Upregulation of heme oxygenase-1 by ginsenoside Ro attenuates lipopolysaccharide-induced inflammation in macrophage cells

Kim, Sokho,Oh, Myung-Hoon,Kim, Bum-Seok,Kim, Won-Il,Cho, Ho-Seong,Park, Byoung-Yong,Park, Chul,Shin, Gee-Wook,Kwon, Jungkee The Korean Society of Ginseng 2015 Journal of Ginseng Research Vol.39 No.4

Background: The beneficial effects of ginsenoside species have been well demonstrated in a number of studies. However, the function of ginsenoside Ro (GRo), an oleanane-type saponin, has not been sufficiently investigated. Thus, the aim of the present study was to investigate the anti-inflammatory effects of GRo in vitro using the Raw 264.7 mouse macrophage cell line treated with lipopolysaccharide (LPS), and to clarify the possible mechanism of GRo involving heme oxygenase-1 (HO-1), which itself plays a critical role in self-defense in the presence of inflammatory stress. Methods: Raw 264.7 cells were pretreated with GRo (up to $200{\mu}M$) for 1 h before treatment with 1 mg/mL LPS, and both cell viability and inflammatory markers involving HO-1 were evaluated. Results: GRo significantly increased cell viability in a dose dependent manner following treatment with LPS, and decreased levels of reactive oxygen species and nitric oxide. GRo decreased inflammatory cytokines such as nitric oxide synthase and cyclooxygenase-2 induced by LPS. Moreover, GRo increased the expression of HO-1 in a dose dependent manner. Cotreatment of GRo with tin protoporphyrin IX, a selective inhibitor of HO-1, not only inhibited upregulation of HO-1 induced by GRo, but also reversed the anti-inflammatory effect of GRo in LPS treated Raw 264.7 cells. Conclusion: GRo induces anti-inflammatory effects following treatment with LPS via upregulation of HO-1.

서울의 Penicillinase Producing Neisseria Gonorrhoeae 발생빈도(1996)

김재홍,황동규,전재홍,김윤석,김중환,김용준,이창균,임동진,김현수,조창근,김경문,박상훈,전우형,김희성,이호정,차명수,김갑형,김형석,김석우,황지환,박병순,권오상,이민수,송기훈,성소영,이인섭,부태성 대한화학요법학회 1999 대한화학요법학회지 Vol.17 No.2

Background : In recent years, gonorrhea has been panedemic and remains one of the most commom STDs in the world, especially in developing countries. Objective & Methods: For the detection of a more effective therapeutic regimen and assessing the prevalence of PPNG, we have been trying to study the patients who have visited the VD Clinic of Choong-Ku Public Health Center in Seoul since 1980 by means of the chromogenic cephalosporin method. Results: In 1996, 139 strains of N. gonorrhoeae were isolated, among which 53(39.0%) were PPNG. Conclusion: Our results suggests that after a peak of 74.3% in 1993, the prevalence of PPNG in Seoul is gradually declining.

Upregulation of heme oxygenase-1 by ginsenoside Ro attenuates lipopolysaccharide-induced inflammation in macrophage cells

Sokho Kim,Myung-Hoon Oh,Bum-Seok Kim,Won-Il Kim,Ho-Seong Cho,Byoung-Yong Park,Chul Park,Gee-Wook Shin,Jungkee Kwon 고려인삼학회 2015 Journal of Ginseng Research Vol.39 No.4

Background: The beneficial effects of ginsenoside species have been well demonstrated in a number of studies. However, the function of ginsenoside Ro (GRo), an oleanane-type saponin, has not been suffi- ciently investigated. Thus, the aim of the present study was to investigate the anti-inflammatory effects of GRo in vitro using the Raw 264.7 mouse macrophage cell line treated with lipopolysaccharide (LPS), and to clarify the possible mechanism of GRo involving heme oxygenase-1 (HO-1), which itself plays a critical role in self-defense in the presence of inflammatory stress. Methods: Raw 264.7 cells were pretreated with GRo (up to 200mM) for 1 h before treatment with 1 mg/ mL LPS, and both cell viability and inflammatory markers involving HO-1 were evaluated. Results: GRo significantly increased cell viability in a dose dependent manner following treatment with LPS, and decreased levels of reactive oxygen species and nitric oxide. GRo decreased inflammatory cytokines such as nitric oxide synthase and cyclooxygenase-2 induced by LPS. Moreover, GRo increased the expression of HO-1 in a dose dependent manner. Cotreatment of GRo with tin protoporphyrin IX, a selective inhibitor of HO-1, not only inhibited upregulation of HO-1 induced by GRo, but also reversed the anti-inflammatory effect of GRo in LPS treated Raw 264.7 cells. Conclusion: GRo induces anti-inflammatory effects following treatment with LPS via upregulation of HO-1.

Nutlin-3 induces HO-1 expression by activating JNK in a transcription-independent manner of p53

CHOE, YUN-JEONG,LEE, SUN-YOUNG,KO, KYUNG WON,SHIN, SEOK JOON,KIM, HO-SHIK Spandidos Publications 2014 International journal of oncology Vol.44 No.3

A recent study reported that p53 can induce HO-1 by directly binding to the putative p53 responsive element in the HO-1 promoter. In this study, we report that nutlin-3, a small molecule antagonist of HDM2, induces the transcription of HO-1 in a transcription-independent manner of p53. Nutlin-3 induced HO-1 expression at the level of transcription in human cancer cells such as U2OS and RKO cells. This induction of HO-1 did not occur in SAOS cells in which p53 was mutated and was prevented by knocking down the p53 protein using p53 siRNA transfection, but not by PFT-alpha, an inhibitor of the transcriptional activity of p53. Accompanying HO-1 expression, nutlin-3 stimulated the accumulation of ROS and the phosphorylation of MAPKs such as JNK, p38 MAPK and ERK1/2. Nutlin-3-induced HO-1 expression was suppressed by TEMPO, a ROS scavenger, and chemical inhibitors of JNK and p38 MAPK but not ERK1/2. In addition, nutlin-3-induced phosphorylation of JNK but not p38 MAPK was inhibited by TEMPO. Notably, the levels of nutlin-3-induced ROS were correlated with the mitochondrial translocation of p53 and this induction was prevented by PFT-beta, an inhibitor of the mitochondrial translocation of p53. Consistent with the effect of the ROS scavenger and MAPK inhibitors, PFT-beta reduced HO-1 expression and the phosphorylation of JNK induced by nutlin-3. In the experiments of analyzing cell death, the knockdown of HO-1 augmented nutlin-3-induced apoptosis. Collectively, these results suggest that nutlin-3 induces HO-1 expression via the activation of both JNK which is dependent on ROS generated by p53 translocated to the mitochondria and p38 MAPK which appears to be stimulated by a ROS-independent mechanism, and this HO-1 induction may inhibit nutlin-3-induced apoptosis, constituting a negative feedback loop of p53-induced apoptosis.

Combined Gene Therapy with Hypoxia-Inducible Factor-1α and Heme Oxygenase-1 for Therapeutic Angiogenesis

Bhang, Suk Ho,Kim, Ju Hee,Yang, Hee Seok,La, Wan-Geun,Lee, Tae-Jin,Kim, Ga Hee,Kim, Hyun Ah,Lee, Minhyung,Kim, Byung-Soo Mary Ann Liebert 2011 Tissue engineering. Part A Vol.17 No.7

<P>Transfection with either hypoxia-inducible factor-1α (HIF-1α) or heme oxygenase-1 (HO-1) gene can induce neovascularization in ischemic tissues. Although expression of transfected HIF-1α gene occurs rapidly, the expressed HIF-1α protein degrades quickly, limiting its therapeutic efficacy. Meanwhile, expressed HO-1 protein does not rapidly undergo degradation, but gene expression occurs a couple of days after transfection, resulting in apoptosis and a delay in angiogenesis in ischemic tissues at the incipient period of HO-1 gene transfection. We hypothesize that combined delivery of HIF-1α and HO-1 gene will enhance antiapoptosis and neovascularization in ischemic tissue compared with HIF-1α or HO-1 single-gene therapy. To test this hypothesis, ischemic mouse hindlimbs were treated with HIF-1α and/or HO-1 gene therapy. The combined gene therapy proved superior to both single-gene therapies, resulting in rapid expression of HIF-1α gene and long-term maintenance of expressed HO-1 protein. The apoptosis in the ischemic region was significantly less, and angiogenic growth factor secretion and angiogenesis were greater in the combined gene therapy than in either of the single-gene therapies. Our results suggest that a combined gene therapy of HIF-1α and HO-1 enhances the transfection of both genes and improves angiogenesis compared with either single-gene therapy.</P>

Disruption of rsmA Gene of Pectobacterium carotovorum subsp. carotovorum LY34 and Effect on Pathogenicity

Kim, Min Keun,Kang, Tae Ho,Kim, Sung Kyum,Jeong, Yu Seok,Yun, Han Dae,Kim, Hoon The Korean Society for Applied Biological Chemistr 2012 Applied Biological Chemistry (Appl Biol Chem) Vol.55 No.6

The rsmA gene was cloned from soft-rot bacterium Pectobacterium carotovorum subsp. carotovorum LY34 (Pcc LY34), and its role in pathogenicity was investigated by marker exchange mutagenesis. From a cosmid library of Pcc LY34 genomic DNA, a positive clone carrying the rsmA gene was selected, and the gene was cloned by polymerase chain reaction (PCR) amplification. The gene is 186 bp in size and encodes a protein of 62 amino acids with a predicted molecular mass of 6,839 Da. The calculated pI of the RsmA is 8.16. The phylogenetic tree showed that the RsmA of Pcc LY34 appeared genetically identical to the CsrA of Pectobacterium atrosepticum SCRI1043 (100% identity) and similar to the CsrA of Yersinia pestis KIM10+(98.3%). The gene was disrupted by the $Km^r$ gene, and the cells became mutated (i.e., $RsmA^-$ mutant). The pathogenicity test revealed that the disease rating of the $RsmA^-$ mutant only differed slightly from that of the wild type on a slice of potato tuber and a Chinese cabbage stalk. These results suggest that RsmA is not an essential factor for the pathogenicity of Pcc LY34 and that the rsmA gene of Pcc LY34 is not completely derepressed in the $RsmA^-$ mutant for virulence-related genes, contrary to the results of Erwinia carotovora subsp. carotovora $RsmA^-$ mutant, which proved hypervirulent for celery petioles. These results showed that the microenvironmental conditions of the host and/or strain of pathogen are important for the coordination of virulence gene expression.

Azithromycin으로 치료한 임신 중 쓰쓰가무시병 1예

김광석,최진욱,서호종,김기훈,박성호,서광섭,고성만,김순혜,김호정 대한감염학회 2001 감염 Vol.33 No.5

We report a case of tsutsugamushi disease in a 26 year-old pregnant woman who was treated with azithromycin. Her gestation period was 27 weeks and she admitted with fever, rash, and eschar on the right shoulder. Currently recommended medications for the treatment of scrub typhus are doxycycline or chloramphenicol. But, these drugs are class D drugs according to the U.S. Food and Drug Administration (FDA) Fetal Risk Summary, so they couldn't be used to treat pregnant women. Recently, a few case reports suggested that azithromycin, a relatively new macrolide antibiotic, was effective and safe for the treatment of scrub typhus in pregnant women. And, there is no evidence that azithromycin causes harmful effects to the developing fetus or to children. On the basis of current in vivo test that confirms the effectiveness of azithromycin, it may be the drug of choice for the treatment of scrub typhus in pregnant women and children. (Korean J Infect Dis 33:380-382, 2001)

대퇴동맥을 통한 경피적 관동맥 중재시술 환자의 천자부위 지혈을 위한 Angioseal^(�) 사용과 고식적 용수 압박법의 비교 : 전향적 연구

김용훈,권현철,김필호,안석진,유철웅,최진호,이상철,김준수,김덕경,전은석,이상훈,홍경표,박정의,서정돈 대한내과학회 2004 대한내과학회지 Vol.66 No.5

목적 : 경피적 관동맥 중재술은 최근 양적 및 질적으로 급격한 발전을 보였지만 시술 시 천자부위의 혈관 합병증은 아직 해결해야 할 문제점이다. 저자들은 대퇴동맥을 통한 경피적 관동맥 중재술을 환자에게 천자부위 지혈을 위한 혈관폐쇄기구인 안지오실의 안전성과 유용성을 고식적인 용수 압박법과 비교 연구하고자 하였다. 방법 : 2002년 4월부터 2003년 5월 사이에 삼성서울병원 심장혈관센터에서 대퇴동맥을 통한 경피적 관동맥 중재술을 성공적으로 시행한 200명의 환자(안지오실 사용군: A군, 100명, 고식적 용수압박법 사용군 B군, 100명)를 대상으로 시술 후 주요 합병증 및 경한 합병증, 지혈 후 환자가 자리에 앉기까지의 시간, 보행개시 가능시간, 총 재원 기간과 시술 1주 후의 합병증을 전향적으로 조사하여 비교 연구하였다. 결론 : 두 군에서 연령, 성별, 기저질환, 심혈관 질환의 위험요소, 시술의 종류, 시술 중 사용한 헤파린의 양, clopidogrel의 양, ticlopidine의 양, 지혈 시 수축기와 확장기혈압, ACT (activated clotting time)는 차이가 없었다. A군이 B군에 비해 시술 후 자리에 앉기까지의 시간 (A군: 4.3±0.3시간, B군: 13.7±0.8시간, p=0.004) 및 보행개시까지의 시간(A군: 6.8±0.5시간, B군: 18.8±2.1시간, p=0.013)이 유의하게 짧았다. 시술 후 주요 합병증은 두군 모두에서 관찰되지 않았으며, 경한 합병증의 전체발생은 A군에서 유의하게 적었다(A군: 28명, B군: 19명, p=0.003). 반상출혈의 경우는 A군에서 유의하게 낮았지만(A군: 3명, B군: 12명, p=0.01), 혈종, 출혈의 발생은 두군간에 차이가 없었다. 총 재원기간에는 두 군간에 차이가 없었다(p=0.239). 시술 1주 후 경과관찰에서 주요합병증은 역시 두 군 모두에서 관찰되지 않았으며, 경한 합병증의 전체발생은 두 군에서 차이가 없었다(A군: 15명, B군: 13명 p=0.418), 반상출혈의 빈도는 차이가 없었지만 혈종의 발생은 A군에서 더 낮았다(A군: 2명, B군:6명, p=0.004). 두 군 모두에서 출혈은 발생하지 않았다. 결론 : 대퇴동맥을 통한 경피적 관동맥 중재술을 시행한 환자에서 안지오실의 사용은 고식적 용수 압박법에 비해 환자의 침상 안정시간을 줄여 조기 활동개시가 가능하게 하였으며 국소합병증의 위험도를 일부 낮추어, 시술에 따른 환자의 불편을 현저하게 감소시킬 수 있다고 할 수 있을 것으로 기대된다. Background : Although the number and the quality of percutaneous coronary intervention have been recently increased dramatically, the vascular complication at puncture site is still the major cause of patients' morbidity. We evaluated the safety and efficacy of newly of newly-developed collagen-based arterial closure device, Angioseal after transfemoral percuatenous coronary intervention. Methods : This study was designed as a prospective single center non-randomized comparative study. A total 200 patients undergoing transfemoral percutaneous coronary intervention were enrolled between April 2002 and May 2003. They were divided into two groups; Angioseal group (group A, n=100) and manual compression group (group B, n=100). The baseline clinical and angiographic characteristics were reviewed. The time to sit up, the time to ambulation, the duration of hospital stay, major and minor vascular puncture site complications were monitored. The patients were followed-up for 1 week after procedure by telephone. Results : The baseline clinical characteriwtics, clinical diagnosis, cardiocascular risk factors, typesof procedure, doses and numbers of anticoagulants were similar between two groups. The blood pressure and activated clotting time were also similar. The time to sit up (group A: 4.3±0.3 hours, group B: 13.7±0.8 hours, p=0.004) and the time to ambulation (group A: 6.8±0.5 hours, group B: 18.8±2.1 hours, p=0.013) were shorter in group A. No major vascular complications were noted. The incidence of hematoma and bleeding were not significantly different between two groups. The incidence of ecchymosis, however, was significantly lower in group A (group A:12%, group B: 3%, p=0.001) The duration of gospital stay was similar between groups. During 7 days of follow-up period incidence of hematoma was significantly lower in group A (p=0.004). Although the incidence of ecchymosis was not significantly different between two groups. Conclusion : The angioseal may be associated with earlier ambulation and less patients' morbidity with low incidence of local complication rate compared to manual compression after transfemoral percutaneous coronary intervention.

정신분열병 환자의 가족부담 척도 개발에 대한 예비연구

김철권,조진석,서지민,김용관,김호찬,김현수,김상수,제영묘 大韓神經精神醫學會 1999 신경정신의학 Vol.38 No.3

연구목적 : 정신분열병 환자의 가족이 느끼는 부담을 측정하기 위한 가족부담 척도를 개발하기 위함이다. 방 법 : 200명의 정신분열병 환자 가족과의 비구조적 면담과 외국 부담척도 고찰을 통하여 94문항을 수집하였고 그 다음에 전문가들과 가족들이 문항 및 영역을 분류하고 통합하여 최종적으로 36문항을 선정하였다. 그리고 정신분열병 환자의 가족 135명, 불안장애 환자의 가족 22명, 기분부전장애 및 신체화 장애 환자의 가족 26명, 치매 환자의 가족 49명을 대상으로 신뢰도와 타당도를 검증하였다. 결 과 : 자료분석 결과 검사-재검사 신뢰도, 내적 일치도, 감별타당도 모두 높게 나타났으며, 요인분석을 통해 다섯 가지 구성요인이 추출되었다. 결 론 : 본 가족부담 척도는 정신분열병을 포함한 만성 정신질환을 앓고 있는 환자의 호전과 가족의 부담을 덜어주기 위한 다양한 프로그램의 효과를 검증하는데 유용하게 사용되어질 수 있을 것이다. Objectives : This preliminary study was carried out to develop the Family Burden Scale(FBS) of the schizophrenics. Methods : Ninety-four items were collected by interviewing in a free unstructured format with one relative of each 200 schizophrenic patients and reviewing foreign FBS's. Several professionals and relatives were asked to group and integrate them into several categories. Finally 36 burden items were chosen to constitute a FBS. The FBS was administered to the relatives of 135 schizophrenic, 22 anxiety disorder, 26 dysthymic disorder and somatization disorder, and 49 dementia patients for examining the reliability and validity. Results : The FBS showed high test-retest reliability, internal consistency, and discriminant validity. The results of the factor analysis revealed five-factor solution. Conclusion : The FBS can be used to evaluate the effectiveness of various programs intended not only to reduce decompensation among schizophrenics, but also to alleviate family burden.

석청(Mad-honey) 복용 후 유발된 부정맥 1예

김용철,김남호,김승환,최준호,박은미,이상재,이은미,유남진,윤경호,오석규,정진원 圓光大學校 醫科學硏究所 2008 圓光醫科學 Vol.23 No.2

석청에 포함된 grayanotoxin에 의해 독성 작용이 나올 수 있으며, 이러한 독성 작용은 일반적으로 24시간 이내 저절로 회복된다. 최근에 본 저자들은 석청 복용 후 발생한 심실빈맥을 경험하였기에 보고하는 바이다. 49세 남자가 호흡곤란으로 내원하였으며, 내원당시 분당 40회 정도의 동성 서맥이 관찰되었고, 수액을 투여하던 중 심실 빈맥이 발생하였다. 항부정맥제를 투여 후 정상 동율동으로 전환되었으며, 특별한 이상 없이 4일 후 퇴원하였다. Mad-honey intoxication caused by the consumption of honey producted from the nectar of rhododendrons. The grayanotoxins cause the intoxication. The toxic effects of mad-honey poisoning are rarely fatal and generally last for no more than 24 hours. We experienced one case, a 49 years-old man who presented with dyspnea after ingestion of mad-honey. He showed marked sinus bradycardia with < 40 beats per minute on admission. The cardiac rhythm was changed to ventricular tachycardia immediately. These features resolved completely in 24 hours with continuous infusion of amiodarone(600 mg per day) and fluids. We report the case of intoxication of mad-honey as a presentation of fatal cardiac arrhythmia.