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

ABSTRACT Hepatocellular utility is observed by measuring the hepatocellular enzymes. Changes in its serum levels are related to liver dysfunction. Liver is one of the immunoprotective organs. Continuous use of immunosuppressive drugs can cause oral candidiasis and give effects to liver function. Hyperbaric oxygen treatment (HBOT), while reducing fungal infections, can also repair the liver function. The aim of this study was to investigate the alanine transaminase (ALT) and aspartate transaminase (AST) levels of immunosuppressed rats with oral candidiasis treated with hyperbaric oxygen. Twelve Wistar rats were divided into three groups: K− (normal/ healthy), K+ (oral candidiasis immunosuppressed rats), and P (oral candidiasis immunosuppressed rats treated hyperbaric oxygen). K+ and P groups were immunosuppressed by giving dexamethasone 0.5 mg/day/rat orally for 14 days, added with tetracycline 1 mg/day/rat. HBOT was given in five days successively. Blood serum of rats in all groups were taken to calculate the ALT and AST levels. ALT and AST levels in K+ showed higher value than K− and P groups. The data were analysed with one-way ANOVA test and showed significant difference in ALT levels (p < 0.05), while in AST levels there was no significant difference among the groups (p > 0.05). This study showed that HBOT affected the ALT and AST levels of immunosuppressed rats with oral candidiasis.
Carcinoma, Hepatocellular ; Hyperbaric Oxygenation ; Immunocompromised Host ; Candidiasis, Oral--therapy ; Alanine Transaminase ; Aspartate Aminotransferases

ABSTRACT Methanolic extract from the leaves of Acanthus ilicifolius L. (A. ilicifolius L.) is a potent inhibitor of Candida albicans (C. albicans) growth and anti-inflammatory. C. albicans causes oral candidiasis in immunosuppressive condition. Mitogen-activated protein kinase (MAPK) signalling via p38 appears to discriminate between yeast and hyphal cells of C. albicans. Activation of p38 MAPK by hyphae results in the upregulation of proinflammatory cytokines. The p38 MAPK activation is known to impair corticosteroid action. The research was conducted to investigate the effect of methanolic extract A. ilicifolius L. treatment of oral candidiasis with the immunosuppressive condition through enhancement of p38 MAPK expression in the epithelial cells. Immunosuppressed conditions were obtained when 16 healthy male Rattus norvergicus (Wistar) was given oral administration of dexamethasone and tetracycline for 14 days and induced with C. albicans (ATCC-10231) 1 McFarland. The subjects were divided into four groups (n = 4/group): immunosuppression (IS), immunosuppression with oral candidiasis without treatment (ISC), immunosuppression with oral candidiasis and nystatin treatment (ISC+N), and immunosuppression with oral candidiasis and A. ilicifolius L. treatment (ISC+AI), and were treated for 14 days. Later, the rats were euthanised, and their tongue were biopsied. The p38 MAPK expression was subjected to immunohistochemical examination, observed under a microscope (400× magnification) and statistically analysed (one-way ANOVA, LSD-test, p < 0.05). The p38 MAPK expression of ISC+AI (36.05 ± 1.54) was higher than IS (26 ± 2.32), ISC (26.4 ± 3.71), IS+N (34.2 ± 0.99). Significant differences existed between ISC+AI and ISC+N to IS and ISC (p < 0.05). No significant differences were present between IS and ISC; ISC+AI and ISC+N (p > 0.05). Therefore, this treatment could enhance p38 MAPK expression in oral candidiasis with the immunosuppressed condition.
Acanthaceae ; Candidiasis, Oral ; Immunosuppression Therapy ; p38 Mitogen-Activated Protein Kinases

The hyphal development of Candida albicans (C. albicans) has been considered as an essential virulent factor for host cell damage. However, the missing link between hyphae and virulence of C. albicans is also been discovered. Here, we identified that the null mutants of ERG3 and ERG11, two key genes in ergosterol biosynthesis pathway, can form typical hyphae but failed to cause the oral mucosal infection in vitro and in vivo for the first time. In particular, the erg3Δ/Δ and erg11Δ/Δ strains co-cultured with epithelial cells significantly reduced the adhesion, damage, and cytokine (interleukin-1α (IL-1α)) production, whereas the invasion was not affected in vitro. Importantly, they were incapable of extensive hyphal invasion, formation of micro-abscesses, and tongue epithelium damage compared to wild type due to the decrease of the colonization and epithelial infection area in a murine oropharyngeal candidiasis model. The fluconazole (FLC), an antifungal targeted at ergosterol biosynthesis, relieved the epithelial infection of C. albicansin vitro and in vivo even under non-growth inhibitory dosage confirming the virulent contribution of ergosterol biosynthesis pathway. The erg3Δ/Δ and erg11Δ/Δ strains were cleared by macrophages similar to wild type, whereas their virulence factors including agglutinin-like sequence 1 (Als1), secreted aspartyl proteinase 6 (Sap6), and hyphal wall protein-1 (Hwp1) were significantly reduced indicated that the non-toxicity might not result from the change on immune tolerance but the defective virulence. The incapacity of erg3Δ/Δ and erg11Δ/Δ in epithelial infection highlights the contribution of ergosterol biosynthesis pathway to C. albicans pathogenesis and fluconazole can not only eliminate the fungal pathogens but also reduced their virulence even at low dosage.
Animals ; Antifungal Agents ; pharmacology ; Candida albicans ; drug effects ; genetics ; pathogenicity ; Candidiasis, Oral ; drug therapy ; genetics ; microbiology ; Fluconazole ; pharmacology ; Genes, Fungal ; genetics ; Mice ; Microscopy, Electron, Scanning ; Potassium Channels ; genetics ; Virulence

BACKGROUND: Skin disorders are common in human immunodeficiency virus (HIV)-infected patients in Korea. However, introduction of highly active antiretroviral therapy (HAART) has changed the skin manifestations of HIV infection. OBJECTIVE: We evaluated the frequency of skin disorders and their immune status using CD4+ T lymphocyte counts in HIV infected patients. METHODS: A retrospective study of 134 HIV-infected patients who visited in our clinic was carried out from September 2008 to July 2011. All subjects underwent complete physical examination to detect their skin disorders as well as necessary diagnostic procedures by consultation with the dermatologist. RESULTS: Tinea infection (including tinea corporis, tinea pedis and onychomycosis) was the most common skin disorder identified. Patients with a CD4+ T lymphocyte count of less than 200 cells/mm3 showed a significantly higher prevalence of syphilis, oral candidiasis and drug eruption compared with patients with a CD4+ T lymphocyte count of over 200 cells/mm3. CONCLUSION: Numerous skin disorders were demonstrated in HIV-infected patients. Among them, tinea infection was the most common skin manifestation in 134 HIV-infected patients. Moreover, Syphilis, oral candidiasis and drug eruption were associated with low CD4+ T lymphocyte counts. Further evaluation is necessary to confirm the trend towards changes in skin manifestations in HIV infected patients.
Antiretroviral Therapy, Highly Active ; Candidiasis, Oral ; Drug Eruptions ; HIV ; HIV Infections ; Humans ; Korea ; Lymphocyte Count* ; Lymphocytes* ; Physical Examination ; Prevalence ; Retrospective Studies ; Skin Manifestations ; Skin* ; Syphilis ; Tinea ; Tinea Pedis

The aim of present study was to prepare buccal tablets of fluconazole for oral candidiasis. The dosage forms were designed to release the drug above the minimum inhibitory concentration for prolonged period of time so as to reduce the frequency of administration and to overcome the side effects of systemic treatment. The buccal tablets were prepared by using Carbopol 71G and Noveon AA-1 by direct compression method. Microcrystalline cellulose was used as the filler and its effect was also studied. The prepared dosage forms were evaluated for physicochemical properties, in vitro release studies and mucoadhesive properties using sheep buccal mucosa as a model tissue. Tablets containing 50% of polymers (Carbopol & Noveon) were found to be the best with moderate swelling along with favorable bioadhesion force, residence time and in vitro drug release. The in vitro drug release studies revealed that drug released for 8 h, which in turn may reduce dosing frequency and improved patient compliance in oral candidiasis patients.
Acrylates ; administration & dosage ; chemistry ; pharmacokinetics ; Acrylic Resins ; administration & dosage ; chemistry ; pharmacokinetics ; Adhesiveness ; Administration, Buccal ; Animals ; Candidiasis, Oral ; drug therapy ; Cellulose ; administration & dosage ; chemistry ; Delayed-Action Preparations ; Drug Combinations ; Drug Stability ; Excipients ; Fluconazole ; administration & dosage ; chemistry ; pharmacokinetics ; Mouth Mucosa ; metabolism ; Polymers ; administration & dosage ; Sheep ; Tablets

Most clinicians dread seeing the patient presenting with a primary complaint of a burning pain on one or more oral mucosal surfaces. Unlike most other clinical conditions presenting in a dental office, burning mouth syndrome is recently, advances have been made towards clarifying the possible etiology of the disorder and testing the possible therapeutic modalities available. This article attempts to summarize the "state of the art" today.
Burning Mouth Syndrome ; diagnosis ; drug therapy ; etiology ; Candidiasis, Oral ; diagnosis ; Diagnosis, Differential ; Glossalgia ; diagnosis ; Humans ; Paresthesia ; diagnosis ; Xerostomia ; diagnosis

AIMTo identify heterogeneity of Candida albicans (C. albicans) isolated from the population with cancer in China by using identification medium, subculture molecular typing, and antifungal susceptibility test.

METHODOLOGYOral cheek mucosal specimens from 52 cancer patients receiving chemotherapy were cultured on CHROMagar Candida plates for Candida identification. All the C. albicans colonies on the plates were subcultured and reconfirmed by API20C, then submitted to the antifungal drug susceptibility test with fluconazole and molecular typing using randomly amplified polymorphic DNA-PCR (RAPD) with primers RSD6 and RSD12.

RESULTS54% (28/52) patients were oral yeast carriage in which C. albicans predominated. More than 7 C. albicans colonies were isolated from each of 12 patients (Group A), while less than 5 colonies were isolated from each of 16 patients (Group B). RSD6 and RSD12 were successful in eliciting 17 (A1-A17) and 2 (B1-B2) genotypes, respectively from among the 205 isolates. The two primers were combined to generate 21 genotypes. The C. albicans isolates obtained from the same patient and episode showed a diversity for fluconazole revealed by MIC50 and MIC90.

CONCLUSIONThe heterogeneity of the C. albicans colonies isolated from the same patients can be detected. C. albicans with varied fluconazole susceptibility and genotypic characteristics may coexist in the same oral Candida population.

Adult ; Aged ; Antifungal Agents ; pharmacology ; Candida albicans ; classification ; genetics ; isolation & purification ; Candida glabrata ; classification ; isolation & purification ; Candidiasis, Oral ; microbiology ; China ; DNA, Fungal ; analysis ; Drug Resistance, Fungal ; genetics ; Female ; Fluconazole ; pharmacology ; Genetic Heterogeneity ; Genotype ; Hematologic Neoplasms ; drug therapy ; Humans ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Mouth Mucosa ; microbiology ; Mycology ; methods ; Neoplasms ; drug therapy ; Young Adult

OBJECTIVETo observe the effect of xiaomi granules (XMG) for treatment of HIV/AIDS oral candidiasis.

METHODSForty patients in the treated group were treated by XMG and 40 patients in the control group were treated with anticandine. The therapeutic course for both groups was two weeks. Changes of clinical symptoms, oral candida microscopic examination and cultured before and after treatment as well as the safety of treatment were observed, and a follow-up study was implemented two weeks after ending medication to compare the relapse rate between groups.

RESULTSSymptoms as oral greasy-sticky, thirsty, asthenia, abdominal distension and anorexia were improved after treatment in both groups (P < 0.05). The improvements of oral greasy-sticky and thirsty in the treated group were better than those in the control group (P < 0.05). The effective rate and relapse rate in the treated group was 90.0% (36/40) and 11.1% (4/36) respectively, while in the control group, 72. 5% (29/40) and 31.0% (9/29) respectively.

CONCLUSIONXMG could improve the clinical symptoms with high efficacy and low relapse rate, shows a better effect than that of anticandine in treating HIV/AIDS oral candidiasis.

AIDS-Related Opportunistic Infections ; drug therapy ; Acquired Immunodeficiency Syndrome ; microbiology ; Adult ; Candidiasis, Oral ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Follow-Up Studies ; HIV Infections ; microbiology ; Humans ; Male ; Middle Aged ; Treatment Outcome

We describe two patients with fungal keratitis refractory to standard antifungal therapy whose conditions were managed with voriconazole. The first case is a patient with endophthalmitis and corneal ulcer due to Candida parapsilosis after receiving a corneal transplant. The patient was treated with amphotericin but showed no signs of improvement. Topical voriconazole, oral voriconazole, and intravitreal voriconazole yielded signs of improvement. The second case is a 63-year-old male who underwent a month of empiric treatment with 0.2% topical amphotericin for fungal keratitis but showed no signs of improvement. Treatment was then provided with 1% voriconazole. Both cases showed effective treatment with voriconazole. Voriconazole may be considered as a new method to treat fungal keratitis refractory to standard antifungal therapy.
Administration, Oral ; Antifungal Agents/*administration & dosage ; Candidiasis/diagnosis/*drug therapy/microbiology ; Cornea/microbiology/pathology ; Diagnosis, Differential ; Dose-Response Relationship, Drug ; Eye Infections, Fungal/diagnosis/*drug therapy/microbiology ; Follow-Up Studies ; Humans ; Keratitis/diagnosis/*drug therapy/microbiology ; Male ; Middle Aged ; Ophthalmic Solutions ; Pyrimidines/*administration & dosage ; Triazoles/*administration & dosage