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2.
Braz J Microbiol ; 54(1): 531-541, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36422848

RESUMEN

The emergence of itraconazole (ITZ)-resistant Sporothrix brasiliensis in feline and canine cases in southern Brazil has hampered the clinical cure of animal sporotrichosis, encouraging the search for therapeutic alternatives. The promising use of plants extracts from Lamiaceae family is known; however, there are no studies with its major compounds, as γ-terpinene (γTER), 1,8-cineole (1,8CIN), p-coumaric acid (pCOU), and quercetin (QUER). For the first time, we evaluated the antifungal, synergistic, cytotoxic activities and action mechanism of these compounds against S. brasiliensis. For this, 28 S. brasiliensis from cats (n = 24) and dogs (n = 4) and standard strains of S. brasiliensis and S. schenckii (n = 4) were tested by M38-A2 (CLSI), revealing non-wild-type (WT) isolates to ITZ on 54.2% (13/24) and 75% (03/04) of feline and canine isolates, respectively. Of the compounds, γTER stood out against all isolates (MIC/MFC 0.75 to > 3 mg/ml; MIC50 3 mg/ml). However, 1,8CIN, pCOU, and QUER showed little or no activity (MIC50 > 3 mg/ml). Thus, γTER was selected for checkerboard assay, whose combination with ITZ showed synergistic (WT isolates) and indifferent (non-WT isolates) interaction. For action mechanism (sorbitol protection and ergosterol effect), γTER acted in membrane by complexing with fungal ergosterol and at the cell wall level, showing two possible pathways as antifungal target. Finally, cytotoxicity (MTT assay) showed that γTER was the safest compound on MDBK cells, even at a concentration of 3 mg/ml (90.16%). Our findings support that γTER is a potent antifungal candidate for the control of sporotrichosis, including against non-WT S. brasiliensis.


Asunto(s)
Sporothrix , Esporotricosis , Animales , Gatos , Perros , Itraconazol/uso terapéutico , Antifúngicos/uso terapéutico , Esporotricosis/microbiología , Quercetina/uso terapéutico , Eucaliptol/uso terapéutico , Pruebas de Sensibilidad Microbiana
5.
Braz J Microbiol ; 52(1): 73-80, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32476087

RESUMEN

INTRODUCTION: The treatment of human and animal sporotrichosis is often performed with antifungal agents; however, the emergence of antifungal-resistant strains of Sporothrix species has been reported. We aimed to discuss the ability of Sporothrix species in developing resistance to the conventional antifungals and mechanisms for this. METHODOLOGY: Published data on databases (PubMed, Science Direct, Google Scholar) were investigated using a combination of keywords from 2008 to 2019 by the StArt tool. RESULTS: The minimal inhibitory concentrations values based on the Clinical and Laboratory Standards Institute (CLSI) from eight references were classified according to the epidemiological cutoff values in wild-type or non-wild-type strains. In this way, non-wild-type S. schenckii and, mainly, S. brasiliensis isolates were recognized on itraconazole, amphotericin B, terbinafine, and voriconazole, which are strains that deserve more attention toward antifungal control, with a probable risk of mutation to antifungal resistance. Among the few reviewed studied on antifungal resistance, the melanin production capacity (DHN-melanin, L-DOPA melanin, and pyomelanin), the low genetic diversity due to the abnormal number of chromosomes, and the mutation in cytochrome P450 are some of the factors for developing resistance mechanism. CONCLUSIONS: The emergence of Sporothrix species with in vitro antifungal resistance was evidenced and the possible mechanisms for resistance development may be due to the melanin production capacity, genetic diversity and mutations in cytochrome P450. Further studies should be carried out targeting gene expression for the development of antifungal resistance on Sporothrix species in order to prospect new therapeutic targets for human and veterinary use.


Asunto(s)
Antifúngicos/farmacología , Farmacorresistencia Fúngica , Sporothrix/efectos de los fármacos , Esporotricosis/tratamiento farmacológico , Animales , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Humanos , Pruebas de Sensibilidad Microbiana , Mutación , Sporothrix/genética , Sporothrix/fisiología , Esporotricosis/microbiología
6.
Med Mycol ; 59(1): 58-66, 2021 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-32407486

RESUMEN

The number of deaths due to systemic fungal infections is increasing alarmingly, which is aggravated by the limitations of traditional treatments and multidrug resistance. Therefore, the research and development of new therapeutic options against pathogenic fungi is an urgent need. To evaluate the fungicidal activity of a synthetic compound, 1,3-bis-(3,4-dichlorophenoxy)propan-2-aminium chloride (2j), through time-kill studies and pharmacokinetics/pharmacodynamics (PK/PD) modeling. The protective effect of the compound was also evaluated using the Drosophila melanogaster minihost model of candidiasis. Mathematical modeling of time-kill data of compound 2j was performed to obtain PD characteristics. Additionally, Toll-deficient D. melanogaster flies were infected with a Candida albicans strain and treated with 2j. We observed that compound 2j demonstrated a time- and dose-dependent fungicidal effect against Candida spp. and dermatophytes, even at low concentrations, and rapidly achieved kill rates reaching the maximum effect in less than one hour. The efficacy of the compound against systemic candidiasis in D. melanogaster flies was comparable to that achieved by fluconazole. These results support the potential of compound 2j as a systemic antifungal agent candidate and serve as a starting point for further studies involving mammalian animal models.


Asunto(s)
Antifúngicos/farmacología , Candida albicans/efectos de los fármacos , Candidiasis/tratamiento farmacológico , Candidiasis/veterinaria , Drosophila melanogaster/efectos de los fármacos , Fluconazol/farmacología , Pruebas de Sensibilidad Microbiana/veterinaria , Animales , Modelos Animales de Enfermedad , Humanos , Concentración 50 Inhibidora
7.
Nat Prod Res ; 35(17): 2977-2981, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31621419

RESUMEN

Thirty Wistar rats subcutaneously infected by an itraconazole-resistant Sporothrix brasiliensis received the oral daily treatment (n = 10, each) of control (CTL, saline solution), itraconazole (ITZ, 10 mg/kg) and marjoram essential oil (MRJ, 80 mg/kg) for 30 days. Weekly, the clinical evaluation and euthanasia for histopathology and fungal burden were performed. Only animals from MRJ evolved to the remission of the cutaneous lesion with a mild to absent presence of yeasts in footpad, besides decreased the fungal burden in the systemic organs compared to CTL and ITZ (p < 0.05), preventing the fungal spread, mainly in the liver and spleen. The antifungal activity may have been attributed to the majority composition of terpinen-4-ol (34.09%), γ-terpinene (14.28%) and α-terpinene (9.6%), which the mode of action was at the level of ergosterol complexation. These findings highlighted the antifungal and the systemic protective effects of MRJ, supporting the promising use in the treatment of cutaneous sporotrichosis.


Asunto(s)
Antifúngicos/farmacología , Aceites Volátiles , Origanum , Sporothrix , Esporotricosis , Animales , Antifúngicos/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Aceites Volátiles/farmacología , Origanum/química , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Ratas , Ratas Wistar , Sporothrix/efectos de los fármacos , Esporotricosis/tratamiento farmacológico
10.
Mycopathologia ; 185(4): 685-690, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32524348

RESUMEN

Despite advances in fungal diagnostics and antifungal therapy, mortality associated with candidaemia remains very high, particularly in developing countries. In this study, we reviewed the Brazilian literature on candidaemia over the last 20 years (1999-2019), with the aim to document if mortality rates changed over the years in Brazil. Variables studied included number of patients with candidaemia per study, age, most prevalent Candida species and use of antifungals. Selected manuscripts evaluated a median of 114 patients, the majority being men (54.4%). Median age was 45 year-old. The most prevalent species in all studies was C. albicans (37.3%), followed by C. parapsilosis (23.0%). An increase in use of echinocandins occurred in recent years, with a proportional decrease in the use of fluconazole and amphotericin B. Surprisingly, mortality of candidaemia has remained unchanged over the years in the largest Latin American country, regardless of treatment with echinocandins. Potential explanations for these findings are discussed.


Asunto(s)
Candidemia/mortalidad , Antifúngicos/uso terapéutico , Brasil/epidemiología , Candida , Candidemia/tratamiento farmacológico , Equinocandinas , Femenino , Fluconazol , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad
11.
Braz. j. infect. dis ; 24(3): 191-200, May-June 2020. tab, graf
Artículo en Inglés | LILACS, Coleciona SUS | ID: biblio-1132446

RESUMEN

ABSTRACT Introduction: Cytomegalovirus may cause severe disease in immunocompromised patients. Nowadays, quantitative polymerase chain reaction is the gold-standard for both diagnosis and monitoring of cytomegalovirus infection. Most of these assays use cytomegalovirus automated molecular kits which are expensive and therefore not an option for small laboratories, particularly in the developing world. Objective: This study aimed to optimize and validate an in-house cytomegalovirus quantitative polymerase chain reaction test calibrated using the World Health Organization Standards, and to perform a cost-minimization analysis, in comparison to a commercial cytomegalovirus quantitative polymerase chain reaction test. Study design: The methodology consisted of determining: optimization, analytical sensitivity, analytical specificity, precision, curve variability analysis, and inter-laboratorial reproducibility. Patients (n = 30) with known results for cytomegalovirus tested with m2000 RealTime System (Abbott Laboratories, BR) were tested with the in-house assay, as well as patients infected with other human herpes virus, in addition to BK virus. A cost-minimization analysis was performed, from a perspective of the laboratory, assuming diagnostic equivalence of the methodologies applied in the study. Results: The in-house assay had a limit of detection and quantification of 60.3 IU/mL, with no cross-reactivity with the other viral agents tested. Moreover, the test was precise and had a R 2 of 0.954 when compared with the m2000 equipment. The cost analysis showed that the assay was economically advantageous costing a median value of 37.8% and 82.2% in comparison to the molecular test in use at the hospital and the m2000 equipment, respectively. Conclusions: These results demonstrated that in-house quantitative polymerase chain reaction testing is an attractive alternative in comparison to automated molecular platforms, being considerably less expensive and as efficacious as the commercial methods.


Asunto(s)
Humanos , Juego de Reactivos para Diagnóstico , Infecciones por Citomegalovirus/diagnóstico , Citomegalovirus , ADN Viral , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Carga Viral , Costos y Análisis de Costo , Reacción en Cadena en Tiempo Real de la Polimerasa
12.
Toxicon ; 182: 7-12, 2020 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-32376361

RESUMEN

Fumonisin B1 is a mycotoxin produced by Fusarium verticillioides and Fusarium proliferatum found in various crops, particularly maize. Besides carcinogenicity, other manifestations have been registered in different animals and in humans. In the case of humans, epidemiological studies have reported high prevalence of esophageal cancer in populations exposed to fumonisins. This study aimed to evaluate the minimum concentration of FB1 capable of inducing cytotoxicity (cell viability test), genotoxicity (comet assay) and mutagenicity (micronucleus) in cultured human leukocytes and to evaluate the effectiveness of in silico tests to predict FB1 toxicity. All concentrations analyzed (200; 100; 50; 5; 0.5; 0.05; 0.005 µg/mL and 300; 30; 3; 1; 0.1; 0.01 fg/mL) except the lowest demonstrated dose-dependent toxicity in all parameters analyzed (p < 0.05 to p < 0.0001). As for predictions, only the Lazar software showed carcinogenicity of FB1 for rats. Thus, it is evident that FB1 is able to induce dose-dependent damage at low concentrations, and that computational tests, although desirable for prediction, are not effective as biological tests to determine toxicity, at least of FB 1 and within the experimental conditions tested.


Asunto(s)
Carcinógenos Ambientales/toxicidad , Fumonisinas/toxicidad , Contención de Riesgos Biológicos , Humanos
13.
Braz J Infect Dis ; 24(3): 191-200, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32450055

RESUMEN

INTRODUCTION: Cytomegalovirus may cause severe disease in immunocompromised patients. Nowadays, quantitative polymerase chain reaction is the gold-standard for both diagnosis and monitoring of cytomegalovirus infection. Most of these assays use cytomegalovirus automated molecular kits which are expensive and therefore not an option for small laboratories, particularly in the developing world. OBJECTIVE: This study aimed to optimize and validate an in-house cytomegalovirus quantitative polymerase chain reaction test calibrated using the World Health Organization Standards, and to perform a cost-minimization analysis, in comparison to a commercial cytomegalovirus quantitative polymerase chain reaction test. STUDY DESIGN: The methodology consisted of determining: optimization, analytical sensitivity, analytical specificity, precision, curve variability analysis, and inter-laboratorial reproducibility. Patients (n=30) with known results for cytomegalovirus tested with m2000 RealTime System (Abbott Laboratories, BR) were tested with the in-house assay, as well as patients infected with other human herpes virus, in addition to BK virus. A cost-minimization analysis was performed, from a perspective of the laboratory, assuming diagnostic equivalence of the methodologies applied in the study. RESULTS: The in-house assay had a limit of detection and quantification of 60.3IU/mL, with no cross-reactivity with the other viral agents tested. Moreover, the test was precise and had a R2 of 0.954 when compared with the m2000 equipment. The cost analysis showed that the assay was economically advantageous costing a median value of 37.8% and 82.2% in comparison to the molecular test in use at the hospital and the m2000 equipment, respectively. CONCLUSIONS: These results demonstrated that in-house quantitative polymerase chain reaction testing is an attractive alternative in comparison to automated molecular platforms, being considerably less expensive and as efficacious as the commercial methods.


Asunto(s)
Infecciones por Citomegalovirus/diagnóstico , Citomegalovirus , Juego de Reactivos para Diagnóstico , Costos y Análisis de Costo , ADN Viral , Humanos , Reacción en Cadena en Tiempo Real de la Polimerasa , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Carga Viral
14.
Mycoses ; 63(2): 197-211, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31657052

RESUMEN

BACKGROUND: Fungal infections are highly prevalent and are responsible for high rates of morbidity and mortality. In this context, the search for new treatment alternatives is very relevant. OBJECTIVES: Analyse chemical compounds for antifungal potential against dermatomycosis fungi. METHODS: The antifungal activity of 121 compounds, intermediates or derivatives of 1,3-bis(aryloxy)propane substituted at C-2 (111 compounds) and isothiouronium derivatives (10 compounds) was investigated through susceptibility tests, mechanism of action, toxicity and hydrogel incorporation. RESULTS: The compound 1,3-bis(3,4-dichlorophenoxy)propan-2-aminium chloride (2j) was the most active fungicide against dermatophytes and Candida spp., at very low concentrations (0.39-3.12 µg/mL), including action on resistant and multidrug-resistant clinical strains. Compound 2j has presented a promising toxicity profile, showing selectivity index >10, relative to human lymphocytes. The compound was classified as non-irritant by the HET-CAM test and did not cause histopathological alterations in pig ear skin, thus presenting an excellent perspective for topical application. 2j targets the fungal cell wall, which was confirmed by scanning electron microscopy, which also indicated the additional ability of 2j to inhibit the Candida albicans pseudohyphae formation and biofilm of Microsporum canis. Compound 2j was incorporated in a hydrogel with bioadhesive potential. The results of the human skin permeation showed that 2j remained significantly in the epidermis, ideally for the dermatomycosis treatment. CONCLUSIONS: Therefore, the compound 2j demonstrated the potential for antifungal drug development, with a action mechanism elucidated and already applied in a semisolid formulation as a new therapeutic option for fungal skin infections.


Asunto(s)
Antifúngicos/farmacología , Arthrodermataceae/efectos de los fármacos , Candida/efectos de los fármacos , Linfocitos/efectos de los fármacos , Propano/análogos & derivados , Animales , Antifúngicos/química , Supervivencia Celular , Células Cultivadas , Pollos , Membrana Corioalantoides/efectos de los fármacos , Oído Externo/efectos de los fármacos , Epidermis/efectos de los fármacos , Ergosterol/metabolismo , Femenino , Citometría de Flujo , Humanos , Hidrogeles , Concentración de Iones de Hidrógeno , Concentración 50 Inhibidora , Masculino , Pruebas de Sensibilidad Microbiana , Microscopía Electrónica de Rastreo , Propano/química , Propano/farmacología , Reología , Relación Estructura-Actividad , Porcinos
15.
Saudi Pharm J ; 27(8): 1064-1074, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31885466

RESUMEN

Development of new antimicrobial agents, capable of combating resistant and multidrug-resistant fungal and bacterial clinical strains, is necessary. This study presents the synthesis and antimicrobial screening of 42 2-substituted-1,4-benzenediols, being 10 novel compounds. In total, 23 compounds showed activity against fungi and/or bacteria. Benzenediol compounds 2, 5, 6, 8, 11, and 12 demonstrated broad spectrum antimicrobial actions, including resistant and multidrug-resistant species of dermatophytes (Trichophyton mentagrophytes), Candida spp. and the ESKAPE panel of bacteria. Minimum inhibitory concentrations of these compounds for fungi and bacterial strains ranged from 25 to 50 µg/ml and 8-128 µg/ml, respectively. The antifungal mechanism of action is related to the fungal cell wall of dermatophytes and membrane disruption to dermatophytes and yeasts, in the presence of compound 8. Specific structural changes, such as widespread thinning along the hyphae and yeast lysis, were observed by scanning electron microscopy. The effects of compound 8 on cell viability are dose-dependent; however they did not cause genotoxicity and mutagenicity in human leukocyte cells nor haemolysis. Moreover, the compounds were identified as nonirritant by the ex-vivo Hen's egg test-chorioallantoic membrane (HET-CAM). The furan-1,4-benzenediol compound 5 showed in vivo efficacy to combat S. aureus infection using embryonated chicken eggs. Therefore, the compounds 8, and 5 are promising as hits for the development of new antimicrobial drugs with reduced toxicity.

16.
J Fungi (Basel) ; 6(1)2019 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-31861302

RESUMEN

Histoplasmosis is an emerging fungal disease, with global distribution. The disseminated form of the disease is a more severe infection, generally associated with AIDS. Classic diagnostic methods for histoplasmosis consist of microscopy, culture, and histopathology. More recently, the importance of Histoplasma antigen detection has dominated the literature on histoplasmosis diagnosis, but the relevance of molecular assays has not been as much studied. Here we describe the results of a systematic literature review focusing on studies that mainly compared immunological techniques (Histoplasma urine antigen detection) with molecular tests for the diagnosis of histoplasmosis. In addition to the review of comparative studies using such diagnostic techniques, the literature on polymerase chain reaction (PCR) tests in patients with disseminated histoplasmosis is also summarized. Two studies reported the comparison between immunological and molecular methods applied simultaneously for the diagnosis of disseminated histoplasmosis. PCR demonstrates a satisfactory performance assisting in the detection of Histoplasma spp. DNA in clinical samples.

17.
Mycoses ; 62(10): 860-873, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31271676

RESUMEN

Experimental alternative ex vivo models that simulate infectious processes in vivo are of fundamental importance for the evaluation of new drugs, since in some cases, their execution does not depend on the approval of an ethics committee in research. Although studies using alternative infectious models to evaluate the efficacy of antifungal molecules have been increasingly described and reported, there is no critical consensus that establishes the most appropriate ones regarding the type of infection. Numerous studies contemplate ex vivo protocols of fungal infections on nails, corneas, dentinal tubules and skin and reveal counterpoints and concordances not yet finely confronted. In this minireview, we propose a critical analysis of the main ex vivo models of fungal infections for the evaluation of new antifungal candidates for both topical and systemic use, as opposed to the advantages and disadvantages of the traditional in vivo models employed in preclinical research.


Asunto(s)
Antifúngicos/aislamiento & purificación , Antifúngicos/uso terapéutico , Evaluación Preclínica de Medicamentos/métodos , Modelos Teóricos , Micosis/tratamiento farmacológico , Micosis/patología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad
18.
Folia Microbiol (Praha) ; 64(4): 509-519, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30734157

RESUMEN

Dermatophytes are the etiological agents of cutaneous mycoses, including the prevalent nail infections and athlete's foot. Candida spp. are opportunistic and emerging pathogens, causing superficial to deeper infections related to high mortality rates. As a consequence of prolonged application of antifungal drugs, the treatment failures combined with multidrug-resistance have become a serious problem in clinical practice. Therefore, novel alternative antifungals are required urgently. δ-Lactones have attracted great interest owing to their wide range of biological activity. This article describes the antifungal activity of synthetic δ-lactones against yeasts of the genus Candida spp. and dermatophytes (through the broth microdilution method), discusses the pathways by which the compounds exert this action (toward the fungal cell wall and/or membrane), and evaluates the toxicity to human leukocytes and chorioallantoic membrane (by the hen's egg test-chorioallantoic membrane). Two of the compounds in the series presented broader spectrum of antifungal activity, including against resistant fungal species. The mechanism of action was related to damage in the fungal cell wall and membrane, with specific target action dependent on the type of substituent present in the δ-lactone structure. The damage in the fungal cell was corroborated by electron microscopy images, which evidenced lysed and completely altered cells after in vitro treatment with δ-lactones. Toxicity was dose dependent for the viability of human leukocytes, but none of the compounds was mutagenic, genotoxic, or membrane irritant when evaluated at higher concentrations than MIC. In this way, δ-lactones constitute a class with excellent perspectives regarding their potential applications as antifungals.


Asunto(s)
Antifúngicos/química , Antifúngicos/farmacología , Lactonas/química , Lactonas/farmacología , Antifúngicos/toxicidad , Arthrodermataceae/efectos de los fármacos , Candida/efectos de los fármacos , Pared Celular/efectos de los fármacos , Desarrollo de Medicamentos , Humanos , Lactonas/toxicidad , Leucocitos/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Relación Estructura-Actividad
19.
Microb Pathog ; 105: 30-36, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28185949

RESUMEN

Oxidative stress has been considered as a pathological mechanism that contributes to initiation and progression of cardiac injury during the Trypanosoma evansi infection. In this sense, the natural compounds with antioxidant and free radical scavenger abilities, such the Achyrocline satureioides essential oil loaded in nanocapsules (AS-NC), may be considered important approach to minimize the cardiac damage. Thus, the aim of this study was to investigate whether AS-NC treatment is able to prevents or reduce the cardiac oxidative damage in infected rats with T. evansi. Heart samples from rats infected by T. evansi showed increased reactive oxygen species (ROS), thiobarbituric reactive-acid substances (TBARS) and glutathione reduced (GSH) levels, while catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities decreased compared with uninfected and untreated animals. Also, the seric biomarkers of cardiac function increased in the infected animals compared with uninfected animals. AS-NC treatment reduced ROS and TBARS levels, ameliorate cardiac CAT and SOD activities of infected rats, and reduced seric biomarkers of cardiac function. AS-NC treatment protected the heart from oxidative stress caused by T. evansi, which might be due to its antioxidant properties. AS-NC might be considered a promising therapeutic agent against oxidative stress, when associated with nanotechnology.


Asunto(s)
Achyrocline/química , Antioxidantes/farmacología , Miocardio/patología , Nanocápsulas/administración & dosificación , Aceites Volátiles/farmacología , Tripanosomiasis/tratamiento farmacológico , Animales , Antioxidantes/administración & dosificación , Catalasa/análisis , Femenino , Aceites Volátiles/administración & dosificación , Oxidantes , Ratas Wistar , Superóxido Dismutasa/análisis , Resultado del Tratamiento
20.
Exp Parasitol ; 166: 144-9, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27109312

RESUMEN

The aims of this study were to develop nerolidol-loaded nanospheres, and to evaluate their efficacy in vitro and in vivo against Trypanosoma evansi, as well as to determine their physicochemical properties, morphology, and any possible side effect in vitro against peripheral blood mononuclear cell (PBMC). The nanospheres showed an adequate particle size (149.5 nm), narrow particle distribution (0.117), negative zeta potential (-12.8 mV), and pH of 6.84, such as observed by transmission electron microscopy. In vitro, a trypanocidal effect of nerolidol and nanospheres containing nerolidol was observed at 0.5, 1.0, and 2.0%, i.e., both treatments showed a faster trypanocidal effect compared to chemotherapy (diminazene aceturate - D.A.). T. evansi infected mice were used to evaluate the effects of nerolidol-loaded nanospheres regarding pre-patent period, longevity, and therapeutic efficacy. Oral administration of nerolidol-loaded nanospheres at 1.0 mL/kg/day during 10 days increased mice survival (66.66%) compared to 0% and 33.33% of mice survival when treated with nerolidol in its free form and D.A., respectively. Cytotoxic study indicated that both treatments showed no side effects in vitro against PBMC, an important marker used in toxicological surveys. Therefore, nanoencapsulation increased the therapeutic efficacy of nerolidol against T. evansi, and can be used as an alternative treatment for T. evansi infection.


Asunto(s)
Diminazeno/análogos & derivados , Sesquiterpenos/farmacología , Tripanocidas/farmacología , Trypanosoma/efectos de los fármacos , Administración Oral , Adulto , Animales , Criopreservación , Diminazeno/farmacología , Diminazeno/toxicidad , Perros , Resistencia a Medicamentos , Femenino , Humanos , Concentración de Iones de Hidrógeno , Leucocitos Mononucleares/efectos de los fármacos , Ratones , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Nanosferas , Parasitemia/tratamiento farmacológico , Parasitemia/parasitología , Tamaño de la Partícula , Ratas , Sesquiterpenos/administración & dosificación , Sesquiterpenos/toxicidad , Tripanocidas/administración & dosificación , Tripanocidas/toxicidad , Trypanosoma/ultraestructura , Tripanosomiasis/tratamiento farmacológico , Tripanosomiasis/parasitología , Adulto Joven
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