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A new concept in the topical treatment of onychomycosis with cyanoacrylate, undecylenic acid, and hydroquinone

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The authors report a pilot study of a new approach for the topical treatment of onychomycosis using physiologic principles of fungal growth and serial debridement. In total, 154 patients were studied for 1 year with mild, moderate, and severe nail disease. Negative mycologic cultures in these 3 groups were 100%, 65%, and 35%, respectively. All patients reported subjective improvement in the first 3 months.
... Moreover, onychomycosis is caused by T. rubrum. 60 Additionally, McDonough et al. in 2002 found that the medium-chain fatty acids (MCFAs) undecanoic acid (11:0), 10-undecenoic acid (11:1 Delta 10), and lauric acid (12:0) can affect the growth of Saccharomyces cerevisiae in a dosedependent manner. 61 This study is a companion to that of Ells and co-workers, who in 2009 demonstrated that the polyunsaturated fatty acid arachidonic acid (20:4) may increase the antifungal sensitivity of biofilms formed by two closely related Candida species, thus resulting in a decrease in the dose of the antimycotic agent needed to inhibit biofilm formation. ...
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In this study, the n-hexane fraction of soft coral Nephthea sp. gathered from the Red Sea was evaluated for its antidermatophyte activity. The antidermatophyte activity was performed versus different fungi, including Microsporum canis, Trichophyton gypseum, and Microsporum mentagrophytes, using a broth microdilution method. The n-hexane fraction showed minimum inhibitory concentrations (MICs) against the tested dermatophytes of 104.2 ± 20.8, 125 ± 0.0, and 83.33 ± 20.83 μg/mL respectively. The chemical constitution of the lipoidal matter (n-hexane fraction) was characterized by gas chromatography coupled with a mass spectrometer (GC-MS). The unsaponifiable fraction (USAP) of Nephthea sp. showed relative percentages of hydrocarbons and vitamins of 69.61% and 3.26%, respectively. Moreover, the percentages of saturated and unsaturated fatty acids were 53.67% and 42.05%, respectively. In addition, a molecular networking study (MN) of the GC-MS analysis performed using the Global Natural Products Social Molecular Networking (GNPS) platform was described. The molecular docking study illustrated that the highest binding energy score for spathulenol toward the CYP51 enzyme was -8.3674 kcal/mol, which predicted the mode of action of the antifungal activity, and then the results were confirmed by the inhibitory effect of Nephthea sp. against CYP51 with an IC50 value of 12.23 μg/mL. Our results highlighted the antifungal potential of Nephthea sp. metabolites.
... It is a derivative of castor oil, and it is used in various marketed formulations for the treatment of nail and skin infections. Clinical practices have also supported the use of UA in inhibiting the fungal infections with negative fungal culture for prolonged periods of time [17][18][19]. ...
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Onychomycosis is a prominent fungal infection that causes discoloration, thickening, and mutilation leading to the separation of the nail from the nail bed. Treatment modalities for onychomycosis may include oral, topical, or combination therapy with antifungals and at times may require chemical or surgical intervention. The burden of side effects of antifungals is enormous, and therefore using molecular docking-based drug selection in context with the target keratin protein would ensure better disease management. Ciclopirox, Amorolfine HCl, Efinaconazole, Tioconazole, and Tavaborole were submitted for assessment, revealing that Amorolfine HCl is the best fit. Consequently, two formulations (Nail lacquer and nanoemulgel) were developed from Amorolfine HCl to validate the in silico screening outcomes. The formulations were further fortified with over-the-counter ingredients vis-a-vis with vitamin E in nail lacquer and undecylenic acid in nanoemulgel for their prominent roles in improving nail health. Both the formulations were systematically designed, optimized, and characterized. Amorolfine HCl containing nanoemulgel (NEG) was developed using undecylenic acid as an oil phase and thioglycolic acid as a penetration enhancer. The quality parameters evaluated were particle size, the zeta potential for nanoemulsion (NE) (78.04 ± 4.724 nm and −0.7mV, respectively), in vitro cumulative drug release (96.74% for NE and 88.54% for NEG), and transungual permeation (about 73.49% for NEG and 54.81% for NE). Nail lacquer was evaluated for the drying time, non-volatile content, and blush test. In vitro cumulative drug release of the developed nail lacquer and comparator marketed formulations were around 81.5% and 75%, respectively. Similarly, the transungual drug permeation was 6.32 μg/cm2 and 5.89 μg/cm2, respectively, in 24 h. The in silico guided preparation of both formulations containing Amorolfine HCl and over the counter ingredients is amenable for therapeutic use against onychomycosis and will be evaluated in the in vivo model.
... Undecylenic acid is an unsaturated fatty acid used for the treatment of nail fungal infections [45,46]. Our results indicate that undecylenic acid elicited concentrationdependent increase in the SPR response upon injection to the immobilized PAS domain of EAG channels while showing no concentration-dependent changes upon injection to the immobilized PAS domains of ERG and ELK channels (Fig. 3). ...
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Background: KCNH family of potassium channels is responsible for diverse physiological functions ranging from the regulation of neuronal excitability and cardiac contraction to the regulation of cancer progression. KCNH channels contain a Per-Arn-Sim (PAS) domain in their N-terminal and cyclic nucleotide-binding homology (CNBH) domain in their C-terminal regions. These intracellular domains shape the function of KCNH channels and are important targets for drug development. Methods: Here we describe a surface plasmon resonance (SPR)-based screening method aimed in identifying small molecule binders of PAS and CNBH domains for three KCNH channel subfamilies: ether-à-go-go (EAG), EAG-related gene (ERG), and EAG-like K+ (ELK). The method involves purification of the PAS and CNBH domains, immobilization of the purified domains on the SPR senor chip and screening small molecules in a chemical library for binding to the immobilized domains using changes in the SPR response as a reporter of the binding. The advantages of this method include low quantity of purified PAS and CNBH domains necessary for the implementation of the screen, direct assessment of the small molecule binding to the PAS and CNBH domains and easiness of assessing KCNH subfamily specificity of the small molecule binders. Results: Using the SPR-based method we screened the Spectrum Collection Library of 2560 compounds against the PAS and CNBH domains of the three KCNH channel subfamilies and identified a pool of small molecules that bind to the PAS or CNBH domains. To further evaluate the effectiveness of the screen we tested the functional effect of one of the identified mEAG PAS domain specific small molecule binders on currents recorded from EAG channels. Undecylenic acid inhibited currents recorded from EAG channels in a concentration-dependent manner with IC50 of ~ 1 μM. Conclusion: Our results show that the SPR-based method is well suited for identifying small molecule binders of KCNH channels and can facilitate drug discovery for other ion channels as well.
... This activity was showed by crude hydromethanolic extract and chloroform fraction, with both having MIC of 10 µg/mL, that got refined to 5 µg/mL in case of pure compound govanic acid. In previous reports fatty acids have been associated with antifungal activity especially against T. rubrum due to their interaction with fungal cell membrane and fatty acid metabolism [15,16]. Present study confirms earlier finding and herein report a pure compound having good activity against T. rubrum. ...
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A crude hydro-methanolic extract of Trillium govanianum ex D. Don (Melanthiaceae,Trilliaceae) rhizomes and its subsequent solvents soluble fractions were tested against different fungal strains i.e. Trichophyton rubrum ATCC 40051, Aspergillus niger ATCC 16888, Candida albicans ATCC 18804, Microsporum canis ATCC 32903 and Fusarium lini ATCC 16888. The hydro-methanolic extract showed significant activity against T. rubrum and M. canis with 80 and 75% inhibitions respectively. Among the fractions, chloroform soluble fraction showed 90% inhibition, with minimum inhibitory concentration (MIC) of 10µg/mL against T. rubrum followed by ethyl acetate, butanol and n-hexane fractions. The bio-activity guided isolation of chloroform soluble fraction leads to a new trihydroxylated fatty acid, named govanic acid (1) along with two known phytoecdysteroids i.e. 20-hydroxyecdysone (2) and 5, 20-dihydroxyecdysone (3). The structures of isolated compounds were elucidated through 1D, 2D-NMR spectroscopic data analysis. All compounds (1-3) in T. govanianum are reported herein for the first time. Compound 1 showed significant activity against T. rubrum with 70% inhibition and MIC value of 5 µg/mL, but lack of activity against the other test strains.
... This effect seems to be associated with acidification of cell cytoplasmic pH. A number of other fatty acids also do this with the effect enhanced as the number of carbon atoms increases [149]. ...
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Onychomycosis (fungal nail infections) are very common worldwide but are fortunately not often lethal. Several powerful drugs have been introduced into clinical practice in recent years, but these infections remain difficult to cure primarily due to the difficulties drugs face in penetrating to the site of the infection in therapeutic concentrations. The nature of the disease, the causative fungi, and the characteristics of the drugs employed to treat this condition are discussed in this review.
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Background: Onychomycosis is the most common nail disease seen in clinical practice. Inclusion of diverse groups in onychomycosis clinical trials subjects is necessary to generalize efficacy data. Objectives: We aimed to systematically review race and ethnicity reporting and representation, as well as, treatment outcomes in onychomycosis clinical trials. Methods: A PubMed search for onychomycosis clinical trials was performed in August 2020. Primary clinical trial data were included and post-hoc analyses were excluded. Categorical variables were compared using chi-squared and Fisher's exact tests. Statistical significance was set at P<0.05. Photos in articles were categorized by Fitzpatrick skin type. Results: Only 32/182 (17.5%) trials reported on race and/or ethnicity and only one trial compared treatment efficacy in different subgroups. Darker skin colors were infrequently depicted in articles. Topical treatment, location with ≥ 1 US-based site, industry funding type, and publication date after 2000 were significantly associated with reporting of racial/ethnic data (P<0.05 for all comparisons). Limitations: Demographics on excluded subjects and methods of recruitment were not available. Assigning Fitzpatrick skin type is inherently subjective. Conclusions: This study highlights a need for consistent reporting of races and ethnicities of onychomycosis clinical trial participants with subgroup analyses of treatment efficacies.
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Onychomycosis is a condition that makes up at least 50% of the nail disorders that dermatologists see in their office. Many individuals are turning to home remedies due to the high cost of prescription and/or procedures and the potential side effects due to systemic therapy. Multiple essential oils such as eucalyptus oil, clove oil, tea tree oil, thyme oil, lavender oil, and oregano oil, have been tested in vitro for their antifungal properties and may represent new options for future topical formulations to treat onychomycosis. Some other treatments said to have been performed on patients and to have achieved a mycological cure are povidone‐iodine/dimethyl sulfoxide, undecylenic acid and snakegrass root. Oral home remedies for onychomycosis have no evidence to support them, although patients report trying the following: apple cider vinegar, probiotics, olive leaf extract, as well as oral homeopathic spray as part of the ZetaClear two‐part treatment kit.
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Melasma is an irregular brown or grayish-brown facial hypermelanosis, often affecting women, especially those living in areas of intense UV radiation. The precise cause of melasma remains unknown; however, there are many possible contributing factors. Because of its dermal component and tendency to relapse, melasma is often difficult to treat. The use of broad-spectrum (UVA + UVB) sunscreen is important, as is topical hydroquinone, the most common treatment for melasma. Other lightening agents include retinoic acid (tretinoin) and azelaic acid. Combination therapies such as hydroquinone, tretinoin, and corticosteroids have been used in the treatment of melasma, and are thought to increase efficacy as compared with monotherapy. Kojic acid, isopropylcatechol, N-acetyl-4-cysteaminylphenol, and flavonoid extracts are other compounds that have been investigated for their ability to produce hypopigmentation, but their efficacy, safety, or trial design indicates that the interventions would need further study before they could be recommended. Chemical peels, laser treatments, and intense pulsed light therapy are additional therapeutic modalities that have been used to treat melasma.
Philadelphia: Lea & Febiger; 1986.5. Crissey JT, Lang H., Parish LC Manual of Medical Mycology
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