Ki Young Jeong

Prognostic value of N-terminal pro-brain natriuretic peptide in hospitalised patients with community-acquired pneumonia

Background The prognostic role of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with community-acquired pneumonia (CAP) has not been evaluated. The aim of the present study was to investigate whether NT-proBNP level could predict mortality in hospitalised CAP patients. Methods We performed a structured medical record review of all hospitalised CAP patients from May 2003 to October 2006, and classified patients into the 30-day survival and non-survival group. Data included demographic and clinical characteristics, and laboratory findings including NT-proBNP levels. The APACHE II scores, PSI (pneumonia severity index) and CURB65 (confusion, urea, respiratory rate, blood pressure and aged 65 or more) scores were calculated. Comparisons between survivors and non-survivors were made with χ2, non-parametric tests and logistic regression and ROC analysis were used to compare the ability of NT-proBNP (adjusted for age, heart failure and creatinine), APACHE II, PSI and CURB65 to predict mortality. Results Of 502 patients, 61 (12.2%) died within 30 days. NT-proBNP levels were measured in 167 patients and were significantly higher in non-survivors compared to survivors (median 841.7 (IQR 267.1–3137.3) pg/ml vs 3658.0 (1863.0–7025.0) pg/ml, p=0.019). NT-proBNP was an independent predictor of mortality (adjusted OR 1.53; 95% CI 1.16 to 2.02, p=0.002). The AUC for NT-proBNP was 0.712 (95% CI, 0.613 to 0.812), which was comparable to those of PSI (0.749, p=0.531) and CURB65 (0.698, p=0.693), but inferior to that of APACHE II (0.831, p=0.037). Adding NT-proBNP to APACHE II, PSI and CURB65 did not significantly increase the AUCs, respectively. Conclusions NT-proBNP level is an independent predictor of mortality in hospitalised CAP patients. The performance of NT-proBNP level is comparable to those of PSI and CURB65 in predicting mortality.

Antioxidant effects of selenium on lung injury in paraquat intoxicated rats

Context. Paraquat (PQ) causes lethal intoxication by inducing oxidant injury to the lung. Selenium is a cofactor for glutathione peroxidase (GPx), which is one of the major endogenous antioxidant enzymes. Objective. To determine whether selenium post-treatment activates GPx, decreases lung injury, and improves survival in PQ intoxicated rats. Materials and methods. Male Spraque–Dawley rats were categorized into three groups: sham (n = 6), PQ (n = 12), and PQ + Se (n = 12). In the PQ and PQ + Se groups, 50 mg/kg of PQ was administered intraperitoneally. After 10 minutes, 60 μg/kg of Se (PQ + Se) or saline (PQ) was administered via the tail vein. Six rats per group were euthanized 6 hours or 24 hours later. Lung tissues were harvested for the measurement of GPx activity, reduced glutathione (GSH), glutathione disulfide (GSSG) and malondialdehyde (MDA) and for histological analysis. Using separated set of rats, survival of PQ (n = 10) and PQ + Se (n = 10) were observed for 72 hours. Results. GPx activity in the PQ group at the 6-hour and 24-hour time points was lower than in the sham group (p < 0.006). GPx activity in the PQ + Se group at the 6-hour and 24-hour time points was higher than in the PQ group at the same time (p < 0.006). GPx activity in the PQ + Se group at 24 hours was higher than at 6-hour time point and also higher than in the sham group (p < 0.006). The GSH/GSSG ratio in the PQ + Se group at 24 hours was lower than that in the sham group (p < 0.006). MDA levels in the PQ group at 6 hours and 24 hours were higher than in the sham group (p < 0.006). MDA levels at 24 hours in the PQ + Se group was lower than in the PQ group (p < 0.006). Acute lung injury (ALI) scores in the PQ group at 6 hours and 24 hours were higher than in the sham group (p < 0.006). ALI scores at 24 hours in the PQ + Se group were lower than in the PQ group. Survival rates did not differ between PQ and PQ + Se (p = 0.869). Conclusion. Single dose of selenium post-treatment activates GPx and attenuates lipid peroxidation and lung injury early after paraquat intoxication, but does not improve 72 hours of survival.

Prolonged therapeutic hypothermia is more effective in attenuating brain apoptosis in a Swine cardiac arrest model.

Objectives:To investigate whether 48 hours of therapeutic hypothermia is more effective to attenuate brain apoptosis than 24 hours and to determine whether the antiapoptotic effects of therapeutic hypothermia are associated with the suppressions of the cleavage of protein kinase C-&dgr;, the cytosolic release of cytochrome c, and the cleavage of caspase 3 in a swine cardiac arrest model. Design:Prospective laboratory study. Setting:University laboratory. Subjects:Male domestic pigs (n = 24). Interventions:After 6 minutes of no-flow time that was induced by ventricular fibrillation, cardiopulmonary resuscitation was provided, and the return of spontaneous circulation was achieved. The animals were randomly assigned to the following groups: sham, normothermia, 24 hours of therapeutic hypothermia, or 48 hours of therapeutic hypothermia. Therapeutic hypothermia (core temperature, 32–34°C) was maintained for 24 or 48 hours post return of spontaneous circulation, and the animals were rewarmed for 8 hours. At 60 hours post return of spontaneous circulation, the animals were killed, and brain tissues were harvested. Measurements and Main Results:We examined cellular apoptosis and neuronal damage in the brain hippocampal cornu ammonis 1 region. We also measured the cleavage of protein kinase C-&dgr;, the cytosolic release of cytochrome c, and the cleavage of caspase 3 in the hippocampus. The 48 hours of therapeutic hypothermia attenuated cellular apoptosis and neuronal damage when compared with normothermia. There was also a decrease in the cleavage of protein kinase C-&dgr;, the cytosolic release of cytochrome c, and the cleavage of caspase 3. However, 24 hours of therapeutic hypothermia did not significantly attenuate cellular apoptosis or neuronal damage. Conclusions:We found that 48 hours of therapeutic hypothermia was more effective in attenuating brain apoptosis than 24 hours of therapeutic hypothermia. We also found that the antiapoptotic effects of therapeutic hypothermia were associated with the suppressions of the cleavage of protein kinase C-&dgr;, the cytosolic release of cytochrome c, and the cleavage of caspase 3.

Niacin Suppresses the Mitogen-activated Protein Kinase Pathway and Attenuates Brain Injury After Cardiac Arrest in Rats*

Objectives:To determine whether niacin attenuates brain injury and improves neurological outcome after cardiac arrest in rats and if its therapeutic benefits are associated with suppression of the mitogen-activated protein kinase pathway. Design:Prospective laboratory study. Setting:University laboratory. Subjects:Male Sprague-Dawley rats (n = 77). Interventions:After 6 minutes of no flow time induced by ventricular fibrillation, cardiopulmonary resuscitation was provided and return of spontaneous circulation was achieved. Animals were then administered vehicle, single low dose (360 mg/kg; at 1 hr postreturn of spontaneous circulation), single high dose (1080 mg/kg; at 1 hr), or repeated low dose of niacin (360 mg/kg/d for 3 d; at 1, 24, and 48 hr) through an orogastric tube. Measurements and Main Results:Neurologic deficit scales were scored at 24 hours, 72 hours, and 7 days postreturn of spontaneous circulation. Single high dose of niacin improved neurologic deficit scales at 48 hours and 7 days, and repeated low dose of niacin improved neurologic deficit scales at 7 days. Then, a separate set of animals were killed at 72 hours postreturn of spontaneous circulation, and brain tissues were harvested. Single high dose and repeated low dose of niacin attenuated cellular apoptosis and neuronal damage in hippocampal cornu ammonis 1 and decreased axonal injury and microglial activation in corpus callosum. They increased nicotinamide adenine dinucleotide, reduced nicotinamide adenine dinucleotide phosphate and reduced glutathione levels, and decreased malondialdehyde level in brain tissues. Furthermore, they suppressed the phosphorylations of p38 and c-Jun N-terminal kinase/stress-activated protein kinase and the cleavage of caspase 3. However, they failed to enhance extracellular signal-regulated kinases 1/2 phosphorylation. Conclusions:Single high dose and repeated low dose of niacin attenuated brain injury and improved neurological outcome after cardiac arrest in rats. Their therapeutic benefits were associated with suppressions of the phosphorylations of p38 and c-Jun N-terminal kinase/stress-activated protein kinase and the cleavage of caspase 3.

The therapeutic effect and mechanism of niacin on acute lung injury in a rat model of hemorrhagic shock: Down-regulation of the reactive oxygen species-dependent nuclear factor κB pathway.

BACKGROUND The purpose of the current study was to investigate the protective effect of niacin on acute lung injury by the down-regulation of the nuclear factor &kgr;B (NF-&kgr;B) pathway in hemorrhagic shock (HS) rats. METHODS HS was induced in male Sprague-Dawley rats by withdrawing blood to maintain a mean arterial pressure of 20 mm Hg to 25 mm Hg for 40 minutes. The rats were resuscitated by the reinfusion of the drawn blood, and a vehicle (HS), a low-dose of niacin (360 mg/kg, HS + LD-NA), or a high dose of niacin (1,080 mg/kg, HS + HD-NA) were administered orally. The survival of the subjects was observed for 72 hours, and a separate set of animals was killed at 6 hours after HS induction. We measured cytoplasmic phosphorylated inhibitor &kgr;B-&agr; and inhibitor &kgr;B-&agr; expressions, nuclear NF-&kgr;B p65 expression, NF-&kgr;B p65 DNA-binding activity, MEK partner 1 activity, tumor necrosis factor &agr; (TNF-&agr;), interleukin 6 (IL-6), IL-8, nicotinamide adenine dinucleotide (NAD+), reduced nicotinamide adenine dinucleotide phosphate, reduced glutathione, glutathione disulfide, malondialdehyde levels, and histologic damage in the lung tissue. We also measured TNF-&agr;, IL-6, and IL-8 levels in the serum. RESULTS The survival rates of the sham, HS, HS + LD-NA, and HS + HD-NA groups were 6 of 6 (100%), 0 of 9 (0%), 1 of 9 (11.1%), and 3 of 9 (33.3%), respectively. A high dose of niacin increased lung NAD+, nicotinamide adenine dinucleotide phosphate levels, and glutathione–glutathione disulfide ratios; decreased lung malondialdehyde levels; down-regulated the NF-&kgr;B pathway; suppressed TNF-&agr;, IL-6, and IL-8 levels in the lung tissue and serum; and attenuated histologic lung damage. CONCLUSION A high dose of niacin attenuated lung inflammation, suppressed proinflammatory cytokine release, reduced histologic lung damage, and improved survival after HS in rats. Its therapeutic benefits were associated with the down-regulation of the reactive oxygen species–dependent NF-&kgr;B pathway.

The effect of glutamine on cerebral ischaemic injury after cardiac arrest

OBJECTIVES The aim of this study is to investigate whether glutamine (GLN) enhances heat shock protein-25 (Hsp-25) and heat shock protein-72 (Hsp-72) expressions and attenuates cerebral ischaemic injury in rat cardiac arrest model. METHODS Rats survived from cardiac arrest model were randomly assigned to CPR+GLN group (0.75 g/kg of alanyl-glutamine, n=6) or CPR group (same volume of 0.9% saline, n=6). Additional 6 rats were used for SHAM group. For the outcome measures, neurologic deficit score (NDS, 0-80) was checked at 24h and 72 h after cardiac arrest. At 72 h after cardiac arrest, rats were euthanised and the brain was harvested. Then, right hemisphere was used for cresyl-violet and TUNEL staining. Left hemisphere was used for Western blot analysis of phosphorylated heat shock factor-1 (p-HSF-1), Hsp-25, Hsp-72, and cleaved caspase-3. Kruskal-Wallis test and Mann-Whitney U post hoc test with Bonferroni correction were used for the analysis. RESULTS Resuscitation variables were not different between CPR and CPR+GLN. NDS in CPR+GLN was higher than that in CPR (p<0.017) and lower than that in SHAM (p<0.017) at both 24h and 72 h. p-HSF-1, Hsp-25 and Hsp-72 expressions in CPR+GLN were significantly enhanced (p<0.017) than those in other groups. Cleaved caspase-3 expression in CPR was significantly higher (p<0.017) than in SHAM and CPR+GLN. Ischaemic and TUNEL-positive neurons were more frequently observed in CPR than in CPR+GLN. CONCLUSIONS Glutamine attenuates cerebral ischaemic injury in cardiac arrest model of rats and this is associated with the enhancement of Hsp-25 and Hsp-72 expressions.