RESUMO
We analyzed the relationship between itraconazole (ITZ) and hydroxy-itraconazole (OH-ITZ) levels in 1,223 human samples. Overall, there was a statistically significant correlation between ITZ and OH-ITZ levels (Pearson's r, 0.7838), and OH-ITZ levels were generally higher than ITZ levels (median OH-ITZ:ITZ ratio, 1.73; range, 0.13 to 8.96). However, marked variability was observed throughout the range of ITZ concentrations. Thus, it is difficult to predict OH-ITZ concentrations based solely on ITZ levels.
Assuntos
Antifúngicos , Itraconazol , Antifúngicos/uso terapêutico , HumanosRESUMO
Herein, we investigated the surface characterization and biocompatibility of a denture-lining material containing Cnidium officinale extracts and its antifungal efficacy against Candida albicans. To achieve this, a denture-lining material containing various concentrations of C. officinale extract and a control group without C. officinale extract were prepared. The surface characterization and biocompatibility of the samples were investigated. In addition, the antifungal efficacy of the samples on C. albicans was investigated using spectrophotometric growth and a LIVE/DEAD assay. The results revealed that there was no significant difference between the biocompatibility of the experimental and control groups (p > 0.05). However, there was a significant difference between the antifungal efficiency of the denture material on C. albicans and that of the control group (p < 0.05), which was confirmed by the LIVE/DEAD assay. These results indicate the promising potential of the C. officinale extract-containing denture-lining material as an antifungal dental material.
Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Cnidium/química , Reembasadores de Dentadura , Extratos Vegetais/farmacologia , Antifúngicos/química , Antifúngicos/toxicidade , Linhagem Celular , Cor , Reembasadores de Dentadura/microbiologia , Fibroblastos/efeitos dos fármacos , Humanos , Teste de Materiais , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Extratos Vegetais/toxicidade , Propriedades de SuperfícieRESUMO
AIM: The study aimed to investigate the antifungal effects of herbal extracts and fluconazole on heat-polymerized acrylic denture base resin as a denture cleanser. MATERIALS AND METHODS: Several essential oils, such as origanum oil and grape seed oil and commercially available antifungal agent fluconazole were used as denture cleansers and their antifungal efficacy was evaluated using a spectrophotometer. Overall, 68 samples were obtained and were divided into four groups, each containing 17 samples. These samples were immersed in Sabouraud dextrose broth consisting of Candida albicans for 16 hours and later in these antifungal solutions for 8 hours and their antifungal efficacy was measured. Data were subjected to an ANOVA test. RESULTS: Among the study groups origanum oil showed the maximum antifungal activity with a mean optical density at 0.072 ± 0.014 followed by fluconazole (0.094 ± 0.155), and least by grape seed oil (0.190 ± 0.071). CONCLUSION: Results of this in vitro study showed that origanum oil was more effective than commercially available antifungal agents, and among the tested groups oregano oil was a potential agent in lowering the C. albicans colony. CLINICAL SIGNIFICANCE: Origanum oil, being a herbal product, can be considered as a denture cleanser and also be used as an effective alternative to commercially available antifungal agents without any side effects.
Assuntos
Antifúngicos , Fluconazol , Resinas Acrílicas , Antifúngicos/farmacologia , Bases de Dentadura , Higienizadores de Dentadura , Fluconazol/farmacologia , Temperatura Alta , Extratos Vegetais/farmacologiaRESUMO
AIM AND OBJECTIVE: This paper aims to compare the antifungal efficacy of four concentrations of Minthostachys mollis essential oil (MEO) against Candida albicans ATCC 10231. MATERIALS AND METHODS: This study was conducted in vitro. Ten kilograms of M. mollis (Muña) were collected in the city of Tarma, Peru. The plant was then dried in the shade at room temperature (21°C), and the essential oil was obtained through distillation. C. albicans ATCC 10231 was cultured at a MacFarland scale of 0.5, which corresponds to a concentration of 3 × 108 CFU/mL. Each plate was filled with one of the four MEO concentrations (25, 50, 75, or 100%), dimethyl sulfoxide (negative control), or fluconazole (positive control), a known antifungal agent. After incubation, each plate was examined using the Kirby-Bauer method. RESULTS: Compared to MEO 25%, MEO 50%, and MEO 75%, MEO 100% had the highest antifungal efficacy at 24, 48, and 72 hours of evaluation, with an average of 18.9 ± 0.7, 18.2 ± 0.7, and 17.0 ± 0.4 mm, respectively. However, fluconazole had higher efficacy (27.9 ± 0.5, 27.5 ± 0.5, and 23.7 ± 0.7 mm, respectively). Post hoc analysis showed that there were significant differences between all concentrations of the MEO groups and their respective positive and negative control groups (p <0.001). CONCLUSION: Among the MEO groups, the pure concentration (MEO 100%) had the highest antifungal efficacy. However, fluconazole presented greater efficacy, and the differences were statistically significant. CLINICAL SIGNIFICANCE: This research allowed to know the efficacy of this natural resource against one of the most prevalent fungi in the oral cavity. Therefore, a line of research could be opened to deepen its potential benefits for oral health.
Assuntos
Candida albicans , Óleos Voláteis , Antifúngicos/farmacologia , Fluconazol/farmacologia , Testes de Sensibilidade Microbiana , Óleos Voláteis/farmacologiaRESUMO
BACKGROUND: The microbiome of Severe-Early Childhood Caries (S-ECC), is characterized by an ecosystem comprising bacterial and fungal species, with a predominance of Candida species. Hence, an anti-cariogen effective against both bacteria and fungi would be valuable in the management of S-ECC. Here we evaluate the antifungal effect of silver diamine fluoride (SDF) against 35-clinical yeast isolates (Ten-each of C. albicans, C. krusei, C. tropicalis and five C. glabrata strains) from dentinal caries-lesions from S-ECC. RESULTS: Disc-diffusion and time-kill assays as well as MIC50 and MIC90 evaluations against therapeutic concentrations confirmed the broad-spectrum anti-candidal potency of SDF. Ultrastructural images revealed morphologic aberrations of yeast-cell walls on exposure to SDF. All C. krusei and C. glabrata isolates were significantly more sensitive to SDF, relative to the standard antifungal fluconazole. Further, SDF appears to effectively abrogate filamentation of C. albicans even at very low concentrations. CONCLUSIONS: Our data, for the first time, elucidate the antifungal potency of SDF, in addition to its known antibacterial activity, in the management of S-ECC.
Assuntos
Antifúngicos/farmacologia , Candida/crescimento & desenvolvimento , Cárie Dentária/prevenção & controle , Compostos de Amônio Quaternário/farmacologia , Compostos de Prata/farmacologia , Biofilmes/efeitos dos fármacos , Candida/classificação , Candida/efeitos dos fármacos , Candida/ultraestrutura , Parede Celular/efeitos dos fármacos , Parede Celular/ultraestrutura , Criança , Farmacorresistência Fúngica/efeitos dos fármacos , Fluoretos Tópicos/farmacologia , Humanos , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: Matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI-MSI) is a mass spectrometry-based technique, which can be applied for compound-specific imaging of pharmaceuticals in tissues samples. MALDI-MSI technology is widely used to visualise penetration and distribution profile through different tissues but has never been used with nail tissue. OBJECTIVES: This study used MALDI-MSI technology to visualise distribution profile and penetration into ex vivo human mycosis-infected toenails of three antifungal active ingredients amorolfine, ciclopirox and naftifine contained in topical onychomycosis nail treatment preparations, marketed as Loceryl® , Ciclopoli® and Exoderil® . METHODS: Three mycosis-infected toenails were used for each treatment condition. Six and twenty-four hours after one single topical application of antifungal drugs, excess of formulation was removed, nails were cryo-sectioned at a thickness of 20 µm, and MALDI matrix was deposited on each nail slice. Penetration and distribution profile of amorolfine, ciclopirox and naftifine in the nails were analysed by MALDI-MSI. RESULTS: All antifungal actives have been visualised in the nail by MALDI-MSI. Ciclopirox and naftifine molecules showed a highly localised distribution in the uppermost layer of the nail plate. In comparison, amorolfine diffuses through the nail plate to the deep layers already 6 hours after application and keeps diffusing towards the lowest nail layers within 24 hours. CONCLUSIONS: This study shows for the first-time distribution and penetration of certain antifungal actives into human nails using MALDI-MSI analysis. The results showed a more homogeneous distribution of amorolfine to nail and a better penetration through the infected nails than ciclopirox and naftifine.
Assuntos
Antifúngicos/farmacologia , Onicomicose/diagnóstico por imagem , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Administração Tópica , Alilamina/administração & dosagem , Alilamina/análogos & derivados , Alilamina/farmacologia , Alilamina/uso terapêutico , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Ciclopirox/administração & dosagem , Ciclopirox/farmacologia , Ciclopirox/uso terapêutico , Humanos , Laca , Morfolinas/administração & dosagem , Morfolinas/farmacologia , Morfolinas/uso terapêutico , Unhas/microbiologia , Unhas/patologia , Onicomicose/tratamento farmacológicoRESUMO
BACKGROUND: Studies investigating the penetration of amorolfine through the nail have shown the highest concentration in the uppermost layer and measurable antifungal activity even in the lower layers of the nail. OBJECTIVES: This pilot, ex vivo study compared the penetration of antifungal concentrations of amorolfine 5% nail lacquer in different layers of healthy, human cadaver toenails with that of terbinafine 10% nail solution, ciclopirox 8% nail lacquer and naftifine 1% nail solution. Moreover, the effect of nail filing prior to application on the penetration of amorolfine 5% was assessed. METHODS: Unfiled (n = 3) and filed (n = 3) nails were used for each antimycotic agent and amorolfine 5% nail lacquer, respectively. Twenty-four hours after topical application, the nails were sliced (10 µm), solubilised and added to agar plates seeded with Trichophyton rubrum. Zones of growth inhibition were measured. RESULTS: Only amorolfine penetrated the nails at sufficient concentrations to inhibit growth of T rubrum at different nail depths. In contrast, the comparators did not show antifungal efficacy. Nail filing resulted in larger zones of inhibition for amorolfine compared with those of intact nails. CONCLUSIONS: Unlike its comparators, a single application of amorolfine 5% nail lacquer resulted in antifungal efficacy within the nail plate. Nail filing increased the antifungal efficacy of amorolfine 5% nail lacquer.
Assuntos
Antifúngicos/administração & dosagem , Antifúngicos/farmacocinética , Laca , Morfolinas/administração & dosagem , Morfolinas/farmacocinética , Unhas/química , Administração Tópica , Alilamina/administração & dosagem , Alilamina/análogos & derivados , Alilamina/farmacocinética , Cadáver , Ciclopirox/administração & dosagem , Ciclopirox/farmacocinética , Humanos , Projetos Piloto , Terbinafina/administração & dosagem , Terbinafina/farmacocinética , Trichophyton/efeitos dos fármacos , Trichophyton/crescimento & desenvolvimentoRESUMO
Clotrimazole is widely used for the management of cutaneous candidiasis infection. The low solubility of clotrimazole and excipient-related topical side effects (of currently available marketed products) cause the compromised efficacy of the therapy with poor patient compliance. In the present investigation, a clotrimazole nanocrystal-based nanogel was developed. Clotrimazole nanocrystals were optimized with studying the impact of individual process parameters of the media milling technique. The optimum level of individual process parameters was considered in the development of optimized batches. A promising result was obtained with a non-ionic stabilizer, polysorbate 80, at a concentration of 1.5%w/v, showing a distinct reduction in the particle size from above 31 µm to 264 nm and a polydispersity index of 0.211 with media milling at 1500 rpm for 6 h. This result was found to be in concordance with the TEM images, revealing a sharp diminution in particle morphology. Powder X-ray diffraction and differential scanning calorimetry results revealed crystallinity of clotrimazole (CTZ) in nanocrystal form. The optimized nanocrystal suspension was formulated into nanogel with carbopol 934, having a viscosity of 86.43 ± 2.06 Pa s at 25°C, which enhanced the ease of application of CTZ nanocrystals topically. A diffusion study showed around 82% of CTZ is transported across the membrane with the flux of 110.07 µg cm-2 h-1. In vivo results of the nanogel revealed improvement in CTZ release with 52% CTZ retention in different strata of the skin. The developed nanogel showed a significant improvement in the eradication of fungal infection within 10 days of application over Candida albicans-induced Wistar rat model. In a nutshell, the CTZ nanocrystal-loaded nanogel could achieve the goal of retaining CTZ in skin layers providing a prolonged effect and was able to treat cutaneous candidiasis in a short span with improved compliance for the candidiasis patients.
Assuntos
Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Candidíase Cutânea/tratamento farmacológico , Clotrimazol/administração & dosagem , Clotrimazol/uso terapêutico , Animais , Antifúngicos/efeitos adversos , Candida albicans/efeitos dos fármacos , Candidíase Cutânea/microbiologia , Clotrimazol/efeitos adversos , Difusão , Composição de Medicamentos , Irritantes , Nanopartículas , Tamanho da Partícula , Ratos , Ratos Wistar , Absorção Cutânea , Difração de Raios XRESUMO
By selecting a unique combination of lipids and amphotericin B, the liposome composition for AmBisome® (L-AmBis) has been optimized resulting in a formulation that is minimally toxic, targets to fungal cell walls, and distributes into and remains for days to weeks in various host tissues at drug levels above the MIC for many fungi. Procedures have been standardized to ensure that large scale production of the drug retains the drug's low toxicity profile, favorable pharmacokinetics and antifungal efficacy. Tissue accumulation and clearance with single or multiple intravenous administration is similar in uninfected and infected animal species, with tissue accumulation being dose-dependent and the liver and spleen retaining the most drug. The efficacy in animals appears to be correlated with drug tissue levels although the amount needed in a given organ varies depending upon the type of infection. The long-term tissue retention of bioactive L-AmBis in different organs suggests that for some indications, prophylactic and intermittent drug dosing would be efficacious reducing the cost and possible toxic side-effects. In addition, preliminary preclinical studies using non-intravenous routes of delivery, such as aerosolized L-AmBis, catheter lock therapy, and intravitreal administration, suggest that alternative routes could possibly provide additional therapeutic applications for this antifungal drug.
Assuntos
Anfotericina B/administração & dosagem , Anfotericina B/farmacologia , Antifúngicos/administração & dosagem , Antifúngicos/farmacologia , Micoses/tratamento farmacológico , Anfotericina B/efeitos adversos , Anfotericina B/farmacocinética , Animais , Antifúngicos/efeitos adversos , Antifúngicos/farmacocinética , Química Farmacêutica , Relação Dose-Resposta a Droga , Liberação Controlada de Fármacos , Humanos , Lipossomos , Fígado/metabolismo , Baço/metabolismo , Distribuição TecidualRESUMO
Dermatophytoses are common superficial fungal infections affecting both humans and animals. They are provoked by filamentous fungi called dermatophytes specialized in the degradation of keratinized structures, which allows them to induce skin, hair and nail infections. Despite their high incidence, little investigation has been performed for the understanding of these infections compared to fungal opportunistic infections and most of the studies were based on in vitro experiments. The development of animal models for dermatophyte research is required to evaluate new treatments against dermatophytoses or to increase knowledge about fungal pathogenicity factors or host immune response mechanisms. The guinea pig has been the most often used animal model to evaluate efficacy of antifungal compounds against dermatophytes, while mouse models were preferred to study the immune response generated during the disease. Here, we review the relevant animal models that were developed for dermatophyte research and we discuss the advantages and disadvantages of the selected species, especially guinea pig and mouse.
Assuntos
Arthrodermataceae/imunologia , Dermatomicoses/microbiologia , Dermatomicoses/patologia , Modelos Animais de Doenças , Animais , Antifúngicos/isolamento & purificação , Antifúngicos/uso terapêutico , Dermatomicoses/tratamento farmacológico , Dermatomicoses/imunologia , Cobaias , Interações Hospedeiro-Patógeno , CamundongosRESUMO
This study determined ME1111 onychopharmacokinetics and possible topical antifungals' clinical efficacy in human great toenails using an in vitro finite dose model. ME1111 topical formulations in 1, 5, 10 or 15% for 3 days observation and 1, 5 or 10% for 14 days observation, respectively, were used to determine ME1111 penetration rate and transungual kinetics. ME1111 concentrations in the deeper nail (ventral/intermediate layers) and a cotton pad/nail bed, were several orders of magnitude greater than MIC90 and MFC90 for three major dermatophytes. ME1111 concentrations 3 days after a single and 14 days after multiple dosing of 10% formulation were 253 and 7991 µg/g nail, respectively, and superior to those of 8% ciclopirox control. ME1111 concentration (µg equivalent/cm3) in the cotton pad following 10% ME1111 multiple applications increased linearly throughout the 336 h experiment and was significantly greater than that of 8% ciclopirox. Flux rate of ME1111 averaged as 50.9 µg/cm3/day, which was ca. two orders of magnitude greater than the MIC90 values. The novel antifungal ME1111 penetrated well into human nail plate and its concentrations in the deeper nail and cotton pad after application of 10% formulation were significantly greater than those of ciclopirox.
Assuntos
Antifúngicos/farmacocinética , Dermatoses do Pé/metabolismo , Onicomicose/metabolismo , Fenóis/farmacocinética , Pirazóis/farmacocinética , Administração Tópica , Antifúngicos/administração & dosagem , Relação Dose-Resposta a Droga , Dermatoses do Pé/tratamento farmacológico , Humanos , Onicomicose/tratamento farmacológico , Fenóis/administração & dosagem , Pirazóis/administração & dosagemRESUMO
Clotrimazole (CTZ) is a broad spectrum antimycotic agent known to be very effective locally for the treatment of fungal skin infections. The aim of this study was to study the effect of chitosan-coated microemulsion (CME) for topical delivery of CTZ and also evaluate its in vitro antifungal efficacy, ex vivo permeation and retention ability on the skin surface. The pseudo-ternary phase diagrams were developed using clove oil as oil phase, Tween 80 and propylene glycol as surfactant and co-surfactant, respectively, and distilled water as aqueous phase. CME was prepared by the drop wise addition of chitosan solution to the optimized microemulsion. Physicochemical parameters (globule size, zeta potential, drug content, viscosity and pH) and in vitro release of CME were studied. The in vitro antifungal efficacy of CME and ME was studied by cup-plate method against Candida albicans. Ex vivo drug permeation study was also carried out in a modified diffusion cell, using rat skin. The developed CME displayed an average globule size less than 50 nm and a positive surface charge, acceptable physico-chemical behavior, and exhibited sustained drug release in in vitro study. In in vitro anti-fungal study, CME showed greater values of zone of inhibition as compared to ME due to its prolonged action as well as fungistatic nature of chitosan. In ex vivo study, CME showed better retention and sustained permeation property than ME due to the mucoadhesive property of chitosan. These results suggest that positively charged CMEs could be used as novel topical formulation for its ability to retain on the skin and its ability to sustain the release of the drug.
Assuntos
Anti-Infecciosos Locais/administração & dosagem , Anti-Infecciosos Locais/farmacocinética , Quitosana/química , Clotrimazol/administração & dosagem , Clotrimazol/farmacocinética , Emulsões/química , Administração Cutânea , Animais , Anti-Infecciosos Locais/farmacologia , Antifúngicos/administração & dosagem , Antifúngicos/farmacocinética , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candidíase/tratamento farmacológico , Clotrimazol/farmacologia , Tamanho da Partícula , Transição de Fase , Ratos WistarRESUMO
Cryptococcus neoformans infection is an important cause of meningitis in HIV/AIDS endemic regions. Antifungals for its management include amphotericin B, flucytosine, and fluconazole. Recently, treatment of this mycosis with sertraline has been studied with variable clinical outcomes. The aim of the study was to assess the in vitro antifungal effect of sertraline against clinical isolates of Cryptococcus spp. as well as its in vivo activity in a murine model of cryptococcal meningoencephalitis. The in vitro susceptibility to fluconazole, amphotericin B, voriconazole and sertraline of 153 Cryptococcus spp. strains were evaluated according to CLSI procedures. Fungal tissue burden, serum antigenaemia and histopathology, together with the therapeutic efficacy of amphotericin B (3 mg/kg), fluconazole (15 mg/kg), and sertraline (3, 10, and 15 mg/kg) were evaluated in mice intracranially inoculated with one isolate of Cryptococcus neoformans. All strains were susceptible to the antifungals studied and exhibited growth inhibition with sertraline at clinically relevant concentrations. Sertraline at a dose of 15 mg/kg reduced the fungal burden in the brain and spleen with an efficacy comparable to that of fluconazole. In conclusion, sertraline exhibited an excellent in vitro-in vivo anti-cryptococcal activity, representing a possible new alternative for the clinical management of meningeal cryptococcosis.
Assuntos
Antifúngicos/administração & dosagem , Antifúngicos/farmacologia , Criptococose/tratamento farmacológico , Criptococose/microbiologia , Cryptococcus neoformans/efeitos dos fármacos , Sertralina/administração & dosagem , Sertralina/farmacologia , Estruturas Animais/microbiologia , Animais , Contagem de Colônia Microbiana , Criptococose/patologia , Cryptococcus neoformans/isolamento & purificação , Modelos Animais de Doenças , Fungemia/microbiologia , Histocitoquímica , Humanos , Masculino , Camundongos , Resultado do TratamentoRESUMO
Cold atmospheric pressure plasma (CAP) has potential to be utilized as an alternative method for sterilization in food industries without thermal damage or toxic residues. In contrast to the bactericidal effects of CAP, information regarding the efficacy of CAP against eukaryotic microorganisms is very limited. Therefore, herein we investigated the effects of CAP on the budding yeast Saccharomyces cerevisiae, with a focus on the cellular response to CAP. The CAP treatment caused oxidative stress responses including the nuclear accumulation of the oxidative stress responsive transcription factor Yap1, mitochondrial fragmentation, and enhanced intracellular oxidation. Yeast cells also induced the expression of heat shock protein (HSP) genes and formation of Hsp104 aggregates when treated with CAP, suggesting that CAP denatures proteins. As phenomena unique to eukaryotic cells, the formation of cytoplasmic mRNP granules such as processing bodies and stress granules and changes in the intracellular localization of Ire1 were caused by the treatment with CAP, indicating that translational repression and endoplasmic reticulum (ER) stress were induced by the CAP treatment. These results suggest that the fungicidal effects of CAP are attributed to the multiple severe stresses.
Assuntos
Antifúngicos/farmacologia , Pressão Atmosférica , Temperatura Baixa , Microscopia de Fluorescência , Gases em Plasma/farmacologia , Saccharomyces cerevisiae/efeitos dos fármacos , Núcleo Celular/química , Estresse do Retículo Endoplasmático , Perfilação da Expressão Gênica , Proteínas de Choque Térmico/análise , Estresse Oxidativo , Proteínas de Saccharomyces cerevisiae/análise , Fatores de Transcrição/análiseRESUMO
BACKGROUND/OBJECTIVES: We aimed to assess the antifungal efficacy and impact of a denture cleanser containing Cnidium officinale extract on the surface characteristics of denture base materials, as well as its physical and biological properties. METHODS: The experimental denture cleansers were formulated with C. officinale at concentrations of 100 and 150 µg/mL, combined with 1% cocamidopropyl betaine as a natural surfactant. Antifungal efficacy was evaluated using zone-of-inhibition assays against Candida albicans, revealing inhibition zones of 20 ± 1.8 mm for the 100 µg/mL concentration and 23.6 ± 1.6 mm for the 150 µg/mL concentration. Surface property assessments-including hardness, roughness, color stability, and solubility measurements-demonstrated no significant differences compared to the control group. Biological evaluations included the quantification of polyphenol and flavonoid content. RESULTS: The C. officinale-based cleanser showed significant antifungal activity without affecting the hardness, roughness, color stability, or solubility of denture base materials. Biological tests revealed no cytotoxicity and minimal mucosal irritation. Polyphenol and flavonoid contents were quantitatively measured, revealing higher concentrations in the experimental groups, which were correlated with significant antifungal activity. These compounds are known for their roles in disrupting microbial processes and enhancing antimicrobial effects. These findings suggest that the C. officinale-based denture cleanser effectively inhibits C. albicans while preserving the physical properties of denture base materials. CONCLUSIONS: This study highlights the potential of C. officinale in denture cleanser formulations, promoting denture hygiene and oral health. Future research should prioritize long-term clinical evaluations and formulation optimization.
RESUMO
BACKGROUND: Chromoblastomycosis is the World Health Organization (WHO)-recognized fungal implantation disease that eventually leads to severe mutilation. Cladophialophora carrionii (C. carrionii) is one of the agents. However, the pathogenesis of C. carrionii is not fully investigated yet. METHODS: We investigated the pathogenic potential of the fungus in a Galleria mellonella (G. mellonella) larvae infection model. Six strains of C. carrionii, and three of its environmental relative C. yegresii were tested. The G. mellonella model was also applied to determine antifungal efficacy of amphotericin B, itraconazole, voriconazole, posaconazole, and terbinafine. RESULTS: All strains were able to infect the larvae, but virulence potentials were strain-specific and showed no correlation with clinical background of the respective isolate. Survival of larvae also varied with infection dose, and with growth speed and melanization of the fungus. Posaconazole and voriconazole exhibited best activity against Cladophialophora, followed by itraconazole and terbinafine, while limited efficacy was seen for amphotericin B. CONCLUSION: Infection behavior deviates significantly between strains. In vitro antifungal susceptibility of tested strains only partly explained the limited treatment efficacy in vivo.
RESUMO
Xiaozhou mustard (Brassica napiformis) root tuber, a traditional fermented vegetable, has a long history in Rongan County, Guangxi Province. However, the frequent occurrence of root tuber sour rot by Geotrichum candidum (G. candidum) has seriously reduced Xiaozhou mustard production and quality in recent years. The objective of the present study is to investigate the antifungal efficacy of 2-chloro-5-trifluoromethoxybenzeneboronic acid (Cl-F-BBA) against G. candidum and its possible mechanisms. The results revealed that a concentration of 0.25 mg/mL Cl-F-BBA completely halted mycelial growth and spore germination. Furthermore, a slightly lower concentration of 0.20 mg/mL was sufficient to compromise the integrity of the plasma membrane in mycelia and mitochondria, leading to a reduction in respiratory rate, activities of malate dehydrogenase (MDH), and succinate dehydrogenase (SDH), ATP content, and energy charge. This concentration also significantly disordered antioxidant metabolism, resulting in the accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA), and caused intracellular leakage in mycelia. In vivo experiments further demonstrated that Xiaozhou mustard root tubers treated with Cl-F-BBA exhibited markedly lower decay rates and lesion diameters compared to the control group. In summary, Cl-F-BBA presents a promising solution for controlling root tuber sour rot in Xiaozhou mustard caused by G. candidum.
Assuntos
Geotrichum , Doenças das Plantas , Raízes de Plantas , Geotrichum/efeitos dos fármacos , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/microbiologia , Raízes de Plantas/crescimento & desenvolvimento , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Mostardeira , Ácidos Borônicos/farmacologia , Antifúngicos/farmacologia , Micélio/efeitos dos fármacos , Micélio/crescimento & desenvolvimento , Espécies Reativas de Oxigênio/metabolismo , Tubérculos/microbiologiaRESUMO
Candida albicans Is a leading cause of nosocomial bloodstream infections, particularly in immunocompromised patients. Current therapeutic strategies are insufficient, highlighting the need for effective vaccines. This study aimed to evaluate the efficacy of a dual-antigen fusion protein vaccine (AH) targeting the Als3 and Hyr1 proteins of C. albicans, using AlPO4 as an adjuvant. The AH vaccine was constructed by fusing Als317-432 and Hyr125-350 proteins, and its immunogenicity was tested in BALB/c mice and New Zealand white rabbits. Mice received three intramuscular doses of the vaccine combined with AlPO4, followed by a lethal challenge with C. albicans SC5314. Survival rates, antibody responses, cytokine production, fungal burdens, and organ pathology were assessed. The vaccine's efficacy was also validated using rabbit serum. Mice vaccinated with the AH-AlPO4 combination exhibited significantly higher antibody titers, particularly IgG and its subclasses, compared to controls (p < .001). The survival rate of vaccinated mice was 80% post-infection, significantly higher than the control group (p < .01). Vaccinated mice showed reduced fungal loads in the blood, kidneys, spleen, and liver (p < .05). Increased levels of interferon gamma and interleukin (IL)-17A were observed, indicating robust T helper (Th) 1 and Th17 cell responses. Vaccination mitigated organ damage, with kidney and liver pathology scores significantly lower than those of unvaccinated mice (p < .05). Rabbit serum with polyclonal antibodies demonstrated effective antifungal activity, confirming vaccine efficacy across species. The AH-AlPO4 vaccine effectively induced strong immune responses, reduced fungal burden, and protected against organ pathology in C. albicans infections. These findings support further development of dual-antigen vaccine strategies.
Candida, a fungus, is a major cause of bloodstream infections, especially in critical care settings. This study focused on developing a vaccine to protect against Candida infection. The vaccine targeted two key proteins, Als3p and Hyr1p, found on the surface of Candida, using a combination of these proteins. To create the vaccine, we used Als3p and Hyr1p to form a fusion protein called AH, and tested the vaccine on mice, administering it with different adjuvants (substances that enhance the immune response). The results showed that the AH vaccine, particularly when combined with the adjuvant AlPO4, induced a strong immune response in mice. This response included the production of specific antibodies and immune cells that are crucial for defending against Candida infections. Furthermore, mice receiving the AH-AlPO4 vaccine showed significantly better survival rates and lower levels of fungal infection compared to the control group or another experimental group. The vaccine also protected vital organs, such as the kidneys and liver, from Candida-induced damage. Additionally, we used rabbit serum to validate the efficacy of the vaccine, providing cross-species confirmation of its effectiveness. The study demonstrated the potential of the AH vaccine in eliciting robust immune responses and reducing the severity of Candida albicans infections. In summary, this research introduces a promising AH vaccine, which shows effectiveness in protecting against Candida infections. The study's innovative approach and positive results contribute to the ongoing efforts to develop vaccines against fungal infections, addressing a critical healthcare challenge. Further research is needed to explore the vaccine's long-term effectiveness and safety for potential use in clinical settings.
Assuntos
Adjuvantes Imunológicos , Anticorpos Antifúngicos , Antígenos de Fungos , Candida albicans , Candidíase , Vacinas Fúngicas , Camundongos Endogâmicos BALB C , Proteínas Recombinantes de Fusão , Animais , Vacinas Fúngicas/imunologia , Vacinas Fúngicas/administração & dosagem , Candida albicans/imunologia , Candidíase/prevenção & controle , Candidíase/imunologia , Anticorpos Antifúngicos/sangue , Anticorpos Antifúngicos/imunologia , Coelhos , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/genética , Camundongos , Feminino , Antígenos de Fungos/imunologia , Antígenos de Fungos/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Proteínas Fúngicas/imunologia , Proteínas Fúngicas/administração & dosagem , Citocinas , Vacinação/métodos , Imunoglobulina G/sangue , Modelos Animais de Doenças , Interleucina-17/imunologia , Interferon gama/imunologia , Eficácia de Vacinas , Análise de Sobrevida , Compostos de AlúmenRESUMO
Miconazole nitrate (MCNR), an antifungal drug, is used to treat superficial infections. The objective of the current study was to assess the antifungal effectiveness of MCNR-loaded transethosomal gel (MNTG) against Candida albicans in an in vivo rat model. The outcomes were compared with those of the miconazole nitrate gel (MNG) and marketed Daktarin® cream (2%) based on histopathological and hematological studies. The results of the skin irritation test revealed the safety profile of the MNTG. The MNTG demonstrated the greatest antifungal activity in the histological analysis and the visible restoration of the skin, and the rats revealed an apparent evidence of recovery. Compared to the untreated group, the treated group's lymphocyte and white blood cells counts increased, but their eosinophil counts decreased. In conclusion, MNTG exhibited the greatest antifungal activity, which might be connected to the improved skin permeability of the transethosome's nanosized vesicles. Therefore, it could be considered a promising carrier for topical usage and the treatment of cutaneous candidiasis. More clinical research needs to be performed in order to demonstrate its effectiveness and safe usage in humans.
RESUMO
INTRODUCTION: The oral cavity is considered to be one of the most intricate environments in the human body. It is known to harbor commensal microorganisms that do not cause diseases, such as Candida albicans, a yeast fungus that has a carriage rate that tends to increase with age. It is worth noting that C. albicans can be readily identified within the flora of the gastrointestinal tract in 80% of healthy patients. Traditional medicine has alternatively been shown to play a key role in various health amenities with a wide spectrum anti-microbial effect against various yeast molds. OBJECTIVES: To evaluate the antifungal efficacy of pure garlic, onion, and lemon juice extracts against C. albicans. Materials and methods: C. albicans (ATCC 10231) were sub-cultured in brain agar followed by anaerobic incubation for 48 hours at 37°C. Ten plates were used for each of the materials studied to evaluate their antifungal efficacy against C. albicans. The efficiency of commercially available fresh garlic, onion, and lemon was tested in isolation against C. albicans. One-way ANOVA and chi-square were used for comparison between the different materials. The inhibition zone was measured, and the level of statistical significance was set at ≤0.05. RESULTS: The diameter of inhibition zones has been measured along the vertical and horizontal axis. No inhibition zones were observed for the onion and lemon extracts used in this study whereas the garlic extract exhibited inhibition zones with altered sizes (4.89 ± 0.275). A highly significant difference was observed between groups (P = 0.000) and between garlic and the other materials (P = 0.000). CONCLUSIONS: Pure garlic showed a highly significant antifungal efficacy when compared to the onion and lemon juice extracts against C. albicans. Further studies are needed using different concentrations of onion, lemon, and lemon peel juice to confirm their antifungal efficacy in addition to their actual antimicrobial benefits.