Assessing liver injury associated with antimycotics:Concise literature review and clues from data mining of the FAERS database

AIM: To inform clinicians on the level of hepatotoxicrisk among antimycotics in the post-marketing setting,following the marketing suspension of oral ketocon-azole for drug-induced liver injury(DILI).METHODS: The publicly available international FAERSdatabase(2004-2011) was used to extract DILI cases(including acute liver failure events), where antimycot-ics with systemic use or potential systemic absorptionwere reported as suspect or interacting agents. The re-porting pattern was analyzed by calculating the report-ing odds ratio and corresponding 95%CI, a measure ofdisproportionality, with time-trend analysis where ap-propriate.RESULTS: From 1687284 reports submitted over the8-year period, 68115 regarded liver injury. Of these,2.9% are related to antimycotics(1964 cases, of which 112 of acute liver failure). Eleven systemic antimycotics(including ketoconazole and the newer triazole deriva-tives voriconazole and posaconazole) and terbinafine(used systemically to treat onychomicosis) generated a significant disproportionality, indicating a post-market-ing signal of risk.CONCLUSION: Virtually all antimycotics with systemic action or absorption are commonly reported in clinically significant cases of DILI. Clinicians must be aware of this aspect and monitor patients in case switch is con-sidered, especially in critical poly-treated patients under chronic treatment.

A method of active conformation search based on active and inactive analogues, and its application to allylamine antimycotics

A new program ACSBAIA (Active Conformation Search Based on Active and Inactive Analogues ) for determination of the active conformations was developed based on the rationales that specific functional groups of active analogues could reach and interact with the active site of target receptor by means of the change of conformations, but that of inactive analogues could not interact with theactive site owing to conformational restriction. The program consisted of 4 sub-programs: conformation sampling system, active conformation constraint system, inactive conformation exclusion system, and activity prediction system. Pharmacophoric conformation of allylamine antimycotics was studied by this method. Activities of 2 analogues were predicted and tested. The results suggested that the method was scientific and practical. The application of this method was not restricted by the three-dimensional structural knowledge of target receptor. In the absence of structural information about the receptor, the method was particularly applicable.

Effect of heat treatment on antimycotic activity of Sahara honey

Objective:To evaluate the influence of the temperature on honey colour,polyphenol contents and antimycotic capacity and to evaluate the correlation between these parameters.Methods:Sahara honey were heated up to 25,50,75 and 100℃for 15,30 and 60 min,and their colour intensity,polyphenol contents and antimycotic capacity.The Folin-Ciocalteu test was used to determine the total polyphenol contents(TPC).The antimycotic activity was evaluated both by agar diffusion method and micro wells dilution method against the Candida albicans(C.albicans)and Candida glabrata(C.glabrata).Results:Initial values for TPC in Sahara honey ranged from 0.55 to 1.14 mg of gallic acid per kg of honey,with the average value of 0.78 mg of gallic acid per kg of honey.The TPC values after heat-treatment were 0.54 to 1.54 with the average value of 1.49 mg.The minimal inhibitory concentrations before heat-treatment of Sahara honey against C.albicans and C.glabrata ranged from 3.06%-12.5%and 50%respectively.After heat-treatment the minimal inhibitory concentrations between 12.5%and 50%for C.albicans and C.glabrata,respectively.The diameters of inhibition zones of Sahara honey with 50%concentration varied from(12.67-15.00)mm by C.albicans to(14.33-15.67)mm by C.glabrata.The diameters of inhibition zones after heat-treatment at 25 and 50°C for 15.30 and 60 min ranged from(2.00-18.67)mm by C.albicans to(8.00-16.67)mm by C.glabrata.Statistically significant relations between the TPC and the colour intensity of Sahara honey(r=0.99,P<0.05).Furthermore,the results showed that the TPC and colour is not correlated with the antimycotic capacity.Conclusions:To our knowledge this is the first report on the antimycotic capacity of Sahara honey.

Quinolinium Structure as Labeled Biomarkers

In this study the compatible chemical and biological investigations of several N-phenylquinolinium derivatives have been carried out in order to find the most perspective quinolinium structures for the nuclear-chemical synthesis of tritium labeled biomarkers.

Potential Application of a Wine Extract in Skin Care: How to Benefit from the Antibacterial, Antioxidant and Elastase Inhibiting Properties

Since plant polyphenols have many beneficial properties on health, the aim of this study was to evaluate the potential use of a phenolic wine extract, a by-product of wine production, for skin care on HaCaT cells. In these studies, a significant reduction of reactive oxygen species formation in HaCaT cells and severe elastase inhibition was observed. In contrast, the wine extract caused a major increase in lipase activity. The extract showed no influence on cell proliferation, but an immunomodulatory effect on the release of the interleukins IL-6 and IL-8 was found. The phenolic wine extract demonstrated a strong activity against gram-positive and gram-negative pathogens, yeasts, and fungi. Overall, our results show that the investigated phenolic wine extract is a promising ingredient for anti-aging skin care, could contribute to the improvement of skin appearance and health, and may positively affect cellulite.