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The New England Journal of Medicine Jan 2024The cyclooxygenase inhibitor ibuprofen may be used to treat patent ductus arteriosus (PDA) in preterm infants. Whether selective early treatment of large PDAs with... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The cyclooxygenase inhibitor ibuprofen may be used to treat patent ductus arteriosus (PDA) in preterm infants. Whether selective early treatment of large PDAs with ibuprofen would improve short-term outcomes is not known.
METHODS
We conducted a multicenter, randomized, double-blind, placebo-controlled trial evaluating early treatment (≤72 hours after birth) with ibuprofen for a large PDA (diameter of ≥1.5 mm with pulsatile flow) in extremely preterm infants (born between 23 weeks 0 days' and 28 weeks 6 days' gestation). The primary outcome was a composite of death or moderate or severe bronchopulmonary dysplasia evaluated at 36 weeks of postmenstrual age.
RESULTS
A total of 326 infants were assigned to receive ibuprofen and 327 to receive placebo; 324 and 322, respectively, had data available for outcome analyses. A primary-outcome event occurred in 220 of 318 infants (69.2%) in the ibuprofen group and 202 of 318 infants (63.5%) in the placebo group (adjusted risk ratio, 1.09; 95% confidence interval [CI], 0.98 to 1.20; P = 0.10). A total of 44 of 323 infants (13.6%) in the ibuprofen group and 33 of 321 infants (10.3%) in the placebo group died (adjusted risk ratio, 1.32; 95% CI, 0.92 to 1.90). Among the infants who survived to 36 weeks of postmenstrual age, moderate or severe bronchopulmonary dysplasia occurred in 176 of 274 (64.2%) in the ibuprofen group and 169 of 285 (59.3%) in the placebo group (adjusted risk ratio, 1.09; 95% CI, 0.96 to 1.23). Two unforeseeable serious adverse events occurred that were possibly related to ibuprofen.
CONCLUSIONS
The risk of death or moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age was not significantly lower among infants who received early treatment with ibuprofen than among those who received placebo. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Baby-OSCAR ISRCTN Registry number, ISRCTN84264977.).
Topics: Humans; Infant, Newborn; Anti-Inflammatory Agents, Non-Steroidal; Bronchopulmonary Dysplasia; Ductus Arteriosus, Patent; Ibuprofen; Infant, Extremely Premature; Cyclooxygenase Inhibitors; Double-Blind Method; Time Factors; Treatment Outcome
PubMed: 38265644
DOI: 10.1056/NEJMoa2305582 -
The New England Journal of Medicine Nov 2000Each year, clinical upper gastrointestinal events occur in 2 to 4 percent of patients who are taking nonselective nonsteroidal antiinflammatory drugs (NSAIDs). We... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
BACKGROUND
Each year, clinical upper gastrointestinal events occur in 2 to 4 percent of patients who are taking nonselective nonsteroidal antiinflammatory drugs (NSAIDs). We assessed whether rofecoxib, a selective inhibitor of cyclooxygenase-2, would be associated with a lower incidence of clinically important upper gastrointestinal events than is the nonselective NSAID naproxen among patients with rheumatoid arthritis.
METHODS
We randomly assigned 8076 patients who were at least 50 years of age (or at least 40 years of age and receiving long-term glucocorticoid therapy) and who had rheumatoid arthritis to receive either 50 mg of rofecoxib daily or 500 mg of naproxen twice daily. The primary end point was confirmed clinical upper gastrointestinal events (gastroduodenal perforation or obstruction, upper gastrointestinal bleeding, and symptomatic gastroduodenal ulcers).
RESULTS
Rofecoxib and naproxen had similar efficacy against rheumatoid arthritis. During a median follow-up of 9.0 months, 2.1 confirmed gastrointestinal events per 100 patient-years occurred with rofecoxib, as compared with 4.5 per 100 patient-years with naproxen (relative risk, 0.5; 95 percent confidence interval, 0.3 to 0.6; P<0.001). The respective rates of complicated confirmed events (perforation, obstruction, and severe upper gastrointestinal bleeding) were 0.6 per 100 patient-years and 1.4 per 100 patient-years (relative risk, 0.4; 95 percent confidence interval, 0.2 to 0.8; P=0.005). The incidence of myocardial infarction was lower among patients in the naproxen group than among those in the rofecoxib group (0.1 percent vs. 0.4 percent; relative risk, 0.2; 95 percent confidence interval, 0.1 to 0.7); the overall mortality rate and the rate of death from cardiovascular causes were similar in the two groups.
CONCLUSIONS
In patients with rheumatoid arthritis, treatment with rofecoxib, a selective inhibitor of cyclooxygenase-2, is associated with significantly fewer clinically important upper gastrointestinal events than treatment with naproxen, a nonselective inhibitor.
Topics: Adult; Arthritis, Rheumatoid; Cardiovascular Diseases; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Duodenal Obstruction; Female; Gastric Outlet Obstruction; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Humans; Isoenzymes; Lactones; Male; Membrane Proteins; Middle Aged; Naproxen; Peptic Ulcer; Proportional Hazards Models; Prostaglandin-Endoperoxide Synthases; Sulfones
PubMed: 11087881
DOI: 10.1056/NEJM200011233432103 -
Marine Drugs Feb 2021Among the brain tumors, glioma is the most common. In general, different biochemical mechanisms, involving nicotinic acetylcholine receptors (nAChRs) and the arachidonic... (Comparative Study)
Comparative Study
Among the brain tumors, glioma is the most common. In general, different biochemical mechanisms, involving nicotinic acetylcholine receptors (nAChRs) and the arachidonic acid cascade are involved in oncogenesis. Although the engagement of the latter in survival and proliferation of rat C6 glioma has been shown, there are practically no data about the presence and the role of nAChRs in C6 cells. In this work we studied the effects of nAChR antagonists, marine snail α-conotoxins and snake α-cobratoxin, on the survival and proliferation of C6 glioma cells. The effects of the lipoxygenase and cyclooxygenase inhibitors either alone or together with α-conotoxins and α-cobratoxin were studied in parallel. It was found that α-conotoxins and α-cobratoxin promoted the proliferation of C6 glioma cells, while nicotine had practically no effect at concentrations below 1 µL/mL. Nordihydroguaiaretic acid, a nonspecific lipoxygenase inhibitor, and baicalein, a 12-lipoxygenase inhibitor, exerted antiproliferative and cytotoxic effects on C6 cells. nAChR inhibitors weaken this effect after 24 h cultivation but produced no effects at longer times. Quantitative real-time polymerase chain reaction showed that mRNA for α4, α7, β2 and β4 subunits of nAChR were expressed in C6 glioma cells. This is the first indication for involvement of nAChRs in mechanisms of glioma cell proliferation.
Topics: Animals; Brain Neoplasms; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cobra Neurotoxin Proteins; Conotoxins; Cyclooxygenase Inhibitors; Glioma; Lipoxygenase Inhibitors; Nicotine; Nicotinic Antagonists; Rats; Receptors, Nicotinic; Time Factors
PubMed: 33669933
DOI: 10.3390/md19020118 -
Biological & Pharmaceutical Bulletin 2012Appropriate long-term drinking of red wine is associated with a reduced risk for lifestyle-related diseases such as cardiovascular disease and cancer, making... (Review)
Review
Appropriate long-term drinking of red wine is associated with a reduced risk for lifestyle-related diseases such as cardiovascular disease and cancer, making resveratrol, a constituent of grapes and various other plants, an attractive compound to be studied. Historically, resveratrol has been identified as a phytoalexin, antioxidant, cyclooxygenase (COX) inhibitor, peroxisome proliferator-activated receptor (PPAR) activator, endothelial nitric oxide synthase (eNOS) inducer, silent mating type information regulation 2 homolog 1 (SIRT1) activator, and more. Despite scepticism concerning the biological availability of resveratrol, a growing body of in vivo evidence indicates that resveratrol has protective effects in several stress and disease models. Here, we provide a review of the studies on resveratrol, especially with respect to COX, PPAR, and eNOS activities, and discuss its potential for promoting human health.
Topics: Animals; Cyclooxygenase Inhibitors; Humans; Nitric Oxide Synthase Type III; Peroxisome Proliferator-Activated Receptors; Resveratrol; Sirtuin 1; Stilbenes
PubMed: 22382311
DOI: 10.1248/bpb.35.273 -
Gut Nov 2005The role of selective cyclooxygenase (COX)-2 inhibitors in medical practice has become controversial since evidence emerged that their use is associated with an...
The role of selective cyclooxygenase (COX)-2 inhibitors in medical practice has become controversial since evidence emerged that their use is associated with an increased risk of myocardial infarction. Selective COX-2 inhibitors were seen as successor to non-selective non-steroidal anti-inflammatory drugs, in turn successors to aspirin. The importance of pain relief means that such drugs have always attracted attention. The fact that they work through inhibition of cyclooxygenase, are widespread, and have multiple effects also means that adverse effects that were unanticipated (even though predictable) have always emerged. In this paper I therefore present an historical perspective so that the lessons of the past may be applied to the present.
Topics: Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; History, 19th Century; History, 20th Century; Humans; Membrane Proteins; Myocardial Infarction; Prostaglandin-Endoperoxide Synthases
PubMed: 16227351
DOI: 10.1136/gut.2005.065003 -
Scientific Reports Feb 2021The beneficial effects of Cyclooxygenases (COX) inhibitors on human health have been known for thousands of years. Nevertheless, COXs, particularly COX-1, have been...
The beneficial effects of Cyclooxygenases (COX) inhibitors on human health have been known for thousands of years. Nevertheless, COXs, particularly COX-1, have been linked to a plethora of human diseases such as cancer, heart failure, neurological and neurodegenerative diseases only recently. COXs catalyze the first step in the biosynthesis of prostaglandins (PGs) and are among the most important mediators of inflammation. All published structural work on COX-1 deals with the ovine isoenzyme, which is easier to produce in milligram-quantities than the human enzyme and crystallizes readily. Here, we report the long-sought structure of the human cyclooxygenase-1 (hCOX-1) that we refined to an R/R of 20.82/26.37, at 3.36 Å resolution. hCOX-1 structure provides a detailed picture of the enzyme active site and the residues crucial for inhibitor/substrate binding and catalytic activity. We compared hCOX-1 crystal structure with the ovine COX-1 and human COX-2 structures by using metrics based on Cartesian coordinates, backbone dihedral angles, and solvent accessibility coupled with multivariate methods. Differences and similarities among structures are discussed, with emphasis on the motifs responsible for the diversification of the various enzymes (primary structure, stability, catalytic activity, and specificity). The structure of hCOX-1 represents an essential step towards the development of new and more selective COX-1 inhibitors of enhanced therapeutic potential.
Topics: Amino Acid Sequence; Animals; Binding Sites; Catalysis; Cyclooxygenase 1; Cyclooxygenase Inhibitors; Enzyme Stability; Glycosylation; Humans; Models, Molecular; Molecular Structure; Protein Binding; Protein Conformation; Protein Interaction Domains and Motifs; Recombinant Proteins; Sheep; Solvents; Structure-Activity Relationship; Substrate Specificity
PubMed: 33619313
DOI: 10.1038/s41598-021-83438-z -
Respiratory Physiology & Neurobiology Jan 2022This study investigated whether intermittent hypoxia (IH) induces airway hyperresponsiveness (AHR) and associated with lung inflammation. Male Brown Norway rats were...
This study investigated whether intermittent hypoxia (IH) induces airway hyperresponsiveness (AHR) and associated with lung inflammation. Male Brown Norway rats were exposed to 14-day IH or room air (RA) for 6 h/day. One day after the last exposure, total lung resistance to various doses of methacholine was measured as an index of bronchoconstrictive responses. Compared with RA controls, methacholine significantly induced an augmented bronchoconstriction in IH-exposed rats. Moreover, IH exposure evoked lung inflammation which was reflected by increased inflammatory cell infiltration, concentrations of interleukin-6 and prostaglandin E in bronchoalveolar lavage fluid, and lung lipid peroxidation. IH-induced AHR and lung inflammation were completely abolished by daily intraperitoneal injection of N-acetylcysteine (an antioxidant) or ibuprofen (a cyclooxygenase inhibitor), but not by apocynin (an inhibitor of NADPH oxidase) or vehicle. In conclusion, AHR and lung inflammation occur after 14-day IH exposure, with endogenous reactive oxygen species and cyclooxygenase metabolites being responsible for these responses.
Topics: Animals; Antioxidants; Cyclooxygenase Inhibitors; Disease Models, Animal; Hypoxia; Male; Oxidative Stress; Pneumonia; Prostaglandin-Endoperoxide Synthases; Rats; Reactive Oxygen Species; Respiratory Hypersensitivity
PubMed: 34537372
DOI: 10.1016/j.resp.2021.103787 -
BioMed Research International 2018In traditional medicine, many pharmacological activities have already been ascribed to the genus of plant. These include antirheumatic antispasmodic, anthelmintic,...
INTRODUCTION
In traditional medicine, many pharmacological activities have already been ascribed to the genus of plant. These include antirheumatic antispasmodic, anthelmintic, diuretic, hypoglycemic, and anticancer effects. The recent investigation aimed to characterize and estimate the chemical composition, anti-inflammatory, antioxidant, and anticancer potentials of the essential oil isolated by the microwave-ultrasonic apparatus from leaves collected from Palestine.
METHODS
The essential oil (EO) was analyzed by Gas Chromatography equipped with mass spectrometry (GC-MS), while its anticancer activity was evaluated against HeLa cervical adenocarcinoma cells. The ability of EO to inhibit the conversion of Arachidonic Acid (AA) to PGH by ovine COX-1 and human recombinant COX-2 was determined using a COX inhibitor screening assay. In addition, the antioxidant activity of the EO was evaluated on the basis of the scavenging activity with a stable 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, while Trolox was used as a positive control.
RESULTS
Forty-four molecules were identified in EO, representing 100% of the total EO. Agarospirol was found to be the most abundant component (45.53%) followed by caryophyllene (19.35%). However, the cyclooxygenase inhibitor assay revealed that has potential COX-1 and Cox-2 inhibitory activity with IC values of 0.25 g/ml and 0.5 g/ml, respectively. Moreover, the EO showed moderate antioxidant capacity with an IC value of 16.98±0.84 g/ml in comparison with the positive control Trolox, which has an antioxidant potential with an IC value of 2.09±0.17 g/ml. In addition, 250, 125, 62.5, 31.25, 15.625, 7.67, and 3.84 mg/ml of EO treatments inhibited mitochondrial activity (cell viability) significantly and extremely by 90-95%.
CONCLUSION
The current study provided data that revealed that the EO could be a suitable candidate for use as a novel anticancer, anti-inflammatory, and antioxidant medication. Further clinical trials would be required to ensure these effects and to allow the design of suitable pharmaceutical dosage forms from this natural oil.
Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cyclooxygenase Inhibitors; Gas Chromatography-Mass Spectrometry; Humans; Oils, Volatile; Sheep; Teucrium
PubMed: 30151381
DOI: 10.1155/2018/4034689 -
Mediators of Inflammation 2014Cyclooxygenases and lipoxygenases are proinflammatory enzymes; the former affects platelet aggregation, vasoconstriction, vasodilatation and later the development of...
Cyclooxygenases and lipoxygenases are proinflammatory enzymes; the former affects platelet aggregation, vasoconstriction, vasodilatation and later the development of atherosclerosis. Red wines from Georgia and central and western Europe inhibited cyclooxygenase-1 (COX-1) activity in the range of 63-94%, cyclooxygenase-2 (COX-2) activity in the range of 20-44% (tested at a concentration of 5 mL/L), and 5-lipoxygenase (5-LOX) activity in the range of 72-84% (at a concentration of 18.87 mL/L). White wines inhibited 5-LOX in the range of 41-68% at a concentration of 18.87 mL/L and did not inhibit COX-1 and COX-2. Piceatannol (IC50 = 0.76 μM) was identified as a strong inhibitor of 5-LOX followed by luteolin (IC50 = 2.25 μM), quercetin (IC50 = 3.29 μM), and myricetin (IC50 = 4.02 μM). trans-Resveratrol was identified as an inhibitor of COX-1 (IC50 = 2.27 μM) and COX-2 (IC50 = 3.40 μM). Red wine as a complex mixture is a powerful inhibitor of COX-1, COX-2, and 5-LOX, the enzymes involved in eicosanoid biosynthetic pathway.
Topics: Arachidonate 5-Lipoxygenase; Catalysis; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Enzyme Activation; Flavonoids; Humans; Quercetin; Resveratrol; Stilbenes; Wine
PubMed: 24976682
DOI: 10.1155/2014/178931 -
Texas Heart Institute Journal 2005The totality of data--the vascular biology and dinical trial data available to date--support the following conclusions: if COX-2 inhibitors are to be used, they should... (Review)
Review
The totality of data--the vascular biology and dinical trial data available to date--support the following conclusions: if COX-2 inhibitors are to be used, they should be considered as 2nd- or 3rd-line agents. They should be used for brief periods of time among patients who are at low risk for cardiovascular events. It is worth pointing out that COX-2 inhibitors were designed initially for use in patients at risk for bleeding ulcers, to minimize gastrointestinal toxicity. Large healthcare databases show, however, that the largest growth of COX-2-inhibitor use has occurred among individuals at low risk for GI side effects. COX-2 inhibitors increase the risk for cardiovascular events. The risk differs, to some degree, across agents, and does appear to be dose related. The relationship between cardiovascular risk and duration of therapy is an important question that requires further consideration. Early risk, from the perspective of pathobiology, may differ from long-term risk. The mechanism of cardiovascular risk is multifactorial and relates to sites of COX-2 synthesis, expression within the vasculature, and related local consequences of an imbalance between thromboxane A2 and prostacyclin. Considered collectively, increased platelet aggregation, hypertension, endothelial cell dysfunction, impaired angiogenesis, and destabilization of the atherosclerotic plaque matrix are important contributors to the "prothrombotic environment." Randomized clinical trials are required to better understand the hazards among individuals at low and high risk for cardiovascular events.
Topics: Cardiovascular Diseases; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Endothelium, Vascular; Humans; Risk Factors
PubMed: 16392224
DOI: No ID Found