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https://www.readbyqxmd.com/read/29351405/acute-down-regulation-of-mir-199a-attenuates-sepsis-induced-acute-lung-injury-by-targeting-sirt1
#1
Yang Liu, Hao Guan, Ju-Lei Zhang, Zhao Zheng, Hong-Tao Wang, Ke Tao, Shi-Chao Han, Lin-Lin Su, Dahai Hu
MiR-199a is a novel gene regulator with an important role in inflammation and lung injury. However, its role in the pathogenesis of sepsis-induced acute respiratory distress syndrome (ARDS) is currently unknown. Our study explored the role of miR-199a in sepsis-induced ARDS and its mechanism of action. First, we found that LPS could up-regulate miR-199a in alveolar macrophages. Down-regulation of miR-199a inhibited the up-regulation of inflammatory cytokines in alveolar macrophages and induced the remission of histopathologic changes, the reduction of pro-inflammatory cytokines, and the up-regulation of apoptosis protein expression in an ARDS lung, showing a protective role for miR-199a...
January 10, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29350381/macrophage-migration-inhibitory-factor-knockout-attenuates-endotoxin-induced-cardiac-dysfunction-in-mice
#2
Jie Zhang, Xin Zhang, Yuqi Cui, Lianqun Cui, Peng Zhao
BACKGROUND: The accumulated evidence suggests that macrophage migration inhibitory factor (MIF) plays a key role not only in acute and chronic inflammatory diseases but also in cardiovascular disease. The cardiac dysfunction is related to lipopolysaccharide (LPS) in sepsis. AIM: This study was designed to examine whether MIF mediates LPS-induced cardiac dysfunction and address the mechanisms. METHODS: Echocardiography, immunohistochemical analysis, cell shortening/relengthening and intracellular Ca2+ fluorescence evaluation were performed in whole hearts and isolated cardiomyocytes from C57 and MIF knockout mice treated with or without LPS...
January 19, 2018: Kardiologia Polska
https://www.readbyqxmd.com/read/29346034/coagulopathy-in-severe-sepsis-interconnectivity-of-coagulation-and-the-immune-system
#3
Jason M Samuels, Hunter B Moore, Ernest E Moore
BACKGROUND: Disseminated intravascular coagulation (DIC) remains a challenging complication of infection with inadequate treatment and significant morbidity and mortality rates. METHODS: Review of the English-language literature. RESULTS: Disseminated intravascular coagulation arises from the immune system's response to microbial invasion, as well as the byproducts of cell death that result from severe sepsis. This response triggers the coagulation system through an interconnected network of cellular and molecular signals, which developed originally as an evolutionary mechanism intended to isolate micro-organisms via fibrin mesh formation...
January 18, 2018: Surgical Infections
https://www.readbyqxmd.com/read/29344053/an-overview-of-exposure-to-ethanol-containing-substances-and-ethanol-intoxication-in-children-based-on-three-illustrated-cases
#4
REVIEW
Kam Lun Hon, Alexander Kc Leung, Eddie Cheung, Bryan Lee, Michelle Mc Tsang, Alcy R Torres
Alcohol addiction and intoxication are major health problems worldwide. Acute alcohol intoxication is well reported in adults and adolescents but less frequently reported in children of younger ages. We report three anonymized cases of pediatric ethanol exposure and illustrate the different mechanisms of intoxication. In all cases, a focused history is the key to prompt diagnosis and timely management. Physicians should be aware of this potential poison in children presented with acute confusional or encephalopathic state...
2018: Drugs in Context
https://www.readbyqxmd.com/read/29344006/histone-deacetylase-2-hdac2-attenuates-lipopolysaccharide-lps-induced-inflammation-by-regulating-pai-1-expression
#5
Wen-Feng Fang, Yu-Mu Chen, Chiung-Yu Lin, Hui-Lin Huang, Hua Yeh, Ya-Ting Chang, Kuo-Tung Huang, Meng-Chih Lin
Background: Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection, and is primarily characterized by an uncontrolled systemic inflammatory response. In the present study, we developed an effective adjunct therapy mediated by a novel mechanism, to attenuate overt inflammation. LPS-treated macrophages were adopted as an in vitro model of endotoxin-induced inflammation during sepsis. Experiments were carried out using primary mouse peritoneal macrophages and the murine macrophage cell line RAW264...
2018: Journal of Inflammation
https://www.readbyqxmd.com/read/29343648/par1-agonists-stimulate-apc-like-endothelial-cytoprotection-and-confer-resistance-to-thromboinflammatory-injury
#6
Karen De Ceunynck, Christian G Peters, Abhishek Jain, Sarah J Higgins, Omozuanvbo Aisiku, Jennifer L Fitch-Tewfik, Sharjeel A Chaudhry, Chris Dockendorff, Samir M Parikh, Donald E Ingber, Robert Flaumenhaft
Stimulation of protease-activated receptor 1 (PAR1) on endothelium by activated protein C (APC) is protective in several animal models of disease, and APC has been used clinically in severe sepsis and wound healing. Clinical use of APC, however, is limited by its immunogenicity and its anticoagulant activity. We show that a class of small molecules termed "parmodulins" that act at the cytosolic face of PAR1 stimulates APC-like cytoprotective signaling in endothelium. Parmodulins block thrombin generation in response to inflammatory mediators and inhibit platelet accumulation on endothelium cultured under flow...
January 17, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29343555/antagonism-of-integrin-cd11b-affords-protection-against-endotoxin-shock-and-polymicrobial-sepsis-via-attenuation-of-hmgb1-nucleocytoplasmic-translocation-and-extracellular-release
#7
Huiting Zhou, Yanhong Li, Huan Gui, He Zhao, Ming Wu, Gang Li, Yiping Li, Zhenjiang Bai, Zhimin Yin, H Paul Redmond, Jian Wang, Jiang Huai Wang, Zhihui Zhao
High mobility group box 1 (HMGB1), a chromatin-binding nuclear protein, plays a critical role in sepsis by acting as a key "late-phase" inflammatory mediator. Integrin CD11b is essential for inflammatory cell activation and migration, thus mediating inflammatory responses. However, it is unclear whether CD11b participates in the development of sepsis. In this study, we report that CD11b contributes to LPS-induced endotoxin shock and microbial sepsis, as antagonism of CD11b with the CD11b blocking Ab or CD11b inhibitor Gu-4 protects mice against LPS- and microbial sepsis-related lethality, which is associated with significantly diminished serum HMGB1 levels...
January 17, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29343482/par1-biased-signaling-is-required-for-activated-protein-c-in-vivo-benefits-in-sepsis-and-stroke
#8
Ranjeet K Sinha, Yaoming Wang, Zhen Zhao, Xiao Xu, Laurent Burnier, Naveen Gupta, José A Fernandez, Greg Martin, Sergey Kupriyanov, Laurent O Mosnier, Berislav V Zlokovic, John H Griffin
Activated Protein C (APC) cleaves protease activated receptor (PAR)1 in vitro at R46 to initiate beneficial cell signaling; however, thrombin and APC can cleave at R41. To elucidate PAR1-dependent aspects of pharmacologic APC's in vivo mechanisms, we generated C57BL/6 mouse strains carrying QQ41 or QQ46 point mutations in PAR1 (F2r gene). Using these strains, we determined whether or not recombinant murine signaling-selective APC mutants would reduce septic death or provide neuroprotection against ischemic stroke when mice carried PAR1 homozygous mutations that prevent cleavage at either R41 or R46...
January 17, 2018: Blood
https://www.readbyqxmd.com/read/29343292/global-trends-in-the-awareness-of-sepsis-insights-from-search-engine-data-between-2012-and-2017
#9
Craig S Jabaley, James M Blum, Robert F Groff, Vikas N O'Reilly-Shah
BACKGROUND: Sepsis is an established global health priority with high mortality that can be curtailed through early recognition and intervention; as such, efforts to raise awareness are potentially impactful and increasingly common. We sought to characterize trends in the awareness of sepsis by examining temporal, geographic, and other changes in search engine utilization for sepsis information-seeking online. METHODS: Using time series analyses and mixed descriptive methods, we retrospectively analyzed publicly available global usage data reported by Google Trends (Google, Palo Alto, CA, USA) concerning web searches for the topic of sepsis between 24 June 2012 and 24 June 2017...
January 17, 2018: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/29341864/comparison-of-acute-kidney-injury-of-different-aetiology-reveals-in-common-mechanisms-of-tissue-damage
#10
Michael Hultström, Mediha Becirovic-Agic, Sofia Jönsson
Acute kidney injury (AKI) is a syndrome of reduced glomerular filtration rate (GFR) and urine production caused by a number of different diseases. It is associated with renal tissue damage. This tissue damage can cause tubular atrophy and interstitial fibrosis that leads to nephron loss and progression of chronic kidney disease (CKD). This review describes the in-common mechanisms behind tissue damage in AKI caused by different underlying diseases. Comparing six high-quality microarray studies of renal gene expression after AKI in disease models (gram-negative sepsis, gram-positive sepsis, ischemia-reperfusion, malignant hypertension, rhabdomyolysis and cisplatin toxicity) identified 5254 differentially expressed genes in at least one of the AKI models...
December 20, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/29339458/co-association-between-group-b-streptococcus-and-candida-albicans-promotes-interactions-with-vaginal-epithelium
#11
Grace R Pidwill, Sara Rego, Howard F Jenkinson, Richard J Lamont, Angela H Nobbs
Group B Streptococcus (GBS) is a leading cause of neonatal sepsis, pneumonia and meningitis worldwide. In the majority of cases, GBS is transmitted vertically from mother to neonate, making maternal vaginal colonisation a key risk factor for neonatal disease. The fungus Candida albicans is an opportunistic pathogen of the female genitourinary tract, and the causative agent of vaginal thrush. Carriage of C. albicans has been shown to be an independent risk factor for vaginal colonisation by GBS. However, the nature of interactions between these two microbes is poorly understood...
January 16, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29339423/immune-protection-against-lethal-fungal-bacterial-intra-abdominal-infections
#12
Elizabeth A Lilly, Melanie Ikeh, Evelyn E Nash, Paul L Fidel, Mairi C Noverr
Polymicrobial intra-abdominal infections (IAIs) are clinically prevalent and cause significant morbidity and mortality, especially those involving fungi. Our laboratory developed a mouse model of IAI and demonstrated that intraperitoneal inoculation with Candida albicans or other virulent non-albicans Candida (NAC) species plus Staphylococcus aureus resulted in 70 to 80% mortality in 48 to 72 h due to robust local and systemic inflammation (sepsis). Surprisingly, inoculation with Candida dubliniensis or Candida glabrata with S...
January 16, 2018: MBio
https://www.readbyqxmd.com/read/29332515/vasoplegia-in-patients-with-sepsis-and-septic-shock-pathways-and-mechanisms
#13
A-M Burgdorff, M Bucher, J Schumann
Sepsis is one of the most frequent causes of death among patients in intensive care units. Many therapeutic strategies have been assessed without the desired success rates. A key risk factor for death is hypotension due to vasodilatation with vascular hyposensitivity. However, the pathways underlying this process remain unclear. Endotoxemia induces inflammatory mediators, and this is followed by vasoplegia and decreased cardiac contractility. Although inhibition of these mediators diminishes mortality rates in animal models, this phenomenon has not been confirmed in humans...
January 1, 2018: Journal of International Medical Research
https://www.readbyqxmd.com/read/29329913/predicting-extubation-outcomes-a-model-incorporating-heart-rate-characteristics-index
#14
Nitin Goel, Mallinath Chakraborty, William John Watkins, Sujoy Banerjee
OBJECTIVE: To test the hypothesis that in neonates on mechanical ventilation, heart rate characteristics index (HRCi) can be combined with a clinical model for predicting extubation outcomes in neonates. STUDY DESIGN: HRCi and clinical data for all intended intubation-extubation events (episodes) were retrospectively analyzed between June 2014 and January 2015. Each episode started 6 hours pre-extubation or at the time of primary intubation if ventilation duration was shorter than 6 hours (baseline)...
January 10, 2018: Journal of Pediatrics
https://www.readbyqxmd.com/read/29327977/status-and-challenges-of-predicting-and-diagnosing-sepsis-in-burn-patients
#15
Mile Stanojcic, Roohi Vinaik, Marc G Jeschke
Burns are a common form of trauma that account for more than 300,000 deaths each year worldwide. Survival rates have improved over the past decades because of improvements in nutritional and fluid support, burn wound care, and infection control practices. Death, however, remains unacceptably high. The primary cause of death has changed over the last decades from anoxic causes to now predominantly infections and sepsis. Sepsis and septic complications are not only major contributors to poor outcomes, but they further result in longer hospital stay and higher healthcare costs...
January 12, 2018: Surgical Infections
https://www.readbyqxmd.com/read/29327516/cardiac-biomarkers-and-myocardial-dysfunction-in-septicemia
#16
Deep Chandh Raja, Sanjay Mehrotra, Avinash Agrawal, Abhishek Singh, Kamlesh Kumar Sawlani
Objectives: Cardiac biomarkers have been studied in sepsis in the past and various mechanisms for their rise have been elucidated. However their association with severity of sepsis, mortality and myocardial dysfunction warrants further studies. We have studied three different cardiac biomarkers- troponin T (trop T), creatine phosphokinase MB isoform (CPK MB) and NT pro brain natriuretic peptide (NT Pro BNP) in patients with septicemia. We have attempted to observe the levels of these biomarkers in sepsis, their individual abilities to predict the severity of sepsis, mortality and association with myocardial dysfunction noted in echocardiography...
December 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/29327282/ziziphus-spina-christi-leaf-extract-pretreatment-inhibits-liver-and-spleen-injury-in-a-mouse-model-of-sepsis-via-anti-oxidant-and-anti-inflammatory-effects
#17
Mohamed A Dkhil, Saleh Al-Quraishy, Ahmed E Abdel Moneim
Sepsis is a systemic response to infection that can result in acute hepatic and splenic damage. Ziziphus spina-christi (L.) is a wild tree used as a medicinal plant by ancient Egyptians. However, little is known about the mechanism underlying its effects on sepsis. The current study investigated the protective effects of a Z. spina-christi leaf extract (ZSCLE) on liver and spleen damage in a male C57BL/6 mouse model of sepsis, induced by cecal ligation and puncture (CLP). Prior to CLP, ZSCLE was administered daily for five consecutive days via oral gavage at doses of 100, 200, or 300 mg/kg...
January 11, 2018: Inflammopharmacology
https://www.readbyqxmd.com/read/29325753/induced-hypothermia-in-patients-with-septic-shock-and-respiratory-failure-cass-a-randomised-controlled-open-label-trial
#18
Theis Skovsgaard Itenov, Maria Egede Johansen, Morten Bestle, Katrin Thormar, Lars Hein, Louise Gyldensted, Anne Lindhardt, Henrik Christensen, Stine Estrup, Henrik Planck Pedersen, Matthew Harmon, Uday Kant Soni, Silvia Perez-Protto, Nicolai Wesche, Ulrik Skram, John Asger Petersen, Thomas Mohr, Tina Waldau, Lone Musaeus Poulsen, Ditte Strange, Nicole P Juffermans, Daniel I Sessler, Else Tønnesen, Kirsten Møller, Dennis Karsten Kristensen, Alessandro Cozzi-Lepri, Jens D Lundgren, Jens-Ulrik Jensen
BACKGROUND: Animal models of serious infection suggest that 24 h of induced hypothermia improves circulatory and respiratory function and reduces mortality. We tested the hypothesis that a reduction of core temperature to 32-34°C attenuates organ dysfunction and reduces mortality in ventilator-dependent patients with septic shock. METHODS: In this randomised, controlled, open-label trial, we recruited patients from ten intensive care units (ICUs) in three countries in Europe and North America...
January 8, 2018: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/29324628/ulinastatin-protects-against-lps-induced-acute-lung-injury-by-attenuating-tlr4-nf-%C3%AE%C2%BAb-pathway-activation-and-reducing-inflammatory-mediators
#19
Chao Cao, Chengfen Yin, Songtao Shou, Jun Wang, Lechang Yu, Xuening Li, Yanfen Chai
Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), remain the leading causes of morbidity and mortality in intensive care units. Ulinastatin (UTI), a serine protease inhibitor, possesses anti-inflammatory properties and has been suggested to modulate lipopolysaccharide (LPS)-induced sepsis; thus, it is now widely used in the treatment of pancreatitis, sepsis, and septic shock. Toll-like receptor 4 (TLR4), an essential LPS signaling receptor, plays a critical role in the activation of innate immunity...
January 10, 2018: Shock
https://www.readbyqxmd.com/read/29324626/vascular-effects-of-adrenomedullin-and-the-anti-adrenomedullin-antibody-adrecizumab-in-sepsis
#20
Christopher Geven, Andreas Bergmann, Matthijs Kox, Peter Pickkers
Sepsis remains a major scientific and medical challenge, for which, apart from significant refinements in supportive therapy, treatment has barely changed over the last few decades. During sepsis, both vascular tone and vascular integrity are compromised, and contribute to the development of shock. The free circulating peptide adrenomedullin (ADM) is involved in regulation of the endothelial barrier function and tone of blood vessels. Several animal studies have shown that ADM administration improves outcome of sepsis...
January 10, 2018: Shock
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