ABSTRACT
The multidrug resistance-associated protein (MRP1) mediates cellular efflux of various xenobiotics and cellular resistance to heavy metals. Previously we reported that MRP1 mediates resistance to mercury exposure and possible mechanism mediating MRP1 expression after mercury exposure. This study was designed to investigate the role of reactive oxygen species (ROS) and glutathione on the resistance of AML-2/DX100 cells to mercuric chloride. The MRP1 overexpressing cells (AML-2/DX100) cells showed less scavenging activity to ROS induced by mercury while no difference in the basal glutathione levels between AML-2/WT and AML-2/DX100 cells. Mercury induced the activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) but not c-jun-N-terminal kinase in AML-2/DX100 cells. The specific inhibitor for p38 MAPK and ERK, and antioxidant decreased the production of MRP1 and therefore resistance of AML-2/DX100 cells against mercury exposure. These results suggest that induction of ROS and downstream p38 MAPK and ERK were involved in the resistance of cells to mercury by expression MRP1 in AML-2/DX100 cells.
Subject(s)
Drug Resistance, Neoplasm , Glutathione/metabolism , Mercuric Chloride/pharmacology , Reactive Oxygen Species/metabolism , Acetylcysteine/pharmacology , Blotting, Western , Cell Line, Tumor , Cell Survival/drug effects , Dose-Response Relationship, Drug , Down-Regulation/drug effects , Extracellular Signal-Regulated MAP Kinases/metabolism , Flavonoids/pharmacology , Humans , Hydrogen Peroxide/pharmacology , Imidazoles/pharmacology , Multidrug Resistance-Associated Proteins/metabolism , Probenecid/pharmacology , Pyridines/pharmacology , Pyrrolidines/pharmacology , Signal Transduction/drug effects , Thiocarbamates/pharmacology , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
OBJECTIVES: To analyse the risk factors for nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infections caused by different clonal types. METHODS: A total of 134 non-duplicate nosocomial MRSA isolates were analysed for clonal types by molecular typing techniques. The medical records of 90 patients who had documented MRSA infection were evaluated retrospectively. RESULTS: Two predominant MRSA clones of sequence types (STs) ST239 (n = 75) and ST5 (n = 39) accounted for 85% of the isolates. Management of patients in the departments of orthopaedic surgery, neurosurgery and plastic surgery was identified as a risk factor for infection with MRSA of ST239, while the presence of intravascular catheters was a risk factor for infection with ST5. Pulmonary infection was significantly higher in the patients infected with ST239 strains than in the patients infected with ST5 strains (P < 0.05). The overall mean duration of antimicrobial therapy for the patients with ST239 infection was significantly more than that for the patients with ST5 infection (P < 0.05). CONCLUSIONS: ST239 and ST5 were the predominant MRSA clones in the study hospital. Risk factors were significantly different between ST239 and ST5 strains. The results of this study will be of use in designing larger prospective epidemiological studies for MRSA infection based on clonal types.
Subject(s)
Cross Infection/microbiology , Methicillin Resistance , Staphylococcal Infections/microbiology , Staphylococcus aureus/classification , Staphylococcus aureus/drug effects , Adult , Catheterization , Cross Infection/epidemiology , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , Female , Hospitals , Humans , Inpatients , Korea , Male , Middle Aged , Molecular Epidemiology , Patient Care Management , Pneumonia, Staphylococcal/microbiology , Polymerase Chain Reaction , Retrospective Studies , Risk Factors , Sequence Analysis, DNA , Staphylococcal Infections/epidemiology , Staphylococcus aureus/genetics , Surgical Wound Infection/microbiologyABSTRACT
The lack of a universally applicable definition of terrorism has confounded the understanding of terrorism since the term was first coined in 18th Century France. Although a myriad of definitions of terrorism have been advanced over the years, virtually all of these definitions have been crisis-centered, frequently reflecting the political perspectives of those who seek to define it. In this article, we deconstruct these previously used definitions of terrorism in order to reconstruct a definition of terrorism that is consequence-centered, medically relevant, and universally harmonized. A universal medical and public health definition of terrorism will facilitate clinical and scientific research, education, and communication about terrorism-related events or disasters. We propose the following universal medical and public definition of terrorism: The intentional use of violence--real or threatened--against one or more non-combatants and/or those services essential for or protective of their health, resulting in adverse health effects in those immediately affected and their community, ranging from a loss of well-being or security to injury, illness, or death.
