Rubrum Infection Research Articles

The Role of Thickening Agent Proportions in Optimizing Nanoemulsion Gel for Dermatophytosis Treatment.

Adjusting thickening agent proportions in nanoemulsion gel (NG) balances its transdermal and topical delivery properties, making it more effective for dermatophytosis treatment. Carbomer 940 and α-pinene were used as model thickening agent and antifungal, respectively. A series of α-pinene NGs (αNG1, αNG2, αNG3) containing 0.5%, 0.75% and 1% (w/w) Carbomer 940 were developed and evaluated for stability, rheological properties, and skin irritation; assessed for ex vivo skin permeation, deposition, and fluorescent imaging of drug distribution within skin layers; and tested in vivo for efficacy against Trichophyton rubrum infection in guinea pigs, with PAS (Periodic Acid-Schiff) staining confirming fungal clearance. The steady-state skin flux rates of α-pinene over 24hours were αNG1 (46.93±2.52μg/cm²/h) > αNG2 (26.01±2.65μg/cm²/h) > αNG3 (11.36±1.69μg/cm²/h). The α-pinene deposition in the epidermis/dermis for αNG1 decreased substantially from 2h (62.74 ± 3.36μg/cm²) to 12h (11.7 ± 2.24μg/cm²). In contrast, αNG2 showed relatively sustained deposition with 2h (25.54 ± 2.67μg/cm²), 6h (57.32 ± 4.62μg/cm²) and 12h (23.69 ± 3.29μg/cm²). αNG3 exhibited a slow increase from 2h (18.32 ± 2.11μg/cm²) to 12h (36.78 ± 3.22μg/cm²). The αNG2 exhibited the highest efficacy and fungal clearance rates (71.42%, 79.17%), followed by αNG1 (55.34% and 60.42%), and αNG3(43.21%, 52.08%). Fluorescent imaging confirmed αNG2's higher drug deposition within the epidermis/dermis, while PAS staining showed a potent fungal clearance with αNG2. This study demonstrates that Carbomer 940 proportions significantly impact the transdermal performance of αNG. αNG2, with a moderate proportion, optimally enhances skin drug delivery and deposition, achieving superior therapeutic outcomes. These findings highlight the importance of optimizing thickening agent proportions to improve the efficacy of topical nanoemulsion gels.

Trace-elements driven up-regulation of secreted proteases expression in the human-pathogenic fungus Trichophyton rubrum.

Trichophyton rubrum is a widespread human pathogenic fungus, colonizing keratinized tissue of outer body-parts. Thereby, the pathogen is relying on nutrients available from the host. The invasive mechanism of the pathogen is relaying on secreted proteases, which hydrolyze skin-proteins for subsequent up-take. In this study, we analyzed the gene expression of secreted proteases by RNAseq. In the results, we show the expression profile of 31 secreted protease genes under three conditions: keratin medium and keratin medium with trace-elements or with glucose. By adding trace-elements to keratin medium, the expression of secreted proteases increased from 1.8 % to 3.3 %. Across all groups of secreted proteases, higher expression was observed. The genes SUB4, MEP1, MEP3, MEP5, MEP9, LAP1, LAP2 and MCPA were significantly stronger expressed, whereby MEP5 (∼6 fold) and SUB4 (∼5.8 fold) were strongest up-regulated. We discuss the influence and significance of trace-elements on secreted proteases. Further, we speculate about the disturbed nutritional immunity in psoriatic and atopic skin as factor for increased risk of getting severe T. rubrum infections.

In Situ Expression of TNF-α and IL-10 in Human Dermatophytosis Lesions due to Trichophyton rubrum.

Dermatophytosis is a very common superficial mycosis, but there are few studies about the human immune response to dermatophytes. We aim to analyze the in situ expression of TNF-α and IL-10 in human dermatophytosis. Expression of TNF-α and IL-10 were evaluated in skin samples from 10 patients with dermatophytosis and 12 healthy subjects using an immunohistochemistry assay. TNF-α and IL-10 were significantly elevated in lesions from patients with dermatophytosis compared to healthy controls. These data illustrate the balance of pro- and anti-inflammatory cytokines suggesting Trichophyton rubrum infection could control the local immune response.

Ocimum basilicum and Lagenaria siceraria Loaded Lignin Nanoparticles as Versatile Antioxidant, Immune Modulatory, Anti-Efflux, and Antimicrobial Agents for Combating Multidrug-Resistant Bacteria and Fungi.

Lignin nanoparticles emerged as a promising alternative for drug delivery systems owing to their biodegradability and bioactive properties. This study investigated the antimicrobial activity of the ethanolic extract of Ocimum basilicum-loaded lignin nanoparticles (OB-LNPs) and Lagenaria siceraria seed oil-loaded lignin nanoparticles (LS-LNPs) to find a solution for antimicrobial resistance. OB-LNPs and LS-LNPs were tested for their antimicrobial potential against Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, Staphylococcus aureus, Salmonella enterica, Trichophyton mentagrophytes, Trichophyton rubrum, and Microsporum canis. OB-LNPs and LS-LNPs were further tested for their anti-efflux activity against ciprofloxacin-resistant Salmonella enterica strains and for treating Salmonella infection in a rat model. We also investigated the antifungal efficacy of OB-LNPs and LS-LNPs for treating T. rubrum infection in a guinea pig model. Both OB-LNPs and LS-LNPs showed strong antimicrobial potential against S. Typhimurium and T. rubrum infections. LS-LNPs showed antibacterial activity against Salmonella enterica species with a MIC range of 0.5-4 µg/mL and antifungal activity against T. rubrum with a MIC range of 0.125-1 µg/mL. OB-LNPs showed antibacterial activity against Salmonella enterica species with a MIC range of 0.5-2 µg/mL and antifungal activity against T. rubrum with a MIC range of 0.25-2 µg/mL. OB-LNPs and LS-LNPs downregulated the expression of ramA and acrB efflux pump genes (fold change values ranged from 0.2989 to 0.5434; 0.4601 to 0.4730 for ramA and 0.3842-0.6199; 0.5035-0.8351 for acrB). Oral administration of OB-LNPs and LS-LNPs in combination with ciprofloxacin had a significant effect on all blood parameters, as well as on liver and kidney function parameters. Oxidative stress mediators, total antioxidant capacity, and malondialdehyde were abolished by oral administration of OB-LNPs and LS-LNPs (0.5 mL/rat once daily for 5 days). Interferon-γ and tumor necrosis factor-α were also reduced in comparison with the positive control group and the ciprofloxacin-treated group. Histopathological examination of the liver and intestine of OB-LNPs and LS-LNPs-treated rats revealed an elevation in Salmonella clearance. Treatment of T. rubrum-infected guinea pigs with OB-LNPs and LS-LNPs topically in combination with itraconazole resulted in a reduction in lesion scores, microscopy, and culture results. In conclusion, OB-LNPs and LS-LNPs possess immunomodulatory and antioxidant potential and can be used as naturally derived nanoparticles for drug delivery and treatment of Salmonellosis and dermatophytosis infections.

Method development and validation of a new stability indicating HPLC and LC-ESI-MS/MS methods for the determination of Tavaborole

Tavaborole, a topical antifungal agent containing Boron is used for the treatment of onychomycosis, an infection of the nail and nail bed caused by Trichophyton rubrum or Trichophyton mentagrophytes infection. Tavaborole is chemically known as 5 - Fluoro -1,3 - dihydro -2,1-benzoxaborol -1-ol. It acts by inhibiting Leucyl-tRNA synthetase an essential fungal enzyme required for protein synthesis. AB SCIEX Instruments LC-ESI-MS/MS (Model no. 5068379-Y) QTRAP Enabled Triple Quad 5500+ with Agilent Zorbox C18 (150 mm x 4.6 mm x 3 µm) column and PDA detector was employed for the present study. The total run time was 10 mins and the detection wavelength was 254 nm. A mixture of 5 mM Ammonium formate: Methanol (30: 70) was used as mobile phase on isocratic mode with 1 ml/min as flow rate. Tavaborole has shown linearity over the concentration range 0.5-100 μg/ml and the proposed method was validated as per ICH guidelines. The proposed method is found to be simple, precise, accurate and suitable for the quantification of the marketed formulations of Tavaborole. Stress degradation studies were performed and the method is found to be selective and specific. Keywords: Tavaborole, Stability indicating, LC-ESI-MS/MS, Validation.

The Efficacy of Extract from Various Parts of Blumea Lacera in Preventing and Treating Bacteria (Escherichia Coli) and Fungal (Trichophyton Rubrum) Infections in Humans as Well as Controlling Mosquitoes (Aedes Aegypti) in the Environment

In Ayurveda, Blumea lacera extraction has been found cast-off in the management of various sympathetic of diseases and is also found to exhibit hypoglycaemic, anti-diarrhoeal, larvicidal, antioxidant and antimicrobial properties. Blumea lacera extraction contain astringent, stomachic, antipyretic, and diuretic, cure bronchitis and fever. To find out the most suitable part of the plant Blumea lacera which will be used for killing the mosquito larvae. How do the plant extraction produce effect on the different stages of larvae, 1st, 2nd, 3rd, and 4th, stages. Different doses of extraction. Blumea Lacera plant, cut in their different parts of plant separately, i.e., leaves, root, stem, and bud and grind them with different solvents like methanol: leaves, root, stem and bud. Distilled water: leaves, root, stem and bud. Benzene: leaves, root, stem and bud, and kept them at room temperature openly to evaporate the excess number of solvents. Mosquitoes larvae (Aedes aegypti) and culture them at room temperature by providing them only filtered rain water and mixture of (3gm pedigree +1gm yeast). Our main focus was on that whether the different solvent extraction is effective against mosquitoes’ larvae, if it is then how much effective? Then the most effective extraction was methanolic leaves extraction, it mostly affected the 1st stage of mosquitoes’ larvae at 1500 microliter it killed 90% 1st stage population of mosquitoes’ larvae. Methanolic leaves extraction showed antibacterial property, antifungal property and larvicidal property.

Cytomorphological findings of Trichophyton rubrum infection in an elderly hypertensive woman.

Trichophyton is a dermatophytic fungi causing superficial skin infections which affects outermost layer of the epidermis, stratum corneum, and mainly involves feet, groin, scalp, and nails. Invasion into the dermis occurs mainly in immunocompromised patients. A 75-year-old hypertensive female presented with a nodular swelling on the dorsum of right foot for 1 month. The swelling was 1.0 × 1.0 cm and gradually progressive in nature. FNAC revealed many thin filamentous branching and fungal hyphae along with foreign body granulomas and suppurative acute inflammation. The swelling was excised and sent for histopathological examination which confirmed the above findings. Periodic Acid Schiff stain showed fungal hyphae in both cytology smear as well as histopathology section. On fungal culture, microconidia with septate hyphae suggestive of Trichophyton rubrum was seen. Trichophytons mainly affect immunocompromised and diabetic patients, however, may present as nodular lesions without any history of superficial dermatophytosis as seen in the present case. The characteristic cytological picture helped to clinch the diagnosis in this case and facilitated further management.

Development of indirect ELISA and its evaluation in comparison with KOH hydrolysis and fungal culture for the immuno diagnosis of Trichophyton rubrum and Trichophyton mentagrophytes infection in humans

Trichophyton is a keratinophilic fungus that can invade keratinized tissues of humans and cause superficial mycoses called dermatophytosis. The objective of this study was to develop and evaluate indirect ELISA in comparison with gold standard methods such as direct microscopic examination of KOH mounts and fungal culture for the diagnosis of Trichophyton infection in humans. The present investigation reports the production and partial purification of T. rubrum mycelial antigens and production of specific polyclonal antibodies. It also reports the development and optimization of indirect ELISA and evaluation of its potential in comparison with gold standard methods for the diagnosis of Trichophyton infection in humans. The diagnostic sensitivity and specificity of Trichophyton indirect ELISA was 93.75% and 93.33% respectively. The positive and negative predictive values were high as well, found to be 93.75% and 90.00% respectively indicating usefulness of the assay. In all comparisons, the correlation coefficient (r) value was >0.5 indicating strong correlation between KOH hydrolysis test, fungal culture method and indirect ELISA. A significant correlation coefficient of 0.856 (P < 0.0001) was obtained between indirect ELISA and fungal culture method. This shows a good agreement between fungal culture method and indirect ELISA. The present study clearly shows diagnostic performance of Trichophyton indirect ELISA developed in this study is efficient as fungal culture method for the diagnosis of Trichophyton infection in humans.

128 TSG-6 protein delays the invasion of fungal dermatophytes in reconstructed human epidermis

TSG-6 is an anti-inflammatory protein interacting with hyaluronan (HA) in the extracellular matrix (ECM) of epidermis and overproduced in pathological contexts such as in fungal infection. Dermatophytosis are widespread superficial infections of keratinized structures, especially produced by Trichophyton rubrum in humans. However, involvements of TSG-6 protein in pathophysiology of this dermatophytosis are not yet fully understood. The development of T. rubrum infection was characterized on TSG-6+/+ and TSG-6-/- reconstructed epidermis (RHE).

Peptidase Regulation in Trichophyton rubrum Is Mediated by the Synergism Between Alternative Splicing and StuA-Dependent Transcriptional Mechanisms.

Trichophyton rubrum is the most common causative agent of dermatophytosis worldwide and uses keratinized substrates such as skin and nails as its main source of nutrition during infection. Its pathogenic character relies on colonization and viability maintenance at the target host sites. Since fungal physiology must adapt and respond to host conditions for the successful establishment of infection, biological mechanisms are constantly being triggered by T. rubrum to guarantee its survival in the host environment. The ability of this fungus to sense and modulate the secretion of specific proteases according to environmental pH signaling is considered as a pivotal virulence factor for effective invasion and persistence of infection in the host. Transcriptional regulation of genes encoding specific proteases, such as peptidases, is a key biological process that drives physiological modulation to meet fungal requirements. It accomplishes a robust balance among transcript isoforms that can be directed to perform distinct cellular functions. Thus, alternative splicing mechanisms are suitable for fungal cells to establish a balance toward reprogramming protein translation to impair or boost physiological conditions. In this study, we investigated the role of alternative splicing, especially intron retention events, in generating isoforms of virulence factors in T. rubrum mediated by transcriptional coordination of the protein StuA, a recently described transcription factor in this fungus. By analyzing the previous gene expression data provided by RNA-sequencing and after validation by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), we observed that two peptidase-coding genes (TERG_00734 and TERG_04614) could be direct targets of alternative splicing in the presence of keratin. Furthermore, protease isoforms generated by alternative splicing in T. rubrum were also detected in a co-culture with human keratinocytes, highlighting the role of these proteins in keratin deconstruction. Our results strongly suggest the influence of StuA on the regulation of virulence factors in T. rubrum and dermatophyte infections by triggering the transcription of the peptidase genes mentioned above in an alternative splicing-independent balance. The results elucidate how fungal cells drive alternate splicing to promote physiological adaptations and show that transcriptional regulation and virulence traits are robust elements required for dermatophyte infection.

The Dermatophyte Trichophyton rubrum Induces Neutrophil Extracellular Traps Release by Human Neutrophils.

Neutrophils are the first leukocytes recruited to the site of infection and are thought to be responsible for fungal elimination from the skin such as dermatophytes. Neutrophils are able to secrete reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) that can kill different fungi, including Aspergillus, spp., Candida albicans, and Phialophora verrucosa. However, NET production in response to Trichophyton rubrum, the main etiologic agent of dermatophytosis, has yet to be studied. We demonstrated that human neutrophils produce NETs against different morphotypes of T. rubrum in a dose-dependent manner and NET formation is dependent on ROS production. In addition, ROS production by human neutrophils in response to T. rubrum is dependent on NADPH oxidase, but not on fungal viability. NETs mediated killing of T. rubrum. Collectively, these results demonstrate that T. rubrum was able to trigger the production of NETs, suggesting that these extracellular structures may represent an important innate immune effector mechanism controlling physiological response to T. rubrum infection.

Fabrication and Characterization of Polymeric Pharmaceutical Emulgel Co-Loaded with Eugenol and Linalool for the Treatment of Trichophyton rubrum Infections.

Trichophyton rubrum (T. rubrum) is the main cause of chronic dermatophytosis which is highly prevalent worldwide. This study was aimed to fabricate and characterize polymeric emulgel of eugenol and linalool for the treatment of T. rubrum infections. Using the slow emulsification method, the emulgel was prepared and characterized for thermodynamic stability, pH analysis, viscosity, spreadability, swelling behavior, %drug content, surface morphology, globules size, polydispersity index, surface charge (mV), thermal behavior, in vitro drug release and XRD studies. Biological activities of emulgel were conducted against T. rubrum in vitro and in vivo. Results indicated that emulgel formulations were thermodynamically stable. The pH of the formulations was within an acceptable range for skin. The viscosity and spreadability were optimum for the better patient compliance. The swelling behavior was 111.10 ± 1.25% after 90 min. The drug content was within the official pharmacopeia limit i.e., 100 ± 10%. The surface morphology revealed by scanning electron microscopy showed a spherical-shaped structure with characteristic larger cracks and wrinkles. The droplet size, PDI, and surface charge of the optimized emulgel were 888.45 ± 8.78 nm, 0.44 and −20.30 mV, respectively. The emulgel released 84.32% of eugenol and 76.93% of linalool after 12 h. There was complete disappearance of the diffraction peaks corresponding to the drugs after XRD analysis. In rabbits, the infection was safely and completely recovered after 12 days and the emulgel produced significant effects (p < 0.05) similar to the standard product Clotrim®. It is concluded that the eugenol–linalool emulgel best described all its physical properties and can be applied topically for the treatment of T. rubrum infections.

Preliminary Study on Antifungal Mechanism of Aqueous Extract of Cnidium monnieri Against Trichophyton rubrum.

Trichoderma rubrum (T. rubrum) is one of the important pathogens because it is the cause of most dermatomycosis. The treatment of Trichophyton rubrum infection is time-consuming and very expensive; it is easy for the infections to reoccur, leading to therapeutic failures, persistence, and chronic infection. These issues have inspired researchers to study natural alternative therapies instead. Cnidium monnieri (L.), as a kind of traditional Chinese medicine, has a variety of pharmacological activities and a wide range of applications, so it has a high potential for researching and economic value. We detected the effect of aqueous extract of C. monnieri (L.) on the activity of T. rubrum by Cell Count Kit-8 assay (CCK-8), and we found that 128 and 256 μg/ml of aqueous extracts of C. monnieri (L.) co-cultured with T. rubrum for 24 h showed the inhibitory effect on T. rubrum. The results of scanning electron microscopy (SEM) and transmission electron microscopy (TEM) confirmed that aqueous extract of C. monnieri (L.) damaged the T. rubrum. At the same time, mass spectrometry screening with T. rubrum before and after the treatment of 256 μg/ml of aqueous extracts of C. monnieri (L.) showed that 966 differentially expressed proteins were detected, including 524 upregulated differentially expressed genes (DEGs) and 442 downregulated DEGs. The most significantly downregulated protein was chitin synthase (CHS); and the results of qRT-PCR and Western blotting demonstrated that the expression level of CHS was downregulated in the 256 μg/ml group compared with the control group. The study showed that the aqueous extract of C. monnieri (L.) could destroy the morphology of mycelia and the internal structure of T. rubrum, and it could inhibit the growth of T. rubrum. The antifungal effect of aqueous extract of C. monnieri (L.) may be related to the downregulation of the expression of CHS in T. rubrum, and CHS may be one of the potential targets of its antifungal mechanism. We concluded that aqueous extract from C. monnieri (L.) may be a potential candidate for antifungal agents.

Disseminated Deep Dermal Trichophyton Rubrum Infection in a Heart Transplant Recipient

<h3>Introduction</h3> The dermatophyte Trichophyton rubrum (T. rubrum) is one of the most common causes of superficial cutaneous mycoses. Although these are often seen in immunosuppressed heart transplant recipients, reports of deep dermatophytoses are rare. Accounts of extensive T. rubrum are even scarcer. We report a case of disseminated deep T. rubrum infection in a heart transplant patient, successfully treated with itraconazole. <h3>Case Report</h3> A 62 year-old systemically well male one year post-cardiac transplantation presented with a 4-month history of painless discharging erythematous nodules. These ranged from 1 to 6 cm in diameter on his upper limbs, lower abdomen, perineum and upper thighs. Histology from skin biopsy showed deep dermal granulomatous inflammation with filamentous fungal hyphae. Mycological studies isolated T. rubrum. This was treated with oral itraconazole and careful dose reduction of tacrolimus. After one month, the patient described a reduction in size of nodules and absence of new lesions. Following three months of itraconazole, the patient achieved a near complete response. The infection remained adequately controlled two months after itraconazole cessation. <h3>Summary</h3> There have been 5 published reports of deep T. rubrum infection over the last 10 years in PubMed, MEDLINE and EMBASE¹. A condition distinct from superficial dermatophytosis, deep dermatophytosis occurs in immunosuppressed individuals with defective cell-mediated immunity². Cases in solid-organ transplant recipients have been described predominantly in kidney recipients³. Disseminated infection has been reported in various bodily sites with the presentation of papulo-nodular lesions⁴ alongside invasive and extensive forms³. Careful monitoring of immunosuppressant level is required to prevent complications when itraconazole (an enzyme inhibitor) is added⁵. Deep dermatophytosis such as T. rubrum should be included in the differential diagnosis of erythematous skin nodules in immunosuppressed patients.

Human primary epidermal organoids enable modeling of dermatophyte infections

Technology of generating human epidermal derivatives with physiological relevance to in vivo epidermis is continuously investigated for improving their effects on modeling of human natural dermatological status in basic and clinical studies. Here, we report a method of robust establishment and expansion of human primary epidermal organoids (hPEOs) under a chemically defined condition. hPEOs reconstruct morphological, molecular, and functional features of human epidermis and can expand for 6 weeks. Remarkably, hPEOs are permissive for dermatophyte infections caused by Trichophyton Rubrum (T. rubrum). The T. rubrum infections on hPEOs reflect many aspects of known clinical pathological reactions and reveal that the repression on IL-1 signaling may contribute to chronic and recurrent infections with the slight inflammation caused by T. rubrum in human skin. Thus, our present study provides a new insight into the pathogenesis of T. rubrum infections and indicates that hPEOs are a potential ex vivo model for both basic studies of skin diseases and clinical studies of testing potential antifungal drugs.

Effective photodynamic treatment of Trichophyton species with Rose Bengal.

Photodynamic therapy (PDT) with Rose Bengal has previously achieved eradication of Trichophyton rubrum infections causing toenail onychomycosis; however, its antifungal activity against other clinically relevant dermatophytes has yet to be studied. Here, we test the efficacy of PDT using Rose Bengal (140 μM) and 532 nm irradiation (101 J/cm2 ) against Trichophyton mentagrophytes and Trichophyton interdigitale spores, in comparison to T. rubrum. A significant reduction (>99%) of T. mentagrophytes and T. interdigitale was observed, while actual eradication of viable T. rubrum was achieved (99.99%). Laser irradiation alone inhibited growth of T. rubrum (55.2%) and T. mentagrophytes (45.2%) significantly more than T. interdigitale (25.5%) (P = .0086), which may indicate an increased presence of fungal pigments, xanthomegnin and melanin. The findings suggest that Rose Bengal-PDT can act against a broader spectrum of fungal pathogens, and with continued development may be employed in a wider range of clinical antifungal applications.

Beyond the Superficial: Disseminated Trichophyton rubrum Infection in a Kidney Transplant Recipient

Superficial dermatophyte infections are common in the general population and are readily treated with topical antifungals. Deeper invasion is rare, and dissemination to visceral organs is extremely uncommon. We describe a 66-year-old renal transplant recipient who developed disseminated Trichophyton rubrum infection while undergoing treatment for acute humoral rejection. The infection presented as a facial rash with subsequent dissemination to the lungs and chest wall. All sites of infection improved with combination administration of oral posaconazole and terbinafine. In this work, we review the available literature regarding management of disseminated Trichophyton infection and discuss therapeutic interventions for disseminated dermatophytosis in immunosuppressed hosts.

Preparation, and Assessment of Antidermatophyte Activity of Miconazole-Urea Water-Soluble Film.

Cutaneous mycoses, particularly tinea pedis caused by Trichophyton rubrum, are commonly known infections in humans. They are still considered as a major public health problem worldwide affecting the quality of life due to prolonged period of treatment and development of drug resistance, which leads to recurrence of infections. The objective of our study was to assess the effectiveness of miconazole in the presence and absence of urea, as a penetration enhancer, against T. rubrum and to formulate both of them in a water-soluble film to be applied topically for the purpose of treating tinea pedis caused by this fungus. Drug combination revealed synergism where miconazole minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) (0.5 and 1 mg/L) were considerably declined to 0.001 and 0.004 mg/L, respectively, when combined with 20% urea. This enhanced drug interaction activity against the test strain was explained by the alterations raised on the morphology and ultrastructures observed microscopically. Minimal fungicidal dose of miconazole/urea combination displayed plasmolysis and shrink cytoplasm; however, necrotic cells with punctured walls and degraded cytoplasmic content were observed at high fungicidal dose. Water-soluble films, prepared using increasing values of miconazole MFC and urea, were transparent, smooth, uniform, and flexible. Their physicochemical characters showed homogeneity in weight, thickness, drug content, and folding endurances with normal surface pH values, indicating the reproducibility of the preparation method. The novel simulation model for the film mechanism of action supported the idea and the suggested application method of the new dosage form. Evaluation of these films was carried in vitro using disk diffusion assay as well as in vivo using guinea pig dermatophytosis model. The in vitro assessment revealed an increase in the inhibition zone diameters in a concentration-dependent manner upon using 10 or 20% of urea combined with miconazole. In vivo test showed that combination of 0.004 mg/L miconazole with 20% urea (M + U20) showed the highest efficacy percentage (95.83%), which was statistically superior to the infected untreated control (p < 0.001) in fungal burden reduction as well as improvement in clinical scores (p < 0.001). This work supports the hypothesis and suggests a new promising dosage form for the treatment of T. rubrum infections.

Corrigendum: A Trichophyton Rubrum infection model based on the reconstructed human epidermis - Episkin®.

Corrigendum: A Trichophyton Rubrum infection model based on the reconstructed human epidermis - Episkin®.

Production of anti-Trichophyton rubrum egg yolk immunoglobulin and its therapeutic potential for treating dermatophytosis

The aim of this study was to estimate the therapeutic potential of specific egg yolk immunoglobulin (IgY) on dermatophytosis caused by Trichophyton rubrum. The IgY was produced by immunizing hens with cell wall proteins of T. rubrum, extracted from eggs by PEG precipitation and then purified by ammonium sulfate precipitation. The cross-reactivity (CR) with other fungi, growth inhibition on T. rubrum in vitro and therapeutic effect on T. rubrum infection in BALB/C mice of the specific IgY were then evaluated. Anti- T. rubrum cell wall proteins IgY (anti-trCWP IgY) presented a certain degree of cross-reactivity with different fungi. In the in vitro and in vivo activity researches, Anti-trCWP IgY showed a significant dose-dependent growth inhibitory effect on T. rubrum in vitro and a significant dose-dependent therapeutic effect on T. rubrum infection in BALB/C mice.