scholarly journals Inhibition of Cerebral High-Mobility Group Box 1 Protein Attenuates Multiple Organ Damage and Improves T Cell-Mediated Immunity in Septic Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Chao Ren ◽  
Xiu-hua Li ◽  
Yao Wu ◽  
Ning Dong ◽  
Ya-lin Tong ◽  
...  
Keyword(s):  
Cecal Ligation ◽  
High Mobility ◽  
Organ Damage ◽  
Multiple Organ ◽  
High Mobility Group ◽  
Organ Injury ◽  
Cell Mediated Immunity ◽  
Functional Changes ◽  
Multiple Organs ◽  
Major Factors

Sepsis remains one of the leading causes of mortality in intensive care units, but there is a shortage of effective treatments. A dysregulated host immune response and multiple organ injury are major factors for the pathogenesis and progression of sepsis, which require specific mechanism and treatment. In the present study, we performed an intracerebroventricular (ICV) injection of BoxA, a specific antagonist of high-mobility group box 1 protein (HMGB1), in septic rats that were produced by cecal ligation and puncture surgery; we further assessed the functional changes of multiple organs and splenic T lymphocytes. We found that the inhibition of cerebral HMGB1 significantly alleviated multiple organ damage under septic exposure, including damage to the heart, liver, lungs, and kidneys; reversed the immune dysfunction of T cells; and increased the survival of septic rats. These data suggest that central HMGB1 might be a potential therapeutic target for septic challenge and that inhibition of brain HMGB1 can protect against multiple organ dysfunction induced by sepsis.

scholarly journals The Protective Effect of Lidocaine on Septic Rats via the Inhibition of High Mobility Group Box 1 Expression and NF-κB Activation

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Huan-Liang Wang ◽  
Yan-Qiu Xing ◽  
Ying-Xue Xu ◽  
Fei Rong ◽  
Wei-Fu Lei ◽  
...  
Keyword(s):  
Protective Effect ◽  
Cecal Ligation ◽  
High Mobility ◽  
Inhibitory Effect ◽  
High Mobility Group ◽  
Organ Injury ◽  
Hmgb1 Level ◽  
Multiple Organs ◽  
Hmgb1 Expression ◽  
Local Anesthetic Drug

Lidocaine, a common local anesthetic drug, has anti-inflammatory effects. It has demonstrated a protective effect in mice from septic peritonitis. However, it is unknown whether lidocaine has effects on high mobility group box 1 (HMGB1), a key mediator of inflammation. In this study, we investigated the effect of lidocaine treatment on serum HMGB1 level and HMGB1 expression in liver, lungs, kidneys, and ileum in septic rats induced by cecal ligation and puncture (CLP). We found that acute organ injury induced by CLP was mitigated by lidocaine treatment and organ function was significantly improved. The data also demonstrated that lidocaine treatment raised the survival of septic rats. Furthermore, lidocaine suppressed the level of serum HMGB1, the expression of HMGB1, and the activation of NF-κB p65 in liver, kidneys, lungs, and ileum. Taken together, these results suggest that lidocaine treatment exerts its protective effection on CLP-induced septic rats. The mechanism was relative to the inhibitory effect of lidocaine on the mRNA expression level of HMGB1 in multiple organs, release of HMGB1 to plasma, and activation of NF-κB.

scholarly journals Laboratory Markers in the Management of Pediatric Polytrauma: Current Role and Areas of Future Research

2021 ◽  
Vol 9 ◽  
Author(s):  
Birte Weber ◽  
Ina Lackner ◽  
Christian Karl Braun ◽  
Miriam Kalbitz ◽  
Markus Huber-Lang ◽  
...  
Keyword(s):  
Imaging Techniques ◽  
Lactate Concentration ◽  
Organ Damage ◽  
Severe Trauma ◽  
Multiple Organ ◽  
Organ Injury ◽  
Future Research ◽  
Acid Base Balance ◽  
Early Assessment ◽  
Laboratory Markers

Severe trauma is the most common cause of mortality in children and is associated with a high socioeconomic burden. The most frequently injured organs in children are the head and thorax, followed by the extremities and by abdominal injuries. The efficient and early assessment and management of these injuries is essential to improve patients' outcome. Physical examination as well as imaging techniques like ultrasound, X-ray and computer tomography are crucial for a valid early diagnosis. Furthermore, laboratory analyses constitute additional helpful tools for the detection and monitoring of pediatric injuries. Specific inflammatory markers correlate with post-traumatic complications, including the development of multiple organ failure. Other laboratory parameters, including lactate concentration, coagulation parameters and markers of organ injury, represent further clinical tools to identify trauma-induced disorders. In this review, we outline and evaluate specific biomarkers for inflammation, acid-base balance, blood coagulation and organ damage following pediatric polytrauma. The early use of relevant laboratory markers may assist decision making on imaging tools, thus contributing to minimize radiation-induced long-term consequences, while improving the outcome of children with multiple trauma.

scholarly journals CO2Pneumoperitoneum Preservesβ-Arrestin 2 Content and Reduces High Mobility Group Box-1 (HMGB-1) Expression in an Animal Model of Peritonitis

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Angela Simona Montalto ◽  
Alessandra Bitto ◽  
Letteria Minutoli ◽  
Pietro Impellizzeri ◽  
Gaetano Costa ◽  
...  
Keyword(s):  
Bacterial Load ◽  
Cecal Ligation ◽  
Signal Transduction Pathway ◽  
High Mobility ◽  
Receptor Activation ◽  
High Mobility Group ◽  
Male Rats ◽  
Toll Like Receptor ◽  
To Receive ◽  
Lung And Kidney

Laparoscopy (LS) has been shown to decrease the inflammatory sequelae of endotoxemia.β-arrestin 2 plays an important function in signal transduction pathway of TLR4. High mobility group box-1 (HMGB-1) is involved in the delayed systemic inflammatory response. We investigated the effects of CO2insufflation on liver, lung, and kidney expression of bothβ-arrestin 2 and HMGB-1 during sepsis. Cecal ligation and puncture (CLP) was performed in male rats and 6 h later the animals were randomly assigned to receive a CO2pneumoperitoneum or laparotomy. Animals were euthanized; liver, lung, and kidney were removed for the evaluation ofβ-arrestin 2 and HMGB-1 expression. Immunohistochemical detection of myeloperoxidase (MPO) was investigated in lung and liver and bacterial load was determined in the peritoneal fluid. CO2pneumoperitoneum reduced peritoneal bacterial load, increased the expression ofβ-arrestin 2, and blunted the expression of the potent proinflammatory HMGB-1 in liver, lung, and kidney compared with laparotomy. Liver and lung MPO was markedly reduced in rats subjected to LS compared with laparotomy. We believe that CO2exerts an early protective effect by reducing bacterial load and likely toll-like receptor activation which in turn leads to a preservedβ-arrestin 2 expression and a reduced HMGB-1 expression.

scholarly journals Acteoside improves survival in cecal ligation and puncture-induced septic mice via blocking of high mobility group box 1 release

2013 ◽  
Vol 35 (4) ◽  
pp. 348-354 ◽  
Author(s):  
Eun Sun Seo ◽  
Bo Kang Oh ◽  
Jhang Ho Pak ◽  
Soon-Ho Yim ◽  
Sangilyandi Gurunathan ◽  
...  
Keyword(s):  
Cecal Ligation ◽  
High Mobility ◽  
High Mobility Group ◽  
Cecal Ligation And Puncture

scholarly journals Relationship Between Serum Severe Acute Respiratory Syndrome Coronavirus 2 Nucleic Acid and Organ Damage in Coronavirus 2019 Patients: A Cohort Study

2020 ◽  
Author(s):  
Dan Xu ◽  
Fuling Zhou ◽  
Wenbo Sun ◽  
Liangjun Chen ◽  
Lan Lan ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Severe Acute Respiratory Syndrome ◽  
Troponin I ◽  
Demographic Data ◽  
Organ Damage ◽  
Multiple Organ ◽  
Serum Samples ◽  
Cardiac Damage ◽  
Multiple Organs ◽  
Laboratory Biomarkers

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide and has the ability to damage multiple organs. However, information on serum SARS-CoV-2 nucleic acid (RNAemia) in patients affected by coronavirus disease 2019 (COVID-19) is limited. Methods Patients who were admitted to Zhongnan Hospital of Wuhan University with laboratory-confirmed COVID-19 were tested for SARS-COV-2 RNA in serum from 28 January 2020 to 9 February 2020. Demographic data, laboratory and radiological findings, comorbidities, and outcomes data were collected and analyzed. Results Eighty-five patients were included in the analysis. The viral load of throat swabs was significantly higher than of serum samples. The highest detection of SARS-CoV-2 RNA in serum samples was between 11 and 15 days after symptom onset. Analysis to compare patients with and without RNAemia provided evidence that computed tomography and some laboratory biomarkers (total protein, blood urea nitrogen, lactate dehydrogenase, hypersensitive troponin I, and D-dimer) were abnormal and that the extent of these abnormalities was generally higher in patients with RNAemia than in patients without RNAemia. Organ damage (respiratory failure, cardiac damage, renal damage, and coagulopathy) was more common in patients with RNAemia than in patients without RNAemia. Patients with vs without RNAemia had shorter durations from serum testing SARS-CoV-2 RNA. The mortality rate was higher among patients with vs without RNAemia. Conclusions In this study, we provide evidence to support that SARS-CoV-2 may have an important role in multiple organ damage. Our evidence suggests that RNAemia has a significant association with higher risk of in-hospital mortality.

Significance of TNF in hemorrhage-related hemodynamic alterations, organ injury, and mortality in rats

1997 ◽  
Vol 272 (5) ◽  
pp. H2219-H2226 ◽  
Author(s):  
S. Bahrami ◽  
Y. M. Yao ◽  
G. Leichtfried ◽  
H. Redl ◽  
I. Marzi ◽  
...  
Keyword(s):  
Survival Rate ◽  
Hemorrhagic Shock ◽  
Peripheral Resistance ◽  
Resistance Index ◽  
Organ Damage ◽  
Multiple Organ ◽  
Organ Injury ◽  
Tnf Alpha ◽  
Control Group ◽  
Necrosis Factor Alpha

To evaluate the role of tumor necrosis factor-alpha (TNF-alpha) in hemodynamic alterations, multiple organ damage, and mortality caused by hemorrhagic shock, we employed a monoclonal antibody to TNF-alpha (TNF-alpha MAb) in anesthetized rats subjected to prolonged hemorrhagic shock (mean arterial pressure of 30–x35 mmHg for 180 min) followed by resuscitation over 50 min. Treatment of rats with 20.0 mg/kg TNF-alpha MAb 15 min after the end of resuscitation significantly decreased the total peripheral resistance index (P = 0.031) and provided remarkable protection from multiple organ damage compared with controls. The 48-h survival rate was significantly higher in the treatment group (73.3%) than in the control group (26.7%; P = 0.029). The results suggest that TNF-alpha induced by hemorrhagic shock in rats is an important mediator of pathophysiological alterations associated with cardiovascular abnormalities, multiple organ injury, and even lethality. Postresuscitation treatment with TNF-alpha MAb, even after an initial TNF-alpha formation had occurred, significantly attenuated the cardiovascular consequences and improved the survival rate. Thus monoclonal antibodies to TNF-alpha might provide new prospects in the treatment of hemorrhage-related disorders.

Glutamine induces heat shock protein and protects against endotoxin shock in the rat

2001 ◽  
Vol 90 (6) ◽  
pp. 2403-2410 ◽  
Author(s):  
Paul E. Wischmeyer ◽  
Madelyn Kahana ◽  
Rachel Wolfson ◽  
Hongyu Ren ◽  
Mark M. Musch ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Organ Damage ◽  
Endotoxin Shock ◽  
Organ Injury ◽  
Sprague Dawley ◽  
Multiple Organs ◽  
Enhanced Expression ◽  
Endotoxemic Shock ◽  
Laboratory Models

Enhanced expression of heat shock protein (HSP) has been shown to be protective against laboratory models of septic shock. Induction of HSPs to improve outcome in human disease has not been exploited because laboratory induction agents are themselves toxic and not clinically relevant. In this study, we demonstrate that a single dose of intravenous glutamine causes a rapid and significant increase in HSP25 and HSP72 expression in multiple organs of the unstressed Sprague-Dawley rat. With the utilization of a fluid-resuscitated rat model of endotoxemia, mortality was dramatically reduced by glutamine administration concomitant with the endotoxin injury. Endotoxin-treated animals given glutamine exhibited dramatic increases in tissue HSP expression and marked reduction of end-organ damage. These data suggest glutamine may protect against mortality and attenuate end-organ injury in endotoxemic shock via enhanced HSP expression. Furthermore, glutamine confers protection when administered at the initiation of sepsis, rather than as pretreatment. Thus glutamine appears to be a clinically viable enhancer of HSP expression and may prove beneficial in the therapy of sepsis and sepsis-induced organ injury.

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