Caspofungin activity against clinical isolates of azole cross-resistant Candida glabrata overexpressing efflux pump genes.

OBJECTIVES: Several studies have documented the potent in vitro activity of caspofungin against Candida spp. This is of special concern for Candida glabrata infections that are often resistant to many azole antifungal agents and, consequently, difficult to treat. The aim of the present study was to expand the data on the in vitro activity of caspofungin against azole-resistant isolates of C. glabrata. METHODS: A total of 50 clinical isolates of C. glabrata were tested for susceptibility to caspofungin. The isolates were cross-resistant to multiple azoles, including fluconazole, itraconazole, ketoconazole and voriconazole. Expression of the resistance-related CgCDR1 and CgCDR2 genes was evaluated by quantitative RT-PCR analysis. The MICs of caspofungin were determined by using the National Committee for Clinical Laboratory Standards M27-A2 reference method. RESULTS: C. glabrata isolates exhibited increased expression of the CDR efflux pump(s), and this was in accordance with their high-level azole resistance. In contrast, all the isolates were highly susceptible to caspofungin (100% of isolates were inhibited at <or=1 mg/L). CONCLUSIONS: Our results represent further evidence for the excellent antifungal potency of caspofungin, particularly against C. glabrata isolates expressing cross-resistance to azoles

Is technology optimism justified? A discussion towards a comprehensive narrative

This paper is based on a discussion developed by one of the thematic working groups at the Biennial International Workshop Advances in Energy Studies (BIWAES) 2017 hold in Naples, Italy. The topic was the role of technology in energy transition and global problems. Owing to the heterogeneity of the participants in the working group, different viewpoints were put together, leading to some shared conclusions. In particular, the role played by the different narratives used in discussing the role of technology in facing global problems was pointed out as the origin of cognitive dissonance. The presented reflections address some conceptual weaknesses in the current debate on technology and global issues, framed in global policies that appear incapable to obtain tangible results. The technology optimism seems, in fact, to be based on the elusive use of both the concepts of technology and sustainability, that are put together for narrative purposes without an explicit conceptual assessment. On one hand, the factual role of technology and its beneficiary are almost never clearly addressed in the debate. On the other hand, the fact that any new technology will serve the cause of sustainability is not questioned whatsoever, without taking into account the social, political and ethical framework in which technology is supposed to be operated

Lymphocyte TRPV 1-4 gene expression and MIF blood levels in a young girl clinically diagnosed with HSAN IV.

OBJECTIVE: Patients with congenital insensitivity to pain are unable to sense pain and temperature. They undergo many injuries, inflammatory state, and infections. Various mutations in the neurotrophic tyrosine kinase receptor gene have been implicated in this disorder. We measured the leukocyte expression of transient receptor potential vanilloid (TRPV) 1-4 genes and the blood macrophage migration inhibitory factor (MIF) concentration in a young girl clinically diagnosed with congenital insensitivity to pain. The investigation may help to define the interplay between nerve growth factor and TRPV 1-4 channels and between these sensors and MIF in this disease, and in broader terms in nociception. METHODS: TRPV 1-4 gene expression (real-time polymerase chain reaction) and MIF concentration (enzyme-linked immunosorbent assay) were determined in the blood of the girl, her family, and control participants. Statistical analysis of gene expression was carried out between samples and controls with a mathematical model based on the correction for exact polymerase chain reaction efficiencies, and the mean crossing point deviation between samples and controls. RESULTS: The TRPV 1--4 gene expression rates did not significantly differ from the values found in the control group. TRPV1 was almost doubly upregulated. MIF levels were much higher than the reference value. DISCUSSION: The high increase in the MIF concentration (likely due to the chronic or recurrent inflammatory state) may have contributed to the normal expression of TRPV 1-4 and to the relative upregulation of TRPV1. The role of this cytokine on the expression of these genes deserves further investigation

Lymphocyte TRPV 1-4 Gene Expression and MIF Blood Levels in a Young Girl Clinically Diagnosed With HSAN IV

7OBJECTIVE: Patients with congenital insensitivity to pain are unable to sense pain and temperature. They undergo many injuries, inflammatory state, and infections. Various mutations in the neurotrophic tyrosine kinase receptor gene have been implicated in this disorder. We measured the leukocyte expression of transient receptor potential vanilloid (TRPV) 1-4 genes and the blood macrophage migration inhibitory factor (MIF) concentration in a young girl clinically diagnosed with congenital insensitivity to pain. The investigation may help to define the interplay between nerve growth factor and TRPV 1-4 channels and between these sensors and MIF in this disease, and in broader terms in nociception. METHODS: TRPV 1-4 gene expression (real-time polymerase chain reaction) and MIF concentration (enzyme-linked immunosorbent assay) were determined in the blood of the girl, her family, and control participants. Statistical analysis of gene expression was carried out between samples and controls with a mathematical model based on the correction for exact polymerase chain reaction efficiencies, and the mean crossing point deviation between samples and controls. RESULTS: The TRPV 1--4 gene expression rates did not significantly differ from the values found in the control group. TRPV1 was almost doubly upregulated. MIF levels were much higher than the reference value. DISCUSSION: The high increase in the MIF concentration (likely due to the chronic or recurrent inflammatory state) may have contributed to the normal expression of TRPV 1-4 and to the relative upregulation of TRPV1. The role of this cytokine on the expression of these genes deserves further investigation.nonenoneBachiocco V; Bergamaschi R; Spinsanti G; Lima M; Romagnoli R; Sorda G; A. ALOISIBachiocco, V; Bergamaschi, R; Spinsanti, Giacomo; Lima, M; Romagnoli, Roberta; Sorda, Giuseppina; Aloisi, ANNA MARI