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cecal ligation and. puncture

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https://www.readbyqxmd.com/read/27909955/suppressive-effects-of-dabrafenib%C3%A2-on-endothelial-protein-c-receptor-shedding
#1
Sae-Kwang Ku, Jongdoo Kim, Sang Chan Kim, Jong-Sup Bae
Beyond its role in the activation of protein C, the endothelial cell protein C receptor (EPCR) plays an important role in the cytoprotective pathway. EPCR can be shed from the cell surface, which is mediated by tumor necrosis factor-α converting enzyme (TACE). Dabrafenib (DAB) is a B-Raf inhibitor and initially used for the treatment of metastatic melanoma therapy. However, little is known about the effects of DAB on EPCR shedding. We investigated this issue by monitoring the effects of DAB on phorbol-12-myristate 13-acetate (PMA)-, tumor necrosis factor (TNF)-α-, interleukin (IL)-1β-induced EPCR shedding in human umbilical vein endothelial cells (HUVECs), and cecal ligation and puncture (CLP)-mediated EPCR shedding in mice and underlying mechanism...
December 1, 2016: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/27904994/rapamycin-protects-sepsis-induced-cognitive-impairment-in-mouse-hippocampus-by-enhancing-autophagy
#2
Wenyu Liu, Jia'nan Guo, Jie Mu, Linyu Tian, Dong Zhou
The purpose of this study is to test the hypothesis that the mammalian target of rapamycin (mTOR) signaling pathway might mediate neuroprotection in a mouse model of septic encephalopathy and also to identify the role of autophagy. Mice were subjected to cecal ligation and puncture (CLP) or a sham operation, and all 50 mice were randomly assigned to five groups: sham, CLP+ saline, CLP+ rapamycin (1, 5, 10 mg/kg) groups. Two weeks after the operation, Morris water maze was conducted for behavioral test; Nissl staining was used for observing glia infiltration; immunohistochemical staining and biochemical measures in hippocampi were performed to detect mTOR targets and autophagy indicators...
December 1, 2016: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/27902475/osthole-protects-sepsis-induced-acute-kidney-injury-via-down-regulating-nf-%C3%AE%C2%BAb-signal-pathway
#3
Chen Yu, Peng Li, Dong Qi, Lei Wang, Hong-Lin Qu, Yue-Juan Zhang, Xue-Kai Wang, Hua-Ying Fan
BACKGROUND AND PURPOSE: As a natural coumarin derivative from the Cnidium monnieri(L)Cusson fruit, osthole consists of 7-methoxy-8-isopentenoxy-coumarin. The purpose of this research is to study the mechanism and effect of osthole on sepsis-induced acute kidney injury. EXPERIMENTAL APPROACH: The protective effect of osthole on mouse macrophage RAW 264.7 and HK-2 cells induced by LPS in vitro and on acute kidney injury model induced by sepsis and established by puncture and cecal ligation (CLP) in vivo were tested...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899278/benznidazole-the-trypanocidal-drug-used-for-chagas-disease-induces-hepatic-nrf2-activation-and-attenuates-the-inflammatory-response-in-a-murine-model-of-sepsis
#4
Flavia Lambertucci, Omar Motiño, Silvina Villar, Juan Pablo Rigalli, María de Luján Alvarez, Viviana Catania, Paloma Martín-Sanz, Cristina Ester Carnovale, Ariel Darío Quiroga, Daniel Eleazar Francés, María Teresa Ronco
Molecular mechanisms on sepsis progression are linked to the imbalance between reactive oxygen species (ROS) production and cellular antioxidant capacity. Previous studies demonstrated that benznidazole (BZL), known for its antiparasitic action on Trypanosoma cruzi, has immunomodulatory effects, increasing survival in C57BL/6 mice in a model of polymicrobial sepsis induced by cecal ligation puncture (CLP). The mechanism by which BZL inhibits inflammatory response in sepsis is poorly understood. Also, our group recently reported that BZL is able to activate the nuclear erythroid 2-related factor 2 (NRF2) in vitro...
November 26, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27895015/protective-effects-of-human-and-mouse-soluble-scavenger-like-cd6-lymphocyte-receptor-in-a-lethal-model-of-polymicrobial-sepsis
#5
Mario Martínez-Florensa, Marta Consuegra-Fernández, Fernando Aranda, Noelia Armiger-Borràs, Marianna Di Scala, Esther Carrasco, Jerónimo Pachón, Jordi Vila, Gloria González-Aseguinolaza, Francisco Lozano
Sepsis still constitutes an unmet clinical need, which could benefit from novel adjunctive strategies to conventional antibiotic therapy. The soluble form of the scavenger-like human CD6 lymphocyte receptor (shCD6) binds to key pathogenic components from Gram-positive and -negative bacteria, and shows time- and dose-dependent efficacy in mouse models of monobacterial sepsis. The objective of the present work was to demonstrate the effectiveness of infusing mouse and human sCD6 by different systemic routes, either alone or as adjunctive therapy to gold-standard antibiotics, in a lethal model of polymicrobial sepsis...
November 28, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27889435/role-of-hmgb1-translocation-to-neuronal-nucleus-in-rat-model-with-septic-brain-injury
#6
Yafei Li, Xihong Li, Yi Qu, Jichong Huang, Tingting Zhu, Fengyan Zhao, Shiping Li, Dezhi Mu
High-mobility Group Box-1 (HMGB1) is a central late proinflammatory cytokine that triggers the inflammatory response during sepsis. However, whether HMGB1 is involved in the pathogenesis of septic brain damage is unknown. In this study, we investigated the role of HMGB1 in regulating brain injury in a rat model of sepsis. Wistar rats were subjected to cecal ligation and puncture (CLP) to induce septic brain injury. Hematoxylin and eosin staining was used to detect pathological changes in the cortex. The cellular localization of HMGB1 was determined using immunostaining...
November 23, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27880847/activation-of-both-the-calpain-and-ubiquitin-proteasome-systems-contributes-to-septic-cardiomyopathy-through-dystrophin-loss-disruption-and-mtor-inhibition
#7
Ana Caroline Silva Freitas, Maria Jose Figueiredo, Erica Carolina Campos, Danilo Figueiredo Soave, Simone Gusmao Ramos, Herbert B Tanowitz, Mara Rúbia N Celes
Cardiac dysfunction caused by the impairment of myocardial contractility has been recognized as an important factor contributing to the high mortality in sepsis. Calpain activation in the heart takes place in response to increased intracellular calcium influx resulting in proteolysis of structural and contractile proteins with subsequent myocardial dysfunction. The purpose of the present study was to test the hypothesis that increased levels of calpain in the septic heart leads to disruption of structural and contractile proteins and that administration of calpain inhibitor-1 (N-acetyl-leucinyl-leucinyl-norleucinal (ALLN)) after sepsis induced by cecal ligation and puncture prevents cardiac protein degradation...
2016: PloS One
https://www.readbyqxmd.com/read/27878684/bakuchiol-protects-against-acute-lung-injury-in-septic-mice
#8
Xinxin Zhang, Ning Chang, Yong Zhang, Mingxiang Ye, Zhiping Han, Jie Li, Jian Zhang
Sepsis is a systemic inflammatory reaction that may lead to multiple organ damage and acute lung injury (ALI). Bakuchiol (Bak) has been reported to confer protection against inflammation and oxidative stress. However, its effect on sepsis-induced acute lung injury remains unclear. In the present study, male C57BL/6 mice were subjected to cecal ligation and puncture (CLP), and Bak (15, 30, 60 mg/kg) was administered intragastrically after 0 and 3 h of surgery. Lung water content was detected. Pathologic changes in lung tissues were evaluated via hematoxylin and eosin (H&E) staining...
November 23, 2016: Inflammation
https://www.readbyqxmd.com/read/27878281/etomidate-inhibits-nuclear-factor-%C3%AE%C2%BAb-through-decreased-expression-of-glucocorticoid-receptor-in-septic-rats
#9
Yu Zhang, Ruo-Meng Li, Chun Wang, Na Liu, Shen Lv, Jun-Yu Xiong
The present study aimed to investigate the effect of etomidate administered prior to or following cecal ligation and puncture (CLP) on the expression of glucocorticoid receptor (GR) and lymphocyte apoptosis in septic rats. Right jugular vein catheterization was performed on female Sprague‑Dawley rats under isoflurane anesthesia, and CLP surgery was performed to induce sepsis 3 days following catheterization. The rats were randomly divided into five groups. All groups were infused with 2 ml of either etomidate or 5‰ dimethyl sulfoxide (DMSO) at 1 ml/h for 2 h from 6 h post‑surgery...
November 16, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27878209/preclinical-models-of-overwhelming-sepsis-implicate-the-neural-system-that-encodes-contextual-fear-memory
#10
Patricio T Huerta, Sergio Robbiati, Tomás Salvador Huerta, Anchal Sabharwal, Rose A Berlin, Maya Frankfurt, Bruce T Volpe
Long-term sepsis survivors sustain cryptic brain injury that leads to cognitive impairment, emotional imbalance, and increased disability burden. Suitable animal models of sepsis, such as cecal ligation and puncture (CLP), have permitted the analysis of abnormal brain circuits that underlie post-septic behavioral phenotypes. For instance, we have previously shown that CLP-exposed mice exhibit impaired spatial memory together with depleted dendritic arbors and decreased spines in the apical dendrites of pyramidal neurons in the CA1 region of the hippocampus...
November 17, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27875749/systematic-investigation-on-the-turning-point-of-over-inflammation-to-immunosuppression-in-clp-mice-model-and-their-characteristics
#11
Dongmei Deng, Xiaoli Li, Chao Liu, Zhaoxia Zhai, Bin Li, Mei Kuang, Pan Li, Shenglan Shang, Yi Song, Yanyan Cen, Rongxin Qin, Yonglin Lu, Yibo Zhao, Hao Cheng, Jiang Zheng, Hong Zhou
Immunosuppression is involved in refractory innate and adaptive immune responses and is considered to be the predominant driving force for mortality in sepsis. The cecal ligation and puncture (CLP) model is regarded as a golden standard model for sepsis study, but the turning point of over-inflammation to immunosuppression was reported differently. Herein, systematic investigation on the turning point of over-inflammation to immunosuppression in CLP mice model was carried out. The results showed only the mortality of mice challenged with of Pseudomonas aeruginosa on Day 1 not other days after the surgery was higher than that of other mice with Sham surgery, suggesting Day 1 after the CLP surgery might be the turning point...
November 19, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27861506/chronic-alcohol-ingestion-delays-t-cell-activation-and-effector-function-in-sepsis
#12
Lindsay M Margoles, Rohit Mittal, Nathan J Klingensmith, John D Lyons, Zhe Liang, Mara A Serbanescu, Maylene E Wagener, Craig M Coopersmith, Mandy L Ford
Sepsis is the leading cause of death in intensive care units in the US, and it is known that chronic alcohol use is associated with higher incidence of sepsis, longer ICU stays, and higher mortality from sepsis. Both sepsis and chronic alcohol use are associated with immune deficits such as decreased lymphocyte numbers, impaired innate immunity, delayed-type hypersensitivity reactions, and susceptibility to infections; however, understanding of specific pathways of interaction or synergy between these two states of immune dysregulation is lacking...
2016: PloS One
https://www.readbyqxmd.com/read/27850999/1363-effect-of-ulinastatin-on-microcirculation-during-sepsis-in-a-rat-cecal-ligation-and-puncture-model
#13
Xiaozhu Zhai, Longyuan Jiang, Zhengfei Yang, Tao Yu, Cai Wen, Houzhen Zheng, Joseph Ornato, Wanchun Tang
No abstract text is available yet for this article.
December 2016: Critical Care Medicine
https://www.readbyqxmd.com/read/27846855/changes-in-ceftriaxone-pharmacokinetics-pharmacodynamics-during-the-early-phase-of-sepsis-a-prospective-experimental-study-in-the-rat
#14
Valentina Selmi, Beatrice Loriga, Luca Vitali, Martina Carlucci, Alessandro Di Filippo, Giulio Carta, Eleonora Sgambati, Lorenzo Tofani, Angelo Raffaele De Gaudio, Andrea Novelli, Chiara Adembri
BACKGROUND: Sepsis is characterized by the loss of the perm-selectivity properties of the glomerular filtration barrier (GFB) with consequent albuminuria. We examined whether the pharmacokinetics-pharmacodynamics (PK/PD) of ceftriaxone (CTX), an extensively protein-bound 3rd generation cephalosporin, is altered during early sepsis and whether an increase in urinary loss of bound-CTX, due to GFB alteration, can occur in this condition. METHODS: A prospective, experimental, randomized study was carried out in adult male Sprague-Dawley rats...
November 15, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27837177/protection-of-resveratrol-on-acute-kidney-injury-in-septic-rats
#15
Y Gan, S Tao, D Cao, H Xie, Q Zeng
AIM: The aim of the study is to investigate protective effect of resveratrol (Res) on acute kidney injury (AKI) in sepsis. METHODS: Rats in sham group received sham operation; in sham + Res received sham operation and Res (3 mg/kg); in cecal ligation and puncture (CLP) established as sepsis; in CLP + Res (3 mg/kg) with sepsis and Res (3 mg/kg); and in CLP + Res (10 mg/kg) with sepsis and Res (10 mg/kg). Survival rate, serum indexes, inflammatory factors, NF-κB-P65, and SIRT1 were detected...
November 11, 2016: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/27836913/immunoreceptor-cd300a-on-mast-cells-and-dendritic-cells-regulates-neutrophil-recruitment-in-a-murine-model-of-sepsis
#16
Kankanam Gamage Sanath Udayanga, Yoshiyuki Nakamura, Chigusa Nakahashi-Oda, Akira Shibuya
Sepsis is a life-threatening syndrome caused by abnormal host immune responses against bacterial infection. Although innate immune cells are known to be important in the pathogenesis of sepsis, how their activation is regulated during sepsis remains incompletely understood. Here we examined the role of the inhibitory immunoreceptor CD300a, which is expressed on various types of myeloid cells, in the pathogenesis of sepsis induced by cecal ligation and puncture (CLP). To this end, we used mice in which CD300a was specifically deleted on mast cells (MCs; Cd300a(fl/fl) Mcpt5-Cre), dendritic cells (DCs; Cd300a(fl/fl) Itgax-Cre), or macrophages and neutrophils (Cd300a(fl/fl) Lyz2-Cre)...
November 11, 2016: International Immunology
https://www.readbyqxmd.com/read/27835904/tuftsin-prevents-the-negative-immunoregulation-of-neuropilin-1highcd4-cd25-regulatory-t-cells-and-improves-survival-rate-in-septic-mice
#17
Yu-Lei Gao, Mu-Ming Yu, Song-Tao Shou, Ying Yao, Yan-Cun Liu, Li-Jun Wang, Bin Lu, Yan-Fen Chai
Our previous research showed that neuropilin (Nrp) -1highCD4+CD25+Regulatory T cells (Tregs) exhibited primary negative immunoregulation in sepsis induced immune dysfunction. Tuftsin is the typical ligand of Nrp-1. Herein, we investigated the potential therapeutic value and mechanisms of tuftsin in sepsis. Sepsis per se markedly decreased the serum concentration of tuftsin, administration of tuftsin improved the survival rate of septic mice with cecal ligation and puncture (CLP). In vitro study, tuftsin prevented the negative immunoregulation of Nrp-1highCD4+CD25+Tregs, including weakening the expression of forkhead/winged helix transcription factor (Foxp)- 3/cytotoxic T lymphocyte associated antigen (CTLA)-4, inhibiting the secretion of transforming growth factor (TGF)-β, and weakening the immunosuppressive function of Nrp-1highCD4+CD25+Tregs to conventional CD4+CD25-T cells...
November 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/27831972/the-role-of-thioredoxin-1-in-suppression-sepsis-through-inhibiting-mitochonrial-induced-apoptosis-in-spleen
#18
Guobing Chen, Xiang Li, Mengbing Huang, Xiaoshuang Zhou, Ye Li, Xiaoqin Mao, Jie Bai
Sepsis is a serious public health issue and the leading cause of death in critically ill patients in intensive care units. Thioredoxin-1 (Trx-1) is a protein of regulating redox, as well as a modulator of inflammation and apoptosis. Our previous study reported that Trx-1 decreased endoplasmic reticulum mediated inflammation involved in lung in a model of experimental sepsis. However, its effect on mitochondrial -mediated apoptosis in spleen has not been reported. We studied whether Trx-1 could prevent spleen cells apoptosis in sepsis...
November 9, 2016: Shock
https://www.readbyqxmd.com/read/27822777/critical-role-of-endogenous-histamine-in-promoting-end-organ-tissue-injury-in-sepsis
#19
Mizuki Hattori, Mitsuaki Yamazaki, Wakana Ohashi, Satoshi Tanaka, Kohshi Hattori, Kenichiro Todoroki, Toshio Fujimori, Hiroshi Ohtsu, Naoyuki Matsuda, Yuichi Hattori
BACKGROUND: Histamine assumes an important role as a major mediator in various pathologic disorders associated with inflammation and immune reactions. However, the involvement of histamine in the pathological conditions and symptoms of sepsis remains entirely unknown. In this study, we establish that histamine is identified as a contributory mediator to promoting the development of organ injury in sepsis. METHODS: Histidine decarboxylase (HDC) gene knockout (HDC(-/-)) mice, histamine H1-/H2-receptor gene-double knockout (H1R(-/-)/H2R(-/-)) mice, and their littermate wild-type (WT) C57BL/6J mice underwent cecal ligation and puncture (CLP) or sham operation...
December 2016: Intensive Care Medicine Experimental
https://www.readbyqxmd.com/read/27819302/protective-effect-of-cl-amidine-against-clp-induced-lethal-septic-shock-in-mice
#20
Ting Zhao, Baihong Pan, Hasan B Alam, Baoling Liu, Roderick T Bronson, Qiufang Deng, Erxi Wu, Yongqing Li
Production of innate and adaptive immune cells from hematopoietic stem cells, and maturation of T lymphocytes are effective immune responses to fight severe microbial infection. In sepsis, this emergency myelopoiesis is damaged, leading to failure of bacterial clearance, and excessive stress-induced steroids cause immature T-lymphocyte apoptosis in thymus. We recently found that Cl-amidine, a peptidylarginine deiminase (PAD) inhibitor, improves survival in a mouse model of cecal ligation and puncture (CLP)-induced septic shock...
November 7, 2016: Scientific Reports
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