hagen, F.; Govender, N.; Guarro, J.; Johnson, E.; Lass-Florl, C.; Lockhart, S.; Martins, M.; Meis, J.; Melhem, M.; Ostrosky-Zeichner, L.; Pelaez, T.; Pfaller, M.; Schell,
Fonte: Amer Soc Microbiology Publicador: Amer Soc Microbiology
Tipo: Artigo de Revista Científica
Publicado em //2012 Português
Relevância na Pesquisa
66.38%
Clinical breakpoints (CBPs) are not available for the Cryptococcus neoformans-Cryptococcus gattii species complex. MIC distributions were constructed for the wild type (WT) to establish epidemiologic cutoff values (ECVs) for C. neoformans and C. gattii versus amphotericin B and flucytosine. A total of 3,590 amphotericin B and 3,045 flucytosine CLSI MICs for C. neoformans (including 1,002 VNI isolates and 8 to 39 VNII, VNIII, and VNIV isolates) and 985 and 853 MICs for C. gattii, respectively (including 42 to 259 VGI, VGII, VGIII, and VGIV isolates), were gathered in 9 to 16 (amphotericin B) and 8 to 13 (flucytosine) laboratories (Europe, United States, Australia, Brazil, Canada, India, and South Africa) and aggregated for the analyses. Additionally, 442 amphotericin B and 313 flucytosine MICs measured by using CLSI-YNB medium instead of CLSI-RPMI medium and 237 Etest amphotericin B MICs for C. neoformans were evaluated. CLSI-RPMI ECVs for distributions originating in ≥3 laboratories (with the percentages of isolates for which MICs were less than or equal to ECVs given in parentheses) were as follows: for amphotericin B, 0.5 μg/ml for C. neoformans VNI (97.2%) and C. gattii VGI and VGIIa (99.2 and 97.5%, respectively) and 1 μg/ml for C. neoformans (98.5%) and C. gattii nontyped (100%) and VGII (99.2%) isolates; for flucytosine...

NANOPARTÍCULAS MAGNÉTICAS FUNCIONALIZADAS COM BICAMADAS DE LAURATO/LAURATO E LAURATO/PLURONIC: ESTUDO DA ASSOCIAÇÃO COM ANFOTERICINA; MAGNETIC NANOPARTICLES FUNCTIONALIZED WITH AMPHOTERICIN B OF BILAYERS LAURATE/LAURATE AND LAURATE/PLURONIC: STUDY OF THE ASSOCIATION WITH AMPHOTERICIN B

SILVA, Joel Rocha da
Fonte: Universidade Federal de Goiás; BR; UFG; Mestrado em Química; Educação em Química Publicador: Universidade Federal de Goiás; BR; UFG; Mestrado em Química; Educação em Química
Tipo: Dissertação Formato: application/pdf
Português
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66.35%
Magnetite nanoparticles were prepared by the coprecipitation of ions Fe2+ and Fe3+ using ammonia solution as precipitating agent. Maghemite nanoparticles were prepared by forced oxidation of magnetite nanoparticles in acidic medium using nitrate ions as oxidizing agent. The magnetic nanoparticles were used to the preparation of aqueous magnetic fluids samples by the functionalization of the nanoparticles with bilayers of laurate/laurate and laurate/Pluronic. Aliquots of the magnetic fluids were dried and the resultant powders were characterized by chemical analysis (the contents of ions Fe2+ and Fe3+), X-ray powder diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). The contents of ions Fe2+ and Fe3+ in all the samples showed that the nanoparticles are not pure magnetite or maghemite phases. X-ray powder diffraction (XRD) indicated the existence of inverse cubic spinel phase, but didn't permit the distinction between magnetite and maghemite phases. Based on the results of chemical and XRD analyses, the nanoparticles could be better characterized as reduced maghemite, which mean maghemite phase containing ions Fe2+. The average sizes of the oxide nanoparticles estimated by XRD were around of 10 nm. FTIR analyses showed that the nanoparticles were functionalized with bilayers of laurate/laurate and laurate/Pluronic. FTIR analyses also were indicative of the maghemite phase. The hydrodynamic size of the functionalized nanoparticles measured by PCS were in the range of 70-90 nm for the samples based on laurate and in the range of 100-200 nm for the samples containing Pluronic. The measurements of zeta potential showed that the magnetic fluids based on laurate bilayers presented better colloidal stability than that one based on bilayers of laurate/Pluronic. On the other hand...

Topical Treatment Using Amphotericin B and DMSO for an Atypically Located Equine Cutaneous Pythiosis

Martins Dias, Deborah Penteado; Sampaio Doria, Renata Gebara; Pereira, Rodrigo Norberto; Canola, Paulo Alescio; Di Filippo, Paula Alessandra
Fonte: UNIV FED RIO GRANDE DO SUL; PORTO ALEGRE RS Publicador: UNIV FED RIO GRANDE DO SUL; PORTO ALEGRE RS
Tipo: Artigo de Revista Científica
Português
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66.33%
Background: Cutaneous lesions by Pythium insidiosum infection are commonly observed in horses, especially in those living at flooded environments. Equine pythiosis is characterized by the development of tumoral masses that are frequently located at distal limbs, ventral abdomen, thorax, breast and face. The lesions are usually granulomatous, serosanguineous and ulcerated, most often destroyed by self-mutilation due to the intense pruritus. The proposed treatment includes surgical excision followed by antifungal drugs administration, which can be done systemically or topically. Amphotericin B and dimethyl sulfoxide (DMSO) in association has been successfully used for cutaneous pythiosis topical treatment due to the DMSO property to carry any substance through plasmatic membranes. Case: The present report concerns a 12-year-old mixed breed gelding presenting with self-mutilation of a tumoral mass located at the left flank. The owners reported that the horse had initially presented a small wound that had evolved to a 20-cm in diameter mass in 4 weeks. Tissue samples were collected, processed and stained by the Gomori's methenamine silver (GMS) method. The histopathological analysis revealed Pythium insidiosum hyphae in a granulomatous tissue...

Alteration in cellular viability, pro-inflammatory cytokines and nitric oxide production in nephrotoxicity generation by Amphotericin B: Involvement of PKA pathway signaling

França, F. D.; Ferreira, A. F.; Lara, R. C.; Rossoni, J. V.; Costa, D. C.; Moraes, K. C M; Tagliati, C. A.; Chaves, M. M.
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
66.36%
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); Conselho Nacional de Pesquisa (CNPq); Amphotericin B is one of the most effective antifungal agents; however, its use is often limited owing to adverse effects, especially nephrotoxicity. The purpose of this study was to evaluate the effect of inhibiting the PKA signaling pathway in nephrotoxicity using Amphotericin B from the assessment of cell viability, pro-inflammatory cytokines and nitric oxide (NO) production in LLC-PK1 and MDCK cell lines. Amphotericin B proved to be cytotoxic for both cell lines, as assessed by the mitochondrial enzyme activity (MTT) assay; caused DNA fragmentation, determined by flow cytometry using the propidium iodide (PI) dye; and activated the PKA pathway (western blot assay). In MDCK cells, the inhibition of the PKA signaling pathway (using the H89 inhibitor) caused a significant reduction in DNA fragmentation. In both cells lines the production of interleukin-6 (IL)-6 proved to be a dependent PKA pathway, whereas tumor necrosis factor-alpha (TNF-α) was not influenced by the inhibition of the PKA pathway. The NO production was increased when cells were pre-incubated with H89 followed by Amphotericin B, and this production produced a dependent PKA pathway in LLC-PK1 and MDCK cells lines. Therefore...

Detecção radiométrica da atividade metabólica do Paracoccidioides brasiliensis e da sua sensibilidade à Anfotericina B e ao Dietilestilbestrol; Radiometric detection of metabolic activity of Paracoccidioides brasiliensis and its susceptibility to amphotericin B and diethylstilbestrol

Camargo, Edwaldo E.; Sato, Maria K.; Del Negro, Gilda M. B.; Lacaz, Carlos da Silva
Fonte: Universidade de São Paulo. Instituto de Medicina Tropical de São Paulo Publicador: Universidade de São Paulo. Instituto de Medicina Tropical de São Paulo
Tipo: info:eu-repo/semantics/article; info:eu-repo/semantics/publishedVersion; ; ; ; ; Formato: application/pdf
Publicado em 01/10/1987 Português
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A paracoccidiodomicose (blastomicose sul-americana) é uma doença sistêmica muito mais freqüente no sexo masculino, causada pelo fungo dimórfico Paracoccidioides brasiliensis. Um sistema radiométrico foi utilizado para estudar a atividade metabólica e o efeito deftrogas sobre este fungo "in vitro". A forma Y do fungo, cultivada em Sabouraud líquido, foi inoculada em frascos estéreis contendo o meio aeróbio 6B, juntamente com 2,0 uCi de substâncias marcadas com carbono-14. Frascos-controle, preparados da mesma forma, foram inoculados com fungos autoclavados. Para estudar os efeitos da anfotericina B (AB) (0,1 e 10 μg/ml) e do dietilestilbestrol (DEB) (1, 5 e 10 μg/ml), controles adicionais foram preparados, contendo fungos viáveis mas não a droga. Todos os frascos foram incubados a 35°C e o metabolismo medido diariamente com uma máquina Bactec. A produção de 14CO2 pelo P. brasiliensis foi lenta e pôde ser acompanhada por 50 dias. Concentrações de 10 μg/ml de AB e 5 μg/ml de DEB inibiram o metabolismo e tiveram efeito fungicida. Os resultados com DEB poderiam explicar a baixa incidência da doença em mulheres. Esta técnica é promissora para estudar as vias metabólicas, investigar substâncias marcadas mais adequadas para tornar mais rápida a detecção radiométrica do fungo e para acompanhar os efeitos de outras drogas e fatores sobre o metabolismo do P. brasiliensis "in vitro".; Paracoccidioidomycosis (South American blastomycosis) is a systemic disease...