• The Korean Journal of Physiology and Pharmacology
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• 제25권4호
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• pp.375-383
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• 2021

The intestinal barrier function disrupted in sepsis, while little is known about the variation in different phases of sepsis. In this study, mouse models of sepsis were established by caecal ligation and puncture (CLP). The H&E staining of sections and serum diamine oxidase concentration were evaluated at different timepoint after CLP. TUNEL assay and EdU staining were performed to evaluate the apoptosis and proliferation of intestinal epithelium. Relative protein expression was assessed by Western blotting and serum concentrations of pro-inflammatory cytokines was measured by ELISA. The disruption of intestinal barrier worsened in the first 24 h after the onset of sepsis and gradually recovered over the next 24 h. The percentage of apoptotic cell increased in the first 24 h and dropped at 48 h, accompanied with the proliferative rate of intestinal epithelium inhibited in the first 6 h and regained in the later period. Furthermore, the activity of nuclear factor kappa B (NF-κB) presented similar trend with the intestinal barrier function, shared positive correction with apoptosis of intestinal epithelium. These findings reveal the conversion process of intestinal barrier function in sepsis and this process is closely correlated with the activity of NF-κB signaling.

• 대한임상검사과학회지
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• 제53권4호
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• pp.309-316
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• 2021

패혈증은 감염원에 의한 생리학적 반응으로 장기의 기능을 손상시켜 조기에 치료하지 않으면 사망에 이르게 하는 기전을 유발한다. 이에 높은 감도, 특이도, 신속 정확도를 가진 바이오마커는 병원균의 미생물학적 검증에 필요한 제한성과 경과 시간을 감안할 때 패혈증을 비감염성 전신성 염증 반응 증후군(SIRS)과 구별하는 것이 획기적일 것으로 판단된다. 또한 항생제를 사용하기 전에 정확한 감염 진단이 중요하고 임상적으로 요구된다. 해당하는 후보물질인 프로칼시토닌, 젖산, C-반응성 단백질, 사이토카인, 프로아드레노매듈린(ProADM)이 진단에 활용된다. 급성 호흡기 감염 환자에서 프로칼시토닌으로 유도되는 항생제 치료는 항생제 노출과 항생제 부작용을 효과적으로 감소시키면서 사망률을 개선한다. 입원환자에 있어서 패혈증 선별검사에 대한 근거 마련은 제한적이다. 임상의사, 연구원 및 건강검진 의사의 전문가 집단은 일반 입원 환자의 패혈증 인식에 대한 스크리닝 도구, 향후 연구 또는 정책을 시행할 때 새로운 바이오마커의 발견과 한계점을 고려해야 한다. 바이오마커 사용은 항상 임상 평가와 상관관계가 있어야 하지만 소아 패혈증에서도 특히 바이오마커의 사용은 기대된다. 따라서 바이오마커의 활용에 있어서 특정된 전염증성 사이토카인 및 단백질 수준이 상승하는 것에 대해 패혈증의 초기 단계에서 사망률을 예측하는 것에 대해 향상된 진단법을 제공할 수 있다.

• Pediatric Infection and Vaccine
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• 제30권1호
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• pp.12-19
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• 2023

목적: 패혈증은 개발도상국에서 연간 사망률의 30-50%를 차지하는 신생아 사망의 가장 흔한 원인이다. 본 연구는 신생아 패혈증 사망률의 예후인자를 알아보고자 하였다. 방법: 2021년 4월부터 2021년 9월까지 R. Sosodoro Djatikoesoemo 주지사 병원 신생아 중환자실에서 패혈증을 진단받은 121명의 신생아를 대상으로 후향적 코호트 연구로 진행되었다. 연구대상자 선정기준은 신생아 중환자실에 입원하고 패혈증을 진단받은 생후 0-28일된신생아였다. 임상 기록이 불완전한 경우와 선천적 기형을 가진 경우는 제외하였다. 성별, 재태주령, 분만방식, 출생체중, APGAR 점수, 출생지, 혈액배양에 대해 카이제곱 검정을 시행하였고 백혈구, 림프구, 호중구, 혈소판, C반응단백 (C-reactive protein, CRP) 및 체류 기간에 대하여서는 정규성 검정을 한 후 Mann-Whitney 테스트로 분석하였다. 결과: 출생체중 (P=0.038), 임신주수 (P=0.009), 혈액배양 (P=0.014)은 신생아 패혈증 결과에 유의한 상관관계를 보였고, Mann-Whitney 검사는 혈소판 (P=0.018), CRP (P=0.002) 및 재원기간 (P<0.001)에서 유의한 차이를 보였다. 다변량 분석에서 신생아 패혈증 사망률과 관련된 세 가지 예후 인자는 미숙아 (오즈비 [odds ratio, OR], 3.906; 95% 신뢰구간 [confidence interval, CI], 1.344-11.356; P=0.012), 저체중 출생 (OR, 2.833; 95% CI, 1.030-7.790; P=0.044), 그람 음성 박테리아 (OR, 4.821; 95% CI, 1.018-22.842; P=0.047)인 것으로 나타났다. 결론: 미숙아, 저체중아, 그람 음성균 감염이 신생아 패혈증의 예후와 관련이 있었다.

• Archives of Pharmacal Research
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• 제27권2호
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• pp.232-238
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• 2004

Trolox is a hydrophilic analogue of vitamin E. The aim of this study was to investigate its effects on hepatic injury, especially alteration in cytochrome P450 (CYP)-dependent drug metabolism during polymicrobial sepsis. Rats were subjected to polymicrobial sepsis by cecal ligation and puncture (CLP). The rats were treated intravenously with Trolox (2.5 mg/kg) or vehicle, immediately after CLP. Serum aminotransferases and lipid peroxidation levels were markedly increased 24 h after CLP. This increase was attenuated by Trolox. Total CYP content and NADPH-P450 reductase activity decreased significantly 24 h after CLP. This decrease in CYP content was attenuated by Trolox. At 24 h after CLP, there was a significant decrease in the activity of these CYP isozymes: CYP1A1, 1A2, 2B1, and 2E1. However, Trolox differentially inhibited the decrease in CYP isozyme activity. Trolox had little effect on the decrease in CYP1A1 activity but Trolox significantly attenuated decreases in CYP1A2 and 2E1 activities. In fact, Trolox restored CYP2B1 activity to the level of activity found in control rats. Our findings suggest that Trolox reduces hepatocellular damage as indicated by abnormalities in hepatic drug-metabolizing function during sepsis. Our data also indicates that this protection is, in part, caused by decreased lipid peroxidation.

• Tuberculosis and Respiratory Diseases
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• 제73권1호
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• pp.1-10
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• 2012

Care of patients with sepsis has improved over the last decade. However, in the recent two years, there was no significant progress in the development of a new drug for critically ill patients. In January 2011, it was announced that the worldwide phase 3 randomized trial of a novel anti-Toll-like receptor-4 compound, eritoran tetrasodium, had failed to demonstrate an improvement in the mortality of patients with severe sepsis. In October 2011, Xigris (drotrecogin alfa, a recombinant activated protein C) was withdrawn from the market following the failure of its worldwide trial that had attempted to demonstrate improved outcome. These announcements were disappointing. The recent failure of 2 promising drugs to further reduce mortality suggests that new approaches are needed. A study was published showing that sepsis can be associated to a state of immunosuppression and loss of immune function in human. However, the timing, incidence, and nature of the immunosuppression remain poorly characterized, especially in humans. This emphasizes the need for a better understanding of sepsis as well as new therapeutic strategies. Many clinical experiences of the extracorporeal membrane oxygenator (ECMO) treatment for adult acute respiratory distress syndrome (ARDS) patients, which is caused by the H1N1 influenza A virus, were reported. The use of ECMO in severe respiratory failure, particularly in the treatment of adult ARDS, is occurring more commonly.

• 대한화상학회지
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• 제23권2호
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• pp.37-41
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• 2020

Purpose: The purpose of this study was to investigate the usefulness of Procalcitonin (PCT) as a predictor of mortality in patients with burn sepsis, which is closely related to mortality. Methods: A retrospective study was conducted on 912 PCT patients diagnosed with burn sepsis in patients who survived fluid resuscitation for at least 3 days, aged 18 years or older who were admitted to Burn Intensive Care Unit (BICU) of Hallym University Hangang Sacred Heart Hospital from January 2008 to December 2018. Results: Compared with the surviving group, TBSA (31%:65%), Inhalation (59.66%:74.23%) and ABSI (8 points:12 points) were statistically significantly higher in the death group. Looking at the changes in PCT levels in each survival and death group from Week 1 to Week 4, there was a statistically significant difference in PCT levels in the survival and death groups each week (P<0.001). Although there were statistical differences between the survival and death groups in each state (P<0.001), there was no difference in PCT values for each state in both groups (P=0.090). Conclusion: In burn patients suspected of sepsis, the use of PCT is useful for predicting survival and death. It is necessary to conduct research based on prospective study through systematization of measurement standards and data from multiple institutions to increase the utilization of PCT through research that complements the limitations.

• Journal of Yeungnam Medical Science
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• 제16권1호
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• pp.60-68
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• 1999

전국의 신생아 수련 병원에 설문지를 보내어 각 병원의 1997년 1월부터 12월까지 출생한 신생아 중 패혈증으로 진단되고 혈액 배양 검사에서 균이 검출된 경우, 병록지를 통해 후향적 조사를 실시하였고, 37개 병원에서 참여해 34.9%의 응답율을 나타내었으며, 결과는 다음과 같다. 1) 신생아 패혈증의 발생 빈도는 평균 0.73%(0~2.95%)였고, 남녀 비는 1.15:1이었다. 2) 신생아 패혈증의 원인균은 candida류를 포함하여 64종의 균이 검출되었다. 가장 흔한 원인균은 S. aureus였고, S. epidermidis, CONS의 순으로 많았다. 3) 조기 신생아 패혈증의 가장 흔한 원인균은 S. aureus였으며 CONS와 S. epidermidis가 그 다음으로 많았다. 후기 신생아 패혈증도 S. aureus가 가장 많이 검출되었고. S. epidermidis, CONS의 순으로 많았다. 4) 신생아 패혈증에 관련된 산모의 위험인자는 조기 파수가 104명(21.8%)으로 가장 많았고, 그 외에 난산, 태아의 빈맥, 융모양막염, 산모감염의 순이었다. 5) 신생아 패혈증과 연관된 국소 감염의 분포는 73명(26.1%)의 환아에서 폐렴이 동반되어 가장 많은 빈도를 보였고, 요로 감염, 뇌막염, 관절염의 순으로 많았다. 6) 신생아의 병원내 감염의 가장 흔한 원인균으로는 S. spidermidis가 가장 많았고, S. aureus, Entero-bacter의 순이었다. 7) 도관과 관련된 신생아 패혈증의 원인균은, S. aureus가 가장 많았고, S. epidermidis, Enterobacter의 순으로 많았다. Candida는 8례에서 발견되었다. 8) 그람 양생균의 항생제에 대한 반응검사에서 Penicillin이나 oxacillin에 대해 S. aureus, S. epidermidis, CONS 모두 30% 이하의 감수성을 보였다. Vacomycin에 대해서는 S. aureus, CONS, Enterococcus 각각 1례에서 내성을 나타내었다. 9) 그람 음성균의 항생제에 대한 반응검사에서 Gentamicin에 대해서 60% 정도의 감수성을 나타내었고, amikacin에 대해서는 80% 이상의 감수성을 보였다. Piperacillin과 aztreonam에 대해서, Pseudomonas가 100%의 감수성, ticarcillin에 대해서는 Klebsiella가 100%의 감수성을 나타내었다.

• Archives of Pharmacal Research
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• 제27권11호
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• pp.1123-1126
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• 2004

The bioassay-guided fractionation of protective agents against sepsis-induced lethality from the root cortex of Paeonia suffruticosa ANDREWS (Ranunculaceae) led to the isolation of eight known compounds: paeonol (1), 2,5-dihydroxy-4-methoxyacetophenone (2), acetovanillone (3), paeonoside (4), paeoniflorin (5), oxypaeoniflorin (6), apiopaeonoside (7), and methyl 3-hydroxy-4-methoxybenzoate (8). Among them, 3 showed the highest survival rate (100% with a dose of 30 mg/kg versus 17% for the control experiment) and reduced alanine aminotransferase level to be a half of the control value on the sepsis model induced by lipopolysaccharide/D-galactosamine.

• Tuberculosis and Respiratory Diseases
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• 제78권3호
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• pp.156-160
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• 2015

Severe sepsis and septic shock is a life-threatening disease. It is combined with multi-organ failure. In the past decade, early goal directed therapy has been proposed as an effective treatment strategy for better outcome. Recent epidemiologic studies showed that the outcome of sepsis has been improved with the introduction of early goal directed therapy. However, it is unclear which elements of early goal directed therapy contributed to the better outcome. Recent prospective and randomized trials suggested that some elements of early goal directed therapy did not have any effect on the outcome benefit. In this paper, recent articles about early goal directed therapy will be reviewed and the effectiveness of individual elements of early goal directed therapy will be discussed.

• The Korean Journal of Physiology and Pharmacology
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• 제22권4호
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• pp.399-408
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• 2018

A lipidomic study on extensive plasma lipids in bacterial peritonitis (cecal ligation and puncture, CLP)-induced sepsis in mice was done at 24 h post-CLP. The effects of administration of lysophosphatidylcholine (LPC) and lysophosphatidic acid (LPA), compounds known to have beneficial effects in CLP, on the sepsis-induced plasma lipid changes were also examined. Among the 147 plasma lipid species from 13 lipid subgroups (fatty acid [FA], LPA, LPC, lysophosphatidylethanolamine [LPE], phosphatidic acid [PA], phosphatidylcholine [PC], phosphatidylethanolamine [PE], phosphatidylinositol [PI], monoacylglyceride [MG], diacylglyceride [DG], triacylglyceride [TG], sphingomyelin [SM], and ceramide [Cer]) analyzed in this study, 40 and 70 species were increased, and decreased, respectively, in the CLP mice. Treatments with LPC and LPA affected 14 species from 7 subgroups, and 25 species from 9 subgroups, respectively. These results could contribute to finding the much needed reliable biomarkers of sepsis.