Sung Koo Jung

Glutamine attenuates acute lung injury by inhibition of high mobility group box protein-1 expression during sepsis.

Heat shock protein 70 (HSP70) is reported as the main factor responsible for the beneficial effects of glutamine (GLN) and as a negative regulator of high mobility group box protein-1 (HMGB-1) expression. Our aim was to determine whether GLN attenuates acute lung injury (ALI) by the inhibition of HMGB-1 expression during sepsis. Male Sprague-Dawley rats were subjected to caecal ligation and puncture (CLP) to induce sepsis. GLN or saline was administered through tail vein 1 h after CLP. Then, quercetin (Q), an inhibitor of HSP70, was utilised to assess the role of the enhanced HSP70. We observed the survival of the subjects. At 24 h post-CLP, we measured lung HSP70, phosphorylated heat shock factor-1 (HSF-1-p) and HMGB-1 expressions, NF-kappaB DNA-binding activity and ALI occurrence. We also measured serum HSP70, IL-6 and HMGB-1 concentrations. GLN improved survival during sepsis. In GLN-treated rats, lung HSP70 and HSF-1-p expressions were enhanced, lung HMGB-1 expression and NF-kappaB DNA-binding activity were suppressed, and ALI was attenuated. Furthermore, in GLN-administered rats, serum HSP70 concentration was higher, and serum IL-6 and HMGB-1 concentrations were lower than those in non-treated rats. Q inhibited the enhancement of HSP70 and HSF-1-p expressions and abrogated the GLN-mediated benefits. In conclusion, GLN attenuated ALI and improved survival by the inhibition of HMGB-1 expression during sepsis in rats. These benefits were associated with the enhancement of HSP70 expression by GLN.

Association between polymorphism in intron 1 of cocaine- and amphetamine-regulated transcript gene with alcoholism, but not with bipolar disorder and schizophrenia in Korean population

Cocaine- and amphetamine-regulated transcript (CART) peptide is a novel neuropeptide involved in feeding, drug reward, and stress. We hypothesized that the polymorphism of CART gene might be related with susceptibility to neuropsychiatric diseases such as alcoholism, bipolar disorder, and schizophrenia. The polymorphism (rs2239670) in intron 1 was selected for study among other single nucleotide polymorphisms (SNPs) located at the area of CART gene, because it had not been tested until to date. The study included patients of alcoholism (100), bipolar disorder (76) and schizophrenia (169) from the Korean population. Healthy controls for bipolar disorder and schizophrenia consisted of 333 individuals. For alcoholism, both patient group and control subjects included only male. The restriction fragment length polymorphism (RFLP) using the AvaII restriction enzyme was designed to analyze the selected SNP. The distribution of GG, GA, and AA genotypes in the 333 controls was 50.2, 41.1, and 8.7%, respectively. The frequency of G and A alleles in the 333 controls was 70.7 and 29.3%, respectively. The distribution of genotype and allele frequencies of the AvaII polymorphism showed a significant difference between alcoholism and controls (P = 0.037 and P = 0.044). However, the AvaII polymorphism of the CART gene did not show association with bipolar disorder and schizophrenia. In conclusion, we report for the first time that the AvaII polymorphism (rs2239670) in intron 1 of the CART gene is associated with alcoholism in the Korean male population.

Effect of an Independent‐capacity Protocol on Overcrowding in an Urban Emergency Department

OBJECTIVES The authors hypothesized that a new strategy, termed the independent-capacity protocol (ICP), which was defined as primary stabilization at the emergency department (ED) and utilization of community resources via transfer to local hospitals, would reduce ED overcrowding without requiring additional hospital resources. METHODS This is a before-and-after trial that included all patients who visited an urban, tertiary care ED in Korea from July 2006 to June 2008. To improve ED throughput, introduction of the ICP gave emergency physicians (EPs) more responsibility and authority over patient disposition, even when the patients belonged to another specific clinical department. The ICP utilizes the ED as a temporary, nonspecific place that cares for any patient for a limited time period. Within 48 hours, EPs, associated specialists, and transfer coordinators perform secondary assessment and determine patient disposition. If the hospital is full and cannot admit these patients after 48 hours, the EP and transfer coordinators move the patients to other appropriate community facilities. We collected clinical data such as sex, age, diagnosis, and treatment. The main outcomes included ED length of stay (LOS), the numbers of admissions to inpatient wards, and the mortality rate. RESULTS A total of 87,309 patients were included. The median number of daily patients was 114 (interquartile range [IQR] = 104 to 124) in the control phase and 124 (IQR = 112 to 135) in the ICP phase. The mean ED LOS decreased from 15.1 hours (95% confidence interval [CI] = 14.8 to 15.3) to 13.4 hours (95% CI = 13.2 to 13.6; p < 0.001). The mean LOS in the emergency ward decreased from 4.5 days (95% CI = 4.4 to 4.6 days) to 3.1 days (95% CI = 3.0 to 3.2 days; p < 0.001). The percentage of transfers from the ED to other hospitals decreased from 3.5% to 2.5% (p < 0.001). However, transfers from the emergency ward to other hospitals increased from 2.9% to 8.2% (p < 0.001). Admissions to inpatient wards from the ED were significantly reduced, and admission from the emergency ward did not change. The ED mortality and hospital mortality rates did not change (p = 0.15 and p = 0.10, respectively). CONCLUSIONS After introduction of the ICP, ED LOS decreased without an increase in hospital capacity.

Comparison of a Pulsatile Blood Pump and a Peristaltic Roller Pump During Hemoperfusion Treatment in a Canine Model of Paraquat Poisoning

This study examined the treatment efficacy and the damage to the blood during hemoperfusion for treating paraquat poisoning using two blood pump mechanisms. Paraquat-poisoned animal models were prepared. A conventional hemodialysis machine, AK90, with a peristaltic roller pump and a cardiopulmonary support system, T-PLS, with a pulsatile blood pump were used during the animal experiments. A total of 12 dogs were treated with hemoperfusion using a charcoal column. Six dogs were treated with hemoperfusion and T-PLS, and the other six were treated with AK90. A paraquat dose of 30 mg/kg was administrated by an intravenous injection. Both pumps maintained blood flow rates of 125 mL/min measured by an ultrasonic flowmeter. For anticoagulation, heparin was administrated by an initial bolus (250 IU/kg) and a continuous injection (100 IU/kg/h). During the experiments, T-PLS and AK90 showed a similar toxin removal efficacy. Both devices decreased the plasma paraquat concentration to 10% of the initial dose within 4-h hemoperfusion. The two pumps showed similar hemolysis properties with acceptable levels. Although T-PLS was developed as a cardiopulmonary bypass system, it can also be used as a hemoperfusion treatment device.

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.