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Polish Journal of Veterinary Sciences Jun 2023Yeast infections such as otitis externa and seborrheic dermatitis in dogs and cats are frequently associated with secondary infection. It is part of the normal...
Yeast infections such as otitis externa and seborrheic dermatitis in dogs and cats are frequently associated with secondary infection. It is part of the normal cutaneous microflora of most warm-blooded vertebrates, however, under certain conditions, it can become a causative agent of infection that needs to be treated pharmacologically. Azole derivatives are the drugs of the first choice. An interesting trend in developing resistance is the use of natural substances, which include manuka honey with confirmed antimicrobial properties. The main intention of this research was to evaluate the mutual effect of manuka honey in combination with four conventional azole antifungals - clotrimazole, fluconazole, itraconazole, and miconazole - on 14 isolates obtained from dogs and 1 reference strain. A slightly modified M27-A3 method (CLSI 2008) and the checkerboard test (Nikolić et al. 2017) were used for this purpose. Our results show an additive effect of all 4 antifungals with manuka honey concurrent use. Based on the determined values of fractional inhibitory concentration index (FICI - 0.74±0.03 when manuka honey combined with clotrimazole, 0.96±0.08 with fluconazole, 1.0±0 with miconazole and 1.16±0.26 with itraconazole), it was found in all cases that the effect of substances used is more pronounced in mutual combination than when used separately.
Topics: Animals; Cats; Dogs; Antifungal Agents; Fluconazole; Itraconazole; Miconazole; Clotrimazole; Cat Diseases; Honey; Dog Diseases; Azoles
PubMed: 37389413
DOI: 10.24425/pjvs.2023.145037 -
3 Biotech Jul 2023The COVID-19 survivors and long-term steroid administered patients exhibit a variety of fungal co-infections. The lives of COVID-19 patients and survivors are hampered... (Review)
Review
The COVID-19 survivors and long-term steroid administered patients exhibit a variety of fungal co-infections. The lives of COVID-19 patients and survivors are hampered by fungal species of the genera , , and . There have been cases of mucormycosis, aspergillosis, and candidiasis in COVID-19 patients. The treatments given to these opportunistic fungal infections include polyene like amphotericin B, azoles including imidazoles like ketoconazole, miconazole, and triazoles like fluconazole, voriconazole, itraconazole, Echinocandin derivatives like- caspofungin, micafungin, immunomodulatory therapy, granulocyte transfusion, etc. A successful recovery and the reduction of fatalities depend on prompt diagnosis and treatment. To reduce mortality, advanced techniques to identify such uncommon infections at a very early stage are necessary. This review's goal is to provide a summary of the systemic and superficial opportunistic fungal infections that the COVID-19 survivors were dealing with, including information on illness incidence, pathogenicity, and treatment.
PubMed: 37309405
DOI: 10.1007/s13205-023-03648-2 -
AMIA ... Annual Symposium Proceedings.... 2020The development of novel drugs in response to changing clinical requirements is a complex and costly method with uncertain outcomes. Postmarket pharmacovigilance is...
The development of novel drugs in response to changing clinical requirements is a complex and costly method with uncertain outcomes. Postmarket pharmacovigilance is essential as drugs often have under-reported side effects. This study intends to use the power of digital media to discover the under-reported side effects of marketed drugs. We have collected tweets for 11 different Drugs (Alprazolam, Adderall, Fluoxetine, Venlafaxine, Adalimumab, Lamotrigine, Quetiapine, Trazodone, Paroxetine, Metronidazole and Miconazole). We have compiled a vast adverse drug reactions (ADRs) lexicon that is used to filter health related data. We constructed machine learning models for automatically annotating the huge amount of publicly available Twitter data. Our results show that on average 43 known ADRs are shared between Twitter and FAERS datasets. Moreover, we were able to recover on average 7 known side effects from Twitter data that are not reported on FAERS. Our results on Twitter dataset show a high concordance with FAERS, Medeffect and Drugs.com. Moreover, we manually validated some of the under-reported side effect predicted by our model using literature search. Common known and under-reported side effects can be found at https://github.com/cbrl-nuces/Leveraging-digital-media-data-for-pharmacovigilance.
Topics: Diagnostic Tests, Routine; Drug-Related Side Effects and Adverse Reactions; Humans; Internet; Machine Learning; Pharmacovigilance; Social Media
PubMed: 33936417
DOI: No ID Found -
Journal of Obstetrics and Gynaecology :... Dec 2023At concentrations achieved following systemic administration, the primary effect of imidazoles and triazoles on fungi is inhibition of 14-α-sterol demethylase, a... (Review)
Review
At concentrations achieved following systemic administration, the primary effect of imidazoles and triazoles on fungi is inhibition of 14-α-sterol demethylase, a microsomal cytochrome P450 (CYP) enzyme. Imidazoles and triazoles impair the biosynthesis of ergosterol for the cytoplasmic membrane and lead to the accumulation of 14-α-methyl sterols. The synthetic imidazole miconazole is additionally able to increase intracellular reactive oxygen species, at least in part through inhibition of fungal catalase and peroxidase. This unique feature of miconazole is probably the basis for its fungicidal activity in , in addition to the fungistatic mode of action. Studies show that miconazole is superior to nystatin treatment and demonstrate its impact as one of the best options in managing vulvovaginal candidiasis. Regarding recurrent vulvovaginal candidiasis, several new drugs are currently developed to ensure effective treatment also for this group of patients.
Topics: Female; Humans; Miconazole; Candidiasis, Vulvovaginal; Antifungal Agents; Imidazoles; Nystatin; Candida albicans; Cytochrome P-450 Enzyme System
PubMed: 37029724
DOI: 10.1080/01443615.2023.2195001 -
ACS Nano Apr 2023Prodrug nanoassemblies combine the advantages of prodrug and nanomedicines, offering great potential in targeting the lesion sites and specific on-demand drug release,...
Prodrug nanoassemblies combine the advantages of prodrug and nanomedicines, offering great potential in targeting the lesion sites and specific on-demand drug release, maximizing the therapeutic performance while minimizing their side effects. However, there is still lacking a facile pathway to prepare the lipid prodrug nanoassemblies (LPNAs). Herein, we report the LPNAs via the dynamic covalent boronate between catechol and boronic acid. The resulting LPNAs possess properties like drug loading in a dynamic covalent manner, charge reversal in an acidic microenvironment, and specific drug release at an acidic and/or oxidative microenvironment. Our methodology enables the encapsulation and delivery of three model drugs: ciprofloxacin, bortezomib, and miconazole. Moreover, the LPNAs are often more efficient in eradicating pathogens or cancer cells than their free counterparts, both and . Together, our LPNAs with intriguing properties may boost the development of drug delivery and facilitate their clinical applications.
Topics: Prodrugs; Drug Delivery Systems; Bortezomib; Boronic Acids; Lipids; Nanoparticles; Drug Liberation
PubMed: 36999933
DOI: 10.1021/acsnano.2c12233 -
Acta Crystallographica. Section E,... Feb 2024The crystal structure of the new triclinic polymorph of miconazole {MIC; CHClNO; systematic name:...
The crystal structure of the new triclinic polymorph of miconazole {MIC; CHClNO; systematic name: ()-1-[2-(2,4-di-chloro-benz-yloxy)-2-(2,4-di-chloro-phen-yl)eth-yl]-1-imidazole} is reported and compared with the monoclinic form of solvent-free miconazole previously reported [Kaspiaruk & Chęcińska (2022 ▸). C, 343-350]. A comparison shows a different orientation of imidazole and one di-chloro-phenyl ring between polymorphic mol-ecules. In the crystal structure of the title compound, only weak halogen bonds and C-H⋯π(arene) inter-actions are found. Hirshfeld surface analysis and energy framework calculations complement the comparison of the two polymorphic forms of the miconazole drug.
PubMed: 38333136
DOI: 10.1107/S2056989024000276 -
Internal and Emergency Medicine Sep 2020
Topics: Humans; Male; Miconazole; Middle Aged; Pregnadienetriols; Pruritus; Tinea Pedis; Trichophyton
PubMed: 32200518
DOI: 10.1007/s11739-020-02311-5 -
The Journal of Antibiotics Jul 2024Antibiotic resistance is a major health problem worldwide. Pseudomonas aeruginosa is a Gram-negative pathogen with an arsenal of virulence factors and elevated...
Antibiotic resistance is a major health problem worldwide. Pseudomonas aeruginosa is a Gram-negative pathogen with an arsenal of virulence factors and elevated antimicrobial resistance. It is a leading cause of nosocomial infections with high morbidity and mortality. The significant time and effort required to develop new antibiotics can be circumvented using alternative therapeutic strategies, including anti-virulence targets. This study aimed to investigate the anti-virulence activity of the FDA-approved drugs miconazole and phenothiazine against P. aeruginosa. The phenotypic effect of sub-inhibitory concentrations of miconazole and phenothiazine on biofilm, pyocyanin, protease, rhamnolipid and hemolysin activities in PAO1 strain was examined. qRT-PCR was used to assess the effect of drugs on quorum-sensing genes that regulate virulence. Further, the anti-virulence potential of miconazole and phenothiazine was evaluated in silico and in vivo. Miconazole showed significant inhibition of Pseudomonas virulence by reducing biofilm-formation approximately 45-48%, hemolytic-activity by 59%, pyocyanin-production by 47-49%, rhamnolipid-activity by approximately 42-47% and protease activity by 36-40%. While, phenothiazine showed lower anti-virulence activity, it inhibited biofilm (31-35%), pyocyanin (37-39%), protease (32-40%), rhamnolipid (35-40%) and hemolytic activity (47-56%). Similarly, there was significantly reduced expression of RhlR, PqsR, LasI and LasR following treatment with miconazole, but less so with phenothiazine. In-silico analysis revealed that miconazole had higher binding affinity than phenothiazine to LasR, RhlR, and PqsR QS-proteins. Furthermore, there was 100% survival in mice injected with PAO1 treated with miconazole. In conclusion, miconazole and phenothiazine are promising anti-virulence agents for P. aeruginosa.
Topics: Pseudomonas aeruginosa; Quorum Sensing; Miconazole; Phenothiazines; Biofilms; Virulence; Anti-Bacterial Agents; Animals; Microbial Sensitivity Tests; Pyocyanine; Pseudomonas Infections; Virulence Factors; Mice; Molecular Docking Simulation; Glycolipids
PubMed: 38724627
DOI: 10.1038/s41429-024-00731-5 -
Environmental Toxicology Feb 2021Autophagy plays a dual function in cancer progression; autophagy activation can support cancer cell survival or contribute to cell death. Miconazole, a Food and Drug...
Autophagy plays a dual function in cancer progression; autophagy activation can support cancer cell survival or contribute to cell death. Miconazole, a Food and Drug Administration-approved antifungal drug, has been implicated in oncology research recently. Miconazole was found to exert antitumor effects in various tumors, including bladder cancer (BC). However, whether it provokes protective autophagy has been never discussed. We provide evidence that miconazole induces protective autophagy in BC for the first time. The results indicated that 1A/1B-light chain 3 (LC3)-II processing and p62 expression were elevated after miconazole exposure. Also, adenosine monophosphate-activated protein kinase phosphorylation was increased after miconazole treatment. We also confirmed the autophagy-promoting effect of miconazole in the presence of bafilomycin A1 (Baf A1). The result indicates that a combination treatment of miconazole and Baf A1 improved LC3-II processing, confirming that miconazole promoted autophagic flux. The acridine orange, Lysotracker, and cathepsin D staining results indicate that miconazole increased lysosome formation, revealing its autophagy-promoting function. Finally, miconazole and autophagy inhibitor 3-methyladenine cotreatment further reduced the cell viability and induced apoptosis in BC cells, proving that miconazole provokes protective autophagy in BC cells. Our findings approve that miconazole has an antitumor effect in promoting cell apoptosis; however, its function of protective autophagy is needed to be concerned in cancer treatment.
Topics: Apoptosis; Autophagy; Cell Line, Tumor; Cell Survival; Humans; Lysosomes; Macrolides; Miconazole; Microtubule-Associated Proteins; Phosphorylation; Protein Kinases; Urinary Bladder Neoplasms
PubMed: 32981224
DOI: 10.1002/tox.23024