Thiazolidinediones alter cell energy metabolism. They are used to treat or are being considered for the treatment of disorders that feature mitochondrial impairment. Their mitochondrial effects, however, have not been comprehensively studied under long-term exposure conditions. We used the human neuronlike NT2 cell line to directly assess the long-term effects of a thiazolidinedione drug, pioglitazone, on mitochondria. At micromolar concentrations, pioglitazone increased mitochondrial DNA (mtDNA) content, levels of mtDNA and nuclear-encoded electron transport chain subunit proteins, increased oxygen consumption, and elevated complex I and complex IV V max activities. Pioglitazone treatment was also associated with increased cytoplasmic but reduced mitochondrial peroxide levels. Our data suggest that pioglitazone induces mitochondrial biogenesis and show that pioglitazone reduces mitochondrial oxidative stress in a neuron-like cell line. For these reasons pioglitazone may prove useful in the treatment of mitochondriopathies.

AngioVac Cannula can be used safely and effectively as an adjunctive method for patients with large lead vegetation.

The RecG helicase of Escherichia coli unwinds both Holliday junction (HJ) and replication fork DNA substrates. Our lab previously identified and characterized peptides (WRWYCR and KWWCRW) that block the activity of RecG on these substrates. We determined that the peptides bind HJ DNA and prevent the binding of RecG. Herein, we present further evidence that the peptides are competitive inhibitors of RecG binding to its substrates. We have generated structural models of interactions between WRWYCR and a junction substrate. Using the fluorescent probe 2-aminopurine, we show that inhibitors interact with highest affinity with HJs (Kd = 14 nM) and ∼4- to 9-fold more weakly with replication fork substrates. The fluorescence assay results agree with the structural model, and predict the molecular basis for interactions between HJ-trapping peptides and branched DNA molecules. Specifically, aromatic amino acids in the peptides stack with bases at the center of the DNA substrates. These interactions are stabilized by hydrogen bonds to the DNA and by intrapeptide interactions. These peptides inhibit several proteins involved in DNA repair in addition to RecG, have been useful as tools to dissect recombination, and possess antibiotic activity. Greater understanding of the peptides’ mechanism of action will further increase their utility.

The topical use of essential oils requires dilution into a carrier oil; however, scientific evidence regarding the antimicrobial efficacy and cytotoxicity when a carrier oil is combined with an essential oil is lacking. This study sets out to determine the antimicrobial activity and cytotoxicity of 23 essential oils combined with six known carrier oils. Gas chromatography-mass spectrometry/flame ionization detector (GC-MS/FID) was used to characterize the methyl esters of the carrier oils. The antimicrobial activity of the carrier oils alone and in combination with the essential oils was investigated using the broth microdilution assay against 11 skin pathogens and the cytotoxicity was determined using the brine shrimp lethality assay. The interactive profiles of the combinations for both antimicrobial activity and the cytotoxicity were analysed and calculated using the fractional inhibitory concentration index (ΣFIC). The carrier oils demonstrated no antimicrobial antagonism when combined with the essential oils and the overall cytotoxicity of the majority of the combinations was decreased. The carrier oils that could be identified as enhancing the antimicrobial activity and decreasing the cytotoxicity were Aloe vera Mill. and Simmondsia chinensis C.K.Schneid (Jojoba oil), with an overall reduction in essential oil cytotoxicity of 87.5% at 24 hrs and 85% at 48 hrs by A. vera. Five of the essential oils (when diluted in A. vera and S. chinensis carrier oils) demonstrated enhanced antimicrobial activity against pathogens such as Brevibacterium epidermidis, B. linens, and P. aeruginosa with MIC values ranging from 0.09 to 0.50 mg/mL (and ΣFIC 0.14-0.39). The study could conclude that the carrier oils are complementary to essential oil formulations, mostly reducing cytotoxicity and in some cases enhancing the antimicrobial activity.

No abstract