• BMB Reports
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• 제54권11호
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• pp.545-550
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• 2021

Anisomycin is known to inhibit eukaryotic protein synthesis and has been established as an antibiotic and anticancer drug. However, the molecular targets of anisomycin and its mechanism of action have not been explained in macrophages. Here, we demonstrated the anti-inflammatory effects of anisomycin both in vivo and in vitro. We found that anisomycin decreased the mortality rate of macrophages in cecal ligation and puncture (CLP)- and lipopolysaccharide (LPS)-induced acute sepsis. It also declined the gene expression of proinflammatory mediators such as inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin-1β as well as the nitric oxide and proinflammatory cytokines production in macrophages subjected to LPS-induced acute sepsis. Furthermore, anisomycin attenuated nuclear factor (NF)-κB activation in LPS-induced macrophages, which correlated with the inhibition of phosphorylation of NF-κB-inducing kinase and IκB kinase, phosphorylation and IκBα proteolytic degradation, and NF-κB p65 subunit nuclear translocation. These results suggest that anisomycin prevented acute inflammation by inhibiting NF-κB-related inflammatory gene expression and could be a potential therapeutic candidate for sepsis.

• 한국동물위생학회지
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• 제47권2호
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• pp.89-94
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• 2024

A 5-year-old spayed female mixed-breed dog, previously receiving 7 months of immunosuppressive therapy for pemphigus foliaceus, presented to our referral hospital with a history of dog bites on the right forelimb, chest, and flank 4 days prior to presentation. Physical examination revealed a rectal temperature of 38.6℃; heart rate of 130 beats per minute; panting; systolic blood pressure of 60 mmHg; and swelling, purulent discharge, warmth, pain, and lameness in the right forelimb. The laboratory investigation revealed neutropenia and elevated C-reactive protein levels. Suppurative neutrophilic infiltration with bacterial infection was detected by impression cytology of the pus on the right forelimb. Based on the results of the clinical examinations and laboratory tests, the dog was diagnosed with dog bite-induced sepsis with pemphigus. Meropenem and metronidazole were prescribed. Clinical signs, neutropenia, and C-reactive protein levels markedly improved after 5 days. Subsequently, pemphigus foliaceus relapsed in the dog, and it is currently undergoing re-administration of immunosuppressive medications. To the best of our knowledge, this is the first case report of successful management of dog bite-induced sepsis in a dog undergoing long-term immunosuppressive therapy.

• 대한영상의학회지
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• 제83권5호
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• pp.1104-1108
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• 2022

심근 석회화는 다양한 원인으로 인해서 발생할 수 있다. 하지만 패혈증과 신부전으로 인해서 발생하는 경우는 흔하지 않다. 저자들은 컴퓨터단층촬영과 자기공명영상에서 패혈증과 신부전을 회복한 환자에서 급속하게 좌심실벽에 미만성 석회화를 보이는 증례를 보고하고자 한다.

• 사상체질의학회지
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• 제25권4호
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• pp.432-441
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• 2013

Objectives Despite the treatment with antibiotics, patients with sepsis has a high mortality (80%) in the underlying disease group. The aim of this study was to report the improvement of septic condition of the cholangiocarcinoma patient after the treatment with Handayeolso-tang, Fel Tauri, and antibiotics. Methods We retrospectively reviewed the medical records. The patient's subjective symptoms such as chilling and abdominal pain were evaluated by NRS and the performance status was evaluated by ECOG. This case was literally compared with relevant published studies on prognosis of sepsis. Results Despite poor prognostic factor(MEDS score 18), the patient's symptoms such as fever, chilling, abdominal pain, and diarrhea and ECOG(Eastern Cooperative Oncology Group) improved. The patient was hemodynamically stabilized on 3rd day from the treatment, and her laboratory test results were normalized on 7th day. Conclusions A female patient of metastatic cholangiocarcinoma came to the hospital for cholangitis, later causing septic shock. Both her symptoms and laboratory tests showed significant improvement after the treatment of antibiotics, Handayeolso-tang and Fel Tauri. To our knowledge, this is the first case reporting the synergistic combination of Korean oriental medicine and Western medicine approaching to sepsis.

• Journal of Dental Anesthesia and Pain Medicine
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• 제15권3호
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• pp.135-140
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• 2015

Background: Identifying early markers of septic complications can aid in the diagnosis and therapeutic management of hospitalized patients. In this study, the utility of procalcitonin (PCT) vs. C-reactive protein (CRP) as early markers of sepsis was compared. Methods: A series of 2,697 consecutive blood samples was collected from hospitalized patients and serum PCT and CRP levels were measured. Patients were categorized by PCT level as follows: < 0.05 ng/ml, 0.05-0.49 ng/ml, 0.5-1.99 ng/ml, 2-9.99 ng/ml, and > 10 ng/ml. Diagnostic utility was analyzed by receiver operating characteristic (ROC) curves. Results: Mean CRP levels varied among the five PCT categories at $0.31{\pm}2.87$, $5.65{\pm}6.26$, $13.78{\pm}8.01$, $12.15{\pm}10.16$, and $17.77{\pm}10.59$, respectively (P < 0.05). PCT and CRP differed between positive and negative blood culture groups (PCT: 15.9 vs. 4.78 mg/dl;CRP: 11.5 ng/ml vs. 9.57 ng/ml;P < 0.05). The areas under the ROC curves (PCT, 95% confidence interval [CI]: 0.743, range: 0.698-0.789 at a threshold of 0.5 ng/ml; CRP, 95% CI: 0.540, range: 0.478-0.602 at a threshold of 8 mg/l) differed for PCT and CRP (P < 0.05). Conclusions: Therefore, PCT is a reliable marker for sepsis diagnosis and is more relevant than CRP in patients with a positive blood culture. These findings can be useful for the treatment of critically ill sepsis patients.

• BMB Reports
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• 제49권4호
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• pp.214-219
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• 2016

A nucleosomal protein, high mobility group box 1 (HMGB1) is known to be a late mediator of sepsis. Dabrafenib is a B-Raf inhibitor and initially used for the treatment of metastatic melanoma therapy. Inhibition of HMGB1 and renewal of vascular integrity is appearing as an engaging therapeutic strategy in the administration of severe sepsis or septic shock. Here, we examined the effects of dabrafenib (DAB) on the modulation of HMGB1-mediated septic responses. DAB inhibited the release of HMGB1 and downregulated HMGB1-dependent inflammatory responses by enhancing the expressions of cell adhesion molecules (CAMs) in human endothelial cells. In addition, treatment with DAB inhibited the HMGB1 secretion by CLP and sepsis-related mortality and pulmonary injury. This study demonstrated that DAB could be alternative therapeutic options for sepsis or septic shock via the inhibition of the HMGB1 signaling pathway.

• 대한응급의학회지
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• 제29권5호
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• pp.474-484
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• 2018

Objective: The time to positivity (TTP) of blood culture reflects bacterial load and has been reported to be associated with outcome in bloodstream infections. This study was performed to evaluate the relationship between the TTP of blood culture and the mortality rates associated with sepsis and septic shock according to the site of infection. Methods: We performed a retrospective cohort study on patients with sepsis and septic shock. The rates of blood culture positivity and mortality as well as the relationship between the TTP and 28-day mortality rate were compared among patients with different sites of infection, such as the lungs, abdomen, urogenital tract, and other sites. Results: A total of 2,668 patients were included, and the overall mortality rate was 21.6%. The rates of blood culture positivity and mortality were different among the different infection sites. There was no relationship between the TTP and mortality rates of total, lung, and urogenital infections. Patients with abdominal infections showed a negative correlation between the TTP and 28-day mortality rate. In patients with abdominal infections, a TTP<20 hours was independently associated with 28-day mortality compared with patients with negative blood culture (hazard ratio, 1.73; 95% confidence interval, 1.16-2.58). However, there was no difference in mortality rates of patients with a $TTP{\geq}20$ hours and a negative blood culture. Conclusion: The shorter TTP in patients with abdominal infections in sepsis and septic shock was associated with a higher 28-day mortality rate.

• 대한융합한의학회지
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• 제4권1호
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• pp.19-27
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• 2022

Objectives: TSepsis and subsequent acute lung injury (ALI) is a critical state of health caused by infection or endotoxins. This study was conducted to evaluate the effect of Water Extract of Aconiti Lateralis Preparata Radix (AR) on lipopolysaccharide (LPS)-induced sepsis in C57BL/6 mice. Methods: Male C57BL/6 mice were intraperitoneally injected with LPS to induce sepsis and ALI. AR was orally fed twice at 30 min and 180 min after LPS injection. At 24 h post injection, mice were sacrificed, bronchoalveolar lavage fluid (BALF) and blood was collected, and lung tissue was harvested. Hematoxylin and eosin staining was performed in lung tissues, wet/dry ratio of the lung tissue was measured, and the serum cytokine and chemokine levels were analyzed. Results: AR revoked the LPS-induced pathological changes in lung tissues, such as abnormal histological structures, immune cell infiltration and lung edema. Also, AR suppressed the neutrophil infiltration into the lung which was greatly increased by LPS injection based on the cell content of collected BALF. Serum cytokines and chemokines were measured, and AR reversed the LPS-induced increase of cytokines such as interleukin 1 beta, interleukin 6, tumor necrosis factor alpha and chemokines including C-X-C motif chemokine ligand 1 and 2. Conclusion: TAR showed a protective effect in the pathological progress of LPS-induced ALI. Especially, AR suppressed lung edema and infiltration of neutrophils by inhibiting cytokine and chemokine expressions. Such results demonstrate the potential of AR as a therapeutic agent for sepsis and sepsis-induced ALI.

• Neonatal Medicine
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• 제16권2호
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• pp.163-171
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• 2009

목 적 : 15년간 VLBWI에서 생후 3일내 발생한 조기 패혈증의 발생률과 원인균 및 위험인자를 분석하고 사망률에 대해 알아보고자 하였다. 방 법 : 1994년 11월부터 2008년 12월까지 삼성서울병원 신생아집중치료실에 입원한 출생체중 1,500 g 미만의 VLBWI 1,124명을 대상으로 의무기록을 후향적으로 분석하여 조기 패혈증의 발생률, 원인균, 위험인자 및 사망률에 대해 조사하였다. 결 과 : VLBWI의 3일내 조기 패혈증의 발생률은 1.5% (17명)였다. 조기 패혈증 원인균은 그람 양성균이 64.7% (11종), 그람 음성균 35.2% (6종)보다 높게 나타났고 Staphylococcus aureus (23.5%, 4명), Escherichia coli (23.5%, 4명), Enterococcus (17.6%, 3명) 순으로 많았다. 조기 패혈증과 관련된 위험인자는 질식 분만 (adjusted OR, 3.7; 95% CI, 1.3-10.3; P=0.01)이었고 전체 사망률은 조기 패혈증 군이 대조군에 비해 3.0배 높았고(adjusted hazard ratio, 3.0; 95% CI, 1.4-6.5; adjusted P=0.0039) 특히 3일 내 사망률은 조기 패혈증 군이 대조군에 비해 6.5배 높았다(adjusted hazard ratio, 6.5; 95% CI, 2.2 18.9; adjusted P=0.0005). 결 론 : VLBWI의 조기 패혈증은 흔하지 않지만 사망률이 매우 높다. 조기 패혈증의 원인균 및 위험인자를 밝혀 적절한 항생제 사용 및 주산기 관리로 조기 패혈증 사망률을 낮출 수 있도록 노력해야 할 것이다.

• Biomolecules & Therapeutics
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• 제28권3호
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• pp.222-229
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• 2020

The process of drug discovery and drug development consumes billions of dollars to bring a new drug to the market. Drug development is time consuming and sometimes, the failure rates are high. Thus, the pharmaceutical industry is looking for a better option for new drug discovery. Drug repositioning is a good alternative technology that has demonstrated many advantages over de novo drug development, the most important one being shorter drug development timelines. In the last two decades, drug repositioning has made tremendous impact on drug development technologies. In this review, we focus on the recent advances in drug repositioning technologies and discuss the repositioned drugs used for inflammatory diseases such as sepsis, asthma, and atopic dermatitis.