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ACS Omega Sep 2023Miconazole (MCZ) is a potential antifungal drug to treat skin infections caused by , (athlete's foot fungal infection), (jock itching in the groin and buttocks), and...
Miconazole (MCZ) is a potential antifungal drug to treat skin infections caused by , (athlete's foot fungal infection), (jock itching in the groin and buttocks), and (red scaly rash on the skin). The current study focused on Hansen parameter-based solvent selection (HSPiP software) and method development optimization using an experimental design tool for sensitive, accurate, reproducible, economic, rapid, robust, and precise methodology to quantify MCZ in rat plasma. Moreover, a Taguchi design was used for screening two independent factors (flow rate and ACN content). Quality by design (QbD) was employed to optimize and identify the right ratio of mobile phase composition and its impact on the peak and retention time. The elution of MCZ was achieved using methanol and acetonitrile (15:85 v/v ratio) at a retention time of 6 min and optimal flow rate (1 mL/min). Finally, the method was validated based on accuracy, precision, linearity, selectiveness, and high recovery at varied concentrations as per the International Council for Harmonization (ICH) guidelines. The method was linear ( = 0.999) over the explored concentration range (250-2000 ng/mL) at 270 nm detection wavelength. The optimized method was used to quantify in vivo pharmacokinetic (PK) study after transdermal application of MCZ-loaded formulations (MCNE11, MNE11, MCZ-Sol, and MCZ-MKT). HSP-oriented solvent selection and quality by design-based optimized process variables and composition in the optimized analytical methodology were quite convincing and have been a cutting-edge MCZ analysis method so far. The validated method was robust, economic, and rapid with high specificity and selectivity.
PubMed: 37780027
DOI: 10.1021/acsomega.3c03713 -
Genes Sep 20235-methylcytosine (5mC) is one of the most important epigenetic modifications. Its increased occurrence in regulatory sequences of genes, such as promoters and enhancers,...
5-methylcytosine (5mC) is one of the most important epigenetic modifications. Its increased occurrence in regulatory sequences of genes, such as promoters and enhancers, is associated with the inhibition of their expression. Methylation patterns are not stable but are sensitive to factors such as the environment, diet, and age. In the present study, we investigated the effects of fungicide miconazole, both alone and in combination with the insecticide Mospilan 20SP, on the methylation status of bovine , , and genes in bovine lymphocytes cultured in vitro. The methylation-specific PCR technique was used for the objectives of this study. We found that miconazole alone at concentrations of 1.25, 2.5, 5, 10, 25, and 50 µg/mL after 24 h exposure probably did not induce changes in methylation for all three genes analysed. The same results were found for the combination of pesticides at 24 h exposure and the following concentrations for each of them: 0.625, 1.25, 2.5, 5, and 12.5 µg/mL. Thus, we can conclude that the fungicide miconazole alone, as well as in combination with the insecticide Mospilan 20SP, was unlikely to cause changes to the methylation of bovine , , and genes.
Topics: Animals; Cattle; Fungicides, Industrial; Insecticides; Lymphocytes; Methylation; Miconazole; Glutathione S-Transferase pi; Glutathione Transferase; Acetylcholinesterase
PubMed: 37761931
DOI: 10.3390/genes14091791 -
Current Medical Mycology Dec 2022, a known zoophilic dermatophyte responsible for favus form in rodents and camels, is occasionally reported to cause human infections.
BACKGROUND AND PURPOSE
, a known zoophilic dermatophyte responsible for favus form in rodents and camels, is occasionally reported to cause human infections.
CASE REPORT
This study aimed to report a case of tinea corporis caused by that experienced annular erythematous pruritic plaque with abundant purulent secretions. In June 2021, a 15-year-old girl with an erythematous cup shape lesion on the right wrist bigger than 3 cm in diameter was examined for tinea corporis. Since March, 2016 her family has kept several camels at home. Direct examination of skin scraping and purulent exudates revealed branching septal hyaline hyphae and arthrospore. Morphological evaluation of the recovered isolate from the culture and sequencing of ITS1-5.8S rDNA-ITS2 region resulted in the identification of . Antifungal susceptibility testing showed that this isolate had low minimum inhibitory concentration (MIC) values for luliconazole, terbinafine, and tolnaftate, but high MICs to itraconazole, fluconazole, posaconazole, miconazole, isavuconazole, ketoconazole, clotrimazole, and griseofulvin. However, the patient was successfully treated with oral terbinafine and topical ketoconazole.
CONCLUSION
It can be said that is often missed or misidentified due to its morphological similarity to / or other similar species. This dermatophyte species is first reported as the cause of tinea corporis in Iran. As expected, a few months after our study, was detected in other areas of Iran, in a few cases.
PubMed: 37736606
DOI: 10.32598/CMM.2023.1344 -
Heliyon Aug 2023Due to the adverse effects associated with long-term administration of antifungal drugs used for treating dermatophytic lesions like tinea unguium, there is a critical... (Review)
Review
Due to the adverse effects associated with long-term administration of antifungal drugs used for treating dermatophytic lesions like tinea unguium, there is a critical need for novel antifungal therapies that exhibit improved absorption and minimal adverse effects. Nanoformulations offer a promising solution in this regard. Topical formulations may penetrate the upper layers of the skin, such as the stratum corneum, and release an appropriate amount of drugs in therapeutic quantities. Liposomes, particularly nanosized ones, used as topical medication delivery systems for the skin, may have various roles depending on their size, lipid and cholesterol content, ingredient percentage, lamellarity, and surface charge. Liposomes can enhance permeability through the stratum corneum, minimize systemic effects due to their localizing properties, and overcome various challenges in cutaneous drug delivery. Antifungal medications encapsulated in liposomes, including fluconazole, ketoconazole, croconazole, econazole, terbinafine hydrochloride, tolnaftate, and miconazole, have demonstrated improved skin penetration and localization. This review discusses the traditional treatment of dermatophytes and liposomal formulations. Additionally, promising liposomal formulations that may soon be available in the market are introduced. The objective of this review is to provide a comprehensive understanding of dermatophyte infections and the role of liposomes in enhancing treatment.
PubMed: 37583758
DOI: 10.1016/j.heliyon.2023.e18960 -
Frontiers in Pharmacology 2023Resting membrane potential is a bioelectric property of all cells. Multiple players govern this property, the ion channels being the most important. Ion channel...
Resting membrane potential is a bioelectric property of all cells. Multiple players govern this property, the ion channels being the most important. Ion channel dysfunction can affect cells' resting membrane potential and could be associated with numerous diseases. Therefore, the drug discovery focus on ion channels has increased yearly. In addition to patch-clamp, cell-based fluorescent assays have shown a rapid and reliable method for searching new ion channel modulators. Here, we used a cell-based membrane potential assay to search for new blockers of the Kv10.1, a potassium channel strongly associated with cancer progression and a promising target in anticancer therapy. We found that fluoxetine and miconazole can inhibit the Kv10.1 channel in the micromolar range. In contrast, BL-1249 potentiates Kv10.1 currents in a dose-dependent manner, becoming the first molecule described as an activator of the channel. These results demonstrate that cell-based membrane potential assay can accelerate the discovery of new Kv10.1 modulators.
PubMed: 37554982
DOI: 10.3389/fphar.2023.1238503 -
Beijing Da Xue Xue Bao. Yi Xue Ban =... Aug 2023Peritoneal dialysis (PD) catheter-related infection (i.e. exit-site infection and tunnel infection) is one of the main causes of PD-related peritonitis. If it cannot be...
Peritoneal dialysis (PD) catheter-related infection (i.e. exit-site infection and tunnel infection) is one of the main causes of PD-related peritonitis. If it cannot be controlled effectively, it could lead to PD technique failure. Therefore, timely and effective diagnosis and treatment and active prevention so as to reduce PD catheter-related infection is an important treatment goal in PD patients. PD catheter exit-site infection (ESI) and tunnel infection can be caused by a variety of microorganisms, mainly bacteria, while fungi are very rare. Few public data can be used to guide treatment of PD catheter-related fungal infection, and there is no related report in China till now. Once fungal peritonitis occurred, the patient can only withdraw from PD treatment. Here, we report a case of fungal PD catheter ESI combined with tunnel infection which was successfully diagnosed and treated in our PD center. A 71-year-old woman came to clinic because of "PD for 5 years, secretions from exit site for 8 days and aggravation for 1 day". The patient suffered from peritonitis, ESI and tunnel infection for many times in the past 5 years, involving a variety of pathogens. Eight days before, she found white viscous discharge from exit site. The subcutaneous cuff completely came out of it and rubbed its skin. The Schaefer exit-site score was 3 points. Due to the suspected ESI 2 months before, the discharge swab for bacterial culture was positive for , so the exit site swab for bacterial culture was done again, and gentamicin injection was applied topically once a day for empirical treatment. The exit site was evaluated one day before: The subcutaneous tunnel was significantly swollen and slightly tender at 2.5 cm away from the exit site, and with white medium amount of viscous secretions. The exit-site score increased to 4 points. Routine test of dialysis effluent was (-). The bacterial culture of the exit-site discharge was rechecked twice, and was positive for two times, so the diagnosis of fungal PD catheter ESI combined with tunnel infection was clear. Immediately we searched for the causes of ESI and tunnel infection. We found that the patient had a suspicious history of gray toenail on the foot. The toenail smear was positive for fungi and visible hyphae. She washed feet with hands every day, and washed clothes on a low bench every day, which made the exit-site and tunnel squeezed for a long time. Based on the above causes, we gave her comprehensive treatment as follows: For ESI and tunnel fungal infections, fluco-nazole was used systemically according to the drug sensitivity results, and miconazole cream was applied to the exit-site locally. For the subcutaneous cuff that came out completely, daily iodophor disinfection was given locally. At the same time, local antifungal treatment was given to the foot. We followed up closely during treatment, evaluated the exit-site every 2-3 days, and took photos of the exit-site to dynamically observe the effect. After 14 days of treatment, the exit-site score continued to be 0-1, the bacterial culture of the exit-site was negative, the cuff culture was negative, and the tunnel B-ultrasound was normal. The patient had been followed up regularly once a month for 60 months, no ESI and tunnel infection occurred. Fungal PD catheter ESI and tunnel infection are rare complications of PD. When the standard anti-infection treatment is ineffective, the possibility of fungal infection should be considered, so as to avoid prolonged use of antibiotics, aggravating fungal infection, and even progressing to fungal peritonitis, leading to withdrawal from PD. Accurate exit-site evaluation is helpful for timely diagnosis and early treatment of ESI and tunnel infection. The exit-site discharge culture and drug sensitivity test before treatment are helpful to identify the pathogen and adjust subsequent treatment. At the same time, repeated discharge culture is required in order to exclude positive fungal culture results caused by contamination. Once fungal catheter-related infection is diagnosed, we should search for possible causes actively, subsequent targeted and comprehensive treatment plays a decisive role for the prognosis of patients.
Topics: Humans; Female; Aged; Catheter-Related Infections; Peritoneal Dialysis; Catheters, Indwelling; Peritonitis; Mycoses
PubMed: 37534662
DOI: 10.19723/j.issn.1671-167X.2023.04.029 -
Journal of Xenobiotics Jul 2023Vulvovaginitis with spp. is the most common infection in women and the rate is increased during pregnancy. Antifungal prescription in pregnant women continues to...
Vulvovaginitis with spp. is the most common infection in women and the rate is increased during pregnancy. Antifungal prescription in pregnant women continues to present challenges and the decision must balance the risk of fetal toxicity with the benefits to the fetus and mother. Starting from the idea that clotrimazole is the most recommended antifungal in candidal vaginitis in pregnancy, we tested the sensitivity of different species of spp. to other azoles, polyenes, and antimetabolites. This retrospective study (January to June 2019) assessed 663 pregnant women hospitalized for various pregnancy-related symptoms in which samples of phage secretion were taken. The laboratory results confirmed 21% of cases, indicating 140 positive mycologic samples. In this study, vaginal candidiasis was mostly related to the first trimester of pregnancy (53.57%,) and less related in the last trimester (17.14%). was the most frequent isolated strain in this study, accounting for 118 cases, followed by 16 strains of and 6 cases of . The highest sensitivity for was found in azoles, mostly in miconazole (93.2%), while was completely resistant to polyene with low sensitivity in antimetabolites and even in some azoles, such as fluconazole. In our study, higher resistance rates to flucytosine were found, with and exhibiting greater resistance than .
PubMed: 37489336
DOI: 10.3390/jox13030023 -
Frontiers in Neurology 2023One of the most prevalent types of epilepsy is temporal lobe epilepsy (TLE), which has unknown etiological factors and drug resistance. The detailed mechanisms...
One of the most prevalent types of epilepsy is temporal lobe epilepsy (TLE), which has unknown etiological factors and drug resistance. The detailed mechanisms underlying potassium channels in human TLE have not yet been elucidated. Hence, this study aimed to mine potassium channel genes linked to TLE using a bioinformatic approach. The results found that Four key TLE-related potassium channel genes (TERKPCGs) were identified: potassium voltage-gated channel subfamily E member () 1, , potassium inwardly rectifying channel, subfamily J, member 11 (), and . A protein-protein interaction (PPI) network was constructed to analyze the relationship between TERKPCGs and other key module genes. The results of gene set enrichment analysis (GSEA) for a single gene indicated that the four TERKPCGs were highly linked to the cation channel, potassium channel, respiratory chain, and oxidative phosphorylation. The mRNA-TF network was established using four mRNAs and 113 predicted transcription factors. A ceRNA network containing seven miRNAs, two mRNAs, and 244 lncRNAs was constructed based on the TERKPCGs. Three common small-molecule drugs (enflurane, promethazine, and miconazole) target , and . Ten small-molecule drugs (glimepiride, diazoxide, levosimendan, and thiamylal et al.) were retrieved for . Compared to normal mice, the expression of , , , and was downregulated in the brain tissue of the epilepsy mouse model at both the transcriptional and translational levels, which was consistent with the trend of human data from the public database. The results indicated that key potassium channel genes linked to TLE were identified based on bioinformatics analysis to investigate the potential significance of potassium channel genes in the development and treatment of TLE.
PubMed: 37483435
DOI: 10.3389/fneur.2023.1175007 -
Scientific Reports Jul 2023Complex sphingolipids and sterols are coordinately involved in various cellular functions, e.g. the formation of lipid microdomains. Here we found that budding yeast...
Complex sphingolipids and sterols are coordinately involved in various cellular functions, e.g. the formation of lipid microdomains. Here we found that budding yeast exhibits resistance to an antifungal drug, aureobasidin A (AbA), an inhibitor of Aur1 catalyzing the synthesis of inositolphosphorylceramide, under impaired biosynthesis of ergosterol, which includes deletion of ERG6, ERG2, or ERG5 involved in the final stages of the ergosterol biosynthesis pathway or miconazole; however, these defects of ergosterol biosynthesis did not confer resistance against repression of expression of AUR1 by a tetracycline-regulatable promoter. The deletion of ERG6, which confers strong resistance to AbA, results in suppression of a reduction in complex sphingolipids and accumulation of ceramides on AbA treatment, indicating that the deletion reduces the effectiveness of AbA against in vivo Aur1 activity. Previously, we reported that a similar effect to AbA sensitivity was observed when PDR16 or PDR17 was overexpressed. It was found that the effect of the impaired biosynthesis of ergosterol on the AbA sensitivity is completely abolished on deletion of PDR16. In addition, an increase in the expression level of Pdr16 was observed on the deletion of ERG6. These results suggested that abnormal ergosterol biosynthesis confers resistance to AbA in a PDR16-dependent manner, implying a novel functional relationship between complex sphingolipids and ergosterol.
Topics: Ergosterol; Depsipeptides; Phytosterols; Sphingolipids
PubMed: 37429938
DOI: 10.1038/s41598-023-38237-z -
European Journal of Pharmaceutical... Sep 2023Miconazole-loaded nanoparticles coated with hyaluronic acid (miconazole-loaded nanoparticles/HA) were developed to overcome the limitations of the conventional therapy...
Miconazole-loaded nanoparticles coated with hyaluronic acid (miconazole-loaded nanoparticles/HA) were developed to overcome the limitations of the conventional therapy of the vulvovaginal candidiasis (VVC). They were synthesized by emulsification and solvent evaporation techniques, characterized by diameter, polydispersity index, zeta potential, encapsulation efficiency, atomic force microscopy (AFM), evaluated in terms of efficacy against C. albicans in vitro, and tested in a murine VVC model. Nanoparticles showed 211nm of diameter with a 0.32 polydispersity index, -53mV of zeta potential, and 90% miconazole encapsulation efficiency. AFM evidenced nanoparticles with a spherical shape. They inhibited the proliferation of C. albicans in vitro and in vivo after a single administration. Nanoparticles released the miconazole directly in the site of action at low therapeutic doses, which was enough to eliminate the fungal burden in the murine VVC model. These systems were rationally designed since the existence of the HA induces their adhesion on the vaginal mucus and their internalization via CD44 receptors, inhibiting the C. albicans. Therefore, miconazole-loaded nanoparticles/HA represent an innovative non-conventional pharmaceutical dosage form to treat the VVC and recurrent VVC.
Topics: Humans; Female; Mice; Animals; Miconazole; Candidiasis, Vulvovaginal; Hyaluronic Acid; Antifungal Agents; Candida albicans; Nanoparticles
PubMed: 37379779
DOI: 10.1016/j.ejps.2023.106508