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Background. Lungs are the target organs most affected by ischemia/reperfusion (I/R) injury, which is exacerbated when hemorrhagic shock occurs. Suppressing various proinflammatory cytokines, inflammation and oxidation that initiate and aggravate lung damage with various drugs or methods provides significant benefits in preventing lung damage. Objectives. This study aims to evaluate the protective effect of clotrimazole (CLT), an antimycotic drug, on lung injury and systemic inflammatory response in rats by creating an experimental model of a ruptured abdominal aortic aneurysm (RAAA). Materials and methods. Thirty-six male Sprague Dawley rats were randomly divided into 5 groups: sham, sham+CLT, sham+polyethylene glycol (PEG), shock+ischemia/reperfusion (SIR), and SIR+CLT. Saline, CLT and PEG were administered in the sham groups without shock and I/R. The hemorrhagic shock was developed in SIR groups by drawing blood for 1 h to keep the mean arterial pressure at 50 mm Hg. After 60 min, the SIR+CLT group was given 20 mg/kg CLT; then, the aortic clamps were opened, and rats were left for 120 min of reperfusion. The blood taken to create hemorrhagic shock was returned in a controlled manner during this time. At the end of the reperfusion procedure, samples were taken for cytokine levels in serum and lung tissue and for other biochemical analyses. Blood gas, histopathological examination and wet/dry weight measurements were performed to assess lung injury. Results. An increase was observed in all parameters in the SIR group compared to the sham group. In the SIR+CLT group, the serum myeloperoxidase (MPO), tumor necrosis factor alpha (TNF-α), lung MPO values, histologically lung injury scores, and lung tissue wet/dry ratio were decreased significantly when compared to the SIR group (p < 0.05). Conclusions. These results indicate that CLT may reduce the systemic inflammatory response and lung injury due to shock and I/R in an experimental model of RAAA. [ABSTRACT FROM AUTHOR]

Although the mitochondrial genome is an attribute of all eukaryotes, some yeast species (called petite-positive) can replicate without mitochondrial DNA (mtDNA). Strains without mtDNA (known as rho− mutants or petite mutants) are respiration-deficient and require fermentable carbon sources (such as glucose) for their metabolism. However, they are compromised in many aspects of fitness and competitiveness. Nevertheless, a few research groups have reported that some petite mutants of Candida glabrata and Saccharomyces cerevisiae manifested higher levels of tolerance to the antifungal fluconazole than their wild-type (WT) counterparts. In this study, we show that elevated tolerance to two or three out of four tested antifungals is a generic feature of at least five petite-positive species of yeasts including C. glabrata (higher tolerance of petites to clotrimazole and miconazole), S. bayanus (tolerance to clotrimazole, fluconazole, and miconazole), S. cerevisiae (tolerance to clotrimazole and fluconazole), S. paradoxus (tolerance to clotrimazole, fluconazole, and miconazole), and S. pastorianus (tolerance to clotrimazole and fluconazole). Comparing the levels of tolerance to the antifungals in WT and petite mutants was based on measuring the diameters of the zones of inhibition (ZOIs) using disc diffusion assays. The mode of inhibition in the majority of WT strains by all antifungals was fungicidal; most of the rho− mutants manifested fungistatic inhibition. We observed partial (not complete) inhibition in WT, with four different types of ZOI patterns that were species- and antifungal-specific. The partial inhibition was characterised by the presence of antifungal-tolerant colonies within ZOI areas. The inability of these colonies selected from ZOIs to grow on glycerol, as a single source of carbon, proved that they were rho− mutants spontaneously generated in the WT populations. The results on the elevated tolerance of petite strains to antifungals are discussed in terms of the prospective positive selection of respiratory-deficient mutants and the various implications of such selection. [ABSTRACT FROM AUTHOR]

A large part of the global population, including both immunocompromised and healthy individuals, suffers from fungal infections. The majority of current drug candidates for treating fungal infections exhibit poor water solubility, which hampers their permeability through biological barriers and limits their bioavailability. Here, we fabricated pea protein isolate (PPI)/poly-(ethylene oxide) nanofibers (PPI/PEO nanofibers), with a high protein content [65% (w/w)] by waterborne electrospinning as an eco-friendly drug delivery system. X-ray diffraction results demonstrated that the solid-state properties of the individual components (PPI and PEO) were retained in the PPI/PEO nanofibers. We then encapsulated the poorly water-soluble drug, clotrimazole (CTZ), in the nanofibers (PPI/PEO/CTZ nanofibers), without heat treatment and/or use of an organic solvent or surfactant to presolubilize CTZ, generating an antifungal delivery system for topical administration. An in vitro study demonstrated that CTZ was successfully loaded in and released from the nanofibers. Additionally, the nanofibers were not toxic to HeLa cells. Finally, based on an antifungal disc agar diffusion study, CTZ-loaded nanofibers were shown to be effective against Candida albicans. The overall results demonstrate the potential of PPI-based nanofibers as a green platform for the generation of CTZ-loaded efficient drug delivery systems for antifungal treatment. [ABSTRACT FROM AUTHOR]

To compare the efficacy of gel foam-soaked pyodine with a single topical application of clotrimazole ointment in the treatment of otomycosis. This randomized controlled trial included 90 patients who presented to ENT OPD with complaints of earache, watery ear discharge, pruritis, and ear blockage and were clinically diagnosed as a case of otomycosis via otoscopy. The external auditory canal of the patient was cleared of fungal debris via suction before treatment. In Group A, the ear canal was filled with 1% clotrimazole ointment by using an IV catheter and syringe and in Group B 10% pyodine-soaked gel foam was placed in the external auditory canal. The patients were followed up on post-treatment days 7 and 14. The results showed that out of 90 patients with otomycosis, the left ear was affected in 50(55.6%) patients and the right ear in 40(44.4%). 8(8.9%) of 90 patients had controlled preexisting diabetes mellitus. On the 7th post-treatment follow-up day, 17 (41.5%) patients in Group A and 28(66.7%) patients in Group B showed no fungal spores. Other symptom resolution was also comparable in both groups. At the 14th day follow-up 33(80.5%) patients in Group A and 38(92.7% patients in Group B showed no fungal hyphae on otoscopy. In terms of treatment response 19(46.34%) patients in Group A and 21(51.21%) patients in Group B showed good treatment response at the end of 2nd post-treatment week with a p-value of 0.798. yodine-soaked gel foam placement in the external auditory canal is a safe and effective method for the treatment of otomycosis with the efficiency of this method comparable to a single topical clotrimazole ointment application. [ABSTRACT FROM AUTHOR]

Background/objectives: Topically applied antifungal agents can induce adverse effects, such as pain and irritation. The transient receptor potential (TRP) channels—TRPA1 and TRPV1—mainly expressed in sensory neurons, act as sensors for detecting irritants. This study aims to evaluate the involvement of nociceptive channels in topical antifungal‐induced pain and irritation. We tested nine topical antifungals belonging five classes: isoconazole, econazole, miconazole, clotrimazole, and ketoconazole as imidazoles; liranaftate as a thiocarbamate; terbinafine as an allylamine; amorolfine as a morpholine; and butenafine as a benzylamine. Methods: Intracellular calcium concentrations ([Ca2+]i) and membrane currents in response to antifungals were measured to estimate channel activity using heterologously expressing cells and isolated mouse sensory neurons. Results: In mouse TRPA1‐expressing cells, all the tested drugs induced an increase in [Ca2+]i, which was abrogated or reduced by a TRPA1 blocker. Although many drugs evoked the TRPA1‐nonspecific [Ca2+]i response at high concentrations, responses to clotrimazole, ketoconazole, and liranaftate were TRPA1 specific and elicited current responses in TRPA1‐expressing cells. In mouse TRPV1‐expressing cells, clotrimazole and ketoconazole elicited [Ca2+]i and current responses. In mouse sensory neurons, liranaftate‐induced increase in [Ca2+]i was abrogated by a TRPA1 blocker and Trpa1 deletion. Responses to ketoconazole were inhibited by TRPA1 and TRPV1 blockers and by the genetic deletion of either channel. Conclusion: These results suggest that topical antifungal‐induced pain and irritation are attributable to the activation of nociceptive TRPA1 and/or TRPV1 channel/s. Consequently, caution should be exercised in the use of topical antifungals with symptoms of pain. [ABSTRACT FROM AUTHOR]

Vulvovaginal candidiasis (VVC) is a prevalent gynecological infection characterized by high incidence and recurrent episodes, causing significant distress in women. This study aims to assess the effectiveness of different clotrimazole and fluconazole treatment regimens for severe vulvovaginal candidiasis (SVVC). A retrospective analysis was conducted on 1303 cases of SVVC among first-time visitors to the gynecology outpatient department at Peking University Shenzhen Hospital between January 2013 and December 2022. Vaginal secretions were systematically collected for fungal culture, with species identification conducted using Chromogenic culture medium and API Candida test reagents. Mycological cure rates were assessed at days 7–14, days 25–35, and day 35 to 6 months after treatment. The three-dose clotrimazole regimen demonstrated significantly higher mycological cure rates (85.7%, 80.0% and 74.6% at three follow-up periods, respectively) compared to the two-dose clotrimazole regimen (76.0%, 61.6%, and 59.8%, all P < 0.05). The three-dose fluconazole regimen showed no significant difference to three-dose clotrimazole regimen, with cure rates of 82.8%, 79.3%, and 75.9% (all P > 0.05). The two-dose fluconazole regimen had cure rates of 74.3%, 56.4% and 51.1%, with no significant difference from two-dose clotrimazole regimen at days 7–14 and 25–35, but lower than three-dose fluconazole regimen at days 25–35 and 35 to 6 months. The three-dose clotrimazole regimen demonstrated higher cure rates in Candida albicans and non-albicans Candida SVVC cases than two-dose regimen. These findings suggest that three-dose antifungal regimens may be more efficacious than two-dose regimens for SVVC. The three-dose clotrimazole regimen could serve as a promising alternative for SVVC management. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to compare the antifungal efficacy of Ganoderma lucidum (G. lucidum) and clotrimazole for treatment of denture stomatitis (DS). Materials and Methods: This double-blind randomized clinical trial was conducted on 50 patients with DS types I and II assigned to two groups (N=25). In the first group, G. lucidum extract was administered in the form of 5% gel while 1% clotrimazole gel was prescribed for the second group. Pain intensity according to the visual analog scale (VAS), and the percentage of DS recovery based on the Budtz-Jorgenson index were evaluated and recorded after 7 and 14 days. Data were analyzed using the Chi-square test, independent samples t-test, repeated measures ANOVA, and logistic regression (alpha=0.05). Results: The percentage of complete recovery on day 7 in the G. lucidum group (28%) was higher than that in the clotrimazole group (16%) but not significantly (P=0.592). Not wearing dentures overnight significantly increased the odds of recovery by 6.56 times, while the odds of recovery decreased by 0.03 times in DS type II, as compared to DS type I (P= 0.009). Conclusion: No significant difference existed between the antifungal efficacy of G. lucidum and clotrimazole for clinical treatment of DS. Thus, Ganoderma may be regarded as an alternative treatment, especially in patients' resistant to azoles. Nonetheless, further clinical studies are required to shed more light on this topic. [ABSTRACT FROM AUTHOR]

Abstract Clotrimazole 1% and Mycozin vaginal cream have been reported to be effective in relieving the symptoms of vulvovaginitis caused by Candida. The resistance to azole compounds, and the side effects of chemical drugs have been reported following azole therapy. It was hypothesized that Mycozin is at least as effective as Clotrimazole in treating vaginal candidiasis. This equivalent, triple-blinded, randomized clinical trial was conducted on 126 patients who complained of vaginal itching referred to Al-Zahra Teaching Hospital, Tabriz, Iran between September 2023 and May 2024. Participants were divided into two groups, i.e., Mycozin (n = 64) and Clotrimazole 1% (n = 62), using the block randomization method. The patient's complaints, clinical signs, the pH and culture of the secretions was recorded before and after treatment. The patient's improvement, level of satisfaction, and side effects were recorded. The data were analyzed using Pearson chi-square test, ANCOVA, and Mann–Whitney U test. There was no statistically significant difference between the two groups regarding the mean pH (Adjusted mean difference: 0.01; 95% Confidence Interval (CI): −0.20 to 0.21, P = 0.965), and microscopic evaluation (Odds Ratio (OR): 0.61; 95% CI; 0.28 to 1.36, P = 0.230). After the treatment the frequency of itching in the Clotrimazole group (N = 13; 22.0%) was lower than that of the Mycozin group (N = 26; 43.3%) (OR: 0.37; 95% CI: 0.17 to 0.82; P = 0.013). There was no statistically significant difference in other symptoms and signs before and after the treatment (P > 0.05). Also, there was no statistically significant difference between the two groups in the level of satisfaction (P = 0.056) and patient improvement (P = 0.074). The side effects of treatment with Mycozin and Clotrimazole were observed in eleven and five patients, respectively. Considering the efficacy of Mycozin vaginal cream in eliminating most of the symptoms and signs associated with vaginal candidiasis and its positive effect in negating the results of culture, it can be used as a suitable alternative in the treatment of vaginal candidiasis in patients interested in herbal medicines and resistant to azole compounds. Trial registration: Iranian Registry of Clinical Trials (IRCT): IRCT20120718010324N77. Date of registration: 20/05/2023; URL: https://irct.behdasht.gov.ir/user/trial/68718/view ; Date of first registration: 31/05/2023.

Aims Vulvovaginal candidiasis (VVC) is a prevalent condition affecting a significant proportion of women worldwide, with recurrent episodes leading to detrimental effects on quality of life. While treatment with clotrimazole is common, the specific alterations it evokes in the vaginal bacteriome and metabolome were previously underexplored. Methods and results In this prospective study, we enrolled reproductive-age women diagnosed with single VVC and conducted comprehensive analyses of vaginal fungi, bacteriome, and metabolome before and after local clotrimazole treatment. We observed a significant reduction in Candida albicans and notable improvements in vaginal cleanliness. Advanced sequencing revealed substantial shifts in the vaginal bacteriome, with an increase in Lactobacillus -dominant communities post-treatment. Our findings identified 17 differentially abundant bacterial species, including notable decreases in pathogenic anaerobes such as Gardnerella vaginalis, Dialister micraerophilus , and Aerococcus christensenii , suggesting a restoration of a healthier microbial balance. Furthermore, metabolomic analysis revealed significant changes in 230 metabolites, particularly within lipid metabolism pathways, with marked downregulation of lipid-related compounds linked to inflammation. Correlation studies indicated a strong interplay between lipid metabolites and specific bacterial species, emphasizing the influence of clotrimazole treatment on microbial and metabolic interactions. Importantly, predictive models using microbiota and metabolite signatures demonstrated high accuracy in distinguishing pre- and post-treatment states. Conclusions This research highlights clotrimazole's dual role in effectively clearing Candida infection and promoting a healthier vaginal microenvironment, paving the way for novel microbial and metabolomic-based diagnostic approaches to enhance VVC management and understand its underlying mechanisms. [ABSTRACT FROM AUTHOR]

Introduction A rise in tinea cruris among Thai Naval Cadets has been observed. Clotrimazole powder has been shown to be effective as an adjunct treatment for tinea cruris; however, its efficacy as a monotherapy is limited. Objectives The aim is to determine the efficacy of 1% clotrimazole cream versus 1% clotrimazole powder in treating tinea cruris. Material and Methods A randomized trial was conducted at the Thai Naval Rating School, Chonburi, Thailand. Naval rating cadets with suspected tinea cruris were randomly assigned to one of two groups: 1% clotrimazole cream or 1% clotrimazole powder, and they were instructed to apply the related medication to the affected lesion twice daily for 4 weeks. Clinical and symptomatic evaluations were carried out at 4 and 8 weeks. Results All 17 and 14 participants who received 1% clotrimazole cream and powder, respectively, were included. After 4 weeks, the clinical cure rates were 76.5% in the cream group and 85.7% in the powder group (P  = .664). All participants were clinically cured within 8 weeks. The self-evaluation of itch severity using a visual analog scale (VAS) revealed no significant difference between the two groups (P  = .343). The dermatology quality of life index decreased as clinical improvement was achieved in both the clotrimazole cream and powder groups (6.0 vs. 7.5 score reductions, respectively; P  = .765). The score for sweat reduction was higher in the 1% clotrimazole powder group compared to the cream group (5.0 vs. 4.0, respectively; P  = .006). Conclusion Monotherapy with 1% clotrimazole powder showed comparable efficacy to 1% clotrimazole cream. Furthermore, the powder treatment reduced sweat more effectively compared to the cream. [ABSTRACT FROM AUTHOR]

This review examined the current state of knowledge on the modifications of commercial soft lining materials (SLMs) with a variety of antifungal compounds: (i) polyene antibiotics, including nystatin and amphotericin B, (ii) azole drugs, including fluconazole, itraconazole, clotrimazole, ketoconazole, and miconazole, and (iii) antiseptics, including chlorhexidine salts to give them anti-Candida albicans properties. The effect of such modifications on the SLMs' physical properties, such as drug release, water sorption, surface properties, bond strength, tensile strength, and hardness, was also analyzed. In effect, this study provided a unique compilation of research results obtained for numerous properties of SLM modified with antifungal compounds that differ in their chemical structure and mechanism of antifungal action. These results might also be useful for prosthetic dentistry, where SLMs are used to prevent and treat candidiasis, the most common disease among denture wearers. [ABSTRACT FROM AUTHOR]

Vaginal candidiasis poses significant health concerns that affect approximately 75% of women globally and often leads to discomfort and a decrease in quality of life. Traditional treatments, despite their effectiveness, may cause discomfort and adverse effects, such as vaginal discharge, bleeding, and dryness, promoting the exploration of alternative formulations. In this study, we aimed to develop a novel therapeutic approach for the treatment of vaginal candidiasis utilizing oleic acid containing emulgels made from thermoresponsive poloxamer-based hydrogels. These emulgels were designed to provide a sustained release of clotrimazole, an antifungal agent. Incorporating oleic acid enhanced the drug's solubility and contributed to vaginal health. The formulations were characterized by their rheological properties, in vitro release, mucoadhesion, and spreadability. We conducted rheological measurements on the hydrogels that served as the base for the emulgels, as well as on the emulgels themselves. The emulgels exhibited continuous rheological behavior with changing temperatures, making them suitable for storage at room temperature. With an increasing HPMC content, we achieved enhanced mucoadhesion, which is beneficial for formulations used in body cavities. Moreover, in vitro release studies revealed sustained drug release profiles, which can be adjusted by varying the ratios of poloxamers and HPMC. These findings suggest that the developed emulgels offer a promising therapeutic option for vaginal candidiasis, addressing both the symptoms and the treatment of discomfort. [ABSTRACT FROM AUTHOR]

The aim of this study was to prepare vaginal suppositories with mucoadhesive properties to prolong the action of antifungal component clotrimazole (CLO). This was achieved by preparing vaginal pessaries on a hydrophilic gel base composed of gelatin and gelatin enriched with PEG 400 (in a 1:1 ratio), and then checking the properties of the obtained vaginal drugs. The prepared globules, containing 100 mg of CLO, were characterized in terms of mass and swelling index, organoleptic analysis was also prepared. In addition, a texture analysis and a study of the dissolution of clotrimazole were performed. On the basis of the obtained results, it was concluded that the modification of the composition of the gelatin–glycerin base by the addition of macrogol had a positive effect on the mucoadhesive properties of the globules. In addition, due to the presence of PEG 400, the globules were stiffer. It was also observed that the presence of CLO reduces the value of the force needed for compression during the texture analysis study. Comparing the CLO release profiles of the prepared globules and commercially available clotrimazole tablets, the release profile for the globules was slower than for the tablets, which indicates the possibility of using mucoadhesive globules as a form of a drug that releases the medicinal substance more slowly at the site of administration. [ABSTRACT FROM AUTHOR]

Aim: This study focuses on developing and evaluating a transferosomal gel containing clotrimazole and miconazole nitrate, antifungal medications used to treat fungal infections, including superficial tinea and nail infections. Materials and Methods: The MI-CTM transferosomes were created using rotary film evaporation and optimized using the Box-Behnken statistical design. They were evaluated for drug concentration, viscosity, Spreadability, pH, and in vitro release kinetics after being embedded in a Carbopol 934 gel. Results: Particle sizes ranging from 145±0.604 nm to 760±0.684 nm and a zeta potential ranging from -2.8 to -41.8, the produced MIC transferosomes exhibited a high EE% ranging from 15.6±0.66%) to (80.25±1.85%). Transferosomes' surface morphology was assessed using a scanning electron microscope, and it was discovered that the vesicles had a spherical form. A 24 hr in vitro release study was conducted for the optimized formulation, showing improved drug release of 86.94% and 89.87% CDR for clotrimazole and miconazole nitrate, respectively. After conducting a kinetic release research, the formulation for miconazole nitrate and the clotrimazole medication followed the non-Fickian transport mechanism described by Peppas and first order kinetics, respectively. There was no noticeable deterioration of the medication based on the stability data, which included no appreciable changes in pH, drug content, or cumulative percentage drug release. Conclusion: Miconazole nitrate and clotrimazole in transferosomal gel, thus, increase medication application frequency while simultaneously enhancing patient compliance. [ABSTRACT FROM AUTHOR]

Objective • To evaluate the impact of clotrimazole suppositories on the distribution of vaginal pathogens and oxidative stress in patients with vaginitis. Methods • A total of 120 patients with vaginitis were recruited from our hospital between January 2021 and December 2022 and were divided into an observation group and a control group using a random envelope method. The control group received treatment with miconazole tablets alone, while the observation group received combined treatment with miconazole tablets and clotrimazole suppositories. Vaginal secretions were collected from the subjects for pathogenic microbial testing. The clinical efficacy of the patients was evaluated, and indicators related to vaginal microecology and microbial imbalance were examined. Serum levels of IL-8, CRP, TNF-α, IL-6, PCT, P, LH, FSH, SOD, MDA, NO, and ET-1 were measured in the subjects. Results • Among patients with vaginitis, bacteria, fungi, and gram-negative cocci accounted for a relatively high proportion, with bacterial infections accounting for more than 30% and fungal and gram-negative cocci infections both exceeding 10%. Pathogenic infections such as Chlamydia and Trichomonas were less than 10%. The observation group showed significantly higher clinical efficacy compared to the control group, with a statistically significant difference (P < .05). Following treatment, the observation group exhibited significantly lower scores for itching, vaginal discharge, and burning sensation compared to the control group, with a statistically significant difference (P < .05). After treatment, the observation group had significantly lower bacterial density and Nugent score, higher cleanliness, positive lactobacilli rate, and pH value compared to the control group, and the difference was statistically significant (P < .05). After treatment, the observation group demonstrated significantly lower blood levels of IL-8, CRP, TNF-α, IL-6, and PCT compared to the control group, with a statistical significance of P < .05. Similarly, the levels of P, LH, and FSH hormones in the observation group were significantly lower than those in the control group, also with a statistical significance of P < .05. In contrast, the levels of SOD and NO in the observation group were significantly higher, while the levels of MDA and ET-1 were significantly lower compared to the control group, with a statistical significance of P < .05. Conclusion • Clotrimazole suppositories have been shown to significantly enhance therapeutic outcomes for patients with vaginitis by alleviating inflammation, rebalancing vaginal microecology, regulating hormone secretion, and mitigating oxidative stress. [ABSTRACT FROM AUTHOR]

Purpose: Candida vaginitis is widely prevalent worldwide and is one of the common gynecological disorders. The aim of this study is to analyze the sensitivity of recurrent vulvovaginal (RVVC) candidiasis to antifungal drugs and its relationship with vaginal microbiota. Patients and Methods: We Isolated and cultured Candida from RVVC patients, mass spectrometry and broth microdilution method were used to identify and determine MIC values of antifungal drugs. Clinical medical records and vaginal microbiota of RVVC patients were also collected. Results: The main pathogens causing RVVC are predominantly Candida albicans (70.26%), but in recent years, there has been an increasing proportion of Candida glabrata(24.46%). However, only 15.70% of Candida albicans were sensitive to Voriconazole, 35.84% to Fluconazole and 25.60% to Itraconazole. No fluconazole-resistant Candida glabrata was found. Most Candida krusei strains were sensitive to voriconazole (81.80%). More important MIC values of triazoles were increased in Candida species, when exposed to clotrimazole. In addition, we found that the vaginal microecology of candida vaginitis and bacterial vaginitis was significantly different. Conclusion: Triazoles resistant Candida species have emerged, leading to the failure of empirical anti-infective therapy. At the same time, the vaginal microecology of candida vaginitis and bacterial vaginitis was significantly different. In addition, a new breakpoint for Candida from RVVC needs to be established. [ABSTRACT FROM AUTHOR]

Vulvovaginal candidiasis (VVC) alters the innate cervicovaginal immunity, which provides an important barrier against viruses and other infections. The incidence of this disease has not decreased in the last 30 years, so effective treatments are still needed. Nanoparticles (NPs) of cellulose acetate phthalate (CAP) and clotrimazole (CLZ) were prepared by the emulsification-diffusion method. NPs were characterized using dynamic light scattering, atomic force microscopy and differential scanning calorimetry; their release profile was determined by the dialysis bag technique and mucoadhesion was evaluated with the mucin-particle method. The growth inhibition study of Candida albicans was carried out using the plate counting technique. Finally, accelerated physical stability tests of NPs were carried out, both in water and in SVF. The CAP-CLZ NPs had an average diameter of 273.4 nm, a PDI of 0.284, smooth surfaces and spherical shapes. In vitro release of CLZ from the CAP NPs was categorized with the Weibull model as a matrix system in which initial release was rapid and subsequently sustained. The inhibition of C. albicans growth by the CAP-CLZ NPs was greater than that of free CLZ, and the CAP-only NPs had a microbicidal effect on C. albicans. The NPs showed poor mucoadhesiveness, which could lead to studies of their mucopenetration capacities. An accelerated physical stability test revealed the erosion of CAP in aqueous media. A nanoparticulate system was developed and provided sustained release of CLZ, and it combined an antifungal agent with a microbial polymer that exhibited antifungal activity against C. albicans. [ABSTRACT FROM AUTHOR]

Clotrimazole (CLZ), traditionally an antifungal agent, unveils promising avenues in cancer therapy, particularly in addressing bladder and prostate cancers. In vitro assessments underscore its remarkable efficacy as a standalone treatment, significantly diminishing cancer cell viability. Mechanistically, CLZ operates through multifaceted pathways, including the inhibition of Ca2+-dependent K+ channels, suppression of glycolysis-related enzymes, and modulation of the ERK-p65 signaling cascade, thus underscoring its potential as a versatile therapeutic agent. Our investigation sheds light on intriguing observations regarding the resilience of UM-UC-5 bladder cancer cells against high doses of paclitaxel (PTX), potentially attributed to heightened levels of the apoptosis-regulating protein Mcl-1. However, synergistic studies demonstrate that the combination of Doxorubicin (DOXO) and CLZ emerges as particularly potent, especially in prostate cancer contexts. This effectiveness could be associated with the inhibition of drug efflux mediated by multidrug resistance-associated protein 1 (MRP1), underscoring the importance of exploring combination therapies in cancer treatment paradigms. In essence, our findings shed light on the anticancer potential of CLZ, emphasizing the significance of tailored approaches considering specific cancer types and molecular pathways in drug repurposing endeavors. While further validation and clinical exploration are warranted, the insights gleaned from this study offer promising prospects for enhancing cancer therapy efficacy. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to compare the antifungal efficacy of Ganoderma lucidum (G. lucidum) and clotrimazole for treatment of denture stomatitis (DS). Materials and Methods: This double-blind randomized clinical trial was conducted on 50 patients with DS types I and II assigned to two groups (N=25). In the first group, G. lucidum extract was administered in the form of 5% gel while 1% clotrimazole gel was prescribed for the second group. Pain intensity according to the visual analog scale (VAS), and the percentage of DS recovery based on the Budtz-Jorgenson index were evaluated and recorded after 7 and 14 days. Data were analyzed using the Chi-square test, independent samples t-test, repeated measures ANOVA, and logistic regression (alpha=0.05). Results: The percentage of complete recovery on day 7 in the G. lucidum group (28%) was higher than that in the clotrimazole group (16%) but not significantly (P=0.592). Not wearing dentures overnight significantly increased the odds of recovery by 6.56 times, while the odds of recovery decreased by 0.03 times in DS type II, as compared to DS type I (P= 0.009).Conclusion: No significant difference existed between the antifungal efficacy of G. lucidum and clotrimazole for clinical treatment of DS. Thus, Ganoderma may be regarded as an alternative treatment, especially in patients’ resistant to azoles. Nonetheless, further clinical studies are required to shed more light on this topic.

Abstract Patients with multiple myeloma (MM) experience relapse and drug resistance; therefore, novel treatments are essential. Clotrimazole (CTZ) is a wide-spectrum antifungal drug with antitumor activity. However, CTZ’s effects on MM are unclear. We investigated CTZ’s effect on MM cell proliferation and apoptosis induction mechanisms. CTZ’s effects on MM.1S, NCI- H929, KMS-11, and U266 cell growth were investigated using Cell Counting Kit-8 (CCK-8) assay. The apoptotic cell percentage was quantified with annexin V-fluorescein isothiocyanate/7-amino actinomycin D staining. Mitochondrial membrane potential (MMP) and cell cycle progression were evaluated. Reactive oxygen species (ROS) levels were measured via fluorescence microscopy. Expression of apoptosis-related and nuclear factor (NF)-κB signaling proteins was analyzed using western blotting. The CCK-8 assay indicated that CTZ inhibited cell proliferation based on both dose and exposure time. Flow cytometry revealed that CTZ decreased apoptosis and MMP and induced G0/G1 arrest. Immunofluorescence demonstrated that CTZ dose-dependently elevated in both total and mitochondrial ROS production. Western blotting showed that CTZ enhanced Bax and cleaved poly ADP-ribose polymerase and caspase-3 while decreasing Bcl-2, p-p65, and p-IκBα. Therefore, CTZ inhibits MM cell proliferation by promoting ROS-mediated mitochondrial apoptosis, inducing G0/G1 arrest, inhibiting the NF-κB pathway, and has the potential for treating MM.

Clotrimazole (CMZ) is a classical antifungal drug for studying crystallization. In this study, a new CMZ polymorph (Form 2) was discovered during the process of nucleation and growth rate determination in the melt. High-quality single crystals were grown from melt microdroplets to determine the crystal structure by x-ray diffraction. Form 2 is metastable and exhibits a disordered structure. The crystal nucleation and growth kinetics of the two CMZ polymorphs were systematically measured. Form 2 nucleates and grows faster than the existing form (Form 1). The maximum nucleation rate of Forms 1 and 2 was observed at 50 °C (1.07 Tg). The summary of the maximum nucleation rate temperature of CMZ and the other six organic compounds indicates that nucleation near Tg in the supercooled liquid is a useful approach to discovering new polymorphs. This study is relevant for the discovering new drug polymorphs through an understanding of nucleation and growth kinetics during melt crystallization. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion Nakaseomyces glabratus (N. glabratus) formerly known as Candida glabrata (C. glabrata), is an endogenous opportunistic pathogen, which is generally located in the gastrointestinal tract but can spread in immunocompromised patients. N. glabratus is the second most common pathogen that causes candidemia in several countries. N. glabratus virulence factors may increase antifungal resistance and reduce the number of available treatment options. High resistance to azoles and increasing resistance to echinocandins have been previously reported in N. glabratus.To establish the distribution of N. glabratus isolates in Europe and its drug susceptibility/resistance in each country over the last 7 years.The search was performed across three databases: PubMed, Scopus and Scielo, using the MeSH terms: “Candida glabrata”, “Nakaseomyces glabratus”, “Europe”, “resistance” and “Epidemiology” exclusively in English. All available information from January 2002 to December 2022 was included, excluding reviews, meta‐analyses and book chapters.Fifty‐seven articles with information on antifungal susceptibility in Europe were retrieved and analysed with a total of 15,400 reported C. glabrata isolates. Remarkably, nations that presented the maximum number of cases during the study period included the United Kingdom (n = 7241, 47.02%), France (n = 3190, 20.71%), Spain (n = 900, 5.84%), Hungary (n = 745, 4.84%) and Italy (n = 486, 3.16%). C. glabrata isolates presented resistance to azoles [voriconazole (n = 2225, 14.45%), fluconazole (n = 1612, 10.47%), itraconazole (n = 337, 2.19%) and clotrimazole (n = 89, 0.58%)], increased resistance to echinocandins, especially to anidulafungin (n = 138, 0.89%), and high sensitivity to amphotericin B.The number of candidemia cases associated with triazole‐resistant N. glabratus isolates have been increasing in Europe. Therefore, echinocandins and amphotericin B can be considered optional empirical treatments; however, antifungal susceptibility testing is required to determine the best therapeutic options. [ABSTRACT FROM AUTHOR]

Background: The emergence of tolerance to antifungal agents in Candida albicans complicates the treatment of fungal infections. Understanding the mechanisms underlying this tolerance is crucial for developing effective therapeutic strategies. Objective: This study aims to elucidate the genetic and molecular basis of ketoconazole tolerance in C. albicans, focusing on the roles of chromosomal aneuploidy, Hsp90, and calcineurin. Methods: The wild-type C. albicans strain SC5314 was exposed to increasing concentrations of ketoconazole (0.015-32 µg/mL) to select for tolerant adaptors. Disk diffusion and spot assays were used to assess tolerance. Wholegenome sequencing identified chromosomal changes in the adaptors. The roles of Hsp90 and calcineurin in maintaining and developing ketoconazole tolerance were investigated using specific inhibitors and knockout strains. Results: Adaptors exhibited tolerance to ketoconazole concentrations up to 16 µg/mL, a significant increase from the parent strain's inhibition at 0.015 µg/mL. All tolerant adaptors showed amplification of chromosome R, with 29 adaptors having trisomy and one having tetrasomy. This aneuploidy was unstable, reverting to euploidy and losing tolerance in drug-free conditions. Both Hsp90 and calcineurin were essential for maintaining and developing ketoconazole tolerance. Inhibition of these proteins resulted in loss of tolerance. The efflux gene CDR1 was not required for the development of tolerance. Chromosome R trisomy and tetrasomy induce cross-tolerance to other azole antifungal agents, including clotrimazole and miconazole, but not to other antifungal classes, such as echinocandins and pyrimidines, exemplified by caspofungin and 5-flucytosine. Conclusion: Ketoconazole tolerance in C. albicans is mediated by chromosomal aneuploidy, specifically chromosome R amplification, and requires Hsp90 and calcineurin. These findings highlight potential targets for therapeutic intervention to combat antifungal tolerance and improve treatment outcomes. [ABSTRACT FROM AUTHOR]

Background and Aim: Scopulariopsis brevicaulis (S. brevicaulis) is an opportunistic pathogen causing both localized and systemic infections. Recent studies indicated DNA sequence variation among S. brevicaulis isolates from different clinical sources. In this study we aimed to isolate and diagnose S. brevicaulis from nail and skin samples of diabetic patients and investigate their phylogenetic diversity based on the internal transcribed spacer 1 (ITS) sequencing. Materials and Methods: Fifty nail and skin samples were collected from diabetic patients suffering from skin lesions. Conventional diagnostic methods were utilized to identify the bacterial and fungal isolates. Fungal DNA was extracted and ITS 1 region was amplified by PCR and sequenced using Sanger method. Multiple sequence alignment and phylogenetic analysis were conducted using Clustal W and MEGA software. Finally, antifungal susceptibility test was performed by disc diffusion method. Results: Based on the culture, microscopic evaluation, and biochemical tests, various types of bacteria and fungi were isolated. Among 50 nail and skin samples, 25 fungal isolates (50%) and 5 bacterial isolates (10%) were recovered. Interestingly, one of the fungal isolates was identified as Scopulariopsis brevicaulis. This isolate was associated with a clinical case involving a 52-year-old male. Phylogenetic analysis of the ITS region showed our isolate (Scopulariopsis brevicaulis) closely matched and clustered in the same clade as those reported in the US, differing from those reported in Iraq (Basrah), Iran, and Turkey. Furthermore, our isolate exhibited a multi-drug resistance pattern against antifungal agents. Conclusion: This study highlights the importance of identifying S. brevicaulis in diabetic patients due to its multi-drug resistance. DNA sequencing and phylogenetic analysis revealed genetic divergence from the strains within the same country and other different countries. [ABSTRACT FROM AUTHOR]