Efeito de extratos vegetais de Hamamelis virginiana, Persea americana, Cynara scolymus L e Stryphnodendron barbatiman Msobre a expressão fenotípica dos fatores de virulência em biofilmes de Candida albicans / Effect of Hamamelis virginiana, Persea americana, Cynara scolymus L and Stryphnodendron barbatiman M plant extracts on the phenotypic expression of virulence factors in biofilms of the Candida albicans

Objetivo: Analisar a expressão fenotípica de fatores de virulência em biofilmes de Candida albicans frente a extratos glicólicos de plantas. Material e Métodos: Os biofilmes de Candida albicans (ATCC 18804) obtidos a partir de incubação de 48 horas foram expostos por 5 minutos e 24 horas a diferentes concentrações de extratos glicólicos de Hamamelis virginiana e Persea americana, Cynara scolymus L e Stryphnodendron barbatiman M, a fim de verificar a ação antifúngica da proteinase, fosfolipase e hemolisina. Resultados: Todos os extratos foram eficazes na redução do biofilme. Em contato por 5 minutos. os extratos reduziram 50% do biofilme. Após 24 horas. o extrato de Persea americana apresentou o biofilme em 90%, seguido de Cynara scolymus, que o interrompeu em 85%. Houve mudança na intensidade da proteinase após 5 minutos e 24 horas, com uma atividade enzimática média de 0,69 em comparação com o controle de 0,49. Cynara scolymus foi o extrato com maior concentração média de 100 mg/ml; a intensidade da fosfolipase foi alterada com Stryphnodendron barbatiman sendo mais efetivo em 24 horas em relação ao controle (p< 0,0001). A secreção de hemolisina foi modificada por Hamamelis virginiana (12,5 mg/ml) após 5 minutos de exposição e em 24 horas. todos os extratos foram capazes de causar alterações na secreção. Conclusão: Os extratos testados apresentam potencial antifúngico em biofilmes de Candida albicans, implicando em redução significativa dos fatores de virulência. Assim, estes podem ser indicados como uma ferramenta terapêutica alternativa para reduzir a morbidade dessas infecções, já que em ambos os tempos de exposição investigados, eles foram capazes de reduzir a secreção enzimática do fungo (AU)

Objective: Analyze the phenotypic expression of virulence factors in Candida albicans biofilms against plant glycolicextracts. Material and Methods: The biofilms of Candida albicans (ATCC 18804) obtained from incubation for 48 hours were exposed for 5 minutes and 24 hours to different concentrations of glycolic extracts of Hamamelis virginiana and Persea americana, Cynara scolymus L and Stryphnodendron barbatiman M, in order to verify the antifungal activity of the proteinase, phospholipase and hemolysin. Results: All extracts were effective in reducing biofilm. In contact for 5 minutes. the extracts reduced 50% of the biofilm. After 24 hours, the Persea americanaextract showed the biofilm at 90%, followed by Cynara scolymus, which interrupted it at 85%, There was a change in proteinase intensity after 5 minutes and 24 hours. with an average enzymatic activity of 0.69 compared to the control of 0.49. Cynara scolymus was the extract with the highest mean concentration of 100 mg/ml; the phospholipase intensity was changed with Stryphnodendron barbatiman being more effective in 24 hours compared to the control (p< 0.0001). The hemolysin secretion was modified by Hamamelis virginiana (12.5 mg/ml) after 5 minutes of exposure, and in 24 hours. all extracts were capable to cause changes in secretion. Conclusion: The tested extracts have antifungal potential in Candida albicans biofilms, implying a significant reduction in virulence factors. Thus, these can be indicated as an alternative therapeutic tool to reduce the morbidity of these infections, as in both investigated exposure times. they were able to reduce theenzymatic secretion of the fungus (AU)

Atividade antifúngica de nanofibras de policaprolactona/nistatina: estudo in vitro e in vivo / Antifungal activity of polycaprolactone/nystatin nanofibers: in vitro and in vivo study

Este estudo avaliou a eficácia in vitro e in vivo de mantas de nanofibras (NF) de policaprolactona (PCL) incorporadas com nistatina (NIS) no tratamento da estomatite protética (EP) em modelos animais. NF foram sintetizadas com diferentes concentrações de NIS, totalizando quatro soluções: PCL puro, PCL/NIS 0,045 g, PCL/NIS 0,090 g e PCL/NIS 0,225 g. A liberação da NIS foi analisada por espectroscopia Ultravioleta-Visível. A capacidade das mantas de inibirem o biofilme de Candida albicans, principal fator etiológico da EP, dividindo-se cinco grupos (N=5) compostos por um grupo com controle de células de C. albicans e com PCL puro, além das três concentrações de NIS. A seguir, foi analisada a viabilidade celular em queratinócitos humanos (HaCat) por meio do teste colorimétrico de resazurina. Cinco grupos foram divididos (N=10): controle celular, PCL puro e as três concentrações de NIS. Em modelos animais de ratos Wistar albinos (N=18), dispositivos palatinos (DP) de resina acrílica foram confeccionados simulando próteses totais e utilizados para a indução da EP. Para isso, DP contaminados com C. albicans foram cimentados na região molar da cavidade bucal dos animais e permaneceram em boca por 48 h. Após esse período, os DP foram removidos e os animais foram divididos em três grupos: (C) controle; (B1) com tratamento por mantas de PCL/NIS 0,045 g e (B2) PCL/NIS 0,225 g, com N=6. Então novos DP, livres de contaminação, foram cimentados na cavidade oral dos animais e permaneceu por mais 48 h. Após esse período, os animais foram eutanasiados, a contagem de UFC/ mL foi realizada e os palatos foram coletados para a análise histológica. A curva padrão de NIS obtida apresentou R2 de 0,99. As três concentrações de NF apresentaram liberação de NIS, com pico no tempo de 6 h e valores de 66,26 µg/ mL para PCL/NIS 0,045 g, de 333,87 µg/ mL para PCL/NIS 0,090 g e 436,51 µg/ mL para PCL/NIS 0,225 g, constantes até o fim do experimento. Os grupos com NIS reduziram em 2,5 log10 de crescimento do biofilme fúngico em relação aos grupos sem tratamento, Controle e PCL, sem diferença estatística significativa. Não foi observada citotoxicidade nas células HaCat, com viabilidade celular de 93,7% para PCL/NIS 0,045 g, 72,6% para PCL/NIS 0,090 g e 72,4% para PCL/NIS 0,225 g. A indução da EP nos três grupos foi possível e, porém, sem redução significativa na contagem de UFC/ mL de C. albicans nos grupos B1 e B2. Na análise histológica do grupo C pôde-se observar infiltração de hifas de Candida na camada queratinizada, presença de células inflamatórias formando micro abscessos e um discreto infiltrado inflamatório no tecido conjuntivo subjacente ao epitélio infectado. Nos grupos B1 e B2 não foram encontradas alterações epiteliais, concluindo-se que as NF demonstraram atividade antifúngica in vitro e foram efetivas na prevenção da penetração de hifas no tecido palatino de animais com DP (AU)

This study evaluated the in vitro and in vivo efficacy of nanofiber (NF) mats of polycaprolactone (PCL) incorporated with nystatin (NIS) in the treatment of denture stomatitis (DS) in animal models. NFs were synthesized with different concentrations of NIS, totaling four solutions: pure PCL, PCL/NIS 0.045 g, PCL/NIS 0.090 g, and PCL/NIS 0.225 g. The release of NIS was analyzed by Ultraviolet-Visible spectroscopy. The ability of the mats to inhibit Candida albicans biofilm, the main etiological factor of DS, was assessed by dividing five groups (N=5) composed of a group with C. albicans cell control and with pure PCL, in addition to the three concentrations of NIS. Next, cell viability in human keratinocytes (HaCat) was analyzed using the resazurin colorimetric test. Five groups were divided (N=10): cell control, pure PCL, and the three concentrations of NIS. In albino Wistar rat animal models (N=18), palatal devices (PD) made of acrylic resin were fabricated to simulate total prostheses and used to induce DS. For this, PD contaminated with C. albicans were cemented in the molar region of the animals' oral cavity and remained in the mouth for 48 hours. After this period, the PDs were removed, and the animals were divided into three groups: (C) control; (B1) treated with PCL/NIS 0.045 g mats, and (B2) PCL/NIS 0.225 g, with N=6. Then new, uncontaminated PDs were cemented in the animals' oral cavity and remained for another 48 hours. After this period, the animals were euthanized, UFC/ mL counts were performed, and the palates were collected for histological analysis. The standard NIS curve obtained showed an R2 of 0.99. The three concentrations of NF showed NIS release, with a peak at 6 h and values of 66.26 µg/ mL for PCL/NIS 0.045 g, 333.87 µg/ mL for PCL/NIS 0.090 g, and 436.51 µg/ mL for PCL/NIS 0.225 g, remaining constant until the end of the experiment. The groups with NIS reduced fungal biofilm growth by 2.5 log10 compared to the untreated groups, Control and PCL, with no significant statistical difference. No cytotoxicity was observed in HaCat cells, with cell viability of 93.7% for PCL/NIS 0.045 g, 72.6% for PCL/NIS 0.090 g, and 72.4% for PCL/NIS 0.225 g. Induction of DS in the three groups was possible; however, there was no significant reduction in UFC/ mL counts of C. albicans in groups B1 and B2. Histological analysis of group C revealed infiltration of Candida hyphae in the keratinized layer, presence of inflammatory cells forming micro abscesses, and a discreet inflammatory infiltrate in the connective tissue underlying the infected epithelium. No epithelial alterations were found in groups B1 and B2, concluding that NFs demonstrated in vitro antifungal activity and were effective in preventing hyphal penetration into palatal tissue in animals with PD.(AU)

Comparative in vitro analysis of the antifungal activity of different calcium silicate-based endodontic sealers

Aim: This study aimed to perform an in vitro comparative analysis of the antifungal activity of different calcium silicate-based endodontic sealers against three fungal species. Methods: The antifungal properties of three calcium silicate-based sealers were tested: Bio-C Sealer, Cambiar a Sealer Plus BC, and MTA-Fillapex. Two commonly used sealers were used as controls: AH Plus and Endomethasone. An agar diffusion test was performed to analyze the antifungal activity of the sealers against Candida albicans, Candida glabrata, Candida tropicalis, and a mixed microbial culture medium. The results were analyzed using ANOVA (p <0.05). Results: Endomethasone exhibited the highest inhibition against all strains examined, maintaining a consistent level of inhibition throughout 7 days. MTA-Fillapex demonstrated the best performance among the calcium silicate-based sealers for the three fungal species (p < 0.05), maintaining stable values over the 7 days, surpassing that of Endomethasone. Nevertheless, MTA-Fillapex only exhibited antimicrobial effect against the mixed culture for the first 24 hours, and no antimicrobial activity was observed at 48 hours, being surpassed by all tested sealers (p < 0.05). Conclusion: Of all silicate-based sealers tested, only MTA-Fillapex exhibited promising antifungal activity. Nevertheless, care must be taken when extrapolating these results, as MTA-Fillapex exhibited poor antimicrobial activity when tested in mixed microbial cultures

Efeitos dos líquidos ativados com plasma atmosférico sobre Candida albicans / Application of plasma activated liquids on Candida albicans

O incremento no número de casos refratários aos tratamentos convencionais e a limitação de opções terapêuticas são alguns dos desafios encontrados no tratamento da candidose bucal, apontando para a necessidade de terapias alternativas. A utilização da tecnologia de plasma de forma indireta, pela exposição prévia de líquidos ex situ, tem mostrado resultados promissores, trazendo inúmeras vantagens para a aplicação clínica. Até o momento, pouco se conhece sobre a atividade antifúngica do líquido ativado com plasma (LAP) e não foram detectados relatos sobre sua aplicabilidade no tratamento da candidose bucal. Com base neste cenário, o objetivo deste projeto foi avaliar a atividade do líquido ativado com plasma sobre Candida albicans, principal agente etiológico da candidose bucal. Para tanto, foram determinadas as condições de obtenção do LAP com maior efeito antifúngico frente a C. albicans. O LAP foi gerado em um reator de plasma tipo arco deslizante (gliding arc). Os gases empregados incluíram argônio, ar comprimido seco e suas misturas em diversas concentrações, ajustando-se o fluxo de gás e a potência conforme necessário. Avaliou-se a eficácia antifúngica de diferentes líquidos ativados contra C. albicans, tanto em estado planctônico quanto em biofilmes, visando identificar o mais efetivo. As espécies reativas dos LAP foram caracterizadas utilizando técnicas espectrofotométricas, juntamente com a avaliação dos parâmetros físico-químicos. Os resultados dos ensaios foram submetidos a análise estatística, estabelecendo-se um nível de significância de 5% para a interpretação dos dados. Observou-se que a solução salina 0,9% ativada com plasma de argônio (S1), água destilada ativada com plasma de argônio (D1) e água destilada ativado com a mistura dos gases argônio e ar comprimido (S2) apresentaram a maior atividade antifúngica sobre células planctônicas de C. albicans quando expostas por 30 minutos ao LAP. O grupo D1 apresentou maior ação frente aos biofilmes de 24 e 48 horas e o S1 frente a biofilmes de 48 horas apenas quando exposto por 30 minutos ao LAP. Ambos os LAPs apresentaram ação antifúngica após terem sido congelados e armazenados por 1 dia após a ativação. Os grupos D1 e S1 não apresentaram perfil citotóxico nos ensaios realizados. Pode-se concluir que os LAPs apresentaram ação inibitória sobre células planctônicas e sobre biofilmes de C. albicans, sem citotoxicidade para células de mamíferos, sugerindo seu potencial como adjuvante às terapias para o controle da candidose.(AU)

The increase in the number of cases refractory to conventional treatments and the limitation of therapeutic options is due to some two challenges encountered in the treatment of oral candidiasis, pointing to the need for alternative therapies. The use of plasma technology indirectly, for the exposition of liquids ex situ, has shown promising results, providing numerous advantages for clinical application. Currently, little is known about the antifungal activity of plasma-activated liquid (LAP) and there are no reports on its applicability in oral candidiasis treatment. Based on this scenario, the objective of this project is to validate the application of plasma-activated liquid as an adjuvant in the treatment of oral candidiasis. Therefore, certain conditions for obtaining LAP have greater antifungal effect against Candida albicans. The LAP was generated in a gliding arc type plasma reactor. The gases used include argon, dry compressed and their mixtures in various concentrations, adjusting the gas flow and power as necessary. The antifungal efficacy of different liquids activated against C. albicans is evaluated, both in the planktonic state and in biofilms, aiming to identify the most effective. The relative species of LAP were characterized using spectrophotometric techniques, together with the evaluation of two physical-chemical parameters. The results of two tests were submitted to statistical analysis, establishing a significance level of 5% for the interpretation of the data. It was observed that the groups that presented the greatest antifungal activity in planktonic cells of C. albicans were the groups of 0.9% saline solution activated with argonium plasma (S1), or of distilled water activated with argonium plasma (D1). e or distilled water activated with a mixture of two argon gases and compressed air (S2). The D1 group presented against biofilms of 24 and 48 hours and the S1 against biofilms of only 48 hours. Both LAPs are presented with antifungal coating and have been frozen and stored for 1 day after activation. The groups D1 and S1 do not present a cytotoxic profile in the tests carried out. It can be concluded that the LAPs have antifungal activity on planktonic cells and on biofilms and do not present a toxicity profile for human cells, being potent adjuvants in therapies for or controlling infections caused by C. albicans (AU)

Antifungal activity of 2-chloro-N-phenylacetamide: a new molecule with fungicidal and antibiofilm activity against fluconazole-resistant Candida spp / Atividade antifúngica de 2-cloro-N-fenilacetamida: uma nova molécula com atividade fungicida e anti-biofilme contra Candida spp. resistentes a fluconazol

In the current context of emerging drug-resistant fungal pathogens such as Candida albicans and Candida parapsilosis, discovery of new antifungal agents is an urgent matter. This research aimed to evaluate the antifungal potential of 2-chloro-N-phenylacetamide against fluconazole-resistant clinical strains of C. albicans and C. parapsilosis. The antifungal activity of 2-chloro-N-phenylacetamide was evaluated in vitro by the determination of the minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), inhibition of biofilm formation and its rupture, sorbitol and ergosterol assays, and association between this molecule and common antifungal drugs, amphotericin B and fluconazole. The test product inhibited all strains of C. albicans and C. parapsilosis, with a MIC ranging from 128 to 256 µg.mL-1, and a MFC of 512-1,024 µg.mL-1. It also inhibited up to 92% of biofilm formation and rupture of up to 87% of preformed biofilm. 2-chloro-N-phenylacetamide did not promote antifungal activity through binding to cellular membrane ergosterol nor it damages the fungal cell wall. Antagonism was observed when combining this substance with amphotericin B and fluconazole. The substance exhibited significant antifungal activity by inhibiting both planktonic cells and biofilm of fluconazole-resistant strains. Its combination with other antifungals should be avoided and its mechanism of action remains to be established.

No atual contexto de patógenos fúngicos resistentes emergentes tais como Candida albicans e Candida parapsilosis, a descoberta de novos agentes antifúngicos é uma questão urgente. Esta pesquisa teve como objetivo avaliar o potencial antifúngico da 2-cloro-N-fenilacetamida contra cepas clínicas de C. albicans e C. parapsilosis resistentes a fluconazol. A atividade antifúngica da substância foi avaliada in vitro através da determinação da concentração inibitória mínima (CIM), concentração fungicida mínima (CFM), ruptura e inibição da formação de biofilme, ensaios de sorbitol e ergosterol, e associação entre esta molécula e antifúngicos comuns, anfotericina B e fluconazol. O produto teste inibiu todas as cepas de C. albicans e C. parapsilosis, com uma CIM variando de 128 a 256 µg.mL-1, e uma CFM de 512-1,024 µg.mL-1. Também inibiu até 92% da formação de biofilme e causou a ruptura de até 87% de biofilme pré-formado. A 2-cloro-N-fenilacetamida não promoveu atividade antifúngica pela ligação ao ergosterol da membrana celular fúngica, tampouco danificou a parede celular. Antagonismo foi observado ao combinar esta substância com anfotericina B e fluconazol. A substância exibiu atividade antifúngica significativa ao inibir tanto as células planctônicas quanto o biofilme das cepas resistentes ao fluconazol. Sua combinação com outros antifúngicos deve ser evitada e seu mecanismo de ação deve ser estabelecido.

Candidiasis oral mixta en pacientes con diabetes de tipo 2: identificación y espectro de sensibilidad / Mixed oral candidiasis in type 2 diabetic patients: Identification and spectrum of sensitivity

Introducción. Los pacientes con diabetes mellitus de tipo 2 son propensos a adquirir infecciones por Candida spp., en ocasiones, causadas por más de una especie. La resistencia de algunas de ellas puede resultar en complicaciones médicas por falla del tratamiento. Objetivos. Determinar la frecuencia y las variedades clínicas de la candidiasis oral mixta en pacientes con diabetes mellitus de tipo 2, las especies de Candida involucradas y sus espectros de sensibilidad a los antifúngicos utilizados como tratamiento. Materiales y métodos. Se hizo un estudio transversal analítico en pacientes con diabetes mellitus de tipo 2, hiperglucemia (superior o igual al 7 % de la hemoglobina glucosilada, HbA1C) y con diagnóstico clínico de candidiasis oral. Mediante técnicas microbiológicas, se identificaron las especies causales de la candidiasis oral. Las pruebas de sensibilidad se llevaron a cabo con el método de difusión en placa con tiras (E-test®). Resultados. Se incluyeron 72 pacientes: 32 (44 %) hombres y 40 (56 %) mujeres, clasificados en tres grupos de edad: jóvenes adultos (17 %), adultos (74 %) y ancianos (9 %), con una media de 51 años. No se encontraron diferencias significativas en la candidiasis oral según los grupos de sexo y edad, ni entre las candidiasis orales mixtas y el sexo, el porcentaje de HbA1C, el tratamiento antihiperglucemiante o el tiempo de diagnóstico de la diabetes mellitus de tipo 2. En el grupo etario de adultos, se encontró una correlación con las candidiasis mixtas o simples. Se encontraron 8 (13 %) casos de candidiasis mixtas: siete con coinfección por dos especies de Candida y uno con coinfección por tres especies. Las especies identificadas en ellos, fueron: Candida albicans, C. glabrata, C. dubliniensis, C. kefyr, C. tropicalis y C. krusei. La mayoría de estas especies presentó sensibilidad a ketoconazol y fluconazol, y mayor resistencia a itraconazol. Conclusiones. Las candidiasis orales mixtas se presentan, aproximadamente, en el 10 % de los pacientes con diabetes mellitus de tipo 2 y el tratamiento puede ser ineficaz cuando no se identifica el agente etiológico.

Introduction. Patients with type 2 diabetes mellitus are susceptible to acquire Candida spp. infections, sometimes involving more than one species. The resistance of some species to antimycotic agents can cause treatment failure. Objectives. To determine the frequency and clinical varieties of mixed oral candidiasis in patients with type 2 diabetes mellitus, the involved species, and its sensitivity spectra when exposed to antifungals used as candidiasis treatment. Materials and methods. We developed an analytical cross-sectional study with 72 patients with type 2 diabetes mellitus with hyperglycemia (HbAIC s 7%) and an oral candidiasis diagnosis. The causal species of oral candidiasis were identified through microbiological techniques, and sensitivity tests were carried out using the diffusion method in a plate with strips (E-test ®). Results. We included 72 patients in the study, 32 (44%) males and 40 (56%) females. Patients were divided into three age groups: young adults (17%), adults (74%), and older adults (9%). The mean age of the patients was 51 years. No significant differences were found between mixed oral candidiasis and groups (sex and age), or between mixed oral candidiasis and gender, glycosylated hemoglobin level (HbA1C), antihyperglycemic treatment, or type 2 diabetes mellitus time of diagnosis. We found a correlation between the adult group and development of mixed or simple oral candidiasis. The results showed eight (13%) cases of mixed oral candidiasis: seven with a coinfection of two species and one with a coinfection of three species. The identified species were Candida albicans, C. glabrata, C. dubliniensis, C. kefyr, C. tropicalis, and C. krusei. Most of these species presented sensitivity against ketoconazole and fluconazole, and higher resistance to itraconazole. Conclusions. Mixed oral candidiasis occurs in approximately 10% of the patients with type 2 diabetes mellitus and its treatment can be ineffective when the etiological agent is not identified.

Evaluación antifúngica del ozono contra Candida albicans: estudio in vitro / Antifungal evaluation of ozone against Candida albicans: in vitro study

Introducción: la Candida albicans (C. albicans) es un patógeno fúngico que puede causar infecciones superficiales o potencialmente mortales. Los biofilms de C. albicans muestran rasgos fenotípicos únicos, el más destacado es su notable resistencia a una amplia variedad de agentes antimicóticos. Una de las alternativas para inhibir el crecimiento de este microorganismo es el ozono debido a sus propiedades bactericidas, fungicidas y virucidas; sin embargo, escasa información ha sido reportada en C. albicans. Objetivo: el objetivo de este estudio fue evaluar el efecto fungicida del ozono en C. albicans. Material y métodos: la metodología consistió en agregar ozono a tubos de ensayo con medios de caldo nutritivo en diversas concentraciones y tiempos de ozonización. El efecto fungicida fue determinado con la determinación del número de colonias de C. albicans en agar nutritivo a través de procedimiento microbiológicos estandarizados por triplicado. Resultados: todas las muestras con ozono mostraron adecuados niveles de inhibición de crecimiento del microorganismo. Además, el efecto fungicida del ozono se encontró para ser significativamente dependiente del tiempo de ozonización y de la concentración. Conclusión: el uso de terapia con ozono podría tener potencial en el control de infecciones micóticas causadas por la presencia de C. albicans (AU)

Introduction: Candida albicans (C. albicans) is a fungal pathogen that can cause superficial or life-threatening infections. Biofilms of C. albicans display unique phenotypic traits, the most prominent being their remarkable resistance to a wide variety of antifungal agents. One of the alternatives to inhibit the growth of this microorganism is ozone due to its bactericidal, fungicidal and virucidal properties; however, little information has been reported on C. albicans. Objective: the objective of this study was to evaluate the fungicidal effect of ozone on C. albicans. Material and methods: the methodology consisted in adding ozone to test tubes with nutrient broth media in various concentrations and ozonation times. The fungicidal effect was determined by determining the number of colonies of C. albicans in nutrient agar through standardized microbiological procedures in triplicate. Results: all the ozone samples showed adequate levels of growth inhibition of the microorganism. Furthermore, the fungicidal effect of ozone was found to be significantly dependent on ozonation time and concentration. Conclusion: the use of ozone therapy could have potential in the control of fungal infections caused by the presence of C. albicans (AU)

Actividad antifúngica y la caracterización física de un dentífrico experimental que contiene carvacrol / Antifungal activity and physical characterization of an experimental dentifrice containing carvacrol

Introduction: The successful treatment of oral candidiasis depends on three essential principles, namely: early and accurate diagnosis, correlation with predisposing factors or underlying diseases that compromise immunity, and appropriate use of antifungal drugs. Objectives: To determine the minimum inhibitory concentration of carvacrol against Candida albicans and to develop and evaluate the in vitro antifungal activity (diameter of inhibition zone) and physical properties (foaming capacity, spreadability and cleaning capacity) of an experimental dentifrice containing carvacrol. Methods: The carvacrol was incorporated into a dentifrice base at different concentrations and tested for its minimum inhibitory concentration and agar diffusion against Candida albicans and the physical properties. Data were analysed by ANOVA. Results: The minimum inhibitory concentration of carvacrol was 1041.67 ± 360.84 µg/mL. The dentifrice containing carvacrol C1 e C2 produced an inhibition zone of 27.50 ± 2.12 mm and 36.66 ± 2.08 mm, respectively (p<0.05). As for the physical properties, the dentifrices showed no foaming capacity, while their cleaning capacity and spreadability remained unaltered. Conclusions: The experimental dentifrices containing carvacrol showed antifungal activity. The incorporation of carvacrol significantly altered the foaming capacity of the formulations, without any significant effects on their cleaning capacity and spreadability(AU)

Introducción: El tratamiento exitoso de la candidiasis oral depende de tres principios esenciales, a saber: diagnóstico temprano y preciso, correlación con factores predisponentes o enfermedades subyacentes que comprometan la inmunidad y uso apropiado de medicamentos antimicóticos. Objetivos: Determinar la concentración inhibitoria mínima de carvacrol contra Candida albicans y desarrollar y evaluar la actividad antifúngica in vitro (diámetro de la zona de inhibición) y las propiedades físicas (capacidad espumante, esparcibilidad y capacidad de limpieza) de un dentífrico experimental que contiene carvacrol. Métodos: El carvacrol se incorporó a una base dentífrica a diferentes concentraciones y se probó su concentración mínima inhibitoria y difusión en agar contra Candida albicans y las propiedades físicas. Los datos fueron analizados por ANOVA. Resultados: La concentración mínima inhibitoria de carvacrol fue 1041,67 ± 360,84 µg/mL. El dentífrico con carvacrol C1 y C2 produjo un halo de inhibición de 27,50 ± 2,12 mm y 36,66 ± 2,08 mm, respectivamente (p < 0,05). En cuanto a las propiedades físicas, los dentífricos no mostraron capacidad espumante, mientras que su capacidad de limpieza y esparcibilidad permanecieron inalteradas. Conclusiones: Los dentífricos experimentales que contenían carvacrol mostraron actividad antifúngica. La incorporación de carvacrol alteró significativamente la capacidad espumante de las formulaciones, sin efectos significativos sobre su capacidad de limpieza y esparcibilidad(AU)

Causative Microorganisms Isolated from Patients with Intra-Abdominal Infections and Their Drug Resistance Profiles: An 11-Year (2011-2021) Single-Center Retrospective Study / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the distribution and antimicrobial susceptibility of causative microorganisms recovered from patients with intra-abdominal infections (IAIs).@*METHODS@#A total of 2,926 bacterial and fungal strains were identified in samples collected from 1,679 patients with IAIs at the Peking Union Medical College Hospital between 2011 and 2021. Pathogenic bacteria and fungi were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Antimicrobial susceptibility testing (AST) was performed using the VITEK 2 compact system and the Kirby-Bauer method. AST results were interpreted based on the M100-Ed31 clinical breakpoints of the Clinical and Laboratory Standards Institute.@*RESULTS@#Of the 2,926 strains identified, 49.2%, 40.8%, and 9.5% were gram-negative bacteria, gram-positive bacteria, and fungi, respectively. Escherichia coli was the most prevalent pathogen in intensive care unit (ICU) and non-ICU patients; however, a significant decrease was observed in the isolation of E. coli between 2011 and 2021. Specifically, significant decreases were observed between 2011 and 2021 in the levels of extended-spectrum β-lactamase (ESBL)-producing E. coli (from 76.9% to 14.3%) and Klebsiella pneumoniae (from 45.8% to 4.8%). Polymicrobial infections, particularly those involving co-infection with gram-positive and gram-negative bacteria, were commonly observed in IAI patients. Moreover, Candida albicans was more commonly isolated from hospital-associated IAI samples, while Staphylococcus epidermidis had a higher ratio in community-associated IAIs. Additionally, AST results revealed that most antimicrobial agents performed better in non-ESBL-producers than in ESBL-producers, while the overall resistance rates (56.9%-76.8%) of Acinetobacter baumanmii were higher against all antimicrobial agents than those of other common gram-negative bacteria. Indeed, Enterococcus faecium, Enterococcus faecalis, S. epidermidis, and S. aureus were consistently found to be susceptible to vancomycin, teicoplanin, and linezolid. Similarly, C. albicans exhibited high susceptibility to all the tested antifungal drugs.@*CONCLUSION@#The distribution and antimicrobial susceptibility of the causative microorganisms from patients with IAIs were altered between 2011 and 2021. This finding is valuable for the implementation of evidence-based antimicrobial therapy and provides guidance for the control of hospital infections.

Artemisinins inhibit oral candidiasis caused by Candida albicans through the repression on its hyphal development / 国际口腔科学杂志·英文版

Candida albicans is the most abundant fungal species in oral cavity. As a smart opportunistic pathogen, it increases the virulence by switching its forms from yeasts to hyphae and becomes the major pathogenic agent for oral candidiasis. However, the overuse of current clinical antifungals and lack of new types of drugs highlight the challenges in the antifungal treatments because of the drug resistance and side effects. Anti-virulence strategy is proved as a practical way to develop new types of anti-infective drugs. Here, seven artemisinins, including artemisinin, dihydroartemisinin, artemisinic acid, dihydroartemisinic acid, artesunate, artemether and arteether, were employed to target at the hyphal development, the most important virulence factor of C. albicans. Artemisinins failed to affect the growth, but significantly inhibited the hyphal development of C. albicans, including the clinical azole resistant isolates, and reduced their damage to oral epithelial cells, while arteether showed the strongest activities. The transcriptome suggested that arteether could affect the energy metabolism of C. albicans. Seven artemisinins were then proved to significantly inhibit the productions of ATP and cAMP, while reduced the hyphal inhibition on RAS1 overexpression strain indicating that artemisinins regulated the Ras1-cAMP-Efg1 pathway to inhibit the hyphal development. Importantly, arteether significantly inhibited the fungal burden and infections with no systemic toxicity in the murine oropharyngeal candidiasis models in vivo caused by both fluconazole sensitive and resistant strains. Our results for the first time indicated that artemisinins can be potential antifungal compounds against C. albicans infections by targeting at its hyphal development.

Chemical constituents from Paris rugosa rhizomes and their antimicrobial activities / 中国中药杂志

Paris rugosa(Melanthiaceae) only grows in Yunnan province of China at present, and its chemical constituents have not been systematically studied. In this study, nine compounds, including one new compound pariposide G(1) and eight known compounds of cerin(2), stigmast-4-en-3-one(3), β-ecdysone(4), ophiopogonin C'(5), methyl protogracillin(6), gracillin(7), parissaponin H(8), and parisyunnanoside G(9), were isolated and identified from the ethanol extract of P. rugosa rhizomes by column chromatography methods and semi-preparative high-performance liquid chromatography(HPLC). Compounds 1-9 were isolated from this plant for the first time. The antibacterial and antifungal activities of all the compounds were evaluated. The results showed that ophiopogonin C' had strong inhibitory effects on Candida albicans [MIC_(90)=(4.68±0.01) μmol·L~(-1)] and the fluconazole-resistant strain of C. albicans [MIC_(90)=(4.66±0.02) μmol·L~(-1)].

Effects of iron accumulation on dental caries, gingivitis, and candida albicans infection in children with beta thalassemia major: A narrative review

Background@#Thalassemia is a common inherited hemolytic disorder characterized by the absence or reduction of one of the globin chains. Beta thalassemia major generally has oral cavity manifestations. Patients with beta thalassemia major often require routine blood transfusion. However, this treatment has the side effect of accumulating iron in the salivary glands, which increase the risk of dental caries, gingivitis, and secondary infection from Candida albicans.@*Objective@#The aim of this review is to explain the relationship of salivary iron levels and the effects of iron accumulation on dental caries, gingivitis, and Candida albicans infection.@*Methods@#A comprehensive search was performed on PubMed, Scopus, and Google Scholar databases using the keywords beta thalassemia major, iron, dental caries, gingivitis, Candida albicans.@*Results@#Iron is an essential micronutrient needed by Candida albicans for its growth and virulence. Blood transfusion in patients with beta thalassemia major can lead to a buildup of iron in the salivary glands and trigger the formation of non-transferrin bound iron (NTBI). NTBI can circulate in plasma and form a reactive oxygen species (ROS) that stimulate the formation of biofilms and increase dental caries. ROS may affect several genes associated with the inflammatory process and increase the incidence of gingivitis. It can also reduce salivary secretion in patients with thalassemia-β major that cause dysbiosis, which triggers an overgrowth of Candida albicans.@*Conclusion@#The excess iron in patients with beta thalassemia major increase the risk of dental caries, gingivitis, and Candida albicans infection.

Mechanism of n-butanol alcohol extract of Baitouweng Decoction in treatment of vulvovaginal candidiasis based on negative regulation of NLRP3 inflammasome via PKCδ/NLRC4/IL-1Ra axis / 中国中药杂志

This study aimed to explore the mechanism of n-butanol alcohol extract of Baitouweng Decoction(BAEB) in the treatment of vulvovaginal candidiasis(VVC) in mice based on the negative regulation of NLRP3 inflammasome via PKCδ/NLRC4/IL-1Ra axis. In the experiment, female C57BL/6 mice were divided randomly into the following six groups: a blank control group, a VVC model group, high-, medium-, and low-dose BAEB groups(80, 40, and 20 mg·kg~(-1)), and a fluconazole group(20 mg·kg~(-1)). The VVC model was induced in mice except for those in the blank control group by the estrogen dependence method. After modeling, no treatment was carried out in the blank control group. The mice in the high-, medium-, and low-dose BAEB groups were treated with BAEB at 80, 40, and 20 mg·kg~(-1), respectively, and those in the fluconazole group were treated with fluconazole at 20 mg·kg~(-1). The mice in the VVC model group received the same volume of normal saline. The general state and body weight of mice in each group were observed every day, and the morphological changes of Candida albicans in the vaginal lavage of mice were examined by Gram staining. The fungal load in the vaginal lavage of mice was detected by microdilution assay. After the mice were killed, the degree of neutrophil infiltration in the vaginal lavage was detected by Papanicolaou staining. The content of inflammatory cytokines interleukin(IL)-1β, IL-18, and lactate dehydrogenase(LDH) in the vaginal lavage was tested by enzyme-linked immunosorbent assay(ELISA), and vaginal histopathology was analyzed by hematoxylin-eosin(HE) staining. The expression and distribution of NLRP3, PKCδ, pNLRC4, and IL-1Ra in vaginal tissues were measured by immunohistochemistry(IHC), and the expression and distribution of pNLRC4 and IL-1Ra in vaginal tissues were detected by immunofluorescence(IF). The protein expression of NLRP3, PKCδ, pNLRC4, and IL-1Ra was detected by Western blot(WB), and the mRNA expression of NLRP3, PKCδ, pNLRC4, and IL-1Ra was detected by qRT-PCR. The results showed that compared with the blank control group, the VVC model group showed redness, edema, and white secretions in the vagina. Compared with the VVC model group, the BAEB groups showed improved general state of VVC mice. As revealed by Gram staining, Papanicolaou staining, microdilution assay, and HE staining, compared with the blank control group, the VVC model group showed a large number of hyphae, neutrophils infiltration, and increased fungal load in the vaginal lavage, destroyed vaginal mucosa, and infiltration of a large number of inflammatory cells. BAEB could reduce the transformation of C. albicans from yeast to hyphae. High-dose BAEB could significantly reduce neutrophil infiltration and fungal load. Low-and medium-dose BAEB could reduce the da-mage to the vaginal tissue, while high-dose BAEB could restore the damaged vaginal tissues to normal levels. ELISA results showed that the content of inflammatory cytokines IL-1β, IL-18, and LDH in the VVC model group significantly increased compared with that in the blank control group, and the content of IL-1β, IL-18 and LDH in the medium-and high-dose BAEB groups was significantly reduced compared with that in the VVC model group. WB and qRT-PCR results showed that compared with the blank control group, the VVC model group showed reduced protein and mRNA expression of PKCδ, pNLRC4, and IL-1Ra in vaginal tissues of mice and increased protein and mRNA expression of NLRP3. Compared with the VVC model group, the medium-and high-dose BAEB groups showed up-regulated protein and mRNA expression of PKCδ, pNLRC4, and IL-1Ra in vaginal tissues and inhibited protein and mRNA expression of NLRP3 in vaginal tissues. This study indicated that the therapeutic effect of BAEB on VVC mice was presumably related to the negative regulation of NLRP3 inflammasome by promoting PKCδ/NLRC4/IL-1Ra axis.

Identification of the target site of antimicrobial peptide AMP-17 against Candida albicans / 生物工程学报

Candida albicans is one of the major causes of invasive fungal infections and a serious opportunistic pathogen in immunocompromised individuals. The antimicrobial peptide AMP-17 has prominent anti-Candida activity, and proteomic analysis revealed significant differences in the expression of cell wall (XOG1) and oxidative stress (SRR1) genes upon the action of AMP-17 on C. albicans, suggesting that AMP-17 may exert anti-C. albicans effects by affecting the expression of XOG1 and SRR1 genes. To further investigate whether XOG1 and SRR1 genes were the targets of AMP-17, C. albicans xog1Δ/Δ and srr1Δ/Δ mutants were constructed using the clustered regulatory interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9) system. Phenotypic observations revealed that deletion of two genes had no significant effect on C. albicans growth and biofilm formation, whereas XOG1 gene deletion affected in vitro stress response and mycelium formation of C. albicans. Drug sensitivity assay showed that the MIC80 values of AMP-17 against xog1Δ/Δ and srr1Δ/Δ mutants increased from 8 μg/mL (for the wild type C. albicans SC5314) to 16 μg/mL, while the MIC80 values against srr1Δ/Δ: : srr1 revertants decreased to the level of the wild type SC5314. In addition, the ability of AMP-17 to inhibit biofilm formation of both deletion strains was significantly reduced compared to that of wild type SC5314, indicating that the susceptibility of the deletion mutants to AMP-17 was reduced in both the yeast state and during biofilm formation. These results suggest that XOG1 and SRR1 genes are likely two of the potential targets for AMP-17 to exert anti-C. albicans effects, which may facilitate further exploration of the antibacterial mechanism of novel peptide antifungal drugs.

Aplicação do plasma de baixa temperatura sob pressão atmosférica como adjuvante ao tratamento da mucosite oral / Application of low temperature atmospheric pressure plasma as an adjuvant in treatment oral mucositis

A mucosite oral é um quadro clínico que acomete frequentemente pacientes sob terapia antineoplásica na região de cabeça e pescoço e caracteriza-se por ulcerações na mucosa que geram intensa dor local, odinofagia, aumento do risco de infecções, do uso de antibióticos e do tempo de hospitalização. A correlação entre mucosite oral, infecção fúngica e o potencial de disseminação fúngica sistêmica foi recentemente descrita. Apesar do impacto desse quadro clínico sobre a qualidade e tempo de vida dos pacientes oncológicos, não há consenso sobre a profilaxia e o protocolo terapêutico. O plasma de baixa temperatura sobre pressão atmosférica (LTAPP) apresenta efeito antimicrobiano, anti-inflamatório e reparador tecidual, o que sugere que possa ser promissor no tratamento da mucosite oral. Os objetivos gerais deste projeto foram divididos em dois subprojetos: 1) Definir os melhores parâmetros in vitro com efeito antifúngico e não tóxico e avaliar o LTAPP no tratamento de lesão de mucosite oral em modelo murino de mucosite por quimioterapia e 2) avaliar se o tratamento com LTAPP pode prevenir a disseminação fúngica sistêmica em ratos a partir de infecção experimental de lesões de mucosite oral por Candida albicans. Para tal, foram incluídos no estudo 100 ratos (Rattus norvegicus) com 90 a 100 dias de idade. No subprojeto 1, a lesão de mucosite oral foi induzida por administração de 5 fluorouracila (5-FU), enquanto no subprojeto 2, utilizou-se 5-FU associada à cisplatina ambas associadas à aplicação tópica de ácido acético 50%. Para o subprojeto 1, os animais foram randomicamente divididos em 2 grupos experimentais (n=30): a) Grupo mucosite; b) Grupo mucosite tratado com LTAPP, avaliados após 1, 5 e 12 dias do tratamento. Durante o período experimental, as lesões foram fotografadas e a gravidade da mucosite classificada por meio da atribuição de escores. Após a eutanásia e o processamento, os cortes histológicos corados por hematoxilina-eosina (HE) foram analisados microscopicamente. Para o subprojeto 2, o estudo de disseminação sistêmica fúngica nos grupos de mucosite infectada com C. albicans tratado ou não com LTAPP foi conduzido pelo isolamento fúngico a partir de amostras de sangue total e macerado dos órgãos. Para tanto foram estudados 2 grupos de ratos (n=20): c) Grupo mucosite infectado com C. albicans e d) Grupo mucosite infectado com C. albicans tratada com LTAPP, avaliados após 24 e 72 h do tratamento. Para ambos os projetos, o melhor parâmetro in vitro foi selecionado, isto é aquele com maior atividade antifúngica e baixa toxicidade. Dessa forma, as lesões foram expostas ao LTAPP de hélio por 5 min na distância de 1,5 cm na potência de 1 W. Os resultados in vitro mostraram que o LTAPP teve efeito antifúngico e baixa toxicidade para células de mamíferos. Os resultados in vivo mostraram que 5-FU afetou a saúde geral dos animais, evidenciada pela perda de peso corporal. Em ambos os grupos, houve reparo tecidual após 12 dias do tratamento, com resolução quase completa da lesão, o que foi corroborado pelos achados microscópicos. O grupo LTAPP exibiu uma tendência maior de redução da lesão, após 12 dias de tratamento. Além disso, o LTAPP apresentou efeito inibitório sobre C. albicans após 5 minutos, de exposição, com redução da recuperação fúngica da língua após 24 h (p<0.05). A disseminação fúngica sistêmica foi reduzida significativamente após 24 e 72 h do tratamento. Com base nos resultados obtidos, conclui-se que o LTAPP é uma ferramenta promissora para futura aplicação clínica em pacientes com mucosite oral. (AU)

Oral mucositis is a clinical condition that frequently affects patients undergoing antineoplastic therapy in the head and neck region and is characterized by mucosal ulcerations that generate intense local pain, odynophagia, increased risks of infections, use of antibiotics and the length of hospital stay. The correlation among oral mucositis, fungal infection and the potential for systemic fungal dissemination has recently been described. Despite the impact of this clinical condition on the quality and life expectancy of cancer patients, there is no consensus on prophylaxis and the therapeutic protocols. Low temperature atmospheric pressure plasma (LTAPP) has antimicrobial, anti-inflammatory and tissue repairing effects, which suggests that it can be promising in the treatment of oral mucositis. The general objectives of this project were divided into two subprojects: 1) Define the best antifungal and non-toxic in vitro parameters and to evaluate the application of LTAPP in the treatment of oral mucositis in murine model for chemotherapy, and 2) to evaluate whether treatment with LTAPP can prevent systemic fungal dissemination in rats from experimental infection of oral mucositis lesions by Candida albicans. A total of 100 rats (Rattus norvegicus) aged 90 to 100 days were included in the study. In subproject 1, oral mucositis lesion was induced by administration of only 5- fluorouracil (5-FU), while in subproject 2, administration and systemic administration of 5-FU associated with cisplatin, both associated with topical application of 50% acetic acid. For subproject 1, the animals were randomly divided into 2 experimental groups (n=30):a) Mucositis group and b) Mucositis group treated with LTAPP evaluated after 1, 5 and 12 days of treatment. During the experimental period, the lesions were photographed, and the severity of mucositis was classified into scores. After euthanasia and processing, the histological cuts stained by hematoxylin-eosin (HE) were analyzed. For subproject 2, the study of fungal systemic dissemination in groups of mucositis infected with C. albicans treated or not with LTAPP was conducted by fungal isolation from whole blood and macerated organs. Therefore, 2 groups of rats (n=20) were studied: c) Mucositis group infected with C. albicans and d) Mucositis group infected with C. albicans treated with LTAPP, evaluated after 24 and 72 h of treatment. For both subprojects, the best in vitro parameter was selected, that is, the one with the greatest antifungal effect and low toxicity. Thus, the lesions were exposed to helium LTAPP for 5 min at a distance of 1.5 cm at power of 1 W. In vitro results showed that LTAPP has an antifungal effect and low toxicity. In vivo results showed that 5-FU affected the general health of animals evidenced by body weight loss. In both groups, there was tissue repair after 12 days of treatment, with almost complete resolution of the lesion, which was corroborated by the microscopic findings. LTAPP group showed a greater trend of reduction of lesion, after 12 days of the treatment. Furthermore, LTAPP showed inhibitory effect on C. albicans after 5 min of exposition, with reduction in fungal recovery from the tongue after 24 h (p<0.05). Reduction in fungal dissemination was observed after 24 and 72 h of LTAPP treatment (p<0.05). Based on the obtained results, it was concluded that LTAPP is a promising tool for future clinical application in patients with oral mucositis.(AU)

Analysis of biofilm formation by Candida albicans in different types of orthodontic fixed appliances and devices / Análise da formação de biofilme por Candida albicans em diferentes tipos de aparelhos e dispositivos ortodônticos fixos

Objective: in this study, biofilm formation by Candida albicans in fixed orthodontic appliances was evaluated. Material and Methods: a total of 300 conventional metal brackets (MC), ceramic (CB), self-ligation (SLB), nickel-titanium (NiTi), and nickel-chromium (NiCr) wires, and ligatures types were organized into thirty groups (n=10). To induce biofilm formation, brackets, wires, and ligatures were joined, sterilized, placed in 24-well plates, contaminated with standardized suspensions of C. albicans (107 cells/mL), and incubated at 37 °C for 48 h with shaking. The biofilms formed were detached using an ultrasonic homogenizer, and suspensions were serially diluted and plated on Sabouraud dextrose agar to determine colony-forming units per mL. Scanning electron microscopy was performed before and after the biofilm formation. Results: lower amount of biofilm formation was observed in the MC group than in the CB and SLB groups (p<0.0001). SLB and CB showed similar biofilm formation rates (p=0.855). In general, the cross-sectional wires .018"x.025" showed higher biofilm formation when associated with the three types of brackets. When brackets, wires, and ligatures were associated, the sets with NiCr wires and SSL ligatures with MC brackets (p=0.0008) and CB (p=0.0003) showed higher biofilm formation. Conclusion: thus, brackets of MC with NiTi and NiCr wires showed lower biofilm formation, regardless of the ligature and cross-sectional or gauge of the wire and, MC and CB brackets with NiCr wires and SSL ligatures were more likely to accumulate biofilms (AU)

Objetivo: neste estudo, a formação de biofilme por Candida albicans em aparelhos ortodônticos fixos foi avaliada. Material e Métodos: um total de 300 bráquetes metálicos convencionais (MC), cerâmicos (CB), autoligados (SLB), com fios de níquel-titânio (NiTi) e níquel-cromo (NiCr) e tipos de ligaduras foram organizados em trinta grupos (n=10). Bráquetes, fios e ligaduras foram unidos, esterilizados, colocados em placas de 24 poços, contaminados com suspensões padronizadas de C. albicans (107 células/mL) e incubados a 37°C por 48 h para a formação de biofilmes. Os biofilmes formados foram rompidos por meio de um homogeneizador ultrassônico e suspensões foram diluídas e semeadas em ágar Sabouraud-dextrose para determinar as unidades formadoras de colônias por mL. A microscopia eletrônica de varredura foi realizada antes e após a formação do biofilme. Resultados: foi observada menor formação de biofilme no grupo MC em comparação aos grupos CB e SLB (p<0,0001). A formação de biofilme foi semelhante nos grupos SLB e CB (p=0,855). Em geral, os fios de seção transversal .018"x.025" apresentaram maior formação de biofilme quando associados aos três tipos de bráquetes. Os conjuntos com fios de NiCr e ligaduras SSL com bráquetes MC (p=0,0008) e CB (p=0,0003) apresentaram maior formação de biofilme. Conclusão: bráquetes MC com fios de NiTi e NiCr apresentaram menor formação de biofilme, independente da ligadura e secção transversal ou bitola do fio e, braquetes MC e CB com fios de NiCr e ligaduras SSL foram mais propensos a acumular biofilmes.(AU)

Propyl (E)-3-(furan-2-yl) Acrylate: a synthetic antifungal potential with a regulatory effect on the biosynthesis of ergosterol in Candida Albicans

Abstract The genus Candida represents the main cause of infections of fungal origin. Some species stand out as disease promoters in humans, such as C. albicans, C. glabrata, C. parapsilosis, and C. tropicalis. This study evaluated the antifungal effects of propyl (E)-3-(furan-2-yl) acrylate. The minimum inhibitory concentration of the synthetic compound, amphotericin B and fluconazole alone against four species of Candida ranged from 64 to 512 µg/mL, 1 to 2 µg/mL, and 32 to 256 µg/mL, respectively. The synergistic effect of the test substance was observed when associated with fluconazole against C. glabrata, there was no antagonism between the substances against any of the tested strains. The potential drug promoted morphological changes in C. albicans, decreasing the amount of resistance, virulence, and reproduction structures, such as the formation of pseudohyphae, blastoconidia, and chlamydospores, ensuring the antifungal potential of this substance. It was also possible to identify the fungicidal profile of the test substance through the study of the growth kinetics of C. albicans. Finally, it was observed that the test compound inhibited the ergosterol biosynthesis by yeast

Demystifying interactions between micro organisms in oral candidiasis biofilm: the key to enhancing treatments

Introduction: candida albicans is a fungal pathogen that can provoke diseases ranging from oral infections to life-threatening systemic disorders. It is now recognized that oral bacteria, such as the genus Streptococcus, establish synergistic relationships with C. albicans, which could potentially increase the fungi's virulence and pathogenicity. Objective: this narrative review aimed to discuss the Candida-Streptococcus mechanisms of interactions and their contribution to increasing oral candidiasis severity. In addition, it provides a background of biofilm formation and potential therapeutical targets. Sources of Data: searches for papers in English were performed in the Pubmed database until May 2022. MeSH and free terms related to the field were used. In vitro studies were selected, tabulated, and qualitative and quantitative data were analyzed descriptively. Synthesis of Data: among the early colonizers bacteria, evidence pointed out that S. gordonnii and S. oralis have major implications in oral candidiasis, in which mixed biofilms increase the infection severity and challenge the host's defense. On the other hand, the outcomes of the interaction between C. albicans and S. mitis, S. sanguinis, or S. mutans remain little explored in the oral candidiasis scenario, albeit evidence pointed out an enhanced fungus population and virulence factors. Conclusion: overall, considering the polymicrobial profile of the infection and the potential to increase Candida-related disease severity, therapeutical strategies should also consider bacteria management.

Introdução: candida albicans é um patógeno fúngico que pode provocar doenças que variam de infecções orais a distúrbios sistêmicos com risco de vida. Hoje se reconhece que as bactérias orais, como o gênero Streptococcus, estabelecem relações sinérgicas com C. albicans, o que pode potencialmente aumentar a virulência e patogenicidade do fungo. Objetivo: esta revisão narrativa teve como objetivo discutir os mecanismos de interação Candida-Streptococcus e sua contribuição para o agravamento da candidíase oral. Além disso, fornece uma breve explanação sobre a formação do biofilme e potenciais alvos terapêuticos. Fonte dos dados: foi realizada pesquisa na base de dados Pubmed para a busca de artigos publicados em Inglês até maio de 2022. Para isso, foram utilizados descritores relacionados ao tema. Estudos in vitro foram selecionados, tabulados e seus resultados quantitativos e qualitativos analisados descritivamente. Síntese dos dados: entre as bactérias denominadas colonizadores iniciais, evidências apontam que S. gordonnii e S. oralis têm implicações importantes na candidíase oral, na qual biofilmes mistos aumentam a gravidade da infecção e desafiam a defesa do hospedeiro. Por outro lado, os desfechos das interações entre C. albicans e S. mitis, S. sanguinis ou S. mutans permanecem pouco explorados no cenário da candidíase oral, apesar de evidências apontarem um aumento dapopulação fúngica e de fatores de virulência. Conclusão: de maneira geral, considerando o perfil polimicrobiano da infecção e o potencial agravamento das doenças provocadas por Candida spp, as estratégias terapêuticas não devem estar focadas apenas no fungo, mas também devem considerar o manejo da bactéria.

Evaluation of interactions of silibinin with the proteins ALS3 and SAP5 against Candida albicans / Avaliação das interações da silibinina com as proteínas ALS3 e SAP5 contra Candida albicans

Objective: to evaluate the molecular interaction of silibinin with the targets ALS3 and SAP5. Methodology: Molecular docking protocols were conducted to analyze the binding interaction of silibinin with ALS3 and SAP5. Results: Eleven interactions of ALS3 with silibinin and four with fluconazole were found, while six interactions were observed of SAP5 with silibinin and four with fluconazole. Conclusion: Molecular docking between silibinin and ALS3 identified important interactions, but no significant interactions were observed with SAP5, even though silibinin can exhibit affinity and interactions with other SAP5 sites.

Objetivo: Avaliar a interação molecular da silibinina com os alvos ALS3 e SAP5. Metodologia: Protocolos de docking molecular foram conduzidos para analisar a interação de ligação da silibinina com ALS3 e SAP5. Resultados: Foram encontradas onze interações de ALS3 com silibinina e quatro com fluconazol, enquanto seis interações foram observadas de SAP5 com silibinina e quatro com fluconazol. Conclusão: Docking molecular entre silibinina e ALS3 identificou interações importantes, mas não foram observadas interações significativas com SAP5, embora a silibinina possa apresentar afinidade e interações com outros sítios SAP5.

Infecção do trato urinário por leveduras do gênero Candida ­ revisão de literatura / Urinary tract infection by yeast of the genus Candida - literature review / Infección del tracto urinario causada por levaduras del género Candida - revisión de la literatura

A ocorrência das infecções do trato urinário (ITU) causadas por leveduras do gênero Candida estão aumentando consideravelmente nas últimas décadas, sendo a Candida albicans a mais comumente diagnosticada como causadora deste tipo de infecções. Contudo, outras espécies, como exemplo da Candida tropicalis, estão emergindo como preocupantes causadores da doença. Neste sentido, o objetivo do presente trabalho é revisar os aspectos relacionados com as ITU causadas por leveduras do gênero Candida. Foi realizada uma pesquisa na base de dados PubMed, buscando artigos sobre a epidemiologia, patogenia e tratamento das ITU causadas por leveduras do gênero Candida. As espécies de Candida são os fungos patogênicos oportunistas mais relevantes causadores de infecções nosocomiais e podem causar infecção no trato urinário, tanto inferior (ureteres, bexiga e uretra) quanto superior (rins), principalmente em pacientes imunocomprometidos. Existem alguns fatores predisponentes, como gênero feminino, idade avançada, diabetes mellitus, hospitalização prolongada, imunossupressão, gravidez, hipertensão, neutropenia, cálculos renais, infecções nosocomiais, terapia antibiótica e procedimentos, como a cateterização, que atuam como facilitadores das ITU por Candida spp. A doença pode ocorrer de forma assintomática, porém, pode evoluir para casos mais graves com comprometimento sistêmico em situações de candidemia que pode causar a morte do paciente, principalmente se tratando de indivíduos imunocomprometidos. Sendo assim, devido ao risco existente, a doença não pode ser negligenciada e um diagnóstico preciso e um tratamento adequado devem ser estabelecidos.

The occurrence of urinary tract infections (UTI) caused by yeasts of the genus Candida has increased considerably in recent decades, with Candida albicans being the most commonly diagnosed as causing this type of infections. However, other species, such as Candida tropicalis, are emerging as worrisome causes of the disease. In this sense, the objective of the present paper is to review the aspects related to the UTI caused by yeasts of the genus Candida. A search was carried out in the PubMed database, searching for articles on the epidemiology, pathogenesis and treatment of UTI caused by yeasts of the genus Candida. Candida species are the most relevant opportunistic pathogenic fungi that cause nosocomial infections and can cause both lower (ureters, bladder and urethra) and upper (kidneys) urinary tract infections, especially in immunocompromised patients. There are some predisposing factors, such as female gender, advanced age, diabetes mellitus, prolonged hospitalization, immunosuppression, pregnancy, hypertension, neutropenia, kidney stones, nosocomial infections, antibiotic therapy and procedures, such as catheterization, that act as facilitators of UTI by Candida spp. The disease can occur asymptomatically, however, it can progress to more severe cases with systemic involvement in situations of candidemia that can cause the death of the patient, especially in immunocompromised individuals. Therefore, due to the existing risk, the disease cannot be neglected and an accurate diagnosis and adequate treatment must be established.

La aparición de infecciones del tracto urinario (ITU) causadas por levaduras del género Candida ha aumentado considerablemente en las últimas décadas. Candida albicans es la infección por levaduras más comúnmente diagnosticada. Sin embargo, otras especies, como la Candida tropicalis, están surgiendo como causa preocupante de la enfermedad. En este sentido, el objetivo del presente trabajo es revisar los aspectos relacionados con la ITU causada por levaduras del género Candida. Se realizó una búsqueda en la base de datos PubMed, buscando artículos sobre la epidemiología, la patogénesis y el tratamiento de la ITU causada por levaduras del género Candida. Las especies de Candida son los hongos patógenos oportunistas más relevantes que causan infecciones nosocomiales y pueden provocar infecciones del tracto urinario inferior (uréteres, vejiga y uretra) y superior (riñones), especialmente en pacientes inmunodeprimidos. Existen algunos factores predisponentes, como el sexo femenino, la edad avanzada, la diabetes mellitus, la hospitalización prolongada, la inmunosupresión, el embarazo, la hipertensión, la neutropenia, los cálculos renales, las infecciones nosocomiales, la terapia con antibióticos y los procedimientos como el cateterismo, que actúan como facilitadores de la ITU por Candida spp. La enfermedad puede presentarse de forma asintomática, pero puede evolucionar a casos más graves con afectación sistémica en situaciones de candidemia que pueden causar la muerte del paciente, especialmente en individuos inmunodeprimidos. Por lo tanto, debido al riesgo existente, no se puede descuidar la enfermedad y se debe establecer un diagnóstico preciso y un tratamiento adecuado.