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1.
Adv Exp Med Biol ; 1308: 225-248, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33861447

RESUMO

Candida albicans is part of the healthy flora in the oral cavity. It can also cause opportunistic infection, which can be deleterious. The most typical type of chronic oral candidiasis is denture stomatitis, and C. albicans is identified as the most crucial organism in this situation. Due to the development of the resistant form of candida, using conventional drugs can sometimes be ineffective. Herbs and naturally imitative bioactive compounds could become a new source for antimycotic therapy. Several review studies suggest that herbal medicine and natural bioactive compounds have antibacterial, antiviral and antifungal effects. Thus, it is hypothesized that these natural products might have beneficial effects on pathogenic oral fungal flora such as C. albicans. Although the effects of herbs have been investigated as antifungal agents in several studies, to the best of our knowledge, the effects of these natural products on C. albicans have not yet been reviewed. Thus, the aim of this study was to review the anti-candida activity (especially C. albicans in oral candidiasis) of herbal medicines and natural bioactive compounds. It is concluded that, in general, medicinal plants and nutraceuticals such as garlic, green tea, propolis, curcumin, licorice root, cinnamon, resveratrol, ginger, and berberine are useful in the treatment of C. albicans in oral candidiasis and could be considered as a safe, accessible, and inexpensive management option in an attempt to prevent and treat oral diseases. However, most of the evidence is based on the in vitro and animal studies, so more clinical trials are needed.


Assuntos
Candidíase Bucal , Preparações Farmacêuticas , Plantas Medicinais , Animais , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida albicans , Candidíase Bucal/tratamento farmacológico , Suplementos Nutricionais , Medicina Herbária
2.
Drug Dev Ind Pharm ; 47(2): 246-258, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33416006

RESUMO

The aim of this work was to prepare and optimize mucoadhesive nanostructured lipid carrier (NLC) impregnated with fluconazole for better management of oral candidiasis. The NLCs were fabricated using an emulsification/sonication technique. The nanoparticles consisted of stearic acid, oleic acid, Pluronic F127, and lecithin. Box-Behnken design, artificial neural networking, and variable weight desirability were employed to optimize the joint effect of drug concentration in the drug/lipid mixture, solid lipid concentration in the solid/liquid lipid mixture, and surfactant concentration in the total mixture on size and entrapment. The optimized NLCs were coated with chitosan. The nanoparticles were characterized by surface charge, spectroscopic, thermal, morphological, mucoadhesion, release, histopathological, and antifungal properties. The nanoparticles are characterized by a particle size of 335 ± 13.5 nm, entrapment efficiency of 73.1 ± 4.9%, sustained release, minor histopathological effects on rabbit oral mucosa, and higher fungal inhibition efficiency for an extended period of time compared with fluconazole solution. Coating the nanoparticles with chitosan increased its adhesion to rabbit oral buccal mucosa and improved its anti-candidiasis activity. It is concluded that mucoadhesive lipid-based nanoparticles amplify the effect of fluconazole on Candida albicans in vitro. This finding warrants pre-clinical and clinical studies in oral candidiasis disease models to corroborate in vitro findings.


Assuntos
Candidíase Bucal , Fluconazol/farmacologia , Lipídeos/química , Nanopartículas , Nanoestruturas , Animais , Candidíase Bucal/tratamento farmacológico , Portadores de Fármacos , Fluconazol/administração & dosagem , Fluconazol/química , Aprendizado de Máquina , Tamanho da Partícula , Coelhos
3.
Oral Dis ; 26 Suppl 1: 91-102, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32862535

RESUMO

Oral candidiasis (OC) is the most prevalent HIV-related oral lesion in patients on combined anti-retroviral therapy (cART) or without cART. Management is challenged in some patients by development of resistance to azole drugs, such as fluconazole. Recent scientific knowledge about OC pathogenesis, the role of OC in the immune reconstitution inflammatory syndrome (IRIS), the relationship of OC with the microbiome, and novelties in OC treatment was discussed in an international workshop format. Literature searches were conducted to address five questions: (a) Considering the pathogenesis of Candida spp. infection, are there any potential therapeutic targets that could be considered, mainly in HIV-infected individuals resistant to fluconazole? (b) Is oral candidiasis part of IRIS in HIV patients who receive cART? (c) Can management of the oral microbiome reduce occurrence of OC in patients with HIV infection? (d) What are the recent advances (since 2015) regarding plant-based and alternative medicines in management of OC? and (e) Is there a role for photodynamic therapy in management of OC in HIV-infected patients? A number of the key areas where further research is necessary were identified to allow a deeper insight into this oral condition that could help to understand its nature and recommend alternatives for care.


Assuntos
Antifúngicos , Candidíase Bucal , Infecções por HIV , Antifúngicos/uso terapêutico , Candidíase Bucal/tratamento farmacológico , Candidíase Bucal/prevenção & controle , Fluconazol/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos
4.
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
6.
BMC Complement Altern Med ; 19(1): 303, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703673

RESUMO

BACKGROUND: Candida albicans is an opportunistic pathogen that causes oral candidiasis and denture stomatitis. It has also been reported to infect oral mucositis lesions in patients who suffer from cancer affecting the head and neck and who receive chemotherapy and radiotherapy treatments. This study aimed to investigate the effects of two cinnamon bark fractions, i.e., an essential oil and an aqueous extract enriched in proanthocyanidins (Cinnulin PF®) on growth, biofilm formation, and adherence properties of C. albicans as well as on oral epithelial cells (barrier integrity, inflammatory response). METHODS: A microplate dilution assay was used to determine antifungal and anti-biofilm properties. A fluorescent assay was used to determine C. albicans adherence to oral epithelial cells. Cytotoxicity toward oral epithelial cells was assessed by determination of cell metabolic activity. Tight junction integrity of gingival keratinocytes was assessed by determination of transepithelial electrical resistance. IL-6 and IL-8 secretion by TNFα-stimulated oral epithelial cells was quantified by ELISA. RESULTS: While Cinnulin PF® did not reduce C. albicans growth, the cinnamon bark oil exhibited high antifungal activity with minimum inhibitory concentrations and minimum fungicidal concentrations in the range of 0.039 to 0.078%. The cinnamon oil was also active against a pre-formed C. albicans biofilm. Interestingly, Cinnulin PF® prevented biofilm formation by C. albicans and attenuated its adherence to oral epithelial cells. At their effective concentrations, the cinnamon oil and the Cinnulin PF® displayed no significant cytotoxicity against oral epithelial cells. In an in vitro model, both cinnamon fractions reinforced the integrity of the oral epithelial barrier. Lastly, Cinnulin PF® inhibited the secretion of interleukin-6 and interleukin-8 by oral epithelial cells stimulated with TNF-α. CONCLUSION: By their ability to attenuate growth, biofilm formation and adherence property of C. albicans, to reinforce the epithelial barrier function, and to exert anti-inflammatory properties the two cinnamon fractions (essential oil, Cinnulin PF®) investigated in the present study may be promising agents for treating oral infections involving C. albicans.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candidíase Bucal/microbiologia , Cinnamomum zeylanicum/química , Células Epiteliais/microbiologia , Boca/microbiologia , Óleos Voláteis/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Candida albicans/fisiologia , Candidíase Bucal/tratamento farmacológico , Linhagem Celular , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Boca/metabolismo , Casca de Planta/química
7.
Clin Exp Dent Res ; 5(5): 580-582, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31687193

RESUMO

Objectives: Neonatal thrush, also called oral candidiasis, is commonly a clinical diagnosis based on white patches on oral mucosal surfaces. Candida albicans is often associated with it. This clinical study aimed to investigate the presence of C. albicans among newborns with or without clinical findings of candidiasis on oral mucosa. Another aim was to investigate how thrush responded to current therapy by acidic liquids such as lingonberry or lemon juice. Material and methods: Swipe samples were collected from 32 healthy, full-term infants younger than 12 months with or without white patches on oral mucosa. Clinical diagnosis of thrush was made by a community nurse based on thick and yellowish white patches. The routine therapy was oral lingonberry or lemon juice or soda water. Disappearing of patches was controlled by a phone call about 2 weeks after the baseline. Both parents and nurses gave background factors by filling a questionnaire. Results: One (3%) infant without clinical signs was diagnosed with Candida parapsilosis, none with C. albicans. Thrush resembling candidiasis was diagnosed clinically in four (12.5%) children. Three out of four parents reported persisting findings after 2 weeks. Only the maternal mastitis and use of antibiotics were significantly associated with thrush (p = .001). C. albicans was not discovered from babies with clinical thrush. Conclusions: Aetiology of the white patches remained unclear. The current way of treating them with acidic liquids is not efficient. Additional studies are needed.


Assuntos
Antifúngicos/uso terapêutico , Candida albicans/efeitos dos fármacos , Candidíase Bucal/tratamento farmacológico , Citrus/química , Doenças do Recém-Nascido/tratamento farmacológico , Vaccinium vitis-Idaea/química , Bebidas , Candidíase Bucal/diagnóstico , Candidíase Bucal/microbiologia , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido/microbiologia
8.
Appl Microbiol Biotechnol ; 103(21-22): 9037-9055, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31659418

RESUMO

The invasion of Candida albicans is one of the most common fungal infections seen in clinical practice, and serious drug resistance has been reported in recent years. Therefore, new anti-C. albicans drugs must be introduced. In this research, it was demonstrated that cinnamaldehyde (CA) shows strong antimicrobial activity, with 0.26 mg/mL CA being the minimum inhibitory concentration to manage C. albicans. Extraordinarily, we detected that CA accumulated the intracellular reactive oxygen species (ROS) and enhanced the calcium concentration in the cytoplasm and mitochondria through flow cytometry. In addition, we observed that C. albicans cells released Cytochrome c from the mitochondria to the cytoplasm, depolarized the mitochondrial membrane potential, and activated the metacaspase when exposed to 0.065, 0.13, 0.26, and 0.52 mg/mL CA. Furthermore, to confirm that CA introduces the C. albicans apoptosis, we discovered that when the phosphatidylserine was exposed, DNA damage and chromatin condensation occurred, which were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and 4',6-diamidino-2-phenylindole (DAPI) staining. Finally, demonstrations of phenotype investigation, colony-forming unit (CFU) counts, and periodic acid-Schiff (PAS) staining were conducted to prove that CA possessed the ability to treat oropharyngeal candidiasis (OPC) and vulvovaginal candidiasis (VVC). From the above, our research indicates that CA is a promising antifungal candidate when applied to C. albicans infections.


Assuntos
Acroleína/análogos & derivados , Antifúngicos/farmacologia , Apoptose/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Candidíase Bucal/tratamento farmacológico , Candidíase Vulvovaginal/tratamento farmacológico , Acroleína/farmacologia , Animais , Cálcio/metabolismo , Candidíase Bucal/microbiologia , Candidíase Bucal/prevenção & controle , Candidíase Vulvovaginal/microbiologia , Candidíase Vulvovaginal/prevenção & controle , Citocromos c/metabolismo , Modelos Animais de Doenças , Feminino , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo
9.
Nutrients ; 11(10)2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31615039

RESUMO

Oral candidiasis (OC) is an increasing health problem due to the introduction of new drugs, population aging, and increasing prevalence of chronic illness. This study systematically reviews the effects of the oral intake of probiotics, prebiotics, and synbiotics on Candida spp. counts (colony-forming units (CFU)/mL) in oral and palatal samples. A literature search was conducted. Twelve studies, eight randomized clinical trials (RCTs), and four pre-post studies, resulted as eligible for the meta-analysis, which was performed through a Bayesian random-effects model. All studies analyzed probiotics, and none of them analyzed prebiotics or synbiotics. The treatments effects were measured in terms of odds ratio (OR) of OC (CFU/mL >102, 103, or 104). The meta-analytic OR was 0.71 (95% credibility interval (CrI): 0.37, 1.32), indicating a beneficial effect of treatment; the I2 index was 56.3%. Focusing only on RCTs, the OR was larger and more precise at 0.53 (95% CrI: 0.27, 0.93). The effect of treatment appeared to be larger on denture wearers. Our findings indicate that the intake of probiotics can have a beneficial effect on OC and that the effects could vary according to the patients' characteristics. Due to the presence of medium-high-risk studies, the results should be interpreted with caution.


Assuntos
Candidíase Bucal/tratamento farmacológico , Probióticos , Antifúngicos/uso terapêutico , Candidíase Bucal/etiologia , Humanos , Fatores de Risco
10.
Acta Dermatovenerol Croat ; 27(3): 137-141, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31542055

RESUMO

Pemphigus vulgaris is an autoimmune disease that mostly affects the mucosa and oral cavity. Candida species can invade the mucosal lesions of these patients and cause diseases. The aim of this study was to identify the fungal agents isolated from mucosal lesions and evaluate antifungal activity profile against the isolates. A total of 25 patients with pemphigus vulgaris with active oral lesions and 25 healthy people serving as a control group were included in this study. Identification of the fungal isolates was performed based on conventional methods and DNA sequence analysis of the internal transcribed spacer (ITS) rDNA gene region. The sequence results were deposited in the NCBI database using the Basic Local Alignment Search Tool. Antifungal activity of fluconazole, itraconazole, ketoconazole, posaconazole, econazole, and amphotericin B against the isolates were evaluated based on the CLSI M-44 A protocol. Oral candidiasis was detected in 20% of the patients. Candida species isolated from oral lesions of patients with pemphigus were identified as Candida albicans 22/25, Candida glabrata 2/25, and Candida dubliniensis 1/25. All of the isolates were sensitive to amphotericin and econazole, 96% to fluconazole and posaconazole, and 92% to ketoconazole and itraconazole. One patient showed a profile resistant to fluconazole, posaconazole, and ketoconazole, simultaneously. Ninety six percent of control group isolates were sensitive to six antifungals. Candida albicans was the most prevalent species isolated from oral lesions of patients with pemphigus vulgaris and the control group. Amphotericin B and econazole were the most effective antifungals against the isolates.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Candidíase Bucal/microbiologia , Pênfigo/microbiologia , Adulto , Anfotericina B/farmacologia , Candidíase Bucal/tratamento farmacológico , Candidíase Bucal/patologia , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Econazol/farmacologia , Feminino , Fluconazol/farmacologia , Humanos , Itraconazol/farmacologia , Cetoconazol/farmacologia , Masculino , Pênfigo/tratamento farmacológico , Pênfigo/patologia , Triazóis/farmacologia
11.
Infect Immun ; 87(12)2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31527130

RESUMO

Candida-associated denture stomatitis (DS) is a persistent and chronic oral infection of the denture-bearing palatal mucosa. DS stems from the ability of the fungal opportunistic pathogen Candida albicans to adhere to denture material and invade palatal tissue. Although DS is the most prevalent form of oral candidiasis, there are currently no feasible therapeutic strategies for the prevention of this recurrent condition. We developed a peptide-based antimicrobial bioadhesive formulation specifically designed for oral topical formulation. In this study, we aimed to evaluate the applicability of the novel formulation for the prevention of C. albicans colonization on denture material and development of clinical disease. To that end, using the latest technological advances in dental digital design and three-dimensional (3D) printing, we fabricated an intraoral device for rats with universal fit. The device was successfully installed and used to develop clinical DS. Importantly, by taking a preventative therapeutic approach, we demonstrated the potential clinical utility of the novel formulation as a safe and feasible prophylactic agent against DS.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candidíase Bucal/prevenção & controle , Cimentos Dentários/farmacologia , Estomatite sob Prótese/prevenção & controle , Animais , Antifúngicos/química , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Candida albicans/crescimento & desenvolvimento , Candidíase Bucal/tratamento farmacológico , Candidíase Bucal/microbiologia , Cimentos Dentários/química , Dentaduras/microbiologia , Modelos Animais de Doenças , Masculino , Mucosa Bucal/microbiologia , Ratos , Ratos Sprague-Dawley , Estomatite sob Prótese/tratamento farmacológico , Estomatite sob Prótese/microbiologia
12.
AAPS PharmSciTech ; 20(7): 297, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31444661

RESUMO

Miconazole nitrate (MZ) is a BCS class II antifungal poorly water-soluble drug with limited dissolution properties and gastrointestinal side effects. Self-nanoemulsifying delivery system-based gel of MZ can improve both solubility and oral mucosal absorption with enhanced antifungal activity. The study aims to formulate MZ self-nanoemulsion (MZ-NE) and combine it within hyaluronic acid-based gel. MZ solubility in various oils, surfactants, and cosurfactant used in NE formulations were evaluated. Mixture design was implemented to optimize the levels of NE components as a formulation variable to study their effects on the mean globule size and antifungal inhibition zones. Further, the optimized MZ-NE was loaded into a hyaluronic acid gel base. Rheological behavior of the prepared gel was assessed. Ex vivo permeability of optimized formulation across buccal mucous of sheep and inhibition against Candida albicans were examined. Mixture design was used to optimize the composition of MZ-NE formulation as 22, 67, and 10% for clove oil, Labrasol, and propylene glycol, respectively. The optimized formulation indicated globule size of 113 nm with 29 mm inhibition zone. Pseudoplastic flow with thixotropic behavior was observed, which is desirable for oral gels. The optimized formulation exhibited higher ex vivo skin permeability and enhanced antifungal activity by 1.85 and 2.179, respectively, compared to MZ-SNEDDS, and by 1.52 and 1.72 folds, respectively, compared to marketed gel. Optimized MZ-NE hyaluronic acid-based oral gel demonstrated better antifungal activity, indicating its potential in oral thrush pharmacotherapy.


Assuntos
Antifúngicos/administração & dosagem , Candidíase Bucal/tratamento farmacológico , Química Farmacêutica/métodos , Ácido Hialurônico/administração & dosagem , Miconazol/administração & dosagem , Nanocápsulas/administração & dosagem , Administração Oral , Animais , Antifúngicos/síntese química , Antifúngicos/farmacocinética , Candidíase Bucal/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Emulsões/administração & dosagem , Emulsões/síntese química , Emulsões/farmacocinética , Ácido Hialurônico/síntese química , Ácido Hialurônico/farmacocinética , Hidrogéis/administração & dosagem , Hidrogéis/síntese química , Hidrogéis/farmacocinética , Miconazol/síntese química , Miconazol/farmacocinética , Nanocápsulas/química , Ovinos
13.
Photodiagnosis Photodyn Ther ; 27: 402-407, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31284075

RESUMO

BACKGROUND: Antimicrobial photodynamic therapy (aPDT) has been considered an alternative therapeutic modality for the treatment of Candida infections. However, most studies are focused mainly on microorganism's inactivation efficiency. Here, we evaluated the efficacy of aPDT mediated by chloro-aluminum phthalocyanine encapsulated in cationic nanoemulsions (ClAlP-NE) to treat oral candidiasis in vivo and its effect on the adhesion and biofilm formation of Candida albicans. METHODS: For this, mice were immunosuppressed and inoculated with C. albicans to produce oral candidiasis. aPDT and Nystatin were applied for 5 successive sessions. Next, the microbiological evaluation was determined (CFU/ml) and the analyses of virulence factors (adhesion capacity and biofilm formation) were performed. Data were analyzed by Two-way ANOVA (α = 0.05). RESULTS: aPDT was as effective as Nystatin reducing 1.4 and 2.0 log10 of the cell viability (p ≤ 0.0001), respectively. Both treatments reduced the adhesion capacity and biofilm formation of C. albicans (p ≤ 0.0001) CONCLUSION: : ClAlP-NE-mediated aPDT was effective in reducing the virulence factors of C. albicans and also to treat induced oral candidiasis in mice.


Assuntos
Biofilmes/efeitos dos fármacos , Candidíase Bucal/tratamento farmacológico , Indóis/uso terapêutico , Compostos Organometálicos/uso terapêutico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Animais , Antifúngicos/uso terapêutico , Candida albicans/efeitos dos fármacos , Emulsões , Indóis/administração & dosagem , Camundongos , Nanopartículas , Nistatina/uso terapêutico , Compostos Organometálicos/administração & dosagem
14.
Artigo em Inglês | MEDLINE | ID: mdl-31332066

RESUMO

Oral candidiasis (OC) caused by the fungal pathogen Candida albicans is the most common opportunistic infection in immunocompromised populations. The dramatic increase in resistance to common antifungal agents has emphasized the importance of identifying alternative therapeutic options. Antimicrobial peptides have emerged as promising drug candidates due to their antimicrobial properties; specifically, histatin-5 (Hst-5), a peptide naturally produced and secreted by human salivary glands, has demonstrated potent activity against C. albicans However, as we previously demonstrated vulnerability for Hst-5 to proteolysis by C. albicans proteolytic enzymes at specific amino acid residues, a new variant (K11R-K17R) was designed with amino acid substitutions at the identified cleavage sites. The new resistant peptide demonstrated no cytotoxicity to erythrocytes or human oral keratinocytes. To evaluate the potential of the new peptide for clinical application, we utilized our FDA-approved polymer-based bioadhesive hydrogel as a delivery system and developed a therapeutic formulation specifically designed for oral topical application. The new formulation was demonstrated to be effective against C. albicans strains resistant to the traditional antifungals, and the in vitro therapeutic efficacy was found to be comparable to that of the common topical antifungal agents in clinical use. Importantly, in addition to its antifungal properties, our findings also demonstrated that the new peptide variant induces cell proliferation and rapid cell migration of human oral keratinocytes, indicative of wound healing properties. The findings from this study support the progression of the novel formulation as a therapeutic agent against oral candidiasis, as well as a therapeutic modality for promoting wound healing.


Assuntos
Anti-Infecciosos/farmacologia , Antifúngicos/farmacologia , Hidrogéis/farmacologia , Peptídeos/farmacologia , Cicatrização/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Candidíase Bucal/tratamento farmacológico , Candidíase Bucal/microbiologia , Linhagem Celular , Histatinas/farmacologia , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/microbiologia
15.
BMC Oral Health ; 19(1): 140, 2019 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-31291932

RESUMO

BACKGROUND: To systematically review and assess the in vivo effectiveness and safety of probiotics for prophylaxis and treating oral candidiasis. METHODS: A literature search for studies published in English until August 1, 2018 was conducted in the following databases: PubMed, EMBASE, Cochrane Library, and Web of Science. Randomized controlled clinical trials and experimental mouse animal model studies comparing probiotics (at any dosage and in any form) with control groups (placebo, blank control or other agents) and reporting outcomes of the prophylactic and therapeutic effects were considered for inclusion. A descriptive study and, potentially, a meta-analysis were planned. RESULTS: Six randomized controlled clinical trials and 5 controlled experiments of mouse animal models were included in the systematic review. Four randomized controlled clinical trials comparing a probiotics group with a placebo/blank control group in 480 elderly and denture wearers were included in the meta-analysis. The overall combined odds ratio of the (random effects) meta-analysis was 0.24 (95% CI =0.09-0.63, P < 0.01). The overall combined odds ratio of the (fixed effects) sensitivity analysis was 0.39 (95% CI =0.25-0.60, P < 0.01) by excluding a study with the smallest sample size. These analyses showed that there was a statistically significant difference in the effect of probiotics compared with the control groups in elderly and denture wearers. The remaining 2 studies compared probiotics with other agents in a population aged 18-75 years and children aged 6-14 years respectively, and were analyzed descriptively. Meta-analysis and descriptive analyses indicated that probiotics were potentially effective in reducing morbidity, improving clinical symptoms and reducing oral Candida counts in oral candidiasis. The biases of the included studies were low or uncertain. The relatively common complaints reported were gastrointestinal discomfort and unpleasant taste, and no severe adverse events were reported. CONCLUSIONS: Probiotics were superior to the placebo and blank control in preventing and treating oral candidiasis in the elderly and denture wearers. Although probiotics showed a favorable effect in treating oral candidiasis, more evidence is required to warrant their effectiveness when compared with conventional antifungal treatments. Moreover, data on the safety of probiotics are still insufficient, and further research is needed.


Assuntos
Candidíase Bucal/tratamento farmacológico , Probióticos/uso terapêutico , Idoso , Animais , Antifúngicos , Candida , Criança , Humanos , Camundongos , Razão de Chances
16.
Photodiagnosis Photodyn Ther ; 27: 193-197, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31185323

RESUMO

BACKGROUND: Candida species have an influence in the pathogenesis of denture stomatitis. The current study aimed to investigate the efficacy of indocyanine green (ICG)-mediated photodynamic therapy (PDT) in combination with nystatin mouthwash (PDT + nystatin) for the treatment of denture stomatitis in comparison with routine antifungal therapy with nystatin alone. METHODS: In this double-blind randomized clinical trial, 66 patients were randomly assigned into PDT + nystatin (n = 33) and nystatin (n = 33) groups, both groups were treated 3-times a day (15 days) with nystatin mouthwash, and PDT was performed twice once a week for the PDT + nystatin group. Briefly, ICG was applied on the palatal lesion and laser irradiation was performed using a diode laser (810 nm, 56 J/cm2). Nystatin group was also treated with sham laser in order to eliminate the possible psychological effects. The clinical and mycological evaluations were carried out at the baseline, during treatment, and the end of follow-up. Patients who completed the treatment and follow-up were eligible for statistical analysis (each group 28 cases). RESULTS: Patient treatment with nystatin or PDT + nystatin reduced the lesions extension. Candida species were isolated from all patients and the number of Candida CFU in both groups showed a significant reduction at each post-treatment visit; however, the mean reduction achieved in the PDT + nystatin group was significantly higher than nystatin alone. CONCLUSIONS: ICG-mediated PDT in combination with nystatin mouthwash can improve the clinical feature of denture stomatitis with no adverse effects; therefore, it could be used as an alternative to the currently available antifungal therapy using nystatin alone.


Assuntos
Antifúngicos/uso terapêutico , Candidíase Bucal/tratamento farmacológico , Nistatina/uso terapêutico , Fotoquimioterapia/métodos , Estomatite sob Prótese/tratamento farmacológico , Idoso , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Verde de Indocianina/uso terapêutico , Lasers Semicondutores , Masculino , Pessoa de Meia-Idade , Nistatina/administração & dosagem , Fármacos Fotossensibilizantes/uso terapêutico , Estomatite sob Prótese/microbiologia
17.
Oral Dis ; 25(6): 1573-1580, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31177581

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of Streptococcus salivarius K12 as an adjuvant in treating oral candidiasis. METHODS: A total of 56 patients were participated in the randomized, double-blinded, placebo-controlled clinical trial. The S. salivarius K12 or placebo lozenges plus nystatin tablets were given for up to 4 weeks at 1-week interval and then followed up for 1 week thereafter. We collected and analyzed the mycological and clinical data, treatment course, and safety data. RESULTS: At the end of the treatment, significant differences were found in the mycological cure rates between K12 group and control group (90.48% and 55.56%, respectively, p = 0.008). Survival analysis demonstrated no statistical difference in overall cure rates comprehensively considering mycological cure, clinical improvement, and recurrence (p = 0.078), while statistical difference was found in mycological cure (p = 0.013) between the two groups. The median treatment courses of K12 group and control group were 3 weeks and 4 weeks, respectively. No severe events were reported during the study. CONCLUSION: Streptococcus salivarius K12 exhibited potential efficacy and safety as an adjuvant in treating oral candidiasis by enhancing mycological cure and shortening the treatment course of conventional antifungal therapy in this randomized, double-blinded, placebo-controlled clinical trial. Further large-scale clinical studies are desired to accumulate more evidence for its clinical applications.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Candida albicans/efeitos dos fármacos , Candidíase Bucal/tratamento farmacológico , Candidíase Bucal/terapia , Nistatina/administração & dosagem , Nistatina/uso terapêutico , Probióticos/administração & dosagem , Administração Oral , Antibacterianos/efeitos adversos , Candidíase Bucal/microbiologia , Método Duplo-Cego , Humanos , Nistatina/efeitos adversos , Probióticos/efeitos adversos , Recidiva , Streptococcus salivarius
18.
Med Princ Pract ; 28(6): 552-558, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31247626

RESUMO

OBJECTIVE: Candidal adherence to denture acrylic surfaces (DAS) and oral buccal epithelial cells (BEC), formation of candidal germ tubes (GT), candidal cell surface hydrophobicity (CSH), and hemolysin production are important pathogenic traits of Candida. The antifungal drug-induced post-antifungal effect (PAFE) also impacts the virulence of Candida. Candida dubliniensis isolates are associated with the causation of oral candidiasis which could be managed with posaconazole. Thus far there is no evidence on posaconazole-induced PAFE and its impact on adhesion-related attributes and production of hemolysin by C. dubliniensis isolates. Hence, the PAFE, adhesion to DAS and BEC, formation of GT, CSH, and hemolysin production of 20 oral C. dubliniensis isolates after brief exposure to posaconazole was ascertained. MATERIALS AND METHODS: The PAFE, adherence to DAS and BEC, formation of GT, candidal CSH, and hemolysin production were investigated by hitherto described in vitro assays. RESULTS: The mean PAFE (h) induced by posaconazole on C. dubliniensis isolates was 1.66. Exposure to posaconazole suppressed the ability of C. dubliniensis to adhere to DAS, BEC, formation of candidal GT, candidal CSH and to produce hemolysin by a reduction of 44, 33, 34, 36, and 15% (p < 0.005 to p < 0.001), respectively. CONCLUSION: Exposure of C. dubliniensis isolates to posaconazole for a brief period induced an antimycotic impact by subduing its growth in addition to suppressing pathogenic adherence-associated attributes, as well as production of hemolysin.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candidíase Bucal/tratamento farmacológico , Adesão Celular/efeitos dos fármacos , Proteínas Hemolisinas/efeitos dos fármacos , Triazóis/farmacologia , Candida/isolamento & purificação , Candidíase Bucal/microbiologia , Técnicas In Vitro , Testes de Sensibilidade Microbiana
19.
Ann Otol Rhinol Laryngol ; 128(10): 903-910, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31072118

RESUMO

OBJECTIVE: In laryngology practice, vocal fold leukoplakia is frequently evaluated by suspension laryngoscopy and biopsy examination upon the patient's complaints of hoarseness and dysphonia. The purpose of the present study is to investigate and analyze risk factors, diagnosis, treatment, and follow-up results of cases with Candida leukoplakia. STUDY DESIGN: Retrospective case control study. SETTING: Tertiary medical center. SUBJECTS AND METHODS: Patients with a diagnosis of vocal fold leukoplakia who underwent direct laryngoscopy and biopsy between 2007 and 2017 and diagnosed as candida or noncandida in their histopathology were assigned into 2 groups. Then they were compared in terms of their demographic characteristics, predisposing factors, diagnosis, treatment, and follow-up results. RESULTS: Of the 289 vocal fold leukoplakia cases, 36 were candida, and 253 were noncandida. The mean age of the patients with Candida leukoplakia was 60.86 years. As for the age groups, the largest group (26.1%) was in the seventh decade (P < .001). The use of inhaled corticosteroids was a significant risk factor (P < .001). For their medical therapy, the patients were administered fluconazole 200 mg per day for 3 weeks, and the treatment yielded successful results in 91.66% of them. In 5 of the patients, candida leukoplakia and superficial epithelial dysplasia were observed, and no malignant transformation was observed during a mean follow-up of 28 ± 13 months. CONCLUSION: Candidiasis causing vocal fold leukoplakia is rare, and we report the findings of the largest published case series to date. Eliminating predisposing factors and administrating oral fluconazole 200 mg for 3 weeks are sufficient for medical treatment.


Assuntos
Candidíase Bucal/diagnóstico , Candidíase Bucal/patologia , Doenças da Laringe/microbiologia , Doenças da Laringe/patologia , Leucoplasia/microbiologia , Prega Vocal/microbiologia , Prega Vocal/patologia , Administração por Inalação , Corticosteroides/efeitos adversos , Idoso , Antifúngicos/uso terapêutico , Biópsia , Candidíase Bucal/tratamento farmacológico , Estudos de Casos e Controles , Disfonia/etiologia , Feminino , Fluconazol/uso terapêutico , Seguimentos , Rouquidão/etiologia , Humanos , Doenças da Laringe/tratamento farmacológico , Laringoscopia , Leucoplasia/complicações , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
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