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Wang T, Huang X, Sun S, Wang Y, Han L, Zhang T, Zhang T, Chen X. Recent Advances in the Mechanisms of Postoperative Neurocognitive Dysfunction: A Narrative Review. Biomedicines 2025; 13:115. [PMID: 39857699 PMCID: PMC11762480 DOI: 10.3390/biomedicines13010115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Revised: 12/28/2024] [Accepted: 12/30/2024] [Indexed: 01/27/2025] Open
Abstract
Postoperative neurocognitive dysfunction (PND) is a prevalent and debilitating complication in elderly surgical patients, characterized by persistent cognitive decline that negatively affects recovery and quality of life. As the aging population grows, the rising number of elderly surgical patients has made PND an urgent clinical challenge. Despite increasing research efforts, the pathophysiological mechanisms underlying PND remain inadequately characterized, underscoring the need for a more integrated framework to guide targeted interventions. To better understand the molecular mechanisms and therapeutic targets of PND, this narrative review synthesized evidence from peer-reviewed studies, identified through comprehensive searches of PubMed, Embase, Cochrane Library, and Web of Science. Key findings highlight neuroinflammation, oxidative stress, mitochondrial dysfunction, neurotransmitter imbalances, microvascular changes, and white matter lesions as central to PND pathophysiology, with particular parallels to encephalocele- and sepsis-associated cognitive impairments. Among these, neuroinflammation, mediated by pathways such as the NLRP3 inflammasome and blood-brain barrier disruption, emerges as a pivotal driver, triggering cascades that exacerbate neuronal injury. Oxidative stress and mitochondrial dysfunction synergistically amplify these effects, while neurotransmitter imbalances and microvascular alterations, including white matter lesions, contribute to synaptic dysfunction and cognitive decline. Anesthetic agents modulate these interconnected pathways, exhibiting both protective and detrimental effects. Propofol and dexmedetomidine demonstrate neuroprotective properties by suppressing neuroinflammation and microglial activation, whereas inhalational anesthetics like sevoflurane intensify oxidative stress and inflammatory responses. Ketamine, with its anti-inflammatory potential, offers promise but requires further evaluation to determine its long-term safety and efficacy. By bridging molecular insights with clinical practice, this review highlights the critical role of personalized anesthetic strategies in mitigating PND and improving cognitive recovery in elderly surgical patients. It aims to inform future research and clinical decision-making to address this multifaceted challenge.
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Affiliation(s)
- Tingting Wang
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; (T.W.); (X.H.); (S.S.); (Y.W.); (L.H.); (T.Z.); (T.Z.)
- Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Key Laboratory of Anesthesiology and Resuscitation, Huazhong University of Science and Technology, Ministry of Education, Wuhan 430022, China
| | - Xin Huang
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; (T.W.); (X.H.); (S.S.); (Y.W.); (L.H.); (T.Z.); (T.Z.)
- Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Key Laboratory of Anesthesiology and Resuscitation, Huazhong University of Science and Technology, Ministry of Education, Wuhan 430022, China
| | - Shujun Sun
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; (T.W.); (X.H.); (S.S.); (Y.W.); (L.H.); (T.Z.); (T.Z.)
- Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Key Laboratory of Anesthesiology and Resuscitation, Huazhong University of Science and Technology, Ministry of Education, Wuhan 430022, China
| | - Yafeng Wang
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; (T.W.); (X.H.); (S.S.); (Y.W.); (L.H.); (T.Z.); (T.Z.)
- Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Key Laboratory of Anesthesiology and Resuscitation, Huazhong University of Science and Technology, Ministry of Education, Wuhan 430022, China
| | - Linlin Han
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; (T.W.); (X.H.); (S.S.); (Y.W.); (L.H.); (T.Z.); (T.Z.)
- Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Key Laboratory of Anesthesiology and Resuscitation, Huazhong University of Science and Technology, Ministry of Education, Wuhan 430022, China
| | - Tao Zhang
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; (T.W.); (X.H.); (S.S.); (Y.W.); (L.H.); (T.Z.); (T.Z.)
- Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Key Laboratory of Anesthesiology and Resuscitation, Huazhong University of Science and Technology, Ministry of Education, Wuhan 430022, China
| | - Tianhao Zhang
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; (T.W.); (X.H.); (S.S.); (Y.W.); (L.H.); (T.Z.); (T.Z.)
- Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Key Laboratory of Anesthesiology and Resuscitation, Huazhong University of Science and Technology, Ministry of Education, Wuhan 430022, China
| | - Xiangdong Chen
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; (T.W.); (X.H.); (S.S.); (Y.W.); (L.H.); (T.Z.); (T.Z.)
- Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- Key Laboratory of Anesthesiology and Resuscitation, Huazhong University of Science and Technology, Ministry of Education, Wuhan 430022, China
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Meza Monge K, Ardon-Lopez A, Pratap A, Idrovo JP. Targeting Inflammation After Hemorrhagic Shock as a Molecular and Experimental Journey to Improve Outcomes: A Review. Cureus 2025; 17:e77776. [PMID: 39981454 PMCID: PMC11841828 DOI: 10.7759/cureus.77776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/21/2025] [Indexed: 02/22/2025] Open
Abstract
Hemorrhagic shock continues to be a major contributor to trauma-related fatalities globally, posing a significant and intricate pathophysiological challenge. The condition is marked by injury and blood loss, which activate molecular cascades that can quickly become harmful. The inflammatory response exhibits a biphasic pattern, beginning with a hyper-inflammatory phase that transitions into immunosuppression, posing significant obstacles to effective therapeutic interventions. This review article explores the intricate molecular mechanisms driving inflammation in hemorrhagic shock, emphasizing cellular signaling pathways, endothelial dysfunction, and immune activation. We discuss the role of molecular biomarkers in tracking disease progression and stratifying risk, with a focus on markers of endothelial dysfunction and inflammatory mediators as potential prognostic tools. Additionally, we assess therapeutic strategies, spanning traditional approaches like hemostatic resuscitation to advanced immunomodulatory treatments. Despite promising advancements in molecular monitoring and targeted therapies, challenges persist in bridging experimental findings with clinical applications. Future efforts must prioritize understanding the dynamic progression of inflammatory pathways and refining the timing of interventions to improve outcomes in hemorrhagic shock management.
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Affiliation(s)
- Kenneth Meza Monge
- Department of Surgery, Division of GI, Trauma, and Endocrine Surgery, University of Colorado, Aurora, USA
| | - Astrid Ardon-Lopez
- Department of Surgery, Division of Plastic and Reconstructive Surgery, University of Colorado, Aurora, USA
| | - Akshay Pratap
- Department of Surgery, Division of GI, Trauma, and Endocrine Surgery, University of Colorado, Aurora, USA
| | - Juan-Pablo Idrovo
- Department of Surgery, Division of GI, Trauma, and Endocrine Surgery, University of Colorado, Aurora, USA
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Rios KE, Alamneh Y, Werner LM, Leung C, Pavlovic R, Abu-Taleb R, Thanapaul RJRS, Lee S, Hull D, Czintos C, Su W, Getnet D, Antonic V, Bobrov AG. Optimization of a Lethal, Combat-Relevant Model of Sterile Inflammation in Mice for Drug Candidate Screening. Mil Med 2024; 189:694-701. [PMID: 39160880 DOI: 10.1093/milmed/usae233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 03/09/2024] [Accepted: 04/19/2024] [Indexed: 08/21/2024] Open
Abstract
INTRODUCTION Extensive trauma, commonly seen in wounded military Service Members, often leads to a severe sterile inflammation termed systemic inflammatory response syndrome (SIRS), which can progress to multiple organ dysfunction syndrome (MODS) and death. MODS is a serious threat to wounded Service Members, historically causing 10% of all deaths in trauma admissions at a forward deployed combat hospital. The importance of this problem will be exacerbated in large-scale combat operations, in which evacuation will be delayed and care of complex injuries at lower echelons of care may be prolonged. The main goal of this study was to optimize an existing mouse model of lethal SIRS/MODS as a therapeutic screening platform for the evaluation of immunomodulatory drugs. MATERIALS AND METHODS Male C57BL/6 mice were euthanized, and the bones and muscles were collected and blended into a paste termed tissue-bone matrix (TBX). The TBX at 12.5%-20% relative to body weight of each recipient mouse was implanted into subcutaneous pouches created on the dorsum of anesthetized animals. Mice were observed for clinical scores for up to 48 hours postimplantation and euthanized at the preset point of moribundity. To test effects of anesthetics on TBX-induced mortality, animals received isoflurane or ketamine/xylazine (K/X). In a separate set of studies, mice received TBX followed by intraperitoneal injection with 20 mg/kg or 40 mg/kg Eritoran or a placebo carrier. All Eritoran studies were performed in a blinded fashion. RESULTS We observed that K/X anesthesia significantly increased the lethality of the implanted TBX in comparison to inhaled anesthetics. Although all the mice anesthetized with isoflurane and implanted with 12.5% TBX survived for 24 hours, 60% of mice anesthetized with K/X were moribund by 24 hours postimplantation. To mimic more closely the timing of lethal SIRS/MODS following polytrauma in human patients, we extended observation to 48 hours. We performed TBX dose-response studies and found that as low as 15%, 17.5%, and 20% TBX caused moribundity/mortality in 50%, 80%, and 100% mice, respectively, over a 48-hour time period. With 17.5% TBX, we tested if moribundity/mortality could be rescued by anti-inflammatory drug Eritoran, a toll-like receptor 4 antagonist. Neither 20 mg/kg nor 40 mg/kg doses of Eritoran were found to be effective in this model. CONCLUSIONS We optimized a TBX mouse model of SIRS/MODS for the purpose of evaluating novel therapeutic interventions to prevent trauma-related pathophysiologies in wounded Service Members. Negative effects of K/X on lethality of TBX should be further evaluated, particularly in the light of widespread use of ketamine in treatment of pain. By mimicking muscle crush, bone fracture, and necrosis, the TBX model has pleiotropic effects on physiology and immunology that make it uniquely valuable as a screening tool for the evaluation of novel therapeutics against trauma-induced SIRS/MODS.
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Affiliation(s)
- Kariana E Rios
- Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- Oak Ridge Institute for Science and Education, Oak Ridge, TN 37830, USA
| | - Yonas Alamneh
- Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
| | - Lacie M Werner
- Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
| | - Clara Leung
- Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
| | - Radmila Pavlovic
- Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
| | - Rania Abu-Taleb
- Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
| | - Rex J R S Thanapaul
- Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- NRC Research Associateship Programs, National Academies of Sciences, Engineering, and Medicine, Washington, DC 20001, USA
| | - Sunjoo Lee
- Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
| | - Dawn Hull
- Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
| | - Christine Czintos
- Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
- Oak Ridge Institute for Science and Education, Oak Ridge, TN 37830, USA
| | - Wanwen Su
- Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
| | - Derese Getnet
- Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
| | - Vlado Antonic
- Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
| | - Alexander G Bobrov
- Wound Infections Department, Bacterial Diseases Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
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Hietbrink F, Mohseni S, Mariani D, Naess PA, Rey-Valcárcel C, Biloslavo A, Bass GA, Brundage SI, Alexandrino H, Peralta R, Leenen LPH, Gaarder T. What trauma patients need: the European dilemma. Eur J Trauma Emerg Surg 2024; 50:627-634. [PMID: 35798972 PMCID: PMC11249462 DOI: 10.1007/s00068-022-02014-w] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Accepted: 05/23/2022] [Indexed: 11/03/2022]
Abstract
There is a need for implementation and maturation of an inclusive trauma system in every country in Europe, with patient centered care by dedicated surgeons. This process should be initiated by physicians and medical societies, based on the best available evidence, and supported and subsequently funded by the government and healthcare authorities. A systematic approach to organizing all aspects of trauma will result in health gain in terms of quality of care provided, higher survival rates, better functional outcomes and quality of life. In addition, it will provide reliable data for both research, quality improvement and prevention programs. Severely injured patients need surgeons with broad technical and non-technical competencies to provide holistic, inclusive and compassionate care. Here we describe the philosophy of the surgical approach and define the necessary skills for trauma, both surgical and other, to improve outcome of severely injured patients. As surgery is an essential part of trauma care, surgeons play an important role for the optimal treatment of trauma patients throughout and after their hospital stay, including the intensive care unit (ICU). However, in most European countries, it might not be obvious to either the general public, patients or even the physicians that the surgeon must assume this responsibility in the ICU to optimize outcomes. The aim of this paper is to define key elements in terms of trauma systems, trauma-specific surgical skills and active critical care involvement, to organize and optimize trauma care in Europe.
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Affiliation(s)
- Falco Hietbrink
- Department of Surgery, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
| | - Shahin Mohseni
- Division of Trauma and Emergency Surgery, Department of Surgery, Orebro University Hospital and School of Medical Sciences, Orebro University, 702 81, Orebro, Sweden
| | - Diego Mariani
- Department of General Surgery, ASST Ovest Milanese, Milan, Italy
| | - Päl Aksel Naess
- Department of Traumatology, Oslo University Hospital Ulleval, Oslo, Norway
| | | | - Alan Biloslavo
- General Surgery Department, Cattinara University Hospital, Trieste, Italy
| | - Gary A Bass
- Division of Traumatology, Surgical Critical Care and Emergency Surgery, University of Pennsylvania, Philadelphia, USA
| | - Susan I Brundage
- Department of Surgery, R Adams Cowley Shock Trauma Center, Baltimore, USA
| | | | - Ruben Peralta
- Department of Surgery, Trauma Surgery, Hamad General Hospital, Doha, Qatar
- Department of Surgery, Universidad Nacional Pedro Henriquez Urena, Santo Domingo, Dominican Republic
- Hamad Injury Prevention Program, Hamad Trauma Center, Hamad General Hospital, Doha, Qatar
| | - Luke P H Leenen
- Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Tina Gaarder
- Department of Traumatology, Oslo University Hospital Ulleval, Oslo, Norway
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Nijdam TM, Jukema BN, de Fraiture EJ, Spijkerman R, Schuijt HJ, Spoelder M, Bongers CC, Hopman MT, Koenderman L, Hietbrink F, van der Velde D. Identification of neutrophil phenotype categories in geriatric hip fracture patients aids in personalized medicine. OTA Int 2023; 6:e291. [PMID: 38152436 PMCID: PMC10750458 DOI: 10.1097/oi9.0000000000000291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 08/25/2023] [Accepted: 10/08/2023] [Indexed: 12/29/2023]
Abstract
Objectives The number of geriatric hip fracture patients is high and expected to rise in the coming years, and many are frail and at risk for adverse outcomes. Early identification of high-risk patients is crucial to balance treatment and optimize outcome, but remains challenging. Previous research in patients with multitrauma suggested that neutrophil phenotype analysis could aid in early identification of high-risk patients. This pilot study investigated the feasibility and clinical value of neutrophil phenotype analysis in geriatric patients with a hip fracture. Methods A prospective study was conducted in a regional teaching hospital in the Netherlands. At the emergency department, blood samples were collected from geriatric patients with a hip fracture and analyzed using automated flow cytometry. Flow cytometry data were processed using an automated clustering algorithm. Neutrophil activation data were compared with a healthy control cohort. Neutrophil phenotype categories were assessed based on two-dimensional visual assessment of CD16/CD62L expression. Results Blood samples from 45 geriatric patients with a hip fracture were included. Neutrophils showed an increased activation profile and decreased responsiveness to formyl peptides when compared to healthy controls. The neutrophil phenotype of all patients was categorized. The incidence of severe adverse outcome was significantly different between the different categories (P = 0.0331). Moreover, patients with neutrophil phenotype category 0 developed no severe adverse outcomes. Conclusions Using point-of-care fully automated flow cytometry to analyze the neutrophil compartment in geriatric hip fracture patients is feasible and holds clinical value in determining patients at risk for adverse outcome. This study is a first step toward immuno-based precision medicine for identifying geriatric hip fracture patients that are deemed fit for surgery.
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Affiliation(s)
- Thomas M.P. Nijdam
- St. Antonius Ziekenhuis Utrecht, Department of Trauma Surgery, Utrecht, the Netherlands
| | - Bernard N. Jukema
- Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, the Netherlands
- Center for Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Emma J. de Fraiture
- St. Antonius Ziekenhuis Utrecht, Department of Trauma Surgery, Utrecht, the Netherlands
- University Medical Center Utrecht, Department of Trauma Surgery, Utrecht, the Netherlands
| | - Roy Spijkerman
- St. Antonius Ziekenhuis Utrecht, Department of Trauma Surgery, Utrecht, the Netherlands
| | - Henk Jan Schuijt
- St. Antonius Ziekenhuis Utrecht, Department of Trauma Surgery, Utrecht, the Netherlands
| | - Marcia Spoelder
- Department of Physiology, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Coen C.W.G. Bongers
- Department of Physiology, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Maria T.E. Hopman
- Department of Physiology, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Leo Koenderman
- Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, the Netherlands
- Center for Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Falco Hietbrink
- University Medical Center Utrecht, Department of Trauma Surgery, Utrecht, the Netherlands
| | - Detlef van der Velde
- St. Antonius Ziekenhuis Utrecht, Department of Trauma Surgery, Utrecht, the Netherlands
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Sikora JP, Karawani J, Sobczak J. Neutrophils and the Systemic Inflammatory Response Syndrome (SIRS). Int J Mol Sci 2023; 24:13469. [PMID: 37686271 PMCID: PMC10488036 DOI: 10.3390/ijms241713469] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2023] [Revised: 08/24/2023] [Accepted: 08/28/2023] [Indexed: 09/10/2023] Open
Abstract
We are not entirely able to understand, assess, and modulate the functioning of the immune system in clinical situations that lead to a systemic inflammatory response. In the search for diagnostic and treatment strategies (which are still far from perfect), it became very important to study the pathogenesis and participation of endogenous inflammation mediators. This study attempts to more precisely establish the role of neutrophils in individual phenomena occurring during an inflammatory and anti-inflammatory reaction, taking into account their cidal, immunoregulatory, and reparative abilities. Pro- and anticoagulatory properties of endothelium in systemic inflammatory response syndrome (SIRS) are emphasised, along with the resulting clinical implications (the application of immunotherapy using mesenchymal stem/stromal cells (MSCs) or IL-6 antagonists in sepsis and COVID-19 treatment, among others). Special attention is paid to reactive oxygen species (ROS), produced by neutrophils activated during "respiratory burst" in the course of SIRS; the protective and pathogenic role of these endogenous mediators is highlighted. Moreover, clinically useful biomarkers of SIRS (neutrophil extracellular traps, cell-free DNA, DAMP, TREMs, NGAL, miRNA, selected cytokines, ROS, and recognised markers of endothelial damage from the group of adhesins by means of immunohistochemical techniques) related to the neutrophils are presented, and their role in the diagnosing and forecasting of sepsis, burn disease, and COVID-19 is emphasised. Finally, examples of immunomodulation of sepsis and antioxidative thermal injury therapy are presented.
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Affiliation(s)
- Janusz P. Sikora
- Department of Paediatric Emergency Medicine, 2nd Chair of Paediatrics, Central Clinical Hospital, Medical University of Łódź, ul. Sporna 36/50, 91-738 Łódź, Poland;
| | - Jakub Karawani
- Faculty of Medicine, Lazarski University, ul. Świeradowska 43, 02-662 Warsaw, Poland;
| | - Jarosław Sobczak
- Department of Paediatric Emergency Medicine, 2nd Chair of Paediatrics, Central Clinical Hospital, Medical University of Łódź, ul. Sporna 36/50, 91-738 Łódź, Poland;
- Department of Management and Logistics in Healthcare, Medical University of Łódź, ul. Lindleya 6, 90-131 Łódź, Poland
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Abubakar JO, Temidayo DO, Ololade OAH, Abosede OO. Herbal supplements suppress pro-inflammatory cytokines, boost humoral immunity, and modulate adipokines to enhance the productivity traits of rabbit bucks in hot climatic conditions. Trop Anim Health Prod 2023; 55:227. [PMID: 37227575 DOI: 10.1007/s11250-023-03640-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Accepted: 05/16/2023] [Indexed: 05/26/2023]
Abstract
Thermal stress is the main stressor accounting for reduced productivity, compromised immunity, and collapse of thermoregulatory measures in rabbits in the tropics. The current climate change depicts worsening assault of heat stress in the time ahead; hence, the need to develop combative measures for animal productivity. This research investigates the influence of herbal supplements of three tropical herbs Viscum album (mistletoe), Moringa oleifera (Moringa), and Phyllanthus amarus (Phyllanthus) on immune response, oxidative status, adipokines, and growth of eighty weaned rabbits during heat stress in tropical climate. The bucks were fed with four standard diets; a control and others supplemented with each of Moringa, Phyllanthus, and mistletoe for an eight-week feed trial. Performance indicators were monitored and blood were sampled and assayed for hematology, pro-inflammatory cytokines, adipokines, and oxidative status. The result shows that the performance of bucks fed with Phyllanthus and mistletoe supplements was superior to other groups. The neutrophil/lymphocyte ratio was significantly (p < 0.05) lower in the bucks fed with Moringa supplement, with significantly (p < 0.05) highest values obtained in the control group. Total antioxidant activity of the bucks fed with supplements was significantly (p < 0.05) higher than those on control, with the significantly (p < 0.05) highest value recorded in bucks fed with Phyllanthus. Serum lipid peroxidation of the bucks on control was significantly (p < 0.05) highest and significantly (p < 0.05) least value was obtained in bucks on mistletoe. Heat shock protein 70, adiponectin, and leptin of the bucks on control were significantly (p < 0.05) higher than bucks on herbal supplements. Interleukin 6, interleukin β, and tumor necrosis factor α of bucks on control were significantly (p < 0.05) higher than bucks fed on herbal supplements. In conclusion, the inclusion of herbal supplements Moringa, Phyllanthus, or mistletoe suppressed pro-inflammatory cytokines, boost humoral immunity, enhance the anti-oxidative status, and promote the growth of rabbit bucks during thermal discomfort.
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Affiliation(s)
- Jimoh Olatunji Abubakar
- Department of Agricultural Technology, The Federal Polytechnic Ado-Ekiti, Ado-Ekiti, Ekiti State, Nigeria.
| | | | | | - Ojo Olayinka Abosede
- Department of Animal Production, Fisheries and Aquaculture, Kwara State University, Molete, Kwara State, Nigeria
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Dietary 1,3-β-Glucans Affect Growth, Breast Muscle Composition, Antioxidant Activity, Inflammatory Response, and Economic Efficiency in Broiler Chickens. Life (Basel) 2023; 13:life13030751. [PMID: 36983906 PMCID: PMC10054407 DOI: 10.3390/life13030751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Revised: 03/04/2023] [Accepted: 03/08/2023] [Indexed: 03/12/2023] Open
Abstract
Recently, researchers have been intensively looking for novel, safe antibiotic alternatives because of the prevalence of many clinical and subclinical diseases affecting bird flocks and the risks of using antibiotics in subtherapeutic doses as feed additives. The present study intended to evaluate the potential use of 1,3-β-glucans (GLC) as antibiotic alternative growth promotors and assessed the effect of their dietary inclusion on the growth performance, carcass traits, chemical composition of breast muscles, economic efficiency, blood biochemical parameters, liver histopathology, antioxidant activity, and the proinflammatory response of broiler chickens. This study used 200 three-day-old ROSS broiler chickens (50 chicks/group, 10 chicks/replicate, with an average body weight of 98.71 ± 0.17 g/chick). They were assigned to four experimental groups with four dietary levels of GLC, namely 0, 50, 100, and 150 mg kg−1, for a 35-day feeding period. Birds fed diets containing GLC showed an identical different growth rate to the control group. However, the total feed intake (TFI) increased quadratically in the GLC50 and GLC100 groups as compared to that in the control group. GLC addition had no significant effect on the weights of internal and immune organs, except for a decrease in bursal weight in the GLC150 group (p = 0.01). Dietary GLC addition increased the feed cost and total cost at 50 and 100 mg kg−1 doses. The percentages of n-3 and n-6 PUFA in the breast muscle of broiler chickens fed GLC-supplemented diets increased linearly in a dose-dependent manner (p < 0.01). The serum alanine aminotransferase (ALT) level and the uric acid level were quadratically increased in the GLC150 group. The serum levels of total antioxidant capacity, catalase, superoxide dismutase, interleukin-1β, and interferon-gamma linearly increased, while the MDA level decreased in the GLC-fed groups in a dose-dependent manner. Normal histological characterization of different liver structures in the different groups with moderate round cells was noted as a natural immune response around the hepatic portal area. The different experimental groups showed an average percentage of positive immunostaining to the proinflammatory marker transforming growth factor-beta with an increase in the dose of GLC addition. The results suggest that GLC up to 100 mg kg−1 concentration can be used as a feed additive in the diets of broiler chickens and shows no adverse effects on their growth, dressing percentage, and internal organs. GLC addition in diets improves the antioxidant activity and immune response in birds. GLC help enrich the breast muscle with n-3 and n-6 polyunsaturated fatty acids.
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Makarova YA, Ryabkova VA, Salukhov VV, Sagun BV, Korovin AE, Churilov LP. Atherosclerosis, Cardiovascular Disorders and COVID-19: Comorbid Pathogenesis. Diagnostics (Basel) 2023; 13:478. [PMID: 36766583 PMCID: PMC9914751 DOI: 10.3390/diagnostics13030478] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 01/19/2023] [Accepted: 01/26/2023] [Indexed: 02/01/2023] Open
Abstract
The article describes how atherosclerosis and coronavirus disease 19 (COVID-19) may affect each other. The features of this comorbid pathogenesis at various levels (vascular, cellular and molecular) are considered. A bidirectional influence of these conditions is described: the presence of cardiovascular diseases affects different individuals' susceptibility to viral infection. In turn, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can have a negative effect on the endothelium and cardiomyocytes, causing blood clotting, secretion of pro-inflammatory cytokines, and thus exacerbating the development of atherosclerosis. In addition to the established entry into cells via angiotensin-converting enzyme 2 (ACE2), other mechanisms of SARS-CoV-2 entry are currently under investigation, for example, through CD147. Pathogenesis of comorbidity can be determined by the influence of the virus on various links which are meaningful for atherogenesis: generation of oxidized forms of low-density lipoproteins (LDL), launch of a cytokine storm, damage to the endothelial glycocalyx, and mitochondrial injury. The transformation of a stable plaque into an unstable one plays an important role in the pathogenesis of atherosclerosis complications and can be triggered by COVID-19. The impact of SARS-CoV-2 on large vessels such as the aorta is more complex than previously thought considering its impact on vasa vasorum. Current information on the mutual influence of the medicines used in the treatment of atherosclerosis and acute COVID-19 is briefly summarized.
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Affiliation(s)
- Yulia A. Makarova
- Laboratory of the Microangiopathic Mechanisms of Atherogenesis, Saint Petersburg State University, 199034 Saint-Petersburg, Russia
| | - Varvara A. Ryabkova
- Laboratory of the Microangiopathic Mechanisms of Atherogenesis, Saint Petersburg State University, 199034 Saint-Petersburg, Russia
- M.V. Chernorutsky Department of Internal Medicine (Hospital Course), Pavlov First Saint Petersburg State Medical University, 197022 Saint-Petersburg, Russia
| | - Vladimir V. Salukhov
- N.S. Molchanov 1st Clinic for the Improvement of Physicians, S.M. Kirov Military Medical Academy, 194044 Saint-Petersburg, Russia
| | - Boris V. Sagun
- N.S. Molchanov 1st Clinic for the Improvement of Physicians, S.M. Kirov Military Medical Academy, 194044 Saint-Petersburg, Russia
| | - Aleksandr E. Korovin
- Laboratory of the Microangiopathic Mechanisms of Atherogenesis, Saint Petersburg State University, 199034 Saint-Petersburg, Russia
- N.S. Molchanov 1st Clinic for the Improvement of Physicians, S.M. Kirov Military Medical Academy, 194044 Saint-Petersburg, Russia
| | - Leonid P. Churilov
- Laboratory of the Microangiopathic Mechanisms of Atherogenesis, Saint Petersburg State University, 199034 Saint-Petersburg, Russia
- Department of Experimental Tuberculosis, Saint Petersburg Research Institute of Phthisiopulmonology, 191036 Saint-Petersburg, Russia
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Buijs MAS, van den Kieboom J, Sliepen J, Wever KLH, van Breugel JM, Hietbrink F, IJpma FFA, Govaert GAM. Outcome and risk factors for recurrence of early onset fracture-related infections treated with debridement, antibiotics and implant retention: Results of a large retrospective multicentre cohort study. Injury 2022; 53:3930-3937. [PMID: 36307267 DOI: 10.1016/j.injury.2022.10.017] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2022] [Revised: 10/01/2022] [Accepted: 10/15/2022] [Indexed: 11/05/2022]
Abstract
INTRODUCTION Early Fracture-Related Infections (FRIs) are a common entity in hospitals treating trauma patients and are often treated with a Debridement, Antibiotics and Implant Retention (DAIR) procedure. Aims of this study were to 1) evaluate the recurrence rate after DAIR procedures for early onset FRI, 2) establish the number of surgical procedures to gain control of the initial infection and 3) identify independent predictors for recurrence in this cohort. METHODS A retrospective multicentre cohort study was conducted in two level 1 trauma centres. Consecutive patients who underwent a DAIR procedure between January 1st 2015 and July 1st 2020 for confirmed FRI with an onset of <6 weeks after the latest osseous operation were included. Recorded data included patient demographics, treatment characteristics and follow-up. Univariate and multivariate logistic regression analyses were performed to assess predictors for recurrent FRI. RESULTS A total of 141 patients with early FRI were included in this study with a median age of 54.0 years (interquartile range (IQR) 34.5-64.0). The recurrence rate of FRI was 13% (n = 19) at one year follow-up and 18% (n = 25) at 23.1 months (IQR 15.3-36.4) follow-up. Infection control was achieved in 94% (n = 127/135) of cases. In total, 73 patients (52%) underwent at least two surgical procedures to treat the ongoing initial episode of FRI, of whom 54 patients (74%) required two to three procedures and 17 patients (23%) four to five procedures. Predictors for recurrent FRI were use of an intramedullary nail during index operation (odds ratio (OR) 4.0 (95% confidence interval (CI) 1.1-13.8)), need for additional surgical procedures to treat ongoing infection during the treatment period following the first presentation of early FRI (OR 1.9 (95% CI 1.1-3.5)) and a decreased Injury Severity Score (ISS) (inverted OR 1.1 (95% CI 1.0-1.1)). CONCLUSION The recurrence rate after treatment of early onset FRI in patients treated with a DAIR procedure was 18% at 23.1 months follow-up. At least two surgical procedures to gain control of the initial infection were needed in 52% of patients. Independent predictors for recurrent FRI were the use of an intramedullary nail during index operation, need for additional surgical procedures and a decreased ISS.
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Affiliation(s)
- M A S Buijs
- Department of Trauma Surgery, University Medical Centre Utrecht, University of Utrecht, Utrecht, The Netherlands
| | - J van den Kieboom
- Department of Trauma Surgery, University Medical Centre Utrecht, University of Utrecht, Utrecht, The Netherlands
| | - J Sliepen
- Department of Trauma Surgery, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
| | - K L H Wever
- Department of Trauma Surgery, University Medical Centre Utrecht, University of Utrecht, Utrecht, The Netherlands
| | - J M van Breugel
- Department of Trauma Surgery, University Medical Centre Utrecht, University of Utrecht, Utrecht, The Netherlands
| | - F Hietbrink
- Department of Trauma Surgery, University Medical Centre Utrecht, University of Utrecht, Utrecht, The Netherlands
| | - F F A IJpma
- Department of Trauma Surgery, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
| | - G A M Govaert
- Department of Trauma Surgery, University Medical Centre Utrecht, University of Utrecht, Utrecht, The Netherlands.
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de Fraiture EJ, Bongers SH, Jukema BN, Koenderman L, Vrisekoop N, van Wessem KJP, Leenen LPH, Hietbrink F. Visualization of the inflammatory response to injury by neutrophil phenotype categories. Eur J Trauma Emerg Surg 2022; 49:1023-1034. [PMID: 36348032 PMCID: PMC10175373 DOI: 10.1007/s00068-022-02134-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Accepted: 10/10/2022] [Indexed: 11/09/2022]
Abstract
Abstract
Purpose
The risk of infectious complications after trauma is determined by the amount of injury-related tissue damage and the resulting inflammatory response. Recently, it became possible to measure the neutrophil phenotype in a point-of-care setting. The primary goal of this study was to investigate if immunophenotype categories based on visual recognition of neutrophil subsets are applicable to interpret the inflammatory response to trauma. The secondary goal was to correlate these immunophenotype categories with patient characteristics, injury severity and risk of complications.
Methods
A cohort study was conducted with patients presented at a level 1 trauma center with injuries of any severity, who routinely underwent neutrophil phenotyping. Data generated by automated point-of-care flow cytometry were prospectively gathered. Neutrophil phenotypes categories were defined by visual assessment of two-dimensional CD16/CD62L dot plots. All patients were categorized in one of the immunophenotype categories. Thereafter, the categories were validated by multidimensional analysis of neutrophil populations, using FlowSOM. All clinical parameters and endpoints were extracted from the trauma registry.
Results
The study population consisted of 380 patients. Seven distinct immunophenotype Categories (0–6) were defined, that consisted of different neutrophil populations as validated by FlowSOM. Injury severity scores and risk of infectious complications increased with ascending immunophenotype Categories 3–6. Injury severity was similarly low in Categories 0–2.
Conclusion
The distribution of neutrophil subsets that were described in phenotype categories is easily recognizable for clinicians at the bedside. Even more, multidimensional analysis demonstrated these categories to be distinct subsets of neutrophils. Identification of trauma patients at risk for infectious complications by monitoring the immunophenotype category is a further improvement of personalized and point-of-care decision-making in trauma care.
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Affiliation(s)
- Emma J. de Fraiture
- Department of Trauma Surgery, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, Netherlands
- Department of Trauma Surgery, Sint Antonius Hospital, Utrecht, The Netherlands
| | - Suus H. Bongers
- Department of Trauma Surgery, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, Netherlands
- Center for Translational Immunology (CTI), University Medical Center Utrecht, Utrecht, Netherlands
| | - Bernard N. Jukema
- Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, Netherlands
| | - Leo Koenderman
- Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, Netherlands
- Center for Translational Immunology (CTI), University Medical Center Utrecht, Utrecht, Netherlands
| | - Nienke Vrisekoop
- Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, Netherlands
- Center for Translational Immunology (CTI), University Medical Center Utrecht, Utrecht, Netherlands
| | - Karlijn J. P. van Wessem
- Department of Trauma Surgery, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, Netherlands
| | - Luke P. H. Leenen
- Department of Trauma Surgery, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, Netherlands
| | - Falco Hietbrink
- Department of Trauma Surgery, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, Netherlands
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de Fraiture EJ, Vrisekoop N, Leenen LPH, van Wessem KJP, Koenderman L, Hietbrink F. Longitudinal assessment of the inflammatory response: The next step in personalized medicine after severe trauma. Front Med (Lausanne) 2022; 9:983259. [PMID: 36203773 PMCID: PMC9531720 DOI: 10.3389/fmed.2022.983259] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 09/01/2022] [Indexed: 01/13/2023] Open
Abstract
Infections in trauma patients are an increasing and substantial cause of morbidity, contributing to a mortality rate of 5-8% after trauma. With increased early survival rates, up to 30-50% of multitrauma patients develop an infectious complication. Trauma leads to a complex inflammatory cascade, in which neutrophils play a key role. Understanding the functions and characteristics of these cells is important for the understanding of their involvement in the development of infectious complications. Recently, analysis of neutrophil phenotype and function as complex biomarkers, has become accessible for point-of-care decision making after trauma. There is an intriguing relation between the neutrophil functional phenotype on admission, and the clinical course (e.g., infectious complications) of trauma patients. Potential neutrophil based cellular diagnostics include subsets based on neutrophil receptor expression, responsiveness of neutrophils to formyl-peptides and FcγRI (CD64) expression representing the infectious state of a patient. It is now possible to recognize patients at risk for infectious complications when presented at the trauma bay. These patients display increased numbers of neutrophil subsets, decreased responsiveness to fMLF and/or increased CD64 expression. The next step is to measure these biomarkers over time in trauma patients at risk for infectious complications, to guide decision making regarding timing and extent of surgery and administration of (preventive) antibiotics.
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Affiliation(s)
- E. J. de Fraiture
- Department of Trauma Surgery, University Medical Center Utrecht, Utrecht, Netherlands
- Department of Surgery, Sint Antonius Hospital, Nieuwegein, Netherlands
| | - N. Vrisekoop
- Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, Netherlands
- Center for Translational Immunology (CTI), University Medical Center Utrecht, Utrecht, Netherlands
| | - L. P. H. Leenen
- Department of Trauma Surgery, University Medical Center Utrecht, Utrecht, Netherlands
| | - K. J. P. van Wessem
- Department of Trauma Surgery, University Medical Center Utrecht, Utrecht, Netherlands
| | - L. Koenderman
- Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, Netherlands
- Center for Translational Immunology (CTI), University Medical Center Utrecht, Utrecht, Netherlands
| | - F. Hietbrink
- Department of Trauma Surgery, University Medical Center Utrecht, Utrecht, Netherlands
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Akinyemi F, Adewole D. Effects of brown seaweed products on growth performance, plasma biochemistry, immune response, and antioxidant capacity of broiler chickens challenged with heat stress. Poult Sci 2022; 101:102215. [PMID: 36288626 PMCID: PMC9593180 DOI: 10.1016/j.psj.2022.102215] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 09/20/2022] [Accepted: 09/26/2022] [Indexed: 11/28/2022] Open
Abstract
Brown seaweed (Ascophyllum nodosum) is an exceptional bioactive substance known for its excellent antioxidant ability. Given the potential benefits of brown seaweed, the current study was conducted to determine its efficacy on growth performance, blood biochemistry, immunoglobulins (IgG and IgM), and the antioxidant capacity of broiler chickens challenged with heat stress (HS). A total of 336 mixed-sex Ross 308 broiler chicks (one-day-old) were randomly assigned into two groups; The thermoneutral group (TN, broilers were raised at 24 ± 1°C); and the heat stress group (HS; broilers were exposed to 32°C to 34°C, 8 h/d from day 21 to 27; the temperature in the remaining time was same as TN group). All birds in each group were randomly allotted to 4 dietary treatments—Negative control (NC) (without seaweed), NC + 1 mL seaweed extract (SWE) in drinking water, NC + 2 mL SWE in drinking water, and NC + 2% seaweed meal (SWM) in feed. Each treatment was assigned to six replicates with 7 broilers/replicate. Average body weight gain (ABWG), average feed intake (AFI), average water intake (AWI), feed conversion ratio (FCR), and mortality were determined weekly. On day 28, two male birds/cage were euthanized to collect blood and immune organs for subsequent biochemical, antioxidant, and immune status analysis. Data were analyzed as a 4 × 2 factorial analysis of variance using the GLM procedure of Minitab software. Overall, 2% SWM inclusion significantly increased (P < 0.05) the AFI, ABWG, and AWI of broiler chickens irrespective of HS. HS significantly reduced (P < 0.05) AFI and increased (P < 0.05) the bird's rectal temperature, plasma concentrations of sodium, chloride, glucose, amylase, and uric acid compared to TN birds. HS increased (P < 0.05) serum IgM and IgG and decreased plasma glutathione reductase and glutathione peroxidase compared to TN birds, while the activity of superoxide dismutase was not affected by HS and dietary treatments. 1 mL SWE in water and 2% SWM in feed significantly reduced (P < 0.05) the plasma activity of alanine aminotransferase and gamma-glutamyl transferase of heat-stressed broilers, respectively compared to other treatments. Conclusively, dietary supplementation of brown seaweed improved the growth performance of birds irrespective of HS and may help to reduce the negative effects of HS by improving the plasma enzyme activities of heat-stressed birds.
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Affiliation(s)
- Fisayo Akinyemi
- Department of Animal Science and Aquaculture, Faculty of Agriculture, Dalhousie University, Truro, NS, B2N 5E3, Canada
| | - Deborah Adewole
- Department of Animal Science and Aquaculture, Faculty of Agriculture, Dalhousie University, Truro, NS, B2N 5E3, Canada.
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14
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Meilik R, Ben-Assayag H, Meilik A, Berliner S, Zeltser D, Shapira I, Rogowski O, Goldiner I, Shenhar-Tsarfaty S, Wasserman A. Sepsis Related Mortality Associated with an Inflammatory Burst in Patients Admitting to the Department of Internal Medicine with Apparently Normal C-Reactive Protein Concentration. J Clin Med 2022; 11:jcm11113151. [PMID: 35683538 PMCID: PMC9181046 DOI: 10.3390/jcm11113151] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 05/29/2022] [Accepted: 05/31/2022] [Indexed: 02/01/2023] Open
Abstract
Background: Patients who are admitted to the Department of Internal Medicine with apparently normal C-reactive protein (CRP) concentration impose a special challenge due the assumption that they might not harbor a severe and potentially lethal medical condition. Methods: A retrospective cohort of all patients who were admitted to the Department of Internal Medicine with a CRP concentration of ≤31.9 mg/L and had a second CRP test obtained within the next 24 h. Seven day mortality data were analyzed. Results: Overall, 3504 patients were analyzed with a mean first and second CRP of 8.8 (8.5) and 14.6 (21.6) mg/L, respectively. The seven day mortality increased from 1.8% in the first quartile of the first CRP to 7.5% in the fourth quartile of the first CRP (p < 0.0001) and from 0.6% in the first quartile of the second CRP to 9.5% in the fourth quartile of the second CRP test (p < 0.0001), suggesting a clear relation between the admission CRP and in hospital seven day mortality. Conclusions: An association exists between the quartiles of CRP and 7-day mortality as well as sepsis related cause of death. Furthermore, the CRP values 24 h after hospital admission improved the discrimination.
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Affiliation(s)
- Ronnie Meilik
- Department of Internal Medicine “C”, “D”, & “E”, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 64239, Israel; (R.M.); (H.B.-A.); (S.B.); (D.Z.); (I.S.); (O.R.); (A.W.)
| | - Hadas Ben-Assayag
- Department of Internal Medicine “C”, “D”, & “E”, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 64239, Israel; (R.M.); (H.B.-A.); (S.B.); (D.Z.); (I.S.); (O.R.); (A.W.)
| | - Ahuva Meilik
- Clinical Performances Research and Operational Unit, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 64239, Israel;
| | - Shlomo Berliner
- Department of Internal Medicine “C”, “D”, & “E”, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 64239, Israel; (R.M.); (H.B.-A.); (S.B.); (D.Z.); (I.S.); (O.R.); (A.W.)
| | - David Zeltser
- Department of Internal Medicine “C”, “D”, & “E”, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 64239, Israel; (R.M.); (H.B.-A.); (S.B.); (D.Z.); (I.S.); (O.R.); (A.W.)
| | - Itzhak Shapira
- Department of Internal Medicine “C”, “D”, & “E”, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 64239, Israel; (R.M.); (H.B.-A.); (S.B.); (D.Z.); (I.S.); (O.R.); (A.W.)
| | - Ori Rogowski
- Department of Internal Medicine “C”, “D”, & “E”, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 64239, Israel; (R.M.); (H.B.-A.); (S.B.); (D.Z.); (I.S.); (O.R.); (A.W.)
| | - Ilana Goldiner
- Laboratory Medicine, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 64239, Israel;
| | - Shani Shenhar-Tsarfaty
- Department of Internal Medicine “C”, “D”, & “E”, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 64239, Israel; (R.M.); (H.B.-A.); (S.B.); (D.Z.); (I.S.); (O.R.); (A.W.)
- Correspondence:
| | - Asaf Wasserman
- Department of Internal Medicine “C”, “D”, & “E”, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 64239, Israel; (R.M.); (H.B.-A.); (S.B.); (D.Z.); (I.S.); (O.R.); (A.W.)
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Lee EP, Lin MJ, Wu HP. Time-serial expression of toll-like receptor 4 signaling during polymicrobial sepsis in rats. Int J Immunopathol Pharmacol 2022; 36:3946320221090021. [PMID: 35603454 PMCID: PMC9127845 DOI: 10.1177/03946320221090021] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Sepsis caused by aggressive infection is a severe clinical problem with an increasing incidence worldwide. Toll-like receptors and their common adapter myeloid differentiation factor 88 (MyD88) can activate immune responses by recognizing a foreign microbe’s product. This study aimed to identify the different time expression of TLR four signaling pathway in an experimental rodent model of polymicrobial sepsis. A randomized animal study was investigated in rats with septic peritonitis induced by cecal ligation and puncture (CLP). The expressions of MyD88-dependent pathway biomarkers, including MyD88, nuclear factor-κB (NF-κB), and serum tumor necrosis factor-α (TNF-α), were analyzed and compared to the sham controls at the different time points after CLP surgery. CLP-induced sepsis increased liver MyD88 mRNA expression and protein expression compared to the control groups at 2 h after surgery. The MyD88 mRNA and protein expressions in rats with CLP-induced sepsis marked increased at 4 and 6 h, and their NF-κB activities and serum TNF-α levels also increased at 4 h after CLP surgery (both p < .05). The different serial expression of MyD88-ependent pathway during sepsis may be used as biomarkers during sepsis. These results may provide further helpful information for using pro-inflammatory biomarkers of innate immunity such as MyD88 and TNF-α in clinical sepsis or related abdominal surgical emergency in the future.
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Affiliation(s)
- En-Pei Lee
- Division of Pediatric Critical Care Medicine, Department of Pediatrics, Chang Gung Memorial Hospital at Linko, Taiwan
- College of Medicine, Chang Gung University, Taiwan
| | - Mao-Jen Lin
- Division of Cardiology, Department of Medicine, Taichung Tzu Chi Hospital, The Buddhist Tzu Chi Medical Foundation, Taiwan
- Department of Medicine, School of Medicine, Tzu Chi University, Taiwan
| | - Han-Ping Wu
- Department of Pediatric Emergency Medicine, Children Hospital, China Medical University, Taichung, Taiwan
- Department of Medical Research, Children’s Hospital, China Medical University, Taichung, Taiwan
- Department of Medicine, School of Medicine, China Medical University, Taichung, Taiwan
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Zhang Y, Chu JMT, Wong GTC. Cerebral Glutamate Regulation and Receptor Changes in Perioperative Neuroinflammation and Cognitive Dysfunction. Biomolecules 2022; 12:biom12040597. [PMID: 35454185 PMCID: PMC9029551 DOI: 10.3390/biom12040597] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 04/11/2022] [Accepted: 04/15/2022] [Indexed: 12/23/2022] Open
Abstract
Glutamate is the major excitatory neurotransmitter in the central nervous system and is intricately linked to learning and memory. Its activity depends on the expression of AMPA and NMDA receptors and excitatory amino transporters on neurons and glial cells. Glutamate transporters prevent the excess accumulation of glutamate in synapses, which can lead to aberrant synaptic signaling, excitotoxicity, or cell death. Neuroinflammation can occur acutely after surgical trauma and contributes to the development of perioperative neurocognitive disorders, which are characterized by impairment in multiple cognitive domains. In this review, we aim to examine how glutamate handling and glutamatergic function are affected by neuroinflammation and their contribution to cognitive impairment. We will first summarize the current data regarding glutamate in neurotransmission, its receptors, and their regulation and trafficking. We will then examine the impact of inflammation on glutamate handling and neurotransmission, focusing on changes in glial cells and the effect of cytokines. Finally, we will discuss these changes in the context of perioperative neuroinflammation and the implications they have for perioperative neurocognitive disorders.
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Choi MI, Han SY, Jeon HS, Choi ES, Won SE, Lee YJ, Yang JH, Baek CY, Shim H, Mun SJ. The influence of professional oral hygiene care on reducing ventilator-associated pneumonia in trauma intensive care unit patients. Br Dent J 2022; 232:253-259. [PMID: 35217746 DOI: 10.1038/s41415-022-3986-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Accepted: 05/06/2021] [Indexed: 11/09/2022]
Abstract
Aim This study aimed to examine the effects of professional oral hygiene care for the prevention of ventilator-associated pneumonia (VAP) and the improvement of oral hygiene among patients in the trauma intensive care unit (TICU).Materials and methods TICU patients who underwent intubation were randomly assigned to either the experimental group (n = 29) or control group (n = 28). The developed professional oral hygiene care protocol was administered to patients in the experimental group every 24 hours. Additionally, data regarding general characteristics, medical history, oral hygiene status, Clinical Pulmonary Infection Score and quantitative polymerase chain reaction were assessed.Results The incidence of VAP differed between the control group (10.58) and experimental group (0) post intervention. Post-admission bedside oral exam scores with significant differences in oral hygiene were observed in the experimental group (in contrast to the control group) from 48 hours onwards (10.69 ± 3.43, p = 0.06). Staphylococcus aureus and Klebsiella pneumoniae exhibited significant differences in count as professional oral hygiene care continued.Conclusions This study suggests a model in which different health care professionals can cooperate to reduce the incidence of VAP and improve oral health conditions.
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Affiliation(s)
- Ma-I Choi
- Department of Dental Hygiene, College of Software and Digital Healthcare Convergence, Yonsei University, Republic Of Korea
| | - Sun-Young Han
- Department of Dental Hygiene, College of Software and Digital Healthcare Convergence, Yonsei University, Republic Of Korea
| | - Hyun-Sun Jeon
- Department of Dental Hygiene, Yeoju Institute of Technology, Republic Of Korea
| | - Eun-Sil Choi
- Department of Dental Hygiene, The Graduate School, Yonsei University, Republic Of Korea
| | - Seung-Eun Won
- Dental Life Science Research Institute, The Seoul National University Dental Hospital, Republic Of Korea
| | - Ye-Ji Lee
- Dental Hygiene, NYU College of Dentistry, New York, USA
| | - Ji-Hye Yang
- Department of Oral Pathology, Yonsei University College of Dentistry, Republic Of Korea
| | - Chi-Yun Baek
- Department of Nursing, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Republic Of Korea
| | - Hongjin Shim
- Regional Trauma Centre, Department of Surgery, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Republic Of Korea
| | - So-Jung Mun
- Department of Dental Hygiene, Yeoju Institute of Technology, Republic Of Korea.
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Fouladseresht H, Ghamar Talepoor A, Eskandari N, Norouzian M, Ghezelbash B, Beyranvand MR, Nejadghaderi SA, Carson-Chahhoud K, Kolahi AA, Safiri S. Potential Immune Indicators for Predicting the Prognosis of COVID-19 and Trauma: Similarities and Disparities. Front Immunol 2022; 12:785946. [PMID: 35126355 PMCID: PMC8815083 DOI: 10.3389/fimmu.2021.785946] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Accepted: 12/17/2021] [Indexed: 12/15/2022] Open
Abstract
Although cellular and molecular mediators of the immune system have the potential to be prognostic indicators of disease outcomes, temporal interference between diseases might affect the immune mediators, and make them difficult to predict disease complications. Today one of the most important challenges is predicting the prognosis of COVID-19 in the context of other inflammatory diseases such as traumatic injuries. Many diseases with inflammatory properties are usually polyphasic and the kinetics of inflammatory mediators in various inflammatory diseases might be different. To find the most appropriate evaluation time of immune mediators to accurately predict COVID-19 prognosis in the trauma environment, researchers must investigate and compare cellular and molecular alterations based on their kinetics after the start of COVID-19 symptoms and traumatic injuries. The current review aimed to investigate the similarities and differences of common inflammatory mediators (C-reactive protein, procalcitonin, ferritin, and serum amyloid A), cytokine/chemokine levels (IFNs, IL-1, IL-6, TNF-α, IL-10, and IL-4), and immune cell subtypes (neutrophil, monocyte, Th1, Th2, Th17, Treg and CTL) based on the kinetics between patients with COVID-19 and trauma. The mediators may help us to accurately predict the severity of COVID-19 complications and follow up subsequent clinical interventions. These findings could potentially help in a better understanding of COVID-19 and trauma pathogenesis.
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Affiliation(s)
- Hamed Fouladseresht
- Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Atefe Ghamar Talepoor
- Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Nahid Eskandari
- Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Marzieh Norouzian
- Department of Laboratory Sciences, School of Allied Medical Sciences, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Behrooz Ghezelbash
- Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad Reza Beyranvand
- Social Determinants of Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyed Aria Nejadghaderi
- Research Center for Integrative Medicine in Aging, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
- Systematic Review and Meta-Analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Kristin Carson-Chahhoud
- Australian Centre for Precision Health, Allied Health and Human Performance, University of South Australia, Adelaide, SA, Australia
- School of Medicine, The University of Adelaide, Adelaide, SA, Australia
| | - Ali-Asghar Kolahi
- Social Determinants of Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Saeid Safiri
- Social Determinants of Health Research Center, Department of Community Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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AKÇA HŞ, ALGIN A, ÖZDEMİR S, KOÇKARA E, EROĞLU SE. Comparison of the efficacy of trauma scores in predicting prognosis and hospitalization. CUKUROVA MEDICAL JOURNAL 2021. [DOI: 10.17826/cumj.982675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
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20
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Webb EK, Weis CN, Huggins AA, Fitzgerald JM, Bennett K, Bird CM, Parisi EA, Kallenbach M, Miskovich T, Krukowski J, deRoon-Cassini TA, Larson CL. Neural impact of neighborhood socioeconomic disadvantage in traumatically injured adults. Neurobiol Stress 2021; 15:100385. [PMID: 34471656 PMCID: PMC8390770 DOI: 10.1016/j.ynstr.2021.100385] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 08/17/2021] [Accepted: 08/20/2021] [Indexed: 11/30/2022] Open
Abstract
Nearly 14 percent of Americans live in a socioeconomically disadvantaged neighborhood. Lower individual socioeconomic position (iSEP) has been linked to increased exposure to trauma and stress, as well as to alterations in brain structure and function; however, the neural effects of neighborhood SEP (nSEP) factors, such as neighborhood disadvantage, are unclear. Using a multi-modal approach with participants who recently experienced a traumatic injury (N = 185), we investigated the impact of neighborhood disadvantage, acute post-traumatic stress symptoms, and iSEP on brain structure and functional connectivity at rest. After controlling for iSEP, demographic variables, and acute PTSD symptoms, nSEP was associated with decreased volume and alterations of resting-state functional connectivity in structures implicated in affective processing, including the insula, ventromedial prefrontal cortex, amygdala, and hippocampus. Even in individuals who have recently experienced a traumatic injury, and after accounting for iSEP, the impact of living in a disadvantaged neighborhood is apparent, particularly in brain regions critical for experiencing and regulating emotion. These results should inform future research investigating how various levels of socioeconomic circumstances may impact recovery after a traumatic injury as well as policies and community-developed interventions aimed at reducing the impact of socioeconomic stressors.
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Affiliation(s)
- E. Kate Webb
- University of Wisconsin-Milwaukee, Department of Psychology, Milwaukee, WI, USA
| | - Carissa N. Weis
- University of Wisconsin-Milwaukee, Department of Psychology, Milwaukee, WI, USA
| | - Ashley A. Huggins
- University of Wisconsin-Milwaukee, Department of Psychology, Milwaukee, WI, USA
| | | | | | - Claire M. Bird
- Marquette University, Department of Psychology, Milwaukee, WI, USA
| | - Elizabeth A. Parisi
- University of Wisconsin-Milwaukee, Department of Psychology, Milwaukee, WI, USA
| | - Maddy Kallenbach
- University of Wisconsin-Milwaukee, Department of Psychology, Milwaukee, WI, USA
| | - Tara Miskovich
- VA Northern California Healthcare System, Martinez, CA, USA
| | | | - Terri A. deRoon-Cassini
- Medical College of Wisconsin, Department of Surgery, Division of Trauma & Acute Care Surgery, Milwaukee, WI, USA
| | - Christine L. Larson
- University of Wisconsin-Milwaukee, Department of Psychology, Milwaukee, WI, USA
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21
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Javdani M, Barzegar A, Khosravian P, Hashemnia M. Evaluation of Inflammatory Response Due to Use of Controlled Release Drug Delivery System of Chitosan Hydrogel Loaded with Buprenorphine and Ketorolac in Rat with Experimental Proximal Tibial Epiphysis Defect. J INVEST SURG 2021; 35:996-1011. [PMID: 34666588 DOI: 10.1080/08941939.2021.1989728] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Aims:A controlled release drug delivery system loaded with buprenorphine and ketorolac was synthesized and used in the experimental model of bone defect and while evaluating the inflammatory response, the repair process in the defects was investigated.Materials and methods:To determine the effectiveness of the synthesized the mentioned systems, 5 groups were defined; the control group, the chitosan hydrogel receiving group (chitosan group), the ketorolac-loaded chitosan hydrogel group (ketorolac group), the buprenorphine-loaded chitosan hydrogel receiving group (buprenorphine group), and the chitosan hydrogel-loading group loaded with a combination of ketorolac and buprenorphine (ketorolac-buprenorphine group).Results:The results showed that the population of leukocytes (tWBC) and neutrophils on different days of the study in the control group compared to other groups had a significant increase (P < 0.05) while on day 7 of the study in the ketorolac group these parameters decreased significantly compared to other groups (P < 0.05). While examining the histological changes in the experimental defect created in the proximal tibia of rats at different times, some inflammatory indices such as total and differential leukocyte population, plasma concentrations of TNF-α and IL-6 were compared in different groups (P < 0.05). The various evaluated data showed that among the different groups, in the control and ketorolac-buprenorphine groups, there was the lowest and highest control of inflammatory response and bone repair, respectively.Conclusion:In the ketorolac group due to the impact of ketorolac on leukocyte populations the best bone healing can be expected among the different treatment groups.
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Affiliation(s)
- Moosa Javdani
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahrekord University, Shahrekord, Iran
| | - Abolfazl Barzegar
- Veterinary Medicine Student, Faculty of Veterinary Medicine, Shahrekord University, Shahrekord, Iran
| | - Pegah Khosravian
- Medical Plant Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Mohammad Hashemnia
- Department of pathobiology, Faculty of Veterinary Medicine, Razi University, Kermanshah, Iran
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22
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Adeyemi K, Balogun M, Babalola O, Salihu T, Sanusi L, Ore Z, Olagoke F. Dietary supplementation of Solanum aethiopicum and Solanecio biafrae leaves alters stress and immune responses, antioxidant status, and meat quality in broilers raised in a hot-dry environment. Br Poult Sci 2021; 63:82-90. [PMID: 34402340 DOI: 10.1080/00071668.2021.1963675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
1. This study investigated the influence of dietary supplementation of Solanum aethiopicum and Solanecio biafrae leaves, which have nutraceutical properties, on stress response, cytokine expression, antioxidant status, blood chemistry, abdominal fat and meat quality in broilers reared in a hot, dry environment.2. One day old, Ross 308 chicks (n = 350) were randomly allotted to basal diets containing either no supplement (D1); 2.5 g/kg Solanum aethiopicum leaf (SAL; D2); 5 g/kg SAL (D3); 2.5 g/kg Solanecio biafrae leaf (SBL; D4); or 5 g/kg SBL (D5) for 42 d. Birds were reared at 34 ± 2°C and 40-50% relative humidity for 6 h/d from 22-42 d. Each dietary group was replicated in seven pens containing 10 chicks.3. In the period 1-21 d, body weight gain, feed efficiency and feed intake were not influenced by diet. At 22-42 and 1-42 d, birds supplemented with SAL and SBL had higher (P < 0.05) body weight gain and feed efficiency than the D1 birds. Cloaca temperature, carcase cuts and relative organ weight did not differ between diets. The D3 birds had higher (P < 0.05) erythrocytes and haemoglobin compared with other birds. Dietary supplements reduced (P < 0.05) mortality, abdominal fat, serum total cholesterol, corticosterone, glucose and blood aspartate aminotransferase levels.4. The treatments up-regulated (P < 0.05) splenic intelukin-10, and down-regulated (P < 0.05) tumour necrosis factor-α and interleukin-1β genes. A dose-dependent improvement (P < 0.05) in antioxidant enzyme activities and total antioxidant capacity of serum and breast muscle were found in the supplemented birds. The breast meat of the supplemented birds had lower (P < 0.05) carbonyl and malondialdehyde contents, and higher (P < 0.05) water holding capacity and redness compared with the non-supplemented meat.5. These results illustrated that supplementation with either 5 g/kg SAL or 5 g/kg SBL attenuated the deleterious effects of heat stress in broiler chickens.
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Affiliation(s)
- K Adeyemi
- Animal Production, University of Ilorin, Ilorin, Nigeria
| | - M Balogun
- Animal Production, University of Ilorin, Ilorin, Nigeria
| | - O Babalola
- Animal Production, University of Ilorin, Ilorin, Nigeria
| | - T Salihu
- Animal Production, University of Ilorin, Ilorin, Nigeria
| | - L Sanusi
- Animal Production, University of Ilorin, Ilorin, Nigeria
| | - Z Ore
- Animal Production, University of Ilorin, Ilorin, Nigeria
| | - F Olagoke
- Animal Production, University of Ilorin, Ilorin, Nigeria
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23
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Finlay LDB, Conway Morris A, Deane AM, Wood AJT. Neutrophil kinetics and function after major trauma: A systematic review. World J Crit Care Med 2021; 10:260-277. [PMID: 34616661 PMCID: PMC8462018 DOI: 10.5492/wjccm.v10.i5.260] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 05/18/2021] [Accepted: 07/27/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Immune dysfunction following major traumatic injury is complex and strongly associated with significant morbidity and mortality through the development of multiple organ dysfunction syndrome (MODS), persistent inflammation, immunosuppression, and catabolism syndrome and sepsis. Neutrophils are thought to be a pivotal mediator in the development of immune dysfunction.
AIM To provide a review with a systematic approach of the recent literature describing neutrophil kinetics and functional changes after major trauma in humans and discuss hypotheses as to the mechanisms of the observed neutrophil dysfunction in this setting.
METHODS Medline, Embase and PubMed were searched on January 15, 2021. Papers were screened by two reviewers and those included had their reference list hand searched for additional papers of interest. Inclusion criteria were adults > 18 years old, with an injury severity score > 12 requiring admission to an intensive care unit. Papers that analysed major trauma patients as a subgroup were included.
RESULTS Of 107 papers screened, 48 were included in the review. Data were heterogeneous and most studies had a moderate to significant risk of bias owing to their observational nature and small sample sizes. Key findings included a persistently elevated neutrophil count, stereotyped alterations in cell-surface markers of activation, and the elaboration of heterogeneous and immunosuppressive populations of cells in the circulation. Some of these changes correlate with clinical outcomes such as MODS and secondary infection. Neutrophil phenotype remains a promising avenue for the development of predictive markers for immune dysfunction.
CONCLUSION Understanding of neutrophil phenotypes after traumatic injury is expanding. A greater emphasis on incorporating functional and clinically significant markers, greater uniformity in study design and assessment of extravasated neutrophils may facilitate risk stratification in patients affected by major trauma.
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Affiliation(s)
- Liam DB Finlay
- Melbourne Medical School, University of Melbourne, Melbourne 3052, Victoria, Australia
| | - Andrew Conway Morris
- Department of Medicine, University of Cambridge, Cambridge 01223, United Kingdom
| | - Adam M Deane
- Centre for Integrated Critical Care, University of Melbourne, Parkville 3052, Victoria, Australia
- Intensive Care Unit, Royal Melbourne Hospital, Parkville 3052, Victoria, Australia
| | - Alexander JT Wood
- Centre for Integrated Critical Care, University of Melbourne, Parkville 3052, Victoria, Australia
- Intensive Care Unit, Royal Melbourne Hospital, Parkville 3052, Victoria, Australia
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24
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Mannes M, Schmidt CQ, Nilsson B, Ekdahl KN, Huber-Lang M. Complement as driver of systemic inflammation and organ failure in trauma, burn, and sepsis. Semin Immunopathol 2021; 43:773-788. [PMID: 34191093 PMCID: PMC8243057 DOI: 10.1007/s00281-021-00872-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Accepted: 05/23/2021] [Indexed: 02/08/2023]
Abstract
Complement is one of the most ancient defense systems. It gets strongly activated immediately after acute injuries like trauma, burn, or sepsis and helps to initiate regeneration. However, uncontrolled complement activation contributes to disease progression instead of supporting healing. Such effects are perceptible not only at the site of injury but also systemically, leading to systemic activation of other intravascular cascade systems eventually causing dysfunction of several vital organs. Understanding the complement pathomechanism and its interplay with other systems is a strict requirement for exploring novel therapeutic intervention routes. Ex vivo models exploring the cross-talk with other systems are rather limited, which complicates the determination of the exact pathophysiological roles that complement has in trauma, burn, and sepsis. Literature reporting on these three conditions is often controversial regarding the importance, distribution, and temporal occurrence of complement activation products further hampering the deduction of defined pathophysiological pathways driven by complement. Nevertheless, many in vitro experiments and animal models have shown beneficial effects of complement inhibition at different levels of the cascade. In the future, not only inhibition but also a complement reconstitution therapy should be considered in prospective studies to expedite how meaningful complement-targeted interventions need to be tailored to prevent complement augmented multi-organ failure after trauma, burn, and sepsis. This review summarizes clinically relevant studies investigating the role of complement in the acute diseases trauma, burn, and sepsis with important implications for clinical translation.
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Affiliation(s)
- Marco Mannes
- Institute of Clinical and Experimental Trauma-Immunology, University Hospital of Ulm, Helmholtzstr. 8/2, 89081, Ulm, Germany
| | - Christoph Q Schmidt
- Institute of Pharmacology of Natural Products and Clinical Pharmacology, Ulm University, Ulm, Germany
| | - Bo Nilsson
- Department of Immunology, Genetics and Pathology (IGP), Rudbeck Laboratory C5:3, Uppsala University, Uppsala, Sweden
| | - Kristina N Ekdahl
- Department of Immunology, Genetics and Pathology (IGP), Rudbeck Laboratory C5:3, Uppsala University, Uppsala, Sweden.,Linnaeus Center of Biomaterials Chemistry, Linnaeus University, Kalmar, Sweden
| | - Markus Huber-Lang
- Institute of Clinical and Experimental Trauma-Immunology, University Hospital of Ulm, Helmholtzstr. 8/2, 89081, Ulm, Germany.
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Teuben MPJ, Hollman A, Blokhuis T, Pfeifer R, Spijkerman R, Teuber H, Pape HC, Leenen LPH. Splenectomy is associated with altered leukocyte kinetics after severe trauma. Eur J Med Res 2021; 26:26. [PMID: 33722293 PMCID: PMC7958390 DOI: 10.1186/s40001-021-00497-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Accepted: 03/04/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Inadequate activation of the innate immune system after trauma can lead to severe complications such as Acute Respiratory Distress Syndrome and Multiple Organ Dysfunction Syndrome. The spleen is thought to modulate the cellular immune system. Furthermore, splenectomy is associated with improved outcome in severely injured trauma patients. We hypothesized that a splenectomy alters the cellular immune response in polytrauma. METHODS All adult patients with an ISS ≥ 16 and suffering from splenic or hepatic injuries were selected from our prospective trauma database. Absolute leukocyte numbers in peripheral blood were measured. White blood cell kinetics during the first 14 days were compared between splenectomized patients, patients treated surgically for liver trauma and nonoperatively treated individuals. RESULTS A total of 129 patients with a mean ISS of 29 were included. Admission characteristics and leukocyte numbers were similar in all groups, except for slightly impaired hemodynamic status in patients with operatively treated liver injuries. On admission, leukocytosis occurred in all groups. During the first 24 h, leukopenia developed gradually, although significantly faster in the operatively treated patients. Thereafter, leukocyte levels normalized in all nonoperatively treated cases whereas leukocytosis persisted in operatively treated patients. This effect was significantly more prominent in splenectomized patients than all other conditions. CONCLUSIONS This study demonstrates that surgery for intra-abdominal injuries is associated with an early drop in leucocyte numbers in peripheral blood. Moreover, splenectomy in severely injured patients is associated with an altered cellular immune response reflected by a persistent state of prominent leukocytosis after trauma.
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Affiliation(s)
- Michel Paul Johan Teuben
- Department of Trauma, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. .,Department of Traumatology, University Hospital Zurich, Raemistrasse 100, 8006, Zurich, Switzerland.
| | - Arne Hollman
- Department of Trauma, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - Taco Blokhuis
- Department of Surgery, Maastricht University Medical Centre, P. Debyelaan 25, 6229 HX, Maastricht, The Netherlands
| | - Roman Pfeifer
- Department of Traumatology, University Hospital Zurich, Raemistrasse 100, 8006, Zurich, Switzerland
| | - Roy Spijkerman
- Department of Trauma, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - Henrik Teuber
- Department of Traumatology, University Hospital Zurich, Raemistrasse 100, 8006, Zurich, Switzerland
| | - Hans-Christoph Pape
- Department of Traumatology, University Hospital Zurich, Raemistrasse 100, 8006, Zurich, Switzerland
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Goel A, Ncho CM, Choi YH. Regulation of gene expression in chickens by heat stress. J Anim Sci Biotechnol 2021; 12:11. [PMID: 33431031 PMCID: PMC7798204 DOI: 10.1186/s40104-020-00523-5] [Citation(s) in RCA: 72] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Accepted: 11/16/2020] [Indexed: 01/10/2023] Open
Abstract
Abstract High ambient temperatures are a critical challenge in the poultry industry which is a key producer of the animal-based food. To evaluate heat stress levels, various parameters have been used, including growth rates, blood metabolites, and hormones. The most recent advances have explored expression profiling of genes that may play vital roles under stress. A high ambient temperature adversely affects nutrient uptake and is known to modulate the expression of genes encoding for sodium-dependent glucose transporters, glucose transporters, excitatory amino acid transporters, and fatty acid-binding proteins which are responsible for the absorption of macronutrients in the intestine. Various defensive activities are stimulated to protect the cell of different tissues from the heat-generated stress, including expression of early stress response genes coding for heat shock protein (HSP), c-FOS like protein, brain-derived neurotrophic factor (BDNF), and neuronal nitric oxide synthase (nNOS); antioxidant enzyme genes such as superoxide dismutase (SOD), catalase (CAT), and nicotinamide adenine dinucleotide phosphate oxidase (NOX4); and immune-related genes such as cytokines and toll-like receptors (TLRs). The potential role of HSPs in protecting the cell from stress and their presence in several tissues make them suitable markers to be evaluated under heat stress. BDNF and c-FOS genes expressed in the hypothalamus help cells to adapt to an adverse environment. Heat causes damage to the cell by generating reactive oxygen species (ROS). The NOX4 gene is the inducer of ROS under heat stress, which is in turns controlled by antioxidant enzymes such as SOD and CAT. TLRs are responsible for protecting against pathogenic attacks arising from enhanced membrane permeability, and cytokines help in controlling the pathogen and maintaining homeostasis. Thus, the evaluation of nutrient transporters and defense mechanisms using the latest molecular biology tools has made it possible to shed light on the complex cellular mechanism of heat-stressed chickens. As the impacts of heat stress on the above-mentioned aspects are beyond the extent to which the reduced growth performance could be explained, heat stress has more specific effects on the regulation of these genes than previously thought. Graphical abstract Effect of heat exposure on the nutrient transporters, antioxidants, and immune inflammation in chickens. Most of the nutrient transporters were suppressed under heat stress. Increase in the production of reactive oxygen species resulted in enhanced production of antioxidant enzymes. Expression of various proinflammatory cytokines and toll-like receptors were enhanced due to heat stress in chicken.
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Affiliation(s)
- Akshat Goel
- Department of Animal Science, Gyeongsang National University, Jinju, 52828, Republic of Korea.,Division of Applied Life Sciences (BK21 Plus Program), Gyeongsang National University, Jinju, 52828, Republic of Korea
| | - Chris Major Ncho
- Department of Animal Science, Gyeongsang National University, Jinju, 52828, Republic of Korea
| | - Yang-Ho Choi
- Department of Animal Science, Gyeongsang National University, Jinju, 52828, Republic of Korea. .,Division of Applied Life Sciences (BK21 Plus Program), Gyeongsang National University, Jinju, 52828, Republic of Korea. .,Institute of Agriculture and Life Sciences, Gyeongsang National University, Jinju, 52828, Republic of Korea.
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27
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Relja B, Land WG. Damage-associated molecular patterns in trauma. Eur J Trauma Emerg Surg 2020; 46:751-775. [PMID: 31612270 PMCID: PMC7427761 DOI: 10.1007/s00068-019-01235-w] [Citation(s) in RCA: 100] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Accepted: 09/27/2019] [Indexed: 12/13/2022]
Abstract
In 1994, the "danger model" argued that adaptive immune responses are driven rather by molecules released upon tissue damage than by the recognition of "strange" molecules. Thus, an alternative to the "self versus non-self recognition model" has been provided. The model, which suggests that the immune system discriminates dangerous from safe molecules, has established the basis for the future designation of damage-associated molecular patterns (DAMPs), a term that was coined by Walter G. Land, Seong, and Matzinger. The pathological importance of DAMPs is barely somewhere else evident as in the posttraumatic or post-surgical inflammation and regeneration. Since DAMPs have been identified to trigger specific immune responses and inflammation, which is not necessarily detrimental but also regenerative, it still remains difficult to describe their "friend or foe" role in the posttraumatic immunogenicity and healing process. DAMPs can be used as biomarkers to indicate and/or to monitor a disease or injury severity, but they also may serve as clinically applicable parameters for optimized indication of the timing for, i.e., secondary surgeries. While experimental studies allow the detection of these biomarkers on different levels including cellular, tissue, and circulatory milieu, this is not always easily transferable to the human situation. Thus, in this review, we focus on the recent literature dealing with the pathophysiological importance of DAMPs after traumatic injury. Since dysregulated inflammation in traumatized patients always implies disturbed resolution of inflammation, so-called model of suppressing/inhibiting inducible DAMPs (SAMPs) will be very briefly introduced. Thus, an update on this topic in the field of trauma will be provided.
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Affiliation(s)
- Borna Relja
- Experimental Radiology, Department of Radiology and Nuclear Medicine, Otto von Guericke University Magdeburg, Magdeburg, Germany.
- Department of Trauma, Hand and Reconstructive Surgery, University Hospital Frankfurt, Goethe University Frankfurt am Main, 60590, Frankfurt, Germany.
| | - Walter Gottlieb Land
- Molecular ImmunoRheumatology, INSERM UMR_S1109, Laboratory of Excellence Transplantex, University of Strasbourg, Strasbourg, France
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Zhang S, Ou J, Luo Z, Kim IH. Effect of dietary β-1,3-glucan supplementation and heat stress on growth performance, nutrient digestibility, meat quality, organ weight, ileum microbiota, and immunity in broilers. Poult Sci 2020; 99:4969-4977. [PMID: 32988533 PMCID: PMC7598134 DOI: 10.1016/j.psj.2020.06.036] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Revised: 06/06/2020] [Accepted: 06/16/2020] [Indexed: 01/15/2023] Open
Abstract
The objective of this study was to determine the effect of dietary β-1,3-glucan supplementation and heat stress (HS) on growth performance, nutrient digestibility, meat quality, organ weight, ileum microbiota, and immunity in broiler. A total of 1,440 1-day-old Ross 308 male chicks with an average initial BW of 43.06 ± 1.94 g were sorted into 6 (2 × 3) treatments, 14 replications per treatment. This trail included 2 factors: the dosage of β-1,3-glucan (0, 100 g/T, and 200 g/T) and feeding condition (HS and normal). During the whole trial, significant impacts were observed in BW gain, feed intake，feed conversion rate, and the digestibility of DM and energy between normal treatments and HS treatments (P < 0.05). From day 21 to 35, HS-challenged birds fed the diet with 200 g/T β-1,3-glucan had a lower feed conversion rate than those fed the diet with 0 or 100 g/T β-1,3-glucan (P < 0.05). Moreover, the HS-exposed birds that fed the diet with β-1,3-glucan indicated a greater energy digestibility than those fed the nontreatment diet (P < 0.05). Besides, β-1,3-glucan supplementation could elevate meat pH of all birds and decrease cooking loss significantly of HS-exposed birds (P < 0.05). The HS birds fed the β-1,3-glucan diet obtained a reduced amount of Escherichia coli in the ileum than those fed the nontreatment diet (P < 0.05). Besides, β-1,3-glucan supplementation lowered the level of tumor necrosis factor-α in HS-exposed birds significantly (P < 0.05). These results indicated 100 and 200 g/T β-1,3-glucan supplementation, under HS condition or not, can increase growth performance without a negative response on immunity. Under HS condition, the addition of β-1,3-glucan at dosage from 100 to 200 g/T in the diet can increase energy digestibility, decrease cooking loss, reduce E. coli mount in the ileum, and the tumor necrosis factor-α concentration.
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Affiliation(s)
- Song Zhang
- Department of Animal Resource & Science, Dankook University, Cheonan, Choongnam 330-714, South Korea; Department of Animal Intestinal Health, Kemin Industries (China)Co., Zhuhai 519040, P. R. China
| | - Jiwen Ou
- Department of Animal Intestinal Health, Kemin Industries (China)Co., Zhuhai 519040, P. R. China
| | - Zheng Luo
- Department of Animal Intestinal Health, Kemin Industries (China)Co., Zhuhai 519040, P. R. China
| | - In Ho Kim
- Department of Animal Resource & Science, Dankook University, Cheonan, Choongnam 330-714, South Korea.
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Zhu H, Wang X, Wang X, Liu B, Yuan Y, Zuo X. Curcumin attenuates inflammation and cell apoptosis through regulating NF-κB and JAK2/STAT3 signaling pathway against acute kidney injury. Cell Cycle 2020; 19:1941-1951. [PMID: 32615888 DOI: 10.1080/15384101.2020.1784599] [Citation(s) in RCA: 59] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Curcumin alleviates septic acute kidney injury (SAKI); however, the underlying mechanism remained unclear. To explore this, SAKI cell model and mice model were conducted by using LPS and cecal ligation and puncture (CLP), respectively. Cell counting kit-8 (CCK-8) and enzyme-linked immunosorbent assay (ELISA) assays indicated that LPS reduced the viability, but upregulated the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6, whereas Curcumin pretreatment had no effect on viability, but reduced the levels of TNF-α and IL-6. Further assays showed that Curcumin partly attenuated the LPS-induced injury as the viability was enhanced, TNF-α and IL-6 expressions and cell apoptosis rates were reduced. Western blot analysis indicated that Janus kinase (JAK) 2/signal transducer and activator of transcription (STAT) 3, p-65-NF-κB and cell apoptosis pathways were activated by LPS but suppressed by Curcumin. Mice SAKI model further indicated that the serum Cystatin C (Cys-C), creatinine (Cr) and blood urea nitrogen (BUN) were increased within 24 h of model construction while those indicators were decreased at 48 h. Pretreated with Curcumin, NF-κB inhibitor (PDTC) or JAK2 inhibitor (AG-490) could weaken the renal histological injury and the increased serum Cys-C, Cr and BUN, IL-6 and TNF-α induced by CLP. Moreover, PDTC, AG-490 and Curcumin all significantly reversed the previously increased expressions of p-JAK2/STAT3, p-p65 and proapoptotic proteins in the mice with AKI. The present study revealed that Curcumin attenuated SAKI through inhibiting NF-κB and JAK2/STAT3 signaling pathways, and proposed that Curcumin could be a potential therapeutic agent for treating SAKI.
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Affiliation(s)
- Hongkun Zhu
- Department of Critical Care Medicine, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine , Nanjing, China
| | - Xinjun Wang
- Second Clinical Medical College, Nanjing University of Chinese Medicine , Nanjing, China
| | - Xiaoxiao Wang
- GCP Center, The First Affiliated Hospital of Nanjing University of Chinese Medicine , Nanjing, China
| | - Bei Liu
- First Clinical Medical College, Nanjing University of Chinese Medicine , Nanjing, China
| | - Yizhen Yuan
- First Clinical Medical College, Nanjing University of Chinese Medicine , Nanjing, China
| | - Xiangrong Zuo
- Department of Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University , Nanjing, China
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Tornadic Shear Stress Induces a Transient, Calcineurin-Dependent Hypervirulent Phenotype in Mucorales Molds. mBio 2020; 11:mBio.01414-20. [PMID: 32605990 PMCID: PMC7327176 DOI: 10.1128/mbio.01414-20] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
Trauma-related necrotizing myocutaneous mucormycosis (NMM) has a high morbidity and mortality in victims of combat-related injuries, geometeorological disasters, and severe burns. Inspired by the observation that several recent clusters of NMM have been associated with extreme mechanical forces (e.g., during tornados), we studied the impact of mechanical stress on Mucoralean biology and virulence in a Drosophila melanogaster infection model. In contrast to other experimental procedures to exert mechanical stress, tornadic shear challenge (TSC) by magnetic stirring induced a hypervirulent phenotype in several clinically relevant Mucorales species but not in Aspergillus or Fusarium Whereas fungal growth rates, morphogenesis, and susceptibility to noxious environments or phagocytes were not altered by TSC, soluble factors released in the supernatant of shear-challenged R. arrhizus spores rendered static spores hypervirulent. Consistent with a rapid decay of TSC-induced hypervirulence, minimal transcriptional changes were revealed by comparative RNA sequencing analysis of static and shear-challenged Rhizopus arrhizus However, inhibition of the calcineurin/heat shock protein 90 (hsp90) stress response circuitry by cyclosporine and tanespimycin abrogated the increased pathogenicity of R. arrhizus spores following TSC. Similarly, calcineurin loss-of-function mutants of Mucor circinelloides displayed no increased virulence capacity in flies after undergoing TSC. Collectively, these results establish that TSC induces hypervirulence specifically in Mucorales and point out the calcineurin/hsp90 pathway as a key orchestrator of this phenotype. Our findings invite future studies of topical calcineurin inhibitor treatment of wounds as an adjunct mitigation strategy for NMM following high-energy trauma.IMPORTANCE Given the limited efficacy of current medical treatments in trauma-related necrotizing mucormycosis, there is a dire need to better understand the Mucoralean pathophysiology in order to develop novel strategies to counteract fungal tissue invasion following severe trauma. Here, we describe that tornadic shear stress challenge transiently induces a hypervirulent phenotype in various pathogenic Mucorales species but not in other molds known to cause wound infections. Pharmacological and genetic inhibition of calcineurin signaling abrogated hypervirulence in shear stress-challenged Mucorales, encouraging further evaluation of (topical) calcineurin inhibitors to improve therapeutic outcomes of NMM after combat-related blast injuries or violent storms.
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Abstract
INTRODUCTION Organ dysfunction remains a major cause of morbidity after trauma. The development of organ dysfunction is determined by the inflammatory response, in which neutrophils are important effector cells. A femoral fracture particularly predisposes for the development of organ dysfunction. This study investigated the chronologic relation between neutrophil characteristics and organ dysfunction in trauma patients with a femoral fracture. METHODS Patients with a femoral fracture presenting at the University Medical Center Utrecht between 2007 and 2013 were included. Data of neutrophil characteristics from standard hematological analyzers were recorded on a daily basis until the 28th day of hospital stay or until discharge. Generalized Estimating Equations were used to compare outcome groups. RESULTS In total 157 patients were analyzed, of whom 81 had polytrauma and 76 monotrauma. Overall mortality within 90 days was 6.4% (n = 10). Eleven patients (7.0%) developed organ dysfunction. In patients who developed organ dysfunction a significant increase in neutrophil count (P = 0.024), a significant increase in neutrophil cell size (P = 0.026), a significant increase in neutrophil complexity (P < 0.004), and a significant decrease in neutrophil lobularity (P < 0.001) were seen after trauma. The rise in neutrophil cell size preceded the clinical manifestation of organ dysfunction in every patient. CONCLUSION Patients who develop organ dysfunction postinjury show changes in neutrophil characteristics before organ dysfunction becomes clinically evident. These findings regarding post-traumatic organ dysfunction may contribute to the development of new prognostic tools for immune-mediated complications in trauma patients. LEVEL OF EVIDENCE Level II, etiologic study.
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Hesselink L, Spijkerman R, de Fraiture E, Bongers S, Van Wessem KJP, Vrisekoop N, Koenderman L, Leenen LPH, Hietbrink F. New automated analysis to monitor neutrophil function point-of-care in the intensive care unit after trauma. Intensive Care Med Exp 2020; 8:12. [PMID: 32172430 PMCID: PMC7072076 DOI: 10.1186/s40635-020-0299-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2019] [Accepted: 02/26/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Patients often develop infectious complications after severe trauma. No biomarkers exist that enable early identification of patients who are at risk. Neutrophils are important immune cells that combat these infections by phagocytosis and killing of pathogens. Analysis of neutrophil function used to be laborious and was therefore not applicable in routine diagnostics. Hence, we developed a quick and point-of-care method to assess a critical part of neutrophil function, neutrophil phagosomal acidification. The aim of this study was to investigate whether this method was able to analyze neutrophil functionality in severely injured patients and whether a relation with the development of infectious complications was present. RESULTS Fifteen severely injured patients (median ISS of 33) were included, of whom 6 developed an infection between day 4 and day 9 after trauma. The injury severity score did not significantly differ between patients who developed an infection and patients who did not (p = 0.529). Patients who developed an infection showed increased acidification immediately after trauma (p = 0.006) and after 3 days (p = 0.026) and a decrease in the days thereafter to levels in the lower normal range. In contrast, patients who did not develop infectious complications showed high-normal acidification within the first days and increased tasset to identify patients at risk for infections after trauma and to monitor the inflammatory state of these trauma patients. CONCLUSION Neutrophil function can be measured in the ICU setting by rapid point-of-care analysis of phagosomal acidification. This analysis differed between trauma patients who developed infectious complications and trauma patients who did not. Therefore, this assay might prove a valuable asset to identify patients at risk for infections after trauma and to monitor the inflammatory state of these trauma patients. TRIAL REGISTRATION Central Committee on Research Involving Human Subjects, NL43279.041.13. Registered 14 February 2014. https://www.toetsingonline.nl/to/ccmo_search.nsf/Searchform?OpenForm.
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Affiliation(s)
- Lillian Hesselink
- Department of Trauma Surgery, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, the Netherlands.
- Center for Translational Immunology, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, the Netherlands.
- Department of Trauma Surgery, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, the Netherlands.
| | - Roy Spijkerman
- Department of Trauma Surgery, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, the Netherlands
- Center for Translational Immunology, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, the Netherlands
| | - Emma de Fraiture
- Department of Trauma Surgery, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, the Netherlands
- Center for Translational Immunology, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, the Netherlands
| | - Suzanne Bongers
- Department of Trauma Surgery, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, the Netherlands
- Center for Translational Immunology, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, the Netherlands
| | - Karlijn J P Van Wessem
- Department of Trauma Surgery, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, the Netherlands
| | - Nienke Vrisekoop
- Center for Translational Immunology, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, the Netherlands
| | - Leo Koenderman
- Department of Respiratory Medicine, Wilhelmina Children's Hospital, Lundlaan 6, 3584, EA, Utrecht, the Netherlands
- Center for Translational Immunology, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, the Netherlands
| | - Luke P H Leenen
- Department of Trauma Surgery, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, the Netherlands
| | - Falco Hietbrink
- Department of Trauma Surgery, University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, the Netherlands
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Mörs K, Wagner N, Sturm R, Störmann P, Vollrath JT, Marzi I, Relja B. Enhanced pro-inflammatory response and higher mortality rates in geriatric trauma patients. Eur J Trauma Emerg Surg 2019; 47:1065-1072. [PMID: 31875239 DOI: 10.1007/s00068-019-01284-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Accepted: 12/05/2019] [Indexed: 11/30/2022]
Abstract
BACKGROUND Age has been associated with increased morbidity and mortality after traumatic injury. Disregarding trauma-related factors, this may be caused by the diminished ability to cope with stressors due to limited reserve, the so-called frailty. Inflammation is assumed to promote frailty, and thus, pro-inflammatory markers may constitute as being predictive factors in geriatric trauma patients (TP). Here, we analyzed the influence of age on systemic inflammatory markers and outcome parameters in TP. PATIENTS AND METHODS 204 TP with injury severity score (ISS) ≥ 16 were included and grouped to younger vs. geriatric, defining an age of 65 as cut-off. ISS, vital signs, physiological parameters, stay at the intensive-care unit (ICU) or in-hospital, and outcome parameters were analyzed. Systemic fibrinogen, interleukin (IL)-6, and IL-10 levels were determined upon admission. A p value < 0.05 was considered statistically significant. RESULTS 43 geriatric and 161 younger TP were included. ISS (24.19 ± 9.59 vs. 26.93 ± 9.68) was comparable between both groups. Abbreviated Injury Scale (AIS) ≥ 3 of head trauma was more prevalent in geriatric TP (74.42 vs. 64.59%). In both groups, there were significantly more male than female patients; however, this disparity was significantly more distinct in younger TP. Geriatric group showed significantly lower shock indices, higher fibrinogen, and lower IL-10 levels (all p < 0.05). A significant spearman´s rank correlation with age was found for fibrinogen (positive correlation, r = 0.364, p < 0.05), and for IL-10 (negative correlation, r = - 0.168, p < 0.05). In-hospital mortality was significantly increased in geriatric TP. CONCLUSIONS An enhanced inflammatory response is associated with higher mortality rates in geriatric trauma patients.
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Affiliation(s)
- Katharina Mörs
- Department of Trauma, Hand and Reconstructive Surgery, University Hospital Frankfurt, Goethe University, 60590, Frankfurt, Germany.
| | - Nils Wagner
- Department of Trauma, Hand and Reconstructive Surgery, University Hospital Frankfurt, Goethe University, 60590, Frankfurt, Germany
| | - Ramona Sturm
- Department of Trauma, Hand and Reconstructive Surgery, University Hospital Frankfurt, Goethe University, 60590, Frankfurt, Germany
| | - Philipp Störmann
- Department of Trauma, Hand and Reconstructive Surgery, University Hospital Frankfurt, Goethe University, 60590, Frankfurt, Germany
| | - Jan Tilmann Vollrath
- Department of Trauma, Hand and Reconstructive Surgery, University Hospital Frankfurt, Goethe University, 60590, Frankfurt, Germany
| | - Ingo Marzi
- Department of Trauma, Hand and Reconstructive Surgery, University Hospital Frankfurt, Goethe University, 60590, Frankfurt, Germany
| | - Borna Relja
- Department of Trauma, Hand and Reconstructive Surgery, University Hospital Frankfurt, Goethe University, 60590, Frankfurt, Germany.,Experimental Radiology, Department of Radiology and Nuclear Medicine, Otto Von Guericke University Magdeburg, 39120, Magdeburg, Germany
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Duran Y, Karaboğa İ. Effect of hesperetin on systemic inflammation and hepatic injury after blunt chest trauma in rats. Biotech Histochem 2019; 95:297-304. [PMID: 31850807 DOI: 10.1080/10520295.2019.1691265] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
We investigated the protective effect of hesperetin on hepatic damage after blunt chest trauma in rats using histological and biochemical methods. We used 18 adult male rats in three groups of six: control, chest trauma and chest trauma + hesperetin. Chest trauma was caused by dropping a metal cylinder onto the right hemithorax. Hesperetin, 100 mg/kg, was administered orally for 7 days. At the end of the seventh day, liver tissue samples were obtained. Serum tumor necrosis factor-alpha (TNF-α), interleukin 1-beta (IL-1β), alanine aminotransferase (AST), aspartate transferase (ALT) and lactate dehydrogenase (LDH) enzyme activities were measured in blood samples taken from the heart. The general structure of liver tissue was investigated using hematoxylin and eosin staining. Nuclear factor kappa beta (Nf-κβ) expression in liver tissue was determined by the indirect immunohistochemical method. Apoptosis was determined using the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) method. Decreased TNF-α, AST and ALT enzyme activity, fewer histopathological changes and lower Nf-kB expression were observed in the hesperetin treated group compared to the chest trauma group. We also found reduced hepatic apoptosis in the chest trauma + hesperetin group compared to the chest trauma group. Hesperetine inhibits liver damage by reducing proinflammatory cytokines and by suppressing Nf-κβ activity in a blunt chest trauma model in rats.
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Affiliation(s)
- Yasin Duran
- Tekirdag Namık Kemal University, Faculty of Medicine, Department of General Surgery, 59030, Tekirdag, Turkey
| | - İhsan Karaboğa
- Tekirdag Namık Kemal University, School of Health, Department of Emergency and Disaster Management, 59030, Tekirdag, Turkey
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Mortaz E, Zadian SS, Shahir M, Folkerts G, Garssen J, Mumby S, Adcock IM. Does Neutrophil Phenotype Predict the Survival of Trauma Patients? Front Immunol 2019; 10:2122. [PMID: 31552051 PMCID: PMC6743367 DOI: 10.3389/fimmu.2019.02122] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2019] [Accepted: 08/23/2019] [Indexed: 12/14/2022] Open
Abstract
According to the World Health Organization (WHO), trauma is responsible for 10% of deaths and 16% of disabilities worldwide. This is considerably higher than those for malaria, tuberculosis, and HIV/AIDS combined. While the human suffering and death caused by injury is well-recognized, injury has a significant medical care cost. Better prediction of the state of trauma patients in the days immediately after trauma may reduce costs. Traumatic injuries to multiple organs can cause dysfunction in all systems of the body especially the immune system placing patients at high risk of infections and inflammatory complications which are often fatal. Neutrophils are the most abundant leukocyte in the human circulation and are crucial for the prevention of microbial disease. Significant changes in neutrophil functions such as enhanced chemotaxis, Neutrophil extracellular trap (NET)-induced cell death (NETosis), and phagocytosis occur early after injury followed by prolonged functional defects such as phagocytosis, killing mechanisms, and receptor expression. Analysis of these changes may improve the prediction of the patient's condition over time. We provide a comprehensive and up-to-date review of the literature investigating the effect of trauma on neutrophil phenotype with an underlying goal of using this knowledge to examine the predictive potential of neutrophil alterations on secondary complications in patients with traumatic injuries. We conclude that alterations in neutrophil surface markers and functions may be potential biomarkers that predict the outcome of trauma patients.
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Affiliation(s)
- Esmaeil Mortaz
- Department of Immunology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyed Sajjad Zadian
- Department of Immunology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mehri Shahir
- Department of Immunology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Gert Folkerts
- Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands
| | - Johan Garssen
- Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands.,Nutricia Research Centre for Specialized Nutrition, Utrecht, Netherlands
| | - Sharon Mumby
- National Heart and Lung Institute, Imperial College London, London, United Kingdom
| | - Ian M Adcock
- National Heart and Lung Institute, Imperial College London, London, United Kingdom.,Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, The University of Newcastle, Newcastle, NSW, Australia
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Jiao Y, Yang S, Min G, Zhang Y, Du X, Wang Q. Comprehensive transcriptome analysis reveal key molecular events in the pearl oyster after pre-grafting conditioning. FISH & SHELLFISH IMMUNOLOGY 2019; 92:241-248. [PMID: 31195116 DOI: 10.1016/j.fsi.2019.06.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Revised: 06/03/2019] [Accepted: 06/09/2019] [Indexed: 06/09/2023]
Abstract
Pre-grafting conditioning is a crucial procedure before transplant surgery during pearl production. To investigate the molecular response of the pearl oyster Pinctada fucata martensii to conditioning, we constructed two hemocyte transcriptomes from pearl oysters with and without conditioning. A total of 134,222,686 raw reads were generated and assembled using the reference genome of the pearl oyster. Transcriptome analysis revealed 3,074 differentially expressed genes (DEGs). Gene ontology and pathway enrichment analyses revealed that these DEGs were mainly associated with "microtubule-based process", "regulation of actin cytoskeleton", and "cell cycle". All related genes were over-expressed in pearl oysters after conditioning. Some nucleotide-binding oligomerization domain-like receptors (NLR), toll-like receptor, myd88, proinflammatory cytokine interleukin-17 (IL-17), and apoptosis-related genes were highly expressed in pearl oysters after conditioning, indicating that conditioning induced the immune response of pearl oysters. "Fatty acid biosynthesis" (FA biosynthesis) was included in the enriched terms, and all eight FA synthase genes in this pathway were highly induced after conditioning. Four tandemly duplicated arginine kinase genes (PmAK) were found in the genome of P. f. martensii, gene structure and sequence analysis indicated PmAK genes were more diverse compared with that from human and zebra fish. The four tandemly duplicated PmAKs were highly up-regulated after conditioning. These findings will help to elucidate the responding molecular events after conditioning and explain the high pearl oyster survival rate with conditioning after transplantation, thereby providing useful information in perfecting the conditioning method to improve pearl oyster survival rate after transplantation.
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Affiliation(s)
- Yu Jiao
- Fishery College, Guangdong Ocean University, Zhanjiang, 524025, China; Pearl Breeding and Processing Engineering Technology Research Centre of Guangdong Province, Zhanjiang, 524088, China
| | - Shuai Yang
- Fishery College, Guangdong Ocean University, Zhanjiang, 524025, China
| | - Guanjie Min
- Fishery College, Guangdong Ocean University, Zhanjiang, 524025, China
| | - Yuting Zhang
- Fishery College, Guangdong Ocean University, Zhanjiang, 524025, China
| | - Xiaodong Du
- Fishery College, Guangdong Ocean University, Zhanjiang, 524025, China; Pearl Breeding and Processing Engineering Technology Research Centre of Guangdong Province, Zhanjiang, 524088, China
| | - Qingheng Wang
- Fishery College, Guangdong Ocean University, Zhanjiang, 524025, China; Pearl Breeding and Processing Engineering Technology Research Centre of Guangdong Province, Zhanjiang, 524088, China.
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Saleh KMM, Al-Zghoul MB. Effect of Acute Heat Stress on the mRNA Levels of Cytokines in Broiler Chickens Subjected to Embryonic Thermal Manipulation. Animals (Basel) 2019; 9:E499. [PMID: 31362400 PMCID: PMC6719976 DOI: 10.3390/ani9080499] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Revised: 07/07/2019] [Accepted: 07/22/2019] [Indexed: 02/03/2023] Open
Abstract
Heat stress significantly impacts the immunity and cytokine expression of chickens. However, the effects of embryonic thermal manipulation (TM) on cytokine expression in broiler chickens (broilers) is unclear. The objective of the current study was to evaluate the effects of TM on the splenic mRNA expression dynamics of certain cytokines-namely, IFN-α, IFN-β, IFN-γ, IL-4, IL-8, IL-15, IL-16, IL-17, and IL-18-in broilers during subsequent exposure to acute heat stress (AHS). TM was performed by elevating the incubation temperature to 39 °C at 65% relative humidity (RH) for 18 h daily during embryonic days (ED) 10-18. On post-hatch day 28, AHS was carried out for 7 h at 40 °C. At 0 h and after 1, 3, 5, and 7 h of AHS, splenic tissues were collected from all study groups to evaluate mRNA expression by relative-quantitative real-time (RT)-PCR. Plasma was collected to measure IL-4, IL-8, and IFN-γ levels. At 0 h, TM significantly reduced the basal mRNA level of IFN-β and the plasma level of IFN-γ and IL-8. Moreover, AHS significantly decreased IFN-β in control chicks, decreased IL-4 in both TM and control chicks, and increased IFN-γ and IL-16 in TM chicks. IFN-α, IL-8, IL-15, IL-17, and IL-18 expression all significantly increased during AHS in both TM and control chicks, but expression dynamics were improved in TM chicks for all cytokines (except IL-17). AHS resulted in increased plasma IFN-γ levels in TM chicks only, and increased IL-8 levels at 3 and 5 h of AHS in TM chicks, but at 7 h in control chicks. Lastly, 3 h of AHS increased IL-4 plasma levels in control chicks. The results of this study may indicate that TM has a long-term effect on cytokine expression dynamics of broilers, especially during AHS. Therefore, TM may improve heat tolerance acquisition by increasing the expression of signaling proteins important to tissue stability and to repair mechanisms that are employed during and/or after heat stress recovery.
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Affiliation(s)
- Khaled M M Saleh
- Department of Applied Biological Sciences, Faculty of Science and Art, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan
| | - Mohammad B Al-Zghoul
- Department of Basic Medical Veterinary Sciences, Faculty of Veterinary Medicine, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan.
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Hesselink L, Spijkerman R, van Wessem KJP, Koenderman L, Leenen LPH, Huber-Lang M, Hietbrink F. Neutrophil heterogeneity and its role in infectious complications after severe trauma. World J Emerg Surg 2019; 14:24. [PMID: 31164913 PMCID: PMC6542247 DOI: 10.1186/s13017-019-0244-3] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Accepted: 05/13/2019] [Indexed: 02/06/2023] Open
Abstract
Background Trauma leads to a complex inflammatory cascade that induces both immune activation and a refractory immune state in parallel. Although both components are deemed necessary for recovery, the balance is tight and easily lost. Losing the balance can lead to life-threatening infectious complications as well as long-term immunosuppression with recurrent infections. Neutrophils are known to play a key role in these processes. Therefore, this review focuses on neutrophil characteristics and function after trauma and how these features can be used to identify trauma patients at risk for infectious complications. Results Distinct neutrophil subtypes exist that play their own role in the recovery and/or development of infectious complications after trauma. Furthermore, the refractory immune state is related to the risk of infectious complications. These findings change the initial concepts of the immune response after trauma and give rise to new biomarkers for monitoring and predicting inflammatory complications in severely injured patients. Conclusion For early recognition of patients at risk, the immune system should be monitored. Several neutrophil biomarkers show promising results and analysis of these markers has become accessible to such extent that they can be used for point-of-care decision making after trauma.
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Affiliation(s)
- Lillian Hesselink
- Department of Trauma Surgery, University Medical Centre Utrecht, Utrecht, The Netherlands
- Laboratory of Translational Immunology and Department of Respiratory Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands
| | - Roy Spijkerman
- Department of Trauma Surgery, University Medical Centre Utrecht, Utrecht, The Netherlands
- Laboratory of Translational Immunology and Department of Respiratory Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands
| | | | - Leo Koenderman
- Laboratory of Translational Immunology and Department of Respiratory Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands
| | - Luke P. H. Leenen
- Department of Trauma Surgery, University Medical Centre Utrecht, Utrecht, The Netherlands
| | - Markus Huber-Lang
- Institute of Clinical and Experimental Trauma Immunology, University Hospital of Ulm, Ulm, Germany
| | - Falco Hietbrink
- Department of Trauma Surgery, University Medical Centre Utrecht, Utrecht, The Netherlands
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Al-Zghoul MB, Saleh KM, Ababneh MMK. Effects of pre-hatch thermal manipulation and post-hatch acute heat stress on the mRNA expression of interleukin-6 and genes involved in its induction pathways in 2 broiler chicken breeds. Poult Sci 2019; 98:1805-1819. [PMID: 30365012 DOI: 10.3382/ps/pey499] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Accepted: 10/04/2018] [Indexed: 01/10/2023] Open
Abstract
In response to heat stress, interleukin-6 (IL-6) expression is upregulated in broiler chickens. The main aim of the present study was to evaluate the cumulative effects of thermal manipulation (TM) and subsequent acute heat stress (AHS) on the mRNA expression of IL-6 and genes involved in its induction pathways. The studied genes include IL-6, IL-1β, TNF-α, TLR2, TLR4, NFκB50, NFκB65, Hsp70, and HSF3 in the spleen and liver tissues. TM was carried out at 39°C for 18 h and 65% relative humidity during days 10 to 18 of embryonic development, while AHS was stimulated by raising the temperature to 40°C for 7 h on post-hatch day 28. During AHS at 0, 1, 3, 5, and 7 h, the spleen and liver were collected from all groups to measure the mRNA expression by relative-quantitation real-time RT-PCR, and the blood was collected to measure plasma IL-6 level. TM significantly reduced Tc during AHS for both breeds from 1 to 7 h time intervals. TM resulted in enhanced basal mRNA expression of IL-6, HSF3, and Hsp70, but decreased the basal mRNA level of TLR4. During heat stress, TM enhanced the expression dynamics of Hsp70, HSF3, IL-6, IL-1β, TNF-α, TLR2, TLR4, NFκB50, and NFκB65. The results of the current study indicate that TM enhanced the heat tolerance through improving the protective immunological response to heat stress by enhancing the expression of IL-6 and modulating the expression of genes important in its induction pathways.
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Affiliation(s)
| | - Khaled Musa Saleh
- Department of Applied Biological Sciences, Faculty of Science and Art, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110
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Pathophysiology of Acute Illness and Injury. OPERATIVE TECHNIQUES AND RECENT ADVANCES IN ACUTE CARE AND EMERGENCY SURGERY 2019. [PMCID: PMC7122041 DOI: 10.1007/978-3-319-95114-0_2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
The pathophysiology of acute illness and injury recognizes three main effectors: infection, trauma, and ischemia-reperfusion injury. Each of them can act by itself or in combination with the other two in developing a systemic inflammatory reaction syndrome (SIRS) that is a generalized reaction to the morbid event. The time course of SIRS is variable and influenced by the number and severity of subsequent insults (e.g., reparative surgery, acquired hospital infections). It occurs simultaneously with a complex of counter-regulatory mechanisms (compensatory anti-inflammatory response syndrome, CARS) that limit the aggressive effects of SIRS. In adjunct, a progressive dysfunction of the acquired (lymphocytes) immune system develops with increased risk for immunoparalysis and associated infectious complications. Both humoral and cellular effectors participate to the development of SIRS and CARS. The most important humoral mediators are pro-inflammatory (IL-1β, IL-6, IL-8, IL-12) and anti-inflammatory (IL-4, IL-10) cytokines and chemokines, complement, leukotrienes, and PAF. Effector cells include neutrophils, monocytes, macrophages, lymphocytes, and endothelial cells. The endothelium is a key factor for production of remote organ damage as it exerts potent chemo-attracting effects on inflammatory cells, allows for leukocyte trafficking into tissues and organs, and promotes further inflammation by cytokines release. Moreover, the loss of vasoregulatory properties and the increased permeability contribute to the development of hypotension and tissue edema. Finally, the disseminated activation of the coagulation cascade causes the widespread deposition of microthrombi with resulting maldistribution of capillary blood flow and ultimately hypoxic cellular damage. This mechanism together with increased vascular permeability and vasodilation is responsible for the development of the multiple organ dysfunction syndrome (MODS).
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Diagnostic Utility of Serum Neutrophil Gelatinase-Associated Lipocalin in Polytraumatized Patients Suffering Acute Kidney Injury: A Prospective Study. BIOMED RESEARCH INTERNATIONAL 2018; 2018:2687584. [PMID: 30533430 PMCID: PMC6247699 DOI: 10.1155/2018/2687584] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/11/2018] [Revised: 09/27/2018] [Accepted: 10/23/2018] [Indexed: 11/18/2022]
Abstract
Introduction The incidence of acute kidney injury (AKI) considerably increases the mortality rate in polytrauma victims. Undoubtedly, early identification of patients at risk is crucial for timely implementation of preventive strategies in order to improve their prognosis. Therefore, we aimed to investigate if serum neutrophil gelatinase-associated lipocalin (sNGAL) may serve as a diagnostic biomarker of early AKI in polytrauma victims, especially considering patients needing renal replacement theory (RRT). Material and Methods Forty consecutive polytrauma victims (ISS ≥ 16, AISThorax ≥ 1, age ≥ 18 years, survival time ≥ 48 hours), directly admitted to our level I trauma center within one posttraumatic hour, were enrolled in our prospective study. sNGAL-levels were assessed at admission (initial) and on day 2 after trauma. AKI was diagnosed by an increase of serum creatinine (sCr) level of at least 0.3 mg/dl within 48 hours. Results Out of 30 men and 10 women (mean age, 43 years; mean ISS, 29), seven patients developed AKI, four of them needing RRT. AKI was diagnosed in 86% of the affected individuals until day 2. Day2-sNGAL-levels were higher in the AKI-group, compared to the no-AKI-group (p=0.049), and in patients treated with RRT than in individuals not needing RRT (p=0.037). Noteworthy, in patients not needing RRT sNGAL-levels significantly decreased from initial to day2-measurement (p=0.040). Furthermore, at any time point during our observation period polytraumatized patients with AKI and day2-sNGAL-levels of at least 181.0 ng/mL presented with higher sCr-levels compared to polytraumatized patients without AKI and day2-sNGAL-levels lower than 181.0 ng/mL (p≤0.029). Conclusion In polytrauma victims suffering AKI an increase in sNGAL-level from initial to day2-assessment may signalize deterioration in kidney function and thus indicate AKI progression. Unlike initial sNGAL-levels day2-sNGAL-levels might be an appropriate tool to define AKI and to signify the need of RRT in polytraumatized patients.
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Major trauma and acceleration of the ageing process. Ageing Res Rev 2018; 48:32-39. [PMID: 30316759 DOI: 10.1016/j.arr.2018.10.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Revised: 09/07/2018] [Accepted: 10/08/2018] [Indexed: 12/30/2022]
Abstract
It is well established that numerous factors can affect the rate at which we age biologically. Diet, physical activity, lifestyle and our genes all play a major role in influencing the ageing trajectory and longevity. Major trauma affects millions globally, is the major cause of death in young adults and could influence ageing processes but has largely been ignored by biogenterologists. The long-term health consequences of physical trauma are well known in the medical community, how trauma effects the ageing process at a molecular level is not. It has long been difficult to assess ageing trajectories due to the absence of a biomarker of biological rather than chronological age. Recent advances in epigenetics have helped by identifying specific DNA methylation sites as good indicators of biological age. Recent investigations into the impact of psychological trauma and the associated physical stress on accelerating ageing as measured by epigenetic drift are promising. The physical and metabolic stress which is synonymous with physical trauma may also accelerate the ageing process. We suggest that long term epigenetic profiling is required to understand to what degree the ageing trajectory is altered by trauma, which will in turn add support for the development of novel therapies to improve health outcomes for survivors of traumatic injury.
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Mortaz E, Alipoor SD, Adcock IM, Mumby S, Koenderman L. Update on Neutrophil Function in Severe Inflammation. Front Immunol 2018; 9:2171. [PMID: 30356867 PMCID: PMC6190891 DOI: 10.3389/fimmu.2018.02171] [Citation(s) in RCA: 266] [Impact Index Per Article: 38.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2018] [Accepted: 09/03/2018] [Indexed: 12/17/2022] Open
Abstract
Neutrophils are main players in the effector phase of the host defense against micro-organisms and have a major role in the innate immune response. Neutrophils show phenotypic heterogeneity and functional flexibility, which highlight their importance in regulation of immune function. However, neutrophils can play a dual role and besides their antimicrobial function, deregulation of neutrophils and their hyperactivity can lead to tissue damage in severe inflammation or trauma. Neutrophils also have an important role in the modulation of the immune system in response to severe injury and trauma. In this review we will provide an overview of the current understanding of neutrophil subpopulations and their function during and post-infection and discuss the possible mechanisms of immune modulation by neutrophils in severe inflammation.
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Affiliation(s)
- Esmaeil Mortaz
- Department of Immunology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Clinical Tuberculosis and Epidemiology Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shamila D Alipoor
- Molecular Medicine Department, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
| | - Ian M Adcock
- Priority Research Centre for Asthma and Respiratory Disease, Hunter Medical Research Institute, University of Newcastle, Newcastle, NSW, Australia.,Airways Disease Section, Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, United Kingdom
| | - Sharon Mumby
- Airways Disease Section, Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, United Kingdom
| | - Leo Koenderman
- Laboratory of Translational Immunology, Department of Respiratory Medicine, University Medical Centre Utrecht, Utrecht, Netherlands
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Hesselink L, Bastian OW, Heeres M, ten Berg M, Huisman A, Hoefer IE, van Solinge WW, Koenderman L, van Wessem KJP, Leenen LPH, Hietbrink F. An increase in myeloid cells after severe injury is associated with normal fracture healing: a retrospective study of 62 patients with a femoral fracture. Acta Orthop 2018; 89:585-590. [PMID: 30080430 PMCID: PMC6202765 DOI: 10.1080/17453674.2018.1501974] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Background and purpose-Nonunion is common in femoral fractures. Previous studies suggested that the systemic immune response after trauma can interfere with fracture healing. Therefore, we investigated whether there is a relation between peripheral blood cell counts and healing of femur fractures. Patients and methods-62 multi-trauma patients with a femoral fracture presenting at the University Medical Centre Utrecht between 2007 and 2013 were retrospectively included. Peripheral blood cell counts from hematological analyzers were recorded from the 1st through the 14th day of the hospital stay. Generalized estimating equations were used to compare outcome groups. Results-12 of the 62 patients developed nonunion of the femoral fracture. The peripheral blood-count curves of total leukocytes, neutrophils, monocytes, lymphocytes, and platelets were all statistically significantly lower in patients with nonunion, coinciding with significantly higher CRP levels during the first 2 weeks after trauma in these patients. Interpretation-Patients who developed femoral nonunion after major trauma demonstrated lower numbers of myeloid cells in the peripheral blood than patients with normal fracture healing. This absent rise of myeloid cells seems to be related to a more severe post-traumatic immune response.
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Affiliation(s)
- Lillian Hesselink
- Department of Trauma Surgery, University Medical Center Utrecht, Utrecht; ,Correspondence:
| | - Okan W Bastian
- Department of Trauma Surgery, University Medical Center Utrecht, Utrecht;
| | - Marjolein Heeres
- Department of Trauma Surgery, University Medical Center Utrecht, Utrecht;
| | - Maarten ten Berg
- Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht;
| | - Albert Huisman
- Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht;
| | - Imo E Hoefer
- Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht;
| | - Wouter W van Solinge
- Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht;
| | - Leo Koenderman
- Laboratory for Translational Immunology and Department of Respiratory Medicine, University Medical Center Utrecht Wilhelmina Children’s Hospital, Utrecht, The Netherlands
| | | | - Luke P H Leenen
- Department of Trauma Surgery, University Medical Center Utrecht, Utrecht;
| | - Falco Hietbrink
- Department of Trauma Surgery, University Medical Center Utrecht, Utrecht;
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Haldar R, Shaashua L, Lavon H, Lyons YA, Zmora O, Sharon E, Birnbaum Y, Allweis T, Sood AK, Barshack I, Cole S, Ben-Eliyahu S. Perioperative inhibition of β-adrenergic and COX2 signaling in a clinical trial in breast cancer patients improves tumor Ki-67 expression, serum cytokine levels, and PBMCs transcriptome. Brain Behav Immun 2018; 73:294-309. [PMID: 29800703 DOI: 10.1016/j.bbi.2018.05.014] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Revised: 05/10/2018] [Accepted: 05/18/2018] [Indexed: 12/18/2022] Open
Abstract
Catecholamines and prostaglandins are secreted abundantly during the perioperative period in response to stress and surgery, and were shown by translational studies to promote tumor metastasis. Here, in a phase-II biomarker clinical trial in breast cancer patients (n = 38), we tested the combined perioperative use of the β-blocker, propranolol, and the COX2-inhibitor, etodolac, scheduled for 11 consecutive perioperative days, starting 5 days before surgery. Blood samples were taken before treatment (T1), on the mornings before and after surgery (T2&T3), and after treatment cessation (T4). Drugs were well tolerated. Results based on a-priori hypotheses indicated that already before surgery (T2), serum levels of pro-inflammatory IL-6, CRP, and IFNγ, and anti-inflammatory, cortisol and IL-10, increased. At T2 and/or T3, drug treatment reduced serum levels of the above pro-inflammatory cytokines and of TRAIL, as well as activity of multiple inflammation-related transcription factors (including NFκB, STAT3, ISRE), but not serum levels of cortisol, IL-10, IL-18, IL-8, VEGF and TNFα. In the excised tumor, treatment reduced the expression of the proliferation marker Ki-67, and positively affected its transcription factors SP1 and AhR. Exploratory analyses of transcriptome modulation in PBMCs revealed treatment-induced improvement at T2/T3 in several transcription factors that in primary tumors indicate poor prognosis (CUX1, THRa, EVI1, RORa, PBX1, and T3R), angiogenesis (YY1), EMT (GATA1 and deltaEF1/ZEB1), proliferation (GATA2), and glucocorticoids response (GRE), while increasing the activity of the oncogenes c-MYB and N-MYC. Overall, the drug treatment may benefit breast cancer patients through reducing systemic inflammation and pro-metastatic/pro-growth biomarkers in the excised tumor and PBMCs.
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Affiliation(s)
- Rita Haldar
- Sagol School of Neuroscience and School of Psychological Sciences, Tel Aviv University, Israel
| | - Lee Shaashua
- Sagol School of Neuroscience and School of Psychological Sciences, Tel Aviv University, Israel
| | - Hagar Lavon
- Sagol School of Neuroscience and School of Psychological Sciences, Tel Aviv University, Israel
| | - Yasmin A Lyons
- Department of Gynecologic Oncology and Reproductive Medicine, Division of Surgery, M.D. Anderson Cancer Center at University of Texas, Huston, TX, USA
| | - Oded Zmora
- Department of Surgery and Transplantation, Sheba Medical Center, Ramat Gan, Israel
| | - Eran Sharon
- Department of Surgery, Rabin Medical Center, Beilinson Hospital, Petach-Tikva, Israel
| | - Yehudit Birnbaum
- Department of Surgery, Rabin Medical Center, Beilinson Hospital, Petach-Tikva, Israel
| | - Tanir Allweis
- Department of Surgery, Kaplan Medical Center, Rehovot, Israel
| | - Anil K Sood
- Department of Gynecologic Oncology and Reproductive Medicine, Division of Surgery, M.D. Anderson Cancer Center at University of Texas, Huston, TX, USA
| | - Iris Barshack
- Department of Pathology, Sheba Medical Center, Ramat Gan, Israel
| | - Steve Cole
- Department of Medicine, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Shamgar Ben-Eliyahu
- Sagol School of Neuroscience and School of Psychological Sciences, Tel Aviv University, Israel.
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Chakraborty S, Karasu E, Huber-Lang M. Complement After Trauma: Suturing Innate and Adaptive Immunity. Front Immunol 2018; 9:2050. [PMID: 30319602 PMCID: PMC6165897 DOI: 10.3389/fimmu.2018.02050] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Accepted: 08/20/2018] [Indexed: 12/21/2022] Open
Abstract
The overpowering effect of trauma on the immune system is undisputed. Severe trauma is characterized by systemic cytokine generation, activation and dysregulation of systemic inflammatory response complementopathy and coagulopathy, has been immensely instrumental in understanding the underlying mechanisms of the innate immune system during systemic inflammation. The compartmentalized functions of the innate and adaptive immune systems are being gradually recognized as an overlapping, interactive and dynamic system of responsive elements. Nonetheless the current knowledge of the complement cascade and its interaction with adaptive immune response mediators and cells, including T- and B-cells, is limited. In this review, we discuss what is known about the bridging effects of the complement system on the adaptive immune system and which unexplored areas could be crucial in understanding how the complement and adaptive immune systems interact following trauma.
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Affiliation(s)
- Shinjini Chakraborty
- Institute of Clinical and Experimental Trauma-Immunology, University Hospital of Ulm, Ulm, Germany
| | - Ebru Karasu
- Institute of Clinical and Experimental Trauma-Immunology, University Hospital of Ulm, Ulm, Germany
| | - Markus Huber-Lang
- Institute of Clinical and Experimental Trauma-Immunology, University Hospital of Ulm, Ulm, Germany
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Leiblein M, Ponelies N, Johnson T, Marzi J, Kontradowitz K, Geiger E, Marzi I, Henrich D. Increased extracellular ubiquitin in surgical wound fluid provides a chemotactic signal for myeloid dendritic cells. Eur J Trauma Emerg Surg 2018; 46:153-163. [PMID: 30159662 DOI: 10.1007/s00068-018-1001-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Accepted: 08/20/2018] [Indexed: 12/18/2022]
Abstract
PURPOSE Myeloid dendritic cells (MDC) decline significantly after multiple traumas which might be due to an increased migration into injured regions. Ubiquitin is released from dying cells and is increased in serum after trauma. Ubiquitin can bind to the chemokine receptor CXCR4. Thus, we hypothesized that elevated ubiquitin provides a chemotactic signal for MDC to injured regions. METHODS Surgical wound fluid (SWF) and serum from patients with mono-trauma (n = 20) were used to simulate the humoral situation in injured tissue. MDC were identified by flow cytometry. Chemotaxis was measured using transwell migration assays. Ubiquitin and CXCL12 (natural CXCR4 ligand) were determined by ELISA. RESULTS MDC express CXCR4 and fluorescence-labeled ubiquitin binds to MDC. Ubiquitin exerts a dose-dependent chemotactic effect (fourfold at 100 ng/mL, p < 0.05). Ubiquitin concentration was sixfold higher in SWF (p < 0.05), whereas CXCL12 was increased in serum. MDC migration towards SWF was significantly reduced (- 40%, p < 0.05), if ubiquitin was neutralized by specific antibodies. CONCLUSIONS Ubiquitin is increased in SWF and exerts a significant chemotactic effect on MDC. This mechanism might play a role in attraction of immune cells to injured regions and might contribute to the decline of circulating MDC in multiple traumas.
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Affiliation(s)
- Maximilian Leiblein
- Department of Trauma-, Hand- and Reconstructive Surgery, University Hospital Frankfurt, Frankfurt am Main, Germany.
| | - Norbert Ponelies
- Department of Orthopaedics and Trauma Surgery, University Medical Center Mannheim of University Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany
| | - Theresa Johnson
- Department of Trauma-, Hand- and Reconstructive Surgery, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Julian Marzi
- Department of Trauma-, Hand- and Reconstructive Surgery, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Kerstin Kontradowitz
- Department of Trauma-, Hand- and Reconstructive Surgery, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Emanuel Geiger
- Department of Trauma-, Hand- and Reconstructive Surgery, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Ingo Marzi
- Department of Trauma-, Hand- and Reconstructive Surgery, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Dirk Henrich
- Department of Trauma-, Hand- and Reconstructive Surgery, University Hospital Frankfurt, Frankfurt am Main, Germany
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Abstract
This review summarizes a short list of currently discussed trauma-induced danger-associated molecular patterns (DAMP). Due to the bivalent character and often pleiotropic effects of a DAMP, it is difficult to describe its "friend or foe" role in post-traumatic inflammation and regeneration, both systemically as well locally in tissues. DAMP can be used as biomarkers to indicate or monitor disease or injury severity, but also may serve as clinically applicable parameters for better indication and timing of surgery. Due to the inflammatory processes at the local tissue level or the systemic level, the precise role of DAMP is not always clear to define. While in vitro and experimental studies allow for the detection of these biomarkers at the different levels of an organism-cellular, tissue, circulation-this is not always easily transferable to the human setting. Increased knowledge exploring the dual role of DAMP after trauma, and concentrating on their nuclear functions, transcriptional targets, release mechanisms, cellular sources, multiple functions, their interactions and potential therapeutic targeting is warranted.
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Affiliation(s)
- Borna Relja
- Department of Trauma, Hand and Reconstructive Surgery, University Hospital Frankfurt, Goethe University, 60590, Frankfurt, Germany.
| | - Katharina Mörs
- Department of Trauma, Hand and Reconstructive Surgery, University Hospital Frankfurt, Goethe University, 60590, Frankfurt, Germany
| | - Ingo Marzi
- Department of Trauma, Hand and Reconstructive Surgery, University Hospital Frankfurt, Goethe University, 60590, Frankfurt, Germany
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Osteoimmunology: Effects of Standard Orthopaedic Interventions on Inflammatory Response and Early Fracture Healing. J Am Acad Orthop Surg 2018; 26:343-352. [PMID: 29659378 DOI: 10.5435/jaaos-d-16-00646] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
Achieving fracture union is highly dependent on the initial inflammatory phase of fracture healing, which is influenced by both the local and systemic inflammatory environments. The rapidly emerging field of osteoimmunology involves the study of the interactions between the immune system and the skeletal system. Recent research has advanced the current state of knowledge regarding the effects of the surrounding soft-tissue injury, fracture hematoma, and the method of fracture fixation on the inflammatory phase of fracture healing. Acute systemic inflammation, as seen in patients with polytrauma, and chronic systemic inflammation, as seen in patients with diabetes or rheumatoid arthritis, affects the inflammatory phase of fracture healing. The use of NSAIDs can influence early fracture healing. Understanding the effects of standard orthopaedic interventions on the local and systemic inflammatory responses and early fracture healing is important for optimizing fracture union.
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50
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Wagner N, Dieteren S, Franz N, Köhler K, Mörs K, Nicin L, Schmidt J, Perl M, Marzi I, Relja B. Ethyl pyruvate ameliorates hepatic injury following blunt chest trauma and hemorrhagic shock by reducing local inflammation, NF-kappaB activation and HMGB1 release. PLoS One 2018; 13:e0192171. [PMID: 29420582 PMCID: PMC5805235 DOI: 10.1371/journal.pone.0192171] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2017] [Accepted: 01/17/2018] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND The treatment of patients with multiple trauma including blunt chest/thoracic trauma (TxT) and hemorrhagic shock (H) is still challenging. Numerous studies show detrimental consequences of TxT and HS resulting in strong inflammatory changes, organ injury and mortality. Additionally, the reperfusion (R) phase plays a key role in triggering inflammation and worsening outcome. Ethyl pyruvate (EP), a stable lipophilic ester, has anti-inflammatory properties. Here, the influence of EP on the inflammatory reaction and liver injury in a double hit model of TxT and H/R in rats was explored. METHODS Female Lewis rats were subjected to TxT followed by hemorrhage/H (60 min, 35±3 mm Hg) and resuscitation/R (TxT+H/R). Reperfusion was performed by either Ringer`s lactated solution (RL) alone or RL supplemented with EP (50 mg/kg). Sham animals underwent all surgical procedures without TxT+H/R. After 2h, blood and liver tissue were collected for analyses, and survival was assessed after 24h. RESULTS Resuscitation with EP significantly improved haemoglobin levels and base excess recovery compared with controls after TxT+H/R, respectively (p<0.05). TxT+H/R-induced significant increase in alanine aminotransferase levels and liver injury were attenuated by EP compared with controls (p<0.05). Local inflammation as shown by increased gene expression of IL-6 and ICAM-1, enhanced ICAM-1 and HMGB1 protein expression and infiltration of the liver with neutrophils were also significantly attenuated by EP compared with controls after TxT+H/R (p<0.05). EP significantly reduced TxT+H/R-induced p65 activation in liver tissue. Survival rates improved by EP from 50% to 70% after TxT+H/R. CONCLUSIONS These data support the concept that the pronounced local pro-inflammatory response in the liver after blunt chest trauma and hemorrhagic shock is associated with NF-κB. In particular, the beneficial anti-inflammatory effects of ethyl pyruvate seem to be regulated by the HMGB1/NF-κB axis in the liver, thereby, restraining inflammatory responses and liver injury after double hit trauma in the rat.
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Affiliation(s)
- Nils Wagner
- Department of Trauma Surgery, University Hospital Frankfurt, Goethe-University, Frankfurt, Germany
| | - Scott Dieteren
- Department of Trauma Surgery, University Hospital Frankfurt, Goethe-University, Frankfurt, Germany
| | - Niklas Franz
- Department of Trauma Surgery, University Hospital Frankfurt, Goethe-University, Frankfurt, Germany
| | - Kernt Köhler
- Institute of Veterinary Pathology, Justus Liebig University Giessen, Giessen, Germany
| | - Katharina Mörs
- Department of Trauma Surgery, University Hospital Frankfurt, Goethe-University, Frankfurt, Germany
| | - Luka Nicin
- Department of Trauma Surgery, University Hospital Frankfurt, Goethe-University, Frankfurt, Germany
| | - Julia Schmidt
- Department of Trauma Surgery, University Hospital Frankfurt, Goethe-University, Frankfurt, Germany
| | - Mario Perl
- BG-Trauma Center Murnau, Murnau, Germany
| | - Ingo Marzi
- Department of Trauma Surgery, University Hospital Frankfurt, Goethe-University, Frankfurt, Germany
| | - Borna Relja
- Department of Trauma Surgery, University Hospital Frankfurt, Goethe-University, Frankfurt, Germany
- * E-mail:
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