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Sample records for lps-induced septic shock

  1. Thalidomide protects mice against LPS-induced shock

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    Moreira A.L.

    1997-01-01

    Full Text Available Thalidomide has been shown to selectively inhibit TNF-a production in vitro by lipopolysaccharide (LPS-stimulated monocytes. TNF-a has been shown to play a pivotal role in the pathophysiology of endotoxic shock. Using a mouse model of LPS-induced shock, we investigated the effects of thalidomide on the production of TNF-a and other cytokines and on animal survival. After injection of 100-350 µg LPS into mice, cytokines including TNF-a, IL-6, IL-10, IL-1ß, GM-CSF and IFN-g were measured in the serum. Administration of 200 mg/kg thalidomide to mice before LPS challenge modified the profile of LPS-induced cytokine secretion. Serum TNF-a levels were reduced by 93%, in a dose-dependent manner, and TNF-a mRNA expression in the spleens of mice was reduced by 70%. Serum IL-6 levels were also inhibited by 50%. Thalidomide induced a two-fold increase in serum IL-10 levels. Thalidomide treatment did not interfere with the production of GM-CSF, IL-1ß or IFN-g. The LD50 of LPS in this model was increased by thalidomide pre-treatment from 150 µg to 300 µg in 72 h. Thus, at otherwise lethal doses of LPS, thalidomide treatment was found to protect animals from death

  2. Inhibition of IRAK-4 activity for rescuing endotoxin LPS-induced septic mortality in mice by lonicerae flos extract

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    Park, Sun Hong; Roh, Eunmiri [College of Pharmacy, Chungbuk National University, Cheongju 361-763 (Korea, Republic of); Kim, Hyun Soo [Pharmaceutical R and D Center, Huons Co., Ltd., Anyang (Korea, Republic of); Baek, Seung-Il [College of Pharmacy, Chungbuk National University, Cheongju 361-763 (Korea, Republic of); Choi, Nam Song [Pharmaceutical R and D Center, Huons Co., Ltd., Anyang (Korea, Republic of); Kim, Narae; Hwang, Bang Yeon; Han, Sang-Bae [College of Pharmacy, Chungbuk National University, Cheongju 361-763 (Korea, Republic of); Kim, Youngsoo, E-mail: youngsoo@chungbuk.ac.kr [College of Pharmacy, Chungbuk National University, Cheongju 361-763 (Korea, Republic of)

    2013-12-13

    Highlights: •Lonicerae flos extract (HS-23) is a clinical candidate, Phase I for sepsis treatment. •Here, HS-23 or its major constituents rescued LPS-induced septic mortality in mice. •As a mechanism, they directly inhibited IRAK-4-catalyzed kinase activity. •Thus, they suppressed LPS-induced expression of NF-κB/AP-1-target inflammatory genes. -- Abstract: Lonicerae flos extract (HS-23) is a clinical candidate currently undergoing Phase I trial in lipopolysaccharide (LPS)-injected healthy human volunteers, but its molecular basis remains to be defined. Here, we investigated protective effects of HS-23 or its major constituents on Escherichia coli LPS-induced septic mortality in mice. Intravenous treatment with HS-23 rescued LPS-intoxicated C57BL/6J mice under septic conditions, and decreased the levels of cytokines such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β and high-mobility group box-1 (HMGB-1) in the blood. Chlorogenic acid (CGA) and its isomers were assigned as major constituents of HS-23 in the protection against endotoxemia. As a molecular mechanism, HS-23 or CGA isomers inhibited endotoxin LPS-induced autophosphorylation of the IL-1 receptor-associated kinase 4 (IRAK-4) in mouse peritoneal macrophages as well as the kinase activity of IRAK-4 in cell-free reactions. HS-23 consequently suppressed downstream pathways critical for LPS-induced activation of nuclear factor (NF)-κB or activating protein 1 (AP-1) in the peritoneal macrophages. HS-23 also inhibited various toll-like receptor agonists-induced nitric oxide (NO) production, and down-regulated LPS-induced expression of NF-κB/AP-1-target inflammatory genes in the cells. Taken together, HS-23 or CGA isomers exhibited anti-inflammatory therapy against LPS-induced septic mortality in mice, at least in part, mediated through the inhibition of IRAK-4.

  3. Effects and mechanisms of cavidine protecting mice against LPS-induced endotoxic shock

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    Li, Weifeng, E-mail: liwf@mail.xjtu.edu.cn; Zhang, Hailin; Niu, Xiaofeng, E-mail: niuxf@mail.xjtu.edu.cn; Wang, Xiumei; Wang, Yu; He, Zehong; Yao, Huan

    2016-08-15

    LPS sensitized mice are usually considered as an experimental model of endotoxin shock. The present study aims to evaluate effects of cavidine on LPS-induced endotoxin shock. Mice were intraperitoneally administrated with cavidine (1, 3 and 10 mg/kg) or DEX (5 mg/kg) at 1 and 12 h before injecting LPS (30 mg/kg) intraperitoneally. Blood samples, liver, lung and kidney tissues were harvested after LPS injection. The study demonstrated that pretreatment with cavidine reduced the mortality of mice during 72 h after endotoxin injection. In addition, cavidine administration significantly attenuated histological pathophysiology features of LPS-induced injury in lung, liver and kidney. Furthermore, cavidine administration inhibited endotoxin-induced production of pro-inflammatory cytokines including TNF-α, IL-6 and HMGB1. Moreover, cavidine pretreatment attenuated the phosphorylation of mitogen-activated protein kinase primed by LPS. In summary, cavidine protects mice against LPS-induced endotoxic shock via inhibiting early pro-inflammatory cytokine TNF-α, IL-6 and late-phase cytokine HMGB1, and the modulation of HMGB1 may be related with MAPK signal pathway. - Highlights: • Cavidine significantly reduced mortality in mice during 72 h after LPS injection. • Cavidine attenuated histopathological changes in lung, liver and kidney. • Cavidine decreased the level of early inflammatory cytokine TNF-α, IL-6 in LPS- stimulated mice. • Cavidine inhibited late inflammatory cytokine HMGB1 through MAPK pathway.

  4. Sepsis and septic shock

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    Hotchkiss, Richard S.; Moldawer, Lyle L.; Opal, Steven M.; Reinhart, Konrad; Turnbull, Isaiah R.; Vincent, Jean-Louis

    2017-01-01

    For more than two decades, sepsis was defined as a microbial infection that produces fever (or hypothermia), tachycardia, tachypnoea and blood leukocyte changes. Sepsis is now increasingly being considered a dysregulated systemic inflammatory and immune response to microbial invasion that produces organ injury for which mortality rates are declining to 15–25%. Septic shock remains defined as sepsis with hyperlactataemia and concurrent hypotension requiring vasopressor therapy, with in-hospital mortality rates approaching 30–50%. With earlier recognition and more compliance to best practices, sepsis has become less of an immediate life-threatening disorder and more of a long-term chronic critical illness, often associated with prolonged inflammation, immune suppression, organ injury and lean tissue wasting. Furthermore, patients who survive sepsis have continuing risk of mortality after discharge, as well as long-term cognitive and functional deficits. Earlier recognition and improved implementation of best practices have reduced in-hospital mortality, but results from the use of immunomodulatory agents to date have been disappointing. Similarly, no biomarker can definitely diagnose sepsis or predict its clinical outcome. Because of its complexity, improvements in sepsis outcomes are likely to continue to be slow and incremental. PMID:28117397

  5. Sepsis and Septic Shock Strategies.

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    Armstrong, Bracken A; Betzold, Richard D; May, Addison K

    2017-12-01

    Three therapeutic principles most substantially improve organ dysfunction and survival in sepsis: early, appropriate antimicrobial therapy; restoration of adequate cellular perfusion; timely source control. The new definitions of sepsis and septic shock reflect the inadequate sensitivity, specify, and lack of prognostication of systemic inflammatory response syndrome criteria. Sequential (sepsis-related) organ failure assessment more effectively prognosticates in sepsis and critical illness. Inadequate cellular perfusion accelerates injury and reestablishing perfusion limits injury. Multiple organ systems are affected by sepsis and septic shock and an evidence-based multipronged approach to systems-based therapy in critical illness results in improve outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Control groups in recent septic shock trials

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    Pettilä, Ville; Hjortrup, Peter B; Jakob, Stephan M

    2016-01-01

    PURPOSE: The interpretation of septic shock trial data is profoundly affected by patients, control intervention, co-interventions and selected outcome measures. We evaluated the reporting of control groups in recent septic shock trials. METHODS: We searched for original articles presenting......, and mortality outcomes, and calculated a data completeness score to provide an overall view of quality of reporting. RESULTS: A total of 24 RCTs were included (mean n = 287 patients and 71 % of eligible patients were randomized). Of the 24 studies, 14 (58 %) presented baseline data on vasopressors and 58...... % the proportion of patients with elevated lactate values. Five studies (21 %) provided data to estimate the proportion of septic shock patients fulfilling the Sepsis-3 definition. The mean data completeness score was 19 out of 36 (range 8-32). Of 18 predefined control group characteristics, a mean of 8 (range 2...

  7. The Septic Shock 3.0 Definition and Trials: A Vasopressin and Septic Shock Trial Experience.

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    Russell, James A; Lee, Terry; Singer, Joel; Boyd, John H; Walley, Keith R

    2017-06-01

    The Septic Shock 3.0 definition could alter treatment comparisons in randomized controlled trials in septic shock. Our first hypothesis was that the vasopressin versus norepinephrine comparison and 28-day mortality of patients with Septic Shock 3.0 definition (lactate > 2 mmol/L) differ from vasopressin versus norepinephrine and mortality in Vasopressin and Septic Shock Trial. Our second hypothesis was that there are differences in plasma cytokine levels in Vasopressin and Septic Shock Trial for lactate less than or equal to 2 versus greater than 2 mmol/L. Retrospective analysis of randomized controlled trial. Multicenter ICUs. We compared vasopressin-to-norepinephrine group 28- and 90-day mortality in Vasopressin and Septic Shock Trial in lactate subgroups. We measured 39 cytokines to compare patients with lactate less than or equal to 2 versus greater than 2 mmol/L. Patients with septic shock with lactate greater than 2 mmol/L or less than or equal to 2 mmol/L, randomized to vasopressin or norepinephrine. Concealed vasopressin (0.03 U/min.) or norepinephrine infusions. The Septic Shock 3.0 definition would have decreased sample size by about half. The 28- and 90-day mortality rates were 10-12 % higher than the original Vasopressin and Septic Shock Trial mortality. There was a significantly (p = 0.028) lower mortality with vasopressin versus norepinephrine in lactate less than or equal to 2 mmol/L but no difference between treatment groups in lactate greater than 2 mmol/L. Nearly all cytokine levels were significantly higher in patients with lactate greater than 2 versus less than or equal to 2 mmol/L. The Septic Shock 3.0 definition decreased sample size by half and increased 28-day mortality rates by about 10%. Vasopressin lowered mortality versus norepinephrine if lactate was less than or equal to 2 mmol/L. Patients had higher plasma cytokines in lactate greater than 2 versus less than or equal to 2 mmol/L, a brisker cytokine response to infection. The Septic

  8. Severe sepsis and septic shock [author's reply

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    Angus, Derek C.; van der Poll, Tom

    2013-01-01

    To the Editor: We would like to address two potentially confusing issues concerning venous oxygen saturation (Svo(2)) as presented in Table 1 of the review by Angus and van der Poll (Aug. 29 issue).(1) First, Table 1 suggests that Svo(2) is raised in sepsis, severe sepsis, and septic shock.

  9. Dopamine versus noradrenaline in septic shock

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    Bo Xu

    2011-10-01

    Full Text Available BackgroundThe ‘Surviving Sepsis’ Campaign guidelines recommend theuse of dopamine or noradrenaline as the first vasopressor inseptic shock. However, information that guides clinicians inchoosing between dopamine and noradrenaline as the firstvasopressor in patients with septic shock is limited.ObjectiveThis article presents a review of the literature regarding theuse of dopamine versus noradrenaline in patients with septicshock.ResultsTwo randomised controlled trials (RCT and two largeprospective cohort studies were analysed. RCT data showeddopamine was associated with increased arrhythmic events.One cohort study found dopamine was associated with higher30-day mortality. The other cohort study found noradrenalinewas associated with higher 28-day mortality.DiscussionData on the use of dopamine versus noradrenaline in patientswith septic shock is limited. Following the recent SOAP IIstudy, there is now strong evidence that the use of dopaminein septic shock is associated with significantly morecardiovascular adverse events, compared tonoradrenaline.ConclusionNoradrenaline should be used as the initial vasopressor inseptic shock to avoid the arrhythmic events associatedwith dopamine.

  10. The Antimalarial Chloroquine Suppresses LPS-Induced NLRP3 Inflammasome Activation and Confers Protection against Murine Endotoxic Shock

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    Xiaoli Chen

    2017-01-01

    Full Text Available Activation of the NLRP3 inflammasome, which catalyzes maturation of proinflammatory cytokines like IL-1β and IL-18, is implicated and essentially involved in many kinds of inflammatory disorders. Chloroquine (CQ is a traditional antimalarial drug and also possesses an anti-inflammatory property. In this study, we investigated whether CQ suppresses NLRP3 inflammasome activation and thereby confers protection against murine endotoxic shock. CQ attenuated NF-κB and MAPK activation and prohibited expression of IL-1β, IL-18, and Nlrp3 in LPS treated murine bone marrow-derived macrophages (BMDMs, demonstrating its inhibitory effect on the priming signal of NLRP3 activation. Then, CQ was shown to inhibit caspase-1 activation and ASC specks formation in BMDMs, which indicates that CQ also suppresses inflammasome assembly, the second signal for NLRP3 inflammasome activation. In a murine endotoxic shock model, CQ effectively improved survival and markedly reduced IL-1β and IL-18 production in serum, peritoneal fluid, and lung tissues. Moreover, CQ reduced protein levels of NLRP3 and caspases-1 p10 in lung homogenates of mice with endotoxic shock, which may possibly explain its anti-inflammatory activity and life protection efficacy in vivo. Overall, our results demonstrate a new role of CQ that facilitates negative regulation on NLRP3 inflammasome, which thereby confers protection against lethal endotoxic shock.

  11. Role of echocardiography in reducing shock reversal time in pediatric septic shock: a randomized controlled trial

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    Ahmed A. EL‐Nawawy

    2018-01-01

    Conclusion: Serial echocardiography provided crucial data for early recognition of septic myocardial dysfunction and hypovolemia that was not apparent on clinical assessment, allowing a timely management and resulting in shock reversal time reduction among children with septic shock.

  12. The Impact of the Sepsis-3 Septic Shock Definition on Previously Defined Septic Shock Patients.

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    Sterling, Sarah A; Puskarich, Michael A; Glass, Andrew F; Guirgis, Faheem; Jones, Alan E

    2017-09-01

    The Third International Consensus Definitions Task Force (Sepsis-3) recently recommended changes to the definitions of sepsis. The impact of these changes remains unclear. Our objective was to determine the outcomes of patients meeting Sepsis-3 septic shock criteria versus patients meeting the "old" (1991) criteria of septic shock only. Secondary analysis of two clinical trials of early septic shock resuscitation. Large academic emergency departments in the United States. Patients with suspected infection, more than or equal to two systemic inflammatory response syndrome criteria, and systolic blood pressure less than 90 mm Hg after fluid resuscitation. Patients were further categorized as Sepsis-3 septic shock if they demonstrated hypotension, received vasopressors, and exhibited a lactate greater than 2 mmol/L. We compared in-hospital mortality in patients who met the old definition only with those who met the Sepsis-3 criteria. Four hundred seventy patients were included in the present analysis. Two hundred (42.5%) met Sepsis-3 criteria, whereas 270 (57.4%) met only the old definition. Patients meeting Sepsis-3 criteria demonstrated higher severity of illness by Sequential Organ Failure Assessment score (9 vs 5; p definition demonstrated significant mortality benefit following implementation of a quantitative resuscitation protocol (35% vs 10%; p = 0.006). In this analysis, 57% of patients meeting old definition for septic shock did not meet Sepsis-3 criteria. Although Sepsis-3 criteria identified a group of patients with increased organ failure and higher mortality, those patients who met the old criteria and not Sepsis-3 criteria still demonstrated significant organ failure and 14% mortality rate.

  13. Red blood cell transfusion during septic shock in the ICU

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    Perner, A; Smith, S H; Carlsen, S

    2012-01-01

    Transfusion of red blood cells (RBCs) remains controversial in patients with septic shock, but current practice is unknown. Our aim was to evaluate RBC transfusion practice in septic shock in the intensive care unit (ICU), and patient characteristics and outcome associated with RBC transfusion....

  14. Current Opinions in Pediatric Septic Shock

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    José Irazuzta

    2009-11-01

    Full Text Available Objectives: Our aim is to describe the current clinical practice related to the management of septic shock (SS. Methods: Review of medical literature using the MEDLINE database. Articles were selected according to their relevancy to the objective and according to the author’s opinion. Summary of the findings: The outcome from SS is dependent on an early recognition and a sequential implementation of time-sensitive goal-directed therapies. The goals of the resuscitation are rapid restoration of micro circulation and improved organ tissue perfusion. Clinical and laboratory markers are needed to assess the adequacy of the treatments. Initial resuscitation involves the use of isotonic solutions (>60ml/kg either crystalloid (normal saline or colloid infusion often followed by vasoactive medications. Altered pharmacokinetics and pharmacodynamics responses dictate that vasoactive agents should be adjusted to achieve predetermined goals. An assessment of central venous pressure complements clinical and serological findings to tailor therapies. Elective airway instrumentation and mechanical ventilation as well as adjunctive therapy with stress dose of corticosteroid are indicated in selected populations. In neonates, a special attention to the presence of electrolyte imbalance and increase pulmonary vascular resistance needs to be considered early. Conclusions: Septic shock hemodynamic is a changing process that requires frequent assessment and therapeutic adjustments.

  15. Red blood cell transfusion in septic shock

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    Rosland, Ragnhild G; Hagen, Marte U; Haase, Nicolai

    2014-01-01

    Sepsis-related Organ Failure Assessment (SOFA) scores (days 1 and 5), more days in shock (5 (3-10) vs. 2 (2-4), p = 0.0001), more days in ICU (10 (4-19) vs. 4 (2-8), p = 0.0001) and higher 90-day mortality (66 vs. 43%, p = 0.001). The latter association was lost after adjustment for admission category....../dl and independent of shock day and bleeding. Patients with cardiovascular disease were transfused at higher haemoglobin levels. Transfused patients had higher Simplified Acute Physiology Score (SAPS) II (56 (45-69) vs. 48 (37-61), p = 0.0005), more bleeding episodes, lower haemoglobin levels days 1 to 5, higher...... and SAPS II and SOFA-score on day 1. CONCLUSIONS: The decision to transfuse patients with septic shock was likely affected by disease severity and bleeding, but haemoglobin level was the only measure that consistently differed between transfused and non-transfused patients....

  16. Evaluation of Coagulation Profiles in Dogs with Septic Shock

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    YILMAZ, Zeki; YALÇIN, Ebru

    2002-01-01

    The aim of the this study was to observe possible changes in coagulation profiles in dogs with septic shock. A total of 30 dogs (control group n=10, test group n=20) were used as materials in this study. Although different diseases leading to septic shock were diagnosed in dogs in the test group, dogs were selected on the basis of septic shock criteria such as fever or hypothermia, hypotension, leukopenia or leukocytosis and thrombocytopenia. In addition to the results of rutine clinical and...

  17. Lung protein leakage in feline septic shock.

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    Schützer, K M; Larsson, A; Risberg, B; Falk, A

    1993-06-01

    The aim of the present study was to explore lung microvascular leakage of protein and water in a feline model of septic shock, using a double isotope technique with external gamma camera detection and gravimetric lung water measurements. The experiments were performed on artificially ventilated cats. One group of cats (n = 8) was given an infusion of live Escherichia coli bacteria, and another group (n = 5) served as a control group receiving saline. Plasma transferrin was radiolabeled in vivo with indium-113m-chloride, and erythrocytes were labeled with technetium-99m. The distribution of these isotopes in the lungs was continuously measured with a gamma camera. A normalized slope index (NSI) was calculated, indicative of the transferrin accumulation corrected for changes in local blood volume that reflect protein leakage. In the septic group there was a protein leakage after bacterial infusion, with a NSI of 39 x 10(-4) +/- 5 x 10(-4) min-1 (mean +/- SEM), and the PaO2 diminished from 21 +/- 1 to 9.5 +/- 1 kPa. In control cats a slight protein leakage with a NSI of 9 +/- 10(-4) +/- 2 x 10(-4) min-1 was detected, probably caused by the operative procedure, but PaO2 did not change. Wet-to-dry-weight ratios of postmortem lungs were not significantly different between the groups. It was concluded that an intravenous infusion of live E. coli bacteria induces a lung capillary protein leakage without increased lung water and a concomitantly disturbed gas exchange.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Higher vs. lower haemoglobin threshold for transfusion in septic shock

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    Rygård, S L; Holst, L B; Wetterslev, J

    2017-01-01

    . a lower haemoglobin threshold. METHODS: In post-hoc analyses of the full trial population of 998 patients from the Transfusion Requirements in Septic Shock (TRISS) trial, we investigated the intervention effect on 90-day mortality in patients with severe comorbidity (chronic lung disease, haematological......BACKGROUND: Using a restrictive transfusion strategy appears to be safe in sepsis, but there may be subgroups of patients who benefit from transfusion at a higher haemoglobin level. We explored if subgroups of patients with septic shock and anaemia had better outcome when transfused at a higher vs.......51), in those who had undergone surgery (P = 0.99) or in patients with septic shock by the new definition (P = 0.20). CONCLUSION: In exploratory analyses of a randomized trial in patients with septic shock and anaemia, we observed no survival benefit in any subgroups of transfusion at a haemoglobin threshold...

  19. Andrographolide Attenuates LPS-Induced Cardiac Malfunctions Through Inhibition of IκB Phosphorylation and Apoptosis in Mice

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    Jinlong Zhang

    2015-11-01

    Full Text Available Background/Aims: Cardiac malfunction is a common complication in sepsis and significantly increases the mortality of patients in septic shock. However, no studies have examined whether andrographolide (And reduces LPS-induced myocardial malfunction. Methods: Left ventricular systolic and diastolic functions were examined using echocardiography. TNF-a and IL-1ß protein levels were detected by an enzyme-linked immunosorbent assay (ELISA. NO oxidation products were determined using Griess reagent. Protein expression levels of inhibitors of NF-κBa (IκB and phospho-IκB were determined via Western blot. Oxidative injury was determined by measuring myocardial lipid peroxidation and superoxide dismutase activity. Cardiac apoptosis was examined by terminal deoxynucleotidyl transferase-mediated dUTP nickend-labeling (TUNEL and cardiac caspase 3/7 activity. Results: And blunted LPS-induced myocardial malfunctions in mice. LPS induced TNF-a, IL-1ß, and NO production as well as I-κB phosphorylation. Cardiac apoptosis was attenuated via incubation with And, but the extent of oxidative injury remained unaffected. Conclusion: And prevents LPS-induced cardiac malfunctions in mice by inhibiting TNF-a, IL-1ß, and NO production, IκB phosphorylation, and cardiac apoptosis, indicating that And may be a potential agent for preventing myocardial malfunction during sepsis.

  20. Lower versus Higher Hemoglobin Threshold for Transfusion in Septic Shock

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    Holst, Lars B; Haase, Nicolai; Wetterslev, Jørn

    2014-01-01

    BACKGROUND: Blood transfusions are frequently given to patients with septic shock. However, the benefits and harms of different hemoglobin thresholds for transfusion have not been established. METHODS: In this multicenter, parallel-group trial, we randomly assigned patients in the intensive care...... unit (ICU) who had septic shock and a hemoglobin concentration of 9 g per deciliter or less to receive 1 unit of leukoreduced red cells when the hemoglobin level was 7 g per deciliter or less (lower threshold) or when the level was 9 g per deciliter or less (higher threshold) during the ICU stay...... were similar in the two intervention groups. CONCLUSIONS: Among patients with septic shock, mortality at 90 days and rates of ischemic events and use of life support were similar among those assigned to blood transfusion at a higher hemoglobin threshold and those assigned to blood transfusion...

  1. 5-Androstenediol Ameliorates Pleurisy, Septic Shock, and Experimental Autoimmune Encephalomyelitis in Mice

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    Ferdinando Nicoletti

    2010-01-01

    Full Text Available Androstenediol (androst-5-ene-3β,17β-diol; 5-AED, a natural adrenal steroid, has been shown to suppress experimental autoimmune encephalomyelitis (EAE in female SJL/J mice. We here report that 5-AED limits inflammation and proinflammatory cytokines including TNFα in murine models of carrageenan-induced pleurisy and lippopolysaccaride- (LPS induced septic shock. 5-AED binds to and transactivates sex steroid receptors with the same general rank order of potency (ERβ > ERα ≫ AR. 5-AED provides benefit in EAE in a dose-dependent fashion, even when treatment is delayed until onset of disease. The minimally effective dose may be as low as 4 mg/kg in mice. However, benefit was not observed when 5-AED was given in soluble formulation, leading to a short half-life and rapid clearance. These observations suggest that treatment with 5-AED limits the production of pro-inflammatory cytokines in these animal models and, ultimately, when formulated and administered properly, may be beneficial for patients with multiple sclerosis and other Th1-driven autoimmune diseases.

  2. Drotrecogin alfa (activated) in adults with septic shock.

    NARCIS (Netherlands)

    Ranieri, V.M.; Thompson, B.T.; Barie, P.S.; Dhainaut, J.F.; Douglas, I.S.; Finfer, S.; Gardlund, B.; Marshall, J.C.; Rhodes, A.; Artigas, A.; Payen, D.; Tenhunen, J.; Al-Khalidi, H.R.; Thompson, V.; Janes, J.; Macias, W.L.; Vangerow, B.; Williams, M.D.; Pickkers, P.; Raemaekers, J.M.; et al.,

    2012-01-01

    BACKGROUND: There have been conflicting reports on the efficacy of recombinant human activated protein C, or drotrecogin alfa (activated) (DrotAA), for the treatment of patients with septic shock. METHODS: In this randomized, double-blind, placebo-controlled, multicenter trial, we assigned 1697

  3. Quantitative assessment of the microcirculation in healthy volunteers and in patients with septic shock

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    Edul, Vanina S. Kanoore; Enrico, Carolina; Laviolle, Bruno; Vazquez, Alejandro Risso; Ince, Can; Dubin, Arnaldo

    2012-01-01

    The microcirculation of septic patients has been characterized only semiquantitatively. Our goal was to characterize the sublingual microcirculation in healthy volunteers and patients with septic shock quantitatively. Our hypotheses were that 1) hyperdynamic blood flow is absent in septic shock; 2)

  4. Role of echocardiography in reducing shock reversal time in pediatric septic shock: a randomized controlled trial

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    Ahmed A. EL-Nawawy

    Full Text Available Abstract Objective: To evaluate the role of echocardiography in reducing shock reversal time in pediatric septic shock. Methods: A prospective study conducted in the pediatric intensive care unit of a tertiary care teaching hospital from September 2013 to May 2016. Ninety septic shock patients were randomized in a 1:1 ratio for comparing the serial echocardiography-guided therapy in the study group with the standard therapy in the control group regarding clinical course, timely treatment, and outcomes. Results: Shock reversal was significantly higher in the study group (89% vs. 67%, with significantly reduced shock reversal time (3.3 vs. 4.5 days. Pediatric intensive care unit stay in the study group was significantly shorter (8 ± 3 vs. 14 ± 10 days. Mortality due to unresolved shock was significantly lower in the study group. Fluid overload was significantly lower in the study group (11% vs. 44%. In the study group, inotropes were used more frequently (89% vs. 67% and initiated earlier (12[0.5-24] vs. 24[6-72] h with lower maximum vasopressor inotrope score (120[30-325] vs. 170[80-395], revealing predominant use of milrinone (62% vs. 22%. Conclusion: Serial echocardiography provided crucial data for early recognition of septic myocardial dysfunction and hypovolemia that was not apparent on clinical assessment, allowing a timely management and resulting in shock reversal time reduction among children with septic shock.

  5. Transfusion requirements in septic shock (TRISS) trial - comparing the effects and safety of liberal versus restrictive red blood cell transfusion in septic shock patients in the ICU

    DEFF Research Database (Denmark)

    Holst, Lars B; Haase, Nicolai; Wetterslev, Jørn

    2013-01-01

    Requirements in Septic Shock (TRISS) trial is a multicenter trial with assessor-blinded outcome assessment, randomising 1,000 patients with septic shock in 30 Scandinavian ICUs to receive transfusion with pre-storage leuko-depleted RBC suspended in saline-adenine-glucose and mannitol (SAGM) at haemoglobin...

  6. The intensive care medicine research agenda on septic shock

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    Perner, Anders; Gordon, Anthony C; Angus, Derek C

    2017-01-01

    Septic shock remains a global health challenge with millions of cases every year, high rates of mortality and morbidity, impaired quality of life among survivors and relatives, and high resource use both in developed and developing nations. Care and outcomes are improving through organisational i...... and translational work. In this review, international experts summarize the current position of clinical research in septic shock and propose a research agenda to advance this field....... initiatives and updated clinical practice guidelines based on clinical research mainly carried out by large collaborative networks. This progress is likely to continue through the collaborative work of the established and merging trials groups in many parts of the world and through refined trial methodology...

  7. Continuation of Statin Therapy and Vasopressor Use in Septic Shock.

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    Zechmeister, Carrie; Hurren, Jeff; McNorton, Kelly

    2015-07-01

    Studies have evaluated the use of statins in sepsis; however, no human studies have explored their effect on vasopressor requirements in septic shock. The primary objective was to determine the effect of prehospital statin continuation on duration of vasopressor therapy in patients with septic shock. Secondary objectives included maximum and average vasopressor dose and in-hospital mortality. This was a retrospective, institutional board-approved, observational cohort study in a community teaching hospital; 119 adult intensive care unit (ICU) patients with an ICD-9 code for septic shock and prehospital statin therapy were evaluated. Multivariate analyses were performed to address confounders. Of the 1229 patients screened, 119 (10%) met inclusion criteria; 73 patients (61%) had a statin continued within 24 hours of ICU admission. Crude analysis demonstrated no difference in vasopressor duration in the statin versus no statin group (3.3 vs 4.8 days; P = 0.21). There was no difference in either maximum (17.9 ± 16.1 vs 23.8 ± 21.7 µg/min norepinephrine equivalents [NEQs]; P = 0.1) or average vasopressor dose (9.5 ± 8.4 vs 12.1 ± 11.5 µg/min NEQ; P = 0.17). There was a decrease in mortality in the statin patients (43% vs 67 %; P = 0.05). On adjustment for potential confounders, there was no difference in any outcome, with a persistent trend toward lower mortality in the statin group. Continuation of prehospital statin therapy decreased neither duration nor dose of vasopressors in patients with septic shock but yielded a trend toward decreased mortality. © The Author(s) 2015.

  8. [Our experience in Fournier's gangrene with severe septic shock].

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    Lukász, Péter; Ecsedy, Gábor; Lovay, Zoltán; Nagy, István; Kári, Dániel; Vörös, Attila; Ender, Ferenc

    2014-06-01

    Fournier's gangrene is a rare, rapidly progressing necrotizing fasciitis, which involves the genital area and perineum, progresses towards the thighs and abdominal wall through fascial plains. In our surgical department we treated seven patients with Fournier's gangrene between 2007 and 2011. Early diagnosis, immediate radical surgical debridement, necrosectomy, appropriate antibiotics and intensive care are all required and necessary for the successful treatment. Despite appropriate therapy, two patients were lost in septic shock.

  9. Tension pneumocephalus mimicking septic shock: a case report.

    Science.gov (United States)

    Miranda, Caroline; Mahta, Ali; Wheeler, Lee Adam; Tsiouris, A John; Kamel, Hooman

    2018-02-01

    Tension pneumocephalus can lead to rapid neurologic deterioration. We report for the first time its association with aseptic systemic inflammatory response syndrome mimicking septic shock and the efficacy of prompt neurosurgical intervention and critical care support in treating this condition. A 64-year-old man underwent 2-stage olfactory groove meningioma resection. The patient developed altered mental status and gait instability on postoperative day 6. Imaging showed significant pneumocephalus. The patient subsequently developed worsening mental status, respiratory failure, and profound shock requiring multiple vasopressors. Bedside needle decompression, identification and repair of the cranial fossa defect, and critical care support led to improved mental status and reversal of shock and multiorgan dysfunction. Thorough evaluation revealed no evidence of an underlying infection. In this case, tension pneumocephalus incited an aseptic systemic inflammatory response syndrome mimicking septic shock. Prompt neurosurgical correction of pneumocephalus and critical care support not only improved neurologic status, but also reversed shock. Such a complication indicates the importance of close monitoring of patients with progressive pneumocephalus.

  10. Tension pneumocephalus mimicking septic shock: a case report

    Directory of Open Access Journals (Sweden)

    Caroline Miranda, MD

    2018-02-01

    Full Text Available Tension pneumocephalus can lead to rapid neurologic deterioration. We report for the first time its association with aseptic systemic inflammatory response syndrome mimicking septic shock and the efficacy of prompt neurosurgical intervention and critical care support in treating this condition. A 64-year-old man underwent 2-stage olfactory groove meningioma resection. The patient developed altered mental status and gait instability on postoperative day 6. Imaging showed significant pneumocephalus. The patient subsequently developed worsening mental status, respiratory failure, and profound shock requiring multiple vasopressors. Bedside needle decompression, identification and repair of the cranial fossa defect, and critical care support led to improved mental status and reversal of shock and multiorgan dysfunction. Thorough evaluation revealed no evidence of an underlying infection. In this case, tension pneumocephalus incited an aseptic systemic inflammatory response syndrome mimicking septic shock. Prompt neurosurgical correction of pneumocephalus and critical care support not only improved neurologic status, but also reversed shock. Such a complication indicates the importance of close monitoring of patients with progressive pneumocephalus.

  11. Norepinephrine kinetics and dynamics in septic shock and trauma patients.

    Science.gov (United States)

    Beloeil, H; Mazoit, J-X; Benhamou, D; Duranteau, J

    2005-12-01

    There is considerable variability in the inter-patient response to norepinephrine. Pharmacokinetic studies of dopamine infusion in volunteers and in patients have also shown large variability. The purpose of this study was to define the pharmacokinetics of norepinephrine in septic shock and trauma patients. After Ethical Committee approval and written informed family consent, 12 patients with septic shock and 11 trauma patients requiring norepinephrine infusion were studied. Norepinephrine dose was increased in three successive steps of 0.1 mg kg(-1) min(-1) at 15-min intervals (20% maximum allowed increase in arterial pressure). Arterial blood was sampled before and at 0.5, 13, and 15 min after each infusion rate change and 30 s, 1, 2, 5, 10, and 15 min after return to baseline dosing. Norepinephrine was assayed by HPLC. The pharmacokinetics were modelled using NONMEM (one-compartment model). The effects of group, body weight (BW), gender and SAPS II (Simplified Acute Physiology Score II) [Le Gall JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. J Am Med Assoc 1993; 270: 2957-63] patients score on clearance (CL) and volume of distribution (V) were tested. Group, gender, and BW did not influence CL or V. CL was negatively related to SAPS II. CL and T(1/2) varied from 3 litre min(-1) and 2 min, respectively, when SAPS II=20 to 0.9 litre min(-1) and 6.8 min when SAPS II=60. In trauma patients and in septic shock patients, norepinephrine clearance is negatively related to SAPS II.

  12. Lower versus higher hemoglobin threshold for transfusion in septic shock.

    Science.gov (United States)

    Holst, Lars B; Haase, Nicolai; Wetterslev, Jørn; Wernerman, Jan; Guttormsen, Anne B; Karlsson, Sari; Johansson, Pär I; Aneman, Anders; Vang, Marianne L; Winding, Robert; Nebrich, Lars; Nibro, Helle L; Rasmussen, Bodil S; Lauridsen, Johnny R M; Nielsen, Jane S; Oldner, Anders; Pettilä, Ville; Cronhjort, Maria B; Andersen, Lasse H; Pedersen, Ulf G; Reiter, Nanna; Wiis, Jørgen; White, Jonathan O; Russell, Lene; Thornberg, Klaus J; Hjortrup, Peter B; Müller, Rasmus G; Møller, Morten H; Steensen, Morten; Tjäder, Inga; Kilsand, Kristina; Odeberg-Wernerman, Suzanne; Sjøbø, Brit; Bundgaard, Helle; Thyø, Maria A; Lodahl, David; Mærkedahl, Rikke; Albeck, Carsten; Illum, Dorte; Kruse, Mary; Winkel, Per; Perner, Anders

    2014-10-09

    Blood transfusions are frequently given to patients with septic shock. However, the benefits and harms of different hemoglobin thresholds for transfusion have not been established. In this multicenter, parallel-group trial, we randomly assigned patients in the intensive care unit (ICU) who had septic shock and a hemoglobin concentration of 9 g per deciliter or less to receive 1 unit of leukoreduced red cells when the hemoglobin level was 7 g per deciliter or less (lower threshold) or when the level was 9 g per deciliter or less (higher threshold) during the ICU stay. The primary outcome measure was death by 90 days after randomization. We analyzed data from 998 of 1005 patients (99.3%) who underwent randomization. The two intervention groups had similar baseline characteristics. In the ICU, the lower-threshold group received a median of 1 unit of blood (interquartile range, 0 to 3) and the higher-threshold group received a median of 4 units (interquartile range, 2 to 7). At 90 days after randomization, 216 of 502 patients (43.0%) assigned to the lower-threshold group, as compared with 223 of 496 (45.0%) assigned to the higher-threshold group, had died (relative risk, 0.94; 95% confidence interval, 0.78 to 1.09; P=0.44). The results were similar in analyses adjusted for risk factors at baseline and in analyses of the per-protocol populations. The numbers of patients who had ischemic events, who had severe adverse reactions, and who required life support were similar in the two intervention groups. Among patients with septic shock, mortality at 90 days and rates of ischemic events and use of life support were similar among those assigned to blood transfusion at a higher hemoglobin threshold and those assigned to blood transfusion at a lower threshold; the latter group received fewer transfusions. (Funded by the Danish Strategic Research Council and others; TRISS ClinicalTrials.gov number, NCT01485315.).

  13. Experimental models of sepsis and septic shock: an overview

    Directory of Open Access Journals (Sweden)

    Garrido Alejandra G.

    2004-01-01

    Full Text Available Sepsis remains a major cause of morbidity and mortality in surgical patients and trauma victims, mainly due to sepsis-induced multiple organ dysfunction. In contrast to preclinical studies, most clinical trials of promising new treatment strategies for sepsis have fails to demonstrate efficacy. Although many reasons could account for this discrepancy, the misinterpretation of preclinical data obtained from experimental studies, and especially the use of animal models that do not adequately mimic human sepsis may have been contributing factors. In this review, the benefits and limitations of various animal models of sepsis are discussed to clarify the extend to which findings are relevant to human sepsis, particularly with respect to the subsequent design and execution of clinical trials. Such models include intravascular infusion of endotoxin or live bacteria, bacterial peritonitis, cecal ligation and perforation, soft tissue infection, pneumonia or meningitis models, using different animal species including rats, mice, rabbits, dogs, pigs, sheep and nonhuman primates. Despite several limitations, animal models remain essential in the development of all new therapies for sepsis and septic shock, because they provide fundamental information about the pharmacokinetics, toxicity, and mechanism of drug action that cannot be duplicated by other methods. New therapeutic agents should be studies in infection models, even after the initiation of the septic process. Furthermore, debility conditions need to be reproduced to avoid the exclusive use of healthy animals, which often do not represent the human septic patient.

  14. Developing a New Definition and Assessing New Clinical Criteria for Septic Shock For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

    NARCIS (Netherlands)

    Shankar-Hari, Manu; Phillips, Gary S.; Levy, Mitchell L.; Seymour, Christopher W.; Liu, Vincent X.; Deutschman, Clifford S.; Angus, Derek C.; Rubenfeld, Gordon D.; Singer, Mervyn; Angus, Derek; Annane, Djilalli; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon; Chiche, Jean-Daniel; Coopersmith, Craig; Deutschman, Cliff; Hotchkiss, Richard; Levy, Mitchell; Marshall, John; Martin, Greg; Opal, Steve; Rubenfeld, Gordon; Seymour, Christopher; van der Poll, Tom; Vincent, Jean-Louis

    2016-01-01

    IMPORTANCE Septic shock currently refers to a state of acute circulatory failure associated with infection. Emerging biological insights and reported variation in epidemiology challenge the validity of this definition. OBJECTIVE To develop a new definition and clinical criteria for identifying

  15. Refractory septic shock in children: a European Society of Paediatric and Neonatal Intensive Care definition

    NARCIS (Netherlands)

    Morin, Luc; Ray, Samiran; Wilson, Clare; Remy, Solenn; Benissa, Mohamed Rida; Jansen, Nicolaas J. G.; Javouhey, Etienne; Peters, Mark J.; Kneyber, Martin; De Luca, Daniele; Nadel, Simon; Schlapbach, Luregn Jan; Maclaren, Graeme; Tissieres, Pierre

    2016-01-01

    Purpose Although overall paediatric septic shock mortality is decreasing, refractory septic shock (RSS) is still associated with high mortality. A definition for RSS is urgently needed to facilitate earlier identification and treatment. We aim to establish a European society of paediatric and

  16. Survivors of septic shock caused by Neisseria meningitidis in childhood: psychosocial outcomes in young adulthood

    NARCIS (Netherlands)

    Vermunt, Lindy C.; Buysse, Corinne M.; Joosten, Koen F.; Duivenvoorden, Hugo J.; Hazelzet, Jan A.; Verhulst, Frank C.; Utens, Elisabeth M.

    2011-01-01

    To investigate long-term psychosocial outcomes in young adults who survived septic shock caused by Neisseria meningitidis (meningococcal septic shock) during childhood. A cross-sectional study. The psychological investigation took place in the department of Child and Adolescent Psychiatry of the

  17. Survivors of septic shock caused by Neisseria meningitidis in childhood : Psychosocial outcomes in young adulthood

    NARCIS (Netherlands)

    Vermunt, Lindy C.; Buysse, Corinne M.; Joosten, Koen F.; Duivenvoorden, Hugo J.; Hazelzet, Jan A.; Verhulst, Frank C.; Utens, Elisabeth M.

    Objective: To investigate long-term psychosocial outcomes in young adults who survived septic shock caused by Neisseria meningitidis (meningococcal septic shock) during childhood. Design: A cross-sectional study. Setting: The psychological investigation took place in the department of Child and

  18. Initial fluid resuscitation of patients with septic shock in the intensive care unit

    DEFF Research Database (Denmark)

    Carlsen, Sarah; Perner, A

    2011-01-01

    Fluid is the mainstay of resuscitation of patients with septic shock, but the optimal composition and volume are unknown. Our aim was to evaluate the current initial fluid resuscitation practice in patients with septic shock in the intensive care unit (ICU) and patient characteristics and outcome...

  19. A holistic approach for perfusion assessment in septic shock: Basic foundations and clinical applications

    NARCIS (Netherlands)

    Hernández Poblete, G.W.

    2013-01-01

    A fundamental challenge in septic shock resuscitation is to evaluate tissue perfusion. In this thesis, we review the basic foundations for the development of a comprehensive and holistic model for perfusion assessment in septic shock, and outline its application to evaluate the impact of

  20. Refractory septic shock in children : a European Society of Paediatric and Neonatal Intensive Care definition

    NARCIS (Netherlands)

    Morin, Luc; Ray, Samiran; Wilson, Clare; Remy, Solenn; Benissa, Mohamed Rida; Jansen, Nicolaas J. G.; Javouhey, Etienne; Peters, Mark J.; Kneyber, Martin; De Luca, Daniele; Nadel, Simon; Schlapbach, Luregn Jan; Maclaren, Graeme; Tissieres, Pierre

    2016-01-01

    Although overall paediatric septic shock mortality is decreasing, refractory septic shock (RSS) is still associated with high mortality. A definition for RSS is urgently needed to facilitate earlier identification and treatment. We aim to establish a European society of paediatric and neonatal

  1. Novel Mechanism of Attenuation of LPS-Induced NF-κB Activation by the Heat Shock Protein 90 Inhibitor, 17-N-allylamino-17-demethoxygeldanamycin, in Human Lung Microvascular Endothelial Cells

    Science.gov (United States)

    Thangjam, Gagan S.; Dimitropoulou, Chistiana; Joshi, Atul D.; Barabutis, Nektarios; Shaw, Mary C.; Kovalenkov, Yevgeniy; Wallace, Chistopher M.; Fulton, David J.; Patel, Vijay

    2014-01-01

    Heat shock protein (hsp) 90 inhibition attenuates NF-κB activation and blocks inflammation. However, the precise mechanism of NF-κB regulation by hsp90 in the endothelium is not clear. We investigated the mechanisms of hsp90 inhibition by 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) on NF-κB activation by LPS in primary human lung microvascular endothelial cells. Transcriptional activation of NF-κB was measured by luciferase reporter assay, gene expression by real-time RT-PCR, DNA binding of transcription factors by chromatin immunoprecipitation assay, protein–protein interaction by coimmunoprecipitation/immunoblotting, histone deacetylase (HDAC)/histone acetyltransferase enzyme activity by fluorometry, and nucleosome eviction by partial microccocal DNase digestion. In human lung microvascular endothelial cells, 17-AAG–induced degradation of IKBα was accomplished regardless of the phosphorylation/ubiquitination state of the protein. Hence, 17-AAG did not block LPS-induced NF-κB nuclear translocation and DNA binding activity. Instead, 17-AAG blocked the recruitment of the coactivator, cAMP response element binding protein binding protein, and prevented the assembly of a transcriptionally competent RNA polymerase II complex at the κB elements of the IKBα (an NF-κB–responsive gene) promoter. The effect of LPS on IKBα mRNA expression was associated with rapid deacetylation of histone-H3(Lys9) and a dramatic down-regulation of core histone H3 binding. Even though treatment with an HDAC inhibitor produced the same effect as hsp90 inhibition, the effect of 17-AAG was independent of HDAC. We conclude that hsp90 inhibition attenuates NF-κB transcriptional activation by preventing coactivator recruitment and nucleosome eviction from the target promoter in human lung endothelial cells. PMID:24303801

  2. GSK621 activates AMPK signaling to inhibit LPS-induced TNFα production

    International Nuclear Information System (INIS)

    Wu, Yong-hong; Li, Quan; Li, Ping; Liu, Bei

    2016-01-01

    LPS stimulation in macrophages/monocytes induces TNFα production. We here tested the potential effect of GSK621, a novel AMP-activated protein kinase (AMPK) activator, against the process. In RAW264.7 macrophages, murine bone marrow-derived macrophages (BMDMs), and chronic obstructive pulmonary disease (COPD) patients' monocytes, GSK621 significantly inhibited LPS-induced TNFα protein secretion and mRNA synthesis. Inhibition of AMPK, through AMPKα shRNA knockdown or dominant negative mutation (T172A), almost abolished GSK621's suppression on TNFα in RAW264.7 cells. Reversely, forced-expression of a constitutively-active AMPKα (T172D) mimicked GSK621 actions and reduced LPS-induced TNFα production. Molecularly, GSK621 suppressed LPS-induced reactive oxygen species (ROS) production and nuclear factor kappa B (NFκB) activation. In vivo, GSK621 oral administration inhibited LPS-induced TNFα production and endotoxin shock in mice. In summary, GSK621 activates AMPK signaling to inhibit LPS-induced TNFα production in macrophages/monocytes. - Highlights: • GSK621 inhibits LPS-induced TNFα production/expression in RAW264.7 cells and BMDMs. • GSK621 inhibits LPS-induced TNFα production/expression in COPD patients' PBMCs. • GSK621's inhibition on TNFα production by LPS requires AMPK activation. • GSK621 inhibits LPS-induced ROS production and NFκB activation, dependent on AMPK. • GSK621 oral administration inhibits LPS-induced TNFα production and endotoxin shock in mice.

  3. Hydrocortisone fails to abolish NF-κB1 protein nuclear translocation in deletion allele carriers of the NFKB1 promoter polymorphism (-94ins/delATTG and is associated with increased 30-day mortality in septic shock.

    Directory of Open Access Journals (Sweden)

    Simon T Schäfer

    Full Text Available BACKGROUND: Previous investigations and meta-analyses on the effect of glucocorticoids on mortality in septic shock revealed mixed results. This heterogeneity might be evoked by genetic variations. Such candidate is a promoter polymorphism (-94ins/delATTG of the gene encoding the ubiquitous transcription-factor nuclear-factor-κB (NF-κB which binds to recognition elements in the promoter of several genes encoding for the innate immune-system. In turn, hydrocortisone inhibits NF-κB nuclear translocation and thus transcription of key immune-response regulators. Accordingly, we tested the hypotheses that hydrocortisone has a NFKB1 genotype dependent effect on 1 NF-κB1 nuclear translocation evoked by lipopolysaccharide (LPS in monocytes in vitro, and 2 mortality in septic shock. METHODS: Monocytes of volunteers with the homozygous insertion (II; n = 5 or deletion (DD; n = 6 NFKB1 genotype were incubated with 10 µgml-1 LPS ± hydrocortisone (10-5M, and NF-κB1 nuclear translocation was assessed (immunofluorescence. Furthermore, we analyzed 30-day-mortality in 160 patients with septic shock stratified for both genotype and hydrocortisone therapy. RESULTS: Hydrocortisone inhibited LPS induced nuclear translocation of NF-κB1 in II (25%±11;p = 0.0001 but not in DD genotypes (51%±15;p = n.s.. Onehundredandfour of 160 patients with septic shock received hydrocortisone, at the discretion of the intensivist. NFKB1 deletion allele carriers (ID/DD receiving hydrocortisone had a much greater 30-day-mortality (57.6% than II genotypes (24.4%; HR:3.18, 95%-CI:1.61-6.28;p = 0.001. In contrast, 30-day mortality was 22.2% in ID/DD and 25.0% in II genotypes without hydrocortisone therapy. Results were similar when using propensity score matching to account for possible bias in the intensivists' decision to administer hydrocortisone. CONCLUSION: Hydrocortisone fails to inhibit LPS induced nuclear NF-κB1 translocation in deletion allele

  4. Hydrocortisone Fails to Abolish NF-κB1 Protein Nuclear Translocation in Deletion Allele Carriers of the NFKB1 Promoter Polymorphism (-94ins/delATTG) and Is Associated with Increased 30-Day Mortality in Septic Shock

    Science.gov (United States)

    Schäfer, Simon T.; Gessner, Sophia; Scherag, André; Rump, Katharina; Frey, Ulrich H.; Siffert, Winfried; Westendorf, Astrid M.; Steinmann, Jörg; Peters, Jürgen; Adamzik, Michael

    2014-01-01

    Background Previous investigations and meta-analyses on the effect of glucocorticoids on mortality in septic shock revealed mixed results. This heterogeneity might be evoked by genetic variations. Such candidate is a promoter polymorphism (-94ins/delATTG) of the gene encoding the ubiquitous transcription-factor nuclear-factor-κB (NF-κB) which binds to recognition elements in the promoter of several genes encoding for the innate immune-system. In turn, hydrocortisone inhibits NF-κB nuclear translocation and thus transcription of key immune-response regulators. Accordingly, we tested the hypotheses that hydrocortisone has a NFKB1 genotype dependent effect on 1) NF-κB1 nuclear translocation evoked by lipopolysaccharide (LPS) in monocytes in vitro, and 2) mortality in septic shock. Methods Monocytes of volunteers with the homozygous insertion (II; n = 5) or deletion (DD; n = 6) NFKB1 genotype were incubated with 10 µgml-1 LPS ± hydrocortisone (10-5M), and NF-κB1 nuclear translocation was assessed (immunofluorescence). Furthermore, we analyzed 30-day-mortality in 160 patients with septic shock stratified for both genotype and hydrocortisone therapy. Results Hydrocortisone inhibited LPS induced nuclear translocation of NF-κB1 in II (25%±11;p = 0.0001) but not in DD genotypes (51%±15;p = n.s.). Onehundredandfour of 160 patients with septic shock received hydrocortisone, at the discretion of the intensivist. NFKB1 deletion allele carriers (ID/DD) receiving hydrocortisone had a much greater 30-day-mortality (57.6%) than II genotypes (24.4%; HR:3.18, 95%-CI:1.61-6.28;p = 0.001). In contrast, 30-day mortality was 22.2% in ID/DD and 25.0% in II genotypes without hydrocortisone therapy. Results were similar when using propensity score matching to account for possible bias in the intensivists' decision to administer hydrocortisone. Conclusion Hydrocortisone fails to inhibit LPS induced nuclear NF-κB1 translocation in deletion allele carriers of the

  5. Is shock index associated with outcome in children with sepsis/septic shock?*.

    Science.gov (United States)

    Yasaka, Yuki; Khemani, Robinder G; Markovitz, Barry P

    2013-10-01

    To investigate the association between PICU shock index (the ratio of heart rate to systolic blood pressure) and PICU mortality in children with sepsis/septic shock. To explore cutoff values for shock index for ICU mortality, how change in shock index over the first 6 hours of ICU admission is associated with outcome, and how the use of vasoactive therapy may affect shock index and its association with outcome. Retrospective cohort. Single-center tertiary PICU. Five hundred forty-four children with the diagnosis of sepsis/septic shock. None. From January 2003 to December 2009, 544 children met International Pediatric Sepsis Consensus Conference of 2005 criteria for sepsis/septic shock. Overall mortality was 23.7%. Among all patients, hourly shock index was associated with mortality: odds ratio of ICU mortality at 0 hour, 1.08, 95% CI (1.04-1.12); odds ratio at 1 hour, 1.09 (1.04-1.13); odds ratio at 2 hours, 1.09 (1.05-1.13); and odds ratio at 6 hours, 1.11 (1.06-1.15). When stratified by age, early shock index was associated with mortality only in children 1-3 and more than or equal to 12 years old. Area under the receiver operating characteristic curve in age 1-3 and more than or equal to 12 years old for shock index at admission was 0.69 (95% CI, 0.58-0.80) and 0.62 (95% CI, 0.52-0.72) respectively, indicating a fair predictive marker. Although higher shock index was associated with increased risk of mortality, there was no particular cutoff value with adequate positive or negative likelihood ratios to identify mortality in any age group of children. The improvement of shock index in the first 6 hours of ICU admission was not associated with outcome when analyzed in all patients. However, among patients whose shock index were above the 50th percentile at ICU admission for each age group, improvement of shock index was associated with lower ICU mortality in children between 1-3 and more than or equal to 12 years old (p = 0.02 and p = 0.03, respectively). When

  6. Necrotizing Fasciitis Secondary to Aeromonas Infection Presenting with Septic Shock

    Directory of Open Access Journals (Sweden)

    Nikhil Bhatia

    2017-01-01

    Full Text Available This report describes a case of necrotizing fasciitis presenting with septic shock due to an Aeromonas infection. The patient cut his foot while mowing the lawn and then spent time in a pool with black mold. He began feeling ill and developed swelling and a quarter-sized black area on his right lower extremity. Despite being hemodynamically unstable with systolic blood pressure in the low 70s, the patient was transferred to our facility from outside hospital 100 miles away. Upon arriving to facility, the patient appeared to be septic and the infected area of skin had grown. Irrigation and debridement were performed and appropriate antibiotic therapy was given; however, the patient subsequently died on hospital day 8. On review of the literature, cases of necrotizing fasciitis due to Aeromonas infection have been treated successfully with the aforementioned therapy; however, there is high mortality associated with these infections, many times related to a delayed diagnosis. Our patient also had multiple poor prognostic factors including hepatic dysfunction and immunosuppression.

  7. The role of immunostimulatory nucleic acids in septic shock

    Science.gov (United States)

    Bleiblo, Farag; Michael, Paul; Brabant, Danielle; Ramana, Chilakamarti V; Tai, TC; Saleh, Mazen; Parrillo, Joseph E; Kumar, Anand; Kumar, Aseem

    2012-01-01

    Sepsis and its associated syndromes represent the systemic host response to severe infection and is manifested by varying degrees of hypotension, coagulopathy, and multiorgan dysfunction. Despite great efforts being made to understand this condition and designing therapies to treat sepsis, mortality rates are still high in septic patients. Characterization of the complex molecular signaling networks between the various components of host-pathogen interactions, highlights the difficulty in identifying a single driving force responsible for sepsis. Although triggering the inflammatory response is generally considered as protective against pathogenic threats, the interplay between the signaling pathways that are induced or suppressed during sepsis may harm the host. Numerous surveillance mechanisms have evolved to discriminate self from foreign agents and accordingly provoke an effective cellular response to target the pathogens. Nucleic acids are not only an essential genetic component, but sensing their molecular signature is also an important quality control mechanism which has evolved to maintain the integrity of the human genome. Evidence that has accumulated recently indicated that distinct pattern recognition receptors sense nucleic acids released from infectious organisms or from damaged host cells, resulting in the modulation of intracellular signalling cascades. Immunoreceptor-mediated detection of these nucleic acids induces antigen-specific immunity, secretion of proinflammatory cytokines and reactive oxygen/nitrogen species and thus are implicated in a range of diseases including septic shock. PMID:22328944

  8. Protective Effect of Argan and Olive Oils against LPS-Induced Oxidative Stress and Inflammation in Mice Livers

    Directory of Open Access Journals (Sweden)

    Soufiane El Kamouni

    2017-10-01

    Full Text Available Sepsis causes severe dysregulation of organ functions, via the development of oxidative stress and inflammation. These pathophysiological mechanisms are mimicked in mice injected with bacterial lipopolysaccharide (LPS. Here, protective properties of argan oil against LPS-induced oxidative stress and inflammation are explored in the murine model. Mice received standard chow, supplemented with argan oil (AO or olive oil (OO for 25 days, before septic shock was provoked with a single intraperitoneal injection of LPS, 16 hours prior to animal sacrifice. In addition to a rise in oxidative stress and inflammatory markers, injected LPS also caused hepatotoxicity, accompanied by hyperglycemia, hypercholesterolemia and hyperuremia. These LPS-associated toxic effects were blunted by AO pretreatment, as corroborated by normal plasma parameters and cell stress markers (glutathione: GSH and antioxidant enzymology (catalase, CAT; superoxide dismutase, SOD and glutathione peroxidase, GPx. Hematoxylin–eosin staining revealed that AO can protect against acute liver injury, maintaining a normal status, which is pointed out by absent or reduced LPS-induced hepatic damage markers (i.e., alanine aminotransferase (ALT and aspartate transaminase (AST. Our work also indicated that AO displayed anti-inflammatory activity, due to down-regulations of genes encoding pro-inflammatory cytokines Interleukin-6 (IL-6 and Tumor Necrosis Factor-α (TNF-α and in up-regulations of the expression of anti-inflammatory genes encoding Interleukin-4 (IL-4 and Interleukin-10 (IL-10. OO provided animals with similar, though less extensive, protective changes. Collectively our work adds compelling evidence to the protective mechanisms of AO against LPS-induced liver injury and hence therapeutic potentialities, in regard to the management of human sepsis. Activations of IL-4/Peroxisome Proliferator-Activated Receptors (IL-4/PPARs signaling and, under LPS, an anti-inflammatory IL-10/Liver

  9. Higher vs. lower fluid volume for septic shock

    DEFF Research Database (Denmark)

    Smith, Søren H; Perner, Anders

    2012-01-01

    .4 (2.2-5.5) vs. 2.0 (1.6-3.0) mmol l-1, P vs. 54 (45-67), P = 0.73), sequential organ failure assessment (SOFA) score (11 (9-13) vs. 11 (9-13), P = 0.78) and 90-day mortality (48 vs...... volumes. Characteristics between these groups were compared using non-parametric and Chi-square statistics. RESULTS: The 164 included patients received median 4.0 l (IQR 2.3-6.3) of fluid during the first day of septic shock. Patients receiving higher volumes (> 4.0 l) on day 1 had higher p-lactate (3....... 53%, P = 0.27) did not differ between groups. The 95 patients who still had shock on day 3 had received 7.5 l (4.3 - 10.8) of fluid by the end of day 3. Patients receiving higher volumes (> 7.5 l) had higher p-lactate (2.6 (1.7-3.4) vs. 1.9 (1.6-2.4) mmol l-1, P

  10. Depressed left ventricular performance. Response to volume infusion in patients with sepsis and septic shock

    International Nuclear Information System (INIS)

    Ognibene, F.P.; Parker, M.M.; Natanson, C.; Shelhamer, J.H.; Parrillo, J.E.

    1988-01-01

    Volume infusion, to increase preload and to enhance ventricular performance, is accepted as initial management of septic shock. Recent evidence has demonstrated depressed myocardial function in human septic shock. We analyzed left ventricular performance during volume infusion using serial data from simultaneously obtained pulmonary artery catheter hemodynamic measurements and radionuclide cineangiography. Critically ill control subjects (n = 14), patients with sepsis but without shock (n = 21), and patients with septic shock (n = 21) had prevolume infusion hemodynamic measurements determined and received statistically similar volumes of fluid resulting in similar increases in pulmonary capillary wedge pressure. There was a strong trend (p = 0.004) toward less of a change in left ventricular stroke work index (LVSWI) after volume infusion in patients with sepsis and septic shock compared with control subjects. The LVSWI response after volume infusion was significantly less in patients with septic shock when compared with critically ill control subjects (p less than 0.05). These data demonstrate significantly altered ventricular performance, as measured by LVSWI, in response to volume infusion in patients with septic shock

  11. N-terminal-pro-brain natriuretic peptide elevations in the course of septic and non-septic shock reflect systolic left ventricular dysfunction assessed by transpulmonary thermodilution

    Directory of Open Access Journals (Sweden)

    A.B. Johan Groeneveld

    2016-03-01

    Conclusions: In septic and non-septic shock, NT-proBNP elevations reflect systolic left ventricular dysfunction and are associated with a poor outcome. They may help recognition of cardiac dysfunction in shock and its management when invasive hemodynamic monitoring is not yet instituted.

  12. Pylephlebitis and Crohn’s disease: A rare case of septic shock

    Directory of Open Access Journals (Sweden)

    Stefano Scaringi

    2017-01-01

    Conclusion: This case highlights the importance of promptly considerate and treat mesenteric pylephlebitis in presence of a septic shock in a Crohn’s disease patient who is not showing clinical signs of peritonitis.

  13. Effect of transcutaneous electrical muscle stimulation on muscle volume in patients with septic shock

    DEFF Research Database (Denmark)

    Poulsen, Jesper Brøndum; Møller, Kirsten; Jensen, Claus V

    2011-01-01

    Objective: Intensive care unit admission is associated with muscle wasting and impaired physical function. We investigated the effect of early transcutaneous electrical muscle stimulation on quadriceps muscle volume in patients with septic shock. Design: Randomized interventional study using...

  14. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

    NARCIS (Netherlands)

    Singer, Mervyn; Deutschman, Clifford S.; Seymour, Christopher Warren; Shankar-Hari, Manu; Annane, Djillali; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon R.; Chiche, Jean-Daniel; Coopersmith, Craig M.; Hotchkiss, Richard S.; Levy, Mitchell M.; Marshall, John C.; Martin, Greg S.; Opal, Steven M.; Rubenfeld, Gordon D.; van der Poll, Tom; Vincent, Jean-Louis; Angus, Derek C.

    2016-01-01

    IMPORTANCE Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need

  15. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

    NARCIS (Netherlands)

    Rhodes, Andrew; Evans, Laura E.; Alhazzani, Waleed; Levy, Mitchell M.; Antonelli, Massimo; Ferrer, Ricard; Kumar, Anand; Sevransky, Jonathan E.; Sprung, Charles L.; Nunnally, Mark E.; Rochwerg, Bram; Rubenfeld, Gordon D.; Angus, Derek C.; Annane, Djillali; Beale, Richard J.; Bellinghan, Geoffrey J.; Bernard, Gordon R.; Chiche, Jean-Daniel; Coopersmith, Craig; de Backer, Daniel P.; French, Craig J.; Fujishima, Seitaro; Gerlach, Herwig; Hidalgo, Jorge Luis; Hollenberg, Steven M.; Jones, Alan E.; Karnad, Dilip R.; Kleinpell, Ruth M.; Koh, Younsuck; Lisboa, Thiago Costa; Machado, Flavia R.; Marini, John J.; Marshall, John C.; Mazuski, John E.; McIntyre, Lauralyn A.; McLean, Anthony S.; Mehta, Sangeeta; Moreno, Rui P.; Myburgh, John; Navalesi, Paolo; Nishida, Osamu; Osborn, Tiffany M.; Perner, Anders; Plunkett, Colleen M.; Ranieri, Marco; Schorr, Christa A.; Seckel, Maureen A.; Seymour, Christopher W.; Shieh, Lisa; Shukri, Khalid A.; Simpson, Steven Q.; Singer, Mervyn; Thompson, B. Taylor; Townsend, Sean R.; van der Poll, Thomas; Vincent, Jean-Louis; Wiersinga, W. Joost; Zimmerman, Janice L.; Dellinger, R. Phillip

    2017-01-01

    Objective: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012!' Design: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings

  16. Evolution of peripheral vs metabolic perfusion parameters during septic shock resuscitation. A clinical-physiologic study

    NARCIS (Netherlands)

    Hernandez, Glenn; Pedreros, Cesar; Veas, Enrique; Bruhn, Alejandro; Romero, Carlos; Rovegno, Maximiliano; Neira, Rodolfo; Bravo, Sebastian; Castro, Ricardo; Kattan, Eduardo; Ince, Can

    2012-01-01

    Purpose: Perfusion assessment during septic shock resuscitation is difficult and usually complex determinations. Capillary refill time (CRT) and central-to-toe temperature difference (Tc-toe) have been proposed as objective reproducible parameters to evaluate peripheral perfusion. The comparative

  17. Timing, method and discontinuation of hydrocortisone administration for septic shock patients

    OpenAIRE

    Ibarra-Estrada, Miguel A; Ch?vez-Pe?a, Quetzalc?atl; Reynoso-Estrella, Claudia I; Rios-Zerme?o, Jorge; Aguilera-Gonz?lez, P?vel E; Garc?a-Soto, Miguel A; Aguirre-Avalos, Guadalupe

    2017-01-01

    AIM To characterize the prescribing patterns for hydrocortisone for patients with septic shock and perform an exploratory analysis in order to identify the variables associated with better outcomes. METHODS This prospective cohort study included 59 patients with septic shock who received stress-dose hydrocortisone. It was performed at 2 critical care units in academic hospitals from June 1st, 2015, to July 31st, 2016. Demographic data, comorbidities, medical management details, adverse effect...

  18. Survival of Primates in Lethal Septic Shock Following Delayed Treatment with Steroid.

    Science.gov (United States)

    1981-02-26

    TECHNICAL REPORT NO. 142 SURVIVAL OF PRIMATES IN LETHAL SEPTIC SHOCK FOLLOWING DELAYED TREAMENT WIn STEROID L. B. Hinshaw, L. T. Archer, B. K. Belier ...2. Schumer W: Steroids in the treatment of clinical septic shock. Ann Surg 184:333-341, 1976. 3. Hinshaw LB, Belier PK, Archer LT, Flournoy DJ, White...not preventable by antibiotic alone. Infect Immun ZS:538-5)7, 1979. 6. Hinshaw LB, Archer LT, Belier -Todd BK, Coalson .JJ, Flournoy DL, Passey R

  19. Gas-Forming Pyogenic Liver Abscess with Septic Shock

    Directory of Open Access Journals (Sweden)

    Muhammad S. Khan

    2015-01-01

    Full Text Available The pyogenic liver abscess caused by Clostridium perfringens (C. perfringens is a rare but rapidly fatal infection. The main virulence factor of this pathogen is its α-toxin (lecithinase, which decomposes the phospholipid in cell membranes leading to cell lysis. Once the bacteria are in blood stream, massive intravascular hemolysis occurs. This can present as anemia on admission with evidence of hemolysis as indicated by low serum haptoglobin, high serum lactate dehydrogenase (LDH, elevated indirect bilirubin, and spherocytosis. The clinical course of C. perfringens septicemia is marked by rapidly deteriorating course with a mortality rate ranging from 70 to 100%. The very rapid clinical course makes it difficult to diagnose on time, and most cases are diagnosed at autopsy. Therefore it is important to consider C. perfringens infection in any severely ill patient with fever and evidence of hemolysis. We present a case of seventy-seven-year-old male with septic shock secondary to pyogenic liver abscess with a brief review of existing literature on C. perfringens.

  20. Eukaryotic elongation factor 2 controls TNF-α translation in LPS-induced hepatitis

    Science.gov (United States)

    González-Terán, Bárbara; Cortés, José R.; Manieri, Elisa; Matesanz, Nuria; Verdugo, ρngeles; Rodríguez, María E.; González-Rodríguez, ρgueda; Valverde, ρngela; Martín, Pilar; Davis, Roger J.; Sabio, Guadalupe

    2012-01-01

    Bacterial LPS (endotoxin) has been implicated in the pathogenesis of acute liver disease through its induction of the proinflammatory cytokine TNF-α. TNF-α is a key determinant of the outcome in a well-established mouse model of acute liver failure during septic shock. One possible mechanism for regulating TNF-α expression is through the control of protein elongation during translation, which would allow rapid cell adaptation to physiological changes. However, the regulation of translational elongation is poorly understood. We found that expression of p38γ/δ MAPK proteins is required for the elongation of nascent TNF-α protein in macrophages. The MKK3/6-p38γ/δ pathway mediated an inhibitory phosphorylation of eukaryotic elongation factor 2 (eEF2) kinase, which in turn promoted eEF2 activation (dephosphorylation) and subsequent TNF-α elongation. These results identify a new signaling pathway that regulates TNF-α production in LPS-induced liver damage and suggest potential cell-specific therapeutic targets for liver diseases in which TNF-α production is involved. PMID:23202732

  1. IL-1B rs16944 polymorphism is related to septic shock and death.

    Science.gov (United States)

    Jiménez-Sousa, María Ángeles; Medrano, Luz M; Liu, Pilar; Almansa, Raquel; Fernández-Rodríguez, Amanda; Gómez-Sánchez, Esther; Rico, Lucía; Heredia-Rodríguez, María; Gómez-Pesquera, Estefanía; Tamayo, Eduardo; Resino, Salvador

    2017-01-01

    IL-1β is a primary mediator of systemic inflammatory response syndrome (SIRS) and it may lead to shock septic. Our aim was to analyse whether IL-1B rs16944 polymorphism is associated with the onset of septic shock and death after major surgery. We performed a case-control study on 467 patients who underwent major cardiac or abdominal surgery. Of them, 205 patients developed septic shock (cases, SS group) and 262 patients developed SIRS (controls, SIRS group). The primary outcome variables were the development of septic shock and death within 90 days after diagnosis of septic shock. The IL-1B rs16944 polymorphism was genotyped by Sequenom's MassARRAY platform. The association analysis was performed under a recessive genetic model (AA vs. GG/GC). The frequency of septic shock was higher in patients with IL-1B rs16944 AA genotype than in patients with IL-1B rs16944 GG/AG genotype when all patients were taken into account (63·6% vs. 41·8%; P = 0·006), cardiac surgery (52·2% vs. 33·3%; P = 0·072) and abdominal surgery (76·2% vs. 50·2%; P = 0·023). However, the IL-1B rs16944 AA genotype was only associated with higher likelihood of septic shock in the analysis of all population [adjusted odds ratio (aOR) = 2·26 (95%CI = 1·03; 4·97; P = 0·042], but not when it was stratified by cardiac surgery (P = 0·175) or abdominal surgery (P = 0·467). Similarly, IL-1B rs16944 AA genotype was also associated with higher likelihood of septic shock-related death in all population [aOR = 2·67 (95%CI = 1·07; 4·97); P = 0·035]. IL-1B rs16944 AA genotype seems to be related to the onset of septic shock and death in patients who underwent major surgery. © 2016 Stichting European Society for Clinical Investigation Journal Foundation.

  2. Renal Blood Flow, Glomerular Filtration Rate, and Renal Oxygenation in Early Clinical Septic Shock.

    Science.gov (United States)

    Skytte Larsson, Jenny; Krumbholz, Vitus; Enskog, Anders; Bragadottir, Gudrun; Redfors, Bengt; Ricksten, Sven-Erik

    2018-06-01

    Data on renal hemodynamics, function, and oxygenation in early clinical septic shock are lacking. We therefore measured renal blood flow, glomerular filtration rate, renal oxygen consumption, and oxygenation in patients with early septic shock. Prospective comparative study. General and cardiothoracic ICUs. Patients with norepinephrine-dependent early septic shock (n = 8) were studied within 24 hours after arrival in the ICU and compared with postcardiac surgery patients without acute kidney injury (comparator group, n = 58). None. Data on systemic hemodynamics and renal variables were obtained during two 30-minute periods. Renal blood flow was measured by the infusion clearance of para-aminohippuric acid, corrected for renal extraction of para-aminohippuric acid. Renal filtration fraction was measured by renal extraction of chromium-51 labeled EDTA. Renal oxygenation was estimated from renal oxygen extraction. Renal oxygen delivery (-24%; p = 0.037) and the renal blood flow-to-cardiac index ratio (-21%; p = 0.018) were lower, renal vascular resistance was higher (26%; p = 0.027), whereas renal blood flow tended to be lower (-19%; p = 0.068) in the septic group. Glomerular filtration rate (-32%; p = 0.006) and renal sodium reabsorption (-29%; p = 0.014) were both lower in the septic group. Neither renal filtration fraction nor renal oxygen consumption differed significantly between groups. Renal oxygen extraction was significantly higher in the septic group (28%; p = 0.022). In the septic group, markers of tubular injury were elevated. In early clinical septic shock, renal function was lower, which was accompanied by renal vasoconstriction, a lower renal oxygen delivery, impaired renal oxygenation, and tubular sodium reabsorption at a high oxygen cost compared with controls.

  3. Diagnostic and prognostic value of procalcitonin in patients with septic shock.

    Science.gov (United States)

    Clec'h, Christophe; Ferriere, Françoise; Karoubi, Philippe; Fosse, Jean P; Cupa, Michel; Hoang, Philippe; Cohen, Yves

    2004-05-01

    To determine whether procalcitonin is a reliable diagnostic and prognostic marker in septic shock compared with nonseptic shock. Prospective controlled trial. Intensive care unit of the Avicenne Teaching Hospital, Bobigny, France. All patients admitted to our intensive care unit over a 12-month period with clinical evidence of shock. None. Echocardiography or pulmonary artery flotation catheter measurements were used to assess hemodynamics, and multiple specimens were obtained for microbiological studies. Standard criteria were used to diagnose septic shock. Serum concentrations of procalcitonin, C-reactive protein, and lactate were determined on the day of shock onset (day 1) and on days 3, 7, and 10. Seventy-five patients were included, 62 in the septic shock group and 13 in the cardiogenic shock group. Serum procalcitonin on day 1 was significantly higher in patients with than without septic shock (median, 14 [0.3-767] ng/mL vs. 1 [0.5-36] ng/mL, p < .01). A cutoff value of 1 ng/mL had 95% sensitivity and 54% specificity for separating patients with and without sepsis. C-reactive protein failed to discriminate between these two groups. Among patients with sepsis, procalcitonin concentrations were significantly higher in those who died than in the survivors, at all four measurement time points (median, 16 [0.15-767] ng/mL vs. 6 [0.2-123] ng/mL, p = .045 on day 1; 6.5 [0.3-135] ng/mL vs. 1.05 [0.11-53] ng/mL, p = .02 on day 10). A cutoff value of 6 ng/mL on day 1 separated patients who died from those who survived with 87.5% sensitivity and 45% specificity. C-reactive protein was not helpful for predicting mortality. Serum lactate was a nonspecific prognostic marker. These data indicate that procalcitonin may be a valuable early diagnostic and prognostic marker in patients with septic shock.

  4. Changes in Insulin-like Growth Factor-1 Level in Patients with Sepsis and Septic Shock

    Directory of Open Access Journals (Sweden)

    Sang Hoon Lee

    2016-11-01

    Full Text Available Background Despite many ongoing, prospective studies on the topic, sepsis still remains one of the main causes of death in hospital. The hormone insulin-like growth factor 1 (IGF-1 has a similar molecular structure to that of insulin. IGF-1 exerts anabolic effects and plays important roles in both normal physiology and pathologic processes. Previous studies have observed low serum IGF-1 level in patients with critical illnesses. Here, we evaluated changes in IGF-1 level based on survival of septic patients. Methods We evaluated 140 patients with sepsis and septic shock (21 with sepsis and 119 with septic shock admitted to the intensive care unit of a university-affiliated hospital in Korea. Serum IGF-1 level was measured on days 0, 1, 3, and 7. Patients with liver disease were excluded from this study. All data were analyzed using SPSS version 20 (SPSS Inc., Chicago, IL, USA. Results Patients with septic shock had significantly lower serum IGF-1 level on days 1 and 3 than patients without septic shock (p = 0.002 and p = 0.007, respectively. Generally, there was a negative relationship between IGF-1 and serum cortisol levels; however, this relationship was only significant on day 3 (p = 0.029. Furthermore, renin showed significantly negative correlation with IGF-1 on day 3 (p = 0.038. IGF-1 level did not show significant difference between survivors and non-survivors. Conclusions Our results showed that IGF-1 was associated with septic shock, and that the IGF-1 axis is severely disrupted in septic patients. Additionally, serum cortisol and renin levels were associated with IGF-1 level.

  5. Decompressive Abdominal Laparotomy for Abdominal Compartment Syndrome in an Unengrafted Bone Marrow Recipient with Septic Shock

    Directory of Open Access Journals (Sweden)

    Derrick J. N. Dauplaise

    2010-01-01

    Full Text Available Objective. To describe a profoundly immunocompromised (panleukopenia child with septic shock who developed abdominal compartment syndrome (ACS and was successfully treated with surgical decompression. Design. Individual case report. Setting. Pediatric intensive care unit of a tertiary children's hospital. Patient. A 32-month-old male with Fanconi anemia who underwent bone marrow transplantation (BMT 5 days prior to developing septic shock secondary to Streptococcus viridans and Escherichia coli ACS developed after massive fluid resuscitation, leading to cardiopulmonary instability. Interventions. Emergent surgical bedside laparotomy and silo placement. Measurements and Main Results. The patient's cardiopulmonary status stabilized after decompressive laparotomy. The abdomen was closed and the patient survived to hospital discharge without cardiac, respiratory, or renal dysfunction. Conclusions. The use of laparotomy and silo placement in an unengrafted BMT patient with ACS and septic shock did not result in additional complications. Surgical intervention for ACS is a reasonable option for high risk, profoundly immunocompromised patients.

  6. Refractory Septic Shock Treated with Nephrectomy under the Support of Extracorporeal Membrane Oxygenation

    Directory of Open Access Journals (Sweden)

    Young Kun Lee

    2015-08-01

    Full Text Available Conventional medical therapies have not been very successful in treating adults with refractory septic shock. The effects of direct hemoperfusion using polymyxin B and veno-arterial extracorporeal membrane oxygenation (ECMO for refractory septic shock remain uncertain. A 66-year-old man was admitted to the emergency department and suffered from sepsis-induced hemodynamic collapse. For hemodynamic improvement, we performed direct hemoperfusion using polymyxin B. Computed tomography scan of this patient revealed emphysematous pyelonephritis (EPN, for which he underwent emergent nephrectomy with veno-arterial ECMO support. To the best of our knowledge, this is the first report of successful treatment of EPN with refractory septic shock using polymyxin B hemoperfusion and nephrectomy under the support of ECMO.

  7. Overcoming the Odds: Long-term psychosocial outcomes in survivors of meningococcal septic shock in childhood, and in their parents

    NARCIS (Netherlands)

    L.C.A.C. Vermunt (Lindy)

    2008-01-01

    textabstractSeptic shock, caused by Neisseria meningitidis with petechiae and/or purpura, also called Meningococcal Septic Shock (MSS), is the most serious form of meningococcal infection in early childhood. MSS is a life-threatening illness in mostly previously healthy children, with an unexpected

  8. A Novel Porcine Model of Septic Shock Induced by Acute Respiratory Distress Syndrome due to Methicillin-resistant Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Shuo Wang

    2017-01-01

    Conclusions: In the present study, we developed a novel porcine model of septic shock induced by ARDS due to severe MRSA pneumonia with characteristic hyperdynamic and hypodynamic phases in 24 h, which mimicked the hemodynamic changing of septic shock in human.

  9. Designing and testing computer based screening engine for severe sepsis/septic shock.

    Science.gov (United States)

    Herasevich, V; Afessa, B; Chute, C G; Gajic, O

    2008-11-06

    This study addresses the role of a sepsis "sniffer", an automatic screening tool for the timely identification of patients with severe sepsis/septic shock, based electronic medical records. During the two months prospective implementation in a medical intensive care unit, 37 of 320 consecutive patients developed severe sepsis/septic shock. The sniffer demonstrated a sensitivity of 48% and specificity of 86%, and positive predictive value 32%. Further improvements are needed prior to the implementation of sepsis sniffer in clinical practice and research.

  10. Septic arthritis and subsequent fatal septic shock caused by Vibrio vulnificus infection

    DEFF Research Database (Denmark)

    Emamifar, Amir; Asmussen Andreasen, Rikke; Andersen, Nanna Skaarup

    2015-01-01

    Vibrio vulnificus is a rare but potential fatal bacterium that can cause severe infections. Wound infections, primary sepsis and gastroenteritis are the most common clinical features. Septic arthritis caused by V. vulnificus is an atypical presentation that has been reported in only two case...

  11. Human recombinant protein C for severe sepsis and septic shock in adult and paediatric patients

    DEFF Research Database (Denmark)

    Martí-Carvajal, Arturo J; Solà, Ivan; Gluud, Christian

    2012-01-01

    Sepsis is a common and frequently fatal condition. Human recombinant activated protein C (APC) has been introduced to reduce the high risk of death associated with severe sepsis or septic shock. This systematic review is an update of a Cochrane review originally published in 2007....

  12. Maximally effective dosing regimens of meropenem in patients with septic shock

    DEFF Research Database (Denmark)

    Sjövall, Fredrik; Alobaid, Abdulaziz S; Wallis, Steven C

    2018-01-01

    was required for both empirical and targeted treatment. In patients with a CL CR of ≤ 100 mL/min, successful concentration targets could be reached with intermittent dosing of 1000 mg/8 h. Conclusions: In patients with septic shock and possible augmented renal clearance, doses should be increased and...

  13. Adrenal gland volume measurement in septic shock and control patients: a pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Nougaret, Stephanie; Aufort, S.; Gallix, B. [Hopital Saint Eloi, Department of Abdominal Imaging, CHU Montpellier, Montpellier, Cedex 5 (France); Jung, B.; Chanques, G.; Jaber, S. [Hopital Saint Eloi, Intensive Care Unit, Department of Critical Care and Anesthesiology: DAR B, CHU Montpellier, Montpellier, Cedex 5 (France)

    2010-10-15

    To compare adrenal gland volume in septic shock patients and control patients by using semi-automated volumetry. Adrenal gland volume and its inter-observer variability were measured with tomodensitometry using semi-automated software in 104 septic shock patients and in 40 control patients. The volumes of control and septic shock patients were compared and the relationship between volume and outcome in intensive care was studied. The mean total volume of both adrenal glands was 7.2 {+-} 2.0 cm{sup 3} in control subjects and 13.3 {+-} 4.7 cm{sup 3} for total adrenal gland volume in septic shock patients (p < 0.0001). Measurement reproducibility was excellent with a concordance correlation coefficient value of 0.87. The increasing adrenal gland volume was associated with a higher rate of survival in intensive care. The present study reports that with semi-automated software, adrenal gland volume can be measured easily and reproducibly. Adrenal gland volume was found to be nearly double in sepsis compared with control patients. The absence of increased volume during sepsis would appear to be associated with a higher rate of mortality and may represent a prognosis factor which may help the clinician to guide their strategy. (orig.)

  14. [Septic shock in a patient with the Fournièr gangrene with fatal outcome].

    Science.gov (United States)

    Zonca, P; Mrázek, T; Matusek, A; Hajek, M; Stiglerová, S; Jurytko, A; Kucera, C; Nieslanik, M

    2009-07-01

    The authors present a case of a patient with developed Fournièr gangrene and septic shock. Fournièr gangrene belongs to the group of local non-specific infection of soft tissues (NSTI). Its incidence is relatively low, but the infection is extraordinary aggressive with a possible lethal end. 39 years old patient with 4 days history of Fournier gangrene's development was admitted in irreversible septic shock. The initial APACHE II score was 36. The delay in treatment was an important factor in the further course of illness with lethal end. Above the mentioned 39 years old patient died because of septic shock. The hemorrhagic cystitis was the original source of infection with further development of Fournièr gangrene according to the pathological record. We often come across all different kinds of stages of sepsis from the MODS to the septic shock for patients with Fournièr gangrene. Causal treatment should be started early. The local surgical excision and wide broad antibiotic administrations are basic treatments in the context of other treatment modalities according to the current patient's needs. The adjuvant hyperbaric oxygen treatment takes place in patients with Fournièr gangrene as well and is beneficial. The following factor even worsens the illness prognosis: delay in diagnostic, higher age, anorectal origin of infection, the amount of organ with dysfunction or failure, diabetes mellitus and significant immunodeficiency.

  15. The aPC treatment improves microcirculation in severe sepsis/septic shock syndrome

    NARCIS (Netherlands)

    Donati, Abele; Damiani, Elisa; Botticelli, Laura; Adrario, Erica; Lombrano, Maria Rita; Domizi, Roberta; Marini, Benedetto; van Teeffelen, Jurgen W. G. E.; Carletti, Paola; Girardis, Massimo; Pelaia, Paolo; Ince, Can

    2013-01-01

    The role of recombinant activated protein C (aPC) during sepsis is still controversial. It showed anti-inflammatory effect and improved the microvascular perfusion in experimental models of septic shock. The present study was aimed at testing the hypothesis that recombinant aPC therapy improves the

  16. Serum thiamine concentration and oxidative stress as predictors of mortality in patients with septic shock.

    Science.gov (United States)

    Costa, Nara Aline; Gut, Ana Lúcia; de Souza Dorna, Mariana; Pimentel, José Alexandre Coelho; Cozzolino, Silvia Maria Franciscato; Azevedo, Paula Schmidt; Fernandes, Ana Angélica Henrique; Zornoff, Leonardo Antonio Mamede; de Paiva, Sergio Alberto Rupp; Minicucci, Marcos Ferreira

    2014-04-01

    The purpose of the study is to determine the influence of serum thiamine, glutathione peroxidase (GPx) activity, and serum protein carbonyl concentrations in hospital mortality in patients with septic shock. This prospective study included all patients with septic shock on admission or during intensive care unit (ICU) stay, older than 18 years, admitted to 1 of the 3 ICUs of the Botucatu Medical School, from January to August 2012. Demographic information, clinical evaluation, and blood sample were taken within the first 72 hours of the patient's admission or within 72 hours after septic shock diagnosis for serum thiamine, GPx activity, and protein carbonyl determination. One hundred eight consecutive patients were evaluated. The mean age was 57.5 ± 16.0 years, 63% were male, 54.6% died in the ICU, and 71.3% had thiamine deficiency. Thiamine was not associated with oxidative stress. Neither vitamin B1 levels nor the GPx activity was associated with outcomes in these patients. However, protein carbonyl concentration was associated with increased mortality. In patients with septic shock, oxidative stress was associated with mortality. On the other hand, thiamine was not associated with oxidative stress or mortality in these patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Adrenal gland volume measurement in septic shock and control patients: a pilot study

    International Nuclear Information System (INIS)

    Nougaret, Stephanie; Aufort, S.; Gallix, B.; Jung, B.; Chanques, G.; Jaber, S.

    2010-01-01

    To compare adrenal gland volume in septic shock patients and control patients by using semi-automated volumetry. Adrenal gland volume and its inter-observer variability were measured with tomodensitometry using semi-automated software in 104 septic shock patients and in 40 control patients. The volumes of control and septic shock patients were compared and the relationship between volume and outcome in intensive care was studied. The mean total volume of both adrenal glands was 7.2 ± 2.0 cm 3 in control subjects and 13.3 ± 4.7 cm 3 for total adrenal gland volume in septic shock patients (p < 0.0001). Measurement reproducibility was excellent with a concordance correlation coefficient value of 0.87. The increasing adrenal gland volume was associated with a higher rate of survival in intensive care. The present study reports that with semi-automated software, adrenal gland volume can be measured easily and reproducibly. Adrenal gland volume was found to be nearly double in sepsis compared with control patients. The absence of increased volume during sepsis would appear to be associated with a higher rate of mortality and may represent a prognosis factor which may help the clinician to guide their strategy. (orig.)

  18. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

    NARCIS (Netherlands)

    Rhodes, Andrew; Evans, Laura E.; Alhazzani, Waleed; Levy, Mitchell M.; Antonelli, Massimo; Ferrer, Ricard; Kumar, Anand; Sevransky, Jonathan E.; Sprung, Charles L.; Nunnally, Mark E.; Rochwerg, Bram; Rubenfeld, Gordon D.; Angus, Derek C.; Annane, Djillali; Beale, Richard J.; Bellinghan, Geoffrey J.; Bernard, Gordon R.; Chiche, Jean-Daniel; Coopersmith, Craig; de Backer, Daniel P.; French, Craig J.; Fujishima, Seitaro; Gerlach, Herwig; Hidalgo, Jorge Luis; Hollenberg, Steven M.; Jones, Alan E.; Karnad, Dilip R.; Kleinpell, Ruth M.; Koh, Younsuk; Lisboa, Thiago Costa; Machado, Flavia R.; Marini, John J.; Marshall, John C.; Mazuski, John E.; McIntyre, Lauralyn A.; McLean, Anthony S.; Mehta, Sangeeta; Moreno, Rui P.; Myburgh, John; Navalesi, Paolo; Nishida, Osamu; Osborn, Tiffany M.; Perner, Anders; Plunkett, Colleen M.; Ranieri, Marco; Schorr, Christa A.; Seckel, Maureen A.; Seymour, Christopher W.; Shieh, Lisa; Shukri, Khalid A.; Simpson, Steven Q.; Singer, Mervyn; Thompson, B. Taylor; Townsend, Sean R.; van der Poll, Thomas; Vincent, Jean-Louis; Wiersinga, W. Joost; Zimmerman, Janice L.; Dellinger, R. Phillip

    2017-01-01

    To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee

  19. Clinical impact of stress dose steroids in patients with septic shock: insights from the PROWESS-Shock trial.

    Science.gov (United States)

    Póvoa, Pedro; Salluh, Jorge I F; Martinez, Maria L; Guillamat-Prats, Raquel; Gallup, Dianne; Al-Khalidi, Hussein R; Thompson, B Taylor; Ranieri, V Marco; Artigas, Antonio

    2015-04-28

    The aim of our study was to evaluate the clinical impact of the administration of intravenous steroids, alone or in conjunction with drotrecogin-alfa (activated) (DrotAA), on the outcomes in septic shock patients. We performed a sub-study of the PROWESS-Shock trial (septic shock patients who received fluids and vasopressors above a predefined threshold for at least 4 hours were randomized to receive either DrotAA or placebo for 96 hours). A propensity score for the administration of intravenous steroids for septic shock at baseline was constructed using multivariable logistic regression. Cox proportional hazards model using inverse probability of treatment weighting of the propensity score was used to estimate the effect of intravenous steroids, alone or in conjunction with DrotAA, on 28-day and 90-day all-cause mortality. A total of 1695 patients were enrolled of which 49.5% received intravenous steroids for treatment of septic shock at baseline (DrotAA + steroids N = 436; DrotAA + no steroids N = 414; placebo + steroids N = 403; placebo + no steroids N = 442). The propensity weighted risk of 28-day as well as 90-day mortality in those treated vs. those not treated with steroids did not differ among those randomized to DrotAA vs. placebo (interaction p-value = 0.38 and p = 0.27, respectively) nor was a difference detected within each randomized treatment. Similarly, the course of vasopressor use and cardiovascular SOFA did not appear to be influenced by steroid therapy. In patients with lung infection (N = 744), abdominal infection (N = 510), Gram-positive sepsis (N = 420) and Gram-negative sepsis (N = 461), the propensity weighted risk of 28-day as well as 90-day mortality in those treated vs. those not treated with steroids did not differ among those randomized to DrotAA vs. placebo nor was a difference detected within each randomized treatment. In the present study of septic shock patients, after

  20. Septic shock after posterior spinal arthrodesis on a patient with Scheuermann kyphosis and multiple body piercings.

    Science.gov (United States)

    Tsirikos, Athanasios I; Subramanian, Ashok Sridhara

    2011-10-15

    A case report. We report septic shock as postoperative complication following an instrumented posterior spinal arthrodesis on a patient with multiple body piercings. The management of this potentially catastrophic complication and outcome of treatment is been discussed. Body piercing has become increasingly more common because of change in culture or as a fashion statement. This has been associated with local or generalized ill effects including tissue injury, skin and systemic infections, and septic shock. There is no clear guideline pathway regarding removal and reinsertion of body piercings in patients who undergo major surgery. Complications following orthopedic or spinal procedures associated with body piercing have not been reported. We reviewed the medical notes and radiographs of an adolescent patient with Scheuermann kyphosis and multiple body piercings who underwent a posterior spinal arthrodesis and developed septic shock. Septic shock developed on postoperative day 2 after reinsertion of all piercings following the patient's request. The patient became systemically very unwell and required intensive medical management, as well as a total course of antibiotics of 3 months. The piercings remained in situ. She did not develop a wound infection despite the presence of bacteremia and spinal instrumentation. The patient had no new piercings subsequent to her deformity procedure. Two and a half years after spinal surgery she reported no medical problems, had a balanced spine with no loss of kyphosis correction and no evidence of nonunion or recurrence of deformity. The development of septic shock as a result of piercing reinsertion in the postoperative period has not been previously reported. This is an important consideration to prevent potentially life-threatening complications following major spinal surgery.

  1. Differential diagnostic value of procalcitonin in surgical and medical patients with septic shock.

    Science.gov (United States)

    Clec'h, Christophe; Fosse, Jean-Philippe; Karoubi, Philippe; Vincent, Francois; Chouahi, Imad; Hamza, Lilia; Cupa, Michel; Cohen, Yves

    2006-01-01

    To assess whether different diagnostic and prognostic cutoff values of procalcitonin should be considered in surgical and in medical patients with septic shock. Prospective observational study. Intensive care unit of the Avicenne teaching hospital, France. All patients with septic shock or noninfectious systemic inflammatory response syndrome within 48 hrs after admission. None. Patients were allocated to one of the following groups: group 1 (surgical patients with septic shock), group 2 (surgical patients with noninfectious systemic inflammatory response syndrome), group 3 (medical patients with septic shock), and group 4 (medical patients with noninfectious systemic inflammatory response syndrome). Procalcitonin at study entry was compared between group 1 and group 2 and between group 3 and group 4 to determine the diagnostic cutoff value in surgical and in medical patients, respectively. Procalcitonin was compared between survivors and nonsurvivors from group 1 and group 3 to determine its prognostic cutoff value. One hundred forty-three patients were included: 31 in group 1, 36 in group 2, 36 in group 3, and 40 in group 4. Median procalcitonin levels (ng/mL [interquartile range]) were higher in group 1 than in group 3 (34.00 [7.10-76.00] vs. 8.40 [3.63-24.70], p = .01). In surgical patients, the best diagnostic cutoff value was 9.70 ng/mL, with 91.7% sensitivity and 74.2% specificity. In medical patients, the best diagnostic cutoff value was 1.00 ng/mL, with 80% sensitivity and 94% specificity. Procalcitonin was a reliable early prognostic marker in medical but not in surgical patients with septic shock. A cutoff value of 6.00 ng/mL had 76% sensitivity and 72.7% specificity for separating survivors from nonsurvivors. The diagnostic cutoff value of procalcitonin was higher in surgical than in medical patients. Early procalcitonin was of prognostic interest in medical patients.

  2. Effects of arm elevation on radial artery pressure: a new method to distinguish hypovolemic shock and septic shock from hypotension.

    Science.gov (United States)

    Xie, Zhiyi; Zhang, Zhenyu; Xu, Yuan; Zhou, Hua; Wu, Sheng; Wang, Zhong

    2018-06-01

    In this prospective observational study, we investigated the variability in radial artery invasive blood pressure associated with arm elevation in patients with different hemodynamic types. We carried out a prospective observational study using data from 73 general anesthesia hepatobiliary postoperative adult patients admitted to an ICU over a 1-year period. A standard procedure was used for the arm elevation test. The value of invasive radial arterial pressure was recorded at baseline, and 30 and 60 s after the arm had been raised from 0° to 90°. We compared the blood pressure before versus after arm elevation, and between hemodynamically stable, hypovolemic shock, and septic shock patient groups. In all 73 patients, systolic arterial pressure (SAP) decreased, diastolic arterial pressure (DAP) increased, and pulse pressure (PP) decreased at 30 and 60 s after arm elevation (Ppressure (MAP) was unchanged (P>0.05). On comparing 30 and 60 s, there was no significant difference in SAP, DAP, PP, or MAP (P>0.05). In 40 hemodynamically stable patients, SAP and PP decreased, and DAP and MAP increased significantly at 30 and 60 s after arm elevation compared with baseline (P0.05). In 17 patients with septic shock, SAP, PP, and MAP decreased significantly versus baseline at 30 and 60 s (P0.05). Comparison of the absolute value of pressure change of septic shock patients at 30 s after raising the arm showed that SAP, DAP, and MAP changes were significantly lower compared with those in hypovolemic shock and hemodynamically stable patients (Parm elevation of SAP. The best cut-off point for the SAP change value was -5 mmHg or less, with a sensitivity of 94.12%, a specificity of 80.36%, a positive likelihood ratio of 4.79 (95% CI: 2.8-8.2), and a negative likelihood ratio of 0.073 (95% CI: 0.01-0.5). Our study shows that hypovolemic shock and septic shock patients have significantly different radial artery invasive blood pressure changes in an arm elevation test

  3. Ion transport in circulatory and/or septic shock

    International Nuclear Information System (INIS)

    Sayeed, M.M.

    1987-01-01

    This review surveys investigations of membrane ion transport in animals in hemorrhagic, endotoxic, or bacteremic shock. The focus of the review is on ion transport studies in the skeletal muscle and liver. Skeletal muscle Na + -K + transport alterations have been shown during the induction of shock via hemorrhage, endotoxin, or live Gram-negative bacteria in the rodent, canine, and primate species. These alterations include impairment of active cellular K + accumulation, increased permeability to 24 Na + and Cl - , and membrane depolarization. The ion transport alterations in the skeletal muscle are compatible with movement of extracellular fluid into the intracellular compartment. Such fluid movements can potentially lead to decreases in circulating plasma volume and thus to circulatory deficits in shock. Studies in the liver of rats subjected to hemorrhagic or endotoxic shock indicated the failure of electrogenic Na + pump. Although the hepatic cellular membrane permeability to Na + relative to permeability to K + appeared unaltered in hemorrhagic shock, endotoxic shock caused an increase in permeability to Na + . Hepatic cellular 45 Ca + regulation also appeared to be adversely affected during endotoxic shock. Alterations in hepatic Na + -K + transport and Ca + regulation could contribute to impairment in hepatic glucose production during shock. Although mechanisms of altered membrane ion transport during shock states remain unknown, such changes could occur prior to any substantial loss of cellular metabolic energy

  4. Triiodothyronine Administration in a Model of Septic Shock: A Randomized Blinded Placebo-Controlled Trial.

    Science.gov (United States)

    Maiden, Matthew J; Chapman, Marianne J; Torpy, David J; Kuchel, Timothy R; Clarke, Iain J; Nash, Coralie H; Fraser, Jonathan D; Ludbrook, Guy L

    2016-06-01

    Triiodothyronine concentration in plasma decreases during septic shock and may contribute to multiple organ dysfunction. We sought to determine the safety and efficacy of administering triiodothyronine, with and without hydrocortisone, in a model of septic shock. Randomized blinded placebo-controlled trial. Preclinical research laboratory. Thirty-two sheep rendered septic with IV Escherichia coli and receiving protocol-guided sedation, ventilation, IV fluids, and norepinephrine infusion. Two hours following induction of sepsis, 32 sheep received a 24-hour IV infusion of 1) placebo + placebo, 2) triiodothyronine + placebo, 3) hydrocortisone + placebo, or 4) triiodothyronine + hydrocortisone. Primary outcome was the total amount of norepinephrine required to maintain a target mean arterial pressure; secondary outcomes included hemodynamic and metabolic indices. Plasma triiodothyronine levels increased to supraphysiological concentrations with hormonal therapy. Following 24 hours of study drug infusion, the amount of norepinephrine required was no different between the study groups (mean ± SD μg/kg; placebo + placebo group 208 ± 392; triiodothyronine + placebo group 501 ± 370; hydrocortisone + placebo group 167 ± 286; triiodothyronine + hydrocortisone group 466 ± 495; p = 0.20). There was no significant treatment effect on any hemodynamic variable, metabolic parameter, or measure of organ function. A 24-hour infusion of triiodothyronine, with or without hydrocortisone, in an ovine model of septic shock did not markedly alter norepinephrine requirement or any other physiological parameter.

  5. Cystatin C as an early marker of acute kidney injury in septic shock.

    Science.gov (United States)

    Ortuño-Andériz, F; Cabello-Clotet, N; Vidart-Simón, N; Postigo-Hernández, C; Domingo-Marín, S; Sánchez-García, M

    2015-03-01

    To describe the utility of determining plasma cystatinC concentrations in the diagnosis of acute incident kidney injury in septic shock. Prospective series of 50 patients with septic shock and plasma creatinine levels <2mg/dL hospitalized in an intensive care unit. Clinical and laboratory follow-ups were conducted, with measurements of cystatinC, urea and plasma creatinine levels from the diagnosis of septic shock to 5days later. The severity of the septic shock was assessed with the RIFLE scale. Twenty patients (40%) developed acute kidney injury: 8 (16%) were categorized as RIFLE-R, 5 (10%) as RIFLE-I and 7 (14%) as RIFLE-F. All patients categorized as RIFLE-F required extracorporeal renal clearance. Eighteen (36%) patients died, 8 (20%) of whom had developed acute kidney injury in their evolution. There was poor correlation between plasma creatinine and cystatin C levels (r=.501; P=.001), which disappeared upon reaching any degree of renal impairment on the RIFLE scale. CystatinC levels increased earlier and were better able to identify patients who would develop serious renal function impairment (RIFLE-F) than creatinine and urea levels. The initial cystatinC levels were related to mortality at 30days (OR=1.16; 95%CI: 03-.85). For patients who developed acute septic kidney injury, the plasma cystatinC levels increased before the classical markers of renal function. CystatinC also constitutes a severity biomarker that correlates with progression to RIFLE-F, the need for extrarenal clearance and, ultimately, mortality. This precocity could be useful for starting measures that prevent the progression of renal dysfunction. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  6. Pulmonary extraction of biogenic amines during septic shock

    International Nuclear Information System (INIS)

    Kerstein, M.D.; Kohler, J.; Gould, S.; Moseley, P.

    1982-01-01

    The effect of live Escherichia coli on the pulmonary extraction of the biogenic amines 14 C 5-hydroxytryptamine, (5-HT) and 3 H-epinephrine was investigated. The labeled isotopes were injected into a central venous catheter and collected from an aortic catheter. One hundred per cent of the labeled epinephrine was recovered in the control and septic state. Only 32.8 +/- 3.6% SEM of the 5-hydroxytryptamine was recovered before sepsis and 42.5 +/- 4.9% SEM after sepsis. During sepsis, mean arterial pressure fell to 58 mm Hg from 121 mm Hg. Pulmonary shunt increased from .7 +/- .05 SEM to .33 +/- .09 SEM

  7. A case of Lemierre's syndrome with septic shock and complicated parapneumonic effusions requiring intrapleural fibrinolysis

    Directory of Open Access Journals (Sweden)

    Daniel P. Croft

    2015-01-01

    Full Text Available Lemierre's syndrome is a septic thrombophlebitis of the internal jugular vein, which can lead to severe systemic illness. We report a case of an otherwise healthy 26-year-old man who suffered from pharyngitis followed by septic shock requiring intubation and vasopressor support from Fusobacterium necrophorum bacteremia. The septic emboli to his lungs caused complicated bilateral parapneumonic effusions, which recurred after initial drainage. He required bilateral chest tubes and intrapleural tPA to successfully drain his effusions. His fever curve and overall condition improved with the resolution of his effusions and after a 33-day hospitalization, he recovered without significant disability. The severity of his illness and difficult to manage complicated parapneumonic effusions were the unique facets of this case. Using an evidence-based approach of tPA and DNase for complicated parapneumonic effusions in Lemierre's syndrome can be safe and effective.

  8. Aqueous Extract of Oldenlandia diffusa Suppresses LPS-Induced ...

    African Journals Online (AJOL)

    ... potential transcriptional factor for regulating the expression of iNOS, COX-2 and TNF-α. As expected, AEOD suppressed the LPS-induced degradation and phosphorylation of IκBα and sustained the expression of p65 in the cytosol. Furthermore, AEOD substantially inhibited the LPS-induced DNA binding activity of NF-κB.

  9. Accuracy of a real-time continuous glucose monitoring system in children with septic shock: A pilot study

    OpenAIRE

    Prabhudesai, Sumant; Kanjani, Amruta; Bhagat, Isha; Ravikumar, Karnam G.; Ramachandran, Bala

    2015-01-01

    Aims: The aim of this prospective, observational study was to determine the accuracy of a real-time continuous glucose monitoring system (CGMS) in children with septic shock. Subjects and Methods: Children aged 30 days to 18 years admitted to the Pediatric Intensive Care Unit with septic shock were included. A real-time CGMS sensor was used to obtain interstitial glucose readings. CGMS readings were compared statistically with simultaneous laboratory blood glucose (BG). Results: Nineteen chil...

  10. [Septic shock due to infective endocarditis of stimulation system of implantable cardioverter-defibrillator].

    Science.gov (United States)

    Porubčinová, I; Porubčin, S; Stančák, B; Beňa, M; Sabol, F

    2012-01-01

    We present a case of a 60-year old patient hospitalized at the Department of Infectious Diseases and Travel Medicine, Medical faculty of UPJS and L. Pasteurs University Hospital in Kosice with suspected gastroenteritis. The patient was admitted to an intensive care unit because of the signs of septic shock. Within one hour from admission, the patient was administered early goal directed therapy for septic shock. Subsequently, infectious endocarditis of stimulation electrodes and tricuspid valve was identified as the origin of the infection. The stimulation system was then explanted from a stabilized and afebrile patient at the Department of cardiac Surgery of Eastern Slovak Institute of Cardiac and Vascular Diseases in Kosice. This case should emphasise frequently atypical course of this serious disease and the need for early identification of severe sepsis to enable timely management to affect mortality.

  11. Association between fluid balance and mortality in patients with septic shock

    DEFF Research Database (Denmark)

    Cronhjort, M; Hjortrup, P B; Holst, L B

    2016-01-01

    and a comparably low cumulative fluid balance, there was no association between fluid balance and mortality. However, the study design and the limited power preclude strong conclusions. There is an urgent need for high-quality trials assessing the benefit and harm of different fluid volume strategies in patients......BACKGROUND: Several studies have shown an association between a positive fluid balance and increased mortality in patients with septic shock. This may have led to a more restrictive use of intravenous fluids. The association between fluid accumulation and mortality in the setting of a more...... restrictive use of intravenous fluids, however, is uncertain. We therefore aimed to investigate the association between a cumulative fluid balance 3 days after randomization and 90-day mortality in a recent Nordic multicentre cohort of patients with septic shock. METHODS: A post hoc analysis of patients from...

  12. Raoultella planticola bacteremia-induced fatal septic shock following burn injury.

    Science.gov (United States)

    Yumoto, Tetsuya; Naito, Hiromichi; Ihoriya, Hiromi; Tsukahara, Kohei; Ota, Tomoyuki; Watanabe, Toshiyuki; Nakao, Atsunori

    2018-05-04

    Raoultella planticola, a Gram-negative, aerobic bacillus commonly isolated from soil and water, rarely causes invasive infections in humans. Septic shock from R. planticola after burn injury has not been previously reported. A 79-year-old male was admitted to the emergency intensive care unit after extensive flame burn injury. He accidently caught fire while burning trash and plunged into a nearby tank filled with contaminated rainwater to extinguish the fire. The patient developed septic shock on day 10. The blood culture detected R. planticola, which was identified using the VITEK-2 biochemical identification system. Although appropriate antibiotic treatment was continued, the patient died on day 12. Clinicians should be aware of fatal infections in patients with burn injury complicated by exposure to contaminated water.

  13. Enrollment into a time sensitive clinical study in the critical care setting: results from computerized septic shock sniffer implementation

    Science.gov (United States)

    Pieper, Matthew S; Pulido, Juan; Gajic, Ognjen

    2011-01-01

    Objective Recruitment of patients into time sensitive clinical trials in intensive care units (ICU) poses a significant challenge. Enrollment is limited by delayed recognition and late notification of research personnel. The objective of the present study was to evaluate the effectiveness of the implementation of electronic screening (septic shock sniffer) regarding enrollment into a time sensitive (24 h after onset) clinical study of echocardiography in severe sepsis and septic shock. Design We developed and tested a near-real time computerized alert system, the septic shock sniffer, based on established severe sepsis/septic shock diagnostic criteria. A sniffer scanned patients' data in the electronic medical records and notified the research coordinator on call through an institutional paging system of potentially eligible patients. Measurement The performance of the septic shock sniffer was assessed. Results The septic shock sniffer performed well with a positive predictive value of 34%. Electronic screening doubled enrollment, with 68 of 4460 ICU admissions enrolled during the 9 months after implementation versus 37 of 4149 ICU admissions before sniffer implementation (p<0.05). Efficiency was limited by study coordinator availability (not available at nights or weekends). Conclusions Automated electronic medical records screening improves the efficiency of enrollment and should be a routine tool for the recruitment of patients into time sensitive clinical trials in the ICU setting. PMID:21508415

  14. Enrollment into a time sensitive clinical study in the critical care setting: results from computerized septic shock sniffer implementation.

    Science.gov (United States)

    Herasevich, Vitaly; Pieper, Matthew S; Pulido, Juan; Gajic, Ognjen

    2011-01-01

    Recruitment of patients into time sensitive clinical trials in intensive care units (ICU) poses a significant challenge. Enrollment is limited by delayed recognition and late notification of research personnel. The objective of the present study was to evaluate the effectiveness of the implementation of electronic screening (septic shock sniffer) regarding enrollment into a time sensitive (24 h after onset) clinical study of echocardiography in severe sepsis and septic shock. We developed and tested a near-real time computerized alert system, the septic shock sniffer, based on established severe sepsis/septic shock diagnostic criteria. A sniffer scanned patients' data in the electronic medical records and notified the research coordinator on call through an institutional paging system of potentially eligible patients. The performance of the septic shock sniffer was assessed. The septic shock sniffer performed well with a positive predictive value of 34%. Electronic screening doubled enrollment, with 68 of 4460 ICU admissions enrolled during the 9 months after implementation versus 37 of 4149 ICU admissions before sniffer implementation (p<0.05). Efficiency was limited by study coordinator availability (not available at nights or weekends). Automated electronic medical records screening improves the efficiency of enrollment and should be a routine tool for the recruitment of patients into time sensitive clinical trials in the ICU setting.

  15. Diagnostic value of Pentraxin-3 in patients with sepsis and septic shock in accordance with latest sepsis-3 definitions.

    Science.gov (United States)

    Hamed, Sonja; Behnes, Michael; Pauly, Dominic; Lepiorz, Dominic; Barre, Max; Becher, Tobias; Lang, Siegfried; Akin, Ibrahim; Borggrefe, Martin; Bertsch, Thomas; Hoffmann, Ursula

    2017-08-09

    Pentraxin-3 (PTX-3) is an acute-phase protein involved in inflammatory and infectious processes. This study assesses its diagnostic and prognostic value in patients with sepsis or septic shock in a medical intensive care unit (ICU). The study includes 213 ICU patients with clinical criteria of sepsis and septic shock. 77 donors served as controls. Plasma levels of PTX-3, procalcitonin (PCT) and interleukin-6 were measured on day 1, 3 and 8. PTX-3 correlated with higher lactate levels as well as with APACHE II and SOFA scores (p = 0.0001). PTX-3 levels of patients with sepsis or septic shock were consistently significantly higher than in the control group (p ≤ 0.001). Plasma levels were able to discriminate sepsis and septic shock significantly on day 1, 3 and 8 (range of AUC 0.73-0.92, p = 0.0001). Uniform cut-off levels were defined at ≥5 ng/ml for at least sepsis, ≥9 ng/ml for septic shock (p = 0.0001). PTX-3 reveals diagnostic value for sepsis and septic shock during the first week of intensive care treatment, comparable to interleukin-6 according to latest Sepsis-3 definitions. NCT01535534 . Registered 14.02.2012.

  16. Impact of Dobutamine in Patients With Septic Shock: A Meta-Regression Analysis.

    Science.gov (United States)

    Nadeem, Rashid; Sockanathan, Shivani; Singh, Mukesh; Hussain, Tamseela; Kent, Patrick; AbuAlreesh, Sarah

    2017-05-01

    Septic shock frequently requires vasopressor agents. Conflicting evidence exists for use of inotropes in patients with septic shock. Data from English studies on human adult septic shock patients were collected. A total of 83 studies were reviewed, while 11 studies with 21 data sets including 239 patients were pooled for meta-regression analysis. For VO2, pooled difference in means (PDM) was 0.274. For cardiac index (CI), PDM was 0.783. For delivery of oxygen, PDM was -0.890. For heart rate, PDM was -0.714. For left ventricle stroke work index, PDM was 0.375. For mean arterial pressure, PDM was -0.204. For mean pulmonary artery pressure, PDM was 0.085. For O2 extraction, PDM was 0.647. For PaCO2, PDM was -0.053. For PaO2, PDM was 0.282. For pulmonary artery occlusive pressure, PDM was 0.270. For pulmonary capillary wedge pressure, PDM was 0.300. For PVO2, PDM was -0.492. For right atrial pressure, PDM was 0.246. For SaO2, PDM was 0.604. For stroke volume index, PDM was 0.446. For SvO2, PDM was -0.816. For systemic vascular resistance, PDM was -0.600. For systemic vascular resistance index, PDM was 0.319. Meta-regression analysis was performed for VO2, DO2, CI, and O2 extraction. Age was found to be significant confounding factor for CI, DO2, and O2 extraction. APACHE score was not found to be a significant confounding factor for any of the parameters. Dobutamine seems to have a positive effect on cardiovascular parameters in patients with septic shock. Prospective studies with larger samples are required to further validate this observation.

  17. Refractory septic shock in children: a European Society of Paediatric and Neonatal Intensive Care definition.

    Science.gov (United States)

    Morin, Luc; Ray, Samiran; Wilson, Clare; Remy, Solenn; Benissa, Mohamed Rida; Jansen, Nicolaas J G; Javouhey, Etienne; Peters, Mark J; Kneyber, Martin; De Luca, Daniele; Nadel, Simon; Schlapbach, Luregn Jan; Maclaren, Graeme; Tissieres, Pierre

    2016-12-01

    Although overall paediatric septic shock mortality is decreasing, refractory septic shock (RSS) is still associated with high mortality. A definition for RSS is urgently needed to facilitate earlier identification and treatment. We aim to establish a European society of paediatric and neonatal intensive care (ESPNIC) experts' definition of paediatric RSS. We conducted a two-round Delphi study followed by an observational multicentre retrospective study. One hundred and fourteen paediatric intensivists answered a clinical case-based, two-round Delphi survey, identifying clinical items consistent with RSS. Multivariate analysis of these items in a development single-centre cohort (70 patients, 30 % mortality) facilitated development of RSS definitions based on either a bedside or computed severity score. Both scores were subsequently tested in a validation cohort (six centres, 424 patients, 11.6 % mortality). From the Delphi process, the draft definition included evidence of myocardial dysfunction and high blood lactate levels despite high vasopressor treatment. When assessed in the development population, each item was independently associated with the need for extracorporeal life support (ECLS) or death. Resultant bedside and computed septic shock scores had high discriminative power against the need for ECLS or death, with areas under the receiver operating characteristics curve of 0.920 (95 % CI 0.89-0.94), and 0.956 (95 % CI 0.93-0.97), respectively. RSS defined by a bedside score equal to or higher than 2 and a computed score equal to or higher than 3.5 was associated with a significant increase in mortality. This ESPNIC definition of RSS accurately identifies children with the most severe form of septic shock.

  18. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

    Science.gov (United States)

    Singer, Mervyn; Deutschman, Clifford S; Seymour, Christopher Warren; Shankar-Hari, Manu; Annane, Djillali; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon R; Chiche, Jean-Daniel; Coopersmith, Craig M; Hotchkiss, Richard S; Levy, Mitchell M; Marshall, John C; Martin, Greg S; Opal, Steven M; Rubenfeld, Gordon D; van der Poll, Tom; Vincent, Jean-Louis; Angus, Derek C

    2016-02-23

    Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. To evaluate and, as needed, update definitions for sepsis and septic shock. A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock

  19. Shoulder Pain after Fall, Septic Shock, and Pyomyositis Associated with Breast Cancer Chemotherapy and Lymphedema

    Directory of Open Access Journals (Sweden)

    Hiromitsu Kitayama

    2016-11-01

    Full Text Available Background: As a symptom of pyomyositis, sepsis usually follows local inflammation signs. Here, we report pyomyositis with lymphedema of upper extremity in which septic shock and poor local findings initially presented during chemotherapy for breast cancer. Case Report: An 80-year-old woman presented with chronic right shoulder pain during chemotherapy for the recurrent disease. She had a history of postmastectomy lymphedema, diabetes mellitus, and repeated hyaluronic acid injections to the shoulder joint. The pain suddenly worsened with septic shock and no apparent local signs. Magnetic resonance imaging revealed myonecrosis, and no pus was yielded by ultrasound-guided needle aspiration. After 2 weeks of recovery by conservative medical management, surgical drainage was performed. Late formulated massive intramuscular pus showed severe neutrophil infiltration and myonecrosis. Conclusion: Pyomyositis can develop into septic shock with poor local signs. Myelosuppression after chemotherapy can cause myonecrosis without macroabscess, and magnetic resonance imaging was useful for the diagnosis of this condition. When unspecified local pain appears during cancer chemotherapy we should consider this disease, too.

  20. Thiamine in septic shock patients with alcohol use disorders: An observational pilot study.

    Science.gov (United States)

    Holmberg, Mathias Johan; Moskowitz, Ari; Patel, Parth Vijay; Grossestreuer, Anne Victoria; Uber, Amy; Stankovic, Nikola; Andersen, Lars Wiuff; Donnino, Michael William

    2018-02-01

    Alcohol-use disorders (AUDs) have been associated with increased sepsis-related mortality. As patients with AUDs are often thiamine deficient, we investigated practice patterns relating to thiamine administration in patients with AUDs presenting with septic shock and explored the association between receipt of thiamine and mortality. We performed a retrospective cohort study of patients presenting with septic shock between 2008 and 2014 at a single tertiary care center. We identified patients with an AUD diagnosis, orders for microbial cultures and use of antibiotics, vasopressor dependency, and lactate levels≥4mmol/L. We excluded those who received thiamine later than 48h of sepsis onset. We included 53 patients. Thirty-four (64%) patients received thiamine. Five patients (15%) received their first thiamine dose in the emergency department. The median time to thiamine administration was 9 (quartiles: 4, 18) hours. The first thiamine dose was most often given parenterally (68%) and for 100mg (88%). In those receiving thiamine, 15/34 (44%) died, compared to 15/19 (79%) of those not receiving thiamine, p=0.02. A considerable proportion of patients with AUDs admitted for septic shock do not receive thiamine. Thiamine administration in this patient population was associated with decreased mortality. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Septic Shock following Prostate Biopsy: Aggressive Limb Salvage for Extremities after Pressor-Induced Ischemic Gangrene

    Directory of Open Access Journals (Sweden)

    Jocelyn Lu, BS

    2017-09-01

    Full Text Available Summary:. Vasopressors used to treat patients with septic shock can cause ischemic necrosis of appendages such as the ears and nose, as well as the extremities. Cases of quadruple-extremity necrosis have high morbidity and mortality, and a profound negative impact on quality of life. This case report details the successful limb salvage and return to function using free tissue transfer as a means to salvage bilateral lower extremities in a patient who suffered vasopressor-induced ischemia of upper and lower extremities after prostate biopsy–induced septic shock. Septic shock following transrectal ultrasound–guided prostate biopsy is a rare, yet life-threatening complication. Successful treatment included thorough planning and staging of therapies such as awaiting tissue demarcation and serial surgical debridement to adequately prepare the tissue bed for free tissue transfer. Adjunctive treatments such as hyperbaric oxygen therapy, negative-pressure wound therapy, and meticulous wound care played a crucial role in wound healing. This vigilant planning and coordinated care resulted in the successful lower extremity salvage, consisting of bilateral transmetatarsal amputations and free tissue transfer to both limbs. We present our long-term follow-up of a functional ambulatory patient after catastrophic, life-threatening infection and appropriate multidisciplinary care.

  2. Lactate clearance cut off for early mortality prediction in adult sepsis and septic shock patients

    Science.gov (United States)

    Sinto, R.; Widodo, D.; Pohan, H. T.

    2018-03-01

    Previous lactate clearance cut off for early mortality prediction in sepsis and septic shock patient was determined by consensus from small sample size-study. We investigated the best lactate clearance cut off and its ability to predict early mortality in sepsis and septic shock patients. This cohort study was conducted in Intensive Care Unit of CiptoMangunkusumo Hospital in 2013. Patients’ lactate clearance and eight other resuscitationendpoints were recorded, and theoutcome was observed during the first 120 hours. The clearance cut off was determined using receiver operating characteristic (ROC) analysis, and its ability was investigated with Cox’s proportional hazard regression analysis using other resuscitation endpoints as confounders. Total of 268 subjects was included, of whom 70 (26.11%) subjects died within the first 120 hours. The area under ROC of lactate clearance to predict early mortality was 0.78 (95% % confidence interval [CI] 0.71-0.84) with best cut off was <7.5% (sensitivity and specificity 88.99% and 81.4% respectively). Compared with group achieving lactate clearance target, group not achieving lactate clearance target had to increase early mortality risk (adjusted hazard ratio 13.42; 95%CI 7.19-25.07). In conclusion, the best lactate clearance cut off as anearly mortality predictor in sepsis and septic shock patients is 7.5%.

  3. Prognostic value of brachioradialis muscle oxygen saturation index and vascular occlusion test in septic shock patients.

    Science.gov (United States)

    Marín-Corral, J; Claverias, L; Bodí, M; Pascual, S; Dubin, A; Gea, J; Rodriguez, A

    2016-05-01

    To compare rSO2 (muscle oxygen saturation index) static and dynamic variables obtained by NIRS (Near Infrared Spectroscopy) in brachioradialis muscle of septic shock patients and its prognostic implications. Prospective and observational study. Intensive care unit. Septic shock patients and healthy volunteers. The probe of a NIRS device (INVOS 5100) was placed on the brachioradialis muscle during a vascular occlusion test (VOT). Baseline, minimum and maximum rSO2 values, deoxygenation rate (DeOx), reoxygenation slope (ReOx) and delta value. Septic shock patients (n=35) had lower baseline rSO2 (63.8±12.2 vs. 69.3±3.3%, p<0.05), slower DeOx (-0.54±0.31 vs. -0.91±0.35%/s, p=0.001), slower ReOx (2.67±2.17 vs. 9.46±3.5%/s, p<0.001) and lower delta (3.25±5.71 vs. 15.1±3.9%, p<0.001) when compared to healthy subjects (n=20). Among septic shock patients, non-survivors showed lower baseline rSO2 (57.0±9.6 vs. 69.8±11.3%, p=0.001), lower minimum rSO2 (36.0±12.8 vs. 51.3±14.8%, p<0.01) and lower maximum rSO2 values (60.6±10.6 vs. 73.3±11.2%, p<0.01). Baseline rSO2 was a good mortality predictor (AUC 0.79; 95%CI: 0.63-0.94, p<0.01). Dynamic parameters obtained with VOT did not improve the results. Septic shock patients present an important alteration of microcirculation that can be evaluated by NIRS with prognostic implications. Monitoring microvascular reactivity in the brachioradialis muscle using VOT with our device does not seem to improve the prognostic value of baseline rSO2. Copyright © 2015 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

  4. Rapid induction of autoantibodies during ARDS and septic shock

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    Meduri G Umberto

    2010-10-01

    Full Text Available Abstract Background Little is known about the induction of humoral responses directed against human autoantigens during acute inflammation. We utilized a highly sensitive antibody profiling technology to study autoantibodies in patients with acute respiratory distress syndrome (ARDS and severe sepsis, conditions characterized by intensive immune activation leading to multiple organ dysfunction. Methods Using Luciferase Immunoprecipitation Systems (LIPS, a cohort of control, ARDS and sepsis patients were tested for antibodies to a panel of autoantigens. Autoantibody titers greater than the mean plus 3 SD of the 24 control samples were used to identify seropositive samples. Available longitudinal samples from different seropositive ARDS and sepsis patient samples, starting from within the first two days after admission to the intensive care, were then analyzed for changes in autoantibody over time. Results From screening patient plasma, 57% of ARDS and 46% of septic patients without ARDS demonstrated at least one statistically significant elevated autoantibody compared to the controls. Frequent high titer antibodies were detected against a spectrum of autoantigens including potassium channel regulator, gastric ATPase, glutamic decarboxylase-65 and several cytokines. Analysis of serial samples revealed that several seropositive patients had low autoantibodies at early time points that often rose precipitously and peaked between days 7-14. Further, the use of therapeutic doses of corticosteroids did not diminish the rise in autoantibody titers. In some cases, the patient autoantibody titers remained elevated through the last serum sample collected. Conclusion The rapid induction of autoantibodies in ARDS and severe sepsis suggests that ongoing systemic inflammation and associated tissue destruction mediate the break in tolerance against these self proteins.

  5. Protocol Adherence for Severe Sepsis and Septic Shock Management in the Emergency Department; a Clinical Audit

    Directory of Open Access Journals (Sweden)

    Mostafa Alavi-Moghaddam

    2016-12-01

    Full Text Available Introduction: Although significant development in the field of medicine is achieved, sepsis is still a major issue threatening humans’ lives. This study was aimed to audit the management of severe sepsis and septic shock patients in emergency department (ED according to the present standard guidelines.Method: This is a prospective audit on approaching adult septic patients who were admitted to ED. The audit checklist was created based on the protocols of Surviving Sepsis Campaign and British Royal College recommendations. The mean knowledge score and the compliance rate of studied measures regarding standard protocols were calculated using SPSS version 21.Results: 30 emergency medicine residents were audited (63.3% male. The mean knowledge score of studied residents regarding standard guidelines were 5.07 ± 1.78 (IQR = 2 in pre education and 8.17 ± 1.31 (IQR = 85 in post education phase (p < 0.001. There was excellent compliance with standard in 4 (22% studied measures, good in 2 (11%, fair in 1 (6%, weak in 2 (11%, and poor in 9 (50%. 64% of poor compliance measures correlated to therapeutic factors. After training, score of 5 measures including checking vital signs in < 20 minute, central vein pressure measurement in < 1 hour, blood culture request, administration of vasopressor agents, and high flow O2 therapy were improved clinically, but not statistically.Conclusion: The protocol adherence in management of severe sepsis and septic shock for urine output measurement, central venous pressure monitoring, administration of inotrope agents, blood transfusion, intravenous antibiotic and hydration therapy, and high flow O2 delivery were disappointingly low. It seems training workshops and implementation of Clinical audit can improve residents’ adherence to current standard guidelines regarding severe sepsis and septic shock.

  6. Targeted tissue perfusion versus macrocirculation-guided standard care in patients with septic shock (TARTARE-2S)

    DEFF Research Database (Denmark)

    Pettilä, Ville; Merz, Tobias; Wilkman, Erika

    2016-01-01

    at least 200 patients with septic shock in four European intensive care units (ICUs) to test whether a tissue perfusion-guided treatment strategy based on capillary refill time, peripheral temperature, arterial lactate concentrations, and accepting lower MAP levels, leads to a faster resolution of shock...

  7. Short- and long-term mortality in patients with community-acquired severe sepsis and septic shock

    DEFF Research Database (Denmark)

    Storgaard, Merete; Hallas, Jesper; Gahrn-Hansen, Bente

    2013-01-01

    Background: Severe sepsis and septic shock have a high 30-day mortality (10-50%), but the long-term mortality is not well described. The purpose of this study was to describe long-term mortality among patients with community-acquired severe sepsis or septic shock compared to a population-based re......Background: Severe sepsis and septic shock have a high 30-day mortality (10-50%), but the long-term mortality is not well described. The purpose of this study was to describe long-term mortality among patients with community-acquired severe sepsis or septic shock compared to a population...... extracted from the National Danish Patient Registry. We analyzed the hazard ratio for mortality at predefined intervals. Results: Absolute mortality within the first 30 days was 69/211 (33%, 95% confidence interval (CI) 25-41%), with a cumulative mortality of 121/211 (57%, 95% CI 48-69%) for the entire...... follow-up. Among septic patients who survived the first 30 days, the mortality hazard ratio was 2.7 (95% CI 1.7-4.3) until day 365, and among septic patients who survived the first year, the 1-4 y mortality hazard ratio was 2.3 (95% CI 1.7-3.3), compared to the community-based reference persons...

  8. Pressor Response to Noradrenaline in the Setting of Septic Shock: Anything New under the Sun—Dexmedetomidine, Clonidine? A Minireview

    Directory of Open Access Journals (Sweden)

    A. Géloën

    2015-01-01

    Full Text Available Progress over the last 50 years has led to a decline in mortality from ≈70% to ≈20% in the best series of patients with septic shock. Nevertheless, refractory septic shock still carries a mortality close to 100%. In the best series, the mortality appears related to multiple organ failure linked to comorbidities and/or an intense inflammatory response: shortening the period that the subject is exposed to circulatory instability may further lower mortality. Treatment aims at reestablishing circulation within a “central” compartment (i.e., brain, heart, and lung but fails to reestablish a disorganized microcirculation or an adequate response to noradrenaline, the most widely used vasopressor. Indeed, steroids, nitric oxide synthase inhibitors, or donors have not achieved overwhelming acceptance in the setting of septic shock. Counterintuitively, α2-adrenoceptor agonists were shown to reduce noradrenaline requirements in two cases of human septic shock. This has been replicated in rat and sheep models of sepsis. In addition, some data show that α2-adrenoceptor agonists lead to an improvement in the microcirculation. Evidence-based documentation of the effects of alpha-2 agonists is needed in the setting of human septic shock.

  9. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

    Science.gov (United States)

    Rhodes, Andrew; Evans, Laura E; Alhazzani, Waleed; Levy, Mitchell M; Antonelli, Massimo; Ferrer, Ricard; Kumar, Anand; Sevransky, Jonathan E; Sprung, Charles L; Nunnally, Mark E; Rochwerg, Bram; Rubenfeld, Gordon D; Angus, Derek C; Annane, Djillali; Beale, Richard J; Bellinghan, Geoffrey J; Bernard, Gordon R; Chiche, Jean-Daniel; Coopersmith, Craig; De Backer, Daniel P; French, Craig J; Fujishima, Seitaro; Gerlach, Herwig; Hidalgo, Jorge Luis; Hollenberg, Steven M; Jones, Alan E; Karnad, Dilip R; Kleinpell, Ruth M; Koh, Younsuck; Lisboa, Thiago Costa; Machado, Flavia R; Marini, John J; Marshall, John C; Mazuski, John E; McIntyre, Lauralyn A; McLean, Anthony S; Mehta, Sangeeta; Moreno, Rui P; Myburgh, John; Navalesi, Paolo; Nishida, Osamu; Osborn, Tiffany M; Perner, Anders; Plunkett, Colleen M; Ranieri, Marco; Schorr, Christa A; Seckel, Maureen A; Seymour, Christopher W; Shieh, Lisa; Shukri, Khalid A; Simpson, Steven Q; Singer, Mervyn; Thompson, B Taylor; Townsend, Sean R; Van der Poll, Thomas; Vincent, Jean-Louis; Wiersinga, W Joost; Zimmerman, Janice L; Dellinger, R Phillip

    2017-03-01

    To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

  10. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

    Science.gov (United States)

    Rhodes, Andrew; Evans, Laura E; Alhazzani, Waleed; Levy, Mitchell M; Antonelli, Massimo; Ferrer, Ricard; Kumar, Anand; Sevransky, Jonathan E; Sprung, Charles L; Nunnally, Mark E; Rochwerg, Bram; Rubenfeld, Gordon D; Angus, Derek C; Annane, Djillali; Beale, Richard J; Bellinghan, Geoffrey J; Bernard, Gordon R; Chiche, Jean-Daniel; Coopersmith, Craig; De Backer, Daniel P; French, Craig J; Fujishima, Seitaro; Gerlach, Herwig; Hidalgo, Jorge Luis; Hollenberg, Steven M; Jones, Alan E; Karnad, Dilip R; Kleinpell, Ruth M; Koh, Younsuk; Lisboa, Thiago Costa; Machado, Flavia R; Marini, John J; Marshall, John C; Mazuski, John E; McIntyre, Lauralyn A; McLean, Anthony S; Mehta, Sangeeta; Moreno, Rui P; Myburgh, John; Navalesi, Paolo; Nishida, Osamu; Osborn, Tiffany M; Perner, Anders; Plunkett, Colleen M; Ranieri, Marco; Schorr, Christa A; Seckel, Maureen A; Seymour, Christopher W; Shieh, Lisa; Shukri, Khalid A; Simpson, Steven Q; Singer, Mervyn; Thompson, B Taylor; Townsend, Sean R; Van der Poll, Thomas; Vincent, Jean-Louis; Wiersinga, W Joost; Zimmerman, Janice L; Dellinger, R Phillip

    2017-03-01

    To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

  11. Mortality predictors in renal transplant recipients with severe sepsis and septic shock.

    Science.gov (United States)

    de Carvalho, Mônica Andrade; Freitas, Flávio Geraldo Rezende; Silva Junior, Hélio Tedesco; Bafi, Antônio Toneti; Machado, Flávia Ribeiro; Pestana, José Osmar Medina

    2014-01-01

    The growing number of renal transplant recipients in a sustained immunosuppressive state is a factor that can contribute to increased incidence of sepsis. However, relatively little is known about sepsis in this population. The aim of this single-center study was to evaluate the factors associated with hospital mortality in renal transplant patients admitted to the intensive care unit (ICU) with severe sepsis and septic shock. Patient demographics and transplant-related and ICU stay data were retrospectively collected. Multiple logistic regression was conducted to identify the independent risk factors associated with hospital mortality. A total of 190 patients were enrolled, 64.2% of whom received kidneys from deceased donors. The mean patient age was 51 ± 13 years (males, 115 [60.5%]), and the median APACHE II was 20 (16-23). The majority of patients developed sepsis late after the renal transplantation (2.1 [0.6-2.3] years). The lung was the most common infection site (59.5%). Upon ICU admission, 16.4% of the patients had ≤ 1 systemic inflammatory response syndrome criteria. Among the patients, 61.5% presented with ≥ 2 organ failures at admission, and 27.9% experienced septic shock within the first 24 hours of ICU admission. The overall hospital mortality rate was 38.4%. In the multivariate analysis, the independent determinants of hospital mortality were male gender (OR = 5.9; 95% CI, 1.7-19.6; p = 0.004), delta SOFA 24 h (OR = 1.7; 95% CI, 1.2-2.3; p = 0.001), mechanical ventilation (OR = 30; 95% CI, 8.8-102.2; prenal transplant patients with severe sepsis and septic shock was associated with male gender, admission from the wards, worse SOFA scores on the first day and the presence of hematologic dysfunction, mechanical ventilation or advanced graft dysfunction.

  12. Septic shock in pregnancy due to pyogenic sacroiliitis: a case report

    Directory of Open Access Journals (Sweden)

    Moros María Lapresta

    2009-03-01

    Full Text Available Abstract Introduction Lower back pain due to sacroiliac joint dysfunction is a common symptom during pregnancy. However, infection of the sacroiliac joint is rare, even more so if no predisposing factors are present. Case presentation After the onset of unspecific acute pain in the left buttock region, a 31-year-old pregnant woman developed septic shock due to pyogenic sacroiliitis. The medical and obstetric management, treatment applied and patient's experience are described. Conclusion The correct diagnosis and treatment of pyogenic sacroiliitis during pregnancy may avoid joint and bone destruction in addition to maternal and fetal complications.

  13. Comparison of Hydroxocobalamin Versus Norepinephrine Versus Saline in a Swine Model of Servere Septic Shock

    Science.gov (United States)

    2016-05-20

    Versus Saline in a Swine Model of Severe Septic Shock presented at/published to SURF Conference, San Antonio, TX 20 May 2016 with MDWJ 41-108, and has...of Wilford Hall Ambulatory Surgical Center (WHASC) internship and residency programs. 3. Please know that if you are a Graduate Health Sciences...must complete page two of this form: a. In Section 2, add the funding source for your study (e.g., S9 MOW CRD Graduate Health Sciences Education (GHSE

  14. Acute Neonatal Parotitis with Late-Onset Septic Shock due to Streptococcus agalactiae

    Directory of Open Access Journals (Sweden)

    M. Boulyana

    2014-01-01

    Full Text Available Acute neonatal parotitis (ANP is a very rare disease. Most cases are managed conservatively; early antibiotics and adequate hydration may reduce the need for surgery. The most common cause of ANP is Staphylococcus aureus. We report a rare case of acute neonatal parotitis with late-onset septic shock due to Streptococcus agalactiae. The diagnosis was confirmed with ultrasound and isolation of Streptococcus agalactiae from blood culture. The patient was treated successfully with 10 days of intravenous antibiotics and supportive measures. Despite being rare, streptococcal ANP should be considered in the etiological diagnosis of neonatal sepsis. Early diagnosis and appropriate antibiotic might prevent serious complications.

  15. Is there any role for terlipressin in the extremely low birth weight infant with refractory septic shock?

    Directory of Open Access Journals (Sweden)

    Francesca Bissolo

    2012-10-01

    Full Text Available Terlipressin, a synthetic long-acting analogue of vasopressin, has been investigated as a second line vasopressor in adults and children with refractory septic shock, i.e. not responding to fluid resuscitation and high-dose catecholamine administration. Little experience is available about the safety and efficacy of terlipressin in term and preterm newborns. We report the case of an extremely low birth weight infant with severe septic shock, unresponsive to fluids, noradrenalin and hydrocortisone, in whom terlipressin was attempted as a rescue drug. Despite three doses of terlipressin, administered 6-hourly, the patient remained profoundly hypotensive and eventually died. Further studies are required before any recommendation on the use of terlipressin in term or preterm newborns with septic shock can be made.

  16. Influenza A/H1N1 septic shock in a patient with systemic lupus erythematosus. A case report

    Directory of Open Access Journals (Sweden)

    Tselios Konstantinos

    2011-12-01

    Full Text Available Abstract Background Immunocompromised patients, such as systemic lupus erythematosus (SLE sufferers have an increased risk of mortality, following influenza infection. In the recent pandemic, influenza A H1NI virus caused 18449 deaths, mainly because of adult respiratory distress syndrome or bacterial co-infections. Case Presentation In this case report, an SLE patient with viral-induced septic shock, without overt pulmonary involvement, is discussed. The patient was administered oseltamivir and supportive treatment, including wide-spectrum antibiotics, vasopressors and steroids, according to the guidelines proposed for bacterial sepsis and septic shock. She finally survived and experienced a lupus flare soon after intensive care unit (ICU discharge. Conclusions To our knowledge, this is the first case to report severe septic shock from influenza A/H1N1 virus, without overt pulmonary involvement.

  17. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

    Science.gov (United States)

    Singer, Mervyn; Deutschman, Clifford S.; Seymour, Christopher Warren; Shankar-Hari, Manu; Annane, Djillali; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon R.; Chiche, Jean-Daniel; Coopersmith, Craig M.; Hotchkiss, Richard S.; Levy, Mitchell M.; Marshall, John C.; Martin, Greg S.; Opal, Steven M.; Rubenfeld, Gordon D.; van der Poll, Tom; Vincent, Jean-Louis; Angus, Derek C.

    2016-01-01

    IMPORTANCE Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. OBJECTIVE To evaluate and, as needed, update definitions for sepsis and septic shock. PROCESS A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). KEY FINDINGS FROMEVIDENCE SYNTHESIS Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. RECOMMENDATIONS Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a

  18. Prognostic impact of isolated right ventricular dysfunction in sepsis and septic shock: an 8-year historical cohort study.

    Science.gov (United States)

    Vallabhajosyula, Saraschandra; Kumar, Mukesh; Pandompatam, Govind; Sakhuja, Ankit; Kashyap, Rahul; Kashani, Kianoush; Gajic, Ognjen; Geske, Jeffrey B; Jentzer, Jacob C

    2017-09-07

    Echocardiographic myocardial dysfunction is reported commonly in sepsis and septic shock, but there are limited data on sepsis-related right ventricular dysfunction. This study sought to evaluate the association of right ventricular dysfunction with clinical outcomes in patients with severe sepsis and septic shock. Historical cohort study of adult patients admitted to all intensive care units at the Mayo Clinic from January 1, 2007 through December 31, 2014 for severe sepsis and septic shock, who had an echocardiogram performed within 72 h of admission. Patients with prior heart failure, cor-pulmonale, pulmonary hypertension and valvular disease were excluded. Right ventricular dysfunction was defined by the American Society of Echocardiography criteria. Outcomes included 1-year survival, in-hospital mortality and length of stay. Right ventricular dysfunction was present in 214 (55%) of 388 patients who met the inclusion criteria-isolated right ventricular dysfunction was seen in 100 (47%) and combined right and left ventricular dysfunction in 114 (53%). The baseline characteristics were similar between cohorts except for the higher mechanical ventilation use in patients with isolated right ventricular dysfunction. Echocardiographic findings demonstrated lower right ventricular and tricuspid valve velocities in patients with right ventricular dysfunction and lower left ventricular ejection fraction and increased mitral E/e' ratios in patients with combined right and left ventricular dysfunction. After adjustment for age, comorbidity, illness severity, septic shock and use of mechanical ventilation, isolated right ventricular dysfunction was independently associated with worse 1-year survival-hazard ratio 1.6 [95% confidence interval 1.2-2.1; p = 0.002) in patients with sepsis and septic shock. Isolated right ventricular dysfunction is seen commonly in sepsis and septic shock and is associated with worse long-term survival.

  19. The epidemiology of adults with severe sepsis and septic shock in Scottish emergency departments.

    Science.gov (United States)

    Gray, Alasdair; Ward, Kirsty; Lees, Fiona; Dewar, Colin; Dickie, Sarah; McGuffie, Crawford

    2013-05-01

    The Surviving Sepsis Campaign (SSC) promotes a bundle approach to the care of septic patients to improve outcome. Some have questioned the capability of delivering the bundle in emergency departments (EDs). The authors report the epidemiology and 6 h bundle compliance of patients with severe sepsis/septic shock presenting to Scottish EDs. Analysis of the previously reported Scottish Trauma Audit Group sepsis database was performed including 20 mainland Scottish EDs. A total of 308,910 attendances were screened (between 2 March and 31 May 2009), and 5285 of 27,046 patients were identified after case note review and included on the database. This analysis includes patients who had severe sepsis/septic shock before leaving the ED. Epidemiological, severity of illness criteria, and ED management data were analysed. 626 patients (median age 73; M/F ratio 1:1; 637 presentations) met entrance criteria. The median number of cases per site was 16 (range 3-103). 561 (88.1%) patients arrived by ambulance. The most common source of infection was the respiratory tract (n=411, 64.5%) The most common physiological derangements were heart rate (n=523, 82.1%), respiratory rate (n=452, 71%) and white cell count (n=432, 67.8%). The median hospital stay was 9 days (IQR 4-17 days). 201 (31.6%) patients were admitted to critical care within 2 days, 130 (20.4%) directly from the ED. 180 patients (28.3%) died. There was poor compliance with all aspect of the SSC resuscitation bundle. Sepsis presentations are of variable frequency but have typical epidemiology and clinical outcomes. SSC bundle resuscitation uptake is poor in Scottish EDs.

  20. Experimental models of acute infection and Toll-like receptor driven septic shock.

    Science.gov (United States)

    Ferstl, Ruth; Spiller, Stephan; Fichte, Sylvia; Dreher, Stefan; Kirschning, Carsten J

    2009-01-01

    Mainly Gram-negative and Gram-positive bacterial infections, but also other infections such as with fungal or viral pathogens, can cause the life-threatening clinical condition of septic shock. Transgression of the host immune response from a local level limited to the pathogen's place of entry to the systemic level is recognised as a major mode of action leading to sepsis. This view has been established upon demonstration of the capacity of specific pathogen-associated molecular patterns (PAMPs) to elicit symptoms of septic shock upon systemic administration. Immune stimulatory PAMPs are agonists of soluble, cytoplasmic, as well as/or cell membrane-anchored and/or -spanning pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs). However, reflection of pathogen-host crosstalk triggering sepsis pathogenesis upon an infection by a host response to challenge with an isolated PAMP is incomplete. Therefore, an experimental model more reflective of pathogen-host interaction requires experimental host confrontation with a specific pathogen in its viable form resulting in a collective stimulation of a variety of specific PRRs. This chapter describes methods to analyse innate pathogen sensing by the host on both a cellular and systemic level.

  1. Cost analysis of real-time polymerase chain reaction microbiological diagnosis in patients with septic shock.

    Science.gov (United States)

    Alvarez, J; Mar, J; Varela-Ledo, E; Garea, M; Matinez-Lamas, L; Rodriguez, J; Regueiro, B

    2012-11-01

    Antibiotic treatment for septic shock is generally prescribed on an empirical basis using broad-spectrum antibiotics. Molecular diagnostic techniques can detect the presence of microbial DNA in blood within a few hours and facilitate early, targeted treatment. The aim of this study was to evaluate the economic impact of a real-time polymerase chain reaction technique, LightCycler SeptiFast (LSC), in patients with sepsis. A cost-minimisation study was carried out in patients admitted with a diagnosis of severe sepsis or septic shock to the intensive care unit of a university hospital. The stay in the intensive care unit, hospital admission, 28-day and six-month mortality, and the economic cost of the clinical process were also evaluated. The study involved 48 patients in the LSC group and 54 patients in the control group. The total cost was €42,198 in the control group versus €32,228 in the LCS group with statistically significant differences (P average net saving of €9970 per patient. The mortality rate was similar in both groups. The main finding of this study was the significant economic saving afforded by the use of the LCS technique, due to the shortening of intensive care unit stay and the use of fewer antibiotics.

  2. Central venous pressure and shock index predict lack of hemodynamic response to volume expansion in septic shock: a prospective, observational study.

    Science.gov (United States)

    Lanspa, Michael J; Brown, Samuel M; Hirshberg, Eliotte L; Jones, Jason P; Grissom, Colin K

    2012-12-01

    Volume expansion is a common therapeutic intervention in septic shock, although patient response to the intervention is difficult to predict. Central venous pressure (CVP) and shock index have been used independently to guide volume expansion, although their use is questionable. We hypothesize that a combination of these measurements will be useful. In a prospective, observational study, patients with early septic shock received 10-mL/kg volume expansion at their treating physician's discretion after brief initial resuscitation in the emergency department. Central venous pressure and shock index were measured before volume expansion interventions. Cardiac index was measured immediately before and after the volume expansion using transthoracic echocardiography. Hemodynamic response was defined as an increase in a cardiac index of 15% or greater. Thirty-four volume expansions were observed in 25 patients. A CVP of 8 mm Hg or greater and a shock index of 1 beat min(-1) mm Hg(-1) or less individually had a good negative predictive value (83% and 88%, respectively). Of 34 volume expansions, the combination of both a high CVP and a low shock index was extremely unlikely to elicit hemodynamic response (negative predictive value, 93%; P = .02). Volume expansion in patients with early septic shock with a CVP of 8 mm Hg or greater and a shock index of 1 beat min(-1) mm Hg(-1) or less is unlikely to lead to an increase in cardiac index. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012.

    Science.gov (United States)

    Dellinger, R P; Levy, Mitchell M; Rhodes, Andrew; Annane, Djillali; Gerlach, Herwig; Opal, Steven M; Sevransky, Jonathan E; Sprung, Charles L; Douglas, Ivor S; Jaeschke, Roman; Osborn, Tiffany M; Nunnally, Mark E; Townsend, Sean R; Reinhart, Konrad; Kleinpell, Ruth M; Angus, Derek C; Deutschman, Clifford S; Machado, Flavia R; Rubenfeld, Gordon D; Webb, Steven; Beale, Richard J; Vincent, Jean-Louis; Moreno, Rui

    2013-02-01

    To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Recommendations were classified into three groups: (1) those directly targeting severe sepsis; (2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and (3) pediatric considerations. Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 h of the recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B

  4. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012.

    Science.gov (United States)

    Dellinger, R Phillip; Levy, Mitchell M; Rhodes, Andrew; Annane, Djillali; Gerlach, Herwig; Opal, Steven M; Sevransky, Jonathan E; Sprung, Charles L; Douglas, Ivor S; Jaeschke, Roman; Osborn, Tiffany M; Nunnally, Mark E; Townsend, Sean R; Reinhart, Konrad; Kleinpell, Ruth M; Angus, Derek C; Deutschman, Clifford S; Machado, Flavia R; Rubenfeld, Gordon D; Webb, Steven A; Beale, Richard J; Vincent, Jean-Louis; Moreno, Rui

    2013-02-01

    To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Some recommendations were ungraded (UG). Recommendations were classified into three groups: 1) those directly targeting severe sepsis; 2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and 3) pediatric considerations. Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 hr of recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de

  5. Central venous oxygen saturation in septic shock - a marker of cardiac output, microvascular shunting and/or dysoxia?

    DEFF Research Database (Denmark)

    Haase, Nicolai; Perner, Anders

    2011-01-01

    Shock therapy aims at increasing central venous oxygen saturation (ScvO2), which is a marker of inadequate oxygen delivery. In this issue of Critical Care, Textoris and colleagues challenge this notion by reporting that high levels of ScvO2 are associated with mortality in patients with septic sh...

  6. Arterial bicarbonate may be a useful indicator of inadequate cortisol response in children with catecholamine resistant septic shock

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    M B Maralihalli

    2013-01-01

    Full Text Available Objective: To study the clinical and biochemical parameters that can predict cortisol insufficiency in children with septic shock. Design: prospective, observational study. Setting: tertiary health-care center. Patients/Subjects: Fifty children admitted with the catecholamine resistant septic shock to a tertiary health-care center. Materials and Methods: At the time of hospitalization all patients underwent detailed clinical evaluation including, history and physical examination, evaluation with the complete blood count, serum cortisol, renal function tests, liver function tests, prothrombin time activated partial thromboplastin time, arterial blood gas analysis, urine analysis, chest roentgenogram, ultrasonography of the abdomen and chest, urine, and blood culture for bacteria and fungi. Results: Out of 50 children with the catecholamine resistant septic shock, seven had adrenal insufficiency (serum cortisol <18 μg/dl. Of all parameters studied, only arterial bicarbonate at the time of admission to intensive care predicted adrenal insufficiency. On Receptor operative characteristic curve analysis, a bicarbonate level of 10.9 mEq/L had the best accuracy to predict adrenal insufficiency. Conclusion: Arterial bicarbonate may be used as a rapid test for provisional identification of adrenal insufficiency among children with the catecholamine resistant septic shock.

  7. [Management of severe sepsis and septic shock in a tertiary care urban hospital emergency department: opportunities for improvement].

    Science.gov (United States)

    Monclús Cols, Ester; Capdevila Reniu, Aina; Roedberg Ramos, Desirée; Pujol Fontrodona, Gabriel; Ortega Romero, Mar

    2016-01-01

    To describe the characteristics of early management of severe sepsis and septic shock in a hospital emergency department that does not have a specific triage category to identify patients in these states. To determine opportunities for improvement. Prospective cohort study from March 2014 to March 2015. On each day during the study period, we included the first patient with signs compatible with septic shock. We recorded the severity level assigned according to the Andorran Triage Model and the main clinical and epidemiological variables. Patients were followed until hospital discharge. Fifty patients (35 men) with septic shock (mean age 65 years) were included. Thirty-five were at triage level 1 or 2 and 15 were at level 3. Patients initially classified as level 1-2 had significantly higher heart rates than level 3 patients (mean 110 vs 90 bpm, respectively; P=.003) and respiratory rates (mean 27 vs 18 breaths per minute; P=.001). Patients classified as level 1-2 also had significantly shorter care times than level 3 patients: time from arrival to examination room entry, 18 vs 117 minutes, respectively (P=.002); time from arrival to the first antibiotic dose (85 vs 231 minutes (P=.001). Medical care for patients with septic shock in this emergency department needs to improve in terms of earlier diagnosis and better compliance with guidelines for initial therapeutic management.

  8. Self-esteem in children and adolescents after septic shock caused by Neisseria meningitidis: scars do matter

    NARCIS (Netherlands)

    Vermunt, Lindy C.; Buysse, Corinne M.; Joosten, Koen F.; Oranje, Arnold P.; Hazelzet, Jan A.; Verhulst, Frank C.; Utens, Elisabeth M.

    2008-01-01

    To investigate self-esteem and its relation to scars, amputations, and orthopedic sequelae in children and adolescents long term after meningococcal septic shock (MSS) caused by Neisseria meningitidis. The Dutch versions of the Self-Perception Profile for Children (SPP-C; 8-11 years) and the

  9. Immediate effects of chest physiotherapy on hemodynamic, metabolic, and oxidative stress parameters in subjects with septic shock.

    Science.gov (United States)

    dos Santos, Rafael S; Donadio, Márcio V F; da Silva, Gabriela V; Blattner, Clarissa N; Melo, Denizar A S; Nunes, Fernanda B; Dias, Fernando S; Squizani, Eamim D; Pedrazza, Leonardo; Gadegast, Isabella; de Oliveira, Jarbas R

    2014-09-01

    Septic shock presents as a continuum of infectious events, generating tissue hypoxia and hypovolemia, and increased oxidative stress. Chest physiotherapy helps reduce secretion, improving dynamic and static compliance, as well as improving secretion clearance and preventing pulmonary complications. The purpose of this study was to evaluate the immediate effect of chest physiotherapy on hemodynamic, metabolic, inflammatory, and oxidative stress parameters in subjects in septic shock. We conducted a quasi-experimental study in 30 subjects in septic shock, who underwent chest physiotherapy, without associated heart diseases and with vasopressors stress were evaluated before and 15 min after physiotherapy. Thirty subjects with a mean age of 61.8 ± 15.9 y and Sequential Organ Failure Assessment of 8 (range 6-10) were included. Chest physiotherapy caused a normalization of pH (P = .046) and P(aCO2) (P = .008); reduction of lactate (P = .001); and an increase in P(aO2) (P = .03), arterial oxygen saturation (P = .02), and P(aO2)/F(IO2) (P = .034), 15 min after it was applied. The results indicate that chest physiotherapy has immediate effects, improving oxygenation and reducing lactate and oxidative damage in subjects in septic shock. However, it does not cause alterations in the inflammatory and hemodynamic parameters. Copyright © 2014 by Daedalus Enterprises.

  10. Epidemiology, Prognosis, and Evolution of Management of Septic Shock in a French Intensive Care Unit: A Five Years Survey

    Directory of Open Access Journals (Sweden)

    Nicolas Boussekey

    2010-01-01

    Full Text Available Purpose. To evaluate the epidemiology, prognosis, and management of septic shock patients hospitalized in our intensive care unit (ICU. Materiel and Methods. Five-year monocenter observational study including 320 patients. Results. ICU mortality was 54.4%. Independent mortality risk factors were mechanical ventilation (OR=4.97, Simplify Acute Physiology Score (SAPS II > 60 (OR=4.28, chronic alcoholism (OR=3.38, age >65 years (OR=2.65, prothrombin ratio <40% (OR=2.37, and PaO2/FiO2 ratio <150 (OR=1.91. These six mortality risk factors recovered allow screening immediately septic shock patients with a high mortality risk. Morbidity improved with time (diminution of septic shock complications, increase of the number of days alive free from mechanical ventilation and vasopressors on day 28, concomitant to an evolution of the management (earlier institution of all replacement and medical therapies and more initial volume expansion. There was no difference in mortality. Conclusion. Our study confirms a high mortality rate in septic shock patients despite a new approach of treatment.

  11. Hospital staff education on severe sepsis/septic shock and hospital mortality: an original hypothesis

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    Capuzzo Maurizia

    2012-11-01

    Full Text Available Abstract Background Signs of serious clinical events overlap with those of sepsis. We hypothesised that any education on severe sepsis/septic shock may affect the outcome of all hospital patients. We designed this study to assess the trend of the mortality rate of adults admitted to hospital for at least one night in relationship with a hospital staff educational program dedicated to severe sepsis/septic shock. Methods This study was performed in six Italian hospitals in the same region. Multidisciplinary Sepsis Teams members were selected by each hospital management among senior staff. The education included the following steps: i the Teams were taught about adult learning, problem based learning, and Surviving Sepsis guidelines, and provided with educational material (literature, electronic presentations, scenarios of clinical cases for training and booklets; ii they started delivering courses and seminars each to their own hospital staff in the last quarter of 2007. To analyse mortality, we selected adult patients, admitted for at least one night to the wards or units present in all the study hospitals and responsible for 80% of hospital deaths. We fitted a Poisson model with monthly hospital mortality rates from December 2003 to August 2009 as dependent variable. The effect of the educational program on hospital mortality was measured as two dummy variables identifying a first (November 2007 to December 2008 and a second (January to August 2009 education period. The analysis was adjusted for a linear time trend, seasonality and monthly average values of age, Charlson score, length of stay in hospital and urgent/non-urgent admission. Results The hospital staff educated reached 30.6% at the end of June 2009. In comparison with the pre-education period, the Relative Risk of death of the patient population considered was 0.93 (95% confidence interval [CI] 0.87-0.99; p 0.025 for in-patients in the first, and 0.89 (95% CI 0.81-0.98; p 0.012 for

  12. Clinical effect of alprostadil in patients with septic shock associated with acute respiratory distress syndrome

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    Li-ping LIU

    2017-10-01

    Full Text Available Objective To evaluate the clinical efficacy of alprostadil in patients with septic shock associated with acute respiratory distress syndrome (ARDS, and to explore its possible mechanism. Methods From January 2015 to June 2016, patients with septic shock associated with ARDS and meeting the inclusion criteria were involved in the study in department of critical care medicine in First Hospital of Lanzhou University and randomly divided into the control group and alprostadil group. The standard treatment was given in control group, alprostadil 10μg 2/d was given in alprostadil group on base of standard treatment. Monitoring indexes were recorded in 1, 3 and 6 days after enrollment. General condition of patients, APACHE Ⅱ score, ventilator conditions (PO2, PCO2, RR, PEEP, FiO2, oxygenation index, airway resistance, lung compliance, mechanical ventilation time, ICU stay time, hospital follow-up, 28-day follow-up, immune index (CD4+/CD8+, inflammatory markers (CRP, PCT, IL-6 were monitored. Results Sixty-five patients were included in this study, 32 in control group and 33 in alprostadil group. At 3 and 6 days after the treatment, APACHE Ⅱ score, respiratory rate (RR, the inspired oxygen concentration (FiO2, airway resistance, and C reactive protein (CRP, procalcitonin (PCT -6 and interleukin (IL-6 levels significantly decreased, compared with pretreatment and 1 day posttreatment, in the two groups and lower in alprostadil group than in the control group on the 6th day (P<0.05; at the same time, these indexes such as arterial partial pressure of oxygen (PaO2, lung compliance, oxygenation index, CD4+/CD8+ significantly increased 3 and 6 days after the treatment compared with pretreatment and 1 day posttreatment in the two groups, and on the 6th day, significantly higher in the alprostadil group than in the control group (P<0.05. Time of mechanical ventilation, ICU stay and hospital stay in the alprostadil group was respectively lower than that in

  13. Salivary Cortisol Can Replace Free Serum Cortisol Measurements in Patients With Septic Shock

    Science.gov (United States)

    Orlander, Philip R.

    2011-01-01

    Background: There is a renewed interest in adrenal function during severe sepsis. Most studies have used total serum cortisol levels; however, only free serum cortisol is biologically active. The aim of this study was to determine the validity of salivary cortisol levels as a surrogate for free serum cortisol levels during septic shock. Methods: Fifty-seven patients with septic shock were studied to determine the correlation between total serum cortisol and salivary cortisol to free serum cortisol levels. Thirty-eight patients were included in the salivary to free serum cortisol correlation. Salivary cortisol level was tested by enzyme immunoassay. Serum total cortisol, free cortisol, and cortisol-binding globulin (CBG) levels were determined by liquid chromatography-mass spectrometry, equilibrium analysis, and radioimmunoassay, respectively. Results: The mean ± SD age was 56.6 ± 18.5 years. Fifty-seven percent were women. APACHE (Acute Physiology and Chronic Health Evaluation) II score median was 26, Simplified Acute Physiology Score II median was 61, and Sequential Organ Failure Assessment median was 13. The correlation between salivary and free serum cortisol levels was 0.79 (95% CI, 0.63-0.89; P cortisol and total serum cortisol levels was 0.86 (95% CI, 0.78-0.92; P cortisol level was 2.27 ± 1.64 μg/dL. The mean ± SD salivary cortisol level was 2.60 ± 2.69 μg/dL. The mean ± SD total serum cortisol level was 21.56 ± 8.71 μg/dL. The mean ± SD CBG level was 23.54 ± 8.33 mg/dL. Conclusions: Salivary cortisol level can be used as a surrogate of free serum cortisol level in patients with septic shock with very good correlation. Salivary cortisol testing is noninvasive, easy to perform, and can be conducted daily. Trial registry: ClinicalTrials.gov; No.: NCT00523198; URL: www.clinicaltrials.gov PMID:21816912

  14. A Case of Invasive Pneumococcal Infection with Septic Shock and Rare Complications

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    John R. Woytanowski

    2017-01-01

    Full Text Available Invasive pneumococcus is a serious illness with potentially devastating outcomes. A 64-year-old female with a medical history of psoriatic arthritis and diabetes was transferred from an outside hospital for ventilator dependent respiratory failure and altered mental status. She initially presented with worsening back pain and was found to have leukocytosis with bandemia and acute renal failure but she was in septic shock upon arrival to our tertiary care center. Her blood cultures grew Streptococcus pneumoniae and MRI of the brain revealed pus within the posterior lateral ventricles and multiple infarcts. MRI of the spine revealed a psoas abscess. Transesophageal echocardiogram revealed mitral valve vegetation and her right eye developed endogenous endophthalmitis. She was treated with intravenous and intravitreal antibiotics and underwent drainage of the abscess with no improvement in mental status. Repeat imaging revealed multiple new thalamic, basal ganglia, and parietal lobe infarcts likely from septic emboli. After a protracted ICU stay, the patient’s family opted for comfort care. The incidence of invasive pneumococcal infections has declined rapidly since the advent of antibiotics and vaccines. With the growing incidence of antibiotic resistance as well as the emergence of new immunomodulating drugs for various pathologies, there is a concern that invasive infections will reemerge. Ventriculitis and endogenous endophthalmitis are very rare complications of pneumococcal bacteremia.

  15. The Role of Adjunctive Therapies in Septic Shock by Gram Negative MDR/XDR Infections.

    Science.gov (United States)

    Busani, Stefano; Roat, Erika; Serafini, Giulia; Mantovani, Elena; Biagioni, Emanuela; Girardis, Massimo

    2017-01-01

    Patients with septic shock by multidrug resistant microorganisms (MDR) are a specific sepsis population with a high mortality risk. The exposure to an initial inappropriate empiric antibiotic therapy has been considered responsible for the increased mortality, although other factors such as immune-paralysis seem to play a pivotal role. Therefore, beyond conventional early antibiotic therapy and fluid resuscitation, this population may benefit from the use of alternative strategies aimed at supporting the immune system. In this review we present an overview of the relationship between MDR infections and immune response and focus on the rationale and the clinical data available on the possible adjunctive immunotherapies, including blood purification techniques and different pharmacological approaches.

  16. The Role of Adjunctive Therapies in Septic Shock by Gram Negative MDR/XDR Infections

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    Stefano Busani

    2017-01-01

    Full Text Available Patients with septic shock by multidrug resistant microorganisms (MDR are a specific sepsis population with a high mortality risk. The exposure to an initial inappropriate empiric antibiotic therapy has been considered responsible for the increased mortality, although other factors such as immune-paralysis seem to play a pivotal role. Therefore, beyond conventional early antibiotic therapy and fluid resuscitation, this population may benefit from the use of alternative strategies aimed at supporting the immune system. In this review we present an overview of the relationship between MDR infections and immune response and focus on the rationale and the clinical data available on the possible adjunctive immunotherapies, including blood purification techniques and different pharmacological approaches.

  17. Basic and advanced echocardiographic evaluation of myocardial dysfunction in sepsis and septic shock.

    Science.gov (United States)

    Vallabhajosyula, S; Pruthi, S; Shah, S; Wiley, B M; Mankad, S V; Jentzer, J C

    2018-01-01

    Sepsis continues to be a leading cause of mortality and morbidity in the intensive care unit. Cardiovascular dysfunction in sepsis is associated with worse short- and long-term outcomes. Sepsis-related myocardial dysfunction is noted in 20%-65% of these patients and manifests as isolated or combined left or right ventricular systolic or diastolic dysfunction. Echocardiography is the most commonly used modality for the diagnosis of sepsis-related myocardial dysfunction. With the increasing use of ultrasonography in the intensive care unit, there is a renewed interest in sepsis-related myocardial dysfunction. This review summarises the current scope of literature focused on sepsis-related myocardial dysfunction and highlights the use of basic and advanced echocardiographic techniques for the diagnosis of sepsis-related myocardial dysfunction and the management of sepsis and septic shock.

  18. More complications in patients with septic shock treated with dextran compared with crystalloids

    DEFF Research Database (Denmark)

    Rasmussen, Anders Mølgaard; Peter Jakobsen, Rasmus; Strøm, Thomas

    2015-01-01

    INTRODUCTION: In recent years, the safety-profile of synthetic colloids has been questioned. The purpose of the present study was to elucidate the safety-profile of the colloid dextran-70 in relation to acute kidney injury (AKI) and death. METHODS: We conducted a retrospective, observational study...... of patients admitted to our intensive care unit with septic shock and treated with dextran-70 in the period from 1 January 2009 to 31 December 2009. The controls were included from 1 March 2012 to 28 February 2013 when dextran-70 was replaced with crystalloids. RESULTS: There were 91 patients in the dextran...... group and 150 patients in the non-dextran group. The urinary output was 17.93 ml/kg/24 h in the dextran group and 27.87 in the non-dextran group (p dextran group and in 23% in the non-dextran group (p

  19. Application of a simplified definition of diastolic function in severe sepsis and septic shock.

    Science.gov (United States)

    Lanspa, Michael J; Gutsche, Andrea R; Wilson, Emily L; Olsen, Troy D; Hirshberg, Eliotte L; Knox, Daniel B; Brown, Samuel M; Grissom, Colin K

    2016-08-04

    Left ventricular diastolic dysfunction is common in patients with severe sepsis or septic shock, but the best approach to categorization is unknown. We assessed the association of common measures of diastolic function with clinical outcomes and tested the utility of a simplified definition of diastolic dysfunction against the American Society of Echocardiography (ASE) 2009 definition. In this prospective observational study, patients with severe sepsis or septic shock underwent transthoracic echocardiography within 24 h of onset of sepsis (median 4.3 h). We measured echocardiographic parameters of diastolic function and used random forest analysis to assess their association with clinical outcomes (28-day mortality and ICU-free days to day 28) and thereby suggest a simplified definition. We then compared patients categorized by the ASE 2009 definition and our simplified definition. We studied 167 patients. The ASE 2009 definition categorized only 35 % of patients. Random forest analysis demonstrated that the left atrial volume index and deceleration time, central to the ASE 2009 definition, were not associated with clinical outcomes. Our simplified definition used only e' and E/e', omitting the other measurements. The simplified definition categorized 87 % of patients. Patients categorized by either ASE 2009 or our novel definition had similar clinical outcomes. In both definitions, worsened diastolic function was associated with increased prevalence of ischemic heart disease, diabetes, and hypertension. A novel, simplified definition of diastolic dysfunction categorized more patients with sepsis than ASE 2009 definition. Patients categorized according to the simplified definition did not differ from patients categorized according to the ASE 2009 definition in respect to clinical outcome or comorbidities.

  20. Thrombopoietin modulates cardiac contractility in vitro and contributes to myocardial depressing activity of septic shock serum.

    Science.gov (United States)

    Lupia, Enrico; Spatola, Tiziana; Cuccurullo, Alessandra; Bosco, Ornella; Mariano, Filippo; Pucci, Angela; Ramella, Roberta; Alloatti, Giuseppe; Montrucchio, Giuseppe

    2010-09-01

    Thrombopoietin (TPO) is a humoral growth factor that has been shown to increase platelet activation in response to several agonists. Patients with sepsis have increased circulating TPO levels, which may enhance platelet activation, potentially participating to the pathogenesis of multi-organ failure. Aim of this study was to investigate whether TPO affects myocardial contractility and participates to depress cardiac function during sepsis. We showed the expression of the TPO receptor c-Mpl on myocardial cells and tissue by RT-PCR, immunofluorescence and western blotting. We then evaluated the effect of TPO on the contractile function of rat papillary muscle and isolated heart. TPO did not change myocardial contractility in basal conditions, but, when followed by epinephrine (EPI) stimulation, it blunted the enhancement of contractile force induced by EPI both in papillary muscle and isolated heart. An inhibitor of TPO prevented TPO effect on cardiac inotropy. Treatment of papillary muscle with pharmacological inhibitors of phosphatidylinositol 3-kinase, NO synthase, and guanilyl cyclase abolished TPO effect, indicating NO as the final mediator. We finally studied the role of TPO in the negative inotropic effect exerted by human septic shock (HSS) serum and TPO cooperation with TNF-alpha and IL-1beta. Pre-treatment with the TPO inhibitor prevented the decrease in contractile force induced by HSS serum. Moreover, TPO significantly amplified the negative inotropic effect induced by TNF-alpha and IL-1beta in papillary muscle. In conclusion, TPO negatively modulates cardiac inotropy in vitro and contributes to the myocardial depressing activity of septic shock serum.

  1. Effects of a selective iNOS inhibitor versus norepinephrine in the treatment of septic shock.

    Science.gov (United States)

    Su, Fuhong; Huang, Hongchuan; Akieda, Kazuki; Occhipinti, Giovanna; Donadello, Katia; Piagnerelli, Michael; De Backer, Daniel; Vincent, Jean-Louis

    2010-09-01

    Inhibition of NOS is not beneficial in septic shock; selective inhibition of the inducible form (iNOS) may represent a better option. We compared the effects of the selective iNOS inhibitor BYK191023 with those of norepinephrine (NE) in a sheep model of septic shock. Twenty-four anesthetized, mechanically ventilated ewes received 1.5 g/kg body weight of feces into the abdominal cavity to induce sepsis. Animals were randomized into three groups (each n = 8): NE-only, BYK-only, and NE + BYK. The sublingual microcirculation was evaluated with sidestream dark-field videomicroscopy. MAP was higher in the NE + BYK group than in the other groups, but there were no significant differences in cardiac index or systemic vascular resistance. Mean pulmonary arterial pressure was lower in BYK-treated animals than in the NE-only group. PaO2/FiO2 was higher and lactate concentration lower in the BYK groups than in the NE-only group. Mesenteric blood flow was higher in BYK groups than in the NE-only group. Renal blood flow was higher in the NE + BYK group than in the other groups. Functional capillary density and proportion of perfused vessels were higher in the BYK groups than in the NE-only group 18 h after induction of peritonitis. Survival times were similar in the three groups. In this model of peritonitis, selective iNOS inhibition had more beneficial effects than NE on pulmonary artery pressures, gas exchange, mesenteric blood flow, microcirculation, and lactate concentration. Combination of this selective iNOS inhibitor with NE allowed a higher arterial pressure and renal blood flow to be maintained.

  2. ELABELA Improves Cardio-Renal Outcome in Fatal Experimental Septic Shock.

    Science.gov (United States)

    Coquerel, David; Chagnon, Frédéric; Sainsily, Xavier; Dumont, Lauralyne; Murza, Alexandre; Côté, Jérôme; Dumaine, Robert; Sarret, Philippe; Marsault, Éric; Salvail, Dany; Auger-Messier, Mannix; Lesur, Olivier

    2017-11-01

    Apelin-13 was recently proposed as an alternative to the recommended β-adrenergic drugs for supporting endotoxin-induced myocardial dysfunction. Since Apelin-13 signals through its receptor (Apelin peptide jejunum) to exert singular inotropic/vasotropic actions and to optimize body fluid balance, this candidate pathway might benefit septic shock management. Whether the newly discovered ELABELA (ELA), a second endogenous ligand of the Apelin peptide jejunum receptor highly expressed in the kidney, further improves cardio-renal impairment remains unknown. Interventional study in a rat model of septic shock (128 adult males) to assess the effects of ELA and Apelin-13 on vascular and cardio-renal function. Experiments were performed in a tertiary care University-based research institute. Polymicrobial sepsis-induced cardiac dysfunction was produced by cecal ligation puncture to assess hemodynamic efficacy, cardioprotection, and biomechanics under acute or continuous infusions of the apelinergic agonists ELA or Apelin-13 (39 and 15 µg/kg/hr, respectively) versus normal saline. Apelinergic agonists improved 72-hour survival after sepsis induction, with ELA providing the best clinical outcome after 24 hours. Apelinergic agonist infusion counteracted cecal ligation puncture-induced myocardial dysfunction by improving left ventricular pressure-volume relationship. ELA-treated cecal ligation puncture rats were the only group to 1) display a significant improvement in left ventricular filling as shown by increased E-wave velocity and left ventricular end-diastolic volume, 2) exhibit a higher plasma volume, and 3) limit kidney injury and free-water clearance. These beneficial renal effects were superior to Apelin-13, likely because full-length ELA enabled a distinctive regulation of pituitary vasopressin release. Activation of the apelinergic system by exogenous ELA or Apelin-13 infusion improves cardiovascular function and survival after cecal ligation puncture

  3. The Prevalence and Significance of Overt Disseminated Intravascular Coagulation in Patients with Septic Shock in the Emergency Department According to the Third International Consensus Definition

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    Byuk Sung Ko

    2016-11-01

    Full Text Available Background The prevalence and prognostic value of overt disseminated intravascular coagulation (DIC in patients with septic shock presenting to emergency departments (EDs is poorly understood, particularly following the release of a new definition of septic shock. The purpose of this study was to investigate the prevalence and prognostic value of DIC in septic shock. Methods We performed retrospective review of 391 consecutive patients with septic shock admitting to the ED of tertiary care, university-affiliated hospital during a 16-month. Septic shock was defined as fluid-unresponsive hypotension requiring vasopressor to maintain a mean arterial pressure of 65 mmHg or greater, and serum lactate level ≥ 2 mmol/L. Overt DIC was defined as an International Society on Thrombosis and Hemostasis (ISTH score ≥ 5 points. The primary endpoint was 28-day mortality. Results Of 391 patients with septic shock, 290 were included in the present study. The mean age was 65.6 years, the 28-day mortality rate was 26.9%, and the prevalence of overt DIC was 17.6% (n = 51 according to the ISTH score. The median DIC score was higher in non-survivors than in survivors (5.0 vs. 2.0, p = 0.001. Significant higher risk of mortality was observed in overt DIC patients compared to those without (28.2% vs. 13.7%, p = 0.005. Multivariable logistic regression analysis identified DIC to be independently associated with 28-day mortality (odds ratio, 2.689 [95% confidence interval, 1.390-5.201]. Conclusions Using the ISTH criteria of DIC, overt DIC in septic shock was found to be common among patients admitting to the ED and to be associated with higher mortality when it is accompanied with septic shock. Efforts are required to identify presence of overt DIC during the initial treatment of septic shock in patients presenting the the ED.

  4. Clostridium sordellii as a Cause of Fatal Septic Shock in a Child with Hemolytic Uremic Syndrome

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    Rebekah Beyers

    2014-01-01

    Full Text Available Clostridium sordellii is a toxin producing ubiquitous gram-positive anaerobe, mainly associated with trauma, soft tissue skin infections, and gynecologic infection. We report a unique case of a new strain of Clostridium sordellii (not present in the Center for Disease Control (CDC database infection induced toxic shock syndrome in a previously healthy two-year-old male with colitis-related hemolytic uremic syndrome (HUS. The patient presented with dehydration, vomiting, and bloody diarrhea. He was transferred to the pediatric critical care unit (PICU for initiation of peritoneal dialysis (PD. Due to increased edema and intolerance of PD, he was transitioned to hemodialysis through a femoral vascular catheter. He subsequently developed severe septic shock with persistent leukocytosis and hypotension, resulting in subsequent death. Stool culture confirmed Shiga toxin producing Escherichia coli 0157:H7. A blood culture was positively identified for Clostridium sordellii. Clostridium sordelli is rarely reported in children; to our knowledge this is the first case described in a pediatric patient with HUS.

  5. Aminoglycosides in septic shock: an overview, with specific consideration given to their nephrotoxic risk.

    Science.gov (United States)

    Boyer, Alexandre; Gruson, Didier; Bouchet, Stéphane; Clouzeau, Benjamin; Hoang-Nam, Bui; Vargas, Frédéric; Gilles, Hilbert; Molimard, Mathieu; Rogues, Anne-Marie; Moore, Nicholas

    2013-04-01

    Aminoglycoside nephrotoxicity has been reported in patients with sepsis, and several risk factors have been described. Once-daily dosing and shorter treatment have reduced nephrotoxicity risk, and simplified aminoglycoside monitoring. This review focuses on nephrotoxicity associated with aminoglycosides in the subset of patients with septic shock or severe sepsis. These patients are radically different from those with less severe sepsis. They may have, for instance, renal impairment due to the shock per se, sepsis-related acute kidney injury, frequent association with pre-existing risk factors for renal failure such as diabetes, dehydration and other nephrotoxic treatments. In this category of patients, these risk factors might modify substantially the benefit-risk ratio of aminoglycosides. In addition, aminoglycoside administration in critically ill patients with sepsis is complicated by an extreme inter- and intra-individual variability in drug pharmacokinetic/pharmacodynamic characteristics: the volume of distribution (Vd) is frequently increased while the elimination constant can be either increased or decreased. Consequently, and although its effect on nephrotoxicity has not been explored, a different administration schedule, i.e. a high-dose once daily (HDOD), and several therapeutic drug monitoring (TDM) options have been proposed in these patients. This review describes the historical perspective of these different options, including those applying to subsets of patients in which aminoglycoside administration is even more complex (obese intensive care unit [ICU] patients, patients needing continuous or discontinuous renal replacement therapy [CRRT/DRRT]). A simple linear dose adjustment according to aminoglycoside serum concentration can be classified as low-intensity TDM. Nomograms have also been proposed, based on the maximum (peak) plasma concentration (Cmax) objectives, weight and creatinine clearance. The Sawchuk and Zaske method (based on the

  6. An Innovative Approach for The Integration of Proteomics and Metabolomics Data In Severe Septic Shock Patients Stratified for Mortality.

    Science.gov (United States)

    Cambiaghi, Alice; Díaz, Ramón; Martinez, Julia Bauzá; Odena, Antonia; Brunelli, Laura; Caironi, Pietro; Masson, Serge; Baselli, Giuseppe; Ristagno, Giuseppe; Gattinoni, Luciano; de Oliveira, Eliandre; Pastorelli, Roberta; Ferrario, Manuela

    2018-04-27

    In this work, we examined plasma metabolome, proteome and clinical features in patients with severe septic shock enrolled in the multicenter ALBIOS study. The objective was to identify changes in the levels of metabolites involved in septic shock progression and to integrate this information with the variation occurring in proteins and clinical data. Mass spectrometry-based targeted metabolomics and untargeted proteomics allowed us to quantify absolute metabolites concentration and relative proteins abundance. We computed the ratio D7/D1 to take into account their variation from day 1 (D1) to day 7 (D7) after shock diagnosis. Patients were divided into two groups according to 28-day mortality. Three different elastic net logistic regression models were built: one on metabolites only, one on metabolites and proteins and one to integrate metabolomics and proteomics data with clinical parameters. Linear discriminant analysis and Partial least squares Discriminant Analysis were also implemented. All the obtained models correctly classified the observations in the testing set. By looking at the variable importance (VIP) and the selected features, the integration of metabolomics with proteomics data showed the importance of circulating lipids and coagulation cascade in septic shock progression, thus capturing a further layer of biological information complementary to metabolomics information.

  7. Statistical analysis plan for the Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock (ADRENAL) trial

    DEFF Research Database (Denmark)

    Billot, Laurent; Venkatesh, Balasubramanian; Myburgh, John

    2017-01-01

    BACKGROUND: The Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock (ADRENAL) trial, a 3800-patient, multicentre, randomised controlled trial, will be the largest study to date of corticosteroid therapy in patients with septic shock. OBJECTIVE: To describe a statistical...... and statisticians and approved by the ADRENAL management committee. All authors were blind to treatment allocation and to the unblinded data produced during two interim analyses conducted by the Data Safety and Monitoring Committee. The data shells were produced from a previously published protocol. Statistical...... analyses are described in broad detail. Trial outcomes were selected and categorised into primary, secondary and tertiary outcomes, and appropriate statistical comparisons between groups are planned and described in a way that is transparent, available to the public, verifiable and determined before...

  8. [Consequences of autopsies for the living : Causes of death in the clinical diagnosis "septic and toxic shock"].

    Science.gov (United States)

    Ozretić, L; Schwindowski, A; Dienes, H-P; Büttner, R; Drebber, U; Fries, J W U

    2017-09-01

    There is reason to believe that the diagnosis of septic and toxic shock, as indicated on the death certificate, cannot be confirmed as the cause of death without autopsy and subsequent histological analysis. The external examination of the corpse can therefore not represent the sole basis for a reliable statement about the infection status of a corpse, e. g. as a prerequisite for embalming. The validity of autopsy in determining septic and toxic shock as the cause of death is demonstrated in 7 exemplary cases. Decades of experience in a university pathology institute have shown that an external examination of the corpse alone is not suitable for certifying the cause of death if an infectious disease is suspected. Consequently, only autopsy with subsequent histological analysis provides reliable statements on the etiopathogenesis of the underlying process. Possible problems and discrepancies between clinical and pathological diagnoses are discussed on the basis of several cases with or without autoptic confirmation of the septic shock. The case of a missionary from Africa infected with Lassa virus serves to point out the seriousness of the threat an undiagnosed infection may represent to the attending staff. During the treatment of patients suspected to have an infectious cause of fever of unknown origin, compliance with the usual safety regulations, including adequate disinfecting measures, is essential. In cases with fatal outcome, not infrequently under the clinical picture of a septic and toxic shock, autopsy should be regularly performed to confirm the type of infection and the infectious cause of death. Rapid and open communication between the professional groups involved plays a crucial role in this process.

  9. Vascular ATP-sensitive potassium channels are over-expressed and partially regulated by nitric oxide in experimental septic shock.

    Science.gov (United States)

    Collin, Solène; Sennoun, Nacira; Dron, Anne-Gaëlle; de la Bourdonnaye, Mathilde; Montemont, Chantal; Asfar, Pierre; Lacolley, Patrick; Meziani, Ferhat; Levy, Bruno

    2011-05-01

    To study the activation and expression of vascular (aorta and small mesenteric arteries) potassium channels during septic shock with or without modulation of the NO pathway. Septic shock was induced in rats by peritonitis. Selective inhibitors of vascular K(ATP) (PNU-37883A) or BK(Ca) [iberiotoxin (IbTX)] channels were used to demonstrate their involvement in vascular hyporeactivity. Vascular response to phenylephrine was measured on aorta and small mesenteric arteries mounted on a wire myograph. Vascular expression of potassium channels was studied by PCR and Western blot, in the presence or absence of 1400W, an inducible NO synthase (iNOS) inhibitor. Aortic activation of the transcriptional factor nuclear factor-kappaB (NF-κB) was assessed by electrophoretic mobility shift assay. Arterial pressure as well as in vivo and ex vivo vascular reactivity were reduced by sepsis and improved by PNU-37883A but not by IbTX. Sepsis was associated with an up-regulation of mRNA and protein expression of vascular K(ATP) channels, while expression of vascular BK(Ca) channels remained unchanged. Selective iNOS inhibition blunted the sepsis-induced increase in aortic NO, decreased NF-κB activation, and down-regulated vascular K(ATP) channel expression. Vascular K(ATP) but not BK(Ca) channels are activated, over-expressed, and partially regulated by NO via NF-κB activation during septic shock. Their selective inhibition restores arterial pressure and vascular reactivity and decreases lactate concentration. The present data suggest that selective vascular K(ATP) channel inhibitors offer potential therapeutic perspectives for septic shock.

  10. Acute respiratory distress syndrome and septic shock in a cat with disseminated toxoplasmosis.

    Science.gov (United States)

    Evans, Natashia A; Walker, Julie M; Manchester, Alison C; Bach, Jonathan F

    2017-07-01

    To describe acute respiratory distress syndrome (ARDS) and septic shock in a cat with disseminated toxoplasmosis. A 2-year-old neutered male domestic shorthair cat was presented for acute respiratory distress. At the time of presentation it had been receiving cyclosporine for treatment of eosinophilic dermatitis. Thoracic radiographs revealed severe mixed nodular interstitial and alveolar patterns. An endotracheal wash was performed, which confirmed a diagnosis of pulmonary toxoplasmosis. Despite initial treatment with oxygen supplementation and intravenous clindamycin, the cat developed refractory hypoxemia and hypotension requiring mechanical ventilation and vasopressor support within 24 hours of hospital admission. Cardiac arrest occurred 56 hours after admission. Necropsy was performed and histopathology revealed protozoal organisms disseminated throughout the heart, lungs, liver, and brain. The clinical and necropsy findings presented here are consistent with ARDS secondary to disseminated toxoplasmosis in a cat. This is the first detailed report of ARDS in a cat. Toxoplasma titer testing and antimicrobial prophylaxis should be considered in cats prior to immunosuppressive treatment with cyclosporine. © Veterinary Emergency and Critical Care Society 2017.

  11. More complications in patients with septic shock treated with dextran compared with crystalloids.

    Science.gov (United States)

    Rasmussen, Anders Mølgaard; Jakobsen, Rasmus; Strøm, Thomas; Carlsson, Marcela; Dahler-Eriksen, Bjarne; Toft, Palle

    2015-02-01

    In recent years, the safety-profile of synthetic colloids has been questioned. The purpose of the present study was to elucidate the safety-profile of the colloid dextran-70 in relation to acute kidney injury (AKI) and death. We conducted a retrospective, observational study of patients admitted to our intensive care unit with septic shock and treated with dextran-70 in the period from 1 January 2009 to 31 December 2009. The controls were included from 1 March 2012 to 28 February 2013 when dextran-70 was replaced with crystalloids. There were 91 patients in the dextran group and 150 patients in the non-dextran group. The urinary output was 17.93 ml/kg/24 h in the dextran group and 27.87 in the non-dextran group (p dextran group and in 23% in the non-dextran group (p dextran group compared with 15% in the control group (p dextran group and 35% in the non-dextran group (p = 0.08). Patients in the dextran group had significantly more bleeding episodes, a higher need for CRRT and a lower urinary output than patients in the non-dextran group. Due to study design, it cannot be concluded that the use of dextran-70 is causally related to the development of AKI.

  12. Variability in targeted arterial oxygenation levels in patients with severe sepsis or septic shock

    DEFF Research Database (Denmark)

    Dahl, R. M.; Grønlykke, L.; Haase, N.

    2015-01-01

    of arterial oxygen (PaO2 ) and mortality. METHODS: We extracted data from two Scandinavian clinical trials of ICU patients with severe sepsis or septic shock. We calculated average PaO2 and fraction of inspired oxygen (FiO2 ) from trial inclusion and the following 5 days, and assessed the association between...... PaO2 and 90-day mortality. RESULTS: The median PaO2 was 9.8 kPa [5-95% range 6.4-19.9] and FiO2 was 0.51 [5-95% range 0.27-1.00], respectively. Eight hundred and five of 1,770 patients (45%) died. The relative risk of mortality was 1.43 [95% CI: 1.19-1.65] in patients with average PaO2 ....29 [95% CI: 0.84-1.68] in patients with average PaO2 ≥ 16 kPa, as compared to patients with average PaO2 10-12 kPa. The relative risk of mortality was 1.38 [95% CI: 1.17-1.58] in patients with an average FiO2 0.60-0.80 and 2.10 [95% CI: 1.88-2.23] in patients with an average FiO2 ≥ 0.80 as compared...

  13. Glycaemic variability in patients with severe sepsis or septic shock admitted to an Intensive Care Unit.

    Science.gov (United States)

    Silveira, L M; Basile-Filho, A; Nicolini, E A; Dessotte, C A M; Aguiar, G C S; Stabile, A M

    2017-08-01

    Sepsis is associated with morbidity and mortality, which implies high costs to the global health system. Metabolic alterations that increase glycaemia and glycaemic variability occur during sepsis. To verify mean body glucose levels and glycaemic variability in Intensive Care Unit (ICU) patients with severe sepsis or septic shock. Retrospective and exploratory study that involved collection of patients' sociodemographic and clinical data and calculation of severity scores. Glycaemia measurements helped to determine glycaemic variability through standard deviation and mean amplitude of glycaemic excursions. Analysis of 116 medical charts and 6730 glycaemia measurements revealed that the majority of patients were male and aged over 60 years. Surgical treatment was the main reason for ICU admission. High blood pressure and diabetes mellitus were the most usual comorbidities. Patients that died during the ICU stay presented the highest SOFA scores and mean glycaemia; they also experienced more hypoglycaemia events. Patients with diabetes had higher mean glycaemia, evaluated through standard deviation and mean amplitude of glycaemia excursions. Organic impairment at ICU admission may underlie glycaemic variability and lead to a less favourable outcome. High glycaemic variability in patients with diabetes indicates that monitoring of these individuals is crucial to ensure better outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Hydrocortisone Therapy in Catecholamine-Resistant Pediatric Septic Shock: A Pragmatic Analysis of Clinician Practice and Association With Outcomes.

    Science.gov (United States)

    Nichols, Blake; Kubis, Sherri; Hewlett, Jennifer; Yehya, Nadir; Srinivasan, Vijay

    2017-09-01

    The 2012 Surviving Sepsis Campaign pediatric guidelines recommend stress dose hydrocortisone in children experiencing catecholamine-dependent septic shock with suspected or proven absolute adrenal insufficiency. We evaluated whether stress dose hydrocortisone therapy in children with catecholamine dependent septic shock correlated with random serum total cortisol levels and was associated with improved outcomes. Retrospective cohort study. Non-cardiac PICU. Critically ill children (1 mo to 18 yr) admitted between January 1, 2013, and December 31, 2013, with catecholamine dependent septic shock who had random serum total cortisol levels measured prior to potential stress dose hydrocortisone therapy. None. The cohort was dichotomized to random serum total cortisol less than 18 mcg/dL and greater than or equal to 18 mcg/dL. Associations of stress dose hydrocortisone with outcomes: PICU mortality, PICU and hospital length of stay, ventilator-free days, and vasopressor-free days were examined. Seventy children with catecholamine-dependent septic shock and measured random serum total cortisol levels were eligible (16% PICU mortality). Although 43% (30/70) had random serum total cortisol less than 18 μg/dL, 60% (42/70) received stress dose hydrocortisone. Children with random serum total cortisol less than 18 μg/dL had lower severity of illness and lower Vasopressor Inotrope Scores than those with random serum total cortisol greater than or equal to 18 μg/dL (all p stress dose hydrocortisone had higher severity of illness and PICU mortality than those without stress dose hydrocortisone (all p stress dose hydrocortisone (21.1 vs 18.7 μg/dL; p = 0.69). In children with random serum total cortisol less than 18 μg/dL, stress dose hydrocortisone was associated with greater PICU and hospital length of stay and fewer ventilator-free days (all p stress dose hydrocortisone was associated with greater PICU mortality and fewer ventilator-free days and vasopressor-free days (all

  15. Skeletal Muscle and Lymphocyte Mitochondrial Dysfunctions in Septic Shock Trigger ICU-Acquired Weakness and Sepsis-Induced Immunoparalysis

    Directory of Open Access Journals (Sweden)

    Quentin Maestraggi

    2017-01-01

    Full Text Available Fundamental events driving the pathological processes of septic shock-induced multiorgan failure (MOF at the cellular and subcellular levels remain debated. Emerging data implicate mitochondrial dysfunction as a critical factor in the pathogenesis of sepsis-associated MOF. If macrocirculatory and microcirculatory dysfunctions undoubtedly participate in organ dysfunction at the early stage of septic shock, an intrinsic bioenergetic failure, sometimes called “cytopathic hypoxia,” perpetuates cellular dysfunction. Short-term failure of vital organs immediately threatens patient survival but long-term recovery is also severely hindered by persistent dysfunction of organs traditionally described as nonvital, such as skeletal muscle and peripheral blood mononuclear cells (PBMCs. In this review, we will stress how and why a persistent mitochondrial dysfunction in skeletal muscles and PBMC could impair survival in patients who overcome the first acute phase of their septic episode. First, muscle wasting protracts weaning from mechanical ventilation, increases the risk of mechanical ventilator-associated pneumonia, and creates a state of ICU-acquired muscle weakness, compelling the patient to bed. Second, failure of the immune system (“immunoparalysis” translates into its inability to clear infectious foci and predisposes the patient to recurrent nosocomial infections. We will finally emphasize how mitochondrial-targeted therapies could represent a realistic strategy to promote long-term recovery after sepsis.

  16. Frontline Science: HMGB1 induces neutrophil dysfunction in experimental sepsis and in patients who survive septic shock.

    Science.gov (United States)

    Grégoire, Murielle; Tadié, Jean-Marc; Uhel, Fabrice; Gacouin, Arnaud; Piau, Caroline; Bone, Nathaniel; Le Tulzo, Yves; Abraham, Edward; Tarte, Karin; Zmijewski, Jaroslaw W

    2017-06-01

    Sepsis is accompanied by the initial activation of proinflammatory pathways and long-lasting immunosuppression that appears to contribute to late-occurring mortality. Although high-mobility group box 1 (HMGB1) is involved in many aspects of inflammation, its role in sepsis-induced immune suppression remains unclear. In this study, we examined HMGB1's contribution to neutrophil NADPH oxidase activity dysfunction and associated neutrophil-dependent bacterial clearance in mice subjected to sepsis and in patients who survive septic shock. Using a murine model of polymicrobial septic peritonitis, we demonstrated that treatment with anti-HMGB1 Ab significantly diminished sepsis-induced dysfunction of neutrophil NADPH oxidase activity. In a subsequent set of experiments, we found that blocking HMGB1 preserved the ability of neutrophils from patients recovering from septic shock to activate NADPH oxidase. Taken together, our data suggest that HMGB1 accumulation in the late phase of sepsis plays a specific role in the development of postsepsis immunosuppression and specifically affects neutrophil-dependent antibacterial defense mechanisms. Thus, blocking HMGB1 may be a promising therapeutic intervention to diminish the adverse effects of sepsis-induced immunosuppression. © Society for Leukocyte Biology.

  17. Prognosis of patients excluded by the definition of septic shock based on their lactate levels after initial fluid resuscitation: a prospective multi-center observational study.

    Science.gov (United States)

    Ko, Byuk Sung; Kim, Kyuseok; Choi, Sung-Hyuk; Kang, Gu Hyun; Shin, Tae Gun; Jo, You Hwan; Ryoo, Seung Mok; Beom, Jin Ho; Kwon, Woon Yong; Han, Kap Su; Choi, Han Sung; Chung, Sung Phil; Suh, Gil Joon; Lim, Tae Ho; Kim, Won Young

    2018-02-24

    Septic shock can be defined both by the presence of hyperlactatemia and need of vasopressors. Lactate levels should be measured after volume resuscitation (as per the Sepsis-3 definition). However, currently, no studies have evaluated patients who have been excluded by the new criteria for septic shock. The aim of this study was to determine the clinical characteristics and prognosis of these patients, based on their lactate levels after initial fluid resuscitation. This observational study was performed using a prospective, multi-center registry of septic shock, with the participation of 10 hospitals in the Korean Shock Society, between October 2015 and February 2017. We compared the 28-day mortality between patients who were excluded from the new definition (defined as lactate level definition of septic shock. These patients, in whom perfusion was restored, demonstrated significantly lower age, platelet count, and initial and subsequent lactate levels (all p < 0.01). Similarly, significantly lower 28-day mortality was observed in these patients than in those who had not been excluded (8.2% vs 25.5%, p = 0.02). In-hospital mortality and the maximum SOFA score were also significantly lower in the excluded patients group (p = 0.03, both). It seems reasonable for septic shock to be defined by the lactate levels after volume resuscitation. However, owing to the small number of patients in whom lactate levels were improved, further study is warranted.

  18. Association Between Muscle Wasting and Muscle Strength in Patients WHO Developed Severe Sepsis and Septic Shock.

    Science.gov (United States)

    Borges, Rodrigo Cerqueira; Soriano, Francisco Garcia

    2018-05-11

    To evaluate the association between the rectus femoris cross-sectional area (RFCSA) and the muscular strength obtained at the bedside in patients forwarded to the intensive care unit (ICU) for severe sepsis and septic shock. A prospective cohort study. RFCSA was assessed by ultrasound on the following day of the ICU admission and monitored during hospitalization. The patients performed clinical tests of muscle strength (Medical Research Council (MRC) scale and handgrip dynamometry), when they could understand the verbal commands of the examiners. In 37 patients hospitalized for sepsis there was a significant decline in RFCSA of 5.18 (4.49-5.96)cm on the 2nd day of ICU for 4.37 (3.71-5.02)cm at hospital discharge. Differently, the handgrip strength showed an increase from the awakening of 12.00 (7.00-20.00)Kgf to 19.00 (14.00-26.00)Kgf until hospital discharge. Patients in mechanical ventilation had a greater tendency to decline in the RFCSA compared to patients who did not receive mechanical ventilation, however without being significant (p = 0.08). There was a negative association between RFCSA delta (2nd day of ICU - ICU discharge) and handgrip strength (r = 0.51, p < 0.05), and a male and SOFA score positive association with the RFCSA delta. There was an association of RFCSA with clinical muscle strength tests. In addition, it has been shown that sepsis can lead to short-term muscle degradation, regardless of whether they are submitted to mechanical ventilation or not.

  19. Early, Goal-Directed Therapy for Septic Shock - A Patient-Level Meta-Analysis.

    Science.gov (United States)

    Rowan, Kathryn M; Angus, Derek C; Bailey, Michael; Barnato, Amber E; Bellomo, Rinaldo; Canter, Ruth R; Coats, Timothy J; Delaney, Anthony; Gimbel, Elizabeth; Grieve, Richard D; Harrison, David A; Higgins, Alisa M; Howe, Belinda; Huang, David T; Kellum, John A; Mouncey, Paul R; Music, Edvin; Peake, Sandra L; Pike, Francis; Reade, Michael C; Sadique, M Zia; Singer, Mervyn; Yealy, Donald M

    2017-06-08

    After a single-center trial and observational studies suggesting that early, goal-directed therapy (EGDT) reduced mortality from septic shock, three multicenter trials (ProCESS, ARISE, and ProMISe) showed no benefit. This meta-analysis of individual patient data from the three recent trials was designed prospectively to improve statistical power and explore heterogeneity of treatment effect of EGDT. We harmonized entry criteria, intervention protocols, outcomes, resource-use measures, and data collection across the trials and specified all analyses before unblinding. After completion of the trials, we pooled data, excluding the protocol-based standard-therapy group from the ProCESS trial, and resolved residual differences. The primary outcome was 90-day mortality. Secondary outcomes included 1-year survival, organ support, and hospitalization costs. We tested for treatment-by-subgroup interactions for 16 patient characteristics and 6 care-delivery characteristics. We studied 3723 patients at 138 hospitals in seven countries. Mortality at 90 days was similar for EGDT (462 of 1852 patients [24.9%]) and usual care (475 of 1871 patients [25.4%]); the adjusted odds ratio was 0.97 (95% confidence interval, 0.82 to 1.14; P=0.68). EGDT was associated with greater mean (±SD) use of intensive care (5.3±7.1 vs. 4.9±7.0 days, P=0.04) and cardiovascular support (1.9±3.7 vs. 1.6±2.9 days, P=0.01) than was usual care; other outcomes did not differ significantly, although average costs were higher with EGDT. Subgroup analyses showed no benefit from EGDT for patients with worse shock (higher serum lactate level, combined hypotension and hyperlactatemia, or higher predicted risk of death) or for hospitals with a lower propensity to use vasopressors or fluids during usual resuscitation. In this meta-analysis of individual patient data, EGDT did not result in better outcomes than usual care and was associated with higher hospitalization costs across a broad range of patient and

  20. [The impacts of low-dose corticosteroids infusion given in different manners on refractory septic shock patients].

    Science.gov (United States)

    Chen, Zhi; Yang, Chunli; He, Huiwei; He, Zhaohui

    2015-06-01

    To discuss the influence of different ways of low-dose corticosteroids infusion on hemodynamics, changes in blood glucose level and prognosis in patients with refractory septic shock. A prospective single-blind randomized controlled trial was conducted. Refractory septic shock patients admitted to the Department of Critical Care Medicine of Jiangxi Provincial People's Hospital from April 1st, 2013 to October 31st, 2014 were enrolled for the study. The patients were divided into control group and research group by random number table. Besides conventional treatment for septic shock, patients in control group were given 200 mg/d hydrocortisone intravenous infusion lasting for 2 hours, while those of research group were given 8.33 mg/h hydrocortisone per hour with an intravenous pump. Treatment lasted for 5 continuous days for both groups. The changes in heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP) and arterial blood lactic acid in both groups were observed at the time of enroldment and 6 hours, 24 hours, 48 hours, and 5 days after the treatment. With a dynamic blood glucose monitor, mean blood glucose (MBG) level, largest amplitude of glycemic excursions (LAGE), glucose variability (GV), and the ratio of hyperglycaemia time were recorded. The duration of shock, length of intensive care unit (ICU) stay, total length of hospital stay, and 28-day mortality of both groups were recorded. Seventy-nine septic shock patients were assigned to the treatment, with 41 in control group, and 38 in research group. Compared with control group, 6-hour MAP in research group was obviously lowered [mmHg (1 mmHg=0.133 kPa): 66.31±4.38 vs. 68.58±4.86, t=1.062, P=0.033], but there were no significant differences in HR, MAP, CVP, lactic acid clearance and norepinephrine (NE) utilization rates at other time points between two groups. No significant difference in MBG was found between research group and control group (mmol/L: 8.69±2.14 vs. 9.95±3.87, t=1

  1. Population pharmacokinetics of piperacillin in the early phase of septic shock: does standard dosing result in therapeutic plasma concentrations?

    Science.gov (United States)

    Öbrink-Hansen, Kristina; Juul, Rasmus Vestergaard; Storgaard, Merete; Thomsen, Marianne Kragh; Hardlei, Tore Forsingdal; Brock, Birgitte; Kreilgaard, Mads; Gjedsted, Jakob

    2015-11-01

    Antibiotic dosing in septic shock patients poses a challenge for clinicians due to the pharmacokinetic (PK) variability seen in this patient population. Piperacillin-tazobactam is often used for empirical treatment, and initial appropriate dosing is crucial for reducing mortality. Accordingly, we determined the pharmacokinetic profile of piperacillin (4 g) every 8 h, during the third consecutive dosing interval, in 15 patients treated empirically for septic shock. We developed a population pharmacokinetic model to assess empirical dosing and to simulate alternative dosing regimens and modes of administration. Time above the MIC (T>MIC) predicted for each patient was evaluated against clinical breakpoint MIC for Pseudomonas aeruginosa (16 mg/liter). Pharmacokinetic-pharmacodynamic (PK/PD) targets evaluated were 50% fT>4×MIC and 100% fT>MIC. A population PK model was developed using NONMEM, and data were best described by a two-compartment model. Central and intercompartmental clearances were 3.6 liters/h (relative standard error [RSE], 15.7%) and 6.58 liters/h (RSE, 16.4%), respectively, and central and peripheral volumes were 7.3 liters (RSE, 11.8%) and 3.9 liters (RSE, 9.7%), respectively. Piperacillin plasma concentrations varied considerably between patients and were associated with levels of plasma creatinine. Patients with impaired renal function were more likely to achieve predefined PK/PD targets than were patients with preserved or augmented renal function. Simulations of alternative dosing regimens showed that frequent intermittent bolus dosing as well as dosing by extended and continuous infusion increases the probability of attaining therapeutic plasma concentrations. For septic shock patients with preserved or augmented renal function, dose increment or prolonged infusion of the drug needs to be considered. (This study has been registered at ClinicalTrials.gov under registration no. NCT02306928.). Copyright © 2015, American Society for Microbiology

  2. An increase in mean platelet volume from baseline is associated with mortality in patients with severe sepsis or septic shock.

    Directory of Open Access Journals (Sweden)

    Chan Ho Kim

    Full Text Available Mean platelet volume (MPV is suggested as an index of inflammation, disease activity, and anti-inflammatory treatment efficacy in chronic inflammatory disorders; however, the effect of MPV on sepsis mortality remains unclear. Therefore, we investigated whether the change in MPV between hospital admission and 72 hours (ΔMPV72h-adm predicts 28-day mortality in severe sepsis and/or septic shock.We prospectively enrolled 345 patients admitted to the emergency department (ED who received standardized resuscitation (early goal-directed therapy for severe sepsis and/or septic shock between November 2007 and December 2011. Changes in platelet indices, including ΔMPV72h-adm, were compared between survivors and non-survivors by linear mixed model analysis. The prognostic value of ΔMPV72h-adm for 28-day mortality was ascertained by Cox proportional hazards model analysis.Thirty-five (10.1% patients died within 28 days after ED admission. MPV increased significantly during the first 72 hours in non-survivors (P = 0.001 and survivors (P < 0.001; however, the rate of MPV increase was significantly higher in non-survivors (P = 0.003. Nonetheless, the difference in the platelet decline rate over the first 72 hours did not differ significantly between groups (P = 0.360. In multivariate analysis, ΔMPV72h-adm was an independent predictor of 28-day mortality, after adjusting for plausible confounders (hazard ratio, 1.44; 95% confidence interval, 1.01-2.06; P = 0.044.An increase in MPV during the first 72 hours of hospitalization is an independent risk factor for adverse clinical outcomes. Therefore, continuous monitoring of MPV may be useful to stratify mortality risk in patients with severe sepsis and/or septic shock.

  3. Predictive value of N-terminal pro-brain natriuretic peptide in severe sepsis and septic shock.

    Science.gov (United States)

    Varpula, Marjut; Pulkki, Kari; Karlsson, Sari; Ruokonen, Esko; Pettilä, Ville

    2007-05-01

    The aim of this study was to evaluate the predictive value of N-terminal pro-brain natriuretic peptide (NT-proBNP) on mortality in a large, unselected patient population with severe sepsis and septic shock. Prospective observational cohort study about incidence and prognosis of sepsis in 24 intensive care units in Finland (the FINNSEPSIS study). A total of 254 patients with severe sepsis or septic shock. After informed consent, the blood tests for NT-proBNP analyses were drawn on the day of admission and 72 hrs thereafter. Patients' demographic data were collected, and intensive care unit and hospital mortality and basic hemodynamic and laboratory data were recorded daily. NT-proBNP levels at admission were significantly higher in hospital nonsurvivors (median, 7908 pg/mL) compared with survivors (median, 3479 pg/mL; p = .002), and the difference remained after 72 hrs (p = .002). The receiver operating characteristic curves of admission and 72-hr NT-proBNP levels for hospital mortality resulted in area under the curve values of 0.631 (95% confidence interval, 0.549-0.712; p = .002) and 0.648 (95% confidence interval, 0.554-0.741; p = .002), respectively. In logistic regression analyses, NT-proBNP values at 72 hrs after inclusion and Simplified Acute Physiology Score for the first 24 hrs were independent predictors of hospital mortality. Pulmonary artery occlusion pressure (p < .001), plasma creatinine clearance (p = .001), platelet count (p = .03), and positive blood culture (p = .04) had an independent effect on first-day NT-proBNP values, whereas after 72 hrs, only plasma creatinine clearance (p < .001) was significant in linear regression analysis. NT-proBNP values are frequently increased in severe sepsis and septic shock. Values are significantly higher in nonsurvivors than survivors. NT-proBNP on day 3 in the intensive care unit is an independent prognostic marker of mortality in severe sepsis.

  4. New therapy strategies for treatment of severe sepsis and septic shock in Intensive care unit of Clinical centre in Kragujevac

    Directory of Open Access Journals (Sweden)

    Jevđić Jasna

    2008-01-01

    Full Text Available INTRODUCTION Despite numerous advances in medicine, the mortality rate of severe sepsis and septic shock remains high, 30-50%. New therapy strategies include: early goaldirected therapy, fluid replacement, early and appropriate antimicrobials, source of infection control, use of corticosteroids, vasopressors and inotropic therapy, use of recombinant activated protein C, tight glucose control, low-tidal-volume mechanical ventilation. They have been shown to improve the outcomes. The adequacy and speed of treatment influence the outcome, too. OBJECTIVE The objective was to evaluate if new therapy strategies had been integrated in our routine practice. METOD Patients with severe sepsis or septic shock, who were treated in the Intensive Care Unit (ICU over a ten-month period, were analyzed retrospectively. The descriptive epidemiological method was applied. Central venous catheterization, central venous pressure, antibiotics, fluid resuscitation, mechanical ventilation, vasopressors, corticosteroids, blood administration, deep vein thrombosis prophylaxis, stress ulcer prophylaxis, glucose control, were evaluated. RESULTS 27 patients were analyzed. Patient characteristics were: age, 49.9 years (18-77 with 30-day in-hospital mortality rate of 48.1%. All patients received broad-spectrum antibiotics. Blood cultures were obtained in 85.2% patients. Adequate antimicrobial treatment was applied to 59.3% and 74.1% patients had central venous pressure monitoring. Average central venous pressure was 8.47±5.6 mm Hg (-2- 20. Aggressive fluid therapy was given to 33.3% of the cases and 66.7% of the patients with septic shock received vasoactive drugs while 29.6% received corticosteroids. Red blood cell transfusions were applied in 59.3% of patients. All patients received stress ulcer prophylaxis, and 37% of them deep vein thrombosis prophylaxis. The average value of morning glucose was 9.11±5.03 mmol/l (3.7-22.0. 63% of patients were mechanically ventilated

  5. An Emergency Department Validation of the SEP-3 Sepsis and Septic Shock Definitions and Comparison With 1992 Consensus Definitions.

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    Henning, Daniel J; Puskarich, Michael A; Self, Wesley H; Howell, Michael D; Donnino, Michael W; Yealy, Donald M; Jones, Alan E; Shapiro, Nathan I

    2017-10-01

    The Third International Consensus Definitions Task Force (SEP-3) proposed revised criteria defining sepsis and septic shock. We seek to evaluate the performance of the SEP-3 definitions for prediction of inhospital mortality in an emergency department (ED) population and compare the performance of the SEP-3 definitions to that of the previous definitions. This was a secondary analysis of 3 prospectively collected, observational cohorts of infected ED subjects aged 18 years or older. The primary outcome was all-cause inhospital mortality. In accordance with the SEP-3 definitions, we calculated test characteristics of sepsis (quick Sequential Organ Failure Assessment [qSOFA] score ≥2) and septic shock (vasopressor dependence plus lactate level >2.0 mmol/L) for mortality and compared them to the original 1992 consensus definitions. We identified 7,754 ED patients with suspected infection overall; 117 had no documented mental status evaluation, leaving 7,637 patients included in the analysis. The mortality rate for the overall population was 4.4% (95% confidence interval [CI] 3.9% to 4.9%). The mortality rate for patients with qSOFA score greater than or equal to 2 was 14.2% (95% CI 12.2% to 16.2%), with a sensitivity of 52% (95% CI 46% to 57%) and specificity of 86% (95% CI 85% to 87%) to predict mortality. The original systemic inflammatory response syndrome-based 1992 consensus sepsis definition had a 6.8% (95% CI 6.0% to 7.7%) mortality rate, sensitivity of 83% (95% CI 79% to 87%), and specificity of 50% (95% CI 49% to 51%). The SEP-3 septic shock mortality was 23% (95% CI 16% to 30%), with a sensitivity of 12% (95% CI 11% to 13%) and specificity of 98.4% (95% CI 98.1% to 98.7%). The original 1992 septic shock definition had a 22% (95% CI 17% to 27%) mortality rate, sensitivity of 23% (95% CI 18% to 28%), and specificity of 96.6% (95% CI 96.2% to 97.0%). Both the new SEP-3 and original sepsis definitions stratify ED patients at risk for mortality, albeit with

  6. The Impact of Timing of Antibiotics on Outcomes in Severe Sepsis and Septic Shock: A Systematic Review and Meta-analysis

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    Sterling, Sarah A.; Miller, W. Ryan; Pryor, Jason; Puskarich, Michael A.; Jones, Alan E.

    2015-01-01

    Objectives We sought to systematically review and meta-analyze the available data on the association between timing of antibiotic administration and mortality in severe sepsis and septic shock. Data Sources and Study Selection A comprehensive search was performed using a pre-defined protocol. Inclusion criteria: adult patients with severe sepsis or septic shock, reported time to antibiotic administration in relation to ED triage and/or shock recognition, and mortality. Exclusion criteria: immunosuppressed populations, review article, editorial, or non-human studies. Data Extraction Two reviewers screened abstracts with a third reviewer arbitrating. The effect of time to antibiotic administration on mortality was based on current guideline recommendations: 1) administration within 3 hours of ED triage; 2) administration within 1 hour of severe sepsis/septic shock recognition. Odds Ratios (OR) were calculated using a random effect model. The primary outcome was mortality. Data Synthesis 1123 publications were identified and 11 were included in the analysis. Among the 11 included studies, 16,178 patients were evaluable for antibiotic administration from ED triage. Patients who received antibiotics more than 3 hours after ED triage (antibiotic administration from severe sepsis/septic shock recognition. Patients who received antibiotics more than 1 hour after severe sepsis/shock recognition (5 hours in antibiotic administration from severe sepsis/shock recognition. Conclusion Using the available pooled data we found no significant mortality benefit of administering antibiotics within 3 hours of ED triage or within 1 hour of shock recognition in severe sepsis and septic shock. These results suggest that currently recommended timing metrics as measures of quality of care are not supported by the available evidence. PMID:26121073

  7. Facilitating the transition from physiology to hospital wards through an interdisciplinary case study of septic shock.

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    Li, Albert S; Berger, Kenneth I; Schwartz, David R; Slater, William R; Goldfarb, David S

    2014-04-12

    In order to develop clinical reasoning, medical students must be able to integrate knowledge across traditional subject boundaries and multiple disciplines. At least two dimensions of integration have been identified: horizontal integration, bringing together different disciplines in considering a topic; and vertical integration, bridging basic science and clinical practice. Much attention has been focused on curriculum overhauls, but our approach is to facilitate horizontal and vertical integration on a smaller scale through an interdisciplinary case study discussion and then to assess its utility. An interdisciplinary case study discussion about a critically ill patient was implemented at the end of an organ system-based, basic sciences module at New York University School of Medicine. Three clinical specialists-a cardiologist, a pulmonologist, and a nephrologist-jointly led a discussion about a complex patient in the intensive care unit with multiple medical problems secondary to septic shock. The discussion emphasized the physiologic underpinnings behind the patient's presentation and the physiologic considerations across the various systems in determining proper treatment. The discussion also highlighted the interdependence between the cardiovascular, respiratory, and renal systems, which were initially presented in separate units. After the session students were given a brief, anonymous three-question free-response questionnaire in which they were asked to evaluate and freely comment on the exercise. Students not only took away physiological principles but also gained an appreciation for various thematic lessons for bringing basic science to the bedside, especially horizontal and vertical integration. The response of the participants was overwhelmingly positive with many indicating that the exercise integrated the material across organ systems, and strengthened their appreciation of the role of physiology in understanding disease presentations and guiding

  8. Comparison of procalcitonin and high-sensitivity C-reactive protein for the diagnosis of sepsis and septic shock in the oldest old patients.

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    Zhang, Hongmin; Wang, Xiaoting; Zhang, Qing; Xia, Ying; Liu, Dawei

    2017-08-01

    Although the role of serum procalcitonin (PCT) and high-sensitivity C-reactive protein (hs-CRP) in the diagnosis of sepsis and septic shock is well studied, it has not been investigated among oldest old patients. The aim of our study is to determine the role of PCT and hs-CRP in the assessment of sepsis and septic shock in this specific group of patients in the ICU. This is a prospective observational study. Patients >85 years of age admitted to the ICU from May 1st, 2016 to February 1st, 2017 were evaluated. Patients were divided into a sepsis and septic shock group(sepsis/SS) and a non-sepsis group. Serum levels of PCT, hs-CRP and the WBC were measured within 12 h of admission. A total of 70 patients aged 85 years and older were enrolled in this study. Fifty patients were labelled as sepsis/SS and the other 20 were labelled non-sepsis. A ROC analysis showed that the area under the curves (AUC) of hs-CRP and PCT for the discrimination of sepsis/SS patients were 0.825 (95% confidence interval[CI]: 0.73-0.92; P sepsis/SS group, 27 patients had sepsis, while the other 23 patients had septic shock. The ROC analysis showed that the AUCs of hs-CRP and PCT for the discrimination of septic shock patients from sepsis patients were 0.751 (95% CI: 0.62-0.88; P = 0.002) and 0.719 (95% CI:0.57-0.86; p = 0.007), respectively. For the oldest old patients, hs-CRP is not inferior to PCT in the diagnosis of sepsis and septic shock.

  9. Comparison of severity of illness scoring systems in the prediction of hospital mortality in severe sepsis and septic shock

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    Crowe Colleen

    2010-01-01

    Full Text Available Background : New scoring systems, including the Rapid Emergency Medicine Score (REMS, the Mortality in Emergency Department Sepsis (MEDS score, and the confusion, urea nitrogen, respiratory rate, blood pressure, 65 years and older (CURB-65 score, have been developed for emergency department (ED use in various patient populations. Increasing use of early goal directed therapy (EGDT for the emergent treatment of sepsis introduces a growing population of patients in which the accuracy of these scoring systems has not been widely examined. Objectives : To evaluate the ability of the REMS, MEDS score, and CURB-65 score to predict mortality in septic patients treated with modified EGDT. Materials and Methods : Secondary analysis of data from prospectively identified patients treated with modified EGDT in a large tertiary care suburban community hospital with over 85,000 ED visits annually and 700 inpatient beds, from May 2007 through May 2008. We included all patients with severe sepsis or septic shock, who were treated with our modified EGDT protocol. Our major outcome was in-hospital mortality. The performance of the scores was compared by area under the ROC curves (AUCs. Results : A total of 216 patients with severe sepsis or septic shock were treated with modified EGDT during the study period. Overall mortality was 32.9%. Calculated AUCs were 0.74 [95% confidence interval (CI: 0.67-0.81] for the MEDS score, 0.62 (95% CI: 0.54-0.69 for the REMS, and 0.59 (95% CI: 0.51-0.67 for the CURB-65 score. Conclusion : We found that all three ED-based systems for scoring severity of illness had low to moderate predictive capability. The MEDS score demonstrated the largest AUC of the studied scoring systems for the outcome of mortality, although the CIs on point estimates of the AUC of the REMS and CURB-65 scores all overlap.

  10. Imbalances in serum angiopoietin concentrations are early predictors of septic shock development in patients with post chemotherapy febrile neutropenia

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    Lorand-Metze Irene

    2010-05-01

    Full Text Available Abstract Background Febrile neutropenia carries a high risk of sepsis complications, and the identification of biomarkers capable to identify high risk patients is a great challenge. Angiopoietins (Ang - are cytokines involved in the control microvascular permeability. It is accepted that Ang-1 expression maintains endothelial barrier integrity, and that Ang-2 acts as an antagonizing cytokine with barrier-disrupting functions in inflammatory situations. Ang-2 levels have been recently correlated with sepsis mortality in intensive care units. Methods We prospectively evaluated concentrations of Ang-1 and Ang-2 at different time-points during febrile neutropenia, and explored the diagnostic accuracy of these mediators as potential predictors of poor outcome in this clinical setting before the development of sepsis complications. Results Patients that evolved with septic shock (n = 10 presented higher levels of Ang-2 measured 48 hours after fever onset, and of the Ang-2/Ang-1 ratio at the time of fever onset compared to patients with non-complicated sepsis (n = 31. These levels correlated with sepsis severity scores. Conclusions Our data suggest that imbalances in the concentrations of Ang-1 and Ang-2 are independent and early markers of the risk of developing septic shock and of sepsis mortality in febrile neutropenia, and larger studies are warranted to validate their clinical usefulness. Therapeutic strategies that manipulate this Ang-2/Ang-1 imbalance can potentially offer new and promising treatments for sepsis in febrile neutropenia.

  11. Application of the new Sepsis-3 definition in a cohort of patients with severe sepsis and septic shock admitted to Intensive Care Unit from the Emergency Department.

    Science.gov (United States)

    García-Gigorro, Renata; Molina-Collado, Zaira; Sáez-de la Fuente, Ignacio; Sanchez-Izquierdo, José Ángel; Montejo González, Juan Carlos

    2018-04-18

    After the publication of the new definition for sepsis and septic shock, our objective is to analyse the evolution of patients admitted to ICU with an infection process using the previous and new recommendations. This is a sub-analysis of a previous observational prospective study. We included 98 patients admitted to ICU from the emergency department due to infection during an 18-month period. We studied the clinical evolution during ICU admission and hospital mortality. According to Sepsis-2 definition, 78% percent had septic shock and using Sepsis-3 criteria, 52%; hospital mortality was 29 and 41%, respectively. The RR of hospital mortality of septic shock was 10.3 (95% CI: 2.8-37.5) compared to patients without shock. The 30-day probability survival of patients with sepsis and septic shock were 78% and 68%, respectively (long rank definition could help improve the evaluation of risk of hospital death. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

  12. Intermedin attenuates LPS-induced inflammation in the rat testis.

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    Lei Li

    Full Text Available First reported as a vasoactive peptide in the cardiovascular system, intermedin (IMD, also known as adrenomedullin 2 (ADM2, is a hormone with multiple potent roles, including its antioxidant action on the pulmonary, central nervous, cardiovascular and renal systems. Though IMD may play certain roles in trophoblast cell invasion, early embryonic development and cumulus cell-oocyte interaction, the role of IMD in the male reproductive system has yet to be investigated. This paper reports our findings on the gene expression of IMD, its receptor components and its protein localization in the testes. In a rat model, bacterial lippolysaccharide (LPS induced atypical orchitis, and LPS treatment upregulated the expression of IMD and one of its receptor component proteins, i.e. receptor activity modifying protein 2 (RAMP2. IMD decreased both plasma and testicular levels of reactive oxygen species (ROS production, attenuated the increase in the gene expression of the proinflammatory cytokines tumor necrosis factor alpha (TNFα, interleukin 6 (IL6 and interleukin 1 beta (IL1β, rescued spermatogenesis, and prevented the decrease in plasma testosterone levels caused by LPS. The restorative effect of IMD on steroidogenesis was also observed in hydrogen peroxide-treated rat primary Leydig cells culture. Our results indicate IMD plays an important protective role in spermatogenesis and steroidogenesis, suggesting therapeutic potential for IMD in pathological conditions such as orchitis.

  13. Selepressin, a novel selective vasopressin V1A agonist, is an effective substitute for norepinephrine in a phase IIa randomized, placebo-controlled trial in septic shock patients

    DEFF Research Database (Denmark)

    Russell, James A; Vincent, Jean-Louis; Kjølbye, Anne Louise

    2017-01-01

    BACKGROUND: Vasopressin is widely used for vasopressor support in septic shock patients, but experimental evidence suggests that selective V1A agonists are superior. The initial pharmacodynamic effects, pharmacokinetics, and safety of selepressin, a novel V1A-selective vasopressin analogue, was e...

  14. The effect of sepsis and septic shock on the viscoelastic properties of clot quality and mass using rotational thromboelastometry: A prospective observational study.

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    Davies, Gareth R; Lawrence, Matthew; Pillai, Suresh; Mills, Gavin M; Aubrey, Robert; Thomas, Dafydd; Williams, Rhodri; Morris, Keith; Evans, Phillip Adrian

    2018-04-01

    The study purpose was to define changes in coagulation across the sepsis spectrum using rotational thromboelastometry (ROTEM). Sepsis patients were recruited on admission to the Emergency Department and Intensive Care Units of a large teaching hospital in Wales. ROTEM markers of clot development and fibrinolysis were determined, as well as standard coagulation markers. A healthy control group matched for age and gender was also recruited (n=44). 100 patients were recruited (50 sepsis, 20 severe sepsis and 30 septic shock). Maximum clot firmness was significantly higher in the sepsis (p<0.001) and severe sepsis (p=0.012) groups than the healthy control (71.6±4.5 and 70.4±4.1 vs 64.4 respectively). In septic shock there was prolonged clot development; however, maximum clot firmness remained normal. Fibrinolytic function was significantly impaired in septic shock, which was also significantly associated with 28-day mortality (p<0.001). ROTEM indicated significantly enhanced clot structural development in sepsis and severe sepsis, which could be indicative of a hypercoagulable phase. In septic shock, despite there being a prolongation of clotting pathways and impaired fibrinolysis, clot mass was comparably normal, suggestive of the development of a clot with healthy characteristics. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Behavioural, emotional, and post-traumatic stress problems in children and adolescents, long term after septic shock caused by Neisseria meningitidis

    NARCIS (Netherlands)

    Vermunt, L. C. A. C.; Buysse, C. M. P.; Joosten, K. F. M.; Hazelzet, J. A.; Verhulst, F. C.; Utens, E. M. W. J.

    2008-01-01

    To assess the occurrence of a wide range of behavioural, emotional, and post-traumatic stress problems in children and adolescents, long term after septic shock caused by Neisseria meningitidis (MSS). This study included 6- to 17-year-old patients who survived MSS and were admitted to the PICU of

  16. [The predictive value of dynamic arterial elastance in arterial pressure response after norepinephrine dosage reduction in patients with septic shock].

    Science.gov (United States)

    Liang, F M; Yang, T; Dong, L; Hui, J J; Yan, J

    2017-05-01

    Objective: To assess whether dynamic arterial elastance(Ea(dyn))can be used to predict the reduction of arterial pressure after decreasing norepinephrine (NE) dosage in patients with septic shock. Methods: A prospective observational cohort study was conducted. Thirty-two patients with septic shock and mechanical ventilationwere enrolledfrom January 2014 to December 2015 in ICU of Wuxi People's Hospital of Nanjing Medical University. Hemodynamic parameters were recorded by pulse contour cardiac output(PiCCO)monitoring technology before and after decreasing norepinephrine dosage. Ea(dyn) was defined as the ratio of pulse pressure variation (PPV) to stroke volume variation (SVV). Mean arterial pressure(MAP) variation was calculated after decreasing the dose of NE. Response was defined as a ≥15% decrease of MAP. AUC was plotted to assess the value of Ea(dyn) in predicting MAP response. Results: A total of 32 patients were enrolled in our study, with 13 responding to NE dose decrease where as the other 19 did not. Ea(dyn) was lower in responders than in nonresponders (0.77±0.13 vs 1.09±0.31, P blood pressure variation, diastolic blood pressure variation, systemic vascular resistance variation and MAP variation( r =0.621, P =0.000; r =0.735, P =0.000; r =0.756, P =0.000; r =0.568, P =0.000 respectively). However, stoke volume variation, baseline level of systemic vascular resistance and NE baseline dose were not correlated with Ea(dyn) baseline value( r =0.264, P =0.076; r =0.078, P =0.545; r =0.002, P =0.987 respectively). Ea(dyn)≤0.97 predicted a decrease of MAP when decreasing NE dose, with an area under the receiver-operating characteristic curve of 0.85.The sensitivity was 100.0% and specificity was 73.7%. Conclusions: In septic shock patients treated with NE, Ea(dyn) is an index to predict the decrease of arterial pressure in response to NE dose reduction.

  17. A peptide of heparin cofactor II inhibits endotoxin-mediated shock and invasive Pseudomonas aeruginosa infection.

    Directory of Open Access Journals (Sweden)

    Martina Kalle

    Full Text Available Sepsis and septic shock remain important medical problems with high mortality rates. Today's treatment is based mainly on using antibiotics to target the bacteria, without addressing the systemic inflammatory response, which is a major contributor to mortality in sepsis. Therefore, novel treatment options are urgently needed to counteract these complex sepsis pathologies. Heparin cofactor II (HCII has recently been shown to be protective against Gram-negative infections. The antimicrobial effects were mapped to helices A and D of the molecule. Here we show that KYE28, a 28 amino acid long peptide representing helix D of HCII, is antimicrobial against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungus Candida albicans. Moreover, KYE28 binds to LPS and thereby reduces LPS-induced pro-inflammatory responses by decreasing NF-κB/AP-1 activation in vitro. In mouse models of LPS-induced shock, KYE28 significantly enhanced survival by dampening the pro-inflammatory cytokine response. Finally, in an invasive Pseudomonas infection model, the peptide inhibited bacterial growth and reduced the pro-inflammatory response, which lead to a significant reduction of mortality. In summary, the peptide KYE28, by simultaneously targeting bacteria and LPS-induced pro-inflammatory responses represents a novel therapeutic candidate for invasive infections.

  18. A peptide of heparin cofactor II inhibits endotoxin-mediated shock and invasive Pseudomonas aeruginosa infection.

    Science.gov (United States)

    Kalle, Martina; Papareddy, Praveen; Kasetty, Gopinath; van der Plas, Mariena J A; Mörgelin, Matthias; Malmsten, Martin; Schmidtchen, Artur

    2014-01-01

    Sepsis and septic shock remain important medical problems with high mortality rates. Today's treatment is based mainly on using antibiotics to target the bacteria, without addressing the systemic inflammatory response, which is a major contributor to mortality in sepsis. Therefore, novel treatment options are urgently needed to counteract these complex sepsis pathologies. Heparin cofactor II (HCII) has recently been shown to be protective against Gram-negative infections. The antimicrobial effects were mapped to helices A and D of the molecule. Here we show that KYE28, a 28 amino acid long peptide representing helix D of HCII, is antimicrobial against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungus Candida albicans. Moreover, KYE28 binds to LPS and thereby reduces LPS-induced pro-inflammatory responses by decreasing NF-κB/AP-1 activation in vitro. In mouse models of LPS-induced shock, KYE28 significantly enhanced survival by dampening the pro-inflammatory cytokine response. Finally, in an invasive Pseudomonas infection model, the peptide inhibited bacterial growth and reduced the pro-inflammatory response, which lead to a significant reduction of mortality. In summary, the peptide KYE28, by simultaneously targeting bacteria and LPS-induced pro-inflammatory responses represents a novel therapeutic candidate for invasive infections.

  19. Procalcitonin as a diagnostic biomarker for septic shock and bloodstream infection in burn patients from the Formosa Fun Coast dust explosion

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    Rui-Xin Wu

    2017-12-01

    Full Text Available Background/Purpose: Infection is the most common cause of death following burn injury. The study was conducted to compare the diagnostic value of serum procalcitonin (PCT with the other current benchmarks as early predictors of septic shock and bloodstream infection in burn patients. Methods: We included 24 patients admitted to the Burn Unit of a medical center from June 2015 to December 2015 from the Formosa Fun Coast dust explosion. We categorized all patients at initial admission into either sepsis or septic shock groups. Laboratory tests including the worst PCT and C-reactive protein (CRP levels, platelet (PLT, and white blood cell (WBC count were performed at <48 h after admission. Patients were also classified in two groups with subsequent bacteremia and non-bacteremia groups during hospitalization. Results: Significantly higher PCT levels were observed among participants with septic shock compared to those with sepsis (47.19 vs. 1.18 ng/mL, respectively; p < 0.001. Patients with bacteremia had significantly elevated PCT levels compared to patients without bacteremia (29.54 versus 1.81 ng/mL, respectively, p < 0.05. No significant differences were found in CRP levels, PLT, and WBC count between the two groups. PCT levels showed reasonable discriminative power (cut-off: 5.12 ng/mL; p = 0.01 in predicting of bloodstream infection in burn patients and the area under receiver operating curves was 0.92. Conclusions: PCT levels can be helpful in determining the septic shock and bloodstream infection in burn patients but CRP levels, PLT, and WBC count were of little diagnostic value. Keywords: Procalcitonin, Septic shock, Bloodstream infection, Burn patient, Formosa fun coast dust explosion

  20. Ginger extract inhibits LPS induced macrophage activation and function

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    Bruch David

    2008-01-01

    Full Text Available Abstract Background Macrophages play a dual role in host defence. They act as the first line of defence by mounting an inflammatory response to antigen exposure and also act as antigen presenting cells and initiate the adaptive immune response. They are also the primary infiltrating cells at the site of inflammation. Inhibition of macrophage activation is one of the possible approaches towards modulating inflammation. Both conventional and alternative approaches are being studied in this regard. Ginger, an herbal product with broad anti inflammatory actions, is used as an alternative medicine in a number of inflammatory conditions like rheumatic disorders. In the present study we examined the effect of ginger extract on macrophage activation in the presence of LPS stimulation. Methods Murine peritoneal macrophages were stimulated by LPS in presence or absence of ginger extract and production of proinflammatory cytokines and chemokines were observed. We also studied the effect of ginger extract on the LPS induced expression of MHC II, B7.1, B7.2 and CD40 molecules. We also studied the antigen presenting function of ginger extract treated macrophages by primary mixed lymphocyte reaction. Results We observed that ginger extract inhibited IL-12, TNF-α, IL-1β (pro inflammatory cytokines and RANTES, MCP-1 (pro inflammatory chemokines production in LPS stimulated macrophages. Ginger extract also down regulated the expression of B7.1, B7.2 and MHC class II molecules. In addition ginger extract negatively affected the antigen presenting function of macrophages and we observed a significant reduction in T cell proliferation in response to allostimulation, when ginger extract treated macrophages were used as APCs. A significant decrease in IFN-γ and IL-2 production by T cells in response to allostimulation was also observed. Conclusion In conclusion ginger extract inhibits macrophage activation and APC function and indirectly inhibits T cell activation.

  1. Role of Combining Peripheral with Sublingual Perfusion on Evaluating Microcirculation and Predicting Prognosis in Patients with Septic Shock.

    Science.gov (United States)

    Pan, Pan; Liu, Da-Wei; Su, Long-Xiang; He, Huai-Wu; Wang, Xiao-Ting; Yu, Chao

    2018-05-20

    Measurement of general microcirculation remains difficult in septic shock patients. The peripheral perfusion index (PI) and sublingual microcirculation monitoring are thought to be possible methods. This study was performed to determine whether assessing microcirculation by PI and a new parameter, proportion of perfusion vessel change rate (△PPV) from sublingual microcirculation monitoring, can be associated with patients' outcome. A prospective observational study was carried out, including 74 patients with septic shock in a mixed intensive care unit. Systemic hemodynamic variables were obtained at T0 and 6 h after (T6). PI and sublingual microcirculation indicators were obtained using a bedside monitor and a sidestream dark-field device, respectively. The t-test, analysis of variance, Mann-Whitney U-test, Kruskal-Wallis test, receiver operating characteristic curve analysis with the Hanley-McNeil test, survival curves using the Kaplan-Meier method, and the log-rank (Mantel-Cox) test were used to statistical analysis. Systemic hemodynamics and microcirculation data were obtained and analyzed. Patients were divided into two groups based on whether the first 6 h lactate clearance (LC) was ≥20%; PI and △PPV were lower at T6 in the LC <20% group compared with LC ≥20% (PI: 1.52 [0.89, 1.98] vs. 0.79 [0.44, 1,81], Z = -2.514, P = 0.012; △PPV: 5.9 ± 15.2 vs. 17.9 ± 20.0, t = -2.914, P = 0.005). The cutoff values of PI and △PPV were 1.41% and 12.1%, respectively. The cutoff value of the combined indicators was 1.379 according to logistic regression. Area under the curve demonstrated 0.709 (P < 0.05), and the sensitivity and specificity of using combined indicators were 0.622 and 0.757, respectively. Based on the PI and △PPV cutoff, all the participants were divided into the following groups: (1) high PI and high △PPV group, (2) high PI and low △PPV group, (3) low PI and high △PPV group, and (4) low PI and low △PPV group. The highest Sequential

  2. The choice of catecholamines in septic shock: more and more good arguments to strengthen the known position, but don't lose the faith!

    Science.gov (United States)

    Meier-Hellmann, Andreas

    2006-01-01

    The choice of catecholamines for hemodynamic stabilisation in septic shock patients has been an ongoing debate for several years. Several studies have investigated the regional effects in septic patients. Because of an often very small sample size, because of inconsistent results and because of methodical problems in the monitoring techniques used in these studies, however, it is not possible to provide clear recommendations concerning the use of catecholamines in sepsis. Prospective and adequate-sized studies are necessary because outcome data are completely lacking.

  3. The Absence of Fever Is Associated With Higher Mortality and Decreased Antibiotic and IV Fluid Administration in Emergency Department Patients With Suspected Septic Shock.

    Science.gov (United States)

    Henning, Daniel J; Carey, Jeremy R; Oedorf, Kimie; Day, Danielle E; Redfield, Colby S; Huguenel, Colin J; Roberts, Jonathan C; Sanchez, Leon D; Wolfe, Richard E; Shapiro, Nathan I

    2017-06-01

    This study evaluates whether emergency department septic shock patients without a fever (reported or measured) receive less IV fluids, have decreased antibiotic administration, and suffer increased in-hospital mortality. This was a secondary analysis of a prospective, observational study of patients with shock. The study was conducted in an urban, academic emergency department. The original study enrolled consecutive adult (aged 18 yr or older) emergency department patients from November 11, 2012, to September 23, 2013, who met one of the following shock criteria: 1) systolic blood pressure less than 90 mm Hg after at least 1L IV fluids, 2) new vasopressor requirement, or 3) systolic blood pressure less than 90 mm Hg and IV fluids held for concern of fluid overload. The current study is limited to patients with septic shock. Patients were grouped as febrile if they had a subjective fever or a measured temperature >100.4°F documented in the emergency department; afebrile patients lacked both. Among 378 patients with septic shock, 207 of 378 (55%; 50-60%) were febrile by history or measurement. Afebrile patients had lower rates of antibiotic administration in the emergency department (81% vs 94%; p < 0.01), lower mean volumes of IV fluids (2,607 vs 3,013 mL; p < 0.01), and higher in-hospital mortality rates (33% vs 11%; p < 0.01). After adjusting for bicarbonate less than 20 mEq/L, lactate concentration, respiratory rate greater than or equal to 24 breaths/min, emergency department antibiotics, and emergency department IV fluids volume, being afebrile remained a significant predictor of in-hospital mortality (odds ratio, 4.3; 95% CI, 2.2-8.2; area under the curve = 0.83). In emergency department patients with septic shock, afebrile patients received lower rates of emergency department antibiotic administration, lower mean IV fluids volume, and suffered higher in-hospital mortality.

  4. Prescribing patterns of hydrocortisone in septic shock: a single-center experience of how surviving sepsis guidelines are interpreted and translated into bedside practice.

    Science.gov (United States)

    Contrael, Katlynd M; Killian, Alley J; Gregg, Sara R; Buchman, Timothy G; Coopersmith, Craig M

    2013-10-01

    The Surviving Sepsis Campaign suggests giving hydrocortisone to septic patients only if their "blood pressure is poorly responsive to fluid resuscitation and vasopressor therapy." Because the definition of "poorly responsive" is not provided, the purpose of this study was to identify prescribing triggers for hydrocortisone in septic shock. Retrospective chart review of patients with septic shock over 17 months, who received hydrocortisone, followed by a survey of all intensivists who attended in the study ICUs to determine whether provider attitudes matched clinical practice. Eight ICUs in an academic hospital and a hybrid academic/community hospital. A total of 155 patients with septic shock in whom vasopressors were initiated and hydrocortisone was prescribed. Ninety-nine patients (64%) were already receiving two vasopressors before hydrocortisone was prescribed. An additional 22 patients were on a single high-dose vasopressor prior to corticosteroid initiation. Of patients who survived to have their hydrocortisone dose changed, 57% had their corticosteroids tapered, whereas 43% were abruptly discontinued. Seventy-six percent of patients were no longer on vasopressors when the first dosing change was made. Twenty-seven out of 36 intensivists (75%) completed the survey. The majority (72%) defined "poorly responsive to vasopressors" as the presence of two vasopressors, and 70% stated that they required patients to be off vasopressors prior to altering the corticosteroid dose. Significant variability exists when corticosteroids are prescribed for septic shock, with the most common interpretation in our institution of "poorly responsive to fluid resuscitation and vasopressor therapy" being the presence of two vasopressors. The method and timing of corticosteroid discontinuation also differed among providers. Self-described prescribing patterns from intensivists closely matched their actual behavior, suggesting variability is due to differing interpretations of the

  5. A survey of critical care nurses' practices and perceptions surrounding early intravenous antibiotic initiation during septic shock.

    Science.gov (United States)

    Roberts, Russel J; Alhammad, Abdullah M; Crossley, Lindsay; Anketell, Eric; Wood, LeeAnn; Schumaker, Greg; Garpestad, Erik; Devlin, John W

    2017-08-01

    Delays in antibiotic administration after severe sepsis recognition increases mortality. While physician and pharmacy-related barriers to early antibiotic initiation have been well evaluated, those factors that affect the speed by which critical care nurses working in either the emergency department or the intensive care unit setting initiate antibiotic therapy remains poorly characterized. To evaluate the knowledge, practices and perceptions of critical care nurses regarding antibiotic initiation in patients with newly recognised septic shock. A validated survey was distributed to 122 critical care nurses at one 320-bed academic institution with a sepsis protocol advocating intravenous(IV) antibiotic initiation within 1hour of shock recognition. Among 100 (82%) critical care nurses responding, nearly all (98%) knew of the existence of the sepsis protocol. However, many critical care nurses stated they would optimise blood pressure [with either fluid (38%) or both fluid and a vasopressor (23%)] before antibiotic initiation. Communicated barriers to rapid antibiotic initiation included: excessive patient workload (74%), lack of awareness IV antibiotic(s) ordered (57%) or delivered (69%), need for administration of multiple non-antibiotic IV medications (54%) and no IV access (51%). Multiple nurse-related factors influence IV antibiotic(s) initiation speed and should be incorporated into sepsis quality improvement efforts. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Comparison of the effects of albumin and crystalloid on mortality in adult patients with severe sepsis and septic shock: a meta-analysis of randomized clinical trials.

    Science.gov (United States)

    Xu, Jing-Yuan; Chen, Qi-Hong; Xie, Jian-Feng; Pan, Chun; Liu, Song-Qiao; Huang, Li-Wei; Yang, Cong-Shan; Liu, Ling; Huang, Ying-Zi; Guo, Feng-Mei; Yang, Yi; Qiu, Hai-Bo

    2014-12-15

    The aim of this study was to examine whether albumin reduced mortality when employed for the resuscitation of adult patients with severe sepsis and septic shock compared with crystalloid by meta-analysis. We searched for and gathered data from MEDLINE, Elsevier, Cochrane Central Register of Controlled Trials and Web of Science databases. Studies were eligible if they compared the effects of albumin versus crystalloid therapy on mortality in adult patients with severe sepsis and septic shock. Two reviewers extracted data independently. Disagreements were resolved by discussion with other two reviewers until a consensus was achieved. Data including mortality, sample size of the patients with severe sepsis, sample size of the patients with septic shock and resuscitation endpoints were extracted. Data were analyzed by the methods recommended by the Cochrane Collaboration Review Manager 4.2 software. A total of 5,534 records were identified through the initial search. Five studies compared albumin with crystalloid. In total, 3,658 severe sepsis and 2,180 septic shock patients were included in the meta-analysis. The heterogeneity was determined to be non-significant (P = 0.86, I(2) = 0%). Compared with crystalloid, a trend toward reduced 90-day mortality was observed in severe sepsis patients resuscitated with albumin (odds ratio (OR) 0.88; 95% CI, 0.76 to 1.01; P = 0.08). However, the use of albumin for resuscitation significantly decreased 90-day mortality in septic shock patients (OR 0.81; 95% CI, 0.67 to 0.97; P = 0.03). Compared with saline, the use of albumin for resuscitation slightly improved outcome in severe sepsis patients (OR 0.81; 95% CI, 0.64 to 1.08; P = 0.09). In this meta-analysis, a trend toward reduced 90-day mortality was observed in severe sepsis patients resuscitated with albumin compared with crystalloid and saline. Moreover, the 90-day mortality of patients with septic shock decreased significantly.

  7. Inhibition of miR-155 Protects Against LPS-induced Cardiac Dysfunction and Apoptosis in Mice

    Directory of Open Access Journals (Sweden)

    Hui Wang

    2016-01-01

    Full Text Available Sepsis-induced myocardial dysfunction represents a major cause of death in intensive care units. Dysregulated microRNAs (miR-155 has been implicated in multiple cardiovascular diseases and miR-155 can be induced by lipopolysaccharide (LPS. However, the role of miR-155 in LPS-induced cardiac dysfunction is unclear. Septic cardiac dysfunction in mice was induced by intraperitoneal injection of LPS (5 mg/kg and miR-155 was found to be significantly increased in heart challenged with LPS. Pharmacological inhibition of miR-155 using antagomiR improved cardiac function and suppressed cardiac apoptosis induced by LPS in mice as determined by echocardiography, terminal deoxynucleotidyl transferase nick-end labeling (TUNEL assay, and Western blot for Bax and Bcl-2, while overexpression of miR-155 using agomiR had inverse effects. Pea15a was identified as a target gene of miR-155, mediating its effects in controlling apoptosis of cardiomyocytes as evidenced by luciferase reporter assays, quantitative real time-polymerase chain reaction, Western blot, and TUNEL staining. Noteworthy, miR-155 was also found to be upregulated in the plasma of patients with septic cardiac dysfunction compared to sepsis patients without cardiac dysfunction, indicating a potential clinical relevance of miR-155. The receiver-operator characteristic curve indicated that plasma miR-155 might be a biomarker for sepsis patients developing cardiac dysfunction. Therefore, inhibition of miR-155 represents a novel therapy for septic myocardial dysfunction.

  8. Simultaneous use of traditional Chinese medicine (Si-Ni-Tang to treat septic shock patients: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Wu Shin-Hwar

    2011-08-01

    Full Text Available Abstract Background Even though there are continually upgraded recommendations for managing sepsis, such as "Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock", mortality is still high. Si-Ni-Tang, a remedy documented in Shanghan Lun, a medical collection from ancient China, is used for treating patients with sepsis and septic shock. Using a well-designed clinical trial, we are eager to survey the effectiveness of the concurrent use of this remedy in restoring these patients' hemodynamic status, or "Yang Qi". Methods/Design Patients admitted to our medical intensive care units with the diagnosis of septic shock, defined as persistent hypotension induced by sepsis despite adequate fluid resuscitation, are eligible for participation. The inclusion criteria include: age from 20 to 85 years, conditions meeting the definition of septic shock, use of vasopressors within 24 hours of entering the study, and use of a nasogastric tube for feeding. The enrolled patients are randomly allocated either to the Si-Ni-Tang group or the placebo group. The prescription of the trial drugs (Si-Ni-Tang/placebo is 2.25 grams 4 times a day for 7 days or till shock reversal (if shock reversal occurs in less than 7 days. Data, including duration of vasopressor infusion, gender, age, co-morbidities, APACHE II score, predicted mortality, ICU mortality, ICU length of stay, hospital mortality, hospital length of stay, source of sepsis, and culture results, are collected for the following analysis. Discussion Si-Ni-Tang is composed of processed Zingiber officinale, Glycyrrhiza uralensis, and Aconitum carmichaeli. Zingiber officinale and Glycyrrhiza uralensis are found to have the ability to reduce pro-inflammatory cytokine production, to inhibit lipopolisaccharide-induced macrophage activation and function, and to lessen the bacterial load and suppress acute and chronic inflammation. Aconitum carmichaeli is known to have

  9. [The effect of body temperature control on organ function and prognosis in patients with refractory septic shock].

    Science.gov (United States)

    Wang, Xiaoting; Liu, Dawei; Yang, Yanli; Zhou, Xiang; Chai, Wenzhao; Long, Yun; Zhang, Hongmin; Zhang, Qing; He, Huaiwu

    2014-04-01

    To investigate the effect of body temperature control on organ function and prognosis in patients with refractory septic shock. A total of 67 eligible patients with the body temperature over 38.5 °C were enrolled in the study and all patients were treated with a water-flow cooling blanket to control the body temperature below 38.3 °C for 72 hours. The core and peripheral temperature was tested at 1 hour interval. All patients were devised into the following two groups according to their mean core temperature within the 72 hours: the HT group with a mean core temperature ≥ 37.5 °C and the LT group with a mean core temperature temperature increased above 38.5 °C. Thirty-four patients (50.7%) were classified into the HT group, while thirty-three patients (49.3%) were in the LT group. Compared with the HT group, higher mortality rate at Day 28 was observed in the LT group (69.7% vs 35.3%, P = 0.005). Significant difference in the increase of sepsis-related organ failure assessment (SOFA) score was found between of the HT and the LT groups (1.30 ± 0.90 vs 2.30 ± 2.10, P = 0.02). Statistical differences were observed between the two groups in mean core temperature [(37.90 ± 0.30) °C vs (36.80 ± 0.60) °C, P peripheral temperature [(37.20 ± 0.30) °C vs (36.30 ± 0.60) °C, P temperature [(36.90 ± 0.30)°C vs (35.80 ± 0.60) °C, P peripheral temperature [(36.20 ± 0.40) °C vs (35.50 ± 0.60) °C, P peripheral temperature.Statistical difference was also shown in troponin I, fibrinogen, partial thromboplastin and activated partial thromboplastin between the two groups. Cox regression analysis revealed that the mean core temperature was the only independent predictor for the mortality rate at Day 28. Body temperature control within the normal range may exert potentially detrimental effect on organ function and prognosis in patients with refractory septic shock with fever.

  10. Procalcitonin as a diagnostic biomarker for septic shock and bloodstream infection in burn patients from the Formosa Fun Coast dust explosion.

    Science.gov (United States)

    Wu, Rui-Xin; Chiu, Chih-Chien; Lin, Tzu-Chao; Yang, Ya-Sung; Lee, Yi; Lin, Jung-Chung; Chang, Feng-Yee

    2017-12-01

    Infection is the most common cause of death following burn injury. The study was conducted to compare the diagnostic value of serum procalcitonin (PCT) with the other current benchmarks as early predictors of septic shock and bloodstream infection in burn patients. We included 24 patients admitted to the Burn Unit of a medical center from June 2015 to December 2015 from the Formosa Fun Coast dust explosion. We categorized all patients at initial admission into either sepsis or septic shock groups. Laboratory tests including the worst PCT and C-reactive protein (CRP) levels, platelet (PLT), and white blood cell (WBC) count were performed at <48 h after admission. Patients were also classified in two groups with subsequent bacteremia and non-bacteremia groups during hospitalization. Significantly higher PCT levels were observed among participants with septic shock compared to those with sepsis (47.19 vs. 1.18 ng/mL, respectively; p < 0.001). Patients with bacteremia had significantly elevated PCT levels compared to patients without bacteremia (29.54 versus 1.81 ng/mL, respectively, p < 0.05). No significant differences were found in CRP levels, PLT, and WBC count between the two groups. PCT levels showed reasonable discriminative power (cut-off: 5.12 ng/mL; p = 0.01) in predicting of bloodstream infection in burn patients and the area under receiver operating curves was 0.92. PCT levels can be helpful in determining the septic shock and bloodstream infection in burn patients but CRP levels, PLT, and WBC count were of little diagnostic value. Copyright © 2017. Published by Elsevier B.V.

  11. Combining central venous-to-arterial partial pressure of carbon dioxide difference and central venous oxygen saturation to guide resuscitation in septic shock.

    Science.gov (United States)

    Du, Wei; Liu, Da-Wei; Wang, Xiao-Ting; Long, Yun; Chai, Wen-Zhao; Zhou, Xiang; Rui, Xi

    2013-12-01

    Central venous oxygen saturation (Scvo2) is a useful therapeutic target when treating septic shock. We hypothesized that combining Scvo2 and central venous-to-arterial partial pressure of carbon dioxide difference (△Pco2) may provide additional information about survival. We performed a retrospective analysis of 172 patients treated for septic shock. All patients were treated using goal-directed therapy to achieve Scvo2 ≥ 70%. After 6 hours of treatment, we divided patients into 4 groups based on Scvo2 (<70% or ≥ 70%) and △Pco2 (<6 mm Hg or ≥ 6 mm Hg). Overall, 28-day mortality was 35.5%. For patients in whom the Scvo2 target was not achieved at 6 hours, mortality was 50.0%, compared with 29.5% in those in whom Scvo2 exceeded 70% (P = .009). In patients with Scvo2 ≥ 70%, mortality was lower if △Pco2 was <6 mm Hg than if △Pco2 was ≥ 6 mm Hg (56.1% vs 16.1%, respectively; P < .001) and 6-hour lactate clearance was superior (0.01 ± 0.61 vs 0.21 ± 0.31, respectively; P = .016). The combination of Scvo2 and △Pco2 appears to predict outcome in critically ill patients resuscitated from septic shock better than Scvo2 alone. Patients who meet both targets appear to clear lactate more efficiently. © 2013.

  12. Prevention of LPS-Induced Acute Lung Injury in Mice by Progranulin

    Directory of Open Access Journals (Sweden)

    Zhongliang Guo

    2012-01-01

    Full Text Available The acute respiratory distress syndrome (ARDS, a clinical complication of severe acute lung injury (ALI in humans, is a leading cause of morbidity and mortality in critically ill patients. Despite decades of research, few therapeutic strategies for clinical ARDS have emerged. Here we carefully evaluated the effect of progranulin (PGRN in treatment of ARDS using the murine model of lipopolysaccharide (LPS-induced ALI. We reported that administration of PGRN maintained the body weight and survival of ALI mice. We revealed that administration of PGRN significantly reduced LPS-induced pulmonary inflammation, as reflected by reductions in total cell and neutrophil counts, proinflammatory cytokines, as well as chemokines in bronchoalveolar lavage (BAL fluid. Furthermore, administration of PGRN resulted in remarkable reversal of LPS-induced increases in lung permeability as assessed by reductions in total protein, albumin, and IgM in BAL fluid. Consistently, we revealed a significant reduction of histopathology changes of lung in mice received PGRN treatment. Finally, we showed that PGRN/TNFR2 interaction was crucial for the protective effect of PGRN on the LPS-induced ALI. Our findings strongly demonstrated that PGRN could effectively ameliorate the LPS-induced ALI in mice, suggesting a potential application for PGRN-based therapy to treat clinical ARDS.

  13. A qualitative feasibility study to inform a randomised controlled trial of fluid bolus therapy in septic shock.

    Science.gov (United States)

    O'Hara, Caitlin B; Canter, Ruth R; Mouncey, Paul R; Carter, Anjali; Jones, Nicola; Nadel, Simon; Peters, Mark J; Lyttle, Mark D; Harrison, David A; Rowan, Kathryn M; Inwald, David; Woolfall, Kerry

    2018-01-01

    The Fluids in Shock (FiSh) Trial proposes to evaluate whether restrictive fluid bolus therapy (10 mL/kg) is more beneficial than current recommended practice (20 mL/kg) in the resuscitation of children with septic shock in the UK. This qualitative feasibility study aimed to explore acceptability of the FiSh Trial, including research without prior consent (RWPC), potential barriers to recruitment and participant information for a pilot trial. Qualitative interview study involving parents of children who had presented to a UK emergency department or been admitted to a paediatric intensive care unit with severe infection in the previous 3 years. Twenty-one parents (seven bereaved) were interviewed 16 (median) months since their child's hospital admission (range: 1-41). All parents said they would have provided consent for the use of their child's data in the FiSh Trial. The majority were unfamiliar with RWPC, yet supported its use. Parents were initially concerned about the change from currently recommended treatment, yet were reassured by explanations of the current evidence base, fluid bolus therapy and monitoring procedures. Parents made recommendations about the timing of the research discussion and content of participant information. Bereaved parents stated that recruiters should not discuss research immediately after a child's death, but supported a personalised postal 'opt-out' approach to consent. Findings show that parents whose child has experienced severe infection supported the proposed FiSh Trial, including the use of RWPC. Parents' views informed the development of the pilot trial protocol and site staff training. ISRCTN15244462-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  14. Effect of mechanical ventilation on systemic oxygen extraction and lactic acidosis during early septic shock in rats.

    Science.gov (United States)

    Griffel, M I; Astiz, M E; Rackow, E C; Weil, M H

    1990-01-01

    We studied the effect of mechanical ventilation on systemic oxygen extraction and lactic acidosis in peritonitis and shock in rats. Sepsis was induced by cecal ligation and perforation. After tracheostomy, rats were randomized to spontaneous breathing (S) or mechanical ventilation with paralysis (V). Five animals were studied in each group. The V animals were paralyzed with pancuronium bromide to eliminate respiratory effort. Mechanical ventilation consisted of controlled ventilation using a rodent respirator with periodic adjustment of minute ventilation to maintain PaCO2 and pH within normal range. Arterial and central venous blood gases and thermodilution cardiac output were measured at baseline before abdominal surgery, and sequentially at 0.5, 3.5, and 6 h after surgery. At 6 h, cardiac output was 193 +/- 30 ml/kg.min in S animals and 199 +/- 32 ml/kg.min in V animals (NS). The central venous oxygen saturation was 27.4 +/- 4.7% in S animals and 30.0 +/- 6.4% in V animals (NS). Systemic oxygen extraction was 70 +/- 5% in S animals and 67 +/- 6% in V animals (NS). Arterial lactate was 2.4 +/- 0.4 mmol/L in S animals and 2.2 +/- 0.5 mmol/L in V animals (NS). The S animals developed lethal hypotension at 6.6 +/- 0.4 h compared to 6.8 +/- 0.4 h in V animals (NS). These data suggest that mechanical ventilation does not decrease systemic oxygen extraction or ameliorate the development of lactic acidosis during septic shock.

  15. A qualitative feasibility study to inform a randomised controlled trial of fluid bolus therapy in septic shock

    Science.gov (United States)

    O’Hara, Caitlin B; Canter, Ruth R; Mouncey, Paul R; Carter, Anjali; Jones, Nicola; Nadel, Simon; Peters, Mark J; Lyttle, Mark D; Harrison, David A; Rowan, Kathryn M; Inwald, David; Woolfall, Kerry

    2018-01-01

    Objective The Fluids in Shock (FiSh) Trial proposes to evaluate whether restrictive fluid bolus therapy (10 mL/kg) is more beneficial than current recommended practice (20 mL/kg) in the resuscitation of children with septic shock in the UK. This qualitative feasibility study aimed to explore acceptability of the FiSh Trial, including research without prior consent (RWPC), potential barriers to recruitment and participant information for a pilot trial. Design Qualitative interview study involving parents of children who had presented to a UK emergency department or been admitted to a paediatric intensive care unit with severe infection in the previous 3 years. Participants Twenty-one parents (seven bereaved) were interviewed 16 (median) months since their child’s hospital admission (range: 1–41). Results All parents said they would have provided consent for the use of their child’s data in the FiSh Trial. The majority were unfamiliar with RWPC, yet supported its use. Parents were initially concerned about the change from currently recommended treatment, yet were reassured by explanations of the current evidence base, fluid bolus therapy and monitoring procedures. Parents made recommendations about the timing of the research discussion and content of participant information. Bereaved parents stated that recruiters should not discuss research immediately after a child’s death, but supported a personalised postal ‘opt-out’ approach to consent. Conclusions Findings show that parents whose child has experienced severe infection supported the proposed FiSh Trial, including the use of RWPC. Parents’ views informed the development of the pilot trial protocol and site staff training. Trial registration number ISRCTN15244462—results. PMID:28847877

  16. Fatal Candida septic shock during systemic chemotherapy in lung cancer patient receiving corticosteroid replacement therapy for hypopituitarism. A case report

    International Nuclear Information System (INIS)

    Morichika, Daisuke; Sato-Hisamoto, Akiko; Hotta, Katsuyuki

    2014-01-01

    Invasive candidiasis has increased as nosocomial infection recently in cancer patients who receive systemic chemotherapy, and the timely risk assessment for developing such specific infection is crucial. Especially in those concomitantly with hypopituitarism, febrile neutropenia with candidiasis can cause severe stress and lead potentially to sudden fatal outcome when the temporal steroid coverage for the adrenal insufficiency is not fully administered. We report a 72-year-old male case diagnosed as non-small-cell lung cancer, Stage 3A. He had received a steroid replacement therapy for the prior history of hypophysectomy due to pituitary adenoma with hydrocortisone of 3.3 mg/day, equivalent to prednisolone of 0.8 mg/day. This very small dosage of steroid was hardly supposed to weaken his immune system, but rather potentially led to an inappropriate supplementation of his adrenal function, assuming that the serum sodium and chlorine levels decreased. On Day 6 of second cycle of chemotherapy with carboplatin and paclitaxel, he developed sudden febrile neutropenia, septic shock and ileus, leading to death. After his death, the venous blood culture on Day 7 detected Candida albicans. Autopsy findings showed a massive necrotizing enterocolitis with extensive Candida invasion into submucous tissue. In conclusion, this case may suggest that (1) immediate initiation of antifungal therapy soon after the careful risk assessment of Candida infection and (2) adequate administration of both basal steroid replacement therapy and temporal steroid coverage for febrile neutropenia might have improved his fatal outcome. (author)

  17. Endogenous brain IL-1 mediates LPS-induced anorexia and hypothalamic cytokine expression.

    Science.gov (United States)

    Layé, S; Gheusi, G; Cremona, S; Combe, C; Kelley, K; Dantzer, R; Parnet, P

    2000-07-01

    The present study was designed to determine the role of endogenous brain interleukin (IL)-1 in the anorexic response to lipopolysaccharide (LPS). Intraperitoneal administration of LPS (5-10 microgram/mouse) induced a dramatic, but transient, decrease in food intake, associated with an enhanced expression of proinflammatory cytokine mRNA (IL-1beta, IL-6, and tumor necrosis factor-alpha) in the hypothalamus. This dose of LPS also increased plasma levels of IL-1beta. Intracerebroventricular pretreatment with IL-1 receptor antagonist (4 microgram/mouse) attenuated LPS-induced depression of food intake and totally blocked the LPS-induced enhanced expression of proinflammatory cytokine mRNA measured in the hypothalamus 1 h after treatment. In contrast, LPS-induced increases in plasma levels of IL-1beta were not altered. These findings indicate that endogenous brain IL-1 plays a pivotal role in the development of the hypothalamic cytokine response to a systemic inflammatory stimulus.

  18. 4G/5G polymorphism of PAI-1 gene is associated with multiple organ dysfunction and septic shock in pneumonia induced severe sepsis: prospective, observational, genetic study

    Science.gov (United States)

    2010-01-01

    Introduction Activation of inflammation and coagulation are closely related and mutually interdependent in sepsis. The acute-phase protein, plasminogen activator inhibitor-1 (PAI-1) is a key element in the inhibition of fibrinolysis. Elevated levels of PAI-1 have been related to worse outcome in pneumonia. We aimed to evaluate the effect of functionally relevant 4G/5G polymorphism of PAI-1 gene in pneumonia induced sepsis. Methods We enrolled 208 Caucasian patients with severe sepsis due to pneumonia admitted to an intensive care unit (ICU). Patients were followed up until ICU discharge or death. Clinical data were collected prospectively and the PAI-1 4G/5G polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism technique. Patients were stratified according to the occurrence of multiple organ dysfunction syndrome, septic shock or death. Results We found that carriers of the PAI-1 4G/4G and 4G/5G genotypes have a 2.74-fold higher risk for multiple organ dysfunction syndrome (odds ratio [OR] 95% confidence interval [CI] = 1.335 - 5.604; p = 0.006) and a 2.57-fold higher risk for septic shock (OR 95%CI = 1.180 - 5.615; p = 0.018) than 5G/5G carriers. The multivariate logistic regression analysis adjusted for independent predictors, such as age, nosocomial pneumonia and positive microbiological culture also supported that carriers of the 4G allele have a higher prevalence of multiple organ dysfunction syndrome (adjusted odds ratio [aOR] = 2.957; 95%CI = 1.306 -6.698; p = 0.009) and septic shock (aOR = 2.603; 95%CI = 1.137 - 5.959; p = 0.024). However, genotype and allele analyses have not shown any significant difference regarding mortality in models non-adjusted or adjusted for acute physiology and chronic health evaluation (APACHE) II. Patients bearing the 4G allele had higher disseminated intravascular coagulation (DIC) score at admission (p = 0.007) than 5G/5G carriers. Moreover, in 4G allele carriers the length of ICU stay

  19. 4G/5G polymorphism of PAI-1 gene is associated with multiple organ dysfunction and septic shock in pneumonia induced severe sepsis: prospective, observational, genetic study.

    Science.gov (United States)

    Madách, Krisztina; Aladzsity, István; Szilágyi, Agnes; Fust, George; Gál, János; Pénzes, István; Prohászka, Zoltán

    2010-01-01

    Activation of inflammation and coagulation are closely related and mutually interdependent in sepsis. The acute-phase protein, plasminogen activator inhibitor-1 (PAI-1) is a key element in the inhibition of fibrinolysis. Elevated levels of PAI-1 have been related to worse outcome in pneumonia. We aimed to evaluate the effect of functionally relevant 4G/5G polymorphism of PAI-1 gene in pneumonia induced sepsis. We enrolled 208 Caucasian patients with severe sepsis due to pneumonia admitted to an intensive care unit (ICU). Patients were followed up until ICU discharge or death. Clinical data were collected prospectively and the PAI-1 4G/5G polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism technique. Patients were stratified according to the occurrence of multiple organ dysfunction syndrome, septic shock or death. We found that carriers of the PAI-1 4G/4G and 4G/5G genotypes have a 2.74-fold higher risk for multiple organ dysfunction syndrome (odds ratio [OR] 95% confidence interval [CI] = 1.335 - 5.604; p = 0.006) and a 2.57-fold higher risk for septic shock (OR 95%CI = 1.180 - 5.615; p = 0.018) than 5G/5G carriers. The multivariate logistic regression analysis adjusted for independent predictors, such as age, nosocomial pneumonia and positive microbiological culture also supported that carriers of the 4G allele have a higher prevalence of multiple organ dysfunction syndrome (adjusted odds ratio [aOR] = 2.957; 95%CI = 1.306 -6.698; p = 0.009) and septic shock (aOR = 2.603; 95%CI = 1.137 - 5.959; p = 0.024). However, genotype and allele analyses have not shown any significant difference regarding mortality in models non-adjusted or adjusted for acute physiology and chronic health evaluation (APACHE) II. Patients bearing the 4G allele had higher disseminated intravascular coagulation (DIC) score at admission (p = 0.007) than 5G/5G carriers. Moreover, in 4G allele carriers the length of ICU stay of non-survivors was longer

  20. Compound edaravone alleviates lipopolysaccharide (LPS)-induced acute lung injury in mice.

    Science.gov (United States)

    Zhang, Zhengping; Luo, Zhaowen; Bi, Aijing; Yang, Weidong; An, Wenji; Dong, Xiaoliang; Chen, Rong; Yang, Shibao; Tang, Huifang; Han, Xiaodong; Luo, Lan

    2017-09-15

    Acute lung injury (ALI) represents an unmet medical need with an urgency to develop effective pharmacotherapies. Compound edaravone, a combination of edaravone and borneol, has been developed for treatment of ischemia stroke in clinical phase III study. The purpose of the present study is to investigate the anti-inflammatory effect of compound edaravone on lipopolysaccharide (LPS)-induced inflammatory response in RAW264.7 cells and the therapeutic efficacy on LPS-induced ALI in mice. Edaravone and compound edaravone concentration-dependently decreased LPS-induced interleukin-6 (IL-6) production and cyclooxygenase-2 (COX-2) expression in RAW264.7 cells. The efficiency of compound edaravone was stronger than edaravone alone. In the animal study, compound edaravone was injected intravenously to mice after intratracheal instillation of LPS. It remarkably alleviated LPS-induced lung injury including pulmonary histological abnormalities, polymorphonuclear leukocyte (PMN) infiltration and extravasation. Further study demonstrated that compound edaravone suppressed LPS-induced TNF-α and IL-6 increase in mouse serum and bronchoalveolar lavage (BAL) fluid, and inhibited LPS-induced nuclear factor-κB (NF-κB) activation and COX-2 expression in mice lung tissues. Importantly, our findings demonstrated that the compound edaravone showed a stronger protective effect against mouse ALI than edaravone alone, which suggested the synergies between edaravone and borneol. In conclusion, compound edaravone could be a potential novel therapeutic drug for ALI treatment and borneol might produce a synergism with edaravone. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. The anti-inflammatory effect of TR6 on LPS-induced mastitis in mice.

    Science.gov (United States)

    Hu, Xiaoyu; Fu, Yunhe; Tian, Yuan; Zhang, Zecai; Zhang, Wenlong; Gao, Xuejiao; Lu, Xiaojie; Cao, Yongguo; Zhang, Naisheng

    2016-01-01

    [TRIAP]-derived decoy peptides have anti-inflammatory properties. In this study, we synthesized a TRIAP-derived decoy peptide (TR6) containing, the N-terminal portion of the third helical region of the [TIRAP] TIR domain (sequence "N"-RQIKIWFQNRRMKWK and -KPGFLRDPWCKYQML-"C"). We evaluated the effects of TR6 on lipopolysaccharide-induced mastitis in mice. In vivo, the mastitis model was induced by LPS administration for 24h, and TR6 treatment was initiated 1h before or after induction of LPS. In vitro, primary mouse mammary epithelial cells and neutrophils were used to investigate the effects of TR6 on LPS-induced inflammatory responses. The results showed that TR6 significantly inhibited mammary gland hisopathologic changes, MPO activity, and LPS-induced production of TNF-α, IL-1β and IL-6. In vitro, TR6 significantly inhibited LPS-induced TNF-α and IL-6 production and phosphorylation of NF-κB and MAPKs. In conclusion, this study demonstrated that the anti-inflammatory effect of TR6 against LPS-induced mastitis may be due to its ability to inhibit TLR4-mediated NF-κB and MAPK signaling pathways. TR6 may be a promising therapeutic reagent for mastitis treatment. Copyright © 2015. Published by Elsevier B.V.

  2. Effect of 60Co γ-rays on PWM and LPS induced lymphocytes

    International Nuclear Information System (INIS)

    Su Liaoyuan; Liu Keliang; Liu Fenju

    1987-01-01

    The relationship between lymphocytes induced by PWM (pokeweed mitogen) and LPS (lipopolysaccharide) was investigated by means of 3 H-TdR incorporation. The study showed that, in vitro, PWM-induced cells were able to promote the stimulating effect of LPS to B lymphocytes. The stimulating effect of PWM-induced cells was obviously weakened after PWM cells being irradiated with γ-rays. When PWM-induced cells and LPS-induced cells were incubated together, with one kind of cells exposed to 60 Co γ-ray, incorporation value of 3 H-TdR became much smaller and the synergetic function disappeared, especially, when PWM-induced cells were irradiated. For patients suffering from carcinoma of nasopharynx, while treated with 60 Co γ-rays, the incorporation value in LPS-induced cells approached normal level, meanwhile, the incorporation value in PEM-induced cells reduced significantly and the stimulating effect of PWM-induced cells on LPS-induced cells became much weaker. The facts described above demonstrated that PWM-induced cells have the function of T-helper cells and play more important role in the synergy than LPS-induced cells

  3. Modulation of LPS induced inflammatory response by Lawsonyl monocyclic terpene from the marine derived Streptomyces sp.

    Digital Repository Service at National Institute of Oceanography (India)

    Ali, A.; Khajuria, A.; Sidiq, T.; AshokKumar; Thakur, N.L.; Naik, D.; Vishwakarma, R.A.

    . The effect of Lawsonone (1) was elucidated on the immune cells (splenocytes and macrophages) collected from BALB/c mice. Study was carried out to find the effect of Lawsonone (1) on Con-A and LPS stimulated splenocyte proliferation, LPS-induced NO, IL-1beta...

  4. Inhibition of LPS-induced splenocyte proliferation by ortho-substituted polychlorinated biphenyl congeners

    International Nuclear Information System (INIS)

    Smithwick, L. Ashley; Smith, Andrew; Quensen, John F.; Stack, Allison; London, Lucille; Morris, Pamela J.

    2003-01-01

    Polychlorinated biphenyls (PCBs) are persistent environmental contaminants, and their ubiquitous nature has prompted studies of their potential health hazards. As a result of their lipophilic nature, PCBs accumulate in breast milk and subsequently affect the health of offspring of exposed individuals. Biological effects of PCBs in animals have mostly been attributed to coplanar congeners, although effects of ortho congeners also have been demonstrated. To investigate the relationship of immunotoxicity and chlorine substitution pattern, the effects of PCB congeners and mixtures of ortho and non-ortho-substituted constituents of Aroclor 1242 on splenocytes from C57B1/6 mice were examined. The immunotoxic endpoints investigated included splenocyte viability, lipopolysaccharide (LPS)-induced splenocyte proliferation, and LPS-induced antibody secretion. Congeners with multiple ortho chlorines preferentially inhibited splenocyte proliferation as compared with non- or mono-ortho-substituted congeners. However, mixtures of non- and mono-ortho-substituted congeners and multi-ortho-substituted congeners inhibited LPS-induced splenocyte proliferation and antibody secretion at similar concentrations. Exposure of splenocytes to these mixtures did not activate the aryl hydrocarbon receptor (AhR) signal transduction pathway. These results suggest individual multi-ortho-substituted congeners preferentially inhibit LPS-induced splenocyte proliferation, while congeners not exhibiting an effect individually may have additive effects in a mixture to produce an immunotoxic response through an AhR-independent pathway

  5. Effects of N-acetylcysteine and terbutaline treatment on hemodynamics and regional albumin extravasation in porcine septic shock

    International Nuclear Information System (INIS)

    Groeneveld, A.B.; den Hollander, W.; Straub, J.; Nauta, J.J.; Thijs, L.G.

    1990-01-01

    We studied the therapeutic effects of continuously infused N-acetylcysteine, an O2 radical scavenger (N, n = 6), and terbutaline, a beta 2-agonist (T, n = 6), versus dextrose (controls C, N = 6) on hemodynamics and regional albumin extravasation in porcine septic shock. After instrumentation, injection of 99mTc-labeled red blood cells, and baseline measurements, pigs received a 90 min infusion of 11 +/- 9 X 10(8).kg-1 live Escherichia coli bacteria. Thereafter, therapy was started, and 131I human serum albumin was injected. Images were obtained hourly using a gamma camera and a computer until 5 hours after baseline. Regions of interest were drawn in the 99mTc images, yielding regional 131I/99mTc radioactivity ratios, with blood samples as reference. From these ratios, an albumin leak index, a rate constant of transvascular albumin transport, was calculated. Control pigs developed pulmonary hypertension, arterial hypotension, hemoconcentration, and lactic acidemia. In spite of tachycardia and unchanged filling pressures, cardiac output fell. In arterial blood, white cell count, PO2, albumin level, and colloid osmotic pressure fell. The albumin leak index (X10(-3).min-1) measured 1.56 +/- 0.59 over the lungs and 2.87 +/- 1.19 over the abdomen in C, confirming previously found increased albumin flux in both lung and abdomen, the latter exceeding the former. Neither N nor T significantly affected hemodynamic and biochemical changes. The drugs neither decreased the regional albumin leak index nor attenuated the formation of albumin-rich ascites found at autopsy. However, the lung albumin index obtained at autopsy was significantly reduced with N (P less than .01 vs. C), at similar gravimetrically determined extravascular lung water (EVLW). EVLW positively correlated with pulmonary albumin extravasation in C and T but not in N

  6. Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine

    Science.gov (United States)

    Brierley, Joe; Carcillo, Joseph A.; Choong, Karen; Cornell, Tim; DeCaen, Allan; Deymann, Andreas; Doctor, Allan; Davis, Alan; Duff, John; Dugas, Marc-Andre; Duncan, Alan; Evans, Barry; Feldman, Jonathan; Felmet, Kathryn; Fisher, Gene; Frankel, Lorry; Jeffries, Howard; Greenwald, Bruce; Gutierrez, Juan; Hall, Mark; Han, Yong Y.; Hanson, James; Hazelzet, Jan; Hernan, Lynn; Kiff, Jane; Kissoon, Niranjan; Kon, Alexander; Irazusta, Jose; Lin, John; Lorts, Angie; Mariscalco, Michelle; Mehta, Renuka; Nadel, Simon; Nguyen, Trung; Nicholson, Carol; Peters, Mark; Okhuysen-Cawley, Regina; Poulton, Tom; Relves, Monica; Rodriguez, Agustin; Rozenfeld, Ranna; Schnitzler, Eduardo; Shanley, Tom; Skache, Sara; Skippen, Peter; Torres, Adalberto; von Dessauer, Bettina; Weingarten, Jacki; Yeh, Timothy; Zaritsky, Arno; Stojadinovic, Bonnie; Zimmerman, Jerry; Zuckerberg, Aaron

    2013-01-01

    Background The Institute of Medicine calls for the use of clinical guidelines and practice parameters to promote “best practices” and to improve patient outcomes. Objective 2007 update of the 2002 American College of Critical Care Medicine Clinical Guidelines for Hemodynamic Support of Neonates and Children with Septic Shock. Participants Society of Critical Care Medicine members with special interest in neonatal and pediatric septic shock were identified from general solicitation at the Society of Critical Care Medicine Educational and Scientific Symposia (2001–2006). Methods The Pubmed/MEDLINE literature database (1966–2006) was searched using the keywords and phrases: sepsis, septicemia, septic shock, endotoxemia, persistent pulmonary hypertension, nitric oxide, extracorporeal membrane oxygenation (ECMO), and American College of Critical Care Medicine guidelines. Best practice centers that reported best outcomes were identified and their practices examined as models of care. Using a modified Delphi method, 30 experts graded new literature. Over 30 additional experts then reviewed the updated recommendations. The document was subsequently modified until there was greater than 90% expert consensus. Results The 2002 guidelines were widely disseminated, translated into Spanish and Portuguese, and incorporated into Society of Critical Care Medicine and AHA sanctioned recommendations. Centers that implemented the 2002 guidelines reported best practice outcomes (hospital mortality 1%–3% in previously healthy, and 7%– 10% in chronically ill children). Early use of 2002 guidelines was associated with improved outcome in the community hospital emergency department (number needed to treat = 3.3) and tertiary pediatric intensive care setting (number needed to treat = 3.6); every hour that went by without guideline adherence was associated with a 1.4-fold increased mortality risk. The updated 2007 guidelines continue to recognize an increased likelihood that

  7. The novel role of platelet-activating factor in protecting mice against lipopolysaccharide-induced endotoxic shock.

    Directory of Open Access Journals (Sweden)

    Young-Il Jeong

    Full Text Available BACKGROUND: Platelet-activating factor (PAF has been long believed to be associated with many pathophysiological processes during septic shock. Here we present novel activities for PAF in protecting mice against LPS-mediated endotoxic shock. PRINCIPAL FINDINGS: In vivo PAF treatment immediately after LPS challenge markedly improved the survival rate against mortality from endotoxic shock. Administration of PAF prominently attenuated LPS-induced organ injury, including profound hypotension, excessive polymorphonuclear neutrophil infiltration, and severe multiple organ failure. In addition, PAF treatment protects against LPS-induced lymphocytes apoptosis. These protective effects of PAF was correlated with significantly decreases in the production of the inflammatory mediators such as TNF-alpha, IL-1beta, IL-12, and IFN-gamma, while increasing production of the anti-inflammatory cytokine IL-10 in vivo and in vitro. CONCLUSIONS: Taken together, these results suggest that PAF may protect mice against endotoxic shock via a complex mechanism involving modulation of inflammatory and anti-inflammatory mediators.

  8. Tanshinone IIA Sodium Sulfonate Attenuates LPS-Induced Intestinal Injury in Mice

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    Xin-Jing Yang

    2018-01-01

    Full Text Available Background. Tanshinone IIA sodium sulfonate (TSS is known to possess anti-inflammatory effects and has exhibited protective effects in various inflammatory conditions; however, its role in lipopolysaccharide- (LPS- induced intestinal injury is still unknown. Objective. The present study is designed to explore the role and possible mechanism of TSS in LPS-induced intestinal injury. Methods. Male C57BL/6J mice, challenged with intraperitoneal LPS injection, were treated with or without TSS 0.5 h prior to LPS exposure. At 1, 6, and 12 h after LPS injection, mice were sacrificed, and the small intestine was excised. The intestinal tissue injury was analyzed by HE staining. Inflammatory factors (TNF-α, IL-1β, and IL-6 in the intestinal tissue were examined by ELISA and RT-PCR. In addition, expressions of autophagy markers (microtubule-associated light chain 3 (LC3 and Beclin-1 were detected by western blot and RT-PCR. A number of autophagosomes were also observed under electron microscopy. Results. TSS treatment significantly attenuated small intestinal epithelium injury induced by LPS. LPS-induced release of inflammatory mediators, including TNF-α, IL-1β, and IL-6, were markedly inhibited by TSS. Furthermore, TSS treatment could effectively upregulate LPS-induced decrease of autophagy levels, as evidenced by the increased expression of LC3 and Beclin-1, and more autophagosomes. Conclusion. The protective effect of TSS on LPS-induced small intestinal injury may be attributed to the inhibition of inflammatory factors and promotion of autophagy levels. The present study may provide novel insight into the molecular mechanisms of TSS on the treatment of intestinal injury.

  9. Edaravone abrogates LPS-induced behavioral anomalies, neuroinflammation and PARP-1.

    Science.gov (United States)

    Sriram, Chandra Shaker; Jangra, Ashok; Gurjar, Satendra Singh; Mohan, Pritam; Bezbaruah, Babul Kumar

    2016-02-01

    Poly(ADP-ribose) polymerase-1 (PARP-1) is a DNA nick-sensor enzyme that functions at the center of cellular stress response and affects the immune system at several key points, and thus modulates inflammatory diseases. Our previous study demonstrated that lipopolysaccharide (LPS)-induced depressive-like behavior in mice can be ameliorated by 3-aminobenzamide, which is a PARP-1 inhibitor. In the present study we've examined the effect of a free radical scavenger, edaravone pretreatment against LPS-induced anxiety and depressive-like behavior as well as various hippocampal biochemical parameters including PARP-1. Male Swiss albino mice were treated with edaravone (3 & 10mg/kgi.p.) once daily for 14days. On the 14th day 30min after edaravone treatment mice were challenged with LPS (1mg/kgi.p.). After 3h and 24h of LPS administration we've tested mice for anxiety and depressive-like behaviors respectively. Western blotting analysis of PARP-1 in hippocampus was carried out after 12h of LPS administration. Moreover, after 24h of LPS administration serum corticosterone, hippocampal BDNF, oxido-nitrosative stress and pro-inflammatory cytokines were estimated by ELISA. Results showed that pretreatment of edaravone (10mg/kg) ameliorates LPS-induced anxiety and depressive-like behavior. Western blotting analysis showed that LPS-induced anomalous expression of PARP-1 significantly reverses by the pretreatment of edaravone (10mg/kg). Biochemical analyses revealed that LPS significantly diminishes BDNF, increases pro-inflammatory cytokines and oxido-nitrosative stress in the hippocampus. However, pretreatment with edaravone (10mg/kg) prominently reversed all these biochemical alterations. Our study emphasized that edaravone pretreatment prevents LPS-induced anxiety and depressive-like behavior, mainly by impeding the inflammation, oxido-nitrosative stress and PARP-1 overexpression. Copyright © 2015. Published by Elsevier Inc.

  10. Soluble membrane receptors, interleukin 6, procalcitonin and C reactive protein as prognostic markers in patients with severe sepsis and septic shock.

    Directory of Open Access Journals (Sweden)

    Juan-Jesús Ríos-Toro

    Full Text Available The objective of this study was to explore the diagnostic and prognostic value of soluble triggering receptor expressed on myeloid cell 1 (sTREM-1, soluble cluster of differentiation 14 (sCD14, soluble cluster of differentiation 163 (sCD163, interleukin-6 (IL-6, procalcitonin (PCT, and C-reactive protein (CRP serum levels for patients with severe sepsis and septic shock in an intensive care unit (ICU.Fifty patients admitted at the ICU with the diagnosis of severe sepsis or septic shock were studied. SOFA and APACHE II scores as well as serum biomarkers were measured at days 0, 2 and 5. The influence of these variables on 28-day mortality was analyzed. Twenty healthy individuals served as controls.Baseline serum concentrations of sTREM-1, sCD163, IL-6 and PCT correlated with SOFA score. Only sTREM-1 levels correlated with APACHE II score. The 28-day mortality rate for all patients was 42%. The absence of risk factors for infection, presence of septic shock, baseline values of sCD14 and decrease of PCT and IL-6 from baseline to day 5 were variables associated to mortality in the univariate analysis. The unique independent factor associated to mortality in the multivariate analysis was a decrease of PCT higher than 50% from days 0 to 5.Serum levels of sTREM-1 are correlated with the severity of sepsis. A 50% decrease of PCT was the unique variable associated with survival in the multivariate analysis.

  11. Association between exposure to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers prior to septic shock and acute kidney injury.

    Science.gov (United States)

    Suberviola, B; Rodrigo, E; González-Castro, A; Serrano, M; Heras, M; Castellanos-Ortega, Á

    To evaluate the association between angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) use prior to a septic shock episode and the development, prognosis and long-term recovery from acute kidney injury (AKI). A single-centre, prospective observational study was carried out between September 2005 and August 2010. Patients admitted to the ICU of a third level hospital. A total of 386 septic shock patients were studied. None. Use of ACEIs/ARBs, AKI development, recovery of previous creatinine levels and time to recovery. A total of 386 patients were included, of which 312 (80.8%) developed AKI during ICU stay and 23% were receiving ACEIs/ARBs. The percentage of patients on ACEIs/ARBs increased significantly in relation to more severe stages of AKI irrespective of the kind of AKI score. After adjusting for confounders, the development of AKI was independently associated to the use of ACEIs/ARBs (OR 2.19; 95%CI 1.21-3.84; p=.04). With respect to the recovery of kidney function, the group of patients on ACEIs/ARBs had significantly higher creatinine levels at ICU discharge and needed hemodialysis more frequently thereafter. However, use of ACEIs/ARBs affected neither recovery of previous creatinine levels nor significantly delayed recovery. The use of ACEIs/ARBs before septic shock episodes was correlated to AKI development and severity, but did not affect the recovery of kidney function after sepsis resolution. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

  12. GSK-3β Inhibition Attenuates LPS-Induced Death but Aggravates Radiation-Induced Death via Down-Regulation of IL-6

    Directory of Open Access Journals (Sweden)

    Bailong Li

    2013-12-01

    Full Text Available Background: Exposure of high dose ionizing radiation is lethal. Signal pathways involved in radiation biology reaction still remain illdefined. Lipopolysaccharides (LPS, the ligands of Toll-like receptor 4(TLR4, could elicit strong immune responses. Glycogen synthase kinase-3β(GSK-3β promotes the production of inflammatory molecules and cell migration. Inhibition of GSK-3β provides protection against inflammation in animal models. The aim of the study was to investigate role of GSK-3β in LPS shock and ionizing radiation. Methods: WT or IL-6-/-mice or cells were pretreated with SB216763, a GSK-3β inhibitor, and survival of the mice was determined. Cell viability was assayed by Cell Counting Kit. Apoptosis was assayed by Annexin V-PI double staining. Serum concentrations of IL-6 and TNF-α were determined by ELISA. Results: SB216763 attenuated LPS induced mice or cell death but aggravated radiation induced mice or cell death. SB216763 reduced IL-6, but not TNF-α levels in vivo. IL-6-/- mice were more resistant to LPS-induced death but less resistant to radiation-induced death than wild type mice. Conclusions: Inhibition of GSK-3β conferred resistance to LPS shock but fostered death induced by ionizing radiation. Inhibition of GSK-3β was effective by reducing IL-6.

  13. Evidence Underpinning the Centers for Medicare & Medicaid Services' Severe Sepsis and Septic Shock Management Bundle (SEP-1): A Systematic Review.

    Science.gov (United States)

    Pepper, Dominique J; Jaswal, Dharmvir; Sun, Junfeng; Welsh, Judith; Natanson, Charles; Eichacker, Peter Q

    2018-04-17

    This article has been corrected. To see what has changed, please read the Letter to the Editor and the authors' response. The original version (PDF) is appended to this article as a Supplement. The Severe Sepsis and Septic Shock Early Management Bundle (SEP-1), the sepsis performance measure introduced in 2015 by the Centers for Medicare & Medicaid Services (CMS), requires the reporting of up to 5 hemodynamic interventions, as many as 141 tasks, and 3 hours to document for a single patient. To evaluate whether moderate- or high-level evidence shows that use of the 2015 SEP-1 or its hemodynamic interventions improves survival in adults with sepsis. PubMed, Embase, Scopus, Web of Science, and ClinicalTrials.gov from inception to 28 November 2017 with no language restrictions. Randomized and observational studies of death among adults with sepsis who received versus those who did not receive either the entire SEP-1 bundle or 1 or more SEP-1 hemodynamic interventions, including serial lactate measurements; a fluid infusion of 30 mL/kg of body weight; and assessment of volume status and tissue perfusion with a focused examination, bedside cardiovascular ultrasonography, or fluid responsiveness testing. Two investigators independently extracted study data and assessed each study's risk of bias; 4 authors rated level of evidence by consensus using CMS criteria published in 2013. High- or moderate-level evidence required studies to have no confounders and low risk of bias. Of 56 563 references, 20 studies (18 reports) met inclusion criteria. One single-center observational study reported lower in-hospital mortality after implementation of the SEP-1 bundle. Sixteen studies (2 randomized and 14 observational) reported increased survival with serial lactate measurements or 30-mL/kg fluid infusions. None of the 17 studies were free of confounders or at low risk of bias. In 3 randomized trials, fluid responsiveness testing did not alter survival. Few trials, poor-quality and

  14. Progesterone modulates the LPS-induced nitric oxide production by a progesterone-receptor independent mechanism.

    Science.gov (United States)

    Wolfson, Manuel Luis; Schander, Julieta Aylen; Bariani, María Victoria; Correa, Fernando; Franchi, Ana María

    2015-12-15

    Genital tract infections caused by Gram-negative bacteria induce miscarriage and are one of the most common complications of human pregnancy. LPS administration to 7-day pregnant mice induces embryo resorption after 24h, with nitric oxide playing a fundamental role in this process. We have previously shown that progesterone exerts protective effects on the embryo by modulating the inflammatory reaction triggered by LPS. Here we sought to investigate whether the in vivo administration of progesterone modulated the LPS-induced nitric oxide production from peripheral blood mononuclear cells from pregnant and non-pregnant mice. We found that progesterone downregulated LPS-induced nitric oxide production by a progesterone receptor-independent mechanism. Moreover, our results suggest a possible participation of glucocorticoid receptors in at least some of the anti-inflammatory effects of progesterone. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Typhi–Induced Septic Shock and Acute Respiratory Distress Syndrome in a Previously Healthy Teenage Patient Treated With High-Dose Dexamethasone

    Directory of Open Access Journals (Sweden)

    Melissa Brosset Ugas MD

    2016-05-01

    Full Text Available Typhoid fever is commonly characterized by fever and abdominal pain. Rare complications include intestinal hemorrhage, bowel perforation, delirium, obtundation, and septic shock. Herein we describe the case of a previously healthy 16-year-old male without history of travel, diagnosed with typhoid fever complicated by septic shock and acute respiratory distress syndrome treated with high-dose dexamethasone. This case details severe complications of typhoid fever that are uncommonly seen in developed countries, and the successful response to high-dose dexamethasone as adjunct therapy. High-dose dexamethasone treatment has reportedly decreased Salmonella Typhi mortality, but controlled studies specifically performed in children are lacking, and most reports of its use are over 30 years old and all have originated in developing countries. Providers should include Salmonella Typhi in the differential diagnosis of the pediatric patient with fever, severe abdominal pain, and enteritis, and be aware of its potentially severe complications and the limited data on safety and efficacy of adjunctive therapies that can be considered in addition to antibiotics.

  16. From amino acids polymers, antimicrobial peptides, and histones, to their possible role in the pathogenesis of septic shock: a historical perspective

    Directory of Open Access Journals (Sweden)

    Ginsburg I

    2017-02-01

    Full Text Available Isaac Ginsburg,1 Peter Vernon van Heerden,2 Erez Koren1 1Institute of Dental Sciences, Faculty of Dental Medicine, The Hebrew University of Jerusalem, 2General Intensive Care Unit, Hadassah University Hospital, Jerusalem, Israel Abstract: This paper describes the evolution of our understanding of the biological role played by synthetic and natural antimicrobial cationic peptides and by the highly basic nuclear histones as modulators of infection, postinfectious sequelae, trauma, and coagulation phenomena. The authors discuss the effects of the synthetic polymers of basic poly α amino acids, poly l-lysine, and poly l-arginine on blood coagulation, fibrinolysis, bacterial killing, and blood vessels; the properties of natural and synthetic antimicrobial cationic peptides as potential replacements or adjuncts to antibiotics; polycations as opsonizing agents promoting endocytosis/phagocytosis; polycations and muramidases as activators of autolytic wall enzymes in bacteria, causing bacteriolysis and tissue damage; and polycations and nuclear histones as potential virulence factors and as markers of sepsis, septic shock, disseminated intravasclar coagulopathy, acute lung injury, pancreatitis, trauma, and other additional clinical disorders Keywords: histones, sepsis, septic shock

  17. Principles of fluid management and stewardship in septic shock: it is time to consider the four D's and the four phases of fluid therapy.

    Science.gov (United States)

    Malbrain, Manu L N G; Van Regenmortel, Niels; Saugel, Bernd; De Tavernier, Brecht; Van Gaal, Pieter-Jan; Joannes-Boyau, Olivier; Teboul, Jean-Louis; Rice, Todd W; Mythen, Monty; Monnet, Xavier

    2018-05-22

    In patients with septic shock, the administration of fluids during initial hemodynamic resuscitation remains a major therapeutic challenge. We are faced with many open questions regarding the type, dose and timing of intravenous fluid administration. There are only four major indications for intravenous fluid administration: aside from resuscitation, intravenous fluids have many other uses including maintenance and replacement of total body water and electrolytes, as carriers for medications and for parenteral nutrition. In this paradigm-shifting review, we discuss different fluid management strategies including early adequate goal-directed fluid management, late conservative fluid management and late goal-directed fluid removal. In addition, we expand on the concept of the "four D's" of fluid therapy, namely drug, dosing, duration and de-escalation. During the treatment of patients with septic shock, four phases of fluid therapy should be considered in order to provide answers to four basic questions. These four phases are the resuscitation phase, the optimization phase, the stabilization phase and the evacuation phase. The four questions are "When to start intravenous fluids?", "When to stop intravenous fluids?", "When to start de-resuscitation or active fluid removal?" and finally "When to stop de-resuscitation?" In analogy to the way we handle antibiotics in critically ill patients, it is time for fluid stewardship.

  18. PTEN gene and phosphorylation of Akt protein expression in the LPS-induced lung fibroblast

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    Mao-lin HUANG

    2014-09-01

    Full Text Available Objective: To investigate PTEN gene expression and the Akt phosphorylation of protein expression in the LPS-induced lung fibroblast, to initially reveal the relation between PTEN gene and the Akt phosphorylated proteins to LPS-induced lung fibroblast proliferation mechanism. Methods: BrdU experiments was performed to evaluate the LPS-induced lung fibroblast proliferation,  RT-PCR and Western Blot analysis were used to analyze the PTEN gene expression and Western blot was performed to analyze Akt phosphorylated protein expression. Results: PTEN mRNA level of the experimental group were significantly lower than the control group (P<0.05 with LPS simulation for 24h and 72h , and there were no significant difference between the experimental group and control group the experimental group and control group (P>0.05 . PTEN protein expression levels of the experimental group were significantly lower than the control group (P<0.05 , at 72h, and PTEN mRNA levels had no significant differences between these of the experimental and control group at 6h,12h and 24h(p>0.05. Phosphorylation Akt protein level (relative to total Akt protein was significantly higer than the control group (P<0.05 at 24h and 72h, and phosphorylation Akt protein levels had no significant differences between these of the experimental and control group at 6h and 12h (P>0.05 .Conclusion: PTEN gene and phosphorylation Akt protein involve in LPS-induced lung fibroblast proliferation signal transduction pathway.

  19. Teuvincenone F Suppresses LPS-Induced Inflammation and NLRP3 Inflammasome Activation by Attenuating NEMO Ubiquitination

    OpenAIRE

    Zhao, Xibao; Pu, Debing; Zhao, Zizhao; Zhu, Huihui; Li, Hongrui; Shen, Yaping; Zhang, Xingjie; Zhang, Ruihan; Shen, Jianzhong; Xiao, Weilie; Chen, Weilin

    2017-01-01

    Inflammation causes many diseases that are serious threats to human health. However, the molecular mechanisms underlying regulation of inflammation and inflammasome activation are not fully understood which has delayed the discovery of new anti-inflammatory drugs of urgent clinic need. Here, we found that the natural compound Teuvincenone F, which was isolated and purified from the stems and leaves of Premna szemaoensis, could significantly inhibit lipopolysaccharide (LPS)?induced pro-inflamm...

  20. Piracetam Attenuates LPS-Induced Neuroinflammation and Cognitive Impairment in Rats.

    Science.gov (United States)

    Tripathi, Alok; Paliwal, Pankaj; Krishnamurthy, Sairam

    2017-11-01

    The present study was performed to investigate the effect of piracetam on neuroinflammation induced by lipopolysaccharide (LPS) and resulting changes in cognitive behavior. Neuroinflammation was induced by a single dose of LPS solution infused into each of the lateral cerebral ventricles in concentrations of 1 μg/μl, at a rate of 1 μl/min over a 5-min period, with a 5-min waiting period between the two infusions. Piracetam in doses of 50, 100, and 200 mg/kg i.p. was administered 30 min before LPS infusion and continued for 9 days. On ninth day, the behavioral test for memory and anxiety was done followed by blood collection and microdissection of the hippocampus (HIP) and prefrontal cortex brain regions. Piracetam attenuated the LPS-induced decrease in coping strategy to novel environment indicating anxiolytic activity. It also reversed the LPS-induced changes in the known arm and novel arm entries in the Y-maze test indicating amelioration of spatial memory impairment. Further, piracetam moderated LPS-induced decrease in the mitochondrial complex enzyme activities (I, II, IV, and V) and mitochondrial membrane potential. It ameliorated changes in hippocampal lipid peroxidation and nitrite levels including the activity of superoxide dismutase. Piracetam region specifically ameliorated LPS-induced increase in the level of IL-6 in HIP indicating anti-neuroinflammatory effect. Further, piracetam reduced HIP Aβ (1-40) and increased blood Aβ level suggesting efflux of Aβ from HIP to blood. Therefore, the present study indicates preclinical evidence for the use of piracetam in the treatment of neuroinflammatory disorders.

  1. Anti-Inflammatory Effects of Berberine Hydrochloride in an LPS-Induced Murine Model of Mastitis

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    Xichun Wang

    2018-01-01

    Full Text Available Berberine hydrochloride is an isoquinoline type alkaloid extracted from Berberidaceae, Rutaceae, and other plants. Previous reports have shown that berberine hydrochloride has anti-inflammatory properties. However, the underlying molecular mechanisms remain unclear. In this study, a lipopolysaccharide- (LPS- induced murine model of mastitis was established to explore the anti-inflammatory action of berberine hydrochloride. Sixty mice that had been lactating for 5–7 days were randomly divided into six groups, including control, LPS, three berberine hydrochloride treatment groups (5, 10, and 20 mg/kg, and a dexamethasone (DEX (5 mg/kg group. Berberine hydrochloride was administered intraperitoneally 1 h before and 12 h after LPS-induced mastitis, and all mice were sacrificed 24 h after LPS induction. The pathological and histopathological changes of the mammary glands were observed. The concentrations and mRNA expressions of TNF-α, IL-1β, and IL-6 were measured by ELISA and qRT-PCR. The activation of TLR4 and NF-κB signaling pathways was analyzed by Western blot. Results indicated that berberine hydrochloride significantly attenuated neutrophil infiltration and dose-dependently decreased the secretion and mRNA expressions of TNF-α, IL-1β, and IL-6 within a certain range. Furthermore, berberine hydrochloride suppressed LPS-induced TLR4 and NF-κB p65 activation and the phosphorylation of I-κB. Berberine hydrochloride can provide mice robust protection from LPS-induced mastitis, potentially via the TLR4 and NF-κB pathway.

  2. Anti-Inflammatory Effects of Berberine Hydrochloride in an LPS-Induced Murine Model of Mastitis

    Science.gov (United States)

    Feng, Shibin; Ding, Nana; He, Yanting; Li, Cheng; Li, Manman; Ding, Xuedong; Ding, Hongyan; Li, Jinchun

    2018-01-01

    Berberine hydrochloride is an isoquinoline type alkaloid extracted from Berberidaceae, Rutaceae, and other plants. Previous reports have shown that berberine hydrochloride has anti-inflammatory properties. However, the underlying molecular mechanisms remain unclear. In this study, a lipopolysaccharide- (LPS-) induced murine model of mastitis was established to explore the anti-inflammatory action of berberine hydrochloride. Sixty mice that had been lactating for 5–7 days were randomly divided into six groups, including control, LPS, three berberine hydrochloride treatment groups (5, 10, and 20 mg/kg), and a dexamethasone (DEX) (5 mg/kg) group. Berberine hydrochloride was administered intraperitoneally 1 h before and 12 h after LPS-induced mastitis, and all mice were sacrificed 24 h after LPS induction. The pathological and histopathological changes of the mammary glands were observed. The concentrations and mRNA expressions of TNF-α, IL-1β, and IL-6 were measured by ELISA and qRT-PCR. The activation of TLR4 and NF-κB signaling pathways was analyzed by Western blot. Results indicated that berberine hydrochloride significantly attenuated neutrophil infiltration and dose-dependently decreased the secretion and mRNA expressions of TNF-α, IL-1β, and IL-6 within a certain range. Furthermore, berberine hydrochloride suppressed LPS-induced TLR4 and NF-κB p65 activation and the phosphorylation of I-κB. Berberine hydrochloride can provide mice robust protection from LPS-induced mastitis, potentially via the TLR4 and NF-κB pathway.

  3. A central role for the mammalian target of rapamycin in LPS-induced anorexia in mice.

    Science.gov (United States)

    Yue, Yunshuang; Wang, Yi; Li, Dan; Song, Zhigang; Jiao, Hongchao; Lin, Hai

    2015-01-01

    Bacterial lipopolysaccharide (LPS), also known as endotoxin, induces profound anorexia. However, the LPS-provoked pro-inflammatory signaling cascades and the neural mechanisms underlying the development of anorexia are not clear. Mammalian target of rapamycin (mTOR) is a key regulator of metabolism, cell growth, and protein synthesis. This study aimed to determine whether the mTOR pathway is involved in LPS-induced anorexia. Effects of LPS on hypothalamic gene/protein expression in mice were measured by RT-PCR or western blotting analysis. To determine whether inhibition of mTOR signaling could attenuate LPS-induced anorexia, we administered an i.c.v. injection of rapamycin, an mTOR inhibitor, on LPS-treated male mice. In this study, we showed that LPS stimulates the mTOR signaling pathway through the enhanced phosphorylation of mTOR(Ser2448) and p70S6K(Thr389). We also showed that LPS administration increased the phosphorylation of FOXO1(Ser256), the p65 subunit of nuclear factor kappa B (Panorexia by decreasing the phosphorylation of p70S6K(Thr389), FOXO1(Ser256), and FOXO1/3a(Thr) (24) (/) (32). These results suggest promising approaches for the prevention and treatment of LPS-induced anorexia. © 2015 Society for Endocrinology.

  4. The Protective Effect of Melatonin on Neural Stem Cell against LPS-Induced Inflammation

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    Juhyun Song

    2015-01-01

    Full Text Available Stem cell therapy for tissue regeneration has several limitations in the fact that transplanted cells could not survive for a long time. For solving these limitations, many studies have focused on the antioxidants to increase survival rate of neural stem cells (NSCs. Melatonin, an antioxidant synthesized in the pineal gland, plays multiple roles in various physiological mechanisms. Melatonin exerts neuroprotective effects in the central nervous system. To determine the effect of melatonin on NSCs which is in LPS-induced inflammatory stress state, we first investigated nitric oxide (NO production and cytotoxicity using Griess reagent assays, LDH assay, and neurosphere counting. Also, we investigated the effect of melatonin on NSCs by measuring the mRNA levels of SOX2, TLX, and FGFR-2. In addition, western blot analyses were performed to examine the activation of PI3K/Akt/Nrf2 signaling in LPS-treated NSCs. In the present study, we suggested that melatonin inhibits NO production and protects NSCs against LPS-induced inflammatory stress. In addition, melatonin promoted the expression of SOX2 and activated the PI3K/Akt/Nrf2 signaling under LPS-induced inflammation condition. Based on our results, we conclude that melatonin may be an important factor for the survival and proliferation of NSCs in neuroinflammatory diseases.

  5. The NALP3/Cryopyrin-Inflammasome Complex is Expressed in LPS-Induced Ocular Inflammation

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    José F. González-Benítez

    2008-01-01

    Full Text Available In the inflammosome complex, NALP3 or NALP1 binds to ASC and activates caspase-1 which induces IL-1β. In murine LPS-induced ocular inflammation, the production of IL-1β is increased. We suggest that NALP3- or NALP1-inflammasome complex can be participating in the LPS-induced ocular inflammation. In this work, eye, brain, testis, heart, spleen, and lung were obtained from C3H/HeN mice treated with LPS for 3 to 48 hours, and the expression of NALP1b, NALP3, ASC, caspase-1, IL-1β, and IL-18 was determined. Infiltrated leukocytes producing IL-1β in the anterior chamber were found at 12-hour posttreatment. A high upregulated expression of NALP3, ASC, caspase-1, IL-1β, and IL-18 was found at the same time when infiltrated leukocytes were observed. NALP1b was not detected in the eye of treated mice. NALP3 was also overexpressed in heart and lung. These results suggest that NALP3-, but not NALP1-inflammosome complex, is participating in the murine LPS-induced ocular inflammation.

  6. Bee Venom Decreases LPS-Induced Inflammatory Responses in Bovine Mammary Epithelial Cells.

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    Jeong, Chang Hee; Cheng, Wei Nee; Bae, Hyojin; Lee, Kyung Woo; Han, Sang Mi; Petriello, Michael C; Lee, Hong Gu; Seo, Han Geuk; Han, Sung Gu

    2017-10-28

    The world dairy industry has long been challenged by bovine mastitis, an inflammatory disease, which causes economic loss due to decreased milk production and quality. Attempts have been made to prevent or treat this disease with multiple approaches, primarily through increased abuse of antibiotics, but effective natural solutions remain elusive. Bee venom (BV) contains a variety of peptides ( e.g. , melittin) and shows multiple bioactivities, including prevention of inflammation. Thus, in the current study, it was hypothesized that BV can reduce inflammation in bovine mammary epithelial cells (MAC-T). To examine the hypothesis, cells were treated with LPS (1 μg/ml) to induce an inflammatory response and the anti-inflammatory effects of BV (2.5 and 5 μg/ml) were investigated. The cellular mechanisms of BV against LPS-induced inflammation were also investigated. Results showed that BV can attenuate expression of an inflammatory protein, COX2, and pro-inflammatory cytokines such as IL-6 and TNF-α. Activation of NF-κB, an inflammatory transcription factor, was significantly downregulated by BV in cells treated with LPS, through dephosphorylation of ERK1/2. Moreover, pretreatment of cells with BV attenuated LPS-induced production of intracellular reactive oxygen species ( e.g. , superoxide anion). These results support our hypothesis that BV can decrease LPS-induced inflammatory responses in bovine mammary epithelial cells through inhibition of oxidative stress, NF-κB, ERK1/2, and COX-2 signaling.

  7. Is the inferior vena cava diameter measured by bedside ultrasonography valuable in estimating the intravascular volume in patients with septic shock?

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    Mortaza Talebi Doluie

    2016-07-01

    Full Text Available Introduction:Resuscitation should be initiated immediately in shock. Early goal-directed therapy is an established algorithm for the resuscitation in septic shock. The first step is to maintain cardiac preload. Central venous pressure (CVP plays an important role in goal-directed therapy. Central venous catheterization is invasive and time-consuming in emergency conditions. There are some alternative and noninvasive methods for estimating the intravascular volume such as measuring the inferior vena cava (IVC diameter by ultrasonography. Methods: We searched PubMed, Google scholar, and Scopus databases with keywords (central venous pressure OR venous pressure OR CVP AND (ultrasonography OR sonography AND (sepsis OR septic shock AND (inferior vena cava OR IVC.Result: The search resulted in 2550 articles. The articles were appraised regarding the relevance, type of article, and statistical methods. Finally, 12 articles were selected. The number of patients was between 30 and 83 cases (mean age=57-67 years, intubated and non-intubated in each study. The IVC diameter was measured in respiratory cycle by bedside ultrasonography in longitudinal subxiphoid view and caval index was calculated, then they were compared with the CVP measured by central venous catheter.Discussion: CVP is an indicator of intravascular fluid status and right heart function. CVP measurement is an invasive method and of course with some complications. The IVC is the biggest vein of venous system with low-pressure; expansion of the vein reflects intravascular volume.Conclusion: It seems that IVC diameter measured by ultrasonography could be used as an alternative method for the determination of CVP in the emergency or critical patients.

  8. Hyperin protects against LPS-induced acute kidney injury by inhibiting TLR4 and NLRP3 signaling pathways

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    Chunzhi, Gong; Zunfeng, Li; Chengwei, Qin; Xiangmei, Bu; Jingui, Yu

    2016-01-01

    Hyperin is a flavonoid compound derived from Ericaceae, Guttifera, and Celastraceae that has been shown to have various biological effects, such as anti-inflammatory and anti-oxidant effects. However, there is no evidence to show the protective effects of hyperin on lipopolysaccharide (LPS)-induced acute kidney injury (AKI). Therefore, we investigated the protective effects and mechanism of hyperin on LPS-induced AKI in mice. The levels of TNF-α, IL-6, and IL-1β were tested by ELISA. The effects of hyperin on blood urea nitrogen (BUN) and serum creatinine were also detected. In addition, the expression of TLR4, NF-κB, and NLRP3 were detected by western blot analysis. The results showed that hyperin significantly inhibited LPS-induced TNF-α, IL-6, and IL-1β production. The levels of BUN and creatinine were also suppressed by hyperin. Furthermore, LPS-induced TLR4 expression and NF-κB activation were also inhibited by hyperin. In addition, treatment of hyperin dose-dependently inhibited LPS-induced NLRP3 signaling pathway. In conclusion, the results showed that hyperin inhibited LPS-induced inflammatory response by inhibiting TLR4 and NLRP3 signaling pathways. Hyperin has potential application prospects in the treatment of sepsis-induced AKI. PMID:27813491

  9. Role of Admission Troponin-T and Serial Troponin-T Testing in Predicting Outcomes in Severe Sepsis and Septic Shock.

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    Vallabhajosyula, Saraschandra; Sakhuja, Ankit; Geske, Jeffrey B; Kumar, Mukesh; Poterucha, Joseph T; Kashyap, Rahul; Kashani, Kianoush; Jaffe, Allan S; Jentzer, Jacob C

    2017-09-09

    Troponin-T elevation is seen commonly in sepsis and septic shock patients admitted to the intensive care unit. We sought to evaluate the role of admission and serial troponin-T testing in the prognostication of these patients. This was a retrospective cohort study from 2007 to 2014 on patients admitted to the intensive care units at the Mayo Clinic with severe sepsis and septic shock. Elevated admission troponin-T and significant delta troponin-T were defined as ≥0.01 ng/mL and ≥0.03 ng/mL in 3 hours, respectively. The primary outcome was in-hospital mortality. Secondary outcomes included 1-year mortality and lengths of stay. During this 8-year period, 944 patients met the inclusion criteria with 845 (90%) having an admission troponin-T ≥0.01 ng/mL. Serial troponin-T values were available in 732 (78%) patients. Elevated admission troponin-T was associated with older age, higher baseline comorbidity, and severity of illness, whereas significant delta troponin-T was associated with higher severity of illness. Admission log 10 troponin-T was associated with unadjusted in-hospital (odds ratio 1.6; P =0.003) and 1-year mortality (odds ratio 1.3; P =0.04), but did not correlate with length of stay. Elevated delta troponin-T and log 10 delta troponin-T were not significantly associated with any of the primary or secondary outcomes. Admission log 10 troponin-T remained an independent predictor of in-hospital mortality (odds ratio 1.4; P =0.04) and 1-year survival (hazard ratio 1.3; P =0.008). In patients with sepsis and septic shock, elevated admission troponin-T was associated with higher short- and long-term mortality. Routine serial troponin-T testing did not add incremental prognostic value in these patients. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  10. The effects of aspirin, flurbiprofen, and NO-donating acetylsalicylic acid (NCX 4016) on mice models of endotoxic and septic shock.

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    Ulu, Nadir; Iskit, Alper Bektaş; Sökmensüer, Cenk; Güç, Mustafa Oğuz

    2015-01-01

    Nitric oxide-donating nonsteroidal antiinflammatory drugs (NO-NSAIDs) are a promising new class of antiinflammatory agents, which are obtained by adding NO-donating moieties to the existing conventional NSAID molecules. The aim of this study was to investigate the effects of aspirin, flurbiprofen, and NO-donating acetylsalicylic acid (NCX 4016) on cecal ligation and puncture (CLP) and endotoxin-induced septic shock (LPS) models in mice. Overall survival and spleen and liver weights were monitored in LPS and CLP models. Histopathological examinations of liver and spleen were performed at the end of the experimental protocols. NCX 4016 was able to reverse the increased spleen weight in CLP-operated animals, whereas aspirin or flurbiprofen did not. Similar to the results of the CLP model, none of the drugs modified the survival rates in the LPS model. Flurbiprofen in particular produced significant histopathological damage in spleens and livers, which was less significant with aspirin. NCX 4016 did not cause any liver damage. NCX 4016 has the potential to be used in septic states, while special attention has to be paid to the effects of aspirin and flurbiprofen on the liver and spleen.

  11. Insuficiência adrenal na criança com choque séptico Adrenal insufficiency in children with septic shock

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    Carlos H. Casartelli

    2003-11-01

    for diagnosing and treating adrenal insufficiency in patients with septic shock. SOURCES OF DATA: Articles published in Brazilian and foreign journals selected through these publications' websites and Medline, as well as references cited in key articles. SUMMARY OF THE FINDINGS: The literature reports a range betwen 17 and 54 % for the finding of adrenal insufficiency in patients with septic shock. There is no consensus for diagnosing adrenal insufficiency in patients suffering from critical diseases, particularly in patients with septic shock. The presence of volume-refractory and catecholamine-resistant septic shock suggests this condition, while basal cortisol under 25 µg/dl is a diagnostic criterion indicating adrenal insufficiency. The adrenal stimulation test is a useful resource for identifying patients with relative adrenal insufficiency. Our testing option for adrenal stimulation in children is the use of corticotropin in low doses (0.5 µg/1,73 m². An increase of less than 9 µg/dl in the value of postcorticotropin-stimulated cortisol suggests the presence of occult (relative adrenal insufficiency. In patients with septic shock presenting adrenal insufficiency, either suspected or confirmed, the administration of hydrocortisone in shock or stress doses can be vital for a favorable clinical outcome. CONCLUSIONS: The existing data, although controversial, already provides a basis to determine when to begin hormone replacement therapy, the serum level of cortisol accepted as adequate, and the choice of corticotropin doses for performing the adrenal stimulation test and diagnosing occult or relative adrenal insufficiency in patients with septic shock.

  12. Molecular hydrogen reduces LPS-induced neuroinflammation and promotes recovery from sickness behaviour in mice.

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    Stefan Spulber

    Full Text Available Molecular hydrogen has been shown to have neuroprotective effects in mouse models of acute neurodegeneration. The effect was suggested to be mediated by its free-radical scavenger properties. However, it has been shown recently that molecular hydrogen alters gene expression and protein phosphorylation. The aim of this study was to test whether chronic ad libitum consumption of molecular hydrogen-enriched electrochemically reduced water (H-ERW improves the outcome of lipopolysaccharide (LPS-induced neuroinflammation. Seven days after the initiation of H-ERW treatment, C57Bl/6 mice received a single injection of LPS (0.33 mg/kg i.p. or an equivalent volume of vehicle. The LPS-induced sickness behaviour was assessed 2 h after the injection, and recovery was assessed by monitoring the spontaneous locomotor activity in the homecage for 72 h after the administration of LPS. The mice were killed in the acute or recovery phase, and the expression of pro- and antiinflammatory cytokines in the hippocampus was assessed by real-time PCR. We found that molecular hydrogen reduces the LPS-induced sickness behaviour and promotes recovery. These effects are associated with a shift towards anti-inflammatory gene expression profile at baseline (downregulation of TNF- α and upregulation of IL-10. In addition, molecular hydrogen increases the amplitude, but shortens the duration and promotes the extinction of neuroinflammation. Consistently, molecular hydrogen modulates the activation and gene expression in a similar fashion in immortalized murine microglia (BV-2 cell line, suggesting that the effects observed in vivo may involve the modulation of microglial activation. Taken together, our data point to the regulation of cytokine expression being an additional critical mechanism underlying the beneficial effects of molecular hydrogen.

  13. Deubiquitinase USP12 promotes LPS induced macrophage responses through inhibition of IκBα

    International Nuclear Information System (INIS)

    Nayak, Tapan Kumar Singh; Alamuru-Yellapragada, Neeraja P.; Parsa, Kishore V.L.

    2017-01-01

    Post translational modifications, ubiquitination and its reversal by deubiquitination play an important role in regulating innate immune system. USP12 is a poorly studied deubiquitinase reported to regulate T-cell receptor signalling however the functional role of USP12 in macrophages, the principal architects of inflammation, is unknown. Thus, in this study we probed the involvement of USP12 in macrophage mediated inflammatory responses using bacterial endotoxin, LPS, as the model system. Here, we observed that the expression of USP12 was altered in time dependent manner in LPS stimulated RAW 264.7 macrophages at both mRNA and protein levels as revealed by qPCR and western blot analysis, respectively. Further analysis showed that LPS reduced the levels of Sp1 which enhanced the transcriptional levels of USP12. We observed that siRNA mediated ablation of USP12 expression in mouse macrophages suppressed the induction of LPS-induced iNOS and IL-6 expression but failed to alter IFN-β synthesis, oxidative stress and phagocytic ability of macrophages. Mechanistic analysis suggest that USP12 may be required for the activation of NFκB pathway as knockdown of USP12 reduced the inhibitory phosphorylation of IκBα, a well characterized inhibitor of NFκB nuclear translocation. Further, USP12 was observed to be required for LPS elicited phosphorylation of ERK1/2 and p38. Collectively, our data suggest that USP12 may be a key mediator of LPS stimulated macrophage responses. - Highlights: • USP12 levels are significantly altered in LPS stimulated macrophages. • USP12 is required for LPS induced iNOS and IL6 expression. • USP12 is crucial for LPS induced phosphorylation of IκBα, ERK1/2, p38.

  14. Suppression of LPS-induced inflammatory responses in macrophages infected with Leishmania

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    Kelly Ben L

    2010-02-01

    Full Text Available Abstract Background Chronic inflammation activated by macrophage innate pathogen recognition receptors such as TLR4 can lead to a range of inflammatory diseases, including atherosclerosis, Crohn's disease, arthritis and cancer. Unlike many microbes, the kinetoplastid protozoan pathogen Leishmania has been shown to avoid and even actively suppress host inflammatory cytokine responses, such as LPS-induced IL-12 production. The nature and scope of Leishmania-mediated inflammatory cytokine suppression, however, is not well characterized. Advancing our knowledge of such microbe-mediated cytokine suppression may provide new avenues for therapeutic intervention in inflammatory disease. Methods We explored the kinetics of a range of cytokine and chemokine responses in primary murine macrophages stimulated with LPS in the presence versus absence of two clinically distinct species of Leishmania using sensitive multiplex cytokine analyses. To confirm that these effects were parasite-specific, we compared the effects of Leishmania uptake on LPS-induced cytokine expression with uptake of inert latex beads. Results Whilst Leishmania uptake alone did not induce significant levels of any cytokine analysed in this study, Leishmania uptake in the presence of LPS caused parasite-specific suppression of certain LPS-induced pro-inflammatory cytokines, including IL-12, IL-17 and IL-6. Interestingly, L. amazonensis was generally more suppressive than L. major. We also found that other LPS-induced proinflammatory cytokines, such as IL-1α, TNF-α and the chemokines MIP-1α and MCP-1 and also the anti-inflammatory cytokine IL-10, were augmented during Leishmania uptake, in a parasite-specific manner. Conclusions During uptake by macrophages, Leishmania evades the activation of a broad range of cytokines and chemokines. Further, in the presence of a strong inflammatory stimulus, Leishmania suppresses certain proinflammatory cytokine responses in a parasite

  15. Effects of Early Continuous Venovenous Hemofiltration on E-Selectin, Hemodynamic Stability, and Ventilatory Function in Patients with Septic-Shock-Induced Acute Respiratory Distress Syndrome

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    Jian-biao Meng

    2016-01-01

    Full Text Available Objective. To investigate the effects of 72-hour early-initiated continuous venovenous hemofiltration (ECVVH treatment in patients with septic-shock-induced acute respiratory distress syndrome (ARDS (not acute kidney injury, AKI with regard to serum E-selectin and measurements of lung function and hemodynamic stability. Methods. This prospective nonblinded single institutional randomized study involved 51 patients who were randomly assigned to receive or not receive ECVVH, an ECVVH group (n=24 and a non-ECVVH group (n=27. Besides standard therapies, patients in ECVVH group underwent CVVH for 72 h. Results. At 0 and 24 h after initiation of treatment, arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2 ratio, extravascular lung water index (EVLWI, and E-selectin level were not significantly different between groups (all P>0.05. Compared to non-ECVVH group, PaO2/FiO2 is significantly higher and EVLWI and E-selectin level are significantly lower in ECVVH group (all P<0.05 at 48 h and 72 h after initiation of treatment. The lengths of mechanical ventilation and stay in intensive care unit (ICU were shorter in ECVVH group (all P<0.05, but there was no difference in 28-day mortality between two groups. Conclusions. In patients with septic-shock-induced ARDS (not AKI, treatment with ECVVH in addition to standard therapies improves endothelial function, lung function, and hemodynamic stability and reduces the lengths of mechanical ventilation and stay in ICU.

  16. Venous-to-arterial carbon dioxide difference in the resuscitation of patients with severe sepsis and septic shock: A systematic review.

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    Diaztagle Fernández, J J; Rodríguez Murcia, J C; Sprockel Díaz, J J

    2017-10-01

    The way to assess tissue perfusion during the resuscitation of patients with severe sepsis and septic shock is a current subject of research and debate. Venous oxygen saturation and lactate concentration have been the most frequently used criteria, though they involve known limitations. The venous-to-arterial difference of carbon dioxide (pCO 2 delta) is a parameter than can be used to indicate tissue perfusion, and its determination therefore may be useful in these patients. A qualitative systematic review of the literature was made, comprising studies that assessed pCO 2 delta in adult patients with severe sepsis or septic shock, and published between January 1966 and November 2016 in the Medline-PubMed, Embase-Elsevier, Cochrane Library, and LILACS databases. There was no language restriction. The PRISMA statement was followed, and methodological quality was evaluated. Twelve articles were included, all of an observational nature, and including 10 prospective studies (9 published since 2010). Five documented greater mortality among patients with high pCO 2 delta values, in 3 cases even when achieving venous oxygen saturation targets. In 4 studies, a high pCO 2 delta was related to lower venous oxygen saturation and higher lactate levels, and another 3 documented lesser percentage lactate reductions. The parameter pCO 2 delta has been more frequently assessed in the management of patients with severe sepsis during the last few years. The studies demonstrate its correlation to mortality and other clinical outcomes, defining pCO 2 delta as a useful tool in the management of these patients. Copyright © 2017 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

  17. Função adrenal na sepse e choque séptico Adrenal function in sepsis and septic shock

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    Cristiane Freitas Pizarro

    2007-11-01

    Full Text Available OBJETIVO: Rever os critérios diagnósticos e o tratamento de insuficiência adrenal, em pacientes da faixa etária pediátrica, com sepse grave e choque séptico. FONTES DOS DADOS: Os artigos foram selecionados através das bases de dados MEDLINE (1966-junho 2007, Embase (1994-2007 e Cochrane Library (2000-2007. As seguintes palavras-chave foram utilizadas: choque séptico, sepse, corticosteróides, insuficiência adrenal e crianças. SÍNTESE DOS DADOS: Não existe um critério bem estabelecido e aceito para definir insuficiência adrenal em pacientes criticamente enfermos. A incidência de insuficiência adrenal varia de acordo com o critério utilizado, podendo alcançar desde valores inferiores a 15% até superiores a 61%. O teste rápido de estímulo com hormônio adrenocorticotrófico (ACTH é largamente utilizado como um teste simples para a identificação de não responsividade adrenocortical, mas existe muita discussão quanto à dose de corticotropina a ser utilizada. A dose de 250 µg é a dose padrão. Recentemente, baixas doses de corticotropina (1 µg têm sido propostas, com a sugestão de que elas possam ter uma maior sensibilidade. Dúvidas ainda persistem quanto à eficácia da reposição com baixas doses de corticosteróides em crianças com choque refratário às catecolaminas. Mais estudos são necessários para determinar se o tratamento de tais pacientes alteraria morbidade e/ou mortalidade. CONCLUSÃO: Insuficiência adrenal é comum em crianças com sepse grave e choque séptico e pode contribuir para o desenvolvimento de choque refratário às catecolaminas. Contudo, dúvidas ainda persistem em relação à eficácia da terapêutica com baixas doses de corticosteróides.OBJECTIVE:To review diagnostic criteria and treatment of adrenal insufficiency in pediatric patients with severe sepsis and septic shock. SOURCES: Articles were selected using MEDLINE (1966-June 2007, Embase (1994-2007 and Cochrane Library (2000

  18. Sepse e choque séptico no período neonatal: atualização e revisão de conceitos Neonatal sepsis and septic shock: concepts update and review

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    Rita de Cássia Silveira

    2010-09-01

    Full Text Available A sepse neonatal e a síndrome da resposta inflamatória sistêmica, que antecede o choque séptico, se manifestam como um estado não específico, o que pode retardar o diagnóstico precoce do choque séptico, razão pela qual a mortalidade desta condição permanece elevada. O diagnóstico precoce envolve a suspeita de choque séptico em todo recém nascido apresentando taquicardia, desconforto respiratório, dificuldade de alimentação, tônus alterado, cor alterada, taquipnéia e perfusão reduzida, especialmente na presença de histórico materno de infecção periparto, como corioamnionite ou ruptura prolongada de membranas ovulares. O presente artigo tem como objetivo revisar o conhecimento atual a respeito das peculiaridades do período neonatal, da dinâmica da circulação fetal e da variável idade gestacional. O choque séptico no recém-nascido não é choque séptico do adulto pequeno. No recém-nascido, o choque séptico é predominantemente frio, caracterizado por redução do débito cardíaco e alta resistência vascular sistêmica (vasoconstrição. O tempo é fundamental no tratamento para reversão do choque séptico. A revisão da literatura, baseada em buscas em bases indexadas, fornece subsídios para o manejo do recém-nascido.The nonspecific presentation of neonatal sepsis and systemic inflammatory response syndrome preceding septic shock delay the early diagnosis of septic shock and increase its mortality rate. Early diagnosis involves suspecting septic shock in every newborn with tachycardia, respiratory distress, difficult feeding, altered tonus and skin coloration, tachypnea and reduced perfusion, specially in case of maternal peripartum infection, chorioamnionitis or long-term membranes rupture. This article aims to review current knowledge on neonatal period peculiarities, fetal circulation dynamics, and the pregnancy age variable. Newborn septic shock is not just a small adult shock. In the newborn, the septic

  19. Attenuated effects of chitosan-capped gold nanoparticles on LPS-induced toxicity in laboratory rats

    International Nuclear Information System (INIS)

    Stefan, Marius; Melnig, Viorel; Pricop, Daniela; Neagu, Anca; Mihasan, Marius; Tartau, Liliana; Hritcu, Lucian

    2013-01-01

    The impact of nanoparticles in medicine and biology has increased rapidly in recent years. Gold nanoparticles (AuNP) have advantageous properties such as chemical stability, high electron density and affinity to biomolecules. However, the effects of AuNP on human body after repeated administration are still unclear. Therefore, the purpose of the present study was to evaluate the effects of gold-11.68 nm (AuNP1, 9.8 μg) and gold-22.22 nm (AuNP2, 19.7 μg) nanoparticles capped with chitosan on brain and liver tissue reactivity in male Wistar rats exposed to lipopolysaccharide (LPS from Escherichia coli serotype 0111:B4, 250 μg) upon 8 daily sessions of intraperitoneal administration. Our results suggest that the smaller size of chitosan-capped AuNP shows the protective effects against LPS-induced toxicity, suggesting a very high potential for biomedical applications. - Highlights: ► Smaller size of chitosan-capped gold nanoparticles acts against LPS-induced toxicity. ► Larger size of chitosan-capped gold nanoparticles agglomerated inside neurons and induced toxicity in combination with LPS. ► Chitosan has excellent biocompatible proprieties. ► Smaller size of chitosan-capped gold nanoparticles demonstrates great potential in biomedical applications.

  20. High Mortality in Severe Sepsis and Septic Shock Patients with Do-Not-Resuscitate Orders in East Asia.

    Science.gov (United States)

    Huang, Chun-Ta; Chuang, Yu-Chung; Tsai, Yi-Ju; Ko, Wen-Je; Yu, Chong-Jen

    2016-01-01

    Severe sepsis is a potentially deadly illness and always requires intensive care. Do-not-resuscitate (DNR) orders remain a debated issue in critical care and limited data exist about its impact on care of septic patients, particularly in East Asia. We sought to assess outcome of severe sepsis patients with regard to DNR status in Taiwan. A retrospective cohort study was conducted in intensive care units (ICUs) between 2008 and 2010. All severe sepsis patients were included for analysis. Primary outcome was association between DNR orders and ICU mortality. Volume of interventions was used as proxy indicator to indicate aggressiveness of care. Sixty-seven (9.4%) of 712 patients had DNR orders on ICU admission, and these patients were older and had higher disease severity compared with patients without DNR orders. Notably, DNR patients experienced high ICU mortality (90%). Multivariate analysis revealed that the presence of DNR orders was independently associated with ICU mortality (odds ratio: 6.13; 95% confidence interval: 2.66-14.10). In propensity score-matched cohort, ICU mortality rate (91%) in the DNR group was statistically higher than that (62%) in the non-DNR group (p central venous catheterization were more commonly used in DNR patients than in non-DNR patients. From the Asian perspective, septic patients placed on DNR orders on ICU admission had exceptionally high mortality. In contrast to Western reports, DNR patients received more ICU interventions, reflecting more aggressive approach to dealing with this patient population. The findings in some ways reflect differences between East and West cultures and suggest that DNR status is an important confounder in ICU studies involving severely septic patients.

  1. Glycolipids from spinach suppress LPS-induced vascular inflammation through eNOS and NK-κB signaling.

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    Ishii, Masakazu; Nakahara, Tatsuo; Araho, Daisuke; Murakami, Juri; Nishimura, Masahiro

    2017-07-01

    Glycolipids are the major constituent of the thylakoid membrane of higher plants and have a variety of biological and pharmacological activities. However, anti-inflammatory effects of glycolipids on vascular endothelial cells have not been elucidated. Here, we investigated the effect of glycolipids extracted from spinach on lipopolysaccharides (LPS)-induced endothelial inflammation and evaluated the underlying molecular mechanisms. Treatment with glycolipids from spinach had no cytotoxic effects on cultured human umbilical vein endothelial cells (HUVECs) and significantly blocked the expression of LPS-induced interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), and intracellular adhesion molecule-1 (ICAM-1) in them. Glycolipids treatment also effectively suppressed monocyte adhesion to HUVECs. Treatment with glycolipids inhibited LPS-induced NF-κB phosphorylation and nuclear translocation. In addition, glycolipids treatment significantly promoted endothelial nitric oxide synthase (eNOS) activation and nitric oxide (NO) production in HUVECs. Furthermore, glycolipids treatment blocked LPS-induced inducible NOS (iNOS) expression in HUVECs. Pretreatment with a NOS inhibitor attenuated glycolipids-induced suppression of NF-κB activation and adhesion molecule expression, and abolished the glycolipids-mediated suppression of monocyte adhesion to HUVECs. These results indicate that glycolipids suppress LPS-induced vascular inflammation through attenuation of the NF-κB pathway by increasing NO production in endothelial cells. These findings suggest that glycolipids from spinach may have a potential therapeutic use for inflammatory vascular diseases. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. Inhibitory mechanism of chroman compound on LPS-induced nitric oxide production and nuclear factor-κB activation

    International Nuclear Information System (INIS)

    Kim, Byung Hak; Reddy, Alavala Matta; Lee, Kum-Ho; Chung, Eun Yong; Cho, Sung Min; Lee, Heesoon; Min, Kyung Rak; Kim, Youngsoo

    2004-01-01

    6-Hydroxy-7-methoxychroman-2-carboxylic acid phenylamide (KL-1156) is a novel chemically synthetic compound. In the present study, the chroman KL-1156 compound was found to inhibit lipopolysaccharide (LPS)-induced nitric oxide production in macrophages RAW 264.7. KL-1156 compound attenuated LPS-induced synthesis of both mRNA and protein of inducible nitric oxide synthase (iNOS), in parallel, and inhibited LPS-induced iNOS promoter activity, indicating that the chroman compound down-regulated iNOS expression at transcription level. As a mechanism of the anti-inflammatory action shown by KL-1156 compound, suppression of nuclear factor (NF)-κB has been documented. KL-1156 compound exhibited a dose-dependent inhibitory effect on LPS-induced NF-κB transcriptional activity in macrophages RAW 264.7. Furthermore, the compound inhibited LPS-induced nuclear translocation of NF-κB p65 and DNA binding activity of NF-κB complex, in parallel, but did not affect IκBα degradation. Taken together, this study demonstrated that chroman KL-1156 compound interfered with nuclear translocation step of NF-κB p65, which was attributable to its anti-inflammatory action

  3. Antimicrobial resistance patterns, clinical features, and risk factors for septic shock and death of nosocomial E coli bacteremia in adult patients with hematological disease: A monocenter retrospective study in China.

    Science.gov (United States)

    Ma, Jie; Li, Ning; Liu, Yajie; Wang, Chong; Liu, Xiaoyan; Chen, Shengmei; Xie, Xinsheng; Gan, Silin; Wang, Meng; Cao, Weijie; Wang, Fang; Liu, Yanfan; Wan, Dingming; Sun, Ling; Sun, Hui

    2017-05-01

    The aim of this retrospective analysis was to evaluate the antimicrobial resistance, clinical features, and risk factors for septic shock and death of nosocomial E coli bacteremia in adult patients in a single hematological center in China. A retrospective case-control study of 157 adult hematological patients with 168 episodes of E coli bacteremia was initiated from April 2012 to July 2015. Antimicrobial susceptibility as well as antimicrobial co-resistance rates were analyzed. Clinical features and outcomes were also studied. In addition, risk factors for septic shock and death were investigated. Among the 553 positive blood isolates during the study period, the prevalence of E coli was 33.3% and ESBL production strains represented 61.9% of those examined. In all the E coli strains isolated, 85.6% were multidrug-resistance (MDR), 2.4% were extensive drug resistance (XDR), and 6.0% were resistant to carbapenems. More MDR phenotype was noted in ESBL-EC strains (98.6% vs 62.8%, PE coli (94.0% and 92.0%, respectively), but lower co-resistance rates to other antibiotics. Carbapenem resistant strains retained full sensitivity to tigecycline and 60% to amikacin. Piperacillin/tazobatam was the third sensitive drug to both ESBL-EC (77.1%) and non-ESBL-EC (86.0%). In our series, 81.6% episodes received appropriate initial antibiotic treatment and no significant decrease in it was found in bacteremia due to ESBL E coli and patients with neutropenia, septic shock. Septic shock was noted in 15.5% patients and the overall 30-day mortality rate was 21.7%. Multivariate analysis revealed that induction chemotherapy (OR 2.126; 95% CI 1.624-11.332; P = .003) and polymicrobial infection (OR 3.628; 95% CI 1.065-21.219; P = .041) were risk factors for septic shock, whereas male (OR 2.223; 95% CI 1.132-12.022; P E coli bacteremia which is still a major life-threatening problem, especially for patients with septic shock. For empirical antimicrobial therapy, combination based on

  4. Septic encephalopathy and septic encephalitis‬‬.

    Science.gov (United States)

    Tauber, Simone C; Eiffert, Helmut; Brück, Wolfgang; Nau, Roland

    2017-02-01

    During the last two decades, septic encephalopathy (SE) was recognized as a clinically relevant problem with a high prevalence in patients at admission and during their hospital stay. SE is a condition associated with increased mortality and morbidity such as long-term cognitive impairment. Areas covered: This review illustrates the pathophysiology of sepsis-associated encephalopathy and encephalitis involving blood-brain-barrier dysfunction and neuroinflammation caused by endothelial and microglial activation by endogenous or pathogen-derived compounds, hypoxia by impaired microvascular regulation and septic shock as well as imbalance of neurotransmitters. The continuum between septic-embolic and septic-metastatic encephalitis and SE is underlined by histological findings. The options of technical examinations and biomarkers to diagnose SE are discussed together with established therapeutic options as well as current experimental approaches. Expert commentary: An outlook for clinicians is provided including promising diagnostic approaches by means of new imaging techniques. Clinical trials with drugs already established for other indications such as statins, erythropoietin and minocycline are warranted in the future.

  5. Lignans from Arctium lappa and their inhibition of LPS-induced nitric oxide production.

    Science.gov (United States)

    Park, So Young; Hong, Seong Su; Han, Xiang Hua; Hwang, Ji Sang; Lee, Dongho; Ro, Jai Seup; Hwang, Bang Yeon

    2007-01-01

    A new butyrolactone sesquilignan, isolappaol C (1), together with four known lignans, lappaol C (2), lappaol D (3), lappaol F (4), and diarctigenin (5), were isolated from the methanolic extract of the seeds from the Arctium lappa plant. The structure of isolappaol C (1) was determined by spectral analysis including 1D- and 2D-NMR. All the isolates were evaluated for their inhibitory effects on the LPS-induced nitric oxide production using murine macrophage RAW264.7 cells. Lappaol F (4) and diarctigenin (5) strongly inhibited NO production in the LPS-stimulated RAW264.7 cells with IC(50) values of 9.5 and 9.6 microM, respectively.

  6. Caffeoyl glucosides from Nandina domestica inhibit LPS-induced endothelial inflammatory responses.

    Science.gov (United States)

    Kulkarni, Roshan R; Lee, Wonhwa; Jang, Tae Su; Lee, JungIn; Kwak, Soyoung; Park, Mi Seon; Lee, Hyun-Shik; Bae, Jong-Sup; Na, MinKyun

    2015-11-15

    Endothelial dysfunction is a key pathological feature of many inflammatory diseases, including sepsis. In the present study, a new caffeoyl glucoside (1) and two known caffeoylated compounds (2 and 3) were isolated from the fruits of Nandina domestica Thunb. (Berberidaceae). The compounds were investigated for their effects against lipopolysaccharide (LPS)-mediated endothelial inflammatory responses. At 20 μM, 1 and 2 inhibited LPS-induced hyperpermeability, adhesion, and migration of leukocytes across a human endothelial cell monolayer in a dose-dependent manner suggesting that 1 and 2 may serve as potential scaffolds for the development of therapeutic agents to treat vascular inflammatory disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. NF-κB regulation of endothelial cell function during LPS-induced toxemia and cancer

    Science.gov (United States)

    Kisseleva, Tatiana; Song, Li; Vorontchikhina, Marina; Feirt, Nikki; Kitajewski, Jan; Schindler, Christian

    2006-01-01

    The transcription factor NF-κB is an important regulator of homeostatic growth and inflammation. Although gene-targeting studies have revealed important roles for NF-κB, they have been complicated by component redundancy and lethal phenotypes. To examine the role of NF-κB in endothelial tissues, Tie2 promoter/enhancer–IκBαS32A/S36A transgenic mice were generated. These mice grew normally but exhibited enhanced sensitivity to LPS-induced toxemia, notable for an increase in vascular permeability and apoptosis. Moreover, B16-BL6 tumors grew significantly more aggressively in transgenic mice, underscoring a new role for NF-κB in the homeostatic response to cancer. Tumor vasculature in transgenic mice was extensive and disorganized. This correlated with a marked loss in tight junction formation and suggests that NF-κB plays an important role in the maintenance of vascular integrity and response to stress. PMID:17053836

  8. Impact of training status on LPS-induced acute inflammation in humans

    DEFF Research Database (Denmark)

    Olesen, Jesper; Biensø, Rasmus Sjørup; Meinertz, S.

    2015-01-01

    The aim of the present study was to examine the impact of training status on the ability to induce a lipopolysaccharide (LPS)-induced inflammatory response systemically as well as in skeletal muscle (SkM) and adipose tissue (AT) in human subjects. Methods: Seventeen young (23.8 ± 2.5 years of age......) healthy male subjects were included in the study with eight subjects assigned to a trained (T) group and nine subjects assigned to an untrained (UT) group. On the experimental day, catheters were inserted in the femoral artery and vein of one leg for blood sampling and a bolus of 0.3 ng LPS•kg-1 body...... weight was injected into an antecubital vein in the forearm. Femoral arterial blood flow was measured before (Pre) the LPS injection and continuously throughout the experiment by Ultrasound Doppler and arterial and venous blood samples were drawn Pre and 30, 60, 90 and 120 min after the LPS injection...

  9. Andrographolide protects against LPS-induced acute lung injury by inactivation of NF-κB.

    Directory of Open Access Journals (Sweden)

    Tao Zhu

    Full Text Available Nuclear factor-κB (NF-κB is a central transcriptional factor and a pleiotropic regulator of many genes involved in acute lung injury. Andrographolide is found in the plant of Andrographis paniculata and widely used in Traditional Chinese Medicine, exhibiting potently anti-inflammatory property by inhibiting NF-κB activity. The purpose of our investigation was designed to reveal the effect of andrographolide on various aspects of LPS induced inflammation in vivo and in vitro.In vivo, BALB/C mice were subjected to LPS injection with or without andrographolide treatments to induce ALI model. In vitro, MLE-12 cells were stimulated with LPS in the presence and absence of andrographolide. In vivo, pulmonary inflammation, pulmonary edema, ultrastructure changes of type II alveolar epithelial cells, MPO activity, total cells, neutrophils, macrophages, TNF-α, IL-6 and IL-1β in BALF, along with the expression of VCAM-1 and VEGF were dose-dependently attenuated by andrographolide. Meanwhile, in vitro, the expression of VCAM-1 and VEGF was also reduced by andrographolide. Moreover, our data showed that andrographolide significantly inhibited the ratios of phospho-IKKβ/total IKKβ, phospho-IκBα/total IκBα and phospho-NF-κB p65/total NF-κB p65, and NF-κB p65 DNA binding activities, both in vivo and in vitro.These results indicate that andrographolide dose-dependently suppressed the severity of LPS-induced ALI, more likely by virtue of andrographolide-mediated NF-κB inhibition at the level of IKKβ activation. These results suggest andrographolide may be considered as an effective and safe drug for the potential treatment of ALI.

  10. Andrographolide Protects against LPS-Induced Acute Lung Injury by Inactivation of NF-κB

    Science.gov (United States)

    Zhu, Tao; Wang, Dao-xin; Zhang, Wei; Liao, Xiu-qing; Guan, Xian; Bo, Hong; Sun, Jia-yang; Huang, Ni-wen; He, Jing; Zhang, Yun-kun; Tong, Jing; Li, Chang-yi

    2013-01-01

    Background Nuclear factor-κB (NF-κB) is a central transcriptional factor and a pleiotropic regulator of many genes involved in acute lung injury. Andrographolide is found in the plant of Andrographis paniculata and widely used in Traditional Chinese Medicine, exhibiting potently anti-inflammatory property by inhibiting NF-κB activity. The purpose of our investigation was designed to reveal the effect of andrographolide on various aspects of LPS induced inflammation in vivo and in vitro. Methods and Results In vivo, BALB/C mice were subjected to LPS injection with or without andrographolide treatments to induce ALI model. In vitro, MLE-12 cells were stimulated with LPS in the presence and absence of andrographolide. In vivo, pulmonary inflammation, pulmonary edema, ultrastructure changes of type II alveolar epithelial cells, MPO activity, total cells, neutrophils, macrophages, TNF-α, IL-6 and IL-1β in BALF, along with the expression of VCAM-1 and VEGF were dose-dependently attenuated by andrographolide. Meanwhile, in vitro, the expression of VCAM-1 and VEGF was also reduced by andrographolide. Moreover, our data showed that andrographolide significantly inhibited the ratios of phospho-IKKβ/total IKKβ, phospho-IκBα/total IκBα and phospho-NF-κB p65/total NF-κB p65, and NF-κB p65 DNA binding activities, both in vivo and in vitro. Conclusions These results indicate that andrographolide dose-dependently suppressed the severity of LPS-induced ALI, more likely by virtue of andrographolide-mediated NF-κB inhibition at the level of IKKβ activation. These results suggest andrographolide may be considered as an effective and safe drug for the potential treatment of ALI. PMID:23437127

  11. LPS-induced systemic inflammation is more severe in P2Y12 null mice.

    Science.gov (United States)

    Liverani, Elisabetta; Rico, Mario C; Yaratha, Laxmikausthubha; Tsygankov, Alexander Y; Kilpatrick, Laurie E; Kunapuli, Satya P

    2014-02-01

    Thienopyridines are a class of antiplatelet drugs that are metabolized in the liver to several metabolites, of which only one active metabolite can irreversibly antagonize the platelet P2Y12 receptor. Possible effects of these drugs and the role of activated platelets in inflammatory responses have also been investigated in a variety of animal models, demonstrating that thienopyridines could alter inflammation. However, it is not clear whether it is caused only by the P2Y12 antagonism or whether off-target effects of other metabolites also intervene. To address this question, we investigated P2Y12 KO mice during a LPS-induced model of systemic inflammation, and we treated these KO mice with a thienopyridine drug (clopidogrel). Contrary to the reported effects of clopidogrel, numbers of circulating WBCs and plasma levels of cytokines were increased in LPS-exposed KO mice compared with WT in this inflammation model. Moreover, both spleen and bone marrow show an increase in cell content, suggesting a role for P2Y12 in regulation of bone marrow and spleen cellular composition. Finally, the injury was more severe in the lungs of KO mice compared with WT. Interestingly, clopidogrel treatments also exerted protective effects in KO mice, suggesting off-target effects for this drug. In conclusion, the P2Y12 receptor plays an important role during LPS-induced inflammation, and this signaling pathway may be involved in regulating cell content in spleen and bone marrow during LPS systemic inflammation. Furthermore, clopidogrel may have effects that are independent of P2Y12 receptor blockade.

  12. IGF-1 attenuates LPS induced pro-inflammatory cytokines expression in buffalo (Bubalus bubalis) granulosa cells.

    Science.gov (United States)

    Onnureddy, K; Ravinder; Onteru, Suneel Kumar; Singh, Dheer

    2015-03-01

    Interaction between immune and endocrine system is a diverse process influencing cellular function and homeostasis in animals. Negative energy balance (NEB) during postpartum period in dairy animals usually suppresses these systems resulting in reproductive tract infection and infertility. These negative effects could be due to competition among endocrine and immune signaling pathways for common signaling molecules. The present work studied the effect of IGF-1 (50 ng/ml) on LPS (1 μg/ml) mediated pro-inflammatory cytokine expression (IL-1β, TNF-α, IL-6) and aromatase (CYP19A1) genes' expressions as well as proliferation of buffalo granulosa cells. The crosstalk between LPS and IGF-1 was also demonstrated through studying the activities of downstream signaling molecules (ERK1/2, Akt, NF-κB) by western blot and immunostaining. Gene expression analysis showed that IGF-1 significantly reduced the LPS induced expression of IL-1β, TNF-α and IL-6. LPS alone inhibited the CYP19A1 expression. However, co-treatment with IGF-1 reversed the inhibitory effect of LPS on CYP19A1 expression. LPS alone did not affect granulosa cell proliferation, but co-treatment with IGF-1, and IGF-1 alone enhanced the proliferation. Western blot results demonstrated that LPS caused the nuclear translocation of the NF-κB and increased the phosphorylation of ERK1/2 and Akt maximum at 15 min and 60 min, respectively. Nonetheless, co-treatment with IGF-1 delayed LPS induced phosphorylation of ERK1/2 (peak at 120 min), while promoting early Akt phosphorylation (peak at 5 min) with no effect on NF-κB translocation. Overall, IGF-1 delayed and reversed the effects of LPS, suggesting that high IGF-1 levels may combat infection during critical periods like NEB in postpartum dairy animals. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Probiotics and Probiotic Metabolic Product Improved Intestinal Function and Ameliorated LPS-Induced Injury in Rats.

    Science.gov (United States)

    Deng, Bo; Wu, Jie; Li, Xiaohui; Men, Xiaoming; Xu, Ziwei

    2017-11-01

    In the present study, we sought to determine the effects of Bacillus subtilis (BAS) and Bacillus licheniformis (BAL) in rats after lipopolysaccharide (LPS)-induced acute intestinal inflammation. We also determined whether the B. subtilis metabolic product (BASM) is as effective as the live-cell probiotic. 60 male SD rats were randomly assigned to five groups and administered a diet containing 0.05% B. licheniformis (BAL group), 0.05% B. subtilis (BAS group), 0.5% B. subtilis metabolic product (BASM group), or a basic diet (PC group and NC group) for 40 days. On day 40, BAL, BAS, BASM, and NC groups were injected with 4 mg/kg body weight LPS. 4 h later, all rats were anesthetized and sacrificed. The results showed that the administration of B. licheniformis and B. subtilis improved intestinal function as evidenced by histology, increased enzyme activity, and mucosal thickness. They also increased the number of intraepithelial lymphocytes and decreased mucosal myeloperoxidase activity and plasma TNF-α. In addition, the cecal content of B. subtilis-treated rats had significantly increased microbial diversity, decreased numbers of Firmicutes, and increased numbers of Bacteroidetes as compared to rats fed basic diets. Similar to BAS group, the cecal content of B. licheniformis-treated rats decreased the number of Firmicutes. Administration of B. subtilis metabolic product had similar effects on intestinal function, inflammation response, and microbial diversity as B. subtilis but these effects were attenuated. In conclusion, administration of probiotic strains B. licheniformis or B. subtilis improved intestinal function, ameliorated the inflammation response, and modulated microflora after LPS-induced acute inflammation in rats. Non-living cells also exerted probiotic properties but live cells tended to function better.

  14. A systematic review and meta-analysis of early goal-directed therapy for septic shock: the ARISE, ProCESS and ProMISe Investigators.

    Science.gov (United States)

    Angus, D C; Barnato, A E; Bell, D; Bellomo, R; Chong, C-R; Coats, T J; Davies, A; Delaney, A; Harrison, D A; Holdgate, A; Howe, B; Huang, D T; Iwashyna, T; Kellum, J A; Peake, S L; Pike, F; Reade, M C; Rowan, K M; Singer, M; Webb, S A R; Weissfeld, L A; Yealy, D M; Young, J D

    2015-09-01

    To determine whether early goal-directed therapy (EGDT) reduces mortality compared with other resuscitation strategies for patients presenting to the emergency department (ED) with septic shock. Using a search strategy of PubMed, EmBase and CENTRAL, we selected all relevant randomised clinical trials published from January 2000 to January 2015. We translated non-English papers and contacted authors as necessary. Our primary analysis generated a pooled odds ratio (OR) from a fixed-effect model. Sensitivity analyses explored the effect of including non-ED studies, adjusting for study quality, and conducting a random-effects model. Secondary outcomes included organ support and hospital and ICU length of stay. From 2395 initially eligible abstracts, five randomised clinical trials (n = 4735 patients) met all criteria and generally scored high for quality except for lack of blinding. There was no effect on the primary mortality outcome (EGDT: 23.2% [495/2134] versus control: 22.4% [582/2601]; pooled OR 1.01 [95% CI 0.88-1.16], P = 0.9, with heterogeneity [I(2) = 57%; P = 0.055]). The pooled estimate of 90-day mortality from the three recent multicentre studies (n = 4063) also showed no difference [pooled OR 0.99 (95% CI 0.86-1.15), P = 0.93] with no heterogeneity (I(2) = 0.0%; P = 0.97). EGDT increased vasopressor use (OR 1.25 [95% CI 1.10-1.41]; P < 0.001) and ICU admission [OR 2.19 (95% CI 1.82-2.65); P < 0.001]. Including six non-ED randomised trials increased heterogeneity (I(2) = 71%; P < 0.001) but did not change overall results [pooled OR 0.94 (95% CI 0.82 to 1.07); P = 0.33]. EGDT is not superior to usual care for ED patients with septic shock but is associated with increased utilisation of ICU resources.

  15. N-terminal pro-brain natriuretic peptide and cardiac troponin I for the prognostic utility in elderly patients with severe sepsis or septic shock in intensive care unit: A retrospective study.

    Science.gov (United States)

    Cheng, Hui; Fan, Wei-Ze; Wang, Sheng-Chi; Liu, Zhao-Hui; Zang, Hui-Ling; Wang, Li-Zhong; Liu, Hong-Juan; Shen, Xiao-Hui; Liang, Shao-Qing

    2015-06-01

    Using biomarkers to predict mortality in patient with severe sepsis or septic shock is of importance, as these patients frequently have high mortality and unsatisfied outcome. N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) play extremely important roles in prognostic value in the mortality of severe sepsis and septic shock. The present study was retrospectively designed to evaluate the predicting mortality of NT-proBNP and cTnI in elderly patients with severe sepsis or septic shock administered in the intensive care unit (ICU) and also to evaluate whether the predicting ability of Acute Physiology and Chronic Health Evaluation II (APACHE-II) score or C-reactive protein (CRP) was increased in combination with the biomarkers. A cohort of 430 patients (aged ≥65 years) with severe sepsis or septic shock admitted to our ICU between October 2011 and December 2013 was included in the study. Patient data including clinical, laboratory, and survival and mortality were collected. All patients were examined with NT-proBNP, cTnI, CRP, and APACHE-II score and were categorized as the survived and deceased groups according to the outcome 30 days after ICU treatment. The levels of NT-proBNP and cTnI (P pro-brain natriuretic peptide and cTnI were superior to CRP in predicting mortality. The predicting ability of APACHE-II score was improved only when combined with NT-proBNP and cTnI. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Subject-specific cardiovascular system model-based identification and diagnosis of septic shock with a minimally invasive data set: animal experiments and proof of concept

    International Nuclear Information System (INIS)

    Geoffrey Chase, J; Starfinger, Christina; Hann, Christopher E; Lambermont, Bernard; Ghuysen, Alexandre; Kolh, Philippe; Dauby, Pierre C; Desaive, Thomas; Shaw, Geoffrey M

    2011-01-01

    A cardiovascular system (CVS) model and parameter identification method have previously been validated for identifying different cardiac and circulatory dysfunctions in simulation and using porcine models of pulmonary embolism, hypovolemia with PEEP titrations and induced endotoxic shock. However, these studies required both left and right heart catheters to collect the data required for subject-specific monitoring and diagnosis—a maximally invasive data set in a critical care setting although it does occur in practice. Hence, use of this model-based diagnostic would require significant additional invasive sensors for some subjects, which is unacceptable in some, if not all, cases. The main goal of this study is to prove the concept of using only measurements from one side of the heart (right) in a 'minimal' data set to identify an effective patient-specific model that can capture key clinical trends in endotoxic shock. This research extends existing methods to a reduced and minimal data set requiring only a single catheter and reducing the risk of infection and other complications—a very common, typical situation in critical care patients, particularly after cardiac surgery. The extended methods and assumptions that found it are developed and presented in a case study for the patient-specific parameter identification of pig-specific parameters in an animal model of induced endotoxic shock. This case study is used to define the impact of this minimal data set on the quality and accuracy of the model application for monitoring, detecting and diagnosing septic shock. Six anesthetized healthy pigs weighing 20–30 kg received a 0.5 mg kg −1 endotoxin infusion over a period of 30 min from T0 to T30. For this research, only right heart measurements were obtained. Errors for the identified model are within 8% when the model is identified from data, re-simulated and then compared to the experimentally measured data, including measurements not used in the

  17. Ilexgenin A, a novel pentacyclic triterpenoid extracted from Aquifoliaceae shows reduction of LPS-induced peritonitis in mice.

    Science.gov (United States)

    Sun, Weidong; Liu, Chang; Zhang, Yaqi; Qiu, Xia; Zhang, Li; Zhao, Hongxia; Rong, Yi; Sun, Yun

    2017-02-15

    Ilexgenin A (IA) is a novel pentacyclic triterpenoid, which extracted from leaves of Ilex hainanensis Merr. In the present study, we aim to explore anti-inflammatory activity of IA on LPS-induced peritonitis and its underlying molecular mechanism. The results determined that IA was capable of suppressing peritonitis in mice induced by intraperitoneal (i.p.) injection of lipopolysaccaride (LPS). Furthermore, the results showed that IA dramatically inhibited levels of inflammatory cells infiltration in peritoneal cavity and serum in LPS-induced mice peritonitis model. Besides, IA could dramatically inhibit levels of inflammatory cytokines (IL-1β, IL-6 and TNF-α) in peritoneal cavity in LPS-induced mice peritonitis model. In vitro study, the results showed that IA inhibited production of IL-1β, IL-6 and TNF-α at transcriptional and translational levels in RAW 264.7 cells induced by LPS. Furthermore, IA could suppress the LPS-induced activation of Akt and downstream degradation and phosphorylation of kappa B-α (IκB-α). Moreover, IA could significantly inhibit ERK 1/2 phosphorylation in RAW 264.7 cells induced by LPS. These results were concurrent with molecular docking which revealed ERK1/2 inhibition. These results demonstrated that IA might as an anti-inflammatory agent candidate for inflammatory disease therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Class A CpG Oligonucleotide Priming Rescues Mice from Septic Shock via Activation of Platelet-Activating Factor Acetylhydrolase

    Directory of Open Access Journals (Sweden)

    Yoshinari Yamamoto

    2017-08-01

    Full Text Available Sepsis is a life-threatening, overwhelming immune response to infection with high morbidity and mortality. Inflammatory response and blood clotting are caused by sepsis, which induces serious organ damage and death from shock. As a mechanism of pathogenesis, platelet-activating factor (PAF induces excessive inflammatory responses and blood clotting. In this study, we demonstrate that a Class A CpG oligodeoxynucleotide (CpG-A1585 strongly induced PAF acetylhydrolase, which generates lyso-PAF. CpG-A1585 rescued mice from acute lethal shock and decreased fibrin deposition, a hallmark of PAF-induced disseminated intravascular coagulation. Furthermore, CpG-A1585 improved endotoxin shock induced by lipopolysaccharide, which comprises the cell wall of Gram-negative bacteria and inhibits inflammatory responses induced by cytokines such as interleukin-6 and tumor necrosis factor-α. These results suggest that CpG-A1585 is a potential therapeutic target to prevent sepsis-related induction of PAF.

  19. Terlipressina como novo recurso terapêutico no choque séptico Terlipressin as a new therapeutic agent in septic shock

    Directory of Open Access Journals (Sweden)

    Valter Nilton Felix

    2006-06-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A terlipressina tem sido inserida em protocolos de suporte hemodinâmico da sepse, como recurso em casos de choque refratário, o que motiva análise crítica a respeito do assunto. CONTEÚDO: Foram revistas para a análise terapias hemodinâmicas com objetivos finais bem delineados e novas recomendações para reanimação volêmica, uso de vasopressores e agentes inotrópicos em adultos e crianças sépticos. CONCLUSÕES: A terlipressina tem sido considerada nova alternativa nos cuidados intensivos da sepse, embora ainda controversa.BACKGROUND AND OBJECTIVES: The hemodynamic support of sepsis is now formulated trying to insert terlipressin as salvage drug in catecholamine resistant shock, justifying a broad critical analysis. CONTENTS: The analysis included hemodynamic therapies with defined specific goals and new recommendations for fluid resuscitation, vasopressor therapy, and inotropic therapy of septic in adult and pediatric patients. CONCLUSIONS: Terlipressin appears as a new but controversial alternative for vasopressor therapy in sepsis.

  20. The direct costs of intensive care management and risk factors for financial burden of patients with severe sepsis and septic shock.

    Science.gov (United States)

    Khwannimit, Bodin; Bhurayanontachai, Rungsun

    2015-10-01

    The costs of severe sepsis care from middle-income countries are lacking. This study investigated direct intensive care unit (ICU) costs and factors that could affect the financial outcomes. A prospective cohort study was conducted in the medical ICU of a tertiary referral university teaching hospital in Thailand. A total of 897 patients were enrolled in the study, with 683 (76.1%) having septic shock. Community-, nosocomial, and ICU-acquired infections were documented in 574, 282, and 41 patients, respectively. The median ICU costs per patient were $2716.5 ($1296.1-$5367.6) and $599.9 ($414.3-$948.6) per day. The ICU costs accounted for 64.7% of the hospital costs. In 2008 to 2011, the ICU costs significantly decreased by 40% from $3542.5 to $2124.9, whereas, the daily ICU costs decreased only 3.3% from $609.7 to $589.7. By multivariate logistic regression analysis, age, nosocomial or ICU infection, admission from the emergency department, number of organ failures, ICU length of stay, and fluid balance the first 72 hours were independently associated with ICU costs. The ICU costs of severe sepsis management significantly declined in our study. However, the ICU costs were a financial burden accounting for two thirds of the hospital costs. It is essential for intensivists to contribute a high standard of care within a restricted budget. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Risk factors and outcomes of sepsis-induced myocardial dysfunction and stress-induced cardiomyopathy in sepsis or septic shock: A comparative retrospective study.

    Science.gov (United States)

    Jeong, Han Saem; Lee, Tae Hyub; Bang, Cho Hee; Kim, Jong-Ho; Hong, Soon Jun

    2018-03-01

    While both sepsis-induced myocardial dysfunction (SIMD) and stress-induced cardiomyopathy (SICMP) are common in patients with sepsis, the pathogenesis of the 2 diseases is different, and they require different treatment strategies. Thus, we aimed to investigate risk factors and outcomes between the 2 diseases.This retrospective study enrolled patients diagnosed with sepsis or septic shock, admitted to intensive care unit via emergency department in Korea University Anam Hospital, and who underwent transthoracic echocardiography within the first 24 hours of admission.In all, 25 patients with SIMD and 27 patients with SICMP were enrolled. Chronic obstructive pulmonary disease and a history of heart failure (HF) were more prevalent in both the SIMD and SICMP groups than in the control group. In the SIMD and SICMP groups, levels of inflammatory cytokines were similar. Serum troponin level was significantly elevated in the SICMP and SIMD group compared to the control group. N-terminal pro-brain natriuretic peptide (NT pro-BNP) level was significantly elevated in the SIMD group compared to the SICMP group or control group. The in-hospital mortality rate in the SIMD and SICMP group was about 40%, showing increased trends compared with the control group. The in-hospital mortality rate was significantly increased in SIMD group with EFshock.

  2. Long-term nicotine exposure dampens LPS-induced nerve-mediated airway hyperreactivity in murine airways.

    Science.gov (United States)

    Xu, Yuan; Cardell, Lars-Olaf

    2017-09-01

    Nicotine is a major component of cigarette smoke. It causes addiction and is used clinically to aid smoke cessation. The aim of the present study is to investigate the effect of nicotine on lipopolysaccharide (LPS)-induced airway hyperreactivity (AHR) and to explore the potential involvement of neuronal mechanisms behind nicotine's effects in murine models in vivo and in vitro. BALB/c mice were exposed to nicotine in vivo via subcutaneous Alzet osmotic minipumps containing nicotine tartate salt solution (24 mg·kg -1 ·day -1 ) for 28 days. LPS (0.1 mg/ml, 20 µl) was administered intranasally for 3 consecutive days during the end of this period. Lung functions were measured with flexiVent. For the in vitro experiments, mice tracheae were organcultured with either nicotine (10 μM) or vehicle (DMSO, 0.1%) for 4 days. Contractile responses of the tracheal segments were measured in myographs following electric field stimulation (EFS; increasing frequencies of 0.2 to 12.8 Hz) before and after incubation with 10 µg/ml LPS for 1 h. Results showed that LPS induced AHR to methacholine in vivo and increased contractile responses to EFS in vitro. Interestingly, long-term nicotine exposure markedly dampened this LPS-induced AHR both in vitro and in vivo. Tetrodotoxin (TTX) inhibited LPS-induced AHR but did not further inhibit nicotine-suppressed AHR in vivo. In conclusion, long-term nicotine exposure dampened LPS-induced AHR. The effect of nicotine was mimicked by TTX, suggesting the involvement of neuronal mechanisms. This information might be used for evaluating the long-term effects of nicotine and further exploring of how tobacco products interact with bacterial airway infections. Copyright © 2017 the American Physiological Society.

  3. Protective Effect of Phillyrin on Lethal LPS-Induced Neutrophil Inflammation in Zebrafish

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    Liling Yang

    2017-10-01

    Full Text Available Background/Aims: Forsythia suspensa Vahl. (Oleaceae fruits are widely used in traditional Chinese medicine to treat pneumonia, typhoid, dysentery, ulcers and oedema. Antibacterial and anti-inflammatory activities have been reported for phillyrin (PHN, the main ingredient in Forsythia suspensa Vahl fruits, in vitro. However, the underlying mechanisms in vivo remain poorly defined. In this study, we discovered that PHN exerted potent anti-inflammatory effects in lethal LPS-induced neutrophil inflammation by suppressing the MyD88-dependent signalling pathway in zebrafish. Methods: LPS-yolk microinjection was used to induce a lethal LPS-infected zebrafish model. The effect of PHN on the survival of zebrafish challenged with lethal LPS was evaluated using survival analysis. The effect of PHN on neutrophil inflammation grading in vivo was assessed by tracking neutrophils with a transgenic line. The effects of PHN on neutrophil production and migration were analysed by SB+ cell counts during consecutive hours after modelling. Additionally, key cytokines and members of the MyD88 signalling pathway that are involved in inflammatory response were detected using quantitative RT-PCR. To assess gene expression changes during consecutive hours after modelling, the IL-1β, IL-6, TNF-α, MyD88, TRIF, ERK1/2, JNK, IκBa and NF-κB expression levels were measured. Results: PHN could protect zebrafish against a lethal LPS challenge in a dose-dependent manner, as indicated by decreased neutrophil infltration, reduced tissue necrosis and increased survival rates. Up-regulated IL-1β, IL-6 and TNF-α expression also showed the same tendencies of depression by PHN. Critically, PHN significantly inhibited the LPS-induced activation of MyD88, IκBa, and NF-κB but did not affect the expression of ERK1/2 MAPKs or JNK MAPKs in LPS-stimulated zebrafish. Additionally, PHN regulated the MyD88/IκBα/NF-κB signalling pathway by controlling IκBα, IL-1β, IL-6, and TNF

  4. Tratamiento quirúrgico de las complicaciones del shock meningocóccico grave Surgical treatment of the severe meningococcal septic shock complications

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    P. Casteleiro Roca

    2010-06-01

    Full Text Available El shock meningocóccico es una entidad relativamente frecuente y de pronóstico muy grave, que provoca fallo multiorgánico con una alta mortalidad y que precisa ingreso en Unidad de Cuidados Intensivos. En los casos grandes puede provocar necrosis de tejidos mediante una fisiopatología poco clara. En los últimos años la supervivencia de estos pacientes ha aumentado debido al diagnóstico precoz y a medidas de reanimación más agresivas. Como consecuencia encontramos un aumento del número de pacientes con necrosis extensas de tejidos que precisan tratamiento. Lo fundamental ante el diagnóstico de un shock meningocóccico es establecer el tratamiento médico precoz con medidas de reanimación agresivas y antibioterapia. Sugerimos que la necrosis extensa de tejidos que sufren estos pacientes debe tratarse como si se tratase de un paciente quemado, realizando curas diarias con sulfadiacina argéntica y cirugías seriadas (desbridamiento - amputación - cobertura tan pronto como la situación clínica del paciente lo permita. Es necesario un seguimiento muy cercano de estos pacientes, dada la necesidad de cirugías secundarias que van a precisar a lo largo de su vida, así como la realización de pruebas de imagen para descartar la presencia de osteomielitis secundarias.Meningococcal shock is a relatively frequent disease with a serious prognosis, that causes a multiorganic failure with high mortality and Intensive Care Unit admission. Serious meningococcal shock causes tissue necrosis by uncertain physiopathology. In the last years, there is an increase of the survival, as a result of early diagnosis and aggressive resuscitation. So, there is an increase of patient's tissue necrosis that needs surgery. The most important aspect in front of meningococcal shock is to establish early medical treatment with aggressive resuscitation and antibiotics. Tissue necrosis should be treated like burn patient: argentic sulfadiazine daily cure and serial

  5. Suppressor of cytokine signaling 1 expression during LPS-induced inflammation and bone loss in rats

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    João Antonio Chaves de SOUZA

    2017-10-01

    Full Text Available Abstract This study aimed to characterize the dynamics of suppressor of cytokine signaling (SOCS1 expression in a rat model of lipopolysaccharide-induced periodontitis. Wistar rats in the experimental groups were injected three times/week with LPS from Escherichia coli on the palatal aspect of the first molars, and control animals were injected with vehicle (phosphate-buffered saline. Animals were sacrificed 7, 15, and 30 days after the first injection to analyze inflammation (stereometric analysis, bone loss (macroscopic analysis, gene expression (qRT-PCR, and protein expression/activation (Western blotting. The severity of inflammation and bone loss associated with LPS-induced periodontitis increased from day 7 to day 15, and it was sustained through day 30. Significant (p < 0.05 increases in SOCS1, RANKL, OPG, and IFN-γ gene expression were observed in the experimental group versus the control group at day 15. SOCS1 protein expression and STAT1 and NF-κB activation were increased throughout the 30-day experimental period. Gingival tissues affected by experimental periodontitis express SOCS1, indicating that this protein may potentially downregulate signaling events involved in inflammatory reactions and bone loss and thus may play a relevant role in the development and progression of periodontal disease.

  6. Involvement of mitogen-activated protein kinases and NFκB in LPS-induced CD40 expression on human monocytic cells

    International Nuclear Information System (INIS)

    Wu Weidong; Alexis, Neil E.; Chen Xian; Bromberg, Philip A.; Peden, David B.

    2008-01-01

    CD40 is a costimulatory molecule linking innate and adaptive immune responses to bacterial stimuli, as well as a critical regulator of functions of other costimulatory molecules. The mechanisms regulating lipopolysaccharide (LPS)-induced CD40 expression have not been adequately characterized in human monocytic cells. In this study we used a human monocytic cell line, THP-1, to investigate the possible mechanisms of CD40 expression following LPS exposure. Exposure to LPS resulted in a dose- and time-dependent increase in CD40 expression. Further studies using immunoblotting and pharmacological inhibitors revealed that mitogen-activated protein kinases (MAPKs) and NFκB were activated by LPS exposure and involved in LPS-induced CD40 expression. Activation of MAPKs was not responsible for LPS-induced NFκB activation. TLR4 was expressed on THP-1 cells and pretreatment of cells with a Toll-like receptor 4 (TLR4) neutralizing antibody (HTA125) significantly blunted LPS-induced MAPK and NFκB activation and ensuing CD40 expression. Additional studies with murine macrophages expressing wild type and mutated TLR4 showed that TLR4 was implicated in LPS-induced ERK and NFκB activation, and CD40 expression. Moreover, blockage of MAPK and NFκB activation inhibited LPS-induced TLR4 expression. In summary, LPS-induced CD40 expression in monocytic cells involves MAPKs and NFκB

  7. SvO(2)-guided resuscitation for experimental septic shock: effects of fluid infusion and dobutamine on hemodynamics, inflammatory response, and cardiovascular oxidative stress.

    Science.gov (United States)

    Rosário, André Loureiro; Park, Marcelo; Brunialti, Milena Karina; Mendes, Marialice; Rapozo, Marjorie; Fernandes, Denise; Salomão, Reinaldo; Laurindo, Francisco Rafael; Schettino, Guilherme Paula; Azevedo, Luciano Cesar P

    2011-12-01

    The pathogenetic mechanisms associated to the beneficial effects of mixed venous oxygen saturation (SvO(2))-guided resuscitation during sepsis are unclear. Our purpose was to evaluate the effects of an algorithm of SvO(2)-driven resuscitation including fluids, norepinephrine and dobutamine on hemodynamics, inflammatory response, and cardiovascular oxidative stress during a clinically resembling experimental model of septic shock. Eighteen anesthetized and catheterized pigs (35-45 kg) were submitted to peritonitis by fecal inoculation (0.75 g/kg). After hypotension, antibiotics were administered, and the animals were randomized to two groups: control (n = 9), with hemodynamic support aiming central venous pressure 8 to 12 mmHg, urinary output 0.5 mL/kg per hour, and mean arterial pressure greater than 65 mmHg; and SvO(2) (n = 9), with the goals above, plus SvO(2) greater than 65%. The interventions lasted 12 h, and lactated Ringer's and norepinephrine (both groups) and dobutamine (SvO(2) group) were administered. Inflammatory response was evaluated by plasma concentration of cytokines, neutrophil CD14 expression, oxidant generation, and apoptosis. Oxidative stress was evaluated by plasma and myocardial nitrate concentrations, myocardial and vascular NADP(H) oxidase activity, myocardial glutathione content, and nitrotyrosine expression. Mixed venous oxygen saturation-driven resuscitation was associated with improved systolic index, oxygen delivery, and diuresis. Sepsis induced in both groups a significant increase on IL-6 concentrations and plasma nitrate concentrations and a persistent decrease in neutrophil CD14 expression. Apoptosis rate and neutrophil oxidant generation were not different between groups. Treatment strategies did not significantly modify oxidative stress parameters. Thus, an approach aiming SvO(2) during sepsis improves hemodynamics, without any significant effect on inflammatory response and oxidative stress. The beneficial effects associated

  8. [Predictive value of central venous-to-arterial carbon dioxide partial pressure difference for fluid responsiveness in septic shock patients: a prospective clinical study].

    Science.gov (United States)

    Liu, Guangyun; Huang, Huibin; Qin, Hanyu; Du, Bin

    2018-05-01

    To evaluate the accuracy of central venous-to-arterial carbon dioxide partial pressure difference (Pcv-aCO 2 ) before and after rapid rehydration test (fluid challenge) in predicting the fluid responsiveness in patients with septic shock. A prospective observation was conducted. Forty septic shock patients admitted to medical intensive care unit (ICU) of Peking Union Medical College Hospital from October 2015 to June 2017 were enrolled. All of the patients received fluid challenge in the presence of invasive hemodynamic monitoring. Heart rate (HR), blood pressure, cardiac index (CI), Pcv-aCO 2 and other physiological variables were recorded at 10 minutes before and immediately after fluid challenge. Fluid responsiveness was defined as an increase in CI greater than 10% after fluid challenge, whereas fluid non-responsiveness was defined as no increase or increase in CI less than 10%. The correlation between Pcv-aCO 2 and CI was explored by Pearson correlation analysis. Receiver operating characteristic (ROC) curves were established to evaluate the discriminatory abilities of baseline and the changes after fluid challenge in Pcv-aCO 2 and other physiological variables to define the fluid responsiveness. The patients were separated into two groups according to the initial value of Pcv-aCO 2 . The cut-off value of 6 mmHg (1 mmHg = 0.133 kPa) was chosen according to previous studies. The discriminatory abilities of baseline and the change in Pcv-aCO 2 (ΔPcv-aCO 2 ) were assessed in each group. A total of 40 patients were finally included in this study. Twenty-two patients responded to the fluid challenge (responders). Eighteen patients were fluid non-responders. There was no significant difference in baseline physiological variable between the two groups. Fluid challenge could increase CI and blood pressure significantly, decrease HR notably and had no effect on Pcv-aCO 2 in fluid responders. In non-responders, blood pressure was increased significantly and CI, HR, Pcv

  9. Kaempferol slows intervertebral disc degeneration by modifying LPS-induced osteogenesis/adipogenesis imbalance and inflammation response in BMSCs.

    Science.gov (United States)

    Zhu, Jun; Tang, Haoyu; Zhang, Zhenhua; Zhang, Yong; Qiu, Chengfeng; Zhang, Ling; Huang, Pinge; Li, Feng

    2017-02-01

    Intervertebral disc (IVD) degeneration is a common disease that represents a significant cause of socio-economic problems. Bone marrow-derived mesenchymal stem cells (BMSCs) are a potential autologous stem cell source for the nucleus pulposus regeneration. Kaempferol has been reported to exert protective effects against both osteoporosis and obesity. This study explored the effect of kaempferol on BMSCs differentiation and inflammation. The results demonstrated that kaempferol did not show any cytotoxicity at concentrations of 20, 60 and 100μM. Kaempferol enhanced cell viability by counteracting the lipopolysaccharide (LPS)-induced cell apoptosis and increasing cell proliferation. Western blot analysis of mitosis-associated nuclear antigen (Ki67) and proliferation cell nuclear antigen (PCNA) further confirmed the increased effect of kaempferol on LPS-induced decreased viability of BMSCs. Besides, kaempferol elevated LPS-induced reduced level of chondrogenic markers (SOX-9, Collagen II and Aggrecan), decreased the level of matrix-degrading enzymes, i.e., matrix metalloprotease (MMP)-3 and MMP-13, suggesting the osteogenesis of BMSC under kaempferol treatment. On the other hand, kaempferol enhanced LPS-induced decreased expression of lipid catabolism-related genes, i.e., carnitine palmitoyl transferase-1 (CPT-1). Kaempferol also suppressed the expression of lipid anabolism-related genes, i.e., peroxisome proliferators-activated receptor-γ (PPAR-γ). The Oil red O staining further convinced the inhibition effect of kaempferol on BMSCs adipogenesis. In addition, kaempferol alleviated inflammatory by reducing the level of pro-inflammatory cytokines (i.e., interleukin (IL)-6) and increasing anti-inflammatory cytokine (IL-10) via inhibiting the nucleus translocation of nuclear transcription factor (NF)-κB p65. Taken together, our research indicated that kaempferol may serve as a novel target for treatment of IVD degeneration. Copyright © 2016 Elsevier B.V. All rights

  10. 3-hydroxymorphinan is neurotrophic to dopaminergic neurons and is also neuroprotective against LPS-induced neurotoxicity.

    Science.gov (United States)

    Zhang, Wei; Qin, Liya; Wang, Tongguang; Wei, Sung-Jen; Gao, Hui-ming; Liu, Jie; Wilson, Belinda; Liu, Bin; Zhang, Wanqin; Kim, Hyoung-Chun; Hong, Jau-Shyong

    2005-03-01

    The purpose of this study was to develop a novel therapy for Parkinson's disease (PD). We recently reported that dextromethorphan (DM), an active ingredient in a variety of widely used anticough remedies, protected dopaminergic neurons in rat primary mesencephalic neuron-glia cultures against lipopolysaccharide (LPS)-mediated degeneration and provided potent protection for dopaminergic neurons in a MPTP mouse model. The underlying mechanism for the protective effect of DM was attributed to its anti-inflammatory activity through inhibition of microglia activation. In an effort to develop more potent compounds for the treatment of PD, we have screened a series of analogs of DM, and 3-hydroxymorphinan (3-HM) emerged as a promising candidate for this purpose. Our study using primary mesencephalic neuron-glia cultures showed that 3-HM provided more potent neuroprotection against LPS-induced dopaminergic neurotoxicity than its parent compound. The higher potency of 3-HM was attributed to its neurotrophic effect in addition to the anti-inflammatory effect shared by both DM and 3-HM. First, we showed that 3-HM exerted potent neuroprotective and neurotrophic effects on dopaminergic neurons in rat primary mesencephalic neuron-glia cultures treated with LPS. The neurotrophic effect of 3-HM was glia-dependent since 3-HM failed to show any protective effect in the neuron-enriched cultures. We subsequently demonstrated that it was the astroglia, not the microglia, that contributed to the neurotrophic effect of 3-HM. This conclusion was based on the reconstitution studies, in which we added different percentages of microglia (10-20%) or astroglia (40-50%) back to the neuron-enriched cultures and found that 3-HM was neurotrophic after the addition of astroglia, but not microglia. Furthermore, 3-HM-treated astroglia-derived conditioned media exerted a significant neurotrophic effect on dopaminergic neurons. It appeared likely that 3-HM caused the release of neurotrophic factor

  11. SOX6 and PDCD4 enhance cardiomyocyte apoptosis through LPS-induced miR-499 inhibition.

    Science.gov (United States)

    Jia, Zhuqing; Wang, Jiaji; Shi, Qiong; Liu, Siyu; Wang, Weiping; Tian, Yuyao; Lu, Qin; Chen, Ping; Ma, Kangtao; Zhou, Chunyan

    2016-02-01

    Sepsis-induced cardiac apoptosis is one of the major pathogenic factors in myocardial dysfunction. As it enhances numerous proinflammatory factors, lipopolysaccharide (LPS) is considered the principal mediator in this pathological process. However, the detailed mechanisms involved are unclear. In this study, we attempted to explore the mechanisms involved in LPS-induced cardiomyocyte apoptosis. We found that LPS stimulation inhibited microRNA (miR)-499 expression and thereby upregulated the expression of SOX6 and PDCD4 in neonatal rat cardiomyocytes. We demonstrate that SOX6 and PDCD4 are target genes of miR-499, and they enhance LPS-induced cardiomyocyte apoptosis by activating the BCL-2 family pathway. The apoptosis process enhanced by overexpression of SOX6 or PDCD4, was rescued by the cardiac-abundant miR-499. Overexpression of miR-499 protected the cardiomyocytes against LPS-induced apoptosis. In brief, our results demonstrate the existence of a miR-499-SOX6/PDCD4-BCL-2 family pathway in cardiomyocytes in response to LPS stimulation.

  12. Effect of curcumin (Curcuma longa extract) on LPS-induced acute lung injury is mediated by the activation of AMPK.

    Science.gov (United States)

    Kim, Joungmin; Jeong, Seong-Wook; Quan, Hui; Jeong, Cheol-Won; Choi, Jeong-Il; Bae, Hong-Beom

    2016-02-01

    Curcumin, a biphenolic compound extracted from turmeric (Curcuma longa), possesses potent anti-inflammatory activity. The present study investigated whether curcumin could increase 5' adenosine monophosphate-activated protein kinase (AMPK) activity in macrophages and modulate the severity of lipopolysaccharide (LPS)-induced acute lung injury. Macrophages were treated with curcumin and then exposed (or not) to LPS. Acute lung injury was induced by intratracheal administration of LPS in BALB/c mice. Curcumin increased phosphorylation of AMPK and acetyl-CoA carboxylase (ACC), a downstream target of AMPK, in a time- and concentration-dependent manner. Curcumin did not increase phosphorylation of liver kinase B1, a primary kinase upstream of AMPK. STO-609, an inhibitor of calcium(2+)/calmodulin-dependent protein kinase kinase, diminished curcumin-induced AMPK phosphorylation, but transforming growth factor-beta-activated kinase 1 inhibitor did not. Curcumin also diminished the LPS-induced increase in phosphorylation of inhibitory κB-alpha and the production of tumor necrosis factor alpha (TNF-α), macrophage inflammatory protein (MIP)-2, and interleukin (IL)-6 by macrophages. Systemic administration of curcumin significantly decreased the production of TNF-α, MIP-2, and IL-6 as well as neutrophil accumulation in bronchoalveolar lavage fluid, and also decreased pulmonary myeloperoxidase levels and the wet/dry weight ratio in mice subjected to LPS treatment. These results suggest that the protective effect of curcumin on LPS-induced acute lung injury is associated with AMPK activation.

  13. Resolution of LPS-induced airway inflammation and goblet cell hyperplasia is independent of IL-18

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    Lyons C Rick

    2007-03-01

    Full Text Available Abstract Background The resolution of inflammatory responses in the lung has not been described in detail and the role of specific cytokines influencing the resolution process is largely unknown. Methods The present study was designed to describe the resolution of inflammation from 3 h through 90 d following an acute injury by a single intratracheal instillation of F344/N rats with LPS. We documented the inflammatory cell types and cytokines found in the bronchoalveolar lavage fluid (BALF, and epithelial changes in the axial airway and investigated whether IL-18 may play a role in the resolution process by reducing its levels with anti-IL-18 antibodies. Results Three major stages of inflammation and resolution were observed in the BALF during the resolution. The first stage was characterized by PMNs that increased over 3 h to 1 d and decreased to background levels by d 6–8. The second stage of inflammation was characterized by macrophage influx reaching maximum numbers at d 6 and decreasing to background levels by d 40. A third stage of inflammation was observed for lymphocytes which were elevated over d 3–6. Interestingly, IL-18 and IL-9 levels in the BALF showed a cyclic pattern with peak levels at d 4, 8, and 16 while decreasing to background levels at d 1–2, 6, and 12. Depletion of IL-18 caused decreased PMN numbers at d 2, but no changes in inflammatory cell number or type at later time points. Conclusion These data suggest that IL-18 plays a role in enhancing the LPS-induced neutrophilic inflammation of the lung, but does not affect the resolution of inflammation.

  14. Niclosamide suppresses RANKL-induced osteoclastogenesis and prevents LPS-induced bone loss

    Energy Technology Data Exchange (ETDEWEB)

    Cheon, Yoon-Hee [Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749 (Korea, Republic of); Kim, Ju-Young [Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749 (Korea, Republic of); Baek, Jong Min; Ahn, Sung-Jun [Department of Anatomy, School of Medicine, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749 (Korea, Republic of); So, Hong-Seob, E-mail: jeanso@wku.ac.kr [Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749 (Korea, Republic of); Oh, Jaemin, E-mail: jmoh@wku.ac.kr [Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749 (Korea, Republic of); Department of Anatomy, School of Medicine, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749 (Korea, Republic of); Institute for Skeletal Disease, Wonkwang University School of Medicine, Iksan, Jeonbuk 570-749 (Korea, Republic of)

    2016-02-05

    Niclosamide (5-chloro-salicyl-(2-chloro-4-nitro) anilide) is an oral anthelmintic drug used for treating intestinal infection of most tapeworms. Recently, niclosamide was shown to have considerable efficacy against some tumor cell lines, including colorectal, prostate, and breast cancers, and acute myelogenous leukemia. Specifically, the drug was identified as a potent inhibitor of signal transducer and activator of transcription 3 (STAT3), which is associated with osteoclast differentiation and function. In this study, we assessed the effect of niclosamide on osteoclastogenesis in vitro and in vivo. Our in vitro study showed that receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclast differentiation was inhibited by niclosamide, due to inhibition of serine–threonine protein kinase (Akt) phosphorylation, inhibitor of nuclear factor-kappaB (IκB), and STAT3 serine{sup 727}. Niclosamide decreased the expression of the major transcription factors c-Fos and NFATc1, and thereafter abrogated the mRNA expression of osteoclast-specific genes, including TRAP, OSCAR, αv/β3 integrin (integrin αv, integrin β3), and cathepsin K (CtsK). In an in vivo model, niclosamide prevented lipopolysaccharide-induced bone loss by diminishing osteoclast activity. Taken together, our results show that niclosamide is effective in suppressing osteoclastogenesis and may be considered as a new and safe therapeutic candidate for the clinical treatment of osteoclast-related diseases such as osteoporosis. - Highlights: • We first investigated the anti-osteoclastogenic effects of niclosamide in vitro and in vivo. • Niclosamide impairs the activation of the Akt-IκB-STAT3 ser{sup 727} signaling axis. • Niclosamide acts a negative regulator of actin ring formation during osteoclast differentiation. • Niclosamide suppresses LPS-induced bone loss in vivo. • Niclosamide deserves new evaluation as a potential treatment target in various bone diseases.

  15. Fisetin administration improves LPS-induced acute otitis media in mouse in vivo

    Science.gov (United States)

    Li, Peng; Chen, Dan; Huang, Yang

    2018-01-01

    Acute otitis media is one of the most common infectious diseases worldwide in spite of the widespread vaccination. The present study was conducted to explore the effects of fisetin on mouse acute otitis media models. The animal models were established by lipopolysaccharide (LPS) injection into the middle ear of mice via the tympanic membrane. Fisetin was administered to mice for ten days through intragastric administration immediate after LPS application. Hematoxylin and eosin (H&E) staining was performed and the pro-inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6 and VEGF, were measured through enzyme-linked immunosorbent assay (ELISA) method and RT-qPCR analysis. Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway was detected by immunoblotting assays. Reactive oxygen species (ROS) generated levels were determined through assessment of anti-oxidants, and TXNIP/MAPKs signaling pathways were explored to reveal the possible molecular mechanism for acute otitis media progression and the function of fisetin. Fisetin reduced mucosal thickness caused by LPS. In fisetin-treated animals, pro-inflammatory cytokine release was downregulated accompanied with TLR4/NF-κB inactivation. ROS production was significantly decreased in comparison to the LPS-treated group. The TXNIP/MAPKs signaling pathway was inactivated for fisetin treatment in LPS-induced mice with acute otitis media. The above results indicated that fisetin improved acute otitis media through inflammation and ROS suppression via inactivating TLR4/NF-κB and TXNIP/MAPKs signaling pathways. PMID:29568876

  16. Fisetin administration improves LPS-induced acute otitis media in mouse in vivo.

    Science.gov (United States)

    Li, Peng; Chen, Dan; Huang, Yang

    2018-07-01

    Acute otitis media is one of the most common infectious diseases worldwide in spite of the widespread vaccination. The present study was conducted to explore the effects of fisetin on mouse acute otitis media models. The animal models were established by lipopolysaccharide (LPS) injection into the middle ear of mice via the tympanic membrane. Fisetin was administered to mice for ten days through intragastric administration immediate after LPS application. Hematoxylin and eosin (H&E) staining was performed and the pro-inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6 and VEGF, were measured through enzyme-linked immunosorbent assay (ELISA) method and RT-qPCR analysis. Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway was detected by immunoblotting assays. Reactive oxygen species (ROS) generated levels were determined through assessment of anti-oxidants, and TXNIP/MAPKs signaling pathways were explored to reveal the possible molecular mechanism for acute otitis media progression and the function of fisetin. Fisetin reduced mucosal thickness caused by LPS. In fisetin-treated animals, pro-inflammatory cytokine release was downregulated accompanied with TLR4/NF-κB inactivation. ROS production was significantly decreased in comparison to the LPS-treated group. The TXNIP/MAPKs signaling pathway was inactivated for fisetin treatment in LPS-induced mice with acute otitis media. The above results indicated that fisetin improved acute otitis media through inflammation and ROS suppression via inactivating TLR4/NF-κB and TXNIP/MAPKs signaling pathways.

  17. Near-infrared spectroscopy during stagnant ischemia estimates central venous oxygen saturation and mixed venous oxygen saturation discrepancy in patients with severe left heart failure and additional sepsis/septic shock

    OpenAIRE

    Mo?ina, Hugo; Podbregar, Matej

    2010-01-01

    Introduction Discrepancies of 5-24% between superior vena cava oxygen saturation (ScvO2) and mixed venous oxygen saturation (SvO2) have been reported in patients with severe heart failure. Thenar muscle tissue oxygenation (StO2) measured with near-infrared spectroscopy (NIRS) during arterial occlusion testing decreases slower in sepsis/septic shock patients (lower StO2 deoxygenation rate). The StO2 deoxygenation rate is influenced by dobutamine. The aim of this study was to determine the rela...

  18. Intranuclear interactomic inhibition of NF-κB suppresses LPS-induced severe sepsis

    International Nuclear Information System (INIS)

    Park, Sung-Dong; Cheon, So Yeong; Park, Tae-Yoon; Shin, Bo-Young; Oh, Hyunju; Ghosh, Sankar; Koo, Bon-Nyeo; Lee, Sang-Kyou

    2015-01-01

    Suppression of nuclear factor-κB (NF-κB) activation, which is best known as a major regulator of innate and adaptive immune responses, is a potent strategy for the treatment of endotoxic sepsis. To inhibit NF-κB functions, we designed the intra-nuclear transducible form of transcription modulation domain (TMD) of RelA (p65), called nt-p65-TMD, which can be delivered effectively into the nucleus without influencing the cell viability, and work as interactomic inhibitors via disruption of the endogenous p65-mediated transcription complex. nt-p65-TMD effectively inhibited the secretion of pro-inflammatory cytokines, including TNF-α, IL-1β, or IL-6 from BV2 microglia cells stimulated by lipopolysaccharide (LPS). nt-p65-TMD did not inhibit tyrosine phosphorylation of signaling mediators such as ZAP-70, p38, JNK, or ERK involved in T cell activation, but was capable of suppressing the transcriptional activity of NF-κB without the functional effect on that of NFAT upon T-cell receptor (TCR) stimulation. The transduced nt-p65-TMD in T cell did not affect the expression of CD69, however significantly inhibited the secretion of T cell-specific cytokines such as IL-2, IFN-γ, IL-4, IL-17A, or IL-10. Systemic administration of nt-p65-TMD showed a significant therapeutic effect on LPS-induced sepsis model by inhibiting pro-inflammatory cytokines secretion. Therefore, nt-p65-TMD can be a novel therapeutics for the treatment of various inflammatory diseases, including sepsis, where a transcription factor has a key role in pathogenesis, and further allows us to discover new functions of p65 under normal physiological condition without genetic alteration. - Highlights: • The nt-p65-TMD is intra-nuclear interactomic inhibitor of endogenous p65. • The nt-p65-TMD effectively inhibited the secretion of pro-inflammatory cytokines. • The excellent therapeutic potential of nt-p65-TMD was confirmed in sepsis model

  19. Intranuclear interactomic inhibition of NF-κB suppresses LPS-induced severe sepsis

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sung-Dong [Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Cheon, So Yeong [Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Park, Tae-Yoon; Shin, Bo-Young [Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Oh, Hyunju; Ghosh, Sankar [Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Koo, Bon-Nyeo, E-mail: koobn@yuhs.ac [Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Lee, Sang-Kyou, E-mail: sjrlee@yonsei.ac.kr [Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)

    2015-08-28

    Suppression of nuclear factor-κB (NF-κB) activation, which is best known as a major regulator of innate and adaptive immune responses, is a potent strategy for the treatment of endotoxic sepsis. To inhibit NF-κB functions, we designed the intra-nuclear transducible form of transcription modulation domain (TMD) of RelA (p65), called nt-p65-TMD, which can be delivered effectively into the nucleus without influencing the cell viability, and work as interactomic inhibitors via disruption of the endogenous p65-mediated transcription complex. nt-p65-TMD effectively inhibited the secretion of pro-inflammatory cytokines, including TNF-α, IL-1β, or IL-6 from BV2 microglia cells stimulated by lipopolysaccharide (LPS). nt-p65-TMD did not inhibit tyrosine phosphorylation of signaling mediators such as ZAP-70, p38, JNK, or ERK involved in T cell activation, but was capable of suppressing the transcriptional activity of NF-κB without the functional effect on that of NFAT upon T-cell receptor (TCR) stimulation. The transduced nt-p65-TMD in T cell did not affect the expression of CD69, however significantly inhibited the secretion of T cell-specific cytokines such as IL-2, IFN-γ, IL-4, IL-17A, or IL-10. Systemic administration of nt-p65-TMD showed a significant therapeutic effect on LPS-induced sepsis model by inhibiting pro-inflammatory cytokines secretion. Therefore, nt-p65-TMD can be a novel therapeutics for the treatment of various inflammatory diseases, including sepsis, where a transcription factor has a key role in pathogenesis, and further allows us to discover new functions of p65 under normal physiological condition without genetic alteration. - Highlights: • The nt-p65-TMD is intra-nuclear interactomic inhibitor of endogenous p65. • The nt-p65-TMD effectively inhibited the secretion of pro-inflammatory cytokines. • The excellent therapeutic potential of nt-p65-TMD was confirmed in sepsis model.

  20. Double-Blind Prospective Randomized Controlled Trial of Dopamine Versus Epinephrine as First-Line Vasoactive Drugs in Pediatric Septic Shock.

    Science.gov (United States)

    Ventura, Andréa M C; Shieh, Huei Hsin; Bousso, Albert; Góes, Patrícia F; de Cássia F O Fernandes, Iracema; de Souza, Daniela C; Paulo, Rodrigo Locatelli Pedro; Chagas, Fabiana; Gilio, Alfredo E

    2015-11-01

    The primary outcome was to compare the effects of dopamine or epinephrine in severe sepsis on 28-day mortality; secondary outcomes were the rate of healthcare-associated infection, the need for other vasoactive drugs, and the multiple organ dysfunction score. Double-blind, prospective, randomized controlled trial from February 1, 2009, to July 31, 2013. PICU, Hospital Universitário da Universidade de São Paulo, Brazil. Consecutive children who are 1 month to 15 years old and met the clinical criteria for fluid-refractory septic shock. Exclusions were receiving vasoactive drug(s) prior to hospital admission, having known cardiac disease, having already participated in the trial during the same hospital stay, refusing to participate, or having do-not-resuscitate orders. Patients were randomly assigned to receive either dopamine (5-10 μg/kg/min) or epinephrine (0.1-0.3 μg/kg/min) through a peripheral or intraosseous line. Patients not reaching predefined stabilization criteria after the maximum dose were classified as treatment failure, at which point the attending physician gradually stopped the study drug and started another catecholamine. Physiologic and laboratory data were recorded. Baseline characteristics were described as proportions and mean (± SD) and compared using appropriate statistical tests. Multiple regression analysis was performed, and statistical significance was defined as a p value of less than 0.05. Baseline characteristics and therapeutic interventions for the 120 children enrolled (63, dopamine; 57, epinephrine) were similar. There were 17 deaths (14.2%): 13 (20.6%) in the dopamine group and four (7%) in the epinephrine group (p=0.033). Dopamine was associated with death (odds ratio, 6.5; 95% CI, 1.1-37.8; p=0.037) and healthcare-associated infection (odds ratio, 67.7; 95% CI, 5.0-910.8; p=0.001). The use of epinephrine was associated with a survival odds ratio of 6.49. Dopamine was associated with an increased risk of death and healthcare

  1. A risk-model for hospital mortality among patients with severe sepsis or septic shock based on German national administrative claims data.

    Science.gov (United States)

    Schwarzkopf, Daniel; Fleischmann-Struzek, Carolin; Rüddel, Hendrik; Reinhart, Konrad; Thomas-Rüddel, Daniel O

    2018-01-01

    Sepsis is a major cause of preventable deaths in hospitals. Feasible and valid methods for comparing quality of sepsis care between hospitals are needed. The aim of this study was to develop a risk-adjustment model suitable for comparing sepsis-related mortality between German hospitals. We developed a risk-model using national German claims data. Since these data are available with a time-lag of 1.5 years only, the stability of the model across time was investigated. The model was derived from inpatient cases with severe sepsis or septic shock treated in 2013 using logistic regression with backward selection and generalized estimating equations to correct for clustering. It was validated among cases treated in 2015. Finally, the model development was repeated in 2015. To investigate secular changes, the risk-adjusted trajectory of mortality across the years 2010-2015 was analyzed. The 2013 deviation sample consisted of 113,750 cases; the 2015 validation sample consisted of 134,851 cases. The model developed in 2013 showed good validity regarding discrimination (AUC = 0.74), calibration (observed mortality in 1st and 10th risk-decile: 11%-78%), and fit (R2 = 0.16). Validity remained stable when the model was applied to 2015 (AUC = 0.74, 1st and 10th risk-decile: 10%-77%, R2 = 0.17). There was no indication of overfitting of the model. The final model developed in year 2015 contained 40 risk-factors. Between 2010 and 2015 hospital mortality in sepsis decreased from 48% to 42%. Adjusted for risk-factors the trajectory of decrease was still significant. The risk-model shows good predictive validity and stability across time. The model is suitable to be used as an external algorithm for comparing risk-adjusted sepsis mortality among German hospitals or regions based on administrative claims data, but secular changes need to be taken into account when interpreting risk-adjusted mortality.

  2. Correlation of left ventricular systolic dysfunction determined by low ejection fraction and 30-day mortality in patients with severe sepsis and septic shock: a systematic review and meta-analysis.

    Science.gov (United States)

    Sevilla Berrios, Ronaldo A; O'Horo, John C; Velagapudi, Venu; Pulido, Juan N

    2014-08-01

    The prognostic implications of myocardial dysfunction in patients with sepsis and its association with mortality are controversial. Several tools have been proposed to evaluate cardiac function in these patients, but their usefulness beyond guiding therapy is unclear. We review the value of echocardiographic estimate of left ventricular ejection fraction (LVEF) in the setting of severe sepsis and/or septic shock and its correlation with 30-day mortality. We conducted a systematic review and meta-analysis to evaluate the prognostic functionality of newly diagnosed LV systolic dysfunction by transthoracic echocardiography on critical ill patients admitted to the intensive care unit with severe sepsis or septic shock. A search of EMBASE and PubMed, Ovide MEDLINE, and Cochrane CENTRAL medical databases yielded 7 studies meeting inclusion criteria reporting on a total of 585 patients. The pooled sensitivity of depressed LVEF for mortality was 52% (95% confidence interval [CI], 29%-73%), and pooled specificity was 63% (95% CI, 53%-71%). Summary receiver operating characteristic curve showed an area under the curve of 0.62 (95% CI, 0.58-0.67). The overall mortality diagnostic odd ratio for septic patients with LV systolic dysfunction was 1.92 (95% CI, 1.27-2.899). Statistical heterogeneity of studies was moderate. The presence of new LV systolic dysfunction associated with sepsis and defined as low LVEF is neither a sensitive nor a specific predictor of mortality. These findings are limited because of the heterogeneity and underpower of the studies. Further research into this method is warranted. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Suporte farmacológico a lactentes e crianças com choque séptico Pharmacologic support of infants and children in septic shock

    Directory of Open Access Journals (Sweden)

    José Irazuzta

    2007-05-01

    resposta hemodinâmica do CS é um processo variável que requer avaliação e ajustes terapêuticos freqüentes.OBJECTIVES: Septic shock (SS is a frequent cause for admission to the pediatric intensive care unit, requiring prompt recognition and intervention to improve outcome. Our aim is to review the relevant literature related to the diagnosis and management of SS and present a sequential management for its treatment. SOURCES: Non-systematic review of medical literature using the MEDLINE database. Articles were selected according to their relevance to the objective and according to the authors’ opinions. SUMMARY OF THE FINDINGS: The outcome of sepsis and SS is dependent on the early recognition and implementation of time-sensitive goal-directed therapies. These include rapid aggressive fluid resuscitation followed by a well-designed pharmacotherapy. The goals of the resuscitation are the restoration of microcirculation and improved organ tissue perfusion. Clinical and laboratory markers are needed to assess the adequacy of the treatments. Altered pharmacokinetic and pharmacodynamic responses dictate that vasoactive agents should be adjusted to achieve the predetermined goals. In initial resuscitation with isotonic solutions (> 60 mL/kg, either crystalloid (normal saline or colloid infusion could be used. Despite adequate fluid resuscitation, if: (a wide pulse pressure, low blood pressure, or bounding pulses (high cardiac output, low systemic vascular resistance - SVR are present, norepinephrine should be considered; (b prolonged capillary refill, weak pulses, narrow pulse pressure, normotensive (low cardiac output, high SVR, dopamine, epinephrine or dobutamine should be considered. Adjunctive therapy with stress dose of corticosteroid is indicated in selected populations. CONCLUSIONS: Septic shock hemodynamics is a changing process that requires frequent assessment and therapeutic adjustments.

  4. Anthocyanins protect against LPS-induced oxidative stress-mediated neuroinflammation and neurodegeneration in the adult mouse cortex.

    Science.gov (United States)

    Khan, Muhammad Sohail; Ali, Tahir; Kim, Min Woo; Jo, Myeung Hoon; Jo, Min Gi; Badshah, Haroon; Kim, Myeong Ok

    2016-11-01

    Several studies provide evidence that reactive oxygen species (ROS) are key mediators of various neurological disorders. Anthocyanins are polyphenolic compounds and are well known for their anti-oxidant and neuroprotective effects. In this study, we investigated the neuroprotective effects of anthocyanins (extracted from black soybean) against lipopolysaccharide (LPS)-induced ROS-mediated neuroinflammation and neurodegeneration in the adult mouse cortex. Intraperitoneal injection of LPS (250 μg/kg) for 7 days triggers elevated ROS and oxidative stress, which induces neuroinflammation and neurodegeneration in the adult mouse cortex. Treatment with 24 mg/kg/day of anthocyanins for 14 days in LPS-injected mice (7 days before and 7 days co-treated with LPS) attenuated elevated ROS and oxidative stress compared to mice that received LPS-injection alone. The immunoblotting results showed that anthocyanins reduced the level of the oxidative stress kinase phospho-c-Jun N-terminal Kinase 1 (p-JNK). The immunoblotting and morphological results showed that anthocyanins treatment significantly reduced LPS-induced-ROS-mediated neuroinflammation through inhibition of various inflammatory mediators, such as IL-1β, TNF-α and the transcription factor NF- k B. Anthocyanins treatment also reduced activated astrocytes and microglia in the cortex of LPS-injected mice, as indicated by reductions in GFAP and Iba-1, respectively. Anthocyanins also prevent overexpression of various apoptotic markers, i.e., Bax, cytosolic cytochrome C, cleaved caspase-3 and PARP-1. Immunohistochemical fluoro-jade B (FJB) and Nissl staining indicated that anthocyanins prevent LPS-induced neurodegeneration in the mouse cortex. Our results suggest that dietary flavonoids, such as anthocyanins, have antioxidant and neuroprotective activities that could be beneficial to various neurological disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Acute and chronic effects of treatment with mesenchymal stromal cells on LPS-induced pulmonary inflammation, emphysema and atherosclerosis development.

    Directory of Open Access Journals (Sweden)

    P Padmini S J Khedoe

    Full Text Available COPD is a pulmonary disorder often accompanied by cardiovascular disease (CVD, and current treatment of this comorbidity is suboptimal. Systemic inflammation in COPD triggered by smoke and microbial exposure is suggested to link COPD and CVD. Mesenchymal stromal cells (MSC possess anti-inflammatory capacities and MSC treatment is considered an attractive treatment option for various chronic inflammatory diseases. Therefore, we investigated the immunomodulatory properties of MSC in an acute and chronic model of lipopolysaccharide (LPS-induced inflammation, emphysema and atherosclerosis development in APOE*3-Leiden (E3L mice.Hyperlipidemic E3L mice were intranasally instilled with 10 μg LPS or vehicle twice in an acute 4-day study, or twice weekly during 20 weeks Western-type diet feeding in a chronic study. Mice received 0.5x106 MSC or vehicle intravenously twice after the first LPS instillation (acute study or in week 14, 16, 18 and 20 (chronic study. Inflammatory parameters were measured in bronchoalveolar lavage (BAL and lung tissue. Emphysema, pulmonary inflammation and atherosclerosis were assessed in the chronic study.In the acute study, intranasal LPS administration induced a marked systemic IL-6 response on day 3, which was inhibited after MSC treatment. Furthermore, MSC treatment reduced LPS-induced total cell count in BAL due to reduced neutrophil numbers. In the chronic study, LPS increased emphysema but did not aggravate atherosclerosis. Emphysema and atherosclerosis development were unaffected after MSC treatment.These data show that MSC inhibit LPS-induced pulmonary and systemic inflammation in the acute study, whereas MSC treatment had no effect on inflammation, emphysema and atherosclerosis development in the chronic study.

  6. Human umbilical cord mesenchymal stem cells reduce systemic inflammation and attenuate LPS-induced acute lung injury in rats

    Directory of Open Access Journals (Sweden)

    Li Jianjun

    2012-09-01

    Full Text Available Abstract Background Mesenchymal stem cells (MSCs possess potent immunomodulatory properties and simultaneously lack the ability to illicit immune responses. Hence, MSCs have emerged as a promising candidate for cellular therapeutics for inflammatory diseases. Within the context of this study, we investigated whether human umbilical cord-derived mesenchymal stem cells (UC-MSCs could ameliorate lipopolysaccharide- (LPS- induced acute lung injury (ALI in a rat model. Methods ALI was induced via injection of LPS. Rats were divided into three groups: (1 saline group(control, (2 LPS group, and (3 MSC + LPS group. The rats were sacrificed at 6, 24, and 48 hours after injection. Serum, bronchoalveolar lavage fluid (BALF, and lungs were collected for cytokine concentration measurements, assessment of lung injury, and histology. Results UC-MSCs increased survival rate and suppressed LPS-induced increase of serum concentrations of pro-inflammatory mediators TNF-α, IL-1β, and IL-6 without decreasing the level of anti-inflammatory cytokine IL-10. The MSC + LPS group exhibited significant improvements in lung inflammation, injury, edema, lung wet/dry ratio, protein concentration, and neutrophil counts in the BALF, as well as improved myeloperoxidase (MPO activity in the lung tissue. Furthermore, UC-MSCs decreased malondialdehyde (MDA production and increased Heme Oxygenase-1 (HO-1 protein production and activity in the lung tissue. Conclusion UC-MSCs noticeably increased the survival rate of rats suffering from LPS-induced lung injury and significantly reduced systemic and pulmonary inflammation. Promoting anti-inflammatory homeostasis and reducing oxidative stress might be the therapeutic basis of UC-MSCs.

  7. The LPS-induced neutrophil recruitment into rat air pouches is mediated by TNFα: likely macrophage origin

    Directory of Open Access Journals (Sweden)

    C-D. Arreto

    1997-01-01

    Full Text Available The role of resident cells during the lipopolysaccharide (LPS-induced neutrophil recruitment into rat air pouches was investigated. In this model, LPS (Escherichia coli, O55: B5 strain; 2–2000 ng induced a dose– and time-dependent neutrophil recruitment accompanied by the generation of a tumour necrosis factor-α (TNFα-like activity. Dexamethasone (0.05–5 mug and cycloheximide (6 ng, injected 2 h before LPS into the pouches, inhibited the neutrophil recruitment and the generation of the TNFα-like activity, while the H1-receptor antagonist mepyramine (1 and 4 mg/kg, i.p., 0.5 h before LPS and the PAF-receptor antagonist WEB 2170 (0.05 and 1 mg/kg, i.p., 0.5 h before LPS had no effect. Purified alveolar macrophages (AM were used to replenish the pouches of cycloheximide-treated recipient rats. AM provided by PBS-treated animals led to the recovery of the LPS-induced neutrophil recruitment and of the TNFα-like formation contrasting with those from cycloheximide-treated animals (1 mg/kg, i.p.. When delivered in situ, liposome-encapsulated clodronate, a macrophage depletor, significantly impaired both the LPSinduced neutrophil recruitment and the TNFα-like activity. An anti-murine TNFα polyclonal antibody (0.5 h before LPS was also effective. These results emphasize the pivotal role of macrophages for LPS-induced neutrophil recruitment via the formation of TNFα.

  8. Protection against LPS-induced cartilage inflammation and degradation provided by a biological extract of Mentha spicata

    Directory of Open Access Journals (Sweden)

    Kott Laima S

    2010-05-01

    Full Text Available Abstract Background A variety of mint [Mentha spicata] has been bred which over-expresses Rosmarinic acid (RA by approximately 20-fold. RA has demonstrated significant anti-inflammatory activity in vitro and in small rodents; thus it was hypothesized that this plant would demonstrate significant anti-inflammatory activity in vitro. The objectives of this study were: a to develop an in vitro extraction procedure which mimics digestion and hepatic metabolism, b to compare anti-inflammatory properties of High-Rosmarinic-Acid Mentha spicata (HRAM with wild-type control M. spicata (CM, and c to quantify the relative contributions of RA and three of its hepatic metabolites [ferulic acid (FA, caffeic acid (CA, coumaric acid (CO] to anti-inflammatory activity of HRAM. Methods HRAM and CM were incubated in simulated gastric and intestinal fluid, liver microsomes (from male rat and NADPH. Concentrations of RA, CA, CO, and FA in simulated digest of HRAM (HRAMsim and CM (CMsim were determined (HPLC and compared with concentrations in aqueous extracts of HRAM and CM. Cartilage explants (porcine were cultured with LPS (0 or 3 μg/mL and test article [HRAMsim (0, 8, 40, 80, 240, or 400 μg/mL, or CMsim (0, 1, 5 or 10 mg/mL, or RA (0.640 μg/mL, or CA (0.384 μg/mL, or CO (0.057 μg/mL or FA (0.038 μg/mL] for 96 h. Media samples were analyzed for prostaglandin E2 (PGE2, interleukin 1β (IL-1, glycosaminoglycan (GAG, nitric oxide (NO and cell viability (differential live-dead cell staining. Results RA concentration of HRAMsim and CMsim was 49.3 and 0.4 μg/mL, respectively. CA, FA and CO were identified in HRAMsim but not in aqueous extract of HRAM. HRAMsim (≥ 8 μg/mL inhibited LPS-induced PGE2 and NO; HRAMsim (≥ 80 μg/mL inhibited LPS-induced GAG release. RA inhibited LPS-induced GAG release. No anti-inflammatory or chondroprotective effects of RA metabolites on cartilage explants were identified. Conclusions Our biological extraction procedure produces

  9. Pyrrolizidine alkaloids from Liparis nervosa with inhibitory activities against LPS-induced NO production in RAW264.7 macrophages.

    Science.gov (United States)

    Huang, Shuai; Zhou, Xian-li; Wang, Cui-juan; Wang, You-song; Xiao, Feng; Shan, Lian-hai; Guo, Zhi-yun; Weng, Jie

    2013-09-01

    Six pyrrolizidine alkaloids were isolated from the whole herb of Liparis nervosa together with two previously known ones. Their structures were elucidated by extensive spectroscopic analyses and chemical reactions. The cytotoxicity of the isolates was evaluated against A549, HepG2, and MCF-7 human cancer cell lines; however, no significant growth inhibition was observed. All compounds were evaluated for the inhibition of LPS-induced nitric oxide (NO) production in RAW264.7 macrophages, and most significantly inhibited NO production with IC50 values in the range of 2.16-38.25 μM. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. High dosage of dextran 70 is associated with severe bleeding in patients admitted to the intensive care unit for septic shock

    DEFF Research Database (Denmark)

    Hvidt, Lisa Nebelin; Perner, Anders

    2012-01-01

    Synthetic colloids are frequently used in fluid resuscitation of septic patients. Despite this, little is known about the potential side effects including the risk of renal failure and bleeding. As practice has changed, we performed a before-and-after study of fluid resuscitation and outcome in p...

  11. Salidroside Reduces Cell Mobility via NF-κB and MAPK Signaling in LPS-Induced BV2 Microglial Cells

    Directory of Open Access Journals (Sweden)

    Haixia Hu

    2014-01-01

    Full Text Available The unregulated activation of microglia following stroke results in the production of toxic factors that propagate secondary neuronal injury. Salidroside has been shown to exhibit protective effects against neuronal death induced by different insults. However, the molecular mechanisms responsible for the anti-inflammatory activity of salidroside have not been elucidated clearly in microglia. In the present study, we investigated the molecular mechanism underlying inhibiting LPS-stimulated BV2 microglial cell mobility of salidroside. The protective effect of salidroside was investigated in microglial BV2 cell, subjected to stretch injury. Moreover, transwell migration assay demonstrated that salidroside significantly reduced cell motility. Our results also indicated that salidroside suppressed LPS-induced chemokines production in a dose-dependent manner, without causing cytotoxicity in BV2 microglial cells. Moreover, salidroside suppressed LPS-induced activation of nuclear factor kappa B (NF-κB by blocking degradation of IκBα and phosphorylation of MAPK (p38, JNK, ERK1/2, which resulted in inhibition of chemokine expression. These results suggest that salidroside possesses a potent suppressive effect on cell migration of BV2 microglia and this compound may offer substantial therapeutic potential for treatment of ischemic strokes that are accompanied by microglial activation.

  12. A TLR4/MD2 fusion protein inhibits LPS-induced pro-inflammatory signaling in hepatic stellate cells

    International Nuclear Information System (INIS)

    Schnabl, Bernd; Brandl, Katharina; Fink, Marina; Gross, Philipp; Taura, Kojiro; Gaebele, Erwin; Hellerbrand, Claus; Falk, Werner

    2008-01-01

    Activated hepatic stellate cells (HSCs) play a key role in hepatic fibrogenesis. In injured liver they are the main extracellular matrix protein producing cell type and further perpetuate hepatic injury by secretion of pro-inflammatory mediators. Since LPS-mediated signaling through toll-like receptor 4 (TLR4) has been identified as key fibrogenic signal in HSCs we aimed to test TLR4 as potential target of therapy via ligand-binding soluble receptors. Incubation of human HSCs with a fusion protein between the extracellular domain of TLR4 and MD2 which binds LPS inhibited LPS-induced NFκB and JNK activation. TLR4/MD2 abolished LPS-induced secretion of IL-6, IL-8, MCP1, and RANTES in HSCs. In addition, TLR4/MD2 fused to human IgG-Fc neutralized LPS activity. Since TLR4 mutant mice are resistant to liver fibrosis, the TLR4/MD2 soluble receptor might represent a new therapeutic molecule for liver fibrogenesis in vivo

  13. Apigenin inhibits d-galactosamine/LPS-induced liver injury through upregulation of hepatic Nrf-2 and PPARγ expressions in mice.

    Science.gov (United States)

    Zhou, Rui-Jun; Ye, Hua; Wang, Feng; Wang, Jun-Long; Xie, Mei-Lin

    2017-11-04

    Apigenin is a natural flavonoid compound widely distributed in a variety of vegetables, medicinal plants and health foods. This study aimed to examine the protective effect of apigenin against d-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced mouse liver injury and to investigate the potential biochemical mechanisms. The results showed that after oral administration of apigenin 100-200 mg/kg for 7 days, the levels of serum alanine aminotransferase and aspartate aminotransferase were decreased, and the severity of liver injury was alleviated. Importantly, apigenin pretreatment increased the levels of hepatic nuclear factor erythroid 2-related factor 2 (Nrf-2) and peroxisome proliferator-activated receptor γ (PPARγ) protein expressions as well as superoxide dismutase, catalase, glutathione S-transferase and glutathione reductase activities, decreased the levels of hepatic nuclear factor-κB (NF-κB) protein expression and tumor necrosis factor-α. These findings demonstrated that apigenin could prevent the D-GalN/LPS-induced liver injury in mice, and its mechanisms might be associated with the increments of Nrf-2-mediated antioxidative enzymes and modulation of PPARγ/NF-κB-mediated inflammation. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Isoalantolactone inhibits LPS-induced inflammation via NF-κB inactivation in peritoneal macrophages and improves survival in sepsis.

    Science.gov (United States)

    He, Guodong; Zhang, Xu; Chen, Yanhua; Chen, Jing; Li, Li; Xie, Yubo

    2017-06-01

    Sepsis, a clinical syndrome occurring in patients following infection or injury, is a leading cause of mortality worldwide. It involves uncontrolled inflammatory response resulting in multi-organ failure and even death. Isoalantolactone (IAL), a sesquiterpene lactone, is known for its anti-cancer effects. Nevertheless, little is known about the anti-inflammatory effects of IAL, and the role of IAL in sepsis is unclear. In this study, we demonstrated that IAL decreased lipopolysaccharide (LPS)-mediated production of nitric oxide, PEG 2 and cytokines (IL-6, TNF-α) in peritoneal macrophages and RAW 264.7 macrophages. Moreover, molecular mechanism studies indicated that IAL plays an anti-inflammatory role by inhibiting LPS-induced activation of NF-κB pathway in peritoneal macrophages. In vivo, IAL reduced the secretion of IL-6 and TNF-α in serum, and increased the survival rate of mice with LPS-induced sepsis. In addition, IAL attenuated the activation of NF-κB pathway in liver. Taken together, our data suggest that IAL may represent a potentially new drug candidate for the treatment of sepsis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. Adrenaline stimulates the proliferation and migration of mesenchymal stem cells towards the LPS-induced lung injury.

    Science.gov (United States)

    Wu, Xiaodan; Wang, Zhiming; Qian, Mengjia; Wang, Lingyan; Bai, Chunxue; Wang, Xiangdong

    2014-08-01

    Bone marrow-derived mesenchymal stem cells (BMSCs) could modulate inflammation in experimental lung injury. On the other hand, adrenergic receptor agonists could increase DNA synthesis of stem cells. Therefore, we investigated the therapeutic role of adrenaline-stimulated BMSCs on lipopolysaccharide (LPS)-induced lung injury. BMSCs were cultured with adrenergic receptor agonists or antagonists. Suspensions of lung cells or sliced lung tissue from animals with or without LPS-induced injury were co-cultured with BMSCs. LPS-stimulated alveolar macrophages were co-cultured with BMSCs (with adrenaline stimulation or not) in Transwell for 6 hrs. A preliminary animal experiment was conducted to validate the findings in ex vivo study. We found that adrenaline at 10 μM enhanced proliferation of BMSCs through both α- and β-adrenergic receptors. Adrenaline promoted the migration of BMSCs towards LPS-injured lung cells or lung tissue. Adrenaline-stimulated BMSCs decreased the inflammation of LPS-stimulated macrophages, probably through the expression and secretion of several paracrine factors. Adrenaline reduced the extent of injury in LPS-injured rats. Our data indicate that adrenaline-stimulated BMSCs might contribute to the prevention from acute lung injury through the activation of adrenergic receptors, promotion of proliferation and migration towards injured lung, and modulation of inflammation. © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  16. Fenoterol inhibits LPS-induced AMPK activation and inflammatory cytokine production through β-arrestin-2 in THP-1 cell line

    International Nuclear Information System (INIS)

    Wang, Wei; Zhang, Yuan; Xu, Ming; Zhang, You-Yi; He, Bei

    2015-01-01

    The AMP-activated protein kinase (AMPK) pathway is involved in regulating inflammation in several cell lines. We reported that fenoterol, a β 2 -adrenergic receptor (β 2 -AR) agonist, had anti-inflammatory effects in THP-1 cells, a monocytic cell line. Whether the fenoterol anti-inflammatory effect involves the AMPK pathway is unknown. In this study, we explored the mechanism of β 2 -AR stimulation with fenoterol in a lipopolysaccharide (LPS)-induced inflammatory cytokine secretion in THP-1 cells. We studied whether fenoterol and β-arrestin-2 or AMPKα1 subunit knockdown could affect LPS-induced AMPK activation, nuclear factor-kappa B (NF-κB) activation and inflammatory cytokine secretion. LPS-induced AMPK activation and interleukin 1β (IL-1β) release were reduced with fenoterol pretreatment of THP-1 cells. SiRNA knockdown of β-arrestin-2 abolished the fenoterol inhibition of LPS-induced AMPK activation and interleukin 1β (IL-1β) release, thus β-arrestin-2 mediated the anti-inflammatory effects of fenoterol on LPS-treated THP-1 cells. In addition, siRNA knockdown of AMPKα1 significantly attenuated the LPS-induced NF-κB activation and IL-1β release, so AMPKα1 was a key signaling molecule involved in LPS-induced inflammatory cytokine production. These results suggested the β 2 -AR agonist fenoterol inhibited LPS-induced AMPK activation and IL-1β release via β-arrestin-2 in THP-1 cells. The exploration of these mechanisms may help optimize therapeutic agents targeting these pathways in inflammatory diseases. - Highlights: • β 2 -AR agonist fenoterol exerts its protective effect on LPS-treated THP-1 cells. • Fenoterol inhibits LPS-induced AMPK activation and IL-1β production. • β-arrestin2 mediates fenoterol-inhibited AMPK activation and IL-1β release. • AMPKα1 is involved in LPS-induced NF-κB activation and IL-1β production

  17. Fenoterol inhibits LPS-induced AMPK activation and inflammatory cytokine production through β-arrestin-2 in THP-1 cell line

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Wei [Department of Respiratory Medicine, Peking University Third Hospital, Beijing (China); Department of Infectious Diseases, Peking University Third Hospital, Beijing (China); Zhang, Yuan [Department of Respiratory Medicine, Peking University Third Hospital, Beijing (China); Xu, Ming; Zhang, You-Yi [Department of Institute of Vascular Medicine and Beijing Key Laboratory of Cardiovascular Receptors Research, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Peking University Third Hospital, Beijing (China); He, Bei, E-mail: puh3_hb@bjmu.edu.cn [Department of Respiratory Medicine, Peking University Third Hospital, Beijing (China)

    2015-06-26

    The AMP-activated protein kinase (AMPK) pathway is involved in regulating inflammation in several cell lines. We reported that fenoterol, a β{sub 2}-adrenergic receptor (β{sub 2}-AR) agonist, had anti-inflammatory effects in THP-1 cells, a monocytic cell line. Whether the fenoterol anti-inflammatory effect involves the AMPK pathway is unknown. In this study, we explored the mechanism of β{sub 2}-AR stimulation with fenoterol in a lipopolysaccharide (LPS)-induced inflammatory cytokine secretion in THP-1 cells. We studied whether fenoterol and β-arrestin-2 or AMPKα1 subunit knockdown could affect LPS-induced AMPK activation, nuclear factor-kappa B (NF-κB) activation and inflammatory cytokine secretion. LPS-induced AMPK activation and interleukin 1β (IL-1β) release were reduced with fenoterol pretreatment of THP-1 cells. SiRNA knockdown of β-arrestin-2 abolished the fenoterol inhibition of LPS-induced AMPK activation and interleukin 1β (IL-1β) release, thus β-arrestin-2 mediated the anti-inflammatory effects of fenoterol on LPS-treated THP-1 cells. In addition, siRNA knockdown of AMPKα1 significantly attenuated the LPS-induced NF-κB activation and IL-1β release, so AMPKα1 was a key signaling molecule involved in LPS-induced inflammatory cytokine production. These results suggested the β{sub 2}-AR agonist fenoterol inhibited LPS-induced AMPK activation and IL-1β release via β-arrestin-2 in THP-1 cells. The exploration of these mechanisms may help optimize therapeutic agents targeting these pathways in inflammatory diseases. - Highlights: • β{sub 2}-AR agonist fenoterol exerts its protective effect on LPS-treated THP-1 cells. • Fenoterol inhibits LPS-induced AMPK activation and IL-1β production. • β-arrestin2 mediates fenoterol-inhibited AMPK activation and IL-1β release. • AMPKα1 is involved in LPS-induced NF-κB activation and IL-1β production.

  18. Investigating the CYP2E1 Potential Role in the Mechanisms Behind INH/LPS-Induced Hepatotoxicity

    Directory of Open Access Journals (Sweden)

    Hozeifa M. Hassan

    2018-03-01

    Full Text Available Tuberculosis (TB is one of the oldest infectious diseases that affected humankind and remains one of the world’s deadliest communicable diseases that could be considered as global emergency, but the discovery and development of isoniazid (INH in the 1950s paved the way to an effective single and/or combined first-line anti-TB therapy. However, administration of INH induces severe hepatic toxicity in some patients. Previously, we establish a rat model of INH hepatotoxicity utilizing the inflammatory stress theory, in which bacterial lipopolysaccharide (LPS potentially enhanced INH toxicity. These enhancing activities ranged between augmenting the inflammatory stress, oxidative stress, alteration of bile acid homeostasis, and CYP2E1 over-expression. Although pre-treatment with dexamethasone (DEX helped overcome both inflammatory and oxidative stress which ended-up in alleviation of LPS augmenting effects, but still minor toxicities were being detected, alongside with CYP2E1 over expression. This finding positively indicated the corner-stone role played by CYP2E1 in the pathogenesis of INH/LPS-induced liver damage. Therefore, we examined whether INH/LPS co-treatment with CYP2E1 inhibitor diallyl sulfide (DAS and DEX can protect against the INH/LPS-induced hepatotoxicity. Our results showed that pre-administration of both DAS and DEX caused significant reduction in serum TBA, TBil, and gamma-glutamyl transferase levels. Furthermore, the histopathological analysis showed that DAS and DEX could effectively reverse the liver lesions seen following INH/LPS treatment and protect against hepatic steatosis as indicated by absence of lipid accumulation. Pre-treatment with DAS alone could not completely block the CYP2E1 protein expression following INH/LPS treatment, as appeared in the immunoblotting and immunohistochemistry results. This is probably due to the fact that the combined enhancement activities of both INH and LPS on CYP2E1 protein expression

  19. Sphingosine-1-Phosphate (S1P) Is a Feasible Biomarker in Predicting the Efficacy of Polymyxin B-Immobilized Fiber Direct Hemoperfusion (PMX-DHP) in Patients with Septic Shock.

    Science.gov (United States)

    Inoue, Satoshi; Sakamoto, Yuichiro; Koami, Hiroyuki; Yamada C, Kosuke; Nagashima, Futoshi; Miike, Toru; Iwamura, Takashi; Obata, Toru

    2018-01-01

    The aim of this study was to identify a useful biomarker to predict the efficacy of polymyxin B-immobilized fiber direct hemoperfusion (PMX-DHP) in patients with septic shock. The 44 patients included in this study were divided into two groups. Group A had an increase in systolic blood pressure (SBP) over 30 mmHg after PMX-DHP treatment. Group B had an increase in SBP less than 30 mmHg after PMX-DHP treatment. We evaluated the clinical characteristics and demographics of both groups. We also assessed whether the cause of sepsis affected the efficacy of PMX-DHP and compared the prognosis of both groups. Finally, we investigated whether there were any significant differences in the levels of sepsis-related biomarkers, including sphingosine-1-phosphate (S1P), between both groups before PMX-DHP in an effort to identify a biomarker that could predict the efficacy of PMX-DHP. PMX-DHP significantly increased SBP regardless of the cause of sepsis. Although there was some tendency, PMX-DHP did not significantly improve the prognosis of effective cases in comparison with non-effective cases, probably because of the limited number of patients included. Among the sepsis-related biomarkers, only S1P values were significantly different between the two groups before PMX-DHP, and S1P levels were significantly increased after treatment in the effective cases. S1P levels prior to PMX-DHP can be used to predict its efficacy. In addition, continuous monitoring of S1P levels can indicate the effectiveness of PMX-DHP in patients with septic shock.

  20. Complement C1q regulates LPS-induced cytokine production in bone marrow-derived dendritic cells.

    Science.gov (United States)

    Yamada, Masahide; Oritani, Kenji; Kaisho, Tsuneyasu; Ishikawa, Jun; Yoshida, Hitoshi; Takahashi, Isao; Kawamoto, Shinichirou; Ishida, Naoko; Ujiie, Hidetoshi; Masaie, Hiroaki; Botto, Marina; Tomiyama, Yoshiaki; Matsuzawa, Yuji

    2004-01-01

    We show here that C1q suppresses IL-12p40 production in LPS-stimulated murine bone marrow-derived dendritic cells (BMDC). Serum IL-12p40 concentration of C1q-deficient mice was higher than that of wild-type mice after intraperitoneal LPS-injection. Because neither globular head of C1q (gC1q) nor collagen-like region of C1q (cC1q) failed to suppress LPS-induced IL-12p40 production, both gC1q and cC1q, and/or some specialized conformation of native C1q may be required for the inhibition. While C1q did not affect mRNA expression of Toll-like receptor 4 (TLR4), MD-2, and myeloid differentiation factor 88 (MyD88), BMDC treated with C1q showed the reduced activity of NF-kappaB and the delayed phosphorylation of p38, c-Jun N-terminal kinase, and extracellular signal-regulated kinase after LPS-stimulation. CpG oligodeoxynucleotide-induced IL-12p40 and TNF-alpha production, another MyD88-dependent TLR-mediated signal, was also suppressed by C1q treatment. Therefore, C1q is likely to suppress MyD88-dependent pathway in TLR-mediated signals. In contrast, C1q failed to suppress colony formation of B cells responding to LPS or LPS-induced CD40 and CD86 expression on BMDC in MyD88-deficient mice, indicating that inhibitory effects of C1q on MyD88-independent pathways may be limited. Taken together, C1q may regulate innate and adaptive immune systems via modification of signals mediated by interactions between invading pathogens and TLR.

  1. Inhibition of TNF-alpha production contributes to the attenuation of LPS-induced hypophagia by pentoxifylline.

    Science.gov (United States)

    Porter, M H; Hrupka, B J; Altreuther, G; Arnold, M; Langhans, W

    2000-12-01

    Cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) are assumed to mediate anorexia during bacterial infections. To improve our understanding of the role that these two cytokines serve in mediating infection during anorexia, we investigated the ability of pentoxifylline (PTX), a potent inhibitor of TNF-alpha production, to block the anorectic effects of the bacterial products lipopolysaccharide (LPS) and muramyl dipeptide (MDP) in rats. Intraperitoneally injected PTX (100 mg/kg body wt) completely eliminated the anorectic effect of intraperitoneally injected LPS (100 microg/kg body wt) and attenuated the anorectic effect of a higher dose of intraperitoneally injected LPS (250 microg/kg body wt). Concurrently, PTX pretreatment suppressed low-dose LPS-induced TNF-alpha production by more than 95% and IL-1beta production 39%, as measured by ELISA. Similarly, high-dose LPS-induced TNF-alpha production was reduced by approximately 90%. PTX administration also attenuated the tolerance that is normally observed with a second injection of LPS. In addition, PTX pretreatment attenuated the hypophagic effect of intraperitoneally injected MDP (2 mg/kg body wt) but had no effect on the anorectic response to intraperitoneally injected recombinant human TNF-alpha (150 ug/kg body wt). The results suggest that suppression of TNF-alpha production is sufficient to attenuate LPS- and MDP-induced anorexia. This is consistent with the hypothesis that TNF-alpha plays a major role in the anorexia associated with bacterial infection.

  2. Low tidal volume ventilation ameliorates left ventricular dysfunction in mechanically ventilated rats following LPS-induced lung injury.

    Science.gov (United States)

    Cherpanath, Thomas G V; Smeding, Lonneke; Hirsch, Alexander; Lagrand, Wim K; Schultz, Marcus J; Groeneveld, A B Johan

    2015-10-07

    High tidal volume ventilation has shown to cause ventilator-induced lung injury (VILI), possibly contributing to concomitant extrapulmonary organ dysfunction. The present study examined whether left ventricular (LV) function is dependent on tidal volume size and whether this effect is augmented during lipopolysaccharide(LPS)-induced lung injury. Twenty male Wistar rats were sedated, paralyzed and then randomized in four groups receiving mechanical ventilation with tidal volumes of 6 ml/kg or 19 ml/kg with or without intrapulmonary administration of LPS. A conductance catheter was placed in the left ventricle to generate pressure-volume loops, which were also obtained within a few seconds of vena cava occlusion to obtain relatively load-independent LV systolic and diastolic function parameters. The end-systolic elastance / effective arterial elastance (Ees/Ea) ratio was used as the primary parameter of LV systolic function with the end-diastolic elastance (Eed) as primary LV diastolic function. Ees/Ea decreased over time in rats receiving LPS (p = 0.045) and high tidal volume ventilation (p = 0.007), with a lower Ees/Ea in the rats with high tidal volume ventilation plus LPS compared to the other groups (p tidal volume ventilation without LPS (p = 0.223). A significant interaction (p tidal ventilation and LPS for Ees/Ea and Eed, and all rats receiving high tidal volume ventilation plus LPS died before the end of the experiment. Low tidal volume ventilation ameliorated LV systolic and diastolic dysfunction while preventing death following LPS-induced lung injury in mechanically ventilated rats. Our data advocates the use of low tidal volumes, not only to avoid VILI, but to avert ventilator-induced myocardial dysfunction as well.

  3. Aloe vera downregulates LPS-induced inflammatory cytokine production and expression of NLRP3 inflammasome in human macrophages.

    Science.gov (United States)

    Budai, Marietta M; Varga, Aliz; Milesz, Sándor; Tőzsér, József; Benkő, Szilvia

    2013-12-01

    Aloe vera has been used in traditional herbal medicine as an immunomodulatory agent inducing anti-inflammatory effects. However, its role on the IL-1β inflammatory cytokine production has not been studied. IL-1β production is strictly regulated both at transcriptional and posttranslational levels through the activity of Nlrp3 inflammasome. In this study we aimed to determine the effect of Aloe vera on the molecular mechanisms of Nlrp3 inflammasome-mediated IL-1β production in LPS-activated human THP-1 cells and monocyte-derived macrophages. Our results show that Aloe vera significantly reduced IL-8, TNFα, IL-6 and IL-1β cytokine production in a dose dependent manner. The inhibitory effect was substantially more pronounced in the primary cells. We found that Aloe vera inhibited the expression of pro-IL-1β, Nlrp3, caspase-1 as well as that of the P2X7 receptor in the LPS-induced primary macrophages. Furthermore, LPS-induced activation of signaling pathways like NF-κB, p38, JNK and ERK were inhibited by Aloe vera in these cells. Altogether, we show for the first time that Aloe vera-mediated strong reduction of IL-1β appears to be the consequence of the reduced expression of both pro-IL-1β as well as Nlrp3 inflammasome components via suppressing specific signal transduction pathways. Furthermore, we show that the expression of the ATP sensor P2X7 receptor is also downregulated by Aloe vera that could also contribute to the attenuated IL-1β cytokine secretion. These results may provide a new therapeutic approach to regulate inflammasome-mediated responses. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. LPS-induced lung inflammation in marmoset monkeys - an acute model for anti-inflammatory drug testing.

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    Sophie Seehase

    Full Text Available Increasing incidence and substantial morbidity and mortality of respiratory diseases requires the development of new human-specific anti-inflammatory and disease-modifying therapeutics. Therefore, new predictive animal models that closely reflect human lung pathology are needed. In the current study, a tiered acute lipopolysaccharide (LPS-induced inflammation model was established in marmoset monkeys (Callithrix jacchus to reflect crucial features of inflammatory lung diseases. Firstly, in an ex vivo approach marmoset and, for the purposes of comparison, human precision-cut lung slices (PCLS were stimulated with LPS in the presence or absence of the phosphodiesterase-4 (PDE4 inhibitor roflumilast. Pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-α and macrophage inflammatory protein-1 beta (MIP-1β were measured. The corticosteroid dexamethasone was used as treatment control. Secondly, in an in vivo approach marmosets were pre-treated with roflumilast or dexamethasone and unilaterally challenged with LPS. Ipsilateral bronchoalveolar lavage (BAL was conducted 18 hours after LPS challenge. BAL fluid was processed and analyzed for neutrophils, TNF-α, and MIP-1β. TNF-α release in marmoset PCLS correlated significantly with human PCLS. Roflumilast treatment significantly reduced TNF-α secretion ex vivo in both species, with comparable half maximal inhibitory concentration (IC(50. LPS instillation into marmoset lungs caused a profound inflammation as shown by neutrophilic influx and increased TNF-α and MIP-1β levels in BAL fluid. This inflammatory response was significantly suppressed by roflumilast and dexamethasone. The close similarity of marmoset and human lungs regarding LPS-induced inflammation and the significant anti-inflammatory effect of approved pharmaceuticals assess the suitability of marmoset monkeys to serve as a promising model for studying anti-inflammatory drugs.

  5. MiR-125b Inhibits LPS-Induced Inflammatory Injury via Targeting MIP-1α in Chondrogenic Cell ATDC5

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    Jinling Jia

    2018-03-01

    Full Text Available Background/Aims: Chondrocyte apoptosis is largely responsible for cartilage degeneration in osteoarthritis (OA. MicroRNAs (miRNAs play an important role in chondrogenesis and cartilage remodeling. This study explored the effect of miR-125b on inflammatory injury in chondrogenic cells. Methods: LPS was used to simulate inflammatory injury in murine chondrogenic ATDC5 cell lines. Targeting effect of miR-125b on MIP-1α 3’UTR was assessed by dual luciferase activity assay. Regulatory effect of miR-125b on MIP-1α expression and the potential regulatory mechanism on inflammatory injury were assessed by Western blot. Results: miR-125b expression was decreased in LPS-induced ATDC5 cells and overexpression of miR-125b inhibited LPS-induced cell viability decline, the rise of apoptosis and inflammatory factors’ productions. MIP-1α expression was negatively related to miR-125b, and miR-125b directly targeted with 3’UTR of MIP-1α. Knockdown of miR-125b promoted LPS-induced inflammatory response via upregulation of MIP-1α. miR-125b expression in LPS-induced ATDC5 cells was negatively related with activations of NF-κB and JNK signaling pathways. Overexpression of miR-125b inhibited LPS-induced inflammation injury via suppressing MIP-1α expression and inhibiting activations of NF-κB and JNK signaling pathways. Conclusion: miR-125b could play an important role in inflammatory injury of chondrogenic cells and miR-125b affected inflammatory injury of ATDC5 cells via regulating expression of MIP-1α and regulating NF-κB and JNK signaling pathways.

  6. Postdiarrheal Shiga Toxin-Mediated Hemolytic Uremic Syndrome Similar to Septic Shock Síndrome urémico hemolítico símil shock séptico, posterior a diarrea mediada por toxina shiga

    Directory of Open Access Journals (Sweden)

    Patricia G. Valles

    2005-10-01

    Full Text Available The inflammatory response of host endothelial cells is included in the development of vascular damage observed in enterohemorrhagic Escherichia coli (EHEC infection, resulting in hemolytic uremic syndrome (HUS. The response to a non-conventional treatment for a group of D+ HUS (diarrhea positive HUS patients, with clinical hemodynamic parameters of septic shock was evaluated in this prospective study (1999-2003. Twelve children 2.8 ± 0.6 years old, with D+ HUS produced by E. coli infection with serological evidence of Shiga toxin, presenting severe unstable hemodynamic parameters and neurological dysfunction at onset, were studied. The protocol included fresh frozen plasma infusions, methylprednisolone pulses (10mg/k/day for three consecutive days and plasma exchange for five days, starting after admission to the intensive care unit (ICU. The twelve patients with increased pediatric risk of mortality (PRISM score: 18 ± 2 after admission to intensive care unit (ICU, required dialysis for 17.4 ± 4 days, mechanical ventilator assistance for 10 ± 1 days and early inotropic drugs support for 10.5 ± 1 days. Neurological dysfunction included generalized tonic-clonic seizures lasting for 5.4 ± 1 days, n:8. Focal seizures were present in the remaining patients. Dilated cardiomyopathy was present in 6 children. Eight children suffered hemorrhagic colitis. Nine patients survived. Within one year of the injury, neurological sequelae, Glasgow outcome scale (GOS 3 and 4, were present in two patients, chronic renal failure in one patient. We suggest that early introduction of this protocol could benefit D+ HUS patients with hemodynamic instability and neurological dysfunction at onset. Further studies are likely to elucidate the mechanisms involved in this early adverse clinical presentation of D+ HUS patients.La respuesta inflamatoria de la célula endotelial se incluye en el desarrollo del daño vascular observado en la infección por Escherichia coli

  7. Functional Toll-like receptor 4 expressed in lactotrophs mediates LPS-induced proliferation in experimental pituitary hyperplasia

    International Nuclear Information System (INIS)

    Sabatino, María Eugenia; Sosa, Liliana del Valle; Petiti, Juan Pablo; Mukdsi, Jorge Humberto; Mascanfroni, Iván Darío; Pellizas, Claudia Gabriela; Gutiérrez, Silvina; Torres, Alicia Inés; De Paul, Ana Lucía

    2013-01-01

    Toll like receptor 4 (TLR4) has been characterized for its ability to recognize bacterial endotoxin lipopolysaccharide (LPS). Considering that infections or inflammatory processes might contribute to the progression of pituitary tumors, we analyzed the TLR4 functional role by evaluating the LPS effect on lactotroph proliferation in primary cultures from experimental pituitary tumors, and examined the involvement of PI3K-Akt and NF-κB activation in this effect. In addition, the role of 17β-estradiol as a possible modulator of LPS-induced PRL cell proliferation was further investigated. In estrogen-induced hyperplasic pituitaries, LPS triggered lactotroph cell proliferation. However, endotoxin failed to increase the number of lactotrophs taking up BrdU in normal pituitaries. Moreover, incubation with anti-TLR4 antibody significantly reduced LPS-induced lactotroph proliferation, suggesting a functional role of this receptor. As a sign of TLR4 activation, an LPS challenge increased IL-6 release in normal and tumoral cells. By flow cytometry, TLR4 baseline expression was revealed at the plasma membrane of tumoral lactotrophs, without changes noted in the percentage of double PRL/TLR4 positive cells after LPS stimulus. Increases in TLR4 intracellular expression were detected as well as rises in CD14, p-Akt and NF-κB after an LPS challenge, as assessed by western blotting. The TLR4/PRL and PRL/NF-κB co-localization was also corroborated by immunofluorescence and the involvement of PI3K/Akt signaling in lactotroph proliferation and IL-6 release was revealed through the PI3K inhibitor Ly-294002. In addition, 17β-estradiol attenuated the LPS-evoked increase in tumoral lactotroph proliferation and IL-6 release. Collectively these results demonstrate the presence of functional TLR4 in lactotrophs from estrogen-induced hyperplasic pituitaries, which responded to the proliferative stimulation and IL-6 release induced by LPS through TLR4/CD14, with a contribution of the PI3K

  8. Functional Toll-like receptor 4 expressed in lactotrophs mediates LPS-induced proliferation in experimental pituitary hyperplasia

    Energy Technology Data Exchange (ETDEWEB)

    Sabatino, María Eugenia; Sosa, Liliana del Valle; Petiti, Juan Pablo; Mukdsi, Jorge Humberto [Centro de Microscopía Electrónica, Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Av. Enrique Barros y Enfermera Gordillo, Ciudad Universitaria, CP 5000, Córdoba (Argentina); Mascanfroni, Iván Darío; Pellizas, Claudia Gabriela [Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Av. Haya de la Torre y Medina Allende, Ciudad Universitaria, CP 5000, Córdoba (Argentina); Gutiérrez, Silvina; Torres, Alicia Inés [Centro de Microscopía Electrónica, Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Av. Enrique Barros y Enfermera Gordillo, Ciudad Universitaria, CP 5000, Córdoba (Argentina); De Paul, Ana Lucía, E-mail: adepaul@cmefcm.uncor.edu [Centro de Microscopía Electrónica, Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Av. Enrique Barros y Enfermera Gordillo, Ciudad Universitaria, CP 5000, Córdoba (Argentina)

    2013-11-15

    Toll like receptor 4 (TLR4) has been characterized for its ability to recognize bacterial endotoxin lipopolysaccharide (LPS). Considering that infections or inflammatory processes might contribute to the progression of pituitary tumors, we analyzed the TLR4 functional role by evaluating the LPS effect on lactotroph proliferation in primary cultures from experimental pituitary tumors, and examined the involvement of PI3K-Akt and NF-κB activation in this effect. In addition, the role of 17β-estradiol as a possible modulator of LPS-induced PRL cell proliferation was further investigated. In estrogen-induced hyperplasic pituitaries, LPS triggered lactotroph cell proliferation. However, endotoxin failed to increase the number of lactotrophs taking up BrdU in normal pituitaries. Moreover, incubation with anti-TLR4 antibody significantly reduced LPS-induced lactotroph proliferation, suggesting a functional role of this receptor. As a sign of TLR4 activation, an LPS challenge increased IL-6 release in normal and tumoral cells. By flow cytometry, TLR4 baseline expression was revealed at the plasma membrane of tumoral lactotrophs, without changes noted in the percentage of double PRL/TLR4 positive cells after LPS stimulus. Increases in TLR4 intracellular expression were detected as well as rises in CD14, p-Akt and NF-κB after an LPS challenge, as assessed by western blotting. The TLR4/PRL and PRL/NF-κB co-localization was also corroborated by immunofluorescence and the involvement of PI3K/Akt signaling in lactotroph proliferation and IL-6 release was revealed through the PI3K inhibitor Ly-294002. In addition, 17β-estradiol attenuated the LPS-evoked increase in tumoral lactotroph proliferation and IL-6 release. Collectively these results demonstrate the presence of functional TLR4 in lactotrophs from estrogen-induced hyperplasic pituitaries, which responded to the proliferative stimulation and IL-6 release induced by LPS through TLR4/CD14, with a contribution of the PI3K

  9. Protocolised Management In Sepsis (ProMISe): a multicentre randomised controlled trial of the clinical effectiveness and cost-effectiveness of early, goal-directed, protocolised resuscitation for emerging septic shock.

    Science.gov (United States)

    Mouncey, Paul R; Osborn, Tiffany M; Power, G Sarah; Harrison, David A; Sadique, M Zia; Grieve, Richard D; Jahan, Rahi; Tan, Jermaine C K; Harvey, Sheila E; Bell, Derek; Bion, Julian F; Coats, Timothy J; Singer, Mervyn; Young, J Duncan; Rowan, Kathryn M

    2015-11-01

    Early goal-directed therapy (EGDT) is recommended in international guidance for the resuscitation of patients presenting with early septic shock. However, adoption has been limited and uncertainty remains over its clinical effectiveness and cost-effectiveness. The primary objective was to estimate the effect of EGDT compared with usual resuscitation on mortality at 90 days following randomisation and on incremental cost-effectiveness at 1 year. The secondary objectives were to compare EGDT with usual resuscitation for requirement for, and duration of, critical care unit organ support; length of stay in the emergency department (ED), critical care unit and acute hospital; health-related quality of life, resource use and costs at 90 days and at 1 year; all-cause mortality at 28 days, at acute hospital discharge and at 1 year; and estimated lifetime incremental cost-effectiveness. A pragmatic, open, multicentre, parallel-group randomised controlled trial with an integrated economic evaluation. Fifty-six NHS hospitals in England. A total of 1260 patients who presented at EDs with septic shock. EGDT (n = 630) or usual resuscitation (n = 630). Patients were randomly allocated 1 : 1. All-cause mortality at 90 days after randomisation and incremental net benefit (at £20,000 per quality-adjusted life-year) at 1 year. Following withdrawals, data on 1243 (EGDT, n = 623; usual resuscitation, n = 620) patients were included in the analysis. By 90 days, 184 (29.5%) in the EGDT and 181 (29.2%) patients in the usual-resuscitation group had died [p = 0.90; absolute risk reduction -0.3%, 95% confidence interval (CI) -5.4 to 4.7; relative risk 1.01, 95% CI 0.85 to 1.20]. Treatment intensity was greater for the EGDT group, indicated by the increased use of intravenous fluids, vasoactive drugs and red blood cell transfusions. Increased treatment intensity was reflected by significantly higher Sequential Organ Failure Assessment scores and more advanced

  10. Cytosolic NADP(+)-dependent isocitrate dehydrogenase protects macrophages from LPS-induced nitric oxide and reactive oxygen species.

    Science.gov (United States)

    Maeng, Oky; Kim, Yong Chan; Shin, Han-Jae; Lee, Jie-Oh; Huh, Tae-Lin; Kang, Kwang-il; Kim, Young Sang; Paik, Sang-Gi; Lee, Hayyoung

    2004-04-30

    Macrophages activated by microbial lipopolysaccharides (LPS) produce bursts of nitric oxide and reactive oxygen species (ROS). Redox protection systems are essential for the survival of the macrophages since the nitric oxide and ROS can be toxic to them as well as to pathogens. Using suppression subtractive hybridization (SSH) we found that cytosolic NADP(+)-dependent isocitrate dehydrogenase (IDPc) is strongly upregulated by nitric oxide in macrophages. The levels of IDPc mRNA and of the corresponding enzymatic activity were markedly increased by treatment of RAW264.7 cells or peritoneal macrophages with LPS or SNAP (a nitric oxide donor). Over-expression of IDPc reduced intracellular peroxide levels and enhanced the survival of H2O2- and SNAP-treated RAW264.7 macrophages. IDPc is known to generate NADPH, a cellular reducing agent, via oxidative decarboxylation of isocitrate. The expression of enzymes implicated in redox protection, superoxide dismutase (SOD) and catalase, was relatively unaffected by LPS and SNAP. We propose that the induction of IDPc is one of the main self-protection mechanisms of macrophages against LPS-induced oxidative stress.

  11. Endogenous PGI2 signaling through IP inhibits neutrophilic lung inflammation in LPS-induced acute lung injury mice model.

    Science.gov (United States)

    Toki, Shinji; Zhou, Weisong; Goleniewska, Kasia; Reiss, Sara; Dulek, Daniel E; Newcomb, Dawn C; Lawson, William E; Peebles, R Stokes

    2018-04-13

    Endogenous prostaglandin I 2 (PGI 2 ) has inhibitory effects on immune responses against pathogens or allergens; however, the immunomodulatory activity of endogenous PGI 2 signaling in endotoxin-induced inflammation is unknown. To test the hypothesis that endogenous PGI 2 down-regulates endotoxin-induced lung inflammation, C57BL/6 wild type (WT) and PGI 2 receptor (IP) KO mice were challenged intranasally with LPS. Urine 6-keto-PGF 1α , a stable metabolite of PGI 2, was significantly increased following the LPS-challenge, suggesting that endogenous PGI 2 signaling modulates the host response to LPS-challenge. IPKO mice had a significant increase in neutrophils in the BAL fluid as well as increased proteins of KC, LIX, and TNF-α in lung homogenates compared with WT mice. In contrast, IL-10 was decreased in LPS-challenged IPKO mice compared with WT mice. The PGI 2 analog cicaprost significantly decreased LPS-induced KC, and TNF-α, but increased IL-10 and AREG in bone marrow-derived dendritic cells (BMDCs) and bone marrow-derived macrophages (BMMs) compared with vehicle-treatment. These results indicated that endogenous PGI 2 signaling attenuated neutrophilic lung inflammation through the reduced inflammatory cytokine and chemokine and enhanced IL-10. Copyright © 2018. Published by Elsevier Inc.

  12. Alliin, a Garlic (Allium sativum Compound, Prevents LPS-Induced Inflammation in 3T3-L1 Adipocytes

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    Saray Quintero-Fabián

    2013-01-01

    Full Text Available Garlic (Allium sativum L. has been used to alleviate a variety of health problems due to its high content of organosulfur compounds and antioxidant activity. The main active component is alliin (S-allyl cysteine sulfoxide, a potent antioxidant with cardioprotective and neuroprotective actions. In addition, it helps to decrease serum levels of glucose, insulin, triglycerides, and uric acid, as well as insulin resistance, and reduces cytokine levels. However its potential anti-inflammatory effect is unknown. We examined the effects of alliin in lipopolysaccharide- (LPS- stimulated 3T3-L1 adipocytes by RT-PCR, Western blot, and microarrays analysis of 22,000 genes. Incubation of cells for 24 h with 100 μmol/L alliin prevented the increase in the expression of proinflammatory genes, IL-6, MCP-1, and Egr-1 in 3T3-L1 adipocytes exposed to 100 ng/mL LPS for 1 h. Interestingly, the phosphorylation of ERK1/2, which is involved in LPS-induced inflammation in adipocytes, was decreased following alliin treatment. Furthermore, the gene expression profile by microarrays evidentiate an upregulation of genes involved in immune response and downregulation of genes related with cancer. The present results have shown that alliin is able to suppress the LPS inflammatory signals by generating an anti-inflammatory gene expression profile and by modifying adipocyte metabolic profile.

  13. Pulmonary permeability assessed by fluorescent-labeled dextran instilled intranasally into mice with LPS-induced acute lung injury.

    Directory of Open Access Journals (Sweden)

    Honglei Chen

    Full Text Available Several different methods have been used to assess pulmonary permeability in response to acute lung injury (ALI. However, these methods often involve complicated procedures and algorithms that are difficult to precisely control. The purpose of the current study is to establish a feasible method to evaluate alterations in lung permeability by instilling fluorescently labeled dextran (FITC-Dextran intranasally.For the mouse model of direct ALI, lipopolysaccharide (LPS was administered intranasally. FITC-Dextran was instilled intranasally one hour before the mice were euthanized. Plasma fluorescence intensities from the LPS group were significantly higher than in the control group. To determine the reliability and reproducibility of the procedure, we also measured the lung wet-to-dry weight ratio, the protein concentration of the bronchoalveolar lavage fluid, tight and adherens junction markers and pathological changes. Consistent results were observed when the LPS group was compared with the control group. Simultaneously, we found that the concentration of plasma FITC-Dextran was LPS dose-dependent. The concentration of plasma FITC-Dextran also increased with initial intranasal FITC-Dextran doses. Furthermore, increased fluorescence intensity of plasma FITC-Dextran was found in the intraperitoneally LPS-induced ALI model.In conclusion, the measurement of FITC-Dextran in plasma after intranasal instillation is a simple, reliable, and reproducible method to evaluate lung permeability alterations in vivo. The concentration of FITC-Dextran in the plasma may be useful as a potential peripheral biomarker of ALI in experimental clinical studies.

  14. Pulmonary permeability assessed by fluorescent-labeled dextran instilled intranasally into mice with LPS-induced acute lung injury.

    Science.gov (United States)

    Chen, Honglei; Wu, Shaoping; Lu, Rong; Zhang, Yong-guo; Zheng, Yuanyuan; Sun, Jun

    2014-01-01

    Several different methods have been used to assess pulmonary permeability in response to acute lung injury (ALI). However, these methods often involve complicated procedures and algorithms that are difficult to precisely control. The purpose of the current study is to establish a feasible method to evaluate alterations in lung permeability by instilling fluorescently labeled dextran (FITC-Dextran) intranasally. For the mouse model of direct ALI, lipopolysaccharide (LPS) was administered intranasally. FITC-Dextran was instilled intranasally one hour before the mice were euthanized. Plasma fluorescence intensities from the LPS group were significantly higher than in the control group. To determine the reliability and reproducibility of the procedure, we also measured the lung wet-to-dry weight ratio, the protein concentration of the bronchoalveolar lavage fluid, tight and adherens junction markers and pathological changes. Consistent results were observed when the LPS group was compared with the control group. Simultaneously, we found that the concentration of plasma FITC-Dextran was LPS dose-dependent. The concentration of plasma FITC-Dextran also increased with initial intranasal FITC-Dextran doses. Furthermore, increased fluorescence intensity of plasma FITC-Dextran was found in the intraperitoneally LPS-induced ALI model. In conclusion, the measurement of FITC-Dextran in plasma after intranasal instillation is a simple, reliable, and reproducible method to evaluate lung permeability alterations in vivo. The concentration of FITC-Dextran in the plasma may be useful as a potential peripheral biomarker of ALI in experimental clinical studies.

  15. A rhodium(III) complex inhibits LPS-induced nitric oxide production and angiogenic activity in cellulo.

    Science.gov (United States)

    Liu, Li-Juan; Lin, Sheng; Chan, Daniel Shiu-Hin; Vong, Chi Teng; Hoi, Pui Man; Wong, Chun-Yuen; Ma, Dik-Lung; Leung, Chung-Hang

    2014-11-01

    Metal-containing complexes have arisen as viable alternatives to organic molecules as therapeutic agents. Metal complexes possess a number of advantages compared to conventional carbon-based compounds, such as distinct geometries, interesting electronic properties, variable oxidation states and the ability to arrange different ligands around the metal centre in a precise fashion. Meanwhile, nitric oxide (NO) plays key roles in the regulation of angiogenesis, vascular permeability and inflammation. We herein report a novel cyclometalated rhodium(III) complex as an inhibitor of lipopolysaccharides (LPS)-induced NO production in RAW264.7 macrophages. Experiments suggested that the inhibition of NO production in cells by complex 1 was mediated through the down-regulation of nuclear factor-κB (NF-κB) activity. Furthermore, complex 1 inhibited angiogenesis in human umbilical vein endothelial cells (HUVECs) as revealed by an endothelial tube formation assay. This study demonstrates that kinetically inert rhodium(III) complexes may be potentially developed as effective anti-angiogenic agents. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Reversible tetraplegia after percutaneous nephrostolithotomy and septic shock: a case of critical illness polyneuropathy and myopathy with acute onset and complete recovery

    Directory of Open Access Journals (Sweden)

    Li Hai

    2013-02-01

    Full Text Available Abstract Background Critical illness polyneuropathy (CIP and critical illness myopathy (CIM are complications causing weakness of respiratory and limb muscles in critically ill patients. As an important differential diagnosis of Guillain-Barré syndrome (GBS, CIP and CIM should be diagnosed with caution, after a complete clinical and laboratory examination. Although not uncommon in ICU, CIP and CIM as severe complications of percutaneous nephrostolithotomy (PNL have not been documented in literature. Case presentation A 48-year-old Chinese woman was referred to our hospital, complaining of occasional pain in the right lower back for one month. Lithiasis was diagnosed by ultrasonographical and radiological examinations on the urinary system. PNL was indicated and performed. The patient developed CIP and CIM on the fourth day after PNL. Early recognition and treatment of the severe complications contributed to a satisfactory recovery of the patient. Conclusion This case expands our understanding of the complications of PNL and underscores the importance of differentiating CIP/CIM from GBS in case of such patients developing weakness after the treatment. Clinical characteristics and examination results should be carefully evaluated to make the diagnosis of CIP or CIM. Both anti-septic prophylaxis and control of hyperglycemia might be effective for the prevention of CIP or CIM; aggressive treatment on sepsis and multiple organ failure is considered to be the most effective measure to reduce the incidence of CIP/CIM.

  17. Análise exploratória dos fatores relacionados ao prognóstico em idosos com sepse grave e choque séptico Related prognostic factors in elderly patients with severe sepsis and septic shock

    Directory of Open Access Journals (Sweden)

    Roberta de Lima Machado

    2009-03-01

    Full Text Available OBJETIVOS: O objetivo deste estudo foi avaliar variáveis relacionadas à mortalidade intra-hospitalar em 28 dias, de idosos com diagnóstico de sepse grave ou choque séptico em unidade de terapia intensiva clínica. MÉTODOS: Cento e cinqüenta e dois pacientes, com idade > 65 anos internados com sepse grave ou choque séptico foram acompanhados durante 28 dias e as variáveis foram coletadas nos dias 1, 3, 5, 7, 14 e 28 de internação. Para a comparação das variáveis categóricas, empregaram-se os testes Qui-quadrado e para as variáveis contínuas o teste de Mann-Whitney ou teste T, quando apropriado. Todos os testes foram bicaudais com erro alfa de 0,05. RESULTADOS: A média da idade foi de 82,0 �� 9,0 anos, com 64,5% de mulheres, sendo a mortalidade de 47,4%. Foram relacionados ao óbito: índice Acute Physiologic and Chronic Heatlh Evaluation II (p OBJECTIVES: The objective of this study was to evaluate variables related to intra hospital mortality at 28 days, of aged persons with severe sepsis and septic shock in a clinical ICU. METHODS: One hundred and fifty-two patients aged > 65 years with severe sepsis and septic shock were followed for 28 days and the variables were collected on days 1, 3, 5, 7, 14 and 28 of stay. To compare categorical variables the Chi-square test was used and the Mann-Whitney or t test for continuous variables. All tests were double-tailed, alpha error of 0.05. RESULTS: Mean age was 82.0 ± 9.0 years and 64.5% were female. Mortality was of 47.4%. Related to death were the following: Acute Physiological and Chronic Heath Evaluation II score (p < 0.001, Sequential Organ Failure Assessment score on days 1, 3, 5, 7 (p < 0.001, length of stay in intensive care (p < 0.001, number of organ failures (p < 0.001, high serum lactate on day 3 (p = 0.05, positive troponin I (p < 0.01, echocardiographic variables (systolic diameter p = 0.005; diastolic diameter p = 0.05; shortening fraction p = 0.02, previous renal

  18. Lipoxin A4 and platelet activating factor are involved in E. coli or LPS-induced lung inflammation in CFTR-deficient mice.

    Directory of Open Access Journals (Sweden)

    Haiya Wu

    Full Text Available CFTR (cystic fibrosis transmembrane conductance regulator is expressed by both neutrophils and platelets. Lack of functional CFTR could lead to severe lung infection and inflammation. Here, we found that mutation of CFTR (F508del or inhibition of CFTR in mice led to more severe thrombocytopenia, alveolar neutrocytosis and bacteriosis, and lower lipoxin A4/MIP-2 (macrophage inhibitory protein-2 or lipoxin A4/neutrophil ratios in the BAL (bronchoalveolar lavage during acute E. coli pneumonia. In vitro, inhibition of CFTR promotes MIP-2 production in LPS-stimulated neutrophils; however, lipoxin A4 could dose-dependently suppress this effect. In LPS-induced acute lung inflammation, blockade of PSGL-1 (P-selectin glycoprotein ligand-1 or P-selectin, antagonism of PAF by WEB2086, or correction of mutated CFTR trafficking by KM11060 could significantly increase plasma lipoxin A4 levels in F508del relevant to wildtype mice. Concurrently, F508del mice had higher plasma platelet activating factor (PAF levels and PAF-AH activity compared to wildtype under LPS challenge. Inhibiting hydrolysis of PAF by a specific PAF-AH (PAF-acetylhydrolase inhibitor, MAFP, could worsen LPS-induced lung inflammation in F508del mice compared to vehicle treated F508del group. Particularly, depletion of platelets in F508del mice could significantly decrease plasma lipoxin A4 and PAF-AH activity and deteriorate LPS-induced lung inflammation compared to control F508del mice. Taken together, lipoxin A4 and PAF are involved in E. coli or LPS-induced lung inflammation in CFTR-deficient mice, suggesting that lipoxin A4 and PAF might be therapeutic targets for ameliorating CFTR-deficiency deteriorated lung inflammation.

  19. Rhizoma Coptidis Inhibits LPS-Induced MCP-1/CCL2 Production in Murine Macrophages via an AP-1 and NF?B-Dependent Pathway

    OpenAIRE

    Remppis, Andrew; Bea, Florian; Greten, Henry Johannes; Buttler, Annette; Wang, Hongjie; Zhou, Qianxing; Preusch, Michael R.; Enk, Ronny; Ehehalt, Robert; Katus, Hugo; Blessing, Erwin

    2010-01-01

    Introduction. The Chinese extract Rhizoma coptidis is well known for its anti-inflammatory, antioxidative, antiviral, and antimicrobial activity. The exact mechanisms of action are not fully understood. Methods. We examined the effect of the extract and its main compound, berberine, on LPS-induced inflammatory activity in a murine macrophage cell line. RAW 264.7 cells were stimulated with LPS and incubated with either Rhizoma coptidis extract or berberine. Activation of AP-1 and NFB was anal...

  20. Hydroxysafflor Yellow A Inhibits LPS-Induced NLRP3 Inflammasome Activation via Binding to Xanthine Oxidase in Mouse RAW264.7 Macrophages

    Directory of Open Access Journals (Sweden)

    Xiaolong Xu

    2016-01-01

    Full Text Available Hydroxysafflor yellow A (HSYA is an effective therapeutic agent for inflammatory diseases and autoimmune disorders; however, its regulatory effect on NLRP3 inflammasome activation in macrophages has not been investigated. In this study, we predicted the potential interaction between HSYA and xanthine oxidase (XO via PharmMapper inverse docking and confirmed the binding inhibition via inhibitory test (IC50 = 40.04 μM. Computation docking illustrated that, in this HSYA-XO complex, HSYA was surrounded by Leu 648, Leu 712, His 875, Leu 873, Ser 876, Glu 879, Phe 649, and Asn 650 with a binding energy of −5.77 kcal/M and formed hydrogen bonds with the hydroxyl groups of HSYA at Glu 879, Asn 650, and His 875. We then found that HSYA significantly decreased the activity of XO in RAW264.7 macrophages and suppressed LPS-induced ROS generation. Moreover, we proved that HSYA markedly inhibited LPS-induced cleaved caspase-1 activation via suppressing the sensitization of NLRP3 inflammasome and prevented the mature IL-1β formation from pro-IL-1β form. These findings suggest that XO may be a potential target of HSYA via direct binding inhibition and the combination of HSYA-XO suppresses LPS-induced ROS generation, contributing to the depression of NLRP3 inflammasome and inhibition of IL-1β secretion in macrophages.

  1. The inhibition of LPS-induced splenocyte proliferation by ortho-substituted and microbially dechlorinated polychlorinated biphenyls is associated with a decreased expression of cyclin D2

    International Nuclear Information System (INIS)

    Smithwick, L. Ashley; Quensen, John F.; Smith, Andrew; Kurtz, David T.; London, Lucille; Morris, Pamela J.

    2004-01-01

    Immunological effects of polychlorinated biphenyls (PCBs) have been demonstrated in our laboratories with the preferential inhibition of lipopolysaccharide (LPS)-induced splenocyte proliferation by ortho-substituted PCB congeners. An investigation of the mechanism behind this immunotoxicity revealed an interruption in the progression of murine lymphocytes from G 0 /G 1 into S phase by Aroclor 1242 and the di-ortho-substituted congener, 2,2'-chlorobiphenyl (CB), whereas, a non-ortho-substituted congener, 4,4'-CB, did not affect cell cycle progression. This interruption of cell cycle progression by 2,2'-CB and Aroclor 1242 was associated with a decreased expression of the cell cycle regulatory protein, cyclin D2, while expression was not affected by exposure to the non-ortho-substituted 4,4'-CB. These results suggest the preferential inhibition of LPS-induced splenocyte proliferation by ortho-substituted congeners is a result of a decreased expression of cyclin D2, which leads to an interruption in cell cycle progression. In addition, PCB mixtures with an increased percentage of chlorines in the ortho position following an environmentally occurring degradation process inhibited LPS-induced proliferation, interrupted cell cycle progression, and decreased cyclin D2 expression. This study provides evidence for a mechanism of action of the immunological effects of ortho-substituted individual congeners as well as environmentally relevant mixtures enriched in congeners with this substitution pattern

  2. Rhizoma coptidis Inhibits LPS-Induced MCP-1/CCL2 Production in Murine Macrophages via an AP-1 and NFB-Dependent Pathway

    Directory of Open Access Journals (Sweden)

    Andrew Remppis

    2010-01-01

    Full Text Available Introduction. The Chinese extract Rhizoma coptidis is well known for its anti-inflammatory, antioxidative, antiviral, and antimicrobial activity. The exact mechanisms of action are not fully understood. Methods. We examined the effect of the extract and its main compound, berberine, on LPS-induced inflammatory activity in a murine macrophage cell line. RAW 264.7 cells were stimulated with LPS and incubated with either Rhizoma coptidis extract or berberine. Activation of AP-1 and NFB was analyzed in nuclear extracts, secretion of MCP-1/CCL2 was measured in supernatants. Results. Incubation with Rhizoma coptidis and berberine strongly inhibited LPS-induced monocyte chemoattractant protein (MCP-1 production in RAW cells. Activation of the transcription factors AP-1 and NFB was inhibited by Rhizoma coptidis in a dose- and time-dependent fashion. Conclusions. Rhizoma coptidis extract inhibits LPS-induced MCP-1/CCL2 production in vitro via an AP-1 and NFB-dependent pathway. Anti-inflammatory action of the extract is mediated mainly by its alkaloid compound berberine.

  3. Rhizoma Coptidis Inhibits LPS-Induced MCP-1/CCL2 Production in Murine Macrophages via an AP-1 and NFκB-Dependent Pathway

    Science.gov (United States)

    Remppis, Andrew; Bea, Florian; Greten, Henry Johannes; Buttler, Annette; Wang, Hongjie; Zhou, Qianxing; Preusch, Michael R.; Enk, Ronny; Ehehalt, Robert; Katus, Hugo; Blessing, Erwin

    2010-01-01

    Introduction. The Chinese extract Rhizoma coptidis is well known for its anti-inflammatory, antioxidative, antiviral, and antimicrobial activity. The exact mechanisms of action are not fully understood. Methods. We examined the effect of the extract and its main compound, berberine, on LPS-induced inflammatory activity in a murine macrophage cell line. RAW 264.7 cells were stimulated with LPS and incubated with either Rhizoma coptidis extract or berberine. Activation of AP-1 and NFκB was analyzed in nuclear extracts, secretion of MCP-1/CCL2 was measured in supernatants. Results. Incubation with Rhizoma coptidis and berberine strongly inhibited LPS-induced monocyte chemoattractant protein (MCP)-1 production in RAW cells. Activation of the transcription factors AP-1 and NFκB was inhibited by Rhizoma coptidis in a dose- and time-dependent fashion. Conclusions. Rhizoma coptidis extract inhibits LPS-induced MCP-1/CCL2 production in vitro via an AP-1 and NFκB-dependent pathway. Anti-inflammatory action of the extract is mediated mainly by its alkaloid compound berberine. PMID:20652055

  4. Pseudane-VII Isolated from Pseudoalteromonas sp. M2 Ameliorates LPS-Induced Inflammatory Response In Vitro and In Vivo

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    Mi Eun Kim

    2017-11-01

    Full Text Available The ocean is a rich resource of flora, fauna, food, and biological products. We found a wild-type bacterial strain, Pseudoalteromonas sp. M2, from marine water and isolated various secondary metabolites. Pseudane-VII is a compound isolated from the Pseudoalteromonas sp. M2 metabolite that possesses anti-melanogenic activity. Inflammation is a response of the innate immune system to microbial infections. Macrophages have a critical role in fighting microbial infections and inflammation. Recent studies reported that various compounds derived from natural products can regulate immune responses including inflammation. However, the anti-inflammatory effects and mechanism of pseudane-VII in macrophages are still unknown. In this study, we investigated the anti-inflammatory effects of pseudane-VII. In present study, lipopolysaccharide (LPS-induced nitric oxide (NO production was significantly decreased by pseudane-VII treatment at 6 μM. Moreover, pseudane-VII treatment dose-dependently reduced mRNA levels of pro-inflammatory cytokines including inos, cox-2, il-1β, tnf-α, and il-6 in LPS-stimulated macrophages. Pseudane-VII also diminished iNOS protein levels and IL-1β secretion. In addition, Pseudane-VII elicited anti-inflammatory effects by inhibiting ERK, JNK, p38, and nuclear factor (NF-κB-p65 phosphorylation. Consistently, pseudane-VII was also shown to inhibit the LPS-stimulated release of IL-1β and expression of iNOS in mice. These results suggest that pseudane-VII exerted anti-inflammatory effects on LPS-stimulated macrophage activation via inhibition of ERK, JNK, p38 MAPK phosphorylation, and pro-inflammatory gene expression. These findings may provide new approaches in the effort to develop anti-inflammatory therapeutics.

  5. Pseudane-VII Isolated from Pseudoalteromonas sp. M2 Ameliorates LPS-Induced Inflammatory Response In Vitro and In Vivo.

    Science.gov (United States)

    Kim, Mi Eun; Jung, Inae; Lee, Jong Suk; Na, Ju Yong; Kim, Woo Jung; Kim, Young-Ok; Park, Yong-Duk; Lee, Jun Sik

    2017-11-01

    The ocean is a rich resource of flora, fauna, food, and biological products. We found a wild-type bacterial strain, Pseudoalteromonas sp. M2, from marine water and isolated various secondary metabolites. Pseudane-VII is a compound isolated from the Pseudoalteromonas sp. M2 metabolite that possesses anti-melanogenic activity. Inflammation is a response of the innate immune system to microbial infections. Macrophages have a critical role in fighting microbial infections and inflammation. Recent studies reported that various compounds derived from natural products can regulate immune responses including inflammation. However, the anti-inflammatory effects and mechanism of pseudane-VII in macrophages are still unknown. In this study, we investigated the anti-inflammatory effects of pseudane-VII. In present study, lipopolysaccharide (LPS)-induced nitric oxide (NO) production was significantly decreased by pseudane-VII treatment at 6 μM. Moreover, pseudane-VII treatment dose-dependently reduced mRNA levels of pro-inflammatory cytokines including inos , cox-2 , il-1β , tnf-α , and il-6 in LPS-stimulated macrophages. Pseudane-VII also diminished iNOS protein levels and IL-1β secretion. In addition, Pseudane-VII elicited anti-inflammatory effects by inhibiting ERK, JNK, p38, and nuclear factor (NF)-κB-p65 phosphorylation. Consistently, pseudane-VII was also shown to inhibit the LPS-stimulated release of IL-1β and expression of iNOS in mice. These results suggest that pseudane-VII exerted anti-inflammatory effects on LPS-stimulated macrophage activation via inhibition of ERK, JNK, p38 MAPK phosphorylation, and pro-inflammatory gene expression. These findings may provide new approaches in the effort to develop anti-inflammatory therapeutics.

  6. BQ-123 prevents LPS-induced preterm birth in mice via the induction of uterine and placental IL-10.

    Science.gov (United States)

    Olgun, Nicole S; Hanna, Nazeeh; Reznik, Sandra E

    2015-02-01

    Preterm birth (PTB), defined as any delivery occurring prior to the completion of 37 weeks' gestation, currently accounts for 11-12% of all births in the United States. Maternal genito-urinary infections account for up to 40% of all PTBS and induce a pro-inflammatory state in the host. The potent vasoconstrictor Endothelin-1 (ET-1) is known to be upregulated in the setting of infection, and elicits its effect by binding to the ETA receptor. We have previously shown that antagonism of the ETA receptor with BQ-123 is capable of preventing LPS-induced PTB in mice. We hypothesize that the administration of BQ-123 post LPS exposure will dismantle a positive feedback loop observed with pro-inflammatory cytokines upstream of ET-1. On GD 15.5, pregnant C57BL/6 mice were injected with PBS, LPS, BQ-123, or LPS+BQ-123. Changes at both the level of transcription and translation were observed in uterus and placenta in the ET-1 axis and in pro- and anti-inflammatory cytokines over the course of 12h. We discovered that BQ-123, when administered 10h post LPS, is capable of increasing production of uterine and placental Interleukin-10, causing a shift away from the pro-inflammatory state. We also observed that antagonism of the ETA receptor decreased IL-1β and TNFα in the placenta while also decreasing transcription of ET-1 in the uterus. Our results reinforce the role of ET-1 at the maternal fetal interface and highlight the potential benefit of ETA receptor blockade via the suppression of ET-1, and induction of a Th2 cytokine dominant state. Copyright © 2014. Published by Elsevier Inc.

  7. Licofelone Attenuates LPS-induced Depressive-like Behavior in Mice: A Possible Role for Nitric Oxide.

    Science.gov (United States)

    Mousavi, Seyyedeh Elaheh; Saberi, Pegah; Ghasemkhani, Naeemeh; Fakhraei, Nahid; Mokhtari, Rezvan; Dehpour, Ahmad Reza

    2018-01-01

    Licofelone, a dual cyclooxygenase/5-lipoxygenase inhibitor, possesses antioxidant, antiapoptotic, neuroprotective, and anti-inflammatory properties. The aim of the present study was to investigate the effect of licofelone on lipopolysaccharide (LPS)-induced depression in a mouse model and also a possible role for nitric oxide (NO). To elucidate the role of NO on this effect of licofelone (5 and 20 mg/kg, i.p.), L-NAME, a non-specific NO synthase (NOS) inhibitor; aminoguanidine (AG), a specific inducible NOS (iNOS) inhibitor; 7-nitroindazole (7-NI) a preferential neuronal NOS inhibitor (nNOS) and; L-arginine (L-Arg), as a NO donor, were used. The animal's behaviors were evaluated employing forced swimming test (FST), tail suspension test (TST) and open field test (OFT). LPS (0.83 mg/kg, i.p.) induced depressive-like behavior increasing immobility time in FST and TST. Conversely, licofelone (20 mg/kg i.p.) reversed the depressive effect of LPS and lowered the immobility time in FST and TST. On the other hand, pretreatment with L-Arg also reversed the antidepressant-like effect of licofelone (20 mg/kg) in FST and TST. On the other hand, L-NAME (10 and 30 mg/kg), AG (50 and 100 mg/kg) and 7-NI (60 mg/kg) could potentiate licofelone (5 mg/kg) and lowered the immobility duration. NO down-regulation possibly through iNOS and nNOS inhibition may involve in the antidepressant property of licofelone. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

  8. BQ-123 prevents LPS-induced preterm birth in mice via the induction of uterine and placental IL-10

    International Nuclear Information System (INIS)

    Olgun, Nicole S.; Hanna, Nazeeh; Reznik, Sandra E.

    2015-01-01

    Preterm birth (PTB), defined as any delivery occurring prior to the completion of 37 weeks' gestation, currently accounts for 11–12% of all births in the United States. Maternal genito-urinary infections account for up to 40% of all PTBS and induce a pro-inflammatory state in the host. The potent vasoconstrictor Endothelin-1 (ET-1) is known to be upregulated in the setting of infection, and elicits its effect by binding to the ET A receptor. We have previously shown that antagonism of the ET A receptor with BQ-123 is capable of preventing LPS-induced PTB in mice. We hypothesize that the administration of BQ-123 post LPS exposure will dismantle a positive feedback loop observed with pro-inflammatory cytokines upstream of ET-1. On GD 15.5, pregnant C57BL/6 mice were injected with PBS, LPS, BQ-123, or LPS + BQ-123. Changes at both the level of transcription and translation were observed in uterus and placenta in the ET-1 axis and in pro- and anti-inflammatory cytokines over the course of 12 h. We discovered that BQ-123, when administered 10 h post LPS, is capable of increasing production of uterine and placental Interleukin-10, causing a shift away from the pro-inflammatory state. We also observed that antagonism of the ET A receptor decreased IL-1β and TNFα in the placenta while also decreasing transcription of ET-1 in the uterus. Our results reinforce the role of ET-1 at the maternal fetal interface and highlight the potential benefit of ET A receptor blockade via the suppression of ET-1, and induction of a Th2 cytokine dominant state. - Highlights: • The pro-inflammatory response to LPS in the uterus and placenta is ET-1 dependent. • ET A blockade triggers up-regulation of IL-10 in uterus and placenta. • A positive feedback loop drives ET-1 expression in gestational tissue

  9. Nfkb1 inhibits LPS-induced IFN-β and IL-12 p40 production in macrophages by distinct mechanisms.

    Directory of Open Access Journals (Sweden)

    Xixing Zhao

    Full Text Available Nfkb1-deficient murine macrophages express higher levels of IFN-β and IL-12 p40 following LPS stimulation than control macrophages, but the molecular basis for this phenomenon has not been completely defined. Nfkb1 encodes several gene products including the NF-κB subunit p50 and its precursor p105. p50 is derived from the N-terminal of 105, and p50 homodimers can exhibit suppressive activity when overexpressed. The C-terminal region of p105 is necessary for LPS-induced ERK activation and it has been suggested that ERK activity inhibits both IFN-β and IL-12 p40 following LPS stimulation. However, the contributions of p50 and the C-terminal domain of p105 in regulating endogenous IFN-β(Ifnb and IL-12 p40 (Il12b gene expression in macrophages following LPS stimulation have not been directly compared.We have used recombinant retroviruses to express p105, p50, and the C-terminal domain of p105 (p105ΔN in Nfkb1-deficient murine bone marrow-derived macrophages at near endogenous levels. We found that both p50 and p105ΔN inhibited expression of Ifnb, and that inhibition of Ifnb by p105ΔN depended on ERK activation, because a mutant of p105ΔN (p105ΔNS930A that lacks a key serine necessary to support ERK activation failed to inhibit. In contrast, only p105ΔN but not p50 inhibited Il12b expression. Surprisingly, p105ΔNS930A retained inhibitory activity for Il12b, indicating that ERK activation was not necessary for inhibition. The differential effects of p105ΔNS930A on Ifnb and Il12b expression inversely correlated with the function of one of its binding partners, c-Rel. This raised the possibility that p105ΔNS930A influences gene expression by interfering with the function of c-Rel.These results demonstrate that Nfkb1 exhibits multiple gene-specific inhibitory functions following TLR stimulation of murine macrophages.

  10. BQ-123 prevents LPS-induced preterm birth in mice via the induction of uterine and placental IL-10

    Energy Technology Data Exchange (ETDEWEB)

    Olgun, Nicole S., E-mail: Nicole.olgun02@stjohns.edu [Department of Pharmaceutical Sciences, St. John' s University, 8000 Utopia Parkway, Jamaica, NY, 11439 (United States); Women and Children' s Research Laboratory, Winthrop University Hospital, 259 1st Street, Mineola, NY, 11501 (United States); Hanna, Nazeeh, E-mail: Nhanna@winthrop.org [Women and Children' s Research Laboratory, Winthrop University Hospital, 259 1st Street, Mineola, NY, 11501 (United States); Department of Pediatrics, Winthrop University Hospital, 259 1st Street, Mineola, NY, 11501 (United States); Reznik, Sandra E., E-mail: Rezniks@stjohns.edu [Department of Pharmaceutical Sciences, St. John' s University, 8000 Utopia Parkway, Jamaica, NY, 11439 (United States); Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461 (United States); Department of Obstetrics and Gynecology and Women' s Health, Albert Einstein College of Medicine, Bronx, NY 10461 (United States)

    2015-02-01

    Preterm birth (PTB), defined as any delivery occurring prior to the completion of 37 weeks' gestation, currently accounts for 11–12% of all births in the United States. Maternal genito-urinary infections account for up to 40% of all PTBS and induce a pro-inflammatory state in the host. The potent vasoconstrictor Endothelin-1 (ET-1) is known to be upregulated in the setting of infection, and elicits its effect by binding to the ET{sub A} receptor. We have previously shown that antagonism of the ET{sub A} receptor with BQ-123 is capable of preventing LPS-induced PTB in mice. We hypothesize that the administration of BQ-123 post LPS exposure will dismantle a positive feedback loop observed with pro-inflammatory cytokines upstream of ET-1. On GD 15.5, pregnant C57BL/6 mice were injected with PBS, LPS, BQ-123, or LPS + BQ-123. Changes at both the level of transcription and translation were observed in uterus and placenta in the ET-1 axis and in pro- and anti-inflammatory cytokines over the course of 12 h. We discovered that BQ-123, when administered 10 h post LPS, is capable of increasing production of uterine and placental Interleukin-10, causing a shift away from the pro-inflammatory state. We also observed that antagonism of the ET{sub A} receptor decreased IL-1β and TNFα in the placenta while also decreasing transcription of ET-1 in the uterus. Our results reinforce the role of ET-1 at the maternal fetal interface and highlight the potential benefit of ET{sub A} receptor blockade via the suppression of ET-1, and induction of a Th2 cytokine dominant state. - Highlights: • The pro-inflammatory response to LPS in the uterus and placenta is ET-1 dependent. • ET{sub A} blockade triggers up-regulation of IL-10 in uterus and placenta. • A positive feedback loop drives ET-1 expression in gestational tissue.

  11. EARLY GOAL DIRECTED THERAPY AT SEPTIC SYOK

    Directory of Open Access Journals (Sweden)

    Ayu Widyanti

    2013-04-01

    Full Text Available Sepsis is the most commom cause of death in children with critically ill. Using WHO criteria (severe sepsis defined as sepsis with acidosis, hypotension or both, it was determined that in 1995 there were more than 42.000 cases of severe sepsis in children in the United States with mortality rate was 10.3%. To answer that finding, evicende based protocol was made, it called early goal directed therapy (EGDT. EGDT is a comprehensive strategy to evaluate patient with septic shock include, challenge of fluid, antibiotic, vasopressor, measurement of central vein oxygen saturation, PRC transfusion, administering inotropic dan mechanic ventilation. All of these must be done in the first 6 hours since sepsis or septic shock was found, because if there is a delay of resuscitation, anything we do to increase oxygenation level of the cell will be useless.

  12. Mechanical ventilation with high tidal volumes attenuates myocardial dysfunction by decreasing cardiac edema in a rat model of LPS-induced peritonitis

    Directory of Open Access Journals (Sweden)

    Smeding Lonneke

    2012-03-01

    Full Text Available Abstract Background Injurious mechanical ventilation (MV may augment organ injury remote from the lungs. During sepsis, myocardial dysfunction is common and increased endothelial activation and permeability can cause myocardial edema, which may, among other factors, hamper myocardial function. We investigated the effects of MV with injuriously high tidal volumes on the myocardium in an animal model of sepsis. Methods Normal rats and intraperitoneal (i.p. lipopolysaccharide (LPS-treated rats were ventilated with low (6 ml/kg and high (19 ml/kg tidal volumes (Vt under general anesthesia. Non-ventilated animals served as controls. Mean arterial pressure (MAP, central venous pressure (CVP, cardiac output (CO and pulmonary plateau pressure (Pplat were measured. Ex vivo myocardial function was measured in isolated Langendorff-perfused hearts. Cardiac expression of endothelial vascular cell adhesion molecule (VCAM-1 and edema were measured to evaluate endothelial inflammation and leakage. Results MAP decreased after LPS-treatment and Vt-dependently, both independent of each other and with interaction. MV Vt-dependently increased CVP and Pplat and decreased CO. LPS-induced peritonitis decreased myocardial function ex vivo but MV attenuated systolic dysfunction Vt-dependently. Cardiac endothelial VCAM-1 expression was increased by LPS treatment independent of MV. Cardiac edema was lowered Vt-dependently by MV, particularly after LPS, and correlated inversely with systolic myocardial function parameters ex vivo. Conclusion MV attenuated LPS-induced systolic myocardial dysfunction in a Vt-dependent manner. This was associated with a reduction in cardiac edema following a lower transmural coronary venous outflow pressure during LPS-induced coronary inflammation.

  13. Allium cepa L. and Quercetin Inhibit RANKL/Porphyromonas gingivalis LPS-Induced Osteoclastogenesis by Downregulating NF-κB Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Tatiane Oliveira

    2015-01-01

    Full Text Available Objectives. We evaluated the in vitro modulatory effects of Allium cepa L. extract (AcE and quercetin (Qt on osteoclastogenesis under inflammatory conditions (LPS-induced. Methods. RAW 264.7 cells were differentiated with 30 ng/mL of RANKL, costimulated with PgLPS (1 µg/mL, and treated with AcE (50–1000 µg/mL or Qt (1.25, 2.5, or 5 µM. Cell viability was determined by alamarBlue and protein assays. Nuclei morphology was analysed by DAPI staining. TRAP assays were performed as follows: p-nitrophenyl phosphate was used to determine the acid phosphatase activity of the osteoclasts and TRAP staining was used to evaluate the number and size of TRAP-positive multinucleated osteoclast cells. Von Kossa staining was used to measure osteoclast resorptive activity. Cytokine levels were measured on osteoclast precursor cell culture supernatants. Using western blot analysis, p-IκBα and IκBα degradation, inhibitor of NF-kappaB, were evaluated. Results. Both AcE and Qt did not affect cell viability and significantly reduced osteoclastogenesis compared to control. We observed lower production of IL-6 and IL-1α and an increased production of IL-3 and IL-4. AcE and Qt downregulated NF-κB pathway. Conclusion. AcE and Qt may be inhibitors of osteoclastogenesis under inflammatory conditions (LPS-induced via attenuation of RANKL/PgLPS-induced NF-κB activation.

  14. Quince (Cydonia oblonga Miller) peel polyphenols modulate LPS-induced inflammation in human THP-1-derived macrophages through NF-κB, p38MAPK and Akt inhibition

    International Nuclear Information System (INIS)

    Essafi-Benkhadir, Khadija; Refai, Amira; Riahi, Ichrak; Fattouch, Sami; Karoui, Habib; Essafi, Makram

    2012-01-01

    Highlights: ► Quince peel polyphenols inhibit LPS-induced secretion of TNF-α and IL-8. ► Quince peel polyphenols augment LPS-induced secretion of IL-10 and IL-6. ► Quince peel polyphenols-mediated inhibition of LPS-induced secretion of TNF-α is partially mediated by IL-6. ► The anti-inflammatory effects of quince polyphenols pass through NF-κB, p38MAPK and Akt inhibition. -- Abstract: Chronic inflammation is a hallmark of several pathologies, such as rheumatoid arthritis, gastritis, inflammatory bowel disease, atherosclerosis and cancer. A wide range of anti-inflammatory chemicals have been used to treat such diseases while presenting high toxicity and numerous side effects. Here, we report the anti-inflammatory effect of a non-toxic, cost-effective natural agent, polyphenolic extract from the Tunisian quince Cydonia oblonga Miller. Lipopolysaccharide (LPS) treatment of human THP-1-derived macrophages induced the secretion of high levels of the pro-inflammatory cytokine TNF-α and the chemokine IL-8, which was inhibited by quince peel polyphenolic extract in a dose-dependent manner. Concomitantly, quince polyphenols enhanced the level of the anti-inflammatory cytokine IL-10 secreted by LPS-treated macrophages. We further demonstrated that the unexpected increase in IL-6 secretion that occurred when quince polyphenols were associated with LPS treatment was partially responsible for the polyphenols-mediated inhibition of TNF-α secretion. Biochemical analysis showed that quince polyphenols extract inhibited the LPS-mediated activation of three major cellular pro-inflammatory effectors, nuclear factor-kappa B (NF-κB), p38MAPK and Akt. Overall, our data indicate that quince peel polyphenolic extract induces a potent anti-inflammatory effect that may prove useful for the treatment of inflammatory diseases and that a quince-rich regimen may help to prevent and improve the treatment of such diseases.

  15. Chilean Strawberry Consumption Protects against LPS-Induced Liver Injury by Anti-Inflammatory and Antioxidant Capability in Sprague-Dawley Rats

    OpenAIRE

    Molinett, Sebastian; Nuñez, Francisca; Moya-León, María Alejandra; Zúñiga-Hernández, Jessica

    2015-01-01

    The Chilean strawberry fruit has high content of antioxidants and polyphenols. Previous studies evidenced antioxidant properties by in vitro methods. However, the antioxidant effect and its impact as functional food on animal health have not been evaluated. In this study, rats were fed with a Chilean strawberry aqueous extract (4 g/kg of animal per day) and then subjected to LPS-induced liver injury (5 mg/kg). Transaminases and histological studies revealed a reduction in liver injury in rats...

  16. Anti-Inflammatory Activity of Heterocarpin from the Salt Marsh Plant Corydalis heterocarpa in LPS-Induced RAW 264.7 Macrophage Cells

    Directory of Open Access Journals (Sweden)

    You Ah Kim

    2015-08-01

    Full Text Available The inhibitory effect of three chromones 1–3 and two coumarins 4–5 on the production of nitric oxide (NO was evaluated in LPS-induced RAW 264.7 macrophage cells. Among the compounds tested heterocarpin (1, a furochromone, significantly inhibited its production in a dose-dependent manner. In addition, heterocarpin suppressed prostaglandin E2 (PGE2 production and expression of cytokines such as inducible nitric oxide synthase (iNOS, cyclooxygenase-2 (COX-2, tumor necrosis factor-α (TNF-α, interleukin-1β (IL-1β and interleukin-6 (IL-6.

  17. Septic Systems Case Studies

    Science.gov (United States)

    A collection of septic systems case studies to help community planners, elected officials, health department staff, state officials, and interested citizens explore alternatives for managing their decentralized wastewater treatment systems.

  18. [Proteus mirabilis septic arthritis].

    Science.gov (United States)

    Sbiti, Mohammed; Bouhamidi, Bahia; Louzi, Lhoussaine

    2017-01-01

    Acute septic arthritis is rare. It is associated with poor prognosis in terms of mortality and morbidity. We report the case of a 61-year old patient with spontaneous Proteus mirabilis septic arthritis. He suffered from complicated diabetes associated with positive blood cultures and synovial fluid cultures. Patient's evolution was favorable thanks to early diagnosis and initiation of adequate antibiotic therapy. Proteus mirabilis septic arthritis is rare. On that basis we conducted a literature review of cases of Proteus mirabilis pyogenic arthritis to highlight the risk factors, pathogenesis, treatment and evolution of these diseases. Diagnosis is commonly based on microbiological analysis, early articular puncture biopsy is performed before the initiation of antibiotic treatment, direct examination, culture and antibiogram which are useful as guidance for antibiotic therapy. Septic arthritis is a diagnostic and therapeutic emergency; early management of this disease allows total healing without after-effects.

  19. Moringa fruit inhibits LPS-induced NO/iNOS expression through suppressing the NF-κ B activation in RAW264.7 cells.

    Science.gov (United States)

    Lee, Hyo-Jin; Jeong, Yun-Jeong; Lee, Tae-Sung; Park, Yoon-Yub; Chae, Whi-Gun; Chung, Il-Kyung; Chang, Hyeun-Wook; Kim, Cheorl-Ho; Choi, Yung-Hyun; Kim, Wun-Jae; Moon, Sung-Kwon; Chang, Young-Chae

    2013-01-01

    In this study, we evaluated the anti-inflammatory effects of moringa (Moringa oleifera Lam.), a natural biologically active substance, by determining its inhibitory effects on pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated macrophage RAW264.7 cells. Extracts from different parts of moringa (root, leaf, and fruit) reduced LPS-induced nitric oxide (NO) release in a dose-dependent manner. The moringa fruit extract most effectively inhibited LPS-induced NO production and levels of inducible nitric oxide synthase (iNOS). The moringa fruit extract also was shown to suppress the production of inflammatory cytokines including IL-1β, TNF-α, and IL-6. Furthermore, moringa fruit extract inhibited the cytoplasmic degradation of I κ B -α and the nuclear translocation of p65 proteins, resulting in lower levels of NF -κ B transactivation. Collectively, the results of this study demonstrate that moringa fruit extract reduces the levels of pro-inflammatory mediators including NO , IL-1β, TNF-α, and IL-6 via the inhibition of NF -κ B activation in RAW264.7 cells. These findings reveal, in part, the molecular basis underlying the anti-inflammatory properties of moringa fruit extract.

  20. Kaempferol alleviates LPS-induced neuroinflammation and BBB dysfunction in mice via inhibiting HMGB1 release and down-regulating TLR4/MyD88 pathway.

    Science.gov (United States)

    Cheng, Xiao; Yang, Ying-Lin; Yang, Huan; Wang, Yue-Hua; Du, Guan-Hua

    2018-03-01

    Kaempferol is a natural flavonoid with many biological activities including anti-oxidation and anti-inflammation. Nevertheless, its anti-neuroinflammation role and the relevant mechanism remain unclear. The present study was to investigate effects of kaempferol against LPS-induced neuroinflammation and blood-brain barrier dysfunction as well as the mechanism in mice. BALB/c mice were treated with LPS 5mg/kg to induce inflammation after pre-treatment with kaempferol 25, 50, or 100mg/kg for 7days. The results showed that kaempferol reduced the production of various pro-inflammatory factors and inflammatory proteins including IL-1β, IL-6, TNF-α, MCP-1, COX-2 and iNOS in brain tissues. In addition, kaempferol also protected BBB integrity and increased BBB related proteins including occludin-1, claudin-1 and CX43 in brain of LPS-induced mice. Furthermore, kaempferol significantly reduced HMGB1 level and suppressed TLR4/MyD88 inflammatory pathway in both transcription level and translation level. These results collectively suggested that kaempferol might be a promising neuroprotective agent for alleviating inflammatory responses and BBB dysfunction by inhibiting HMGB1 release and down-regulating TLR4/MyD88 inflammatory pathway. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Therapeutic effect of methyl salicylate 2-O-β-d-lactoside on LPS-induced acute lung injury by inhibiting TAK1/NF-kappaB phosphorylation and NLRP3 expression.

    Science.gov (United States)

    Yang, Shengqian; Yu, Ziru; Yuan, Tianyi; Wang, Lin; Wang, Xue; Yang, Haiguang; Sun, Lan; Wang, Yuehua; Du, Guanhua

    2016-11-01

    Acute lung injury (ALI), characterized by pulmonary edema and inflammatory cell infiltration, is a common syndrome of acute hypoxemic respiratory failure. Methyl salicylate 2-O-β-d-lactoside (MSL), a natural derivative of salicylate extracted from Gaultheria yunnanensis (Franch.) Rehder, was reported to have potent anti-inflammatory effects on the progression of collagen or adjuvant-induced arthritis in vivo and in vitro. The aim of this study is to investigate the therapeutic effect of MSL on lipopolysaccharide (LPS)-induced acute lung injury and reveal underlying molecular mechanisms. Our results showed that MSL significantly ameliorated pulmonary edema and histological severities, and inhibited IL-6 and IL-1β production in LPS-induced ALI mice. MSL also reduced MPO activity in lung tissues and the number of inflammatory cells in BALF. Moreover, we found that MSL significantly inhibited LPS-induced TAK1 and NF-κB p65 phosphorylation, as well as the expression of NLRP3 protein in lung tissues. Furthermore, MSL significantly inhibited LPS-induced TAK1 and NF-κB p65 phosphorylation in Raw264.7 cells. In addition, MSL significantly inhibited nuclear translocation of NF-κB p65 in cells treated with LPS in vitro. Taken together, our results suggested that MSL exhibited a therapeutic effect on LPS-induced ALI by inhibiting TAK1/NF-κB phosphorylation and NLRP3 expression. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. [Surgical intensive care medicine. Current therapy concepts for septic diseases].

    Science.gov (United States)

    Niederbichler, A D; Ipaktchi, K; Jokuszies, A; Hirsch, T; Altintas, M A; Handschin, A E; Busch, K H; Gellert, M; Steinau, H-U; Vogt, P M; Steinsträsser, L

    2009-10-01

    The clinical appearance of septic disorders is characterized by an enormous dynamic. The sepsis-induced dysbalance of the immune system necessitates immediate and aggressive therapeutic interventions to prevent further damage progression of the disease to septic shock and multiple organ failure. This includes supportive therapy to normalize and maintain organ and tissue perfusion as well as the identification of the infection focus. In cases where an infectious focus is identified, surgical source control frequently is a key element of the treatment strategy besides pharmacologic and supportive measures. The integrative approach of the management of septic patients requires rapid communication between the involved medical disciplines and the nursing personnel. Therefore, this article outlines current therapeutic concepts of septic diseases as well as central nursing aspects.

  3. Quince (Cydonia oblonga Miller) peel polyphenols modulate LPS-induced inflammation in human THP-1-derived macrophages through NF-{kappa}B, p38MAPK and Akt inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Essafi-Benkhadir, Khadija [Laboratoire d' epidemiologie Moleculaire et Pathologie Experimentale Appliquee Aux Maladies Infectieuses, Institut Pasteur de Tunis (Tunisia); Refai, Amira [Laboratoire de Recherche sur la Transmission, le Controle et l' immunobiologie des Infections, Institut Pasteur de Tunis (Tunisia); Riahi, Ichrak [Laboratoire d' epidemiologie Moleculaire et Pathologie Experimentale Appliquee Aux Maladies Infectieuses, Institut Pasteur de Tunis (Tunisia); Fattouch, Sami [Laboratory LIP-MB National Institute of Applied Sciences and Technology, Tunis (Tunisia); Karoui, Habib [Laboratoire d' epidemiologie Moleculaire et Pathologie Experimentale Appliquee Aux Maladies Infectieuses, Institut Pasteur de Tunis (Tunisia); Essafi, Makram, E-mail: makram.essafi@pasteur.rns.tn [Laboratoire de Recherche sur la Transmission, le Controle et l' immunobiologie des Infections, Institut Pasteur de Tunis (Tunisia)

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer Quince peel polyphenols inhibit LPS-induced secretion of TNF-{alpha} and IL-8. Black-Right-Pointing-Pointer Quince peel polyphenols augment LPS-induced secretion of IL-10 and IL-6. Black-Right-Pointing-Pointer Quince peel polyphenols-mediated inhibition of LPS-induced secretion of TNF-{alpha} is partially mediated by IL-6. Black-Right-Pointing-Pointer The anti-inflammatory effects of quince polyphenols pass through NF-{kappa}B, p38MAPK and Akt inhibition. -- Abstract: Chronic inflammation is a hallmark of several pathologies, such as rheumatoid arthritis, gastritis, inflammatory bowel disease, atherosclerosis and cancer. A wide range of anti-inflammatory chemicals have been used to treat such diseases while presenting high toxicity and numerous side effects. Here, we report the anti-inflammatory effect of a non-toxic, cost-effective natural agent, polyphenolic extract from the Tunisian quince Cydonia oblonga Miller. Lipopolysaccharide (LPS) treatment of human THP-1-derived macrophages induced the secretion of high levels of the pro-inflammatory cytokine TNF-{alpha} and the chemokine IL-8, which was inhibited by quince peel polyphenolic extract in a dose-dependent manner. Concomitantly, quince polyphenols enhanced the level of the anti-inflammatory cytokine IL-10 secreted by LPS-treated macrophages. We further demonstrated that the unexpected increase in IL-6 secretion that occurred when quince polyphenols were associated with LPS treatment was partially responsible for the polyphenols-mediated inhibition of TNF-{alpha} secretion. Biochemical analysis showed that quince polyphenols extract inhibited the LPS-mediated activation of three major cellular pro-inflammatory effectors, nuclear factor-kappa B (NF-{kappa}B), p38MAPK and Akt. Overall, our data indicate that quince peel polyphenolic extract induces a potent anti-inflammatory effect that may prove useful for the treatment of inflammatory diseases and that a quince

  4. Lipopolysaccharide (LPS)-binding protein stimulates CD14-dependent Toll-like receptor 4 internalization and LPS-induced TBK1-IKKϵ-IRF3 axis activation.

    Science.gov (United States)

    Tsukamoto, Hiroki; Takeuchi, Shino; Kubota, Kanae; Kobayashi, Yohei; Kozakai, Sao; Ukai, Ippo; Shichiku, Ayumi; Okubo, Misaki; Numasaki, Muneo; Kanemitsu, Yoshitomi; Matsumoto, Yotaro; Nochi, Tomonori; Watanabe, Kouichi; Aso, Hisashi; Tomioka, Yoshihisa

    2018-05-14

    Toll-like receptor 4 (TLR4) is an indispensable immune receptor for lipopolysaccharide (LPS), a major component of the Gram-negative bacterial cell wall. Following LPS stimulation, TLR4 transmits the signal from the cell surface and becomes internalized in an endosome. However, the spatial regulation of TLR4 signaling is not fully understood. Here, we investigated the mechanisms of LPS-induced TLR4 internalization and clarified the roles of the extracellular LPS-binding molecules, LPS-binding protein (LBP), and glycerophosphatidylinositol-anchored protein (CD14). LPS stimulation of CD14-expressing cells induced TLR4 internalization in the presence of serum, and an inhibitory anti-LBP mAb blocked its internalization. Addition of LBP to serum-free cultures restored LPS-induced TLR4 internalization to comparable levels of serum. The secretory form of the CD14 (sCD14) induced internalization but required a much higher concentration than LBP. An inhibitory anti-sCD14 mAb was ineffective for serum-mediated internalization. LBP lacking the domain for LPS transfer to CD14 and a CD14 mutant with reduced LPS binding both attenuated TLR4 internalization. Accordingly, LBP is an essential serum molecule for TLR4 internalization, and its LPS transfer to membrane-anchored CD14 (mCD14) is a prerequisite. LBP induced the LPS-stimulated phosphorylation of TBK1, IKKϵ, and IRF3, leading to IFN-β expression. However, LPS-stimulated late activation of NFκB or necroptosis were not affected. Collectively, our results indicate that LBP controls LPS-induced TLR4 internalization, which induces TLR adaptor molecule 1 (TRIF)-dependent activation of the TBK1-IKKϵ-IRF3-IFN-β pathway. In summary, we showed that LBP-mediated LPS transfer to mCD14 is required for serum-dependent TLR4 internalization and activation of the TRIF pathway. Copyright © 2018, The American Society for Biochemistry and Molecular Biology.

  5. Molecular and Cellular Mechanisms of Septic Shock

    Science.gov (United States)

    1988-03-01

    due to gastric dilation - volvulus (6Y). The LAL-chromogenic procedure iýs sensitive and reliable for detecting plasma LPS. LPS has a short initial T 1/2...portal injections of endotoxin. and intestinal ischemia. Endotoxin (LPS) was quantitated in canine plasma using the Limulus amebocyte lysate (LAL...CV=1O), and stability of diluted, heat-treated, frozen samples (at least 8 wk). Analysis of canine plasma samples following sublethal IV (jugular or

  6. An interesting septic embolism

    Directory of Open Access Journals (Sweden)

    Funda Uluorman

    2014-01-01

    Full Text Available Septic pulmonary embolism is a rare disease but mortality and morbidity of it is high. Septic pulmonary emboli comes from infected heart valves, thrombophlebitis, and pulmonary artery catheter or infected pacemaker wires as many sources [1,2]. In recent years, pacemaker is a common treatment of the bradiarrhythmia that is persisted in the etiology of septic embolism, its applications has started to pick up [3]. There is the growing number of patients with pacemaker, according to this the frequency of pacemaker lead infection and the number of patients at risk for right-sided endocarditis increase [4]. The patients don't have specific clinical and radiological features because of this it is very difficult to define, so the diagnosis is often delayed [5]. A detailed medical history, a detailed physical examination in diagnosis and evaluation of good additional imaging methods is very important. Early diagnosis and proper treatment, the implementation of the management, can provide good results.

  7. Characterization of recombinant human HBP/CAP37/azurocidin, a pleiotropic mediator of inflammation-enhancing LPS-induced cytokine release from monocytes.

    Science.gov (United States)

    Rasmussen, P B; Bjørn, S; Hastrup, S; Nielsen, P F; Norris, K; Thim, L; Wiberg, F C; Flodgaard, H

    1996-07-15

    Neutrophil-derived heparin-binding protein (HBP) is a strong chemoattractant for monocytes. We report here for the first time the expression of recombinant HBP. A baculovirus containing the human HBP cDNA mediated in insect cells the secretion of a 7-residue N-terminally extended HBP form (pro-HBP). Deletion of the pro-peptide-encoding cDNA sequence resulted in correctly processed HBP at the N-terminus. Electrospray mass spectrum analysis of recombinant HBP yielded a molecular weight of 27.237 +/- 3 amu. Consistent with this mass is a HBP form of 225 amino acids (mature part +3 amino acid C-terminal extension). The biological activity of recombinant HBP was confirmed by its chemotactic action towards monocytes. Furthermore, we have shown that recombinant HBP stimulates in a dose-dependent manner the lipopolysaccharide (LPS)-induced cytokine release from human monocytes.

  8. Scandoside Exerts Anti-Inflammatory Effect Via Suppressing NF-κB and MAPK Signaling Pathways in LPS-Induced RAW 264.7 Macrophages

    Directory of Open Access Journals (Sweden)

    Jingyu He

    2018-02-01

    Full Text Available The iridoids of Hedyotis diffusa Willd play an important role in the anti-inflammatory process, but the specific iridoid with anti-inflammatory effect and its mechanism has not be thoroughly studied. An iridoid compound named scandoside (SCA was isolated from H. diffusa and its anti-inflammatory effect was investigated in lipopolysaccharide (LPS-induced RAW 264.7 macrophages. Its anti-inflammatory mechanism was confirmed by in intro experiments and molecular docking analyses. As results, SCA significantly decreased the productions of nitric oxide (NO, prostaglandin E2 (PGE2, tumor necrosis factor-α (TNF-α and interleukin-6 (IL-6 and inhibited the levels of inducible nitric oxide synthase (iNOS, cyclooxygenase-2 (COX-2, TNF-α and IL-6 messenger RNA (mRNA expression in LPS-induced RAW 264.7 macrophages. SCA treatment suppressed the phosphorylation of inhibitor of nuclear transcription factor kappa-B alpaha (IκB-α, p38, extracellular signal-regulated kinase (ERK and c-Jun N-terminal kinase (JNK. The docking data suggested that SCA had great binding abilities to COX-2, iNOS and IκB. Taken together, the results indicated that the anti-inflammatory effect of SCA is due to inhibition of pro-inflammatory cytokines and mediators via suppressing the nuclear transcription factor kappa-B (NF-κB and mitogen-activated protein kinase (MAPK signaling pathways, which provided useful information for its application and development.

  9. Progesterone is essential for protecting against LPS-induced pregnancy loss. LIF as a potential mediator of the anti-inflammatory effect of progesterone.

    Directory of Open Access Journals (Sweden)

    Julieta Aisemberg

    Full Text Available Lipopolysaccharide (LPS administration to mice on day 7 of gestation led to 100% embryonic resorption after 24 h. In this model, nitric oxide is fundamental for the resorption process. Progesterone may be responsible, at least in part, for a Th2 switch in the feto-maternal interface, inducing active immune tolerance against fetal antigens. Th2 cells promote the development of T cells, producing leukemia inhibitory factor (LIF, which seems to be important due to its immunomodulatory action during early pregnancy. Our aim was to evaluate the involvement of progesterone in the mechanism of LPS-induced embryonic resorption, and whether LIF can mediate hormonal action. Using in vivo and in vitro models, we provide evidence that circulating progesterone is an important component of the process by which infection causes embryonic resorption in mice. Also, LIF seems to be a mediator of the progesterone effect under inflammatory conditions. We found that serum progesterone fell to very low levels after 24 h of LPS exposure. Moreover, progesterone supplementation prevented embryonic resorption and LPS-induced increase of uterine nitric oxide levels in vivo. Results show that LPS diminished the expression of the nuclear progesterone receptor in the uterus after 6 and 12 h of treatment. We investigated the expression of LIF in uterine tissue from pregnant mice and found that progesterone up-regulates LIF mRNA expression in vitro. We observed that LIF was able to modulate the levels of nitric oxide induced by LPS in vitro, suggesting that it could be a potential mediator of the inflammatory action of progesterone. Our observations support the view that progesterone plays a critical role in a successful pregnancy as an anti-inflammatory agent, and that it could have possible therapeutic applications in the prevention of early reproductive failure associated with inflammatory disorders.

  10. Involvement of JNK and NF-κB pathways in lipopolysaccharide (LPS)-induced BAG3 expression in human monocytic cells.

    Science.gov (United States)

    Wang, Hua-Qin; Meng, Xin; Liu, Bao-Qin; Li, Chao; Gao, Yan-Yan; Niu, Xiao-Fang; Li, Ning; Guan, Yifu; Du, Zhen-Xian

    2012-01-01

    Lipopolysaccharide (LPS) is an outer-membrane glycolipid component of Gram-negative bacteria known for its fervent ability to activate monocytic cells and for its potent proinflammatory capabilities. Bcl-2-associated athanogene 3 (BAG3) is a survival protein that has been shown to be stimulated during cell response to stressful conditions, such as exposure to high temperature, heavy metals, proteasome inhibition, and human immunodeficiency virus 1 (HIV-1) infection. In addition, BAG3 regulates replication of Varicella-Zoster Virus (VZV) and Herpes Simplex Virus (HSV) replication, suggesting that BAG3 could participate in the host response to infection. In the current study, we found that LPS increased the expression of BAG3 in a dose- and time-dependent manner. Actinomycin D completely blocked the LPS-induced BAG3 accumulation, as well as LPS activated the proximal promoter of BAG3 gene, supported that the induction by LPS occurred at the level of gene transcription. LPS-induced BAG3 expression was blocked by JNK or NF-κB inhibition, suggesting that JNK and NF-κB pathways participated in BAG3 induction by LPS. In addition, we also found that induction of BAG3 was implicated in monocytic cell adhesion to extracellular matrix induced by LPS. Overall, the data support that BAG3 is induced by LPS via JNK and NF-κB-dependent signals, and involved in monocytic cell-extracellular matrix interaction, suggesting that BAG3 may have a role in the host response to LPS stimulation. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Xanthohumol ameliorates lipopolysaccharide (LPS-induced acute lung injury via induction of AMPK/GSK3β-Nrf2 signal axis

    Directory of Open Access Journals (Sweden)

    Hongming Lv

    2017-08-01

    Full Text Available Abundant natural flavonoids can induce nuclear factor-erythroid 2 related factor 2 (Nrf2 and/or AMP-activated protein kinase (AMPK activation, which play crucial roles in the amelioration of various inflammation- and oxidative stress-induced diseases, including acute lung injury (ALI. Xanthohumol (Xn, a principal prenylflavonoid, possesses anti-inflammation and anti-oxidant activities. However, whether Xn could protect from LPS-induced ALI through inducing AMPK/Nrf2 activation and its downstream signals, are still poorly elucidated. Accordingly, we focused on exploring the protective effect of Xn in the context of ALI and the involvement of underlying molecular mechanisms. Our findings indicated that Xn effectively alleviated lung injury by reduction of lung W/D ratio and protein levels, neutrophil infiltration, MDA and MPO formation, and SOD and GSH depletion. Meanwhile, Xn significantly lessened histopathological changes, reactive oxygen species (ROS generation, several cytokines secretion, and iNOS and HMGB1 expression, and inhibited Txnip/NLRP3 inflammasome and NF-κB signaling pathway activation. Additionally, Xn evidently decreased t-BHP-stimulated cell apoptosis, ROS generation and GSH depletion but increased various anti-oxidative enzymes expression regulated by Keap1-Nrf2/ARE activation, which may be associated with AMPK and GSK3β phosphorylation. However, Xn-mediated inflammatory cytokines and ROS production, histopathological changes, Txnip/NLRP3 inflammasome and NF-κB signaling pathway in WT mice were remarkably abrogated in Nrf2-/- mice. Our experimental results firstly provided a support that Xn effectively protected LPS-induced ALI against oxidative stress and inflammation damage which are largely dependent upon upregulation of the Nrf2 pathway via activation of AMPK/GSK3β, thereby suppressing LPS-activated Txnip/NLRP3 inflammasome and NF-κB signaling pathway. Keywords: Xanthohumol, Acute lung injury, Oxidative stress

  12. Kaempferol and Chrysin Synergies to Improve Septic Mice Survival.

    Science.gov (United States)

    Harasstani, Omar A; Tham, Chau Ling; Israf, Daud A

    2017-01-06

    Previously, we reported the role of synergy between two flavonoids-namely, chrysin and kaempferol-in inhibiting the secretion of a few major proinflammatory mediators such as tumor necrosis factor -alpha (TNF-α), prostaglandin E₂ (PGE₂) , and nitric oxide (NO) from lipopolysaccharide (LPS)-induced RAW 264.7 cells. The present study aims to evaluate the effects of this combination on a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Severe sepsis was induced in male ICR mice ( n = 7) via the CLP procedure. The effects of chrysin and kaempferol combination treatment on septic mice were investigated using a 7-day survival study. The levels of key proinflammatory mediators and markers-such as aspartate aminotransferase (AST), TNF-α, and NO-in the sera samples of the septic mice were determined via ELISA and fluorescence determination at different time point intervals post-CLP challenge. Liver tissue samples from septic mice were harvested to measure myeloperoxidase (MPO) levels using a spectrophotometer. Moreover, intraperitoneal fluid (IPF) bacterial clearance and total leukocyte count were also assessed to detect any antibacterial effects exerted by chrysin and kaempferol, individually and in combination. Kaempferol treatment improved the survival rate of CLP-challenged mice by up to 16%. During this treatment, kaempferol expressed antibacterial, antiapoptotic and antioxidant activities through the attenuation of bacterial forming units, AST and NO levels, and increased polymorphonuclear leukocyte (PMN) count in the IPF. On the other hand, the chrysin treatment significantly reduced serum TNF-α levels. However, it failed to significantly improve the survival rate of the CLP-challenged mice. Subsequently, the kaempferol/chrysin combination treatment significantly improved the overall 7-day survival rate by 2-fold-up to 29%. Kaempferol and chrysin revealed some synergistic effects by acting individually upon multiple

  13. Bacterial sepsis after extracorporeal shock-wave lithotripsy (ESWL) of calyceal diverticular stone.

    Science.gov (United States)

    Oh, Mi Mi; Kim, Jin Wook; Kim, Jong Wook; Chae, Ji Yun; Yoon, Cheol Yong; Park, Hong Seok; Park, Min Gu; Moon, Du Geon

    2013-02-01

    Most calyceal diverticula are asymptomatic but symptoms occur when there is urinary stasis leading to infection and calculi. Septic shock after ESWL of calyceal stone occurs rarely. A 24-year-old woman had septic shock due to after extracorporeal shock-wave lithotripsy (ESWL) of asymptomatic calyceal diverticular stone.

  14. Soluble β-(1,3)-glucans enhance LPS-induced response in the monocyte activation test, but inhibit LPS-mediated febrile response in rabbits: Implications for pyrogenicity tests.

    Science.gov (United States)

    Pardo-Ruiz, Zenia; Menéndez-Sardiñas, Dalia E; Pacios-Michelena, Anabel; Gabilondo-Ramírez, Tatiana; Montero-Alejo, Vivian; Perdomo-Morales, Rolando

    2016-01-01

    In the present study, we aimed to determine the influence of β-(1,3)-d-glucans on the LPS-induced pro-inflammatory cytokine response in the Monocyte Activation Test (MAT) for pyrogens, and on the LPS-induced febrile response in the Rabbit Pyrogen Test (RPT), thus evaluating the resulting effect in the outcome of each test. It was found that β-(1,3)-d-glucans elicited the production of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α, also known as endogenous pyrogens, but not enough to classify them as pyrogenic according to MAT. The same β-(1,3)-d-glucans samples were non-pyrogenic by RPT. However, β-(1,3)-d-glucans significantly enhanced the LPS-induced pro-inflammatory cytokines response in MAT, insomuch that samples containing non-pyrogenic concentrations of LPS become pyrogenic. On the other hand, β-(1,3)-d-glucans had no effect on sub-pyrogenic LPS doses in the RPT, but surprisingly, inhibited the LPS-induced febrile response of pyrogenic LPS concentrations. Thus, while β-(1,3)-d-glucans could mask the LPS pyrogenic activity in the RPT, they exerted an overstimulation of pro-inflammatory cytokines in the MAT. Hence, MAT provides higher safety since it evidences an unwanted biological response, which is not completely controlled and is overlooked by the RPT. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. p38 mitogen-activated protein kinase up-regulates LPS-induced NF-κB activation in the development of lung injury and RAW 264.7 macrophages

    International Nuclear Information System (INIS)

    Kim, Hee J.; Lee, Hui S.; Chong, Young H.; Kang, Jihee Lee

    2006-01-01

    Clarification of the key regulatory steps that lead to nuclear factor-kappa B (NF-κB) under cellular and pathological conditions is very important. The action of p38 mitogen-activated protein kinase (MAPK) on the upstream of NF-κB activation remains controversial. To examine this issue using an in vivo lung injury model, SB203580, a p38 MAPK inhibitor was given intraorally 1 h prior to lipopolysaccharide (LPS) treatment (intratracheally). The mice were sacrificed 4 h after LPS treatment. SB203580 substantially suppressed LPS-induced rises in p38 MAPK phosphorylation, neutrophil recruitment, total protein content in bronchoalveolar lavage fluid, and apoptosis of bronchoalveolar cells. Furthermore, SB203580 blocked LPS-induced NF-κB activation in lung tissue through down-regulation of serine phosphorylation, degradation of IκB-α, and consequent translocation of the p65 subunit of NF-κB to the nucleus. It is likely that, in cultured RAW 264.7 macrophages, SB203580 also blocked LPS-induced NF-κB activation in a dose-dependent manner. SB203580 inhibited LPS-induced serine phosphorylation, degradation of IκB-α, and tyrosine phosphorylation of p65 NF-κB. These data indicate that p38 MAPK acts upstream of LPS-induced NF-κB activation by modulating the phosphorylation of IκB-α and p65 NF-κB during acute lung injury. Because LPS-stimulated macrophages may contribute to inflammatory lung injury, the inhibition of the p38 MAPK-mediated intracellular signaling pathway leading to NF-κB activation represents a target for the attenuation of lung inflammation and parenchymal damage

  16. Propofol pretreatment attenuates LPS-induced granulocyte-macrophage colony-stimulating factor production in cultured hepatocytes by suppressing MAPK/ERK activity and NF-κB translocation

    International Nuclear Information System (INIS)

    Jawan, Bruno; Kao, Y.-H.; Goto, Shigeru; Pan, M.-C.; Lin, Y.-C.; Hsu, L.-W.; Nakano, Toshiaki; Lai, C.-Y.; Sun, C.-K.; Cheng, Y.-F.; Tai, M.-H.

    2008-01-01

    Propofol (PPF), a widely used intravenous anesthetic for induction and maintenance of anesthesia during surgeries, was found to possess suppressive effect on host immunity. This study aimed at investigating whether PPF plays a modulatory role in the lipopolysaccharide (LPS)-induced inflammatory cytokine expression in a cell line of rat hepatocytes. Morphological observation and viability assay showed that PPF exhibits no cytotoxicity at concentrations up to 300 μM after 48 h incubation. Pretreatment with 100 μM PPF for 24 h prior to LPS stimulation was performed to investigate the modulatory effect on LPS-induced inflammatory gene production. The results of semi-quantitative RT-PCR demonstrated that PPF pretreatment significantly suppressed the LPS-induced toll-like receptor (TLR)-4, CD14, tumor necrosis factor (TNF)-α, and granulocyte-macrophage colony-stimulating factor (GM-CSF) gene expression. Western blotting analysis showed that PPF pretreatment potentiated the LPS-induced TLR-4 downregulation. Flow cytometrical analysis revealed that PPF pretreatment showed no modulatory effect on the LPS-upregulated CD14 expression on hepatocytes. In addition, PPF pretreatment attenuated the phosphorylation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and IκBα, as well as the nuclear translocation of NF-κB primed by LPS. Moreover, addition of PD98059, a MAPK kinase inhibitor, significantly suppressed the LPS-induced NF-κB nuclear translocation and GM-CSF production, suggesting that the PPF-attenuated GM-CSF production in hepatocytes may be attributed to its suppressive effect on MAPK/ERK signaling pathway. In conclusion, PPF as an anesthetic may clinically benefit those patients who are vulnerable to sepsis by alleviating sepsis-related inflammatory response in livers

  17. Análise da qualidade de vida após a alta hospitalar em sobreviventes de sepse grave e choque séptico Analysis of quality of life following hospital discharge among survivors of severe sepsis and septic shock

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    Glauco Adrieno Westphal

    2012-06-01

    Full Text Available OBJETIVO: Descrever a repercussão da sepse grave e do choque séptico sobre a qualidade de vida após a alta hospitalar. MÉTODOS: Estudo controlado realizado em dois hospitais gerais de Joinville, Santa Catarina, Brasil, envolvendo pacientes internados com sepse grave ou choque séptico no período de agosto de 2005 a novembro de 2007. Os pacientes foram contatados por telefone entre junho e novembro de 2009. Os sobreviventes responderam ao Short Form-36, um questionário de qualidade de vida, dois anos após a alta. O questionário também foi respondido por um grupo controle composto de pessoas que habitavam o mesmo domicílio dos sobreviventes, sem internação recente e com idade mais próxima possível à do paciente. RESULTADOS: De 217 pacientes com sepse grave ou choque séptico, 112 (51,6% sobreviveram à internação. A sobrevida pós-alta hospitalar foi de 41,02% em 180 dias, 37,4% após um ano, 34¡3% em 18 meses e 32,3% em dois anos. Trinta e seis sobreviventes responderam ao Short Form-36. Houve comprometimento da qualidade de vida dos sobreviventes (No. = 36 em relação ao grupo controle (No. = 36 nos domínios: capacidade funcional (59 ± 32 versus 91 ± 18; P OBJECTIVE: Describe the impact of severe sepsis and septic shock on patients' quality of life following hospital discharge. METHODS: A controlled study conducted in two general hospitals of Joinville, Santa Catarina, Brazil, of in-patients with severe sepsis or septic shock during the period of August 2005 through November 2007. The patients were contacted by telephone between June and November 2009. The study group responded to Short Form-36, a questionnaire on the quality of life, two years after being discharged from hospital. The questionnaire was also answered by a control group composed of people who lived at the same residence as the study subjects, had no recent hospitalization, and were close in age. Results: Of 217 patients with severe sepsis or septic shock

  18. Glucose transport and milk secretion during manipulated plasma insulin and glucose concentrations and during LPS-induced mastitis in dairy cows.

    Science.gov (United States)

    Gross, J J; van Dorland, H A; Wellnitz, O; Bruckmaier, R M

    2015-08-01

    In dairy cows, glucose is essential as energy source and substrate for milk constituents. The objective of this study was to investigate effects of long-term manipulated glucose and insulin concentrations in combination with a LPS-induced mastitis on mRNA abundance of glucose transporters and factors involved in milk composition. Focusing on direct effects of insulin and glucose without influence of periparturient endocrine adaptations, 18 dairy cows (28 ± 6 weeks of lactation) were randomly assigned to one of three infusion treatments for 56 h (six animals each). Treatments included a hyperinsulinemic hypoglycaemic clamp (HypoG), a hyperinsulinemic euglycaemic clamp (EuG) and a control group (NaCl). After 48 h of infusions, an intramammary challenge with LPS from E. coli was performed and infusions continued for additional 8 h. Mammary gland biopsies were taken before, at 48 (before LPS challenge) and at 56 h (after LPS challenge) of infusion, and mRNA abundance of genes involved in mammary gland metabolism was measured by RT-qPCR. During the 48 h of infusions, mRNA abundance of glucose transporters GLUT1, 3, 4, 8, 12, SGLT1, 2) was not affected in HypoG, while they were downregulated in EuG. The mRNA abundance of alpha-lactalbumin, insulin-induced gene 1, κ-casein and acetyl-CoA carboxylase was downregulated in HypoG, but not affected in EuG. Contrary during the intramammary LPS challenge, most of the glucose transporters were downregulated in NaCl and HypoG, but not in EuG. The mRNA abundance of glucose transporters in the mammary gland seems not to be affected by a shortage of glucose, while enzymes and milk constituents directly depending on glucose as a substrate are immediately downregulated. During LPS-induced mastitis in combination with hypoglycaemia, mammary gland metabolism was more aligned to save glucose for the immune system compared to a situation without limited glucose availability during EuG. Journal of Animal Physiology and Animal

  19. Evidence for CB2 receptor involvement in LPS-induced reduction of cAMP intracellular levels in uterine explants from pregnant mice: pathophysiological implications.

    Science.gov (United States)

    Salazar, Ana Inés; Carozzo, Alejandro; Correa, Fernando; Davio, Carlos; Franchi, Ana María

    2017-07-01

    What is the role of the endocannabinoid system (eCS) on the lipopolysaccharide (LPS) effects on uterine explants from 7-day pregnant mice in a murine model of endotoxin-induced miscarriage? We found evidence for cannabinoid receptor type2 (CB2) involvement in LPS-induced increased prostaglandin-F2α (PGF2α) synthesis and diminished cyclic adenosine monophosphate (cAMP) intracellular content in uterine explants from early pregnant mice. Genital tract infections by Gram-negative bacteria are a common complication of human pregnancy that results in an increased risk of pregnancy loss. LPS, the main component of the Gram-negative bacterial wall, elicits a strong maternal inflammatory response that results in embryotoxicity and embryo resorption in a murine model endotoxin-induced early pregnancy loss. We have previously shown that the eCS mediates the embryotoxic effects of LPS, mainly via CB1 receptor activation. An in vitro study of mice uterine explants was performed to investigate the eCS in mediating the effects of LPS on PGF2α production and cAMP intracellular content. Eight to 12-week-old virgin female BALB/c or CD1 (wild-type [WT] or CB1-knockout [CB1-KO]) mice were paired with 8- to 12-week-old BALB/c or CD1 (WT or CB1-KO) males, respectively. On day 7 of pregnancy, BALB/c, CD1 WT or CD1 CB1-KO mice were euthanized, the uteri were excised, implantation sites were removed and the uterine tissues were separated from decidual and embryo tissues. Uterine explants were cultured and exposed for an appropriate amount of time to different pharmacological treatments. The tissues were then collected for cAMP assay and PGF2α content determination by radioimmunoassay. In vitro treatment of uteri explants from 7-day pregnant BALB/c or CD1 (WT or CB1-KO) mice with LPS induced an increased production of PGF2α (P Investigaciones Científicas y Técnicas (PIP 2012/0061). Dr Carlos Davio was funded by Agencia Nacional para la Promoción Científica y Tecnológica (PICT 2013

  20. Plumbagin, a vitamin K3 analogue, abrogates lipopolysaccharide-induced oxidative stress, inflammation and endotoxic shock via NF-κB suppression.

    Science.gov (United States)

    Checker, Rahul; Patwardhan, Raghavendra S; Sharma, Deepak; Menon, Jisha; Thoh, Maikho; Sandur, Santosh K; Sainis, Krishna B; Poduval, T B

    2014-04-01

    Plumbagin has been reported to modulate cellular redox status and suppress NF-κB. In the present study, we investigated the effect of plumbagin on lipopolysaccharide (LPS)-induced endotoxic shock, oxidative stress and inflammatory parameters in vitro and in vivo. Plumbagin inhibited LPS-induced nitric oxide, TNF-α, IL-6 and prostaglandin-E2 production in a concentration-dependent manner in RAW 264.7 cells without inducing any cell death. Plumbagin modulated cellular redox status in RAW cells. Plumbagin treatment significantly reduced MAPkinase and NF-κB activation in macrophages. Plumbagin prevented mice from endotoxic shock-associated mortality and decreased serum levels of pro-inflammatory markers. Plumbagin administration ameliorated LPS-induced oxidative stress in peritoneal macrophages and splenocytes. Plumbagin also attenuated endotoxic shock-associated changes in liver and lung histopathology and decreased the activation of ERK and NF-κB in liver. These findings demonstrate the efficacy of plumbagin in preventing LPS-induced endotoxemia and also provide mechanistic insights into the anti-inflammatory effects of plumbagin.

  1. Attenuation of LPS-induced inflammation by ICT, a derivate of icariin, via inhibition of the CD14/TLR4 signaling pathway in human monocytes.

    Science.gov (United States)

    Wu, Jinfeng; Zhou, Junmin; Chen, Xianghong; Fortenbery, Nicole; Eksioglu, Erika A; Wei, Sheng; Dong, Jingcheng

    2012-01-01

    To evaluate the anti-inflammatory potential of ICT in LPS stimulated human innate immune cells. 3, 5, 7-Trihydroxy-4'-methoxy-8-(3-hydroxy-3- methylbutyl)-flavone (ICT) is a novel derivative of icariin, the major active ingredient of Herba Epimedii, an herb used in traditional Chinese medicine. We previously demonstrated its anti-inflammatory potential in a murine macrophage cell line as well as in mouse models. We measured TNF-α production by ELISA, TLR4/CD14 expression by flow cytometry, and NF-κB and MAPK activation by western blot all in LPS-stimulated PBMC, human monocytes, or THP-1 cells after treatment with ICT. ICT inhibited LPS-induced TNF-α production in THP-1 cells, PBMCs and human monocytes in a dose-dependent manner. ICT treatment resulted in down-regulation of the expression of CD14/TLR4 and attenuated NF-κB and MAPK activation induced by LPS. We illustrate the anti-inflammatory property of ICT in human immune cells, especially in monocytes. These effects were mediated, at least partially, via inhibition of the CD14/TLR4 signaling pathway. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Chilean Strawberry Consumption Protects against LPS-Induced Liver Injury by Anti-Inflammatory and Antioxidant Capability in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Sebastian Molinett

    2015-01-01

    Full Text Available The Chilean strawberry fruit has high content of antioxidants and polyphenols. Previous studies evidenced antioxidant properties by in vitro methods. However, the antioxidant effect and its impact as functional food on animal health have not been evaluated. In this study, rats were fed with a Chilean strawberry aqueous extract (4 g/kg of animal per day and then subjected to LPS-induced liver injury (5 mg/kg. Transaminases and histological studies revealed a reduction in liver injury in rats fed with strawberry aqueous extract compared with the control group. Additionally, white strawberry supplementation significantly reduced the serum levels and gene expression of TNF-α, IL-6, and IL-1β cytokines compared with nonsupplemented rats. The level of F2-isoprostanes and GSH/GSSG indicated a reduction in liver oxidative stress by the consumption of strawberry aqueous extract. Altogether, the evidence suggests that dietary supplementation of rats with a Chilean white strawberry aqueous extract favours the normalization of oxidative and inflammatory responses after a liver injury induced by LPS.

  3. Chilean Strawberry Consumption Protects against LPS-Induced Liver Injury by Anti-Inflammatory and Antioxidant Capability in Sprague-Dawley Rats.

    Science.gov (United States)

    Molinett, Sebastian; Nuñez, Francisca; Moya-León, María Alejandra; Zúñiga-Hernández, Jessica

    2015-01-01

    The Chilean strawberry fruit has high content of antioxidants and polyphenols. Previous studies evidenced antioxidant properties by in vitro methods. However, the antioxidant effect and its impact as functional food on animal health have not been evaluated. In this study, rats were fed with a Chilean strawberry aqueous extract (4 g/kg of animal per day) and then subjected to LPS-induced liver injury (5 mg/kg). Transaminases and histological studies revealed a reduction in liver injury in rats fed with strawberry aqueous extract compared with the control group. Additionally, white strawberry supplementation significantly reduced the serum levels and gene expression of TNF-α, IL-6, and IL-1β cytokines compared with nonsupplemented rats. The level of F2-isoprostanes and GSH/GSSG indicated a reduction in liver oxidative stress by the consumption of strawberry aqueous extract. Altogether, the evidence suggests that dietary supplementation of rats with a Chilean white strawberry aqueous extract favours the normalization of oxidative and inflammatory responses after a liver injury induced by LPS.

  4. SOCS3 Expression Correlates with Severity of Inflammation, Expression of Proinflammatory Cytokines, and Activation of STAT3 and p38 MAPK in LPS-Induced Inflammation In Vivo

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    João Antônio Chaves de Souza

    2013-01-01

    Full Text Available SOCS3 is an inducible endogenous negative regulator of JAK/STAT pathway, which is relevant in inflammatory conditions. We used a model of LPS-induced periodontal disease in rats to correlate SOCS3 expression with the inflammatory status. In vitro we used a murine macrophage cell line to assess the physical interaction between SOCS3 and STAT3 by coimmunoprecipitation. 30 ug of LPS from Escherichia coli were injected in the gingival tissues on the palatal aspect of first molars of the animals 3x/week for up to 4 weeks. Control animals were injected with the vehicle (PBS. The rats were sacrificed at 7, 15, and 30 days. Inflammation and gene expression were assessed by stereometric analysis, immunohistochemistry, RT-qPCR, and western blot. LPS injections increased inflammation, paralleled by an upregulation of SOCS3, of the proinflammatory cytokines IL-1β, IL-6, and TNF-α and increased phosphorylation of STAT3 and p38 MAPK. SOCS3 expression accompanied the severity of inflammation and the expression of proinflammatory cytokines, as well as the activation status of STAT3 and p38 MAPK. LPS stimulation in a macrophage cell line in vitro induced transient STAT3 activation, which was inversely correlated with a dynamic physical interaction with SOCS3, suggesting that this may be a mechanism for SOCS3 regulatory function.

  5. Protective Effect of the Fruit Hull of Gleditsia sinensis on LPS-Induced Acute Lung Injury Is Associated with Nrf2 Activation

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    Jun-Young Choi

    2012-01-01

    Full Text Available The fruit hull of Gleditsia sinensis (FGS has been prescribed as a traditional eastern Asian medicinal remedy for the treatment of various respiratory diseases, but the efficacy and underlying mechanisms remain poorly characterized. Here, we explored a potential usage of FGS for the treatment of acute lung injury (ALI, a highly fatal inflammatory lung disease that urgently needs effective therapeutics, and investigated a mechanism for the anti-inflammatory activity of FGS. Pretreatment of C57BL/6 mice with FGS significantly attenuated LPS-induced neutrophilic lung inflammation compared to sham-treated, inflamed mice. Reporter assays, semiquantitative RT-PCR, and Western blot analyses show that while not affecting NF-κB, FGS activated Nrf2 and expressed Nrf2-regulated genes including GCLC, NQO-1, and HO-1 in RAW 264.7 cells. Furthermore, pretreatment of mice with FGS enhanced the expression of GCLC and HO-1 but suppressed that of proinflammatory cytokines in including TNF-α and IL-1β in the inflamed lungs. These results suggest that FGS effectively suppresses neutrophilic lung inflammation, which can be associated with, at least in part, FGS-activating anti-inflammatory factor Nrf2. Our results suggest that FGS can be developed as a therapeutic option for the treatment of ALI.

  6. Emu Oil Reduces LPS-Induced Production of Nitric Oxide and TNF-α but not Phagocytosis in RAW 264 Macrophages.

    Science.gov (United States)

    Miyashita, Tadayoshi; Minami, Kazuhiro; Ito, Minoru; Koizumi, Ryosuke; Sagane, Yoshimasa; Watanabe, Toshihiro; Niwa, Koichi

    2018-04-01

    Emu is the second-largest extant bird native to Australia. Emu oil, obtained from the emu's fat deposits, is used as an ingredient in cosmetic skincare products. Emu oil has been reported to improve several inflammatory symptoms; however, the mechanisms of these anti-inflammatory effects are largely unknown. This study investigated the effects of emu oil on the inflammatory macrophage response in vitro. A murine macrophage cell line, RAW 264, was incubated in culture media supplemented with or without emu oil and stimulated with lipopolysaccharide (LPS). We determined phagocytic activity by measuring the number of fluorescent microspheres taken up by the cells. The phagocytic activity of RAW 264 cells in the presence of LPS was unaffected by emu oil. We also determined production of nitric oxide (NO) and tumor necrosis factor (TNF)-α in the culture medium using the Griess reaction and an enzyme-linked immunosorbent assay, respectively, and the protein expression of inducible NO synthase (iNOS) using western blotting. The results indicated that emu oil reduced the LPS-induced production of NO, TNF-α, and iNOS expression in a dose-dependent manner. The results suggested that emu oil does not reduce the phagocytic clearance rate of inflammatory matter; however, it does reduce the production of NO and TNF-α in macrophages. These latter products enhance the inflammatory response and emu oil thereby demonstrated anti-inflammatory properties.

  7. Protective Effects of Bifidobacterium on Intestinal Barrier Function in LPS-Induced Enterocyte Barrier Injury of Caco-2 Monolayers and in a Rat NEC Model.

    Science.gov (United States)

    Ling, Xiang; Linglong, Peng; Weixia, Du; Hong, Wei

    2016-01-01

    Zonulin protein is a newly discovered modulator which modulates the permeability of the intestinal epithelial barrier by disassembling intercellular tight junctions (TJ). Disruption of TJ is associated with neonatal necrotizing enterocolitis (NEC). It has been shown bifidobacterium could protect the intestinal barrier function and prophylactical administration of bifidobacterium has beneficial effects in NEC patients and animals. However, it is still unknown whether the zonulin is involved in the gut barrier dysfunction of NEC, and the protective mechanisms of bifidobacterium on intestinal barrier function are also not well understood. The present study aims to investigate the effects of bifidobacterium on intestinal barrier function, zonulin regulation, and TJ integrity both in LPS-induced enterocyte barrier injury of Caco-2 monolayers and in a rat NEC model. Our results showed bifidobacterium markedly attenuated the decrease in transepithelial electrical resistance and the increase in paracellular permeability in the Caco-2 monolayers treated with LPS (P zonulin release (P zonulin (P zonulin protein release and improvement of intestinal TJ integrity.

  8. Protective effects of total alkaloids from Dendrobium crepidatum against LPS-induced acute lung injury in mice and its chemical components.

    Science.gov (United States)

    Hu, Yang; Ren, Jie; Wang, Lei; Zhao, Xin; Zhang, Mian; Shimizu, Kuniyoshi; Zhang, Chaofeng

    2018-05-01

    Dendrobium crepidatum was one of the sources of Herba Dendrobii, a famous and precious traditional Chinese medicine. Indolizine-type alkaloids are the main characteristic ingredients of D. crepidatum, which possesses a variety of changeable skeletons. In the present study, we found that the total alkaloids of D. crepidatum (TAD) can inhibit the production of nitric oxide (NO) in lipopolysaccharide (LPS)-activated macrophages and showed protective effects against LPS-induced acute lung injury (ALI) in mice through downregulating the TLR4-mediated MyD88/MAPK signaling pathway. Further phytochemical study showed that six previously undescribed indolizine-type compounds, including a racemic mixture (dendrocrepidine A-E) were isolated from TAD. Meanwhile, dendrocrepidine F was separated into a pair of enantiomers by a chiral chromatography, and their absolute configurations were assigned by single-crystal X-ray diffraction analysis. The isomer (-)-dendrocrepidine F showed higher anti-inflammatory effects by inhibiting NO production in LPS-treated macrophages with an IC 50 value of 13.3 μM. Taken together, indolizine-type alkaloids are the active components of D. crepidatum through downregulating the TLR4-mediated pathway, indicating some kind of therapy of TAD for ALI treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Intervention of Dietary Dipeptide Gamma-l-Glutamyl-l-Valine (γ-EV) Ameliorates Inflammatory Response in a Mouse Model of LPS-Induced Sepsis.

    Science.gov (United States)

    Chee, MacKenzie E; Majumder, Kaustav; Mine, Yoshinori

    2017-07-26

    Sepsis, the systemic inflammatory response syndrome (SIRS) with infection is one of the leading causes of death in critically ill patients in the developed world due to the lack of effective antisepsis treatments. This study examined the efficacy of dietary dipeptide gamma-l-glutamyl-l-valine (γ-EV), which was characterized previously as an anti-inflammatory peptide, in an LPS-induced mouse model of sepsis. BALB/c mice were administered γ-EV via oral gavage followed by an intraperitoneal injection of LPS to induce sepsis. The γ-EV exhibited antisepsis activity by reducing the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β in plasma and small intestine. γ-EV also reduced the phosphorylation of the signaling proteins JNK and IκBα. We concluded that γ-EV could possess an antisepsis effect against bacterial infection in intestine. This study proposes a signaling mechanism whereby the calcium-sensing receptor (CaSR) allosterically activated by γ-EV stimulates the interaction of β-arrestin2 with the TIR(TLR/IL-1R) signaling proteins TRAF6, TAB1, and IκBα to suppress inflammatory signaling.

  10. Insuficiência adrenal relativa como preditora de gravidade de doença e mortalidade do choque séptico Relative adrenal insufficiency as a predictor of disease severity and mortality in severe septic shock

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    Daniele Dalegrave

    2012-12-01

    to 250 µg of intravenously administered adrenocorticotropic hormone are related to disease severity and, hence, mortality. METHODS: This is a retrospective study in a medical-surgical intensive care unit of a university hospital. We studied 69 consecutive patients with septic shock over a 1-yr period; these patients underwent a short 250-µg adrenocorticotropic hormone test because they exhibited >6 hours of progressive hemodynamic instability requiring repeated fluid challenges and vasopressor treatment to maintain blood pressure. The test was performed by intravenously injecting 250 µg of synthetic adrenocorticotropic hormone and measuring cortisol immediately before injection, 30 minutes post-injection and 60 minutes post-injection. RESULTS: The mean APACHE II score was 22±7. The intensive care unit mortality rate at day 28 was 55%. Median baseline cortisol levels (19 [11-27] µg/dL versus 24 [18-34] µg/dL, p=0.047 and median baseline cortisol/albumin ratios (7.6 [4.6-12.3] versus 13.9 [8.8-18.5]; p=0.01 were lower in survivors than in non-survivors. Responders and non-responders had similar baseline clinical data and outcomes. The variables that were significantly correlated with outcome based on the area under the ROC curves (AUC were APACHE II (AUC=0.67 [0.535 to 0.781], baseline cortisol (µg/dl (AUC=0.662 [0.536 to 0.773], peak cortisol (µg/dl (AUC=0.642 [0.515 to 0.755] and baseline cortisol/albumin (AUC=0.75 [0.621 to 0.849]. CONCLUSIONS: Increased basal cortisol is associated with mortality and disease severity. Cortisol responses upon adrenocorticotropic hormone stimulation were not related to outcome. The cortisol/albumin ratio does not predict unfavorable outcomes better than total cortisol levels or help to improve the accuracy of the adrenocorticotropic hormone test.

  11. Parâmetros de prática clínica para suporte hemodinâmico a pacientes pediátricos e neonatais em choque séptico Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock

    Directory of Open Access Journals (Sweden)

    Joseph A. Carcillo

    2002-12-01

    (mortalidade de 9% versus 27%. A fisiopatologia do choque e a resposta a terapias variam de acordo com a idade do paciente. Por exemplo, insuficiência cardíaca é uma das causas predominantes de morte entre pacientes neonatais e pediátricos, enquanto insuficiência vascular é causa predominante de morte entre adultos. Agentes inotrópicos, vasodilatadores (crianças, óxido nítrico inalado (neonatos e oxigenação por membrana extracorpórea podem ser contribuições mais importantes para a sobrevivência de populações pediátricas, enquanto vasopressores podem contribuir mais diretamente para a sobrevivência de pacientes adultos. Conclusões: As diretrizes do American College of Critical Care Medicine para o suporte hemodinâmico de pacientes adultos em choque séptico têm pouca aplicação no cuidado de pacientes neonatais ou pediátricos. São necessários estudos para determinar se as diretrizes do American College of Critical Care Medicine para o suporte hemodinâmico de pacientes neonatais ou pediátricos serão implementadas e associadas a uma melhor evolução.Background: the Institute of Medicine has called for the development of clinical guidelines and practice parameters to develop "best practice" and potentially improve patient outcome. Objective: to provide American College of Critical Care Medicine clinical guidelines for hemodynamic support of neonates and children with septic shock. Setting: individual members of the Society of Critical Care Medicine with special interest in neonatal and pediatric septic shock were identified from literature review and general solicitation at Society of Critical Care Medicine Educational and Scientific Symposia (1998-2001. Methods: the MEDLINE literature database was searched with the following age-specific keywords: sepsis, septicemia, septic shock, endotoxemia, persistent pulmonary hypertension, nitric oxide, and extracorporeal membrane oxygenation. More than 30 experts graded literature and drafted specific

  12. Septic-embolic and septic-metabolic brain abscess

    International Nuclear Information System (INIS)

    Weber, W.; Henkes, H.; Kuehne, D.; Felber, S.; Jaenisch, W.; Woitalla, D.

    2000-01-01

    The hematogeneous spread of bacteria, fungi and protozoa may also reach the brain vessels, which happens mostly through septic emboli. From such an embolus a metastatic focal encephalitis and later a septic-embolic brain abscess may arise. The most frequently underlying infections that may cause septic emboli are bacterial endocarditis as well as bacterial infections of artificial heart valve prostheses. Congenital heart malformations with a right-to-left shunt also play here a certain role. Basically, however, all septic conditions and bacteriemias may cause septic-embolic brain abscesses. They occur frequently as multiple lesions. MRI is superior to CT in depicting the different stages of evolution from focal encephalitis, through the hardly encapsulated early abscess, to the formation of a membrane and later a dense fibrous capsule. The medical treatment of a brain abscess requires properly performed CT or MRI follow-up examinations in order to realize early enough a possible growing of such a lesion. (orig.) [de

  13. Pulmonary Septic Emboli due to Azygos Vein Septic Thrombosis

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    Ginius Pradhan

    2013-01-01

    Full Text Available The triad of extrapulmonary infection, contiguous septic vein thrombosis, and septic pulmonary embolism is a rare complex but associated with significant morbidity and mortality. Septic azygos vein thrombosis is extremely rare and potentially serious since it may also cause pulmonary emboli and sudden death. We report a case of a 32-year-old woman with history of IV drug abuse who presented with epidural abscess and methicillin-resistant S. aureus (MRSA bacteremia. Later she developed signs of septic pulmonary embolism secondary to septic azygos vein thrombosis. With early diagnosis, appropriate antimicrobial therapy, and control of the infectious source, resolution of the illness can be expected for most patients with avoidance of potential complications.

  14. Carabrol suppresses LPS-induced nitric oxide synthase expression by inactivation of p38 and JNK via inhibition of I-κBα degradation in RAW 264.7 cells

    International Nuclear Information System (INIS)

    Lee, Hwa Jin; Lim, Hyo Jin; Lee, Da Yeon; Jung, Hyeyoun; Kim, Mi-Ran; Moon, Dong-Cheul; Kim, Keun Il; Lee, Myeong-Sok; Ryu, Jae-Ha

    2010-01-01

    Carabrol, isolated from Carpesium macrocephalum, showed anti-inflammatory potential in LPS-induced RAW 264.7 murine macrophages. In present study, carabrol demonstrated the inhibitory activity on pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α. In addition, mRNA and protein levels of iNOS and COX-2 were reduced by carabrol. Molecular analysis revealed that these suppressive effects were correlated with the inactivation of p38 and JNK via inhibition of NF-κB activation. Immunoblotting showed that carabrol suppressed LPS-induced degradation of I-κBα and decreased nuclear translocation of p65. Taken together, these results suggest that carabrol can be a modulator of pro-inflammatory signal transduction pathway in RAW 264.7 cells.

  15. Oleoylethanolamide exerts anti-inflammatory effects on LPS-induced THP-1 cells by enhancing PPARα signaling and inhibiting the NF-κB and ERK1/2/AP-1/STAT3 pathways.

    Science.gov (United States)

    Yang, Lichao; Guo, Han; Li, Ying; Meng, Xianglan; Yan, Lu; Dan Zhang; Wu, Sangang; Zhou, Hao; Peng, Lu; Xie, Qiang; Jin, Xin

    2016-10-10

    The present study aimed to examine the anti-inflammatory actions of oleoylethanolamide (OEA) in lipopolysaccharide (LPS)-induced THP-1 cells. The cells were stimulated with LPS (1 μg/ml) in the presence or absence of OEA (10, 20 and 40 μM). The pro-inflammatory cytokines were evaluated by qRT-PCR and ELISA. The THP-1 cells were transiently transfected with PPARα small-interfering RNA, and TLR4 activity was determined with a blocking test using anti-TLR4 antibody. Additionally, a special inhibitor was used to analyse the intracellular signaling pathway. OEA exerted a potent anti-inflammatory effect by reducing the production of pro-inflammatory cytokines and TLR4 expression, and by enhancing PPARα expression. The modulatory effects of OEA on LPS-induced inflammation depended on PPARα and TLR4. Importantly, OEA inhibited LPS-induced NF-κB activation, IκBα degradation, expression of AP-1, and the phosphorylation of ERK1/2 and STAT3. In summary, our results demonstrated that OEA exerts anti-inflammatory effects by enhancing PPARα signaling, inhibiting the TLR4-mediated NF-κB signaling pathway, and interfering with the ERK1/2-dependent signaling cascade (TLR4/ERK1/2/AP-1/STAT3), which suggests that OEA may be a therapeutic agent for inflammatory diseases.

  16. Enhanced Inhibitory Effect of Ultra-Fine Granules of Red Ginseng on LPS-induced Cytokine Expression in the Monocyte-Derived Macrophage THP-1 Cells

    Directory of Open Access Journals (Sweden)

    Hong-Yeoul Kim

    2008-08-01

    Full Text Available Red ginseng is one of the most popular traditional medicines in Korea because its soluble hot-water extract is known to be very effective on enhancing immunity as well as inhibiting inflammation. Recently, we developed a new technique, called the HACgearshift system, which can pulverize red ginseng into the ultra-fine granules ranging from 0.2 to 7.0 μm in size. In this study, the soluble hot-water extract of those ultra-fine granules of red ginseng (URG was investigated and compared to that of the normal-sized granules of red ginseng (RG. The high pressure liquid chromatographic analyses of the soluble hot-water extracts of both URG and RG revealed that URG had about 2-fold higher amounts of the ginsenosides, the biologically active components in red ginseng, than RG did. Using quantitative RT-PCR, cytokine profiling against the Escherichia coli lipopolysaccharide (LPS in the monocyte-derived macrophage THP-1 cells demonstrated that the URG-treated cells showed a significant reduction in cytokine expression than the RG-treated ones. Transcription expression of the LPS-induced cytokines such as TNF-α, IL-1β, IL-6, IL-8, IL-10, and TGF-β was significantly inhibited by URG compared to RG. These results suggest that some biologically active and soluble components in red ginseng can be more effectively extracted from URG than RG by standard hot-water extraction.

  17. Mesenchymal Stem Cells Alleviate LPS-Induced Acute Lung Injury in Mice by MiR-142a-5p-Controlled Pulmonary Endothelial Cell Autophagy

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    Zichao Zhou

    2016-01-01

    Full Text Available Background/Aims: Damages of pulmonary endothelial cells (PECs represent a critical pathological process during acute lung injury (ALI, and precede pulmonary epithelial cell injury, and long-term lung dysfunction. Transplantation of mesenchymal stem cells (MSCs has proven therapeutic effects on ALI, whereas the underlying mechanisms remain ill-defined. Method: We transplanted MSCs in mice and then induced ALI using Lipopolysaccharides (LPS. We analyzed the changes in permeability index and lung histology. Mouse PECs were isolated by flow cytometry based on CD31 expression and then analyzed for autophagy-associated factors LC3 and Beclin-1 by Western blot. Beclin-1 mRNA was determined by RT-qPCR. In vitro, we performed bioinformatics analyses to identify the MSCs-regulated miRNAs that target Beclin-1, and confirmed that the binding was functional by 3'-UTR luciferase reporter assay. Results: We found that MSCs transplantation significantly reduced the severity of LPS-induced ALI in mice. MSCs increased autophagy of PECs to promote PEC survival. MSCs increased Beclin-1 protein but not mRNA. MiR-142a-5p was found to target the 3'-UTR of Beclin-1 mRNA to inhibit its protein translation in PECs. MSCs reduced the levels of miR-142a-5p in PECs from LPS-treated mice. Conclusion: MSCs may alleviate LPS-ALI through downregulation of miR-142a-5p, which allows PECs to increase Beclin-1-mediated cell autophagy.

  18. Distinct alterations in motor & reward seeking behavior are dependent on the gestational age of exposure to LPS-induced maternal immune activation.

    Science.gov (United States)

    Straley, Megan E; Van Oeffelen, Wesley; Theze, Sarah; Sullivan, Aideen M; O'Mahony, Siobhain M; Cryan, John F; O'Keeffe, Gerard W

    2017-07-01

    The dopaminergic system is involved in motivation, reward and the associated motor activities. Mesodiencephalic dopaminergic neurons in the ventral tegmental area (VTA) regulate motivation and reward, whereas those in the substantia nigra (SN) are essential for motor control. Defective VTA dopaminergic transmission has been implicated in schizophrenia, drug addiction and depression whereas dopaminergic neurons in the SN are lost in Parkinson's disease. Maternal immune activation (MIA) leading to in utero inflammation has been proposed to be a risk factor for these disorders, yet it is unclear how this stimulus can lead to the diverse disturbances in dopaminergic-driven behaviors that emerge at different stages of life in affected offspring. Here we report that gestational age is a critical determinant of the subsequent alterations in dopaminergic-driven behavior in rat offspring exposed to lipopolysaccharide (LPS)-induced MIA. Behavioral analysis revealed that MIA on gestational day 16 but not gestational day 12 resulted in biphasic impairments in motor behavior. Specifically, motor impairments were evident in early life, which were resolved by adolescence, but subsequently re-emerged in adulthood. In contrast, reward seeking behaviors were altered in offspring exposed MIA on gestational day 12. These changes were not due to a loss of dopaminergic neurons per se in the postnatal period, suggesting that they reflect functional changes in dopaminergic systems. This highlights that gestational age may be a key determinant of how MIA leads to distinct alterations in dopaminergic-driven behavior across the lifespan of affected offspring. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Septic bursitis in immunocompromised patients.

    Science.gov (United States)

    Roschmann, R A; Bell, C L

    1987-10-01

    A retrospective analysis of 29 patients with septic bursitis was undertaken to ascertain if immunocompromised patients differed in their clinical presentations, type of organisms cultured, and outcome when compared with their non-immunocompromised cohorts. Thirty episodes of septic bursitis occurred in 29 patients, 43 percent of which occurred in immunocompromised patients. Despite similar clinical presentations, the bursae of immunocompromised patients took three times longer to sterilize and had a much higher bursal white blood cell count when compared with the bursae of non-immunocompromised patients. The bacteriologic spectrum was essentially identical in both groups; there were no cases in which gram-negative organisms were recovered from infected bursae. No cases of septic bursitis were seen in neutropenic patients. The most common factors contributing to an immunocompromised state were alcoholism or steroid therapy. A successful resolution of septic bursitis was seen in all the patients in the immunocompromised groups.

  20. Regulation of ENaC-mediated alveolar fluid clearance by insulin via PI3K/Akt pathway in LPS-induced acute lung injury.

    Science.gov (United States)

    Deng, Wang; Li, Chang-Yi; Tong, Jin; Zhang, Wei; Wang, Dao-Xin

    2012-03-30

    Stimulation of epithelial sodium channel (ENaC) increases Na(+) transport, a driving force of alveolar fluid clearance (AFC) to keep alveolar spaces free of edema fluid that is beneficial for acute lung injury (ALI). It is well recognized that regulation of ENaC by insulin via PI3K pathway, but the mechanism of this signaling pathway to regulate AFC and ENaC in ALI remains unclear. The aim of this study was to investigate the effect of insulin on AFC in ALI and clarify the pathway in which insulin regulates the expression of ENaC in vitro and in vivo. A model of ALI (LPS at a dose of 5.0 mg/kg) with non-hyperglycemia was established in Sprague-Dawley rats receiving continuous exogenous insulin by micro-osmotic pumps and wortmannin. The lungs were isolated for measurement of bronchoalveolar lavage fluid(BALF), total lung water content(TLW), and AFC after ALI for 8 hours. Alveolar epithelial type II cells were pre-incubated with LY294002, Akt inhibitor and SGK1 inhibitor 30 minutes before insulin treatment for 2 hours. The expressions of α-,β-, and γ-ENaC were detected by immunocytochemistry, reverse transcriptase polymerase chain reaction (RT-PCR) and western blotting. In vivo, insulin decreased TLW, enchanced AFC, increased the expressions of α-,β-, and γ-ENaC and the level of phosphorylated Akt, attenuated lung injury and improved the survival rate in LPS-induced ALI, the effects of which were blocked by wortmannin. Amiloride, a sodium channel inhibitor, significantly reduced insulin-induced increase in AFC. In vitro, insulin increased the expressions of α-,β-, and γ-ENaC as well as the level of phosphorylated Akt but LY294002 and Akt inhibitor significantly prevented insulin-induced increase in the expression of ENaC and the level of phosphorylated Akt respectively. Immunoprecipitation studies showed that levels of Nedd4-2 binding to ENaC were decreased by insulin via PI3K/Akt pathway. Our study demonstrated that insulin alleviated pulmonary edema and

  1. Regulation of ENaC-mediated alveolar fluid clearance by insulin via PI3K/Akt pathway in LPS-induced acute lung injury

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    Deng Wang

    2012-03-01

    Full Text Available Abstract Background Stimulation of epithelial sodium channel (ENaC increases Na+ transport, a driving force of alveolar fluid clearance (AFC to keep alveolar spaces free of edema fluid that is beneficial for acute lung injury (ALI. It is well recognized that regulation of ENaC by insulin via PI3K pathway, but the mechanism of this signaling pathway to regulate AFC and ENaC in ALI remains unclear. The aim of this study was to investigate the effect of insulin on AFC in ALI and clarify the pathway in which insulin regulates the expression of ENaC in vitro and in vivo. Methods A model of ALI (LPS at a dose of 5.0 mg/kg with non-hyperglycemia was established in Sprague-Dawley rats receiving continuous exogenous insulin by micro-osmotic pumps and wortmannin. The lungs were isolated for measurement of bronchoalveolar lavage fluid(BALF, total lung water content(TLW, and AFC after ALI for 8 hours. Alveolar epithelial type II cells were pre-incubated with LY294002, Akt inhibitor and SGK1 inhibitor 30 minutes before insulin treatment for 2 hours. The expressions of α-,β-, and γ-ENaC were detected by immunocytochemistry, reverse transcriptase polymerase chain reaction (RT-PCR and western blotting. Results In vivo, insulin decreased TLW, enchanced AFC, increased the expressions of α-,β-, and γ-ENaC and the level of phosphorylated Akt, attenuated lung injury and improved the survival rate in LPS-induced ALI, the effects of which were blocked by wortmannin. Amiloride, a sodium channel inhibitor, significantly reduced insulin-induced increase in AFC. In vitro, insulin increased the expressions of α-,β-, and γ-ENaC as well as the level of phosphorylated Akt but LY294002 and Akt inhibitor significantly prevented insulin-induced increase in the expression of ENaC and the level of phosphorylated Akt respectively. Immunoprecipitation studies showed that levels of Nedd4-2 binding to ENaC were decreased by insulin via PI3K/Akt pathway. Conclusions Our study

  2. LPS-induced release of IL-6 from glia modulates production of IL-1beta in a JAK2-dependent manner

    LENUS (Irish Health Repository)

    Minogue, Aedín M

    2012-06-14

    AbstractBackgroundCompelling evidence has implicated neuroinflammation in the pathogenesis of a number of neurodegenerative conditions. Chronic activation of both astrocytes and microglia leads to excessive secretion of proinflammatory molecules such as TNFα, IL-6 and IL-1β with potentially deleterious consequences for neuronal viability. Many signaling pathways involving the mitogen-activated protein kinases (MAPKs), nuclear factor κB (NFκB) complex and the Janus kinases (JAKs)\\/signal transducers and activators of transcription (STAT)-1 have been implicated in the secretion of proinflammatory cytokines from glia. We sought to identify signaling kinases responsible for cytokine production and to delineate the complex interactions which govern time-related responses to lipopolysaccharide (LPS).MethodsWe examined the time-related changes in certain signaling events and the release of proinflammatory cytokines from LPS-stimulated co-cultures of astrocytes and microglia isolated from neonatal rats.ResultsTNFα was detected in the supernatant approximately 1 to 2 hours after LPS treatment while IL-1β and IL-6 were detected after 2 to 3 and 4 to 6 hours, respectively. Interestingly, activation of NFκB signaling preceded release of all cytokines while phosphorylation of STAT1 was evident only after 2 hours, indicating that activation of JAK\\/STAT may be important in the up-regulation of IL-6 production. Additionally, incubation of glia with TNFα induced both phosphorylation of JAK2 and STAT1 and the interaction of JAK2 with the TNFα receptor (TNFR1). Co-treatment of glia with LPS and recombinant IL-6 protein attenuated the LPS-induced release of both TNFα and IL-1β while potentiating the effect of LPS on suppressor of cytokine signaling (SOCS)3 expression and IL-10 release.ConclusionsThese data indicate that TNFα may regulate IL-6 production through activation of JAK\\/STAT signaling and that the subsequent production of IL-6 may impact on the release of

  3. Protective Effects of Bifidobacterium on Intestinal Barrier Function in LPS-Induced Enterocyte Barrier Injury of Caco-2 Monolayers and in a Rat NEC Model.

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    Xiang Ling

    Full Text Available Zonulin protein is a newly discovered modulator which modulates the permeability of the intestinal epithelial barrier by disassembling intercellular tight junctions (TJ. Disruption of TJ is associated with neonatal necrotizing enterocolitis (NEC. It has been shown bifidobacterium could protect the intestinal barrier function and prophylactical administration of bifidobacterium has beneficial effects in NEC patients and animals. However, it is still unknown whether the zonulin is involved in the gut barrier dysfunction of NEC, and the protective mechanisms of bifidobacterium on intestinal barrier function are also not well understood. The present study aims to investigate the effects of bifidobacterium on intestinal barrier function, zonulin regulation, and TJ integrity both in LPS-induced enterocyte barrier injury of Caco-2 monolayers and in a rat NEC model. Our results showed bifidobacterium markedly attenuated the decrease in transepithelial electrical resistance and the increase in paracellular permeability in the Caco-2 monolayers treated with LPS (P < 0.01. Compared with the LPS group, bifidobacterium significantly decreased the production of IL-6 and TNF-α (P < 0.01 and suppressed zonulin release (P < 0.05. In addition, bifidobacterium pretreatment up-regulated occludin, claudin-3 and ZO-1 expression (P < 0.01 and also preserved these proteins localization at TJ compared with the LPS group. In the in vivo study, bifidobacterium decreased the incidence of NEC from 88 to 47% (P < 0.05 and reduced the severity in the NEC model. Increased levels of IL-6 and TNF-α in the ileum of NEC rats were normalized in bifidobacterium treated rats (P < 0.05. Moreover, administration of bifidobacterium attenuated the increase in intestinal permeability (P < 0.01, decreased the levels of serum zonulin (P < 0.05, normalized the expression and localization of TJ proteins in the ileum compared with animals with NEC. We concluded that bifidobacterium may

  4. Early fluid loading for septic patients: Any safety limit needed?

    Science.gov (United States)

    Gong, Yi-Chun; Liu, Jing-Tao; Ma, Peng-Lin

    2018-02-01

    Early adequate fluid loading was the corner stone of hemodynamic optimization for sepsis and septic shock. Meanwhile, recent recommended protocol for fluid resuscitation was increasingly debated on hemodynamic stability vs risk of overloading. In recent publications, it was found that a priority was often given to hemodynamic stability rather than organ function alternation in the early fluid resuscitation of sepsis. However, no safety limits were used at all in most of these reports. In this article, the rationality and safety of early aggressive fluid loading for septic patients were discussed. It was concluded that early aggressive fluid loading improved hemodynamics transitorily, but was probably traded off with a follow-up organ function impairment, such as worsening oxygenation by reduction of lung aeration, in a part of septic patients at least. Thus, a safeguard is needed against unnecessary excessive fluids in early aggressive fluid loading for septic patients. Copyright © 2017 Daping Hospital and the Research Institute of Surgery of the Third Military Medical University. Production and hosting by Elsevier B.V. All rights reserved.

  5. Septic tank additive impacts on microbial populations.

    Science.gov (United States)

    Pradhan, S; Hoover, M T; Clark, G H; Gumpertz, M; Wollum, A G; Cobb, C; Strock, J

    2008-01-01

    Environmental health specialists, other onsite wastewater professionals, scientists, and homeowners have questioned the effectiveness of septic tank additives. This paper describes an independent, third-party, field scale, research study of the effects of three liquid bacterial septic tank additives and a control (no additive) on septic tank microbial populations. Microbial populations were measured quarterly in a field study for 12 months in 48 full-size, functioning septic tanks. Bacterial populations in the 48 septic tanks were statistically analyzed with a mixed linear model. Additive effects were assessed for three septic tank maintenance levels (low, intermediate, and high). Dunnett's t-test for tank bacteria (alpha = .05) indicated that none of the treatments were significantly different, overall, from the control at the statistical level tested. In addition, the additives had no significant effects on septic tank bacterial populations at any of the septic tank maintenance levels. Additional controlled, field-based research iswarranted, however, to address additional additives and experimental conditions.

  6. Changes in muscle tissue oxygenation during stagnant ischemia in septic patients.

    Science.gov (United States)

    Pareznik, Roman; Knezevic, Rajko; Voga, Gorazd; Podbregar, Matej

    2006-01-01

    To determine changes in the rate of thenar muscles tissue deoxygenation during stagnant ischemia in patients with severe sepsis and septic shock. Prospective observational study in the medical ICU of a general hospital. Consecutive patients admitted to ICU with septic shock (n=6), severe sepsis (n=6), localized infection (n=3), and healthy volunteers (n=15). Upper limb ischemia was induced by rapid automatic pneumatic cuff inflation around upper arm. Thenar muscle tissue oxygen saturation (StO2) was measured continuously by near-infrared spectroscopy before and during upper limb ischemia. StO(2) before intervention was comparable in patients with septic shock, severe sepsis, or localized infection and healthy volunteers (89 [65, 92]% vs. 82 [72, 91]% vs. 87 [85, 92]% vs. 83 [79, 93]%, respectively; p>0.1). The rate of StO(2) decrease during stagnant ischemia after initial hemodynamic stabilization was slower in septic shock patients than in those with severe sepsis or localized infection and in controls (-7.0 [-3.6, -11.0] %/min vs. -10.4 [-7.8, -13.3] %/min vs. -19.5 [-12.3, -23.3] vs. -37.4 [-27.3, -56.2] %/min, respectively; p=0.041). At ICU discharge the rate of StO2 decrease did not differ between the septic shock, severe sepsis, and localized infection groups (-17.0 [-9.3, -28.9] %/min vs. -19.9 [-13.3, -23.6] %/min vs. -23.1 [-20.7, -26.2] %/min, respectively), but remained slower than in controls (p<0.01). The rate of StO2 decrease was correlated with Sequential Organ Failure Assessment (SOFA) score (r=0.739, p<0.001). After hemodynamic stabilization thenar muscle tissue oxygen saturation during stagnant ischemia decreases slower in septic shock patients than in patients with severe sepsis or localized infection and in healthy volunteers. During ICU stay and improvement of sepsis the muscle tissue deoxygenation rate increases in survivors of both septic shock and severe sepsis and was correlated with SOFA score.

  7. Protection against septic shock and suppression of tumor necrosis factor alpha and nitric oxide production on macrophages and microglia by a standard aqueous extract of Mangifera indica L. (VIMANG). Role of mangiferin isolated from the extract.

    Science.gov (United States)

    Garrido, Gabino; Delgado, René; Lemus, Yeny; Rodríguez, Janet; García, Dagmar; Núñez-Sellés, Alberto J

    2004-08-01

    The present study illustrates the effects of a standard aqueous extract, used in Cuba under the brand name of VIMANG, from the stem bark of Mangifera indica L. on the production of tumor necrosis factor alpha (TNFalpha) and nitric oxide (NO) in in vivo and in vitro experiments. In vivo was determined by the action of the extract and its purified glucosylxanthone (mangiferin) on TNFalpha in a murine model of endotoxic shock using Balb/c mice pre-treated with lipopolysaccharide (LPS) 0.125 mg kg(-1), i.p. In vitro, M. indica extract and mangiferin were tested on TNFalpha and NO production in activated macrophages (RAW264.7 cell line) and microglia (N9 cell line) stimulated with LPS (10ng ml(-1)) and interferon gamma (IFNgamma, 2U ml(-1)). M. indica extract reduced dose-dependently TNFalpha production in the serum (ED50 = 64.5 mg kg(-1)) and the TNFalpha mRNA expression in the lungs and livers of mice. Mangiferin also inhibited systemic TNFalpha at 20 mg kg(-1). In RAW264.7, the extract inhibited TNFalpha (IC50 = 94.1 microg ml(-1)) and NO (IC50 = 64.4 microg ml(-1)). In microglia the inhibitions of the extract were IC50 = 76.0 microg ml(-1) (TNFalpha) and 84.0 microg ml(-1) (NO). These findings suggest that the anti-inflammatory response observed during treatment with M. indica extract must be related with inhibition of TNFalpha and NO production. Mangiferin, a main component in the extract, is involved in these effects. The TNFalpha and NO inhibitions by M. indica extract and mangiferin on endotoxic shock and microglia are reported here for the first time. Copyright 2004 Elsevier Ltd.

  8. Short-term heating reduces the anti-inflammatory effects of fresh raw garlic extracts on the LPS-induced production of NO and pro-inflammatory cytokines by downregulating allicin activity in RAW 264.7 macrophages.

    Science.gov (United States)

    Shin, Jung-Hye; Ryu, Ji Hyeon; Kang, Min Jung; Hwang, Cho Rong; Han, Jaehee; Kang, Dawon

    2013-08-01

    Garlic has a variety of biologic activities, including anti-inflammatory properties. Although garlic has several biologic activities, some people dislike eating fresh raw garlic because of its strong taste and smell. Therefore, garlic formulations involving heating procedures have been developed. In this study, we investigated whether short-term heating affects the anti-inflammatory properties of garlic. Fresh and heated raw garlic extracts (FRGE and HRGE) were prepared with incubation at 25 °C and 95 °C, respectively, for 2 h. Treatment with FRGE and HRGE significantly reduced the LPS-induced increase in the pro-inflammatory cytokine concentration (TNF-α, IL-1β, and IL-6) and NO through HO-1 upregulation in RAW 264.7 macrophages. The anti-inflammatory effect was greater in FRGE than in HRGE. The allicin concentration was higher in FRGE than in HRGE. Allicin treatment showed reduced production of pro-inflammatory cytokines and NO and increased HO-1 activity. The results show that the decrease in LPS-induced NO and pro-inflammatory cytokines in RAW 264.7 macrophages through HO-1 induction was greater for FRGE compared with HRGE. Additionally, the results indicate that allicin is responsible for the anti-inflammatory effect of FRGE. Our results suggest a potential therapeutic use of allicin in the treatment of chronic inflammatory disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Skipjack tuna (Katsuwonus pelamis) eyeball oil exerts an anti-inflammatory effect by inhibiting NF-κB and MAPK activation in LPS-induced RAW 264.7 cells and croton oil-treated mice.

    Science.gov (United States)

    Jeong, Da-Hyun; Kim, Koth-Bong-Woo-Ri; Kim, Min-Ji; Kang, Bo-Kyeong; Ahn, Dong-Hyun

    2016-11-01

    The effect of tuna eyeball oil (TEO) on lipopolysaccharide (LPS)-induced inflammation in macrophage cells was investigated. TEO had no cytotoxicity in cell viability as compared to the control in LPS induced RAW 264.7 cells. TEO reduced the levels of NO and pro-inflammatory cytokines by up to 50% in a dose-dependent manner. The expression of NF-κB and MAPKs as well as iNOS and COX-2 proteins was reduced by TEO, which suggests that its anti-inflammatory activity is related to the suppression of the NF-κB and MAPK signaling pathways. The rate of formation of ear edema was reduced compared to that in the control at the highest dose tested. In an acute toxicity test, no mice were killed by TEO doses of up to 5000mg/kg body weight during the two week observation period. These results suggested that TEO may have a significant effect on inflammatory factors and be a potential anti-inflammatory therapeutic. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. 4-Phenylbutyric Acid Reveals Good Beneficial Effects on Vital Organ Function via Anti-Endoplasmic Reticulum Stress in Septic Rats.

    Science.gov (United States)

    Liu, Liangming; Wu, Huiling; Zang, JiaTao; Yang, Guangming; Zhu, Yu; Wu, Yue; Chen, Xiangyun; Lan, Dan; Li, Tao

    2016-08-01

    Sepsis and septic shock are the common complications in ICUs. Vital organ function disorder contributes a critical role in high mortality after severe sepsis or septic shock, in which endoplasmic reticulum stress plays an important role. Whether anti-endoplasmic reticulum stress with 4-phenylbutyric acid is beneficial to sepsis and the underlying mechanisms are not known. Laboratory investigation. State Key Laboratory of Trauma, Burns and Combined Injury. Sprague-Dawley rats. Using cecal ligation and puncture-induced septic shock rats, lipopolysaccharide-treated vascular smooth muscle cells, and cardiomyocytes, effects of 4-phenylbutyric acid on vital organ function and the relationship with endoplasmic reticulum stress and endoplasmic reticulum stress-mediated inflammation, apoptosis, and oxidative stress were observed. Conventional treatment, including fluid resuscitation, vasopressin, and antibiotic, only slightly improved the hemodynamic variable, such as mean arterial blood pressure and cardiac output, and slightly improved the vital organ function and the animal survival of septic shock rats. Supplementation of 4-phenylbutyric acid (5 mg/kg; anti-endoplasmic reticulum stress), especially administered at early stage, significantly improved the hemodynamic variables, vital organ function, such as liver, renal, and intestinal barrier function, and animal survival in septic shock rats. 4-Phenylbutyric acid application inhibited the endoplasmic reticulum stress and endoplasmic reticulum stress-related proteins, such as CCAAT/enhancer-binding protein homologous protein in vital organs, such as heart and superior mesenteric artery after severe sepsis. Further studies showed that 4-phenylbutyric acid inhibited endoplasmic reticulum stress-mediated cytokine release, apoptosis, and oxidative stress via inhibition of nuclear factor-κB, caspase-3 and caspase-9, and increasing glutathione peroxidase and superoxide dismutase expression, respectively. Anti

  11. Inferior vena cava obstruction and shock

    Directory of Open Access Journals (Sweden)

    Megri Mohammed

    2018-01-01

    Full Text Available Shock is one of the most challenging life-threatening conditions with high mortality and morbidity; the outcomes are highly dependent on the early detection and management of the condition. Septic shock is the most common type of shock in the Intensive Care Unit. While not as common as other subsets of shock, obstructive shock is a significant subtype due to well defined mechanical and pathological causes, including tension pneumothorax, massive pulmonary embolism, and cardiac tamponade. We are presenting a patient with obstructive shock due to inferior vena cava obstruction secondary to extensive deep venous thrombosis. Chance of survival from obstructive shock in our patient was small; however, there was complete and immediate recovery after treatment of the obstruction on recognizing the affected vessels. This case alerts the practicing intensivist and the emergency medicine physician to consider occlusion of the great vessels other than the pulmonary artery or aorta as causes of obstructive shock.

  12. Synthesis and optimization of novel allylated mono-carbonyl analogs of curcumin (MACs) act as potent anti-inflammatory agents against LPS-induced acute lung injury (ALI) in rats.

    Science.gov (United States)

    Zhu, Heping; Xu, Tingting; Qiu, Chenyu; Wu, Beibei; Zhang, Yali; Chen, Lingfeng; Xia, Qinqin; Li, Chenglong; Zhou, Bin; Liu, Zhiguo; Liang, Guang

    2016-10-04

    A series of novel symmetric and asymmetric allylated mono-carbonyl analogs of curcumin (MACs) were synthesized using an appropriate synthetic route and evaluated experimentally thru the LPS-induced expression of TNF-α and IL-6. Most of the obtained compounds exhibited improved water solubility as a hydrochloride salt compared to lead molecule 8f. The most active compound 7a was effective in reducing the Wet/Dry ratio in the lungs and protein concentration in bronchoalveolar lavage fluid. Meanwhile, 7a also inhibited mRNA expression of several inflammatory cytokines, including TNF-α, IL-6, IL-1β, and VCAM-1, in Beas-2B cells after Lipopolysaccharide (LPS) challenge. These results suggest that 7a could be therapeutically beneficial for use as an anti-inflammatory agent in the clinical treatment of acute lung injury (ALI). Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. Anti-neuroinflammatory Activity of Elephantopus scaber L. via Activation of Nrf2/HO-1 Signaling and Inhibition of p38 MAPK Pathway in LPS-Induced Microglia BV-2 Cells

    Directory of Open Access Journals (Sweden)

    Chim-Kei Chan

    2017-06-01

    Full Text Available Elephantopus scaber L. (family: Asteraceae has been traditionally utilized as a folkloric medicine and scientifically shown to exhibit anti-inflammatory activities in various in vivo inflammatory models. Given the lack of study on the effect of E. scaber in neuroinflammation, this study aimed to investigate the anti-neuroinflammatory effect and the underlying mechanisms of ethyl acetate fraction from the leaves of E. scaber (ESEAF on the release of pro-inflammatory mediators in lipopolysaccharide (LPS-induced microglia cells (BV-2. Present findings showed that ESEAF markedly attenuated the translocation of NF-κB to nucleus concomitantly with the significant mitigation on the LPS-induced production of NO, iNOS, COX-2, PGE2, IL-1β, and TNF-α. These inflammatory responses were reduced via the inhibition of p38. Besides, ESEAF was shown to possess antioxidant activities evident by the DPPH and SOD scavenging activities. The intracellular catalase enzyme activity was enhanced by ESEAF in the LPS-stimulated BV-2 cells. Furthermore, the formation of ROS induced by LPS in BV-2 cells was reduced upon the exposure to ESEAF. Intriguingly, the reduction of ROS was found in concerted with the activation of Nrf2 and HO-1. It is conceivable that the activation promotes the scavenging power of antioxidant enzymes as well as to ameliorate the inflammatory response in LPS-stimulated BV-2 cells. Finally, the safety profile analysis through oral administration of ESEAF at 2000 mg/kg did not result in any mortalities, adverse effects nor histopathologic abnormalities of organs in mice. Taken altogether, the cumulative findings suggested that ESEAF holds the potential to develop as nutraceutical for the intervention of neuroinflammatory disorders.

  14. Regulation of LPS-induced mRNA expression of pro-inflammatory cytokines via alteration of NF-κB activity in mouse peritoneal macrophages exposed to fluoride.

    Science.gov (United States)

    Tian, Yuhu; Huo, Meijun; Li, Guangsheng; Li, Yanyan; Wang, Jundong

    2016-10-01

    F toxicity to immune system, especially to macrophage, has been studied a lot recently. Nuclear factor-kappa B (NF-κB), as a transcription factor, plays a central role in immune and inflammatory responses via the regulation of downstream gene expression. Recent studies indicated that fluoride effect on inflammatory cytokine secretion, however, the molecular mechanism was less understood. In our study, peritoneal macrophages (PMs) were divided several groups and were administrated sodium fluoride (NaF, 50, 100, 200, 400, 800 μM) and/or lipopolysaccharide (LPS, 30 ng/mg). The mRNA expression of p65, inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) in macrophages exposed to fluoride was determined by quantitative real-time RT-PCR respectively. The translocation of NF-κB from cytoplasm to nucleus, which in a way reflects NF-κB activity, was demonstrated by Immunofluorescence and ELISA. Our results showed that fluoride had a dose-dependent effect on NF-κB activity, which coincided with LPS-induced mRNA expression of its downstream genes, iNOS and IL-1β. Fluoride alone causes no effect on gene expression. However, the mRNA expression of TNF-α showed non-NF-κB-dependent manner. Therefore, we come to the conclusion that fluoride can regulate LPS-induced mRNA expression of iNOS and IL-1β via NF-κB pathway in mouse peritoneal macrophages. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Saturação venosa central e mista de oxigênio no choque séptico: existe diferença clinicamente relevante? Central and mixed venous oxygen saturation in septic shock: is there a clinically relevant difference?

    Directory of Open Access Journals (Sweden)

    Flavia Ribeiro Machado

    2008-12-01

    Full Text Available INTRODUÇÃO: A medida da saturação venosa central de oxigênio (SvcO2 tem sido proposta como alternativa a saturação venosa mista (SvO2, com grau de concordância variável nos dados atualmente disponíveis. Esse estudo objetivou avaliar as possíveis diferenças entre a SvO2 e a SvcO2 ou saturação venosa atrial de oxigênio (SvaO2, com ênfase na interferência do débito cardíaco, e o impacto delas no manejo clínico do paciente séptico. MÉTODOS: Estudo prospectivo observacional em pacientes com choque séptico monitorizados com cateter de artéria pulmonar. Foi obtido sangue simultaneamente para determinação da SvcO2, SvO2 e SvaO2. Realizado testes de correlação linear (significativos se pINTRODUCTION: Central venous oxygen saturation (SvcO2 has been proposed as an alternative for mixed venous oxygen saturation (SvO2, with a variable level of acceptance according to available data. This study aimed to evaluate possible differences between SvO2 and SvcO2 or atrial venous saturation (SvaO2, with emphasis on the role of cardiac output and their impact on clinical management of the septic patient. METHODS: This is an observational, prospective study of patients with septic shock monitored by pulmonary artery catheter. Blood was obtained simultaneously for SvcO2, SvO2 and SvaO2 determination. Linear correlation (significant if p<0.05 and agreement analysis (Bland-Altman were performed with samples and subgroups according to cardiac output. Moreover, agreement about clinical management based on these samples was evaluated. RESULTS: Sixty one measurements from 23 patients were obtained, median age of 65.0 (49.0-75.0 years and mean APACHE II of 27.7±6.3. Mean values of SvO2, SvcO2 and SvaO2 were 72.20±8.26%, 74.61±7.60% and 74.64±8.47%. Linear correlation test showed a weak correlation between SvO2 and SvcO2 (r=0.61, p<0.0001 and also between SvO2 and SvaO2 (r=0.70, p<0.0001. Agreements between SvcO2/SvO2 and SvaO2/SvO2 were -2.40

  16. Septic trochanteric bursitis in an adolescent.

    Science.gov (United States)

    Makki, Daoud; Watson, Alex James

    2010-01-01

    Trochanteric bursitis, whether septic or inflammatory in origin, is a condition that affects middle-aged patients. Here we report the rare case of an adolescent with septic trochanteric bursitis (treated successfully with intravenous antibiotics), review the available literature on septic bursitis, illustrate the importance of prompt recognition and treatment of this condition in any age group, and describe the clinical presentation and the radiologic findings.

  17. Combined milrinone and enteral metoprolol therapy in patients with septic myocardial depression

    Science.gov (United States)

    Schmittinger, Christian A; Dünser, Martin W; Haller, Maria; Ulmer, Hanno; Luckner, Günter; Torgersen, Christian; Jochberger, Stefan; Hasibeder, Walter R

    2008-01-01

    Introduction The multifactorial etiology of septic cardiomyopathy is not fully elucidated. Recently, high catecholamine levels have been suggested to contribute to impaired myocardial function. Methods This retrospective analysis summarizes our preliminary clinical experience with the combined use of milrinone and enteral metoprolol therapy in 40 patients with septic shock and cardiac depression. Patients with other causes of shock or cardiac failure, patients with beta-blocker therapy initiated more than 48 hours after shock onset, and patients with pre-existent decompensated congestive heart failure were excluded. In all study patients, beta blockers were initiated only after stabilization of cardiovascular function (17.7 ± 15.5 hours after shock onset or intensive care unit admission) in order to decrease the heart rate to less than 95 beats per minute (bpm). Hemodynamic data and laboratory parameters were extracted from medical charts and documented before and 6, 12, 24, 48, 72, and 96 hours after the first metoprolol dosage. Adverse cardiovascular events were documented. Descriptive statistical methods and a linear mixed-effects model were used for statistical analysis. Results Heart rate control (65 to 95 bpm) was achieved in 97.5% of patients (n = 39) within 12.2 ± 12.4 hours. Heart rate, central venous pressure, and norepinephrine, arginine vasopressin, and milrinone dosages decreased (all P milrinone dosages were increased in nine (22.5%) and six (15%) patients, respectively. pH increased (P < 0.001) whereas arterial lactate (P < 0.001), serum C-reactive protein (P = 0.001), and creatinine (P = 0.02) levels decreased during the observation period. Twenty-eight-day mortality was 33%. Conclusion Low doses of enteral metoprolol in combination with phosphodiesterase inhibitors are feasible in patients with septic shock and cardiac depression but no overt heart failure. Future prospective controlled trials on the use of beta blockers for septic cardiomyopathy

  18. MR imaging of septic sacroiliitis

    Energy Technology Data Exchange (ETDEWEB)

    Stuerzenbecher, A.; Hamm, B.; Bollow, M. [Humboldt-Universitaet, Berlin (DD). Bereich Medizin (Charite); Braun, J. [Freie Univ. Berlin (Germany). Universitaetsklinikum Benjamin Franklin; Paris, S. [Unfallkrankenhaus Berlin (Germany). Dept. of Radiology; Biedermann, T. [Krankenhaus Berlin-Buch (Germany). II. Kinderklinik

    2000-08-01

    Objective. To investigate the diagnostic value of magnetic resonance (MR) imaging in detecting septic sacroiliitis and to determine whether the MR characteristics allow this entity to be differentiated from sacroiliitis in spondylarthropathy (SpA).Patients and design. The imaging findings of 11 patients with septic sacroiliitis were retrospectively analyzed by two experienced radiologists. Radiographic surveys of the pelvis as well as computed tomography (CT) and MR images of the sacroiliac joints were available in all cases. Seven of the patients additionally underwent a follow-up MR examination. The MR imaging protocol comprised combinations of coronal and transverse T1-weighted spin-echo (SE) or fast SE sequences, T2-weighted gradient-echo (GE) sequences and short tau inversion recovery sequence (STIR) sequences as well as dynamic contrast- enhanced T1-weighted acquisitions.Results. Three patients with a short disease history showed anterior and/or posterior subperiosteal infiltrations (''lava cleft phenomenon''), transcapsular infiltrations of juxta-articular muscle layers, which obscured the fasciae, and periarticular bone marrow edema. The eight patients with more advanced stages of sacroiliitis additionally showed abscess formation, sequestration, and erosion. At follow-up MR examination (n=7) under systemic antibiotic treatment, the morphologic characteristics showed progression (n=1), regression (n=4), unchanged findings (n=1), or a mixed response (n=1). Clinical improvement precedes resolution of the MR findings.Conclusions. Anterior and/or posterior subperiosteal infiltrations and transcapsular infiltrations of juxta-articular muscle layers were depicted in all patients. These MR imaging findings are characteristic of septic sacroiliitis and may be used to differentiate this entity from sacroiliitis in SpA. (orig.)

  19. Pseudomonas Septic Arthritis | Thanni | Nigerian Journal of ...

    African Journals Online (AJOL)

    BACKGROUND: Septic arthritis due to pseudomonas species is unusual and when it occurs, there is often an underlying cause like immune depression, intravenous drug abuse or a penetrating injury. PATIENT AND METHOD: We report a case of pseudomonas septic arthritis complicating cannulation of a leg vein following ...

  20. Enhancement of antinociception by coadminstration of minocycline and a non-steroidal anti-inflammatory drug indomethacin in naïve mice and murine models of LPS-induced thermal hyperalgesia and monoarthritis

    Directory of Open Access Journals (Sweden)

    Masocha Willias

    2010-12-01

    Full Text Available Abstract Background Minocycline and a non-steroidal anti-inflammatory drug (NSAID indomethacin, have anti-inflammatory activities and are both used in the management of rheumatoid arthritis. However, there are no reports on whether coadministration of these drugs could potentiate each other's activities in alleviating pain and weight bearing deficits during arthritis. Methods LPS was injected to BALB/c mice intraperitoneally (i.p. to induce thermal hyperalgesia. The hot plate test was used to study thermal nociception in naïve BALB/c and C57BL/6 mice and BALB/c mice with LPS-induced thermal hyperalgesia and to evaluate antinociceptive effects of drugs administered i.p. Monoarthritis was induced by injection of LPS intra-articularly into the right hind (RH limb ankle joint of C57BL/6 mice. Weight bearing changes and the effect of i.p. drug administration were analyzed in freely moving mice using the video-based CatWalk gait analysis system. Results In naïve mice indomethacin (5 to 50 mg/kg had no significant activity, minocycline (25 to 100 mg/kg produced hyperalgesia to thermal nociception, however, coadministration of minocycline 50 mg/kg with indomethacin 5 or 10 mg/kg produced significant antinociceptive effects in the hot plate test. A selective inhibitor of COX-1, FR122047 (10 mg/kg and a selective COX-2 inhibitor, CAY10404 (10 mg/kg had no significant antinociceptive activities to thermal nociception in naïve mice, however, coadministration of minocycline, with CAY10404 but not FR122047 produced significant antinociceptive effects. In mice with LPS-induced hyperalgesia vehicle, indomethacin (10 mg/kg or minocycline (50 mg/kg did not produce significant changes, however, coadministration of minocycline plus indomethacin resulted in antinociceptive activity. LPS-induced RH limb monoarthritis resulted in weight bearing (RH/left hind (LH limb paw pressure ratios and RH/LH print area ratios deficits. Treatment with indomethacin (1 mg/kg or

  1. Septic Shock after Conservative Management for Placenta Accreta

    Directory of Open Access Journals (Sweden)

    Ying-Cheng Chiang

    2006-03-01

    Conclusion: At present, there is no consensus about the optimal treatment for placenta accreta. Conservative treatment appears to be an alternative in selected patients, but the complications such as sepsis should be carefully identified and appropriately managed.

  2. Pathophysiology of septic shock: From bench to bedside.

    Science.gov (United States)

    McConnell, Kevin W; Coopersmith, Craig M

    2016-04-01

    Our understanding of sepsis and its resultant outcomes remains a paradox. On the one hand, we know more about the pathophysiology of sepsis than ever before. However, this knowledge has not been successfully translated to the bedside, as the vast majority of clinical trials for sepsis have been negative. Yet even in the general absence of positive clinical trials, mortality from sepsis has fallen to its lowest point in history, in large part due to educational campaigns that stress timely antibiotics and hemodynamic support. While additional improvements in outcome will assuredly result from further compliance with evidence based practices, a deeper understanding of the science that underlies the host response in sepsis is critical to the development of novel therapeutics. In this review, we outline immunopathologic abnormalities in sepsis, and then look at potential approaches to therapeutically modulate them. Ultimately, an understanding of the science underlying sepsis should allow the critical care community to utilize precision medicine to combat this devastating disease on an individual basis leading to improved outcomes. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  3. Association between sympathoadrenal activation, fibrinolysis, and endothelial damage in septic patients

    DEFF Research Database (Denmark)

    Johansson, Pär I; Haase, Nicolai; Perner, Anders

    2014-01-01

    for Severe Sepsis/Septic Shock trial who were expected not to receive catecholamines at screening preintervention (baseline) and had baseline blood sampled. Clinical, outcome data, and measurements of plasma concentration (p-) biomarkers reflecting sympathoadrenal activation, endothelial activation......-type plasminogen activator, and plasminogen activator inhibitor 1 (PAI-1) and negatively with PAI-1/tissue-type plasminogen activator ratio (all PPAI-1 (all P

  4. Septic pulmonary embolism caused by a Klebsiella pneumoniae liver abscess: clinical characteristics, imaging findings, and clinical courses

    Directory of Open Access Journals (Sweden)

    Deng-Wei Chou

    2015-06-01

    Full Text Available OBJECTIVES: Septic pulmonary embolism caused by a Klebsiella (K. pneumoniae liver abscess is rare but can cause considerable morbidity and mortality. However, clinical information regarding this condition is limited. This study was conducted to elucidate the full disease spectrum to improve its diagnosis and treatment. METHOD: We reviewed the clinical characteristics, imaging findings, and clinical courses of 14 patients diagnosed with septic pulmonary embolism caused by a K. pneumoniae liver abscess over a period of 9 years. RESULTS: The two most prevalent symptoms were fever and shortness of breath. Computed tomography findings included a feeding vessel sign (79%, nodules with or without cavities (79%, pleural effusions (71%, peripheral wedge-shaped opacities (64%, patchy ground-glass opacities (50%, air bronchograms within a nodule (36%, consolidations (21%, halo signs (14%, and lung abscesses (14%. Nine (64% of the patients developed severe complications and required intensive care. According to follow-up chest radiography, the infiltrates and consolidations were resolved within two weeks, and the nodular opacities were resolved within one month. Two (14% patients died of septic shock; one patient had metastatic meningitis, and the other had metastatic pericarditis. CONCLUSION: The clinical presentations ranged from insidious illness with fever and respiratory symptoms to respiratory failure and septic shock. A broad spectrum of imaging findings, ranging from nodules to multiple consolidations, was detected. Septic pulmonary embolism caused by a K. pneumoniae liver abscess combined with the metastatic infection of other vital organs confers a poor prognosis.

  5. 8-Hydroxyquinoline inhibits iNOS expression and nitric oxide production by down-regulating LPS-induced activity of NF-κB and C/EBPβ in Raw 264.7 cells

    International Nuclear Information System (INIS)

    Kim, Young-Ho; Woo, Kyung Jin; Lim, Jun Hee; Kim, Shin; Lee, Tae Jin; Jung, Eun Mi; Lee, Jin-Man; Park, Jong-Wook; Kwon, Taeg Kyu

    2005-01-01

    In activated macrophage, large amounts of nitric oxide (NO) are generated by inducible nitric oxide synthase (iNOS), resulting in acute or chronic inflammatory disorders. In Raw 264.7 cells stimulated with lipopolysaccharide (LPS) to mimic inflammation, 8-hydroxyquinoline (8HQ) inhibited the LPS-induced expression of both iNOS protein and mRNA in a parallel dose-dependent manner. 8HQ did not enhance the degradation of iNOS mRNA. To investigate the mechanism by which 8HQ inhibits iNOS gene expression, we examined the activation of MAP kinases in Raw 264.7 cells. We did not observe any significant change in the phosphorylation of MAPKs between LPS alone and LPS plus 8HQ-treated cells. Moreover, 8HQ significantly inhibited the DNA-binding activity of nuclear factor-κB (NF-κB) and CCAAT/enhancer-binding protein β (C/EBPβ), but not activator protein-1 and cAMP response element-binding protein. Taken together, these results suggest that 8HQ acts to inhibit inflammation through inhibition of NO production and iNOS expression through blockade of C/EBPβ DNA-binding activity and NF-κB activation

  6. Clinical characteristics and outcomes of septic bursitis.

    Science.gov (United States)

    Lieber, Sarah B; Fowler, Mary Louise; Zhu, Clara; Moore, Andrew; Shmerling, Robert H; Paz, Ziv

    2017-12-01

    Limited data guide practice in evaluation and treatment of septic bursitis. We aimed to characterize clinical characteristics, microbiology, and outcomes of patients with septic bursitis stratified by bursal involvement, presence of trauma, and management type. We conducted a retrospective cohort study of adult patients admitted to a single center from 1998 to 2015 with culture-proven olecranon and patellar septic bursitis. Baseline characteristics, clinical features, microbial profiles, operative interventions, hospitalization lengths, and 60-day readmission rates were determined. Patients were stratified by bursitis site, presence or absence of trauma, and operative or non-operative management. Of 44 cases of septic bursitis, patients with olecranon and patellar bursitis were similar with respect to age, male predominance, and frequency of bursal trauma; patients managed operatively were younger (p = 0.05). Clinical features at presentation and comorbidities were similar despite bursitis site, history of trauma, or management. The most common organism isolated from bursal fluid was Staphylococcus aureus. Patients managed operatively were discharged to rehabilitation less frequently (p = 0.04). This study of septic bursitis is among the largest reported. We were unable to identify presenting clinical features that differentiated patients treated surgically from those treated conservatively. There was no clear relationship between preceding trauma or bursitis site and clinical course, management, or outcomes. Patients with bursitis treated surgically were younger. Additional study is needed to identify patients who would benefit from early surgical intervention for septic bursitis.

  7. Immune-modulating interventions in critically ill septic patients: pharmacological options

    DEFF Research Database (Denmark)

    Toft, Palle; Tønnesen, Else

    2011-01-01

    Critically ill patients with severe sepsis and septic shock are characterized by a systemic inflammatory response consisting of pro- and anti-inflammatory mediators. Owing to the high mortality of severe sepsis, great efforts have been undertaken within the last 30 years to develop an immune...... insulin therapy have been shown to improve survival in septic patients. However, in later studies, it has been difficult to reproduce these beneficial effects. There appears to be a discrepancy between the promising effects of immune-modulating interventions in animal studies and the effects seen......-modulating therapy to improve survival. Relatively few pharmacological immune-modulating interventions have demonstrated a beneficial impact on survival, while other studies have shown a detrimental effect of such interventions. Among the immune-modulating interventions tested, activated protein C and intensive...

  8. Septic arthritis of the sacroiliac joint

    Science.gov (United States)

    Sebastian, Agata; Błach, Katarzyna; Silicki, Jurand; Wiland, Piotr

    2018-01-01

    Septic arthritis is an inflammation of a joint caused directly by various microorganisms. It is often characterized by many unspecific symptoms. Bacteria is the most often etiological factor. We present a case report of a 76-years old woman with a unilateral septic arthritis of the sacroiliac joint. Bacterial sacroiliitis should be taken into account in patients with sacroiliitis and fever onset. Proper diagnosis can be very often difficult and delayed but fast implementation of antibiotic therapy is extremely important in the treatment process. Diagnostic imaging is crucial to the diagnosis and monitoring of septic arthritis. Magnetic resonance imaging is the most relevant tool for the detection of sacroiliitis, allowing the institution of therapeutic strategies to impede the progression of the disease. PMID:29686444

  9. Evolução de variáveis hemodinâmicas e perfusionais durante o choque séptico experimental tratado com ressuscitação volêmica guiada por metas Hemodynamic and perfusion variables during experimental septic shock treated with goal-directed fluid resuscitation

    Directory of Open Access Journals (Sweden)

    Marcelo Park

    2011-09-01

    gold standard in sepsis therapy, few studies have described hemodynamic and perfusion parameters during this procedure. This study aims to describe these parameters during septic shock without resuscitation and after 12 hours of goal-directed resuscitation. METHODS: Thirteen anesthetized pigs (35-45 kg had peritonitis caused by fecal inoculation (0.75 g/kg. After developing persistent hypotension, both groups were given antibiotics and randomized either to the control group (n=7 or the experimental group (n=6. In the control group, hemodynamic control was optimized to maintain a central venous pressure of 8-12 mmHg, a urinary output above 0.5 mL/kg/hour and a mean arterial blood pressure above 65 mmHg. The experimental group received the above target therapy in addition to maintaining a SvO2 above 65%. The interventions included lactated Ringer's solution and norepinephrine for both groups and dobutamine in the SvO2 group. The animals were treated for 12 hours or until death. RESULTS: Untreated sepsis was associated with significant reductions in SvO2, PvO2, cardiac output and central venous pressure in addition to increased arteriovenous oxygen saturation and veno-arterial CO2 differences. Following resuscitation, these parameters were corrected in both groups. Goal-directed resuscitation was associated with a better hemodynamic profile, characterized by higher SvO2, cardiac output and central venous pressure. CONCLUSIONS: Non-resuscitated sepsis showed a hemodynamic profile suggesting hypovolemia, with worsened perfusion and hemodynamics, which is reversed upon fluid resuscitation. Goal-directed resuscitation is associated with significantly improved hemodynamic and perfusion parameters

  10. [Septic pylephlebitis associated with Enterobacter cloacae septicemia].

    Science.gov (United States)

    Amezyane, T; Abouzahir, A; El Kharrass, A; Bassou, D; Fatihi, J; Hammi, S; Mahassin, F; Ghafir, D; Ohayon, V

    2010-02-01

    Septic pylephlebitis or purulent thrombosis of the portal venous system generally results from a progressive extension of suppurated thrombophlebitis, secondary to an intrabdominal infection. Germs most often found are Escherichia coli and Streptococcus, isolation of Enterobacter cloacae is unusual. We report a particular observation of septic pylephlebitis associated with E. cloacae bacteremia, without biliary, digestive or pancreatic lesion on the CT-scan. The antibiotic sensitivity pattern of the isolated germ and the negative epidemiologic investigation pled in favour of community acquired infection. The infection resolved with antibiotics and anticoagulation, followed by total repermeation of the portal system. Copyright 2009 Elsevier Masson SAS. All rights reserved.

  11. Septic arthritis caused by Peptostreptococcus asaccharolyticus

    Directory of Open Access Journals (Sweden)

    Carlos Costa

    2016-07-01

    Full Text Available Peptostreptococcus spp are commensal organisms, usually involved in periodontal disease. Peptostreptococcus asaccharolyticus is an anaerobic gram-negative cocci, difficult to isolate due to its slow growth. Septic arthritis by this microorganism is a rare entity, but it can occur by hematogenous dissemination from a distant focus. Colonization and growth are more likely to occur in an already damaged articulation. We report the case of a 57 year-old woman with peripheral spondyloarthritis who developed knee septic arthritis by Peptostreptococcus asaccharolyticus.

  12. Domestic wells have high probability of pumping septic tank leachate

    Science.gov (United States)

    Bremer, J. E.; Harter, T.

    2012-08-01

    Onsite wastewater treatment systems are common in rural and semi-rural areas around the world; in the US, about 25-30% of households are served by a septic (onsite) wastewater treatment system, and many property owners also operate their own domestic well nearby. Site-specific conditions and local groundwater flow are often ignored when installing septic systems and wells. In areas with small lots (thus high spatial septic system densities), shallow domestic wells are prone to contamination by septic system leachate. Mass balance approaches have been used to determine a maximum septic system density that would prevent contamination of groundwater resources. In this study, a source area model based on detailed groundwater flow and transport modeling is applied for a stochastic analysis of domestic well contamination by septic leachate. Specifically, we determine the probability that a source area overlaps with a septic system drainfield as a function of aquifer properties, septic system density and drainfield size. We show that high spatial septic system density poses a high probability of pumping septic system leachate. The hydraulic conductivity of the aquifer has a strong influence on the intersection probability. We find that mass balance calculations applied on a regional scale underestimate the contamination risk of individual drinking water wells by septic systems. This is particularly relevant for contaminants released at high concentrations, for substances that experience limited attenuation, and those that are harmful even at low concentrations (e.g., pathogens).

  13. Domestic wells have high probability of pumping septic tank leachate

    Directory of Open Access Journals (Sweden)

    J. E. Bremer

    2012-08-01

    Full Text Available Onsite wastewater treatment systems are common in rural and semi-rural areas around the world; in the US, about 25–30% of households are served by a septic (onsite wastewater treatment system, and many property owners also operate their own domestic well nearby. Site-specific conditions and local groundwater flow are often ignored when installing septic systems and wells. In areas with small lots (thus high spatial septic system densities, shallow domestic wells are prone to contamination by septic system leachate. Mass balance approaches have been used to determine a maximum septic system density that would prevent contamination of groundwater resources. In this study, a source area model based on detailed groundwater flow and transport modeling is applied for a stochastic analysis of domestic well contamination by septic leachate. Specifically, we determine the probability that a source area overlaps with a septic system drainfield as a function of aquifer properties, septic system density and drainfield size. We show that high spatial septic system density poses a high probability of pumping septic system leachate. The hydraulic conductivity of the aquifer has a strong influence on the intersection probability. We find that mass balance calculations applied on a regional scale underestimate the contamination risk of individual drinking water wells by septic systems. This is particularly relevant for contaminants released at high concentrations, for substances that experience limited attenuation, and those that are harmful even at low concentrations (e.g., pathogens.

  14. Use of cryopoor plasma for albumin replacement and continuous antimicrobial infusion for treatment of septic peritonitis in a dog.

    Science.gov (United States)

    Ropski, Meaghan K; Guillaumin, Julien; Monnig, Andrea A; Townsend, Katy; McLoughlin, Mary A

    2017-05-01

    To report the successful management of a dog with septic peritonitis and septic shock secondary to enterectomy dehiscence using novel techniques for identification of intestinal dehiscence and for septic shock treatment. A 5-year-old castrated male Bernese Mountain Dog presented for lethargy 6 days following enterotomy for foreign body obstruction. Septic peritonitis was identified due to dehiscence of the enterotomy site, and resection and anastomosis were performed using a gastrointestinal anastomosis and thoracoabdominal stapling device. Postoperatively the patient experienced severe hypotension, which responded to norepinephrine constant rate infusion (CRI) after failing to improve with fluid therapy or dopamine CRI. Further treatment included antimicrobial CRI and supportive care including careful fluid therapy. Due to low effective circulating volume paired with intersititial fluid overload and large volume abdominal effusion, fluid therapy consisted of a combination of human serum albumin, canine albumin, synthetic colloids, and isotonic crystalloids. Cryopoor plasma (CPP) was used as a source of canine albumin and intravascular volume. On Day 4, food dye was given through a nasogastric tube due to suspicion of dehiscence of the anastomosis site. Dehiscence was confirmed during abdominal exploratory, and a second resection and anastomosis was performed. Abdominal partial closure with vacuum-assisted closure device was performed. Supportive care was continued with CPP CRI and imipenem CRI. Planned relaparotomy to change the vacuum-assisted closure device was performed 48 hours later, with abdominal closure 96 hours after anastomosis. The patient was discharged on Day 15. Recheck 12 months later was normal. This case includes novel techniques such food dye via nasogastric tube to identify anastomosis dehiscence, use of CPP as a source of canine albumin, and antimicrobial CRI in a dog with septic peritonitis. © Veterinary Emergency and Critical Care Society

  15. Correlation between high blood IL-6 level, hyperglycemia, and glucose control in septic patients.

    Science.gov (United States)

    Nakamura, Masataka; Oda, Shigeto; Sadahiro, Tomohito; Watanabe, Eizo; Abe, Ryuzo; Nakada, Taka-Aki; Morita, Yasumasa; Hirasawa, Hiroyuki

    2012-12-12

    The aim of the present study was to investigate the relationship between the blood IL-6 level, the blood glucose level, and glucose control in septic patients. This retrospective observational study in a general ICU of a university hospital included a total of 153 patients with sepsis, severe sepsis, or septic shock who were admitted to the ICU between 2005 and 2010, stayed in the ICU for 7 days or longer, and did not receive steroid therapy prior to or after ICU admission. The severity of stress hyperglycemia, status of glucose control, and correlation between those two factors in these patients were investigated using the blood IL-6 level as an index of hypercytokinemia. A significant positive correlation between blood IL-6 level and blood glucose level on ICU admission was observed in the overall study population (n = 153; r = 0.24, P = 0.01), and was stronger in the nondiabetic subgroup (n = 112; r = 0.42, P glucose control (blood glucose level blood IL-6 level on ICU admission (P blood IL-6 level after ICU admission remained significantly higher and the 60-day survival rate was significantly lower in the failed glucose control group than in the successful glucose control group (P blood IL-6 level was correlated with hyperglycemia and with difficulties in glucose control in septic patients. These results suggest the possibility that hypercytokinemia might be involved in the development of hyperglycemia in sepsis, and thereby might affect the success of glucose control.

  16. Enhanced sludge reduction in septic tanks by increasing temperature.

    Science.gov (United States)

    Pussayanavin, Tatchai; Koottatep, Thammarat; Eamrat, Rawintra; Polprasert, Chongrak

    2015-01-01

    Septic tanks in most developing countries are constructed without drainage trenches or leaching fields to treat toilet wastewater and /or grey water. Due to the short hydraulic retention time, effluents of these septic tanks are still highly polluted, and there is usually high accumulation of septic tank sludge or septage containing high levels of organics and pathogens that requires frequent desludging and subsequent treatment. This study aimed to reduce sludge accumulation in septic tanks by increasing temperatures of the septic tank content. An experimental study employing two laboratory-scale septic tanks fed with diluted septage and operating at temperatures of 40 and 30°C was conducted. At steady-state conditions, there were more methanogenic activities occurring in the sludge layer of the septic tank operating at the temperature of 40°C, resulting in less total volatile solids (TVS) or sludge accumulation and more methane (CH4) production than in the unit operating at 30°C. Molecular analysis found more abundance and diversity of methanogenic microorganisms in the septic tank sludge operating at 40°C than at 30°C. The reduced TVS accumulation in the 40°C septic tank would lengthen the period of septage removal, resulting in a cost-saving in desluging and septage treatment. Cost-benefit analysis of increasing temperatures in septic tanks was discussed.

  17. Radiologic findings of cerebral septic embolism

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jee Young; Kim, Sang Joon; Kim Tae Hoon; Kim, Seung Chul; Kim, Jae Seung; Pai, Hyun Joo [Dankook Univ., Seoul (Korea, Republic of). Coll. of Medicine; Kim, Dong Ik [Yonsei Univ., Seoul (Korea, Republic of). Coll. of Medicine; Chang, Kee Hyun [Seoul National Univ. (Korea, Republic of). Coll. of Medicine; Choi, Woo Suk [Kyung Hee Univ., Seoul (Korea, Republic of). Coll. of Medicine

    1998-01-01

    To determine the MR and CT findings which differentiate cerebral septic embolism from thrombotic infarction. Cerebral septic embolism was confirmed by blood culture in six patients and autopsy in two. The number, size, distribution, contrast enhancement, and hemorrhage of the lesions, as seen on MR and CT, were retrospectively analyzed, and four patients were followed up for between one week and seven months. In a total of eight patients, infective endocarditis (n=5) and sepsis (n=3) caused cerebral septic embolism. The number, of lesions was 3 {approx} 7 in six patients, over 10 in one, and innumerable in one: these varied in size from punctate to 6 cm and were distributed in various areas of the brain. Gyral infarction was noted in five patients: non-enhancing patchy lesions involving the basal ganglia or white matter were found in five, tiny isolated nodular or ring-enhancing small lesions involving the cortex and white matter in three, peripheral rim-enhancing large lesions in one, and numerous enhancing nodules disseminated in the cortex in one. Hemorrhage had occurred in six. follow-up studies in four patients showed that initial lesions had enlarged in two and regressed in two: new lesions had appeared in two. Multiple lesions of different sizes and various patterns which include gyral infarction, patchy or nodular lesion in the cortex, white mater of basal ganglia, and isolated small ring-like or nodular enhancement or frequent hemorrhage are findings which could be helpful in the radiologic diagnosis of cerebral septic embolism. (author). 8 refs., 5 figs.

  18. Radiologic findings of cerebral septic embolism

    International Nuclear Information System (INIS)

    Lee, Jee Young; Kim, Sang Joon; Kim Tae Hoon; Kim, Seung Chul; Kim, Jae Seung; Pai, Hyun Joo; Kim, Dong Ik; Chang, Kee Hyun; Choi, Woo Suk

    1998-01-01

    To determine the MR and CT findings which differentiate cerebral septic embolism from thrombotic infarction. Cerebral septic embolism was confirmed by blood culture in six patients and autopsy in two. The number, size, distribution, contrast enhancement, and hemorrhage of the lesions, as seen on MR and CT, were retrospectively analyzed, and four patients were followed up for between one week and seven months. In a total of eight patients, infective endocarditis (n=5) and sepsis (n=3) caused cerebral septic embolism. The number, of lesions was 3 ∼ 7 in six patients, over 10 in one, and innumerable in one: these varied in size from punctate to 6 cm and were distributed in various areas of the brain. Gyral infarction was noted in five patients: non-enhancing patchy lesions involving the basal ganglia or white matter were found in five, tiny isolated nodular or ring-enhancing small lesions involving the cortex and white matter in three, peripheral rim-enhancing large lesions in one, and numerous enhancing nodules disseminated in the cortex in one. Hemorrhage had occurred in six. follow-up studies in four patients showed that initial lesions had enlarged in two and regressed in two: new lesions had appeared in two. Multiple lesions of different sizes and various patterns which include gyral infarction, patchy or nodular lesion in the cortex, white mater of basal ganglia, and isolated small ring-like or nodular enhancement or frequent hemorrhage are findings which could be helpful in the radiologic diagnosis of cerebral septic embolism. (author). 8 refs., 5 figs

  19. Monocyte expression and soluble levels of the haemoglobin receptor (CD163/sCD163 and the mannose receptor (MR/sMR in septic and critically ill non-septic ICU patients.

    Directory of Open Access Journals (Sweden)

    Anders G Kjærgaard

    Full Text Available BACKGROUND: The diagnosis of sepsis is challenging and there is an unmet need for sensitive and specific diagnostic and prognostic biomarkers. Following activation of macrophages and monocytes, the haptoglobin-haemoglobin receptor (CD163 and the mannose receptor (MR are shed into the circulation (sCD163 and sMR. OBJECTIVE: We investigated monocyte expression of CD163 and MR, and levels of sCD163 and sMR in septic and non-septic patients, and in healthy controls. We hypothesised that these receptors are elevated during sepsis and can be used diagnostic and prognostic. METHODS: Twenty-one patients with severe sepsis or septic shock and 15 critically ill non-septic patients were included in this prospective observational study at three ICUs at Aarhus University Hospital and Randers Regional Hospital, Denmark. Fifteen age- and gender-matched healthy volunteers served as controls. Levels of sCD163 and sMR were measured using a sandwich ELISA and monocyte expression of CD163 and MR was evaluated by flow cytometry during the first four days of ICU stay. The diagnostic and prognostic values of the receptors were assessed using AUROC curves. RESULTS: At ICU admission and during the observation period, monocyte expression of CD163 and levels of sCD163 and sMR were significantly higher in septic patients compared with non-septic patients and healthy controls (p<0.01 for all comparisons. Monocytes did not express MR. The diagnostic values estimated by AUROC were 1.00 for sMR, 0.95 for sCD163, 0.87 for CRP, and 0.75 for monocyte-bound CD163. Among the septic patients, monocyte expression of CD163 was higher in non-survivors compared with survivors at ICU admission (p = 0.02 and during the observation period (p = 0.006. The prognostic value of monocyte-bound CD163 estimated by AUROC at ICU admission was 0.82. CONCLUSION: The macrophage-specific markers CD163, sCD163, and sMR are increased in septic patients. Particularly sMR is a promising new

  20. MR findings of septic cavernous sinus thrombosis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hyeong Lae; Lee, Nam Joon; Lee, Jung Hee; Pyo, Hyeon Soon; Eo, Geun; Kim, Kyo Nam; Kim, Young Soon; Kim, Jang Min [Kwang Myung Sung Ae Hospital, Kwang Myung (Korea, Republic of); Lee, Don Young [Korea University Anam Hospital, Seoul (Korea, Republic of)

    2000-08-01

    To evaluate the MR findings of septic thrombosis of the cavernous sinus. Eleven MR images of six patients with septic cavernous sinus thrombosis obtained over a five-year period and proven clinically or radiologically were retrospectively reviewed. The contour and enhancement pattern of the cavernous sinus, changes in the internal carotid artery, orbit, pituitary gland and sphenoid sinus, and intracranial abnormalities were analyzed and compared with the findings of follow-up studies. In all six patients, contrast study revealed asymmetrical enlargement of the ipsilateral cavernous sinus and multiple irregular filling defects within it. Narrowing of the cavernous portion of the ipsilateral internal carotid artery was noted in five patients, upward displacement of the ipsilateral internal carotid artery in four, ipsilateral proptosis with engorgement of the superior ophthalmic vein in two, pituitary enlargement in five, and inflammatory change in the sphenoid sinus in six. Associated intracranial abnormalities included edema and enhancement in the meninx, temporal lobe, or pons adjacent to the cavernous sinus in four patients, hydrocephalus in one, and cerebral infarction in one. Follow-up MR imaging indicated that the extent of asymmetrical enlargement of the cavernous sinus, filling defects within it, as seen on contrast study, and enlarged pituitary glands had all decreased, without significant interval change. MR imaging is useful in the diagnosis of septic cavernous sinus thrombosis. Asymmetrical enlargement of the cavernous sinus, multiple irregular filling defect within it, as seen on contrast study, and changes in the internal carotid artery are characteristic findings. (author)

  1. Caracterização físico-química da acidose metabólica induzida pela expansão volêmica inicial com solução salina a 0,9% em pacientes com sepse grave e choque séptico Physicochemical characterization of metabolic acidosis induced by normal saline resuscitation of patients with severe sepsis and septic shock

    Directory of Open Access Journals (Sweden)

    Marcelo Park

    2011-06-01

    Full Text Available OBJETIVO: O objetivo deste estudo foi caracterizar e quantificar a acidose metabólica causada pela expansão volêmica inicial na reanimação de pacientes com sepse grave e choque séptico. MÉTODOS: Uma coleta de sangue para caracterização físico-química do equilíbrio ácido-básico antes e após a expansão volêmica com 30 mL/kg de solução salina a 0,9%. O diagnóstico e a quantificação da acidose metabólica foram feitas com o uso do "standard base excess" (SBE. RESULTADOS: Oito pacientes com 58 ± 13 anos e APACHE II de 20 ± 4 foram expandidos com 2000 ± 370 mL de solução salina a 0,9%. Houve queda do pH de 7,404 ± 0,080 para 7,367 ± 0,086 (P=0,018 associada a elevação da PCO2 de 30 ± 5 mmHg para 32 ± 2 mmHg (P=0,215 e queda do SBE de -4,4 ± 5,6 para -6,0 ± 5,7 mEq/L (P=0,039. Esta queda do SBE foi associada ao poder acidificante de dois fatores: elevação não significativa do "strong ion gap" (SIG de 6,1 ± 3,4 para 7,7 ± 4,0 mEq/L (P=0,134 e queda não significativa do "strong ion diference" aparente inorgânico (SIDai de 40 ± 5 para 38 ± 4 mEq/L (P=0,318. Em contraposição, houve queda da albumina sérica de 3,1 ± 1,0 para 2,6 ± 0,8 mEq/L (P=0,003, que teve um poder alcalinizante sobre o SBE. A elevação do cloro sérico de 103 ± 10 para 106 ± 7 mEq/L (POBJECTIVE: The aim of this study was to characterize and quantify metabolic acidosis that was caused by initial volume expansion during the reanimation of patients with severe sepsis and septic shock. METHODS: A blood sample was drawn for physicochemical characterization of the patient's acid-base equilibrium both before and after volume expansion using 30 mL/kg 0.9% saline solution. The diagnosis and quantification of metabolic acidosis were based on the standard base excess (SBE. RESULTS: Eight patients with a mean age of 58 ± 13 years and mean APACHE II scores of 20 ± 4 were expanded using 2,000 ± 370 mL of 0.9% saline solution. Blood pH dropped

  2. Shock absorber

    International Nuclear Information System (INIS)

    Nemeth, J.D.

    1981-01-01

    A shock absorber for the support of piping and components in a nuclear power plant is described. It combines a high degree of stiffness under sudden shocks, e.g. seismic disturbances, with the ability to allow for thermal expansion without resistance when so required. (JIW)

  3. ShockOmics: multiscale approach to the identification of molecular biomarkers in acute heart failure induced by shock.

    Science.gov (United States)

    Aletti, Federico; Conti, Costanza; Ferrario, Manuela; Ribas, Vicent; Bollen Pinto, Bernardo; Herpain, Antoine; Post, Emiel; Romay Medina, Eduardo; Barlassina, Cristina; de Oliveira, Eliandre; Pastorelli, Roberta; Tedeschi, Gabriella; Ristagno, Giuseppe; Taccone, Fabio S; Schmid-Schönbein, Geert W; Ferrer, Ricard; De Backer, Daniel; Bendjelid, Karim; Baselli, Giuseppe

    2016-01-28

    The ShockOmics study (ClinicalTrials.gov identifier NCT02141607) is a multicenter prospective observational trial aimed at identifying new biomarkers of acute heart failure in circulatory shock, by means of a multiscale analysis of blood samples and hemodynamic data from subjects with circulatory shock. Ninety septic shock and cardiogenic shock patients will be recruited in three intensive care units (ICU) (Hôpital Erasme, Université Libre de Bruxelles, Belgium; Hospital Universitari Mutua Terrassa, Spain; Hôpitaux Universitaires de Genève, Switzerland). Hemodynamic signals will be recorded every day for up to seven days from shock diagnosis (time T0). Clinical data and blood samples will be collected for analysis at: i) T1  5 and lactate levels ≥ 2 mmol/L. The exclusion criteria are: expected death within 24 h since ICU admission; > 4 units of red blood cells or >1 fresh frozen plasma transfused; active hematological malignancy; metastatic cancer; chronic immunodepression; pre-existing end stage renal disease requiring renal replacement therapy; recent cardiac surgery; Child-Pugh C cirrhosis; terminal illness. Enrollment will be preceded by the signature of the Informed Consent by the patient or his/her relatives and by the physician in charge. Three non-shock control groups will be included in the study: a) healthy blood donors (n = 5); b) septic patients (n = 10); c) acute myocardial infarction or patients with prolonged acute arrhythmia (n = 10). The hemodynamic data will be downloaded from the ICU monitors by means of dedicated software. The blood samples will be utilized for transcriptomics, proteomics and metabolomics ("-omics") analyses. ShockOmics will provide new insights into the pathophysiological mechanisms underlying shock as well as new biomarkers for the timely diagnosis of cardiac dysfunction in shock and quantitative indices for assisting the therapeutic management of shock patients.

  4. Effect of temperature increments in septic tank efficiency

    International Nuclear Information System (INIS)

    Chi-Tec, M.; Caballero-Arzapalo, N.; Giacoman Vallejo, G.; Mendez-Novelo, R.; Quintal-Franco, C.

    2009-01-01

    Septic tanks are the main sewage disposal system used in Yucatan, Mexico. Septic tank content is stabilized under anaerobic conditions and is considered the temperature has a significant effect on the efficiency. This work was developed in order asses the feasibility to improve communal septic tanks efficiency by increasing content temperature. Temperatures inside the tank were increased using a hybrid heater system (solar and electricity). (Author)

  5. Retainment of the antimicrobial agent triclosan in a septic tank

    DEFF Research Database (Denmark)

    Kirjanova, Ala; Rimeika, Mindaugas; Vollertsen, Jes

    2014-01-01

    Laboratory experiments were conducted to investigate the fate of the antimicrobial agent triclosan (TCS) in a conventional septic tank. The main mechanism of TCS removal from wastewater was identified to be rapid TCS sorption to suspended particles followed by settling of these particles...... to the bottom of the septic tank. Sorption to particles was completed within minutes while the settling took several days. Therefore, in a septic tank the removal of TCS from wastewater is mainly determined by the removal of suspended particles by sedimentation. Over 5 days of hydraulic residence time...... subsequent sorption onto the septic sludge....

  6. demystifying the shock of shocking

    African Journals Online (AJOL)

    (with a pulse), atrial fibrillation and atrial flutter. The energy dose in cardioversion is less (0.5. - 2 J/kg) than in defibrillation (2 - 4 J/kg). In cardioversion the shock is discharged synchronously with the native R wave of the patient. Without synchronisation,. VF can be induced if a shock is delivered during the refractory period ...

  7. Septic and non-septic olecranon bursitis in the accident and emergency department--an approach to management.

    Science.gov (United States)

    Stell, I M

    1996-01-01

    Olecranon bursitis is relatively common. One third of episodes are septic. Most of the remainder are non-septic, with occasional rheumatological causes. Trauma can cause both septic and non-septic olecranon bursitis. Clinical features are helpful in separating septic from non-septic olecranon bursitis, but there may be local erythema in both. Aspiration should be carried out in all cases, and if the presence of infection is still in doubt, microscopy, Gram staining, and culture of the aspirate will resolve the issue. Septic olecranon bursitis should be treated by aspiration, which may need to be repeated, and a long course of antibiotics. Some cases will need admission, and a few will need surgical treatment. Non-septic olecranon bursitis can be managed with aspiration alone. Non-steroidal anti-inflammatory drugs probably hasten symptomatic improvement. Intrabursal corticosteroids produce a rapid resolution but concern remains over their long term local effects. Recovery from septic olecranon bursitis can take months. PMID:8894865

  8. Evidence-based diagnostics: adult septic arthritis.

    Science.gov (United States)

    Carpenter, Christopher R; Schuur, Jeremiah D; Everett, Worth W; Pines, Jesse M

    2011-08-01

    Acutely swollen or painful joints are common complaints in the emergency department (ED). Septic arthritis in adults is a challenging diagnosis, but prompt differentiation of a bacterial etiology is crucial to minimize morbidity and mortality. The objective was to perform a systematic review describing the diagnostic characteristics of history, physical examination, and bedside laboratory tests for nongonococcal septic arthritis. A secondary objective was to quantify test and treatment thresholds using derived estimates of sensitivity and specificity, as well as best-evidence diagnostic and treatment risks and anticipated benefits from appropriate therapy. Two electronic search engines (PUBMED and EMBASE) were used in conjunction with a selected bibliography and scientific abstract hand search. Inclusion criteria included adult trials of patients presenting with monoarticular complaints if they reported sufficient detail to reconstruct partial or complete 2 × 2 contingency tables for experimental diagnostic test characteristics using an acceptable criterion standard. Evidence was rated by two investigators using the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS). When more than one similarly designed trial existed for a diagnostic test, meta-analysis was conducted using a random effects model. Interval likelihood ratios (LRs) were computed when possible. To illustrate one method to quantify theoretical points in the probability of disease whereby clinicians might cease testing altogether and either withhold treatment (test threshold) or initiate definitive therapy in lieu of further diagnostics (treatment threshold), an interactive spreadsheet was designed and sample calculations were provided based on research estimates of diagnostic accuracy, diagnostic risk, and therapeutic risk/benefits. The prevalence of nongonococcal septic arthritis in ED patients with a single acutely painful joint is approximately 27% (95% confidence interval [CI] = 17

  9. Hypovolemic shock

    Science.gov (United States)

    ... the person's position unless they are in immediate danger. Do not give fluids by mouth. If person ... the patient with shock. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. Philadelphia, PA: ...

  10. MRI findings of treated bacterial septic arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Bierry, Guillaume; Huang, Ambrose J.; Chang, Connie Y.; Torriani, Martin; Bredella, Miriam A. [Massachusetts General Hospital and Harvard Medical School, Musculoskeletal Imaging and Intervention, Department of Radiology, Boston, MA (United States)

    2012-12-15

    The purpose of this study was to report the MRI findings that can be encountered in successfully treated bacterial septic arthritis. The study included 12 patients (8 male and 4 female; mean age 38 years, range 9-85) with 13 proven cases of bacterial septic arthritis. The joints involved were hip (n = 3), knee (n = 3), shoulder (n = 2), sacroiliac (n = 2), ankle (n = 1), wrist (n = 1), and elbow (n = 1). MRI examinations following surgical debridement and at initiation of antibiotic therapy and after successful treatment were compared for changes in effusion, synovium, bone, and periarticular soft tissues. Imaging findings were correlated with microbiological and clinical findings. Joint effusions were present in all joints at baseline and regressed significantly at follow-up MRI (p = 0.001). Abscesses were present in 5 cases (38 %), and their sizes decreased significantly at follow-up (p = 0.001). Synovial enhancement and thickening were observed in all joints at both baseline and follow-up MRI. Myositis/cellulitis was present in 10 cases (77 %) at baseline and in 8 cases (62 %) at follow-up MRI. Bone marrow edema was present in 10 joints (77 %) at baseline and persisted in 8 joints (62 %). Bone erosions were found in 8 joints (62 %) and persisted at follow-up MRI in all cases. The sizes of joint effusions and abscesses appear to be the factors with the most potential for monitoring therapy for septic arthritis, since both decreased significantly following successful treatment. Synovial thickening and enhancement, periarticular myositis/cellulitis, and bone marrow edema can persist even after resolution of the infection. (orig.)

  11. MRI findings of treated bacterial septic arthritis

    International Nuclear Information System (INIS)

    Bierry, Guillaume; Huang, Ambrose J.; Chang, Connie Y.; Torriani, Martin; Bredella, Miriam A.

    2012-01-01

    The purpose of this study was to report the MRI findings that can be encountered in successfully treated bacterial septic arthritis. The study included 12 patients (8 male and 4 female; mean age 38 years, range 9-85) with 13 proven cases of bacterial septic arthritis. The joints involved were hip (n = 3), knee (n = 3), shoulder (n = 2), sacroiliac (n = 2), ankle (n = 1), wrist (n = 1), and elbow (n = 1). MRI examinations following surgical debridement and at initiation of antibiotic therapy and after successful treatment were compared for changes in effusion, synovium, bone, and periarticular soft tissues. Imaging findings were correlated with microbiological and clinical findings. Joint effusions were present in all joints at baseline and regressed significantly at follow-up MRI (p = 0.001). Abscesses were present in 5 cases (38 %), and their sizes decreased significantly at follow-up (p = 0.001). Synovial enhancement and thickening were observed in all joints at both baseline and follow-up MRI. Myositis/cellulitis was present in 10 cases (77 %) at baseline and in 8 cases (62 %) at follow-up MRI. Bone marrow edema was present in 10 joints (77 %) at baseline and persisted in 8 joints (62 %). Bone erosions were found in 8 joints (62 %) and persisted at follow-up MRI in all cases. The sizes of joint effusions and abscesses appear to be the factors with the most potential for monitoring therapy for septic arthritis, since both decreased significantly following successful treatment. Synovial thickening and enhancement, periarticular myositis/cellulitis, and bone marrow edema can persist even after resolution of the infection. (orig.)

  12. Shock absorber

    International Nuclear Information System (INIS)

    Housman, J.J.

    1978-01-01

    A shock absorber is described for use in a hostile environment at the end of a blind passage for absorbing impact loads. The shock absorber includes at least one element which occupies the passage and which is comprised of a porous brittle material which is substantially non-degradable in the hostile environment. A void volume is provided in the element to enable the element to absorb a predetermined level of energy upon being crushed due to impact loading

  13. The race against the "septic shark".

    Science.gov (United States)

    Westphal, Martin; Kampmeier, Tim

    2015-01-01

    Great white sharks are responsible for about 10 cases of death annually worldwide, as compared with millions of deaths caused by sepsis. However, the basic principles of avoiding shark attacks and fighting sepsis seem to be similar: avoidance, attention, and speed, if necessary. The present review discusses the current status of the systemic inflammatory response syndrome (SIRS) criteria, which are actually content for discussion because of their low specificity. Current data suggest that one in eight patients with severe sepsis does not fulfill the SIRS criteria and is consequently missed, and therefore the calls for new definitions of sepsis are getting louder. Furthermore, the need for early treatment of sepsis and fast admission to an intensive care unit (ICU) with experienced stuff is reviewed as well as the early and appropriate initiation of therapy, namely antibiotic and volume therapy. A key feature is the analysis of the studies from the so-called "Sepsis Trilogy" (ProCESS, ARISE, and ProMiSe studies), with a focus on the status of early goal-directed therapy (EGDT). The authors of the "Sepsis Trilogy" concluded that there is no benefit regarding survival in septic patients by using EGDT as compared with standard therapy. However, the low mortality of the control groups within the "Sepsis Trilogy" studies as compared with the Rivers et al. study from 2001 leads to the conclusion that there has been an improvement in the therapy of septic patients, most probably due to the early initiation of therapy as a kind of "standard" in sepsis therapy. Finally, the phenomenon of a "large trial disease" is discussed, exemplary in a trial which investigated the maintenance of the "right" mean arterial pressure in sepsis patients. Even if the result of a large randomized trial might be that there is no difference between two study groups, the real exercise is to identify the patient collectives who might benefit or experience harm due to an intervention. In summary, as

  14. Modeling Serum Creatinine in Septic ICU Patients

    DEFF Research Database (Denmark)

    De Gaetano, Andrea; Cortese, Giuliana; Pedersen, Morten Gram

    2004-01-01

    Serum creatinine is a metabolite assumed to be constantly produced by the normally functioning muscle mass and is a good measure for monitoring daily renal function in the intensive care unit (ICU). High serum creatinine levels or an abnormal departure from normal pre-disease basal levels....... The present work details the structure of a model describing observed creatinine serum concentration (CSC) variations, depending on the time-varying septic insult to renal function in ICU patients, as well as the estimation of its parameters. CSC determinations were routinely obtained from 12 patients...

  15. Clinical Features, Short-Term Mortality, and Prognostic Risk Factors of Septic Patients Admitted to Internal Medicine Units

    Science.gov (United States)

    Mazzone, Antonino; Dentali, Francesco; La Regina, Micaela; Foglia, Emanuela; Gambacorta, Maurizia; Garagiola, Elisabetta; Bonardi, Giorgio; Clerici, Pierangelo; Concia, Ercole; Colombo, Fabrizio; Campanini, Mauro

    2016-01-01

    Abstract Only a few studies provided data on the clinical history of sepsis within internal Medicine units. The aim of the study was to assess the short-term mortality and to evaluate the prognostic risk factors in a large cohort of septic patients treated in internal medicine units. Thirty-one internal medicine units participated to the study. Within each participating unit, all admitted patients were screened for the presence of sepsis. A total of 533 patients were included; 78 patients (14.6%, 95%CI 11.9, 18.0%) died during hospitalization; mortality rate was 5.5% (95% CI 3.1, 9.6%) in patients with nonsevere sepsis and 20.1% (95%CI 16.2, 28.8%) in patients with severe sepsis or septic shock. Severe sepsis or septic shock (OR 4.41, 95%CI 1.93, 10.05), immune system weakening (OR 2.10, 95%CI 1.12, 3.94), active solid cancer (OR 2.14, 95% CI 1.16, 3.94), and age (OR 1.03 per year, 95% CI 1.01, 1.06) were significantly associated with an increased mortality risk, whereas blood culture positive for Escherichia coli was significantly associated with a reduced mortality risk (OR 0.46, 95%CI 0.24, 0.88). In-hospital mortality of septic patients treated in internal medicine units appeared similar to the mortality rate obtained in recent studies conducted in the ICU setting. PMID:26825876

  16. Septic Arthritis of The Hip Joint presenting as Acute Abdomen ...

    African Journals Online (AJOL)

    These cases illustrate the maxim that any painful movement of the hip joint with associated unexplained fever should raise suspicion of septic arthritis. The close relationship of the hip joint to the pelvis sometimes confuses hip diseases with pelvic pathologies. Key Words: Septic arthritis, acute abdomen, pathological ...

  17. Leucocyte esterase in the rapid diagnosis of paediatric septic arthritis.

    LENUS (Irish Health Repository)

    Kelly, E G

    2013-02-01

    Septic arthritis may affect any age group but is more common in the paediatric population. Infection is generally bacterial in nature. Prompt diagnosis is crucial, as delayed treatment is associated with lifelong joint dysfunction. A clinical history and application of Kocher\\'s criteria may indicate that there is a septic arthritis. However, definitive diagnosis is made on culture of septic synovial fluid. The culture process can take over 24h for the initial culture to yield bacterial colonies. Leucocyte esterase is released by leucocytes at the site of an infection. We hypothesise that leucocyte esterase can be utilized in the rapid diagnosis of septic arthritis and shorten the time to decisive treatment whilst simultaneously decreasing unnecessary treatment of non-septic joints.

  18. Comparing the effect of hydroxyethyl starch 130/0.4 with balanced crystalloid solution on mortality and kidney failure in patients with severe sepsis (6S - Scandinavian Starch for Severe Sepsis/Septic Shock trial): Study protocol, design and rationale for a double-blinded, randomised clinical trial

    DEFF Research Database (Denmark)

    Perner, Anders; Haase, Nicolai; Wetterslev, Jørn

    2011-01-01

    ABSTRACT: BACKGROUND: By tradition colloid solutions have been used to obtain fast circulatory stabilisation in shock, but high molecular weight hydroxyethyl starch (HES) may cause acute kidney failure in patients with severe sepsis. Now lower molecular weight HES 130/0.4 is the preferred colloid...... of HES 130/0.4 in patients with severe sepsis. The effects on mortality, dialysis-dependency, time on ventilator, bleeding and markers of resuscitation, metabolism, kidney failure, and coagulation will be assessed. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00962156....

  19. Sand filter clogging by septic tank effluent.

    Science.gov (United States)

    Spychała, M; Błazejewski, R

    2003-01-01

    The aim of this study was to characterise conditions and factors affecting fine sand clogging by septic tank effluent on the basis of physical modelling. The physical model consisted of 12 sand columns dosed with sewage from one household (5 persons), preliminary treated in a septic tank. Hydraulic loadings of the sand filters were equal to 82 mm/d. The mean discharge from sand columns, measured as the effluent volume collected during 10 minutes, decreased significantly over the experiment period from 34 cm3/min in August 2000 to 20 cm3/min in August 2001 at the same temperature of about 20 degrees C. First the columns clogged almost completely after 480 days in December 2001, however six columns had remained unclogged till the end of the experiment (March 2002). The temperature had a significant impact on hydraulic conductivity. A vertical distribution of accumulated mass and biomass was investigated in partly clogged sand. Microscopic survey of the clogging layer showed a presence of live micro-organisms, residuals of dead micro-organisms, particularly pieces of small animal armour and many fibres. These particles accelerated the accumulation of solids in the upper clogging layer. The study indicated that temperature impact on the filter hydraulic conductivity was more significant for biological activity, than for sewage viscosity.

  20. A peptide of heparin cofactor II inhibits endotoxin-mediated shock and invasive Pseudomonas aeruginosa infection

    DEFF Research Database (Denmark)

    Kalle, Martina; Papareddy, Praveen; Kasetty, Gopinath

    2014-01-01

    Sepsis and septic shock remain important medical problems with high mortality rates. Today's treatment is based mainly on using antibiotics to target the bacteria, without addressing the systemic inflammatory response, which is a major contributor to mortality in sepsis. Therefore, novel treatmen...

  1. Salmonella enteridis Septic Arthritis: A Report of Two Cases

    Directory of Open Access Journals (Sweden)

    Esat Uygur

    2013-01-01

    Full Text Available Introduction. Nontyphoidal salmonellosis causes significant morbidity, is transmitted via fecal-oral route, and is a worldwide cause of gastroenteritis, bacteremia, and local infections. Salmonella is a less common etiologic factor for septic arthritis compared with other gram-negative bacteria. Cases. We present two septic arthritis cases with Salmonella enteridis as a confirmed pathogen and also discuss the predisposing factors and treatment. Discussion. Septic arthritis is an orthopedic emergency. The gold standard treatment of septic arthritis is joint debridement, antibiotic therapy according to the culture results, and physiotherapy, which should start in the early postoperative period to prevent limitation of motion. Salmonella is an atypical agent for septic arthritis. It must be particularly kept in mind as an etiologic factor for the acute arthritis of a patient with sickle cell anemia and systemic lupus erythematosus. Clinicians should be cautious that the white blood cell count in synovial fluid can be under 50.000/mm3 in immune compromised individuals with septic arthritis. The inflammatory response can be deficient, or the microorganism may be atypical. Conclusion. Atypical bacteria such as Salmonella species in immune compromised patients can cause joint infections. Therefore, Salmonella species must always be kept in mind for the differential diagnosis of septic arthritis in a clinically relevant setting.

  2. Toxic shock syndrome

    Science.gov (United States)

    Staphylococcal toxic shock syndrome; Toxic shock-like syndrome; TSLS ... Toxic shock syndrome is caused by a toxin produced by some types of staphylococcus bacteria. A similar problem, called toxic shock- ...

  3. Technetium phosphate bone scan in the diagnosis of septic arthritis in childhood

    International Nuclear Information System (INIS)

    Sundberg, S.B.; Savage, J.P.; Foster, B.K.

    1989-01-01

    The technetium phosphate bone scans of 106 children with suspected septic arthritis were reviewed to determine whether the bone scan can accurately differentiate septic from nonseptic arthropathy. Only 13% of children with proved septic arthritis had correct blind scan interpretation. The clinically adjusted interpretation did not identify septic arthritis in 30%. Septic arthritis was incorrectly identified in 32% of children with no evidence of septic arthritis. No statistically significant differences were noted between the scan findings in the septic and nonseptic groups and no scan findings correlated specifically with the presence or absence of joint sepsis

  4. Prognostic value of gasometric parameters of carbon dioxide in resuscitation of septic patients. A bibliography review.

    Science.gov (United States)

    Lamsfus-Prieto, J Á; de Castro-Fernández, R; Hernández-García, A M; Marcano-Rodriguez, G

    2016-04-01

    The anaerobic metabolism is the cornerstone in physiopathology of septic shock. Nowadays we have both the central or mixed venous oxygen saturation and lactate levels to monitoring the metabolism in septic patients. Some studies have shown that normalization of systemic hemodynamic and oxygen metabolism variables not prevent progression to multiorgan damage and death. Recently has been proposed the venous-to-arterial carbon dioxide difference (ΔpvaCO2) as an alternative marker of tissue hypoperfusion, like Cardiac Index. High ΔpvaCO2 predicts adverse outcomes. Also has been proposed both, the ratio between the ΔpvaCO2 and arterial-to-venous oxygen content difference (ΔCavO2): ΔpvaCO2/ΔCavO2; and, the ratio between venous-to-arterial carbon dioxide difference (ΔCvaCO2) and ΔCavO2: ΔCvaCO2/ΔCavO2, as markers of anaerobic metabolism. Both of high ratios are related to high levels of lactate and worse prognosis. Therefore in patients with sepsis the combination of markers of resuscitation could be important to improve the outcomes. Copyright © 2015 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. Protective effect of porphyran isolated from discolored nori (Porphyra yezoensis) on lipopolysaccharide-induced endotoxin shock in mice.

    Science.gov (United States)

    Nishiguchi, Tomoki; Cho, Kichul; Isaka, Shogo; Ueno, Mikinori; Jin, Jun-O; Yamaguchi, Kenichi; Kim, Daekyung; Oda, Tatsuya

    2016-12-01

    Porphyran, a sulfated polysaccharide, isolated from discolored nori (Porphyra yezoensis) (dc-porphyran) and one fraction (F1) purified from dc-porphyran by DEAE-chromatography showed the protective effects on LPS-induced endotoxin shock in mice. Intraperitoneal (i.p.) treatment with dc-porphyran or F1 (100mg/kg) 60min prior to i.p. injection of LPS (30mg/kg) completely protected mice from LPS lethality. At 10mg/kg concentration, F1 demonstrated more protection than dc-porphyran. Intravenous (i.v.) challenge of LPS, even at 20mg/kg, was more lethal than i.p. administration; i.v. injection of F1 (100mg/kg) with LPS significantly improved the survival rate. However, i.v. dc-porphyran (100mg/kg) produced an even lower survival rate than that of LPS alone. We examined pro-inflammatory mediators such as NO and TNF-α in serum. F1 significantly reduced the levels of these markers. Additionally, F1 significantly decreased the malondialdehyde level in the liver, a marker of oxidative stress, while dc-porphyran had almost no effect. Furthermore, F1 significantly decreased the production of TNF-α and NO in peritoneal exudate cells harvested from LPS-challenged mice, while dc-porphyran treatment showed a lesser decrease. Our results suggest that porphyran isolated from discolored nori, especially F1, is capable of suppressing LPS-induced endotoxin shock in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Childhood Pyogenic Septic Arthritis as Seen in a Teaching Hospital ...

    African Journals Online (AJOL)

    accounted for 44 (83%) of the 53 patients seen with pyogenic septic arthritis. ... significantly more involved than the left and the left hip more than right. .... disease, malnutrition, and HIV were the predisposing and ..... fracture care in Nigeria.

  7. Pattern of Microbial Flora in Septic Incomplete Abortion in Port ...

    African Journals Online (AJOL)

    Alasia Datonye

    organisms present in the endocervix and posterior vaginal fornix in 150 women with ... cultured in septic abortion in this environment. The infections are usually ... These are both major hospitals offering tertiary care in Port. Harcourt the capital ...

  8. Safety and vasopressor effect of rosuvastatin in septic patients

    Directory of Open Access Journals (Sweden)

    Hanaa A. El Gendy

    2014-07-01

    Conclusions: Rosuvastatin 20 mg/day in septic patients increased number ABPSPD, decreased time to initial ABPSPD, norepinephrine dose and duration, with no significant elevation in transaminases or CPK.

  9. Retainment of the antimicrobial agent triclosan in a septic tank.

    Science.gov (United States)

    Kirjanova, Ala; Rimeika, Mindaugas; Vollertsen, Jes; Nielsen, Asbjørn Haaning

    2014-01-01

    Laboratory experiments were conducted to investigate the fate of the antimicrobial agent triclosan (TCS) in a conventional septic tank. The main mechanism of TCS removal from wastewater was identified to be rapid TCS sorption to suspended particles followed by settling of these particles to the bottom of the septic tank. Sorption to particles was completed within minutes while the settling took several days. Therefore, in a septic tank the removal of TCS from wastewater is mainly determined by the removal of suspended particles by sedimentation. Over 5 days of hydraulic residence time the initial dissolved TCS concentration of 100 μg L(-1) was reduced by 87 ± 8%. During the first 24 hours, 66-86% of all removed TCS was retained, whereas during the remainder of the experiment a slight but steady decrease in TCS concentration was observed. This was most likely caused by TCS diffusion and its subsequent sorption onto the septic sludge.

  10. Preliminary characterization of abandoned septic tank systems. Volume 1

    International Nuclear Information System (INIS)

    1995-12-01

    This report documents the activities and findings of the Phase I Preliminary Characterization of Abandoned Septic Tank Systems. The purpose of the preliminary characterization activity was to investigate the Tiger Team abandoned septic systems (tanks and associated leachfields) for the purpose of identifying waste streams for closure at a later date. The work performed was not to fully characterize or remediate the sites. The abandoned systems potentially received wastes or effluent from buildings which could have discharged non-domestic, petroleum hydrocarbons, hazardous, radioactive and/or mixed wastes. A total of 20 sites were investigated for the preliminary characterization of identified abandoned septic systems. Of the 20 sites, 19 were located and characterized through samples collected from each tank(s) and, where applicable, associated leachfields. The abandoned septic tank systems are located in Areas 5, 12, 15, 25, and 26 on the Nevada Test Site

  11. Drug sensitivity patterns of bacterial isolates from septic post ...

    African Journals Online (AJOL)

    Background: Wound infections have been a problem in the field of surgery for a long time.Advances in control of infections have not completely eradicated this ... of bacterial isolates from septic postoperative wounds in Jinja hospital, Uganda.

  12. Wound shock: a history of its study and treatment by military surgeons.

    Science.gov (United States)

    Hardaway, Robert M

    2004-04-01

    The treatment of wounds has received considerable attention from the time of the Trojan War. However, it was not until the American Civil War that shock was described as an entity distinct from the wounds themselves and that efforts were directed at more than just treatment of the wound. The need for fluid resuscitation in the treatment of hemorrhagic shock was first recognized in the Spani