RESUMEN
The treatment of feline sporotrichosis is a challenge for veterinary clinicians since refractory cases may occur, due either to patient and/or to pharmacological management errors or due to the development of antifungal resistance. Thus, we aimed to describe the therapeutic history of feline cases infected by itraconazole-resistant Sporothrix brasiliensis in an endemic region of Southern Brazil. Medical records of cats attended at the Veterinary Clinic Hospital (Pelotas/RS, Brazil) between 2016 and 2017 were reviewed. Twelve cases of infection by S. brasiliensis with that showed high minimum inhibitory concentration (MIC) values (≥ 4 µg/mL) to itraconazole by M38-A2 of CLSI were selected. At the hospital consultation, disseminated (cats 1-l0, 12) and localized (cat 11) skin lesions remained in the cats, even after treatment with fluconazole, ketoconazole (02/12), and itraconazole (ITZ, 09/12) performed before this study. High doses (25-100 mg/kg/day) of ITZ for up to 4 months (03/12, cats 2, 6, 12) or over 12 months (05/12, cats 1, 5, 7, 8, 11) did not provide a clinical cure, except for the association of ITZ plus potassium iodide (01/12, cat 12) for 3 months, which proved useful in infections with itraconazole-resistant S. brasiliensis. However, the combined issues of abandonment of therapy by owners for financial reasons, difficulties surrounding therapy administration (03/12, cats 6, 11, 12), and the inappropriate choice of medication (01/12, cat 6), together reflect the reality of this endemic region, which greatly compromises clinical healing. This study highlighted the occurrence of refractory cases by itraconazole-resistant S. brasiliensis in cats from Southern Brazil, as well as the abandonment of treatment and therapeutic errors. We warn of the need for antifungal susceptibility tests to adapt therapeutic protocols in feline sporotrichosis.
Asunto(s)
Antifúngicos/uso terapéutico , Enfermedades de los Gatos/tratamiento farmacológico , Farmacorresistencia Fúngica , Itraconazol/uso terapéutico , Sporothrix/efectos de los fármacos , Esporotricosis/veterinaria , Animales , Brasil , Enfermedades de los Gatos/microbiología , Gatos , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Sporothrix/fisiología , Esporotricosis/tratamiento farmacológico , Esporotricosis/microbiologíaRESUMEN
BACKGROUND: An alternative therapy for sporotrichosis is necessary to reduce the treatment time and raise clinical efficacy. The 5-Aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is a promising platform with which to treat mycoses. However, despite the worldwide prevalence of Sporothrix globosa, a causative agent of sporotrichosis, the effect of ALA-PDT on this pathogen has not been validated. OBJECTIVES: The aim of this study was to evaluate the effect of ALA-PDT on S globosa and the protection of melanin through an in vitro study. The mechanisms involved were also investigated. METHODS: To estimate the survival rate of S globosa treated with ALA-PDT and the protection offered by melanin, the conidia and yeast cells of wild-type S globosa (Mel+), other clinical strains, tricyclazole-treated Mel+ and an albino mutant strain (Mel-) were incubated with and without ALA or irradiation. Reactive oxygen species generation by Mel+ conidia induced by ALA-PDT was assayed. SEM and TEM were conducted to obverse ultrastructural changes in the conidia. A comet assay was performed to evaluate DNA damage. RESULTS: The survival rate of S globosa conidia and yeast cells significantly decreased following incubation with 1.19M ALA and 162 J/cm2 irradiation in vitro. Melanin was not only capable of protecting the conidia against ALA-PDT, but also against ALA or irradiation alone. After induction by ALA-PDT, alterations in reactive oxygen species generation, DNA damage and ultrastructural changes were observed. CONCLUSIONS: ALA-PDT inhibits the survival of S globosa conidia in vitro and therefore has potential for the treatment of sporotrichosis.
Asunto(s)
Ácido Aminolevulínico/farmacología , Antifúngicos/farmacología , Fotoquimioterapia , Sporothrix/efectos de los fármacos , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Piel/microbiología , Piel/patología , Esporas Fúngicas/efectos de los fármacos , Sporothrix/aislamiento & purificación , Sporothrix/patogenicidad , Esporotricosis/tratamiento farmacológico , Esporotricosis/microbiologíaRESUMEN
Sporotrichosis is considered a neglected disease of humans and animals in many regions of the world and is the most frequent implantation mycosis in Latin America. OBJECTIVES: To illustrate the zoonotic importance of the disease, describing a case involving a veterinarian and an infant that acquired the disease from a domestic cat and to describe, genotype and characterize these new isolates. METHODS: Direct examination of tissue samples from the two patients and feline lesions revealed the presence of Sporothrix yeast-like organisms. Fungal cultures and molecular identification of the strains were performed. Since antifungal susceptibility data of animal-borne isolates are scarce, the in vitro susceptibility testing by a microdilution reference method was determined against azoles, amphotericin B and terbinafine. RESULTS: Fungal culture and sequence analysis of the ITS region of rDNA and calmodulin and ß-tubulin genes confirmed the diagnosis and the causative agent as Sporothrix brasiliensis. In all cases, terbinafine was the most active drug, followed by posaconazole, itraconazole and voriconazole; the least active drugs were amphotericine B and fluconazole. Lack of clinical response in the veterinarian and in the infant to itraconazole and potassium iodide, respectively was observed. CONCLUSIONS: This study contributed to the molecular epidemiology of Sporothrix species in Argentina and the characterization of the in vitro susceptibility pattern of S. brasiliensis isolates recovered from a cat and two humans involved in this case of zoonotic sporotrichosis. Bearing in mind the "One Health" concept, the experience described in the present study highlights the need for future strategies for sporotrichosis treatment, control and prevention.
Asunto(s)
Antifúngicos/uso terapéutico , Enfermedades de los Gatos , Esporotricosis/diagnóstico , Esporotricosis/tratamiento farmacológico , Zoonosis/diagnóstico , Zoonosis/tratamiento farmacológico , Adulto , Animales , Antifúngicos/farmacología , Argentina , Enfermedades de los Gatos/diagnóstico , Enfermedades de los Gatos/tratamiento farmacológico , Enfermedades de los Gatos/microbiología , Enfermedades de los Gatos/transmisión , Gatos , Preescolar , Femenino , Genotipo , Humanos , Pruebas de Sensibilidad Microbiana , Técnicas de Diagnóstico Molecular , Técnicas de Tipificación Micológica/métodos , Núcleo Familiar , Filogenia , Sporothrix/clasificación , Sporothrix/efectos de los fármacos , Sporothrix/genética , Sporothrix/aislamiento & purificación , Esporotricosis/microbiología , VeterinariosAsunto(s)
Itraconazol/uso terapéutico , Sporothrix/efectos de los fármacos , Esporotricosis/tratamiento farmacológico , Antifúngicos/uso terapéutico , Preescolar , Cara , Humanos , Masculino , Esporas Fúngicas/efectos de los fármacos , Esporas Fúngicas/fisiología , Sporothrix/fisiología , Esporotricosis/microbiología , Resultado del TratamientoRESUMEN
Oregano (Origanum vulgare) has anti-Sporothrix spp. activity, including against strains that are resistant to antifungal drugs. As the studies are limited to the essential oil, the aim of this study was to evaluate the chemical, antioxidant and cytotoxic properties of polar oregano extracts and their anti-Sporothrix brasiliensis activity. Aerial plant parts were used in the preparation of 10 min (INF10) and 60 min (INF60) infusions, a decoction (DEC) and a hydroalcoholic extract (HAE). Six phenolic acids and four flavonoids were identified and quantified through liquid-chromatography (LC-MS). Extracts in increasing order of total phenolic and flavonoid contents were HAE
Asunto(s)
Antifúngicos/farmacología , Origanum/química , Extractos Vegetales/farmacología , Sporothrix/efectos de los fármacos , Animales , Antioxidantes , Gatos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Perros , Células de Riñón Canino Madin Darby , Pruebas de Sensibilidad Microbiana , Extractos Vegetales/aislamiento & purificación , Esporotricosis/tratamiento farmacológico , Esporotricosis/microbiologíaRESUMEN
In severe cases of sporotrichosis, it is recommended to use amphotericin B deoxycholate (D-AMB) or its lipid formulations and/or in association with itraconazole (ITC). Our aim was to evaluate the antifungal efficacy of a poly-aggregated amphotericin B (P-AMB), a nonlipid formulation, compared with D-AMB on systemic sporotrichosis caused by Sporothrix brasiliensis. In vitro assays showed that Sporothrix schenckii sensu stricto and S. brasiliensis yeast clinical isolates were susceptible to low concentrations of P-AMB and D-AMB. Although P-AMB presented a higher minimal inhibitory concentration (MIC) compared to D-AMB, its cytotoxic effect on renal cells and erythrocytes was lower. For the in vivo assays, male BALB/c mice were intravenously infected with S. brasiliensis yeasts, and P-AMB or D-AMB was administered 3 days post-infection. The efficacy of five therapeutic regimens was tested: intravenous monotherapy with P-AMB or D-AMB, intravenous pulsed-therapy with P-AMB or D-AMB, and intravenous therapy with P-AMB, followed by oral ITC. These treatments increased murine survival and controlled the fungal burden in the liver, spleen, lungs, and kidneys. However, only D-AMB monotherapy or the pulsed-therapies with D-AMB or P-AMB led to 100% survival of the mice 45 days post-infection; only pulsed administration of D-AMB was able to control the fungal load in all organs 45 days post-infection. Accordingly, the histopathological findings showed reductions in the fungal burden and inflammatory reactions in these treatment regimens. Together, our results suggest that the P-AMB formulation could be considered as an alternative drug to D-AMB for treating disseminated sporotrichosis.
Asunto(s)
Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Esporotricosis/tratamiento farmacológico , Anfotericina B/administración & dosificación , Anfotericina B/química , Anfotericina B/farmacología , Animales , Antifúngicos/administración & dosificación , Antifúngicos/química , Antifúngicos/farmacología , Supervivencia Celular/efectos de los fármacos , Recuento de Colonia Microbiana , Ácido Desoxicólico/administración & dosificación , Ácido Desoxicólico/química , Ácido Desoxicólico/farmacología , Ácido Desoxicólico/uso terapéutico , Modelos Animales de Enfermedad , Combinación de Medicamentos , Masculino , Ratones , Ratones Endogámicos BALB C , Pruebas de Sensibilidad Microbiana , Sporothrix/efectos de los fármacos , Sporothrix/crecimiento & desarrollo , Esporotricosis/mortalidad , Tasa de SupervivenciaRESUMEN
Abstract Garlic (Allium sativum L.) is grown all over the world as seasoning and medicinal vegetable since 3,000 BC. Allicin is the main component of garlic, being attributed to it the most of its biological activities, such as bactericidal, antifungal and antiviral actions. However, other compounds of garlic present antioxidant, hypocholesterolemic, vasodilator activities, protective action against different types of cancer, and immunomodulatory. Fungal infections are important causes of morbidity and mortality in people mainly in immunosuppressed ones. Sporothrix schenckii, the causing agent of Sporotrichosis (most common subcutaneous mycosis in Latin America), is dimorphic fungus, of saprophytic life in soil or plants, infecting people and animals mainly through skin injuries and bruises. The main of this work was to evaluate the influence of garlic consuming on immune modulation of healthy and infected Swiss mice in induced way by S. schenckii, since these animals functioning of peritoneal macrophages as well as the nitric oxide and cytokines' production (IL-1β, IL-10 and IL-12) and to evaluate the antifungal potential of garlic with S. schenckii through minimum inhibitory concentration test and colony-forming units. The results showed that garlic offers antifungal potential with S. schenckii. The oral taking of garlic extracts influences the releasing of cytokines by macrophages, regular consuming shows anti-inflammatory effect, and its acute use may take to an inflammatory response. Mice that consumed garlic responded more effectively to fight against the infection.
Resumo O alho (Allium sativum L.) é cultivado em todo o mundo como hortaliça condimentar e medicinal desde 3.000 a. C. A alicina é o principal componente do alho, sendo atribuída a ela a maior parte das suas atividades biológicas, dentre elas as ações bactericida, antifúngica e antiviral. Porém, outros compostos do alho apresentam atividade antioxidante, hipocolesterolemiante, vasodilatadora, ação protetora contra diversos tipos de câncer e imunomoduladora. As infecções por fungos são causas importantes de morbidade e mortalidade no homem principalmente em indivíduos imunossuprimidos. O Sporothrix schenckii, agente causal da esporotricose (micose subcutânea mais comum na América Latina), é fungo dimórfico, de vida saprofítica no solo ou em vegetais, infectando homens e os animais principalmente através de lesões e arranhões na pele. O objetivo desse trabalho foi avaliar a influência do consumo de alho na imunomodulação de camundongos Swiss saudáveis e infectados de forma induzida por S. schenckii, a partir do estado funcional dos macrófagos peritoneais desses animais quanto à produção de óxido nítrico e das citocinas (IL-1β, IL-10 e IL-12) e avaliar o potencial antifúngico do alho frente ao S. schenckii por meio de teste de concentração inibitória mínima e unidades formadoras de colônia. Os resultados demonstraram que o alho apresenta potencial antifúngico frente S. schenckii. A administração oral de extratos de alho influencia a liberação de citocinas por macrófagos, o consumo regular apresenta efeito anti-inflamatório, e seu uso agudo pode gerar uma resposta inflamatória. Camundongos que consumiram alho responderam de forma mais efetiva no combate da infecção.
Asunto(s)
Animales , Masculino , Ratones , Esporotricosis/tratamiento farmacológico , Sporothrix/efectos de los fármacos , Extractos Vegetales/farmacología , Macrófagos Peritoneales/inmunología , Ajo/química , Antifúngicos/farmacología , Citocinas/metabolismo , Macrófagos Peritoneales/efectos de los fármacos , InmunomodulaciónRESUMEN
PURPOSE: Motivated by increasing reports of antifungal resistance in human and animal sporotrichosis, this study evaluated the chemical composition, cytotoxicity and anti-Sporothrix brasiliensis activity of extracts of marjoram (Origanum majorana) and rosemary (Rosmarinus officinalis). METHODOLOGY: Ten (INF10) and 60 min (INF60) infusions, a decoction and a hydroalcoholic extract (HAE, 70â%) were prepared from both plants (10â% w/v). The extract composition was analysed by liquid chromatography/mass spectrometry and the cytotoxicity was evaluated using a colorimetric assay in canine and feline kidney cells. Using a broth microdilution assay (CLSI M38-A2) adapted to the extracts, 30 Sporothrix brasiliensis isolates from dogs, cats and humans, and one Sporothrix schenckii were tested.Results/Key findings. The predominant phenolic compounds found in all extracts were 4-hydroxybenzoic acid, caffeic acid and chlorogenic acid. Luteolin was also one of the predominant compounds, but only in the HAE of marjoram. Extracts of marjoram maintained cell viability in concentrations up to 2.5 mg ml-1 for the feline cell line and up to 10 mg ml-1 for the canine cell line, whereas in rosemary, the cell viability for both kidney lines was maintained with concentrations up to 5 mg ml-1. The activity of rosemary extracts was low or absent. Among the marjoram extracts, HAE was highlighted and had fungistatic activity against Sporothrix brasiliensis (MIC5040 mg ml-1), including in all itraconazole-resistant isolates. S. schenckiisensu stricto was sensitive to marjoram extracts (MIC/MFC ≤5 mg ml-1), with the exception of INF10. CONCLUSION: These findings support the potential usefulness of the HAE of marjoram in the treatment of sporotrichosis.
Asunto(s)
Antifúngicos/farmacología , Origanum/química , Fitoquímicos/farmacología , Extractos Vegetales/farmacología , Rosmarinus/química , Sporothrix/efectos de los fármacos , Animales , Antifúngicos/aislamiento & purificación , Antifúngicos/toxicidad , Gatos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Cromatografía Liquida , Perros , Espectrometría de Masas , Pruebas de Sensibilidad Microbiana , Fitoquímicos/aislamiento & purificación , Fitoquímicos/toxicidad , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/toxicidadRESUMEN
Garlic (Allium sativum L.) is grown all over the world as seasoning and medicinal vegetable since 3,000 BC. Allicin is the main component of garlic, being attributed to it the most of its biological activities, such as bactericidal, antifungal and antiviral actions. However, other compounds of garlic present antioxidant, hypocholesterolemic, vasodilator activities, protective action against different types of cancer, and immunomodulatory. Fungal infections are important causes of morbidity and mortality in people mainly in immunosuppressed ones. Sporothrix schenckii, the causing agent of Sporotrichosis (most common subcutaneous mycosis in Latin America), is dimorphic fungus, of saprophytic life in soil or plants, infecting people and animals mainly through skin injuries and bruises. The main of this work was to evaluate the influence of garlic consuming on immune modulation of healthy and infected Swiss mice in induced way by S. schenckii, since these animals functioning of peritoneal macrophages as well as the nitric oxide and cytokines' production (IL-1ß, IL-10 and IL-12) and to evaluate the antifungal potential of garlic with S. schenckii through minimum inhibitory concentration test and colony-forming units. The results showed that garlic offers antifungal potential with S. schenckii. The oral taking of garlic extracts influences the releasing of cytokines by macrophages, regular consuming shows anti-inflammatory effect, and its acute use may take to an inflammatory response. Mice that consumed garlic responded more effectively to fight against the infection.
Asunto(s)
Antifúngicos/farmacología , Ajo/química , Macrófagos Peritoneales/inmunología , Extractos Vegetales/farmacología , Sporothrix/efectos de los fármacos , Esporotricosis/tratamiento farmacológico , Animales , Citocinas/metabolismo , Inmunomodulación , Macrófagos Peritoneales/efectos de los fármacos , Masculino , RatonesRESUMEN
BACKGROUND: Feline sporotrichosis is common in Malaysia. Thermosensitivity and effects of azole treatment on fungal susceptibility are unknown. OBJECTIVES: To evaluate thermotolerance and antifungal susceptibility of feline Malaysian Sporothrix isolates, compare microdilution (MD) and E-test results, and investigate changes in susceptibility during azole therapy. METHODS: Sporothrix schenckii sensu stricto was isolated from 44 cats. Thermotolerance was determined via culture at 37°C for 7 days. Susceptibility to itraconazole (ITZ), ketoconazole (KTZ) and terbinafine (TRB) was assessed in 40 isolates by MD; to amphotericin B (AMB), KTZ, ITZ, fluconazole (FLC) and posaconazole (POS) by E-test. Results were statistically compared by Pearson's Product Moment. In eight ketoconazole treated cats, susceptibility testing to itraconazole and ketoconazole was repeated every two months for six months. RESULTS: Thermotolerance was observed in 36 of 44 (82%) isolates. Assuming that isolates growing at antifungal concentrations ≥4 mg/mL were resistant, all were resistant on E-test to FLC and AMB, 11 (28%) to POS, 6 (15%) to ITZ and 1 (3%) to KTZ. On MD, 27 of 40 (68%) were resistant to TRB, 2 (5%) to ITZ and 3 (8%) to KTZ. There was no correlation between E-test and MD results (KTZ r = 0.10, P = 0.54, and ITZ r = 0.11, P = 0.48). MD values for ITZ and KTZ did not exceed 4 mg/L during KTZ therapy. CONCLUSION: The majority of feline isolates in Malaysia are thermosensitive. Lack of correlation between E-test and MD suggests that the E-test is unreliable to test antifungal susceptibility for Sporothrix spp. compared to MD. KTZ was the antifungal drug with the lowest MIC. Prolonged KTZ administration may not induce changes in antifungal susceptibility.
Asunto(s)
Antifúngicos/uso terapéutico , Enfermedades de los Gatos/tratamiento farmacológico , Pruebas de Sensibilidad Microbiana/veterinaria , Sporothrix/efectos de los fármacos , Esporotricosis/veterinaria , Anfotericina B/uso terapéutico , Animales , Gatos/microbiología , Técnicas In Vitro , Itraconazol/uso terapéutico , Cetoconazol/uso terapéutico , Malasia , Pruebas de Sensibilidad Microbiana/métodos , Naftalenos/uso terapéutico , Esporotricosis/tratamiento farmacológico , Esporotricosis/microbiología , Terbinafina , Triazoles/uso terapéuticoRESUMEN
Sporotrichosis is a subacute to chronic infection caused by members of the Sporothrix schenckii complex. Itraconazole is the first choice antifungal drug for treating this infection, with terbinafine and potassium iodide as alternatives and amphotericin B used in cases of severe infections. Correlation of antifungal susceptibility data with the clinical outcome of the patients is scarce. The aim of this study was to correlate clinical and mycological data in patients with refractory sporotrichosis. In this work, antifungal susceptibilities, determined according to the reference M38-A2 CLSI protocol, of 25 Sporothrix strains, isolated from seven human cases of sporotrichosis with adversities in the treatment, are presented. Tested drugs included itraconazole, ketoconazole, posaconazole, voriconazole, terbinafine, and amphotericin B. Fungi were identified using the T3B PCR fingerprinting. This method identified all strains as Sporothrix brasiliensis and also demonstrated a high degree of similarity between the strains. In general, voriconazole was ineffective against all strains, and elevated minimal inhibitory concentrations (MICs) were observed for amphotericin B. High itraconazole and terbinafine MICs were not observed in S. brasiliensis isolates from patients of this study. Moreover, a significant increase in itraconazole and terbinafine MIC values from strains isolated from the same patient in different periods was not observed. The results suggest that the antifungal susceptibility to terbinafine and itraconazole determined by the reference method does not play an important role in therapeutic failure of sporotrichosis and that acquisition of resistance during prolonged antifungal treatment is not likely to occur in S. brasiliensis.
Asunto(s)
Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Farmacorresistencia Fúngica , Sporothrix/efectos de los fármacos , Sporothrix/genética , Esporotricosis/tratamiento farmacológico , Esporotricosis/microbiología , Adulto , Anciano , Animales , Gatos , Dermatoglifia del ADN , ADN de Hongos/genética , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Recurrencia , Sporothrix/aislamiento & purificación , Esporotricosis/transmisión , Resultado del Tratamiento , Adulto JovenRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Vismia guianensis (Aubl.) Pers. is traditionally used in North and Northeast of Brazil for the treatment of dermatomycoses. Since the strategy associating immunomodulators with antifungal drugs seems to be promissory to improve the treatment efficacy in fungal infections, we aimed to investigate the antifungal activity of V. guianensis ethanolic extract of leaves (VGL) and bark (VGB) against Sporothrix schenckii ATCC 16345 and their antinflammatory activities. MATERIAL AND METHODS: The extracts were analyzed by HPLC-DAD-IT MS/MS for in situ identification of major compounds. Antifungal activity was evaluated in vitro (microdilution test) and in vivo using a murine model of S. schenckii infection. The production of TNF-α, IFN-γ, IL-4, IL-10 and IL-12 by measured by ELISA, as well as measured the production and inhibition of the NO after treatment with the plant extracts or itraconazole (ITR). RESULTS: Two O-glucosyl-flavonoids and 16 prenylated benzophenone derivatives already described for Vismia were detected. Both VGL and VGB showed significant antifungal activity either in in vitro assay of microdilution (MIC=3.9µg/mL) and in vivo model of infection with reduction of S. schenckii load in spleen. It was also observed a predominance of reduction in the production of NO and the proinflammatory cytokines evaluated except TNFα, but with stimulation of IL-10, as evidence of a potential anti-inflammatory effect associated. CONCLUSION: The results showed that both VGL and VGB have a significant antifungal against S. schenckii and an anti-inflammatory activity. These results can support the use of these extracts for alternative treatment of sporotrichosis.
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Antiinflamatorios/farmacología , Antifúngicos/farmacología , Clusiaceae/química , Extractos Vegetales/farmacología , Sporothrix/efectos de los fármacos , Esporotricosis/prevención & control , Animales , Antiinflamatorios/aislamiento & purificación , Antifúngicos/aislamiento & purificación , Células Cultivadas , Cromatografía Líquida de Alta Presión , Modelos Animales de Enfermedad , Etanol/química , Interferón gamma/metabolismo , Interleucina-10/metabolismo , Interleucina-12/metabolismo , Interleucina-4/metabolismo , Itraconazol/farmacología , Masculino , Ratones Endogámicos BALB C , Óxido Nítrico/metabolismo , Fitoterapia , Corteza de la Planta/química , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta/química , Plantas Medicinales , Solventes/química , Sporothrix/inmunología , Esporotricosis/inmunología , Esporotricosis/metabolismo , Esporotricosis/microbiología , Espectrometría de Masas en Tándem , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
This study evaluated the chemical, cytotoxic and anti-Sporothrix brasiliensis properties of commercial essential oils of rosemary (Rosmarinus officinalis L.), oregano (Origanum vulgare L.) and marjoram (Origanum majorana L.). Chemical composition of the oils was identified through gas chromatography with flame ionization detector, and cytotoxicity was performed through MTT assay in VERO cell line. Anti-S. brasiliensis activity was performed according to the CLSI M38-A2 guidelines using isolates obtained from cats and dogs. The major compounds found were carvacrol in the oregano oil (73.9 %) and 1,8-cineole in rosemary and marjoram oils (49.4 and 20.9 %, respectively). All S. brasiliensis isolates were susceptible to the plant oils, including itraconazole-resistant ones. Marjoram and rosemary oils showed MIC90 of 0.56 and 1.12 mg ml-1, and MFC90 of 4.5 and 9 mg ml-1, respectively. For oregano oil, a strong antifungal activity was observed with MIC90 and MFC90 values ≤0.07 mg ml-1. The weakest cytotoxicity was observed for rosemary oil. Further studies should be undertaken to evaluate the safety and efficacy of these essential oils in sporotrichosis.
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Antifúngicos/farmacología , Aceites Volátiles/farmacología , Origanum/química , Fitoquímicos/farmacología , Rosmarinus/química , Sporothrix/efectos de los fármacos , Animales , Antifúngicos/aislamiento & purificación , Enfermedades de los Gatos/microbiología , Gatos , Supervivencia Celular/efectos de los fármacos , Enfermedades de los Perros/microbiología , Perros , Cromatografía de Gases y Espectrometría de Masas , Pruebas de Sensibilidad Microbiana , Aceites Volátiles/química , Aceites Volátiles/aislamiento & purificación , Aceites Volátiles/toxicidad , Fitoquímicos/análisis , Fitoquímicos/aislamiento & purificación , Fitoquímicos/toxicidad , Sporothrix/aislamiento & purificación , Esporotricosis/microbiología , Esporotricosis/veterinaria , Células VeroRESUMEN
Curcumin, a yellow polyphenol compound, is known to possess antifungal activity for a range of pathogenic fungi. However, the fungicidal mechanism of curcumin (CUR) has not been identified. We have occasionally found that chitin redistributes to the cell wall outer layer of Sporothrix schenckii (S. schenckii) upon sublethal CUR treatment. Whether CUR can affect chitin synthesis via the protein kinase C (PKC) signaling pathway has not been investigated. This study describes a direct fungicidal activity of CUR against S. schenckii demonstrated by the results of a checkerboard microdilution assay and, for the first time, a synergistic effect of CUR with terbinafine (TRB). Furthermore, the results of real-time PCR showed that sublethal CUR upregulated the transcription of PKC, chitin synthase1 (CHS1), and chitin synthase3 (CHS3) in S. schenckii. The fluorescence staining results using wheat germ agglutinin-fluorescein isothiocyanate (WGA-FITC) and calcofluor white (CFW) consistently showed that chitin exposure and total chitin content were increased on the conidial cell wall of S. schenckii by sublethal CUR treatment. A histopathological analysis of mice infected with CUR-treated conidia showed dampened inflammation in the local lesion and a reduced fungal burden. The ELISA results showed proinflammatory cytokine secretion at an early stage from macrophages stimulated by the CUR-treated conidia. The present data led to the conclusion that CUR is a potential antifungal agent and that its fungicidal mechanism may involve chitin accumulation on the cell wall of S. schenckii, which is associated with decreased virulence in infected mice.
Asunto(s)
Antifúngicos/uso terapéutico , Quitina/metabolismo , Curcumina/uso terapéutico , Sporothrix/efectos de los fármacos , Esporotricosis/tratamiento farmacológico , Animales , Células Cultivadas , Quitina Sintasa/genética , Quitina Sintasa/metabolismo , Sinergismo Farmacológico , Femenino , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Ratones , Ratones Endogámicos BALB C , Naftalenos/uso terapéutico , Proteína Quinasa C/genética , Proteína Quinasa C/metabolismo , Sporothrix/patogenicidad , Sporothrix/fisiología , Esporotricosis/inmunología , Terbinafina , Regulación hacia Arriba , VirulenciaRESUMEN
We evaluated the combination of posaconazole with amphotericin B in vitro and in a murine model of systemic infections caused by Sporothrix brasiliensis and Sporothrix schenckii sensu stricto. In vitro data demonstrated a synergistic effect, and although posaconazole alone was effective against sporotrichosis, efficacy in terms of survival and burden reduction was increased with the combination. This combination might be an option against disseminated sporotrichosis, especially when itraconazole or amphotericin B at optimal doses are contraindicated.
Asunto(s)
Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Sporothrix/efectos de los fármacos , Esporotricosis/tratamiento farmacológico , Triazoles/uso terapéutico , Animales , Farmacorresistencia Fúngica Múltiple , Quimioterapia Combinada , Ratones , Pruebas de Sensibilidad Microbiana , Sporothrix/patogenicidadRESUMEN
De-oiled Jatropha curcas seed cake, a plentiful by-product of biodiesel industry was used as substrate for the production of a useful xylanase from Sporotrichum thermophile in solid state fermentation. Under the optimized conditions, 1025U xylanase/g (deoiled seed cake) was produced. The xylanase exhibited half life of 4h at 45°C and 71.44min at 50°C respectively. It was stable in a broad pH range of 7.0-11.0. Km and Vmax were 12.54mg/ml and 454.5U/ml/min respectively. S. thermophile xylanase is an endoxylanase free of exoxylanase activity, hence advantageous for xylan hydrolysis to produce xylooligosachharides. Hydrolysis of oat spelt xylan by S. thermophile xylanase yielded 73% xylotetraose, 15.4% xylotriose and 10% xylobiose. The S. thermophile endoxylanase thus seem potentially useful in the food industries.
Asunto(s)
Biotecnología/métodos , Endo-1,4-beta Xilanasas/biosíntesis , Fermentación , Glucuronatos/biosíntesis , Jatropha/química , Oligosacáridos/biosíntesis , Aceites de Plantas/aislamiento & purificación , Semillas/química , Sporothrix/enzimología , Metabolismo de los Hidratos de Carbono/efectos de los fármacos , Carbono/farmacología , Fermentación/efectos de los fármacos , Humedad , Concentración de Iones de Hidrógeno/efectos de los fármacos , Hidrólisis/efectos de los fármacos , Cinética , Sporothrix/efectos de los fármacos , Especificidad por Sustrato/efectos de los fármacos , Residuos , Xilanos/metabolismoRESUMEN
Jatropha isabellei Müll Arg. belongs to the family Euphorbiaceae. The antioxidant capacity of this plant was evaluated by the DPPH method and inhibition of thiobarbituric acid reactive substances (TBARS). Ethyl acetate fraction demonstrated the best antioxidant capacity against the DPPH free radical and its profile was similar to ascorbic acid. This fraction also presented the best results of phenolics, flavonoids and condensed tannins, showing a positive relation between the phenolic content and antioxidant activity. All fractions and the crude extract were able to inhibit significantly the TBARS production induced by Fe(II) for the two tested concentrations, reaching the basal levels. In this test, ethyl acetate and dichloromethane fraction showed good values for inhibitory concentration. The dichloromethane fraction showed the best results against the fungi Sporothrix schenckii and Fusarium proliferatum and the bacterium of Micrococcus genus. This fraction allowed the isolation of acetil aleuritolic acid and a mixture of sitosterol 3-O-ß-D-glucoside and stigmasterol, described for the first time in this species.
Asunto(s)
Antiinfecciosos/farmacología , Antioxidantes/farmacología , Jatropha/química , Animales , Antiinfecciosos/química , Antioxidantes/química , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Evaluación Preclínica de Medicamentos/métodos , Flavonoides/análisis , Depuradores de Radicales Libres/farmacología , Fusarium/efectos de los fármacos , Glucósidos/química , Glucósidos/aislamiento & purificación , Peroxidación de Lípido/efectos de los fármacos , Masculino , Estructura Molecular , Fenoles/análisis , Extractos Vegetales/química , Extractos Vegetales/farmacología , Ratas Wistar , Sitoesteroles/química , Sitoesteroles/aislamiento & purificación , Sporothrix/efectos de los fármacos , Estigmasterol/aislamiento & purificación , Taninos/análisis , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Triterpenos/aislamiento & purificaciónRESUMEN
We developed a murine model of systemic sporotrichosis by using three strains of each of the two commonest species causing sporotrichosis, i.e., Sporothrix schenckii sensu stricto and Sporothrix brasiliensis, in order to evaluate the efficacy of posaconazole (PSC). The drug was administered at a dose of 2.5 or 5 mg/kg of body weight twice a day by gavage, and one group was treated with amphotericin B (AMB) as a control treatment. Posaconazole, especially at 5 mg/kg, showed good efficacy against all the strains tested, regardless of their MICs, as measured by prolonged survival, tissue burden reduction, and histopathology.
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Antifúngicos/uso terapéutico , Hígado/microbiología , Sporothrix/efectos de los fármacos , Esporotricosis/tratamiento farmacológico , Triazoles/uso terapéutico , Administración Oral , Anfotericina B/administración & dosificación , Anfotericina B/uso terapéutico , Animales , Antifúngicos/administración & dosificación , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Histocitoquímica , Hígado/efectos de los fármacos , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Especificidad de la Especie , Sporothrix/fisiología , Esporotricosis/microbiología , Esporotricosis/mortalidad , Esporotricosis/patología , Tasa de Supervivencia , Resultado del Tratamiento , Triazoles/administración & dosificaciónRESUMEN
Various oxygen containing 1,4-naphthoquinone derivatives have been synthesized chemoselectively by an economical, viable green methodology approach using water as solvent with or without surfactants such as Triton X-100, SDS, LD (laundry detergent), and TBAB, a phase transfer catalyst and evaluated for their in vitro antifungal and antibacterial activity. The antifungal profile of 3, 4a, 4b, and 6 indicated that compounds 3a, 3b, 4b, 6a, and 6c have potent antifungal activity compared to clinically prevalent antifungal drugs Fluconazole and Amphotericin-B against Sporothrix schenckii, Trichophyton mentagraphytes, and Candida parapsilosis and compound 3b has been found to be a lead antifungal agent for further study.
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Antifúngicos/química , Antifúngicos/farmacología , Micelas , Naftoquinonas/química , Naftoquinonas/farmacología , Oxígeno/química , Candida/efectos de los fármacos , Catálisis , Evaluación Preclínica de Medicamentos , Pruebas de Sensibilidad Microbiana , Sporothrix/efectos de los fármacos , Trichophyton/efectos de los fármacos , AguaRESUMEN
BACKGROUND: Itraconazole has become the first choice for treatment of cutaneous sporotrichosis. However, this recommendation is based on case reports and small series. The safety and efficacy of itraconazole were evaluated in 645 patients who received a diagnosis on the basis of isolation of Sporothrix schenckii in Rio de Janeiro, Brazil. METHODS: A standard regimen of itraconazole (100 mg/day orally) was used. Clinical and laboratory adverse events were assessed a grades 1-4. A multivariate Cox model was used to analyze the response to treatment. RESULTS: The median age was 43 years. Lymphocutaneous form occurred in 68.1% and fixed form in 23.1%. Six hundred ten patients (94.6%) were cured with itraconazole (50-400 mg/day): 547 with 100 mg/day, 59 with 200-400 mg/day, and 4 children with 50 mg/day. Three patients switched to potassium iodide, 2 to terbinafine, and 4 to thermotherapy. Twenty-six were lost to follow-up. Clinical adverse events occurred in 18.1% of patients using 100 mg/day and 21.9% of those using 200-400 mg/day. The most frequent clinical adverse events were nausea and epigastric pain. Laboratory adverse events occurred in 24.1%; the most common was hypercholesterolemia, followed by hypertriglyceridemia. Four hundred sixty-two patients (71.6%) completed clinical follow-up, and all remained cured. Only 2 variables were significant in explaining the cure: patients with erythema nodosum healed faster, and lymphocutaneous form took longer to cure. CONCLUSIONS: In the current series, the therapeutic response was excellent with the minimum dose of itraconazole, and there was a low incidence of adverse events and treatment failure.