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https://www.readbyqxmd.com/read/28538086/sphingosine-1-phosphate-receptor-1-agonist-sew2871-causes-severe-cardiac-side-effects-and-does-not-improve-microvascular-barrier-breakdown-in-sepsis
#1
Sven Flemming, Natalie Burkard, Michael Meir, Martin Alexander Schick, Christoph-Thomas Germer, Nicolas Schlegel
BACKGROUND: Endothelial barrier dysfunction is a hallmark in the pathogenesis of sepsis. Sphingosine-1-phosphate (S1P) has been proposed to be critically involved in the maintenance of endothelial barrier function predominately by activating S1P receptor-1 (S1P1). Previous studies have shown that the specific S1P1 agonist SEW2871 improves endothelial barrier function under inflammatory conditions. However, the effectiveness of SEW2871 and potential side effects remained largely unexplored in a clinically relevant model of sepsis...
May 23, 2017: Shock
https://www.readbyqxmd.com/read/28538085/circulating-heparan-sulfate-fragments-attenuate-histone-induced-lung-injury-independently-of-histone-binding
#2
Yanlin Zhang, Sarah M Haeger, Yimu Yang, Kyrie L Dailey, Joshay A Ford, Eric P Schmidt
Extracellular histones are cationic damage-associated molecular pattern molecules capable of directly inducing cellular injury via charge-mediated interactions with plasma membranes. Accordingly, histones released into the plasma during critical illness are known to contribute to the onset and propagation of lung injury. Vascular injury (with consequent degradation of the endothelial glycocalyx) simultaneously releases anionic heparan sulfate fragments (hexa- to octasaccharides in size) into the plasma. It is unknown whether this endogenous release of heparan sulfate fragments modulates charge-dependent histone cytotoxicity, or if exogenous heparan sulfate fragments could therapeutically attenuate histone-induced lung injury...
May 23, 2017: Shock
https://www.readbyqxmd.com/read/28538018/low-serum-angiopoietin-1-high-serum-angiopoietin-2-and-high-ang-2-ang-1-protein-ratio-are-associated-with-early-onset-sepsis-in-surinamese-newborns
#3
Rens Zonneveld, Rianne Jongman, Amadu Juliana, Wilco Zijlmans, Frans Plötz, Grietje Molema, Matijs van Meurs
PURPOSE: Vascular inflammation and leakage in sepsis is mediated by Angiopoietin-1 (Ang-1) and -2 (Ang-2) and their phosphorylation of the endothelial Tie-2 receptor. Levels of Ang-2 change in adults and children during sepsis, which is associated with severity of sepsis. This study investigates levels of Ang-1 and Ang-2 in newborns to gain insight in the vascular pathophysiology of early onset sepsis (EOS) within 72 hours after birth. METHODS: A prospective cohort study was performed amongst 71 Surinamese newborns treated with antibiotics for suspected EOS and 20 control newborns...
May 22, 2017: Shock
https://www.readbyqxmd.com/read/28520696/an-ovine-model-of-hyperdynamic-endotoxemia-and-vital-organ-metabolism
#4
Liam Byrne, Nchafatso G Obonyo, Sara Diab, Kimble Dunster, Margaret Passmore, Ai Ching Boon, Louise See Hoe, Karen Hay, Frank Van Haren, John-Paul Tung, Louise Cullen, Kiran Shekar, Kathryn Maitland, John F Fraser
BACKGROUND: Animal models of endotoxemia are frequently used to understand the pathophysiology of sepsis and test new therapies. However, important differences exist between commonly used experimental models of endotoxemia and clinical sepsis. Animal models of endotoxemia frequently produce hypodynamic shock in contrast to clinical hyperdynamic shock. This difference may exaggerate the importance of hypoperfusion as a causative factor in organ dysfunction. This study sought to develop an ovine model of hyperdynamic endotoxemia and assess if there is evidence of impaired oxidative metabolism in the vital organs...
May 17, 2017: Shock
https://www.readbyqxmd.com/read/28520695/calreticulin-ameliorates-hypoxia-reoxygenation-induced-human-microvascular-endothelial-cell-injury-by-inhibiting-autophagy
#5
You Wang, Tian-Qi Tao, Dan-Dan Song, Xiu-Hua Liu
BACKGROUND: Autophagy has been found to be involved in myocardial ischemia/reperfusion injury. However, the underlying mechanism and significance of autophagy in reperfusion injury remain unclear. Herein, we evaluated the effects of exogenous calreticulin (CRT) on autophagy in hypoxia/reoxygenation (H/R)-treated human microvascular endothelial cells (MECs). METHODS: Human MECs were pretreated with CRT (25 pg/mL) for 30 min, followed by exposure in an incubator filled with a gas mixture of 90% N2, 5% O2, and 5% CO2 for 8-h hypoxia...
May 17, 2017: Shock
https://www.readbyqxmd.com/read/28520694/metabolic-inflammatory-complex-in-sepsis-septic-cachexia-as-a-novel-potential-therapeutic-target
#6
Masao Kaneki
Despite several decades of focused investigation, sepsis remains a major cause of mortality in critically ill patients. Advancements in intensive care have enabled more patients to survive the acute phase of sepsis than previously, but a growing number of them progress to chronic critical illness. The failure of previous randomized clinical trials of anti-inflammatory agents to show any pro-survival benefit in septic patients underscores current thought that simple anti-inflammatory strategies are ineffective because the inhibitory effect of anti-inflammatory agents undermines the immune response to pathogens...
May 17, 2017: Shock
https://www.readbyqxmd.com/read/28509685/modelling-acute-traumatic-haemorrhagic-shock-injury-challenges-and-guidelines-for-preclinical-studies
#7
Jordi L Tremoleda, Sarah A Watts, Penny S Reynolds, Christoph Thiemermann, Karim Brohi
Trauma is responsible for a large proportion of the world's burden of disease, and is by far the biggest killer of young adults. Haemorrhage is the leading cause of preventable death and its effects are directly correlated with the incidence multi-organ failure in survivors. Trauma research is challenging due to patient heterogeneity, limited randomised controlled trials, and in vitro studies that fail to mimic the systemic injury response. Preclinical research remains essential for mechanistic and therapeutic discovery...
May 15, 2017: Shock
https://www.readbyqxmd.com/read/28509684/histone-complexed-dna-fragments-levels-are-associated-with-coagulopathy-endothelial-cell-damage-and-increased-mortality-after-severe-pediatric-trauma
#8
Robert T Russell, Sarah C Christiaans, Tate Nice, Morgan Banks, Vincent Mortellaro, Charity Morgan, Amy Duhachek-Stapelman, Steven J Lisco, Jeffrey D Kerby, Brant M Wagener, Mike K Chen, Jean-François Pittet
BACKGROUND: The release of damage-associated molecular pattern molecules (DAMPs) in the extracellular space secondary to injury has been shown to cause systemic activation of the coagulation system and endothelial cell damage. We hypothesized that pediatric trauma patients with increased levels of histone-complexed DNA fragments (hcDNA) would have evidence of coagulopathy and endothelial damage that would be associated with poor outcomes. METHODS: We conducted a prospective observational study of 149 pediatric trauma patients and 62 control patients at two level 1 pediatric trauma centers from 2013-2016...
May 15, 2017: Shock
https://www.readbyqxmd.com/read/28498300/volatile-decay-products-in-breath-during-peritonitis-shock-are-attenuated-by-enteral-blockade-of-pancreatic-digestive-proteases
#9
Frank A DeLano, Jason Chow, Geert W Schmid-Schönbein
There is a need to develop markers for early detection of organ failure in shock that can be non-invasively measured at point of care. We explore here the use of volatile organic compounds (VOCs) in expired air in a rat peritonitis shock model. Expired breath samples were collected into Tedlar gas bags and analyzed by standardized gas chromatography. The gas chromatograms were digitally analyzed for presence of peak amounts over a range of Kovach indices. Following the induction of peritonitis, selected volatile compounds were detected within about one hour, which remained at elevated amounts over a 6 hours observation period...
May 11, 2017: Shock
https://www.readbyqxmd.com/read/28498299/machine-learning-for-predicting-outcomes-in-trauma
#10
Nehemiah T Liu, Jose Salinas
To date, there are no reviews on machine learning (ML) for predicting outcomes in trauma. Consequently, it remains unclear as to how ML-based prediction models compare in the triage and assessment of trauma patients. The objective of this review was to survey and identify studies involving ML for predicting outcomes in trauma, with the hypothesis that models predicting similar outcomes may share common features but the performance of ML in these studies will differ greatly. MEDLINE and other databases were searched for studies involving trauma and ML...
May 11, 2017: Shock
https://www.readbyqxmd.com/read/28498298/hydrogen-sulfide-a-potential-novel-therapy-for-the-treatment-of-ischemia
#11
Amanda R Jensen, Natalie A Drucker, Sina Khaneki, Michael J Ferkowicz, Mervin C Yoder, Eric R DeLeon, Kenneth R Olson, Troy A Markel
Hydrogen sulfide (H2S) is a novel signaling molecule most recently found to be of fundamental importance in cellular function as a regulator of apoptosis, inflammation, and perfusion. Mechanisms of endogenous H2S signaling are poorly understood, however, signal transmission is thought to occur via persulfidation at reactive cysteine residues on proteins. Although much has been discovered about how H2S is synthesized in the body, less is known about how it is metabolized. Recent studies have discovered a multitude of different targets for H2S therapy, including those related to protein modification, intracellular signaling, and ion channel depolarization...
May 11, 2017: Shock
https://www.readbyqxmd.com/read/28498297/gastrointestinal-colonization-of-candida-albicans-increases-serum-1%C3%A2-3-%C3%AE-d-glucan-without-candidemia-and-worsens-cecal-ligation-and-puncture-sepsis-in-murine-model
#12
Wimonrat Panpetch, Naraporn Somboonna, Dewi Embong Bulan, Jiraphorn Issara-Amphorn, Navaporn Worasilchai, Malcolm Finkelman, Ariya Chindamporn, Tanapat Palaga, Somying Tumwasorn, Asada Leelahavanichkul
The role of intestinal Candida albicans in bacterial sepsis, in the absence of candidemia, was investigated in murine models. Live C. albicans or normal saline solution (NSS) was administered orally once, followed by 5 days of daily oral antibiotic-mixtures (ATB). Cecal ligation and puncture (CLP) was then performed to induce sepsis.Fecal Candida was detected by culture only in models with Candida administration. Oral Candida administration with/without ATB enhanced gut-pathogenic bacteria as determined by microbiome analysis...
May 11, 2017: Shock
https://www.readbyqxmd.com/read/28498296/interleukin-22-prevents-microbial-dysbiosis-and-promotes-intestinal-barrier-regeneration-following-acute-injury
#13
Adam M Hammer, Niya L Morris, Abigail R Cannon, Omair M Khan, Robin C Gagnon, Nellie V Movtchan, Ilse van Langeveld, Xiaoling Li, Bin Gao, Mashkoor A Choudhry
Intestine barrier disruption and bacterial translocation can contribute to sepsis and multiple organ failure- leading causes of mortality in burn-injured patients. Additionally, findings suggest ethanol (alcohol) intoxication at the time of injury worsens symptoms associated with burn injury. We have previously shown that interleukin-22 (IL-22) protects from intestinal leakiness and prevents overgrowth of Gram-negative bacteria following ethanol and burn injury, but how IL-22 mediates these effects has not been established...
May 11, 2017: Shock
https://www.readbyqxmd.com/read/28498295/epidemiology-of-anaphylactic-shock-and-its-related-mortality-in-hospital-patients-in-taiwan-a-nationwide-population-based-study
#14
Fu-Chao Liu, Hung-Jr Chiou, Chang-Fu Kuo, Ting-Ting Chung, Huang-Ping Yu
Anaphylactic shock is potentially life-threatening. However, there is a paucity of data about its incidence and associated mortality, particularly in Asian populations. We aimed to investigate the epidemiology of anaphylactic shock and its related mortality after the hospitalization of patients in the general population of Taiwan. The National Health Insurance Research Database was used to identify patients with anaphylactic shock and estimate its incidence for inpatients sampled from 2005 to 2012. The pattern of anaphylactic shock and anaphylactic shock-related mortality rate was also examined...
May 11, 2017: Shock
https://www.readbyqxmd.com/read/28498294/target-serum-sodium-levels-during-intensive-care-unit-management-of-aneurysmal-subarachnoid-hemorrhage
#15
Tomoya Okazaki, Toru Hifumi, Kenya Kawakita, Hajime Shishido, Daisuke Ogawa, Masanobu Okauchi, Atsushi Shindo, Masahiko Kawanishi, Takashi Tamiya, Yasuhiro Kuroda
INTRODUCTION: Dysnatremia commonly occur in the intensive care unit (ICU)- management of patients with aneurysmal subarachnoid hemorrhage (SAH). However, detailed management strategies have not been provided even by current guidelines. The purposes of this study were to examine the association of abnormal serum sodium levels with unfavorable neurologic outcomes and to identify the target range of serum sodium in patients with SAH. METHODS: We retrospectively reviewed all patients who were consecutively hospitalized with a confirmed diagnosis of SAH between January 2009 and December 2015...
May 11, 2017: Shock
https://www.readbyqxmd.com/read/28492385/the-prognostic-value-of-central-venous-to-arterial-co2-difference-arterial-central-venous-o2-difference-ratio-in-septic-shock-patients-with-central-venous-o2-saturation-%C3%A2-80
#16
Huaiwu He, Yun Long, Dawei Liu, Xiaoting Wang, Bo Tang
BACKGROUND: It is a great challenge for physician to assess the relationship between O2 delivery and O2 consumption in septic shock patients with high ScvO2. Recently, the venous-to-arterial CO2 difference/arterial-central venous O2 difference ratio (P(v-a)CO2/C(a-v)O2) has shown potential for reflecting anaerobic metabolism. Therefore, we evaluated the value of using the P(v-a)CO2/C(a-v)O2 ratio to predict mortality and assess anaerobic metabolism in septic shock patients with high ScvO2 (≥ 80%)...
May 10, 2017: Shock
https://www.readbyqxmd.com/read/28489728/novel-adjunct-drugs-reverse-endothelial-glycocalyx-damage-after-hemorrhagic-shock-in-rats
#17
Ivo P Torres Filho, Luciana N Torres, Christi Salgado, Michael A Dubick
INTRODUCTION: There is interest in the small-volume therapeutic use of adjunct drugs for treating hemorrhagic shock (HS). However, critical information is only partially available on mechanisms of action of promising compounds such as adenosine-lidocaine-Magnesium (ALM), beta-hydroxybutyrate plus melatonin (BHB/M), and poloxamer 188 (P-188). Therefore, we tested the hypothesis that these adjuncts would reverse HS-induced damage to microvascular endothelial glycocalyx and hemodynamics...
May 9, 2017: Shock
https://www.readbyqxmd.com/read/28481840/age-shock-index-is-superior-to-shock-index-and-modified-shock-index-for-predicting-long-term-prognosis-in-acute-myocardial-infarction
#18
Tongtong Yu, Chunyang Tian, Jia Song, Dongxu He, Zhijun Sun, Zhaoqing Sun
BACKGROUND: Shock index (SI) has been reported to help us predict adverse prognosis in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). However, the prognostic value of age SI and modified shock index (MSI) in AMI undergoing PCI is unknown. Moreover, the prognostic performance of admission age SI is not compared with SI, MSI and the Global Registry of Acute Coronary Events (GRACE) risk score. METHODS: 1,864 AMI patients undergoing PCI were analyzed in a retrospective cohort study...
May 5, 2017: Shock
https://www.readbyqxmd.com/read/28472014/protection-by-the-eph-ephrin-system-against-mesenteric-ischemia-reperfusion-injury
#19
Valentina Vivo, Irene Zini, Anna Maria Cantoni, Andrea Grandi, Massimiliano Tognolini, Riccardo Castelli, Vigilio Ballabeni, Simona Bertoni, Elisabetta Barocelli
Mesenteric ischemia-reperfusion (I/R)-induced injury targets primarily endothelial and epithelial cells, leading to a cascade of inflammatory events, eventually culminating in life-threatening syndromes. Hitherto, the role of Eph, the largest family of tyrosine kinase receptors, and of their cell-bound ephrin ligands, whose interaction generates a bidirectional signaling, is still debated in I/R injury. The aim of the present work was therefore to investigate the effects produced by unidirectional activation of forward signaling (administration of chimeric protein ephrinA1-Fc), of reverse signaling (EphA2-Fc), or inhibition of both signals (monomeric EphA2 and the protein-protein interaction inhibitor UniPR1331) on the local and systemic inflammatory responses triggered by mesenteric I/R in mice...
May 2, 2017: Shock
https://www.readbyqxmd.com/read/28472013/reoxygenation-with-100-oxygen-following-hypoxia-in-mice-causes-apoptosis
#20
Yoshiro Nishimura, Masaaki Ueki, Masaki Imanishi, Shuhei Tomita, Masaki Ueno, Jun Morishita, Takashi Nishiyama
After hypoxia, reoxygenation with air is the consensus treatment for full-term neonates; however, the effect of hyperoxic reoxygenation of adults is unknown. The present study was designed to investigate the effects of reoxygenation with 100% oxygen after hypoxia on inflammation and apoptosis in mice. Eight-week-old mice were either subjected to hypoxia in 8% oxygen for 30 min or air served as controls. Following hypoxia, mice underwent reoxygenation for 30 min with 21% or 100% oxygen. Tumour Necrosis Factor-α (TNF-α), Interleukin-1β (IL-1β), caspase-3 and Brain Derived Neurotrophic Factor (BDNF) mRNA study and histopathological study were performed...
May 2, 2017: Shock
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