With the goal of obtaining a novel bioactive compound with significant antifungal activity, a series of 1,3,4-thiadiazole derivatives (3a–3l) were synthesized and characterized. Due to thione-thiol tautomerism in the intermediate compound 2, type of substitution reaction in the final step was determined by two-dimensional (2D) NMR. In vitro antifungal activity of the synthesized compounds was evaluated against eight Candida species. The active compounds 3k and 3l displayed very notable antifungal effects. The probable mechanisms of action of active compounds were investigated using an ergosterol quantification assay. Docking studies on 14-α-sterol demethylase enzyme were also performed to investigate the inhibition potency of compounds on ergosterol biosynthesis. Theoretical absorption, distribution, metabolism, and excretion (ADME) predictions were calculated to seek their drug likeness of final compounds. The results of the antifungal activity test, ergosterol biosynthesis assay, docking study, and ADME predictions indicated that the synthesized compounds are potential antifungal agents, which inhibit ergosterol biosynthesis probably interacting with the fungal 14-α-sterol demethylase.

No abstract

As an immunomodulator, melatonin reportedly exhibits protective effects in severe sepsis/shock induced by bacterial lipopolysaccharides in animal models. The present study was conducted to evaluate the possible protective effects of melatonin against experimental Candida sepsis in rats. A total of 40 adult male Wistar rats were randomly assigned to 4 groups: control, melatonin-treated control, septic, and melatonin-treated septic. Melatonin (200 microg/kg/d, intraperitoneally) injections were begun a week prior to sepsis induction and were continued daily for 3 wk until the end of the study. Cyclophosphamide was administered to animals in all groups as an immunosuppressive agent as a single dose 4 d prior to yeast inoculation. To cause sepsis, the Candida albicans (ATCC 10259) strain was administered intravenously. Amphotericin B was given as an antimycotic therapeutic agent as a single dose to septic rats. Plasma levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), vascular cell adhesion molecule-1, and E-selectin were measured on the first and 15th days of sepsis. IL-6, TNF-alpha, vascular cell adhesion molecule-1, and E-selectin levels of septic rats were higher than those of controls. Melatonin reduced IL-6 levels and shortened time to improvement in animals with Candida sepsis. Levels of TNF-alpha and adhesion molecules in melatonin-treated septic rats were decreased compared with those in septic rats, but this difference was not statistically significant. In light of the current results, investigators conclude that melatonin may have therapeutic benefits in Candida sepsis and in classic antimycotic treatment because of its immune regulatory effects.

To assess the frequency of superficial mycoses in forestry workers and farmers in the rural region of Duzce, a total of 467 residents of the rural region were examined for dermatomycosis infection. Of these, 349 were forestry workers and 118 farmers. All specimens collected were analysed by direct microscopy and culture. Tinea pedis et manus was found in 23 (19.4%), and onycomycosis in 21 (17.7%) farmers. Tinea pedis et manus was found in 50 (14.3%), and onycomycosis in 28 (8%) forestry workers. One tinea corporis, two tinea inguinalis and two erosio interdigitalis cases were determined in the farmer group but no cases of tinea corporis, tinea inguinalis, or erosio interdigitalis were found in the forestry group. In total, five tinea versicolor cases were found in the two groups on clinical examination but no agent positivity was yielded in mycological cultures. The most frequently isolated agent in the two groups was Trichophyton rubrum. The frequencies of superficial mycosis and onychomycosis were found to be higher in the farmer group than in the forestry group, although similar aetiological agents were isolated in both groups. The farmers had greater rates of contact with pathogenic fungi present in soil as well as from infected farm animals than the foresters; furthermore, animal husbandry, and the wearing of rubber shoes and nylon socks were more frequent in the farmer group. These results suggest that habits such as the wearing of rubber shoes and nylon socks, and the practice of animal husbandry may be the most important factors in determining the frequency of superficial mycoses and aetiological agents in forestry workers and farmers. To our knowledge, there is no previous report about dermatophytoses in forestry workers.

The prevalence of H pylori infection was 53.3% for the symptomatic patients in this study, and 47.5% of the isolates showed clarithromycin resistance using melting curve analysis. The PCR-based system used in this study was accurate for the detection of H pylori infection as well as clarithromycin susceptibility testing directly in biopsy specimens.