scholarly journals Effects of Long Chain Omega-3 Fatty Acid Supplementation on the Lipoprotein Oxylipin Response to an Inflammatory Challenge in Humans (P08-127-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Rachel Walker ◽  
Chesney Richter ◽  
Ann Skulas-Ray ◽  
Penny Kris-Etherton ◽  
Gordon Jensen ◽  
...  
Keyword(s):  
Repeated Measures ◽  
Inflammatory Responses ◽  
Ethyl Esters ◽  
Time Dependent ◽  
Omega 3 ◽  
Endotoxin Challenge ◽  
State College ◽  
Funding Sources ◽  
Lps Challenge ◽  
Penn State

Abstract Objectives Oxylipins are derived from polyunsaturated fatty acids (PUFAs) and mediate inflammatory responses, but the time-dependent response of oxylipins to an acute inflammatory challenge in humans is unknown. Although omega-3 acid ethyl esters (O3EEs) reduce plasma triglycerides, it is unclear whether they alter the response of oxylipins in triglyceride rich lipoproteins (TGRLs). We investigated the effect of 3.4 g/d O3EEs on the oxylipin response to an inflammatory challenge. Methods Healthy young men (N = 16) received either placebo or 3.4 g/d O3EEs for 8–12 weeks in a crossover study design. After each treatment period, subjects underwent a low-dose endotoxin challenge (0.6 ng lipopolysaccharide (LPS)/kg body weight). Plasma samples were collected at baseline and 1, 2, 4, 8, 24, 48, 72, and 168 hours after LPS injection. TGRLs were separated from plasma, and esterified oxylipins were hydrolyzed and quantified by LC-MS/MS. Changes over time were assessed by the use of mixed models with repeated measures. Data is reported as mean (95% CI). Results The peak total oxylipin response occurred at 4 hours after LPS injection, with the exception of hydroxyeicosatetraenoic acids (HETEs). Regardless of treatment, the peak concentration of HETEs occurred at 2 hours. This timing differed from that of hydroxyoctadecadienoic acids (HODEs), which peaked at 4 hours (P = 0.004). Of the omega-3 derived oxylipins, O3EE treatment significantly increased hydroxyeicosapentaenoic acids (HEPEs) by 356% (133%, 792%), hydroxydocosahexaenoic acids (HDoHEs) by 172% (34%, 452%), and epoxydocosapentaeinoic acids (EpDPEs) by 316% (76%, 887%) compared to placebo at 4 hours after LPS challenge (P < 0.007). Additionally, O3EE treatment also significantly altered the timing of the HEPE response (pinteraction = 0.004). Conclusions The time-dependent TGRL oxylipin response to inflammatory challenge differs according to oxylipin class, and the timing and magnitude of the response can be altered by O3EE treatment. This is may be a molecular explanation of the anti-inflammatory and pro-resolving effects of O3EEs. Funding Sources Pronova BioPharma; Penn State Clinical & Translational Research Institute, NIH/NCATS Grant # UL1 TR000127; Penn State College of Health and Human Development. Supporting Tables, Images and/or Graphs

PSXV-27 Late-Breaking: Evaluation of antioxidant capacity in receiving beef calves challenged with lipopolysaccharide (LPS)

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 381-382
Author(s):  
Samantha N Barker ◽  
Treylr Jackson ◽  
John Richeson ◽  
Jeff A Carroll ◽  
Nicole C Burdick-Sanchez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Capacity ◽  
Repeated Measures ◽  
Colorimetric Assay ◽  
Post Challenge ◽  
Antioxidant Power ◽  
Blood Samples ◽  
Endotoxin Challenge ◽  
Beef Calves ◽  
Lps Challenge

Abstract The objective of this study was to evaluate antioxidant capacity in plasma of beef calves challenged with LPS. Following an initial feeding period of 40 d, steers (n = 32; 379 kg ± 30.7) were transported to the Livestock Issues Research Unit’s Bovine Immunology Research and Development Complex and challenged intravenously with LPS (0.25 µg/kg BW) on d 41. Blood samples were collected via jugular catheter at -2, 0, 2, 4, 6, 8, 10, 12, 18, 24, 36 and 48 h relative to the LPS challenge at 0 h. Blood samples were processed to isolate plasma for indicators of oxidative stress with a colorimetric assay to determine ferric reducing antioxidant power (FRAP) values via concentration of ferrous iron (µM). Data were analyzed as repeated measures using the GLIMMIX procedure of SAS. Antioxidant values did vary with time (P &lt; 0.001) being greater (P &lt; 0.05) at -2, 0, 2, 36, and 48 h. Antioxidant capacity was reduced at 6 and 8 h (P &lt; 0.05), with the least FRAP value observed at 8 h post-challenge. Antioxidant capacity increased (P &lt; 0.05) again at 10 h, showing similar (P &gt; 0.05) concentrations to those observed at 4 h. By 24 h post-challenge, plasma FRAP values increased (P &lt; 0.05) similar to initial values at -2, 0, and 2 h. It can be inferred that oxidative stress contributes to reduced antioxidant capacity, ultimately interfering with animal growth and productivity. While these values reflect the oxidative stress response to an acute endotoxin challenge, and a subsequent recovery returning to homeostasis within 24 to 48 h, they may also correlate with other physiological and immunological indicators associated with an acute endotoxin challenge.

Abstract 482: Peroxisome Proliferator-Activated Receptor α Modulation with Fenofibrate Does Not Alter the Clinical or Inflammatory Responses to Evoked Endotoxemia in Humans

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Claire K Mulvey ◽  
Jane F Ferguson ◽  
Karen Terembula ◽  
Jennifer Tabita-Martinez ◽  
Rhia Shah ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Low Grade ◽  
Peroxisome Proliferator ◽  
Omega 3 ◽  
Acute Phase Reactants ◽  
Peroxisome Proliferator Activated Receptor ◽  
Amyloid A ◽  
Healthy Humans ◽  
Lps Challenge

Introduction: Inflammation plays a crucial role in the pathophysiology of cardiometabolic disease. Some experimental data and clinical trials suggest that PPAR-α activation and fibrate therapy suppress inflammation in humans, potentially promoting anti-atherogenic actions. Human experimental endotoxemia provides a controlled model for the study of atherogenic inflammatory responses and their modulation in vivo . We hypothesized that fenofibrate would suppress the inflammatory responses to endotoxin (LPS) in healthy humans. Methods: In the Fenofibrate and Omega-3 Fatty Acid Modulation of Endotoxemia study, 36 healthy volunteers (mean age 26 ± 7 years; mean BMI 24 ± 3 kg/m 2 ; 56% male; 72% Caucasian, 19% African, 8% Asian ancestry) were randomized to fenofibrate 145 mg or placebo daily. After 8 weeks of treatment, subjects underwent a low-dose LPS challenge (0.6 ng/kg intravenous bolus). Anthropometric, clinical, and blood measures were collected at baseline, pre-LPS, and serially for 24 hours after LPS exposure. Results: Compared to placebo, fenofibrate reduced total cholesterol (170 ± 35 to 137 ± 31 mg/dL, p=0.009) and tended to decrease triglycerides (78 ± 40 to 57 ± 23 mg/dL, p=0.611) prior to LPS. LPS induced a modest clinical response with increased temperature, heart rate, and blood pressure ( p <0.001 for all). Cytokines and chemokines increased significantly, peaking 2 to 4 hours post-LPS (TNFα 12-fold, IL-6 13-fold, IL-10 9-fold, MCP-1 10-fold; p <0.001 for all). Acute phase reactants also increased, peaking at 24 hours (serum amyloid A (SAA) 14-fold, C-reactive protein (CRP) 9-fold; both p <0.001). Compared to placebo, fenofibrate had no effect on LPS-induced clinical responses, cytokine or chemokine release as measured by peak response or area under the curve (AUC). Fenofibrate also had no effect on plasma CRP or lipid parameters following LPS. Although peak SAA and SAA AUC tended to be lower with fenofibrate vs. placebo, the differences were not statistically significant ( p =0.08 for both). Conclusions: PPAR-α modulation with fenofibrate did not attenuate clinical or inflammatory responses during low-grade human endotoxemia. These data suggest the anti-inflammatory properties of fenofibrate at clinically-relevant dosing are limited.

181 Utilization of the Nutrack Livestock Monitoring System to Identify Changes in General and Spatial Behaviors of Newly Weaned Nursery Exposed to an Endotoxin Challenge

2021 ◽  
Vol 99 (Supplement_1) ◽  
pp. 2-2
Author(s):  
Aaaron J Holliday ◽  
Benny E Mote ◽  
Eric Psota ◽  
Lindsey E Hulbert ◽  
Majid Jaberi-Douraki ◽  
...  
Keyword(s):  
Repeated Measures ◽  
Data Capture ◽  
Continuous Data ◽  
Saline Injection ◽  
Treatment Control ◽  
Weaned Pigs ◽  
Endotoxin Challenge ◽  
E Coli ◽  
Lps Challenge ◽  
Spatial Behaviors

Abstract Incorporation of precision livestock technology has the potential to provide swine producers with the means to rapidly and accurately identify immune-compromised pigs, allowing for accurate and timely interventions. The objective of this study was to utilize the NUtrack System (NUtrack) to identify changes in general (lying, standing and sitting) and spatial behaviors (at the feeder and meters/day) of newly weaned pigs exposed to a lipopolysaccharide (LPS) challenge. To achieve this objective, 12 nursery pens with 192 weaned pigs (16 pigs/pen) were randomly assigned to three treatments (4 pens/treatment): Control (saline injection), Mixed (8 pigs/pen received an LPS challenge and 8 pigs received saline injection) and 100% (all pigs received LPS). The LPS challenge consisted of a bolus subcutaneous injection at 300 µg/kg BW (E. coli O111:B4). Prior to placement, NUtrack was installed above the 12 nursery pens and initiated continuous data capture for the duration of the nursery phase (43 days). Ten days after placement in the nursery pens pigs received the assigned challenge (LPS or sham). Data were analyzed using the MIXED procedure of SAS specific for repeated measures (SAS Inst. Inc., Cary, NC). Regardless of treatment group, general special behaviors were similar (P = &gt;0.28) prior to the LPS challenge (days 1–9). Following LPS challenge (day 10), spatial behaviors decreased (P = &lt;0.01) and time associated with general behaviors increased (P = &lt;0.01) for LPS challenged pigs when compared to pigs not challenged (Control and 50% non-challenged). This change in both general and spatial behaviors remained until day 12. In addition, general and spatial behaviors of the 50% treatment (challenged and non-challenged) were different (P = &lt; 0.03), when compared to Controls. Results suggest precision livestock technology, like the NUtrack System, has the potential to monitor changes in behaviors following an endotoxin challenge.

scholarly journals BAFF Blockade Attenuates Inflammatory Responses and Intestinal Barrier Dysfunction in a Murine Endotoxemia Model

2020 ◽  
Vol 11 ◽  
Author(s):  
Runze Quan ◽  
Chaoyue Chen ◽  
Wei Yan ◽  
Ying Zhang ◽  
Xi Zhao ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Survival Rates ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Barrier Dysfunction ◽  
Protein Levels ◽  
Lps Challenge ◽  
Endotoxemia Model

B cell-activating factor (BAFF) production is increased in septic patients. However, the specific role of BAFF in sepsis remains unknown. This study was designed to investigate the expression and function of BAFF in an experimental endotoxemia model and to identify the potential mechanisms. We established an endotoxemia mouse (6–8 weeks, 20–22 g) model by administering 30 mg/kg lipopolysaccharide (LPS). BAFF levels in the circulating system and organ tissues were measured 4 and 8 h after LPS injection. Survival rates in the endotoxemia mice were monitored for 72 h after BAFF blockade. The effects of BAFF blockade on systemic and local inflammation, organ injuries, and intestinal barrier function were also evaluated 4 h after LPS treatment. BAFF production was systemically and locally elevated after LPS challenge. BAFF blockade improved the survival rate, systemic inflammation, and multi-organ injuries. Moreover, BAFF blockade attenuated both intestinal inflammation and impaired intestinal permeability. BAFF blockade upregulated ZO-1 and occludin protein levels via the NF-κB/MLCK/MLC signaling pathway. These results suggested that BAFF blockade protects against lethal endotoxemia at least partially by alleviating inflammation, multi-organ injuries, and improving intestinal barrier function and provides a novel focus for further research on sepsis and experimental evidence for clinical therapy.

scholarly journals Tobacco Use Changes and Perceived Health Risks among Current Tobacco Users during the COVID-19 Pandemic

2021 ◽  
Vol 18 (4) ◽  
pp. 1795
Author(s):  
Jessica M. Yingst ◽  
Nicolle M. Krebs ◽  
Candace R. Bordner ◽  
Andrea L. Hobkirk ◽  
Sophia I. Allen ◽  
...  
Keyword(s):  
Tobacco Use ◽  
Cigarette Use ◽  
User Research ◽  
Convenience Sample ◽  
State College ◽  
Quit Attempt ◽  
Global Pandemic ◽  
Penn State ◽  
Penn State College ◽  
Current Tobacco

COVID-19 has become a global pandemic, with over 81 million cases worldwide. To assess changes in tobacco use as a result of the pandemic, we surveyed a convenience sample of current tobacco users between April and June 2020. The sample was taken from a tobacco user research registry (n = 3396) from the Penn State College of Medicine in Hershey, Pennsylvania, USA. Participants who responded to the survey and were eligible for this study (n = 291) were 25.6% male, 93% white, and had a mean age of 47.3 (SD = 11.6) years. There were no reports of participants testing positive for COVID-19, but 21.7% reported experiencing symptoms associated with the virus. Most participants (67%) believed that their risk of contracting COVID-19 was the same as non-tobacco users, but 57.7% believed that their risk of serious complications, if infected, was greater compared to non-tobacco users. A total of 28% reported increasing their cigarette use during the pandemic. The most common reasons for increased use were increased stress, more time at home, and boredom while quarantined. Nearly 15% reported decreasing their tobacco use. The most common reasons for reduced use were health concerns and more time around non-smokers (including children). A total of 71 (24.5%) users reported making a quit attempt. Characterizing these pandemic-related changes in tobacco use may be important to understanding the full scope of subsequent health outcomes resulting from the pandemic. Tobacco cessation resources should be tailored to allow for safe, appropriate access for those interested in quitting.

scholarly journals Parenteral Fish-Oil Containing Lipid Emulsions Limit Initial Lipopolysaccharide-Induced Host Immune Responses in Preterm Pigs

Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 205
Author(s):  
William Yakah ◽  
David Ramiro-Cortijo ◽  
Pratibha Singh ◽  
Joanne Brown ◽  
Barbara Stoll ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fish Oil ◽  
Soybean Oil ◽  
Inflammatory Responses ◽  
Postnatal Period ◽  
Lipid Emulsions ◽  
Omega 3 ◽  
Oil Emulsion ◽  
Mixed Oil ◽  
The Impact

Multicomponent lipid emulsions are available for critical care of preterm infants. We sought to determine the impact of different lipid emulsions on early priming of the host and its response to an acute stimulus. Pigs delivered 7d preterm (n = 59) were randomized to receive different lipid emulsions for 11 days: 100% soybean oil (SO), mixed oil emulsion (SO, medium chain olive oil and fish oil) including 15% fish oil (MO15), or 100% fish oil (FO100). On day 11, pigs received an 8-h continuous intravenous infusion of either lipopolysaccharide (LPS—lyophilized Escherichia coli) or saline. Plasma was collected for fatty acid, oxylipin, metabolomic, and cytokine analyses. At day 11, plasma omega-3 fatty acid levels in the FO100 groups showed the highest increase in eicosapentaenoic acid, EPA (0.1 ± 0.0 to 9.7 ± 1.9, p < 0.001), docosahexaenoic acid, DHA (day 0 = 2.5 ± 0.7 to 13.6 ± 2.9, p < 0.001), EPA and DHA-derived oxylipins, and sphingomyelin metabolites. In the SO group, levels of cytokine IL1β increased at the first hour of LPS infusion (296.6 ± 308 pg/mL) but was undetectable in MO15, FO100, or in the animals receiving saline instead of LPS. Pigs in the SO group showed a significant increase in arachidonic acid (AA)-derived prostaglandins and thromboxanes in the first hour (p < 0.05). No significant changes in oxylipins were observed with either fish-oil containing group during LPS infusion. Host priming with soybean oil in the early postnatal period preserves a higher AA:DHA ratio and the ability to acutely respond to an external stimulus. In contrast, fish-oil containing lipid emulsions increase DHA, exacerbate a deficit in AA, and limit the initial LPS-induced inflammatory responses in preterm pigs.

Exogenous phospholipase A2 affects inflammatory gene expression in primary bovine mammary epithelial cells

2019 ◽  
Vol 86 (2) ◽  
pp. 177-180
Author(s):  
Jacqueline P. Kurz ◽  
Mark P. Richards ◽  
Matthew Garcia ◽  
Zhongde Wang
Keyword(s):  
Epithelial Cells ◽  
Phospholipase A2 ◽  
Inflammatory Responses ◽  
Mammary Epithelial Cells ◽  
Constitutive Expression ◽  
Mammary Epithelial ◽  
Inflammatory Factors ◽  
Bovine Mammary Epithelial Cells ◽  
Lps Challenge

AbstractThis Research Communication addresses the hypothesis that exogenously administered phospholipase A2 (PLA2) affects the inflammatory responses of bovine mammary epithelial cells (bMEC) in vitro with the aim of providing preliminary justification of investigation into the uses of exogenously administered PLA2 to manage or treat bovine mastitis. Primary bMEC lines from 11 lactating Holstein dairy cows were established and the expression of 14 pro-inflammatory genes compared under unchallenged and lipopolysaccharide (LPS)-challenged conditions, with and without concurrent treatment with bovine pancreatic PLA2G1B, a secreted form of PLA2. No differences in the expression of these genes were noted between PLA2-treated and untreated bMEC under unchallenged conditions. Following LPS challenge, untreated bMEC exhibited significant downregulation of CXCL8, IL1B, CCL20, and CXCL1. In contrast, PLA2-treated bMEC exhibited significant downregulation of IL1B and CCL20 only. These findings indicate that exogenous PLA2 affects the expression of some pro-inflammatory factors in immune-stimulated bMEC, but does not influence the constitutive expression of these factors. Further investigation of the influence of exogenous PLA2 in the bovine mammary gland is justified.

scholarly journals Growth Arrest-Specific Factor 6 (GAS6) Is Increased in COVID-19 Patients and Predicts Clinical Outcome

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 335
Author(s):  
Albert Morales ◽  
Silvia Rojo Rello ◽  
Helena Cristóbal ◽  
Aida Fiz-López ◽  
Elisa Arribas ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Growth Arrest ◽  
Emergency Admission ◽  
Human Macrophage ◽  
Specific Factor ◽  
Alveolar Cells ◽  
Lps Challenge ◽  
Tam Receptors ◽  
Relevant Role ◽  
Severity Of The Disease

Background: Growth arrest-specific factor 6 (GAS6) and the Tyro3, AXL, and MERTK (TAM) receptors counterbalance pro-inflammatory responses. AXL is a candidate receptor for SARS-CoV-2, particularly in the respiratory system, and the GAS6/AXL axis is targeted in current clinical trials against COVID-19. However, GAS6 and TAMs have not been evaluated in COVID-19 patients at emergency admission. Methods: Plasma GAS6, AXL, and MERTK were analyzed in 132 patients consecutively admitted to the emergency ward during the first peak of COVID-19. Results: GAS6 levels were higher in the SARS-CoV-2-positive patients, increasing progressively with the severity of the disease. Patients with initial GAS6 at the highest quartile had the worst outcome, with a 3-month survival of 65%, compared to a 90% survival for the rest. Soluble AXL exhibited higher plasma concentration in deceased patients, without significant differences in MERTK among SARS-CoV-2-positive groups. GAS6 mRNA was mainly expressed in alveolar cells and AXL in airway macrophages. Remarkably, THP-1 human macrophage differentiation neatly induces AXL, and its inhibition (bemcentinib) reduced cytokine production in human macrophages after LPS challenge. Conclusions: Plasma GAS6 and AXL levels reflect COVID-19 severity and could be early markers of disease prognosis, supporting a relevant role of the GAS6/AXL system in the immune response in COVID-19.

Effects of omega-3 acid ethyl esters and aspirin, alone and in combination, on platelet function in healthy subjects

2008 ◽  
Vol 100 (10) ◽  
pp. 634-641 ◽  
Author(s):  
Mark K. Larson ◽  
Joseph H. Ashmore ◽  
Kristina A. Harris ◽  
Jessica L. Vogelaar ◽  
James V. Pottala ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Combined Therapy ◽  
Significant Risk ◽  
Ethyl Esters ◽  
Omega 3 ◽  
Heart Attacks ◽  
Impedance Aggregometry ◽  
Patients At Risk ◽  
Clinically Significant

SummaryOmega-3 fatty acids (n-3 FA) from oily fish are clinically useful for lowering triglycerides and reducing risk of heart attacks. Accordingly, patients at risk are often advised to take both aspirin and n-3 FA. However, both of these agents can increase bleeding times, and the extent to which the combination inhibits platelet function is unknown. The purpose of this pilot study was to determine the effects of a prescription omega-3 FA product (P-OM3) and aspirin, alone and in combination, on platelet aggregation assessed by whole blood impedance aggregometry (WBA). Ten healthy volunteers provided blood samples on four separate occasions: Day 1, baseline; Day 2, one day after taking aspirin (2 x 325 mg tablets); Day 29, after 28 days of P-OM3 (4 capsules/day); and Day 30, after one day of combined P-OM3 and aspirin. WBA was tested with two concentrations of collagen, with ADP and with a thrombin receptor activating peptide (TRAP). Compared to baseline, aspirin alone inhibited aggregation only with low-dose collagen stimulation;P-OM3 alone did not inhibit aggregation with any agonist; and combined therapy inhibited aggregation with all agonists butTRAP. Significant interactions between interventions were not observed in response to any agonist. In conclusion, P-OM3 alone did not inhibit platelet aggregation, but did (with two agonists) when combined with aspirin. Since previous studies have not reported a clinically significant risk for bleeding in subjects on combined therapy, P-OM3 may safely enhance the anti-platelet effect of aspirin.

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