ABSTRACT
Gaucher disease is the most common lysosomal storage disorder. Resveratrol is a natural polyphenol that possesses a wide range of beneficial effects, including anti-inflammatory, anti-oxidant, and neuroprotective activities. The aim of this study was to determine if resveratrol has a therapeutic effect on primary fibroblast cells derived from a patient with type III Gaucher disease. 3-(4,5- Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed to determine the effect of resveratrol on cell survival. The expression levels of apoptosis-inducing factor (AIF), Bcl-2-associated X protein (Bax), caspase-3, acetyl-coenzyme A acetyltransferase 1 (ACAT1), E3- binding protein (E3BP), and citrate synthase (CS) were evaluated by western blotting to characterize the effect of resveratrol treatment on Gaucher disease cells. Thin-layer chromatography (TLC) was carried out to measure changes in glucosylceramide levels in resveratrol-treated patient cells. Resveratrol increased the viability of patient cells compared to that of untreated control cells. Resveratrol treatment dose-dependently decreased AIF, Bax, and cleaved caspase-3 levels, whereas ACAT1, E3BP, and CS expression dose-dependently increased. TLC analysis showed reduced levels of glucosylceramides in resveratrol-treated patient cells. These findings demonstrate that resveratrol can relieve cellular stress due to glucosylceramide accumulation, and suggest that it should be studied further as a new therapeutic approach for the treatment of Gaucher disease.
Subject(s)
Gaucher DiseaseABSTRACT
BACKGROUND: Most imipenem-resistant Acinetobacter baumannii (IRAB) isolates are multiresistant, leaving few options for an effective antimicrobial therapy. We purposed to select possible candidates for the combinations of antimicrobials that are synergistic in vitro for inhibitory or bactericidal activities against IRAB and evaluate the usefulness of double disk synergy test (DDS) in predicting synergistic bactericidal activity. METHODS: Fifty-five IRAB isolates recovered from patients during the period from August 1999 to November 2000 were tested for susceptibilities to amikacin, gentamicin, tobramycin, piperacillin, piperacillin/tazobactam, cefotaxime, cefepime, cefoperazone/sulbactam (C/S), imipenem, meropenem, ciprofloxacin, levofloxacin, trimethoprim/sulfamethoxazole, chloramphenicol, minocycline, and colistin by the Clinical and Laboratory Standard Institute agar dilution method. Three isolates showing different susceptibility profiles were tested for antimicrobial synergy by DDS and then by timekill study (TKS) using DDS-positive combinations. RESULTS: Colistin, C/S, and minocycline were active in 50 (90.9%), 50, and 44 (80.0%) isolates, respectively, and all the other drugs were active in less than 20% of isolates. Minocycline-imipenem, minocycline-C/S, minocycline-amikacin, imipenem-tobramycin, C/S-amikacin, and C/S-tobramycin combinations showed synergistic inhibitory or bactericidal activity by TKS when the same combinations were synergistic in DDS; however, C/S-imipenem was found synergistic on DDS, but not by TKS. CONCLUSIONS: Colistin, C/S, and minocycline were relatively active against IRAB. DDS might help predict the synergistic antimicrobial effect of TKS if one of the combinations was susceptible.