광범위 베타 락탐계 항생제 분해 효소를 생성하는 폐렴간균에 의한 균혈증이 발생한 환자에서 감영의 위험 인자 및 치료 결과

강철인,김성한,방지환,김홍빈,박상원,최영주,오명돈,김의종,최강원 대한감염학회 2003 감염과 화학요법 Vol.35 No.2

목적 : 본 연구는 ESBL을 생성하는 K. pneumoniae에 의한 균혈증 환자에서 감염의 위험 인자 및 치료 결과를 알아보고자 시행하였다. 방법 : 1998년 1월부터 2002년 4월까지 혈액 배양 검사에서 동정된 K. pneumoniae를 대상으로 NCCLS guidelines과 이중 디스크 확산법(double-disk diffusion test)을 이용하여 ESBL 생성 여부를 확인하였다. ESBL 생성 균주에 의한 균혈증 환자 60명(환자군)에 대해 ESBL을 생성하지 않는 균주에 의한 균혈증 환자들(대조군)을 연령, 성별, 균혈증 발생 시점을 고려하여 1:2 또는 1:3으로 배정하였다. 총 159명의 대조군을 선정하였고 후향적인 환자-대조군 연구를 시행하였다. 결과 : 환자군과 대조군 사이에 연령, 성별, APACHE Ⅱ score, 주된 감염 부위의 유의한 차이는 없었다. ESBL을 생성하는 K. pneumoniae에 의한 균혈증이 발생할 독립적인 위험 인자에는 요관 삽입, 균혈증 발생 이전 72시간 동안 침습적인 시술을 받은 경우, 균혈증 발생 이전 30일 동안 투여받은 항생제 개수가 있었다. 초기 항생제 치료 72시간 후의 반응을 평가하였을 때, 완전 반응(complete response)은 대조군에서 더 많았고(13.3% vs. 40.3%, P<0.001), 치료 실패(treatment failure)는 환자군에서 더 많았다(33.3% vs. 11.9%, P<0.001). 7일 사망률은 환자군에서 20% (12/60), 대조군에서 15.6% (25/159)이었고(P=0.451), 30일 사망률은 환자군에서 30% (18/60), 대조군에서 24.5% (39/159)이었다(P=0.410). ESBL 생성 균주에 의한 균혈증이 있는 환자들에서 최종 항생제 치료가 부적절했던 환자들을 제외하고 30일 사망률을 분석하였을 때 효과적인 항생제 치료의 지연은 사망률을 높이지 않았다(11.1% vs. 9.1%, P=1.000). 결론 : ESBL을 생성하는 K. pneumoniae에 의한 균혈증이 있는 환자에서 초기 항균제 치료 72시간 후의 치료 반응률은 낮지만 사망률은 유의하게 증가하지 않았다. 원인균이 동정된 후 최종 치료 항생제의 선정이 적절하다면 초기에 효과적인 항생제 투여의 지연은 사망률을 유의하게 증가시키지는 않았다. Background : This study was conducted to evaluate risk factors for infection and treatment outcome of bloodstream infection due to extended spectrum β-lactamases(ESBL)-producing K. pneumoniae. Methods: ESBL production was evaluated by NCCLS guidelines and/or double-disk synergy test in K. pneumoniae blood isolates stored from January, 1998 to April, 2002. Sixty patients with bloodstream infection due to ESBL-producing K. pneumoniae (case patients) were compared with 159 matched control patients with bloodstream infection of non-ESBL-producing K. pneumoniae. Retrospective case-control study was performed. Results : There were no significant differences in age, sex, APACHE Ⅱ score, and the primary site of infection between the case and control groups. In multivariate analysis, significant independent risk factors associated with bloodstream infection due to ESBL-producing K. pneumoniae were urinary catheterization, invasive procedure within previous 72 hours, and the number of antibiotics administered within previous 30 days. In clinical response at 72 hours after initial antibiotic treatment, complete response rate was higher in the controls (13.3% vs. 40.3%, respectively, P<0.001), however, treatment failure rate was higher in the cases (33.3% vs. 11.9%, respectively, P<0.001). Overall 7-day mortality rates in the cases and the controls were was 20% (12/60) and 15.7% (25/159) (P=0.451), respectively, and overall 30-day mortality rates were 30% (18/60) and 24.5% (39/159), respectively (P=0.410). When the patients with bloodstream infection of ESBL-producing organism were evaluated and the patients who received inadequate definitive antibiotic treatment were excluded, delayed effective antibiotic treatment was found to be not associated with higher mortality. Conclusion : In patients infected with ESBL-producing K. pneumoniae bacteremia, clinical response rate at 72 hours after antimicrobial therapy was lower, but the increase of mortality rate was not significant. Delayed effective antibiotic treatment was not associated with higher mortality, when definitive appropriate antibiotic treatment was prescribed.

황색포도구균의 균혈증에서 초기 항생제 치료가 예후에 미치는 영향

김성한,박완범,이기덕,강철인,최영주,김홍빈,박상원,김의석,오명돈,김의종,최강원 대한감염학회 2002 감염 Vol.34 No.5

사업장 소음 폭로에 의한 일과성 역치 상승과 회복

조수헌,하미나,한상환,주영수,성주헌,강종원,윤덕로,송동빈,이명학,김선태 大韓産業醫學會 1996 대한직업환경의학회지 Vol.8 No.2

To determine the recovery time from noise-induced temporary threshold shift(TTS), a prospective field study was conducted at three worksites where workers are known to be exposed high level of noise. Subjects were selected according to answers on a questionnaire which inquired about otological history and previous noise exposure, including avocational, military and occupational exposures. After excluding employee with past otologic problems, recent exposure to high level noise, and under medications, total 92 employees participated in the study. Among 92 participants, complete consecutive audiometric examinations were carried out at 0∼2 hours, 5∼7 hours, 14∼16 hours after worktime noise exposure on 26 participants wearing hearing protectors and 22 participants wearing no protective devices. The difference between the hearing level 0∼2 hours after noise exposure and 5∼7 hours is statistically significant by paired t-test(p<0.01). The median recovery times calculated from the data of 22 participants wearing no protective hearing devices are 15.6 hours at 4000Hz, and 7.7 hours, 10.3 hours, 8.4 hours at 1000Hz, 2000Hz and 8000Hz respectively. These data suggest that when measuring the pure tone audiometry for noise exposed workers, at least 16 hours noise-free interval is required.

Changes in hippocalcin expression in cortical neurons and glial cells by epigallocatechin gallate administration in an animal model of stroke

Ju-Bin Kang(Ju-Bin Kang),Dong-Ju Park(Dong-Ju Park),Jae-You Kim(Jae-You Kim),Hyeun-Gyoung(Hyeun-Gyoung ),Phil-Ok Koh(Phil-Ok Koh) 한국예방수의학회 2023 예방수의학회지 Vol.47 No.2

Ischemic stroke causes brain damage and neuronal cell death by depriving oxygen and nutrients and releasing excessive levels of glutamate and intracellular calcium. Epigallocatechin gallate (EGCG) is a polyphenolic compound present in green tea. It has antioxidant, anti-inflammatory, and neuroprotective effects. Hippocalcin is a calcium binding protein that regulates calcium concentration, neuronal differentiation, neuronal excitability, and neuronal cell death. In this study, we investigated whether EGCG regulates the expression of hippocalcin in neurons and astrocytes after focal cerebral ischemia. Cerebral ischemia was induced by meddle cerebral artery occlusion (MCAO). EGCG (50 mg/kg) or PBS was injected into the abdominal cavity just before MCAO surgery. Neurobehavioral tests were performed to evaluate the effect of EGCG on neurological behavioral deficits 24 h after MCAO surgery. Immunofluorescence staining was performed to evaluate the positive response to hippocalcin in the cerebral cortex after MCAO surgery. We also detected the positive reactions of neuronal nuclear protein (NeuN) and glial fibrillary acidic protein (GFAP) as markers of neuron and astrocyte, respectively. MCAO caused severe neurological impairment and EGCG treatment attenuated these impairments. MCAO damage reduced the number of NeuN-positive cells and increased the number of GFAP-positive cells. This result indicates a decrease in neurons and an increase in astrocytes. However, EGCG alleviated these changes caused by MCAO damage. MCAO reduced the number of hippocalcin-positive cells in neurons and astrocytes, and EGCG treatment attenuated these reductions. Hippocalcin exerts neuroprotective effect through regulating intracellular calcium concentration. In conclusion, EGCG regulates the expression of hippocalcin in neurons and astrocytes and has neuroprotective effects in focal cerebral ischemia.

Retinoic acid regulates thioredoxin and peroxiredoxin-2 in ischemic-injured cerebral cortex

Ju-Bin Kang,Dong-Ju Park,Murad-Ali Shah,Hyeon-Kyeong Son,Sang-Hyun Park,Phil-Ok Koh 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.1

Chlorogenic acid attenuates change in Bcl-2 and Bax proteins in cerebral ischemia and glutamate-exposed neurons

Ju-Bin Kang, Phil-Ok Koh 한국예방수의학회 2023 예방수의학회지 Vol.47 No.3

Ischemic stroke leads to severe brain damage and high mortality. Chlorogenic acid is a phenolic compound known to have neuroprotective properties. Bcl-2 family protein plays an important role in the regulation of apoptosis. We investigated whether chlorogenic acid exerts neuroprotective effects against ischemic injury by modulating Bcl-2 and Bax proteins. Middle cerebral artery occlusion (MCAO) was performed to induce cerebral ischemia and rats were injected intraperitoneally with phosphate buffered saline or chlorogenic acid (30 mg/kg) for 2 h after MCAO. Cortical tissues were collected 24 h after MCAO injury and reverse transcription-quantitative real time polymerase chain reaction and Western blot analyses were performed to investigate the expression of Bcl-2 and Bax. The regulation of Bcl-2 and Bax proteins by chlorogenic acid during glutamateinduced cell damage were examined. Cells were collected at 24 h after administration of glutamate (5 mM) and chlorogenic acid (10, 30, 50 μM). These results showed a decrease in Bcl-2 expression and an increase in Bax expression in MCAO animals, but chlorogenic acid treatment alleviated these changes by MCAO damage. Glutamate significantly reduced cell viability, and chlorogenic acid treatment alleviated this reduction in a dose-dependent manner. Glutamate induced a decrease in Bcl-2 expression and an increase in Bax expression, but chlorogenic acid treatment alleviated these changes. We found that chlorogenic acid alleviates changes in the expression of Bcl-2 and Bax proteins induced by brain injury. Therefore, our findings provide an evidence that chlorogenic acid has neuroprotective effects against MCAO damage by modulating Bcl-2 and Bax proteins.

Identification of regulated proteins by EGCG in cerebral cortex of middle cerebral artery occlusion animal model

Ju-Bin Kang,Dong-Ju Park,Dong-Kyun Kim,Phil-Ok Koh 한국실험동물학회 2019 한국실험동물학회 학술발표대회 논문집 Vol.2019 No.1

Quercetin ameliorates glutamate toxicity-induced neuronal cell death by controlling calcium-binding protein parvalbumin

Ju-Bin Kang,Dong-Ju Park,Murad-Ali Shah,Phil-Ok Koh 대한수의학회 2022 Journal of Veterinary Science Vol.23 No.2

Background: Glutamate is the main excitatory neurotransmitter. Excessive glutamate causes excitatory toxicity and increases intracellular calcium, leading to neuronal death. Parvalbumin is a calcium-binding protein that regulates calcium homeostasis. Quercetin is a polyphenol found in plant and has neuroprotective effects against neurodegenerative diseases. Objectives: We investigated whether quercetin regulates apoptosis by modulating parvalbumin expression in glutamate induced neuronal damage. Methods: Glutamate was treated in hippocampal-derived cell line, and quercetin or vehicle was treated 1 h before glutamate exposure. Cells were collected for experimental procedure 24 h after glutamate treatment and intracellular calcium concentration and parvalbumin expression were examined. Parvalbumin small interfering RNA (siRNA) transfection was performed to detect the relation between parvalbumin and apoptosis. Results: Glutamate reduced cell viability and increased intracellular calcium concentration, while quercetin preserved calcium concentration and neuronal damage. Moreover, glutamate reduced parvalbumin expression and quercetin alleviated this reduction. Glutamate increased caspase-3 expression, and quercetin attenuated this increase in both parvalbumin siRNA transfected and non-transfected cells. The alleviative effect of quercetin was statistically significant in non-transfected cells. Moreover, glutamate decreased bcl-2 and increased bax expressions, while quercetin alleviated these changes. The alleviative effect of quercetin in bcl-2 family protein expression was more remarkable in non-transfected cells. Conclusions: These results demonstrate that parvalbumin contributes to the maintainace of intracellular calcium concentration and the prevention of apoptosis, and quercetin modulates parvalbumin expression in glutamate-exposed cells. Thus, these findings suggest that quercetin performs neuroprotective function against glutamate toxicity by regulating parvalbumin expression.

Molecular design of large-bandgap host materials and their application to blue phosphorescent organic light-emitting diodes

Kang, Ju Sik,Hong, Tae Ryang,Kim, Hyung Jong,Son, Young Hoon,Bin, Jong-Kwan,Lee, Bang Sook,Yang, Joong Hwan,Kim, JinWuk,Cho, Min Ju,Kwon, Jang Hyuk,Choi, Dong Hoon Elsevier 2015 ORGANIC ELECTRONICS Vol.26 No.-

<P><B>Abstract</B></P> <P>New large-bandgap host materials with carbazole and carboline moieties were designed and synthesized for high-performance blue phosphorescent organic light-emitting diodes (PhOLEDs). The two kinds of host materials, 9-(4-(9<I>H</I>-carbazol-9-yl)phenyl)-6-(9<I>H</I>-carbazol-9-yl)-9<I>H</I>-pyrido[2,3-<I>b</I>]indole (<B>pP2CZCB</B>) and 9-(3-(9<I>H</I>-carbazol-9-yl)phenyl)-6-(9<I>H</I>-carbazol-9-yl)-9<I>H</I>-pyrido[2,3-<I>b</I>]indole (<B>mP2CZCB</B>), displayed promisingly high triplet energies of ∼2.92–2.93eV for enhancing the exothermic energy transfer to bis[2-(4,6-difluorophenyl)pyridinato-C<SUP>2</SUP>,<I>N</I>](picolinato)iridium(III) (FIrpic) in PhOLED devices. It was found that the blue PhOLEDs bearing the new host materials and the FIrpic dopant exhibited markedly higher external quantum efficiencies (EQEs) than a device made with 1,3-bis(<I>N</I>-carbazolyl)benzene (mCP) as the host. In particular, the PhOLED device made with 3wt% FIrpic as the dopant and <B>mP2CZCB</B> as the host material displayed a low driving voltage of 4.13V and the high EQE of 25.3% at 1000cdm<SUP>−2</SUP>.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Two new host materials showed high triplet energies over 2.92eV for blue PhOLED. </LI> <LI> Both host materials exhibited bipolar property. </LI> <LI> EQE of mP2CZCB-based PhOLED is measured to be 25.3% at 1000cd/m<SUP>2</SUP>. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Quercetin ameliorates glutamate toxicity-induced decrease in parvalbumin expression and rise in intracellular calcium in HT22 cells

Ju-Bin Kang,Dong-Ju Park,Phil-Ok Koh 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7

Glutamate is the main excitatory neurotransmitter in neurons. However, excessive glutamate causes excitatory toxicity and increases intracellular calcium, leading to neuronal cell death. Parvalbumin is a calcium binding protein that regulates calcium homeostasis. Quercetin is a polyphenol that present in plant flavonoids and has neuroprotective effects against neurodegenerative diseases. We investigated whether quercetin regulates apoptosis through the expression of pavabumin in neuronal damage caused by glutamate. Glutamate was treated in hippocampal-derived cell lines, and quercetin and/or vehicle was treated 1 h before glutamate exposure. Cells were collected for experimental procedure 24 h after glutamate treatment. Glutamate exposure reduced cell viability and increased intracellular calcium concentration. Quercetin treatment alleviated these changes and exerts neuroprotective effects against glutamate toxicity. Moreover, glutamate exposure reduced parvalbumin expression and quercetin treatment attenuated the decrease in paralbumin expression by glutamate. These changes were confirmed using Western blot and immunocytochemical techniques. Glutamate treatment increased caspase-3 expression, quercetin attenuated this increase caused by glutamate toxicity in both parvalbumin siRNA transfected and non-transfected cells. However, the alleviative effect of quercetin was significant in non-transfected conditions. Caspase-3 is a representative apoptosis associated protein. Glutamate also induced a decrease in bcl-2 and increase in bax, quercetin alleviated glutamate-induced these changes. Bcl-2 expression in siRNA transfected cells was lower than in non-transfected cells. However, the expression of bax was high in siRNA transfected cells. Maintenance of proper calcium concentration is important for cell survival because calcium overload causes cell death. These results indicate that parvalbumin contributes to the prevention of apoptosis and quercetin modulates parvalbumin expression in glutamate-exposured cells. Maintenance of proper calcium concentration is important for cell survival because calcium overload causes cell death. Thus, the results of this study suggest that quercetin can perform neuroprotective function against glutamate toxicity by attenuating intracellular calcium overload and modulating bcl-2 family proteins and caspase-3 through regulating of pavalbumin expression. This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (NRF- 2018R1D1A1B07044074).