Inhibition of c-Jun NH(2)-terminal kinase or extracellular signal-regulated kinase improves lung injury

BACKGROUND: Although in vitro studies have determined that the activation of mitogen-activated protein (MAP) kinases is crucial to the activation of transcription factors and regulation of the production of proinflammatory mediators, the roles of c-Jun NH(2)-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) in acute lung injury have not been elucidated. METHODS: Saline or lipopolysaccharide (LPS, 6 mg/kg of body weight) was administered intratracheally with a 1-hour pretreatment with SP600125 (a JNK inhibitor; 30 mg/kg, IO), or PD98059 (an MEK/ERK inhibitor; 30 mg/kg, IO). Rats were sacrificed 4 hours after LPS treatment. RESULTS: SP600125 or PD98059 inhibited LPS-induced phosphorylation of JNK and ERK, total protein and LDH activity in BAL fluid, and neutrophil influx into the lungs. In addition, these MAP kinase inhibitors substantially reduced LPS-induced production of inflammatory mediators, such as CINC, MMP-9, and nitric oxide. Inhibition of JNK correlated with suppression of NF-κB activation through downregulation of phosphorylation and degradation of IκB-α, while ERK inhibition only slightly influenced the NF-κB pathway. CONCLUSION: JNK and ERK play pivotal roles in LPS-induced acute lung injury. Therefore, inhibition of JNK or ERK activity has potential as an effective therapeutic strategy in interventions of inflammatory cascade-associated lung injury

Cytoprotective Activity of Glycyrrhizae radix Extract Against Arsenite-induced Cytotoxicity

Licorice, Glycyrrhizae radix, is one of the herbal medicines in East Asia that has been commonly used for treating various diseases, including stomach disorders. This study investigated the effect of licorice on arsenite (As)-induced cytotoxicity in H4IIE cells, a rat hepatocyte-derived cell line. Cell viability was significantly diminished in As-treated H4IIE cells in a time and concentration-dependent manner. Furthermore, results from flow cytometric assay and DNA laddering in H4IIE cells showed that As treatment induced apoptotic cell death by activating caspase-3. Licorice (0.1 and 1.0 mg ml−1) treatment significantly inhibited cell death and the activity of caspase-3 in response to As exposure. These results demonstrate that licorice induced a cytoprotective effect against As-induced cell death by inhibition of caspase-3

Linear programming method to construct equated item sets for the implementation of periodical computer-based testing for the Korean Medical Licensing Examination

Purpose This study aimed to identify the best way of developing equivalent item sets and to propose a stable and effective management plan for periodical licensing examinations. Methods Five pre-equated item sets were developed based on the predicted correct answer rate of each item using linear programming. These pre-equated item sets were compared to the ones that were developed with a random item selection method based on the actual correct answer rate (ACAR) and difficulty from item response theory (IRT). The results with and without common items were also compared in the same way. ACAR and the IRT difficulty were used to determine whether there was a significant difference between the pre-equating conditions. Results There was a statistically significant difference in IRT difficulty among the results from different pre-equated conditions. The predicted correct answer rate was divided using 2 or 3 difficulty categories, and the ACAR and IRT difficulty parameters of the 5 item sets were equally constructed. Comparing the item set conditions with and without common items, including common items did not make a significant contribution to the equating of the 5 item sets. Conclusion This study suggested that the linear programming method is applicable to construct equated-item sets that reflect each content area. The suggested best method to construct equated item sets is to divide the predicted correct answer rate using 2 or 3 difficulty categories, regardless of common items. If pre-equated item sets are required to construct a test based on the actual data, several methods should be considered by simulation studies to determine which is optimal before administering a real test

Obstructive Fibrinous Tracheal Pseudomembrane After Tracheal Intubation: A Case Report

Obstructive fibrinous tracheal pseudomembrane is a rare, but potentially fatal complication associated with endotracheal intubation. It has been known that the formation of tracheal pseudomembrane is related with intracuff pressure during endotracheal intubation or infectious cause. But in the patient described in this case, pseudomembrane formation in the trachea was associated with subglottic epithelial trauma or caustic injuries to the trachea caused by aspirated gastric contents during intubation rather than tracheal ischemia due to high cuff pressure. We report a patient with obstructive fibrinous tracheal pseudomembrane after endotracheal intubation who presented with dyspnea and stridor and was treated successfully with mechanical removal using rigid bronchoscopy

In Vitro and in Vivo Phototoxicity on Gastric Mucosa Induced by Methylene Blue

BACKGROUND: Methylene blue (MB) is used endoscopically to demarcate tumors and as a photosensitizer in photodynamic therapy (PDT). However, there are few in vivo studies about its toxicity in healthy stomach tissue. We performed sequential in vitro and in vivo analyses of MB-induced phototoxicity. METHODS: We performed in vitro experiments using the AGS human gastric cancer cell line treated with light-emitting diode (LED) irradiation (3.6 J/cm RESULTS: In vitro, increased concentrations of MB led to higher TUNEL scores. However, cell viability was significantly lower after MB plus LED irradiation than after treatment with MB alone (P \u3c 0.001). In vivo, the TUNEL score was highest immediately after treatment with 0.1% or 0.5% MB plus light irradiation, and the score was significantly higher in the LED illumination plus MB group than in the control group (P \u3c 0.05). The elevated TUNEL score was maintained for 3 days in the MB plus light irradiation group but returned to normal levels on day 10. CONCLUSIONS: : Endoscopic light application with MB 0.5% concentration to the stomach may be regarded as a safe procedure despite some DNA injuries in the early period

Accuracy of three different fecal calprotectin tests in the diagnosis of inflammatory bowel disease

Background/AimsSeveral studies have found that the measurement of fecal calprotectin is useful for the early diagnosis of inflammatory bowel disease (IBD). We compared the effectiveness of three different fecal calprotectin kits for initial diagnosis in patients with suspected IBD.MethodsWe enrolled 31 patients with IBD (18 Crohn's disease [CD], 11 ulcerative colitis [UC], and two intestinal Behçet's disease), five with irritable bowel syndrome (IBS), and five with other colitis (four infectious colitis and one intestinal tuberculosis). Diagnosis was based on clinical, laboratory, and endoscopic examinations. Fecal samples were obtained at the first diagnosis and calprotectin levels were measured using three different kits (Quantum Blue® Calprotectin, EliA™ Calprotectin, and RIDASCREEN® Calprotectin).ResultsThe overall accuracy for differentiating IBD from IBS or other colitis was 94% and 91%, respectively, for Quantum Blue® (cutoff, 50 µg/g); 92% and 89%, respectively, for EliA™ (cutoff, 50 µg/g); and 82% and 76%, respectively, for RIDASCREEN® (cutoff, 50 µg/g). In patients with CD, the results of Quantum Blue® Calprotectin and EliA™ Calprotectin correlated significantly with levels of the Crohn's disease activity index (Spearman's rank correlation coefficient, r=0.66 and r=0.49, respectively). In patients with UC, the results of EliA™ Calprotectin correlated significantly with the Mayo score (r=0.70).ConclusionsFecal calprotectin measurement is useful for the identification of IBD. The overall accuracies of the three fecal calprotectin kits are comparable

The effect of alpha lipoic acid in a porcine in-stent restenosis model

SummaryBackgroundThe aim of this study was to investigate the effect of alpha lipoic acid (α-LA) on a porcine in-stent restenosis (ISR) model.MethodsIn protocol 1, porcine vascular smooth muscle cells (PVSMC) were stimulated by granulocyte-colony stimulating factor (G-CSF) in the presence or absence of α-LA. MTT (3-[4,5-dimethylthiazole-2-yl] 2,5-diphenyl tetrazolium bromide) assay and western blotting were used to determine the cell growth inhibitory rate and anti-inflammatory effect associated with nuclear factor-κb (NF-κb) and extracellular signal-regulated kinase (ERK). In protocol 2, 28 days after balloon overdilation injuries, 24 bare metal stents were placed in coronary artery of 12 pigs. The pigs were randomly divided to receive control diet with or without α-LA (100mg/kg). In protocol 3, 8 control stents and 8 α-LA coated stents were randomly implanted in 2 coronary arteries of 8 pigs and follow-up coronary angiogram and histopathologic assessment were performed 4 weeks after stenting.ResultsProtocol 1. The proliferation of PVSMC was inhibited and protein expression of NF-κb and ERK were attenuated by α-LA pretreatment. Protocol 2. On histopathologic analysis, the neointimal area (4.0±1.0mm2 vs. 1.5±0.7mm2, p<0.001) and histopathologic area of stenosis (66.7±10.7% vs. 24.2±9.7%, p<0.001) were reduced in the α-LA feeding group compared to controls. Protocol 3. On histopathologic analysis, the neointimal area (3.9±0.8mm2 vs. 1.0±0.4mm2, p<0.001), and the histopathologic area of stenosis (67.1±8.8% vs. 17.4±10.0%, p<0.001) were reduced in the α-LA coated stent group compared to the control stent group.Conclusionsα-LA feeding and α-LA coated stents inhibit neointimal hyperplasia in porcine ISR, possibly through inhibiting the activation of NF-κb pathway and proliferation of PVSMC