• Title/Summary/Keyword: Experimental sepsis

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Clinical features and prognostic factors of early-onset sepsis: a 7.5-year experience in one neonatal intensive care unit

  • Kim, Se Jin;Kim, Ga Eun;Park, Jae Hyun;Lee, Sang Lak;Kim, Chun Soo
    • Clinical and Experimental Pediatrics
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    • v.62 no.1
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    • pp.36-41
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    • 2019
  • Purpose: In this study, we investigated the clinical features and prognostic factors of early-onset sepsis (EOS) in neonatal intensive care unit (NICU) patients. Methods: A retrospective analysis was conducted on medical records from January 2010 to June 2017 (7.5 years) of a university hospital NICU. Results: There were 45 cases of EOS (1.2%) in 3,862 infants. The most common pathogen responsible for EOS was group B Streptococcus (GBS), implicated in 10 cases (22.2%), followed by Escherichia coli, implicated in 9 cases (20%). The frequency of gram-positive sepsis was higher in term than in preterm infants, whereas the rate of gram-negative infection was higher in preterm than in term infants (P<0.05). The overall mortality was 37.8% (17 of 45), and 47% of deaths occurred within the first 3 days of infection. There were significant differences in terms of gestational age (26.8 weeks vs. 35.1 weeks) and birth weight (957 g vs. 2,520 g) between the death and survival groups. After adjustments based on the difference in gestational age and birth weight between the 2 groups, gram-negative pathogens (odds ratio [OR], 42; 95% confidence interval [CI], 1.4-1,281.8) and some clinical findings, such as neutropenia (OR, 46; 95% CI, 1.3-1,628.7) and decreased activity (OR, 34; 95% CI, 1.8-633.4), were found to be associated with fatality. Conclusion: The common pathogens found to be responsible for EOS in NICU patients are GBS and E. coli. Gram-negative bacterial infections, decreased activity in the early phase of infection, and neutropenia were associated with poor outcomes.

Prevalence and Risk Factors of Candida Sepsis in Neonatal Intensive Care Unit (신생아 중환자실에서 캔디다 패혈증의 발생 추이와 위험 인자)

  • Choi, Ic Sun;Lim, Suk Hwan;Cho, Chang Yee;Choi, Young Youn;Hwang, Tai Ju
    • Clinical and Experimental Pediatrics
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    • v.45 no.7
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    • pp.836-846
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    • 2002
  • Purpose : With the development of neonatal intensive care and the increased use of systemic antibiotics, candida sepsis has become one of the most important causes of neonatal morbidity and mortality. The purpose of this study was to investigate the prevalence rate and its associated risk factors. Methods : We retrospectively reviewed medical records of 28 cases with candida sepsis who were admitted in the neonatal intensive care unit(NICU) of Chonnam University Hospital from July 1995 to June 2001. Twenty-nine patients without candida sepsis were enrolled for the control group to verify the risk factors. Results : The overall incidence of candida sepsis was 0.61% for all NICU admissions and 3.68% for all very low birth weight infants with the gradual increase of the annual prevalance rate over time. The endotracheal intubation, percutaneous central vein catheter(PCVC), umbilical vein catheter, total parenteral nutrition, intralipid and dopamine were more applied than the control group (P<0.01 for all). The durations of mechanical ventilator care, central catheter appliance, nothing per os, and admission were also significantly longer than the control group(P<0.01 for all). Ampicillin/ sulbactam, ceftazidime, amikacin, netilmicin, teicoplanin and imipenem/cilastatin were significantly more used than the control group(P<0.05). The durations of ampicillin/sulbactam, ceftazidime, netilmicin and imipenem/cilastatin administration were also proved to be significant as the risk factors(P<0.01). Conclusion : The average annual prevalence rate of candida sepsis in NICU for six years was 0.61% with gradual increasing tendency over time. The elimination of the above risk factors is important in decreasing neonatal morbidity and mortality associated with candida sepsis.

Analysis of causative microorganisms and choice of antibiotics according to the onset of neonatal sepsis (신생아 패혈증에서 발현시기에 따른 원인균 분석과 항생제 선택)

  • Sung, June Seung;Kim, Dong Yeon;Kim, Sun Hee;Byun, Hyung Suk;Hwang, Tai Ju;Choi, Young Youn
    • Clinical and Experimental Pediatrics
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    • v.49 no.6
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    • pp.623-629
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    • 2006
  • Purpose : The mortality rate of neonatal sepsis has been decreased, however, the incidence has not significantly decreased because of increased invasive procedures. This study was designed to make guidelines for choosing antibiotics by analyzing the causative microorganisms and their antibiotics sensitivity test according to the onset of neonatal sepsis. Methods : One hundred seven cases of culture proven sepsis in 89 patients admitted to the NICU of Chonnam University Hospital from Jan. 2000 to Dec. 2004, were enrolled. By reviewing the medical records, clinical data, laboratory findings, causative organisms and their antibiotics sensitivity, and mortality were analyzed. Results : The incidence of neonatal sepsis was 1.7 percent and more prevalent in premature and low birth weight infants. 85.4 percent of neonatal sepsis was late onset. Almost all microorganisms(92.9 percent) were gram-positive in early onset, however, two thirds were gram-positive and one third were gram-negative and Candida in late onset. Gram-negative organisms and Candida were more prevalent in patients who had central line. Gram-positive organisms were sensitive to vancomycin, teicoplanin, and gram-negative were sensitive to imipenem, and cefotaxime. Conclusion : Neonatal sepsis was more prevalent in premature and low birth weight infants. More than 90 percent were gram-positive in early onset, however, one third was gram-negative and Candida in late onset. The first choice of antibiotics were a combination of third generation cephalosporin and clindamycin in early onset, and third generation cephalosporin and glycopeptide in late onset. If there is no response to antibiotics treatment, the use of antifungal agents should be considered.

The Methanol Extract of Azadirachta indica A. Juss Leaf Protects Mice Against Lethal Endotoxemia and Sepsis

  • Kim, Woong-Hyun;Song, Hyun-Ok;Jin, Chun-Mei;Hur, Jong-Moon;Lee, Hwa-Sung;Jin, Han-Yong;Kim, Sung-Yeon;Park, Hyun
    • Biomolecules & Therapeutics
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    • v.20 no.1
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    • pp.96-103
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    • 2012
  • In the present study, the inhibitory effect of neem leaf extract (NLE) on lipopolysaccaride (LPS)-induced nitric oxide (NO) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) production was examined both in vitro and in vivo. In vitro study revealed that NLE treatment ($100{\mu}g/ml$) inhibits LPS (100 ng/ml)-induced NO production by 96% and TNF-${\alpha}$ production by 32%. The reduction in NO production is probably conferred by the complete suppression of inducible nitric oxide synthase (iNOS) expression. Interestingly, in vivo NLE significantly improved the survival rate of mice in an experimental sepsis model. Administration of NLE (100 mg/kg) 24 h before LPS treatment (20 mg/kg) improved the survival rate of mice by 60%. The inhibition of plasma NO and TNF-${\alpha}$ production by NLE is likely to account for the improved survival of mice. Our results suggest that NLE may present a promising avenue in the development of therapeutic agents for the treatment of inflammatory diseases.

The relation between serum levels of epidermal growth factor and necrotizing enterocolitis in preterm neonates

  • Ahmed, Heba Mostafa;Kamel, Nsreen Mostafa
    • Clinical and Experimental Pediatrics
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    • v.62 no.8
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    • pp.307-311
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    • 2019
  • Purpose: Necrotizing enterocolitis (NEC) is one of the most serious complications of prematurity. Many risk factors can contribute to the development of NEC. The epidermal growth factor (EGF) plays a major role in intestinal barrier function, increases intestinal enzyme activity, and improves nutrient transport. The aim of this study was to assess the role of epidermal growth factor in the development of NEC in preterm neonates. Methods: In this study, 130 preterm neonates were included and divided into 3 groups, as follows: group 1, 40 preterm neonates with NEC; group 2, 50 preterm neonates with sepsis; and group 3, 40 healthy preterm neonates as controls. The NEC group was then subdivided into medical and surgical NEC subgroups. The serum EGF level was measured using enzyme-linked immunosorbent assay. Results: Serum EGF levels (pg/dL) were significantly lower in the NEC group (median [interquartile range, IQR], 9.6 [2-14]) than in the sepsis (10.1 [8-14]) and control groups (11.2 [8-14], P<0.001), with no significant difference between the sepsis and control groups, and were positively correlated with gestational age (r=0.7, P<0.001). A binary logistic regression test revealed that low EGF levels and gestational ages could significantly predict the development of NEC. The receiver-operating characteristic curve for EGF showed an optimal cutoff value of 8 pg/mL, with 73.3% sensitivity, 98% specificity, and an area under the curve of 0.92. Conclusion: The patients with NEC in this study had significantly lower serum EGF levels (P<0.001), which indicated that EGF could be a reliable marker of NEC in preterm neonates.

Antibacterial Activity of Herbal Complex ABHC for Development of Novel Therapeutic Agent Against Sepsis (패혈증 치료제 개발을 위한 황백이 포함된 생약혼합제제 ABHC의 항균 효능)

  • Lee, Ki Man;Lee, Geum Seon;Kim, Yu Ri;Park, Jun Woo;Boo, Kyung-Jun;Yim, Dongsool;Kang, Tae Jin
    • Korean Journal of Pharmacognosy
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    • v.50 no.3
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    • pp.191-197
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    • 2019
  • Sepsis, an infectious disease, is a life-threatening condition that arises when the response to infection causes injury to tissues and organs. The purpose of this study was to demonstrate whether ABHC-1 and ABHC-2, two functional extracts from herbal complex, have an anti-bacterial effect against Escherchia coli in vivo, in vitro experimental model. ABHC-1 and ABHC-2 showed the antibacterial activity against the bacteria by paper disc method. The minimum inhibitory concentration (MIC) was measured using alamar blue reagent. The MIC was shown at $60{\mu}g/ml$ from ABHC-1 and $500{\mu}g/ml$ from ABHC-2 against E. coli. We next examined the effect of ABHCs on the production of inflammatory cytokine, such as tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), which is related to the induction of inflammation, in RAW 264.7 cell. ABHC-1 and ABHC-2 increased $TNF-{\alpha}$ production of RAW 264.7 cell in a dose-dependent manner while two extract decreased $TNF-{\alpha}$ production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cell in a dose-dependent manner. At a dose of $1{\times}10^8$ E. coli. i.p., non-treated mice were succumbed, while most of mice treated with ABHC-1 were survived. Therefore, our results suggest that ABHC-1 has anti-bacterial activity and can be a novel therapeutic agent against infectious diseases.

CD11b Deficiency Exacerbates Methicillin-Resistant Staphylococcus aureus-Induced Sepsis by Upregulating Inflammatory Responses of Macrophages

  • Hyunsub Sim;Daecheol Jeong;Hye-In Kim;Seongwon Pak;Bikash Thapa;Hyung-Joo Kwon;Keunwook Lee
    • IMMUNE NETWORK
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    • v.21 no.2
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    • pp.13.1-13.19
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    • 2021
  • Macrophages are important for the first line of defense against microbial pathogens. Integrin CD11b, which is encoded by Itgam, is expressed on the surface of macrophages and has been implicated in adhesion, migration, and cell-mediated cytotoxicity. However, the functional impact of CD11b on the inflammatory responses of macrophages upon microbial infection remains unclear. Here, we show that CD11b deficiency resulted in increased susceptibility to sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection by enhancing the pro-inflammatory activities of macrophages. Upon infection with MRSA, the mortality of Itgam knockout mice was significantly higher than that of control mice, which is associated with increased production of TNF-α and IL-6. In response to MRSA, both bone marrow-derived macrophages and peritoneal macrophages lacking CD11b produced elevated amounts of pro-inflammatory cytokines and nitric oxide. Moreover, CD11b deficiency upregulated IL-4-induced expression of anti-inflammatory mediators such as IL-10 and arginase-1, and an immunomodulatory function of macrophages to restrain T cell activation. Biochemical and confocal microscopy data revealed that CD11b deficiency augmented the activation of NF-κB signaling and phosphorylation of Akt, which promotes the functional activation of macrophages with pro-inflammatory and immunoregulatory phenotypes, respectively. Overall, our experimental evidence suggests that CD11b is a critical modulator of macrophages in response to microbial infection.

IM-133N - A Useful Herbal Combination for Eradicating Disease-triggering Pathogens in Mice via Immunotherapeutic Mechanisms

  • Firashathulla, Syed;Inamdar, Mohammed Naseeruddin;Rafiq, Mohamed;Viswanatha, Gollapalle Lakshminarayanashastry;Kumar, Lakkavalli Mohan Sharath;Babu, Uddagiri Venkanna;Ramakrishnan, Shyam;Paramesh, Rangesh
    • Journal of Pharmacopuncture
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    • v.19 no.1
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    • pp.21-27
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    • 2016
  • Objectives: The present study was undertaken to evaluate the immunomodulatory (IM) activity of IM-133N, a herbal combination in various immunotherapeutic experimental models. Methods: The IM activity of IM-133N was evaluated against three experimental models namely, effect of IM-133N against Escherichia coli (E. coli)-induced abdominal sepsis in mice, and carbon clearance test was performed in Wistar albino rats to evaluated the phagocytic potential of IM-133N, in addition IM-133N was evaluated for its immunoglobulin enhancing potential in rats, where the immunoglobulin levels were measured by zinc sulphate turbity (ZST) test. Further, IM-133N was subjected for detailed liquid chromatography-mass spectrometry (LC-MS)/MS analysis to identify the probable active constituents present in it. Results: The findings of the present study has demonstrated very promising IM property of IM-133N in all the experimental models. Briefly, pretreatment with IM-133N at 125, 250, 500 and 1,000 mg/kg, p.o. doses had protected the mice against E. coli-induced abdominal sepsis and mortality, further the effect of IM-133N was found to be significant and dose-dependent. In support of this, in another study administration of IM-133N showed a significant and dose-dependent increase in serum immunoglobulin levels, estimated by ZST test. In line with the above findings, in the carbon clearance test the low doses (125 and 250 mg/kg, p.o.) of IM-133N increased the rate of carbon clearance, whereas the higher doses (500 and 1,000 mg/kg, p.o.) did not sustain the response, and saturation effect was considered as one of the possible reason for futility of higher doses for IM-133N. In addition, A detailed LC-MS/MS analysis of IM-133N showed 17 bioactive phytochemical constituents: namely, apigenin, chaulmoogric acid, mesquitol, quercetin, symphoxanthone, salireposide, ${\beta}$-sitosterol, nonaeicosanol, ${\beta}$-amyrin, betulic acid, oleanolic acid, symplososide, symponoside, symploveroside, symplocomoside, symconoside A and locoracemoside B. Conclusion: These findings suggest that IM-133N possesses significant IM activity and, hence, could be useful for eradicating opportunistic disease-triggering pathogens via immunotherapeutic mechanisms. The findings also suggest IM-133N may also useful in other immunity disorders.

Analysis of neonatal sepsis in one neonatal intensive care unit for 6 years (최근 6년간 단일 신생아중환자실에서 발생한 패혈증 환자의 분석)

  • Chun, Peter;Kong, Seom-Gim;Byun, Shin-Yun;Park, Su-Eun;Lee, Hyung-Du
    • Clinical and Experimental Pediatrics
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    • v.53 no.4
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    • pp.495-502
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    • 2010
  • Purpose : Sepsis is a significant cause of morbidity and mortality in the newborn, particularly in preterm. The objective of this study was to analyze the incidence rate, causative pathogens and clinical features of neonatal sepsis in one neonatal intensive care unit (NICU) for 6 years. Methods : This study was retrospectively performed to review the clinical and laboratory characteristics including sex, gestational age, birth weight, Apgar score, length of hospitalization, length of total parenteral nutrition, presence of central venous catheter, underlying diseases, laboratory findings, microorganisms isolated from blood culture, complications and mortality in 175 patients between January 2003 and December 2008. Results : 1) Sepsis was present in 175 of 3,747 infants for 6 years. There were more gram-positive organisms. 2) The gram-negatives were more prevalent in preterm. There were no significant differences of other clinical features between two groups. 3) Underlying diseases were found in 73.7%, and the most common disease was cardiovascular disease. The most common organisms of gram-positives and gram-negatives were methicillin resistant Staphylococcus aureus (MRSA) and Serratia marcescens. 4) There was statistically significant difference on platelet counts between two groups (P<0.05). 5) Complications were found in 18.3% and septic shock was the most common. MRSA was the most common pathogen in sepsis with complication. 6) The mortality rate was 7.4%. 7) There were differences in monthly blood stream infection/1,000 patient-days. Conclusion : The studies about the factors that can influence neonatal sepsis will contribute to decrease the infection rates in NICUs.