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1.
Int J Nanomedicine ; 15: 4351-4362, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606682

RESUMO

Purpose: The present study synthesized silver nanoparticles (AgNPs) using the aqueous extract of a traditional medicinal product consisting of an oleoresin (a combination of macromolecules of carbohydrates and proteins) exuded from the rhizome of the plant Ferula foetida (asafoetida gum) and evaluated its biological properties. Materials and Methods: The silver nanoparticles synthesized using asafoetida gum (As-AgNPs) were characterized using UV/Vis spectroscopy, fourier infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) with energy dispersive X-ray analysis (EDX), X-ray diffraction (XRD) and transmission electron microscopy (TEM) and EADX. The cytotoxicity and antimicrobial activity As-AgNPs were evaluated against MCF-7 cell lines and selected microbial pathogens, respectively. Results: The synthesized silver nanoparticles were crystalline in nature with a spherical shape. The average particle size was 5.6-8.6 nm. The cytotoxicity of the synthesized As-AgNPs was evaluated against MCF-7 cell lines, and the As-AgNPs were found to be effective in inhibiting the multiplication of cancer cells. The As-AgNPs exhibited significant antimicrobial activity towards E. coli, K. pneumoniae and C. albicans. The MIC of the synthesized As-AgNPs was 7.80 µg/mL for E. coli ATCC 25922, Salmonella sp. WS50- and S. typhi; 15.60 µg/mL for S. typhimurium and S. aureus WS10, and 31.20 µg/mL for K. pneumoniae and S. aureus ATCC 43300-MRSA. In addition, MIC values of 15.60 µg/mL for C. albicans ATCC8436 and 31.20 µg/mL for C. krusei ATCC6258 were obtained. Conclusion: As asafoetida is a good traditional medicine, its involvement in the synthesis of AgNPs led the silver nanoparticles to exhibit good cytotoxic and antimicrobial effects.


Assuntos
Anti-Infecciosos/farmacologia , Ferula/química , Nanopartículas Metálicas/química , Gomas Vegetais/química , Prata/farmacologia , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Humanos , Células MCF-7 , Nanopartículas Metálicas/ultraestrutura , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Extratos Vegetais/química , Staphylococcus aureus/efeitos dos fármacos , Difração de Raios X
2.
PLoS One ; 15(7): e0235746, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32678853

RESUMO

Azole resistant fungal infections remain a health problem for the immune compromised. Current therapies are limited due to rises in new resistance mechanisms. Therefore, it is important to identify new drug targets for drug discovery and novel therapeutics. Arv1 (are1 are2 required for viability 1) function is highly conserved between multiple pathogenic fungal species. Candida albicans (C. albicans) cells lacking CaArv1 are azole hypersusceptible and lack virulence. Saccharomyces cerevisiae (S. cerevisiae) Scarv1 cells are also azole hypersusceptible, a phenotype reversed by expression of CaArv1, indicating conservation in the molecular mechanism for azole susceptibility. To define the relationship between Arv1 function and azole susceptibility, we undertook a structure/function analysis of ScArv1. We identified several conserved amino acids within the ScArv1 homology domain (ScAhd) required for maintaining normal azole susceptibility. Erg11 lanosterol 14-α-demethylase is the rate-limiting enzyme in sterol biosynthesis and is the direct target of azole antifungals, so we used our ScArv1 mutants in order to explore the relationship between ScArv1 and ScErg11. Specific ScArv1 mutants ectopically expressed from a low copy plasmid were unable to restore normal azole susceptibility to Scarv1 cells and had reduced Erg11 protein levels. Erg11 protein stability depended on its ability to form a heterodimeric complex with Arv1. Complex formation was required for maintaining normal azole susceptibility. Scarv1 cells expressing orthologous CaArv1 mutants also had reduced CaErg11 levels, were unable to form a CaArv1-CaErg11 complex, and were azole hypersusceptible. Scarv1 cells expressing CaArv1 mutants unable to interact with CaErg11 could not sustain proper levels of the azole resistant CaErg11Y132F F145L protein. Caarv1/Caarv1 cells expressing CaArv1 mutants unable to interact with CaErg11 were found to lack virulence using a disseminated candidiasis mouse model. Expressing CaErg11Y132F F145L did not reverse the lack of virulence. We hypothesize that the role of Arv1 in Erg11-dependent azole resistance is to stabilize Erg11 protein level. Arv1 inhibition may represent an avenue for treating azole resistance.


Assuntos
Candida albicans/patogenicidade , Candidíase/microbiologia , Sistema Enzimático do Citocromo P-450/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Esterol 14-Desmetilase/metabolismo , Virulência , Sequência de Aminoácidos , Animais , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candidíase/tratamento farmacológico , Sistema Enzimático do Citocromo P-450/genética , Farmacorresistência Fúngica , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Homologia de Sequência , Esterol 14-Desmetilase/genética
3.
J Cancer Res Ther ; 16(3): 470-477, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719253

RESUMO

Objective: The aim of the study is to assess the effect of probiotic bacteria on oral Candida counts in cancer patients who are undergoing head- and neck-radiotherapy in a tertiary care center. Study Design: The study was a randomized clinical trial including 90 patients who just completed head- and neck-radiotherapy. Materials and Methods: Participants were randomly allocated into three equal sized groups, i.e., probiotics group, candid group, and combination groups. Oral rinse samples of the patients were collected before and after the intervention for the identification of Candida. The samples were incubated on Sabouraud's Dextrose Agar with Chloramphenicol at 37°C for 48 h, to assess the counts of colony-forming units/milliliter (CFU/ml) of Candida in saliva, and further on chrome agar plates to identify the Candida spp. Data were analyzed using mixed ANOVA to compare mean CFU/ml of Candida among three groups before and after the intervention. Results: A total of 86 patients were included in the final analysis and there was a statistically significant reduction in mean Candida spp. Counts (CFU/ml) after intervention in all the three groups (P = 0.000) and significant reductions identified in both probiotic and combination therapy groups. Apart from reduction in Candida albicans, significant decrease in Candida glabrata and Candida tropicalis was observed after probiotics usage compared to other groups. Conclusions: The present study suggests that probiotic bacteria were effective in reducing oral Candida spp which can be recommended alone or in combination with traditional antifungal agents for effective reduction in oral Candida in head- and neck-radiotherapy patients.


Assuntos
Candida albicans/efeitos dos fármacos , Candidíase Bucal/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Probióticos/uso terapêutico , Radioterapia/efeitos adversos , Saliva/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Candidíase Bucal/etiologia , Candidíase Bucal/patologia , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Saliva/efeitos dos fármacos , Saliva/efeitos da radiação , Resultado do Tratamento , Adulto Jovem
4.
SAR QSAR Environ Res ; 31(8): 571-583, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32628042

RESUMO

One of the most challenging issues when facing a Quantitative structure-activity relationship (QSAR) classification model is to deal with the descriptor selection. Penalized methods have been adapted and have gained popularity as a key for simultaneously performing descriptor selection and QSAR classification model estimation. However, penalized methods have drawbacks such as having biases and inconsistencies that make they lack the oracle properties. This paper proposes an adaptive penalized logistic regression (APLR) to overcome these drawbacks. This is done by employing a ratio (BWR) of the descriptors between-groups sum of squares (BSS) to the within-groups sum of squares (WSS) for each descriptor as a weight inside the L1-norm. The proposed method was applied to one dataset that consists of a diverse series of antimicrobial agents with their respective bioactivities against Candida albicans. By experimental study, it has been shown that the proposed method (APLR) was more efficient in the selection of descriptors and classification accuracy than the other competitive methods that could be used in developing QSAR classification models. Another dataset was also successfully experienced. Therefore, it can be concluded that the APLR method had significant impact on QSAR analysis and studies.


Assuntos
Antifúngicos/química , Candida albicans/efeitos dos fármacos , Relação Quantitativa Estrutura-Atividade , Modelos Logísticos , Modelos Moleculares
5.
J Mycol Med ; 30(3): 101011, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32693980

RESUMO

INTRODUCTION: Otomycosis, a superficial fungal infection of the external auditory canal (EAC), is a disease with exceptionally high prevalence. AIM: The aim of this study was to determine the prevalence of otomycosis, the distribution of causative species and to evaluate epidemiological characteristics of these infections. METHODOLOGY: The patients' data were collected from record book and database of mycological examinations conducted at Public Health Institute Nis, Serbia. In the period from 2014 to 2018 samples of 1287 patients with symptoms and signs of EAC infection were investigated. Standard mycological methods were used for isolation and determination of fungi. RESULTS: High prevalence of otomycosis was determined in examined patients (22.7%). However, the prevalence rates did not differ significantly in the studied period (p=0.931). The majority of patients were diagnosed with only unilateral EAC infection (82.9%). Considering all patients with otomycosis, mold infections caused by the genus Aspergillus (143/48.9%) were more frequent than Candida spp. ear infections (133/45.6%), with Aspergillus niger and Candida аlbicans being predominant causative agents. Mixed Aspergillus and Candida otomycosis was established in 16 (5.5%) patients. Otomycosis was more common in male subjects (26.8%, p=0.003) who also suffered from Aspergillus otomycosis more frequently (17.5%, p<0.001). The prevalence of these infections increases with age (p=0.005), while they do not show seasonal pattern (p>0.05). CONCLUSION: Noted high prevalence of otomycosis, with both yeasts and non-dermatophyte molds acting as infectious agents which require different treatment, implies the necessity for further epidemiological monitoring of this form of superficial mycoses.


Assuntos
Otomicose/epidemiologia , Otomicose/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/classificação , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Aspergilose/epidemiologia , Aspergilose/microbiologia , Aspergillus niger/efeitos dos fármacos , Aspergillus niger/isolamento & purificação , Candida/classificação , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Candida albicans/efeitos dos fármacos , Candida albicans/isolamento & purificação , Candidíase/tratamento farmacológico , Candidíase/epidemiologia , Candidíase/microbiologia , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Técnicas de Tipagem Micológica , Otomicose/tratamento farmacológico , Prevalência , Sérvia/epidemiologia , Adulto Jovem
6.
PLoS Genet ; 16(7): e1008908, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32639995

RESUMO

The human fungal pathogen Candida albicans is constantly exposed to environmental challenges impacting the cell wall. Signaling pathways coordinate stress adaptation and are essential for commensalism and virulence. The transcription factors Sko1, Cas5, and Rlm1 control the response to cell wall stress caused by the antifungal drug caspofungin. Here, we expand the Sko1 and Rlm1 transcriptional circuit and demonstrate that Rlm1 activates Sko1 cell wall stress signaling. Caspofungin-induced transcription of SKO1 and several Sko1-dependent cell wall integrity genes are attenuated in an rlm1Δ/Δ mutant strain when compared to the treated wild-type strain but not in a cas5Δ/Δ mutant strain. Genome-wide chromatin immunoprecipitation (ChIP-seq) results revealed numerous Sko1 and Rlm1 directly bound target genes in the presence of caspofungin that were undetected in previous gene expression studies. Notable targets include genes involved in cell wall integrity, osmolarity, and cellular aggregation, as well as several uncharacterized genes. Interestingly, we found that Rlm1 does not bind to the upstream intergenic region of SKO1 in the presence of caspofungin, indicating that Rlm1 indirectly controls caspofungin-induced SKO1 transcription. In addition, we discovered that caspofungin-induced SKO1 transcription occurs through self-activation. Based on our ChIP-seq data, we also discovered an Rlm1 consensus motif unique to C. albicans. For Sko1, we found a consensus motif similar to the known Sko1 motif for Saccharomyces cerevisiae. Growth assays showed that SKO1 overexpression suppressed caspofungin hypersensitivity in an rlm1Δ/Δ mutant strain. In addition, overexpression of the glycerol phosphatase, RHR2, suppressed caspofungin hypersensitivity specifically in a sko1Δ/Δ mutant strain. Our findings link the Sko1 and Rlm1 signaling pathways, identify new biological roles for Sko1 and Rlm1, and highlight the complex dynamics underlying cell wall signaling.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/genética , Candida albicans/efeitos dos fármacos , Caspofungina/farmacologia , Proteínas de Domínio MADS/genética , Proteínas Repressoras/genética , Proteínas de Saccharomyces cerevisiae/genética , Antifúngicos/farmacologia , Candida albicans/genética , Candida albicans/patogenicidade , Parede Celular/efeitos dos fármacos , Parede Celular/genética , Proteínas Fúngicas/genética , Regulação Fúngica da Expressão Gênica , Humanos , Fosforilação/efeitos dos fármacos , Saccharomyces cerevisiae/genética , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição/genética
7.
Int J Nanomedicine ; 15: 3681-3693, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32547022

RESUMO

Background: Fungal infections are becoming more prevalent and threatening because of the continuous emergence of azole-resistant fungal infections. The present study was aimed to assess the activity of free Methylglyoxal (MG) or MG-conjugated chitosan nanoparticles (MGCN) against fluconazole-resistant Candida albicans. Materials and Methods: A novel formulation of MGCN was prepared and characterized to determine their size, shape and polydispersity index. Moreover, the efficacy of fluconazole or MG or MGCN was determined against intracellular C. albicans in macrophages and the systematic candidiasis in a murine model. The safety of MG or MGCN was tested in mice by analyzing the levels of hepatic and renal toxicity parameters. Results: Candida albicans did not respond to fluconazole, even at the highest dose of 20 mg/kg, whereas MG and MGCN effectively eliminated C. albicans from the macrophages and infected mice. Mice in the group treated with MGCN at a dose of 10 mg/kg exhibited a 90% survival rate and showed the lowest fungal load in the kidney, whereas the mice treated with free MG at the same dose exhibited 50% survival rate. Moreover, the administration of MG or MGCN did not induce any liver and kidney toxicity in the treated mice. Conclusion: The findings of the present work suggest that MGCN may be proved a promising therapeutic formulation to treat azole-resistant C. albicans infections.


Assuntos
Candidíase/tratamento farmacológico , Quitosana/química , Farmacorresistência Fúngica , Fluconazol/uso terapêutico , Nanopartículas/química , Aldeído Pirúvico/uso terapêutico , Animais , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Candidíase/microbiologia , Modelos Animais de Doenças , Farmacorresistência Fúngica/efeitos dos fármacos , Feminino , Fluconazol/farmacologia , Hifas/efeitos dos fármacos , Hifas/crescimento & desenvolvimento , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Nanopartículas/ultraestrutura , Tamanho da Partícula , Aldeído Pirúvico/farmacologia
8.
Braz Oral Res ; 34: e050, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32578760

RESUMO

Candida infection is an important cause of morbidity and mortality in immunocompromised patients. The increase in its incidence has been associated with resistance to antimicrobial therapy and biofilm formation. The aim of this study was to evaluate the efficacy of tea tree oil (TTO) and its main component - terpinen-4-ol - against resistant Candida albicans strains (genotypes A and B) identified by molecular typing and against C. albicans ATCC 90028 and SC 5314 reference strains in planktonic and biofilm cultures. The minimum inhibitory concentration, minimum fungicidal concentration, and rate of biofilm development were used to evaluate antifungal activity. Results were obtained from analysis of the biofilm using the cell proliferation assay 2,3-Bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) and confocal laser scanning microscopy (CLSM). Terpinen-4-ol and TTO inhibited C. albicans growth. CLSM confirmed that 17.92 mg/mL of TTO and 8.86 mg/mL of terpinen-4-ol applied for 60 s (rinse simulation) interfered with biofilm formation. Hence, this in vitro study revealed that natural substances such as TTO and terpinen-4-ol present promising results for the treatment of oral candidiasis.


Assuntos
Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Óleo de Melaleuca/farmacologia , Terpenos/farmacologia , Resinas Acrílicas , Análise de Variância , Antifúngicos/farmacologia , Biofilmes/crescimento & desenvolvimento , Candida albicans/crescimento & desenvolvimento , Bases de Dentadura/microbiologia , Testes de Sensibilidade Microbiana , Microscopia Confocal , Valores de Referência , Reprodutibilidade dos Testes , Estatísticas não Paramétricas , Óleo de Melaleuca/química , Terpenos/química
9.
Phytomedicine ; 71: 153223, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32460204

RESUMO

BACKGROUND: Candida albicans-related infections are common infections in clinic, among which biofilm-associated infections are most devastating and challenging to overcome. Myricetin (MY) is a plant-derived natural product with various pharmacological activities. Its anti-biofilm effect against C. albicans and its ability to increase the antifungal effect of miconazole nitrate (MN) were unclear and yet need to be explored. HYPOTHESIS/PURPOSE: In this study the anti-biofilm effect of MY and its ability to increase the antifungal effect of MN were investigated in vitro and in vivo. STUDY DESIGN AND METHODS: MY or/and MN were incorporated into a thermosensitive hydrogel (TSH) of poloxamer. The safety of MY or/and MN loaded TSHs towards human umbilical vein endothelial cells (HUVEC) was evaluated by a MTT assay and the in vivo safety towards mice knees was confirmed by histopathological examination. The anti-biofilm effect of MY and its ability to increase the antifungal effect of MN were investigated in vitro with C. albicans ATCC 10231 by broth microdilution method, crystal violet staining and scanning electron microscopy (SEM), as well as in vivo in an established mouse model of periprosthetic joint infection (PJI) by SEM, histological analysis, microorganism culture and detection of the serum levels of interleukin-6 (IL-6). The mechanism of action of MY was analyzed by qRT-PCR assay with C. albicans SC5314. RESULTS: Our results showed that MY and MN incorporated into TSHs exhibited good stability and safety, excellent temperature sensitivity and controlled drug release property. MY (5-640 µg/ml) exhibited no effect on C. albicans cell viability and MY (≥80 µg/ml) showed a significantly inhibitory effect on biofilm formation. MIC50 (the lowest concentrations of drugs resulting in 50% decrease of C. albicans growth) and MIC80 (the lowest concentrations of drugs resulting in 80% decrease of C. albicans growth) of MN were respectively decreased from 2 µg/ml to 0.5 µg/ml and from 4 µg/ml to 2 µg/ml when used in combination with MY (80 µg/ml). The mouse PJI was effectively prevented by MY and MN incorporated into TSH. CONCLUSIONS: Local application of MY and MN incorporated into TSH might be useful for clinical biofilm-associated infections.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Flavonoides/farmacologia , Hidrogéis/química , Miconazol/farmacologia , Animais , Biofilmes/efeitos dos fármacos , Candidíase/tratamento farmacológico , Candidíase/prevenção & controle , Combinação de Medicamentos , Flavonoides/farmacocinética , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos Endogâmicos C57BL , Miconazol/farmacocinética , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/prevenção & controle
10.
Biofouling ; 36(3): 292-307, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32367731

RESUMO

Microbial cells can rapidly form biofilm on endotracheal tubes (ETT) causing ventilator-associated pneumonia, a serious complication in patients receiving mechanical ventilation. A novel polyamide with a good balance of hydrophilic/hydrophobic moieties was used for the embedment of green-reduction silver nanoparticles (AgNPs) for the composite-coated ETT. The films were conformal with a thickness of ∼ 17 ± 3 µm accommodating high loading of 60 ± 35 nm spherical-shaped AgNPs. The coated ETT resulted in a significant difference in reducing both planktonic growth and microbial adhesion of single and mixed-species cultures, compared with uncoated ETT (p < 0.05). A time-kill assay demonstrated rapid bactericidal effects of the coating on bacterial growth and cell adhesion to ETT surface. Biofilm formation by Pseudomonas aeruginosa and Staphylococcus aureus, commonly encountered pathogens, was inhibited by > 96% after incubation for 72 h. Polyamide/AgNP composite-coated ETT provided a broad-spectrum activity against both Gram-positive and Gram-negative bacteria as well as Candida albicans and prolonged antimicrobial activity.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Equipamentos Descartáveis/microbiologia , Nanopartículas Metálicas/química , Nylons/farmacologia , Plâncton/efeitos dos fármacos , Pneumonia Associada à Ventilação Mecânica/microbiologia , Prata/farmacologia , Antibacterianos/química , Biofilmes/crescimento & desenvolvimento , Candida albicans/efeitos dos fármacos , Contaminação de Equipamentos/prevenção & controle , Humanos , Intubação Intratraqueal , Nylons/química , Plâncton/crescimento & desenvolvimento , Plâncton/microbiologia , Pneumonia Associada à Ventilação Mecânica/prevenção & controle , Pseudomonas aeruginosa/efeitos dos fármacos , Prata/química , Staphylococcus aureus/efeitos dos fármacos
11.
Biofouling ; 36(3): 319-331, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32410461

RESUMO

Traditional herbal monomers (THMs) are widely distributed in many traditional Chinese formulas (TCFs) and decoctions (TCDs) and are frequently used for the prevention and treatment of fungal infections. The antifungal activities of five common THMs, including sodium houttuyfonate (SH), berberine (BER), palmatine (PAL), jatrorrhizine (JAT) and cinnamaldehyde (CIN), and their potential for inducing cell wall remodeling (CWR), were evaluated against Candida albicans SC5314 and Candida auris 12372. SH/CIN plus BER/PAL/JAT showed synergistic antifungal activity against both Candida isolates. Furthermore, SH-associated combinations (SH plus BER/PAL/JAT) induced stronger exposure of ß-glucan and chitin than their counterparts, while CIN triggered more marked exposure compared with CIN-associated combinations (CIN plus BER/PAL/JAT). Collectively, this study demonstrated the anti-Candida effect and the CWR induction potential of the five THMs and their associated combinations, providing a possibility of their in vivo application against fungal-associated infections.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candida/efeitos dos fármacos , Parede Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Acroleína/análogos & derivados , Acroleína/farmacologia , Alcanos/farmacologia , Berberina/análogos & derivados , Berberina/farmacologia , Alcaloides de Berberina/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Sulfitos/farmacologia
12.
AAPS PharmSciTech ; 21(5): 143, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32424702

RESUMO

This work aims to improve the functionality of Rosmarinus officinalis L. (rosemary) polyphenols by encapsulation in an optimized proliposome formulation. A 23 Box-Wilson central composite design (CCD) was employed to determine lone and interaction effects of composition variables on moisture content (Xp); water activity (Aw); concentration and retention of rosemary polyphenols-rosmarinic acid (ROA), carnosol (CAR), and carnosic acid (CNA); and recovery of spray-dried proliposomes (SDP). Processing conditions which generate proliposomes with optimum physicochemical properties were determined by multi-response analysis (desirability approach). Antioxidant and antifungal activities were evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH•) sequestering and minimum inhibitory concentration (MIC)/minimum fungicidal concentration (MFC) assays, respectively. SDP exhibited high polyphenol retention, ranging from 62.0 to 100.0% w/w, showing dependence on composition variables and polyphenol lipophilicity. SDP recovery ranged from 20.1 to 45.8%, with Xp and Aw of 1.7 ± 0.14-2.5 ± 0.23% w/w and 0.30 ± 0.004-0.47 ± 0.003, respectively, evidencing product with good chemical and microbiological stability. Optimum liposomal composition was determined, namely, lipid concentration (4.26% w/w), lyophilized extract (LE) concentration (4.48% w/w), and drying aid:(lipid+extract) ratio (7.55% w/w) on wet basis. Relative errors between experimental and predicted values for SDP properties showed concurrence for all responses except CAR retention, being 22% lower. SDP showed high antioxidant activity with IC50 of 9.2 ± 0.2 µg/mL, superior to results obtained for LE (10.8 µg/mL) and butylated hydroxytoluene (BHT), a synthetic antioxidant (12.5 µg/mL). MIC and MFC against Candida albicans (ATCC1023) were 312.5 µg/mL and 1250 µg/mL, respectively, a moderate antimicrobial activity for phytochemical-based products. SDP is shown as a veritable tool to encapsulate hydrophilic and lipophilic rosemary polyphenols generating a product with optimal physicochemical and biological properties.


Assuntos
Lipossomos/química , Polifenóis/química , Rosmarinus/química , Antifúngicos/farmacologia , Antioxidantes/farmacologia , Candida albicans/efeitos dos fármacos , Cápsulas , Dessecação , Composição de Medicamentos , Liofilização , Humanos , Lipídeos/química , Testes de Sensibilidade Microbiana , Folhas de Planta/química , Polifenóis/administração & dosagem , Polifenóis/farmacologia , Água/análise
13.
Int J Nanomedicine ; 15: 2353-2362, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32308387

RESUMO

Purpose: Simple methodology for preparation of metal nanoparticles such as AgNPs uses an methanolic aqueous medium at room temperature or a solvent-free procedure under microwave irradiation. The prepared AgNPs showed a significant antimicrobial effect against Gram-positive bacteria, Gram-negative bacteria, and fungi. Methods: The modified methoxypolyethylene glycol bishydrazino-s-triazine (mPEGTH2) showed remarkable activity for reducing Ag+ to Ag0 in an aqueous methanolic solution and using a solvent-free method (solid phase) under microwave irradiation. In the solid phase synthesis, the size and shape of the AgNPs can be controlled by varying the weight ratio of mPEGTH2 to AgNO3 used. In addition, the antimicrobial activity depends on the ratio of mPEGTH2 to AgNO3. The mPEGTH2-AgNPs (2:1) demonstrated higher antimicrobial activity compared to mPEGTH2-AgNPs (1:1) against Gram-positive bacteria, Gram-negative bacteria, and C.albicans. Results: This work presents simple methods for the synthesis of AgNPs using modified methoxypolyethylene glycol with bishydrazino-s-triazine (mPEGTH2); a solution method, using methanol-water medium at room temperature, and a solvent-free (solid phase) method, employing microwave irradiation or direct heating which could be used for the preparation of AgNPs on large scale. In the solid phase, ratios of mPEGTH2 to AgNO3 (1:1 or 2:1, respectively) are very important to control the size and shape of AgNPs. While in solution phase is not necessary where the molar ratio used is 10:1. Most of the experimental methods resulted in AgNPs ranging in size from 7 to 10 nm as observed from XRD and TEM characterization. The antimicrobial activity of the AgNPs was also dependent on the weight ratio of mPEGTH2 to AgNO3, with a large effect as observed when using the solvent-free method. The mPEGTH2-AgNPs (2:1) demonstrated higher antimicrobial activities compared to mPEGTH2-AgNPs (1:1) against S. aureus, S. epidermidis, E. faecalis, E. coli, P. aeruginosa, S. typhimurium, and C. albicans. In all cases, the MICs and MBCs of mPEGTH2-AgNPs (1:1) were lower than those of mPEGTH2-AgNPs (2:1). Conclusion: In summary, mPEGTH2-AgNPs (2:1) is a promising candidate to kill pathogenic microbes. In particular, the method used for the preparation of AgNPs by using polyethylene glycol polymer modified with bishydrazino-s-triazine has the most potential and would be the most cost-effective method. This method of the synthesis of nanoparticles may be suitable for the preparation of other metal nanoparticles, which would allow for numerous applications in medicinal and industrial.


Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Nanopartículas Metálicas/química , Polietilenoglicóis/química , Prata/química , Antibacterianos/química , Candida albicans/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Micro-Ondas , Pseudomonas aeruginosa/efeitos dos fármacos , Técnicas de Síntese em Fase Sólida/métodos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos
14.
Biofouling ; 36(2): 210-221, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32292058

RESUMO

Surfactin is a type of cyclic lipopeptide biosurfactant implicated in a wide range of applications. Although its antimicrobial activity has been characterized, its effect on Candida albicans physiology remains to be elucidated. The present study evaluated the influence of surfactin-C15 (SF) and its complexes with divalent counterions on C. albicans biofilm formation and preformed biofilms. The SF and metal(II)-SF complexes inhibited biofilm formation and reduced the metabolic activity of mature biofilms in a concentration-dependent manner. The same concentrations of the compounds studied dislodged preexisting biofilms grown on polystyrene plates. Moreover, SF and its metal(II) complexes reduced the mRNA expression of hypha-specific genes HWP1, ALS1, ALS3, ECE1 and SAP4 without exhibiting significant growth inhibition. Further research showed that the compounds tested reduced cellular surface hydrophobicity (CSH). These results suggest that SF and metal(II)-SF complexes could be used as anti-biofilm agents against C. albicans hypha-related infections in clinical practice.


Assuntos
Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Hifas/efeitos dos fármacos , Tensoativos/metabolismo , Aderência Bacteriana/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Candida albicans/crescimento & desenvolvimento , Candida albicans/metabolismo , Proteínas Fúngicas/genética , Proteínas de Fluorescência Verde/genética , Hifas/crescimento & desenvolvimento
15.
Biofouling ; 36(3): 245-255, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32326753

RESUMO

Dental plaque is a biofilm composed of a complex oral microbial community. The accumulation of plaque in the pit and fissures of dental elements often leads to the development of tooth decay (dental caries). Here, potent anti-biofilm materials were developed by incorporating zinc methacrylates or di-n-butyl-dimethacrylate-tin into the light-curable sealant and their physical, mechanical, and biological properties were evaluated. The data revealed that 5% di-n-butyl-dimethacrylate-tin (SnM 5%) incorporated sealant showed strong anti-biofilm efficacy against various single-species (Streptococcus mutans or Streptococcus oralis or Candida albicans) and S. mutans-C. albicans cross-kingdom dual-species biofilms without either impairing the mechanical properties of the sealant or causing cytotoxicities against mouse fibroblasts. The findings indicate that the incorporation of SnM 5% in the experimental pit and fissure self-adhesive sealant may have the potential to be part of current chemotherapeutic strategies to prevent the formation of cariogenic oral biofilms that cause dental caries.


Assuntos
Adesivos/farmacologia , Biofilmes/efeitos dos fármacos , Cárie Dentária/prevenção & controle , Selantes de Fossas e Fissuras/farmacologia , Zinco/química , Adesivos/química , Animais , Biofilmes/crescimento & desenvolvimento , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Cárie Dentária/microbiologia , Humanos , Metacrilatos/química , Camundongos , Microbiota/efeitos dos fármacos , Selantes de Fossas e Fissuras/química , Streptococcus mutans/efeitos dos fármacos , Streptococcus mutans/crescimento & desenvolvimento , Streptococcus oralis/efeitos dos fármacos , Streptococcus oralis/crescimento & desenvolvimento
16.
Int J Nanomedicine ; 15: 2027-2044, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32273700

RESUMO

Purpose: As one of the classic anti-Canidia albicans (CA) and vulvovaginal candidiasis (VVC) drugs, nystatin (NYS) is limited by poor water solubility and easy aggregation. Traditional NYS vaginal delivery formulations do not fully adapt to the specific environment of the vaginal cavity. The use of exopolysaccharides (EPS) has great application potential in emulsifiers, but its use has not been reported in nanoemulsions. In this work, an EPS/NYS nanoemulsion (ENNE) was developed to improve the activities of NYS against CA and VVC. Methods: The ENNE was prepared by ultrasonic method using EPS as an emulsifier, liquid paraffin oil as an oil phase, PEG400 as a co-emulsifier, and NYS as the loaded drug. ENNE preparation was optimized by response surface method. After optimization, in vitro and in vivo analysis of the anti-CA activity; animal experiments; staining with propidium iodide (PI), periodic acid-schiff (PAS), and hematoxylin-eosin (H&E); and cytokine experiments were performed to investigate the therapeutic ability against VVC. Results: The optimal formulation and preparation parameters of ENNE were determined as follows: EPS content of 1.5%, PEG400 content of 3.2%, NYS content of 700 µg/mL, paraffin oil content of 5.0%, ultrasonic time of 15 min, and ultrasonic amplitude of 35%. The ENNE showed an encapsulated structure with an average particle size of 131.1 ± 4.32 nm. ENNE exhibited high storage and pH stability, as well as slow release. The minimum inhibitory concentration (MIC) of ENNE against CA was only 0.125 µg/mL and the inhibition zone was 19.0 ± 0.5 mm, for greatly improved anti-CA effect. The prepared ENNE destroyed the membrane of CA cells, and exhibited good anti-CA effect in vivo and therapeutic ability against VVC. Conclusion: The results of this study will promote the application of EPS in nanotechnology, which should lead to new and effective local drug formulations for treating VVC.


Assuntos
Antifúngicos/administração & dosagem , Candidíase Vulvovaginal/tratamento farmacológico , Emulsões/química , Nanoestruturas/administração & dosagem , Nistatina/administração & dosagem , Administração Intravaginal , Animais , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Citocinas , Emulsificantes/química , Emulsões/administração & dosagem , Feminino , Camundongos Endogâmicos ICR , Testes de Sensibilidade Microbiana , Nanoestruturas/química , Nistatina/farmacologia , Tamanho da Partícula , Polietilenoglicóis/química , Polissacarídeos Bacterianos/química , Ultrassom/métodos
17.
BMC Complement Med Ther ; 20(1): 104, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32245474

RESUMO

BACKGROUND: Peri-implant inflammation resulting from the presence of Candida biofilms may compromise the longevity of implant-supported dentures. This study evaluated the inhibitory effect of Brazilian red propolis on mono-species biofilms of C. albicans (ATCC 90028) and co-culture biofilms of C. albicans (ATCC 90028) and C. glabrata (ATCC 2001), developed on titanium surfaces. METHODS: Titanium specimens were pre-conditioned with artificial saliva and submitted to biofilm formation (1 × 106 CFU/mL). After 24 h (under microaerophilic conditions at 37 °C) biofilms were submitted to treatment for 10 min, according to the groups: sterile saline solution (growth control), 0.12% chlorhexidine and 3% red propolis extract. Treatments were performed every 24 h for 3 days and analyses were conducted 96 h after initial adhesion. After that, the metabolic activity (MTT assay) (n = 12/group), cell viability (CFU counts) (n = 12/group) and surface roughness (optical profilometry) (n = 6/group) were evaluated. Data from viability and metabolic activity assays were evaluated by ANOVA and Tukey tests. Surface roughness analysis was determined by Kruskal Wallis e Mann Whitney tests. RESULTS: Regarding the mono-species biofilm, the cell viability and the metabolic activity showed that both chlorhexidine and red propolis had inhibitory effects and reduced the metabolism of biofilms, differing statistically from the growth control (p < 0.05). With regards the co-culture biofilms, chlorhexidine had the highest inhibitory effect (p < 0.05). The metabolic activity was reduced by the exposure to chlorhexidine and to red propolis, different from the growth control group (p < 0.05). The surface roughness (Sa parameter) within the mono-species and the co-culture biofilms statistically differed among groups (p < 0.05). CONCLUSIONS: Brazilian red propolis demonstrated potential antifungal activity against Candida biofilms, suggesting it is a feasible alternative for the treatment of peri-implantitis.


Assuntos
Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Candida glabrata/efeitos dos fármacos , Própole/farmacologia , Anti-Infecciosos Locais/farmacologia , Brasil , Clorexidina/farmacologia , Propriedades de Superfície , Titânio
18.
Clín. investig. ginecol. obstet. (Ed. impr.) ; 47(1): 3-8, ene.-mar. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-187065

RESUMO

Introducción: Las guías clínicas actuales recomiendan el uso del cerclaje de emergencia (CE) como tratamiento de la insuficiencia cervical con exposición de membranas en gestaciones únicas. Sin embargo, el CE en gestación múltiple es tema de controversia dado que no existen ensayos clínicos randomizados que demuestren su eficacia. Algunos estudios retrospectivos sugieren que el CE también podría prolongar la gestación en embarazos múltiples. El objetivo de nuestro estudio es evaluar los resultados de las gestaciones múltiples que se sometieron a un CE en nuestro centro. Materiales y métodos: Se diseñó un estudio retrospectivo que incluyó los CE realizados en gestaciones gemelares en nuestro centro entre 2007-2016. No fueron tributarias de CE gestaciones con malformaciones fetales, monocoriales-monoamnióticas, triple o superior y finalizaciones activas de la gestación. Variables primarias: latencia al parto espontáneo y edad gestacional al parto. Variables secundarias: mortalidad neonatal, ingreso en UCI neonatal, rotura prematura de membranas pretérmino, corioamnionitis y fallo del cerclaje. Resultados. El estudio incluyó 17 pacientes. La edad gestacional mediana (rango intercuartil) al parto fue de 27,1 (24,5-32,3) semanas y la latencia mediana (rango intercuartil) al parto fue de 43 (21-64) días. Hubo 4/17 (23,5%) casos de parto antes de las 24 semanas de gestación y 2/26 (7,7%) de muerte neonatal. Discusión: Estos resultados muestran que la latencia al parto después del CE en gestación múltiple es remarcable, por lo que podría ser considerado como una opción terapéutica. Sin embargo, se requiere evidencia basada en estudios randomizados para hacer una recomendación firme


Introduction: Current guidelines support the use of physical-examination indicated cerclage (PEIC) as a treatment for cervical insufficiency and membrane exposure in single pregnancies. However, PEIC in twin pregnancies is a controversial issue as no data from random clinical trial are available to demonstrate its efficacy. Few studies suggest that PEIC may prolong pregnancy also in twin pregnancies. The aim of this study was to evaluate the results of twin pregnancies that underwent a PEIC in our health centre. Material and methods: A retrospective review was performed on women that underwent a PEIC from 2007-2016 in our centre. Women were not eligible if they were carrying foetuses with major foetal anomalies, more than two foetuses or monochorionic-monoamniotic pregnancies, or three or more foetuses or requesting an elective termination of pregnancy. Primary outcomes: latency to spontaneous delivery and gestational age (GA) at delivery. Secondary outcomes: neonatal mortality and Neonatal Intensive Care Unit admission, preterm premature rupture of membranes (PPROM), chorioamnionitis and cerclage displacement. Results: The study included a total of 17 women. The median (inter-quartile range) gestational age at delivery was 27.1 (24.5-32.3) weeks, and median (inter-quartile range) latency, from cervical cerclage to delivery, was 43 (21-64) days. There were 4/17 (23.5%) cases of delivery before 24 weeks of pregnancy, and 2/26 (7.7%) cases of neonatal death. Discussion: These results suggest that latency to delivery after PEIC in twins is remarkable. Therefore, it could be considered as an optional management. Nevertheless, evidence based on random clinical trial is required to make firm recommendations on its formal use


Assuntos
Humanos , Feminino , Gravidez , Adulto , Cerclagem Cervical/métodos , Gravidez de Gêmeos/fisiologia , Mortalidade Infantil , Fatores de Risco , Amniocentese/métodos , Estudos Retrospectivos , Idade Gestacional , Trabalho de Parto Prematuro/epidemiologia , Ruptura Prematura de Membranas Fetais , Gardnerella vaginalis/isolamento & purificação , Gardnerella vaginalis/efeitos dos fármacos , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Candida albicans/efeitos dos fármacos , Candida albicans/isolamento & purificação
19.
J Biosci Bioeng ; 130(1): 6-13, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32192842

RESUMO

Defensins are antibacterial peptides that function in the innate immune system. OsAFP1, a defensin identified from Oryza sativa (rice), exhibits antimicrobial activity against rice pathogens. Intriguingly, OsAFP1 was also shown to demonstrate potent antifungal activity against the human pathogenic fungus Candida albicans by inducing apoptosis in target cells, suggesting that OsAFP1 represents a potential new antibiotic candidate; however, further analyses, particularly at the structural level, are required to elucidate the mechanistic underpinnings of OsAFP1 antifungal activity. Here, we determined the three-dimensional structure of OsAFP1 using X-ray crystallography. OsAFP1 features the cysteine-stabilized αß structure highly conserved in plant defensins and presents a dimeric structure that appears necessary for antifungal activity. Superimposition of the OsAFP1 structure with that of Nicotiana alata NaD1 complexed with phosphatidic acid indicated that the target molecule is likely trapped between the S2-S3 loops of each OsAFP1 dimer. In lipid-binding analyses performed using nitrocellulose membranes immobilized with various membrane lipid components, OsAFP1 was found to bind to phosphatidylinositols (PIPs) harboring phosphate groups, particularly PI(3)P. These results indicate that OsAFP1 exerts antifungal activity by binding to PI(3)P contained in the C. albicans cell membrane, thereby applying cellular stress and inducing apoptosis. Furthermore, the OsAFP1 structure and site-specific-mutation analyses revealed that Arg1, His2, Leu4, Arg9, and Phe10 play critical roles in OsAFP1 dimer formation. Thus, our study provides novel insights into the antifungal mechanism of OsAFP1.


Assuntos
Defensinas/química , Defensinas/metabolismo , Oryza/metabolismo , Fosfatidilinositóis/metabolismo , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Antifúngicos/química , Antifúngicos/metabolismo , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candida albicans/metabolismo , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Cristalização , Defensinas/genética , Defensinas/farmacologia , Oryza/química , Oryza/genética , Fosfatidilinositóis/química , Proteínas de Plantas/genética , Proteínas de Plantas/farmacologia
20.
BMC Infect Dis ; 20(1): 231, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32188422

RESUMO

BACKGROUND: The spectrum of yeasts and their antifungal susceptibility profile are poorly known and treatment of fungal disease has remained empirical. The aim of this study is to determine the spectrum and antifungal susceptibility profile of yeasts particularly of Candida species. METHODS: A descriptive study on the composition of Candida species and antifungal susceptibility profile were conducted from January 2018 to September 2018. Clinical samples collected from different sites were cultured on Sabouraud dextrose agar and incubated for an appropriate time. Identification of yeast isolates and their antifungal susceptibility profile were determined by the VITEK 2 compact system. Descriptive statistics such as frequency and percentage of Candida species were calculated using SPSS version 20. RESULTS: Of 209 yeasts recovered, 104(49.8%), 90 (43.1%), 15(7.2%) were C. albicans, non albicans Candida species, and other yeasts, respectively. Among non albicans Candida species, Candida krusei was the commonest isolate. Of other yeast groups, 66.7% was represented by Cryptococcus laurentii. Regardless of Candida species identified, 85.6, 3.9, and 10.5% of the isolates were susceptible, intermediate, and resistant to fluconazole, respectively. C krusei was 100% resistant to the drug. Voriconazole demonstrated the greatest antifungal activity against Candida isolates in which 99.4% of Candida isolates were susceptible. The susceptibility and the resistance rate of Candida isolate to both caspofungin and micafungin were the same being 96 and 4% respectively. However, micafungin was more potent than caspofungin. The susceptibility, resistant, and intermediate rates of yeasts against flucytosine were, 86.2, 6.6, and 7.2%, respectively. CONCLUSIONS: The present study demonstrated the distribution of Candida species in different clinical specimens where the isolation rate of non-albicans Candida species was comparable to Candida albicans. The high resistance rate of C. krusei to fluconazole and flucytosine may demonstrate that the treatment of candidiasis empirically is questionable.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Candidíase/microbiologia , Candida albicans/efeitos dos fármacos , Candida albicans/isolamento & purificação , Caspofungina/farmacologia , Farmacorresistência Fúngica/efeitos dos fármacos , Etiópia , Humanos , Micafungina/farmacologia , Testes de Sensibilidade Microbiana
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