Nonsteroidal Anti-inflammatory Drug Interaction with Prostacyclin Synthase Protects from Miscarriage.
Ontology highlight
ABSTRACT:
SUBMITTER: Velez Edwards DR
PROVIDER: S-EPMC5575303 | biostudies-literature | 2017 Aug
REPOSITORIES: biostudies-literature
Publications
Nonsteroidal Anti-inflammatory Drug Interaction with Prostacyclin Synthase Protects from Miscarriage.
Velez Edwards Digna R DR Edwards Todd L TL Bray Michael J MJ Torstenson Eric E Jones Sarah S Shrubsole Martha J MJ Muff Harvey J HJ Hartmann Katherine E KE
Scientific reports 20170829 1
This study evaluates the relationship between single nucleotide polymorphisms (SNPs) in nonsteroidal anti-inflammatory drug (NSAID) metabolism and related pathways and spontaneous abortion (SAB, gestation < 20 weeks) risk. Women were enrolled in Right from the Start (2004-2010) prospective cohort. Periconceptional NSAIDs reported through the sixth week of pregnancy were obtained from study interviews. We evaluated 201 SNPs in 600 European American women. Interaction analyses between NSAID use an ...[more]
Similar Datasets
Project description:BACKGROUND:Lipid transfer protein (LTP), an abundant protein in fruits, vegetables, and nuts, is a common food allergen in Mediterranean areas causing diverse allergic reactions. Approximately 40% of food-related anaphylaxis induced by LTPs requires nonsteroidal anti-inflammatory drugs (NSAIDs) as a triggering cofactor. OBJECTIVE:We sought to better understand the determinants of NSAID-dependent and NSAID-independent LTP-induced anaphylaxis (LTP-A). METHODS:Selection of patients was based on a proved clinical history of NSAID-dependent or NSAID-independent anaphylaxis to LTPs, positive skin prick test response to LTPs, and serum LTP IgE. Whole-transcriptome (RNA sequencing) analysis of blood cells from 14 patients with NSAID-related LTP-A (NSAID-LTP-A), 7 patients with LTP-A, and 13 healthy control subjects was performed to identify distinct gene expression signatures. RESULTS:Expression of genes regulating gastrointestinal epithelial renewal was altered in both patient sets, particularly in those with LTP-A, who also presented with gene expression profiles characteristic of an inflammatory syndrome. These included altered B-cell pathways, increased neutrophil activation markers, and increased reactive oxygen species levels. Increased expression of the IgG receptor (CD64) in patients with LTP-A was mirrored by the presence of LTP-specific IgG1 and IgG3. Conversely, patients with NSAID-LTP-A were characterized by reduced expression of IFN-?-regulated genes and IFN-? levels, as well as upregulated expression of adenosine receptor 3 (ADORA3) and genes related to adenosine metabolism. CONCLUSIONS:Gene ontology analysis suggests disturbances in gut epithelial homeostasis in both groups with LTP-A, with potential integrity breaches in patients with LTP-A that might explain their distinct inflammatory signatures. Differential regulation in patients with LTP-A and those with NSAID-LTP-A of the IFN-? pathway, IgG receptors, and ADORA3 might provide the pathogenic basis of their distinct responses.
| S-EPMC4715677 | biostudies-literature
Project description:Nonsteroidal anti-inf lammatory drugs (NSAIDs) are widely prescribed for the treatment of inflammatory diseases, but their use is frequently related to hypersensitivity reactions. This review outlines our current knowledge of NSAID hypersensitivity (NHS) with regard to its pathogenic, molecular, and genetic mechanisms, as well as diagnosis and treatment. The presentation of NHS varies from a local (skin and/or airways) reaction to systemic reactions, including anaphylaxis. At the molecular level, NHS reactions can be classified as cross-reactive (mediated by cyclooxygenase inhibition) or selective (specific activation of immunoglobulin E antibodies or T cells). Genetic polymorphisms and epigenetic factors have been shown to be closely associated with NHS, and may be useful as predictive markers. To diagnose NHS, inhalation or oral challenge tests are applied, with the exclusion of any cross-reactive NSAIDs. For patients diagnosed with NHS, absolute avoidance of NSAIDs/aspirin is essential, and pharmacological treatment, including biologics, is often used to control their respiratory and cutaneous symptoms. Finally, desensitization is recommended only for selected patients with NHS. However, further research is required to develop new diagnostic methods and more effective treatments against NHS.
| S-EPMC4855107 | biostudies-literature
Project description:BackgroundNonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce chronic inflammation and risk of many cancers, but their effect on risk of hepatocellular carcinoma (HCC) and death due to chronic liver disease (CLD) has not been investigated.MethodsWe analyzed prospective data on 300504 men and women aged 50 to 71 years in the National Institutes of Health-AARP Diet and Health Study cohort and linked self-reported aspirin and nonaspirin NSAID use with registry-confirmed diagnoses of HCC (n=250) and death due to CLD (n=428, excluding HCC). We calculated hazard rate ratios (RRs) and their two-sided 95% confidence intervals (CIs) using Cox proportional hazard regression models with adjustment for age, sex, race/ethnicity, cigarette smoking, alcohol consumption, diabetes, and body mass index. All tests of statistical significance were two-sided.ResultsAspirin users had statistically significant reduced risks of incidence of HCC (RR = 0.59; 95% CI = 0.45 to 0.77) and mortality due to CLD (RR = 0.55; 95% CI = 0.45 to 0.67) compared to those who did not use aspirin. In contrast, users of nonaspirin NSAIDs had a reduced risk of mortality due to CLD (RR = 0.74; 95% CI= 0.61 to 0.90) but did not have lower risk of incidence of HCC (RR = 1.08; 95% CI = 0.84 to 1.39) compared to those who did not use nonaspirin NSAIDs. The risk estimates did not vary in statistical significance by frequency (monthly, weekly, daily) of aspirin use, but the reduced risk of mortality due to CLD was statistically significant only among monthly users of nonaspirin NSAIDs compared to non-users.ConclusionsAspirin use was associated with reduced risk of developing HCC and of death due to CLD whereas nonaspirin NSAID use was only associated with reduced risk of death due to CLD.
| S-EPMC3514167 | biostudies-literature
Project description:The ability of nonsteroidal anti-inflammatory drugs (NSAIDs) to inhibit cyclooxygenase (Cox)-1 and Cox-2 underlies the therapeutic efficacy of these drugs, as well as their propensity to damage the gastrointestinal (GI) epithelium. This toxic action greatly limits the use of NSAIDs in inflammatory bowel disease (IBD) and other chronic pathologies. Fatty acid amide hydrolase (FAAH) degrades the endocannabinoid anandamide, which attenuates inflammation and promotes GI healing. Here, we describe the first class of systemically active agents that simultaneously inhibit FAAH, Cox-1, and Cox-2 with high potency and selectivity. The class prototype 4: (ARN2508) is potent at inhibiting FAAH, Cox-1, and Cox-2 (median inhibitory concentration: FAAH, 0.031 ± 0.002 µM; Cox-1, 0.012 ± 0.002 µM; and Cox-2, 0.43 ± 0.025 µM) but does not significantly interact with a panel of >100 off targets. After oral administration in mice, ARN2508 engages its intended targets and exerts profound therapeutic effects in models of intestinal inflammation. Unlike NSAIDs, ARN2508 causes no gastric damage and indeed protects the GI from NSAID-induced damage through a mechanism that requires FAAH inhibition. Multitarget FAAH/Cox blockade may provide a transformative approach to IBD and other pathologies in which FAAH and Cox are overactive.
| S-EPMC4447230 | biostudies-literature
Project description:Nonsteroidal anti-inflammatory drug (NSAID)-activated gene (NAG-1), a divergent member of the transforming growth factor beta superfamily, was previously identified as a gene induced by several anti-tumorigenic compounds, including NSAIDs and peroxisome proliferator-activated receptor gamma (PPARgamma) ligands in humans. In this study, canine NAG-1 was characterised from a canine genomic database. Gene induction by some NSAIDs and PPARgamma ligands was demonstrated in canine osteosarcoma cell lines. Phylogenetic analysis indicates that canine NAG-1 is more homologous with the corresponding mouse and rat genes than with human NAG-1. Expression of canine NAG-1 was increased by treatment with piroxicam and SC-560 (NSAIDs) and the PPARgamma ligand rosiglitazone. This study demonstrates that canine NAG-1 is up-regulated by some anti-tumorigenic compounds in osteosarcoma cell lines and may provide an important target of chemotherapy in canine cancer.
| S-EPMC2268959 | biostudies-literature
Project description:Existing drugs are slow to eradicate Mycobacterium tuberculosis (Mtb) in patients and have failed to control tuberculosis globally. One reason may be that host conditions impair Mtb's replication, reducing its sensitivity to most antiinfectives. We devised a high-throughput screen for compounds that kill Mtb when its replication has been halted by reactive nitrogen intermediates (RNIs), acid, hypoxia, and a fatty acid carbon source. At concentrations routinely achieved in human blood, oxyphenbutazone (OPB), an inexpensive anti-inflammatory drug, was selectively mycobactericidal to nonreplicating (NR) Mtb. Its cidal activity depended on mild acid and was augmented by RNIs and fatty acid. Acid and RNIs fostered OPB's 4-hydroxylation. The resultant 4-butyl-4-hydroxy-1-(4-hydroxyphenyl)-2-phenylpyrazolidine-3,5-dione (4-OH-OPB) killed both replicating and NR Mtb, including Mtb resistant to standard drugs. 4-OH-OPB depleted flavins and formed covalent adducts with N-acetyl-cysteine and mycothiol. 4-OH-OPB killed Mtb synergistically with oxidants and several antituberculosis drugs. Thus, conditions that block Mtb's replication modify OPB and enhance its cidal action. Modified OPB kills both replicating and NR Mtb and sensitizes both to host-derived and medicinal antimycobacterial agents.
| S-EPMC3479555 | biostudies-literature
Project description:Introduction:Limited studies have evaluated risk of stroke associated with the use of NSAIDs in patients with end-stage kidney disease. We examined the adverse effects of selective and nonselective NSAID use on the risk of stroke in dialysis patients. Methods:A case-crossover study was conducted using medical claims data from the National Health Insurance Research Database in Taiwan. We identified patients with ischemic and hemorrhagic stroke (defined as International Classification of Diseases, 9th revision, Clinical Modification codes 433, 434, and 436 for ischemic stroke and 430 and 431 for hemorrhagic stroke) from inpatient claims during the period from 2003 to 2012. Conditional logistic regression models with adjustment for potential confounders were used to determine the effects of NSAID use on stroke. Results:A total of 1190 dialysis patients with stroke were identified from 2003 to 2012. The results indicate a 1.31-fold increased risk of stroke related to NSAID use during the 30 days prior to a stroke (AOR = 1.31; 95% CI: 1.03-1.66); likewise, an excessive risk of ischemic stroke was observed (AOR = 1.34; 95% CI: 1.02-1.77). When classifying NSAIDs into selective and nonselective groups, nonselective NSAID use was significantly associated with an increased risk of stroke (AOR = 1.27; 95% CI: 1.00-1.61). Discussion:In summary, the results show supportive evidence that NSAID use increased the risk of stroke in dialysis patients, which suggests the importance of closely monitoring the transient effects of initial NSAID treatment to patients on dialysis.
| S-EPMC5678629 | biostudies-literature
Project description:Nonsteroidal anti-inflammatory drugs (NSAIDs) are used extensively in ophthalmology for pain and photophobia after photorefractive surgery and to reduce miosis, inflammation, and cystoid macular edema following cataract surgery. In recent years, the US Food and Drug Administration has approved new topical NSAIDs and previously approved NSAIDs have been reformulated. These changes may allow for greater drug penetration into the retina and thereby offer additional therapeutic advantages. For example, therapeutic effects on diabetic retinopathy and age-related macular degeneration may now be achievable. We provide an updated review on the scientific rationale and clinical use of NSAIDs for retinal disease.
| S-EPMC3556848 | biostudies-other
Project description:Background Findings of both case control and in vitro investigations suggest that non-steroidal anti-inflammatory drugs (NSAIDs) may play a beneficial role in the occurrence, growth, and subsistence of glioblastoma multiforme (GBM) brain tumor in humans. Objective In the present retrospective cohort study, we assessed the impact of NSAID use on survival in patients diagnosed with and treated for GBM brain tumors. Methods The impact of NSAID use and six other potential prognostic indicators of survival were assessed in 71 patients treated for GBM brain tumors from February 2011 to June 2016. Survival analysis and cross-tabulation analyses were performed to examine the potential relationship between NSAID use and occurrence of intracranial hemorrhage over the course of treatment for GBM. Results Kaplan-Meier analysis revealed no significant difference in survival between patients with and without NSAID use (p = 0.75; 95% CI: 10.12, 18.13). Multiple Cox regression analysis identified only treatment with chemotherapy as imposing any statistically significant effect on survival (Hazard Ratio (HR) = 3.31; p < 0.001; 95% CI: 1.80, 6.07). Cross-tabulation revealed no significant effect of NSAID use on occurrence of hemorrhage during treatment, X2 (2, N = 71) = 0.65, p2-Sided = 0.42, (Fisher's Exact Test: p2-sided = 0.56, p1-sided = 0.31). Conclusion These results suggest that history of NSAID use is not a determinant of survival in GBM patients. More rigorous, prospective investigations of the effect of NSAID use on tumor progression are necessary before the utility of this family of drugs in the treatment of GBM can be adequately appraised.
| S-EPMC6235638 | biostudies-other
Project description:Using implicit solvent model and replica exchange molecular dynamics, we examine the propensity of a nonsteroidal anti-inflammatory drug, naproxen, to interfere with A? fibril growth. We also compare the antiaggregation propensity of naproxen with that of ibuprofen. Naproxen's antiaggregation effect is influenced by two factors. Similar to ibuprofen, naproxen destabilizes binding of incoming A? peptides to the fibril due to direct competition between the ligands and the peptides for the same binding location on the fibril surface (the edge). However, in contrast to ibuprofen, naproxen binding also alters the conformational ensemble of A? monomers by promoting ?-structure. The second factor weakens naproxen's antiaggregation effect. These findings appear to explain the experimental observations, in which naproxen binds to the A? fibril with higher affinity than ibuprofen, yet produces weaker antiaggregation action.
| S-EPMC3034367 | biostudies-literature