1,721,054 research outputs found
Tricyclic antidepressants inhibit Candida albicans growth and biofilm formation
Full text linkCandida albicans is a commensal yeast of the human body, able to form biofilms on solid surfaces such as implanted medical devices, and contributes to nosocomial infections. Biofilms have the capacity to resist higher levels of antifungals compared with planktonic cells, and can develop tolerance to commonly used treatments. The necessity to overcome acquired drug resistance and identify new active molecules with low toxicity is a significant problem. It has been reported that some antidepressants have antibacterial properties, but little is known regarding the effect of these drugs on fungi. This study demonstrated the capacity of three tricyclic antidepressants (doxepin, imipramine and nortriptyline) to inhibit the growth and biofilm formation of Candida spp. The antimicrobial potential of the drugs was assessed by studying gene expression, hyphae formation, biofilm growth and maturation. Their negative impact on the growth of C. albicans and other Candida spp. is shown in vitro and with the hepatic S9 system, which is preliminary to any in-vivo test. This study found that the antidepressants considered can inhibit not only hyphae and biofilm formation, but also kill cells in a mature biofilm. Moreover, cell lysis by nortriptyline was observed, along with its synergistic activity with amphotericin B. These findings suggest that tricyclic antidepressants, particularly nortriptyline, should be studied further in drug repositioning programmes to assess their antimycotic capacity in full
Studio sedimentologico e paleoecologico su alcune sezioni plio-pleistoceniche affioranti presso Cerignola (FG)
No full textConfronto di strumenti per la valutazione della Qualità nei servizi: un’applicazione nel settore assistenza clienti
No full textKnown antimicrobials versus nortriptyline in Candida albicans: Repositioning an old drug for new targets
No full textCandida albicans has the capacity to develop resistance to commonly used antimicrobials, and to solve this problem, drug repositioning and new drug combinations are being studied. Nortriptyline, a tricyclic antidepressant, was shown to have the capacity to inhibit biofilm and hyphae formation, along with the ability to efficiently kill cells in a mature biofilm. To use nortriptyline as a new antimicrobial, or in combination with known drugs to increase their actions, it is important to characterize in more detail the effects of this drug on the target species. In this study, the Candida albicans GRACETM collection and a Haplo insufficiency profiling were employed to identify the potential targets of nortriptyline, and to classify, in a parallel screening with amphotericin B, caspofungin, and fluconazole, general multi-drug resistance genes. The results identified mutants that, during biofilm formation and upon treatment of a mature biofilm, are sensitive or tolerant to nortriptyline, or to general drug treatments. Gene ontology analysis recognized the categories of ribosome biogenesis and spliceosome as enriched upon treatment with the tricyclic antidepressant, while mutants in oxidative stress response and general stress response were commonly retrieved upon treatment with any other drug. The data presented suggest that nortriptyline can be considered a “new” antimicrobial drug with large potential for application to in vivo infection models
Comparing tools for Service Quality Evaluation
Full text linkService quality evaluation is one of the main issues that have recently drawn managers' and researchers' attention. The definition of an evaluation standard not dependent on any particular service context has determined the popularity of many different quality tools. In this paper we show a comparative analysis of the affected tools that are widely used. These are summarized in an orientation map. Moreover we present some results of an experiment carried out with two of the major quality tools (SERVQUAL and QUALITOMETRO). The results identify good qualities as well as weaknesses for both tools. Possible improvement strategies are presente
Protein Aggregation in Unicellular Eukaryotes
No full textThis chapter describes how unicellular eukaryotic cells, especially the budding yeast S. cerevisiae, deal with the presence of misfolded protein, beginning with their detection [in the endoplamic reticulum (ER), cytosol, or nucleus], their attempted refolding, and eventually, their degradation (proteasome or autophagy). It presents examples of proteins that naturally assume amyloid-like structures, and provides an overview of validated humanized yeast models. The accumulation of unfolded or misfolded proteins in the ER leads to ER stress and activation of the unfolded protein response (UPR). Disease-like amyloidogenic proteins were found to accumulate primarily within the IPOD, and not in a JUNQ. In addition to the research on protein aggregation in higher eukaryotic organisms, the study of protein misfolding in eukaryotic unicellular model organisms has been highly instructive in understanding the molecular mechanisms driving the cellular buildup of protein aggregates
Antimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications
No full textThe spreading of antibiotic resistance is responsible annually for over 700,000 deaths worldwide, and the prevision is that this number will increase exponentially. The identification of new antimicrobial treatments is a challenge that requires scientists all over the world to collaborate. Developing new drugs is an extremely long and costly process, but it could be paralleled by drug repositioning. The latter aims at identifying new clinical targets of an “old” drug that has already been tested, approved, and even marketed. This approach is very intriguing as it could reduce costs and speed up approval timelines, since data from preclinical studies and on pharmacokinetics, pharmacodynamics, and toxicity are already available. Antidepressants and antipsychotics have been described to inhibit planktonic and sessile growth of different yeasts and bacteria. The main findings in the field are discussed in this critical review, along with the description of the possible microbial targets of these molecules. Considering their antimicrobial activity, the manuscript highlights important implications that the administration of antidepressants and antipsychotics may have on the gut microbiome
Il rapporto tra l'insediamento di Coppa Nevigata e le variazioni idrografiche nel territorio circostante durante l'età del Bronzo
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