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sepsis AND anti-inflammatory

Gahee Min, Sae-Kwang Ku, Mi Seon Park, Tae-Joo Park, Hyun-Shik Lee, Jong-Sup Bae
A certain nucleosomal protein-high mobility group box-1 (HMGB1)-has recently been established as a late mediator of sepsis, with a relatively wide therapeutic window for pharmacological intervention. Pelargonidin (PEL) is a well-known red pigment found in plants; it has important biological activities that are potentially beneficial for human health. In the present study, we investigated whether PEL can modulate HMGB1-mediated inflammatory responses in human umbilical vein endothelial cells (HUVECs) and in mice...
October 24, 2016: Archives of Pharmacal Research
Aravind T Reddy, Sowmya P Lakshmi, Raju C Reddy
Peroxisome proliferator-activated receptor γ (PPARγ) is now recognized as an important modulator of leukocyte inflammatory responses and function. Its immunoregulatory function has been studied in a variety of contexts, including bacterial infections of the lungs and central nervous system, sepsis, and conditions such as chronic granulomatous disease. Although it is generally believed that PPARγ activation is beneficial for the host during bacterial infections via its anti-inflammatory and antibacterial properties, PPARγ agonists have also been shown to dampen the host immune response and in some cases exacerbate infection by promoting leukocyte apoptosis and interfering with leukocyte migration and infiltration...
2016: PPAR Research
Ankana Daga, Fredrick Dapaah-Siakwan, Sharina Rajbhandari, Cassandra Arevalo, Agnes Salvador
BACKGROUND: Acute kidney injury (AKI) is common in critically ill premature infants. There is a lack of consensus on the diagnostic definition of AKI in very low birth weight (VLBW) infants. The primary aim of this study was to determine the incidence and risk factors for AKI in VLBW infants using the AKI network (AKIN) and pRIFLE (pediatric Risk, Injury, Failure, Loss, End-Stage) criteria and to evaluate whether Clinical Risk Index for Babies (CRIB II) score is a predictor of AKI. The secondary objective was to determine the extent of agreement between the AKIN and pRIFLE criteria in the diagnosis of AKI in VLBW infants...
September 28, 2016: Pediatrics and Neonatology
Yi-Kun Chen, Ying-Kun Xu, Hao Zhang, Jiang-Tao Yin, Xin Fan, Da-Dong Liu, Hai-Yan Fu, Bing Wan
Emodin is an anthraquinone derived from Chinese herb that exerts anti-inflammation effects. This study aimed to investigate whether emodin provides the protection for jejunum injury by inhibiting inflammation. We established a model of sepsis caused by cecal ligation and puncture. Forty-eight male Wistar rats were divided into four groups (n=12). Jejunum injury was assessed by pathological examination. The activity of pJAK1/pSTAT3 and protein levels of Bcl-2 and Bax were detected by Western blot analysis. Inflammatory factors IL-6, TNF-α and procalcitonin were detected by ELISA...
October 18, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Joshua Bloom, Shan Sun, Yousef Al-Abed
Macrophage migration inhibitory factor (MIF) has emerged as a promising drug target in diseases including sepsis, rheumatoid arthritis, and cancer. MIF has multiple properties that favor development of specific, targeted therapies: it is expressed broadly among human cells, has noted roles in diverse inflammatory and oncological processes, and has intrinsic enzymatic activity amenable to high-throughput screening. Despite these advantages, anti-MIF therapy remains well behind other cytokine-targeted therapeutics, with no small molecules in the pipeline for clinical development and anti-MIF antibodies only recently beginning clinical trials...
October 20, 2016: Expert Opinion on Therapeutic Targets
Esther Peters, Bülent Ergin, Asli Kandil, Ebru Gurel-Gurevin, Andrea van Elsas, Rosalinde Masereeuw, Peter Pickkers, Can Ince
Two small clinical trials indicated that administration of bovine intestinal alkaline phosphatase (AP) improves renal function in critically ill patients with sepsis-associated acute kidney injury (AKI), for which the mechanism of action is not completely understood. Here, we investigated the effects of a newly developed human recombinant AP (recAP) on renal oxygenation and hemodynamics and prevention of kidney damage and inflammation in two in vivo AKI models. To induce AKI, male Wistar rats (n=18) were subjected to renal ischemia (30min) and reperfusion (I/R), or sham-operated...
October 16, 2016: Toxicology and Applied Pharmacology
Norma Alva, Ronald Alva, Teresa Carbonell
In clinical and experimental settings, a great deal of effort is being made to protect cells and tissues against harmful conditions and to facilitate metabolic recovery following these insults. Much of the recent attention has focused on the protective role of a natural form of sugar, fructose 1,6-bisphosphate (F16bP). F16bP is a high-energy glycolytic intermediate that has been shown to exert a protective action in different cell types and tissues (including the brain, kidney, intestine, liver and heart) against various harmful conditions...
October 14, 2016: Current Medicinal Chemistry
Meghan MacKenzie, Richard Hall
PURPOSE: Knowledge of how alterations in pharmacogenomics and pharmacogenetics may affect drug therapy in the intensive care unit (ICU) has received little study. We review the clinically relevant application of pharmacogenetics and pharmacogenomics to drugs and conditions encountered in the ICU. SOURCE: We selected relevant literature to illustrate the important concepts contained within. PRINCIPAL FINDINGS: Two main approaches have been used to identify genetic abnormalities - the candidate gene approach and the genome-wide approach...
October 17, 2016: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
Jia Shi, Jian-Bo Yu, Wei Liu, Dan Wang, Yuan Zhang, Li-Rong Gong, Shu-An Dong, Da-Quan Liu
Acute respiratory distress syndrome (ARDS) is one of the most devastating complications of sepsis lacking of effective therapy. Mitochondrial dynamics undergoing continuous fusion and fission play a crucial role in mitochondrial structure and function. Fis1, as a small protein located on the outer membrane of mitochondria, has been thought to be an important protein mediated mitochondrial fission. During ARDS, alveolar macrophages suffer from increased oxidative stress and apoptosis, and also accompanied by disrupted mitochondrial dynamics...
October 14, 2016: Experimental Cell Research
Feng Xu, Taoqun Wen, Feng Wang, Wentao Sang, Nan Zeng
CONTEXT: Several pharmacological studies have shown that cinnamicaldehyde (CA) has anti-inflammatory and anti-tumor effects, but no data show the effects of CA on the endotoxin poisoning. OBJECTIVE: In this work, the protective effect of CA in LPS-induced endotoxin poisoning mice was investigated. MATERIALS AND METHODS: Mice were randomly divided into normal, LPS, LPS +5 mg/kg dexamethasone (DEX), LPS +0.132 g/kg CA, and LPS +0.264 g/kg CA group...
October 18, 2016: Immunopharmacology and Immunotoxicology
Dana Elena Giza, Enrique Fuentes-Mattei, Marc David Bullock, Stefan Tudor, Matthew Joseph Goblirsch, Muller Fabbri, Florea Lupu, Sai-Ching Jim Yeung, Catalin Vasilescu, George Adrian Calin
Regardless of its etiology, once septic shock is established, survival rates drop by 7.6% for every hour antibiotic therapy is delayed. The early identification of the cause of infection and prognostic stratification of patients with sepsis are therefore important clinical priorities. Biomarkers are potentially valuable clinical tools in this context, but to date, no single biomarker has been shown to perform adequately. Hence, in an effort to discover novel diagnostic and prognostic markers in sepsis, new genomic approaches have been employed...
October 14, 2016: Cell Death and Differentiation
Maryse A Wiewel, Matthew B Harmon, Lonneke A van Vught, Brendon P Scicluna, Arie J Hoogendijk, Janneke Horn, Aeilko H Zwinderman, Olaf L Cremer, Marc J Bonten, Marcus J Schultz, Tom van der Poll, Nicole P Juffermans, W Joost Wiersinga
BACKGROUND: Hypothermia is associated with adverse outcome in patients with sepsis. The objective of this study was to characterize the host immune response in patients with hypothermic sepsis in order to determine if an excessive anti-inflammatory response could explain immunosuppression and adverse outcome. Markers of endothelial activation and integrity were also measured to explore potential alternative mechanisms of hypothermia. Finally we studied risk factors for hypothermia in an attempt to find new clues to the etiology of hypothermia in sepsis...
October 14, 2016: Critical Care: the Official Journal of the Critical Care Forum
Suvi T Vaara, Maija Hollmén, Anna-Maija Korhonen, Mikael Maksimow, Tero Ala-Kokko, Marko Salmi, Sirpa Jalkanen, Ville Pettilä
BACKGROUND: CD73 dephosphorylates adenosine monophosphate to adenosine that is an anti-inflammatory molecule inhibiting immune activation and vascular leakage. Therefore, CD73 could be an interesting mediator both in sepsis and acute kidney injury (AKI). We aimed to explore the soluble CD73 (sCD73) levels and their evolution in critically ill patients with severe sepsis and, second, to scrutinize the potential association of sCD73 levels with AKI and 90-day mortality. METHODS: This was a post-hoc laboratory analysis of the prospective, observational FINNAKI study conducted in 17 Finnish ICU during 5 months in 2011-2012...
2016: PloS One
Tamara V Smelaya, Olesya B Belopolskaya, Svetlana V Smirnova, Artem N Kuzovlev, Viktor V Moroz, Arkadiy M Golubev, Noel A Pabalan, Lyubov E Salnikova
The role of host genetic variation in pneumonia development and outcome is poorly understood. We studied common polymorphisms in the genes of proinflammatory cytokines (IL6 rs1800795, IL8 rs4073, IL1B rs16944), anti-inflammatory cytokines (IL10 rs1800896, IL4 rs2243250, IL13 rs20541) and toll-like receptors (TLR2 rs5743708 and rs4696480, TLR4 rs4986791, TLR9 rs352139, rs5743836 and rs187084) in patients with community-acquired pneumonia (CAP) (390 cases, 203 controls) and nosocomial pneumonia (355 cases, 216 controls)...
October 11, 2016: Scientific Reports
Yuan Zong, Huali Zhang
Sepsis is a serious medical problem and is one of the main causes of high mortality in intensive care units. Fifty percent of patients with severe sepsis will develop acute lung injury (ALI). Amentoflavone (AMF) is a polyphenolic compound possessing potent anti-inflammatory activities. The study aimed to explore the protective effects of AMF against ALI in cecal ligation and puncture (CLP)-induced septic rats. The results showed that AMF administration protected against septic ALI, as reflected by marked amelioration of histological injury of lung tissues and decrease of pulmonary edema in CLP-treated rats...
October 8, 2016: Acta Biochimica Polonica
Liu Xianchu, Professor Zheng Lan, Li Qiufang, Liu Yi, Ruan Xiangcheng, Hou Wenqi, Ding Yang
Previous research has demonstrated that lipopolysaccharide (LPS) can induce sepsis and lead to myocardial dysfunction. Naringin has various biological activities in LPS-induced sepsis. In this study, our aim was to investigate the effects of Naringin on LPS-induced cardiac injury and clarify its potential mechanism. We found that in vivo treatment with Naringin significantly ameliorated body weight loss, and attenuated cardiac histopathological changes after LPS challenge. Furthermore, Naringin inhibited LPS-induced increase of TNF-α, IL-1β and IL-6 activities to alleviate inflammatory response in heart...
September 13, 2016: Environmental Toxicology and Pharmacology
Abderahim Gaceb, Luisa Vergori, M C Martinez, Ramaroson Andriantsitohaina
Microvesicles, small membrane vesicles released from cells, have beneficial and/or deleterious effects in sepsis. We previously reported that non-muscle myosin light chain kinase (nmMLCK) deletion protects mice against endotoxic shock by reducing inflammation. Here, we have evaluated the consequences of nmMLCK deletion on microvesicle phenotypes and their effects on mouse aortic endothelial cells in association with vascular inflammation and endothelial dysfunction during endotoxic shock induced by lipopolysaccharide in mice...
2016: Frontiers in Pharmacology
Tracey Ying, Samantha Chan, Stephen Lane, Christine Somerville
AIM: To identify risk factors for acute kidney injury following major orthopaedic surgery. METHODS: We included all patients undergoing major orthopaedic surgery at University Hospital Geelong between 2008 and 2014 in the study. Out of 2188 surgeries audited, we identified cases of acute kidney injury using the RIFLE criteria and matched those to controls 2:1 for age, sex, procedure and chronic kidney disease stage. We reviewed their records for risk factors of postoperative acute kidney injury, including medications such as gentamicin, diuretics, non-steroidal anti-inflammatory drugs and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use...
October 5, 2016: Nephrology
Silvia Cellone Trevelin, Célio Xavier Dos Santos, Raphael Gomes Ferreira, Larissa de Sá Lima, Rangel Leal Silva, Cristoforo Scavone, Rui Curi, José Carlos Alves-Filho, Thiago Mattar Cunha, Pérsio Roxo-Júnior, Maria-Célia Cervi, Francisco Rafael Martins Laurindo, John Stephen Hothersall, Andrew M Cobb, Min Zhang, Aleksandar Ivetic, Ajay M Shah, Lucia Rossetti Lopes, Fernando Queiroz Cunha
The reactive-oxygen-species-(ROS)-generating-enzyme Nox2 is essential for leukocyte anti-microbial activity. However its role in cellular redox homeostasis and, consequently, in modulating intracellular signaling pathways remains unclear. Herein, we show Nox2 activation favors thioredoxin-1 (TRX-1)/p40phox interaction, which leads to exclusion of TRX-1 from the nucleus. In contrast, the genetic deficiency of Nox2 or its pharmacological inhibition with apocynin (APO) results in reductive stress after lipopolysaccharide-(LPS)-cell stimulation, which causes nuclear accumulation of TRX-1 and enhanced transcription of inflammatory mediators through nuclear-factor-(NF)-κB...
October 4, 2016: Scientific Reports
Andriani C Patera, Anne M Drewry, Katherine Chang, Evan R Beiter, Dale Osborne, Richard S Hotchkiss
Sepsis is a heterogeneous syndrome comprising a highly diverse and dynamic mixture of hyperinflammatory and compensatory anti-inflammatory immune responses. This immune phenotypic diversity highlights the importance of proper patient selection for treatment with the immunomodulatory drugs that are entering clinical trials. To better understand the serial changes in immunity of critically ill patients and to evaluate the potential efficacy of blocking key inhibitory pathways in sepsis, we undertook a broad phenotypic and functional analysis of innate and acquired immunity in the same aliquot of blood from septic, critically ill nonseptic, and healthy donors...
September 26, 2016: Journal of Leukocyte Biology
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