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Scientific Reports Jun 2024Azole antifungal drugs are commonly used to treat vulvovaginal candidiasis (VVC). The nephrotoxicity and developmental toxicity of azole drugs have not been...
Azole antifungal drugs are commonly used to treat vulvovaginal candidiasis (VVC). The nephrotoxicity and developmental toxicity of azole drugs have not been systematically analyzed in the real world. We used the FDA Adverse Event Reporting System (FAERS) to investigate the adverse events (AEs) associated with imidazole therapy for VVC. FAERS data (from quarter 1 2004 to quarter 3 2022) were retrieved using OpenVigil 2.1, and AEs were retrieved and standardized according to the Medical Dictionary for Regulatory Activities (MedDRA). In the top 10 System Organ Class (SOC), all four drugs have been found to have kidney and urinary system diseases and pregnancy. We found significant signals, including clotrimazole [bladder transitional cell carcinoma, (report odds ratio, ROR = 291.66)], [fetal death, (ROR = 10.28)], ketoconazole[nephrogenic anemia (ROR = 22.1)], [premature rupture of membranes (ROR = 22.91 46.45, 11, 3)], Miconazole[hematuria (ROR = 19.03)], [neonatal sepsis (ROR = 123.71)], [spontaneous abortion (ROR = 5.98)], Econazole [acute kidney injury (ROR = 4.41)], [spontaneous abortion (ROR = 19.62)]. We also discovered new adverse reactions that were not reported. Therefore, when using imidazole drugs for treatment, it is necessary to closely monitor the patient's renal function, pay attention to the developmental toxicity of the fetus during pregnancy, and be aware of potential adverse reactions that may occur.
Topics: Female; Humans; Candidiasis, Vulvovaginal; Antifungal Agents; Imidazoles; United States; United States Food and Drug Administration; Adverse Drug Reaction Reporting Systems; Pregnancy; Adult; Drug-Related Side Effects and Adverse Reactions; Miconazole; Clotrimazole
PubMed: 38914572
DOI: 10.1038/s41598-024-63315-1 -
International Journal For Parasitology.... Jun 2024Cryptosporidium parvum is a waterborne and foodborne zoonotic protozoan parasite, a causative agent of moderate to severe diarrheal diseases in humans and animals....
Lower micromolar activity of the antifungal imidazoles on the bacterial-type bifunctional aldehyde/alcohol dehydrogenase (AdhE) in Cryptosporidium parvum and in vitro efficacy against the zoonotic parasite.
Cryptosporidium parvum is a waterborne and foodborne zoonotic protozoan parasite, a causative agent of moderate to severe diarrheal diseases in humans and animals. However, fully effective treatments are unavailable for medical and veterinary uses. There is a need to explore new drug targets for potential development of new therapeutics. Because C. parvum relies on anaerobic metabolism to produce ATP, fermentative enzymes in this parasite are attractive targets for exploration. In this study, we investigated the ethanol-fermentation in the parasite and characterized the basic biochemical features of a bacterial-type bifunctional aldehyde/alcohol dehydrogenase, namely CpAdhE. We also screened 3892 chemical entries from three libraries and identified 14 compounds showing >50% inhibition on the enzyme activity of CpAdhE. Intriguingly, antifungal imidazoles and unsaturated fatty acids are the two major chemical groups among the top hits. We further characterized the inhibitory kinetics of selected imidazoles and unsaturated fatty acids on CpAdhE. These compounds displayed lower micromolar activities on CpAdhE (i.e., IC values ranging from 0.88 to 11.02 μM for imidazoles and 8.93 to 35.33 μM for unsaturated fatty acids). Finally, we evaluated the in vitro anti-cryptosporidial efficacies and cytotoxicity of three imidazoles (i.e., tioconazole, miconazole and isoconazole). The three antifungal imidazoles exhibited lower micromolar efficacies against the growth of C. parvum in vitro (EC values ranging from 4.85 to 10.41 μM and selectivity indices ranging from 5.19 to 10.95). The results provide a proof-of-concept data to support that imidazoles are worth being further investigated for potential development of anti-cryptosporidial therapeutics.
PubMed: 38875756
DOI: 10.1016/j.ijpddr.2024.100551 -
International Medical Case Reports... 2024Erythema multiforme is a hypersensitivity reaction caused by various factors, such as viruses, chemicals, and drugs. Electronic cigarettes (e-cigarettes) or vape is a...
INTRODUCTION
Erythema multiforme is a hypersensitivity reaction caused by various factors, such as viruses, chemicals, and drugs. Electronic cigarettes (e-cigarettes) or vape is a battery-powered nicotine delivery device that substitutes for traditional cigarettes. The chemical components of vaping, including propylene glycol and nicotine, can cause hypersensitivity reactions.
OBJECTIVE
To report a case of oral erythema multiforme in an e-cigarettes user, treatment, and review the literature regarding the impact of these devices on oral health.
CLINICAL CASE
A 22-year-old woman came to the Oral Medicine Department with complaints of stomatitis causing pain, eating, and drinking difficulty, which started with fever and pimple-like on the lips. She was an active vape user for one year. Extraoral examination revealed no lesions on other body parts. The serosanguinolent crusts on the lips, an erosive area on the labial commissures and tended to bleed. Intraoral examination revealed white ulcers with yellowish edges and irregular, varying sizes in several parts of the oral mucosa. The anti-HSV-1 IgG laboratory results showed non-reactive, leading to a diagnosis of oral erythema multiforme. Management of oral conditions using 0.9% NaCl compress, dexamethasone mouthwash, and hyaluronic acid, applying 2% miconazole cream on labial commissures and vaseline album cream on the dry lips, and stopping vaping. Oral condition improved in a week of therapy.
CONCLUSION
Erythema multiforme restricted to the mouth is rare, especially associated with electronic cigarettes. Early identification of oral ulcerative disorders is crucial for accurate diagnosis and treatment, where clinicians should consider oral erythema multiforme as a possible diagnosis.
PubMed: 38828364
DOI: 10.2147/IMCRJ.S455640 -
BMC Infectious Diseases May 2024Oral candidiasis (OC) is a prevalent opportunistic infection in patients with human immunodeficiency virus (HIV) infection. The increasing resistance to antifungal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Oral candidiasis (OC) is a prevalent opportunistic infection in patients with human immunodeficiency virus (HIV) infection. The increasing resistance to antifungal agents in HIV-positive individuals suffering from OC raised concerns. Thus, this study aimed to investigate the prevalence of drug-resistant OC in HIV-positive patients.
METHODS
Pubmed, Web of Science, Scopus, and Embase databases were systematically searched for eligible articles up to November 30, 2023. Studies reporting resistance to antifungal agents in Candida species isolated from HIV-positive patients with OC were included. Baseline characteristics, clinical features, isolated Candida species, and antifungal resistance were independently extracted by two reviewers. The pooled prevalence with a 95% confidence interval (CI) was calculated using the random effect model or fixed effect model.
RESULTS
Out of the 1942 records, 25 studies consisting of 2564 Candida species entered the meta-analysis. The pooled prevalence of resistance to the antifungal agents was as follows: ketoconazole (25.5%, 95% CI: 15.1-35.8%), fluconazole (24.8%, 95% CI: 17.4-32.1%), 5-Flucytosine (22.9%, 95% CI: -13.7-59.6%), itraconazole (20.0%, 95% CI: 10.0-26.0%), voriconazole (20.0%, 95% CI: 1.9-38.0%), miconazole (15.0%, 95% CI: 5.1-26.0%), clotrimazole (13.4%, 95% CI: 2.3-24.5%), nystatin (4.9%, 95% CI: -0.05-10.3%), amphotericin B (2.9%, 95% CI: 0.5-5.3%), and caspofungin (0.1%, 95% CI: -0.3-0.6%). Furthermore, there were high heterogeneities among almost all included studies regarding the resistance to different antifungal agents (I > 50.00%, P < 0.01), except for caspofungin (I = 0.00%, P = 0.65).
CONCLUSIONS
Our research revealed that a significant number of Candida species found in HIV-positive patients with OC were resistant to azoles and 5-fluocytosine. However, most of the isolates were susceptible to nystatin, amphotericin B, and caspofungin. This suggests that initial treatments for OC, such as azoles, may not be effective. In such cases, healthcare providers may need to consider prescribing alternative treatments like polyenes and caspofungin.
REGISTRATION
The study protocol was registered in the International Prospective Register of Systematic Reviews as PROSPERO (Number: CRD42024497963).
Topics: Humans; Candidiasis, Oral; Antifungal Agents; HIV Infections; Drug Resistance, Fungal; Candida; Prevalence; Microbial Sensitivity Tests; AIDS-Related Opportunistic Infections; Fluconazole
PubMed: 38822256
DOI: 10.1186/s12879-024-09442-6 -
Plant Disease May 2024Pepper ( L.) is a popular vegetable and condiment consumed around the world. In the Guizhou Province of China, peppers are the most commonly grown crop on 300,000...
Pepper ( L.) is a popular vegetable and condiment consumed around the world. In the Guizhou Province of China, peppers are the most commonly grown crop on 300,000 planted hectares. A variety of diseases routinely occur on peppers in this province, resulting in yield losses (Liu et al., 2022). Root rot is one of the most common symptoms and produces poor root growth and wilting of pepper. In April 2023, symptomatic pepper plants displaying stunting, dwarfism, wilting, and root browning were collected from five fields in Guizhou, with disease incidence ranging from 10% to 20%. The collected rotten roots were cleaned with sterilize distilled water and placed in selective V8 juice agar (V8A) medium (15% clarified V8 juice with 2.5 g/L CaCO and 2% agar) containing nystatin, ampicillin, rifampicin, and miconazole, and incubated at 25℃ for 1 to 2 days (Morita and Tojo, 2007). Eight isolates with similar colony morphology were transferred to V8A medium via hyphal tipping, and incubated at 25℃ in the dark. Colony and sexual structures were observed using a microscope. Mycelium was aseptate and formed white cottony colonies. Globose, intercalary, or terminal hyphal swellings were observed with a diameter of 20.5 to 25 µm (average: 22 µm), and aplerotic oospores had a diameter of 15 to 20 µm (average: 17.5 µm) with a wall thickness of approximately 2 µm. Three representative isolates HSLJ-3, LJG-1, and LJY-2 were chosen for further molecular identification. Sequences of the internal transcribed spacer (ITS) and mitochondrial cytochrome c oxidase subunit 1 () genes were identified using primer sets ITS4/ITS5 (White et al., 1990) and OomCoxI-Levup/OomCoxI-Levlo (Robideau et al., 2011), respectively. All sequences were deposited in GenBank (accession nos. OR554005, PP083310, and PP083420 for ITS, and OR529247, PP093821 and PP093822 for ). BLAST analysis revealed all ITS and sequences exhibited 100% identity with () isolate BR850 (GenBank accession nos. HQ643892.1 and HQ708933.1 for ITS and , respectively). Phylogenetic analysis was performed by the maximum-likelihood method on the CIPRES web portal (https://www.phylo.org/portal2/login!input.action, accessed on 9 January 2024). For pathogenicity tests, each isolate was cultured in V8A medium containing 50 autoclaved wheat seeds at 25℃ for 7 days. Budding pepper seedling (cv. Huaxi) was transplanted into a 0.4 L pot containing sterilized commercial potting mix (Seedling Cultivation Substrate, Hunan Xianghui Agricultural E-commerce Co., Ltd.) which was saturated with deionized water. Eight infected and non-infected wheat seeds were placed near the roots of five pepper seedlings, respectively. Plants were placed in an artificial climate chamber, with a 14 h photoperiod and approximately 75% relative humidity at 25℃. After 14 days, inoculated seedlings showed symptoms of stunting, wilting, and rotting roots similar to those observed in the field. No disease was observed on the non-inoculated control plants. The pathogen was isolated from infected pepper roots and confirmed as by morphological and molecular analyses as previously described. This is the first report of causing root rot on pepper in Guizhou, China. This finding is critical to the discover of treatment options for this pathogen, thereby improving management practices to reduce yield losses in pepper.
PubMed: 38812366
DOI: 10.1094/PDIS-01-24-0127-PDN -
In Vivo Evaluation of Miconazole-Nitrate-Loaded Transethosomal Gel Using a Rat Model Infected with .Pharmaceuticals (Basel, Switzerland) Apr 2024Miconazole nitrate (MCNR), an antifungal drug, is used to treat superficial infections. The objective of the current study was to assess the antifungal effectiveness of...
Miconazole nitrate (MCNR), an antifungal drug, is used to treat superficial infections. The objective of the current study was to assess the antifungal effectiveness of MCNR-loaded transethosomal gel (MNTG) against in an in vivo rat model. The outcomes were compared with those of the miconazole nitrate gel (MNG) and marketed Daktarin cream (2%) based on histopathological and hematological studies. The results of the skin irritation test revealed the safety profile of the MNTG. The MNTG demonstrated the greatest antifungal activity in the histological analysis and the visible restoration of the skin, and the rats revealed an apparent evidence of recovery. Compared to the untreated group, the treated group's lymphocyte and white blood cells counts increased, but their eosinophil counts decreased. In conclusion, MNTG exhibited the greatest antifungal activity, which might be connected to the improved skin permeability of the transethosome's nanosized vesicles. Therefore, it could be considered a promising carrier for topical usage and the treatment of cutaneous candidiasis. More clinical research needs to be performed in order to demonstrate its effectiveness and safe usage in humans.
PubMed: 38794118
DOI: 10.3390/ph17050546 -
Molecules (Basel, Switzerland) May 2024The theoretical interpretation of the vaginal permeability phenomenon, the evaluation of the suitability of five artificial membranes, and the prediction of the... (Comparative Study)
Comparative Study
The theoretical interpretation of the vaginal permeability phenomenon, the evaluation of the suitability of five artificial membranes, and the prediction of the behaviors of vaginal drugs were the main objectives of this study. Franz vertical diffusion cells and different validated HPLC methods were used to measure the permeability of six vaginally administered drugs (econazole, miconazole, metronidazole, clindamycin, lidocaine, and nonoxynol-9). This study was performed (in vitro) on different membranes of polyvinylidene fluoride (PVDF), plain cellulose or cellulose impregnated with isopropyl myristate (IPM), and cellulose combined with PVDF or IPM. The results were compared with those obtained from cow vaginal tissue (ex vivo), where cellulose was proven to be the best simulant. According to the permeability profiles (P), the water solubility of the drugs was considered a necessary criterion for their transport in the membranes or in the tissue, while the size was important for their penetration. Furthermore, it was found that polar compounds show clear superiority when penetrating cellulose or tissue, while non-polar ones show superiority when penetrating the lipophilic PVDF membrane. Finally, a successful attempt was made to predict the P values (|P-predP| < 0.005) of the six drugs under study based on a PLS (Partial Least Squares) in silico simulation model.
Topics: Female; Membranes, Artificial; Vagina; Permeability; Administration, Intravaginal; Animals; Polyvinyls; Cellulose; Cattle; Humans; Solubility; Fluorocarbon Polymers
PubMed: 38792194
DOI: 10.3390/molecules29102334 -
International Journal of Molecular... May 2024Melanoma, arguably the deadliest form of skin cancer, is responsible for the majority of skin-cancer-related fatalities. Innovative strategies concentrate on new...
Melanoma, arguably the deadliest form of skin cancer, is responsible for the majority of skin-cancer-related fatalities. Innovative strategies concentrate on new therapies that avoid the undesirable effects of pharmacological or medical treatment. This article discusses the chemical structures of [(MTZ)AgNO], [(MTZ)Ag]SO, [Ag(MCZ)NO], [Ag(MCZ)BF], [Ag(MCZ)SbF] and [Ag(MCZ)ClO] (MTZ-metronidazole; MCZ-miconazole) silver(I) compounds and the possible relationship between the molecules and their cytostatic activity against melanoma cells. Molecular Hirshfeld surface analysis and computational methods were used to examine the possible association between the structure and anticancer activity of the silver(I) complexes and compare the cytotoxicity of the silver(I) complexes of metronidazole and miconazole with that of silver(I) nitrate, cisplatin, metronidazole and miconazole complexes against A375 and BJ cells. Additionally, these preliminary biological studies found the greatest IC values against the A375 line were demonstrated by [Ag(MCZ)NO] and [(MTZ)AgNO]. The compound [(MTZ)AgNO] was three-fold more toxic to the A375 cells than the reference (cisplatin) and 15 times more cytotoxic against the A375 cells than the normal BJ cells. Complexes of metronidazole with Ag(I) are considered biocompatible at a concentration below 50 µmol/L.
Topics: Humans; Melanoma; Miconazole; Silver; Antineoplastic Agents; Metronidazole; Cell Line, Tumor; Coordination Complexes; Cell Survival; Skin Neoplasms
PubMed: 38791121
DOI: 10.3390/ijms25105081 -
Antibiotics (Basel, Switzerland) May 2024(1) Background: Although accounts for the majority of fungal infections, therapeutic options are limited and require alternative antifungal agents with new targets; (2)...
(1) Background: Although accounts for the majority of fungal infections, therapeutic options are limited and require alternative antifungal agents with new targets; (2) Methods: A biofilm formation assay with RPMI1640 medium was performed with extract. A combination antifungal assay, dimorphic transition assay, and adhesion assay were performed under the biofilm formation condition to determine the anti-biofilm formation effect. qRT-PCR analysis was accomplished to confirm changes in gene expression; (3) Results: extract significantly reduces biofilm formation by 51.65% at 1.56 μg/mL use and therefore increases susceptibility to miconazole. extract also inhibited the dimorphic transition of Candida; nearly 50% of the transition was inhibited when 1.56 μg/mL of the extract was treated. The extract of inhibited the expression of genes related to hyphal development and extracellular matrix of 34.4% and 36.0%, respectively, as well as genes within the Ras1-cAMP-PKA, Cph2-Tec1, and MAP kinase signaling pathways of 25.58%, 7.1% and 15.8%, respectively, at 1.56 μg/mL of extract treatment; (4) Conclusions: extract significantly reduced Candida biofilm formation, which lead to induced antifungal susceptibility to miconazole. It suggests that extract is a promising anti-biofilm candidate of since the biofilm formation of is an excellent target for candidiasis regulation.
PubMed: 38786162
DOI: 10.3390/antibiotics13050434 -
Molecules (Basel, Switzerland) May 2024The main objective of this study was to investigate the metabolism of miconazole, an azole antifungal drug. Miconazole was subjected to incubation with human liver...
Identification of New Hepatic Metabolites of Miconazole by Biological and Electrochemical Methods Using Ultra-High-Performance Liquid Chromatography Combined with High-Resolution Mass Spectrometry.
The main objective of this study was to investigate the metabolism of miconazole, an azole antifungal drug. Miconazole was subjected to incubation with human liver microsomes (HLM) to mimic phase I metabolism reactions for the first time. Employing a combination of an HLM assay and UHPLC-HRMS analysis enabled the identification of seven metabolites of miconazole, undescribed so far. Throughout the incubation with HLM, miconazole underwent biotransformation reactions including hydroxylation of the benzene ring and oxidation of the imidazole moiety, along with its subsequent degradation. Additionally, based on the obtained results, screen-printed electrodes (SPEs) were optimized to simulate the same biotransformation reactions, by the use of a simple, fast, and cheap electrochemical method. The potential toxicity of the identified metabolites was assessed using various in silico models.
Topics: Miconazole; Humans; Chromatography, High Pressure Liquid; Microsomes, Liver; Mass Spectrometry; Electrochemical Techniques; Antifungal Agents; Biotransformation
PubMed: 38731651
DOI: 10.3390/molecules29092160