Reactive nitrogen species derived from NO have been implicated in cancer and other diseases, but their intracellular concentrations are largely unknown. To estimate them under steady-state conditions representative of inflamed tissues, a kinetic model was developed that included the effects of cellular antioxidants, amino acids, proteins, and lipids. For an NO concentration of 1 µM, total peroxynitrite (Per, the sum of ONOO− and ONOOH), NO2·, and N2O3 were calculated to have concentrations in the nM, pM, and fM ranges, respectively. The concentrations of NO2· and N2O3 were predicted to decrease markedly with increases in glutathione (GSH) levels, due to the scavenging of each by GSH. Although lipids accelerate the oxidation of NO by O2 (because of the high solubility of each in hydrophobic media), lipid-phase reactions were calculated to have little effect on NO2· or N2O3 concentrations. The major sources of intracellular NO2· were found to be the reaction of Per with metals and with CO2, whereas the major sinks were its reactions with GSH and ascorbate (AH−). The radical-scavenging ability of GSH and AH− caused 3-nitrotyrosine to be the only tyrosine derivative predicted to be formed at a significant rate. The major GSH reaction product was S-nitrosoglutathione. Analytical (algebraic) expressions are provided for the concentrations of the key reactive intermediates, allowing the calculations to be extended readily.

Dysregulated production of nitric oxide (NO•) and reactive oxygen species (ROS) by inflammatory cells in vivo may contribute to mutagenesis and carcinogenesis. Here we compare cytotoxicity and mutagenicity induced by NO• and ROS in TK6 and AS52 cells, delivered by two methods: a well-characterized delivery system; and a novel adaptation of a system for co-culture. When exposed to preformed NO•, a cumulative dose of 620 µM•min reduced viability of TK6 cells at 24 h to 36% and increased mutation frequencies in the HPRT and TK1 genes to 7.7 × 106 (p < 0.05) and 24.8 × 106 (p < 0.01), 2.7- and 3.7-fold higher than background, respectively. In AS52 cells, cumulative doses of 1700 and 3700 µM•min reduced viability to 49% and 22%, respectively, and increased mutation frequency 10.2- and 14.6-fold higher than the argon control (132 × 106 and 190 × 106, respectively). These data show that TK6 cells were more sensitive than AS52 cells to killing by NO•. However, the two cell lines were very similar in relative susceptibility to mutagenesis; on the basis of fold-increases in MF, average relative sensitivity values [(MFexp/MFcontrol) /cumulative NO• dose] were 5.16 × 10−3 µM−1min−1, and 4.97 × 10−3µM−1min−1 for AS52 cells. When AS52 cells were exposed to reactive species generated by activated macrophages in the co-culture system, cell killing was greatly reduced by addition of NMA to the culture medium, and was completely abrogated by combined additions of NMA and the superoxide scavenger Tiron, indicating the relative importance of NO• to loss of viability. Exposure in the co-culture system for 48 h increased mutation frequency in the gpt gene by more than 9 fold, and NMA plus Tiron again completely prevented the response. Molecular analysis of gpt mutants induced by preformed NO• or by activated macrophages revealed that both doubled the frequency of gene inactivation (40% in induced vs 20% in spontaneous mutants). Sequencing showed that base-substitution mutations dominated the spectra, with transversions (30–40%) outnumbering transitions (10–20%). Virtually all mutations took place at guanine sites in the gene. G:C to T:A transversions accounted for about 30% of both spontaneous and induced mutations; G:C to A:T transitions amounted to 10–20% of mutants; insertions, small deletions and multiple mutations were present at frequencies of 0–10%. Taken together, these results indicate that cell type and proximity to generator cells are critical determinants of cytotoxic and genotoxic responses induced by NO• and reactive species produced by activated macrophages.

Acute post-streptococcal glomerulonephritis (PSGN) is characterized by an abrupt onset of edema, hypertension, and hematuria. Life-threatening diffuse alveolar hemorrhage (DAH) is rarely associated with acute PSGN. There have been only two reported cases worldwide, and no case has been reported previously in Korea. Here, we present a patient who clinically presented with pulmonary-renal syndrome; the renal histology revealed post-infectious glomerulonephritis of immune complex origin. A 59-yr-old woman was admitted with oliguria and hemoptysis two weeks after pharyngitis. Renal insufficiency rapidly progressed, and respiratory distress developed. Chest radiography showed acute progressive bilateral pulmonary infiltrates. The clinical presentation suggested DAH with PSGN. Three days after treatment with high-dose steroids, the respiratory distress and pulmonary infiltrates resolved. Electron microscopy of a renal biopsy specimen sample revealed diffuse proliferative glomerulonephritis with characteristic subendothelial deposits of immune complex ("hump"). The renal function of the patient was restored, and the serum creatinine level was normalized after treatment.

Seasonal influenza is a significant cause of morbidity and mortality of children in Korea. However, few data are available on parental perception and action toward childhood influenza. This study aimed to characterize parental perception and patterns of action in response to influenza and influenza-like illnesses (ILIs), including vaccination and healthcare use. This prospective study involved a random survey of parents whose children were aged 6–59 months. The survey was conducted in October 2014. The study included 638 parents of 824 children younger than 6 years. Most parental information of influenza came from mass media (28.2%) and social media (15.5%). The factor that most often motivated parents to vaccinate their children against influenza was promotion of the government or mass media (36.6%). Negative predictors of immunization included safety concerns about influenza vaccination (28.1%) and mistrust in the vaccine's effectiveness (23.3%). Therefore, correct information about influenza and vaccination from mass media will be one of the cornerstones for implementing a successful childhood immunization program and reducing morbidity and mortality in Korea. Furthermore, to enroll younger children in vaccination programs, and to minimize coverage gaps, public concerns about vaccine safety should be resolved. The demographic data in the present study will be used to provide a deeper insight into a parental perception and will help health care providers increase influenza immunization rate.