RESUMO: A esporotricose é uma das micoses de maior relevância na medicina veterinária, tanto pela sua gravidade, seu potencial zoonótico e seu difícil tratamento. Sabe-se que o aspecto imunológico do gato representa um fator prognóstico determinante. O objetivo desse trabalho foi avaliar a eficácia do imunomodulador timomodulina como adjuvante a terapia antifúngica, itraconazol (ITL) com iodeto de potássio (KI), em gatos com esporotricose disseminada. Trinta e um gatos (n=31) com esporotricose cutânea disseminada foram segregados em dois grupos, o grupo 1 (G1) (n=16) tratado com ITL, KI associada à timomodulina e o grupo 2 (G2) (n=15) apenas ITL e KI. Foi avaliada a resposta clínica aos diferentes tratamentos, levando em consideração a taxa de sobrevivência, tempo de resposta das lesões e progressão do escore de condição corporal. O G1 apresentou taxa de sobrevivência de quase 100% (93,6%), aproximadamente o dobro do encontrado no G2 (53%). Mais que isso, o G1 demonstrou significativamente melhor prognóstico, aprimoramento do escore de condição corporal e menor tempo para remissão dos sinais clínicos extracutâneos (p<0,02). Sendo assim, a associação da timomodulina ao ITL e KI melhora o prognóstico de gatos com esporotricose cutânea disseminada.

ABSTRACT: Feline sporotrichosis is a relevant mycose in veterinary medicine due to its severity and zoonotic potential and the fact that it can be difficult to treat. The immune status of the animal exerts influence on the prognosis of the disease and determines its clinical outcome. This study evaluated the efficacy of the immunomodulatory thymomodulin as an adjunct to antifungal therapy in cats with disseminated sporotrichosis; thymomodulin was used in association with itraconazole (ITL) and potassium iodide (KI) to treat this fungal disease in the feline patient. Thirty-one cats (n=31) diagnosed with disseminated cutaneous sporotrichosis were divided into two groups as follows: Group 1 (G1) (n=16), which included those animals that were treated with thymomodulin in association with ITL and KI, and Group 2 (G2) (n=15) which had pacientsthat received ITL and KI only. The response to different treatment modalities was assessed, considering the survival rate, time frame for the lesions to respond to therapy, and clinical improvement or deterioration according to a body condition score system. Animals from G1 had a survival rate of nearly 100% (93.6%) that was approximately twice higher than the survival rate of those animals from G2 (53%). Moreover, patients from G1 had a significantly better prognosis, improved body condition, and shorter time for remission of the extra cutaneous clinical signs (p<0.02). Our findings showed that the association of thymomodulin with ITL and KI improves the prognosis of cats with disseminated cutaneous sporotrichosis.

Resumo Este estudo avaliou a ação in vitro e in vivo de extratos de Eugenia uniflora em nematódeos gastrintestinais de ovinos. No teste de inibição da eclodibilidade dos ovos, extratos aquosos e hidroalcoólicos foram testados nas concentrações de 40 a 1,25 mg/mL. O efeito citotóxico foi mensurado através do ensaio de MTT em células VERO nas concentrações de 4000 a 1,95 µg/mL. A composição química foi analisada através da marcha fitoquímica qualitativa. No teste in vivo, foram administrados 100 mg/kg, por via oral, do extrato hidroalcoólico por três dias em ovinos naturalmente infectados e realizada coleta de fezes para estimar a redução de ovos por grama de fezes (OPG). Diferentes extratos de E. uniflora inibiram a eclodibilidade dos ovos, com percentual de inibição variando de 14,56 a 99,75%, sendo os hidroalcoólicos mais promissores que os aquosos. Na marcha fitoquímica, compostos com ação anti-helmíntica comprovada foram observados, como flavonoides, saponinas, taninos e triterpenos. Nas condições testadas, os extratos apresentaram citotoxicidade nula a moderada. In vivo, a redução do OPG foi observada apenas no grupo controle (anti-helmíntico). Os extratos de E. uniflora mostraram-se promissores com ação in vitro, necessitando estudos que avaliem outras concentrações e formas de administração in vivo.

Abstract: This study evaluated the in vitro and in vivo action of Eugenia uniflora extracts on sheep gastrointestinal nematode. In the egg hatchability inhibition assay, aqueous and hydroalcoholic extracts were tested in the concentrations ranging from 40 to 1.25 mg/mL. The cytotoxic effect was measured using the MTT assay on VERO cells at concentrations ranging from 4000 to 1.95 μg/mL. The chemical composition was analyzed through the qualitative phytochemical screening. In the in vivo test, 100 mg/kg of the hydroalcoholic extract was administered orally for three days in sheep naturally infected and fecal collection was performed to estimate the egg count per gram of faeces (EPG). Different extracts of E. uniflora inhibited hatchability of eggs with a percentage of inhibition ranging from 14.56 to 99.75%, being the hydroalcoholic most effective than the aqueous. In phytochemical analysis, compounds with anthelmintic action were observed, such as flavonoids, saponins, tannins and triterpenes. Extracts showed moderate to null cytotoxicity under the conditions tested. Reduction of EPG was observed only in control group (anthelmintic). The extracts of E. uniflora proved promising with in vitro action, requiring studies that assess other concentrations and forms of in vivo administration.

Abstract The study aimed to evaluate the anti-Sporothrix sp. activity of the essential oil of Origanum majorana Linn. (marjoram), its chemical analysis, and its cytotoxic activity. A total of 18 fungal isolates of Sporothrix brasiliensis (n: 17) from humans, dogs and cats, and a standard strain of Sporothrix schenckii (n: 1) were tested using the broth microdilution technique (Clinical and Laboratory Standard Institute - CLSI M27-A3) and the results were expressed in minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC). The MIC50 and MIC90 of itraconazole against S. brasiliensis were 2 µg/mL and 8 µg/mL, respectively, and the MFC50 and MFC90 were 2 µg/mL and >16 µg/mL, respectively, with three S. brasiliensis isolates resistant to antifungal. S. schenckii was sensitive at MIC of 1 µg/mL and MFC of 8 µg/mL. For the oil of O. majorana L., all isolates were susceptible to MIC of ≤2.25-9 mg/mL and MFC of ≤2.25-18 mg/mL. The MIC50 and MIC90 were ≤2.25 mg/mL and 4.5 mg/mL, respectively, and the MFC50/90 values were twice more than the MIC. Twenty-two compounds were identified by gas chromatography with a flame ionization detector (CG-FID) and 1,8-cineole and 4-terpineol were the majority. Through the colorimetric (MTT) assay, the toxicity was observed in 70-80% of VERO cells between 0.078 and 5 mg/mL. For the first time, the study demonstrated the satisfactory in vitro anti-Sporothrix sp. activity of marjoram oil and further studies are needed to ensure its safe and effective use.

RESUMO Casos de esporotricose em humanos e animais sem resposta clínica satisfatória têm aumentado, sinal de alarme para o surgimento de cepas resistentes aos antifúngicos convencionais. A urgente busca por alternativas terapêuticas tem incentivado as pesquisas em plantas medicinais com atividade anti-Sporothrix spp. Um levantamento bibliográfico foi realizado com base em artigos científicos sobre a atividade antifúngica in vitro e in vivo de óleos essenciais e extratos de plantas preparados em diferentes solventes contra o complexo Sporothrix schenckii. A metodologia do estudo consistiu em uma revisão bibliográfica em Google Scholar, Science Direct, Pubmed, Bireme e Springer link com artigos desde 1986 até 2015. Foram encontradas 141 espécies de plantas já investigadas, das quais 100 espécies concentradas em 39 famílias botânicas apresentaram atividade anti-Sporothrix spp. confirmada. Combretaceae, Asteraceae e Lamiaceae representaram as famílias botânicas com maior número de espécies vegetais com potencial antifúngico, empregando diferentes metodologias. Entretanto, há poucos estudos com plantas medicinais em infecção experimental animal comprovando sua atividade no tratamento da esporotricose. Reforça-se a necessidade de mais pesquisas relacionadas à padronização de metodologias in vitro e a estudos in vivo relacionados à segurança e potencial tóxico dessas plantas com atividade anti-Sporothrix spp.

ABSTRACT Cases of sporotrichosis in humans and animals without satisfactory clinical response have increased, a warning sign of strains resistant to conventional antifungal agents. The urgent search for alternative therapies was an incentive for research on medicinal plants with anti-Sporothrix spp. properties. A bibliographic survey was performed based on scientific papers about in vitro and in vivo antifungal activity of essential oils and extracts of plants in differents solvents against the fungal of the Sporothrix schenckii complex. The study methodology consisted of a literature review in Google Scholar, Science Direct, Pubmed, Bireme and Springer link with papers from 1986 to 2015. We found 141 species of plants that were investigated, of which 100 species were concentrated in 39 botanical families that had confirmed anti-Sporothrix activity. Combretaceae, Asteraceae and Lamiaceae represented the botanical families with the greatest number of plants species with antifungal potential, using different methodologies. However, there are few studies with medicinal plants in experimental infection in animals that prove their activity in the treatment of sporotrichosis. It reinforces the need for further research related to standardization of in vitro methodologies and in vivo studies related to safety and to toxicity potential of these plants with anti-Sporothrix spp. activity.

Em virtude da resistência dos nematódeos gastrintestinais aos antihelmínticos, diversas pesquisas têm sido desenvolvidas buscando-se alternativas de controle para essas parasitoses. Nesse contexto, o estudo avaliou a ação in vitro de Origanum vulgare sobre ovos de nematódeos gastrintestinais de bovinos. Para avaliar a capacidade de inibição da eclodibilidade dos ovos, diferentes formas de extratos das folhas secas desta planta foram testadas como tintura, extrato hidroalcoólico e extrato aquoso nas concentrações de 0,62 a 80 mg/mL. Cada ensaio foi acompanhado de controle contendo cloridrato de levamisol (0,2 mg/mL), água destilada e álcool de cereais 70° GL nas mesmas concentrações dos produtos. Os resultados dos testes demonstraram que os diferentes extratos de O. vulgare inibiram a eclodibilidade dos ovos de nematódeos gastrintestinais de bovinos com percentual de inibição variando de 8,8 a 100%, sendo a tintura e o extrato hidroalcoólico as formas mais promissoras. Frente a esta propriedade ovicida, o O. vulgare pode representar uma importante fonte de compostos antiparasitários viáveis para o controle das nematodioses em ruminantes.

Due to anthelmintic resistance in nematodes, several research studies have been developed seeking control alternatives to these parasites. This study evaluated the in vitro action of Origanum vulgare on gastrointestinal nematode eggs of cattle. In order to evaluate the ability to inhibit egg hatch, different dried leaves extracts of this plant were tested, such as dye, hydroalcoholic and aqueous extracts at concentrations varying from 0.62 to 80 mg/mL. Each assay was accompanied by control containing levamisole hydrochloride (0.2 mg/mL), distilled water and 70º GL grain alcohol at the same concentration of the extracts. Test results showed that the different O. vulgare extracts inhibited egg hatch of cattle gastrointestinal nematodes at a percentage that varied from 8.8 to 100%; dye and hydroalcoholic extract were the most promising inhibitors. In view of this ovicidal property, O. vulgare may be an important source of viable antiparasitic compounds for nematodiosis control in ruminants.

The oral microbiota of humans and animals is made up of a wide variety of yeasts and bacteria, but microbiota of dogs is not totally described. Although such identification is an important step to establish the etiopathogenesis and adequate therapy for the periodontal disease The aim of this study was to evaluate and correlate oral alterations with the presence of yeasts in oral cavity of female dogs. After clinical evaluation samples from healthy and from dogs with oral diseases were obtained from three different oral sites by swabs, curettes, millimeter periodontal probes and HA membrane tip in cellulose ester. Yeast identification was performed through macroscopic and microscopic colony features and biochemical tests. Dental calculus was the most prevalent occurrence in the oral cavity of 59 females. However, the isolation of yeasts was significantly higher (p < 0.05) in animals suffering from halitosis. Eleven yeast species were identified, namely: Malassezia pachydermatis, Rhodotorula spp., Candida albicans, C. catenulata, C. famata, C. guilliermondii, C. parapsilosis, C. intermedia, Trichosporon asahii, T. mucoides and Cryptococcus albidus. It could be concluded that the yeasts are part of the microbiota from the different sites of the oral cavity of the female canines studied without causing any significant alterations except halitosis.

Using transmission electron microscopy, we studied the presence of melanin and cell wall thickness of clinical isolates of Sporothrix schenckii obtained from cats, dogs and humans as compared to reference strains. We detected differences regarding presence of the melanin among the clinical isolates of S. schenckii and a correlation between presence of melanin and cell wall thickness.

Itraconazol é atualmente considerado a droga de escolha para o tratamento das diferentes formas clínicas da esporotricose. Por outro lado a terbinafina devido a sua excelente atividade in vitro está sendo avaliada quanto ao seu potencial terapêutico frente a diversas infecções fúngicas. O objetivo deste estudo foi determinar a eficácia in vivo da terbinafina e itraconazol em um modelo de esporotricose experimental sistêmica. 120 ratos Wistar receberam uma injeção de 2x10³ células de S. schenckii pela veia lateral da cauda. Após 3 dias os animais foram tratados com terbinafina (250mg/kg) e itraconazol (100mg/kg) e os seus respectivos diluentes. No modelo experimental estudado, a terbinafina e itraconazol se mostraram efetivos reduzindo o número de sintomas clínicos e retroisolamento positivo para o agente. Houve diferenças estatísticas entre os grupos tratados com os antifúngicos em relação aos grupos controle (p<0,05) nas alterações clínicas, achados anatomopatológicos e no retroisolamento do agente, sendo que os animais tratados resultaram na ausência e/ou diminuição de todos os parâmetros avaliados. Quanto aos tratamentos a terbinafina se mostrou com atividade similar ou superior ao itraconazol quando avaliado as alterações anatomopatológicos do testículo (p=0,0004), assim como no retoisolamento do órgão (p=0,0142). Com estes resultados permite-se concluir que os antifúngicos estudados são efetivos no tratamento da esporotricose sistêmica experimental.

Itraconazole is currently considered the drug of choice to treat the diverse clinical presentation of sporotrichosis. On the other hand terbinafine by virtue of its excellent in vitro activity is under comparative evaluation for its therapeutic potential for a wide range of fungal infections. In this study, our aim was to determine the in vivo efficacy of terbinafine and itraconazole on a experimental model of systemic sporotrichosis. 120 rats Wistar received an injection of 2x10³ S. schenckii cells by via the lateral tail vein. After 3 days the animals were treated with terbinafine (250mg/kg) and itraconazole (100 mg/kg) and their respective diluents. In our model, terbinafine and itraconazole were effective in reducing the number of clinical lesions and positive organ cultures. There was statistical difference between the groups treated with the antifungals in relation to the control groups (p<0,05) concerning the clinical alterations, anatomic-pathological findings and in the positive organ cultures of the agent, being that the treated animals resulted in the absence and/or reduction of all the evaluated parameters. As for the treatments, terbinafine showed similar or higher activity that itraconazole in the evaluation of the testicle alteration (p=0,0004), as well as in the positive organ cultures of microorganism from the organ (p=0,0142). With these results it is possible to conclude that the antifungals studied are effective in the treatment of experimental systemic sporotrichosis.