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Cureus Oct 2022Otomycosis is a disease whose acute form affects four in 1,000 persons annually and the chronic form affects 3-5% of the population. It is brought on by various fungi,... (Review)
Review
Otomycosis is a disease whose acute form affects four in 1,000 persons annually and the chronic form affects 3-5% of the population. It is brought on by various fungi, primarily saprophytes which most commonly include the Candida albicans and Aspergillus niger. The disease rarely poses a life-threatening danger, but as it requires prolonged treatment and follow-up and has a significant chance of recurrence, it has a difficult and taxing course. Numerous therapeutic modalities are available for the treatment of otomycosis. In the beginning, the fungal elements are removed by ear toilet - washing or suctioning of the ear canal followed by drying. Topical therapy includes the use of antifungals, of which the most commonly used drugs include clotrimazole or miconazole, often given along with ceftazidime which is an antibacterial. The primary mechanism by which clotrimazole works is by impairing the permeability barrier of the cytoplasmic membrane of the fungi, which causes holes to appear in the cell membrane and leaking out of the contents of the organism, thus killing the fungus and treating the infection. Various studies suggest that following clotrimazole drop therapy, symptoms suggestive of otomycosis are not at risk for recurrence of the disease and due to its economical pricing and easy availability, is frequently recommended by otolaryngologists in the treatment of otomycosis. In this review article, we will discuss about the effectiveness of the drug in different populations, observe treatment failures and relapse of the disease, analyze the ability of clotrimazole drops in preventing relapse of the infection, and observe the role of the drug in reducing the signs and symptoms of the disease.
PubMed: 36381881
DOI: 10.7759/cureus.30098 -
Clinical Oral Investigations Nov 2022To identify the antifungal susceptibility profile of Candida spp. isolated from the human oral cavity was assessed with meta-analyses of observational studies that... (Meta-Analysis)
Meta-Analysis Review
AIM
To identify the antifungal susceptibility profile of Candida spp. isolated from the human oral cavity was assessed with meta-analyses of observational studies that collected samples from the oral cavity of human subjects.
MATERIAL AND METHODS
Isolated Candida albicans tested by E-test®; disk diffusion test; microdilution and macrodilution; Sensititre YeastOne; and/or FungiTest. Search strategies were conducted on the MEDLINE, Embase, CINAHL, Dentistry, and Oral Sciences, Central, Scopus, and LILACS databases, and gray literature sources. Articles were initially screened by title and then their abstracts. Articles that met the conditions for inclusion were read in full, followed by data extraction. A descriptive analysis was conducted of each study, and the data were tabulated. A first meta-analysis was conducted to assess the resistance of antifungals regardless of systemic comorbidities. An additional stratified analysis was conducted by systemic comorbidity groups for the outcome "resistance" to the antifungals.
RESULTS
When not grouping Candida albicans isolates by systemic conditions, the lowest resistance rates to the antifungals tested were observed for amphotericin B, nystatin, flucytosine, and caspofungin. In contrast, the highest resistance rates were observed for miconazole and econazole. There was a high degree of heterogeneity and low resistance in general in all analyses, except for the "several associated comorbidities" group, which had high resistance rates.
CONCLUSIONS
Clinical C. albicans isolates had low antifungal resistance.
CLINICAL RELEVANCE
The presence of concomitant systemic comorbidities appears to be an essential factor that should be considered when evaluating resistance to antifungals for oral isolates.
Topics: Humans; Antifungal Agents; Candida albicans; Candidiasis; Microbial Sensitivity Tests; Drug Resistance, Fungal; Mouth
PubMed: 36167858
DOI: 10.1007/s00784-022-04716-2 -
Pharmaceutics Sep 2022The dapivirine (DPV) vaginal ring was developed by the nonprofit International Partnership for Microbicides (IPM) for reducing the risk of HIV infection. A clinical...
The dapivirine (DPV) vaginal ring was developed by the nonprofit International Partnership for Microbicides (IPM) for reducing the risk of HIV infection. A clinical study (IPM 028) showed that concomitant use of the DPV ring and miconazole (MIC) altered DPV pharmacokinetic profile. In this work, we investigated whether or not DPV transport and permeation contributed to the observed DPV-MIC interaction. Our study evaluated the interaction between DPV and several transporters that are highly expressed in the human female reproductive tract, including MRP1, MRP4, P-gp, BCRP, and ENT1, using vesicular and cellular systems. We also evaluated the impact of DPV/MIC on cellular tight junctions by monitoring transepithelial electrical resistance with the Ussing chamber. Lastly, we evaluated the effect of MIC on DPV permeability across human cervical tissue. Our findings showed that DPV was not a substrate of MRP1, MRP4, P-gp, BCRP, or ENT1 transporters. Additionally, DPV did not inhibit the activity of these transporters. DPV, MIC, and their combination also did not disrupt cellular tight junctions. MIC did not affect DPV tissue permeability but significantly reduced DPV tissue levels. Therefore, our results suggest that the DPV-MIC interaction is not due to these five transporters, altered tight junction integrity, or altered tissue permeability.
PubMed: 36145696
DOI: 10.3390/pharmaceutics14091948 -
Antibiotics (Basel, Switzerland) Sep 2022Phylogenetically diverse fungal species are an increasing cause of severe disease and mortality. Identification of new targets and development of new fungicidal drugs...
Phylogenetically diverse fungal species are an increasing cause of severe disease and mortality. Identification of new targets and development of new fungicidal drugs are required to augment the effectiveness of current chemotherapy and counter increasing resistance in pathogens. Nitroalkenyl benzene derivatives are thiol oxidants and inhibitors of cysteine-based molecules, which show broad biological activity against microorganisms. Nitropropenyl benzodioxole (NPBD), one of the most active antimicrobial derivatives, shows high activity in MIC assays for phylogenetically diverse saprophytic, commensal and parasitic fungi. NPBD was fungicidal to all species except the dermatophytic fungi, with an activity profile comparable to that of Amphotericin B and Miconazole. NPBD showed differing patterns of dynamic kill rates under different growth conditions for and and was rapidly fungicidal for non-replicating vegetative forms and microconidia. It did not induce resistant or drug tolerant strains in major pathogens on long term exposure. A literature review highlights the complexity and interactivity of fungal tyrosine phosphate and redox signaling pathways, their differing metabolic effects in fungal species and identifies some targets for inhibition. A comparison of the metabolic activities of Amphotericin B, Miconazole and NPBD highlights the multiple cellular functions of these agents and the complementarity of many mechanisms. The activity profile of NPBD illustrates the functional diversity of fungal tyrosine phosphatases and thiol-based redox active molecules and contributes to the validation of tyrosine phosphatases and redox thiol molecules as related and complementary selective targets for antimicrobial drug development. NPBD is a selective antifungal agent with low oral toxicity which would be suitable for local treatment of skin and mucosal infections.
PubMed: 36139967
DOI: 10.3390/antibiotics11091188 -
The International Journal of... Nov 2022Cooperative defect is 1 of the earliest manifestations of disease patients with Alzheimer disease (AD) exhibit, but the underlying mechanism remains unclear.
BACKGROUND
Cooperative defect is 1 of the earliest manifestations of disease patients with Alzheimer disease (AD) exhibit, but the underlying mechanism remains unclear.
METHODS
We evaluated the cooperative function of APP/PS1 transgenic AD model mice at ages 2, 5, and 8 months by using a cooperative drinking task. We examined neuropathologic changes in the medial prefrontal cortex (mPFC). Another experiment was designed to observe whether miconazole, which has a repairing effect on myelin sheath, could promote the cooperative ability of APP/PS1 mice in the early AD-like stage. We also investigated the protective effects of miconazole on cultured mouse cortical oligodendrocytes exposed to human amyloid β peptide (Aβ1-42).
RESULTS
We observed an age-dependent impairment of cooperative water drinking behavior in APP/PS1 mice. The AD mice with cooperative dysfunction showed decreases in myelin sheath thickness, oligodendrocyte nuclear heterochromatin percentage, and myelin basic protein expression levels in the mPFC. The cooperative ability was significantly improved in APP/PS1 mice treated with miconazole. Miconazole treatment increased oligodendrocyte maturation and myelin sheath thickness without reducing Aβ plaque deposition, reactive gliosis, and inflammatory factor levels in the mPFC. Miconazole also protected cultured oligodendrocytes from the toxicity of Aβ1-42.
CONCLUSIONS
These results demonstrate that mPFC hypomyelination is involved in the cooperative deficits of APP/PS1 mice. Improving myelination through miconazole therapy may offer a potential therapeutic approach for early intervention in AD.
Topics: Humans; Mice; Animals; Alzheimer Disease; Amyloid beta-Peptides; Miconazole; Mice, Inbred C57BL; Amyloid beta-Protein Precursor; Plaque, Amyloid; Mice, Transgenic; Disease Models, Animal; Presenilin-1
PubMed: 36112386
DOI: 10.1093/ijnp/pyac061 -
Journal of Fungi (Basel, Switzerland) Aug 2022A broad range of topical antifungal formulations containing miconazole or terbinafine as actives are commonly used as efficacious choices for combating fungal skin... (Review)
Review
A broad range of topical antifungal formulations containing miconazole or terbinafine as actives are commonly used as efficacious choices for combating fungal skin infections. Their many benefits, owing to their specific mechanism of action, include their ability to target the site of infection, enhance treatment efficacy and reduce the risk of systemic side effects. Their proven efficacy, and positioning in the treatment of fungal skin infections, is enhanced by high patient compliance, especially when appropriate vehicles such as creams, ointments and gels are used. However, inflammation as a result of fungal infection can often impede treatment, especially when combined with pruritus (itch), an unpleasant sensation that elicits an urge to scratch. The scratching that occurs in response to pruritus frequently accelerates skin damage, ultimately aggravating and spreading the fungal infection. To help overcome this issue, a topical antifungal-corticosteroid combination consisting of miconazole or terbinafine and corticosteroids of varying potencies should be used. Due to their inherent benefits, these topical antifungal-corticosteroid combinations can concomitantly and competently attenuate inflammation, relieve pruritus and treat fungal infection.
PubMed: 36012800
DOI: 10.3390/jof8080812 -
Frontiers in Microbiology 2022Cutaneous candidiasis is one of the most prevalent mycotic infections caused by species. The severity of infection mounts faster when the species shows antifungal...
Cutaneous candidiasis is one of the most prevalent mycotic infections caused by species. The severity of infection mounts faster when the species shows antifungal resistance. In the current retrospective study, we aimed to analyze the occurrence, causes of cutaneous candidiasis, and antifungal susceptibility pattern of isolates from Skin and Venereal Diseases Prevention and Control Hospital of Shantou, located in eastern Guangdong, China. The laboratory data of all patients ( = 3,113) suffering from various skin and venereal infections during January 2012 to December 2021 was analyzed through Excel and GraphPad prism. Our analysis indicate that cutaneous candidiasis was 22.29% ( = 694), of which 78.53% ( = 554) of patients were males and 21.47% ( = 149) of patients were females. The median age of patients with cutaneous candidiasis was 38-year [interquartile range (30-48)]. Most cases occurred in the adult age group (19-50 years). Regarding the species type, the were prominently detected ( = 664, 95.68%), while non- were found only in 30 (4.32%) patients, which were ( = 18), ( = 8), ( = 3), and ( = 1). The susceptibility rate for terbinafine, miconazole, voriconazole, itraconazole, fluconazole, ketoconazole, nystatin, 5-flucytosine and amphotericin B were 10.83, 29.32, 59.39, 78.53, 85.28, 87.75, 99.59, 99.41, and 100%, respectively. Finally, all isolates were found susceptible to all tested azole drugs with exception to miconazole against which 8.33% of isolates showed resistance. The findings of this study will help healthcare officials to establish better antifungal stewardship in the region.
PubMed: 35992679
DOI: 10.3389/fmicb.2022.981181 -
Clinical, Cosmetic and Investigational... 2022Seborrheic dermatitis (SD) is a common chronic inflammatory skin disorder that mostly affects young adults in areas rich in sebaceous glands (scalp, face, and trunk). In... (Review)
Review
Seborrheic dermatitis (SD) is a common chronic inflammatory skin disorder that mostly affects young adults in areas rich in sebaceous glands (scalp, face, and trunk). In adolescents and adults, SD clinical presentation may range from mild patches to diffuse scalp scaling. In infants, it mainly occurs on the scalp as yellowish, scaly patches ("cradle cap"). In adults, several environmental triggers are likely to promote SD development, along with fungal colonization by spp., sebaceous gland activity, as well as immunosuppression, endocrine, neurogenic and iatrogenic factors. In children, early occurrence in the first trimester suggests the role of excessive sebaceous gland activity from maternal hormones, along with cutaneous microbiome alterations. The diagnosis of SD is usually clinical, and specific laboratory and/or instrumental investigations are seldom required. Treatment is aimed at modulating sebum production, reducing skin colonization by spp., and controlling inflammation. In adults, mild-to-moderate scalp SD forms can be managed with topical antifungals (ketoconazole, ciclopirox, miconazole) or antiinflammatory (mild-to-moderate potency corticosteroids) or keratolytic/humectant (propylene glycol) agents. Recommended topical therapeutic options for mild-to-moderate facial or body areas SD include topical ketoconazole, ciclopirox, clotrimazole, mild-to-moderate potency corticosteroids, lithium succinate/gluconate, and topical calcineurin inihibitors (). In severe and/or resistant cases, the use of systemic antifungal drugs (terbinafine, itraconazole), as well as UVB phototherapy, may be considered. In children, scant scientific evidence supports the effectiveness and safety of topical drugs, and "cradle cap" is usually successfully managed with baby shampoos enriched with emollient agents and vegetable oils. Alternatively, similarly to adult scalp SD, medical device shampoos with antiinflammatory and antifungal properties, containing piroctone olamine, bisabolol, alyglicera, telmesteine, may be used. Beyond pharmacological treatments, an appropriate cosmetic approach, if correctly prescribed, may improve therapeutic outcomes.
PubMed: 35967915
DOI: 10.2147/CCID.S284671 -
The Journal of Biological Chemistry Sep 2022Human cytochrome P450 8B1 (CYP8B1) is involved in conversion of cholesterol to bile acids. It hydroxylates the steroid ring at C12 to ultimately produce the bile acid...
Human cytochrome P450 8B1 (CYP8B1) is involved in conversion of cholesterol to bile acids. It hydroxylates the steroid ring at C12 to ultimately produce the bile acid cholic acid. Studies implicated this enzyme as a good drug target for nonalcoholic fatty liver disease and type 2 diabetes, but there are no selective inhibitors known for this enzyme and no structures to guide inhibitor development. Herein, the human CYP8B1 protein was generated and used to identify and characterize interactions with a series of azole inhibitors, which tend to be poorly selective P450 inhibitors. Structurally related miconazole, econazole, and tioconazole bound with submicromolar dissociation constants and were effective inhibitors of the native reaction. CYP8B was cocrystallized with S-tioconazole to yield the first X-ray structure. This inhibitor bound in the active site with its azole nitrogen coordinating the heme iron, consistent with inhibitor binding and inhibition assay data. Additionally, the CYP8B1 active site was compared with similar P450 enzymes to identify features that may facilitate the design of more selective inhibitors. Selective inhibitors should promote a better understanding of the role of CYP8B1 inhibition in normal physiology and disease states and provide a possible treatment for nonalcoholic fatty liver disease and type 2 diabetes.
Topics: Azoles; Bile Acids and Salts; Cholesterol; Cholic Acids; Cytochrome P-450 Enzyme System; Diabetes Mellitus, Type 2; Drug Design; Econazole; Heme; Humans; Iron; Miconazole; Nitrogen; Non-alcoholic Fatty Liver Disease; Steroid 12-alpha-Hydroxylase
PubMed: 35944583
DOI: 10.1016/j.jbc.2022.102344