Subject(s)
Acne Vulgaris/drug therapy , Acquired Hyperostosis Syndrome/drug therapy , Antirheumatic Agents/therapeutic use , Drug Eruptions/drug therapy , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Isotretinoin/adverse effects , Acne Vulgaris/etiology , Acquired Hyperostosis Syndrome/complications , Adolescent , Drug Eruptions/etiology , Humans , Male , Remission Induction , Severity of Illness IndexABSTRACT
AIMS: The influence of an antioxidant, propyl gallate (PG), on the in vitro antifungal activity of itraconazole and fluconazole, was investigated to determine whether PG could increase the antifungal activity and reduce strain resistance. METHODS AND RESULTS: Susceptibility tests were performed against azole-resistant isolates of Candida albicans by the microbroth dilution method in the presence of PG at 400 microg ml-1. PG-triazole combination brought about a marked reduction of inhibitory azole concentration. In particular, the MIC90 for itraconazole and fluconazole dropped from 1 microg ml-1 to 0.125 microg ml-1 and from > 64 microg ml-1-8 microg ml-1, respectively. CONCLUSION: It is likely that more than one mechanism is involved in the above synergistic interaction, including effects of PG on ATP synthesis, thus reducing the ABC transporters activity, or an effect on the target of azole, i.e. the P-450 cytochrome. SIGNIFICANCE AND IMPACT OF THE STUDY: The PG-triazole combination may have a role in future topical antifungal strategies but other studies are warranted.
Subject(s)
Antifungal Agents/pharmacology , Antioxidants/pharmacology , Candida albicans/drug effects , Fluconazole/pharmacology , Imidazoles/pharmacology , Itraconazole/pharmacology , Propyl Gallate/pharmacology , Drug Interactions , Drug Resistance, Microbial , Humans , Microbial Sensitivity Tests/methodsABSTRACT
The MAP kinase (MAPK) p38 plays a key role in regulating inflammatory responses. Here, we demonstrate that beta1 integrin ligation on human NK cells results in the activation of the p38 MAPK signaling pathway, which is required for integrin-triggered IL-8 production. In addition, we identified some of the upstream events accompanying the beta1 integrin-mediated p38 MAPK activation, namely, the activation of the Rac guanine nucleotide exchange factor (GEF) p95 Vav, the small G protein Rac1, and the cytoplasmic kinases Pak1 and MKK3. Finally, we provide direct evidence that p95 Vav and Rac control the activation of p38 MAPK triggered by beta1 integrins.
