scholarly journals Haptoglobin Genotype-Dependent Anti-Inflammatory Signaling in CD163+Macrophages

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
R. Clive Landis ◽  
Pandelis Philippidis ◽  
Jan Domin ◽  
Joseph J. Boyle ◽  
Dorian O. Haskard
Keyword(s):  
Scavenger Receptor ◽  
Intraplaque Hemorrhage ◽  
Phosphatidylinositol 3 Kinase ◽  
Kinase Activation ◽  
Akt Phosphorylation ◽  
Increased Risk ◽  
Haptoglobin Genotype ◽  
Anti Inflammatory ◽  
Inflammatory Signalling ◽  
Inflammatory Macrophage

Intraplaque hemorrhage causes adaptive remodelling of macrophages towards a protective phenotype specialized towards handling iron and lipid overload, denoted Mhem. The Mhem phenotype expresses elevated levels of hemoglobin (Hb) scavenger receptor, CD163, capable of endocytosing pro-oxidant free Hb complexed to acute phase protein haptoglobin (Hp). It is notable that individuals homozygous for the Hp 2 allele (a poorer antioxidant) are at increased risk of cardiovascular disease compared to the Hp 1 allele. In this study, we examined whether scavenging of polymorphic Hp:Hb complexes differentially generated downstream anti-inflammatory signals in cultured human macrophages culminating in interleukin (IL)-10 secretion. We describe an anti-inflammatory signalling pathway involving phosphatidylinositol-3-kinase activation upstream of Akt phosphorylation (pSer473Akt) and IL-10 secretion. The pathway is mediated specifically through CD163 and is blocked by anti-CD163 antibody or phagocytosis inhibitor. However, levels of pSer473Akt and IL-10 were significantly diminished when scavenging polymorphic Hp2-2:Hb complexes compared to Hp1-1:Hb complexes(P<0.05). Impaired anti-inflammatory macrophage signaling through a CD163/pAkt/IL-10 axis may thus represent a possible Hp2-2 disease mechanism in atherosclerosis.

scholarly journals Metformin as an anti-inflammatory agent: a short review

2021 ◽  
Vol 251 (2) ◽  
pp. R11-R22
Author(s):  
Robin Kristófi ◽  
Jan W Eriksson
Keyword(s):  
Chain Complex ◽  
Mitochondrial Respiratory Chain ◽  
Short Review ◽  
Amp Kinase ◽  
Subsequent Increase ◽  
Kinase Activation ◽  
Mitochondrial Respiratory Chain Complex ◽  
Downstream Effects ◽  
Anti Inflammatory ◽  
Inflammatory Signalling

Metformin is a biguanide drug widely used as the initial treatment of type 2 diabetes. Despite its widespread use, its precise mechanisms of action remain incompletely characterised. Its effect in lowering blood glucose is largely related to the suppression of gluconeogenesis in the liver, which is probably accomplished by partial inhibition of the mitochondrial respiratory chain complex 1 with a subsequent increase in intracellular AMP levels and activation of AMP kinase. Several local and systemic anti-inflammatory effects of metformin have been described. Many of these effects seem to be mediated by AMP kinase activation and downstream effects inhibiting mTOR and NF-κB pro-inflammatory signalling cascades. However, there are also studies describing actions independent of AMP kinase action. In this review, we summarise the currently known mechanisms of metformin on inflammatory pathways and the clinical evidence underpinning the use of metformin as a potential anti-inflammatory drug.

Protein Adsorption on Surfaces Functionalized with COOH Groups Promotes Anti-inflammatory Macrophage Responses

2021 ◽  
Vol 13 (6) ◽  
pp. 7021-7036
Author(s):  
Emily Buck ◽  
Seunghwan Lee ◽  
Laura S. Stone ◽  
Marta Cerruti
Keyword(s):  
Protein Adsorption ◽  
Anti Inflammatory ◽  
Inflammatory Macrophage

scholarly journals The Rate of Prescribing Gastrointestinal Prophylaxis with Either a Proton Pump Inhibitor Or an H2-Receptor Antagonist in Nova Scotia Seniors Starting Nonsteroidal Anti-Inflammatory Drug Therapy

2010 ◽  
Vol 24 (8) ◽  
pp. 481-488 ◽  
Author(s):  
Bogdan Superceanu ◽  
Sander Veldhuyzen van Zanten ◽  
Chris Skedgel ◽  
Michael Shepherd ◽  
Ingrid Sketris
Keyword(s):  
Nova Scotia ◽  
Proton Pump Inhibitor ◽  
Proton Pump ◽  
Nonselective Nsaid ◽  
H2 Receptor Antagonist ◽  
Number Of Patients ◽  
Increased Risk ◽  
Gastroprotective Agent ◽  
Anti Inflammatory ◽  
One Year

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used agents that can cause serious gastrointestinal (GI) side effects. For patients at increased risk of NSAID-related GI complications, prophylaxis with either a nonselective NSAID plus gastroprotective agent (GPA) or, alternatively, therapy with a cyclooxygenase-2 selective inhibitor with or without a GPA such as a proton pump inhibitor (PPI), is recommended.AIM: To describe the rate, timing and duration of GI prophylaxis in Nova Scotia seniors receiving nonselective NSAIDs.METHODS: The Nova Scotia Seniors’ Pharmacare Program beneficiaries for the years 1998 to 2002 were studied. A cohort of incident NSAID and GPA users was selected from all nonselective NSAID users (no prescribed NSAID dispensed 12 months before the index month and no GPA dispensed two months before the index prescription). Monthly coprescribing rates were calculated by dividing the number of patients in the cohort using GPAs by the number of NSAID users. GI prophylactic coprescribing was defined as the coprescribing rate present at the first month (index month) of prescribing an NSAID.RESULTS: The cohort consisted of 12,906 patients. Seventy-five per cent of the nonselective NSAID prescriptions dispensed were for up to two months duration, with only 2.3% longer than one year. GI prophylaxis was given to only 3.8% of patients starting NSAIDs who were not on a GPA in the two months before starting NSAIDs. Of this 3.8%, 92.7% of the patients received H2-receptor antagonists (H2RAs), and 7% received PPIs. The rate of H2RA coprescribing increased with the number of consecutive months on an NSAID from 3.5% in the first month to 24.1% at 48 months. For PPIs, the coprescribing rate increased from 0.3% to 1.9% of all NSAID users in the cohort. The rate of gastroprophylaxis coprescribing for patients receiving NSAIDs did not rise with increasing age.CONCLUSION: In Nova Scotian seniors using nonselective NSAIDs, the rate of GI prophylaxis was low. Most patients received H2RAs as GPAs despite evidence that they offer insufficient protection.

scholarly journals THU0417 READMISSION RISK AND QUALITY OF CARE IN PATIENTS PRESENTING TO THE EMERGENCY DEPARTMENT WITH GOUT FLARES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 446.2-446
Author(s):  
L. Brunetti ◽  
J. Vekaria ◽  
P. Lipsky ◽  
N. Schlesinger
Keyword(s):  
Risk Factors ◽  
Emergency Department ◽  
Economic Burden ◽  
Hospital Admissions ◽  
Medical Center ◽  
Research Support ◽  
Increased Risk ◽  
Comorbidity Index ◽  
Anti Inflammatory ◽  
Gout Flares

Background:Gout is the most common form of inflammatory arthritis and its economic burden is substantial, with estimates for the overall cost exceeding $20 billion (US) annually. Contributing to the economic burden are hospital admissions and iatrogenic events associated with pharmacotherapy. Identification of modifiable risk factors would be an important contribution to clinical practice.Objectives:The aim of this study was to identify opportunities for enhancing gout care in patients presenting to the Emergency Department (ED) with gout flares.Methods:This retrospective cohort study used data from electronic medical records (EMR) at a large community hospital. All consecutive patients visiting the medical center ED with a primary diagnosis of gout from 1/1/2016 to 7/1/2019 were included. Patients were then followed for 90 days to determine whether they were readmitted to the ED for any reason. A chart review identified whether they were on appropriate medications in terms of gout flare management. All data were summarized using descriptive statistics. A multiple logistic regression was constructed to identify risk factors for ED utilization within 90 days of the index visit.Results:A total of 214 patients were included in the analysis. Most patients were male (79%), mean age was 59.4 ± 15.6 years, and mean Charlson comorbidity index was 0.5 ± 1.14. The most common medications prescribed during the ED visit included NSAIDs (41.6%), opioids (28%), corticosteroids (26.6%), and colchicine (21%). Allopurinol and febuxostat were initiated in the ED in 4.7% and 0.9%, respectively. Discharge medications for the management of gout included NSAIDs (37%), corticosteroids (34.6%), opioids (23.8%), colchicine (14%), febuxostat (7%), and allopurinol (6.5%). Of the patients sent home with an opioid, 40% were newly prescribed. An anti-inflammatory medication was not prescribed in 29.6% of patients discharged from the ED. Readmission within 90 days was recorded in 16.8% of patients. Of these readmissions, 33.3% were gout-related and 11.1% were cardiac related.After adjusting for age and comorbidity index, patients receiving colchicine were 2.8 times more likely (OR, 2.81; 95% CI, 1.12 to 7.02; p=0.027) to return to the ED within 90 days. The most common cause of readmission in this subset was gout-related (54.5%).Conclusion:Nearly 30% of patients were discharged from the ED without an anti-inflammatory medication, whereas initiation of urate lowering therapy was rare. Opiates were used frequently, but the indication was uncertain. Only 5.6% of subjects revisited the ED for gout-related diagnoses in the subsequent 3 months. Colchicine prescription was associated with an increased risk of gout-related ED utilization within 90 days. Treatment of gout in the ED is sub-optimal and often does not follow established guidelines.Disclosure of Interests: :Luigi Brunetti Grant/research support from: Astellas Pharma, CSL Behring, Consultant of: Horizon Foundation of New Jersey, Janaki Vekaria: None declared, Peter Lipsky Consultant of: Horizon Therapeutics, Naomi Schlesinger Grant/research support from: Pfizer, AMGEN, Consultant of: Novartis, Horizon Pharma, Selecta Biosciences, Olatec, IFM Therapeutics, Mallinckrodt Pharmaceuticals, Speakers bureau: Takeda, Horizon

Abstract 3047: What Are the Effects of Nonsteroidal Anti-Inflammatory Drugs on Post-Cardiothoracic Surgery Outcomes?

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Richard T Ruffin ◽  
Jeffrey Kluger ◽  
Stephanie M Wills ◽  
C M White ◽  
Craig I Coleman
Keyword(s):  
Atrial Fibrillation ◽  
Cardiothoracic Surgery ◽  
Red Blood Cell Transfusion ◽  
Beta Blockade ◽  
Randomized Controlled ◽  
Conflicting Evidence ◽  
Increased Risk ◽  
Inflammatory Drugs ◽  
Surgery Outcomes ◽  
Anti Inflammatory

Background: Two previous studies evaluating nonsteroidal anti-inflammatory drug (NSAID) use following cardiothoracic surgery (CTS) demonstrated conflicting evidence regarding their ability to reduce the incidence of postoperative atrial fibrillation (POAF). Moreover, neither study examined negative cardiovascular outcomes such as stroke and myocardial infarction (MI). Since a recent study evaluating paracoxib/valdecoxib following CTS demonstrated an increased risk of cardiovascular events, we sought to evaluate whether NSAIDs could reduce the incidence of POAF without increasing patients’ risk of stroke or MI. Methods: Patients (n=555) undergoing CTS from the randomized, controlled Atrial Fibrillation Suppression Trials (AFISTs) I, II and III were evaluated in this nested study. Demographic, surgical and medication use characteristics were prospectively collected as part of the AFIST trials. Endpoints included POAF, stroke, MI and the need for red blood cell transfusion. Multivariable logistic regression was used to calculate odds ratios with 95% confidence intervals. Results: The population was 67.8 ± 8.6 years old, 77.1% male, 14.6% underwent valve surgery, 6.1% had prior AF, 12.6% had heart failure and 84.0% and 44.1% received postoperative beta-blockade and prophylactic amiodarone. In total, 127 (22.9%) patients received a NSAID postoperatively. NSAID use was associated with reductions in the odds of POAF and the need for RBC transfusions. (Table ) No elevation in the odds of developing stroke or MI was observed. Conclusions: NSAIDs decreased the odds of developing POAF and the need for RBC transfusions without significantly increasing MI or stroke. Table. Effect of Nonsteroidal Anti-Inflammatory Drugs on Postoperative Outcomes

scholarly journals Ultrasound Elastography: another piece in the puzzle of carotid plaque vulnerability?

2021 ◽  
Author(s):  
Andjoli Davidhi ◽  
Vasileios Rafailidis ◽  
Evangelos Destanis ◽  
Panos Prassopoulos ◽  
Stefanos Foinitsis
Keyword(s):  
Shear Wave ◽  
Carotid Plaque ◽  
Diagnostic Yield ◽  
Imaging Modality ◽  
Shear Wave Elastography ◽  
Ultrasound Elastography ◽  
Intraplaque Hemorrhage ◽  
Plaque Vulnerability ◽  
Carotid Plaques ◽  
Increased Risk

Recent literature has shown that various carotid plaque features, other than stenosis, contribute to plaque vulnerability. Features such as surface morphology and plaque composition with distinct components (e.g. intraplaque hemorrhage, lipid core) have been associated with the increased risk of future cerebrovascular events. Ultrasonography constitutes the first line modality for the assessment of carotid disease and has traditionally been used to grade stenosis with high accuracy. Recenttechnological advances such as contrast-enhanced ultrasound and elastography increased the diagnostic yield of ultrasound in assessing the morphology of carotid plaques. The purpose of this review is to present the available literature on ultrasound elastography of the atherosclerotic carotid. Strain and shear wave elastography allow for the characterization of plaque components, thus indicating its nature and importantly, the plaque’s vulnerability. Shear wave elastography indices appear morerobust than Strain indices. Overall, elastography is a feasible method to distinguish vulnerable carotid plaques. There is, however, a need for larger and longer prospective controlled clinical studies in order to validate elastography as an imaging modality used for the detection of unstable carotid plaques.

Sign in / Sign up

Export Citation Format

Share Document