Study of the Effect of Squalene Epoxidase Activity on Squalene Biosynthesis by Yeast Saccharomyces Cerevisiae VGSh-2

The researchers of this study investigated the biosynthesis of squalene by the yeast S. cerevisiae VGSH-2 through the activity of squalene epoxidase, which is a key enzyme in the conversion of squalene to ergosterol. It has been established that under aerobic conditions the antimycotic drug terbinafine promotes the switching of ergosterol formation to squalene synthesis. This switch occurs through specific inhibition of the squalene epoxidase of the yeast S. cerevisiae VGSH-2, thus increasing the biosynthetic ability of the yeast towards squalene. According to the results of this study, the optimal concentration of terbinofine in the nutrient medium was 0.3 μmol / cm3 . This concentration led to a 5-fold decrease in squalene epoxidase activity and a 7-8 times increase in squalene synthesis. The results obtained can be used to develop a competitive technology for the industrial production of squalene by microbial synthesis. Keywords: squalene, yeast, biosynthesis, inhibition of activity, terbinafine, squalene epoxidase, Saccharomices cerevisiae VGSH-2

Modulating the Antifungal Activity of Antimycotic Drugs with Farnesol

Introduction. Clinical strains of microorganisms, including opportunistic yeast-like fungi (YLF) of the genus Candida, are resistant to currently used antifungal drugs. In this regard, the search for alternative ways to potentiate the activity of antimicrobial agents in relation to the infectious agent is an important and relevant area of research. The study of combinations of existing antimycotic drugs and a medicinal extract of plant origin – farnesol – is one of the promising approaches in the fight against resistant strains of YLF genus Candida. In our previous studies, farnesol has been shown to exhibit relative activity against YLF Candida albicans biofilms. In this study, we used 6 clinical isolates and one museum strain YLF C. albicans to study the effect of farnesol on the antifungal activity of antimycotic drugs.Aim. To prove that farnesol can increase the antifungal activity of certain antimycotics.Materials and methods. To determine the sensitivity of 7 strains of YLF C. albicans to the antimycotic drugs "Nystatin" (NYS 50 µg), "Ketoconazole" (KET 10 µg), "Clotrimazole" (CTR 10 µg), "Amphotericin B" (AMB 10 µg), "Voriconazole" (VRC 10 µg) disk diffusion test was used. A solution of farnesol in concentrations of 100, 50 and 25 µM in a volume of 25 µl was applied to the disk with the antimycotic drug. Sterile physiological (PhS) solution was used as a control (pH 7.0; V = 25 µl).Results and discussion. In 34.3 % of of experiments we can talk about the modulating effect of farnesol solutions on the antifungal activity of antimycotic drugs. In all these cases, the sensitivity of YLF C. albicans to the antimycotic drug increases.Conclusion. The results of this study provide useful information for understanding the mechanism of QS-molecules action with antifungal activity, as well as they are the basis for the practical application of some QS-molecules in the treatment of infectious diseases caused by YLF of the genus Candida. The study demonstrates that farnesol can be recommended as an active substance that improves the sensitivity of YLF Candida to antimycotic drugs, especially in the case of multi-resistant strains Candida.

Evaluation of the Possibility of Using the Method of UV Spectrophotometry for the Development of Quantitative Determination of Naftifine Hydrochloride in its Solution with a Combination of PEG for the Treatment of Fungal Infections

Introduction. An innovative antifungal agent based on hydrochloride with combination of PEG-400 and PEG-1000 has been developed based at the chairs of Sechenov University. This solution is designated for external application as an antifungal agent. Naftifine hydrochloride has a broad spectrum of action against various fungi capable of causing onychomycosis. PEGs, forming part of the developed dosage form, bring about necessary viscosity of the solution (for retention in application area) and do not prevent drug product performance. Naftifine hydrochloride has an apparent UV absorption band with maximum of 256 ± 2 mn, in connection with this, it is supposed to use the UV spectrophotometry method for further development of quantitation method of naftifine hydrochloride detection in tested oral liquid.Aim. To evaluate the feasibility of using the UV spectrophotometry method for development of quantitation of naftifine hydrochloride in its solution with a combination of PEG for mycotic infection treatment.Materials and methods. The substance of naftifine hydrochloride, PEG-400 and PEG-1000, ethyl alcohol 96 %, UV spectrophotometry, «Millipore» filter.Results and discussion. A set of operations was carried out with UV spectrophotometer, including trials of solutions of initial substance of naftifine hydrochloride, PEG solutions, a solution of developed prolonged antimycotic drug and its placebo. The identity of UV spectra of the actual substance in various media was determined, maximum absorption of actual substance and dependence preservation between specified concentration and optical density of the solution were proved. It was found that auxiliary substances included in liquid dosage form do not affect the main characteristics of the UV spectrum of actual substance.Conclusion. The possibility in principle of using the UV spectrophotometry method for quantitative and qualitative analysis of innovative prolonged antimycotic drug – liquid dosage form of naftifine hydrochloride with a combination of PEG has been established.

Evaluation of newer imidazoles in dermatophytosis

<p class="abstract"><strong>Background:</strong> Eberconazole, a newer Imidazole derivative, antimycotic drug. Similarly, sertaconazole and luliconazole are also newer antifungal which all exhibit fungicidal, fungistatic and anti-inflammatory actions. But, sertaconazole in addition have antipruritic effect also.</p><p class="abstract"><strong>Methods:</strong> Randomized, open-labelled, prospective study comprising of 75 patients divided into three equal groups A, B, C of 25 patients each. Group A received eberconazole 1%, Group B received sertaconazole 2% and Group C received luliconazole 1% for twice daily topical application for 4 weeks. Patients were asked to review at 2^nd and 4^th week to record clinical and mycological cure.<strong></strong></p><p class="abstract"><strong>Results:</strong> In this study out of 75, seventy patients completed the complete course of treatment whereas, five patients were not reported for review citing personal reasons. Parameters included are pruritus, erythema, scaling and vesicles in all three groups. In this study, marked relief of pruritus was achieved clinically with eberconazole (72.7%) followed by luliconazole and sertaconazole with 50.0% and 33.3% respectively at 4^th week of treatment phase and reduction of scaling was achieved more with eberconazole (90.9%), sertaconazole (87.5%) and luliconazole (83.3%). All three groups of patients showed successful mycological cure by confirming with negative 10% potassium hydroxide examination at the end of treatment course.</p><p class="abstract"><strong>Conclusions:</strong> Eberconazole 1% cream was better than sertaconazole 2% cream and luliconazole 1% cream in relieving symptoms like pruritus and scaling at the end of treatment phase and follow up.</p>

DYNAMICS OF CLINICAL AND IMMUNOLOGICAL INDICATORS IN COMPLEX TREATMENT OF CANDIDA-ASSOCIATED PERIODONTITIS

Subject. The problem of complex treatment of candida-associated periodontitis is considered. The authors propose a two-component probiotic, which, due to antagonistic activity regarding periodontal pathogenic infection and fungi of the genus Candida, leads to the relief of the inflammatory process, positive dynamics and stabilization of immunological parameters. The aim ― to evaluate the dynamics of clinical and immunological parameters in the complex treatment of candida-associated periodontitis with an average degree of quantitative seeding of periodontal pockets using a two-component probiotic. Methodology. A clinical and laboratory examination of three groups (I, II, III) of patients with Candida-associated periodontitis with an average degree of quantitative contamination of periodontal pockets (> 3 <6 CFU / ml) was carried out. Patients I groups were prescribed the well-known complex treatment including an antimycotic drug, patients II groups included a two-component probiotic locally in the treatment complex, and patients III groups locally and per os. The state of the oral mucosa was assessed, PMA, PI, OHI - S were determined, and indicators of cellular and humoral immunity were examined. Results. The study made it possible to establish that the inclusion of a two-component probiotic in the complex of treatment of candida-associated periodontitis with an average degree of quantitative contamination of periodontal pockets with fungi of the genus Candida contributes to the relief of the inflammatory process, an increase in phagocytosis, the metabolic activity of neutrophils, the concentration of immunoglobulins A, lysozyme levels, and a decrease in the concentration of immunoglobulins. G, positive dynamics of other indicators of immunity and their stabilization. Conclusions. The inclusion of a two-component probiotic from two strains in the complex treatment of chronic hepatitis C associated with fungi of the genus Candida contributes to the rapid relief of the inflammatory process in periodontal tissues, positive dynamics and stabilization of cellular and humoral immunity parameters.

Monitoring and use of antimycotic (micafungin) for systemic use provided by the pharmacy of Marsala Hospital, Italy

Micafungin is an antimycotic drug and represents an important addition to the available therapies for the treatment of systemic fungal infections. Micafungin is used: in the treatment of invasive candidiasis, oesophageal and prophylaxis of <em>Candida</em> infections. It inhibits, in a non-competitive way, the synthesis of 1,3-β-D-glucan, a component of fungal cell wall and is rapidly distributed into the tissues. It has a high-rate respectful bond with plasma protein, which is independent from the concentration of the drug. It is metabolized through the liver, being not subject to intense metabolic transformations until the excretion. There is no evidence of systemic accumulation after repeated use. The steady-state is reached in 4-5 days. Medical records examined at the pharmacy of Marsala Hospital highlight that, from 01/06/2014 to 01/08/2014, in this hospital 12 vials were used by the hospitalized patients in the Department of Intensive Care: 8 patients between 75 and 83 years old had a body weight (BW) higher than 40 kg; 3 patients between 40 and 60 years of age had a BW higher than 40 kg, and one 17 year-old patient had a BW of 40 kg. Two patients needed a dose increase, while for the other 10 patients the first dose resulted sufficient. Mycamine^® was used for the treatment of hypovolemic post-operative shock. The most recorded adverse reactions were anemia, hypokalemia, hypomagnesemia, phlebitis, nausea, liver problems. Given the different weight of the subjects, the dosage was different.